Cardiac resynchronization therapy upregulates cardiac autonomic control.
To determine the effect of cardiac resynchronization therapy (CRT) on sympathetic nervous function in heart failure (HF). Neurohormonal dysregulation and cardiac autonomic dysfunction are associated with HF and contribute to HF progression and its poor prognosis. We hypothesized that mechanical resynchronization improves cardiac sympathetic function in HF. Sixteen consecutive patients receiving CRT for advanced cardiomyopathy and 10 controls were included in this prospective study. NYHA class, 6-minute walk distance, echocardiographic parameters, plasma norepinephrine (NE) were assessed at baseline, 3-month and 6-month follow-up. Cardiac sympathetic function was determined by (123)iodine metaiodobenzylguanidine ((123)I-MIBG) scintigraphy and 24-hour ambulatory electrocardiography. Along with improvement in NYHA class (3.1 +/- 0.3 to 2.1 +/- 0.4, P < 0.001) and LVEF (23 +/- 6% to 33 +/- 12%, P < 0.001), delayed heart/mediastinum (H/M) (123)I-MIBG ratio increased significantly (1.8 +/- 0.7 to 2.1 +/- 0.6, P = 0.04) while the H/M (123)I-MIBG washout rate decreased significantly (54 +/- 25% to 34 +/- 24%, P = 0.01) from baseline to 6-month follow-up. The heart rate variability (HRV) measured in SD of normal-to-normal intervals also increased significantly from baseline (82 +/- 30 ms) to follow-up (111 +/- 32 ms, P = 0.04). The improvement in NYHA after CRT was significantly associated with baseline (123)I-MIBG H/M washout rate (r = 0.65, P = 0.03). The improvement in LVESV index was associated with baseline (123)I-MIBG delayed H/M ratio (r =-0.67, P = 0.02) and H/M washout rate (r = 0.65, P = 0.03). After CRT, improvements in cardiac symptoms and LV function were accompanied by rebalanced cardiac autonomic control as measured by (123)I-MIBG and HRV.


Enhanced oxidation of urea by pH swing during chlorination: pH-dependent reaction mechanism.
Urea reacts with chlorine to form chlorinated ureas (chloroureas), and fully chlorinated urea (tetrachlorourea) is further hydrolyzed into CO2 and chloramines. This study found that the oxidative degradation of urea by chlorination was enhanced by the pH swing, wherein the reaction proceeded under an acidic pH (e.g., pH = 3) in the first stage, and the solution pH was subsequently increased to a neutral or alkaline value (e.g., pH > 7) in the second-stage reaction. The degradation rate of urea by pH-swing chlorination increased with increasing chlorine dose and pH during the second-stage reaction. The pH-swing chlorination was based on the opposite pH dependence of sub-processes comprising urea chlorination. The formation of monochlorourea was favored under acidic pH conditions; however, the subsequent conversion into di- and trichloroureas was favored under neutral or alkaline pH conditions. The deprotonation of monochlorourea (pKa = 9.7 ± 1.1) and dichlorourea (pKa = 5.1 ± 1.4) was suggested to be responsible for the accelerated reaction in the second stage under increased pH conditions. pH-swing chlorination was also effective in degrading urea at low concentrations (micromolar levels). In addition, the total nitrogen concentration significantly decreased during the degradation of urea because of the volatilization of chloramines and the release of other gaseous nitrogen compounds.


Coplanarity Constrained Ultrasound Probe Calibration Based on N-Wire Phantom.
N-wire phantom-based ultrasound probe calibration has been used widely in many freehand tracked ultrasound imaging systems. The calibration matrix is obtained by registering the coplanar point cloud in ultrasound space and non-coplanar point cloud in tracking sensor space based on the least squares method. This method is sensitive to outliers and loses the coplanar information of the fiducial points. In this article, we describe a coplanarity-constrained calibration algorithm focusing on these issues. We verified that the out-of-plane error along the oblique wire in the N-wire phantom followed a normal distribution and used it to remove the experimental outliers and fit the plane with the Levenberg-Marquardt algorithm. Then, we projected the points to the plane along the oblique wire. Coplanarity-constrained point cloud registration was used to calculate the transformation matrix. Compared with the other two commonly used methods, our method had the best calibration precision and achieved 25% and 36% improvement of the mean calibration accuracy than the closed-form solution and in-plane error method respectively at depth 16. Experiments at different depths revealed that our algorithm had better performance in our setup. Our proposed coplanarity-constrained calibration algorithm achieved significant improvement in both precision and accuracy compared with existing algorithms with the same N-wire phantom. It is expected that calibration accuracy will improve when the algorithm is applied to all other N-wire phantom-based calibration procedures.


Mobile elements in the human genome: implications for disease.
Perhaps as much as two-thirds of the mammalian genome is composed of mobile genetic elements ('jumping genes'), a fraction of which is still active or can be reactivated. By their sheer number and mobility, retrotransposons, DNA transposons and endogenous retroviruses have shaped our genotype and phenotype both on an evolutionary scale and on an individual level. Notably, at least the non-long terminal repeat retrotransposons are still able to cause disease by insertional mutagenesis, recombination, providing enzymatic activities for other mobile DNA, and perhaps by transcriptional overactivation and epigenetic effects. Currently, there are nearly 100 examples of known retroelement insertions that cause disease. In this review, we highlight those genome-scale technologies that have expanded our knowledge of the diseases that these mobile elements can elicit, and we discuss the potential impact of these findings for medicine. It is now likely that at least some types of cancer and neurological disorders arise as a result of retrotransposon mutagenesis.


Corticosteroids and human recombinant activated protein C for septic shock.
This article summarizes the current knowledge on the benefit/risk profile from the use of low-dose corticosteroids and activated protein C in treating septic shock. Physicians should consider using low-dose corticosteroids and drotrecogin alpha activated in the treatment of patients who have vasopressor-dependent septic shock with persistent signs of hypoperfusion, organ dysfunction, or hypotension. The optimal timing for initiating these treatments is from 6 to 24 hours from onset of shock. When patients are receiving these drugs, physicians should systematically screen for superinfection and serious bleeding events.


Superoxide dismutase activity in nerve cell culture.
Superoxide dismutase (EC 220.127.116.11) activity was assayed in preparations obtained from several clonal lines of nerve cell culture, by enzymatic and nonenzymatic assays. The enzyme was found in dialyzed homogenates of washed cells and in partially purified fractions. The enzyme was also found in cells which had been grown in media containing 5-bromodeoxyuridine, where cell differentiation was observed.


Size Matters: Arginine-Derived Peptides Targeting the PSMA Receptor Can Efficiently Complex but Not Transfect siRNA.
Oligoarginine sequences conjugated to a short cancer-targeting peptide (CTP) selective for the prostate-specific membrane antigen (PSMA) receptor was developed for selective small interfering RNA (siRNA) delivery to a human metastatic/castration-resistant prostate cancer (PCa) cell line, which expresses PSMA on the surface. The PSMA-Rn (n = 6 and 9) peptides were synthesized by solid-phase peptide synthesis, characterized by liquid chromatography-mass spectrometry (LC-MS) and condensed with glucose-regulated protein (GRP)-silencing siRNAs. Native gels showed formation of stable CTP:siRNA ionic complexes. Furthermore, siRNA release was effected by heparin competition, supporting the peptides' capabilities to act as condensing and releasing agents. However, dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies revealed large anionic complexes that were prone to aggregation and limited cell uptake for RNAi activity. Taken together, these data support the notion that the development of efficient peptide-based siRNA delivery systems is in part contingent on the formulation of discrete nanoparticles that can effectively condense and release siRNA in cells.


Calcium homeostasis modulator 1 gene P86L polymorphism and the risk for alzheimer's disease: A meta-analysis.
Recently, many epidemiological studies have demonstrated an association between P86L polymorphism of calcium homeostasis modulator 1 (CALHM1) and risk for Alzheimer's disease (AD). However, the results of these association studies are inconsistent. In this study, we re-evaluated the relation between CALHM1 P86L polymorphism and risk for AD in a meta-analysis. This meta-analysis was performed using the PubMed, Science Direct, Scopus and Google Scholar databases up to June 2015 using the search terms "CALHM1" and "polymorphism or SNP or variant" in combination with "Alzheimer's disease". A meta-analysis with pooled odds ratios and 95% confidence intervals was carried out to assess the associations between P86L polymorphism and the risks for Alzheimer's disease under four genetic models with fixed or random effects models. Sixteen studies (twenty-four subgroup studies involving 9795 cases and 15,335 controls) were included in our meta-analysis. Our meta-analysis results indicated that several genetic models of CALHM1 P86L polymorphism were significantly associated with increased risk for AD in overall and Caucasian populations. In conclusion, our comprehensive meta-analysis indicated that P86L polymorphism is significantly associated with an increased risk for AD. Our data suggest that CALHM1 polymorphism may be potential biomarker in patients with AD.


Transcricothyroid Endoscopic Subglottic Surgery for Posterior Glottic Stenosis: A Case Report.
Posterior glottic stenosis (PGS) is a rare but life-threatening condition mostly caused by damage to the interarytenoid mucosa by an endotracheal tube. In surgical treatment of PGS, airway patency is prioritized, and the laryngeal functions involved in swallowing and phonation are considerably sacrificed. In the majority of cases, lateralization of a vocal fold or partial excision of a vocal fold and arytenoid cartilage results in glottal closure insufficiency and deterioration of phonatory function. We present the first report of transcricothyroid endoscopic subglottic surgery to treat a 46-year-old man with PGS who was intubated for 10 days. Postoperative hypofunction was not observed in the aerodynamic examination and acoustic analysis, and phonatory function has been maintained within normal limits.


Pharmacogenomics characterization of the MDM2 inhibitor MI-773 reveals candidate tumours and predictive biomarkers.
MI-773 is a recently developed small-molecule inhibitor of the mouse double minute 2 (MDM2) proto-oncogene. Preclinical data on the anti-tumour activity of MI-773 are limited and indicate that tumour cell lines (CLs) with mutated TP53 are more resistant to MI-773 than wild type TP53. Here, we explored the compound's therapeutic potential in vitro using a panel of 274 annotated CLs derived from a diversity of tumours. MI-773 exhibited a pronounced selectivity and moderate potency, with anti-tumour activity in the sub-micromolar range in about 15% of the CLs. The most sensitive tumour types were melanoma, sarcoma, renal and gastric cancers, leukaemia, and lymphoma. A COMPARE analysis showed that the profile of MI-773 was similar to that of Nutlin-3a, the first potent inhibitor of p53-MDM2 interactions, and, in addition, had a superior potency. In contrast, it poorly correlates with profiles of compounds targeting the p53 pathway with another mechanism of action. OMICS analyses confirmed that MI-773 was primarily active in CLs with wild type TP53. In silico biomarker investigations revealed that the TP53 mutation status plus the aggregated expression levels of 11 genes involved in the p53 signalling pathway predicted sensitivity or resistance of CLs to inhibitors of p53-MDM2 interactions reliably. The results obtained for MI-773 could help to refine the selection of cancer patients for therapy.


Linguistic abilities in patients with prefrontal damage.
The language abilities of 21 patients with prefrontal lesions (11 right and 10 left) and 15 matched normal subjects were analyzed, using a linguistic ability test designed to evaluate performance in six areas: automatic language, language production, verbal memory, syntax, derivative words, and comprehension of logical grammatical structures. Significant differences in the obtained scores of all groups were found. In spite of formal conservation of language in patients with frontal damage, their complex and conceptual verbal abilities were severely compromised.


Complete genome sequence of a novel lytic phage of Xanthomonas oryzae pv. oryzae, the bacterial leaf blight pathogen in rice.
Bacteriophage L522, which infects Xanthomonas oryzae pv. oryzae, was isolated from a paddy leaf sample collected in Long An province, Vietnam. The phage shows myovirus morphology based on transmission electron microscopy. It displays a latent period and burst size of approximately 3 h and 63 new virions per infected cell (PFU/infected cell), respectively. The genome of L522 is 44,497 bp in length, with 52% GC content. Of the 63 genes identified, functions were predicted for 26. No virulence or antibiotic-resistance genes were detected. The results of a BLASTn search showed similarity to a previously reported Xanthomonas phage, with 85% average nucleotide sequence identity and 87.15% query coverage. Thus, this L522 is a representative of a new species in the genus Xipdecavirus.


Impacts of existing and planned roads on terrestrial mammal habitat in New Guinea.
New Guinea is one of the last regions in the world with vast pristine areas and is home to many endemic species. However, extensive road development plans threaten the island's biodiversity. We quantified habitat fragmentation due to existing and planned roads for 139 terrestrial mammal species in New Guinea. For each species, we calculated the equivalent connected area (ECA) of habitat, a metric that takes into account the area and connectivity of habitat patches in 3 situations: no roads (baseline situation), existing roads (current), and existing and planned roads combined (future). We assessed the effect of roads as the proportion of the ECA remaining in the current and future situations relative to the baseline. To examine whether there were patterns in these relative ECA values, we fitted beta-regression models relating these values to 4 species characteristics: taxonomic order, body mass, diet, and International Union for the Conservation of Nature Red List status. On average across species, current ECA was 89% (SD 12) of baseline ECA. Shawmayer's coccymys (Coccymys shawmayeri) had the lowest amount of current ECA relative to the baseline (53%). In the future situation, the average remaining ECA was 71% (SD 20) of baseline ECA. Future remaining ECA was below 50% of the baseline for 28 species. The montane soft-furred paramelomys (Paramelomys mollis) had the lowest future ECA relative to the baseline (36%). In general, currently nonthreatened carnivorous species with a large body mass had the greatest reductions of ECA in the future situation. In conclusion, future road development plans imply extensive additional habitat fragmentation for a large number of terrestrial mammal species in New Guinea. It is therefore important to limit the impact of planned roads, for example, by reconsidering the location of planned roads that intersect habitat of the most threatened species, or by the implementation of mitigation measures such as underpasses.


Assessing student response to participation in a simulated malpractice trial in a program of law in medicine.
Results of evaluations for 49 students were examined to determine the effect of a simulated trial on both attitudinal change and cognitive growth in medical students. Plans for further data collection and analysis are discussed.


Development of microscopic systems for high-speed dual-excitation ratiometric Ca2+ imaging.
For quantitative measurements of Ca(2+) concentration ([Ca(2+)]), ratiometric dyes are preferable, because the use of such dyes allows for correction of uneven loading or partitioning of dye within the cell as well as variations in cell thickness. Although dual-excitation ratiometric dyes for measuring [Ca(2+)], such as Fura-2, Fura-Red, and ratiometric-pericam, are widely used for a variety of applications, it has been difficult to use them for monitoring very fast Ca(2+) dynamics or Ca(2+) changes in highly motile cells. To overcome this problem, we have developed three new dual-excitation ratiometry systems. (1) A system in which two laser beams are alternated on every scanning line, allowing us to obtain confocal images using dual-excitation ratiometric dyes. This system increases the rate at which ratio measurements can be made to 200 Hz and provides confocal images at 1-10 Hz depending on the image size. (2) A truly simultaneous dual-excitation ratiometry system that used linearly polarized excitation light and polarization detection, allowing us to obtain ratiometric images without any time lag. This system, however, is based on statistical features of the fluorescence polarization and is limited to samples that contain a large number of fluorophores. In addition, this method requires complicated calculations. (3) An efficient, nearly simultaneous dual-excitation ratiometry system that allows us to rapidly switch between two synchronized excitation-detection components by employing two high-power light-emitting diodes (LEDs) and two high-speed liquid crystal shutters. The open/close operation of the two shutters is synchronized with the on/off switching of the two LEDs. This system increases the rate at which ratio measurements are made to 1 kHz, and provides ratio images at 10-100 Hz depending on the signal intensity.


pH sensitive silica nanotubes as rationally designed vehicles for NSAIDs delivery.
A novel pH-sensitive drug delivery system based on functionalized silica nanotubes was developed for the incorporation of non-steroidal anti-inflammatory drugs (NSAIDs), aimed at a tailored drug release in acidic conditions characteristic of inflamed tissues. Silica nanotubes (SNTs) were synthesized by a nanoporous alumina template assisted sol-gel method. Inner surfaces were physically and chemically modified to improve both the functionalization and subsequent incorporation of the drug. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and transmission electron microscopy (TEM) were used to characterize the designed nanocarriers and their functionalization. To achieve the highest degree of functionalization, three types of aminosilanes were tested and calcination conditions were optimized. APTES was shown to be the most effective aminosilane regarding the functionalization of the SNTs' inner surface and an adequate calcination temperature (220°C) was found to attain mechanical stability without compromising functionalization efficiency. Finally, the incorporation of naproxen into the nanotubes was accessed by fluorescence measurements and drug release studies were performed, revealing that the electrostatic linkage ensures effective release of the drug in the acidic pH typical of inflamed cells, while maintaining the SNT-drug conjugates stable at the typical bloodstream pH.


Type II diabetes mellitus: a review on recent drug based therapeutics.
Diabetes mellitus (DM) is a metabolic disorder that occurs in the body because of decreased insulin activity and/or insulin secretion. Pathological changes such as nephropathy, retinopathy, and cardiovascular complications inevitably occur in the body with the progression of the disease. DM is mainly categorized into 2 sub-types, type I DM and type II DM. While type I DM is generally treated through insulin replacement therapy, type II DM is treated with oral hypoglycaemics. The major drug therapy for type II DM comprises of insulin secretagogues, biguanides, insulin sensitizers, alpha glucosidase inhibitors, incretin mimetics, amylin antagonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors. Dual drug therapies are often recommended in patients who are unable to achieve therapeutic goals with first line oral hypoglycaemic agents as monotherapy. Inspite of the appreciable therapeutic benefits, the conventional dosage forms depicts differential bioavailability and short half-life, mandating frequent dosage and causing greater side effects leading to therapy ineffectiveness and patient non-compliance. Given the pathological complexity of the said disease, nanotechnology-based approaches are more enticing as it comes with added advantage of site-specific drug delivery with higher bioavailability and reduced dosage regimen. In the present review article, we have made an attempt to explore the pathophysiology of type II DM, the conventional treatment approaches (mono and combination therapy) as well as the nano based drug delivery approaches for the treatment of type II DM.


Rules of engagement-12 tips for successful use of "clickers" in the classroom.
Student response system or clickers is an electronic application where a receiver in the instructor's computer captures responses to questions from student keypads. Used effectively, clickers can promote learner engagement and serve to improve learning. It can be used in a variety of ways such as to provide feedback to learners and instructor, to start discussions, for peer evaluation, for formative and summative assessment, to build a learning community, and to experiment on human responses. Using our experience in the use of this technology and literature review, we provide twelve tips for successful use of the student response system. We have found these strategies useful and envisage that the application of these tips can help maximize learner engagement and learning.


Pseudolamproglena boxshalli sp. n. (Lernaeidae: Lamprogleninae) parasitic on gills of Cyprinion macrostomum (Teleostei: Cyprinidae) from the Tigris River, Iraq.
Abstract: A new species of lamproglenine copepods, Pseudolamproglena boxshalli sp. n., is described from gills of the cyprinid fish Cyprinion macrostomum Heckel from the Tigris River in Tikreet, north of Baghdad, Iraq. This is the second species of Pseudolamproglena from Iraq and the fourth in the world. It differs from its three congeners mainly in the armature ofantennule, maxilla, maxilliped, legs 1-4 and caudal ramus.


Ab Initio Complex Transition Dipoles between Autoionizing Resonance States from Real Stabilization Graphs.
Electronic transition dipoles are crucial for investigating light-matter interactions. Transition dipoles between metastable (autoionizing resonance) states become complex within non-Hermitian formalism, analogous to the resonance energies. Herein, we put forward a robust method for evaluating complex transition dipoles based on real ab initio stabilization calculations. The complex transition dipoles are obtained by analytical continuation via the Padé approximant and are identified as stationary solutions in the complex plane. The capability of the new approach is demonstrated for several transition dipoles of the doubly excited helium resonance states, for which exact values are available for comparison. Nevertheless, the method presented here has no inherent limitation and is suitable for polyatomic systems.


Surviving common carotid rupture caused by a cervical abscess.
This article describes the events preceding and following the rupture of the right common carotid artery caused by a cervical abcess. Stent grafting resulted in a good outcome.


Hybrid independent component analysis by adaptive LUT activation function neurons.
The aim of this paper is to present an efficient implementation of unsupervised adaptive-activation function neurons dedicated to one-dimensional probability density estimation, with application to independent component analysis. The proposed implementation is a computationally light improvement to adaptive pseudo-polynomial neurons, recently presented in Fiori, S. (2000a). Blind signal processing by the adaptive activation function neurons. Neural Networks, 13(6), 597-611, and is based upon the concept of 'look-up table' (LUT) neurons.


Invited review: hypertension and atrial fibrillation: epidemiology, pathophysiology, and implications for management.
Hypertension affects around half of the adult population worldwide, being one of the most common cardiovascular disorders. On a population basis, high blood pressure is considered to be the major independent risk factor for atrial fibrillation (AF). The incidence of both diseases has increased significantly in the recent decades and it is expected to continuously surge in the following years. Due to close relation between the both diseases and their frequent coexistence, hypertension and AF become major health priorities. The multidirectional linking between raised blood pressure and AF is based on complex associations including structural, hemodynamic, neuroendocrine, and autonomic mechanisms. Hypertension provokes excessive fibroblasts proliferation and increased collagen accumulation. It also stimulates cardiomyocytes apoptosis and inflammation, leading to diffused fibrosis and left ventricular hypertrophy development. This is mainly driven by renin-angiotensin-aldosterone system (RAAS) activation, and autonomic dysregulation. Moreover, exposure on long-term stretch due to hypertension causes arterial stiffness with subsequent systolic and diastolic function loss resulting in further heart muscle remodeling. All these pathological changes combined seem influence on myocardial electrical activity, triggering AF development. Given the prevalence and frequent lack of symptoms of both disorders, opportunistic arrhythmia screening in hypertensive patients is needed. In all individuals with established diagnosis of AF, adequate anticoagulation has to be considered for stroke prevention. Blood pressure control is also an essential component of a holistic approach to AF care.


Abomasal parasitism in dairy cows in Belgium.
Over a period of one year, from March 1984 to April 1985, the abomasa of 157 dairy cows in East Flanders (Belgium) were collected and examined for the presence of nematodes. Faeces and blood were also collected from the animals. No worms were recovered from 18 cows (11.5%), 118 cows (75%) had a low to moderate worm burden (10-10,000) and 21 cows (13.5%) a high worm burden (greater than 10,000). The geometric mean total number was 2171. Ostertagia ostertagi and Trichostrongylus axei were the main species involved, with the former accounting for 90% of all trichostrongyles recovered. For both worms a seasonal pattern was evident, with the highest worm counts in December-January. Between December and February greater than 97% of the Ostertagia spp. worm burden were EL4. For all animals the average pepsinogen level was 1391 +/- 494 mU tyrosine with no statistically significant relationship between pepsinogen levels and the total number of gastric nematodes. Only 45% of the faeces samples were positive for strongylid eggs with a mean of 43 eggs per gram. The percentage generic composition of L3 larvae collected from faeces was 62% Ostertagia, 18% Trichostrongylus, 6% Cooperia, 4% Oesophagostomum and 0.2% Bunostomum.


Observation, laser photocoagulation or anti-VEGF therapy in the management of retinal arterial macroaneurysms.
To explore the efficacy of observation, laser photocoagulation, and anti-VEGF in the management of retinal arterial macroaneurysm (RAM). We retrospectively included patients diagnosed with RAM at the Peking Union Medical College Hospital (PUMCH) from 2003 to 2021, and comprehensively reviewed cases documented in the literature from multiple databases (PROSPERO protocol CRD42022310417). Patients were categorized into 3 groups: the observation group, anti-VEGF group, and laser photocoagulation group. LogMAR visual acuity (VA) and central retinal thickness (CMT) at the end of the follow-up were analyzed. A total of 14 patients from the PUMCH and 210 patients from the literature review were included. VA and CMT in patients who underwent observation, laser photocoagulation, and anti-VEGF therapies were significantly improved from baseline (p < 0.05), with changes in LogMAR VA improved by -0.34 ± 0.68, -0.17 ± 0.58, and -0.45 ± 0.62 and changes in CMT improved by -148.26 ± 138.99 µm, -185.61 ± 130.37 µm, and -287.45 ± 171.87 µm, respectively. Subgroup analysis revealed that anti-VEGF therapy was used in patients with worse VA than patients who underwent laser photocoagulation (p = 0.010), but achieved better improvement in VA than the laser photocoagulation group (p = 0.049). Patients treated with anti-VEGF also had thicker CMT than the observation group (p = 0.013), and experienced better changes in CMT than the observation, as well as laser photocoagulation groups (p = 0.005; p = 0.047). Observation, anti-VEGF, and laser photocoagulation are effective therapeutic methods for the management of RAM, and anti-VEGF therapy is intended to better improve patients with severe VA and CMT.


Pollinator foraging behavior and pollen collection on the floral morphs of tristylous Pontederia cordata L.
The foraging behavior of the pollinators of tristylous Pontederia cordata was studied to determine if differences in floral morphology would lead to preferential visitation of the floral morphs. Although nectar production is not different in the three floral morphs, differences in the production and size of pollen grains produced by the three anther levels results in the morphs offering variable amounts of resources to pollen-collecting insects. Bumblebees (Bombus spp.) and the solitary bee Melissodes apicata used P. cordata primarily as a nectar source and therefore did not seem to exhibit any morph preference. In contrast, honeybees visited flowers mainly for pollen and preferred to forage on long-level anthers of the short-and mid-styled morphs. An analysis of the composition of corbicular pollen loads indicated that, relative to the frequency of production in the population: 1) honeybees collected an excess of pollen from long-level anthers; 2) bumblebees collected the three types of pollen without any apparent preference; and 3) M. apicata preferentially collected pollen from the short-level anthers - presumably because their proboscides are modified by the presence of tiny hairs. The results suggest that P. cordata in Ontario is serviced by a diverse, unspecialized pollinator fauna which is not co-adapted to the tristylous floral polymorphism.


Seasonal variation in defense behavior in European and scutellata-hybrid honey bees (Apis mellifera) in Southern California.
Nest defense in the honey bee (Apis mellifera) is a complex collective behavior modulated by various interacting social, environmental, and genetic factors. Scutellata-hybrid ("Africanized") honey bees are usually considered to be far more defensive than European honey bees which are therefore preferred for commercial and hobbyist beekeeping. In the most recent zone of scutellata hybridization, the southern USA, the degree to which this defensiveness differs among current strains, and the extent to which defensiveness varies across a season has not been measured. We quantified the levels of A. m. scutellata ancestry in colonies and conducted a seasonal assessment (May through November) of colony nest defensiveness in feral scutellata-hybrid and a popular lineage of European honey bee commonly used in managed environments (sold as A. mellifera ligustica) hives at two apiaries in Southern California. Standard measures of defensiveness were low in both scutellata-hybrid and European colonies during May. Defensiveness increased during the later months of the study in scutellata-hybrid colonies. Most measures of defensiveness did not increase in managed colonies. Defensiveness in the scutellata-hybrids appears lower than what has been previously documented in Brazil and Mexico, possibly due to their lower proportion of A. m. scutellata ancestry.


Viruses and prions of Saccharomyces cerevisiae.
Saccharomyces cerevisiae has been a key experimental organism for the study of infectious diseases, including dsRNA viruses, ssRNA viruses, and prions. Studies of the mechanisms of virus and prion replication, virus structure, and structure of the amyloid filaments that are the basis of yeast prions have been at the forefront of such studies in these classes of infectious entities. Yeast has been particularly useful in defining the interactions of the infectious elements with cellular components: chromosomally encoded proteins necessary for blocking the propagation of the viruses and prions, and proteins involved in the expression of viral components. Here, we emphasize the L-A dsRNA virus and its killer-toxin-encoding satellites, the 20S and 23S ssRNA naked viruses, and the several infectious proteins (prions) of yeast.


Synthesis of π-extended thiadiazole (oxides) and their electronic properties.
The syntheses of extended thiadiazole, thiadiazole oxide, and thiadiazole dioxide heterocycles are described. The electron-accepting heterocycles were investigated by X-ray crystallography and optical as well as electrochemical measurements and supported by DFT calculations. The thiadiazole dioxide heterocycles have reduction potentials of -0.7 V vs ferrocene/ferrocenium, suggesting a viable building block for n-type organic materials.


Synaptic plasticity in the hypoglossal nucleus of female canaries: structural correlates of season, hemisphere, and testosterone treatment.
The caudal portion of the hypoglossal nucleus (nXIIts) contains the motor neurons that control the syrinx in songbirds. In canaries, song occurs seasonally, is principally produced by males, and appears to be produced predominantly by muscles on the left side of the syrinx. The present study measures the effect of seasonal change and manipulation of testosterone levels on synapse number and morphology in nXIIts in adult female canaries. We find that synapse density is lower in testosterone-treated birds than in control birds and lower in fall than in spring. The number of vesicles per presynaptic profile increases in the spring as a result of a general increase in this measure in all synapses. The number of vesicles per presynaptic profile also increases with testosterone treatment, primarily due to an increase in the proportion of synapses associated with unusually high vesicle counts. Together, these changes suggest that large reserves of neurotransmitter may be necessary to sustain singing. Several ultrastructural differences between hemispheres are found. Postsynaptic thickenings are longer, and postsynaptic processes are larger on the left side than on the right side. In the spring, there are more vesicles per synapse on the left than on the right, but this lateralization is reversed in the fall. Thus, lateralization of song production is associated with lateral asymmetries in synapse morphology. These hemispheric differences are relatively small, like those seen at the light microscope level, encouraging further consideration of peripheral as well as CNS sources of functional lateralization. The seasonal and testosterone-induced changes in synapse number and morphology may be components of the periodic reorganization of canary vocalization.


Process of Introduction of Australian Braford Cattle to South America: Configuration of Population Structure and Genetic Diversity Evolution.
This study analyzes the evolution of the population structure and genetic diversity of Braford cattle in South America from 1949 to 2019 to suggest effective strategies for breeding in the future. The percentage of bulls historically increased. The average generational interval decreased to 11.78 years for the current population. Average inbreeding (F) and coancestry (C) are low and show a historically increasing trend (0.001% to 0.002%, respectively). The degree of nonrandom mating (α) increased from -0.0001 to 0.0001 denoting a change in the trend to mate similar individuals. The average relatedness coefficient (ΔR) increased in the current period from 0.002% to 0.004%. A single ancestor explained 4.55% to 7.22% of the population's gene pool. While the effective population size based on the individual inbreeding rate (NeFi) was 462.963, when based on the individual coancestry rate (NeCi), it was 420.168. Genetic diversity loss is small and mainly ascribed to bottlenecks (0.12%) and to unequal contributions of the founders (0.02%). Even if adequate levels of diversity can be found, practices that consider the overuse of individual bulls (conditioned by nature or not), could lead to a long-term reduction in diversity. The present results permit tailoring genetic management strategies that are perfectly adapted to the needs that the population demands internationally.


Tissue-specific corticosteroidogenesis in the rat.
The steroid aldosterone plays a major role in the maintenance of total body sodium homeostasis and also contributes to cardiovascular pathophysiology by mediating cardiac hypertrophy and fibrosis. In addition to classical adrenal production of aldosterone, endogenous tissue production of aldosterone has been observed in various organs; aldosterone biosynthesis in cardiac tissues, however, remains highly controversial. The current study provides a comprehensive evaluation of steroid hormone biosynthethic capabilities in multiple tissues from two distinct rat strains under unstimulated and stimulated conditions. Panels of tissues from Wistar and Sprague-Dawley rats were probed for 11 beta-hydroxylase (P45011beta) and aldosterone synthase (P450aldo) by reverse transcriptase-polymerase chain reaction (RT-PCR). Under unstimulated conditions, cardiac P45011beta and P450aldo were detected only in Wistar rats. Angiotensin II (100 microg/day) stimulated myocardial expression of both enzymes in both strains. Cerebral cortex and mesenteric artery message levels in both strains was reduced by angiotensin II. These data demonstrate the potential for local steroid synthesis in vascular, cardiac, renal, and neuronal tissues, and that biosynthesis of non-adrenal aldosterone may be differentially regulated between strains. This variability may thus resolve in part or whole the current controversy over the existence of non-adrenal steroidogenic systems.


Absorption and isomerization of caffeoylquinic acids from different foods using ileostomist volunteers.
Polyphenols are thought to play important roles in human nutrition and health but these health effects are dependent on their bioavailability. This study is one of a series with the aim of determining possible effects of food matrices on caffeoylquinic acid (CQA) bioavailability using ileostomy volunteers. After a CQA-free diet, ileostomists consumed coffee (746 μmol total CQA), and CQAs in excreted ileal fluid were subsequently identified and quantified with HPLC-diode array detection and HPLC-ESI-MS/MS. In our previous studies, other food sources such as cloudy apple juice (CAJ) (358 μmol CQA) and apple smoothie (AS) (335 μmol CQA) were investigated with the same model. Interesterification of CQA from both apple matrices was observed during gastrointestinal passage, whereas CQA consumed in coffee was not influenced by interesterification reactions. In total, 74.3, 22.4, and 23.8 % of the CQA from CAJ, AS, and coffee, respectively, were absorbed or degraded. Our results show that variations in food matrices and variations in phenolic composition have a major influence on intestinal bioavailability and interesterification of the investigated subclass of polyphenols, the CQAs.


High-resolution cryo-EM using beam-image shift at 200 keV.
Recent advances in single-particle cryo-electron microscopy (cryo-EM) data collection utilize beam-image shift to improve throughput. Despite implementation on 300 keV cryo-EM instruments, it remains unknown how well beam-image-shift data collection affects data quality on 200 keV instruments and the extent to which aberrations can be computationally corrected. To test this, a cryo-EM data set for aldolase was collected at 200 keV using beam-image shift and analyzed. This analysis shows that the instrument beam tilt and particle motion initially limited the resolution to 4.9 Å. After particle polishing and iterative rounds of aberration correction in RELION, a 2.8 Å resolution structure could be obtained. This analysis demonstrates that software correction of microscope aberrations can provide a significant improvement in resolution at 200 keV.


Heart rate variability in white-coat hypertension.
The objective of this study was to compare heart rate variability (HRV) in patients with essential hypertension, in patients with white-coat hypertension and in normotensive control individuals, and to investigate a possible relation between HRV and vasoactive hormones. Patients with essential hypertension (n=19, 61 years, median and interquartile range: 40-66 years), patients with white-coat hypertension (n=8, 52 years, median and interquartile range: 41-64 years) and normotensive participants (n=13, 50 years, median and interquartile range: 39-57 years) participated in the study. HRV was measured at rest in the supine position, during standing and during controlled forced breathing (respiration frequency >20/min). Power spectral density was calculated using Fourier transformation. Controlled breathing caused a decrease in low frequency (LF) variation and LF/high frequency variation (LF/HF) in all blood pressure groups. The decrease in LF was smaller in the hypertensive group (-60 ms2) than in the normotensive group (-139 ms2) (P=0.03; hypertensive group vs. normotensive group). The decrease in LF/HF induced by controlled breathing was -0.9 ms in the hypertensive group, -2.0 ms2 in the white-coat hypertensive group and -2.8 ms2 in the normotensive group, (P=0.037; hypertensive group vs. normotensive group). We found a positive correlation between baseline plasma renin concentration and LF (r=0.330, P=0.037) and LF/HF (r=0.378, P=0.016) at rest. The observed differences in HRV might reflect the impaired responsiveness to autonomic challenge in hypertensive patients. We did not find the HRV spectrum in white-coat hypertension different from the HRV spectrum in hypertension or normotension.


Isolation and sequence analysis of the glycosaminoglycan attachment site of type IX collagen.
Type IX collagen from chick embryonic cartilage is unique among the collagens in that it contains chondroitin sulfate covalently linked to the alpha 2(IX) polypeptide chain. We have isolated and sequenced the glycosaminoglycan-containing peptide released by collagenase digestion from type IX collagen, labeled biosynthetically with [35SO4] and 3H-aminoacids. This peptide was purified by gel filtration and, following chondroitinase ABC digestion, by reverse-phase high performance liquid chromatography. The amino acid sequence obtained for this peptide has 23 residues, beginning and ending with a collagenous sequence, indicating that it spans an internal noncollagenous domain. Comparison of this sequence with the one predicted from cDNA clone pYN 1738 for the alpha 1(IX)chain and pYN 1731 and pDM 222 for the alpha 2(IX)chain revealed the peptide to be the noncollagenous NC3 domain of alpha 2(IX). The glycosylated sequence Val-Glu-Gly-Ser*-Ala-Asp- of type IX collagen does not have the Ser-Gly normally functioning as the attachment sequence but does have an acidic residue preceding the serine which should improve the acceptability of this sequence for the xylosyltransferase. That it is an adequate acceptor can be inferred from the observation that type IX collagen carries a glycosaminoglycan chain on over 70% of the molecules isolated.


Clenbuterol and the horse revisited.
Clenbuterol is a beta(2)-agonist and potent selective bronchodilator that is used to treat bronchospasm in the horse. The drug is normally administered to horses orally as a syrup formulation. Once absorbed into the systemic circulation, clenbuterol has the potential to cause many side effects, including a repartitioning effect and major alterations in cardiac and skeletal muscle function. Recent studies have also reported that clenbuterol can affect bone and the immune, endocrine and reproductive systems. A great deal of information has been published on the beneficial effects of short term therapeutic doses of clenbuterol on the equine respiratory system, although there is limited information about chronic administration, particularly since this has been associated with adverse physiological effects on other systems. This review summarizes the relevant understanding of clenbuterol for clinicians and horse owners who may administer this drug to pleasure and performance horses.


Elucidating the catalytic mechanism of β-secretase (BACE1): a quantum mechanics/molecular mechanics (QM/MM) approach.
In this quantum mechanics/molecular mechanics (QM/MM) study, the mechanisms of the hydrolytic cleavage of the Met2-Asp3 and Leu2-Asp3 peptide bonds of the amyloid precursor protein (WT-substrate) and its Swedish mutant (SW) respectively catalyzed by β-secretase (BACE1) have been investigated by explicitly including the electrostatic and steric effects of the protein environment in the calculations. BACE1 catalyzes the rate-determining step in the generation of Alzheimer amyloid beta peptides and is widely acknowledged as a promising therapeutic target. The general acid-base mechanism followed by the enzyme proceeds through the following two steps: (1) formation of the gem-diol intermediate and (2) cleavage of the peptide bond. The formation of the gem-diol intermediate occurs with the barriers of 19.6 and 16.1 kcal/mol for the WT- and SW-substrate respectively. The QM/MM energetics predict that with the barriers of 21.9 and 17.2 kcal/mol for the WT- and SW-substrate respectively the cleavage of the peptide bond occurs in the rate-determining step. The computed barriers are in excellent agreement with the measured barrier of ∼18.0 kcal/mol for the SW-substrate and in line with the experimental observation that the cleavage of this substrate is sixty times more efficient than the WT-substrate.


Acute hemolysis of transfused A2 red cells by an auto-HI antibody.
Anti-HI is a common cold autoantibody that complicates serologic testing for underlying alloantibodies and has only rarely been associated with hemolysis. An unusual case of an acute hemolytic transfusion reaction (AHTR) due to an anti-HI autoantibody in a subgroup A1 patient transfused with A2 red blood cells (RBCs) is reported. A 56-year-old man presented to the hospital with anemia and gastrointestinal tract bleeding. His medical history was significant for congestive heart failure, obesity, and pulmonary hypertension. On admission, he was noted to have a hemoglobin level of 7.7 g per dL and therefore transfusion of RBCs was ordered. The patient was group A, D- with a reactive antibody screen due to a cold autoantibody with HI specificity. Further serologic investigation did not detect any alloantibodies. The patient was issued an electronically cross-matched group A, D- unit of RBCs. Several hours after the transfusion, he was found to be producing "Coca-cola"-colored urine with gross hemoglobinemia visible in a posttransfusion specimen, indicating an AHTR. A transfusion reaction investigation excluded mistransfusion or a missed alloantibody and instead revealed that the patient's anti-HI had a high thermal amplitude and that the implicated unit of RBCs was from the A2 subgroup. The patient subsequently tolerated transfusion of a unit of group A1 RBCs through a blood warmer without any signs or symptoms of hemolysis. This case illustrates that anti-HI autoantibodies rarely may behave like alloantibodies and cause AHTRs. Subsequent RBC transfusion with an appropriate ABO group or subgroup through a blood warmer is well tolerated.


Reduced Remodeling Biomarkers Tissue Expression in Nanotextured Compared With Polyurethane Implants Capsules: A Study in Rats.
In the biological response to biomaterials, the implant shell plays a key role in immune and inflammatory reactions. We hypothesized that the capsules formed around nanotextured implants exhibit an immunohistochemical behavior different to those formed around polyurethane implants. The aim of this study was to evaluate through immunohistochemistry markers the capsules formed around nanotextured and polyurethane implants. Sixty albino female Wistar rats were divided into 2 groups (nanotextured and polyurethane), with 30 animals in each group. A mini silicone implant was inserted on the back of the animals. After a predetermined period, the animals were killed, and the capsules formed around the implants were studied. The capsules in the 30-, 60-, and 90-day subgroups were analyzed via immunohistochemistry to detect markers for fibroblast α smooth muscle actin (α-SMA), transforming growth factor β (TGF-β), cluster of differentiation 34 (CD34), and CD68, via picrosirius staining to determine the density of type I and III collagen fibers and via hematoxylin and eosin staining to assess capsule thickness. A Wilcoxon-Mann-Whitney test was used to compare the groups, and a Kruskal-Wallis test was used to compare the subgroups. Lower α-SMA, TGF-β, CD34 and CD68 immunoexpression was observed in the nanotextured 30- and 60-day subgroups than in the corresponding polyurethane subgroups. In the 90-day subgroup, more pronounced α-SMA and CD34 immunoexpression was observed in the nanotextured group; however, TGF-β and CD68 immunoexpression remained lower. The nanotextured implants showed reduced capsular thickness and greater formation of type I collagen in all the analyzed subgroups. Nanotextured implants led to reduced immune and inflammatory reactions compared with polyurethane implants according to all analyzed variables.


Promoter methylation of helicase-like transcription factor is associated with the early stages of gastric cancer with family history.
To investigate the clinicopathological significance of promoter methylation of the helicase-like transcription factor (HLTF) in primary gastric cancer. Two-hundred fifty six patients participated in this study. Methylation status of HLTF gene was evaluated in fresh-frozen tissues by the methylation-specific polymerase chain reaction. All statistical analyses were two-sided, with a 5% type I error rate. Aberrant methylation of HLTF was found in 98 (38%) of 256 gastric cancer patients. HLTF methylation was significantly associated with a family history in the early stages of gastric cancer, regardless of histologic types. In intestinal-type cases, HLTF methylation occurred in 15 (56%) of 27 patients with family histories, and in 26 (31%) of 85 patients without family histories (P = 0.02). In diffuse-type cases, patients with family histories were also found to exhibit a higher prevalence of HLTF methylation than those without family histories (61% vs. 34%; P = 0.009). HLTF methylation in both of the histologic types occurred in about 70-90% of the early stage cases in which the patient had a family history and in 15-30% of cases in which the patient did not have a family history. In our multivariate logistic regression analysis, the stage 1-2 cases with family histories were determined to carry a higher risk of HLTF methylation than did the stage 3-4 cases without family histories in both the intestinal-type (OR = 6.01, 95% CI = 1.20-30.01, P = 0.02) and the diffuse-type cancers (OR = 8.25, 95% CI = 1.67-40.86, P = 0.009). These results suggest that HLTF methylation may play a crucial role in the early stages of gastric carcinogenesis in patients with family histories and may be a valuable susceptible marker for the risk of gastric cancer in individuals with family histories.


Preparation and Characterization of Ascosome Vesicles Loaded with Khellin.
Ascorbic acid has a unique role in the prevention and treatment of a large number of chronic diseases, including skin disorders but it can hardly penetrate the skin due to its solubility in water and its high instability. This study explored the formation of phosphatidylcholine-based vesicles upon addition of ascorbyl octanoate or decanoate, and their potential value as drug delivery systems. Khellin, a natural furanochromone with numerous applications in skin pathologies was loaded as model drug in ascosomes. Ascosomes had narrow size distribution, adequate encapsulation efficiency, long-term stability, and antioxidant properties. Increasing amounts of loaded khellin resulted in a reduction of the vesicle average size, without affecting the polydispersity, suggesting a stabilizing effect. Ascorbyl alkanoates produced remarkably different bilayer organizations and different capabilities to accommodate khellin in the hydrophobic pocket of the vesicles. The addition ascorbyl alkanoates reduced the amount of water molecules strongly bound to the polar headgroups. Moreover, the loading of khellin did not induce any significant hydration change in the unilamellar vesicular systems. The narrow size distribution, adequate encapsulation efficiency and long-term stability of ascosomes loaded with khellin, make these nanostructures suitable for dermatological use and other routes of administrations, preserving the biological properties of ascorbic acid.


Anti-aging medicine: a patient/practitioner movement to redefine aging.
Having enjoyed tremendous growth for the past 5 years, the anti-aging medicine movement is redefining aging so that it becomes a target for biomedical intervention. Targeting aging for intervention dislodges popular understandings of aging: for anti-aging practitioners it no longer matters if aging is natural since it can be itself the target of therapy. So-called "age-associated" diseases like cancer are, in this framework, conceived of as symptoms of aging. Anti-aging medicine is a broad term that may comprise groups selling remedies over the Internet, companies touting the "anti-aging"ness of their products, practitioners who work outside of scientific medicine, and practitioners of anti-aging medicine in clinics who believe that their work is strictly scientific. This article, drawing from more than 3 years of ethnographic interviews, participant observation in clinics and conferences, and a review of the literature, considers the last group. It examines the involvement stories of anti-aging medicine practitioners in two Western United States metropolitan cities. These stories reflect the practices of anti-aging medicine practitioners and the accompanying rationale for involvement. Often originally patients themselves, practitioners frame their involvement with the anti-aging movement in three ways. First, they describe aging as it is currently experienced as a time of decline, suffering, and weakness. This anguish is not inevitable, they argue, and their work toward treating aging biomedically is situated as clearly moral. Secondly, intense frustration with the current biomedical environment has motivated practitioners to look for other ways in which to practice: anti-aging medicine is their chosen alternative. Finally, with dramatic expectations of future biotechnologies and disdain for current medical treatments of old age, anti-aging practitioners embrace a scientific revolutionary identity. These stories of migrations from patient to practitioner reveal the values upon which this movement is grounded and how coming to be a part of it is as much about the movement's mission as it is the origins of the migrations.


Assessing uterine electrophysiology prior to elective term induction of labor.
The purpose of this study was to determine if uterine electrophysiological signals gathered from 151 non-invasive biomagnetic sensors spread over the abdomen were associated with successful induction of labor (IOL). Uterine magnetomyogram (MMG) signals were collected using the SARA (SQUID Array for Reproductive Assessment) device from 33 subjects between 37 and 42 weeks gestational age. The signals were post-processed, uterine contractile related MMG bursts were detected, and parameters in the time and frequency domain were extracted. The modified Bishop score calculated at admission was used to determine the method of IOL. Wilcoxon's rank-sum test was used to compare IOL successes and failures for differences in gestational age (GA), parity, modified Bishop's score, maximum oxytocin, and electrophysiological parameters extracted from MMG. The average parity was three times (3x) higher (1.53 versus 0.50; p = 0.039), and the average modified Bishop score was 2x higher (3.32 versus 1.63; p = 0.032) amongst IOL successes than failures, while the average GA and maximum oxytocin showed a small difference. For the MMG parameters, successful IOLs had, on average, 3.5x greater mean power during bursts (0.246 versus 0.070; p = 0.034) and approximately 1.2x greater mean number of bursts (2.05 versus 1.68; p = 0.036) compared to the failed IOLs, but non-significant differences were observed in mean peak frequency, mean burst duration, and mean duration between bursts. The study showed that inductions of labor that took less than 24 h to deliver have a higher mean power in the baseline electrophysiological activity of the uterus when recorded prior to planned induction. The results are indicative that baseline electrophysiological activity measured prior to induction is associated with successful induction.


Protein-protein interaction in electron transfer reactions: the ferredoxin/flavodoxin/ferredoxin:NADP+ reductase system from Anabaena.
Electron transfer reactions involving protein-protein interactions require the formation of a transient complex which brings together the two redox centres exchanging electrons. This is the case for the flavoprotein ferredoxin:NADP+ reductase (FNR) from the cyanobacterium Anabaena, an enzyme which interacts with ferredoxin in the photosynthetic pathway to receive the electrons required for NADP+ reduction. The reductase shows a concave cavity in its structure into which small proteins such as ferredoxin can fit. Flavodoxin, an FMN-containing protein that is synthesised in cyanobacteria under iron-deficient conditions, plays the same role as ferredoxin in its interaction with FNR in spite of its different structure, size and redox cofactor. There are a number of negatively charged amino acid residues on the surface of ferredoxin and flavodoxin that play a role in the electron transfer reaction with the reductase. Thus far, in only one case has charge replacement of one of the acidic residues produced an increase in the rate of electron transfer, whereas in several other cases a decrease in the rate is observed. In the most dramatic example, replacement of Glu at position 94 of Anabaena ferredoxin results in virtually the complete loss of ability to transfer electrons. Charge-reversal of positively charged amino acid residues in the reductase also produces strong effects on the rate of electron transfer. Several degrees of impairment have been observed, the most significant involving a positively charged Lys at position 75 which appears to be essential for the stability of the complex between the reductase and ferredoxin. The results presented in this paper provide a clear demonstration of the importance of electrostatic interactions on the stability of the transient complex formed during electron transfer by the proteins presently under study.


Comparative study of estrogenic potencies of estradiol, tamoxifen, bisphenol-A and resveratrol with two in vitro bioassays.
This study was undertaken to compare the sensitivity of two in vitro screening test methods and to determine the accuracy of predicted response to spiked laboratory water samples. A newly developed enzyme-linked receptor assay (ELRA) and a widely used yeast estrogen screen (YES) assay were selected to evaluate the estrogenic responses. Four natural, pharmaceutical, xenobiotic or phytobiotic chemicals: 17beta-estradiol (E2), tamoxifen, bisphenol-A and resveratrol were examined, and 17beta-E2 was used as a positive control. 17beta-E2 can strongly induce estrogenic response in both test systems, however, ELRA was found to be more sensitive to 17beta-E2 with a detection limit of 0.07 microg/l compared to 0.88 microg/l in YES assay. Similar results were obtained for bisphenol-A and resveratrol, and their estrogen potencies relative to E2 (100%) determined by ELRA were at least 5.6 times greater than produced by YES assay. ELRA was unable to distinguish the anti-estrogen tamoxifen and YES assay is also poor at distinguishing. Comparison of response to spiked laboratory water samples show that ELRA can give accurate determination to all four chemicals with recoveries among 70-120%, while YES can only give accurate determination to 17beta-E2 and bisphenol-A with recoveries among 69-112%. The comparative results provide evidence that ELRA is more suitable for rapid screening estrogenic potency of the environmental samples. Combination of ELRA and mammalian cellular assay will constitute an advantageous test to specify agonistic or antagonistic effects.


A new tailored technique of vermilion repair in unilateral cleft lip.
The deficiency of vermilion on the medial side of the cleft can be augmented by procedures using excess vermilion from the lateral side as described in various other studies.(1) Here we present a technique of vermilion repair in unilateral cleft lip which is a modification of our earlier-described, V-advancement technique based on sound geometrical principles.(2) The new modification was assessed by comparing the results of 40 consecutive cases operated by this technique with 40 cases operated by the earlier-described technique. The surgical outcome as assessed by a panel was found to be significantly better with the newer technique. This technique is much simpler and overcomes some of the shortcomings of the previous technique at the same time retaining its benefits.


Impact of Inoculation with Pseudomonas aestus CMAA 1215T on the Non-target Resident Bacterial Community in a Saline Rhizosphere Soil.
Plant growth reduction caused by osmotic stress, pathogens, and nutrient scarcity can be overcome by inoculation with plant growth-promoting rhizobacteria (PGPR). Knowing the effects of PGPR on the microbial community beyond those on plant growth can bring new options of soil microbiota management. The present study aimed to investigate the effect of inoculation with the newly described Pseudomonas aestus CMAA 1215T [a 1-aminocyclopropane-1-carboxylate (ACC) deaminase and glycine-betaine producer] on the rhizosphere bacterial community of Zea mays in natural (non-salinized) and saline soil. The bacterial community structure was assessed by sequencing the V6-V7 16S ribosomal RNA using the Ion Personal Genome Machine™. The non-metric multidimensional scaling (NMDS) of the OTU profile (ANOSIM P < 0.01) distinguishes all the treatments (with and without inoculation under saline and natural soils). Inoculated samples shared 1234 OTUs with non-inoculated soil. The most abundant classes in all samples were Alphaproteobacteria, Gammaproteobacteria, Actinobacteria, Acidobacteriia, Bacteroidia, Thermoleophilia, Verrucomicrobiae, Ktenodobacteria, and Bacilli. The inoculation, on the other hand, caused an increase in the abundance of the genera Bacillus, Bryobacter, Bradyrhizobium, "Candidatus Xiphinematobacter", and "Candidatus Udaeobacter" independent of soil salinization. "Candidatus Udaeobacter" has the largest Mean Decrease in Gini Values with higher abundance on inoculated salted soil. In addition, Pseudomonas inoculation reduced the abundance of Gammaproteobacteria and Phycisphaerae. Understanding how inoculation modifies the bacterial community is essential to manage the rhizospheric microbiome to create a multi-inoculant approach and to understand its effects on ecological function.


Evoked Potentials During Peripheral Stimulation Confirm Electrode Location in Thalamic Subnuclei in Children With Secondary Dystonia.
Deep brain stimulation is an elective surgical intervention that improves the function and quality of life in children with dystonia and other movement disorders. Both basal ganglia and thalamic nuclei have been found to be relevant targets for treatment of dystonia in children, including the ventral intermediate nucleus of the thalamus, in which stimulation can control dystonic spasms. Electrophysiological confirmation of correct electrode location within the ventralis intermediate nucleus is thus important for the success of the surgical outcome. The present work shows the evoked potentials response during contralateral median-nerve stimulation at the wrist at low frequency (9 Hz) provides physiological evidence of the electrode's localization within the thalamus. We show the correlation between evoked potentials and magnetic resonance imaging (MRI) and computed tomography (CT) in 14 children undergoing implantation of deep brain stimulation electrodes for secondary dystonia. High fidelity and reproducibility of our results provides a new approach to ensure the electrode localization in the thalamic subnuclei.


Finding victory in legal defeat. FTC says ENH can keep Highland Park (Ill.) Hospital, but industry wary of what anti-competitive decision might mean.
Seven years after Evanston Northwestern Healthcare acquired Highland Park Hospital, the Federal Trade Commission has finally issued a ruling saying the deal was anti-competitive. While ENH can keep the hospital, the feds say it must negotiate separately with payers for services at Highland Park. FTC litigator Tom Brock, left, says the case turned on exorbitant price hikes the system extracted from managed-care plans.


The prevalence of psychiatric disease in the significant others of patients with known mood and anxious disease.
Information about the Significant Others (S.O.) of 530 patients with mood and anxious spectrum disorders has been tabulated in this multicentre, retrospective, clinical observational study in order to learn the prevalence of the same mood and/or anxious spectrum diseases in the S.O. of the patients. The 530 outpatients (of age range from 18 to 70 years) with mood and anxious spectrum disorders have been treated by the authors, observed for a seven year period (from January 1995 until May 2003). The patients live in 16 different Italian provinces, but are predominantly from Lombardia and Veneto. Mood disease (includes substance abuse) was present in 72% of the patients and anxious disease was present in 28% (DSM-IV diagnoses based upon clinical interviews). The S.O. (various heterosexual long-term relationships) of each patient was interviewed for this study to establish a DSM-IV diagnosis of any psychiatric disease that might be present. In cases in which the patient had no S.O. or in which information about the S.O. was unavailable, that information was collected. As data was collected, 10 item report was completed for each patient and the respective S.O. Patients had an S.O. with a similar mental disease to their own in 41% of cases; only 16% of the patients chose their S.O. with no mental disease; 18% of the patients did not have any S.O. and in 26% of the cases the health of the S.O. was unknown. In this multicentre, retrospective, clinical observational study, the corresponding Significant Others of 530 patients with mood and anxious spectrum disorders presented with a high percentage of similar disease to the patients. These findings suggest that it may be appropriate to counsel our patients with these diseases to encourage their respective S.O. to undergo a psychiatric evaluation for possible treatable disease: the first objective of an S.O. is preventive care, secondarily the well-being of the partner may improve the treatment outcomes for the patient. Furthermore, eventual studies could demonstrate whether the disease of S.O. precedes couple life (therefore a pre-existent cognitive functioning set out for the partner's choice) and whether it might stem from a difficult interpersonal relationship or chronic stress reaction to a life event.


A common variant of the ABO gene protects against hypertension in a Spanish population.
The objective of this study was to establish whether genetic polymorphisms that could be related to angiotensin-converting enzyme (ACE) levels are associated with hypertension. A total of 10 haplotype-tagging single-nucleotide polymorphisms in ACE, the ACE I/D polymorphism, and 2 polymorphisms in the ABO (rs495828 and rs8176746) were investigated for association with hypertension in 269 hypertensive patients and 254 healthy controls. All analyses were adjusted for age and body mass index, and corrected for multiple testing. Only one polymorphism of the ABO gene (rs495828) presented nominal pointwise P<0.05 values (odds ratio = 0.33, 95% CI 0.19-0.58, P = 6 × 10(-5)) and achieved P<3.8 × 10(-3), the nominal P-value considered significant after Bonferroni correction. Analysis of the genotype frequencies showed that the model that correctly explained the observed association was the recessive model (odds ratio = 0.03, 95% CI 0.01-0.15, P = 1 × 10(-6)). These results indicate that genetic variants that could be related to ACE activity are good predictors of hypertension, and identify ABO as a good candidate gene for genetic studies of hypertension risk. Further studies are required to confirm this association.


A Late Devonian actinopterygian suggests high lineage survivorship across the end-Devonian mass extinction.
Many accounts of the early history of actinopterygians (ray-finned fishes) posit that the end-Devonian mass extinction had a major influence on their evolution. Existing phylogenies suggest this episode could have acted as a bottleneck, paring the early diversity of the group to a handful of survivors. This picture, coupled with increases in taxonomic and morphological diversity in the Carboniferous, contributes to a model of explosive post-extinction radiation. However, most actinopterygians from within a roughly 20-million year (Myr) window surrounding the extinction are poorly known, contributing to uncertainty about the meaning of these patterns. Here, we report an exceptionally preserved fossil from 7 Myr before the extinction that reveals unexpected anatomical features. Palaeoneiros clackorum gen. et sp. nov. nests within a clade of post-Devonian species and, in an expanded phylogenetic analysis, draws multiple lineages of Carboniferous actinopterygians into the Devonian. This suggests cryptic but extensive lineage diversification in the latest Devonian, followed by more conspicuous feeding and locomotor structure diversification in the Carboniferous. Our revised model matches more complex patterns of divergence, survival and diversification around the Devonian/Carboniferous boundary in other vertebrate clades. It also fundamentally recalibrates the onset of diversification early in the history of this major radiation.


Testis-expressed gene 11 inhibits cisplatin-induced DNA damage and contributes to chemoresistance in testicular germ cell tumor.
Testicular germ cell tumor (TGCT) is a rare cancer but the most common tumor among adolescent and young adult males. Patients with advanced TGCT often exhibit a worse prognosis due to the acquisition of therapeutic resistance. Cisplatin-based chemotherapy is a standard treatment for advanced TGCTs initially sensitive to cisplatin, as exemplified by embryonal carcinoma. The acquisition of cisplatin resistance, however, could be a fatal obstacle for TGCT management. To identify cisplatin resistance-related genes, we performed transcriptome analysis for cisplatin-resistant TGCT cells compared to parental cells. In two types of cisplatin-resistant TGCT cell models that we established from patient-derived TGCT cells, and from the NEC8 cell line, we found that mRNA levels of the high-mobility-group nucleosome-binding gene HMGN5 and meiosis-related gene TEX11 were remarkably upregulated compared to those in the corresponding parental cells. We showed that either HMGN5 or TEX11 knockdown substantially reduced the viability of cisplatin-resistant TGCT cells in the presence of cisplatin. Notably, TEX11 silencing in cisplatin-resistant TGCT cells increased the level of cleaved PARP1 protein, and the percentage of double-strand break marker γH2AX-positive cells. We further demonstrated the therapeutic efficiency of TEX11-specific siRNA on in vivo xenograft models derived from cisplatin-resistant patient-derived TGCT cells. Taken together, the present study provides a potential insight into a mechanism of cisplatin resistance via TEX11-dependent pathways that inhibit apoptosis and DNA damage. We expect that our findings can be applied to the improvement of cisplatin-based chemotherapy for TGCT, particularly for TEX11-overexpressing tumor.


[Hemolytic anemia following mitral valve surgery].
Mitral valvuloplasty which is currently the most popular surgical procedure in MVD may be complicated mostly by restenosis or valvular leakage. Hemolysis occurs less frequently and by far less commonly than in prosthetic valves but deserves to be known. Delay between valvuloplasty and hemolytic anemia occurrence may vary within a wide range (from some weeks to several years as in the case we report here). A careful follow-up of the patients who undergo MV repair will help to identify this complication which is related not to the size of the regurgitation flow but to the velocity of the jet. Surgery is the unique treatment of this kind of anemia.


Effect of Altoside (ZR-515) on oxygen consumption, carbon dioxide out put and carbohydrate content of organophosphorus resistant strain of Musca domestica.
The effect of applying JHA ZR-515 at a concentration of 50 microliter/liter water in the larval rearing medium from the first larval instar on oxygen consumption, carbon dioxide out put and total carbohydrates was studied. The oxygen consumed by the pupae previously treated as larvae with ZR-515 was decreased and no adult could emerge. The carbon dioxide out put seems to follow a more or less the pattern of oxygen consumption. The concentration of total carbohydrate content in one day old pupae previously treated as larvae was significantly lower than normals. In three days old there was a marked significant increase and in five days old, the carbohydrate content was significantly higher than controls.


Levetiracetam in progressive myoclonic epilepsy: an exploratory study in 9 patients.
The authors conducted an open study of levetiracetam as add-on therapy in nine patients with well-defined progressive myoclonic epilepsies and refractory myoclonus. Myoclonus was evaluated semiquantitatively (territory, intensity, daily living activities). Five patients had improvement of their myoclonus score. Levetiracetam may benefit myoclonus in progressive myoclonic epilepsy.


The transcription regulator AllR senses both allantoin and glyoxylate and controls a set of genes for degradation and reutilization of purines.
Purines are degraded via uric acid to yield allantoin. Under anaerobic conditions, allantoin is further degraded via carbamoylphosphate to NH(4)+ to provide a nitrogen source and, under aerobic conditions, to 3-phosphoglycerate via glyoxylate for energy production. In this study, we found that a DNA-binding transcription factor AllR, together with AllS, plays a key role in switching control of two pathways, nitrogen assimilation and energy production. The repressor function of AllR is activated in the presence of allantoin, the common substrate for both pathways, leading to repression of the genes for energy production. On the other hand, when glyoxylate is accumulated, AllR is inactivated for derepression of the pathway for energy production. RutR, the master regulator for pyrimidines and arginine, is also involved in this pathway-switching control.


Novel, low-cost solid-liquid-solid process for the synthesis of α-Si3N4 nanowires at lower temperatures and their luminescence properties.
Ultra-long, single crystal, α-Si3N4 nanowires sheathed with amorphous silicon oxide were synthesised by an improved, simplified solid-liquid-solid (SLS) method at 1150 °C without using flowing gases (N2, CH4, Ar, NH3, etc.). Phases, chemical composition, and structural characterisation using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM/HRTEM), Fourier-transform infrared spectroscopy (FT-IR), and X-ray photoelectron spectroscopy (XPS) showed that the nanowires had Si3N4@SiOx core-shell structures. The growth of the nanowires was governed by the solid-liquid-solid (SLS) mechanism. The room temperature photoluminescence (PL) and cathodoluminescence (CL) spectra showed that the optical properties of the α-Si3N4 nanowires can be changed along with the excitation wavelength or the excitation light source. This work can be useful, not only for simplifying the design and synthesis of Si-related nanostructures, but also for developing new generation nanodevices with changeable photoelectronic properties.


[The early cytological diagnosis of carcinoma of the uterine body with the Gravlee jet-washer (author's transl)].
A group of 108 patients who had a curettage for post-menopausal bleeding had a cytologic investigation with the Gravlee jet-washer prior to the curettage. 79 jet-washes (73.1%) were cytologically negative, nine (8.3%) were positive, two (1.8%) were false negative. False positive cytology did not occur. In 18 cases (16.6%) the material was insufficient for cytology. The accuracy of the jet-washings was 82%.


Treatment of murine EAkR lymphosarcoma by surgery combined with systemic or local active BCG immunotherapy applied repeatedly.
A combined treatment modality imcorporating surgery plus BCG immunotherapy was administered to (C57Bl/6 X DBA/2)F1 mice grafted with EAkR lymphosarcoma. A single preoperative local or postoperative systemic BCG administration cured 20-30% of the animals, but did not prolong the survival time of these groups. Repeated s.c. injections of BCG resulted in a significant increase in survival time compared to the group submitted to surgery alone. In contrast, multiple i.v. injections of BCG before and after surgery were no more effective than surgery alone and were less effective than a single postsurgical i.v. injection in producing cures. We have concluded that for local BCG therapy, multiple injections before and after surgery are more effective than a single injection. However, for systemic therapy, multiple injections are less effective than a single injection applied postoperatively.


Phytosterol capsules and serum cholesterol in hypercholesterolemia: a randomized controlled trial.
Phytosterols are recommended in combination with diet therapy to reduce elevated LDL-cholesterol level. Meta-analyses indicate a 10% reduction in LDL-cholesterol from intake of approximately 2 g phytosterols/d incorporated into fat-based foods. However, the cholesterol lowering effect from capsules containing phytosterols is less documented. The pre-specified primary endpoint of the present study was to investigate the effect of capsules with phytosterols on circulating LDL-cholesterol in patients with mild to moderate hypercholesterolemia. In a double-blinded, randomized, placebo-controlled crossover study, 41 men and women were randomized into two four-weeks intervention periods with softgel capsules containing either phytosterols (2.0 g/d) or sunflower oil. There was a three-weeks washout period between the intervention periods. No significant difference in total- or LDL-cholesterol between the phytosterol and the placebo period were observed after four weeks intervention (0.0 mmol/L (95%CI: -0.3 to 0.2), P = 0.74 and -0.1 mmol/L (95%CI: -0.3 to 0.1), P = 0.32, respectively). Daily intake of capsules containing 2 g phytosterols did not reduce total- or LDL-cholesterol significantly in a highly relevant target group for the use of phytosterol products. The present results may emphasize the importance of choosing a suitable dosage-delivery system in order to achieve optimal cholesterol lowering effect. The study was registered at www.clinicaltrials.gov, IDno:NCT00485095.


Enzymatic and non-enzymatic antioxidant status in stage (III) human oral squamous cell carcinoma and treated with radical radio therapy: influence of selenium supplementation.
Oxidative stress is implicated in oral carcinogenesis and has been found to be aggravated during radiotherapy. A great deal of attention has been focused on the possible therapeutic implications of selenium as a potent antioxidant. We determined whether selenium supplementation to radiation treated oral cancer patients render improvement in the antioxidant status against oxidative stress. Blood samples were collected from stage (III) oral cancer patients before initiating radiotherapy (Group B) (n=63) and this group is bifurcated into Group C-patients given radiotherapy alone (n=27) and Group D-patients given radiotherapy and supplemented with selenium (400 mug/day for 6 months) (n=36). Both Group C and D were followed up for 6 months. We evaluated the plasma selenium concentration, non-enzymatic system including GSH, vitamins E, C, A and ceruloplasmin and enzymatic antioxidant system including superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase. The concentrations of selenium, all non-enzymatic antioxidants and the activities of enzymatic antioxidants were found to be lowered in oral cancer patients (Group B), compared to normal (Group A) (p<0.05). Similar decrease in the concentration of selenium and antioxidants status was observed in radiotherapy group (Group C) (p<0.05). On the contrary, selenium group (Group D) showed marked increase in the concentrations of selenium and antioxidant status at 6 months compared to radiation group (Group C) (p<0.05). The observed result represents the antioxidant property of selenium through the improvement of antioxidant defense system. Selenium supplementation could be of great interest in protecting cells against oxidative stress.


A pharmacokinetic study to compare two simultaneous 400 microg doses with a single 800 microg dose of oral transmucosal fentanyl citrate.
It is unknown whether two smaller doses of oral transmucosal fentanyl citrate (OTFC) administered simultaneously are pharmacokinetically equivalent to an identical dose administered as a single unit. This issue has important practical implications when patients are attempting to identify the appropriate dosage of OTFC to control their pain. This open-label, randomized, crossover design study compared the pharmacokinetics of two simultaneously consumed 400 microg OTFC doses with one 800 microg OTFC dose in 12 healthy volunteers. The two treatments were pharmacokinetically equivalent. The maximum concentration produced for each dosage group (Cmax) was 1.09 ng/ml for two 400 microg dose and 1.10 ng/ml for one 800 microg dose. Area under the curve (AUC) was 8.2 ng/ml.hr (SE=1.1) and 7.2 ng/ml.hr (SE=1.0). There were no significant differences between the treatment groups in either the time to peak concentration (Tmax) or the mean residence time (MRT). The results demonstrate the bioequivalence of two 400 microg with one 800 microg OTFC units.


The Role of Steroid Hormone Receptors in the Establishment of Pregnancy in Rodents.
The ovarian hormones, estrogen and progesterone, and their receptors, the estrogen receptor (ER) and progesterone receptor (PR), orchestrate the complex sequence of events required for uterine receptivity and the establishment of pregnancy. The actions of ER, PR, and other steroid hormone receptors (SHRs) direct the uterus through the processes of implantation and decidualization. Due to the ethical concerns of studying pregnancy in humans, genetically engineered rodent models have facilitated many of the discoveries that have elucidated the molecular events directing early pregnancy. This chapter will cover the conserved structure and function of the SHRs. ER and PR will be highlighted for their pivotal roles in uterine receptivity, implantation, and decidualization. The dynamic regulation of ER and PR expression and activity throughout the estrous cycle and early pregnancy, and the importance of SHRs in coordinating paracrine signaling between the endometrial compartments will also be explored. Finally, the roles of androgen receptor (AR) and glucocorticoid receptor (GR) in the establishment of pregnancy will be discussed.


A morphological study of the scaphoid using a mathematical technique and comparative study of the three-dimensional measurements of the scaphoid.
To guide reconstruction of scaphoid non-union, we attempted to create full-scale models of the scaphoid by three-dimensional computed tomography (3D CT) of the healthy side. In this study, we obtained 3D scans of 51 cadaveric hands and studied the difference in morphology between genders and between the left and right sides. The major axis length on a fixed plane and Fourier transformation curve were examined. Ten scaphoid images were also obtained with 3D CT before and after removal from the cadaveric hands. Our findings suggest good correlation between models produced using 3D CT images of the scaphoid alone, and this could serve as an accurate model if the magnification is corrected using the regression line. However, the model using 3D CT images of the intact wrist joint has a large margin of error and its use will not be practical.


Biochar cathode: Reinforcing electro-Fenton pathway against four-electron reduction by controlled carbonization and surface chemistry.
Porous biochars have attracted tremendous interests in electrochemical applications. In this study, a family of biochars were prepared from cellulose subject to different carbonization temperatures ranging from 400 to 700 °C, and the biochars were in-situ activated by a molten salt (ZnCl2) to construct a hierarchically porous architecture. The activated porous biochars (ZnBC) were used as a carbocatalyst for electro-Fenton (EF) oxidation of organic contaminants. Results showed that high-temperature carbonization improved the activity of biochar for four-electron oxygen reduction reaction (ORR) due to the rich carbon defects, while the mild-temperature treatment regulated the species and distribution of oxygen functional groups to increase the production of hydrogen peroxide (H2O2) via a selective two-electron ORR pathway. ZnBC-550 was the best cathode material with a high ORR activity without compromise in H2O2 selectivity; a high production rate of H2O2 (796.1 mg/g/h) was attained at -0.25 V vs RHE at pH of 1. Furthermore, Fe(II) addition induced an electro-Fenton system to attain fast decomposition of various organic pollutants at -0.25 V vs RHE (reversible hydrogen electrode) and pH of 3 with a satisfactory mineralization efficiency toward phenolic pollutants. The EF system maintains its excellent stability for 10 cycles. Hydroxyl radicals were identified as the dominant reactive oxygen species based on in situ electron paramagnetic resonance (EPR) analysis and radical quenching tests. This study gains new insights into electrocatalytic H2O2 production over porous biochars and provides a low-cost, robust and high-performance electro-Fenton cathode for wastewater purification.


The (dys)functional extracellular matrix.
The extracellular matrix (ECM) is a major component of the biomechanical environment with which cells interact, and it plays important roles in both normal development and disease progression. Mechanical and biochemical factors alter the biomechanical properties of tissues by driving cellular remodeling of the ECM. This review provides an overview of the structural, compositional, and mechanical properties of the ECM that instruct cell behaviors. Case studies are reviewed that highlight mechanotransduction in the context of two distinct tissues: tendons and the heart. Although these two tissues demonstrate differences in relative cell-ECM composition and mechanical environment, they share similar mechanisms underlying ECM dysfunction and cell mechanotransduction. Together, these topics provide a framework for a fundamental understanding of the ECM and how it may vary across normal and diseased tissues in response to mechanical and biochemical cues. This article is part of a Special Issue entitled: Mechanobiology.


Tumor induction following intraoperative radiotherapy: late results of the National Cancer Institute canine trials.
Intraoperative radiotherapy has been employed in human cancer research for over a decade. Since 1979, trials to assess the acute and late toxicity of IORT have been carried out at the National Cancer Institute in an adult dog model in an attempt to establish dose tolerance guidelines for a variety of organs. Of the 170 animals entered on 12 studies with a minimum follow-up of 2 years, 148 dogs received IORT; 22 control animals received only surgery. Animals were sacrificed at designated intervals following IORT, usually at 1, 6, 12, 24, and 60 month intervals. 102 of 148 irradiated dogs were sacrificed less than 24 months; 46 dogs were followed greater than or equal to 24 months after IORT. To date, 34 of the 46 animals have been sacrificed; the 12 remaining animals are to be followed to 5 years. These 12 animals have minimum follow-up of 30 months. In the irradiated group followed for greater than or equal to 24 months, 10 tumors have arisen in 9 animals. One animal developed an incidental spontaneous breast carcinoma outside the IORT port, discovered only at scheduled post-mortem exam. The remaining nine tumors arose within IORT ports. Two tumors were benign neural tumors--a neuroma and a neurofibroma. One animal had a "collision" tumor comprised of grade I chondrosarcoma adjacent to grade III osteosarcoma arising in lumbar vertebrae. Two other grade III osteosarcomas, one grade III fibrosarcoma, and one grade III malignant fibrous histiocytoma arose in retroperitoneal/paravertebral sites. An embryonal rhabdomyosarcoma (sarcoma botryoides) arose within the irradiated urinary bladder of one animal. No sham irradiated controls nor IORT animals sacrificed less than 24 months have developed any spontaneous or radiation-induced tumors. The time range of diagnoses of tumors was 24-58 months (median 40 months). The IORT dose range associated with tumor development was 20-35 Gy (median 30 Gy). The carcinogenesis capability of single fraction, high dose radiation in animals is discussed, as are the implications of these data for continued research and clinical usage of IORT in the treatment of humans.


Split right coronary artery and shepherd's crook course of direct origin of the conal artery: An unhitherto association in a case of rheumatic mitral stenosis.
In a 47-year-old lady, planned for redo percutaneous mitral commissurotomy for recurrent mitral valve stenosis, there was incidental detection of splitting of right coronary artery and direct origin and shepherd's crook course of the conal artery. Though these two anomalies have no hemodynamic significance, correct nomenclature and potential clinical implications have been described.


Retraction: A highest stable cluster Au58 (C 1) re-optimized via a density-functional tight-binding (DFTB) approach.
[This retracts the article DOI: 10.1039/C7RA13171B.].


Interferon alpha-armed nanoparticles trigger rapid and sustained STAT1-dependent anti-viral cellular responses.
Interferon-α (IFNα) has enormous potential for anti-proliferative and anti-viral treatments. However, clinical success is still hampered due to its limited bioavailability and thus, lack of sustained modulation of disease-relevant protective programs. Consequently, we here examined whether IFNα immobilized on nanoscale ferromagnetic R-Chitosan carriers is capable of inducing rapid and sustained activation of STAT1 signaling. We report the spontaneous formation of a stable nanoparticle-IFNα protein corona, which was exploited to generate IFNα-loaded spheres, obviating the need to specifically couple the cytokine to the nanoparticles (NPs). Notably, comprehensive experimental approaches ensure that formation of the IFNα NP-corona does not affect the biological activity of the cytokine, as STAT1 signaling was efficiently activated. Employing human prostate cancer and melanoma cell models, we found that the intensity and duration of STAT1 phosphorylation as well as the downstream activation of pathobiologically relevant genes were dose and particle dependent. In comparison with free IFNα, IFNα-loaded spheres resulted in a more sustained biologically relevant STAT1 activation, demonstrated also by conferring innate cellular immunity against vesicular stomatitis virus (VSV) infection. For one, our study demonstrates the advantages of biodegradable IFNα-coated R-Chitosan NPs for controlled cytokine release, and thereby improved therapy. Second, we reveal that the permanent presence of IFNα and not just the initial STAT1 phosphorylation ensures sustained IFNα-dependent signaling.


Targeted Microsurgical Denervation of the Spermatic Cord for Chronic Orchialgia: the Current Standard of Care.
This paper reviews the pathophysiology, current literature, techniques for full microsurgical denervation (MDSC) and targeted microsurgical denervation (TMDSC) of the spermatic cord, and outcomes for these treatment options for patients with chronic scrotal content pain (CSCP) or orchialgia. Significant reduction in pain (77-100%) is reported across various studies for CSCP patients with minimal patient morbidity. The testicular atrophy/loss risk is less than 1%. Testosterone levels do not appear to be affected by TMDSC/MDSC. The outcomes between TMDSC and MDSC are comparable (not statistically significantly different). However, TMDSC is significantly more efficient and a lot less tedious to perform. TMSCD had a shorter microsurgical operative time (21 min vs 53 min, P = 0.0001) than MDSC. Targeted or full microsurgical denervation of the spermatic cord is a safe and effective treatment option that is well published across several studies. The targeted MDSC approach is a more efficient and potentially less risky approach with similar outcomes to full MDSC.


Discovery of a tyrosine-rich sporocyst wall protein in Eimeria tenella.
Eimeria is an important genus of apicomplexan parasites. A defining feature of these parasites is the oocyst, which is transmitted into the environment via the faeces of definitive hosts. The oocyst wall contains cross-linked, tyrosine-rich proteins and protects eight infectious sporozoites, housed in pairs within a second walled structure, the sporocyst. The biochemical basis for sporocyst wall formation is not known. Here, we report the discovery of a novel tyrosine-rich protein, EtSWP1, in Eimeria tenella. Like the tyrosine-rich proteins of the oocyst wall, EtSWP1 is an intrinsically disordered protein with the tyrosine residues concentrated in a specific region of the protein, located immediately following the region of intrinsic disorder. We engineered E. tenella to express mCherry-tagged EtSWP1 and showed that the tagged protein localises specifically to sporocyst walls, indicating that the biochemistry of sporocyst wall assembly is analagous to that of oocyst walls. Tyrosine-rich proteins are known to be key components of the oocyst wall and we now demonstrate, using gene and protein analyses combined with genetic manipulation, that a novel tyrosine-rich protein is specific for the sporocyst wall. This finding is important because it shows that the biochemistry of these two distinct walls is similar and, hence, brings targeted disruption of sporulation and, therefore, potential neutralisation of oocysts in the environment, a step closer.


Quantitative evaluation of the therapeutic effects of antibiotics using silkworms infected with human pathogenic microorganisms.
The injection of bacteria (Staphylococcus aureus, Stenotrophomonas maltophilia) or true fungi (Candida albicans, Candida tropicalis) that are pathogenic to humans into the silkworm hemolymph leads to death of the larvae within 2 days. Antibiotics used for clinical purposes have therapeutic effects on silkworms infected with these pathogens. The 50% effective doses obtained by injection into the silkworm hemolymph are consistent with those reported for mice. Injection of vancomycin and kanamycin into the silkworm hemolymph was effective, but oral administration was not. Chloramphenicol, which is effective by oral administration, appeared in the silkworm hemolymph soon after injection into the midgut, whereas vancomycin did not. Isolated midgut membranes were impermeable to vancomycin. Thus, the ineffectiveness of oral administration of vancomycin to silkworms is due to a lack of intestinal absorption.


Misperceiving facial affect: effects of laterality and individual differences in susceptibility to visual hallucinations.
It has been suggested that certain types of auditory hallucinations may be the by-product of a perceptual system that has evolved to be oversensitive to threat-related stimuli. People with schizophrenia and high schizotypes experience visual as well as auditory hallucinations, and have deficits in processing facial emotions. We sought to determine the relationship between visual hallucination proneness and the tendency to misattribute threat and non-threat related emotions to neutral faces. Participants completed a questionnaire assessing visual hallucination proneness (the Revised Visual Hallucination Scale - RVHS). High scoring individuals (N=64) were compared to low scoring individuals (N=72) on a novel emotion detection task. The high RVHS group made more false positive errors (ascribing emotions to neutral faces) than the low RVHS group, particularly when detecting threat-related emotions. All participants made more false positives when neutral faces were presented to the right visual field than to the left visual field. Our results support continuum models of visual hallucinatory experience in which tolerance for false positives is highest for potentially threatening emotional stimuli and suggest that lateral asymmetries in face processing extend to the misperception of facial emotion.