Mouth opening limitation caused by coronoid hyperplasia: a report of four cases.
Coronoid process hyperplasia is a rare condition that causes mouth opening limitation, otherwise known as trismus. The elongated coronoid processes impinge on the medial surfaces of the zygomatic arches when opening the mouth, which limits movement of the mandible and leads to trismus. Patients with trismus due to coronoid process hyperplasia do not have any definite symptoms such as temporomandibular joint pain or sounds upon clinical examination, and no significant abnormal signs are observed on panoramic radiographs or magnetic resonance images of the temporomandibular joint. Thus, the diagnosis of trismus is usually very difficult. However, computed tomography can help with the diagnosis, and the condition can be treated by surgery and postoperative physical therapy. This paper describes four cases of patients who visited our clinic for trismus and were subsequently diagnosed with coronoid process hyperplasia. Three were successfully treated with a coronoidectomy and postoperative physical therapy.


DISC1 regulates astrogenesis in the embryonic brain via modulation of RAS/MEK/ERK signaling through RASSF7.
Disrupted in schizophrenia 1 (DISC1) is known as a high susceptibility gene for schizophrenia. Recent studies have indicated that schizophrenia might be caused by glia defects and dysfunction. However, there is no direct evidence of a link between the schizophrenia gene DISC1 and gliogenesis defects. Thus, an investigation into the involvement of DISC1 (a ubiquitously expressed brain protein) in astrogenesis during the late stage of mouse embryonic brain development is warranted. Here, we show that suppression of DISC1 expression represses astrogenesis in vitro and in vivo, and that DISC1 overexpression substantially enhances the process. Furthermore, mouse and human DISC1 overexpression rescued the astrogenesis defects caused by DISC1 knockdown. Mechanistically, DISC1 activates the RAS/MEK/ERK signaling pathway via direct association with RASSF7. Also, the pERK complex undergoes nuclear translocation and influences the expression of genes related to astrogenesis. In summary, our results demonstrate that DISC1 regulates astrogenesis by modulating RAS/MEK/ERK signaling via RASSF7 and provide a framework for understanding how DISC1 dysfunction might lead to neuropsychiatric diseases.


Communicating about alcohol consumption to nonharmful drinkers with Hepatitis C: patient and provider perspectives.
Abstaining from alcohol consumption is generally recommended for patients with Hepatitis C(HCV). However, mixed research findings coupled with a lack of consistent guidelines on alcohol consumption and HCV may influence what healthcare providers tell their HCV patients about drinking. This may be more problematic when advising nonharmful drinkers with HCV, a population for whom consumption would not bea problem in the absence of their HCV diagnosis. This study explores what healthcare providers advise their HCV patients who are drinking alcohol at nonharmful levels about alcohol use and what these patients actually hear. We conducted separate focus groups and interviews about alcohol use and HCV with nonharmful drinkers with HCV (N=50) and healthcare providers (N=14) at a metropolitan teaching hospital. All focus groups and interviews were audio-taped, transcribed, and analyzed using NVivo, a qualitative data management and analysis program. We found similar themes about HCV and alcohol consumption (stop completely, occasional drink is ok, cut down, and provision of mixed/ambiguous messages), reported by both providers and patients.Patient respondents who reported hearing "stop completely"were more likely to have had their last medical visit at the gastroenterology (GI) clinic as opposed to the internal medicine (IM) clinic. Furthermore, IM providers were more likely to give their recommendations in"medical language" than were GI providers. To make the best health-related decisions about their disease, HCV patients need consistent information about alcohol consumption. Departments of Internal Medicine can increase provider knowledge about HCV and alcohol use by providing more education and training on HCV.


Proteasomal Degradation of Enhancer of Zeste Homologue 2 in Cholangiocytes Promotes Biliary Fibrosis.
During biliary disease, cholangiocytes become activated by various pathological stimuli, including transforming growth factor β (TGF-β). The result is an epigenetically regulated transcriptional program leading to a pro-fibrogenic microenvironment, activation of hepatic stellate cells (HSCs), and progression of biliary fibrosis. This study evaluated how TGF-β signaling intersects with epigenetic machinery in cholangiocytes to support fibrogenic gene transcription. We performed RNA sequencing in cholangiocytes with or without TGF-β. Ingenuity pathway analysis identified "HSC Activation" as the highly up-regulated pathway, including overexpression of fibronectin 1 (FN), connective tissue growth factor, and other genes. Bioinformatics identified enhancer of zeste homologue 2 (EZH2) as an epigenetic regulator of the cholangiocyte TGF-β response. EZH2 overexpression suppressed TGF-β-induced FN protein in vitro, suggesting FN as a direct target of EZH2-based repression. Chromatin immunoprecipitation assays identified an FN promoter element in which EZH2-mediated tri-methylation of lysine 27 on histone 3 is diminished by TGF-β. TGF-β also caused a 50% reduction in EZH2 protein levels. Proteasome inhibition rescued EZH2 protein and led to reduced FN production. Immunoprecipitation followed by mass spectrometry identified ubiquitin protein ligase E3 component N-recognin 4 in complex with EZH2, which was validated by western blotting in vitro. Ubiquitin mutation studies suggested K63-based ubiquitin linkage and chain elongation on EZH2 in response to TGF-β. A deletion mutant of EZH2, lacking its N-terminal domain, abrogates both TGF-β-stimulated EZH2 degradation and FN release. In vivo, cholangiocyte-selective knockout of EZH2 exacerbates bile duct ligation-induced fibrosis whereas MDR2-/- mice are protected from fibrosis by the proteasome inhibitor bortezomib. Conclusion: TGF-β regulates proteasomal degradation of EZH2 through N-terminal, K63-linked ubiquitination in cholangiocytes and activates transcription of a fibrogenic gene program that supports biliary fibrosis.


Joint Tensor Feature Analysis For Visual Object Recognition.
Tensor-based object recognition has been widely studied in the past several years. This paper focuses on the issue of joint feature selection from the tensor data and proposes a novel method called joint tensor feature analysis (JTFA) for tensor feature extraction and recognition. In order to obtain a set of jointly sparse projections for tensor feature extraction, we define the modified within-class tensor scatter value and the modified between-class tensor scatter value for regression. The k-mode optimization technique and the L(2,1)-norm jointly sparse regression are combined together to compute the optimal solutions. The convergent analysis, computational complexity analysis and the essence of the proposed method/model are also presented. It is interesting to show that the proposed method is very similar to singular value decomposition on the scatter matrix but with sparsity constraint on the right singular value matrix or eigen-decomposition on the scatter matrix with sparse manner. Experimental results on some tensor datasets indicate that JTFA outperforms some well-known tensor feature extraction and selection algorithms.


A flexible ontology for inference of emergent whole cell function from relationships between subcellular processes.
Whole cell responses arise from coordinated interactions between diverse human gene products functioning within various pathways underlying sub-cellular processes (SCP). Lower level SCPs interact to form higher level SCPs, often in a context specific manner to give rise to whole cell function. We sought to determine if capturing such relationships enables us to describe the emergence of whole cell functions from interacting SCPs. We developed the Molecular Biology of the Cell Ontology based on standard cell biology and biochemistry textbooks and review articles. Currently, our ontology contains 5,384 genes, 753 SCPs and 19,180 expertly curated gene-SCP associations. Our algorithm to populate the SCPs with genes enables extension of the ontology on demand and the adaption of the ontology to the continuously growing cell biological knowledge. Since whole cell responses most often arise from the coordinated activity of multiple SCPs, we developed a dynamic enrichment algorithm that flexibly predicts SCP-SCP relationships beyond the current taxonomy. This algorithm enables us to identify interactions between SCPs as a basis for higher order function in a context dependent manner, allowing us to provide a detailed description of how SCPs together can give rise to whole cell functions. We conclude that this ontology can, from omics data sets, enable the development of detailed SCP networks for predictive modeling of emergent whole cell functions.


Young people and caregivers' perceptions of an intervention program for children who deliberately light fires.
A significant number of children and adolescents engage in deliberate fire setting, beyond the scope of curiosity and experimentation. Interventions developed to respond to the needs of such fire setters generally involve educational and/or psychosocial approaches. Research evaluating the effectiveness of these interventions is dominated by outcome studies which rely on recidivism rates determined by either official records or parent reports. There has however, been no process evaluation studies published. This study presents a process analysis which aimed to identify the strengths and weaknesses of a Fire Awareness and Intervention Program in New Zealand, from the perspectives of program consumers. Qualitative research methods were employed, with data being derived from in-depth interviews with young people and their parents/caregivers. The analysis indicated that (a) the FAIP was generally regarded as a positive experience, (b) practitioners' qualities of empathy and understanding are important for developing rapport with the young people and their parents, (c) education-based intervention tailored to the young person's age and developmental level is important, (d) educational resources need to be updated and used flexibly to respond appropriately to the age and developmental level of the young person, and (e) inter-agency and intra-agency relationships need to be developed and maintained, with formal arrangements for reciprocal referral systems developed in order to respond to the needs of the clients. The resulting implications for service providers, along with future research are discussed.


Inter-observer reliability of the arthroscopic quantification of chondropathy of the knee.
Several scoring systems have been proposed in order to quantify the degree of cartilage damage observed by arthroscopy of the knee in patients with osteoarthritis. To evaluate the inter-observer reliability of five different scoring systems of arthroscopic evaluation for chondropathy in osteoarthritis of the knee and to evaluate the utility of a training session between different observations on these scoring systems. Videotapes of knee arthroscopies on five patients with osteoarthritis demonstrating different levels of severity of cartilage damage of the medial tibiofemoral compartment were analyzed by nine observers prior to (pre-training evaluation) and 2 months after a 6 h training session (post-training evaluation) by the following scoring systems: (1) cartilage deterioration by a 100 mm visual analogue scale (VAS), (2) overall assessment of degeneration in the entire medial compartment (cartilage, meniscus, osteophyte) using a 100 mm VAS, (3) French Society of Arthroscopy (SFA) Scoring System, (4) SFA Grading System, (5) American College of Rheumatology (ACR) Scoring System. At the pre-training evaluation, the SFA grading system produced the highest coefficient of reliability (r = 0.94), the other systems recording levels of < or = 0.80. At the post-training evaluation, the coefficient of reliability was r > 0.80 for four of the five scoring systems, with lack of improvement in the ACR Scoring System. There was an improved and acceptable inter-observer reliability for at least 2 months follow-up in four of five evaluated scoring systems of arthroscopically graded osteoarthritis of the knee following a training session. A scoring system using a 100 mm VAS may produce the best inter-observer reliability. These results show that scoring chondropathy is possible and demonstrate the importance of training in the analysis of articular cartilage breakdown.


Splenic cysts: Analysis of 16 cases.
Splenic cysts are known as rare clinical encounter. Classifying into primary (true) and secondary cysts (pseudocysts), true cysts contain cellular epithelial lining and subdivided into parasitic and non-parasitic cysts. This study aimed to determine the outcome of treatment in patients with splenic cyst. All patients with splenic cyst who had been treated in Department of General Surgery of Ghaem and Omid teaching hospitals over a 24-year period were identified. The medical records of these 16 patients were reviewed. The study patients included 11 females (68.75%) and 5 males (31.25%) with average age of 39.8 years. Fifteen cases had true cyst including 11 parasitic cysts (hydatid) and only one pseudocyst. 37.5% of the splenic cysts had coexistent cysts in liver, pelvis, omentum and paracolic regions. Nine patients underwent total splenectomy and 5 cases partial splenectomy and 2 remaining cases received conservative medical treatment. The size of the cysts varied from 6 to 25 centimeter with average size of 14.3 centimeter. All patients with hydatid cysts received albendazole postoperative medical treatment with albendazole for 6 months. All patients recovered after treatment. Open splenectomy whether total or partial is effective and safe in patients with splenec cysts with or without hydatidosis. The outcome of treatment is good without recurrences.


Comparative modelling of human β tubulin isotypes and implications for drug binding.
The protein tubulin is a target for several anti-mitotic drugs, which affect microtubule dynamics, ultimately leading to cell cycle arrest and apoptosis. Many of these drugs, including the taxanes and Vinca alkaloids, are currently used clinically in the treatment of several types of cancer. Another tubulin binding drug, colchicine, although too toxic to be used as a chemotherapeutic agent, is commonly used for the treatment of gout. The main disadvantage that all of these drugs share is that they bind tubulin indiscriminately, leading to the death of both cancerous and healthy cells. However, the broad cellular distribution of several tubulin isotypes provides a platform upon which to construct novel chemotherapeutic drugs that could differentiate between different cell types, reducing the undesirable side effects associated with current chemotherapeutic treatments. Here, we report an analysis of ten human β tubulin isotypes and discuss differences within each of the previously characterized paclitaxel, colchicine and vinblastine binding sites.


Comparative genomics among Saccharomyces cerevisiae × Saccharomyces kudriavzevii natural hybrid strains isolated from wine and beer reveals different origins.
Interspecific hybrids between S. cerevisiae × S. kudriavzevii have frequently been detected in wine and beer fermentations. Significant physiological differences among parental and hybrid strains under different stress conditions have been evidenced. In this study, we used comparative genome hybridization analysis to evaluate the genome composition of different S. cerevisiae × S. kudriavzevii natural hybrids isolated from wine and beer fermentations to infer their evolutionary origins and to figure out the potential role of common S. kudriavzevii gene fraction present in these hybrids. Comparative genomic hybridization (CGH) and ploidy analyses carried out in this study confirmed the presence of individual and differential chromosomal composition patterns for most S. cerevisiae × S. kudriavzevii hybrids from beer and wine. All hybrids share a common set of depleted S. cerevisiae genes, which also are depleted or absent in the wine strains studied so far, and the presence a common set of S. kudriavzevii genes, which may be associated with their capability to grow at low temperatures. Finally, a maximum parsimony analysis of chromosomal rearrangement events, occurred in the hybrid genomes, indicated the presence of two main groups of wine hybrids and different divergent lineages of brewing strains. Our data suggest that wine and beer S. cerevisiae × S. kudriavzevii hybrids have been originated by different rare-mating events involving a diploid wine S. cerevisiae and a haploid or diploid European S. kudriavzevii strains. Hybrids maintain several S. kudriavzevii genes involved in cold adaptation as well as those related to S. kudriavzevii mitochondrial functions.


Mitochondrial fission proteins regulate programmed cell death in yeast.
The possibility that single-cell organisms undergo programmed cell death has been questioned in part because they lack several key components of the mammalian cell death machinery. However, yeast encode a homolog of human Drp1, a mitochondrial fission protein that was shown previously to promote mammalian cell death and the excessive mitochondrial fragmentation characteristic of apoptotic mammalian cells. In support of a primordial origin of programmed cell death involving mitochondria, we found that the Saccharomyces cerevisiae homolog of human Drp1, Dnm1, promotes mitochondrial fragmentation/degradation and cell death following treatment with several death stimuli. Two Dnm1-interacting factors also regulate yeast cell death. The WD40 repeat protein Mdv1/Net2 promotes cell death, consistent with its role in mitochondrial fission. In contrast to its fission function in healthy cells, Fis1 unexpectedly inhibits Dnm1-mediated mitochondrial fission and cysteine protease-dependent cell death in yeast. Furthermore, the ability of yeast Fis1 to inhibit mitochondrial fission and cell death can be functionally replaced by human Bcl-2 and Bcl-xL. Together, these findings indicate that yeast and mammalian cells have a conserved programmed death pathway regulated by a common molecular component, Drp1/Dnm1, that is inhibited by a Bcl-2-like function.


Poly(ADP-ribose) polymerase activity in mononuclear leukocytes of 13 mammalian species correlates with species-specific life span.
Poly(ADP-ribosyl)ation is a eukaryotic posttranslational modification of proteins that is strongly induced by the presence of DNA strand breaks and plays a role in DNA repair and the recovery of cells from DNA damage. We compared poly(ADP-ribose) polymerase (PARP; EC 184.108.40.206) activities in Percoll gradient-purified, permeabilized mononuclear leukocytes from mammalian species of different maximal life span. Saturating concentrations of a double-stranded octameric oligonucleotide were applied to provide a direct and maximal stimulation of PARP. Our results on 132 individuals from 13 different species yield a strong positive correlation between PARP activity and life span (r = 0.84; P << 0.001), with human cells displaying approximately 5 times the activity of rat cells. Intraspecies comparisons with both rat and human cells from donors of all age groups revealed some decline of PARP activity with advancing age, but it was only weakly correlated. No significant polymer degradation was detectable under our assay conditions, ruling out any interference by poly(ADP-ribose) glycohydrolase activity. By Western blot analysis of mononuclear leukocytes from 11 species, using a crossreactive antiserum directed against the extremely well-conserved NAD-binding domain, no correlation between the amount of PARP protein and the species' life spans was found, suggesting a greater specific enzyme activity in longer-lived species. We propose that a higher poly(ADP-ribosyl)ation capacity in cells from long-lived species might contribute to the efficient maintenance of genome integrity and stability over their longer life span.


Adhesive Bowel Obstruction (ABO) in a Stranded Narrow-Ridged Finless Porpoise (Neophocaena asiaeorientalis sunameri).
In this case report, we present a rare occurrence of a narrow-ridged finless porpoise (Neophocaena asiaeorientalis sunameri), discovered on the coast of Jeju Island, Republic of Korea, that was afflicted with adhesive bowel obstruction (ABO), a life-threatening condition that has scarcely been reported in cetaceans. Diagnosis of ABO was confirmed via radiological and clinical assessments. Post-mortem computed tomography and necropsy revealed ABO between two loops of the jejunum at the L8 level. The mesenteric tissue covering the intestinal lesion was severely thickened with increased tension. Both bowel loops were fixed to the mesentery and acutely angulated, leading to asymmetrical thickening of the cross-sectional bowel walls. The intestinal lumen was stenosed because of pressure from the firm mesenteric band, and no fecal matter was observed in the lumen of the posterior bowel or rectum. Calcified nodules were detected, and histological analysis suggested parasitic or suspected post-parasitic infections. The primary cause of the intestinal lesions is presumed to be a reaction related to parasitic infection. However, further investigations would establish a definitive link between parasitic infections and ABO in this species. This case highlights the importance of studying rare medical conditions in wildlife, providing valuable insights into marine mammal health.


Introduction of a partial shift system for house officers in a teaching hospital.
(1) To introduce a partial shift system to reduce the hours of work of preregistration house surgeons to an average of 64 a week to comply with the New Deal for junior doctors; (2) to test linking the partial shift concept to an existing structure of "on call" firms. Formal assessment after three months of a pilot partial shift system for eight house surgeons on three firms instituted on 1 November 1991, followed by questionnaire and interview evaluation at three and six months of a revised system implemented on 1 February 1992. Department of general surgery at St Bartholomew's Hospital, London. 24 house surgeons attached to three surgical firms. In eight weeks each house surgeon worked one week (five shifts) of night duty, one week of "cover" (afternoon and evening) duty, and six weeks of normal daytime hours. Each weekday a house surgeon from the firm on call worked an extended daytime on call shift until 10 pm. Weekend duties were split between two house surgeons from the firm on call. A computer generated graphical display of the rota was used to facilitate leave planning. Average working hours were reduced to below 64 per week, including prospective cover, without detriment to patient care and educational standards. Within the shift system individual house surgeons could be on call with their own firm by day and at weekends. Opinions were equally divided among junior staff as to their preference for either on call or partial shift systems. The principles of this partial shift system are generally applicable and the model can readily be adopted by district general hospitals.


[Neuropsychiatric manifestations of Saethre-Chotzen syndrome].
Four psychiatric patients with SCS are described. All exhibited essential tremor, minimal cerebral dysfunctions, speech disorders, bradyphrenia, disorders of personality with psychasthenie and suspicious traits, restrictions, increased irritability and depressivity, one case of mutism due to abnormal reaction and one of alcohol hallucinosis. The possibility of cosmetic handicap caused by craniofacial dysplasia should be taken into mind and perhaps surgically corrected. Because the craniofacial dysplasia is mostly moderate and the syndactylies are slight the SCS remains often unrecognized, but apart from psychic maldevelopment it is significant as the result of frequent association with other malformations.


Purification and characterization of polyamine oxidase from Ascaris suum.
The interconversion of polyamines in the parasite nematode Ascaris suum by a novel type of polyamine oxidase was demonstrated. The nematode enzyme was clearly distinguishable from monoamine and diamine oxidases as well as from the mammalian polyamine oxidase, as shown by the use of the specific inhibitors pargyline, aminoguanidine and MDL 72527 respectively. All three inhibitors had no effect on the parasite polyamine oxidase, and the enzyme did not accept diamines such as putrescine, cadaverine or histamine as substrates. The parasite polyamine oxidase selectively oxidizes spermine and spermidine but not N-acetylated polyamines, whereas the mammalian tissue-type polyamine oxidase shows preference for the N-acetylated polyamines. These results suggest a regulatory function of the nematode polyamine oxidase in the degradation and interconversion of polyamines in parasite nematodes. The enzyme was purified to homogeneity by gel filtration, preparative isoelectric focusing and subsequent affinity chromatography on spermine- and berenil-Sepharose 4B. With respect to reaction type, the prosthetic group FAD, the molecular mass (66 kDa) and the contents of thiol and carbonyl groups, the polyamine oxidase from A. suum is similar to the isofunctional enzyme of mammalian tissue.


CXCR4 receptor overexpression in mesenchymal stem cells facilitates treatment of acute lung injury in rats.
Novel therapeutic regimens for tissue renewal incorporate mesenchymal stem cells (MSCs) as they differentiate into a variety of cell types and are a stem cell type that is easy to harvest and to expand in vitro. However, surface chemokine receptors, such as CXCR4, which are involved in the mobilization of MSCs, are expressed only on the surface of a small proportion of MSCs, and the lack of CXCR4 expression may underlie the low efficiency of homing of MSCs toward tissue damage, which results in a poor curative effect. Here, a rat CXCR4 expressing lentiviral vector was constructed and introduced into MSCs freshly prepared from rat bone marrow. The influence of CXCR4 expression on migration, proliferation, differentiation, and paracrine effects of MSCs was examined in vitro. The in vivo properties of CXCR4-MSCs were also investigated in a model of acute lung injury in rats induced by lipopolysaccharide. Expression of CXCR4 in MSCs significantly enhanced the chemotactic and paracrine characteristics of the cells in vitro but did not affect self-renewal or differentiation into alveolar and vascular endothelial cells. In vivo, CXCR4 improved MSC homing and colonization of damaged lung tissue, and furthermore, the transplanted CXCR4-MSCs suppressed the development of acute lung injury in part by modulating levels of inflammatory molecules and the neutrophil count. These results indicated that efficient mobilization of MSCs to sites of tissue injury may be due to CXCR4, and therefore, increased expression of CXCR4 may improve their therapeutic potential in the treatment of diseases where tissue damage develops.


Mixed-Metal MOF-Derived Carbon Sponges for Oil Absorption.
In this work, we propose the implementation of three carbon sponges, generated from the carbonization of melamine-formaldehyde sponges coated with different HKUST-type metal-organic frameworks (MOFs) in different thermal conditions. Nowadays, numerous investigations are focused on the development of new technologies for the rapid separation of water/oil mixtures. Several of these processes use hydrophobic materials of different nature for efficient oil capture. Despite these efforts, the water/oil separation still remains a great challenge. The main oil absorbers that are commercially available tend to be expensive and have complex synthesis; however, they usually have an acceptable cost/benefit ratio. Despite this, the passage of time has brought us new generations of materials, which seek to solve the problems in a more efficient way, as in the case of metal-organic frameworks (MOFs), which stand out for the great ease with which their morphological and surface aspects can be controlled. MOFs are extensively investigated in the fields of adsorption and catalysis; the MOF coated sponges do not meet the selectivity and stability standards to be applied in oil spills in water. However, this completely changes when subjected to the pyrolysis process, giving the material an increase in its surface area, hydrophobic and magnetic properties in addition to making the material suitable for its application. Creation of a low-cost 3D template and the study of morphological properties of MOFs, for the formation of carbon-based materials by a fast, simple and low-cost method, promoting the use of new generations of materials to more effectively solve persistent environments. The employed MOF precursors were trimesic acid (BTC), nickel and cobalt salts. The monometallic HKUST type MOFs were synthesized using a simple method of controlled precipitation, which starts from two precursor solutions. The first one consisted of a ligand solution, dissolving the BTC in deionized water. In the case of mixed-metal MOFs, they were synthesized using the same procedure described for monometallic MOFs, but in this case, a mixture of metal salts with a 1:1 molar ratio was performed. The methodology for the production of the sponges decorated with MOF was carried out in two steps. In the first stage, the sponges were subjected to a wash to remove dust and impurities, being rinsed with acetone in an ultrasonic bath for 30 min. The sponges were subsequently immersed in deionized water and subjected to an ultrasonic bath for 10 min. Finally, the sponges were dried at 60°C for 3 h. The second step was the addition of the HKUST-type MOFs to the sponges was carried out by means of the immersion method, preparing a dispersion of the corresponding MOFs in ethanol. It was revealed that the carbon sponges can selectively absorb oil in the water/oil mixture, possessing magnetic and enhanced hydrophobic and superhydrophobic properties. All the pyrolyzed carbon sponges, obtained at 500 and 700°C, were not the most optimal since they had absorption capacities of around 25 g/g and only supported up to 4 absorption cycles. On the other hand, the carbon sponges, obtained at 300°C, had absorption capacities greater than 40 g/g, in addition to being able to be reused up to 12 times without showing significant changes in their absorption capacity and having acceptable hydrophobic characteristics for the removal of oil dispersed in water. Among the three sponges obtained at 300°C, we highlight the sponges coated with BTC-Co, which have the highest absorption capacity (54 g/g) among all fabricated sponges. The sponges obtained in the present work are a promising alternative to the materials that are traditionally used since they have great advantages such as their simple production method, low-cost starting materials and good absorption capacities. This work sheds light on the production of carbon materials from 3D templates decorated with MOFs, through a one-step carbonization process and we demonstrate that these materials have characteristics that make them applicable in the removal of oil dispersed in water, giving us a practical, economic and friendly alternative to the environment.


Microbiological standards for water and their relationship to health risk.
Maintenance of the microbiological quality of water has been used as an important means of preventing waterborne disease throughout the twentieth century. The commonest microbiological tests done on water are for coliforms and Escherichia coli (or faecal coliform). This paper reviews the legislative and other guidance for microbial standards in drinking and bathing waters and considers evidence for the relationship between the microbiological quality of water and risk to human health. In the past measures of the microbiological quality of water correlated well with risks of acquiring gastrointestinal disease. More recent work suggests that gastrointestinal disease is more strongly associated with the presence of enterococci than of E. coli. New diseases such as cryptosporidiosis have been shown to cause outbreaks of waterborne disease when levels of conventional microbiological parameters are satisfactory. In response to this, and because of failure of prosecution in one outbreak, the United Kingdom (UK) Government has introduced new legislation that requires water providers to perform a risk assessment on their water treatment facilities and to implement continuous monitoring for cryptosporidium. A new European directive on drinking water has been introduced and legislation on cryptosporidium in drinking water has been proposed in the UK.


Need and potential of antimicrobial stewardship in community hospitals.
Preventing, reducing, and controlling the emergence of antimicrobial-resistant organisms is a major public health challenge requiring the participation of the entire medical community and public health agencies. Antimicrobial stewardship programs (ASPs) have the potential to integrate the many and sometimes disparate individuals and organizations that rely on antimicrobial agents in an effort to better control antimicrobial prescribing, possibly minimizing the emergence of resistant organisms. Developing and implementing ASPs can be a major challenge for community-based hospitals. In addition to specific and localized patterns of resistance-a consideration for every hospital-community hospitals must develop strategies that appropriately conform to their size, staffing, personnel, and infrastructure. This article reviews the ASP strategies and resources currently available to community hospitals for improving if, when, and how antimicrobial agents are prescribed and delivered.


High-resolution multiplanar CT images of the larynx.
The standard technique for computed tomographic evaluation of the larynx utilizes 5-mm contiguous transaxial sections. Multiplanar images reformatted with these sections have not been of clinical use. We have evaluated the practicality of utilizing coronal and sagittal reformatted images produced from contiguous 1.5-mm transaxial sections. The technique of rapid sequential scanning with automatic table incrementation allows 36 contiguous thin section scans to be acquired in less than 9 minutes. Phantom studies showed a marked improvement in spatial resolution with thin section reconstructions. Preliminary clinical evaluation shows visualization of smaller structures with improved edge definition of both low- and high-contrast structures.


The biopsychosocial adjustment of disabled elderly: a 1-year follow-up.
The objectives of this study were to identify and compare changes in the physical, social, and structural functions and in the family relationships of elderly patients upon hospitalization in a geriatric rehabilitation unit, and 1 year after discharge to the community (in the Negev region of Israel). The study was conducted on 88 elderly people with a mean age of 74 years. The Assessment of Dependency for Long-Term Care Benefits test was used twice as the study instrument for measuring the given objectives, once during the first week following admission to the unit and once 1 year later. At the end of the year there was improvement in most activities of daily living (ADL), a decrease in social roles, an increase in the number of illnesses, greater restrictions in diet, and an increase in use of social services. Changes were observed in the structure of the family social networks, the source of the primary caregiver, and living arrangements. Changes were not observed in the perceived family relationships. In both time periods, married elderly people evaluated family relations as better than did unmarried people. However, unmarried subjects demonstrated greater improvement in physical and social functions. Also, time had a significant effect on social function. Elderly people who were ill for less than 2 months prior to admission demonstrated greater social improvement than those whose illness lasted longer.


Radiographic Outcome Differences in Distraction-Based Growing Rod Constructs Using Tandem Versus Wedding Band Connectors.
Comparative cohort study. To compare coronal deformity control, lengthening efficacy, and sagittal alignment between distraction-based growing rod constructs utilizing tandem versus wedding band connectors. Different construct designs exist for growing rod treatment of early-onset scoliosis. All use a version of a rod connector, with the two main types being tandem and wedding band. Little data exist to quantify the impact of connector choice on radiographic outcomes of treatment. A multicenter database of prospectively and retrospectively collected data on early-onset scoliosis patients was reviewed. Patients of any thoracic or thoracolumbar coronal plane deformity whose initial growing rod treatment was initiated before age 10 years and underwent at least 3 years of dual growing rod treatment with either tandem or wedding band connectors were included. Preoperative, immediate postoperative, and prefinal radiographs were reviewed and compared in regard to major curve magnitude, T1-T12 and T1-S1 spinal length, length of instrumentation, and sagittal plane measures. A total of 209 patients were included. The overall percent change from preoperative to prefinal in all radiographic parameters was not different between the two groups indicating similar efficacy in treatment. After controlling for institutional variation, the improvement of the major coronal Cobb angle from preoperative to prefinal was statistically improved for the tandem group (34° vs. 29°, p = .002) and the difference in T5-T12 kyphosis from preoperative to prefinal was significantly different between the groups (-6° vs. +1.3°, p = .008). We identified little difference in the effects of connector type on radiographic outcomes of patients treated with traditional growing rod, which indicates that both wedding band and tandem connectors function similarly. The small differences detected suggest that tandem connectors may improve major Cobb correction, and wedding band connectors may maintain thoracic kyphosis over time. Level III.


Fragile X protein mitigates TDP-43 toxicity by remodeling RNA granules and restoring translation.
RNA dysregulation is a newly recognized disease mechanism in amyotrophic lateral sclerosis (ALS). Here we identify Drosophila fragile X mental retardation protein (dFMRP) as a robust genetic modifier of TDP-43-dependent toxicity in a Drosophila model of ALS. We find that dFMRP overexpression (dFMRP OE) mitigates TDP-43 dependent locomotor defects and reduced lifespan in Drosophila. TDP-43 and FMRP form a complex in flies and human cells. In motor neurons, TDP-43 expression increases the association of dFMRP with stress granules and colocalizes with polyA binding protein in a variant-dependent manner. Furthermore, dFMRP dosage modulates TDP-43 solubility and molecular mobility with overexpression of dFMRP resulting in a significant reduction of TDP-43 in the aggregate fraction. Polysome fractionation experiments indicate that dFMRP OE also relieves the translation inhibition of futsch mRNA, a TDP-43 target mRNA, which regulates neuromuscular synapse architecture. Restoration of futsch translation by dFMRP OE mitigates Futsch-dependent morphological phenotypes at the neuromuscular junction including synaptic size and presence of satellite boutons. Our data suggest a model whereby dFMRP is neuroprotective by remodeling TDP-43 containing RNA granules, reducing aggregation and restoring the translation of specific mRNAs in motor neurons.


Managing during a merger.
In the November-December 1988 issue of Physician Executive, Dr. Marks' article outlined typical reactions to the uncertainty of being involved in a merger or consolidation. The article introduced the concept of the "merger syndrome," which encompasses executives' stressful reactions to a combination and the development of a crisis management orientation. The bottom line, if the syndrome is allowed to go unchecked, can be marred executive and employee performance and poor financial and operational results. The merger syndrome is a prime reason that two-thirds of all mergers and acquisitions are financial failures. Consumed by their reactions to mergers, executives frequently lose touch with the needs of employees. In this article, the author summarizes steps that can be taken by executives to help their employees cope with the trauma of merger; to minimize negative employee reactions, such as reduced productivity and increased turnover; and to build effective postmerger teams.


Time course of myosin heavy chain transitions in neonatal rats: importance of innervation and thyroid state.
During the postnatal period, rat limb muscles adapt to weight bearing via the replacement of embryonic (Emb) and neonatal (Neo) myosin heavy chains (MHCs) by the adult isoforms. Our aim was to characterize this transition in terms of the six MHC isoforms expressed in skeletal muscle and to determine the importance of innervation and thyroid hormone status on the attainment of the adult MHC phenotype. Neonatal rats were made hypothyroid via propylthiouracil (PTU) injection. In normal and PTU subgroups, leg muscles were unilaterally denervated at 15 days of age. The MHC profiles of plantaris (PLN) and soleus (Sol) muscles were determined at 7, 14, 23, and 30 days postpartum. At day 7, the Sol MHC profile was 55% type I, 30% Emb, and 10% Neo; in the PLN, the pattern was 60% Neo and 25% Emb. By day 30 the Sol and PLN had essentially attained an adult MHC profile in the controls. PTU augmented slow MHC expression in the Sol, whereas in the PLN it markedly repressed IIb MHC by retaining neonatal MHC expression. Denervation blunted the upregulation of IIb in the PLN and of Type I in the Sol and shifted the pattern to greater expression of IIa and IIx MHCs in both muscles. In contrast to previous observations, these findings collectively suggest that both an intact thyroid and innervation state are obligatory for the attainment of the adult MHC phenotype, particularly in fast-twitch muscles.


MOD-4023, a long-acting carboxy-terminal peptide-modified human growth hormone: results of a Phase 2 study in growth hormone-deficient adults.
Growth hormone (GH) replacement therapy currently requires daily injections, which may cause distress and low compliance. C-terminal peptide (CTP)-modified growth hormone (MOD-4023) is being developed as a once-weekly dosing regimen in patients with GH deficiency (GHD). This study's objective is to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of MOD-4023 administered once-weekly in GHD adults. 54 adults with GHD currently treated with daily GH were normalized and randomized into 4 weekly dosing cohorts of MOD-4023 at 18.5%, 37%, 55.5% or 123.4% of individual cumulative weekly molar hGH dose. The study included 2 stages: Stage A assessed the effectiveness and PK/PD profiles of the 4 dosing regimens of MOD-4023. Stage B was an extension period of once-weekly MOD-4023 administration (61.7% molar hGH content) to collect further safety data and confirm the results from Stage A. Dose-dependent response was observed for both PK and PD data of weekly MOD-4023 treatment. Insulin-like growth factor I (IGF-I) SDS levels were maintained within normal range. The 18.5% cohort was discontinued due to low efficacy. MOD-4023 was well tolerated and exhibited favorable safety profile in all dose cohorts. The reported adverse events were consistent with known GH-related side effects. Once-weekly MOD-4023 administration in GHD adults was found to be clinically effective while maintaining a favorable safety profile and may obviate the need for daily injections. Weekly GH injections may improve compliance and overall outcome. The promising results achieved in this Phase 2 study led to a pivotal Phase 3 trial, which is currently ongoing.


Calorie restriction or exercise: effects on coronary heart disease risk factors. A randomized, controlled trial.
Coronary heart disease (CHD) risk factors and the risk of CHD increase with increased adiposity. Fat loss induced by negative energy balance improves all metabolic CHD risk factors. To determine whether fat loss induced by long-term calorie restriction (CR) or increased energy expenditure induced by exercise (EX) has different effects on CHD risk factors in nonobese subjects, we conducted a 1-yr controlled trial involving 48 nonobese subjects who were randomly assigned to one of three groups: CR, 20% CR diet (n = 18); EX, 20% increase in energy expenditure through daily exercise with no increase in energy intake (n = 18); or HL, healthy lifestyle guidelines (n = 10). Subjects were 29 women and 17 men aged 57 +/- 3 yr, with BMI 27.3 +/- 2.0 kg/m(2). Assessments included total body fat by DEXA, lipoproteins, blood pressure, HOMA-IR, C-reactive protein (CRP), and estimated 10-yr CHD risk score. Body fat decreased by 6.3 +/- 3.8 kg in CR, 5.6 +/- 4.4 kg in EX, and 0.4 +/- 1.7 kg in HL, which corresponded to reductions of 24.9, 22.3, and 1.2% of baseline body fat mass, respectively. These CR- and EX-induced energy deficits were accompanied by reductions in most of the major CHD risk factors, including plasma LDL-cholesterol, total cholesterol/HDL ratio, HOMA-IR index, and CRP concentrations that were similar in the two intervention groups. Data from the present study provide evidence that CR- and EX-induced negative energy balance result in substantial and similar improvements in the major risk factors for CHD in normal-weight and overweight middle-aged adults.


ABA is an essential signal for plant resistance to pathogens affecting JA biosynthesis and the activation of defenses in Arabidopsis.
Analyses of Arabidopsis thaliana defense response to the damping-off oomycete pathogen Pythium irregulare show that resistance to P. irregulare requires a multicomponent defense strategy. Penetration represents a first layer, as indicated by the susceptibility of pen2 mutants, followed by recognition, likely mediated by ERECTA receptor-like kinases. Subsequent signaling of inducible defenses is predominantly mediated by jasmonic acid (JA), with insensitive coi1 mutants showing extreme susceptibility. In contrast with the generally accepted roles of ethylene and salicylic acid cooperating with or antagonizing, respectively, JA in the activation of defenses against necrotrophs, both are required to prevent disease progression, although much less so than JA. Meta-analysis of transcriptome profiles confirmed the predominant role of JA in activation of P. irregulare-induced defenses and uncovered abscisic acid (ABA) as an important regulator of defense gene expression. Analysis of cis-regulatory sequences also revealed an unexpected overrepresentation of ABA response elements in promoters of P. irregulare-responsive genes. Subsequent infections of ABA-related and callose-deficient mutants confirmed the importance of ABA in defense, acting partly through an undescribed mechanism. The results support a model for ABA affecting JA biosynthesis in the activation of defenses against this oomycete.


Chlorinated dibenzo-p-dioxins and dibenzofurans and the human immune system. 2. In vitro proliferation of lymphocytes from workers with quantified moderately-increased body burdens.
Lymphocyte proliferation responses were studied in workers with moderately increased body burdens of 2,3,7,8-tetrachlorodibenzo-p-dioxin and other polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/PCDFs, calculated as International Toxicity Equivalencies [I-TE]). Mitogens (pokeweed mitogen [PWM], phytohemagglutinine [PHA], concanavalin A [Con A]), as well as an anti-human monoclonal antibody against CD3 were used as proliferation stimulators in vitro. Additionally, the feasibility of using the lymphocyte response to tetanus toxoid was assessed, and the response to this recall-antigen was included in this trial. No decrease in the capacity of 3H-thymidine incorporation was observed with any of the proliferation stimulators in the group of volunteers with the increased TCDD-body burden when compared with volunteers exhibiting TCDD-concentrations in blood fat within the reference range. Regression analysis revealed a slight trend towards an increase for 3H-thymidine incorporation during the stimulation with PHA only. It can be concluded from our data that moderate increases in the TCDD- or I-TE-body burdens do not induce any medically significant changes in the capacity for proliferation of lymphocytes, measured as 3H-thymidine incorporation.


Experiment study of effect of perfluorohexyloctane on corneal endothelial cells.
To investigate the effect of Perfluorohexyloctane (F6H8) on corneal endothelial cells(CEC) of rabbit eyes. Fifteen New Zealand white rabbits were divided into two groups: experimental group(F6H8) and control group(BSS). All rabbits underwent anterior chamber injection of 0.15 ml F6H8 or BSS. Slit-lamp biomicroscopy and corneal endothelium photography were performed pre-operatively and postoperatively. Histopathological examination and Transmission electron microscopy(TEM) were done after the rabbits were sacrificed. All the corneas were clear. Since 4 weeks after operation, the endothelial cells were markedly irregular in size and shape and the number of endothelial cells was markedly decreased. Multilayered retrocorneal membranes(RCM) grew gradually 2 weeks after surgery. Vacuolar degeneration was seen in some endothelial cells. Nuclear degeneration and edema of plasma were seen in TEM. Corneal endothelial cell degenerated after contacting with F6H8 for 2-4 weeks. As a silicone solvent, it should be removed completely after injection. We don't recommend it to be used as a new intraocular temponade.


Functional traits of three major invasive grasses in a threatened tropical mountain grassland.
The native flora of the Brazilian rupestrian grassland (campos rupestres) is threatened by the spread of invasive grasses. In this study, we evaluated the effect of habitat on the functional traits and CSR ecological strategies of three invasive alien grasses occurring both in the ironstone (IRG) and quartzitic (QRG) rupestrian grassland habitats. Although in both habitats the invasive species predominantly showed a stress-tolerant strategy, they exhibited distinct degrees of stress-tolerance and slightly differences in functional traits values in the IRG compared to the QRG. Habitat type distinctly influenced invasive grasses functional traits and ecological strategies, revealing a species-specific pattern.


Comparison of the lectin-binding pattern in different human melanoma cell lines.
Glycosylation is generally altered in tumour cells in comparison with their normal counterparts. These alterations are thought to be important because they contribute to the abnormal behaviour of cancer cells. Therefore, we have comparatively analysed the glycoproteins in cell extracts from human melanoma (primary site--WM35; metastatic sites-- WM239, WM9 and A375) cell lines using sodium dodecyl sulphate-polyacrylamide gel electrophoresis and lectin staining. The glycoprotein pattern of the WM35 line differed from that of the other cell lines in having less proteins that reacted with Sambucus nigra, Maackia amurensis and Phaseolus vulgaris agglutinins. A glycoprotein of about 70 kDa had a significantly increased reaction with Sambucus nigra agglutinin in all the cell lines from metastatic sites. In the WM9, WM239 and A375 cell lines, additional bands (160-100 kDa) were stained with Phaseolus vulgaris agglutinin, suggesting that cells from metastatic sites contain more glycoproteins with beta1-6 branches. On the other hand, only minor changes in the reaction with Galanthus nivalis agglutinin, a mannose-specific lectin, were detected. Among the proteins showing different lectin staining, one, with an apparent molecular weight of 133 kDa, was recognized by antibodies as N-cadherin. The present results suggest that in human melanoma the expression of branched and sialylated complex type N-oligosaccharides consistently increased in cells from metastatic sites, and support the view that carbohydrates are associated with the acquisition of the metastatic potential of tumour cells.


Thyroid cold acclimation influences on norepinephrine metabolism in brown fat.
Norepinephrine turnover rates and tyrosine hydroxylase activities were determined in the interscapular brown fat pad of the rat during cold acclimation, hyperthyroxinism, and after thyroidectomy. Rats were cold acclimated by placement in a cold room, one rat to a cage, for a period of 6 wk. Hyperthyroxinism was induced by daily subcutaneous injections of L-thyroxine (1 mg/kg) for 6 days. Norepinephrine turnover rate and enzyme activity were determined at the end of each experimental period and at 8 wk after thyroidectomy. The rate of norepinephrine turnover increased during cold acclimation and hyperthyroxinism and decreased after thyroidectomy. Cold acclimation resulted in a significant increase in tyrosine hydroxylase activity, whereas no significant effect on enzyme activity was observed in hyperthyroxinism or after thyroidectomy. None of the conditions produced a change compared to controls in the apparent Km of tyrosine hydroxylase for L-tyrosine. Cold acclimation resulted in a significant decrease in the apparent Km of tyrosine hydroxylase for pterin cofactor, whereas thyroxine treatment and thyroidectomy had no effect.


[Effects of tumor promoting herb Wikstroemia chamaedaphne extract on V79 cells and WB liver cells: I. Correlation between cellular growth and gap junctional intercellular communication].
A Chinese herb, wikstroemia Chamaedaphen (WC) extract, recently has been shown to be a potential tumor promoting agent on uterine cervical carcinoma induced by HSV-2 or MCA in mice. To determine whether the tumor promoting effects of WC extract were mediated through inhibition of gap junctional intercellular communication (GJIC) with relation to cellular growth, experiments were conducted on Chinese hamster V79 cells and rat WB liver cells by utilization of SLDT method for GJIC detection and cell growth curve examination, 3H-TdR incorporation, mitotic index (MI) and Flow Cytometry (FCM) methods. TPA was used for comparative purpose. WC extract inhibited GJIC and stimulated cell growth in a dose (2-200 micrograms/ml) and time (0-72 hr)-dependent manner in both cell lines. Both WC extract and TPA treatments increased V79 cell growth rate. The average cell doubling-time was decreased from 36.5 hr in control V79 cells to 28.2 hr in WC extract (10 micrograms/ml) and 20.9 hr in TPA (50 ng/ml) treatment by the 3rd day. Stimulating effect of both drugs on DNA synthesis of V79 cells was demonstrated. The results of FCM and MI indicated that the cell number of M-phase cells was increased after drug treatment. It is suggested that (1) tumor promoting effect of WC extract might be mediated through inhibition of GJIC: (2) inhibition of GJIC is closely correlated with increased cell growth rate and entry of cell division cycle.


TET2 mutations are associated with specific 5-methylcytosine and 5-hydroxymethylcytosine profiles in patients with chronic myelomonocytic leukemia.
Chronic myelomonocytic leukemia (CMML) has recently been associated with a high incidence of diverse mutations in genes such as TET2 or EZH2 that are implicated in epigenetic mechanisms. We have performed genome-wide DNA methylation arrays and mutational analysis of TET2, IDH1, IDH2, EZH2 and JAK2 in a group of 24 patients with CMML. 249 genes were differentially methylated between CMML patients and controls. Using Ingenuity pathway analysis, we identified enrichment in a gene network centered around PLC, JNK and ERK suggesting that these pathways, whose deregulation has been recently described in CMML, are affected by epigenetic mechanisms. Mutations of TET2, JAK2 and EZH2 were found in 15 patients (65%), 4 patients (17%) and 1 patient (4%) respectively while no mutations in the IDH1 and IDH2 genes were identified. Interestingly, patients with wild type TET2 clustered separately from patients with TET2 mutations, showed a higher degree of hypermethylation and were associated with higher risk karyotypes. Our results demonstrate the presence of aberrant DNA methylation in CMML and identifies TET2 mutant CMML as a biologically distinct disease subtype with a different epigenetic profile.


Recent insights in islet amyloid polypeptide-induced membrane disruption and its role in beta-cell death in type 2 diabetes mellitus.
The presence of fibrillar protein deposits (amyloid) of human islet amyloid polypeptide (hIAPP) in the pancreatic islets of Langerhans is thought to be related to death of the insulin-producing islet beta-cells in type 2 diabetes mellitus (DM2). The mechanism of hIAPP-induced beta-cell death is not understood. However, there is growing evidence that hIAPP-induced disruption of beta-cell membranes is the cause of hIAPP cytotoxicity. Amyloid cytotoxicity by membrane damage has not only been suggested for hIAPP, but also for peptides and proteins related to other misfolding diseases, like Alzheimer's disease, Parkinson's disease, and prion diseases. Here we review the interaction of hIAPP with membranes, and discuss recent progress in the field, with a focus on hIAPP structure and on the proposed mechanisms of hIAPP-induced membrane damage in relation to beta-cell death in DM2.


PCNA is involved in the EndoQ-mediated DNA repair process in Thermococcales.
To maintain genome integrity for transfer to their offspring, and to maintain order in cellular processes, all living organisms have DNA repair systems. Besides the well-conserved DNA repair machineries, organisms thriving in extreme environments are expected to have developed efficient repair systems. We recently discovered a novel endonuclease, which cleaves the 5' side of deoxyinosine, from the hyperthermophilic archaeon, Pyrococcus furiosus. The novel endonuclease, designated as Endonulcease Q (EndoQ), recognizes uracil, abasic site and xanthine, as well as hypoxanthine, and cuts the phosphodiester bond at their 5' sides. To understand the functional process involving EndoQ, we searched for interacting partners of EndoQ and identified Proliferating Cell Nuclear Angigen (PCNA). The EndoQ activity was clearly enhanced by addition of PCNA in vitro. The physical interaction between the two proteins through a PIP-motif of EndoQ and the toroidal structure of PCNA are critical for the stimulation of the endonuclease activity. These findings provide us a clue to elucidate a unique DNA repair system in Archaea.


Stress and Symptom Burden in Oncology Patients During the COVID-19 Pandemic.
No information is available on oncology patients' level of stress and symptom burden during the coronavirus disease 2019 (COVID-19) pandemic. To evaluate for differences in demographic and clinical characteristics, levels of social isolation and loneliness, and the occurrence and severity of common symptoms between oncology patients with low vs. high levels of COVID-19 and cancer-related stress. In addition, to determine which of these characteristics were associated with membership in the high-stressed group. Patients were 18 years and older; had a diagnosis of cancer; and were able to complete an online survey. Of the 187 patients in this study, 31.6% were categorized in the stressed group (Impact of Event Scale-Revised [score of ≥24]). Stressed group's Impact of Event Scale-Revised score exceeds previous benchmarks in oncology patients and equates with probable post-traumatic stress disorder. In this stressed group, patients reported occurrence rates for depression (71.2%), anxiety (78.0%), sleep disturbance (78.0%), evening fatigue (55.9%), cognitive impairment (91.5%), and pain (75.9%). Symptom severity scores equate with clinically meaningful levels for each symptom. We identified alarmingly high rates of stress and an extraordinarily high symptom burden among patients with cancer, exceeding those previously benchmarked in this population and on par with noncancer patients with post-traumatic stress disorder. Given that the COVID-19 pandemic will likely impact cancer care for an indefinite period, clinicians must exhibit increased vigilance in their assessments of patients' level of stress and symptom burden. Moreover, an increase in referrals to appropriate supportive care resources must be prioritized for high-risk patients.


High-Yield Fabrication of Entangled Photon Emitters for Hybrid Quantum Networking Using High-Temperature Droplet Epitaxy.
Several semiconductor quantum dot techniques have been investigated for the generation of entangled photon pairs. Among the other techniques, droplet epitaxy enables the control of the shape, size, density, and emission wavelength of the quantum emitters. However, the fraction of the entanglement-ready quantum dots that can be fabricated with this method is still limited to around 5%, and matching the energy of the entangled photons to atomic transitions (a promising route toward quantum networking) remains an outstanding challenge. Here, we overcome these obstacles by introducing a modified approach to droplet epitaxy on a high symmetry (111)A substrate, where the fundamental crystallization step is performed at a significantly higher temperature as compared with previous reports. Our method drastically improves the yield of entanglement-ready photon sources near the emission wavelength of interest, which can be as high as 95% due to the low values of fine structure splitting and radiative lifetime, together with the reduced exciton dephasing offered by the choice of GaAs/AlGaAs materials. The quantum dots are designed to emit in the operating spectral region of Rb-based slow-light media, providing a viable technology for quantum repeater stations.


Locked plating as an external fixator in treating tibial fractures: A PRISMA-compliant systematic review.
This article is a systematic review of the published literature about the biomechanics, functional outcomes, and complications of a locked plate as an external fixator in treating tibial fractures. We searched the PubMed, Ovid Medline, Embase, ScienceDirect, and Cochrane Library databases to retrieve the relevant studies. Studies published in English and Chinese which assessed adult patients and more than 4 cases who had sustained any type of fresh tibial fracture treated with the external locking plate, provided that they reported functional outcomes, range of motion (ROM), union or complication rates, and the biomechanical studies of external locked plating are also included. The electronic search strategy revealed 248 studies, and 2 studies were identified as relevant through manual search of references. Finally, 12 studies were included in this systematic review. These consist of 3 pure biomechanical studies, 8 case series, and 1 study including both of biomechanics and case series. Due to the heterogeneity of biomechanical studies, we can only conclude that external locked plate shows inferior structural stiffness than internal locked plate. The clinical studies reported that external locked plating gave a satisfactory ROM of the knee and ankle, functional outcomes, union rate, and low complication rate. We can only conclude that external locked plate shows inferior structural stiffness than internal locked plate because of the heterogeneity of biomechanical studies. The clinical studies showed locked plating as an external fixator in treating tibial fractures can be considered as a safe and successful procedure. However, as yet, there is unconvincing evidence that it is superior to standard techniques with regards to clinical and functional outcomes. More and well-designed studies about this technique should be carried out.


Renal replacement therapy in patients with diabetes and end-stage renal disease.
The number of patients who have diabetes and ESRD and are being admitted to renal replacement treatment (RRT) is increasing dramatically worldwide, and in many countries, diabetes has become the single most frequent cause of ESRD. Although the prognosis of patients who have diabetes and are receiving RRT has greatly improved, survival and medical rehabilitation rates continue to be significantly worse than those of nondiabetic patients, mainly because of preexisting severely compromised cardiovascular conditions. The most common RRT modality in patients with diabetes is still hemodialysis, but it gives rise to a number of clinical problems, in particular difficulties in the management of the vascular access and high frequency of intradialytic hypotension. However, patients who have diabetes and are on peritoneal dialysis have to face a progressive increase in peritoneal permeability, loss of ultrafiltration, and peritoneal fibrosis, all phenomena being accelerated in patients with diabetes and ultimately leading to an increased technique failure. The results of observational studies and national registries, although conflicting, suggest that these two dialytic modalities are somehow comparable in terms of outcomes, whereas accumulating evidence shows that both survival and medical rehabilitation of patients with diabetes are significantly better after renal transplantation, which should be the first-choice option for patients who have diabetes and reach ESRD but unfortunately still accounts for only a limited proportion of RRT treatments in these patients.


3D structure of the influenza virus polymerase complex: localization of subunit domains.
The 3D structure of the influenza virus polymerase complex was determined by electron microscopy and image processing of recombinant ribonucleoproteins (RNPs). The RNPs were generated by in vivo amplification using cDNAs of the three polymerase subunits, the nucleoprotein, and a model virus-associated RNA containing 248 nt. The polymerase structure obtained is very compact, with no apparent boundaries among subunits. The position of specific regions of the PB1, PB2, and PA subunits was determined by 3D reconstruction of either RNP-mAb complexes or tagged RNPs. This structural model is available for the polymerase of a negative-stranded RNA virus and provides a general delineation of the complex and its interaction with the template-associated nucleoprotein monomers in the RNP.


The effect of inhaled leukotriene D4 and methacholine on sputum cell differentials in asthma.
The cysteinyl leukotriene LTE4 has been shown to induce airway eosinophilia in asthmatics in vivo. This phenomenon has not yet been reported for LTD4. Hence, we examined the effect of inhaled LTD4 and a control bronchoconstrictor agent, methacholine, on cell differentials in hypertonic saline-induced whole sputum samples of 12 nonsmoking atopic asthmatic subjects (three women, nine men; 21 to 29 yr of age; FEV1, 74 to 120% pred; PC20FEV1 methacholine < 9.6 mg/ml). The study had a cross-over, placebo-controlled design consisting of 4 d separated by > or = 1 wk. On each randomized study day, the subjects inhaled five serial doses of either LTD4 (mean cumulative concentration: 95.7 microM) or methacholine (mean cumulative concentration: 542 mM) or five doses of their respective diluents (PBS/ethanol or PBS). The airway response was measured by FEV1, followed by sputum induction with 4.5% NaCl, 4 h postchallenge. Inflammatory cells (> or = 250) were counted twice on coded cytospins and expressed as percentages of nonsquamous cells. There was no significant difference in the maximal percent fall in FEV1 from baseline between LTD4 (mean +/- SEM, 49.5 +/- 4.4% fall) and methacholine (mean +/- SEM, 55.9 +/- 3.4% fall) (p = 0.11). LTD4 induced a significant increase in the percentage of sputum eosinophils as compared with its diluent (mean +/- SD, 26.6 +/- 21.3% and 10.2 +/- 8.8%, respectively; p = 0.025), whereas a similar trend for methacholine failed to reach significance (mean +/- SD, 19.1 +/- 22.9% and 7.8 +/- 5.8%, respectively; p = 0.11). There was no significant difference in the changes in the percentage of sputum eosinophils between LTD4 and methacholine (mean difference +/- SD, 7.5 +/- 12.5% eosinophils; p = 0.09). We conclude that LTD4 induces eosinophilia in sputum of asthmatic subjects 4 h after inhalation. Our data suggest that LTD4 recruits eosinophils into the airways of asthmatics in vivo, possibly by virtue of direct or indirect chemotactic properties, whereas an additional effect of vigourous airway narrowing per se cannot be excluded.


High incidence of acute self-reported sleep disturbances in patients following arthroscopic-assisted knee surgery.
To evaluate the self-reported incidence of sleep disturbances, defined as ≤7 hours of sleep per 24-hour period, in patients undergoing arthroscopic-assisted knee surgery. Patients who underwent arthroscopic knee surgery over the course of a 4-month period were prospectively included. Patients were excluded if a history of insomnia or other sleep altering medical history was reported. Self-reported sleep metrics included average number of hours of sleep per night, average number of awakenings during sleep per night, perceived quality of sleep, average pain level during sleep and number of hours of physical activity/therapy per week. Data were collected at weeks 1, 3, and 6 postoperatively. Joint circumference was measured on postoperative day 1 and served as an indicator of a knee effusion. Paired t-tests were used to compare preoperative to postoperative hours of sleep. Simple and multiple linear regression were used to evaluate relationships between surgical variables and postoperative sleep metrics. There were 123 patients who underwent arthroscopic knee surgery during the prospective enrolment period; 83 patients were included in the final analysis. The overall incidence of preoperative sleep disturbances was 20% (n=17). The overall incidence of self-reported postoperative sleep disturbances was 99%, 96% and 90% at weeks 1, 3 and 6, respectively. The average number of hours slept was significantly reduced at 1, 3 and 6 weeks postoperatively compared with the preinjury state (p<0.001). Knee joint circumference had a significantly negative correlation with average number of hours of sleep in the first 6 weeks postoperatively (R=-0.704; p=0.001). Surgical variables including severity of surgery, weekly postoperative pain level and weekly hours of postoperative physical therapy were not significant independent predictors of acute postoperative sleep disturbances (p>0.05). Sleep disturbances were commonly reported in patients following arthroscopic knee surgery without correction of sleep metrics by 6 weeks postoperatively. The majority of sleep disturbances in this cohort correlated with an increased knee effusion. A multidisciplinary team approach is recommended to counsel patients regarding the potential for and problems with acute sleep disturbances following arthroscopic knee surgery. Level of evidence: 3.


Bronchoalveolar lavage and transbronchial biopsy for the diagnosis of pulmonary infections in the acquired immunodeficiency syndrome.
The efficacy of bronchoalveolar lavage and transbronchial biopsy in diagnosing lung infection was determined in 276 fiberoptic bronchoscopic examinations done on 171 patients with known or suspected acquired immunodeficiency syndrome. Of 173 pathogens (Pneumocystis carinii, cytomegalovirus, Mycobacterium avium-intracellulare, Cryptococcus neoformans, M. tuberculosis, Coccidioides immitis, and Histoplasma capsulatum) identified during the initial evaluation or in the subsequent month, the initial bronchoscopic examination detected 166 (96%). Bronchoalveolar lavage and transbronchial biopsy had sensitivities of 86% and 87%, respectively. When bronchoscopy included both bronchoalveolar lavage and transbronchial biopsy, the yield for all pathogens was 98% and the sensitivity for P. carinii infections was 100%. Follow-up for at least 3 weeks after examination failed to detect any additional false-negative results. Fiberoptic bronchoscopy is extremely accurate for the detection of pathogens in patients with the acquired immunodeficiency syndrome, especially when bronchoalveolar lavage and transbronchial biopsy are combined. In patients at high risk of complications from transbronchial biopsy, bronchoalveolar lavage is sufficiently accurate to be used alone.


Problem-based learning in undergraduate medical education: can we really implement it in the West African subregion?
A major global pedagogical shift has occurred in the way medicine is taught over the last half a century. Problem-based learning (PBL) has emerged as one of the most popular, of these learner-centred new methods. To examine the evolution and educational principles of PBL and the feasibility of implementing it in the West African subregion. Key literature detailing the history, educational value and principle behind PBL were reviewed. Issues regarding the implication of implementing PBL to West Africa were deduced and suggestions made for the way forward. Since its introduction in McMaster University in Canada in the 60s, PBL has spread all over world. It is rooted in sound educational theories like the Kolb's experiential learning, adult education, collaborative learning, contextual learning and constructivism. Compared to traditionally trained students, PBL students find learning more enjoyable and develop better relational and professional skills. They show more causal reasoning in diagnosis and become better lifelong learners. Issues that may affect its implementation in West Africa include high start up costs, lack of supporting educational technology and relative lack of medical school managers with appropriate medical education background to assess and evaluate such innovations. The evidence for the need for a change from the traditional method of training is overwhelming. Implementation of PBL as an educational method in medical training in the West African subregion is both desirable and practicable if we address some of the issues outlined above.


Medical Image Fusion Based on Fast Finite Shearlet Transform and Sparse Representation.
Clinical diagnosis has high requirements for the visual effect of medical images. To obtain rich detail features and clear edges for fusion medical images, an image fusion algorithm FFST-SR-PCNN based on fast finite shearlet transform (FFST) and sparse representation is proposed, aiming at the problem of poor clarity of edge details that is conducive to maintaining the details of source image in current algorithms. Firstly, the source image is decomposed into low-frequency coefficients and high-frequency coefficients by FFST. Secondly, the K-SVD method is used to train the low-frequency coefficients to obtain the overcomplete dictionary D, and then the OMP algorithm sparsely encodes the low-frequency coefficients to complete the fusion of the low-frequency coefficients. Then, a high-frequency coefficient is applied to excite a pulse-coupled neural network, and the fusion coefficient of the high-frequency coefficient is selected according to the number of ignitions. Finally, the fused low-frequency coefficient and high-frequency coefficient are reconstructed into the fused medical image by FFST inverse transform. The experimental results show that the image fusion result of the proposed algorithm is about 35% higher than the comparison algorithms for the edge information transfer factor QAB/F index and has achieved good results in both subjective visual effects and objective evaluation indicators.


Adult mortality of diseases and injuries attributable to selected metabolic, lifestyle, environmental, and infectious risk factors in Taiwan: a comparative risk assessment.
To facilitate priority-setting in health policymaking, we compiled the best available information to estimate the adult mortality (>30 years) burden attributable to 13 metabolic, lifestyle, infectious, and environmental risk factors in Taiwan. We obtained data on risk factor exposure from nationally representative health surveys, cause-specific mortality from the National Death Registry, and relative risks from epidemiological studies and meta-analyses. We applied the comparative risk assessment framework to estimate mortality burden attributable to individual risk factors or risk factor clusters. In 2009, high blood glucose accounted for 14,900 deaths (95% UI: 11,850-17,960), or 10.4% of all deaths in that year. It was followed by tobacco smoking (13,340 deaths, 95% UI: 10,330-16,450), high blood pressure (11,190 deaths, 95% UI: 8,190-14,190), ambient particulate matter pollution (8,600 deaths, 95% UI: 7,370-9,840), and dietary risks (high sodium intake and low intake of fruits and vegetables, 7,890 deaths, 95% UI: 5,970-9,810). Overweight-obesity and physical inactivity accounted for 7,620 deaths (95% UI: 6,040-9,190), and 7,400 deaths (95% UI: 6,670-8,130), respectively. The cardiometabolic risk factors of high blood pressure, high blood glucose, high cholesterol, and overweight-obesity jointly accounted for 12,120 deaths (95% UI: 11,220-13,020) from cardiovascular diseases. For domestic risk factors, infections from hepatitis B virus (HBV) and hepatitis C virus (HCV) were responsible for 6,300 deaths (95% UI: 5,610-6,980) and 3,170 deaths (95% UI: 1,860-4,490), respectively, and betel nut use was associated with 1,780 deaths from oral, laryngeal, and esophageal cancer (95% UI: 1,190-2,360). The leading risk factors for years of life lost were similar, but the impact of tobacco smoking and alcohol use became larger because the attributable deaths from these risk factors occurred among young adults aged less than 60 years. High blood glucose, tobacco smoking, and high blood pressure are the major risk factors for deaths from diseases and injuries among Taiwanese adults. A large number of years of life would be gained if the 13 modifiable risk factors could be removed or reduced to the optimal level.


An olivine-free mantle source of Hawaiian shield basalts.
More than 50 per cent of the Earth's upper mantle consists of olivine and it is generally thought that mantle-derived melts are generated in equilibrium with this mineral. Here, however, we show that the unusually high nickel and silicon contents of most parental Hawaiian magmas are inconsistent with a deep olivine-bearing source, because this mineral together with pyroxene buffers both nickel and silicon at lower levels. This can be resolved if the olivine of the mantle peridotite is consumed by reaction with melts derived from recycled oceanic crust, to form a secondary pyroxenitic source. Our modelling shows that more than half of Hawaiian magmas formed during the past 1 Myr came from this source. In addition, we estimate that the proportion of recycled (oceanic) crust varies from 30 per cent near the plume centre to insignificant levels at the plume edge. These results are also consistent with volcano volumes, magma volume flux and seismological observations.


Surgical treatment and perioperative management of moyamoya disease associated with glycogen storage disease Type 1a.
The authors report a case of concurrent moyamoya disease and glycogen storage disease Type 1a that was successfully managed with bypass surgery. This 7-year-old Japanese girl, diagnosed with glycogen storage disease Type 1a at the age of 2 years, presented with repeated transient ischemic attacks. Cerebral angiography revealed severe stenosis at the terminal portions of the bilateral internal carotid arteries, with typical moyamoya vessels. The patient underwent superficial temporal artery-middle cerebral artery anastomosis and encephalomyosynangiosis bilaterally, in 2 staged procedures at an interval of 4 months. Despite perioperative administration of glucose, hypoglycemia and metabolic acidosis occurred after both surgeries. The symptoms were milder after the second surgery, in which an increased dose of glucose was used. The patient tolerated the perioperative conditions well under intensified medical treatment, and no further ischemic symptoms occurred.


Molecular characterization and functional significance of the Vti family of SNARE proteins in tick salivary glands.
Exocytosis involves membrane fusion between secretory vesicles and the plasma membrane. The Soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAPs) and their receptor proteins (SNAREs) interact to fuse vesicles with the membrane and trigger the release of their sialosecretome out of the tick salivary gland cells. In this study, we examined the functional significance of the Vti family of SNARE proteins of blood-feeding Amblyomma maculatum and Amblyomma americanum. Vti1A and Vti1B have been implicated in multiple functional roles in vesicle transport. QRT-PCR studies demonstrated that the highest transcriptional expression of vti1a and vti1b genes occurs in unfed salivary glands, suggesting that elevated secretory vesicle formation occurs prior to feeding but continues at low rates after blood feeding commences. Vti1A and Vti1B localize to the secretory vesicles in unfed tick salivary glands in immunofluorescence microscopy studies. Knockdown of vti1a and vti1b by RNA interference resulted in a significant decrease in the engorged tick weight compared to the control during prolonged blood-feeding on the host. RNA interference of vti1a or vti1b impaired oviposition and none of the ticks produced eggs masses. Surprisingly, the double knockdown did not produce a strong phenotype and ticks fed normally on the host and produced egg masses, suggesting a compensatory mechanism exists within the secretory system which may have been activated in the double knockdown. These results suggest an important functional role of the Vti family of SNARE proteins in tick blood feeding and ultimately oviposition. Understanding the basic functions of the Vti family of SNARE proteins in salivary glands may lead to better ways to prevent tick attachment and transmission of tick-borne diseases.


Kinematics of cardiac growth: in vivo characterization of growth tensors and strains.
Progressive growth and remodeling of the left ventricle are part of the natural history of chronic heart failure and strong clinical indicators for survival. Accompanied by changes in cardiac form and function, they manifest themselves in alterations of cardiac strains, fiber stretches, and muscle volume. Recent attempts to shed light on the mechanistic origin of heart failure utilize continuum theories of growth to predict the maladaptation of the heart in response to pressure or volume overload. However, despite a general consensus on the representation of growth through a second order tensor, the precise format of this growth tensor remains unknown. Here we show that infarct-induced cardiac dilation is associated with a chronic longitudinal growth, accompanied by a chronic thinning of the ventricular wall. In controlled in vivo experiments throughout a period of seven weeks, we found that the lateral left ventricular wall adjacent to the infarct grows longitudinally by more than 10%, thins by more than 25%, lengthens in fiber direction by more than 5%, and decreases its volume by more than 15%. Our results illustrate how a local loss of blood supply induces chronic alterations in structure and function in adjacent regions of the ventricular wall. We anticipate our findings to be the starting point for a series of in vivo studies to calibrate and validate constitutive models for cardiac growth. Ultimately, these models could be useful to guide the design of novel therapies, which allow us to control the progression of heart failure.


Emotion Dysregulation as a Prospective Predictor of Suicidal Ideation in an at-Risk Mixed Clinical Sample.
The current study tested whether emotion dysregulation predicts suicidal ideation over the course of 6 months. Community members (N = 298) with elevated suicide risk completed a clinical interview and self-report questionnaires at baseline and month-6 follow-up appointments. Elevated general emotion dysregulation but not subscales significantly predicted increases in suicidal ideation at month-6 follow-up after accounting for initial suicidal ideation, treatment condition, and negative affectivity. Furthermore, general emotion dysregulation as well as lack of awareness and lack of clarity subscales were significantly associated with prior suicide attempts at baseline after accounting for negative affectivity. Findings support the establishment of emotion dysregulation as a risk factor for suicidal ideation and provide evidence for a role in suicide attempts. Findings call for the development of interventions targeting emotion dysregulation in effectively predicting and preventing suicidality.


Incomplete circle of Willis is associated with a higher incidence of neurologic events during carotid eversion endarterectomy without shunting.
A complete circle of Willis (CoW) is considered an important collateral network to maintain blood flow during cross-clamping in carotid endarterectomy (CEA). The aim of this study was to evaluate the impact of an incomplete CoW with isolated middle cerebral artery (iMCA) on immediate neurologic events (INEs) after CEA. We prospectively collected the clinical data and outcomes of 902 patients who underwent CEA under general anesthesia between 2013 and 2015. All patients had preoperative computed tomography angiography of the extracranial and intracranial cerebral circulation. Indications were asymptomatic (52%) and symptomatic (48%) carotid artery disease. Patients who had CEA with shunt (n = 35) and those with inadequate intracranial imaging to assess CoW were excluded (n = 322) only. Computed tomography angiography images were reviewed retrospectively and independently by two vascular radiologists who were blinded for treatment outcomes. Imaging assessment included the vertebral and carotid circulation and each segment of the CoW, which was classified as normal, hypoplastic (diameter < 0.8 mm) or absent. The ipsilateral MCA was considered isolated if there was an absence of the anterior and posterior communicating branches from the contralateral carotid or posterior circulations. INE was defined as any transient ischemic attack (TIA) and stroke diagnosed immediately after the procedure. Of the 545 included patients (331 males; mean age, 69 ± 8 years), 12 (2.2%) had a stroke in the postoperative period. There were 20 INEs (8 strokes and 12 TIAs). A complete CoW was rare; it was only detected in 19 patients (3.5%) and an iMCA was found in 34 patients (6.3%). When at least one collateral circulation was complete (in 330 patients), we observed only four INEs (1.2%). Of the 34 patients with an iMCA, 8 (24%) had INE (6 TIAs and 2 strokes). Overall, iMCA was an independent predictor of INEs (odds ratio, 11.12; 95% confidence interval, 3.57-35.87; P < .001). With logistic regression, the model included hypertension, smoking, diabetes, hyperlipidemia, carotid clamping time (minutes), contralateral significant internal carotid artery stenosis of greater than 90%, ipsilateral significant internal carotid artery stenosis of greater than 90%, preoperative symptoms in 6 months, and iMCA; above iMCA only symptomatic patients had significant risk (odds ratio, 3.34; 95% confidence interval, 1.19-9.73; P = .02), whereas all other parameters were not significant. An iMCA carries more than a 10-fold higher the risk of INEs after CEA with cross-clamping without shunt protection. In these patients, routine shunting is recommended to prevent INEs.


HMGB1 is involved in autophagy inhibition caused by SNCA/α-synuclein overexpression: a process modulated by the natural autophagy inducer corynoxine B.
SNCA/α-synuclein and its rare mutations are considered as the culprit proteins in Parkinson disease (PD). Wild-type (WT) SNCA has been shown to impair macroautophagy in mammalian cells and in transgenic mice. In this study, we monitored the dynamic changes in autophagy process and confirmed that overexpression of both WT and SNCA(A53T) inhibits autophagy in PC12 cells in a time-dependent manner. Furthermore, we showed that SNCA binds to both cytosolic and nuclear high mobility group box 1 (HMGB1), impairs the cytosolic translocation of HMGB1, blocks HMGB1-BECN1 binding, and strengthens BECN1-BCL2 binding. Deregulation of these molecular events by SNCA overexpression leads to autophagy inhibition. Overexpression of BECN1 restores autophagy and promotes the clearance of SNCA. siRNA knockdown of Hmgb1 inhibits basal autophagy and abolishes the inhibitory effect of SNCA on autophagy while overexpression of HMGB1 restores autophagy. Corynoxine B, a natural autophagy inducer, restores the deficient cytosolic translocation of HMGB1 and autophagy in cells overexpressing SNCA, which may be attributed to its ability to block SNCA-HMGB1 interaction. Based on these findings, we propose that SNCA-induced impairment of autophagy occurs, in part, through HMGB1, which may provide a potential therapeutic target for PD.


Paradoxical effects of levetiracetam in people with epilepsy with rhythmic epileptiform discharges.
To elucidate the incidence and risk factors for paradoxical effects (i.e., increased seizure frequency, increased seizure severity, or onset of new seizure types) of levetiracetam (LEV) in people with epilepsy (PWE) and identify the usefulness of electroencephalography (EEG) in predicting these effects. We examined data for consecutive PWE treated with LEV. All PWE underwent EEG and magnetic resonance imaging (MRI) before LEV administration. We also evaluated the incidence of paradoxical LEV effects and conducted multivariate logistic regression analyses to identify the associated factors. In total, 210 (66.2%) of 317 PWEs treated in our department had a history of LEV use. The incidence of paradoxical LEV effects was 5.2% (n = 11) and was significantly associated with a high LEV dose (p = 0.029), high seizure frequency (p = 0.005), temporal lobe epilepsy (p = 0.004), focal awareness seizure (p = 0.004), focal impaired awareness seizure (p = 0.007), spike (p = 0.015), rhythmic epileptiform discharges (REDs; p = 0.003), and MRI-identified focal cortical dysplasia (FCD; p < 0.0001). Multivariate analyses revealed that REDs (odds ratio [OR] = 5.35, p = 0.048, 95% confidence interval [CI]: 1.01-28.21) were independently associated with paradoxical LEV effects. Paradoxical LEV effects occurred in PWE, particularly in those with drug-resistant focal epilepsy. Furthermore, the occurrence of REDs in EEG was an independent factor associated with the paradoxical effects of LEV in PWE.


Increased mutation frequency after herpes simplex virus type 2 infection in non-permissive XC cells.
The effect of herpes simplex virus type 2 (HSV-2) infection on the frequency of mutations at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus was studied in the non-permissive XC cell line. When the cells were infected with 20 to 800 p.f.u./cell, there was initially a lag in cell growth and cell death, but after 4 days there was no difference in growth rate between infected and control cultures. However, the mutation frequency, as determined by the number of 6-thioguanine-resistant colonies, was increased in infected cultures by factors ranging from 2.5 to 10.3. This effect was found to be dependent on the multiplicity of infection. The maximum effect was obtained between 20 and 100 p.f.u./cell while further increase in the amount of virus resulted in a drop in the yield of mutants. The optimum multiplicity of infection was a reproducible characteristic but was variable between viral stocks. When a number of mutant clones were examined they were found to have HGPRT activities ranging from undetectable to 6.9% of wild-type, indicating that the mutations were in the HGPRT gene. These results show that, in a non-productive infection, HSV-2 particles can increase the mutation frequency. The possible mechanisms by which this effect is brought about in the host genome are discussed.


Andrographolide, an Antioxidant, Counteracts Paraquat- Induced Mutagenesis in Mammalian Cells.
Paraquat (1,1'-dimethyl, 4,4'-bipyridinium dichloride; PQ), a commonly used herbicide worldwide, is both toxic and mutagenic. The mutagenic effect of PQ stems from its ability to redox-cycle, generating oxidative stress and subsequently oxidative DNA damage, which miscodes when replication is attempted. Andrographolide (AP1), the major constituent in the leaves of the herbaceous plant Andrographis paniculata, is a diterpenoid with reported antioxidant activity. The present study employed the mammalian cell line AS52 to investigate the protective effect of AP1 against PQ-induced mutagenesis. AP1 induced cytotoxicity in AS52 cells in a dose-dependent manner (IC50 = 15.7 µM), which allowed the selection of a non-lethal dose for the mutagenesis studies. While PQ was mutagenic in AS52 cells as evidenced by the increased levels of 6-TGr mutants, AP1 by itself did not increase the mutation frequency. However, co-treatment with AP1 (1-5 µM) or the antioxidant N-acetylcysteine (2 mM) almost completely counteracted the mutagenicity of PQ (10-100 µM) in AS52 cells. Taken together, these findings suggest that AP1, and likely by extension, A. paniculata extracts, are effective antioxidants that can protect against PQ-induced mutations, and thus could be a promising alternative treatment for PQ poisoning.


Piceatannol attenuates behavioral disorder and neurological deficits in aging mice via activating the Nrf2 pathway.
Aging is a complex process that is accompanied by neurological damage. Chronic injection of d-galactose (d-gal) can accelerate the aging process similar to natural aging and is commonly used to build an aging model to investigate aging. In the present study, the effects of piceatannol on d-gal-induced aging in mice were evaluated. Piceatannol treatment showed an observable anti-aging effect. Results obtained in vivo showed that piceatannol retained spontaneous motor activity and enhanced spatial learning and memory abilities in mice in which aging was induced by d-gal. Morphometric analysis displayed that piceatannol prevented d-gal-induced neuronal loss, increased the number of Nissl bodies, and promoted cell proliferation in the hippocampus and cortex. Piceatannol also significantly decreased the level of MDA and elevated SOD and CAT activity in the hippocampal and cortical tissues. Furthermore, western blotting results revealed that piceatannol treatment noticeably reversed the suppression of Nrf2 nuclear translocation and increased the expressions of HO-1 and NOQ1 in mice with aging induced by d-gal. Furthermore, piceatannol activated the Nrf2 pathway in natural aging mice, whereas treatment with the Nrf2 inhibitor brusatol reversed the increased expressions of Nrf2, HO-1, and NOQ1. In conclusion, treatment with piceatannol ameliorates behavioral disorder and brain injury in an aging mouse model; this suggests that piceatannol is a promising pharmaceutical candidate for the treatment of age-associated diseases.


Peginterferon add-on results in more HBsAg decline compared to monotherapy in HBeAg-positive chronic hepatitis B patients.
It is unknown whether peginterferon (PEG-IFN) add-on to entecavir (ETV) leads to more HBsAg decline compared to PEG-IFN monotherapy or combination therapy, and whether ETV therapy may prevent HBsAg increase after PEG-IFN cessation. We performed a post hoc analysis of 396 HBeAg-positive patients treated for 72 weeks with ETV + 24 weeks PEG-IFN add-on from week 24 to 48 (add-on, n = 85), 72 weeks with ETV monotherapy (n = 90), 52 weeks with PEG-IFN monotherapy (n = 111) and 52 weeks PEG-IFN + lamivudine (combination, n = 110) within 2 randomized trials. HBsAg decline was assessed at the end of PEG-IFN (EOP) and 6 months after PEG-IFN (EOF) discontinuation. Differences in baseline characteristics were accounted for using inversed probability of treatment weights. At EOP, a HBsAg reduction of ≥1log10 IU/mL was more frequently achieved for patients in the add-on or combination therapy arms (both 36%), compared to PEG-IFN mono (20%) or ETV (8%) (add-on vs PEG-IFN mono P = 0.050). At EOF, the HBsAg reduction ≥1log10 IU/mL was only sustained in patients treated with ETV consolidation (add-on vs combination and PEG-IFN mono: 40% vs 23% and 18%, P = 0.029 and P = 0.003, respectively). For add-on, combination, PEG-IFN mono and ETV, the mean HBsAg-level change at EOF was -0.84, -0.81, -0.68 and -0.33 log10 IU/mL, respectively (P > 0.05 for PEG-IFN arms). HBeAg loss at EOF was 36%, 31%, 33% and 20%, respectively (P > 0.05). PEG-IFN add-on for 24 weeks results in more on-treatment HBsAg decline than does 52 weeks of PEG-IFN monotherapy. ETV therapy may maintain the HBsAg reduction achieved with PEG-IFN.


An exploration of the views of Australian mothers on promoting child oral health.
An important role for parents and caregivers in the prevention of dental caries in children is the early establishment of health promoting behaviours. This study aimed to examine mothers' views on barriers and facilitators to promoting child and family oral health. Semi-structured interviews were undertaken with a purposive sample of mothers (n = 32) of young children. Inductive thematic analysis was conducted. Parental knowledge and beliefs, past experiences and child behaviour emerged as major influences on children's oral health. Child temperament and parental time pressures were identified as barriers to good oral health with various strategies reported for dealing with uncooperative children at toothbrushing time. Parental oral health knowledge and beliefs emerged as positive influences on child oral health; however, while most mothers were aware of the common causes of dental caries, very few knew of other risk factors such as bedtime feeding. Parents' own oral health experiences were also seen to positively influence child oral health, regardless of whether these were positive or negative experiences. Understanding parental oral health beliefs is essential to overcoming barriers and promoting enablers for good child oral health. Improving child oral health also requires consideration of child behaviour, family influences, and increasing awareness of lesser-known influencing factors.