Pronator syndrome: clinical and electrophysiological features in seven cases.
The clinical and electrophysiological picture of seven patients with the pronator syndrome is contrasted with other causes of median nerve neuropathy. In general, these patients have tenderness over the pronator teres and weakness of flexor pollicis longus as well as abductor pollicis brevis. Conduction velocity of the median nerve in the proximal forearm is usually slow but the distal latency and sensory nerve action potential at the wrist are normal. Injection of corticosteroids into the pronator teres has produced relief of symptoms in a majority of patients.


A Secure and Verifiable Outsourced Access Control Scheme in Fog-Cloud Computing.
With the rapid development of big data and Internet of things (IOT), the number of networking devices and data volume are increasing dramatically. Fog computing, which extends cloud computing to the edge of the network can effectively solve the bottleneck problems of data transmission and data storage. However, security and privacy challenges are also arising in the fog-cloud computing environment. Ciphertext-policy attribute-based encryption (CP-ABE) can be adopted to realize data access control in fog-cloud computing systems. In this paper, we propose a verifiable outsourced multi-authority access control scheme, named VO-MAACS. In our construction, most encryption and decryption computations are outsourced to fog devices and the computation results can be verified by using our verification method. Meanwhile, to address the revocation issue, we design an efficient user and attribute revocation method for it. Finally, analysis and simulation results show that our scheme is both secure and highly efficient.


Vitamin A deficiency and serum or plasma fibronectin in the rat and in human subjects.
Fibronectin, a high-molecular-weight glycoprotein occurring in plasma and on the surface of many cells, is involved in cell adhesion and other cell-surface phenomena. Vitamin A deficiency in rats resulted in a threefold increase in the concentration of fibronectin in serum, as measured immunochemically. In vitamin A-depleted human subjects, on the other hand, no correlation could be found between plasma retinol and fibronectin levels.


Hemopneumothorax due to subacute right ventricular perforation by a pacemaker lead with subtle clinical presentation.
Subacute right ventricular perforation by a pacemaker lead is a rare complication. Although occasionally asymptomatic, complicated cases are usually evidently symptomatic. Here, we report a 70-year-old man presented with mild left-sided chest pain three days after permanent pacemaker implantation. Suspected of ventricular perforation by the pacemaker lead on chest X-ray, device interrogation revealed non-corroborative parameters. This warranted a computed tomography (CT) scan, which confirmed the diagnosis, detected hemopneumothorax, and helped plan surgical intervention. The patient underwent surgical management with the placement of an epicardial pacemaker lead and was discharged after five days. Our case illustrates a rare report of subtle clinical presentation in a patient with subacute right ventricular perforation by a pacemaker lead complicated by hemopneumothorax. It further recapitulates the role of CT scan in providing definitive diagnostic information in managing such a patient. Anticipation of such a presentation is essential for primary care physicians, who are often a first contact point for a patient in the community. This requires a high index of suspicion in such patients presenting with minimal symptoms. Early recognition and timely referral by a family physician may prevent untoward consequences of device-related complications.


Hidden symmetry in chains of biological coupled oscillators.
We experimentally investigated spatiotemporal patterns in chains of coupled biological oscillators with boundaries and found hidden symmetric patterns that are not straightforwardly derived from explicit geometrical symmetry of the systems. We propose a model of coupled oscillators in chains with a hidden oscillator interconnecting its boundaries. The model can explain all observed patterns including the hidden symmetric ones, while other models such as discrete analogs of Neumann boundary conditions in continuous systems cannot.


A Territorywide Prevalence Study on Blood-Borne and Enteric Viral Hepatitis in Hong Kong.
Viral hepatitis epidemiological data are important for the World Health Organization plan of eliminating viral hepatitis. We aimed to document the prevalence of viral hepatitis A to E in Hong Kong. This community-based study was open to all Hong Kong Chinese citizens aged ≥18 years. Baseline data and risk factors were collected. Hepatitis A-E serology was measured, including hepatitis B e antigen, antibodies to hepatitis B e antigen, antibodies to hepatitis D, hepatitis B virus (HBV) DNA for hepatitis B surface antigen (HBsAg)-positive participants, and antibodies to hepatitis B surface antigen and antibodies to hepatitis B core antigen (anti-HBc) in HBsAg-negative participants. Hepatitis C virus (HCV) RNA and genotypes were determined in anti-HCV-positive participants. A total of 10 256 participants were recruited from February 2015 to July 2016. Overall HBsAg seroprevalence was 7.8% (95% confidence interval [CI], 7.3%-8.3%), which was reduced significantly with HBV vaccination (odds ratio, 0.15 [95% CI, .11-.21]). Among HBsAg-negative participants, anti-HBc seroprevalence increased from 5.4% (<26 years) to 60.1% (>65 years). No hepatitis D virus (HDV) cases were detected. Anti-HCV positivity was 0.5% (95% CI, .3%-.6%). Prevalence of antibodies to hepatitis A virus (anti-HAV) and hepatitis E virus (anti-HEV) was 65.2% (95% CI, 64.2%-66.1%) and 33.3% (95% CI, 32.4%-34.2%), respectively, and were influenced by age, family income, and being born in mainland China. HBV seroprevalence remained high despite universal vaccination. High anti-HBc seroprevalence underlines the potential issue of HBV reactivation during profound immunosuppression. HCV and HDV remained uncommon. Anti-HAV seroprevalence had decreased whereas anti-HEV seroprevalence had risen.


Regulation of brain aquaporins.
Emerging evidence suggests that brain aquaporins (AQP) play important roles for the dynamic regulation of brain water homeostasis and for the regulation of cerebrospinal fluid production. This review deals with the short- and long-term regulation of AQP4 and AQP9, both expressed in astrocytes, and of AQP1, expressed in the choroid plexus. AQP1 and 4 have in other cell types been shown to be regulated by phosphorylation. Phosphorylation affects the gating of AQP4 and the trafficking and insertion into membrane of AQP1. Mercury inhibits the water permeability of AQP1 and AQP9, but not AQP4. The permeability of AQP4 is increased by lead. AQP4 is also regulated by protein-protein interaction. The assembly between AQP4 and syntrophin is required for the proper localization of AQP4 in the astrocyte plasma membrane that faces capillaries. There is evidence from studies on peripheral tissues that steroid hormones regulate the expression of AQP1, AQP4 and AQP9. There is also evidence that the expression of AQP1 can be regulated by ubiquitination, and that osmolality can regulate the expression of AQP1, AQP4 and AQP9. Further insight into the mechanisms by which brain AQPs are regulated will be of utmost clinical importance, since perturbed water flow via brain AQPs has been implicated in many neurological diseases and since, in brain edema, water flow via AQP4 may have a harmful effect.


Internally tagged Vps10p-domain receptors reveal uptake of the neurotrophin BDNF.
The Vps10p-domain (Vps10p-D) receptor family consists of Sortilin, SorLA, SorCS1, SorCS2, and SorCS3. They mediate internalization and intracellular sorting of specific cargo in various cell types, but underlying molecular determinants are incompletely understood. Deciphering the dynamic intracellular itineraries of Vps10p-D receptors is crucial for understanding their role in physiological and cytopathological processes. However, studying their spatial and temporal dynamics by live imaging has been challenging so far, as terminal tagging with fluorophores presumably impedes several of their protein interactions and thus functions. Here, we addressed the lack of appropriate tools and developed functional versions of all family members internally tagged in their ectodomains. We predict folding of the newly designed receptors by bioinformatics and show their exit from the endoplasmic reticulum. We examined their subcellular localization in immortalized cells and primary cultured neurons by immunocytochemistry and live imaging. This was, as far as known, identical to that of wt counterparts. We observed homodimerization of fluorophore-tagged SorCS2 by coimmunoprecipitation and fluorescence lifetime imaging, suggesting functional leucine-rich domains. Through ligand uptake experiments, live imaging and fluorescence lifetime imaging, we show for the first time that all Vps10p-D receptors interact with the neurotrophin brain-derived neurotrophic factor and mediate its uptake, indicating functionality of the Vps10p-Ds. In summary, we developed versions of all Vps10p-D receptors, with internal fluorophore tags that preserve several functions of the cytoplasmic and extracellular domains. These newly developed fluorophore-tagged receptors are likely to serve as powerful functional tools for accurate live studies of the individual cellular functions of Vps10p-D receptors.


Postoperative Anatomic Position of Mandibular Free Flap Neocondyles Affects Patient Symptoms.
Importance: Mandibular condyle reconstruction with vascularized free flaps can re-establish form and function after resection. However, no reports have been published regarding the postoperative anatomic seating of these reconstructions. Objective: To use postoperative axial imaging to determine whether condylar reconstructions migrate and correlate their ultimate location with postoperative symptoms. Design, Setting, and Participants: A prospectively maintained database of free flap cases performed between 2006 and 2019 at a single institution was queried. Twenty-one consecutive patients who underwent reconstructions that involved the mandibular condyle who also had postoperative axial imaging were selected for review. Distances were measured from the reconstructed condyle to the lateral, superior, and posterior aspect of the temporomandibular joint (TMJ), and correlated with postoperative symptoms and jaw function. Main Outcomes and Measures: Condyle displacement, postoperative diet, jaw pain, trismus, and malocclusion. Results: In total, 57% of patients had 1 cm or greater displacement of the condylar reconstruction from the TMJ in at least one vector. Anterior displacement of condyle by >1 cm was associated with jaw misalignment (42.8%) and clicking (14.3%) [odds ratio (OR) 37.3, 95% confidence interval (CI) 1.6-866.9, p = 0.024]. However, 83.3% of these patients were able to return to a normal diet and denied dysphagia. All edentulous patients had acceptable anteroposterior alignment, but 42.8% of dentulous patients had anterior displacement >1 cm (p = 0.12). Inferior displacement >1 cm was associated with dysphagia (OR 23, 95% CI 1.07-494.6, p = 0.04), but not pain or trismus. Eleven patients had multiple postoperative computed tomography scans, on average 21 months apart. The reconstructed location was stable in all 11 patients. Conclusions and Relevance: Patients undergoing free flap reconstruction of the mandibular condyle often return to normal diet, even when their reconstructions do not sit perfectly within the TMJ. Anterior displacement of the neocondyle may be more common in dentulous patients due to stress on the joint from chewing and produces some dysfunction and misalignment. Inferior displacement of the neocondyle may result in dysphagia. The reconstructed condyles are unlikely to migrate over time.


The new group of non-pathogenic plant-associated nitrogen-fixing Burkholderia spp. shares a conserved quorum-sensing system, which is tightly regulated by the RsaL repressor.
A novel group of nitrogen-fixing plant-associated Burkholderia species has emerged in the last few years. The purpose of this investigation was to determine if these species possess an N-acylhomoserine lactone (AHL) quorum-sensing (QS) cell-cell signalling system, and whether it is important for nitrogen fixation and other phenotypic features in Burkholderia kururiensis. It was determined that B. kururiensis, and other members of this Burkholderia species cluster, contain at least one highly conserved system, designated BraI/R, which produces and responds to N-dodecanoyl-3-oxo-homoserine lactone (C12-3-oxo-AHL). The BraI/R AHL QS is not involved in the regulation of nitrogen fixation or in several other important phenotypes, indicating that it may not be a global regulatory system. The BraI/R system is similar to LasI/R of Pseudomonas aeruginosa and, as with lasI/R, there is a repressor gene, rsaL, between the braI/R genes. B. kururiensis normally synthesizes very low levels of C12-3-oxo-AHL, but the situation dramatically changes when RsaL is missing since an rsaL mutant displays a marked increase in AHL production. This unique stringent regulation indicates that RsaL could be an on/off switch for AHL QS in B. kururiensis and the ability to produce very high levels of AHL also questions the role of this molecule in the novel group of Burkholderia. The presence of a well-conserved and distinct AHL QS system among all the diazotrophic Burkholderia is a further indication that they are closely related, and that this system might play an important and conserved role in the lifestyle of this novel group of bacterial species.


The Accuracy of Emergency Physicians in Ultrasonographic Screening of Acute Appendicitis; a Cross Sectional Study.
Diagnostic values reported for ultrasonographic screening of acute appendicitis vary widely and are dependent on the operator's skill, patient's gender, weight, etc. The present study aimed to evaluate the effect of operator skill on the diagnostic accuracy of ultrasonography in detection of appendicitis by comparing the results of ultrasonography done by radiologists and emergency physicians. This prospective diagnostic accuracy was carried out on patients suspected to acute appendicitis presenting to EDs of 2 hospitals. After the initial clinical examinations, all the patients underwent ultrasonography for appendicitis by emergency physician and radiologist, respectively. The final diagnosis of appendicitis was based on either pathology report or 48-hour follow-up. Screening performance characteristics of appendix ultrasonography by emergency physician and radiologist were compared using STATA 11.0 software. 108 patients with the mean age of 23.91 ± 7.46 years were studied (61.1% male). Appendicitis was confirmed for 37 (34.26%) cases. Cohen's kappa coefficient between ultrasonography by the radiologist and emergency physician in diagnosis of acute appendicitis was 0.51 (95% CI: 0.35 - 0.76). Area under the ROC curve of ultrasonography in appendicitis diagnosis was 0.78 (95% CI: 0.69 - 0.86) for emergency physician and 0.88 (95% CI: 0.81 - 0.94) for radiologist (p = 0.052). Sensitivity and specificity of ultrasonography by radiologist and emergency physician in appendicitis diagnosis were 83.87% (95% CI: 67.32 - 93.23), 91.5% (95% CI: 81.89 - 96.52), 72.97% (95% CI: 55.61 - 85.63), and 83.10% (95% CI: 71.94 - 90.59), respectively. Findings of the present study showed that the diagnostic accuracy of ultrasonography carried out by radiologist (89%) is a little better compared to that of emergency physician (80%) in diagnosis of appendicitis, but none are excellent.


Levels of circulating GRP78 and CHOP in endoplasmic reticulum stress pathways in Chinese type 2 diabetic kidney disease patients.
The current study aimed to investigate circulating glucose-regulated protein 78 (GRP78) as well as CCAAT/enhancer-binding protein homologous protein (CHOP) concentrations in Chinese type 2 diabetes mellitus (T2DM) patients, especially those with microalbuminuria. We recruited 67 patients with T2DM and 63 control subjects. We determined circulating GRP78 and CHOP concentrations by ELISA, collected anthropometric data, and measured biochemical parameters in a clinical laboratory. Compared with control groups, patients with T2DM showed decreased circulating levels of GRP78 (0.21 [0.16-0.24] vs 0.16 [0.16-0.19] ng/mL, P < .01) and CHOP ([0.29 ± 0.02] vs [0.27 ± 0.03]ng/mL, P < .01). Reduction in circulating GRP78 and CHOP levels was more pronounced in patients with more severe categories of albuminuria. Amounts of circulating GRP78 correlated directly with serum fasting c-peptide, cystatin-c (Cys-c), creatinine (Cr), blood urea nitrogen (BUN), and uric acid, and inversely with glomerular filtration rates. Circulating CHOP level was positively correlated with age, Cr, BUN, Cys-c, and urinary microalbumin/creatinine (UmALB/Cr). Circulating GRP78 was predicted independently by Cr, BUN, serum uric acid, estimated glomerular filtration rate, and Cys-c, while CHOP depended on age, Cr, BUN, estimated glomerular filtration rate, UmALB/Cr, and Cys-c. After controlling for confounding factors, circulating GRP78 and CHOP expression were significantly associated with diabetic kidney disease (binary logistic regression, P < .01). Patients with T2DM showed increased circulating GRP78 and CHOP concentrations. Receiver operating characteristic areas under the curve for predicting diabetic kidney disease based on GRP78 and CHOP were 0.686 (95% CI: 0.558-0.813) and 0.670 (0.524-0.816), respectively.


Beyond Social Skills: Supporting Peer Relationships and Friendships for School-Aged Children with Autism Spectrum Disorder.
Social impairments are the sine qua non of autism spectrum disorder (ASD). However, children with ASD are capable of forming reciprocal friendships and many people with ASD have a strong desire for friends. Developing and maintaining friendships is associated with many important outcomes, including improved quality of life, mental health, and academic achievement. Children with ASD often attend groups to improve social skills, but strategies for building and maintaining friendships are not consistently addressed or measured following intervention. In this article, our objective is to build an understanding of peer relationships and friendships in school-aged children with ASD and how to best support them. In this article, we describe characteristics of peer relationships and friendships for children with ASD. We discuss current research findings on intervention to improve social skills, peer relationships, and friendships in school-aged children with ASD. Finally, we give suggestions for clinical practice and future research.


A novel, potentially targetable TMEM106B-BRAF fusion in pleomorphic xanthoastrocytoma.
Pleomorphic xanthoastrocytoma (PXA) is a World Health Organization (WHO) Grade II glioma occurring primarily in children and young adults. Most PXAs harbor the known activating mutation BRAF V600E. We report a case of locally recurrent PXA with anaplastic features in a 10-yr-old female. The PXA was negative by immunohistochemical (IHC) staining for BRAF V600E mutation. Whole-exome and transcriptome sequencing of the tumor confirmed the absence of BRAF V600E, but identified copy-number alterations (including loss of the tumor suppressor CDKN2A) and a novel TMEM106B-BRAF fusion. Based on similar BRAF fusion proteins, this novel fusion is predicted to result in activation of BRAF signaling. Demonstration of positive IHC for phospho-ERK1/2 and phospho-MEK1/2 supported this prediction, and implicated MEK inhibitors as a potential therapeutic strategy.


Real-Time PCR Assay for the Diagnosis and Quantification of Co-infections by Diaporthe batatas and Diaporthe destruens in Sweet Potato.
Foot rot disease caused by Diaporthe destruens (formerly Plenodomus destruens) has become a major concern for the production of sweet potato [Ipomoea batatas (L.) Lam.] in Japan. A related fungus Diaporthe batatas, which causes dry rot disease of sweet potato, is native and is widespread in fields in Japan. The similar characteristics of these two pathogens pose a challenge for conventional disease diagnosis. Currently, there are no effective molecular measures for identifying and distinguishing D. destruens and D. batatas. Here, we demonstrate a real-time PCR assay that distinguishes and quantifies D. batatas and D. destruens from co-infected sweet potato. The assay was performed with various simulated DNA combinations of D. batatas and D. destruens ranging from 1:1 to 1:100000. The assay was also used with the ratios of D. batatas: D. destruens: sweet potato DNA ranging from 1:1:1 to 1:1:100000. These assays produced a specific amplification product for each of the pathogens, and quantified the fungal biomass over the entire range tested without detecting false positives. The assay was validated by using infected sweet potato collected from various fields; it showed sufficient sensitivity and specificity to quantify and distinguish D. batatas and D. destruens from these field samples. Thus, our real-time PCR assay would be a useful tool for diagnosis of D. batatas and D. destruens and is expected to provide the foundation for the design of integrated disease management strategies for foot rot disease in sweet potato.


Obesity, Bioactive Lipids, and Adipose Tissue Inflammation in Insulin Resistance.
Obesity is a major risk factor for the development of insulin resistance and type 2 diabetes. The exact mechanism by which adipose tissue induces insulin resistance is still unclear. It has been demonstrated that obesity is associated with the adipocyte dysfunction, macrophage infiltration, and low-grade inflammation, which probably contributes to the induction of insulin resistance. Adipose tissue synthesizes and secretes numerous bioactive molecules, namely adipokines and cytokines, which affect the metabolism of both lipids and glucose. Disorders in the synthesis of adipokines and cytokines that occur in obesity lead to changes in lipid and carbohydrates metabolism and, as a consequence, may lead to insulin resistance and type 2 diabetes. Obesity is also associated with the accumulation of lipids. A special group of lipids that are able to regulate the activity of intracellular enzymes are biologically active lipids: long-chain acyl-CoAs, ceramides, and diacylglycerols. According to the latest data, the accumulation of these lipids in adipocytes is probably related to the development of insulin resistance. Recent studies indicate that the accumulation of biologically active lipids in adipose tissue may regulate the synthesis/secretion of adipokines and proinflammatory cytokines. Although studies have revealed that inflammation caused by excessive fat accumulation and abnormalities in lipid metabolism can contribute to the development of obesity-related insulin resistance, further research is needed to determine the exact mechanism by which obesity-related insulin resistance is induced.


[Effects of organic fertilizer application on accumulation and distribution of assimilates in winter wheat].
To understand the effects of organic fertilizer addition on accumulation and distribution of winter wheat assimilates, we compared organic carbon content in soil and wheat plants, photosynthetic characteristics and assimilation transformation under two different fertilizer treatments, CF (chemical fertilizer only) and OF (organic fertilizer with chemical fertilizer), using 13CO2 pulse labeling method. The results showed that OF increased soil organic carbon content and wheat photosynthetic parameters, resulting in higher organic carbon content and total dry biomass accumulation in wheat plants compared with CF treatment. Compared marking to maturity with that on the 7th day after the same marking, the content and distribution rate of 13C in leaves and stems of two treatments decreased; the 13C content in spikes increased at jointing stage and filling stage, decreased at anthesis stage, and the 13C distribution rate increased at all stages. OF treatment was more beneficial for the transportation of photosynthetic product from leaves to spikes at filling stage, with higher 13C distribution rate in spikes compared with CF treatment. The results of correlation analysis showed that dry matter accumulation was significantly positively correlated with the net input of 13C content and its distribution rate, but negatively correlated with organic carbon content in plants. The net input of 13C content was significantly positively correlated with its distribution rate, and negatively correlated with Fv/Fm and Pn. In conclusion, organic fertilizer application could increase the content of organic carbon in soil, improve wheat plants photosynthetic capacity and transportation of photosynthetic product to spikes, and ultimately increase dry matter accumulation in wheat spikes.


Reduction of pesticide residues in tomatoes and other produce.
There is interest in reducing pesticide residues in fruits and vegetables in order to minimize human exposure. The objectives of this study were to (i) determine the effect of various washing treatments with and without sonication on pesticide removal from tomatoes and (ii) assess the effectiveness of a water wash on select samples using a produce-washing flume. In the first set of experiments, tomatoes were contaminated with acephate, malathion, carbaryl, bifenthrin, cypermethrin, permethrin, cyhalothrin, chlorothalonil, and imidacloprid and were dried overnight. Subsets of the tomatoes were then washed (10°C, 1 min) with one of the following: water, sodium hypochlorite (80 μg/ml, pH 7), peroxyacetic acid (80 μg/ml), or Tween 20 (0.1%) with and without sonication. In general, the effect of sonication depended on the washing treatment and on the pesticide. A separate experiment measured pesticide residues in contaminated samples before and after being washed in a flume (22°C, 1 min). Pesticide residues in contaminated produce were reduced from about 40 to 90% when washed for 1 min in the flume.


Radical scavenging, prolyl endopeptidase inhibitory, and antimicrobial potential of a cultured Himalayan lichen Cetrelia olivetorum.
Lichens are source of natural bioactive compounds which are traditionally used to cure a variety of ailments. The objective of this study is to assess free radical scavenging, prolyl endopeptidase inhibitory (PEPI), and antimicrobial potential of a high altitude lichen species Cetrelia olivetorum (Nyl.) W. L. Culb. & C. F. Culb (Parmeliaceae). Lichen C. olivetorum has been cultured in vitro, and optimized culture conditions were implemented in bioreactor to obtain high quantity of biomass for the study of radical scavenging, PEPI, and antimicrobial activities. Radical scavenging activity of methanol extract of Cetrelia olivetorum (MECO) was tested at 100 µg/mL, PEPI activity at 25 and 50 µg/mL, and antimicrobial activity at 5, 25, 50, and 100 µg/mL conc. All the biological activities of natural thallus extract and its derived culture extract were evaluated spectrophotometrically. Murashige and Skoog medium supplemented with 3% glucose and 100 ppb indole-3-butyric acid (IBA) supported biomass growth at flask level and yielded 5.095 g biomass in bioreactor. MECO of both the cultured and the natural lichen exhibited half inhibiting concentration (IC50) for radical scavenging activities in the range of 50-60 µg/mL, whereas the IC50 value of standard antioxidants was found to be in the range of 12-29 µg/mL. The IC50 value of lichen extract for PEPI activity was 144-288 µg/mL, whereas the IC50 value of standard prolyl endopeptidase inhibitor, Z-pro-prolinal, was 57.73 µg/mL. As far as the antimicrobial activity of MECO is concerned, minimum inhibitory concentration (MIC) value of lichen extracts against tested microorganisms was obtained in the range of 50-104 µg/mL and found to be more effective than commercially available standard erythromycin. Murashige and Skoog medium containing IBA was found to be suitable for maximum biomass production of C. olivetorum under bioreactor conditions. The cultured lichen biomass extract also showed antioxidant, PEPI, and antimicrobial potential. The present study indicates therapeutic potential of Himalayan lichen C. olivetorum against neurodegenerative diseases owing to its radical scavenging, PEPI, and antimicrobial activities. Further, the result encourages its commercial exploitation through mass culture for production of its bioactive components and their use in pharmaceutical and nutraceutical industries.


Electronically driven fragmentation of silver nanocrystals revealed by ultrafast electron crystallography.
We report an ultrafast electron diffraction study of silver nanocrystals under surface plasmon resonance excitation, leading to a concerted fragmentation. By examining simultaneously transient structural, thermal, and Coulombic signatures of the prefragmented state, an electronically driven nonthermal fragmentation scenario is proposed.


Novel experimental design paradigm for development of eco-friendly gradient chromatographic method for simultaneous determination of metronidazole and spiramycin.
This work describes the innovative experimental design-assisted development of a green gradient chromatographic method for concomitant analysis of metronidazole (MTR) and spiramycin (SPR). Two different designs including fractional factorial and Box-Behnken designs were implemented for screening and optimization steps, respectively. The optimum chromatographic conditions involved a mobile phase consisting of ethanol and 20 mM sodium dihydrogen phosphate solution (pH adjusted to 2.5) in the ratio 2:98 (v/v) for 2 min then the ratio changed to 30:70 (v/v). The flow rate was 1.3 mL/minute. Separation and analysis were performed on X-bridge C18 (150 mm × 4.6 mm × 3.5 μm) column with diode array detector set at 230 nm. Column oven temperature was 40°C. A linear response was acquired over the range of 5-125 μg/mL for both drugs. Detection and quantitation limits were 0.86 and 2.62 μg/mL for MTR and 0.92 and 2.83 μg/mL for SPR, respectively. The method was implemented for determination of both drugs in three tablet formulations. The method was proved to be green as evaluated by three assessment tools. The application of experimental designs assists in development of a robust green chromatographic method in gradient elution mode for determination of both drugs within reasonable time.


Spontaneous knotting of an agitated string.
It is well known that a jostled string tends to become knotted; yet the factors governing the "spontaneous" formation of various knots are unclear. We performed experiments in which a string was tumbled inside a box and found that complex knots often form within seconds. We used mathematical knot theory to analyze the knots. Above a critical string length, the probability P of knotting at first increased sharply with length but then saturated below 100%. This behavior differs from that of mathematical self-avoiding random walks, where P has been proven to approach 100%. Finite agitation time and jamming of the string due to its stiffness result in lower probability, but P approaches 100% with long, flexible strings. We analyzed the knots by calculating their Jones polynomials via computer analysis of digital photos of the string. Remarkably, almost all were identified as prime knots: 120 different types, having minimum crossing numbers up to 11, were observed in 3,415 trials. All prime knots with up to seven crossings were observed. The relative probability of forming a knot decreased exponentially with minimum crossing number and Möbius energy, mathematical measures of knot complexity. Based on the observation that long, stiff strings tend to form a coiled structure when confined, we propose a simple model to describe the knot formation based on random "braid moves" of the string end. Our model can qualitatively account for the observed distribution of knots and dependence on agitation time and string length.


Time factor for acute tissue reactions following fractionated irradiation: a balance between repopulation and enhanced radiosensitivity.
Experimental data for acute radiation-induced skin reactions are reviewed. These show that for dose fractionation schedules with gaps, repopulation is initiated after a lag period. After this lag period, the isoeffective dose for a given level of skin reaction first increases rapidly, but then slows. The timing of the lag period is related to the total turnover time of the tissue under investigation and, for example, is shorter in rodent skin than in pig or human skin. At the point when accelerated repopulation is initiated, there is a major shortening of the turnover time of the target cell population. At this time, there is evidence, for a short period, for an increase in radiosensitivity of the surviving stem cells in a number of acutely responding normal tissues. This effect is clearly illustrated by the results of experiments using sequential dose fractionation schedules. Prolongation of the schedule from 'short' to schedules that include irradiation over the period when the cell turnover is accelerated is associated with a marked increase in tissue radiosensitivity. Clinically, this is best illustrated by a comparison of the effects of accelerated fractionation schedules, involving multiple fractions/day, with daily fractionation schedules. The increase in radiosensitivity produced by the prolongation of the treatment from 2 to 4-5 weeks was equivalent to > or =1 Gy day(-1). Comparable findings were obtained from animal studies. In the oral mucosa of mice, the initiation of accelerated cell proliferation in surviving cells is associated with the loss of dose sparing by subsequent dose fractionation due to the loss of the capacity to repair sublethal damage. Studies in pig and human skin have indicated that increased radiosensitivity is associated with a loss of cells in the G1 phase of the cell cycle. A collation of these two sets of findings suggests that the repair of sublethal damage takes place over this phase of the cell cycle. One clinical implication of these findings is that the alpha/beta ratio for acute skin reaction changes with the length of the overall treatment time; it is approximately 4.0 Gy for 'short' fractionation schedules that avoid any shortening of the cell cycle time. This increases to 11.2-13.3 Gy for schedules given in 3-4 weeks and to approximately 35 Gy for schedules given in 5-6 weeks. Results for pig skin were in total agreement with those for human skin.


Cytotoxic Activity and Antibiofilm Efficacy of Biosynthesized Silver Nanoparticles against Methicillin-Resistant Staphylococcus aureus Strains Colonizing Cell Phones.
The interest for green synthesis of metallic nanoparticles (NPs) has acquired particular attention due to its low toxicity and economic feasibility compared with chemical or physical process. Here we carried out an extracellular synthesis approach of silver nanoparticles (AgNPs) using dried orange peel extract. Characterization studies revealed the synthesis of 25-30 nm AgNPs with distinct morphology as observed in transmission electron microscopes. Dynamic light scattering spectroscopy and Fourier transform infrared spectroscopy analyses further characterized nanoparticles confirming their stability and the presence of functional groups. The biological properties of biosynthesized AgNPs were subsequently investigated. Our results revealed anticancer activity of biogenic silver NPs against the B16 melanoma cell line with an IC50 value of 25 µg/ml. Additionally, the developed AgNPs displayed a considerable antagonistic activity against methicillin-resistant Staphylococcus aureus (MRSA) strains colonizing cell phones, with inhibition zones between 12 and 14 mm and minimum inhibitory concentration values between 1.56 and 12.5 µg/ml. Furthermore, the AgNPs exhibited potent antibiofilm activity against MRSA strains with the percent biofilm disruption reaching 80%. Our results highlighted the efficacy of biosynthesized AgNPs against bacterial biofilms and pointed to the exploration of orange peels as a natural and cost-effective strategy.


Update on the current recommendations and outcomes in pregnant women with antiphospholipid syndrome.
Pregnancy morbidity is part of the clinical spectrum of the antiphospholipid syndrome (APS), a chronic autoimmune condition serologically characterized by the persistent positivity of antiphospholipid antibodies (aPL). Antiplatelet and anticoagulant agents are the mainstay of the treatment of obstetric APS. However, there is an ongoing debate about the optimal management of women with most severe aPL-mediated obstetric complications, women not fulfilling APS criteria and those with refractory disease. Unfortunately, the literature cannot provide definite answers to these controversial issues, being flawed by many limitations. The evidence supporting the recommended therapeutic management of different aPL-related obstetrical clinical manifestations is presented, with a critical appraisal of each approach.


Synthesis of novel coumarin-hydrazone hybrids as α-glucosidase inhibitors and their molecular docking studies.
Diabetes mellitus is a metabolic disorder and more than 90% of diabetic patients suffer from type-2 diabetes, which is characterized by hyperglycemia. α-Glucosidase inhibition has become an appropriate approach to tackle high blood glucose levels. The current study was focused on synthesizing coumarin-hydrazone hybrids (7a-i) by using facile chemical reactions. The synthesized compounds were characterized by using 1H-NMR, 13C-NMR, and IR. To evaluate their anti-diabetic capability, all of the conjugates were screened for in vitro α-glucosidase inhibitory activity to reveal their therapeutic importance. All of the compounds (except 7b) demonstrated significant enzyme inhibitory potential with IC50 values ranging between 2.39-57.52 μM, as compared to the standard inhibitor, acarbose (IC50 = 873.34 ± 1.67 μM). Among them, compound 7c is the most potent α-glucosidase inhibitor (IC50 = 2.39 ± 0.05 μM). Additionally, molecular docking was employed to scrutinize the binding pattern of active compounds within the α-glucosidase binding site. The in silico analysis reflects that hydrazone moiety is an essential pharmacophore for the binding of compounds with the active site residues of the enzyme. This study demonstrates that compounds 7c and 7f deserve further molecular optimization for potential application in diabetic management.


Is Psychology Headed in the Right Direction? Yes, No, and Maybe.
In this piece, I first celebrate the growing contribution of psychology to the understanding and solution of pressing social issues. Then, despite these exciting developments, I worry about whether we have created a field that our students want to spend their lives in, and I suggest concerns that might fruitfully be addressed. Finally, I worry about the potential fragmentation of psychology and applaud programs of research that have shown the unique and important contributions to be made when the methods and perspectives of neuroscience, cognitive science, and computational modeling are integrated with those of social, personality, and developmental psychology. In sum, although this is an exciting time for our field, we can do more to ensure its vigor and its truly interdisciplinary nature as we move forward.


Coexistence of Meyerson's with Sutton's naevus after sunburn.
We described the simultaneous occurrence of perinaevic eczema (Meyerson's naevi) and Sutton's halo naevus in one patient. Characteristic clinical and histological features of perinaevic eczema were found around four benign melanocytic naevi on the limbs. In addition, the patient had a typical Sutton's naevus on the back. The association of Meyerson's naevi and Sutton's naevus has been reported only once in the past literature. Both diseases appeared a few weeks after a severe sunburn. The role of sun exposure in the development of eczematiform and/or vitiligoid reactions around melanocytic naevi is discussed.


Cell-free fatty acid acylation of Semliki Forest viral polypeptides with microsomal membranes from eukaryotic cells.
Using [14C]palmitoyl-CoA as donor and deacylated (fatty acid-free) structural proteins of Semliki Forest virus as exogenous acceptors, palmitic acid was incorporated into polypeptide in a cell-free system with microsomes of baby hamster kidney cells, chicken embryo fibroblasts, and rat liver cells. Out of the four viral proteins (E1, E2, E3, and C) only E1 becomes acylated enzymatically. The protein bound fatty acids of the in vitro product are resistant to detergents and to organic extractions but can be released with hydroxylamine thus affording the typical features of acyl-proteins. Fatty acid transfer to E1 requires the presence of microsomes and is abolished when microsomal membranes are omitted or boiled prior to the incubation. Exogenous acceptor protein E1 had to be deacylated prior to the incubation in order to function during acylation in vitro since no fatty acid chains were transferred into untreated viral E1. Acylation of E1 is time- and temperature-dependent and can be stimulated by increasing the concentrations of acceptor protein, microsomal membranes, or of exogenous fatty acid donor. While Mg2+ does not influence the transfer reaction, Mn2+ leads to a dose-dependent inhibition commencing at a concentration of 1 mM. The cell-free acylation activity fails to show high specificity with regard to the chain length or degree of saturation of the acyl chain used as lipid substrate since palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1), and myristic acid (C14:0) are all transferred onto E1 as long as ATP is present in the incubation mixture. The type of detergent and its concentration were found to be critical for this acylation in vitro. Nonidet P-40 or Triton X-100 both up to a 0.2% concentration allowed the reaction while no enzymatic transfer of palmitic acid onto E1 was detected in the presence of octyl-beta-D-glucoside and Tween 20 at the conditions used for the in vitro incubation. However, when acyl transfer onto lipid acceptors was monitored, the incorporation of fatty acids into the neutral- and phospholipids functioned normally in octyl-beta-D-glucoside only, while Nonidet P-40 and Triton X-100 inhibited the acylation of all neutral lipids and of most of the phospholipids completely.(ABSTRACT TRUNCATED AT 400 WORDS)


Plant phosphoproteomics: a long road ahead.
Phosphoproteomics can be defined as the comprehensive study of protein phosphorylation by identification of the phosphoproteins, exact mapping of the phosphorylation sites, quantification of phosphorylation, and eventually, revealing their biological function. Its place in today's research is vitally important to address the most fundamental question - how the phosphorylation events control most, if not all, of the cellular processes in a given organism? Despite the immense importance of phosphorylation, the analysis of phosphoproteins on a proteome-wide scale remains a formidable challenge. Nevertheless, several technologies have been developed, mostly in yeast and mammals, to conduct a large-scale phosphoproteomic study. Some of these technologies have been successfully applied to plants with a few modifications, resulting in documentation of phosphoproteins, phosphorylation site mapping, identification of protein kinase substrates, etc. at the global level. In this review, we summarize in vitro and in vivo approaches for detection and analysis of phosphoproteins including protein kinases and we discuss the importance of phosphoproteomics in understanding plant biology. These approaches along with bioinformatics will help plant researchers to design and apply suitable phosphoproteomic strategies in helping to find answers to their biological questions.


Analysis of herbaceous plant succession and dispersal mechanisms in deglaciated terrain on Mt. Yulong, China.
Ecological succession itself could be a theoretical reference for ecosystem restoration and reconstruction. Glacier forelands are ideal places for investigating plant succession because there are representative ecological succession records at long temporal scales. Based on field observations and experimental data on the foreland of Baishui number 1 Glacier on Mt. Yulong, the succession and dispersal mechanisms of dominant plant species were examined by using numerical classification and ordination methods. Fifty samples were first classified into nine community types and then into three succession stages. The three succession stages occurred about 9-13, 13-102, and 110-400 years ago, respectively. The earliest succession stage contained the association of Arenaria delavayi + Meconopsis horridula. The middle stage contained the associations of Arenaria delavayi + Kobresia fragilis, Carex capilliformis + Polygonum macrophyllum, Carex kansuensis, and also Pedicularis rupicola. The last stage included the associations of Kobresia fragilis + Carex capilliformis, Kobresia fragilis, Kobresia fragilis + Ligusticum rechingerana, and Kobresia fragilis + Ligusticum sikiangense. The tendency of the succession was from bare land to sparse vegetation and then to alpine meadow. In addition, three modes of dispersal were observed, namely, anemochory, mammalichory, and myrmecochory. The dispersal modes of dominant species in plant succession process were evolved from anemochory to zoochory.


A rice spotted leaf gene, Spl7, encodes a heat stress transcription factor protein.
A rice spotted leaf (lesion-mimic) gene, Spl7, was identified by map-based cloning. High-resolution mapping with cleaved amplified polymorphic sequence markers enabled us to define a genomic region of 3 kb as a candidate for Spl7. We found one ORF that showed high similarity to a heat stress transcription factor (HSF). Transgenic analysis verified the function of the candidate gene for Spl7: leaf spot development was suppressed in spl7 mutants with a wild-type Spl7 transgene. Thus, we conclude that Spl7 encodes the HSF protein. The transcript of spl7 was observed in mutant plants. The levels of mRNAs (Spl7 in wild type and spl7 in mutant) increased under heat stress. Sequence analysis revealed only one base substitution in the HSF DNA-binding domain of the mutant allele, causing a change from tryptophan to cysteine.


Intercalated Iron Chalcogenides: Phase Separation Phenomena and Superconducting Properties.
Organic molecule-intercalated layered iron-based monochalcogenides are presently the subject of intense research studies due to the linkage of their fascinating magnetic and superconducting properties to the chemical nature of guests present in the structure. Iron chalcogenides have the ability to host various organic species (i.e., solvates of alkali metals and the selected Lewis bases or long-chain alkylammonium cations) between the weakly bound inorganic layers, which opens up the possibility for fine tuning the magnetic and electrical properties of the intercalated phases by controlling both the doping level and the type/shape and orientation of the organic molecules. In recent years, significant progress has been made in the field of intercalation chemistry, expanding the gallery of intercalated superconductors with new hybrid inorganic-organic phases characterized by transition temperatures to a superconducting state as high as 46 K. A typical synthetic approach involves the low-temperature intercalation of layered precursors in the presence of liquid amines, and other methods, such as electrochemical intercalation, intercalant or ion exchange, and direct solvothermal growths from anhydrous amine-based media, are also being developed. Large organic guests, while entering a layered structure on intercalation, push off the inorganic slabs and modify the geometry of their internal building blocks (edge-sharing iron chalcogenide tetrahedrons) through chemical pressure. The chemical nature and orientation of organic molecules between the inorganic layers play an important role in structural modification and may serve as a tool for the alteration of the superconducting properties. A variety of donor species well-matched with the selected alkali metals enables the adjustment of electron doping in a host structure offering a broad range of new materials with tunable electric and magnetic properties. In this review, the main aspects of intercalation chemistry are discussed, involving the influence of the chemical and electrochemical nature of intercalating species on the crystal structure and critical issues related to the superconducting properties of the hybrid inorganic-organic phases. Mutual relations between the host and organic guests lead to a specific ordering of molecular species between the host layers, and their effect on the electronic structure of the host will be also argued. A brief description of a critical assessment of the association of the most effective chemical and electrochemical methods, which lead to the preparation of nanosized/microsized powders and single crystals of molecularly intercalated phases, with the ease of preparation of phase pure materials, crystal sizes, and the morphology of final products is given together with a discussion of the stability of the intercalated materials connected with the volatility of organic solvents and a possible degradation of host materials.


Instrumental indices for upper limb function assessment in stroke patients: a validation study.
Robotic exoskeletons are increasingly being used in objective and quantitative assessment of upper limb (UL) movements. A set of instrumental indices computed during robot-assisted reaching tasks with the Armeo®Spring has been proven to assess UL functionality. The aim of this study was to test the construct validity of this indices-based UL assessment when used with patients who have had a stroke. Forty-four 45- to 79-year-old stroke patients with a Wolf Motor Function Test ability score (WMFT-FAS) ranging from 10 to 75 and a Motricity Index (MI) ranging from 14 to 33 at shoulder and elbow were enrolled, thus covering a wide range of impairments. Residual UL function was assessed by both the WMFT-FAS and the WMFT-TIME, as well as by a set of 9 numerical indices assessing movement accuracy, velocity and smoothness computed from a 3D endpoint trajectory obtained during the "Vertical Capture" task of the Armeo®Spring device. To explore which variables better represented motor control deficits, the Mann-Whitney U Test was used to compare patients' indices to those obtained from 25 healthy individuals. To explore the inner relationships between indices and construct validity in assessing accuracy, velocity and smoothness, a factor analysis was carried out. To verify the indices concurrent validity, they were compared to both WMFT-FAS and WMFT-TIME by the Spearman's correlation coefficient. Seven indices of stroke subjects were significantly different from those of healthy controls, with effect sizes in the range 0.35-0.74. Factor analysis confirmed that specific subsets of indices belonged to the domains of accuracy, velocity and smoothness (discriminant validity). One accuracy index, both velocity indices and two smoothness indices were significantly correlated with WMFT-FAS and WMFT-TIME (|rho| = 0.31-0.50) (concurrent validity). One index for each of the assessed movement domains was proven to have construct validity (discriminant and concurrent) and was selected. Moreover, the indices were able to detect differences in accuracy, velocity and/or smoothness in patients with the same WMFT level. The proposed index-based UL assessment can be used to integrate and support clinical evaluation of UL function in stroke patients.


Pd(II)-Catalyzed Intramolecular Acetoxylative (3 + 2) Annulation of Propargylic Alcohol and Alkene: Polycyclic Oxa-heterocycle Synthesis and Mechanistic Insight.
A Pd(II)-catalyzed intramolecular and highly selective acetxoylative (3 + 2) annulation of propargylic alcohol and alkene is reported. Mechanistically, a hydroxy-guided regioselective alkyne acetoxypalladation is followed by 6-exo-trig alkene insertion to form an alkyl-Pd(II) intermediate. After oxidation, the resulting cyclometalated alkoxy-Pd(IV)-alkyl undergoes direct reductive elimination to afford a polycyclic oxa-heterocycle. When an additional coordinating site or ligand accessible by palladium is present, an SN2-type C-C reductive elimination of alkyl-Pd(IV) instead occurs along with hydroxy acetylation, affording 3-bicyclo[4.1.0]heptan-5-one products.


Attitudes, Behaviors, and Barriers among Adolescents Living with Obesity, Caregivers, and Healthcare Professionals in Spain: ACTION Teens Survey Study.
Although the prevalence of pediatric obesity is rising, understanding of the perceptions, attitudes, behaviors, and barriers to effective obesity care among Spanish adolescents living with obesity (ALwO), their caregivers, and healthcare professionals (HCPs) is lacking. In 2021, the cross-sectional ACTION Teens survey study was conducted in 10 countries; results from the Spanish cohort are presented herein. The survey was completed by 648 ALwO, 644 caregivers, and 251 HCPs in Spain. A total of 25% of ALwO and 43% of caregivers thought that their/their child's weight was normal, and more caregivers than ALwO perceived the ALwO's health to be at least good (95% vs. 59%, respectively). Only 53% of ALwO and 9% of caregivers reported receiving an obesity diagnosis, despite HCPs reporting they provide diagnoses to 87% of ALwO/caregivers. Although 65% of HCPs felt that ALwO may not be comfortable discussing weight, only 26% of ALwO who had discussed weight with an HCP (n = 488) reported not feeling comfortable. Inability to control hunger was a key barrier to ALwO losing weight identified by ALwO/caregivers, but not HCPs. Improved communication between the three groups, a better understanding of barriers to weight loss, and improved health education on obesity are needed in order to enhance obesity care in Spain.


12 Components of a Strong Vision Health System of Care: Part 2-Vision Screening Tools and Procedures and Vision Health for Children With Special Health Care Needs.
Successful vision screening efforts require the implementation of 12 key components of a strong vision health system of care. The National Center for Children's Vision and Eye Health (NCCVEH) at Prevent Blindness partnered with the National Association of School Nurses (NASN) to provide guidance around these 12 components via a Vision and Eye Health webpage on the NASN website ( https://www.nasn.org/nasn-resources/practice-topics/vision-health ). This online resource is organized according to the 12 Components of a Strong Vison Health System of Care to support school nurses accountable for screening the vision of preschool and K-12 students. This NCCVEH/NASN webpage addresses key activities that support a child's vision health-beginning with parent/caregiver education and ending with an annual evaluation of the school's vision health system. Each of these 12 components will be described in NASN School Nurse. The May 2019 installment provided information about the 12 components approach as a whole and details on Family Education and a Comprehensive Communication/Approval Process. This installment describes Components 3 and 4: Vision Screening Tools and Procedures and Vision Health for Children with Special Health Care Needs.


A study of the existing problems of estimating the information transfer rate in online brain-computer interfaces.
Today, the brain-computer interface (BCI) community lacks a standard method to evaluate an online BCI's performance. Even the most commonly used metric, the information transfer rate (ITR), is often reported differently, even incorrectly, in many papers, which is not conducive to BCI research. This paper aims to point out many of the existing problems and give some suggestions and methods to overcome these problems. First, the preconditions inherent in ITR calculation based on Wolpaw's definition are summarized and several incorrect ITR calculations, which go against the preconditions, are indicated. Then, the issues affecting ITR estimation during the test of online BCI systems are discussed in detail. Finally, a task-oriented online BCI test platform was proposed, which may help BCI evaluations in real-world applications. The guidelines for ITR calculation in online BCIs testing are proposed. The platform executed in the Beijing BCI Competition 2010 shows that it can be used as a common way to compare the online performances (including the ITR) of existing BCI paradigms. The proposed guidelines and task-oriented test platform may reduce the uncertainty and artifacts of online BCI performance evaluation; they provide a relatively objective way to compare different BCI's performances in real-world BCI applications, which is a forward step toward developing standards for BCI performance evaluation.


Predictive validity of the GOSLON Yardstick index in patients with unilateral cleft lip and palate: A systematic review.
Among the various indices developed for measuring the results of treatment in patients born with unilateral cleft lip and palate (UCLP), the GOSLON Yardstick index is the most widely used to assess the efficacy of treatment and treatment outcomes, which in UCLP cases are closely linked to jaw growth. The aim of this study was to conduct a systematic review to validate the predictability of growth using the GOSLON Yardstick in patients born with UCLP. A systematic literature review was conducted in four Internet databases: Medline, Cochrane Library, Scopus and Embase, complemented by a manual search and a further search in the databases of the leading journals that focus on this topic. An electronic search was also conducted among grey literature. The search identified a total of 131 articles. Duplicated articles were excluded and after reading titles and abstracts, any articles not related to the research objective were excluded, leaving a total of 21 texts. After reading the complete text, only three articles fulfilled the inclusion criteria. The results showed a predictive validity of between 42.2% and 64.7%, which points to a lack of evidence in the literature for the predictive validity of the GOSLON Yardstick index used in children born with UCLP.


Cocaine--stimulus generalization to MDA optical isomers: a reevaluation.
It has already been demonstrated that the psychoactive agent 1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDA) produces effects that are both hallucinogen-like and amphetamine or stimulant-like in animals. Hallucinogenic activity is associated primarily with the R(-)-isomer of MDA whereas stimulant activity is primarily associated with the S(+)-isomer. Because a previous report indicates that S(+)MDA fails to substitute for cocaine in rats trained to discriminate cocaine from vehicle, and because these findings are inconsistent with the purported stimulant nature of S(+)MDA, we reinvestigated the effect of both MDA isomers in rats. In this investigation, S(+)MDA doses of 1.25 and 1.5 mg/kg were found to produce > 80% cocaine-appropriate responding in rats trained to discriminate 8 mg/kg of cocaine from saline. However, consistent with a previous report, R(-)MDA resulted only in partial generalization. These new results support the hypothesis that the optical isomers of MDA produce distinguishable stimulus effects in rats and that S(+)MDA is the more stimulant isomer of MDA.


Research update: neurogenesis in adult brain and neuropsychiatric disorders.
Until recently neurogenesis in mammals was considered to occur only during the embryonic and early post-natal periods and to have no significant role in the adult nervous system. However, it is now accepted that neurogenesis occurs in two brain regions in adult mammals, namely, the hippocampus and olfactory bulb. In both regions new neurons arise from a resident population of neural progenitor cells that are maintained throughout adult life. Hippocampal neurogenesis is required for some types of hippocampal-dependent learning. Many factors enhance hippocampal neurogenesis including hormones, growth factors, drugs, neurotransmitters, and physical exercise as well as learning a hippocampal-dependent task. Other factors suppress hippocampal neurogenesis; these include aging, stress, glucocorticoids and stimuli that activate the pituitary/adrenal axis. Recently much attention has become focused on the relevance of hippocampal neurogenesis to the pathophysiology and treatment of mood disorders. Indeed all major pharmacological and non-pharmacological treatments for depression enhance hippocampal neurogenesis and suppressing hippocampal neurogenesis in mice blocks behavioral responses in some antidepressant-sensitive tests. Altered hippocampal neurogenesis may also play a pathophysiological role in neurodegenerative disorders such as Alzheimer's disease. How much neurogenesis occurs normally in other brain regions is unclear. Neural progenitors are found throughout the neuraxis including both neurogenic and non-neurogenic regions. When cultured in vitro or isolated and transplanted back into neurogenic brain regions, these cells can differentiate into neurons although in their in situ location they seem to behave as lineage-restricted glial progenitors. The environmental cues that limit the potential of progenitor cells in non-neurogenic brain regions are unknown. However, an emerging view is that astrocytes, a subset of which also functions as neural progenitor cells, are critical in regulating the local environment. After transplantation into adult brain, neural stem cells are capable of surviving and differentiating into both neurons and glial cells, offering hope that stem cell therapy may be utilized to treat a variety of neurological and perhaps psychiatric disorders. The widespread existence of endogenous neural progenitors even in non-neurogenic brain regions also offers hope that the potential of these cells may be harnessed to repair cellular injuries caused by injuries such as stroke, trauma or neurodegenerative diseases. While obstacles remain to both approaches, stem-cell-based therapies remain an area of intense research interest.


Growth hormone treatment induces a dose-dependent catch-up growth in short children born small for gestational age: a summary of four clinical trials.
In the present study, data from 230 short children born small for gestational age, who were participating in four clinical trials, were pooled and analysed. At the start of GH treatment, median age and height SDS were 5.3 years and -3.2 SDS, respectively. A dose-dependent increase in height SDS was observed following 2 years of GH treatment: 1.1, 1.7 and 2.5 SDS for the three GH treatment groups (0.1, 0.2 and 0.3 IU/kg/day, respectively), compared with an increase of 0.14 SDS in the control group. In a multiple regression analysis, four variables were found to correlate independently with the gain in height SDS following 2 years of GH treatment. These are given below in order of importance: gain in height SDS = 7.7 x dose of GH (IU/kg/day) -0.11 x age (years) -0.08 x parental-adjusted height SDS + 0.05 x birth length SDS (SD = 0.5; r2 = 0.64). At the end of the 2-year study period, a total of 48%, 66% and 90% of patients in the groups given GH at 0.1, 0.2 and 0.3 IU/kg/day, respectively, had a parental-adjusted height greater than -1.0 SDS.


Genomic stability of self-complementary adeno-associated virus 2 during early stages of transduction in mouse muscle in vivo.
Studies have demonstrated that packaging of recombinant adeno-associated virus 2 (rAAV) as self-complementary duplex strand (sc) results in early transgene expression, possibly eliminating rate-limiting second-strand synthesis. In the present study, we evaluated the molecular organization, stability of the sc AAV genome, and transgene expression in the quadriceps muscle of C57BL/6J mice in vivo as compared with single-stranded (ss) AAV. Studies were carried out with rAAV encoding green fluorescent protein (GFP) or human carcinoembryonic antigen (CEA) either as single-stranded or self-complementary duplex strand structures, encapsidated in AAV-2 capsids. Mice were injected with 10(11) particles of the respective viruses and the vector-injected muscles were harvested 1 week, 2 weeks, 3 weeks, or 2 months later. Tissues were processed for total DNA isolation for the analyses of vector genomic configuration and copy number, and for immunostaining of transgene expression. ELISA was done on serum samples to quantitate CEA-specific humoral immune response as a correlate of transgene expression. Results of Southern blot and PCR analyses indicated more disintegration of the monomeric ss AAV DNA in vivo compared with linear sc AAV DNA. The results also indicated efficient conversion of the self-complementary duplex-stranded vector genome to dimer during early time points. As expected, transgene expression was detected at early time points with self-complementary duplex-stranded vector and persisted stably. However, the advantage of higher transgene expression from sc AAV was balanced over time by the single-stranded vector. These data demonstrate that sc AAV provides better stability for transgene structure during the initial stages of transduction and may have better utility in AAV gene therapy in situations, which mandate early transgene expression.


Cyclodehydration of 1,4-butanediol over Zr-Al Catalysts: Effect of Reaction Medium.
The conversion of 1,4-butanediol (BDO) to tetrahydrofuran (THF) in aqueous phase is desirable because BDO production technology is shifting to bio-based aqueous fermentation routes. In this study, liquid-phase cyclodehydration of BDO to THF was studied in two reaction media (pure BDO and aqueous BDO feeds) at 200-240 °C using ZrO2-Al2O3 (ZA) mixed oxides, which were made with a co-precipitation method and were characterized with XRD, BET, SEM/EDX, pyridine and n-butylamine adsorptions. The maximum acidity and the largest surface area occurred at Zr/Al atomic ratios of 1/1 (ZA11) and 1/3 (ZA13), respectively. The reaction exhibited pseudo-first-order; aqueous BDO feed had much greater rate constant than pure BDO feed, ascribed to the acidic properties of adsorbed water molecules (coordinated to surface metal cations) for the former case. For pure BDO feed, linear relation was observed between rate constant and catalyst acidity, and ZA11 reached a THF yield of 90.1% at 240 °C. With aqueous BDO feed, rate constant increased linearly with increasing surface area and ZA13 reached a THF yield of 97.1% at 220 °C. The change of optimum catalyst composition with reaction medium suggests that active sites for catalyzing BDO cyclodehydration changed with the reaction environment.


Influence of etofibrate on LDL-subtype distribution in patients with diabetic dyslipoproteinemia.
Low density lipoprotein (LDL-) particles can be subfractionated in large-buoyant (lb), intermediate-dense (id) and small-dense (sd) LDL-subtypes. Fibrates improve the LDL-subtype profile by reducing proatherogenic sd-LDL which are prominent in diabetic dyslipoproteinemia. We evaluated the effect of etofibrate on the LDL-subtype distribution in patients with type 2 diabetes mellitus (n = 13, 55 +/- 18 years, BMI 27.9 +/- 5.5 kg/m2, HbA1c 10.1 +/- 3.9 %) and diabetic dyslipoproteinemia (triglycerides 343 +/- 253 mg/dl, HDL-cholesterol 36 +/- 7 mg/dl, LDL-cholesterol 110 +/- 37 mg/dl). Plasma lipids (enzymatic methods) and LDL-subtypes (7 LDL-subfractions, density gradient ultracentrifugation) were measured before and during etofibrate therapy (500 mg/d, 7 - 16 weeks). Etofibrate significantly (p < 0.05, Wilcoxon-test) reduced triglycerides (- 31 +/- 60 %) and increased HDL-cholesterol (+ 24 +/- 22 %), whereas total cholesterol and LDL-cholesterol did not change. Cholesterol concentration decreased in sd-LDL by 12 % (p < 0.05), while it increased in id- and lb-LDL (+ 26 %,+ 39 %, respectively). Thus, the LDL-subtype profile showed a relative increase of the fraction of lb- (+ 13 +/- 32 %, n.s.) and id-LDL (+ 23 +/- 33 %, p < 0.05) and a relative decrease of the fraction of sd-LDL (- 19 +/- 18 %, p < 0.05). We conclude that etofibrate not only decreases triglycerides and increases HDL-cholesterol but also improves the LDL-subtype profile and thus may reduce the cardiovascular risk in patients with an abundance of sd-LDL such as diabetic patients.


Cerebrospinal fluid concentrations of neurotensin and corticotropin-releasing factor in pediatric patients.
Cerebrospinal fluid (CSF) concentrations of neurotensin (NT) and corticotropin-releasing hormone (CRF)-like immunoreactive materials (LIM) were measured in 22 infants and children 6 days to 15 years of age. For both neuropeptides there was a marked age-related exponential decline in CSF concentrations. The most prominent decrease in CSF neuropeptide concentrations was seen during the first 24 months of postnatal life. From 1 year and on there was no or only minimal age-associated alteration in CSF neuropeptide concentrations. In this group of children (1-15 years) mean CSF concentrations of NT-LIM and CRF-LIM were 36.8 +/- 4.32 and 65.9 +/- 4.63 pg/ml, respectively. As CSF neuropeptide concentrations are apparently independent of circulating serum concentrations, they may reflect functional activity of neuropeptide-containing neurons and therefore may be of value in the assessment of the role of peptides in the human central nervous system function and behavior.


Comparative proteogenomics profiling of non-small and small lung carcinoma cell lines using mass spectrometry.
Evidences indicated that non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) might originate from the same cell type, which however ended up to be two different subtypes of lung carcinoma, requiring different therapeutic regimens. We aimed to identify the differences between these two subtypes of lung cancer by using integrated proteome and genome approaches. Two representative cell lines for each lung cancer subtype were comparatively analysed by quantitative proteomics, and their corresponding transcriptomics data were obtained from the Gene Expression Omnibus database. The integrated analyses of proteogenomic data were performed to determine key differentially expressed proteins that were positively correlated between proteomic and transcriptomic data. The proteomics analysis revealed 147 differentially expressed proteins between SCLC and NSCLC from a total of 3,970 identified proteins. Combined with available transcriptomics data, we further confirmed 14 differentially expressed proteins including six known and eight new lung cancer related proteins that were positively correlated with their transcriptomics data. These proteins are mainly involved in cell migration, proliferation, and invasion. The proteogenomic data on both NSCLC and SCLC cell lines presented in this manuscript is complementary to existing genomic and proteomic data related to lung cancers and will be crucial for a systems biology-level understanding of the molecular mechanism of lung cancers. The raw mass spectrometry data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD015270.


Measuring Ion Oscillations at the Quantum Level with Fluorescence Light.
We demonstrate an optical method for detecting the mechanical oscillations of an atom with single-phonon sensitivity. The measurement signal results from the interference between the light scattered by a trapped atomic ion and that of its mirror image. We detect the oscillations of the atom in the Doppler cooling limit and reconstruct average trajectories in phase space. We demonstrate single-phonon sensitivity near the ground state of motion after electronically induced transparency cooling. These results could be applied for motion detection of other light scatterers of fundamental interest, such as trapped nanoparticles.


An Ultrastrong and Highly Stretchable Polyurethane Elastomer Enabled by a Zipper-Like Ring-Sliding Effect.
Elastomers with excellent mechanical properties are in substantial demand for various applications, but there is always a tradeoff between their mechanical strength and stretchability. For example, partially replacing strong covalent crosslinking by weak sacrificial bonds can enhance the stretchability but also usually decreases the mechanical strength. To surmount this inherent tradeoff, a supramolecular strategy of introducing a zipper-like sliding-ring mechanism in a hydrogen-bond-crosslinked polyurethane network is proposed. A very small amount (0.5 mol%) of an external additive (pseudo[2]rotaxane crosslinker) can dramatically increase both the mechanical strength and elongation of this polyurethane network by nearly one order of magnitude. Based on the investigation of the relationship between molecular structure and mechanical properties, this enhancement is attributable to a unique molecular-level zipper-like ring-sliding motion, which efficiently dissipates mechanical work in the solvent-free network. This research not only provides a distinct and general strategy for the construction of high-performance elastomers but also paves the way for the practical application of artificial molecular machines toward solvent-free polyurethane networks.


Prediction of renal transporter mediated drug-drug interactions for pemetrexed using physiologically based pharmacokinetic modeling.
Pemetrexed, an anionic anticancer drug with a narrow therapeutic index, is eliminated mainly by active renal tubular secretion. The in vitro to in vivo extrapolation approach used in this work was developed to predict possible drug-drug interactions (DDIs) that may occur after coadministration of pemetrexed and nonsteroidal anti-inflammatory drugs (NSAIDs), and it included in vitro assays, risk assessment models, and physiologically based pharmacokinetic (PBPK) models. The pemetrexed transport and its inhibition parameters by several NSAIDs were quantified using HEK-PEAK cells expressing organic anion transporter (OAT) 3 or OAT4. The NSAIDs were ranked according to their DDI index, calculated as the ratio of their maximum unbound concentration in plasma over the concentration inhibiting 50% (IC50) of active pemetrexed transport. A PBPK model for ibuprofen, the NSAID with the highest DDI index, was built incorporating active renal secretion in Simcyp Simulator. The bottom-up model for pemetrexed underpredicted the clearance by 2-fold. The model we built using a scaling factor of 5.3 for the maximal uptake rate (Vmax) of OAT3, which estimated using plasma concentration profiles from patients given a 10-minute infusion of 500 mg/m(2) of pemetrexed supplemented with folic acid and vitamin B12, recovered the clinical data adequately. The observed/predicted increases in Cmax and the area under the plasma-concentration time curve (AUC0-inf) of pemetrexed when ibuprofen was coadministered were 1.1 and 1.0, respectively. The coadministration of all other NSAIDs was predicted to have no significant impact on the AUC0-inf based on their DDI indexes. The PBPK model reasonably reproduced pemetrexed concentration time profiles in cancer patients and its interaction with ibuprofen.


Indomethacin inhibits renal functional adaptation to nephron loss.
Immediately after unilateral nephrectomy, the glomerular filtration rate (GFR) and urinary excretion rate increase in the remaining transplanted rat kidney. In a previous study, we found that GFR in a transplanted kidney was reduced through an activation of the tubuloglomerular feedback control. Excision of the rat's own remnant kidney then reduced feedback sensitivity and thereby allowed GFR to rise. The present study aimed at investigating whether prostaglandins are involved in this functional adaptation. Clearance and micropuncture experiments were performed before and after administration of indomethacin and after subsequent unilateral nephrectomy. GFR and the urinary excretion rate of electrolytes and water were measured. From proximal tubular stop-flow pressure (PSF) measurements the feedback characteristics were determined as the maximal stop-flow pressure response (delta PSF) to an increase in distal flow and the turning point (TP), i.e. the end proximal flow rate that caused 50% reduction of delta PSF. The results showed that following nephrectomy the tubuloglomerular feedback sensitivity was decreased, with an increased TP and reduced delta PSF. Pretreatment with indomethacin (2 mg/kg BW) prevented not only the change in feedback sensitivity at nephrectomy but also the rise in GFR. These results suggest that the prostaglandins play a possible role as one link in the chain of adaptive events occurring immediately after nephron loss.


Confounding factors of ultrafiltration and protein analysis in extracellular vesicle research.
Identification and validation of extracellular vesicle (EV)-associated biomarkers requires robust isolation and characterization protocols. We assessed the impact of some commonly implemented pre-analytical, analytical and post-analytical variables in EV research. Centrifugal filters with different membrane types and pore sizes are used to reduce large volume biofluids prior to EV isolation or to concentrate EVs. We compared five commonly reported filters for their efficiency when using plasma, urine and EV-spiked PBS. Regenerated cellulose membranes with pore size of 10 kDa recovered EVs the most efficient. Less than 40% recovery was achieved with other filters. Next, we analyzed the effect of the type of protein assays to measure EV protein in colorimetric and fluorometric kits. The fluorometric assay Qubit measured low concentration EV and BSA samples the most accurately with the lowest variation among technical and biological replicates. Lastly, we quantified Optiprep remnants in EV samples from density gradient ultracentrifugation and demonstrate that size-exclusion chromatography efficiently removes Optiprep from EVs. In conclusion, choice of centrifugal filters and protein assays confound EV analysis and should be carefully considered to increase efficiency towards biomarker discovery. SEC-based removal of Optiprep remnants from EVs can be considered for downstream applications.


Low back pain in college athletes. A prospective study correlating lower extremity overuse or acquired ligamentous laxity with low back pain.
A prospective evaluation of the incidence of low back pain in college athletes was undertaken. To evaluate prospectively leg length discrepancy, hip flexor tightness, and lower extremity acquired laxity or overuse as predictive factors for low back pain in college athletes. A pilot study found an association between low back pain and the factors to be studied. Several allusions to the kinetic chain theory appear in the literature, but little prospective research has been done in examining the effects of lower extremity involvement on the back. Two-hundred fifty-seven college athletes representing nine varsity sports were screened during a preseason sports physical examination. Measures of flexibility, ligamentous stability, leg length discrepancy, and overuse syndromes were recorded. Athletes were observed throughout the ensuing year for low back pain requiring treatment by the athletic trainer. Those athletes with low back pain as the result of direct trauma to the region were excluded from the data. Twenty-four athletes (9.3%) received treatment for low back pain. Thirteen of 87 women (15%) compared with 11 of 170 men (6%) required treatment for low back pain (P = 0.048). Of 57 athletes with lower extremity acquired laxity or overuse, low back pain developed in 14 (P < 0.001). Athletes with lower extremity acquired ligamentous laxity or overuse may be at risk for the development of noncontact low back pain during athletic competition. Female athletes with lower extremity involvement appeared to have a higher incidence of low back pain treatment compared with their male counterparts. Inflexibility of the lower extremities or leg length discrepancy were not associated with future low back pain treatment.


Efficacy of intranasal vaccination of field buffaloes against haemorrhagic septicaemia with a live gdhA derivative Pasteurella multocida B:2.
The efficacy of an intranasal haemorrhagic septicaemia vaccine containing live gdhA derivative Pasteurella multocida B:2 was tested in buffaloes in Sabah. Sixty buffaloes, kept grazing in the field with minimal human intervention were devided into three groups of 20 buffaloes per group. Buffaloes of group 1 were exposed intranasal to 5 ml vaccine containing 10(6) CFU/ml of live gdhA derivative P multocida B:2. Buffaloes of group 2 were not exposed to the vaccine but exposed to PBS and were allowed to commingle and graze in the same field as the buffaloes of group 1 while buffaloes of group 3 were similarly exposed to PBS and were grazing separately. Booster was on group 1, two weeks later. Twelve months after the first vaccination, three buffaloes from each group were brought into the experimental house and challenged subcutaneously with 10(9) CFU/ml of live wild-type P multocida B:2. All challenged buffaloes of groups 1 and 2 survived with only mild, transient signs while all control unvaccinated buffaloes developed severe signs of haemorrhagic septicaemia and were euthanased between 28 hours and 38 hours postchallenge with signs and lesions typical of haemorrhagic septicaemia. These data showed that the gdhA mutant strain, given intranasally as two doses two weeks apart, successfully induced systemic immunity in exposed buffaloes and also led to spread of vaccine strain to the in-contact animals, where it acted as an effective live vaccine to protect both exposed buffaloes and in-contact buffaloes against challenge with the virulent parent strain.


Development of the Physical activity and Your Nutrition for Cancer (PYNC) smartphone app for preventing breast cancer in women.
In the U.S., breast cancer accounts for more cancer deaths in women than any site other than lung cancer. Based upon attributable risks, about 30-35% of breast cancers could potentially be prevented by addressing obesity, physical inactivity, increased alcohol consumption, and carcinogenic exposures such as hormone replacement therapy (HRT). We need methods of reducing women's risks of this disease that are attractive and easy to use, widely accessible to diverse women, and able to be easily amended to account for new research. The overall objective of this 12-month project is to develop and test a smartphone app to provide women with information about how they can reduce their risk of breast cancer through healthy behaviors such as physical activity, weight management, restricting caloric intake, consuming a healthy diet and proper nutrition, engaging in regular physical activity, and avoiding carcinogenic exposures such as HRT and alcohol. The specific aims are: (I) to develop a smartphone app for breast cancer prevention using a behavioral framework; (II) to ensure interconnectivity with commercially available products (Fitbit device for monitoring physical activity and the LoseIt! smartphone app for monitoring and tracking diet and nutrition); and (III) to ensure that the mHealth intervention is suitable for women with varying levels of health literacy and eHealth literacy. The app, referred to as Physical activity and Your Nutrition for Cancer (PYNC), is being coded on an iOS platform. Users will be able to access the breast cancer prevention app using their smartphone or tablet. The app's design will ensure interconnectivity with commercially available products for monitoring and tracking physical activity, caloric intake, diet and nutrition. Using the app, it will be feasible for users to connect and sync their Fitbit and LoseIt! accounts so that information collected about physical activity, caloric intake, diet, and nutrition can be conveniently assessed from one portal. The Fitbit device and app provides reminders and allows users to set physical activity goals. Users will be able to access health education information about breast cancer risk-reduction with attractive graphics and visual displays. Future directions will include testing the efficacy of the mHealth intervention in increasing physical activity, improving diet and nutrition, and weight management through a randomized controlled trial, and widespread dissemination and implementation research.


Membranoproliferative glomerulonephritis in a patient with Wilson's disease.
Wilson's disease is an autosomal recessive disorder of hepatobiliary copper metabolism. Glomerular diseases can ensue during the course of Wilson's disease and membranous nephropathy is the eventual pathology in the majority of these cases. Membranoproliferative glomerulonephritis (MPGN) has rarely been reported in patients with Wilson's disease. Further, in this report, we present a patient with Wilson's disease who had developed MPGN during follow-up due to D-penicillamine therapy. This case is presented to draw attention to the rare association of Wilson's disease and MPGN and to discuss the possible underlying causes.


A potential mechanism underlying atypical antipsychotics-induced lipid disturbances.
Previous findings suggested that a four-protein complex, including sterol-regulatory element-binding protein (SREBP), SREBP-cleavage-activating protein (SCAP), insulin-induced gene (INSIG) and progesterone receptor membrane component 1 (PGRMC1), within the endoplasmic reticulum appears to be an important regulator responsible for atypical antipsychotic drug (AAPD)-induced lipid disturbances. In the present study, effects of typical antipsychotic drug and AAPDs as well as treatment outcome of steroid antagonist mifepristone (MIF) on the PGRMC1/INSIG/SCAP/SREBP pathway were investigated in rat liver using real-time quantitative polymerase chain reaction (qPCR) and western blot analysis. In addition, serum triacylglycerol, total cholesterol, free fatty acids and various hormones including progesterone, corticosterone and insulin were measured simultaneously. Following treatment with clozapine or risperidone, both lipogenesis and cholesterogenesis were enhanced via inhibition of PGRMC1/INSIG-2 and activation of SCAP/SREBP expressions. Such metabolic disturbances, however, were not demonstrated in rats treated with aripiprazole (ARI) or haloperidol (HAL). Moreover, the add-on treatment of MIF was effective in reversing the AAPD-induced lipid disturbances by upregulating the expression of PGRMC1/INSIG-2 and subsequent downregulation of SCAP/SREBP. Taken together, our findings suggest that disturbances in lipid metabolism can occur at an early stage of AAPD treatment before the presence of weight gain. Such metabolic defects can be modified by an add-on treatment of steroid antagonist MIF enhancing the PGRMC1 pathway. Thus, it is likely that PGRMC1/INSIG-2 signaling may be a therapeutic target for AAPD-induced weight gain.


The voltage-dependent anion channel in endoplasmic/sarcoplasmic reticulum: characterization, modulation and possible function.
In recent years, it has been recognized that there is a metabolic coupling between the cytosol, ER/SR and mitochondria. In this cross-talk, mitochondrial Ca(2+) homeostasis and ATP production and supply play a major role. The primary transporter of adenine nucleotides, Ca(2+)and other metabolites into and out of mitochondria is the voltage-dependent anion channel (VDAC) located at the outer mitochondrial membrane, at a crucial position in the cell. VDAC has been established as a key player in mitochondrial metabolite and ion signaling and it has also been proposed that VDAC is present in extramitochondrial membranes. Thus, regulation of VDAC, as the main interface between mitochondrial and cellular metabolism, by other molecules is of utmost importance. This article reviews localization and function of VDAC, and focuses on VDAC as a skeletal muscle sarcoplasmic reticulum channel. The regulation of VDAC activity by associated proteins and by inhibitors is also presented. Several aspects of the physiological relevance of VDAC to Ca(2+) homeostasis and mitochondria-mediated apoptosis will be discussed.


Decline in perception of acid regurgitation symptoms from gastroesophageal reflux disease in diabetes mellitus patients.
To determine if a discrepancy exists between subjective symptoms and the grade of endoscopic gastroesophageal reflux disease (GERD) in diabetes mellitus (DM) patients. All 2,884 patients who underwent esophagogastroduodenoscopy completed the modified Gastrointestinal Symptom Rating Scale (GSRS), an interview-based rating scale consisting of 16 items including a question on acid regurgitation. Patients were divided into DM and non-DM groups (1,135 and 1,749 patients, respectively). GERD was diagnosed endoscopically and graded according to the Los Angeles classification. Grade B or more severe GERD was defined as severe endoscopic GERD. The intergroup GSRS score was compared statistically. In severe endoscopic GERD patients, the prevalence of patients with a positive GSRS score in the acid regurgitation question was statistically lower in DM patients than non-DM patients. Of the 60 non-DM patients with severe endoscopic GERD, 40 patients (67%) had a positive GSRS score for acid regurgitation; however, of the 51 DM patients with severe endoscopic GERD, 23 patients (45%) had a positive GSRS score. Multivariate analysis showed that severe endoscopic GERD (OR: 2.01; 95% CI: 1.21-3.33; p = 0.0066), non-DM (OR: 0.74; 95% CI: 0.54-0.94; p = 0.0157), younger age (OR: 0.98; 95% CI: 0.97-0.99; p = 0.0125), and hiatal hernia (OR: 1.46; 95% CI: 1.12-1.90; p = 0.0042) were associated with acid regurgitation symptoms. There is a discrepancy between subjective symptoms and endoscopic GERD grade in DM patients. The ability of DM patients to feel acid regurgitation may be decreased.


[The percutaneous treatment of breast cysts. A proposed new method].
Percutaneous needle aspiration of symptomatic breast cysts has nowadays replaced surgery. The medical literature reports on the accidental breaking of breast cysts during mammography. The authors report their personal experience with the percutaneous treatment of symptomatic breast cysts by cyst wall breaking. Twenty symptomatic breast cysts were treated with US-guided needle aspiration and 6-7 times more air than the aspirated fluid was injected through the same needle left in situ to break the cyst wall. US follow-up scans were performed 3, 6 and 12 months after the percutaneous treatment. The biggest cyst only recurred, while the extant 19 cysts did not. Our treatment exhibited no risks and US and mammographic patterns normalized over time. Our results (95% recovery rate) and the complete absence of any complication prove the effectiveness of this method.


Molecular cloning, functional expression, and mutagenesis of cDNA encoding rye (Secale cereale) seed chitinase-c.
We cloned a complete cDNA encoding rye seed chitinase-c, designated RSC-c, by rapid amplification of cDNA end and PCR procedures. The cDNA of RSC-c consists of 1,018 nucleotides and includes an open reading frame encoding a polypeptide of 266 amino acid residues. A recombinant RSC-c was produced by expression in Escherichia coli Origami(DE3) and purified. rRSC-c had almost the same chitinase activity toward glycolchitin and antifungal activity against Trichoderma sp. as the authentic RSC-c did. RSC-c mutants were subsequently constructed and characterized with respect to their chitinase and antifungal activities. Mutation of Glu67 to Gln completely abolished the chitinase activity and diminished the antifungal activity. Considerable decreases in both activities were observed in the mutations of Trp72 and Ser120 to Ala, and Glu89 to Gln. The roles of these residues in the catalytic event of RSC-c are discussed.


Indolic substances in plasma, cerebrospinal fluid, and frontal cortex of human subjects infused with saline or tryptophan.
Psychiatric patients undergoing the psychosurgical operation of stereotactic subcaudate tractotomy were infused intravenously with either saline or L-tryptophan (15 mg/kg/h). Plasma, lumbar cerebrospinal fluid (CSF), ventricular CSF and a specimen of frontal cortex were collected. The relationships of plasma concentrations of substances claimed to influence brain tryptophan concentration (total tryptophan, free tryptophan, large neutral amino acids) with the concentration of tryptophan in the cortex and CSF were investigated. Tryptophan infusion resulted in plasma tryptophan values comparable to those found after oral doses used in treating depression or insomnia, and about sixfold increases of tryptophan in the cerebral cortex. Increased brain 5-hydroxytryptamine synthesis was indicated by significant rises of CSF 5-hydroxyindoleacetic acid. The concentration of plasma free tryptophan was a better predictor than plasma total tryptophan of cortex tryptophan concentration. As all correlation coefficients of plasma versus brain or plasma versus ventricular CSF tryptophan concentrations were decreased when allowance was made for differences of concentration of large neutral amino acids, the results suggest that the role of these substances within their physiological range as inhibitors of tryptophan transport to the brain may previously have been overemphasised.


Inflammation-Based Scores Increase the Prognostic Value of Circulating Tumor Cells in Primary Breast Cancer.
A correlation between circulating tumor cells (CTCs) and monocytes in metastatic breast cancer (BC), where CTCs and monocyte-to-lymphocyte ratio (MLR) were predictors of overall survival (OS), was recently shown. Herein, we aimed to assess the association between CTCs and the complete blood count (CBC)-derived inflammation-based scores in 284 primary BC patients. CTCs were determined in CD45-depleted peripheral blood mononuclear cells by real time-PCR. This method allowed us to detect a subset of CTCs with an epithelial-to-mesenchymal transition phenotype (CTC EMT), previously associated with inferior outcomes in primary BC. In the present study, CTC EMT positivity (hazard ratio (HR) = 2.4; 95% CI 1.20-4.66, p = 0.013) and elevated neutrophil-to-lymphocyte ratio (NLR) (HR = 2.20; 95% CI 1.07-4.55; p = 0.033) were associated with shorter progression-free survival (PFS) in primary BC patients. Multivariate analysis showed that CTC EMT-positive patients with NLR ≥ 3 had 8.6 times increased risk of disease recurrence (95% CI 2.35-31.48, p = 0.001) compared with CTC EMT-negative patients with NLR < 3. Similarly, disease recurrence was 13.14 times more likely in CTC EMT-positive patients with MLR ≥ 0.34 (95% CI 4.35-39.67, p < 0.001). Given its low methodological and financial demands, the CBC-derived inflammation-based score determination could, after broader validation, significantly improve the prognostication of BC patients.


Spontaneous maturation in Bufo arenarum oocytes: participation of protein kinase C.
Although progesterone is the maturation inducer in amphibians, it has been demonstrated that in Bufo arenarum oocytes resumed meiosis with no need of exogenous hormonal stimulus if derived of their enveloping follicle cells. This phenomenon, called spontaneous maturation, is quite rare in amphibians. In B. arenarum, spontaneous maturation took place only in oocytes obtained during the reproductive period (spring-summer). During this period the oocytes also demonstrated a respiratory activity characteristic of mature oocytes. Interestingly, full-grown B. arenarum oocytes always responded to progesterone regardless of the season in which they were obtained and of their respiratory activity. The disposition of oocytes competent or not competent to mature spontaneously provides a useful system for the study of molecular mechanisms involved in the maturation process. The data presented here indicate that the activation of protein kinase C (PKC) induces germinal vesicle breakdown (GVBD) in denuded oocytes unable to mature spontaneously (winter oocytes) and is involved in the in vitro spontaneous maturation of B. arenarum full-grown oocytes. The inhibition of PKC by 1-(5-isoquinolynyl-sulphonyl-2-methyl-piperazine (H-7) impeded spontaneous maturation in a dose-dependent manner, thus supporting the participation of the PKC pathway during this process. Interestingly phorbol 12-myristate-13-acetate (PMA)-induced GVBD is inhibited by the incubation of the oocytes in dibutyryl cAMP (dbcAMP), indicating that both pathways, PKC and protein kinase A (PKA), are related at a certain point. However, spontaneous GVBD is less sensitive than PMA-induced GVBD to dbcAMP. This fact would support the suggestion that in spontaneous GVBD mechanisms different from activation of PKC are at work.


Morphogenetic characteristics of three Brachiaria brizantha cultivars submitted to nitrogen fertilization.
This study aims to evaluate the morphogenetic characteristics of three cultivars of Brachiaria brizantha subjected to nitrogen fertilization. The design was a randomized block in factorial arrangement 4x3; three cultivars of B. brizantha - Marandu, Piatã, Xaraés and four nitrogen levels - 0, 80, 160 and 240 kg/ha, with three replications. The experimental units consisted of plastic pots filled with 5 dm3 of soil. Thereupon the establishment fertilization, varieties were sowed directly in the pots, leaving, after thinning, five plants per pot. Forty-five days after planting, it was done a standardization cut at 10 cm tall. Nitrogen levels were distributed according to the treatments, divided in three applications. The morphogenetic characteristics were evaluated in three tillers per sampling unit and data were submitted to analysis of variance and regression. For all evaluated characteristics there was no interaction between factors cultivar and nitrogen levels, verifying only the effects of nitrogen on the variables leaf appearance rate and phyllochron. The dose 240 kg/ha of N corresponds to the greater leaf appearance rate. Cultivar Marandu shows the higher leaf blade: pseudostem and ratio of leaf elongation rate and elongation pseudostem, which favors higher forage quality.