Abnormal synaptic pruning during adolescence underlying the development of psychotic disorders.
Excessive synaptic pruning has first been suggested by Irwin Feinberg (1982) as an important pillar in the pathophysiology in schizophrenia (SCZ). This article reviews recent developments highlighting factors implicated in aberrant synaptic pruning and its contribution to disease onset and emergence of cognitive symptoms in SCZ. Unraveling these factors provides new insights for potential prevention and treatment strategies for psychotic disorders. Increased pruning in SCZ was recently confirmed by a positron emission tomography-study employing the novel tracer [11C]UCB-J, demonstrating the consequential loss of synaptic density. Recent evidence supports the contributing role of astrocytes and increased complement-mediated microglial pruning in disease onset and cognitive symptoms in SCZ. Increased microglial pruning is mediated specifically by C4. Furthermore, environmental factors (e.g., infections and stress) can lead to dysbiosis which was recently linked to microglial activation and pruning in SCZ. Recent findings render the pruning machinery a potential target for early treatment and prevention in individuals at high risk for SCZ. Minocycline can improve cognition in SCZ, probably by reducing excessive pruning. Probiotics might also have beneficial effects on cognition, although recent findings are not encouraging. N-acetyl-cysteine recovers functional connectivity in SCZ both in vitro and in vivo, making it an interesting candidate.


Frequency and diversity of small cryptic plasmids in the genus Rahnella.
Rahnella is a widely distributed genus belonging to the Enterobacteriaceae and frequently present on vegetables. Although Rahnella has interesting agro-economical and industrial properties and several strains possess antibiotic resistances and toxin genes which might spread within microbial communities, little is known about plasmids of this genus. Thus, we isolated a number of Rahnella strains and investigated their complements of small plasmids. In total 53 strains were investigated and 11 plasmids observed. Seven belonged to the ColE1 family; one was ColE2-like and three shared homology to rolling circle plasmids. One of them belonged to the pC194/pUB110 family and two showed similarity to poorly characterised plasmid groups. The G+C content of two rolling circle plasmids deviated considerably from that of Rahnella, indicating that their usual hosts might belong to other genera. Most ColE1-like plasmids formed a subgroup within the ColE1 family that seems to be fairly specific for Rahnella. Intriguingly, the multimer resolution sites of all ColE1-like plasmids had the same orientation with respect to the origin of replication. This arrangement might be necessary to prevent inappropriate synthesis of a small regulatory RNA that regulates cell division. Although the ColE1-like plasmids did not possess any mobilisation system, they shared large parts with high sequence identity in coding and non-coding regions. In addition, highly homologous regions of plasmids isolated from Rahnella and the chromosomes of Erwinia tasmaniensis and Photorhabdus luminescens could be identified. For the genus Rahnella we observed plasmid-containing isolates at a frequency of 19%, which is in the average range for Enterobacteriaceae. These plasmids belonged to different groups with members of the ColE1-family most frequently found. Regions of striking sequence homology of plasmids and bacterial chromosomes highlight the importance of plasmids for lateral gene transfer (including chromosomal sequences) to distinct genera.


Update on novel therapies for pancreatic neuroendocrine tumors.
Neuroendocrine tumors (NETs) describe a heterogeneous group of tumors with a wide range of morphologic, functional, and behavioral characteristics. Pancreatic neuroendocrine tumors (pNET) are a subset of NETs which are increasing in incidence and prevalence. These tumors are generally slow growing and behave in an indolent fashion. However, when these tumors spread they can be life threatening and difficult to treat with current modalities. In 2011, the landscape of treatment for pNET was changed with the approval of two targeted agents, sunitinib and everolimus, the first new therapies for this disease in over 20 years. Data from these clinical trials and extensive preclinical work into the underlying molecular pathways in neuroendocrine tumors has generated intense interest in the quest to identify additional effective agents in this challenging disease. At the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, several researchers presented updated data regarding the use of targeted agents, alternative chemotherapeutic agents and combinations of these in the treatment of pNET. Corrie et al. (Abstract #4121) reported data from a chemotherapy clinical trial replacing 5-FU with capecitabine and evaluating the addition of cisplatin in NETs. Several authors reviewed the addition of the anti VEGF monoclonal antibody bevacizumab into combination therapy. Ducreux et al (Abstract #4036) presented results from a trial of chemotherapy plus bevacizumab while Firdaus et al. (Abstract #4127) reported the results of combination therapy with octreotide, bevacizumab, and pertuzumab. Hobday et al. (Abstract #4048) reported positive results of an interim analysis of combination therapy with an mTOR inhibitor and bevacizumab. Kulke et al (Abstract #4125) reported the results of a clinical trial utilizing an antibody targeting the insulin growth factor receptor. Finally, Vinik et al. (Abstract #4118) provided updated survival data form the seminal phase III trial that led to approval of sunitinib in the treatment of pNET. The authors review and summarize these abstracts in this article.


Detection of small traumatic hemorrhages using a computer-generated average human brain CT.
Computed tomography is a standard diagnostic imaging technique for patients with traumatic brain injury (TBI). A limitation is the poor-to-moderate sensitivity for small traumatic hemorrhages. A pilot study using an automatic method to detect hemorrhages [Formula: see text] in diameter in patients with TBI is presented. We have created an average image from 30 normal noncontrast CT scans that were automatically aligned using deformable image registration as implemented in Elastix software. Subsequently, the average image was aligned to the scans of TBI patients, and the hemorrhages were detected by a voxelwise subtraction of the average image from the CT scans of nine TBI patients. An experienced neuroradiologist and a radiologist in training assessed the presence of hemorrhages in the final images and determined the false positives and false negatives. The 9 CT scans contained 67 small haemorrhages, of which 97% was correctly detected by our system. The neuroradiologist detected three false positives, and the radiologist in training found two false positives. For one patient, our method showed a hemorrhagic contusion that was originally missed. Comparing individual CT scans with a computed average may assist the physicians in detecting small traumatic hemorrhages in patients with TBI.


Conservation of potential phosphorylation sites in the NS proteins of the New Jersey and Indiana serotypes of vesicular stomatitis virus.
A full length cDNA copy of the NS mRNA of the Missouri strain (Hazelhurst subtype, New Jersey serotype) of vesicular stomatitis virus (VSV) has been cloned and sequenced. The mRNA is 856 nucleotides long (excluding polyadenylic acid) and encodes a protein of 274 amino acids (mol. wt. 31 000). Comparison with the NS gene of the Ogden strain (Concan subtype, New Jersey serotype) showed 15% difference at the nucleotide level and 10% difference at the amino acid level; the majority of the changes were located in the 3' half of the mRNA. Comparison with the NS genes of two strains representing the Indiana serotype showed about 50% nucleotide and 33% amino acid sequence homology between the serotypes. In a four-way comparison of the proteins, two regions of higher homology were noted which may be of functional importance. Eighteen potential phosphorylation sites (Ser or Thr) were conserved between the four proteins; five of these sites correspond to the residues which have been suggested to be constitutively phosphorylated and may be essential for NS activity.


Inheritable nature of enological quantitative traits is demonstrated by meiotic segregation of industrial wine yeast strains.
Wine yeast strains exhibit a wide variability in their technological properties. The large number of allelic variants and the high degree of heterozygosity explain this genetic variability found among the yeast flora. Furthermore, most enological traits are controlled by polygenic systems presenting complex interactions between the alleles. Taking this into account, we hypothesized that the meiotic segregation of such alleles from a given strain might generate a progeny population with very different technological properties. In this work, a population of 50 progeny clones derived from four industrial wine strains of Saccharomyces cerevisiae was characterized for three major enological traits: ethanol tolerance, volatile-acidity production and hydrogen sulphide production. For this purpose, reliable laboratory fermentation tests were developed in accordance with enological practice. A wide variability in the values of the various parameters was found among spore clones obtained after sporulation. Many clones presenting better aptitudes than the parental strains were obtained. Moreover, analysis of the progeny demonstrated that: (1) traits are in part inheritable; (2) traits are clearly polygenic; (3) broad relations of dominance/recessivity can be established. All these findings constitute an initial step for establishing breeding strategies for wine yeast improvement.


Gaps in diagnosing suspected infection in immunocompromised children with cancer: A systematic review.
While the survival of children with cancer has improved over time, infection remains a major morbidity and mortality risk. We conducted a systematic literature review to determine the unmet needs in diagnosing infection in immunocompromised children with cancer. The comprehensive search strategy followed the guidelines established by the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement, and spanned multiple bibliographic databases and other public sources from January 1, 2012 to June 23, 2022. From 5188 records, 34 unique pediatric-focused studies met inclusion criteria. This review highlights the lack of published data on infectious disease testing in pediatric oncology patients, and the need for well-designed clinical impact and cost-effectiveness studies of both existing and novel diagnostic platforms. Such studies are necessary to optimize diagnostic and antimicrobial stewardship, leading to improvement in patient outcomes.


Socioeconomic status and healthcare utilization disparities among children with epilepsy in the United States: Results from a nationally representative sample.
Epilepsy affects 1% of the US population. Healthcare disparities are well-studied among adults with epilepsy but less so among children. We examined whether children with epilepsy (1) have lower income than or (2) utilize the emergency department (ED) differently from children without epilepsy, and (3) if income moderates ED utilization. Data from the 2016-2019 National Survey of Children's Health were used to identify children with active "epilepsy or seizure disorder". Children with versus without epilepsy were compared. Income and ED visits were modeled with logistic and Poisson regressions. This analysis included 131,326 children; 835 were diagnosed with epilepsy. Estimated population prevalence of epilepsy was 0.6%. Children from higher-income-households were less likely to have epilepsy (aOR: 0.7). Children with epilepsy were more likely to visit EDs (aOR = 10.2), see healthcare professionals (aOR: 2.7), and receive care from specialists (aOR: 10.3). Income moderated the relationship between having epilepsy and ED visits. 7.7% of children with epilepsy did not receive needed healthcare. Some barriers were acquiring appointments (aOR: 3.9) and transportation (aOR: 4.7). In conclusion, children with epilepsy were more likely than children without epilepsy to live in lower-income-households, visit EDs, see healthcare professionals, and not receive needed healthcare. Barrier-specific policy interventions may improve medical access for children with epilepsy.


Anxiety-like behavior and intestinal microbiota changes as strain-and sex-dependent sequelae of mild food allergy in mouse models of cow's milk allergy.
A number of studies have reported comorbidity of food allergies with various neuropsychiatric disorders, such as anxiety, depression, attention-deficit hyperactivity disorder, and autism. However, inconsistent results across clinical studies have left the association between food allergy and behavioral disorders inconclusive. We postulated that the heterogeneities in genetic background among allergic cohorts affect symptom presentation and severity of food allergy, introducing bias in patient selection criteria toward individuals with overt physical reactions. To understand the influence of genetic background on food allergy symptoms and behavioral changes beyond anaphylaxis, we generated mouse models with mild cow's milk allergy by sensitizing male and female C57BL/6J and BALB/cJ mice to a bovine whey protein, β-lactoglobulin (BLG; Bos d 5). We compared strain- and sex-dependent differences in their immediate physical reactions to BLG challenge as well as anxiety-like behavior one day after the challenge. While reactions to the allergen challenge were either absent or mild for all groups, a greater number of BLG-sensitized BALB/cJ mice presented visible symptoms and hypothermia compared to C57BL/6J mice. Interestingly, male mice of both strains displayed anxiety-like behavior on an elevated zero maze without exhibiting cognitive impairment with the cross maze test. Further characterization of plasma cytokines/chemokines and fecal microbiota also differentiated strain- and sex-dependent effects of BLG sensitization on immune-mediator levels and bacterial populations, respectively. These results demonstrated that the genetic variables in mouse models of milk allergy influenced immediate physical reactions to the allergen, manifestation of anxiety-like behavior, levels of immune responses, and population shift in gut microbiota. Thus, stratification of allergic cohorts by their symptom presentations and severity may strengthen the link between food allergy and behavioral disorders and identify a population(s) with specific genetic background that have increased susceptibility to allergy-associated behavioral disorders.


Solid acids as fuel cell electrolytes.
Fuel cells are attractive alternatives to combustion engines for electrical power generation because of their very high efficiencies and low pollution levels. Polymer electrolyte membrane fuel cells are generally considered to be the most viable approach for mobile applications. However, these membranes require humid operating conditions, which limit the temperature of operation to less than 100 degrees C; they are also permeable to methanol and hydrogen, which lowers fuel efficiency. Solid, inorganic, acid compounds (or simply, solid acids) such as CsHSO4 and Rb3H(SeO4)2 have been widely studied because of their high proton conductivities and phase-transition behaviour. For fuel-cell applications they offer the advantages of anhydrous proton transport and high-temperature stability (up to 250 degrees C). Until now, however, solid acids have not been considered viable fuel-cell electrolyte alternatives owing to their solubility in water and extreme ductility at raised temperatures (above approximately 125 degrees C). Here we show that a cell made of a CsHSO4 electrolyte membrane (about 1.5 mm thick) operating at 150-160 degrees C in a H2/O2 configuration exhibits promising electrochemical performances: open circuit voltages of 1.11 V and current densities of 44 mA cm-2 at short circuit. Moreover, the solid-acid properties were not affected by exposure to humid atmospheres. Although these initial results show promise for applications, the use of solid acids in fuel cells will require the development of fabrication techniques to reduce electrolyte thickness, and an assessment of possible sulphur reduction following prolonged exposure to hydrogen.


Barriers to addiction treatment among formerly incarcerated adults with substance use disorders.
Addiction treatment improves substance use and criminal recidivism outcomes among justice-involved individuals with substance use disorders, but is underutilized. Although information exists regarding barriers to addiction treatment among individuals with substance use disorders more generally, less is known about barriers among individuals with previous justice involvement. The purpose of this pilot study was to describe barriers to addiction treatment in a sample of adults with a substance use disorder who participated in a pilot trial of brief interventions and were recently released from jail. Incarcerated individuals who were arrested for an alcohol- or drug-related crime and reported moderate or high alcohol use on the ASSIST (n = 28; 96.4% men) were recruited for a pilot trial of brief interventions to reduce substance use, which were delivered just prior to release from jail. After their release, participants completed the Barriers to Treatment Inventory (BTI), which included 25 numerical items and one open-ended question on additional barriers that provided qualitative data. We described frequency of quantitative responses and qualitatively coded open-ended data using seven previously identified domains of the BTI. The most commonly reported barriers assessed quantitatively were items related to Absence of Problem: "I do not think I have a problem with drugs" (42.8%), Privacy Concerns: "I do not like to talk about my personal life with other people" (35.8%), and Admission Difficulty: "I will have to be on a waiting list for treatment" (28.6%). Items related to Negative Social Support (e.g., "Friends tell me not to go to treatment") were rarely endorsed in this sample. Responses to the open-ended question also related to Absence of Problem, Privacy Concerns, and Admission Difficulty. Additional categories of barriers emerged from the qualitative data, including Ambivalence and Seeking Informal Assistance. In this small sample of adults with a substance use disorder recently released from jail, barriers to treatment were frequently endorsed. Future research on larger samples is needed to understand barriers to treatment specific to justice-involved populations. Clinicians may consider using open-ended questions to explore and address barriers to addiction treatment among individuals with current or recent justice involvement.


'It is not going to change his life but it has picked him up': a qualitative study of perspectives on long term oxygen therapy for people with chronic obstructive pulmonary disease.
Long-term oxygen therapy (LTOT) extends life in patients with chronic obstructive pulmonary disease with severe hypoxaemia. Questionnaire-based studies of the effects of LTOT have not suggested uniformly positive findings. The few qualitative studies suggest that patients report benefits but also concerns about dependency on oxygen therapy. The aim of the study was to explore the views and experiences of COPD patients, their carers and the healthcare professionals who deliver these services, on the long-term use of oxygen therapy. Focus groups were conducted with 16 patients with from the LTOT service, six carers, and nine healthcare professionals (n = 31). Eleven patients with COPD, four carers and one staff manager (n = 16) participated in semi-structured interviews. Interviews and focus group were digitally recorded and field notes were taken. Data were analysed using the thematic network analysis approach. Patients and carers reported the benefits of LTOT including increased social activity, perceived improvements in health status and self-management in routine daily activities. Concerns were raised regarding stigma, dependency on LTOT and deterioration in health status. Staff accounts included negative perceptions, suggesting that LTOT was often inappropriately prescribed and under-used but recommended active patient management to address this challenge. LTOT has some beneficial effects in improving daily activities and social interaction of patients with COPD but also some limitations. Increased support and monitoring by healthcare professionals would address some concerns, as would better information for patients, carers and the general public.


Multicenter clinical study for evaluation of efficacy and safety of transdermal fentanyl matrix patch in treatment of moderate to severe cancer pain in 474 chinese cancer patients.
Although a new matrix formulation fentanyl has been used throughout the world for cancer pain management, few data about its efficacy and clinical outcomes associated with its use in Chinese patients have been obtained. This study aimed to assess the efficacy and safety of the new system in Chinese patients with moderate to severe cancer pain. A total of 474 patients with moderate to severe cancer pain were enrolled in this study and were treated with the new transdermal fentanyl matrix patch (TDF) up to 2 weeks. All the patients were asked to record pain intensity, side effects, quality of life (QOL), adherence and global satisfaction. The initial dose of fentanyl was 25 μg/h titrated with opioid or according to National Comprehensive Cancer Network (NCCN) guidelines. Transdermal fentanyl was changed every three days. After 2 weeks. The mean pain intensity of the 459 evaluated patients decreased significantly from 5.63±1.26 to 2.03±1.46 (P<0.0001). The total remission rate was 91.29%, of which moderate remission rate 53.16%, obvious remission rate 25.49% and complete remission rate 12.64%. The rate of adverse events was 33.75%, 18.78% of which were moderate and 3.80% were severe. The most frequent adverse events were constipation and nausea. No fatal events were observed. The quality of life was remarkably improved after the treatment (P<0.0001). The new TDF is effective and safe in treating patients with moderate to severe cancer pain, and can significantly improve the quality of life.


Bioactivated Implant Surfaces Placed in Healed Sites or Extraction Sockets: A Preliminary Experimental Study in Dogs.
To monitor the early bone reaction in a canine model to a conventional sandblasted and dual acid-etched implant surface (ABT), a nanostructured hydrophilic surface (Nano), a dry salt-bioactivated ultra-hydrophilic surface (Hydro), and a bioactivated nanosurface obtained from the addition of dry salts to the Nano surface (Nano-Active). ABT, Nano, Hydro, and Nano-Active implants were placed in 12 dogs. A randomized split-mouth design was adopted. One implant of each type was placed in the mandible 3 months after tooth extraction in healed sites at the first molar region bilaterally. In the same session, the third and fourth premolars were extracted bilaterally and one implant of each type was immediately placed into the extraction socket. The dogs were euthanized at 14 and 28 days following surgery, and the peri-implant bone reaction was assessed histologically using Stevenel's blue and alizarin red in nondecalcified sections. The postoperative healing was uneventful. The 14-day histologic analysis reported nonsignificant results in terms of difference between the groups, while significant results were found 28 days after surgery. In fact, a significantly higher rate of new bone around the implant was reported in the Nano-Active compared to the Nano groups (51.0% ± 10.2% vs 36.0% ± 10.2%) and Hydro compared to the Nano groups (47.3% ± 10.7% vs 36.0% ± 10.2%). The results obtained indicate that new bone formed after 4 weeks demonstrated a tendency for dry salt-treated bioactivated surfaces to improve bone deposition in the interface in the early stages of healing; however, due to the limited number of dogs, the results failed to show a statistical significance. A study with a significantly larger group of animals should be performed in order to challenge the assumption that ultra-hydrophilic-surface implants might show higher bone-implant contact in immediate postextraction replacement.


Scalable Diastereoselective Electrosynthesis of Spiro[benzofuran-2,2'-furan]-3-ones.
Spirobenzofuran scaffolds, because of their three-dimensional structure, are incorporated into several valuable natural products and drug candidate molecules. Herein, with the assistance of electrosynthesis, we introduce a novel electrochemical approach for achieving spirobenzofurans in a user-friendly and operationally simple undivided cell setup under constant current. This metal-catalyst-free electrochemical procedure afforded spiro[benzofuran-2,2'-furan]-3-ones with high diastereoselectivity. Compatibility with gram-scale synthesis along with the convenient accessibility of reaction instruments and starting materials collectively raised the importance of this protocol compared to previous challenging methods. Furthermore, mechanistic cognizance of this reaction is obtained by the investigation of the cyclic voltammetry spectra of reactants.


Retracted: The Nine RNA Methylation Regulatory Gene Signature Is Associated with the Pathogenesis of Atrial Fibrillation by Modulating the Immune Microenvironment in the Atrial Tissues.
[This retracts the article DOI: 10.1155/2023/7277369.].


Cavity-modified collective Rayleigh scattering of two atoms.
We report on the observation of cooperative radiation of exactly two neutral atoms strongly coupled to the single mode field of an optical cavity, which is close to the lossless-cavity limit. Monitoring the cavity output power, we observe constructive and destructive interference of collective Rayleigh scattering for certain relative distances between the two atoms. Because of cavity backaction onto the atoms, the cavity output power for the constructive two-atom case (N=2) is almost equal to the single-emitter case (N=1), which is in contrast to free-space where one would expect an N^{2} scaling of the power. These effects are quantitatively explained by a classical model as well as by a quantum mechanical model based on Dicke states. We extract information on the relative phases of the light fields at the atom positions and employ advanced cooling to reduce the jump rate between the constructive and destructive atom configurations. Thereby we improve the control over the system to a level where the implementation of two-atom entanglement schemes involving optical cavities becomes realistic.


Tyrosyl and cyclic AMP-dependent protein kinase activities in BHK cells that express viral pp60src.
Protein kinase activities were measured in Rous sarcoma virus-infected baby hamster kidney (BHK) cells that express v-src (BHK [v-src]) and compared with those of revertant and control BHK cells. We observed about a fivefold-higher tyrosine phosphorylating activity in BHK (v-src) cell extracts, which was due to src but not other cellular tyrosyl kinase activities since preincubation with anti-src serum reduced the activity to control cell levels. The cyclic AMP-dependent protein kinase activity was also altered when v-src was expressed. Resolution of the two cyclic AMP-dependent isozymes from the detergent-soluble fraction of cells revealed that the type I activity was selectively decreased about fivefold in BHK (v-src) cells.


Transcriptional activity of erythroid Kruppel-like factor (EKLF/KLF1) modulated by PIAS3 (protein inhibitor of activated STAT3).
Erythroid Kruppel-like factor (EKLF or KLF1) is a transcription factor crucial for red cell development that is directly involved in regulation of a large number of erythroid genes. EKLF serves mostly as an activator of expression of these genes; however, it can act also as a repressor. Here, we present evidence that EKLF interacts with proteins from the PIAS (protein inhibitor of activated STAT) family that convey repressive activity to EKLF in the absence of sumoylation. Our studies identify PIAS3 as a transcriptional corepressor of EKLF for at least a subset of its target genes during erythropoiesis (e.g. β-globin, α-hemoglobin stabilizing protein). We demonstrate an interaction between EKLF and PIAS proteins confirmed by in vivo coimmunoprecipitation assays with both exogenous and endogenous proteins. We identified an LXXLL signature motif located near the N terminus of PIAS proteins that, although not involved in the EKLF-PIAS3 interaction, is required for the transrepression activity. Knockdown of endogenous PIAS3 accelerates differentiation of both murine erythroleukemia cells, as well as fetal liver cells, whereas an increase in PIAS3 levels inhibits this increase. Using chromatin immunoprecipitation assays, we show that PIAS3 preferentially occupies the β-globin promoter in undifferentiated murine erythroleukemia cells. Together these results demonstrate that an interaction between EKLF and PIAS3 provides a novel mode of regulation of EKLF activity in the absence of sumolylation and furthermore shows an important involvement of PIAS proteins in erythropoiesis.


The isolation of large quantities of undamaged cellular organelles and cytosolic enzymes using a low-shear continuous tissue homogenizer.
There is often a need to isolate large quantities of subcellular components such as membrane-coated organelles (e.g., nuclei, lysosomes, and mitochondria), cell membranes, and soluble (cytosolic) proteins. Instruments which can homogenize relatively large masses of tissue, primarily those with rapidly rotating blades and cylinders, are excessively vigorous, often resulting in damaged and/or low yields of the subcellular components. This paper describes procedures for obtaining high yields of undamaged subcellular components using a continuous bulk tissue homogenizer which performs with low shear (the low-shear continuous homogenizer or LSC). This homogenizer is simple in operation, durable and can be used with a variety of tissues. Fibrous tissues are more difficult to homogenize using this instrumentation and require a premincing to small pieces (0.2 to 1.0-cm diam) followed by filtration through 2-4 mesh (two to four apertures per inch). Methods for bulk preparations with enhanced recoveries of undamaged nuclei, and a typical soluble multimeric enzyme, phosphofructokinase, are presented. Electron microscope views of the homogenates show the preserved state of the other subcellular components. The LSC homogenizer requires less physical effort with no "hands on" operation and thus is safer. This homogenizer requires less homogenization time compared to the smaller, hand-held Potter-Elvehjem-type homogenizers. Operations requiring low temperature can be performed at room temperature as long as the continuously passing homogenate solutions are kept chilled.


The effects of riverine physical complexity on anadromy and genetic diversity in steelhead or rainbow trout Oncorhynchus mykiss around the Pacific Rim.
This study explored the relationship between riverine physical complexity, as determined from remotely sensed metrics, and anadromy and genetic diversity in steelhead or rainbow trout Oncorhynchus mykiss. The proportion of anadromy (estimated fraction of individuals within a drainage that are anadromous) was correlated with riverine complexity, but this correlation appeared to be driven largely by a confounding negative relationship between drainage area and the proportion of anadromy. Genetic diversity decreased with latitude, was lower in rivers with only non-anadromous individuals and also decreased with an increasing ratio of floodplain area to total drainage area. Anadromy may be less frequent in larger drainages due to the higher cost of migration associated with reaches farther from the ocean, and the negative relationship between genetic diversity and floodplain area may be due to lower effective population size resulting from greater population fluctuations associated with higher rates of habitat turnover. Ultimately, the relationships between riverine physical complexity and migratory life history or genetic diversity probably depend on the spatial scale of analysis.


Glucose-6-phosphate and Ca2+ sequestration are mutually enhanced in microsomes from liver, brain, and heart.
Microsomes prepared from three rat tissues were examined for their ability to import glucose-6-phosphate (G-6-P). Microsomes from liver, which possess a high level of glucose-6-phosphatase activity, were compared with those from cerebral cortex and cardiac muscle, which are not involved in the export of glucose and in which glucose-6-phosphatase activity is relatively low. In all three, a selective permeability to G-6-P was detected by light scattering. However, the sugar-phosphate specificity of the transport process differed. G-6-P was able to enhance ATP-dependent Ca2+ sequestration in all three types of microsomes. In addition, enzymatic detection of G-6-P after the rapid filtration of microsomes determined that, in the absence of Ca2+ and ATP, a level of intramicrosomal G-6-P approaching a passive equilibrium with the extramicrosomal G-6-P concentration was rapidly achieved in all three tissues. However, under conditions in which Ca2+ was being actively accumulated, the intramicrosomal levels of G-6-P exceeded the equilibrium value by three- to fourfold. This enhanced sequestration was not observed in the presence of Ca2+ or ATP alone or in the presence of a Ca2+ ionophore or an inhibitor of the microsomal Ca2+ ATPase. These data are consistent with a selective import pathway into the endoplasmic/sarcoplasmic reticulum for G-6-P independent of glucose-6-phosphatase activity. In addition, they suggest an alternate explanation for the enhanced sequestration of Ca2+ by the endoplasmic/sarcoplasmic reticulum of intact cells seen when extracellular glucose is increased.


Pulse pressure and systolic blood pressure are powerful independent predictors of cardiovascular disease in diabetic adults: results of an 8.4 years follow-up of Tehran Lipid and Glucose Study (TLGS).
To determine the role of different blood pressure (BP) components as predictors of cardiovascular disease (CVD) in diabetic patients. We followed 828 diabetic patients, aged ≥30 years, without baseline CVD and not taking antihypertensive drugs. The hazard ratios (HRs) for CVD were calculated for a 1 standard deviation (SD) change in each BP measure using Cox proportional regression analysis. During median 8.4 year- follow up, 134 CVD events occurred. Systolic BP (SBP), pulse pressure (PP) and mean arterial pressure (MAP) were independent predictors of CVD with multivariate adjusted hazard ratios (HRs) of 1.35, 1.36 and 1.23 respectively (all p<0.05) and similar discriminatory power (C statistics ≈75%). The multivariate models containing MAP plus one other BP component highlighted the significant improvement in the goodness of fit to predict incident CVD (likelihood ratio test =0.01); however this was not so for SBP and PP. In the elderly subjects, only PP and SBP were significantly associated with CVD. The SBP and PP are significant independent predictors of CVD in all diabetic populations (including younger and elder groups) and other BP components did not add to these measures in risk prediction.


Mentoring University Students with ASD: A Mentee-centered Approach.
This study presents a conceptual understanding of how mentorship is experienced by the participants of a mentorship program for university students with Autism Spectrum Disorder. We interviewed the participants of the Autism Mentorship Initiative at Simon Fraser University. A grounded theory approach was used to systematically organize data from interviews and documents to reveal themes that were salient to the mentees (students with autism; n = 9) and mentors (neurotypical students; n = 9). The following five main themes were identified and interrelated under the core theme of A Mentee-centered Approach: (1) The Natural Progression of the Relationship, (2) The Supportive Mentor, (3) The Meeting Process, (4) Identifying and Implementing Goals, and (5) Learning Together. An in-depth analysis of a mentorship process is described.


Spatial patterns of genetic diversity, community composition and occurrence of native and non-native amphipods in naturally replicated tributary streams.
Worldwide, natural communities are invaded by non-native species, with potentially devastating effects on the native communities. A large part of past research aimed at finding traits and characteristics of the invading species or the invaded community explaining observed invasions. Only recently, the focus shifted on the spatial patterns during invasions per se. Empirical data, however, are limited, as invasions are often unique incidences of a complex spatio-temporal process. In order to identify generalities of invasion patterns, we studied 13 naturally replicated tributary streams draining into Lake Constance, and studied the occurrence of native and non-native amphipods along linear transects from the stream outlets to the upstream headwater reaches. We found repeated spatial patterns of community composition and the occurrence of native and non-native amphipod species across two different years. Specifically, occurrence as well as abundance of two non-native amphipod species decreased from the stream outlets at the lake site towards upstream headwater reaches. Populations of the most common native amphipod species were largest at the uppermost headwater reaches. All populations of this native species, however, showed significant signals of recent genetic bottlenecks, irrespective of the stream position and occurrence of non-native species. Contrary to our expectations, this native species also showed no longitudinal genetic differentiation within individual tributaries as postulated for headwater versus outlet populations. Our results indicate that invasions of river-systems may overall follow predictable patterns on the level of spatial distributions and community composition. However, effects of invading organisms on the genetic diversity and genetic structure of native populations observed at larger scales may not necessarily be directly reflected at the scale of smaller tributaries.


Experience of pergolide in the treatment of Chinese parkinsonian patients with dose-related fluctuations.
To improve dose-related fluctuations in patients with Parkinson's disease, the efficacy of pergolide, a long-acting dopamine receptor agonist, was determined. Using a stringent diagnostic criterion for Parkinson's disease, 20 patients were selected for a short-term open-label trial, and were divided into three groups based on the accuracy of clinical diagnosis. Nineteen patients completed the study. The mean dosage of pergolide was 2.89 mg per day. The total motor score improved by 34.1% during the "on" period and by 34.8% during the "off" period (p < 0.001). The recorded daily off time decreased from 40.3% to 11.5% (p < 0.001). There was no statistically significant difference in the magnitude of response among different groups of patients; however, patients with shorter duration of illness also received significantly lower dosage of pergolide. Hallucination, worsening of peak-dose dyskinesia, and lowering of blood pressure were major adverse effects. Pergolide could not prevent the occurrence of neuroleptic malignant syndrome in one patient. Pergolide is very effective for moderate to advanced Parkinson's disease.


Women's decision-making and uptake of services to prevent mother-to-child HIV transmission in Zambia.
Women's empowerment is associated with engagement in some areas of healthcare, but its role in prevention of mother-to-child HIV transmission (PMTCT) services has not been previously considered. In this secondary analysis, we investigated the association of women's decision-making and uptake of health services for PMTCT. Using data from population-based household surveys, we included women who reported delivery in the 2-year period prior to the survey and were HIV-infected. We measured a woman's self-reported role in decision-making in her own healthcare, making of large purchases, schooling of children, and healthcare for children. For each domain, respondents were categorized as having an "active" or "no active" role. We investigated associations between decision-making and specific steps along the PMTCT cascade: uptake of maternal antiretroviral drugs, uptake of infant HIV prophylaxis, and infant HIV testing. We calculated unadjusted and adjusted odds ratios via logistic regression. From March to December 2011, 344 HIV-infected mothers were surveyed and 276 completed the relevant survey questions. Of these, 190 (69%) took antiretroviral drugs during pregnancy; 175 (64%) of their HIV-exposed infants received antiretroviral prophylaxis; and 160 (58%) had their infant tested for HIV. There was no association between decision-making and maternal or infant antiretroviral drug use. We observed a significant association between decision-making and infant HIV testing in univariate analyses (OR 1.56-1.85; p < 0.05); however, odds ratios for the decision-making indicators were no longer statistically significant predictors of infant HIV testing in multivariate analyses. In conclusion, women who reported an active role in decision-making trended toward a higher likelihood of uptake of infant testing in the PMTCT cascade. Larger studies are needed to evaluate the impact of empowerment initiatives on the PMTCT service utilization overall and infant testing in particular.


Cage effect in supercooled molecular liquids: Local anisotropies and collective solid-like response.
Both local geometry and collective extended excitations drive the moves of a particle in the cage of its neighbours in dense liquids. The strength of their influence is investigated by the molecular dynamics simulations of a supercooled liquid of fully flexible trimers with semirigid or rigid bonds. The rattling in the cage is investigated on different length scales. First, the rattling anisotropy due to local order is characterized by two order parameters sensing the monomers succeeding or failing to escape from the cage. Then the collective response of the surroundings excited by the monomer-monomer collisions is considered. The collective response is initially restricted to the nearest neighbours of the colliding particle by a Voronoi analysis revealing elastic contributions. Then the long-range excitation of the farthest neighbours is scrutinised by searching spatially extended correlations between the simultaneously fast displacements of the caged particle and the surroundings. It is found that the longitudinal component has stronger spatial modulation than the transverse one with a wavelength of about one particle diameter, in close resemblance with experimental findings on colloids. It is concluded that the cage rattling is largely affected by solid-like extended modes.


Manganese catalyzed α-methylation of ketones with methanol as a C1 source.
The direct α-methylation of ketones with methanol under hydrogen borrowing conditions using a well-defined manganese PN3P complex as a pre-catalyst was, for the first time, achieved. The reactions typically proceed at 120 °C for 20 h with 3 mol% pre-catalyst loading and in the presence of NaOtBu (50 mol%) as base. The scope of the reaction was extended to the α-methylation of esters.


Flow-dependent versus spreading-like impairment of brain tissue integrity during focal cerebral ischemia and its consequences for neuroprotective strategies.
Focal cerebral ischemic lesions demonstrate a gradual reduction of blood flow from the rim to the core. Flow reduction induces irreversible damage in the core region, whereas more peripheral tissue, i.e. penumbral tissue, is applicable to therapeutic interventions. Secondary mechanisms for lesion growth involve excitotoxicity, extracellular ion shifts, lactate generation, tissue acidosis, inflammation, spreading depolarization and many other processes. These toxic mediators accumulate in the ischemic core and endanger the still viable rim by diffusion or other spreading-like mechanisms, probably in part largely independent from blood flow. A substantial proportion of hemodynamic penumbral tissue could be demonstrated both in experimental settings and in clinical practice, whereas the precise spatial and temporary contribution of secondary mechanisms is much more difficult to investigate in our patients. Diffusion or spreading-mediated neurotoxicity will affect a small rim around the necrotic lesion. Due to the third power of volumetric analysis this would contribute to a large amount in small experimental lesions, but to a negligible amount of tissue in large clinical lesions and could therefore explain the difference in efficacy of neuroprotective strategies between experimental and clinical setups. Therefore, we discuss the likelihood of direct flow-dependent versus diffusion- or spreading-mediated impairment of endangered tissue in focal cerebral ischemia.


Integrin alpha5beta1 supports the migration of Xenopus cranial neural crest on fibronectin.
During early embryonic development, cranial neural crest cells emerge from the developing mid- and hindbrain. While numerous studies have focused on integrin involvement in trunk neural crest cell migration, comparatively little is known about mechanisms of cranial neural crest cell migration. We show that fibronectin, but not laminin, vitronectin, or type I collagen can support cranial neural crest cell migration and segmentation in vitro. These behaviors require both the RGD and "synergy" sites located within the central cell-binding domain of fibronectin. While these two sites are sufficient for cranial neural crest cell migration, we find that the second Heparin-binding domain of fibronectin can provide additional support for cranial neural crest cell migration in vitro. Finally, using a function blocking monoclonal antibody, we show that cranial neural crest cell migration on fibronectin requires the integrin alpha5beta1.


MRSA in lower limb amputation and the role of antibiotic prophylaxis.
Methicillin Resistant Staphylococcus Aureus (MRSA) colonisation is reported in 3-20% of vascular patients. Many develop infective complications. MRSA is associated with poor prognosis. Aim of the study is to assess MRSA in lower limb amputation and efficacy of antibiotic prophylaxis. Prospective study of lower limb amputation. MRSA screen and wound swabs were taken at operation. Antibiotic prophylaxis included teicoplanin (400 mg) 1 dose at operation. Twenty-five patients underwent 33 primary amputations. At operation 15 legs (45%) were colonised with MRSA and 18 legs (58%) had active wound infection; MRSA (4) and other (14). Following surgery 3 patients died. Twenty-two legs (76%) had primary healing. Infection developed in 7 stumps (24%), MRSA (5) and Pseudomonas (2). Stump infection increased time to wound healing (p<0.0001). MRSA stump infection increased revision amputation (p=0.009) and duration of hospital stay (p<0.0074). MRSA wound infection at operation increased the risk of MRSA stump infection (p=0.007). Non-MRSA wound infection at operation was not associated with a worse outcome. No patient colonised with MRSA at operation developed postoperative MRSA stump infection. MRSA is more prevalent that previously reported. MRSA infection has a poor prognosis. Prophylaxis may be effective for patients colonised with MRSA.


Radiologic manifestations of sclerosing cholangitis with emphasis on MR cholangiopancreatography.
Magnetic resonance cholangiopancreatography (MRCP) is a relatively new, noninvasive cholangiographic technique that is comparable with invasive endoscopic retrograde cholangiopancreatography (ERCP) in the detection and characterization of extrahepatic bile duct abnormalities. The role of MRCP in evaluation of the intrahepatic bile ducts, especially in patients with primary or secondary sclerosing cholangitis, is under investigation. The key cholangiographic features of primary sclerosing cholangitis are randomly distributed annular strictures out of proportion to upstream dilatation. As the fibrosing process worsens, strictures increase and the ducts become obliterated, and the peripheral ducts cannot be visualized to the periphery of the liver at ERCP. In addition, the acute angles formed with the central ducts become more obtuse. With further progression, strictures of the central ducts prevent peripheral ductal opacification at ERCP. Cholangiocarcinoma occurs in 10%-15% of patients with primary sclerosing cholangitis; cholangiographic features that suggest cholangiocarcinoma include irregular high-grade ductal narrowing with shouldered margins, rapid progression of strictures, marked ductal dilatation proximal to strictures, and polypoid lesions. Secondary sclerosing and nonsclerosing processes can mimic primary sclerosing cholangitis at cholangiography. These processes include ascending cholangitis, oriental cholangiohepatitis, acquired immunodeficiency syndrome-related cholangitis, chemotherapy-induced cholangitis, ischemic cholangitis after liver transplantation, eosinophilic cholangitis, and metastases.


Chronic administration of udenafil, a selective phosphodiesterase type 5 inhibitor, promotes erectile function recovery in an animal model of bilateral cavernous nerve crush injury.
Preservation of the cavernous nerves (CNs) during radical prostatectomy is crucial for the patient's erectile function. Despite advances in operative technique, the majority of men report compromised erectile function postprostatectomy or complete loss of potency due to CN trauma even with nerve-sparing modifications. This study was designed to investigate whether repeated dosing of udenafil, a phosphodiesterase type 5 inhibitor, helps to improve erectile function after CN injury. Using the CN crush injury model, 8-week-old male Sprague Dawley rats were divided into the following groups; sham-operated group, bilateral CN crush injury exposed to either no udenafil (vehicle) or udenafil (5, 20 mg/kg) daily for two different durations (4 and 8 weeks, p.o.). At both time points, CN electrical stimulation was used to assess erectile function by measuring the intracavernous pressure. The expressions of hypoxia-inducible factor 1-alpha (HIF-1α), transforming growth factor-beta (TGF-β1), nerve growth factor (NGF), endothelin B receptor (ET(B) ), endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and sonic hedgehog homolog (SHH) in penile tissue were examined. Immunohistochemical antibody staining was performed for NGF, eNOS, nNOS, CD31, and alpha-smooth muscle actin (α-SMA). Additionally, terminal deoxynucleotidyl transferase-mediated nick-end labeling assay was performed to quantify apoptosis and the tissue slides were stained for Masson's trichrome to assess the smooth muscle/collagen ratio. Udenafil improved erectile function in a dose- and time-dependent manner with the maximum erectile function recovery achieved by 20 mg/kg udenafil at an 8-week time point. CN injury increased the expression of HIF-1α, TGF-β1, NGF, and ET(B) , however, decreased the expression of eNOS, nNOS, and SHH. Udenafil significantly suppressed these alterations. The results from the histological analyses show that udenafil markedly reduces apoptosis induced by CN injury and augments the smooth muscle/collagen ratio. CN injury induces significantly impaired erectile function and altered gene/protein expression. Chronic administration of udenafil preserves erectile function and has a beneficial role against the pathophysiological consequences of CN injury.


Some vagaries of the lateral epicondyle.
The early roentgenographic characteristics of ossification of the epiphysis of the normal lateral epicondyle may be misinterpreted as being due to trauma. This is primarily due to the shape of the lateral epicondyle and its apparent separation from the associated metaphysis. The following points are noted. (1) The distal part of the epiphysis fuses with the capitellum before the proximal part unites with the adjacent humerus. This frequently results in the physis appearing like a fracture. (2) The epiphysis forms the most distal part of the lateral supracondylar ridge of the humerus. (3) Ossification of the epiphysis begins at the level of the capitellar physis and proceeds first to a typical silver shape and then to a triangular shape. To assist in distinguishing between the roentgenographic appearance of normal ossification and that of a fracture of a lateral epicondyle, various fractures involving the lateral epicondylar epiphysis, the capitellum, and the associated metaphyses are discussed.


Nutritional composition and safety aspects of edible insects.
Insects, a traditional food in many parts of the world, are highly nutritious and especially rich in proteins and thus represent a potential food and protein source. A compilation of 236 nutrient compositions in addition to amino acid spectra and fatty acid compositions as well as mineral and vitamin contents of various edible insects as derived from literature is given and the risks and benefits of entomophagy are discussed. Although the data were subject to a large variation, it could be concluded that many edible insects provide satisfactorily with energy and protein, meet amino acid requirements for humans, are high in MUFA and/or PUFA, and rich in several micronutrients such as copper, iron, magnesium, manganese, phosphorous, selenium, and zinc as well as riboflavin, pantothenic acid, biotin, and in some cases folic acid. Liabilities of entomophagy include the possible content of allergenic and toxic substances as well as antinutrients and the presence of pathogens. More data are required for a thorough assessment of the nutritional potential of edible insects and proper processing and decontamination methods have to be developed to ensure food safety.


Vision-related tasks in children with visual impairment: a multi-method study.
Functional Vision (FV) is vital for the successful growth of children with visual impairment. However, tasks related to measuring FV have not been thoroughly studied for this population. To address this gap, this study seeks to establish a comprehensive set of vision-related tasks that consider both the difficulty levels of activities and the ages of children with visual impairment. This study utilized a sequential multi-method design, including a scoping review, a qualitative content analysis, and a focus group. Firstly, a scoping review was conducted to identify vision-related tasks based on the literature. Then, to contextualize the vision-related tasks, a qualitative content analysis was carried out. Subsequently, a focus group was conducted to categorize the identified tasks based on their difficulty levels and the children's level of dependency. We utilized the directed content analysis method to analyze the data, using the occupational domain of the Occupational Therapy Practice Framework 4th edition (OTPF-4) as the primary framework. During the review phase, which included 22 studies, and the interview phase, which involved 16 participants, a total of 95 and 85 vision-related tasks were identified, respectively. These tasks were then categorized into 17 activities and five occupations, which included activities of daily living (ADL), instrumental activities of daily living (IADL), education, play, and participation in social activities. Among these occupations, ADL was the easiest, while participation in social activities was the most challenging. Finally, the tasks were arranged based on their difficulty level for children with visual impairment. A comprehensive list of vision-related tasks has been developed based on the difficulty level of the tasks and the degree of dependency of children with visual impairment. This list can be used to develop standardized instruments for assessing FV in children with visual impairment.


High-throughput structural biology in drug discovery: protein kinases.
Structural biology is an invaluable tool in modern drug discovery, providing key insights into the interactions of small-molecule drugs with their protein targets. As in many aspects of the drug discovery process, significant synergies can be realized in structural biology by the contemporaneous pursuit of many target proteins from a single structural and functional class. We will review some of those synergies here using the example of the protein kinases--an important class of drug targets that has recently been the subject of intensive study. We conclude by discussing some of the technical advances in X-ray crystallography that have enabled implementation of high-throughput structural biology as applied to drug lead optimization.


Mg2+ deprivation elicits rapid Ca2+ uptake and activates Ca2+/calcineurin signaling in Saccharomyces cerevisiae.
To learn about the cellular processes involved in Mg(2+) homeostasis and the mechanisms allowing cells to cope with low Mg(2+) availability, we performed RNA expression-profiling experiments and followed changes in gene activity upon Mg(2+) depletion on a genome-wide scale. A striking portion of genes up-regulated under Mg(2+) depletion are also induced by high Ca(2+) and/or alkalinization. Among the genes significantly up-regulated by Mg(2+) starvation, Ca(2+) stress, and alkalinization are ENA1 (encoding a P-type ATPase sodium pump) and PHO89 (encoding a sodium/phosphate cotransporter). We show that up-regulation of these genes is dependent on the calcineurin/Crz1p (calcineurin-responsive zinc finger protein) signaling pathway. Similarly to Ca(2+) stress, Mg(2+) starvation induces translocation of the transcription factor Crz1p from the cytoplasm into the nucleus. The up-regulation of ENA1 and PHO89 upon Mg(2+) starvation depends on extracellular Ca(2+). Using fluorescence resonance energy transfer microscopy, we demonstrate that removal of Mg(2+) results in an immediate increase in free cytoplasmic Ca(2+). This effect is dependent on external Ca(2+). The results presented indicate that Mg(2+) depletion in yeast cells leads to enhanced cellular Ca(2+) concentrations, which activate the Crz1p/calcineurin pathway. We provide evidence that calcineurin/Crz1p signaling is crucial for yeast cells to cope with Mg(2+) depletion stress.


[Cytogenetic markers in chronic lymphocytic leukemia].
Recurrent cytogenetic abnormalities observed in chronic lymphocytic leukaemia (CLL) are frequent. They involve the 13q, 11q, 12q, 17p and 6q chromosomal regions, by decreasing order of frequency. These abnormalities can be isolated or associated. They can also appear during the course of the disease. Some of them, as 11q and 17p deletions, give prognostic information for the management of CLL patients.


Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): infection with Equine Herpesvirus-1.
Equine Herpesvirus-1 infection has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of: Article 7 on disease profile and impacts, Article 5 on the eligibility of the disease to be listed, Article 9 for the categorisation of the disease according to disease prevention and control measures as in Annex IV and Article 8 on the list of animal species related to Equine Herpesvirus-1 infection. The assessment has been performed following a methodology composed of information collection and compilation, and expert judgement on each criterion at individual and collective level. The outcome is the median of the probability ranges provided by the experts, which indicates whether the criterion is fulfilled (66-100%) or not (0-33%), or whether there is uncertainty about fulfilment (33-66%). For the questions where no consensus was reached, the different supporting views are reported. According to the assessment performed, Equine Herpesvirus-1 infection can be considered eligible to be listed for Union intervention according to Article 5 of the Animal Health Law with 33-90% certainty. According to the criteria as in Annex IV of the AHL related to Article 9 of the AHL for the categorisation of diseases according to the level of prevention and control, it was assessed with less than 1% certainty that EHV-1 fulfils the criteria as in Section 1 (category A), 1-5% for the criteria as in Section 2 (category B), 10-66% for the criteria as in Section 3 (category C), 66-90% for the criteria as in Section 4 (category D) and 33-90% for the criteria as in Section 5 (category E). The animal species to be listed for EHV-1 infection according to Article 8(3) criteria are the species belonging to the families of Equidae, Bovidae, Camelidae, Caviidae, Cervidae, Cricetidae, Felidae, Giraffidae, Leporidae, Muridae, Rhinocerontidae, Tapiridae and Ursidae.


Specific oral tolerance induction with food in children: transient or persistent effect on food allergy?
The standard treatment of food allergy is elimination of the incriminated food from the diet. Specific oral tolerance induction (SOTI) seems to be a promising approach for a causal treatment; however, it is unclear whether the tolerance achieved is transient or persistent. We report on a subset of three patients of a larger ongoing study who were treated successfully with SOTI treatment, but experienced a secondary loss of tolerance after a period of allergen avoidance. The patients suffered from IgE-mediated allergy either to cow's milk (CM) (patient A) or hen's egg (HE) (patients B and C), confirmed by double-blind, placebo-controlled food challenge (DBPCFC). SOTI treatment was performed at home on a daily basis until tolerance to a maximum of 250 ml CM or 4.5 g lyophilized HE protein was achieved. The daily maintenance dose was 100 ml CM or 2.5 g HE protein. Patients A, B and C reached tolerance to the maximum dose after 37, 41 and 52 weeks, respectively. According to the protocol, patients A and B performed a strict secondary elimination diet for 2 months prior to a follow-up DBPCFC after a maintenance phase of 27 and 39 weeks, respectively. Patient C discontinued treatment for 2 days after 4 weeks on the maintenance dose. Despite previous tolerance, on re-exposure to the allergen all patients experienced moderate systemic allergic reactions. We conclude that SOTI can induce transient tolerance in food allergy, but does not necessarily lead to its permanent abrogation. Regular allergen intake seems necessary to maintain the established tolerance.


Development of Three-Dimensional Dental Scanning Apparatus Using Structured Illumination.
We demonstrated a three-dimensional (3D) dental scanning apparatus based on structured illumination. A liquid lens was used for tuning focus and a piezomotor stage was used for the shift of structured light. A simple algorithm, which detects intensity modulation, was used to perform optical sectioning with structured illumination. We reconstructed a 3D point cloud, which represents the 3D coordinates of the digitized surface of a dental gypsum cast by piling up sectioned images. We performed 3D registration of an individual 3D point cloud, which includes alignment and merging the 3D point clouds to exhibit a 3D model of the dental cast.


A rational approach to employing high plasma levels of antipsychotics for violence associated with schizophrenia: case vignettes.
Forensic psychiatric settings contain a high prevalence of treatment-resistant violent schizophrenia patients. Clozapine therapy has the most robust data for the management of violence in patients with schizophrenia, but for those who cannot tolerate or refuse clozapine, high-dose antipsychotic treatment to high achieve high plasma levels remains a viable option despite limited evidence for efficacy in controlled trials. This article enumerates rational guidelines for employing high plasma level strategies, emphasizing the appropriate interpretation of, and reaction to high plasma antipsychotic levels in these treatment resistant patients, and the need to push treatment to the limits of tolerability or clinical response.


Advanced nursing assistant education program.
Nursing assistants provide 90% of the care to the elderly residents of nursing homes, but are the least educated direct-care employees. Supervisory workers believe that nursing assistants require additional training to meet the increasingly complex needs of nursing home residents. A day-long training program for experienced nursing assistants was provided to supplement their basic education. Using a pre- and posttest design, the effectiveness of the program for knowledge acquisition and application was tested. Future education needs were identified through a gap analysis. There was a significant improvement in knowledge for nursing assistants attending the program. The attendees expressed interest in receiving additional education on dementia and infection control. All attendees identified a problem unique to their facility and were able to plan a detailed intervention and develop outcome measures for that plan. Nursing assistants enrolled in this advanced training program expressed a desire for additional education to help them advance their caregiving skills. Advanced education is one method to increase job satisfaction among nursing assistants that can improve the quality of care for nursing home residents.


Self-organized criticality in spatial evolutionary game theory.
Self-organized criticality is an important framework for understanding the emergence of scale-free natural phenomena. Cellular automata provide simple interesting models in which to study self-organized criticality. We consider the dynamics of a new class of cellular automata which are constructed as natural spatial extensions of evolutionary game theory. This construction yields a discrete one-parameter family of cellular automata. We show that there is a range of parameter values for which this system exhibits complex dynamics with long range correlations between states in both time and space. In this region the dynamics evolve to a self-organized critical state in which structures exist on all time and length scales, and the relevant statistical measures have power law behaviour.


The Endothelial Nitric Oxide Synthase (NOS3-786T>C) Genetic Polymorphism in Chronic Heart Failure: Effects of Mutant -786C allele on Long-term Mortality.
Nitric oxide plays an important role in the regulation of basal vascular tone and cardiac myocyte function. We investigated the NOS3-786T>C polymorphism in chronic heart failure (CHF) and its effects on long-term mortality. Ninety-one patients with CHF who were referred to the Department of Cardiology of Siyami Ersek Cardiovascular and Thoracic Surgery Center for cardiopulmonary exercise testing between April 2001 and January 2004 and 30 controls were enrolled in this study. Patient were followed prospectively for a period of 1 to 12 years. Patients and controls were divided into three groups: TT, TC and CC, according to their NOS3-786T>C polymorphism. We noted that there was no significant difference in the genotype distribution between patients and controls. There was also no significant difference in endothelial nitric oxide synthase (eNOS) gene polymorphism between ischemic HF and nonischemic HF. During the follow-up period, 61 (67%) deaths occurred. The nonsurvivor group had lower left ventricular ejection fraction (LVEF) (p = 0.01), reduced peak oxygen consumption (p = 0.04) and were of older age (p = 0.001). Age, LVEF, peak oxygen consumption and genotype were found to be predictors of mortality (p < 0.05). Additionally, mortality was significantly increased in -786CC genotype patients compared to TT genotype patients (hazard ratio = 2.2; p = 0.03). By multivariate analysis, age and eNOS genotype were determined to be significant independent predictors of death. Additionally, Kaplan-Meier analysis confirmed that homozygote -786C genotype was associated with an increased risk of death (χ2 = 4.6, p = 0.03). Our findings showed that the NOS3-786T>C polymorphism was associated with an increased risk of mortality in patients with CHF.


177Lu-[DOTA0,Tyr3] octreotate therapy in patients with disseminated neuroendocrine tumors: Analysis of dosimetry with impact on future therapeutic strategy.
(177)Lu-(DOTA0,Tyr3) octreotate is a new treatment modality for disseminated neuroendocrine tumors. According to a consensus protocol, the calculated maximally tolerated absorbed dose to the kidney should not exceed 27 Gy. In commonly used dosimetry methods, planar imaging is used for determination of the residence time, whereas the kidney mass is determined from a computed tomography (CT) scan. Three different quantification methods were used to evaluate the absorbed dose to the kidneys. The first method involved common planar activity imaging, and the absorbed dose was calculated using the medical internal radiation dose (MIRD) formalism, using CT scan-based kidney masses. For this method, 2 region of interest locations for the background correction were investigated. The second method also included single-photon emission computed tomography (SPECT) data, which were used to scale the amplitude of the time-activity curve obtained from planar images. The absorbed dose was calculated as in the planar method. The third method used quantitative SPECT images converted to absorbed dose rate images, where the median absorbed dose rate in the kidneys was calculated in a volume of interest defined over the renal cortex. For some patients, the results showed a large difference in calculated kidney-absorbed doses, depending on the dosimetry method. The 2 SPECT-based methods generally gave consistent values, although the calculations were based on different assumptions. Dosimetry using the baseline planar method gave higher absorbed doses in all patients. The values obtained from planar imaging with a background region of interest placed adjacent to the kidneys were more consistent with dosimetry also including SPECT. For the accumulated tumor absorbed dose, the first 2 of the 4 planned therapy cycles made the major contribution. The results suggested that patients evaluated according to the conventional planar-based dosimetry method may have been undertreated compared with the other methods. Hematology and creatinine did not indicate any restriction for a more aggressive approach, which would be especially useful in patients with more aggressive tumors where there is not time for more protracted therapy.


Prevalence, distribution and risk factors of farmer reported swine influenza infection in Guangdong Province, China.
A cross-sectional study was undertaken to better understand the husbandry, management and biosecurity practices of pig farms in Guangdong Province (GD), China to identify risk factors for farmer reported swine influenza (SI) on their farms. Questionnaires were administered to 153 owners/managers of piggeries (average of 7 from each of the 21 prefectures in GD). Univariable and multivariable logistic regression analyses were used to identify risk factors for farmer reported SI in piggeries during the six months preceding the questionnaire administration. The ability of wild birds to enter piggeries (OR 2.50, 95% CI: 1.01-6.16), the presence of poultry on a pig-farm (OR 3.24, 95% CI: 1.52-6.94) and no biosecurity measures applied to workers before entry to the piggery (OR 2.65, 95% CI: 1.04-6.78) were found to increase the likelihood of SI being reported by farmers in a multivariable logistic regression model. The findings of this study highlight the importance of understanding the local pig industry and the practices adopted when developing control measures to reduce the risk of SI to pig farms.


An optimized prime editing system for efficient modification of the pig genome.
Prime editing (PE) is a recent gene editing technology that can mediate insertions or deletions and all twelve types of base-to-base conversions. However, its low efficiency hampers the application in creating novel breeds and biomedical models, especially in pigs and other important farm animals. Here, we demonstrate that the pig genome is editable using the PE system, but the editing efficiency was quite low as expected. Therefore, we aimed to enhance PE efficiency by modulating both exogenous PE tools and endogenous pathways in porcine embryonic fibroblasts (PEFs). First, we modified the pegRNA by extending the duplex length and mutating the fourth thymine in a continuous sequence of thymine bases to cytosine, which significantly enhanced PE efficiency by improving the expression of pegRNA and targeted cleavage. Then, we targeted SAMHD1, a deoxynucleoside triphosphate triphosphohydrolase (dNTPase) that impedes the reverse transcription process in retroviruses, and found that treatment with its inhibitor, cephalosporin C zinc salt (CPC), increased PE efficiency up to 29-fold (4-fold on average), presumably by improving the reverse transcription process of Moloney murine leukemia virus reverse transcriptase (M-MLV RT) in the PE system. Moreover, PE efficiency was obviously improved by treatment with a panel of histone deacetylase inhibitors (HDACis). Among the four HDACis tested, panobinostat was the most efficient, with an efficiency up to 122-fold (7-fold on average), partly due to the considerable HDACi-mediated increase in transgene expression. In addition, the synergistic use of the three strategies further enhanced PE efficiency in PEFs. Our study provides novel approaches for optimization of the PE system and broadens the application scope of PE in agriculture and biomedicine.


Sperm DNA damage causes genomic instability in early embryonic development.
Genomic instability is common in human embryos, but the underlying causes are largely unknown. Here, we examined the consequences of sperm DNA damage on the embryonic genome by single-cell whole-genome sequencing of individual blastomeres from bovine embryos produced with sperm damaged by γ-radiation. Sperm DNA damage primarily leads to fragmentation of the paternal chromosomes followed by random distribution of the chromosomal fragments over the two sister cells in the first cell division. An unexpected secondary effect of sperm DNA damage is the induction of direct unequal cleavages, which include the poorly understood heterogoneic cell divisions. As a result, chaotic mosaicism is common in embryos derived from fertilizations with damaged sperm. The mosaic aneuploidies, uniparental disomies, and de novo structural variation induced by sperm DNA damage may compromise fertility and lead to rare congenital disorders when embryos escape developmental arrest.


The Effects of Cannabis Use: A Test Among Dual Electronic and Combustible Cigarette Users.
Despite greater rates of cannabis use among those that smoke combustible cigarettes, it is currently unknown whether cannabis use is related to e-cigarette dependence or maladaptive beliefs about combustible cigarettes. Therefore, the current study sought to identify whether adult dual users of combustible and e-cigarettes (ie, dual users) who also used cannabis differed from dual users who did not use cannabis on e-cigarette dependence severity, perceived barriers to quitting, and perception of risks and of benefits of e-cigarettes. Participants were 414 current dual users (48.3% female, Mage = 35.1 years, SD = 10.0), 51% of whom were current cannabis users. Dual users who reported current cannabis use evidenced more severe dependence on e-cigarettes (ηp 2 = 0.12), higher perceived barriers for quitting e-cigarettes (ηp 2 = 0.06), and greater perceived benefits (ηp 2 = 0.03) as well as higher perception of risks (ηp 2 = 0.03) for using e-cigarettes. The results were evident after controlling for the variance associated with sex, age, education, income, and frequency of e-cigarette use. Overall, the current findings suggest cannabis may be an important type of substance use behavior that is relevant to e-cigarette dependence and beliefs about use and quitting among adult dual users. The present data extend current understanding of dual users by contextualizing cannabis use within e-cigarette and combustible cigarette use behaviors and highlight a potential substance use behavior that may be targetable in the framework of nicotine cessation. (Am J Addict 2020;00:00-00).


Hemodynamic effects of unloading the old heart.
A reduction in upright exercise capacity with aging in healthy individuals is accompanied by acute left ventricular (LV) dilatation and impaired LV ejection. To determine whether acute vasodilator administration would improve LV ejection during exercise, sodium nitroprusside (NP) was administered to 16 healthy subjects, ages 64-84 yr, who had been screened for the absence of coronary heart disease by prior exercise thallium scintigraphy. Infusion of NP (0. 3-1.0 microgram. kg(-1). min(-1)), titrated to reduce the resting mean arterial pressure 10% (and eliminate the late augmentation of carotid arterial pressure), increased LV ejection fraction (EF) compared with placebo during upright, maximal graded cycle exercise at all work rates and permitted an equivalent stroke volume and stroke work from a smaller end-diastolic volume. The maximum increase in exercise EF in older subjects during NP infusion was equal to that in healthy, younger (22-39 yr) control subjects. The maximum cycle work rate and cardiac index were unchanged compared with placebo. Thus combined preload and afterload reduction with NP in older individuals improves overall LV ejection phase function: exercise LV stroke work is reduced, EF is increased, and stroke volume is maintained in the setting of a reduced ventricular size. These findings suggest that at least some of the age-associated decline in cardiac function during maximal aerobic exercise may be secondary to adverse loading conditions.


Biorefinery via Achmatowicz Rearrangement: Synthesis of Pentane-1,2,5-triol from Furfuryl Alcohol.
A new scalable synthesis of pentane-1,2,5-triol from the furanics platform has been developed. Excellent yields of up to 92 % are obtained under flow conditions by using readily available catalysts from the existing pool. The strategy exploits the highly functionalized Achmatowicz product as a key intermediate, thus circumventing problems related to the low reactivity of the parent furfural and furfuryl alcohol. Besides expanding the portfolio of biomass-derived C5 alcohols, this strategy may also be further applied for the establishment of a versatile bio-based chemical platform.


A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of murine Lmx1b expression.
Nail patella syndrome (NPS) is an autosomal dominant disorder affecting development of the limb, kidney and eye. NPS is the result of heterozygous loss-of-function mutations in the LIM-homeodomain transcription factor, LMX1B. Recent studies suggest that the NPS phenotype may be more extensive than recognized previously including neurologic and neurobehavioral aspects. To determine whether these findings correlated with the expression of Lmx1b during development, an internal ribosomal entry site-LacZ reporter was inserted into the 3'UTR of the endogenous murine gene. The pattern of Lmx1b expression during the development of the limb, eye and kidney correlates with the NPS phenotype. Additional sites of expression were observed in the central nervous system (CNS). The effects of the absence of Lmx1b in the CNS were determined in lmx1b-/- mice by histology and immunocytochemistry. Lmx1b is required for the differentiation and migration of neurons within the dorsal spinal cord. The inability of afferent sensory neurons to migrate into the dorsal horn is entirely consistent with diminished pain responses in NPS patients.


Novel roles of mechanistic target of rapamycin signaling in regulating fetal growth†.
Mechanistic target of rapamycin (mTOR) signaling functions as a central regulator of cellular metabolism, growth, and survival in response to hormones, growth factors, nutrients, energy, and stress signals. Mechanistic TOR is therefore critical for the growth of most fetal organs, and global mTOR deletion is embryonic lethal. This review discusses emerging evidence suggesting that mTOR signaling also has a role as a critical hub in the overall homeostatic control of fetal growth, adjusting the fetal growth trajectory according to the ability of the maternal supply line to support fetal growth. In the fetus, liver mTOR governs the secretion and phosphorylation of insulin-like growth factor binding protein 1 (IGFBP-1) thereby controlling the bioavailability of insulin-like growth factors (IGF-I and IGF-II), which function as important growth hormones during fetal life. In the placenta, mTOR responds to a large number of growth-related signals, including amino acids, glucose, oxygen, folate, and growth factors, to regulate trophoblast mitochondrial respiration, nutrient transport, and protein synthesis, thereby influencing fetal growth. In the maternal compartment, mTOR is an integral part of a decidual nutrient sensor which links oxygen and nutrient availability to the phosphorylation of IGFBP-1 with preferential effects on the bioavailability of IGF-I in the maternal-fetal interface and in the maternal circulation. These new roles of mTOR signaling in the regulation fetal growth will help us better understand the molecular underpinnings of abnormal fetal growth, such as intrauterine growth restriction and fetal overgrowth, and may represent novel avenues for diagnostics and intervention in important pregnancy complications.


Training Intensity Distribution, Training Volume, and Periodization Models in Elite Swimmers: A Systematic Review.
A well-planned periodized approach allows swimmers to achieve peak performance at the major national and international competitions. To identify the main characteristics of endurance training for highly trained swimmers described by the training intensity distribution (TID), volume, and periodization models. The electronic databases Scopus, PubMed, and Web of Science were searched using a comprehensive list of relevant terms. Studies that investigated the effect of the periodization of training in swimming, with the training load (volume, TID) and periodization reported, were included in the systematic review. A total of 3487 studies were identified, and after removal of duplicates and elimination of papers based on title and abstract screening, 17 articles remained. A further 8 articles were excluded after full text review, leaving a final total of 9 studies in the systematic review. The evidence levels were 1b for intervention studies (n = 3) and 2b for (observational) retrospective studies (n = 6). The sprint swimmers typically followed a polarized and threshold TID, the middle-distance swimmers followed a threshold and pyramidal TID, and the long-distance swimmers primarily followed a pyramidal TID. The periodization model identified in the majority of studies selected is characterized by wave-like cycles in units like mesocycles to promote physiological adaptations and skill acquisition. Highly trained swimmers follow a training volume and TID based on their primary event. There is a need for further experimental studies on the effects of block and reverse periodization models on swimming performance. Although observational studies of training have limited evidence, it is unclear whether a different training/periodization approach would yield better results.


Quantitative survey of multiple CpGs from 5 genes identifies CpG methylation panel discriminating between high- and low-grade cervical intraepithelial neoplasia.
Studies of methylation biomarkers for cervical cancer often involved only few randomly selected CpGs per candidate gene analyzed by methylation-specific PCR-based methods, with often inconsistent results from different laboratories. We evaluated the role of different CpGs from multiple genes as methylation biomarkers for high-grade cervical intraepithelial neoplasia (CIN). We applied a mass spectrometry-based platform to survey the quantitative methylation levels of 34 CpG units from SOX1, PAX1, NKX6-1, LMX1A, and ONECUT1 genes in 100 cervical formalin-fixed paraffin-embedded (FFPE) tissues. We then used nonparametric statistics and Random Forest algorithm to rank significant CpG methylations and support vector machine with 10-fold cross validation and 200 times bootstrap resampling to build a predictive model separating CIN II/III from CIN I/normal subjects. We found only select CpG units showed significant differences in methylation between CIN II/III and CIN I/normal groups, while mean methylation levels per gene were similar between the two groups for each gene except PAX1. An optimal classification model involving five CpG units from SOX1, PAX1, NKX6-1, and LMX1A achieved 81.2% specificity, 80.4% sensitivity, and 80.8% accuracy. Our study suggested that during CIN development, the methylation of CpGs within CpG islands is not uniform, with varying degrees of significance as biomarkers. Our study emphasizes the importance of not only methylated marker genes but also specific CpGs for identifying high-grade CINs. The 5-CpG classification model provides a promising biomarker panel for the early detection of cervical cancer.


Cryptosporidiosis of the stomach.
A patient with acquired immune deficiency syndrome who developed symptoms of partial gastric outlet obstruction during the course of a severe diarrheal illness due to cryptosporidiosis is presented. Endoscopic evaluation of the stomach revealed an inflamed pyloric ring and channel with clinical evidence suggestive of partial outlet obstruction. The finding of cryptosporidial organisms on biopsy of the pylorus highlights the potential for diffuse gastrointestinal involvement by this parasite and offers an alternative explanation for the symptoms of nausea and vomiting associated with the diarrheal illness.


The relationship of collagenolytic activity to stage of human colorectal carcinoma.
Collagenolytic enzymes produced by tumor cells are believed to play a significant role in the destruction of surrounding normal tissue and, in certain experimental animal systems, the ability of tumor cells to degrade type-IV collagen (basement membrane collagen) correlates positively with those cells' metastatic capacity. We measured collagenolytic activity levels of extracts from freshly excised colorectal carcinoma tissues and of conditioned media from primary organ culture (total of 114 tissues from 53 patients) by using purified radiolabelled type-I (rat tail) and type-IV (mouse Engelbreth-Holm-Swarm [EHS] sarcoma) collagens. Both type-IV and type-I collagenolytic activity levels of extracts from tumor and adjacent mucosa ranged from less than 1 to 80 ng/hr/mg wet tissue, and no significant differences between mucosa and carcinoma tissues were observed. In conditioned media, the type-IV collagenolytic activity was low for normal mucosa and benign tumors and slightly higher for carcinoma than for mucosa. In 5 of 32 primary tumors, collagenolytic activity levels were 2-5 times higher than in the rest of the tumors and mucosal tissues. There were no significant differences in collagenolytic activity levels of conditioned media and tissue extract from colorectal carcinoma of different Dukes' stages. Deep and superficial areas of primary tumors released similar type-IV collagenolytic activity levels, suggesting that there was little intratumoral heterogeneity in the release of this enzyme.


The learning curve associated with robotic-assisted total hip arthroplasty.
There are no reports examining the learning curve during the adoption of robotic assisted THA. The purpose of this study was to examine the learning curve of robotic assisted THA as measured by component position, operative time, and complications. The first 105 robotic-assisted THAs performed by a single surgeon were divided into three groups based on the order of surgery. Component position, operative time, intra-operative technical problems, and intra-operative complications were recorded. There was a decreased risk of acetabular component malpositioning with experience (P<0.05). Operative time appeared to decrease with increasing surgical experience (P<0.05). A learning curve was observed, as a decreased incidence of acetabular component outliers and decreased operative time were noted with increased experience.


The use of generic and specific quality-of-life measures in hemodialysis patients treated with erythropoietin. The Canadian Erythropoietin Study Group.
The effect of recombinant human erythropoietin (EPO) on the quality of life and exercise capacity of 118 hemodialysis patients was assessed in a randomized, double-masked placebo-controlled trial. Patients were randomized into three groups: 1) placebo, 2) EPO to achieve a hemoglobin of 95-110 g/L and 3) EPO to achieve a hemoglobin of 115-130 g/L. Patients were followed for six months. Quality of life was assessed using a disease-specific measure [the Kidney Disease Questionnaire (KDQ)] and two generic measures [Sickness Impact Profile (SIP) and the Time Trade OFF (TTO)]. The KDQ contains five dimensions. Functional capacity was assessed with a Six-Minute Walk test (SMW) and an Exercise Stress Test (EST). The mean hemoglobin at six months was 74, 102, and 117 gm/l in groups one, two and three, respectively. There was a marked improvement in quality of life with EPO therapy, but no difference between groups 2 and 3. The outcome measure that was the most responsive to change was the KDQ (P less than .001 for the fatigue and physical symptoms dimensions). The aggregate global (P less than .02) and physical (P = .005) scores of the SIP improved with EPO therapy, the psychosocial score did not. There was no improvement in the TTO. There was an improvement in the EST (P = .02) but not in the SMW. The reproducibility of the outcome measures in placebo-treated patients varied between 0.80 and 0.98 (intra-class correlation coefficient). The correlation among the outcome measures at six months was statistically significant in most cases, as was the correlation of change scores between baseline and six months.


Association of plasma tryptophan concentration with periaqueductal gray matter functional connectivity in migraine patients.
Altered periaqueductal gray matter (PAG) functional connectivity contributes to brain hyperexcitability in migraine. Although tryptophan modulates neurotransmission in PAG projections through its metabolic pathways, the effect of plasma tryptophan on PAG functional connectivity (PAG-FC) in migraine has not been investigated yet. In this study, using a matched case-control design PAG-FC was measured during a resting-state functional magnetic resonance imaging session in migraine without aura patients (n = 27) and healthy controls (n = 27), and its relationship with plasma tryptophan concentration (TRP) was assessed. In addition, correlations of PAG-FC with age at migraine onset, migraine frequency, trait-anxiety and depressive symptoms were tested and the effect of TRP on these correlations was explored. Our results demonstrated that migraineurs had higher TRP compared to controls. In addition, altered PAG-FC in regions responsible for fear-cascade and pain modulation correlated with TRP only in migraineurs. There was no significant correlation in controls. It suggests increased sensitivity to TRP in migraine patients compared to controls. Trait-anxiety and depressive symptoms correlated with PAG-FC in migraine patients, and these correlations were modulated by TRP in regions responsible for emotional aspects of pain processing, but TRP did not interfere with processes that contribute to migraine attack generation or attack frequency.


A conformation-selective IR-UV study of the dipeptides Ac-Phe-Ser-NH2 and Ac-Phe-Cys-NH2: probing the SH···O and OH···O hydrogen bond interactions.
The conformational preferences of peptides are mainly controlled by the stabilizing effect of intramolecular interactions. In peptides with polar side chains, not only the backbone but also the side chain interactions determine the resulting conformations. In this paper, the conformational preferences of the capped dipeptides Ac-Phe-Ser-NH2 (FS) and Ac-Phe-Cys-NH2 (FC) are resolved under laser-desorbed jet cooling conditions using IR-UV ion dip spectroscopy and density functional theory (DFT) quantum chemistry calculations. As serine (Ser) and cysteine (Cys) only differ in an OH (Ser) or SH (Cys) moiety; this subtle alteration allows us to study the effect of the difference in hydrogen bonding for an OH and SH group in detail, and its effect on the secondary structure. IR absorption spectra are recorded in the NH stretching region (3200-3600 cm(-1)). In combination with quantum chemical calculations the spectra provide a direct view of intramolecular interactions. Here, we show that both FS as FC share a singly γ-folded backbone conformation as the most stable conformer. The hydrogen bond strength of OH···O (FS) is stronger than that of SH···O (FC), resulting in a more compact gamma turn structure. A second conformer is found for FC, showing a β turn interaction.


Factors affecting mercury release from dental amalgam exposed to carbamide peroxide bleaching agent.
To assess, in vitro, the effects of aging and surface polishing on mercury release from dental amalgams exposed to 10% carbamide peroxide at two pH levels. Samples of fresh and aged amalgam, polished and unpolished, were treated with 10% carbamide peroxide at pH 4.5 and at pH 6.5 for periods of 1, 4, 7, 10 and 13 days. At each time period, mercury concentrations in solution were measured using a cold-vapor atomic absorption mercury analyzer system and compared to control samples treated with phosphate buffer. Amalgam samples exposed to 10% carbamide peroxide released significantly more mercury in solution than samples exposed to phosphate buffer controls. Mercury release was time-dependent and significantly higher in aged amalgam than in fresh amalgam (P < 0.001). Mercury release was also pH-dependent and higher in unpolished amalgam.


[Biology of the papillomavirus infections: V. Vaccine developments].
Several genotypes of human papillomaviruses (HPV) are recognised as aetiologic factors for cervical cancer, and viral DNA account for more 99% of cases. Thus, prevention of HPV infection by, for example, types 16 and 18, should reduce the world-wide incidence of cervical cancer. Many strategies are being developed for the control of HPV-associated lesions of the uterine cervix: prophylactic vaccines which elicit neutralizing antibodies to prevent HPV infection, and therapeutic vaccines which induce a T-cytotoxic response to early viral oncoproteins. Experimental trials are being conducted to test mucosal immunization with an ideal antigen delivery system. Vaccination strategies elicit a protective antibody response in animal species, but in humans, strategies which are likely to be effective in the control of HPV-associated preneoplastic and neoplastic lesions of the uterine cervix are still under investigation.


Coordinating cancer care: patient and practice management processes among surgeons who treat breast cancer.
The Institute of Medicine has called for more coordinated cancer care models that correspond to initiatives led by cancer providers and professional organizations. These initiatives parallel those underway to integrate the management of patients with chronic conditions. We developed 5 breast cancer patient and practice management process measures based on the Chronic Care Model. We then performed a survey to evaluate patterns and correlates of these measures among attending surgeons of a population-based sample of patients diagnosed with breast cancer between June 2005 and February 2007 in Los Angeles and Detroit (N = 312; response rate, 75.9%). Surgeon practice specialization varied markedly with about half of the surgeons devoting 15% or less of their total practice to breast cancer, whereas 16.2% of surgeons devoted 50% or more. There was also large variation in the extent of the use of patient and practice management processes with most surgeons reporting low use. Patient and practice management process measures were positively associated with greater levels of surgeon specialization and the presence of a teaching program. Cancer program status was weakly associated with patient and practice management processes. Low uptake of patient and practice management processes among surgeons who treat breast cancer patients may indicate that surgeons are not convinced that these processes matter, or that there are logistical and cost barriers to implementation. More research is needed to understand how large variations in patient and practice management processes might affect the quality of care for patients with breast cancer.