Neuronal synchronization along the dorsal visual pathway reflects the focus of spatial attention.
Oscillatory neuronal synchronization, within and between cortical areas, may mediate the selection of attended visual stimuli. However, it remains unclear at and between which processing stages visuospatial attention modulates oscillatory synchronization in the human brain. We thus combined magnetoencephalography (MEG) in a spatially cued motion discrimination task with source-reconstruction techniques and characterized attentional effects on neuronal synchronization across key stages of the human dorsal visual pathway. We found that visuospatial attention modulated oscillatory synchronization between visual, parietal, and prefrontal cortex in a spatially selective fashion. Furthermore, synchronized activity within these stages was selectively modulated by attention, but with markedly distinct spectral signatures and stimulus dependence between regions. Our data indicate that regionally specific oscillatory synchronization at most stages of the human dorsal visual pathway may enhance the processing of attended visual stimuli and suggest that attentional selection is mediated by frequency-specific synchronization between prefrontal, parietal, and early visual cortex.


A multicenter, non-randomized, phase II study of docetaxel and carboplatin administered every 3 weeks as second line chemotherapy in patients with first relapse of platinum sensitive epithelial ovarian, peritoneal or fallopian tube cancer.
In patients with ovarian cancer relapsing at least 6 months after end of primary treatment, the addition of paclitaxel to platinum treatment has been shown to improve survival but at the cost of significant neuropathy. In the first line setting, the carboplatin-docetaxel combination was as effective as the combination of carboplatin and paclitaxel but with less neurotoxicity. This study was initiated to evaluate the feasibility of carboplatin with docetaxel as second line treatment in patients with ovarian, peritoneal or fallopian tube cancer. Patients with stage IC-IV epithelial ovarian, peritoneal or fallopian tube cancer were enrolled at the first relapse after at least 6 months since completion of the first line treatment. Docetaxel 75 mg/m2 was given as an one hour IV infusion followed immediately by carboplatin (AUC=5) given as a 30-60 min. IV infusion on day 1 and repeated every 3 weeks for 6-9 courses. Primary endpoint was toxicity; secondary endpoints were response rate and the time to progression. A total of 74 patients were included. Of these, 50 patients received 6 or more cycles, 13 received 3-5 courses and 11 received less than 3 courses. A total of 398 cycles were given. Grade 3/4 neutropenia was seen in 80% (59 of 74) patients with an incidence of febrile neutropenia of 16%. Grade 2/3 sensory peripheral neuropathy occurred in 7% of patients, but no grade 4 sensory peripheral neuropathy was observed. Sixty patients were evaluable for response. The overall response rate was 70% with 28% complete responses in the response evaluable patient population. Median progression-free survival was 12.4 months (95% CI 10.4-14.4). The three-weekly regimen of docetaxel in combination with carboplatin was feasible and active as second-line treatment of platinum-sensitive ovarian, peritoneal and Fallopian tube cancer. The major toxicity was neutropenia, while the frequency of peripheral neuropathy was low.


The association of thromboembolic complications and the use of tranexamic acid during resection of intracranial meningiomas: systematic review and meta-analysis of randomized controlled trials.
Antifibrinolytics, such as tranexamic acid (TXA), have been shown to decrease intraoperative blood loss across multiple surgical disciplines. However, they carry the theoretical risk of thromboembolic events secondary to induced hypercoagulability. Therefore, the aim of this study was to systematically review the available literature and perform a meta-analysis on the use of TXA in meningioma resection to assess thromboembolic risks. The PubMed, Web of Science, and Google Scholar databases were reviewed for all randomized controlled trials presenting primary data on TXA use during resection of intracranial meningiomas. Data were gathered on operative duration, venous thromboembolic complications, deep venous thrombosis, use of allogeneic blood transfusion, estimated blood loss (EBL), and postoperative hemoglobin. Patients who received TXA were compared with controls who did not receive TXA intraoperatively using random-effects models. A total of 508 unique articles were identified, of which 493 underwent full-text review. Ultimately, 6 studies with 381 total patients (190 receiving TXA) were included in the final analysis. All 6 trials were randomized, blinded, and placebo controlled with a TXA administration rate of a 20-mg/kg load followed by a 1-mg/kg/hr infusion. All studies were performed in lower-middle-income countries. There were no reported instances of venous thromboembolism (VTE) in the TXA and non-TXA cohorts. Patients receiving TXA exhibited fewer allogeneic transfusions (21.5% vs 41.6% [OR 0.26, 95% CI 0.09-0.77], p = 0.02) and lower EBL (MD -282.48 mL [95% CI -367.77 to -197.20 mL], p < 0.001) compared with patients who did not receive TXA, and they also had lower rates of perioperative complications (10.7% vs 19.9% [OR 0.47, 95% CI 0.2-0.95], p = 0.04). Current literature suggests that TXA is not associated with increased risk for VTE when administered during resection of intracranial meningioma. TXA appears to decrease intraoperative blood loss and allogeneic transfusion requirements during meningioma resection and thus may improve the safety of surgical management of this pathology.


Selective activation of angiotensin AT2 receptors attenuates progression of pulmonary hypertension and inhibits cardiopulmonary fibrosis.
Pulmonary hypertension (PH) is a devastating disease characterized by increased pulmonary arterial pressure, which progressively leads to right-heart failure and death. A dys-regulated renin angiotensin system (RAS) has been implicated in the development and progression of PH. However, the role of the angiotensin AT2 receptor in PH has not been fully elucidated. We have taken advantage of a recently identified non-peptide AT2 receptor agonist, Compound 21 (C21), to investigate its effects on the well-established monocrotaline (MCT) rat model of PH. A single s.c. injection of MCT (50 mg·kg(-1) ) was used to induce PH in 8-week-old male Sprague Dawley rats. After 2 weeks of MCT administration, a subset of animals began receiving either 0.03 mg·kg(-1) C21, 3 mg·kg(-1) PD-123319 or 0.5 mg·kg(-1) A779 for an additional 2 weeks, after which right ventricular haemodynamic parameters were measured and tissues were collected for gene expression and histological analyses. Initiation of C21 treatment significantly attenuated much of the pathophysiology associated with MCT-induced PH. Most notably, C21 reversed pulmonary fibrosis and prevented right ventricular fibrosis. These beneficial effects were associated with improvement in right heart function, decreased pulmonary vessel wall thickness, reduced pro-inflammatory cytokines and favourable modulation of the lung RAS. Conversely, co-administration of the AT2 receptor antagonist, PD-123319, or the Mas antagonist, A779, abolished the protective actions of C21. Taken together, our results suggest that the AT2 receptor agonist, C21, may hold promise for patients with PH.


Modeling the Circle of Willis Using Electrical Analogy Method under both Normal and Pathological Circumstances.
The circle of Willis (COW) supports adequate blood supply to the brain. The cardiovascular system, in the current study, is modeled using an equivalent electronic system focusing on the COW. In our previous study we used 42 compartments to model whole cardiovascular system. In the current study, nevertheless, we extended our model by using 63 compartments to model whole CS. Each cardiovascular artery is modeled using electrical elements, including resistor, capacitor, and inductor. The MATLAB Simulink software is used to obtain the left and right ventricles pressure as well as pressure distribution at efferent arteries of the circle of Willis. Firstly, the normal operation of the system is shown and then the stenosis of cerebral arteries is induced in the circuit and, consequently, the effects are studied. In the normal condition, the difference between pressure distribution of right and left efferent arteries (left and right ACA-A2, left and right MCA, left and right PCA-P2) is calculated to indicate the effect of anatomical difference between left and right sides of supplying arteries of the COW. In stenosis cases, the effect of internal carotid artery occlusion on efferent arteries pressure is investigated. The modeling results are verified by comparing to the clinical observation reported in the literature. We believe the presented model is a useful tool for representing the normal operation of the cardiovascular system and study of the pathologies.


A multicenter, prospective, randomized, double-blind, placebo-controlled study to investigate the efficacy of a continuous-combined hormone therapy preparation containing 1mg estradiol valerate/2mg dienogest on hot flushes in postmenopausal women.
To evaluate the effects of an estrogen-reduced, continuous-combined hormone therapy preparation (HT) containing 1mg estradiol valerate (1EV) and 2mg dienogest (2DNG) on the number of moderate and severe hot flushes. This study compared the effects of an oral continuous-combined HT containing 1mg EV and 2mg DNG (1EV/2DNG) with those of placebo. The planned treatment duration was 12 weeks. Data were obtained from 324 postmenopausal women. The primary efficacy variable was the individual relative change of the mean number of moderate and severe hot flushes per week. Weeks 5-12 of treatment were compared with the 2 weeks preceding the treatment phase. Moderate and severe hot flushes were reduced by 80.8+/-30.9% in the 1EV/2DNG group and by 41.5+/-39.4% in the placebo group. This difference was statistically significant (p<0.0001; Wilcoxon's rank sum test). The incidence of all types of hot flushes (mild+moderate+severe) was reduced by 75.2+/-30.2% under 1EV/2DNG and by 35.3+/-37.0% under placebo. In the subset of non-hysterectomized women, exposure to 1EV/2DNG led to 2.4+/-6.2 days with bleeding in the reference period of 84 days of treatment, versus 0.3+/-1.3 days in the placebo group. The safety profile of 1EV/2DNG was very similar to that of placebo. Continuous-combined HT preparation with 1mg EV and 2mg DNG induced a significant reduction of moderate and severe hot flushes compared to placebo (p<0.0001). Thus, this low-estrogen preparation is an effective and safe option for HT.


Inflammatory pseudotumor of the Kidney.
Inflammatory pseudotumor of the kidney or inflammatory myofibroblastic tumor (IMT) is composed of spindle cells admixed with variable amount of proliferating myofibroblasts, fibroblasts, extracellular collagen, lymphocytes and plasma cells. This mainly affects the urinary bladder or prostate. Renal involvement is rare. A 56 year-old man was diagnosed with asymptomatic left sided hydronephrosis while being investigated for rheumatoid arthritis. CT scan imaging showed ill defined fascial plains around the kidney and thickening around the renal hilum suggestive of localized inflammatory change. Worsening intermittent left loin pain with increasing hydronephrosis, significant cortical thinning and marked deterioration of renal function necessitated nephrectomy. Macroscopy showed a hydronephrotic fibrotic kidney with microscopy and immunohistochemistry consistent with a histological diagnosis of IMT. We report a case of an inflammatory pseudotumor of the kidney. It is unique in that the patient presented with painless hydronephrosis followed two years later with progressive deterioration in renal function and worsening loin pain.


Colonoscopy for frank bloody stools associated with cancer chemotherapy.
Diarrhea is a common complication of cancer chemotherapy, while bloody stool is rare. Pseudomembranous colitis has been reported as causing bloody diarrhea after chemotherapy. In this report, we describe nine consecutive patients who presented frank bloody stools within one month after cancer chemotherapy. Patients with a history of pelvic irradiation or with a previously identified colorectal tumor were excluded. Among nine patients, bleeding from tumor undetected before chemotherapy was seen in three, pseudomembranous colitis in four, ischemic colitis in one and methicillin-resistant Staphylococcus aureus enterocolitis in one. Of the three tumors, one was an adenomatous polyp and the other two were metastatic tumors. Two of the four patients with pseudomembranous colitis had not received antibiotics before the onset of colitis. Causes of bloody stools after chemotherapy were various and colonoscopy played an important role in diagnosis and prompt therapy.


Recurrent left atrial myxoma in Carney complex: A case report of a familial pedigree.
Carney complex (CNC) accounts for up to two-thirds of familial cardiac myxoma, which is a rare autosomal dominant syndrome characterized by multiple mucocutaneous lesions and endocrine tumors. Mutation in the cAMP-dependent protein kinase A (PKA) regulatory (R) subunit 1 (PRKAR1A) gene has been identified as a cause of CNC. In this article, we report 3 first-degree relatives with cardiac myxoma who were diagnosed with CNC and underwent surgical resection. The recurrence of cardiac myxoma was detected in a 45-year-old male by echocardiography 5 years after the resection was carried out, without any additional symptoms. Family screening indicated that his brother and his brother's son also had a history of cardiac myxoma. The echocardiography of the patient showed a 43 mm × 28 mm echo mass at the bottom of the atrial septum near anterior mitral leaflet. Sequencing of the patient's genomic DNA obtained from peripheral blood identified a p.E17X (c.491-492delTG) mutation in PRKAR1A, which encodes the type Iα regulatory subunit of protein kinase A. The patient received redo cardiac myxoma resection and mitral valve repair under cardiopulmonary bypass. Echocardiographic surveillance was conducted after the surgery. The patient recovered quickly after the surgery and was discharged without any abnormality detected by echocardiography. Follow-up after 1 year showed no recurrence of the cardiac myxoma. We recommend echocardiographic surveillance of the affected individuals and their first-degree relatives at regular intervals, given the high risk of recurrence and the morbidity and mortality associated with cardiac tumors in any location.


Dual COX inhibition and upper gastrointestinal damage.
Aspirin and non-aspirin NSAIDs injure the gastrointestinal tract principally as a result of their inhibition of prostaglandin synthesis. This is mediated via abrogation of the secretion of mucus and bicarbonate and by reduction in mucosal blood flow. Topical injury and inhibition of platelet thromboxane may also contribute respectively to damage and ulcer bleeding. Recognition of a second cyclooxygenase, COX-2, enabled drugs to be developed that selectively target this enzyme which is expressed in inflamed joints. These have proved to be effective treatments whilst causing little or no acute gastroduodenal injury and reduced ulcers and their complications. Future strategies may capitalise upon the phenomenon of substrate diversion of lipoxygenase products. Balanced cyclooxygenase/lipoxygenase inhibition maybe less harmful than cyclooxygenase inhibition. Also, nitric oxide can subserve many of the protective effects of prostaglandins and NO-donating NSAIDs are under evaluation.


[Current status of robotic urologic surgery in Italy].
The introduction of robot-assisted surgery represents a milestone in the history of surgery. Today, many surgical disciplines make use of the DaVinci robotic system in performing surgery, even complex ones. Italy stands as one of the countries with a greater diffusion of robotics in surgery, particularly in urological surgery. In Italy, every year, numerous urological surgeries are performed with the DaVinci robot; however, costs of this technology are high and, although likely to decrease, constitute a limit to the spread of the same and restricting its use to shared areas.


Collecting (Bellini) duct carcinoma: A clinical study of a rare tumour and review of the literature.
We report our 15-year experience of Collecting (Bellini) duct carcinoma (CDC). We retrospectively analyzed patient and tumour characteristics, clinical manifestations, surgical techniques, clinical outcomes, and salvage therapies. From January 1999 to December 2013, 1042 patients underwent surgical resection of renal neoplasm. We examined all renal tumors and identified 10 cases (0.96%) of CDC. The study group included 8 men and 2 women, with a median age of 62.5 years. Of these 10 patients, 9 were symptomatic (90%). All patients were treated with open nephrectomy. The mean tumour size was 5.7 cm. The pathologic stages were distributed as follows: pT1b in 2 patients (20%); pT2a in 1 patient (10%); pT3a in 3 patients (30%); and pT3b in 4 patients (40%). Grading was assessed according to Fuhrman scale as follows: grade II in 1 patient (10%); grade III in 3 patients (30%); grade IV in 5 patients (50%); undetermined grade in 1 patient (10%). Four patients (40%) relapsed locally. The median time of local recurrence was 4.9 months. Distant metastases occurred in 9 patients (90%): 4/9 at the time of diagnosis and 5/9 after nephrectomy. The median time of distant metastases after surgery was 8.1 months. Six patients received chemotherapy (gemcitabine plus platinum salts). Radiotherapy was performed in 5 patients. One patient had surgery because of local recurrence and 2 patients were irradiated in the area of the local recurrence. The median overall survival was 7.6 months, and only 2 patients survived more than 2 years after the nephrectomy. CDCs of the kidney are aggressive and they have a low survival rate. All patients in our study experienced a relapse of their disease. Local recurrence preceded distant metastases. Results of salvage treatments were poor.


Assessment in Sport and Exercise Psychology: Considerations and Recommendations for Translation and Validation of Questionnaires.
Translating and validating measurement instruments in sport and exercise psychology is not an easy task. Rather, it is a task that requires effort and time, for the process is not limited to a simple translation to translate words from one language to another, just in order to make valid and reliable measure. All researchers should be aware that the only proper way is to adopt rigorous and robust methodologies to conduct the process from the preliminary stage of translation to reaching the validation stage of the psychological variable. Only so is it possible to avoid creating fragile and inadequate psychological assessment instruments that can jeopardize the entire investigation to be held with its use. Thus, the main objective of this work is to promote reflection and discussion on the subject by presenting some considerations and recommendations about translation and validation of questionnaires for psychological assessment applied to sport and exercise domain.


Considerations for Using Alternative Technologies in Nutrient Management on Cape Cod: Beyond Cost and Performance.
Mitigating non-point source nitrogen in coastal estuaries is economically, environmentally, logistically, and socially challenging. On Cape Cod, Massachusetts, nitrogen management includes both traditional, centralized wastewater treatment and sewering as well as a number of alternative technologies. We conducted semi-structured interviews with 37 participants from governmental and non-governmental organizations as well as related industries to identify the barriers and opportunities for the use of alternative technologies to mitigate nitrogen pollution. The interviews were recorded, transcribed, and then analyzed using content analysis and rhetorical analysis. Cost and technical capacity to reduce nitrogen were the most discussed considerations. Beyond those, there were a slew of additional considerations that also impacted whether a technology would be installed, permitted, and socially accepted. These included: maintenance and monitoring logistics, comparisons to sewering, co-benefits, risk/uncertainty, community culture, extent of public engagement, permitting/regulatory challenges, and siting considerations. The insights about these additional considerations are valuable for transferring to other coastal areas managing nutrient impairments that may have not yet factored in these considerations when making decisions about how to meet water quality goals.


An extensive repertoire of type III secretion effectors in Escherichia coli O157 and the role of lambdoid phages in their dissemination.
Several pathogenic strains of Escherichia coli exploit type III secretion to inject "effector proteins" into human cells, which then subvert eukaryotic cell biology to the bacterium's advantage. We have exploited bioinformatics and experimental approaches to establish that the effector repertoire in the Sakai strain of enterohemorrhagic E. coli (EHEC) O157:H7 is much larger than previously thought. Homology searches led to the identification of >60 putative effector genes. Thirteen of these were judged to be likely pseudogenes, whereas 49 were judged to be potentially functional. In total, 39 proteins were confirmed experimentally as effectors: 31 through proteomics and 28 through translocation assays. At the protein level, the EHEC effector sequences fall into >20 families. The largest family, the NleG family, contains 14 members in the Sakai strain alone. EHEC also harbors functional homologs of effectors from plant pathogens (HopPtoH, HopW, AvrA) and from Shigella (OspD, OspE, OspG), and two additional members of the Map/IpgB family. Genes encoding proven or predicted effectors occur in >20 exchangeable effector loci scattered throughout the chromosome. Crucially, the majority of functional effector genes are encoded by nine exchangeable effector loci that lie within lambdoid prophages. Thus, type III secretion in E. coli is linked to a vast phage "metagenome," acting as a crucible for the evolution of pathogenicity.


Assessment of Erysiphe necator Ascospore Release Models for Use in the Mediterranean Climate of Western Oregon.
Predictive models have been developed in several major grape-growing regions to correlate environmental conditions to Erysiphe necator ascospore release; however, these models may not be broadly applicable in regions with different climatic conditions. To assess ascospore release in near-coastal regions of western Oregon, chasmothecia (syn. cleistothecia) were collected prior to leaf drop and placed onto natural and artificial grape trunk segments and overwintered outside. Ascospore release was monitored for three overwintering seasons using custom impaction spore traps from leaf drop (Biologische Bundesanstalt, Bundessortenamt und Chemische Industrie [BBCH] 97) until the onset of the disease epidemic in the following growing season. Airborne inoculum was concurrently monitored in a naturally infested research vineyard. Weather and ascospore release data were used to assess previously developed models and correlate environmental conditions to ascospore release. Ascospore release was predicted by all models prior to bud break (BBCH 08), and was observed from the first rain event following the start of inoculum monitoring until monitoring ceased. Previously developed models overpredicted ascospore release in the Willamette Valley and predicted exhaustion of inoculum prior to bud break. The magnitude of ascospore release could not be correlated to environmental conditions; thus, a binary ascospore release model was developed where release is a function of the collective occurrence of the following factors within a 24-h period: >6 h of cumulative leaf wetness during temperatures >4°C, precipitation >2.5 mm, and relative humidity >80%. The Oregon model was validated using field-collected ascospore datasets, and predicted ascospore release with 66% accuracy (P = 0.02). Extant methods for estimating ascospore release may not be sufficiently accurate to use as predictive models in wet, temperate climatic regions.


Tensile Deformation and Fracture of Unreinforced AZ91 and Reinforced AZ91-C at Temperatures up to 300 °C.
Magnesium alloys are still attractive materials for applications that necessitate light weight due to their low density, moderate strength, and good corrosion resistance. AZ91 is one of the widely applied magnesium alloys due to its very good castability and strength. However, one of the drawbacks of magnesium alloys is the low elastic modulus. So, reinforcing AZ91 with carbon short fibers with the aim of further increasing the strength and improving the elastic modulus is investigated in this study. Squeeze cast AZ91-23 vol.% carbon short carbon (AZ91-C) and the unreinforced AZ91 are deeply examined by tensile testing at different temperatures (20, 100, 150, 200, 250, and 300 °C). Tensile stress-strain curves are measured and the tensile parameters (yield stress, ultimate tensile strength and strain) are defined and presented against the test temperature. Yield stress of AZ91 at 20 °C (109 MPa) is doubled (226 MPa) in the reinforced AZ91-C. Yield stress is found to slightly decrease with increasing the test temperature. Ultimate tensile strength of AZ91 at 20 °C (198 MPa) is increased (262 MPa) in the reinforced AZ91-C. The improvement of the ultimate tensile strength due to reinforcing increases with increasing the test temperature. Flow curves are determined and described by a modified Mecking-Kocks relationship and the flow parameters are determined and described as a function of the test temperature. Microstructure investigation was undertaken of the fractured tensile specimens at the grain boundaries rich in eutectic structure formed at the grain boundaries. Mixed brittle/ductile fracture mode is detected on the fracture surface of unreinforced AZ91, while the SEM investigations show matrix/carbon fiber detachment and fiber fracture as main fracture modes.


Management of infectious fractures with "Non-Contact Plate" (NCP) method.
The aim of this study was to evaluate the outcomes of internal fixation with Non-Contact Plating (NCP) after deep infection caused by previous surgeries of the tibia or femur fractures. The study included 15 patients (4 female and 11 male). The mean age patients was 36.6 years (range, 21-64 years). There were 6 femur and 9 tibia fractures. The mean follow-up period was 25.7 months (range, 15-45 months). The study comprised 11 open and 4 closed fractures. External fixator was used in 3, plate in 4, and intramedullary nail in 8 patients for index surgery. Deep infection was diagnosed via clinical findings, laboratory parameters, and microbiological evaulation. Deep infection was diagnosed within a mean period of 5.5 weeks (range, 2-10 weeks). The infecting organism was methicillin-resistant staphylococcus aureus (MRSA) in 5, methicillin-sensitive staphylococcus aureus (MSSA) in 6, pseudomonas auroginosa in 2, and enterobacteriacea in 2 patients. Union achieved in all patients. Mean time to union was 17 (range, 11-38) weeks. Delayed union was observed in 3 patients who required additional surgeries. Of these one patient developed osteomyelitis. The NCP is an effective alternative method in the treatment of deep infection encountered after internal or external fixation for the tibia, or femur fractures.


Intestinal crypt properties fit a model that incorporates replicative ageing and deep and proximate stem cells.
A model of intestinal crypt organization is suggested based on the assumption that stem cells have a finite replicative life span. The model assumes the existence in a crypt of a quiescent ('deep') stem cell and a few more actively cycling ('proximate') stem cells. Monte Carlo computer simulation of published intestinal crypt mutagenesis data is used to test the model. The results of the simulation indicate that stabilization of the crypt mutant phenotype following treatment with external mutagen is consistent with a stem cell replicative life span of about 40 divisions for mouse colon and 90-100 divisions for mouse small intestine, corresponding to a deep stem cell cycle time of about 3.9 and 8.5 weeks for colon and small intestine, respectively. Simulation of the data obtained for human colorectal crypts suggests that the proximate stem cell cycle time is about 80 h, assuming a replicative life span of 50-150 divisions, and that the deep stem cell divides approximately every 30 weeks.


Muscle performance, voluntary activation and perceived effort in normal subjects and patients with prior poliomyelitis.
Many people previously affected by polio complain of increased fatigue, weakness and pain many years after the initial illness. Although electromyographic abnormalities have been found in these patients, the cause of their increased weakness is not well understood. Previous studies have shown decreased strength and impaired exercise performance in those with prior polio, but the level of voluntary drive to the muscle has not been investigated. The present study investigated maximal voluntary activation without fatigue and both peripheral and central components of muscle fatigue during exercise in 21 subjects with poliomyelitis 20-40 years previously, and 20 healthy, age-matched control subjects. Voluntary activation and strength of the elbow flexors were quantified using twitch interpolation during maximal isometric voluntary contractions both at rest, and during fatigue induced by 45 min of repeated isometric contractions. Compared with the control subjects, patients with prior polio had impaired voluntary activation both when the elbow flexors were not fatigued and during fatiguing submaximal exercise. During exercise, polio subjects also had lower twitch amplitudes and increased subjective fatigue. Central and peripheral fatigue were more marked in those with the post-polio syndrome. The impaired voluntary activation with unfatigued muscles in polio subjects indicates that defective central or reflex drive may contribute to their new weakness.


Healthy Behavior and Sports Drinks: A Systematic Review.
This review article aims to systematically identify the relationship between sports drinks and healthy behavior. This systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline criteria, and eligibility criteria were established using the PICOS tool (population, interventions, comparators, outcomes, and study) from about 1000 records of sports drinks articles identified in the various Web of Science Core Collection databases. The literature review stages determined a reduced set of 15 articles relating these drinkable supplements to healthy behavior. This study concludes that water consumption should be emphasized for non-athletes, sports drinks should be labeled to indicate water consumption and carry a warning label, and more randomized clinical trials should be considered to ensure conclusive results for health decision making.


Inhibition of breast cancer cell growth in vitro and in vivo: effect of restoration of Wwox expression.
The WWOX gene is down-regulated in breast cancer and loss of Wwox expression correlates with important clinical features of breast cancer. Thus, we have examined the effect of restoration of Wwox expression in breast cancer-derived cells. Wwox protein expression was restored by the following: (a) infection with a recombinant adenovirus carrying WWOX cDNA (Ad-WWOX) or (b) treatment with the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, to activate the endogenous WWOX gene, in breast cancer-derived cells in vitro and in vivo. Restoration of Wwox expression led to suppression of growth of Wwox-deficient breast cancer-derived cells, through activation of the intrinsic caspase pathway, but did not affect growth of Wwox-sufficient MCF7 cells. Intratumoral Wwox restoration, through Ad-WWOX infection or endogenous Wwox reactivation by 5-aza-2'-deoxycytidine injection, suppressed tumor growth in nude mice by inducing apoptosis. Alteration of global methylation levels was not observed. The results confirm that overexpression of exogenous Wwox inhibits breast cancer cell growth in vitro and in vivo and, perhaps more importantly, shows that restoration of endogenous Wwox expression, and likely other proteins, by treatment with a de novo methyltransferase inhibitor, also inhibits breast cancer cell growth and reverses breast cancer xenograft growth.


Differential expression of nucleoskeleton- and cytoskeleton-associated proteins in Burkitt lymphoma-derived and Epstein-Barr virus-immortalized lymphoblastoid cell lines.
Mouse monoclonal antibodies raised against nuclear bodies isolated from an EBV-immortalized lymphoblastoid cell line (LCL) known to contain several viral and cellular proteins (Jiang et al., Exp. Cell Res., 197: 314-318, 1991; Szekely et al., J. Gen. Virol., 76: 2423-2432, 1995; Szekely et al., J. Virol., 70: 2562-2568, 1996). Seventy six clones gave detectable immunofluorescence staining on LCLs. Five independent monoclonal antibodies detected a group of apparently novel, high M(r) (> 200,000) proteins that shared common features of subcellular distribution. In LCLs, these proteins were preferentially associated with vimentin filaments in the cytoplasm and with distinct nuclear foci. The appearance of the latter differed from the premyelocytic leukemia-associated protein, EBV nuclear antigen #5, and retinoblastoma-protein-positive bodies that were used for immunization. They seemed to be connected to the cytoplasmic filaments through thin fibrillar nuclear structures. In mitotic cells, these complex structures rearranged into a perichromosomal basket that was associated with vimentin filaments. The target proteins, operationally designated as proteins associated with nuclear dots and cytoplasmic filaments (pNDCFs), were not present in resting human B cells or were expressed at a low level. The level increased considerably after EBV infection or mitogenic stimulation by interleukin 4 and anti-CD40 antibodies. In Burkitt lymphoma (BL) type I lines phenotypically representative of the in vivo tumors, the pNDCFs were either absent or exclusively localized to the nucleus, usually to well-defined nuclear foci. EBV-positive type I BLs often shift to a more LCL-like (type III) phenotype during prolonged in vitro propagation. Type I cells express only EBV nuclear antigen 1 and the surface markers CD10 and CD77, whereas type III express all nine growth-associated EBV-encoded proteins and a gamut of B-cell activation markers. Most of the type III BL cell lines contained increased amounts of pNDCFs bound to cytoplasmic filaments, as seen in the LCLs. We propose that the expression of vimentin-associated pNDCFs should be included in the definition of type III BL phenotype.


Preparation, release and physicochemical characterisation of ethyl butyrate and hexanal inclusion complexes with β- and γ-cyclodextrin.
Complexes of ethyl butyrate and hexanal encapsulated by β-cyclodextrin (β-CD) and γ-cyclodextrin (γ-CD) were prepared by coprecipitation, and gas chromatography was used to quantity the flavour compounds in the complexes. The ethyl butyrate-γ-CD complex had the highest inclusion ratio (12.20%) followed by the ethyl butyrate-β-CD, hexanal-β-CD and hexanal-γ-CD complexes (11.29, 4.41 and 3.33%, respectively). Release experiments were performed under different relative humidities (RH 93, 75 and 52%) and temperatures (4 and 25 °C). The flavour release behaviours of the complexes were described by the Avrami equation. The rate of flavour release was enhanced with both increasing temperature and RH, although the effect of RH was stronger. Physicochemical characterisation using FT-IR, XRD, DSC and SEM analyses demonstrated that crystalline complexes were formed. Both β-CD and γ-CD were able to encapsulate ethyl butyrate and hexanal, and lower RH and temperature were more suitable for the storage of these complexes.


Unexplored Archaeal Diversity in the Great Ape Gut Microbiome.
Archaea are habitual residents of the human gut flora but are detected at substantially lower frequencies than bacteria. Previous studies have indicated that each human harbors very few archaeal species. However, the low diversity of human-associated archaea that has been detected could be due to the preponderance of bacteria in these communities, such that relatively few sequences are classified as Archaea even when microbiomes are sampled deeply. Moreover, the universal prokaryotic primer pair typically used to interrogate microbial diversity has low specificity to the archaeal domain, potentially leaving vast amounts of diversity unobserved. As a result, the prevalence, diversity, and distribution of archaea may be substantially underestimated. Here we evaluate archaeal diversity in gut microbiomes using an approach that targets virtually all known members of this domain. Comparing microbiomes across five great ape species allowed us to examine the dynamics of archaeal lineages over evolutionary time scales. These analyses revealed hundreds of gut-associated archaeal lineages, indicating that upwards of 90% of the archaeal diversity in the human and great ape gut microbiomes has been overlooked. Additionally, these results indicate a progressive reduction in archaeal diversity in the human lineage, paralleling the decline reported for bacteria. IMPORTANCE Our findings show that Archaea are a habitual and vital component of human and great ape gut microbiomes but are largely ignored on account of the failure of previous studies to realize their full diversity. Here we report unprecedented levels of archaeal diversity in great ape gut microbiomes, exceeding that detected by conventional 16S rRNA gene surveys. Paralleling what has been reported for bacteria, there is a vast reduction of archaeal diversity in humans. Our study demonstrates that archaeal diversity in the great ape gut microbiome greatly exceeds that reported previously and provides the basis for further studies on the role of archaea in the gut microbiome.


Determinants of assessing efficiency within auditory attention networks.
The attention network test (ANT) assesses efficiency across alerting, orienting, and executive components of visual attention. This study examined approaches to assessing auditory attention networks, and performance was compared to the visual ANT. Results showed (1) alerting was sufficiently elicited in a pitch discrimination and sound localization task, although these effects were unrelated, (2) weak orienting of attention was elicited through pitch discrimination, which varied based on ISI and conflict level, but robust orienting of attention was found through sound localization, and (3) executive control was sufficiently assessed in both pitch discrimination and sound localization tasks, but these effects were unrelated. Correlation analysis suggested that, unlike alerting and orienting, sound localization auditory executive control functions tap a shared attention network system. Overall, the results suggest that auditory ANT measures are largely task and modality specific, with sound localization offering potential to assess all three attention networks in a single task.


Prevalence of comorbidity of chronic diseases in Australia.
The prevalence of comorbidity is high, with 80% of the elderly population having three or more chronic conditions. Comorbidity is associated with a decline in many health outcomes and increases in mortality and use of health care resources. The aim of this study was to identify, review and summarise studies reporting the prevalence of comorbidity of chronic diseases in Australia. A systematic review of Australian studies (1996 - May 2007) was conducted. The review focused specifically on the chronic diseases included as national health priorities; arthritis, asthma, cancer, cardiovascular disease (CVD), diabetes mellitus and mental health problems. A total of twenty five studies met our inclusion criteria. Over half of the elderly patients with arthritis also had hypertension, 20% had CVD, 14% diabetes and 12% mental health problem. Over 60% of patients with asthma reported arthritis as a comorbidity, 20% also had CVD and 16% diabetes. Of those with CVD, 60% also had arthritis, 20% diabetes and 10% had asthma or mental health problems. There are comparatively few Australian studies that focused on comorbidity associated with chronic disease. However, they do show high prevalence of comorbidity across national health priority areas. This suggests integration and co-ordination of the national health priority areas is critical. A greater awareness of the importance of managing a patients' overall health status within the context of comorbidity is needed together with, increased research on comorbidity to provide an appropriate scientific basis on which to build evidence based care guidelines for these multimorbid patients.


Topological transport in heterostructure of valley photonic crystals.
We propose a heterogeneous structure, which are composed of two valley photonic crystals (VPCs) with opposite valley Chern numbers and air channel. With the increasing width of the air channel, valley-locked waveguide modes are found in topological bandgap by analyzing energy bands. Finite element method (FEM) simulation results show that the fundamental and high order modes are valley-locked, propagating unidirectionally under the excitation of chiral source, and possess higher flux compared to the valley-locked topological edge state in the domain wall. Besides, the immunity to backscattering in bend and couplers, and the robustness to random disorders are discussed in detail. We also investigate the one-way multimode interference (MMI) effect based on valley-locked waveguide modes, and design topological beam splitters. Our study provides a novel idea for topological transport with high flux, and more freedom to design valley-locked waveguide devices, including bends, couplers and splitters.


[Practical experience about the compatibility of PDF converter in ECG information system].
To find a way to view ECG from different manufacturers in electrocardiogram information system. Different format ECG data were transmitted to ECG center by different ways. Corresponding analysis software was used to make the diagnosis reports in the center. Then we use PDF convert to change all ECG reports into PDF format. The electrocardiogram information system manage these PDF format ECG data for clinic user. The ECG reports form several major ECG manufacturers were transformed to PDF format successfully. In the electrocardiogram information system it is freely to view the ECG figure. PDF format ECG report is a practicable way to solve the compatibility problem in electrocardiogram information system.


Hyperoxic ventilated premature baboons have increased p53, oxidant DNA damage and decreased VEGF expression.
Hyperoxia is implicated in the pathogenesis of bronchopulmonary dysplasia (BPD), a chronic lung disease of premature infants. High levels of supplemental oxygen can result in microvascular endothelial cell death and may disrupt lung development. In postnatal animals, hyperoxia inhibits expression of vascular endothelial growth factor (VEGF), which is required for normal vascular development. A potential mechanism of oxygen effects on VEGF is induction of p53, a transcription factor that represses VEGF gene transcription. Oxidant DNA damage can increase p53. We used a moderately premature baboon model of hyperoxia to examine p53, oxidant DNA damage, and VEGF expression. Fetal baboons delivered at 140 d of gestation (75% of term) were ventilated with 100% oxygen or oxygen as needed for 6 or 10 d. Lungs from the 10-d 100% oxygen animals had increased nuclear p53, compared with the oxygen as needed animals. The mechanism of increased p53 was probably related to oxidant DNA damage, which was documented by increased oxidized guanine. Dual fluorescent confocal microscopy found increased oxidized guanine in mitochondrial DNA of distal lung epithelial cells. Distal epithelial cell VEGF expression was decreased and p21, another downstream target of p53, was increased in the distal epithelium of the hyperoxic animals. These data show that p53 is induced in hyperoxic fetal lung epithelium and are consistent with p53 repression of VEGF expression in these cells. The findings suggest that oxidant DNA damage may be a mechanism of increased p53 in hyperoxic fetal lung.


Pulmonary toxicity of indium-tin oxide production facility particles in rats.
Indium-tin oxide (ITO) is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. Occupational exposures to potentially toxic particles generated during ITO production have increased in recent years as the demand for consumer electronics continues to rise. Previous studies have demonstrated cytotoxicity in vitro and animal models have shown pulmonary inflammation and injury in response to various indium-containing particles. In humans, pulmonary alveolar proteinosis (PAP) and fibrotic interstitial lung disease have been observed in ITO facility workers. However, which indium materials or specific processes in the workplace may be the most toxic to workers is unknown. Here we examined the pulmonary toxicity of three different particle samples that represent real-life worker exposures, as they were collected at various production stages throughout an ITO facility. Indium oxide (In2O3), sintered ITO (SITO) and ventilation dust (VD) particles each caused pulmonary inflammation and damage in rats over a time course (1, 7 and 90 days post-intratracheal instillation), but SITO and VD appeared to induce greater toxicity in rat lungs than In2O3 at a dose of 1 mg per rat. Downstream pathological changes such as PAP and fibrosis were observed in response to all three particles 90 days after treatment, with a trend towards greatest severity in animals exposed to VD when comparing animals that received the same dose. These findings may inform workplace exposure reduction efforts and provide a better understanding of the pathogenesis of an emerging occupational health issue.


Sterically Hindered Diarylethenes with a Benzobis(thiadiazole) Bridge: Enantiospecific Transformation and Reversible Photosuperstructures.
ConspectusPhotochromic diarylethenes featuring reversible regulation by external light irradiation have attracted increasing attention in versatile applications such as logic gates, supramolecular systems, liquid crystals, and super-resolution imaging because of their outstanding bistability and fatigue resistance. However, for typical diarylethene systems, there always exist three typical unsolved issues. The first is how to modulate the bistability between the open and closed forms from the viewpoint of ethene bridge aromaticity. The second is how to decrease and avoid the photoinactive parallel conformer in order to achieve a high quantum yield, since the open form possesses the photoactive antiparallel (ap) conformation and the photoinactive parallel (p) conformation. Because of the typical rapid rotation of the flexible side aryl groups, the two conformers cannot be separated efficiently, thereby resulting in a relatively low photocyclization quantum yield. The third is how to fulfill the enantiospecific transformation with reversibility to photomodulate the chirality. Stereochemically, the ap conformer with C2 symmetry can be further subdivided into a pair of enantiomers with P and M helicity originating from the central hexatriene moiety. Similarly, the rapid rotation can also lead to the loss of intrinsic chirality, restricting the development and application of light-driven chiroptical switches. Accordingly, it is desirable to construct a specific diarylethene system to break through these bottlenecks for real versatile applications.Our group has recently developed a unique sterically hindered diarylethene system based on benzobis(thiadiazole) as the ethene bridge for completely solving these issues. We introduce a low-aromaticity benzobis(thiadiazole) unit into the diarylethene as a central ethene bridge with incomparably high bistability. To block or freeze the rotation of flexible side aryls, we further incorporate a large bulky benzothiophene unit to induce a large steric hindrance, or rotation barrier, between the ethene bridge and side aryls, thereby successfully separating multiple conformers of the diarylethenes with high photocyclization quantum yields and enantiospecific photoreaction. Consequently, given such a fantastic building block, we enhance its performance by means of supramolecular self-assembly, thereby realizing unique conformer-dependent self-assembly as well as unprecedented concerted isomerization and enantiospecific photoreaction of photoresponsive metallacycles. In addition, decoration of the intrinsically chiral diarylethenes with mesogenic units can enable us to manipulate the helical superstructure of liquid crystals, thus achieving a multiple anticounterfeiting technique and a quadridimensional manipulable laser. We also unravel the dual aggregation-induced emission (AIE) behavior of the sterically hindered diarylethene, especially as applied in super-resolution imaging.


[Clinical observation of topical steroid for the treatment of chronic rhinosinusitis in Chinese adults].
This study was focused on the clinical effects of topical steroid for chronic rhinosinusitis (CRS) in Chinese adults. The CRS patients were randomly selected in the department of otorhinolaryngology, first affiliated hospital of Sun Yat-sen university between november 2010 and December 2011. Thirty-four CRS patients with polyps (CRSwNP) or CRS without polyps (CRSsNP), no prior surgeries were included. These patients were prescribed to use budesonide nasal spay for three months. Evaluation included visual analog score (VAS), sino-nasal outcome test-20(SNOT-20), CT scan (Lund-Mackay score). SPSS 16.0 software was used to analyze the data. Four patients were lost to follow up, while the other 30 patients finished the 3-months' follow up. Except for smelling disturbance which was not statistically changed (t = 0.902, P > 0.05), VAS for nasal blockage (baseline: 4.84 ± 3.15, after treatment: 2.26 ± 2.27), rhinorrhea (baseline: 6.03 ± 2.93, after treatment: 1.96 ± 2.23), headache (baseline: 1.68 ± 2.66, after treatment: 0.42 ± 0.95), facial pressure (baseline: 2.04 ± 2.97, after treatment: 0.58 ± 1.42) and general symptom (baseline: 6.00 ± 2.75, after treatment: 2.71 ± 1.90) were statistically decreased (t value was 4.386, 6.740, 2.445, 2.980, 6.989, respectively, all P < 0.05). VAS of nasal blockage, rhinorrhea and general symptom were statistically decreased after one-month's treatment (all P < 0.05), but no statistical improvements were observed between first, second and the third month (all P > 0.05). SNOT-20 was significantly decreased after treatment (t = 3.687, P < 0.01). 22.2% patients were cured on CT scan. Topical steroid improves objective symptoms and quality of life in CRS patients. Some of the patients can be cured in CT scores. The symptoms improvements begin from the first month, but do not change during the latter two months.


α6-Containing Nicotinic Acetylcholine Receptor Reconstitution Involves Mechanistically Distinct Accessory Components.
Acetylcholine gates a large family of nicotinic receptor cation channels that control neuronal excitation and neurotransmitter release. These receptors are key targets for neuropsychiatric disorders; however, difficulties in expressing nicotinic acetylcholine (nACh) receptors hamper elaboration of their pharmacology and obscure elucidation of their biological functions. Particularly intriguing are α6-containing nACh receptors, which mediate nicotine-induced dopamine release in striatum-nucleus accumbens. Using genome-wide cDNA screening, we identify three accessory proteins, β-anchoring and -regulatory protein (BARP), lysosomal-associated membrane protein 5 (LAMP5), and SULT2B1, that complement the nACh receptor chaperone NACHO to reconstitute α6β2β3 channel function. Whereas NACHO mediates α6β2β3 assembly, BARP primarily enhances channel gating and LAMP5 and SULT2B1 promote receptor surface trafficking. BARP knockout mice show perturbations in presynaptic striatal nACh receptors that are consistent with BARP modulation of receptor desensitization. These studies unravel the molecular complexity of α6β2β3 biogenesis and enable physiological studies of this crucial neuropharmacological target.


[Polymorphism of hypervariable segment I of mitochondrial DNA in three ethnic groups of the Volga-Ural region].
A population genetic study of the polymorphism in the first hypervariable segment (HVSI) of mitochondrial DNA control region was carried out for three ethnic populations of the Volga-Ural region, Bashkirs, Russians, and Komi-Permyaks. This analysis showed that most of the mtDNA HVSI haplotypes detected in the populations of Bashkirs, Russians and Komi-Permyaks contained the combinations of nucleotide substitutions detected earlier in Asian, European, and Finno-Ugric populations. These findings are consistent with historical, anthropological, and ethnographical data suggesting the presence of European and Mongoloid components of different geographical descent in the gene pool of the contemporary population of the Volga-Ural region. The data on the genetic structure and the phylogenetic relationships between populations of the Volga-Ural region based on modern molecular genetic methods of mitochondrial genome investigation would be a substantial addition to the already existing information for some other regions of Europe and Asia. These data would provide more complete examination of the development of interethnic diversity of mitochondrial gene pools of contemporary ethnic populations with the purpose of reconstructing the genetic demographic processes that accompanied peopling of the Middle Ural and Volga region.


Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin.
The small GTP-binding protein Rab25 is associated with tumor formation and progression. However, recent studies have shown discordant effects of Rab25 on cancer cell progression depending on cell lineage. In the present study, we elucidate the underlying mechanisms by which Rab25 induces cellular invasion. We demonstrate that Rab25 increases β1 integrin levels and subsequent activation of EGFR and upregulation of VEGF-A expression, leading to increased Snail expression, epithelial-to-mesenchymal transition and cancer cell invasiveness. Strikingly, we identify that Snail mediates Rab25-induced cancer cell invasiveness through fascin expression and that ectopic expression of Rab25 aggravates metastasis of ovarian cancer cells to the lung. We thus demonstrate a novel role of a β1 integrin/EGFR/VEGF-A/Snail signaling cascade in Rab25-induced cancer cell aggressiveness through induction of fascin expression, thus providing novel biomarkers and potential therapeutic targets for Rab25-expressing cancer cells.


Synthesis of hierarchical porous bioactive glasses for bone tissue regeneration.
A novel hierarchical porous bioactive glasses were synthesised with cattail stem and triblock polyethylene oxide-propylene oxide block copolymer (P123) as macroporous template and mesoporous template, respectively. The structural and textural properties of materials were characterised by X-ray diffraction, scanning electron microscope, Fourier transform infrared spectroscopy, nitrogen adsorption-desorption, energy dispersive spectrometer and vibrating sample magnetometer technique. The results reveal the bioglasses possess multilevel porous structure with the macroporous size about 50 μm and the mesopore with the diameter of 3.86 nm. Furthermore, metformin HCl was used as the model drug. The drug release kinetics and hydroxyapatite (HAP, (Ca10(PO4)6(OH)2)) inducing-growth ability of the composites were studied, respectively. The system exhibits the fast HAP inducing-growth ability and long-term drug delivery, making them a good candidate for bone tissue regeneration.


The impact of COVID-19 on the sensitivity of D-dimer for pulmonary embolism.
This study seeks to evaluate the test characteristics of D-dimer for pulmonary embolism (PE) in patients with a concurrent diagnosis of COVID-19. We hypothesized that the sensitivity of D-dimer for PE at current institutional cut points would be similar to those without COVID-19. This is a multicenter retrospective observational cohort study across five urban and suburban EDs in the same health care system. The electronic health record was queried for all computed tomography pulmonary angiography (CTPA) studies from December 1, 2019, to October 22, 2020. All ED patients who underwent CTPA had D-dimer and COVID-19 testing completed in a single encounter were included in the study. Baseline demographics were obtained. Test characteristics of D-dimer for PE were calculated for patients with and without COVID-19. Additionally, receiver operator characteristics (ROC) curves were constructed for two different D-dimer assays. There were 1158 patient encounters that met criteria for analysis. Performance of D-dimer testing for PE was similar between COVID-19-positive and -negative patients. In COVID-19-positive patients, the sensitivity was 100% (95% confidence interval [CI] = 87.6%-100%), specificity was 11.9% (95% CI = 7.9%-17.1%), and negative predictive value (NPV) was 100%. In COVID-19-negative patients the sensitivity was 97.6% (95% CI = 91.5%-99.7%), specificity was 14.4% (95% CI = 12.1%-17%), and NPV was 98.3% (95% CI = 93.8%-99.6%). For assay 1 the area under the curve (AUC) for COVID-19-positive patients was 0.76 (95% CI = 0.68-0.83), and for COVID-19-negative patients, 0.73 (95% CI = 0.69-0.77). For assay 2, AUC for COVID-19-positive patients was 0.85 (95% CI = 0.77-0.92), and for COVID-19-negative patients, 0.80 (95% CI = 0.77-0.84). Inspection of the ROC curve for assay 1 revealed that 100% sensitivity was maintained up to a threshold of 0.67 FEU (fibrinogen equivalent units; from 0.50 FEU) with an increase in specificity to 29% (from 18.7%), and for assay 2, 100% sensitivity was maintained up to a threshold of 662 D-dimer units (DDU; from 230 DDU) with an increased specificity to 59% (from 6.1%). Results from this multicenter retrospective study did not find a significant difference in sensitivity of D-dimer for PE due to concomitant COVID-19 infection. Further study is required to determine if PE can safely be excluded based on D-dimer results alone in patients with suspected or proven COVID-19 or if adjusted D-dimer levels could have a role in management.


Prolongation of liver-specific function for primary hepatocytes maintenance in 3D printed architectures.
Isolated primary hepatocytes from the liver are very similar to in vivo native liver hepatocytes, but they have the disadvantage of a limited lifespan in 2D culture. Although a sandwich culture and 3D organoids with mesenchymal stem cells (MSCs) as an attractive assistant cell source to extend lifespan can be used, it cannot fully reproduce the in vivo architecture. Moreover, long-term 3D culture leads to cell death because of hypoxic stress. Therefore, to overcome the drawback of 2D and 3D organoids, we try to use a 3D printing technique using alginate hydrogels with primary hepatocytes and MSCs. The viability of isolated hepatocytes was more than 90%, and the cells remained alive for 7 days without morphological changes in the 3D hepatic architecture with MSCs. Compared to a 2D system, the expression level of functional hepatic genes and proteins was higher for up to 7 days in the 3D hepatic architecture. These results suggest that both the 3D bio-printing technique and paracrine molecules secreted by MSCs supported long-term culture of hepatocytes without morphological changes. Thus, this technique allows for widespread expansion of cells while forming multicellular aggregates, may be applied to drug screening and could be an efficient method for developing an artificial liver.


Influence of Na2O Content and Ms (SiO2/Na2O) of Alkaline Activator on Workability and Setting of Alkali-Activated Slag Paste.
The performance of alkali-activated slag (AAS) paste using activators of strong alkali components is affected by the type, composition, and dosage of the alkaline activators. Promoting the reaction of ground granulated blast furnace slag (GGBFS) by alkaline activators can produce high-strength AAS concrete, but the workability might be drastically reduced. This study is aimed to experimentally investigate the heat release, workability, and setting time of AAS pastes and the compressive strength of AAS mortars considering the Na2O content and the ratio of Na2O to SiO2 (Ms) of binary alkaline activators blended with sodium hydroxide and sodium silicate. The test results indicated that the AAS mortars exhibited a high strength of 25 MPa at 24 h, even at ambient temperature, even though the pastes with an Na2O content of ≥6% and an Ms of ≥1.0 exhibited an abrupt decrease in flowability and rapid setting.


How good are emergency department Senior House Officers at interpreting X-rays following radiographers' triage?
To assess the accuracy of Senior House Officers at interpreting plain X-rays following their triage by radiographers in an emergency department. We collected 2593 patients' records by systematic sampling of all those seen by emergency physicians between January 2002 and April 2002 (ca 10 000 patients) in a UK emergency department. The variables recorded included evidence of X-ray investigations and, when present, the Senior House Officer's diagnosis, the presence (abnormal) or absence of a radiographers red dot and the reference standard diagnosis. A separate category of uncertain (inconclusive) was applied to the Senior House Officer and reference standard diagnosis where appropriate. Diagnostic performance was measured by likelihood ratios with associated pre-test and post-test probabilities. Including the uncertain category as abnormal gave the following results: there were 967 X-rays and those with a red dot had a probability of an abnormality of 80%. Although a further opinion of abnormal by a Senior House Officer increased this probability to 89% when they overrode the red dot opinion of the radiographer, it was incorrect in 26% of cases. Currently, the Senior House Officer contributes to the red dot system by improving on the radiographer in rates of diagnosis of both abnormal and normal X-rays. Further reductions in error rates, however, are unlikely to be achieved until there is a change to the existing system. This may ultimately involve removing some of the responsibility of X-ray interpretation from the Senior House Officer. Any future research should consider the methodological issues highlighted by this study.


Effect of thyroxine and growth hormone on dentin production in maxillary incisors in the rat.
Dentin production and longitudinal growth of maxillary incisors in female rats, age 60--95 d, were determined by the tetracycline technique in hypophysectomized rats after administration of growth hormone and thyroxine during age 75--95 d. Hypophysectomy was performed at age 60 d. Administration of thyroxine resulted in a considerable increase in dentin apposition and longitudinal growth of the tooth. The same effect, but somewhat lower, was registered for growth hormone. Growth hormone and thyroxine administered simultaneously had an additive synergistic effect. Compared with the effect of hypophysectomy and of hormone administration on longitudinal bone growth and cortical bone remodleing the effect on dentin production and longitudinal growth of the maxillary incisors in the same rats is less pronounced and shows a different pattern in reaction, indicating differences in sensitivity for different cell systems and difference in endocrine control.


Primary sex cord-like variant of endometrioid adenocarcinoma arising from endometriosis.
Endometriosis, a relatively common disease generally affecting women in the reproductive age group, is mostly found in the pelvic organs. Although endometriosis is a benign disease, some malignant tumors have been reported to develop in endometriotic lesions, most commonly in the ovary. The relationship between endometriosis and malignancy is not well known, but the majority of endometriosis-associated ovarian malignancies are usually endometrioid adenocarcinomas and clear cell carcinomas. The sex cord-like variant of endometrioid adenocarcinoma is a rare tumor that histologically closely resembles the sex cord-stromal tumor. Despite its rarity, the correct histological diagnosis of the sex cord-like variant of endometrioid adenocarcinoma is crucial to avoid misdiagnosis of a less aggressive tumor. We here report a 53-year-old woman who was diagnosed as having this very rare subtype of endometroid adenocarcinoma curiously arising from an endometriotic lesion at the site of previous salpingo-oophorectomy. The tumor was diagnosed based on light microscopy and immunohistochemistry.


A simulation-based performance analysis of a National Electronic Health Record System.
This paper addresses through simulation experiments a number of technical issues which are raised during the development and operation of a National Electronic Health Record System (NEHRS). The simulation experiments represent the NEHRS performance for a variety of technological infrastructures, within the context of a realistic scenario. The scenario includes the estimation of the delays created in queues during the exchange of Electronic Patient Records (EPR) between different health service points. It is essential to clarify the delays derive from LAN and Internet technologies, the EPR encryption/decryption, the HL7 message generation/parsing, and the databases. The results of this study identify how a number of technical aspects influence the NEHRS development and operation.


[Poststroke mania].
Affective disorders are common among post-stroke patients and mainly presented with disorders of the depressive spectrum. Mania is observed in less than 1% of patients after stroke. Mania could develop after stroke in any vascular territory, however most commonly - in case of lesion location in the right hemisphere. It is suggested that its development is related to the abnormalites of cortico-striato-thalamo-cortical circuitry. Diagnosis and treatment of post-stroke mania is conducted by general principals.


Latitude Determination and Error Analysis for Stationary SINS in Unknow-Position Condition.
The initial geographic latitude information is the key to the self-alignment of the strapdown inertial navigation system (SINS), but how to determine the latitude when the latitude cannot be obtained directly or in a short time? The latitude determination (LD) methods are introduced, including magnitude method, geometric method, and analytical methods 1 and 2, to solve this situation only by the output of the SINS itself. Simulation and experimental test results validate the efficiency of these LD methods. In order to improve the accuracy of the LD, the error of the LD method is derived through comparative analysis. Based on the relationship between LD error and inertial measurement unit (IMU) bias. Partial bias estimation method is introduced and executed during latitude determination. After compensating the estimated IMU bias, the accuracy of the LD will be further improved. Latitude errors are also affected by the latitude where SINS is located. Comprehensive simulation and experimental tests verify the effectiveness of the method. The IMU determined latitude can not only be used to achieve the self-alignment of the SINS, but also to correct the navigation latitude of the long-term SINS, thereby improving the autonomy and positioning accuracy of the navigation system.


Interplay of secondary structures and side-chain contacts in the denatured state of BBA1.
The denatured state of a miniprotein BBA1 is studied under the native condition with the AMBER/Poisson-Boltzmann energy model and with the self-guided enhanced sampling technique. Forty independent trajectories are collected to sample the highly diversified denatured structures. Our simulation data show that the denatured BBA1 contains high percentage of native helix and native turn, but low percentage of native hairpin. Conditional population analysis indicates that the native helix formation and the native hairpin formation are not cooperative in the denatured state. Side-chain analysis shows that the native hydrophobic contacts are more preferred than the non-native hydrophobic contacts in the denatured BBA1. In contrast, the salt-bridge contacts are more or less nonspecific even if their populations are higher than those of hydrophobic contacts. Analysis of the trajectories shows that the native helix mostly initiates near the N terminus and propagates to the C terminus, and mostly forms from 3(10)-helix/turn to alpha helix. The same analysis shows that the native turn is important but not necessary in its formation in the denatured BBA1. In addition, the formations of the two strands in the native hairpin are rather asymmetric, demonstrating the likely influence of the protein environment. Energetic analysis shows that the native helix formation is largely driven by electrostatic interactions in denatured BBA1. Further, the native helix formation is associated with the breakup of non-native salt-bridge contacts and the accumulation of native salt-bridge contacts. However, the native hydrophobic contacts only show a small increase upon the native helix formation while the non-native hydrophobic contacts stay essentially the same, different from the evolution of hydrophobic contacts observed in an isolated helix folding.


Use of the platelet reactivity index by Grotemeyer, platelet function analyzer, and retention test Homburg to monitor therapy with antiplatelet drugs.
In 1974, Wu and Hoak described a method for determining circulating platelet aggregates. This method was modified by Grotemeyer in 1983. The platelet reactivity index (PR) is based on the ratio of platelet aggregates in blood samples obtained in different buffer solutions. Platelet aggregates are resolved when blood is sampled in EDTA-buffer, but remain fixed when EDTA-formalin-buffer is used. Generally, the PR is preferred, because in vitro manipulations of platelets are not necessary, and the results are calculated. PR values above 1.05 are suspicious for elevated platelet aggregation. PR values above 1.2 indicate pathological changes in platelet aggregation. The PR is inexpensive (4.0 euro dollars) and rapid to perform. PR values were used successfully to identify nonresponders to secondary prophylaxis with acetylsalicylic acid (ASA), that is, patients suffering from stroke (33%) and patients after cardiac ischemia (18%). Furthermore, elevated PR values correlated significantly with the incidence of arterial thromboembolic complications. The PR correlated well in our prospective study with values received from the retention test Homburg (RT-H) and the platelet function analyzer (PFA-100). The data indicate that the values of the PR seem to be highly predictive for the evaluation of the ASA therapy. However, the PR is not feasible for the determination of the ASA overdosage.


Real-world efficacy: intravenous palonosetron three-drug regimen for chemotherapy-induced nausea and vomiting with highly emetogenic chemotherapy.
Real-world palonosetron effectiveness was evaluated in an antiemetic regimen with highly emetogenic chemotherapy (HEC). In this Phase IV, prospective, multicenter observational study, HEC-treated cancer patients received palonosetron, a neurokinin 1 receptor antagonist, and dexamethasone. Primary objective was to assess complete response (CR) for acute (≤24 h), delayed and overall (≤120 h) chemotherapy-induced nausea and vomiting. Of 159 patients, 65.4% had breast cancer, 64.8% received anthracycline (doxorubicin)-plus-cyclophosphamide-containing chemotherapy; 155 completed one HEC cycle. CR was 60.0% acute, 39.4% delayed and 34.8% overall, and then increased (all phases) in 69 patients completing four HEC cycles. Anthracycline (doxorubicin) plus cyclophosphamide-receiving patients had especially low CR. Even within a recommended three-drug antiemetic regimen, palonosetron may provide suboptimal chemotherapy-induced nausea and vomiting control with HEC in real-world settings.


[Immunogenicity of recombinant HEV ORF2 protein expressed in pichia pastoris].
To study to immunogenicity of recombinant HEV ORF2 protein expressed in pichia pastoris. BALB/c mice were immunized with the recombinant HEV ORF2 protein. The ability of antiserum to bind HEV was tested using affinity-capture reverse transcription polymerase chain reaction (RT-PCR). Moreover, the recombinant protein was used to immunize BALB/c mice by different routes with different adjuvants. Serum conversion rate of anti-HEV antibody and the ELISA titer were detected. The antiserum could capture native HEV for RT-PCR. As to the immunization effect, the immune response by intramuscular route was better than that of the intraperitoneal route. The protein with alum and CpG adjuvant could elicits more significant immune responses than using the alum adjuvant alone. The best way was to immunize with the protein with alum and CpG adjuvant by intramuscular route with a boosted injection on the 4th week after the first immunization. The ED50 was 0.023 microgram. This is the first report that the antibody elicited by recombinant HEV ORF2 protein expressed in pichia pastoris recognizes native HEV. High immunogenicity of this kind of ORF2 was also demonstrated by inducing strong immune response in mice with good ED50 result. The high immunogenicity of this kind of HEV ORF2 may make a foundation for the development of new type of hepatitis E vaccine.


How Educational Theory Can Inform the Training and Practice of Plastic Surgeons.
It is important to optimize our current learning and teaching models, particularly in a climate of decreased clinical exposure. With technical advancements and clinical care now more accountable, traditional methods of skill acquisition need to be revisited. The past decade has seen changes in plastic surgery curricula. There has also been a shift toward competency-based training programs reflecting the growing emphasis on outcomes-based surgical education. This review explores the role of educational theory in promoting effective learning in practical skills teaching. Key models of educational theory are presented and their application to plastic surgery training to an expert level are highlighted. These models include (1) learning within communities of practice (Lave and Wenger's theory); (2) the role of the zone of proximal development and importance of the availability of expert assistance (Vygotsky's theory); (3) skill acquisition and retention (Dreyfus' and Dreyfus', and Fitts' and Posner's theories); (4) development of expertise after repeated practice and regular reinforcement (Ericsson's theory); and (5) the assessment of competence (Miller's triangle). Future plastic surgeons need to possess a thorough understanding of the technical and nontechnical skills required to manage patients effectively. Surgical educators are therefore compelled to develop practical training programs that can teach each of these skills in a safe, learner-centric manner. It is hoped that new approaches to surgical skills training are designed in light of our understanding of educational theory to optimize the training of the next generation of plastic surgeons.


Effect of alcohols on lactose solubility.
In tests of effects of high (70 to 90% volume/volume) and low (2 and 5% volume/volume) alcohol concentrations, solubility of lactose decreased with increased alcohol concentration and decreased as alcohol chain length increased. Since lactose has lower solubility in alcohol, crystallization would be expected to be speeded by increased supersaturation. Composition of precipitates formed by the action of ethanol changed with time; alpha-lactose precipitated more rapidly at first, then beta-lactose. Time of crystallization was related directly to the percentage of beta-lactose (therefore, the relation was inverse for total alpha). However, the percentage of alpha-hydrate increased with time and with water content. Agitation during crystallization increased production of beta-lactose. Composition of the lactose precipitate varied greatly with concentration of alcohol (ethanol). When ethanol concentration was low, only alpha-hydrate was precipitated whereas at higher concentrations stable anhydrous alpha lactose also was precipitated, with the percentage of total alpha decreasing while the percentage of beta-lactose increased. Crystal shape changed from prisms initially to partially or fully developed tomahawks as time went by or as the percentage of ethanol decreased, and crystal color increased with crystallization time and as ethanol percentage decreased. Choosing long-chain alcohols and controlling suitable parameters enabled recovery of greater amounts and more desirable forms of lactose.


[Complete revascularization of coronary artery].
25 cases of complete revascularization for coronary artery disease by sequential aorto-coronary saphenous bypass operation were performed from April, 1990 to July, 1993. All the patients suffered from three vessels diseases. Left ventricular ejection fraction ranged from 22-60%. Left ventricular end diastolic pressure ranged from 1.3-4.0 kPa. They received grafts from 2-5, 3.6 grafts for a patient in an average. There were no perioperative myocardial infarction and operative death. And they recovered smoothly postoperatively. Angina has been remarkably improved. The paper briefly discussed the technique of this type of the operation and the advantages of the sequential graft bypass operation.


Extraction of Distance Between Interface Trap and Oxide Trap from Random Telegraph Noise in Gate-Induced Drain Leakage.
This paper presents an analysis of the Random Telegraph Noise (RTN) of the Gate-Induced Drain Leakage (GIDL) of a Metal Oxide Semiconductor Field Effect Transistor (MOSFET). The RTN data that was measured and analytical equations are used to extract the values of the parameters for the vertical distance of the oxide trap from the interface and of the energy level of the interface trap. These values and equations allow for the distance r between the interface trap and the oxide trap to be extracted. For the first time, the accurate field enhancement factor γ(F), which depends on the magnitude of the electric field at the Si/SiO2 interface, was used to calculate the current ratio before and after the electron trapping, and the value extracted for r is completely different depending on the enhancement factor that is used.


Differences and Similarities for Spatial and Feature-Based Selective Attentional Orienting.
Using selective attention, we prioritize behaviorally relevant information out of all surrounding stimulation. Attention can be oriented intentionally to spatial and/or non-spatial properties (feature-based attention). When comparing spatial and feature-based attention, previous studies identified a common fronto-parietal network, although some reported specific activation for spatial attention and few found higher activation for feature-based attention. Most studies examining differences between attention types investigated the cueing epoch. We examined reorienting processing (after invalid cueing) and correctly focused attention (after valid cueing) for spatial and feature-based orienting using fMRI in two human samples with 40 participants overall and identical stimuli, stimulus probabilities, and timing for all conditions. A fronto-parietal network including parts of the ventral orienting network was activated for reorienting and focused attention for both attention types. Common activity over validities and attention types was located in bilateral IPL/SMG, bilateral IFG/insula, and the cerebellum. A network of mainly posterior areas showed higher activity for spatial compared to feature-based orienting. Conversely, no specialized areas for spatial focused attention or for feature-based attention (reorienting/focusing) was observed. The posterior clusters specialized for spatial reorienting showed overlapping activity with clusters involved in common spatial and feature-based reorienting as well as focused attention over attention types. Therefore, the results hint at a superordinate fronto-parietal network for both attention types during reorienting and focusing, with a spatial specialization of posterior sub-regions.


Biosynthesis of magnesium oxide and calcium carbonate nanoparticles using Moringa oleifera extract and their effectiveness on the growth, yield and photosynthetic performance of groundnut (Arachis hypogaea L.) genotypes.
Small-scale crop production has been significantly impacted by the heavy price, limited supply, and frequent shortage of inorganic fertilisers, which is partly attributable to the Covid-19 pandemic outbreak and led to rising oil and food prices. Thus, integrating environmentally friendly agricultural practices that can improve crop productivity and advance the sustainability of agricultural cropping systems is critical. This study synthesized and characterised MgO and CaCO3Moringa oleifera nanoparticles and assessed their effects on groundnut genotypes. The effect of biosynthesized MgO and CaCO3 nanoparticles using Moringa oleifera extract on the growth and yield of groundnut genotypes exposed to different concentrations of 50, 100 and 200 mg/L was examined. The experiment was carried laid out in a 3 × 8 factorial completely randomized design (CRD) with eight replicates per treatment. Each plant was sprayed with 5 ml of the solution crystalline size of the MgO and CaCO3 nanoparticles 2.48 nm and 10.30 nm, respectively. Foliar application of nanoparticle treatments was applied weekly except for the negative control. The collected data were subjected to a two-way analysis of variance (ANOVA). Mean separations were done using Tukey's Honest Significant Difference (HSD) at P < 0.05. The findings demonstrated that foliar application of MgO and CaCO3 nanoparticles positively affected groundnut biomass production. The results further revealed that the concentration of 50 mg/L of MgO and 100 mg/L of CaCO3 considerably improved groundnut plant growth, yield, and nodulation in comparison with other treatments. There is a great deal of evidence signifying that foliar applications of 50 mg/L of MgO 100 mg/L CaCO3 contributed greatly to plant growth and crop production. Therefore, 50 mg/L of MgO and 100 mg/L CaCO3 nanoparticles foliar application could be recommended as nano-fertilisers application rate for groundnut production.


[Family history of affective disorders, the gender factor and clinical characteristics of depression].
Analysis of clinical features of development and course of depression in patients with FH of mood disorders taking into account sex differences. This multicenter cross-sectional study included patients over 18 years of age with depressive episode/recurrent depressive disorder. Clinical characteristics of depression, presence of comorbid mental illness and family history (FH) information were obtained in a structured clinical interview. One hundred and seventy-one patients (mean age (M (SD)) 40.87 (15.86) y.o.), including 64.5% of women, were enrolled in the study. FH was revealed in 30.2% of patients. The proportion of FH did not differ in men and women (p=0.375). Generalized anxiety disorder (GAD) was more frequent in FH positive patients (p=0.016). Logistic regression also revealed that FH is a risk factor for concomitant GAD (p=0.019, OR=2.4). The GLM demonstrated a significant joint effect of FH and sex on the maximum duration of a depressive episode (p=0.044), as well on the number of suicide attempts (p=0.055) and the number of depressive episodes as a trend (p=0.072). We have demonstrated the specific interaction of FH of mood disorders with sex on clinical course of depression. Thus, the manifestation of a genetic influence on the clinical phenotype of depression can be significantly moderated by sex.


Learned reward association improves visual working memory.
Statistical regularities in the natural environment play a central role in adaptive behavior. Among other regularities, reward association is potentially the most prominent factor that influences our daily life. Recent studies have suggested that pre-established reward association yields strong influence on the spatial allocation of attention. Here we show that reward association can also improve visual working memory (VWM) performance when the reward-associated feature is task-irrelevant. We established the reward association during a visual search training session, and investigated the representation of reward-associated features in VWM by the application of a change detection task before and after the training. The results showed that the improvement in VWM was significantly greater for items in the color associated with high reward than for those in low reward-associated or nonrewarded colors. In particular, the results from control experiments demonstrate that the observed reward effect in VWM could not be sufficiently accounted for by attentional capture toward the high reward-associated item. This was further confirmed when the effect of attentional capture was minimized by presenting the items in the sample and test displays of the change detection task with the same color. The results showed significantly larger improvement in VWM performance when the items in a display were in the high reward-associated color than those in the low reward-associated or nonrewarded colors. Our findings suggest that, apart from inducing space-based attentional capture, the learned reward association could also facilitate the perceptual representation of high reward-associated items through feature-based attentional modulation.


In vivo models of angiogenesis.
The process of building new blood vessels (angiogenesis) and controlling the propagation of blood vessels (anti-angiogenesis) are fundamental to human health, as they play key roles in wound healing and tissue growth. More than 500 million people may stand to benefit from anti- or pro-angiogenic treatments in the coming decades [National Cancer Institute (USA), Cancer Bulletin, volume 3, no. 9, 2006]. The use of animal models to assay angiogenesis is crucial to the search for therapeutic agents that inhibit angiogenesis in the clinical setting. Examples of persons that would benefit from these therapies are cancer patients, as cancer growth and spread is angiogenesis-dependent, and patients with aberrant angiogenesis in the eye, which may lead to blindness or defective sight. Recently, anti-angiogenesis therapies have been introduced successfully in the clinic, representing a turning point in tumor therapy and the treatment of macular degeneration and heralding a new era for the treatment of several commonly occurring angiogenesis-related diseases. On the other hand, pro-angiogenic therapies that promote compensatory angiogenesis in hypoxic tissues, such as those subjected to ischemia in myocardial or cerebral hypoxia due to occluding lesions in the coronary or cerebral arteries, respectively, and in cases of poor wound healing, are also being developed. In this review, the current major and newly introduced preclinical angiogenesis assays are described and discussed in terms of their specific advantages and disadvantages from the biological, technical, economical and ethical perspectives. These assays include the corneal micropocket, chick chorioallantoic membrane, rodent mesentery, subcutaneous (s.c.) sponge/matrix/alginate microbead, s.c. Matrigel plug, s.c. disc, and s.c. directed in vivo angiogenesis assays, as well as, the zebrafish system and several additional assays. A note on quantitative techniques for assessing angiogenesis in patients is also included. The currently utilized preclinical assays are not equivalent in terms of efficacy or relevance to human disease. Some of these assays have significance for screening, while others are used primarily in studies of dosage-effects, molecular structure activities, and the combined effects of two or more agents on angiogenesis. When invited to write this review, I was asked to describe in some detail the rodent mesenteric-window angiogenesis assay, which has not received extensive coverage in previous reviews.


Chain-length dependence of insertion, desorption, and translocation of a homologous series of 7-nitrobenz-2-oxa-1,3-diazol-4-yl-labeled aliphatic amines in membranes.
We present a complete characterization of the kinetics of interaction between the homologous series of fluorescent fatty amines with the fluorescent moiety 7-nitrobenz-2-oxa-1,3-diazol-4-yl covalently bound to the amine group, NBD-C(n) (n = 8-16), and a lipid bilayer in the liquid disordered phase. The insertion into and the desorption from the lipid bilayer, as well as the rate of translocation across the two bilayer leaflets, has been measured at different temperatures, allowing an estimation of the thermodynamic parameters in the formation of the transition state. This is the first report on the complete characterization of the kinetics of the interaction of a large series of structurally homologous amphiphiles. In a recent paper from this research group, the equilibrium interaction of NBD-C(n) (n = 4-10) with POPC bilayers and serum albumin was reported. This information allows the calculation of the equilibrium distribution of the amphiphiles among the aqueous phase, serum proteins, and biomembranes. The data presented in this manuscript complement its characterization with information on the kinetics of the interactions, making possible the quantitative evaluation of their pharmacokinetics. The rate of translocation is shown to decrease with increasing alkyl chain length up to n = 12, becoming relatively insensitive to further increases in n. The Gibbs free energy variation associated with the rate of desorption from the lipid bilayer increased linearly with n, with ΔΔG(‡o) = 3.4 ± 0.5 kJ mol(-1) per methylene group. It was also found that the process of insertion in the lipid bilayer is not diffusion-limited, although it is close to this limit for the smaller amphiphiles in the homologous series at high temperatures.


A Parental Health Education Model of Children's Food Consumption: Influence on Children's Attitudes, Intention, and Consumption of Healthy and Unhealthy Foods.
This study proposes that parental mediation of television advertising and parental guidance of food consumption differentially influence children's attitude, intention, and behavior toward the consumption of healthy and unhealthy foods. Structural equation modeling based on a survey of 1,119 children aged 9-12 supported our model, revealing that parental education strategies influence children's food consumption in a complex manner that is highly context-dependent. Parental guidance of food consumption enhanced children's healthy food attitude and intention to consume, while reducing the intention to consume unhealthy food. However, parental mediation of television advertising influenced unhealthy food attitude to a greater extent than healthy food attitude. Implications for health promotion and education, as well as parents and policy makers are discussed.


Primary radiation therapy for stage I and II breast cancer.
In 1987 there were estimated to be approximately 130,000 new cases of breast cancer diagnosed in the United States. Presently, about 20-30,000 of these cases are treated with primary radiotherapy, although many more of the 90,000 stage I and II breast cancer cases are eligible for this form of treatment. Appropriate selection must be employed, including the size and site of the primary tumor, the size of the breast, the potential for multifocal disease, and the age of the patient. When proper selection is used, primary radiotherapy for stage I and II disease yields equivalent overall survival and NED survival when compared to traditional mastectomy. The benefit is preservation of the breast with good to excellent cosmesis in the vast majority of patients.


Structural basis for the hydrolytic dehalogenation of the fungicide chlorothalonil.
Cleavage of aromatic carbon-chlorine bonds is critical for the degradation of toxic industrial compounds. Here, we solved the X-ray crystal structure of chlorothalonil dehalogenase (Chd) from Pseudomonas sp. CTN-3, with 15 of its N-terminal residues truncated (ChdT), using single-wavelength anomalous dispersion refined to 1.96 Å resolution. Chd has low sequence identity (<15%) compared with all other proteins whose structures are currently available, and to the best of our knowledge, we present the first structure of a Zn(II)-dependent aromatic dehalogenase that does not require a coenzyme. ChdT forms a "head-to-tail" homodimer, formed between two α-helices from each monomer, with three Zn(II)-binding sites, two of which occupy the active sites, whereas the third anchors a structural site at the homodimer interface. The catalytic Zn(II) ions are solvent-accessible via a large hydrophobic (8.5 × 17.8 Å) opening to bulk solvent and two hydrophilic branched channels. Each active-site Zn(II) ion resides in a distorted trigonal bipyramid geometry with His117, His257, Asp116, Asn216, and a water/hydroxide as ligands. A conserved His residue, His114, is hydrogen-bonded to the Zn(II)-bound water/hydroxide and likely functions as the general acid-base. We examined substrate binding by docking chlorothalonil (2,4,5,6-tetrachloroisophtalonitrile, TPN) into the hydrophobic channel and observed that the most energetically favorable pose includes a TPN orientation that coordinates to the active-site Zn(II) ions via a CN and that maximizes a π-π interaction with Trp227 On the basis of these results, along with previously reported kinetics data, we propose a refined catalytic mechanism for Chd-mediated TPN dehalogenation.


Survival phenotype, selfish individual versus Darwinian phenotype.
Consider and infinitely large asexual population without mutations and direct interactions. The activities of an individual determine the fecundity and the survival probability of individuals, moreover each activity takes time. We view this population model as a simple combination of life history and optimal foraging models. The phenotypes are given by probability distributions on these activities. We concentrate on the following phenotypes defined by optimization of different objective functions: selfish individual (maximizes the average offspring number during life span), survival phenotype (maximizes the probability of non-extinction of descendants) and Darwinian phenotype (maximizes the phenotypic growth rate). We find that the objective functions above can achieve their maximum at different activity distributions, in general. We find that the objective functions above can achieve their maximum at different activity distributions, in general. The novelty of our work is that we let natural selection act on the different objective functions. Using the classical Darwinian reasoning, we show that in our selection model the Darwinian phenotype outperforms all other phenotypes.


Reflections on the interface of bioethics, public policy and science.
This paper discusses the role of ethical considerations in the formulation of public policies aimed at shaping the scientific agenda. Specifically, new and controversial public policy issues will confront us in the twenty-first century as the result of developments on the frontiers of biomedical science. Some of the anxieties in the ethical arena generated by the rapid pace of these developments are likely to result in efforts to place constraints on the shape of the scientific agenda and the application of new knowledge. Our moral propositions, therefore, will be tested and re-tested in their application to evolving social, cultural, and historical circumstances and the ever-changing technological context.


Acute positional vertigo in the emergency department-peripheral vs. central positional nystagmus.
Benign paroxysmal positional vertigo (BPPV) is the most common cause of positional vertigo. However, positional vertigo can also be due to diseases affecting the central vestibular pathways, such as vestibular migraine. Accurate and timely diagnosis enables effective triage and management. To evaluate diagnoses made by emergency clinicians compared to acute vertigo specialists, in patients presenting to an emergency department (ED) with positional vertigo. Following routine ED care, patients with a primary complaint of dizziness, vertigo, light-headedness or unsteadiness, underwent detailed neuro-otological assessment by acute vertigo specialists. Demographics and final diagnoses were recorded and analyzed. Of 71 consented patients (21-91 years; mean 56 years, ±16.7 years, 40 females), ED identified 13 with a peripheral cause of positional vertigo (mean 48.85 years, ±16.19, 8 females). Central positional nystagmus was not noted in any of the patients with positional vertigo seen by the ED clinicians. Acute vertigo specialists diagnosed nine patients with BPPV (age range 50-88 years, mean 66 years, ±12.22, 5 females), and six with central positional nystagmus (age range 23-59 years, mean 41.67 years, ±15.78, 6 females). Positional vertigo should be assessed with positional maneuvers such as Dix-Hallpike and Roll tests in the ED to identify peripheral and central nystagmus features. Central causes are more common in younger females, with the presence of vomiting, and/or a background of motion sensitivity.