Green Synthesis, Characterization and Application of Proanthocyanidins-Functionalized Gold Nanoparticles.
Green synthesis of gold nanoparticles using plant extracts is one of the more promising approaches for obtaining environmentally friendly nanomaterials for biological applications and environmental remediation. In this study, proanthocyanidins-functionalized gold nanoparticles were synthesized via a hydrothermal method. The obtained gold nanoparticles were characterized by ultraviolet and visible spectrophotometry (UV-Vis), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and X-ray diffraction (XRD) measurements. UV-Vis and FTIR results indicated that the obtained products were mainly spherical in shape, and that the phenolic hydroxyl of proanthocyanidins had strong interactions with the gold surface. TEM and XRD determination revealed that the synthesized gold nanoparticles had a highly crystalline structure and good monodispersity. The application of proanthocyanidins-functionalized gold nanoparticles for the removal of dyes and heavy metal ions Ni2+, Cu2+, Cd2+ and Pb2+ in an aqueous solution was investigated. The primary results indicate that proanthocyanidins-functionalized gold nanoparticles had high removal rates for the heavy metal ions and dye, which implies that they have potential applications as a new kind of adsorbent for the removal of contaminants in aqueous solution.


Molecular Communication over Gas Stream Channels using Portable Mass Spectrometry.
The synthetic generation/coding and transmission of olfactory information over a gas stream or an odor network is a new and unexplored field. Application areas vary from the entertainment or advertisement industry to security and telemedicine. However, current technological limitations frustrate the accurate reproduction of decoded and transmitted olfactory data. This study describes the development, testing, and characterization of a novel odor emitter (OE) that is used to investigate the generation-encoding of gaseous standards with odorous characteristics with a regulatable way, for scent transmission purposes. The calibration and the responses of a developed OE were examined using a portable quadrupole mass spectrometer (MS). Experiments were undertaken for a range of volatile organic compounds (VOCs) at different temperatures and flow rates. Individual compounds and mixtures were tested to investigate periodic and dynamic transmission characteristics within two different size tubular containers for distances up to 3 m. Olfactory information transmission is demonstrated using MS as the main molecular sensor for odor detection and monitoring and for the first time spatial encryption of olfactory information is shown. Graphical Abstract .


Polyarthritis and anemia in a hemodialysis patient: systemic lupus erythematosus following treatment with interferon alpha.
Autoimmune manifestations may occur with interferon alpha (IFNalpha) therapy. However IFNalpha-induced systemic lupus erythematosus is a rare event. We report a 33-year-old hemodialysis patient who presented polyarthritis and anemia 4 months after initiation of IFNalpha for chronic hepatitis C. Systemic lupus erythematosus was diagnosed. Clinical symptoms improved rapidly with interruption of the treatment and a low-dose steroid therapy. This is the first case of IFN-induced SLE in a hemodialysis patient to confirm the major role of IFNalpha in the lupus physiopathology. Treatment with steroid therapy does not seem to worsen the HCV infection.


Diagnostic and treatment value of XPNPEP3 in acute myocardial infarction.
At present, acute myocardial infarction (AMI) is a serious cardiovascular disease with high morbidity and mortality. Discovering biomarkers of AMI is important for clinical diagnosis and needs. Therefore, this study aimed to elucidate the role of XPNPEP3 as a potential biomarker for AMI. Expression profiling data were downloaded for AMI patients and healthy patients in the GSE24548 and GSE24519 datasets, respectively. The limma package in R was conducted to determine differentially expressed microRNA (DEmiRNA)/messenger RNA (mRNA) [differentially expressed genes (DEGs)]. TargetScan and Cytoscape were used to build regulatory network of miRNA-mRNA. The Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) were applied to determine immune cell score. The gene set variation analysis (GSVA) package was used to calculate pathway score. Key drugs were determined by protein-protein interaction (PPI) and molecular docking. Totals of 36 DEmiRNAs and 63 DEGs were determined in the GSE24584 dataset and GSE24519 dataset, respectively, and then we constructed a miRNA-mRNA network including 31 DEmiRNAs and 47 DEGs. The correlation analysis between immune cells and 47 DEGs identified that XPNPEP3 was most associated with AMI. Furthermore, XPNPEP3 was negatively correlated with inflammatory response score. A diagnosis model based on XPNPEP3 expression showed an area under the curve (AUC) of 93.38%, and 159 genes were highly correlated with XPNPEP3. Molecular docking analysis showed that DB06909 had the lowest docking score with XPNPEP3, revealing it to be a potential XPNPEP3 inhibitor. This work discovered that XPNPEP3 is correlated with the development of AMI. These findings may provide theoretical basis for the diagnosis and treatment of AMI.


Lessons Learned from Development of De-identification System for Biomedical Research in a Korean Tertiary Hospital.
The Korean government has enacted two laws, namely, the Personal Information Protection Act and the Bioethics and Safety Act to prevent the unauthorized use of medical information. To protect patients' privacy by complying with governmental regulations and improve the convenience of research, Asan Medical Center has been developing a de-identification system for biomedical research. We reviewed Korean regulations to define the scope of the de-identification methods and well-known previous biomedical research platforms to extract the functionalities of the systems. Based on these review results, we implemented necessary programs based on the Asan Medical Center Information System framework which was built using the Microsoft. NET Framework and C#. The developed de-identification system comprises three main components: a de-identification tool, a search tool, and a chart review tool. The de-identification tool can substitute a randomly assigned research ID for a hospital patient ID, remove the identifiers in the structured format, and mask them in the unstructured format, i.e., texts. This tool achieved 98.14% precision and 97.39% recall for 6,520 clinical notes. The search tool can find the number of patients which satisfies given search criteria. The chart review tool can provide de-identified patient's clinical data for review purposes. We found that a clinical data warehouse was essential for successful implementation of the de-identification system, and this system should be tightly linked to an electronic Institutional Review Board system for easy operation of honest brokers. Additionally, we found that a secure cloud environment could be adopted to protect patients' privacy more thoroughly.


Genomic variation among avian rotavirus-like viruses detected by polyacrylamide gel electrophoresis.
The genomes of five turkey and two chicken rotavirus-like virus (RVLV) strains were compared with the genome of a reference turkey RVLV strain by co-electrophoresis in polyacrylamide gels. The genomes of these avian RVLV strains could be distinguished from the reference strain genome by differences in the mobilities of from three to 10 segments.


Adeno-associated viral vector serotype 5 poorly transduces liver in rat models.
Preclinical studies in mice and non-human primates showed that AAV serotype 5 provides efficient liver transduction and as such seems a promising vector for liver directed gene therapy. An advantage of AAV5 compared to serotype 8 already shown to provide efficient correction in a phase 1 trial in patients suffering from hemophilia B, is its lower seroprevalence in the general population. Our goal is liver directed gene therapy for Crigler-Najjar syndrome type I, inherited severe unconjugated hyperbilirubinemia caused by UGT1A1 deficiency. In a relevant animal model, the Gunn rat, we compared the efficacy of AAV 5 and 8 to that of AAV1 previously shown to be effective. Ferrying a construct driving hepatocyte specific expression of UGT1A1, both AAV8 and AAV1 provided an efficient correction of hyperbilirubinemia. In contrast to these two and to other animal models AAV5 failed to provide any correction. To clarify whether this unexpected finding was due to the rat model used or due to a problem with AAV5, the efficacy of this serotype was compared in a mouse and two additional rat strains. Administration of an AAV5 vector expressing luciferase under the control of a liver specific promoter confirmed that this serotype poorly performed in rat liver, rendering it not suitable for proof of concept studies in this species.


A reverse Warburg metabolism in oral squamous cell carcinoma is not dependent upon myofibroblasts.
The reverse Warburg effect describes the phenomenon that epithelial cancer cells take advantage of the metabolic machinery from nearby cancer-associated fibroblast, inducing them to produce lactate and ketones to fuel the high metabolic demands of the epithelial tumour tissues. This is in breast cancer observed as a lack of stromal caveolin-1 (CAV-1) and an increased expression of monocarboxylate transporter 4 (MCT-4) in the tumour stroma, with a concomitant increase in the expression of monocarboxylate transporter 1 (MCT-1) in the epithelial, tumour compartment. The lack of CAV-1 and increased expression of MCT-4 have been shown to have prognostic importance, primarily in patients with breast cancer. However, this phenomenon has only scarcely been described in oral squamous cell carcinoma (OSCC). Given the prognostic importance of myofibroblasts in OSCC, we also examined a potential relationship between the expression of MCT-4 and the presence of myofibroblasts. Paraffin-embedded tissues from 30 patients with OSCC were immunostained with antibodies towards MCT-1, MCT-4, Cav-1, GLUT-1, α-SMA, TOMM20 and KI-67, and evaluated for their specific epithelial and stromal expression. In patients with OSCC, we find an increased expression of MCT-1 and MCT-4 in both the epithelial and stromal compartment, with almost no overlap in their spatial expression. We found a large spatial overlap between α-SMA and MCT-1 in the stroma compartment, but no relationship between MCT-4 and myofibroblasts. Interestingly, we did not observe any relationship between the absence of CAV-1 and the presence of MCT-4 as has been shown in breast carcinomas.


An iPhone application for upper arm posture and movement measurements.
There is a need for objective methods for upper arm elevation measurements for accurate and convenient risk assessments. The aims of this study were (i) to compare a newly developed iOS application (iOS) for measuring upper arm elevation and angular velocity with a reference optical tracking system (OTS), and (ii) to compare the accuracy of the iOS incorporating a gyroscope and an accelerometer with using only an accelerometer, which is standard for inclinometry. The iOS-OTS limits of agreement for static postures (9 subjects) were -4.6° and 4.8°. All root mean square differences in arm swings and two simulated work tasks were <6.0°, and all mean correlation coefficients were >0.98. The mean absolute iOS-OTS difference of median angular velocity was <13.1°/s, which was significantly lower than only using an accelerometer (<43.5°/s). The accuracy of this iOS application compares well to that of today's research methods and it can be useful for practical upper arm measurements.


Assessment of Disease Activity in Takayasu Arteritis: Potential Role of Contrast-Enhanced Ultrasound.
To assess the diagnostic value of intima media thickness measurements and contrast-enhanced ultrasound (CEUS) of the supraaortic arteries in the assessment of disease activity in Takayasu arteritis (TA). Patients with TA and involvement of the carotid and/or subclavian/axillary arteries underwent CEUS imaging in addition to B-mode and color duplex ultrasound. The maximum IMT (mIMT) was measured and high-resolution CEUS of the most prominently thickened vessel segment was performed. Two blinded readers reviewed the CEUS movies, with semiquantitative assessment of microbubble enhancement of the arterial wall (grade 0: no or minimal; grade 1: moderate; grade 2: pronounced). Clinical symptoms, acute phase reactants, and established indices of clinical disease activity (NIH criteria, ITAS score) were recorded. 40 examinations in 17 patients were analyzed. According to clinical judgement, 27 and 13 cases were classified as clinically inactive and active, respectively. An mIMT-cutoff of > 2.7 mm identified active disease with a sensitivity and specificity of 69.2 % and 88.9 %, respectively (area under the curve 0.83). The interobserver agreement of CEUS analysis was substantial (Cohen's kappa 0.76). By consensus reading, 17, 15, and 8 cases were classified as uptake grade 0, grade 1 and grade 2, respectively. Grade 0 uptake was exclusively present in 17 clinically inactive patients. Grade 1 uptake was seen in 10 patients with clinically inactive disease and 5 patients with clinically active disease. Grade 2 uptake was exclusively present in 8 patients with active disease. Both sonographic IMT measurements and high-resolution CEUS are promising in the ad-hoc assessment of disease activity in patients with TA.


Some effects of teaching undergraduate medical students on general practitioner thinking and learning.
This study examined the processes of thinking and learning undertaken by general practitioners (GPs, family physicians) brought about by the presence of undergraduate medical students. A qualitative study was undertaken using critical incident templates (a novel approach in this context) and focus groups. Data were analysed thematically, with iterative discussion between members of the study team after independent analysis. Thirty-eight critical incident templates were returned (40%), of which 27 (28%) were completed. Three themes were identified: challenges to the GP's thinking or learning behaviour (these included having to justify actions and answer questions); changes to the dynamic between doctor and patient (listening to discussion of their condition between doctor and student was reported to change the patient's experience); and additions to the GP's workload. Teaching made GPs' day longer and sometimes caused friction with colleagues. Our data elucidate a range of thinking and learning activities that are brought about by the presence of a student in a GP's consulting room. They show that there are a number of challenges that stimulate these activities. We recommend that undergraduate teaching in general practice be given greater recognition for the stimulus it provides for continuing professional development.


Evidence in oral health promotion-implications for oral health planning.
I have explored the debates on evidence-based oral health promotion and examined the practicality of promoting oral health care within a whole system (social, cultural, and environmental) approach. The use of evidence-based decision-making in health services and planning is a viable mechanism to identify optimal health benefits; however, barriers to the effective adoption of evidence-based health practice, including barriers that apply to oral health promotion, have been identified. Evidence-based oral health promotion highlights the importance of examining health promotion activities within a defined social context-a departure from the focus on improving study designs and research methods. Thus, the basis for evidence in health activities is grounded in social and organizational systems. This could contribute to sustainable health efforts.


Endoscope-Assisted Abscess Drainage Secondary to Endoscope-Assisted Transforaminal Lumbar Interbody Fusion: 1-Year Follow-Up.
Endoscopic discectomy and fusions have been gaining popularity in the recent past and are noted to be safe for their application in elderly population. The procedure involves ultra-small incision for discectomy followed by placement of percutaneous screws in awake patients. Treatment of advanced spinal pathology with endoscope-assisted techniques is challenging. Although not common with the endoscopic approach, postoperative infection can be problematic, as there are no established guidelines on its management. A 76-year-old female patient underwent lumbar 4-5 endoscopic-assisted transforaminal lumbar interbody fusion for severe degenerative changes leading to back and radicular leg pain. She did well postoperatively and was discharged home the following day. She presented to the outside hospital with new onset of severe back pain, sepsis, and positive methicillin-susceptible Staphylococcus aureus with blood culture and demonstrated no improvement while on antibiotics. Initial magnetic resonance imaging revealed postoperative changes only. With positive blood culture and localized pain, she was then offered to undergo a percutaneous drainage of the abscess. Under local anesthesia and intravenous sedation, a small pocket of collection was found along the endoscopic trajectory from previous surgery. After evacuation of the collection, the interbody device was irrigated with vancomycin through endoscope. Postoperatively, immediate symptomatic improvement was noted in back pain. She was discharged home on oxacillin and continues to do well at 12 months' follow-up with excellent fusion. The present case illustrates the successful treatment of a surgical-site infection after endoscope-assisted transforaminal lumbar interbody fusion via a repeat percutaneous endoscopic approach.


Summary of information on human CYP enzymes: human P450 metabolism data.
This chapter is an update of the data on substrates, reactions, inducers, and inhibitors of human CYP enzymes published previously by Rendic and DiCarlo (1), now covering selection of the literature through 2001 in the reference section. The data are presented in a tabular form (Table 1) to provide a framework for predicting and interpreting the new P450 metabolic data. The data are formatted in an Excel format as most suitable for off-line searching and management of the Web-database. The data are presented as stated by the author(s) and in the case when several references are cited the data are presented according to the latest published information. The searchable database is available either as an Excel file (for information contact the author), or as a Web-searchable database (Human P450 Metabolism Database, www.gentest.com) enabling the readers easy and quick approach to the latest updates on human CYP metabolic reactions.


Remittances and migration--the commerce of movement.
"This paper comments upon the role of remittances in a variety of emigrant situations, traces the way remittance patterns change over time and evaluates the importance of remittance payments for personal and national economies. It considers the concept of 'remittance-societies" in the South Pacific and elsewhere, and briefly examines the various mechanisms involved in the emigration-remittance cycle, including the expectation of interactions and interdependence that exists between migrants and their home-based kin, and the sacrifices and hardships often endured by many migrants to meet obligations back home."


Stimulant intolerance in children with Angelman syndrome with hyperactivity: a case series.
Angelman syndrome is a neurogenetic disorder resulting from the loss of expression of the ubiquitin-protein ligase E3A gene on chromosome 15. Problematic behaviors including attention-deficit/hyperactivity disorder (ADHD) symptoms of hyperactivity, impulsivity and inattention are highly prevalent in Angelman syndrome. The efficacy, safety and tolerability of stimulant medications in children with Angelman syndrome for the treatment of ADHD symptoms have not been previously reported. We describe three boys with Angelman syndrome who were treated with open-label stimulant medications for ADHD symptoms. Stimulant medications were highly intolerable, and treatment had to be discontinued after limited dosing in all three cases due to marked increases in hyperactivity and impulsivity along with worsened distractibility. The findings of this study suggest that stimulant medications may be ineffective and poorly tolerated in children with Angelman syndrome.


Rapid activation of the complement system by cuprophane depends on complement component C4.
Hemodialysis with cuprophane dialyzer membranes promotes rapid activation of the complement system, which is thought to be mediated by the alternative pathway. Complete hereditary deficiency of complement C4, a classical pathway component, in two hemodialysis patients provided the opportunity to investigate a possible role of the classical pathway. In two hemodialysis patients with both C4 isotypes, C4A and C4B, and in one patient with C4B deficiency complement activation occurred immediately after the onset of hemodialysis, with peak levels of C3a and terminal complement complex (TCC) after ten to fifteen minutes. In patients with complete C4 deficiency, C3a and TCC remained unchanged for fifteen minutes and increased thereafter, reaching the highest level after thirty minutes. The leukocyte nadir was also delayed from fifteen to thirty minutes. In vitro incubation of normal, C4A- or C4B-deficient serum with cuprophane caused complement activation after fifteen minutes. In contrast, no activation was observed in sera of four C4-deficient patients. The addition of normal serum or purified human C4 restored the capacity for rapid complement activation. In one patient with severe immunoglobulin deficiency, C3a and TCC levels increased only moderately after 25 minutes of cuprophane dialysis. This patient's serum also exhibited delayed complement activation in vitro, which was normalized after pretreatment of cuprophane with immunoglobulins. Preincubation of normal serum with MgEGTA, a blocker of the classical pathway, inhibited rapid complement activation through cuprophane. As basal levels of C4a are markedly increased in hemodialysis patients (3450 +/- 850 ng/ml) compared to healthy controls (224 +/- 81 ng/ml), no further elevation of C4a was detectable during cuprophane hemodialysis. Incubation of normal serum with cuprophane, however, caused a slight increase in C4a after five minutes. These results indicate that the initial deposition of complement C3b on the cuprophane membrane, necessary for activation of the amplification loop of the alternative pathway, is mediated by the classical pathway C3-convertase C4b2a. We propose an extended concept of complement activation through cuprophane, which is based on four steps: (a) binding of anti-polysaccharide antibodies, (b) classical pathway activation, (c) alternative pathway activation and (d) terminal pathway activation.


Ceftriaxone: an update of its use in the management of community-acquired and nosocomial infections.
Ceftriaxone is a parenteral third-generation cephalosporin with a long elimination half-life which permits once-daily administration. It has good activity against Streptococcus pneumoniae, methicillin-susceptible staphylococci, Haemophilus influenzae, Moraxella catarrhalis and Neisseria spp. Although active against Enterobacteriaceae, the recent spread of derepressed mutants which hyperproduce chromosomal beta-lactamases and extended-spectrum beta-lactamases has diminished the activity of all third-generation cephalosporins against these pathogens necessitating careful attention to sensitivity studies. Extensive data from randomised clinical trials confirm the efficacy of ceftriaxone in serious and difficult-to-treat community-acquired infections including meningitis, pneumonia and nonresponsive acute otitis media. Ceftriaxone also has efficacy in other community-acquired infections including uncomplicated gonorrhoea, acute pyelonephritis and various infections in children. In the nosocomial setting, extensive data also confirm the efficacy of ceftriaxone with or without an aminoglycoside in serious Gram-negative infections, pneumonia, spontaneous bacterial peritonitis and as surgical prophylaxis. Outpatient use of ceftriaxone, either as part of a step-down regimen or parenterally, is a distinguishing feature of the data gathered on the agent over the last decade. The review focuses on new applications of the drug and its use in infections in which the causative pathogens or their resistance patterns have changed over the past decade. Ceftriaxone has a good tolerability profile, the most common events being diarrhoea, nausea, vomiting, candidiasis and rash. Ceftriaxone may cause reversible biliary pseudolithiasis, notably at higher dosages of the drug (>/=2 g/day); however, the incidence of true lithiasis is <0.1%. Injection site discomfort or phlebitis can occur after intramuscular or intravenous administration. As a result of its strong activity against S. pneumoniae, ceftriaxone holds an important place, either alone or as part of a combination regimen, in the treatment of invasive pneumococcal infections, including those with reduced beta-lactam susceptibility. Its once-daily administration schedule allows simplification of otherwise complex regimens in a hospital setting and has also contributed to its popularity as a parenteral agent in an ambulatory setting. These properties, together with a well characterised tolerability profile, mean that ceftriaxone is likely to retain its place as an important third-generation cephalosporin in the treatment of serious community-acquired and nosocomial infections.


Copper--alumina--organic matter mixed systems: alumina transformation and copper speciation as revealed by EPR spectroscopy.
The chemical forms and solubility of Cu in alumina-organic matter systems were studied separately (Cu/Al and Cu/OM) and in mixtures (Cu/Al/OM) during long-term (up to 8 years) equilibrations at pH 6 and 7.5. The transformation of alumina was monitored by XRD, while the chemical forms of Cu were probed by EPR spectroscopy. Total dissolved Cu was determined by voltammetry. Alumina transformation to gibbsite was more rapid and complete in the Cu/Al system equilibrated at pH 7.5 than at pH 6. The presence of colloidal organic matter (Cu/Al/OM) retarded the transformation of alumina. This effect was more pronounced in the system aged at pH 7.5, likely due to the higher pH that promotes formation of Al3+--organic matter coordination complexes. As expected, the systems at pH 7.5 resulted in lower dissolved Cu concentrations than corresponding systems at pH 6. After long-term equilibrations (8 and 5 years) at pH 6 and 7.5, however, the alumina-containing coprecipitates resulted in the lowest concentrations of Cu in solution (Cu/Al < Cu/Al/OM < Cu/OM). Analyses by EPR spectroscopy indicated that Cu forms inner-sphere complexes in all systems at both pH values. Changes in the chemical forms of coprecipitated Cu (Cu/Al and Cu/Al/OM systems) occurred with time and included Cu occupying discrete sites where Cu-O-Al bond formation was dominant followed by formation of clusters (Cu-O-Cu associations) and in some cases precipitates. The anisotropic EPR parameters of the Cu/OM systems suggested that stronger interactions exist between Cu and organic matter functional groups as compared to Cu interactions with alumina-containing coprecipitates; yet, Cu solubility was highest in the Cu/OM systems. The geochemical processes described in this investigation may be effective in forest soils and wastewater treatment plants where Al and Fe salts are used as flocculation agents and to remove metal contaminants from solution.


Gap junctions and ovarian folliculogenesis.
Gap junctions are collections of intercellular membrane channels that allow adjacent cells to share small molecules (< 1 kDa). Gap junction channels are composed of connexins, a homologous family of more than 20 proteins. In developing follicles, gap junctions couple the growing oocyte and its surrounding follicle cells into a functional syncytium. This review summarizes evidence on the expression of various connexins in developing follicles and the likely roles that some of the connexins play, on the basis of findings from gene targeting experiments in mice. Gap junctions between cumulus cells contain predominantly connexin43, and this connexin has also been detected using immunoelectron microscopy in a small minority of gap junctions at the oocyte surface. The importance of connexin43 for granulosa cell function is demonstrated by the fact that follicles lacking this connexin arrest in early preantral stages and produce incompetent oocytes. Connexin37 appears to be the only connexin contributed by oocytes to the gap junctions coupling them with granulosa cells, and loss of this connexin interferes with the development of antral follicles. The expression of multiple connexins in developing follicles is thus likely to reflect the multiple functions served by gap junctional communication in folliculogenesis.


Differentiation and transdifferentiation potentials of cancer stem cells.
Tumor cells actively contribute to constructing their own microenvironment during tumorigenesis and tumor progression. The tumor microenvironment contains multiple types of stromal cells that work together with the extracellular matrix and local and systemic factors to coordinately contribute to tumor initiation and progression. Tumor cells and their stromal compartments acquire many genetic and/or epigenetic alternations to facilitate tumor growth and metastasis. The cancer stem cell (CSC) concept has been widely applied to interpreting tumor initiation, growth, metastasis, dormancy and relapse. CSCs have differentiation abilities to generate the original lineage cells that are similar to their normal stem cell counterparts. Interestingly, recent evidence demonstrates that CSCs also have the potential to transdifferentiate into vascular endothelial cells and pericytes, indicating that CSCs can transdifferentiate into other lineage cells for promoting tumor growth and metastasis in some tissue contexts instead of only recruiting stromal cells from local or distant tissues. Although the transdifferentiation of CSCs into tumor stromal cells provides a new dimension that explains tumor heterogeneity, many aspects of CSC transdifferentiation remain elusive. In this review, we summarize the multi-lineage differentiation and transdifferentiation potentials of CSCs as well as discuss their potential contributions to tumor heterogeneity and tumor microenvironment in tumor progression.


Heat waves in the United States: definitions, patterns and trends.
High temperatures and heat waves are related but not synonymous concepts. Heat waves, generally understood to be acute periods of extreme warmth, are relevant to a wide range of stakeholders because of the impacts that these events have on human health and activities and on natural environments. Perhaps because of the diversity of communities engaged in heat wave monitoring and research, there is no single, standard definition of a heat wave. Experts differ in which threshold values (absolute versus relative), duration and ancillary variables to incorporate into heat wave definitions. While there is value in this diversity of perspectives, the lack of a unified index can cause confusion when discussing patterns, trends, and impacts. Here, we use data from the North American Land Data Assimilation System to examine patterns and trends in 15 previously published heat wave indices for the period 1979-2011 across the Continental United States. Over this period the Southeast region saw the highest number of heat wave days for the majority of indices considered. Positive trends (increases in number of heat wave days per year) were greatest in the Southeast and Great Plains regions, where more than 12 % of the land area experienced significant increases in the number of heat wave days per year for the majority of heat wave indices. Significant negative trends were relatively rare, but were found in portions of the Southwest, Northwest, and Great Plains.


Quantitative proteomic and phosphoproteomic analyses of the hippocampus reveal the involvement of NMDAR1 signaling in repetitive mild traumatic brain injury.
The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive impairment. This cognitive impairment is thought to result specifically from damage to the hippocampus. In this study, we detected cognitive impairment in mice 6 weeks after repetitive mild traumatic brain injury using the novel object recognition test and the Morris water maze test. Immunofluorescence staining showed that p-tau expression was increased in the hippocampus after repetitive mild traumatic brain injury. Golgi staining showed a significant decrease in the total density of neuronal dendritic spines in the hippocampus, as well as in the density of mature dendritic spines. To investigate the specific molecular mechanisms underlying cognitive impairment due to hippocampal damage, we performed proteomic and phosphoproteomic analyses of the hippocampus with and without repetitive mild traumatic brain injury. The differentially expressed proteins were mainly enriched in inflammation, immunity, and coagulation, suggesting that non-neuronal cells are involved in the pathological changes that occur in the hippocampus in the chronic stage after repetitive mild traumatic brain injury. In contrast, differentially expressed phosphorylated proteins were mainly enriched in pathways related to neuronal function and structure, which is more consistent with neurodegeneration. We identified N-methyl-D-aspartate receptor 1 as a hub molecule involved in the response to repetitive mild traumatic brain injury , and western blotting showed that, while N-methyl-D-aspartate receptor 1 expression was not altered in the hippocampus after repetitive mild traumatic brain injury, its phosphorylation level was significantly increased, which is consistent with the omics results. Administration of GRP78608, an N-methyl-D-aspartate receptor 1 antagonist, to the hippocampus markedly improved repetitive mild traumatic brain injury-induced cognitive impairment. In conclusion, our findings suggest that N-methyl-D-aspartate receptor 1 signaling in the hippocampus is involved in cognitive impairment in the chronic stage after repetitive mild traumatic brain injury and may be a potential target for intervention and treatment.


Long-term clinical evaluation of platelet-rich plasma in the treatment of human periodontal intraosseous defects: A comparative clinical trial.
To compare the long-term clinical outcomes obtained by the combination of platelet-rich plasma (PRP) and a porous hydroxyapatite at the test site with those obtained from the use of a mixture of hydroxyapatite and saline at the control site in the treatment of human intraosseous defects. Sixty healthy, nonsmoking subjects diagnosed with chronic periodontitis were included in this study. Using a split-mouth design, intraosseous defects were surgically treated with a combination of PRP and a porous hydroxyapatite or a mixture of hydroxyapatite and saline. Clinical measurements and radiographic evaluation were performed at baseline and 1 and 4 years postoperatively. When compared with baseline, the 1-year results showed no significant changes. However, the 4-year results indicated that while both treatment modalities resulted in significant changes in all clinical parameters (probing depth, relative attachment level, gingival recession, and intraosseous defect fill; P < .001), the test group exhibited statistically significant changes compared with the control group: probing depth reduction, 5.8 ± 0.49 mm vs 4.0 ± 0.45 mm (P < .0001); clinical attachment gain, 5.4 ± 1.2 mm vs 3.1 ± 1.1 mm (P < .0001); and defect fill, 3.2 ± 0.8 mm vs 2.1 ± 0.6 mm (P < .0001). Treatment with a combination of PRP and hydroxyapatite compared with hydroxyapatite with saline led to a significantly more favorable clinical improvement in intraosseous periodontal defects.


Effective limitation of blood culture use in the burn unit.
There is little data to support the use of blood culture (BC) testing in the burn patient. Clinical signs (fever, leukocytosis) may not reliably indicate infection; moreover, BC's are expensive, invasive and plagued by false positive results. A policy of critical evaluation of lab utilization was instituted in our burn unit in 1993. By 1997 the use of blood culture testing had decreased by 50%. A retrospective analysis of our change in BC utilization was undertaken to derive practice guidelines for usage of this test. 47 patients with BC testing in 1997 were compared to a cohort of 47 patients from 1993, representing a total of 441 BC episodes. Comparison of 1993 and 1997 patients revealed no significant differences in patient characteristics or outcomes. The mean white blood cell count and maximum temperature on the day of culture were identical for both positive and negative BC episodes. However, BC's drawn during a state of shock were twice as likely to be positive. Patients who experienced positive BC's had larger burns, received more antibiotics, had more indwelling catheters, and had longer lengths of ventilator support and hospital stays. Higher patient acuity or the presence of indwelling catheters increases the likelihood of a positive BC. Substantial limitation of BC's without observed changes in length of stay, ventilator days, or mortality suggests that this test can be safely limited without compromising patient outcomes.


Drug therapies for cognitive impairment and dementia.
Drugs currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer's disease include acetylcholinesterase inhibitor drugs (tacrine [Cognex®], donepezil [Aricept®], rivastigmine [Exelon®, Exelon Patch®], and galantamine [Reminyl®, Razadyne®]) and glutamate-modulating drugs (memantine [Namenda®]). They do not halt the underlying degenerative process but can slow disease progression. Piracetam is a nonprescription noot ropic drug designated by the FDA as an orphan drug for myoclonic seizures. Clinical trials in a diverse group of patients with age-related dementia or cognitive impairment demonstrated a significant benefit, but the methodology of these studies is poor, and long-term effects are unknown. Other therapies discussed in this article include Ginkgo biloba, a nonprescription natural supplement, and Axona", designated by the FDA as a medical food.


Intense turquoise and green colors in brownmillerite-type oxides based on Mn5+ in Ba2In(2-x)Mn(x)O(5+x).
Brownmillerite-type oxides Ba(2)In(2-x)Mn(x)O(5+x) (x = 0.1-0.7) have been prepared and characterized. Magnetic measurements indicate that manganese in as-prepared samples is substituting predominantly as Mn(5+) for all values of x with observed paramagnetic spin-only moments close to values expected for two unpaired electrons. Electron paramagnetic resonance measurements indicate that this Mn(5+) is present in a highly distorted tetrahedral environment. Neutron diffraction structure refinements show that Mn(5+) occupies tetrahedral sites for orthorhombic (x = 0.1) and tetragonal (x = 0.2) phases. For Mn ≥ 0.3 samples, neutron refinements show that the phases are cubic with disordered cations and oxygen vacancies. The colors of the phases change from light yellow (x = 0) to intense turquoise (x = 0.1) to green (x = 0.2, 0.3) or to dark green (x ≥ 0.4). Under reducing conditions, Mn(5+) is reduced to Mn(3+), and Ba(2)In(2-x)Mn(x)O(5+x) phases become black Ba(2)In(2-x)Mn(x)O(5) phases still with the brownmillerite structure.


[The role of PCR in detection of cytomegalovirus in blood and urine of transplanted patients].
Rapid and reliable laboratory diagnosis of cytomegalovirus (CMV) infection in transplanted patients becomes more significant considering possible prevention or moderation of CMV disease. The aim of this study was comparison of CMV isolation in cell culture and CMV detection by PCR in blood and urine samples of transplanted patients. The study comprised 21 patients undergoing immunosuppressive therapy after renal or bone marrow transplantation. MRC-5 cell culture was used for viral isolation. Inoculated cultures were maintained for 4 weeks or until appearance of specific cytopathic effect (CPE). Primers used in PCR were specific for the sequence within egzon 4 of immediate-early 1 (IE-1) gene. Presence of anti-CMV IgG and IgM antibodies was determined by ELISA. PCR was more sensitive for blood (4/21) and urine samples (3/19) than cell culture method--blood (0/21) urine (2/19). Statistically significant correlation was not shown between presence of CMV(determined by PCR) in blood and urine of the same patient.


Cultivation and Nutritional Evaluation of Agaricus bisporus with Tea Residue as Culture Medium.
Different constituents of the cultivation substrate have significant effect on the yield and quality of edible mushrooms. The residue after the extraction of instant tea has exhibited to be biologically significant, and could be used as a substrate for cultivation. This study aimed to investigate the feasibility of tea extraction residue (TER) on button mushroom (Agaricus bisporus) cultivation, as an ingredient in the substrate, and assess the growth status, nutritional values, and sensory characteristics of fruiting body. The results showed that the strains could grow well on the cultivated substrate with 20% addition of TER. The total amount of hydrolyzed amino acids in the fruiting bodies of three TER-based groups (TER accounted for 10%, 20%, and 37.5%, respectively) was higher than that of the control group, and the total amount of essential amino acids was increased by 33.33%, 22.47%, and 9.92% compared with the control group, respectively. In addition, the results of gas chromatography-mass spectrometry (GC-MS) revealed that the addition of TER to the cultivation of substrate significantly enhanced the content of typical mushroom-flavor compounds in button mushroom, such as 1-octen-3-ol, 3-octanol, and 1-octen-3-one. It can be concluded that TER may be an ideal choice for the substrate in commercial cultivation of button mushroom.


[A woman with lumps in her breast].
A 61-year-old woman was examined for multiple lumps and an ulcer in her breast, 23 years after breast-conserving therapy for breast cancer, including surgery, chemotherapy and radiation therapy. Clinical examination and imaging showed extensive calcifications as a late effect of irradiation, which was confirmed by the pathologist after surgery.


Immune and molecular correlates in melanoma treated with immune checkpoint blockade.
Immunotherapy for metastatic melanoma has a decades-long history, and the relatively recent use of checkpoint inhibitors has revolutionized treatment. Durable and sometimes complete remission of metastatic melanoma is now achievable in some patients who receive checkpoint-blocking therapy. However, it is unclear why some patients fare better than others. This review highlights several molecular indicators of response to checkpoint inhibition in metastatic melanoma, focusing on tumor programmed death ligand 1 expression, major histocompatibility complex class I expression, mutational load in the tumor, and T-cell infiltration into the tumor. In addition, clinical correlates of response, notably vitiligo and other immune-related adverse events, can potentially shed light on the mechanisms by which checkpoint blockade may achieve such great success, particularly in melanoma. The authors propose that microphthalmia-associated transcription factor-a key regulator of melanocyte survival, melanin production, and melanoma transformation-produces a molecular landscape in melanocytes and melanoma cells that can make melanomas particularly susceptible to checkpoint blockade and also can result in immune attack on normal melanocytes. Cancer 2017;123:2143-53. © 2017 American Cancer Society.


Prognostic significance of EGFR and COX-2 expression in colorectal cancer and their association. A study in Greek population.
Colon cancer is one of the most common malignancies. Various prognostic markers have been proposed and individualized treatment strategies have been adapted according to tumor molecular and genetic characteristics. The purpose of the present study was to retrospectively analyze a possible association between the expression of COX- 2 and EGFR and clinical and histopathological factors of patients undergoing colon surgery in a Greek population. Data from our department's prospectively collected database were retrieved for a total of 100 consecutive colectomies that were performed in our department. We examined patient age, sex, tumor stage and location of the tumor. Histological data were also retrieved concerning major tumor diameter, histological grade and immunohistochemical expression of cyclooxygenase (COX)-2 and epithermal growth factor receptor (EGFR). There was no difference between tumors of different differentiation in the expression of EGFR (p=0.146), while there was statistically significant difference in the expression of COX-2 between these groups (p=0.001). There was no difference between these patients in the expression of EGFR (p=0.136), while a statistically significant difference was found in the expression of COX-2 between the same patient groups (p<0.005). These data are quite important in order to certify that colorectal cancer molecular and genetic diversity between different study populations is not a confounding factor in the application and clinical implementation of trending individualized decision making in oncological treatments.


Temporary incomplete ischemia of the legs caused by aortic clamping in man: improvement of skeletal muscle metabolism by low molecular dextran.
Temporary infrarenal clamping of the aorta during reconstructive surgery induces incomplete ischemia of the leg muscle. After release of the clamp, severe muscle metabolic derangement with loss of high-energy phosphate compounds has been observed, indicating a dysfunction or damage of the muscle cells. In six patients operated on for occlusive aortoiliac disease, low-molecular-weight dextran (LMWD) was peroperatively administered for optimal volume loading and prevention of clotting. No heparin was used. Before, during and after the clamping period the central hemodynamics were monitored, and glycogen, glucose, lactate, pyruvate, phosphocreatine (PCr), creatine (Cr), ATP, ADP and AMP content in the thigh muscle were analyzed using enzymatic fluorometric techniques. Even though ischemia developed during the occlusion, no decline in the adenylate (ATP + ADP + AMP) or creatine (PCr + Cr) pools occurred after the clamp was released, and the energy charge of the adenine nucleotides remained unchanged. It is suggested that LMDX prevents rheologic changes impairing the microcirculation during and after the ischemic period, and thereby improves oxygenation of the muscle tissue upon reperfusion.


Critical role of vimentin phosphorylation at Ser-56 by p21-activated kinase in vimentin cytoskeleton signaling.
Phosphorylation and spatial reorganization of the vimentin network have been implicated in mediating smooth muscle contraction, cell migration, and mitosis. In this study, stimulation of cultured smooth muscle cells with 5-hydroxytryptamine (5-HT) induced PAK1 phosphorylation at Thr-423 (an indication of p21-activated kinase (PAK) activation). Treatment with PAK led to disassembly of wild-type (but not mutant S56A) vimentin filaments as assessed by an in vitro filament assembly assay. Furthermore, stimulation with 5-HT resulted in the dissociation of Crk-associated substrate (CAS; an adapter protein associated with smooth muscle force development) from cytoskeletal vimentin. Expression of mutant S56A vimentin in cells inhibited the increase in phosphorylation at Ser-56 and in the ratios of soluble to insoluble vimentin (an index of vimentin disassembly) and the dissociation of CAS from cytoskeletal vimentin in response to 5-HT activation compared with cells expressing wild-type vimentin. Because CAS may be involved in PAK activation, PAK phosphorylation was evaluated in cells expressing the S56A mutant. Expression of mutant S56A vimentin depressed PAK phosphorylation at Thr-423 induced by 5-HT. Expression of the S56A mutant also inhibited the spatial reorientation of vimentin filaments in cells in response to 5-HT stimulation. Our results suggest that vimentin phosphorylation at Ser-56 may inversely regulate PAK activation possibly via the increase in the amount of soluble CAS upon agonist stimulation of smooth muscle cells. Additionally, vimentin phosphorylation at this position is critical for vimentin filament spatial rearrangement elicited by agonists.


[Perception of changes in body weight during pregnancy].
ELSPAC (European Longitudinal Study of Pregnancy and Childhood) includes in Czech Republic the set of pregnant women who have their permanent address in Brno and Znojmo district with the term of the delivery between March 1991 and June 1992. Wide and repeated anamnestic and clinical investigations of parents and children making possible prospective analyses pregnancy and development of child. Prospective study. Research Institute of Child Health, Brno. In the set of 7911 women, the relationship between subjective perception of weight and pregnancy in the first and second trimester was investigated. The data were obtained from two questionnaires filled by pregnant woman and obstetricians. In the whole set, 12% of women are concerned with their weight intensively and perception of their weight is rather negative. 5.8% of women show negative relationship to pregnancy at the beginning, in the second trimester it is only the small fragment of all women. The reason for the negative perception of the weight is influenced by somatic, psychic and social aspects. The most important issue is emotional stability. The most common increase in weight was between 8-15 kg, in average 11.34 kg. The increase in weight in pregnancy is, among other reason, mediated by nutrition, smoking and job. Physical and psychical changes occur during the pregnancy. One of very evident changes is also increase in weight. The ability to accept this chance depends especially on emotional stability, food, smoking and job of pregnant women.


ADAM10 and ADAM17 as Biomarkers Linked to Inflammation, Metabolic Disorders and Colorectal Cancer.
ADAM10 and ADAM17 have a role in inflammation and diseases associated with inflammation, such as diabetes, cardiovascular diseases (CVD) or cancer, e.g., colorectal cancer (CRC). The aim of this study was to evaluate whether ADAM10 and ADAM17 could be biomarkers of CRC. To achieve this goal, CRC tumors and a surgical margin from 72 patients with CRC were collected. The concentration of ADAM proteins was measured by the ELISA method. Results were analyzed statistically and compared with selected clinical parameters. We found that ADAM17 protein concentration in the tumor samples was higher in patients with diabetes mellitus type 2 (DMT2) (0.28 vs. 0.2 ng/µg protein; p = 0.01) and in the surgical margin was higher both in patients with coexisting DMT2 (0.22 vs. 0.16 ng/µg protein; p < 0.05) and CVD (0.21 vs. 0.13 ng/µg protein; p < 0.01). The concentration of ADAM10 was higher in the surgical margin than in the tumor (249.34 vs. 228.82 pg/µg protein), and the concentration of ADAM17 was higher in the tumor than in the margin (0.23 vs. 0.18 ng/µg protein), but results were not statistically significant. In conclusion, the results of our study indicate that ADAM10 and ADAM17 may be potential biomarkers in cancer linked with DMT2 and CVD as diseases associated with inflammation.


Outcomes for Standardized Home and Hospital-Based Infusions of Infliximab for Children With Inflammatory Bowel Disease.
Pediatric inflammatory bowel disease (IBD) is commonly treated with infliximab in a hospital setting. Utilization of home infusions (HI) is increasing due to insurance mandates, travel time savings, and convenience. We evaluated adverse outcomes (AOs) of infliximab infusions in children with IBD receiving HI compared to hospital-based infusions. Children receiving HI between September 2016 and September 2018 were retrospectively matched based on age, race, ethnicity, sex, and disease type to a cohort receiving infliximab at a hospital-based center. A survival analysis evaluated the hazard ratio for AOs in HI relative to hospital-infused children over 2 years. AOs were defined as discontinuation of therapy for clinically relevant reasons, IBD-related hospitalizations, and emergency department visits. We included 102 children (51 pairs) (63% male, 91% White, 92% Crohn disease). Disease location, behavior, growth status, and disease severity were similar between the 2 cohorts. Quiescent disease increased from 3% to 93% after 2 years without cohort differences. At baseline, 94% of HI patients and 88% of controls were on 5 mg/kg every 8 weeks as standard maintenance therapy. Within 2 years, only 19% remained on 5 mg/kg and the remainder required increased dosing or decreased interval. The HI cohort had fewer labs obtained ( P < 0.001), though laboratory values, number of clinic visits, and frequency of AOs were similar. Drug durability, AOs, and laboratory values were similar between HI and hospital-based infusions. These findings suggest HI may be as effective as hospital-based infusions, provided a standardized care approach is utilized.


Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice.
Human cervical cancer is the fourth most common carcinoma in women worldwide. However, the emergence of drug resistance calls for continuously developing new anticancer drugs and combination chemotherapy regimens. The present study aimed to investigate the anti-cervical cancer effects of metformin, a first-line therapeutic drug for type 2 diabetes mellitus, and nelfinavir, an HIV protease inhibitor, when used alone or in combination. We found that both metformin and nelfinavir, when used alone, were moderately effective in inhibiting proliferation, inducing apoptosis and suppressing migration and invasion of human cervical cell lines HeLa, SiHa and CaSki. When used in combination, these two drugs acted synergistically to inhibit the growth of human cervical cancer cells in vitro and cervical cancer cell xenograft in vivo in nude mice, and suppress cervical cancer cell migration and invasion. The protein expression of phosphoinositide 3-kinase catalytic subunit PI3K(p110α), which can promote tumor growth, was remarkably downregulated, while the tumor suppressor proteins p53 and p21 were substantially upregulated following the combinational treatment in vitro and in vivo. These results suggest that clinical use of metformin and nelfinavir in combination is expected to have synergistic antitumor efficacy and significant potential for the treatment of human cervical cancer.


The time-course of activation in the dorsal and ventral visual streams during landmark cueing and perceptual discrimination tasks.
Different patterns of high density EEG activity were elicited by the same peripheral stimuli, in the context of Landmark Cueing and Perceptual Discrimination tasks. The C1 component of the visual event-related potential (ERP) at parietal - occipital electrode sites was larger in the Landmark Cueing task, and source localisation suggested greater activation in the superior parietal lobule (SPL) in this task, compared to the Perceptual Discrimination task, indicating stronger early recruitment of the dorsal visual stream. In the Perceptual Discrimination task, source localisation suggested widespread activation of the inferior temporal gyrus (ITG) and fusiform gyrus (FFG), structures associated with the ventral visual stream, during the early phase of the P1 ERP component. Moreover, during a later epoch (171-270ms after stimulus onset) increased temporal-occipital negativity, and stronger recruitment of ITG and FFG were observed in the Perceptual Discrimination task. These findings illuminate the contrasting functions of the dorsal and ventral visual streams, to support rapid shifts of attention in response to contextual landmarks, and conscious discrimination, respectively.


Learning anatomy through Thiel- vs. formalin-embalmed cadavers: Student perceptions of embalming methods and effect on functional anatomy knowledge.
Thiel-embalmed cadavers, which have been adopted for use in anatomy teaching in relatively few universities, show greater flexibility and color retention compared to formalin-embalmed cadavers, properties which might be considered advantageous for anatomy teaching. This study aimed to investigate student attitudes toward the dissection experience with Thiel- compared to formalin/ethanol-embalmed cadavers. It also aimed to determine if one embalming method is more advantageous in terms of learning functional anatomy through the comparison of student anterior forearm functional anatomy knowledge. Student opinions and functional anatomy knowledge were obtained through use of a questionnaire from students at two medical schools, one using Thiel-, and one using more traditional formalin/ethanol-embalmed cadavers. Both the Thiel group and the formalin group of students were surveyed shortly after completing an anterior forearm dissection session. Significant differences (P-values <0.01) in some attitudes were found toward the dissection experience between cohorts using Thiel- vs. formalin-embalmed cadavers. The Thiel group of students felt more confident about recognizing anatomy in the living individual, found it easier to identify and dissect anatomical structures, and indicated more active exploration of functional anatomy due to the retained flexibility of the cadaver. However, on testing, no significant difference in functional anatomy knowledge was found between the two cohorts. Overall, although Thiel embalming may provide an advantageous learning experience in some investigated areas, more research needs to be carried out, especially to establish whether student perception is based on reality, at least in terms of structure identification. Anat Sci Educ 11: 166-174. © 2017 American Association of Anatomists.


Clinical evaluation of the effects of a sonic toothbrush with ultrasound waveguide in disrupting plaque with and without bristle contact.
To assess the in vivo plaque removal efficacy of the newly marketed sonic/ultrasonic toothbrush. Plaque removal resulting from the toothbrush being held approximately 3 mm from the tooth surface was compared versus a no brushing control. Also, plaque removal resulting from the brush being used according to the manufacturer's instructions was compared versus a control of using the brush (with power turned off) like a manual toothbrush would be used. This was a replicate use, four-treatment, examiner-blind, randomized, eight-period crossover design single brushing plaque study involving 31 subjects. The four treatment regimens consisted of (1) brushing for 2 minutes with the Ultreo powered toothbrush according to manufacturer's instructions, (2) brushing for 2 minutes with the Ultreo toothbrush (power turned off) using the brush like a manual toothbrush, (3) having a trained dental hygienist hold the Ultreo toothbrush head 3 mm from tooth surfaces for a total of 2 minutes, or (4) swishing with a dentifrice slurry for 1 minute in the absence of toothbrushing. For each subject, an experienced, calibrated plaque examiner performed the Turesky Modified Quigley-Hein Plaque Index prior to brushing and following brushing. The difference (baseline minus post-regimen) in average scores was calculated for each subject. The difference scores were analyzed for treatment regimen differences using a mixed model ANCOVA (with baseline whole-mouth average score as the covariate and subjects considered random) for a crossover design. Adjusted mean plaque removal scores (baseline plaque score minus post-brushing plaque score) were 0.052 for swishing with a dentifrice slurry, 0.058 for the dental hygienist holding the Ultreo toothbrush approximately 3 mm from tooth surfaces, 0.536 for the Ultreo toothbrush used according to manufacturer's instructions and 0.666 for the Ultreo toothbrush (power turned off) used like a manual toothbrush. The difference between the Ultreo toothbrush held approximately 3 mm from tooth surfaces and swishing with a dentifrice slurry was not statistically significant (P = 0.808). The adjusted mean plaque removal score for the Ultreo toothbrush (power turned off) used like a manual toothbrush was statistically significantly (P < 0.001) greater than the corresponding score for the Ultreo toothbrush used per manufacturer's instructions. Ultreo used like a manual toothbrush had an adjusted mean plaque removal score that was 12.4% greater than that for Ultreo used per manufacturer's instructions. Finally, plaque removal scores for the Ultreo toothbrush used per manufacturer's instructions and used like a manual toothbrush were statistically significantly (P < 0.001) greater than plaque removal scores for the non-brushing treatment regimens.


[The molecular characteristics of T-cell immune reconstitution in leukemia patients after allogeneic hematopoietic stem cell transplantation].
To study the molecular characteristics of CDR3 repertoires of T cell receptor beta chain variable region (TCRBV) of T lymphocytic clones in leukemia recipients after allogeneic hematopoietic stem cell transplantation ( allo-HSCT). RT-PCR was used to amplify 24 subfamily genes of TCRBV from peripheral blood (PB) lymphocytes in twenty-four leukemia patients underwent three kinds of allo-HSCT and in five normal donors as control. The PCR products were further analyzed by genescan to evaluate the clonality of BV subfamily and characteristics of CDR3 and calculate usage rate of BV subfamily. The monoclonal bands which associated with GVHD and CMV infection were obtained by denaturation polyacrylamide gel electrophoresis and sequenced. Comparison of the sequences of TCRBV CDR3 with other CDR3 sequences which associated with GVHD or CMV infection was reported. 2 approximately 19 months after transplantation, there were 6 approximately 14 BV subfamilies expressed and the polyclonal expression reached 33% in nine patients underwent haploidentical bone marrow transplantation(HI-BMT). In five patients underwent matched unrelated peripheral blood stem cell transplantation ( MU-PBSCT), there were 10 approximately 15 BV subfamilies expressed of which 45% were poly-clones. In 10 patients underwent matched sibling bone marrow transplantation(MS-BMT), 10 approximately 16 BV subfamilies were expressed and more than 48% of them were poly-clones. Monoclones and oligo-clones existed in 24 BV subfamilies but no common one monoclone BV subfamilies was found. Immune reconstitution in patients underwent HI-BMT was later than that in other two groups. In 2 patients TCRBV was detected in 2m and 3m after allo-HSCT and found that there was a tendency of increasing usage of BV subfamilies and increasing expression of CDR3 polymorphism. Twenty three TCRBV CDR3 molecules associated with GVHD and CMV infection were compared each other by bioinformatics and found that different cases of the same BV subfamilies may share similarity in amino acid motif, while in different BV subfamilies none appeared to share the same amino acid motif. In 1.5 years after allo-HSCT, the usage of TCRBV subfamilies still restricted. Immune reconstitution in patients underwent HI-BMT was later than that in other two groups. TCRBV CDR3 molecules associated with GVHD and CMV infection showed that different cases of the same BV subfamilies may share similarity in amino acid motif, while in different BV subfamilies none of clones appeared to share the same amino acid motif.


Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection.
Prenatal cytogenetic analysis of 71 fetuses conceived by intracytoplasmic sperm injection (ICSI) resulted in the detection of nine (12.7%) chromosome aberrations including two cases of 47,XXY, four cases involving a 45,X cell line and three autosomal trisomies. Molecular analysis of the parental origin of the deleted or supernumerary chromosome was performed by using polymorphic microsatellite markers. Six cases involving a sex chromosome abnormality were found to be of paternal origin while the two trisomic cases that could be analysed were of maternal origin. Two cases involved the same infertile couple who had two consecutive ICSI pregnancies terminated because of a chromosome abnormality. The replaced embryos in both cases originated from a single batch of ICSI fertilized oocytes of which part was used to initiate the first pregnancy and part was cryopreserved and used to initiate the second pregnancy.


Phagocytosis and fluid-phase pinocytosis.
The generation, flow, directionality and fusion of phagocytic and fluid-phase pinocytic vesicles in cultured macrophages and fibroblasts are reviewed. Specific plasma membrane (PM) receptors, receptor mobility, contractile cytoplasmic elements and lipid composition of the PM serve to regulate the flow of large phagosomes into the perinuclear zone. Fluid-phase vesicles are constitutively generated and carry large quantities of PM, fluid and solutes into the cytoplasm. Quantitative information is cited on the rates of vesicular generation, fusion with other members of the vacuolar system, fluid and solute uptake, and digestion and solute release. The nature and composition of fluid-phase vesicles, phagocytic vacuoles and PM are compared. Once interiorized, PM and its component polypeptides rapidly cycle back to the cell surface. The flow rates of both the centrifugal and the centripetal compartments as well as the fate of a minor degradation pool are illustrated and compared to the turnover of individual membrane polypeptides. Implications of membrane flow for cell shape, motility and new PM insertion are discussed.


Hyperexcitability of distal dendrites in hippocampal pyramidal cells after chronic partial deafferentation.
Traumatic injury to the CNS results in chronic partial deafferentation of subsets of surviving neurons. Such injuries are often followed by a delayed but long-lasting period of aberrant hyperexcitability. The cellular mechanisms underlying this delayed hyperexcitability are poorly understood. We developed an in vitro model of deafferentation and reactive hyperexcitability using organotypic hippocampal slice cultures to study the underlying cellular mechanisms. One week after transection of the Schaffer collateral and temporoammonic afferents to CA1 neurons, brief tetanic stimulation of the residual excitatory synapses produced abnormally prolonged depolarizations, compared with responses in normally innervated neurons. Responses to weak stimulation, in contrast, were unaffected after deafferentation. Direct stimulation of distal apical dendrites using focal photolysis of caged glutamate triggered abnormally prolonged plateau potentials in the deafferented neurons when strong stimulation was given, but responses to weak stimulation were not different from controls. An identical phenotype was produced by chronic "chemical deafferentation" with glutamate receptor antagonists. Responses to strong synaptic and photolytic stimulation were selectively prolonged by small-conductance (SK-type) calcium-activated potassium channel blockers in normally innervated cells but not after deafferentation. No significant changes in SK2 mRNA or protein levels, GABAergic inhibition, glutamate receptor function, input resistance, or action potential parameters were observed after chronic deafferentation. We suggest that a posttranslational downregulation of SK channel function in thin distal dendrites is a significant contributor to deafferentation-induced reactive hyperexcitability.


In vitro kinetics of drug release and pulmonary retention of microencapsulated antibiotic in liposomal formulations in relation to the lipid composition.
In previous in-vivo studies, we demonstrated that liposomal entrapment of tobramycin resulted in an increased availability of the antibiotic in the lungs without increasing bactericidal efficacy (Omri et al. 1994). With the aim of developing liposomal formulations allowing more efficient liposome-bacteria interactions, we studied the influence of lipid composition on both drug release and pulmonary retention of encapsulated tobramycin. The phase transition temperatures of nine liposome-tobramycin formulations consisting of two synthetic phospholipids (distearoyl phosphatidylcholine (DPSC) or dipalmitoyl phosphatidylcholine (DPPC) with dimyristoyl phosphatidyl-glycerol (DPMG) or dimyristoyl phosphatidylcholine (DMPC) were determined by differential scanning calorimetry. Liposomes, varying in terms of membrane fluidity and charge were submitted to in-vitro and in-vivo kinetic studies while retention and release of tobramycin were measured by high-performance liquid chromatography (HPLC). Five less fluid liposome formulations showed absence or very low tobramycin release in in-vitro tests and long term pulmonary retention of tobramycin. Four fluid liposome formulations showed in vitro tests modulated tobramycin release while pulmonary retention of tobramycin was dependent of the presence of charged phospholipids. Administration of charged fluid liposomes in mice showed a low level of tobramycin in the kidneys; non-charged fluid liposomes exhibited a relatively high level of tobramycin retention in the kidneys.


[Prevalence and genotyping of Cryptosporidium spp. and Giardia lamblia in dogs and cats from a pet hospital in Shanghai Municipality].
To investigate the prevalence and genotypes of Cryptosporidium spp. and Giardia lamblia in dogs and cats from a pet hospital in Shanghai Municipality. A total of 145 fresh fecal samples were collected from pet dogs and cats in a pet hospital in Shanghai Municipality during the period from November 2021 to June 2022, including 99 dog fecal samples and 46 cat fecal samples. The small subunit ribosomal ribonucleic acid (SSU rRNA) gene of Cryptosporidium and the triose phosphate isomerase (TPI) gene of G. lamblia were amplified using nested PCR assay, and the positive amplification products were sequenced from both directions. The sequence assembly was performed using the software Clustal X 2.1, and sequence alignment was conducted using BLAST. A phylogenetic tree was created with the Neighbor-Joining method using MEGA 11.0 to identify parasite species or genotype. The overall prevalence of Cryptosporidium and G. lamblia was 20.00% (29/145) in 145 pet dog and cat fecal samples, with the prevalence of 0.69% (1/145) and 19.31% (28/145) in Cryptosporidium and G. lamblia, respectively. G. lamblia was only detected in dog fecal samples, with prevalence of 18.18% (18/99), while the detection rates of Cryptosporidium and G. lamblia were 2.17% (1/46) and 21.74% (10/46) in cat fecal samples. Nucleotide sequence analysis showed that one Cryptosporidium positive sample was characterized as C. felis, and 28 G. lamblia positive samples were all characterized as Giardia assemblage A, which showed 100% sequence homology with human isolates of Giardia. Phylogenetic analysis revealed that the sequences obtained in this study belonged to the same branch with the reported Giardia assemblage A. Cryptosporidium and G. lamblia infection was prevalent in pet dogs and cats from the study pet hospital in Shanghai Municipality, and there is a zoonotic risk for the species and genotype. Intensified surveillance of Cryptosporidium and Giardia infection is recommended in pets and their owners, and improved management of pet keeping is required.


Reliability of electric response audiometry using 80 Hz auditory steady-state responses.
The reliability of the Auditory Steady State Response (ASSR) has not been thoroughly evaluated despite its recent application as a clinical tool for threshold estimation. The purpose of this study was to examine test-retest (TR) reliability of ASSR threshold estimates in an empirical research design. The ASSR, tested using modulation frequencies approximately 80 Hz and above, was evaluated against pure tone audiometry (PTA), and the slow vertex potential (SVP, N1-P2). Sixteen normal-hearing young female adults were tested twice, one week apart. Varying degrees of sensorineural hearing loss of a notched configuration were simulated with filtered masking noise. Test-retest reliability was assessed using Pearson-product moment correlation analysis, supplemented by other post-hoc analyses. Results demonstrated moderately strong TR reliability for ASSR at 1000, 2000 and 4000 Hz (r = 0.83-0.93); however, the reliability of ASSR at 500 Hz was weaker (r = 0.75). Results suggest that ASSR-ERA is a reliable test at mid-high frequencies, at least with the configuration and degrees of simulated sensorineural hearing loss examined in this study.


Theoretical investigation of the mechanism of primary amines reacting with hexamolybdate: an insight into the organoimido functionalization and related reactions of polyoxometalates.
The functionalization of polyoxometalates (POMs), especially with an amino group to yield organonitrogenous derivatives of POMs, is an efficient approach to the enrichment of their structures and the diversification of their properties for various applications. The mechanism for the formation of organonitrogenous-derivatized hexamolybdates was explored by investigating the monofunctionalization of the [Mo(6)O(19)](2-) ion with methylamine using the density functional theory (DFT) method. The calculations show that the direct imidoylization of hexamolybdate with methylamine is both kinetically and thermodynamically unfavorable. However, this imidoylization was found to take place readily in the presence of dimethylcarbodiimide (DMC), for which the free-energy barrier was calculated to be +32.5 kcal mol(-1) in acetonitrile. Moreover, various factors controlling the efficiency of the imidoylization were examined. The calculations show that [W(5)MoO(19)](2-) has a relatively lower reactivity than [Mo(6)O(19)](2-), and that the imidoylization of [W(6)O(19)](2-) is an unfavorable process. With respect to the effect of carbodiimides, it is found that the catalytic activity is directly proportional to the electron-withdrawing effects of the substituents. As to the reactivity of R-NH(2) , the computation results indicate that the free-energy barriers of the substitution reactions are linearly correlated with the basicity constants (pK(b)) of the amino groups. It is noteworthy that the introduction of the proton dramatically decreases the free-energy barrier of the imidoylization of [Mo(6)O(19)](2-) catalyzed by DMC to 24.3 kcal mol(-1) in acetonitrile.


Inhibition of T cell activation by cyclic adenosine 5'-monophosphate requires lipid raft targeting of protein kinase A type I by the A-kinase anchoring protein ezrin.
cAMP negatively regulates T cell immune responses by activation of type I protein kinase A (PKA), which in turn phosphorylates and activates C-terminal Src kinase (Csk) in T cell lipid rafts. Using yeast two-hybrid screening, far-Western blot, immunoprecipitation and immunofluorescense analyses, and small interfering RNA-mediated knockdown, we identified Ezrin as the A-kinase anchoring protein that targets PKA type I to lipid rafts. Furthermore, Ezrin brings PKA in proximity to its downstream substrate Csk in lipid rafts by forming a multiprotein complex consisting of PKA/Ezrin/Ezrin-binding protein 50, Csk, and Csk-binding protein/phosphoprotein associated with glycosphingolipid-enriched microdomains. The complex is initially present in immunological synapses when T cells contact APCs and subsequently exits to the distal pole. Introduction of an anchoring disruptor peptide (Ht31) into T cells competes with Ezrin binding to PKA and thereby releases the cAMP/PKA type I-mediated inhibition of T cell proliferation. Finally, small interfering RNA-mediated knockdown of Ezrin abrogates cAMP regulation of IL-2. We propose that Ezrin is essential in the assembly of the cAMP-mediated regulatory pathway that modulates T cell immune responses.


Determination of clinical and demographic predictors of laboratory-confirmed influenza with subtype analysis.
Rapid influenza diagnosis is important for early identification of outbreaks, effective management of high-risk contacts, appropriate antiviral use, decreased inappropriate antibiotic use and avoidance of unnecessary laboratory testing. Given the inconsistent performance of many rapid influenza tests, clinical diagnosis remains integral for optimizing influenza management. However, reliable clinical diagnostic methods are not well-established. This study assesses predictors of influenza, and its various subtypes, in a broad population at the point of care, across age groups, then evaluates the performance of clinical case definitions composed of identified predictors. Respiratory specimens and demographic and clinical data were obtained from 3- to 80-year-old US military family members presenting for care with influenza-like illness (ILI) from November 2007 to April 2008. Molecular and virus isolation techniques were used to detect and subtype influenza viruses. Associations between influenza diagnosis and demographic/clinical parameters were assessed by logistic regression, including influenza type and subtype analyses. The predictive values of multiple combinations of identified clinical predictors (case definitions), and the Centers for Disease Control and Prevention (CDC) ILI case definition, were estimated. Of 789 subjects, 220 (28%) had laboratory-confirmed influenza (51 A(H1), 46 A(H3), 19 A(unsubtypeable), 67 B, 1 AB coinfection), with the proportion of influenza A to B cases highest among 6- to 17-year-olds (p = 0.019). Independent predictors of influenza included fever, cough, acute onset, body aches, and vaccination status among 6- to 49-year-olds, only vaccination among 3- to 5-year-olds, and only fever among 50- to 80-year-olds. Among 6- to 49-year-olds, some clinical case definitions were highly sensitive (100.0%) or specific (98.6%), but none had both parameters over 60%, though many performed better than the CDC ILI case definition (sensitivity 37.7%, 95% confidence interval 33.6-41.9% in total study population). Patterns of influenza predictors differed across age groups, with most predictors identified among 6- to 49-year-olds. No combination of clinical and demographic predictors served as a reliable diagnostic case definition in the population and influenza season studied. A standardized clinical case definition combined with a point-of-care laboratory test may be the optimal rapid diagnostic strategy available.


Is NMC education reform the beginning of the end for nursing branches?
The Nursing and Midwifery Council has begun its consultation on an education overhaul it describes as 'radical'. Its new standards are designed to ensure all nursing students complete their courses with a solid understanding of physical and mental health care. Some nurses are alarmed by what they see as a move towards a more generic nurse education system; others are disappointed the standards do not go far enough in that direction.


Testing prospective memory: does the value of a borrowed item help people remember to get it back?
The relationship between the value of an item borrowed from a patient for a prospective memory task and the number of cues required by the patient for requesting its return was analyzed in 63 consecutive patients referred for clinical neuropsychological evaluation. The correlation was negligible (rho = -.001). Number of cues needed was better predicted by score on the Mini-Mental State Exam (r = -.541, p <.001) than by subject's age, sex, or education, or the value of the item taken.


Bone disease in chronic alcoholism: the value of plasma osteocalcin measurement.
Osteoporosis is more common in chronic alcoholics than in age-matched controls. Possible aetiological factors are: malabsorption of calcium and vitamin D; liver disease and abnormal parathyroid function. The possibility that alcohol may directly affect osteoblastic function has, however, received little attention. We measured plasma osteocalcin, a protein synthesised specifically by osteoblasts, in chronic alcoholics. Our data show that these have low plasma osteocalcin but normal calcium, magnesium and parathormone, which suggest that alcohol may be directly toxic to osteoblasts.


Open Abdominal Aortic Aneurysm Replacement in the Awake Patient.
Nonintubated aortic surgery using various techniques has been reported, but despite publication of favorable outcomes in select patient groups, awake aortic surgery remains unpopular. Our patient had an abdominal aortic aneurysm that was unsuitable for endovascular repair. Because of the significant respiratory disease, general anesthesia represented an unacceptably high risk. As a result, he underwent open AAA repair via a retroperitoneal approach with the aid of epidural anesthesia. Here, we highlight the benefits of the procedure which offer a select cohort of patients the chance of life-saving surgery.


Organophosphorus Pesticide Multiresidues in Commercialized Asian Rice.
The organophosphorus pesticides (OPPs) commonly used in agricultural practices can pose a risk of potential exposure to humans via food consumption. We describe an analytical method for solid-phase extraction coupled with high-performance liquid chromatography-diode array detector (SPE-HPLC-DAD) for the detection of OPPs (quinalphos, diazinon, and chlorpyrifos) in rice grains. The isolation of targeted residues was initiated with double extraction before SPE-HPLC-DAD, crucially reducing matrix interferences and detecting a wide range of multiple residues in rice grains. Coefficients of 0.9968 to 0.9991 showed a strong linearity, with limits of detection and quantification ranging from 0.36 to 0.68 µg/kg and from 1.20 to 2.28 µg/kg, respectively. High recoveries (80.4-110.3%) were observed at 3 spiking levels (50, 100, and 200 µg/kg), indicating good accuracy. The relative standard deviations of all residues (0.19-8.66%) validated the method precision. Sample analysis of 10 rice grain types (n = 30) available in the Asian market revealed that quinalphos, diazinon, and chlorpyrifos at concentrations of 1.08, 1.11, and 1.79 µg/kg, respectively, remained far below the maximum residue limits (0.01-0.5 mg/kg). However, regular monitoring is necessary to confirm that multiresidue occurrence remains below permissible limits while controlling pests. Environ Toxicol Chem 2020;39:1908-1917. © 2020 SETAC.


[Use of freeze-fracturing to observe the ultrastructure of Candida albicans with scanning electron microscopy].
The development of the techniques of sample preparation for the observation of ultrastructure with scanning electron microscopy (SEM) include, among others, the method O-D-O reported by Tanaka and Naguro in 1981, based on the initial fixing of the specimen (eukaryotic tissue) in 1% OsO4; treatment with dimethyl sulphoxide (DMSO) as a cryoprotectant, followed by cryofracture, removal of cytoplasmatic matrix by psot-fixing with 1% OsO4 and a further conductive stain. In this paper we report the application of the method O-D-O in a culture of Candida albicans modifying the pre-fixing carried out overnight and excepting the osmic maceration, in order to observe the cell ultrastructure of this eukaryotic microorganism with SEM at a normal resolution. Through the tridimensional images obtained, in which we can observe the fracture of Candida albicans without cytoplasmatic matrix but with details of a normal and deformed cell wall, as well as cells conserving their cytoplasmatic matrix where globose and filamentous structures become evident and suggest a pattern of organization and cells with a very clear character of what we believe is the nuclear zone of the microorganism, we night conclude that our method is suitable for eukaryotic unicellular organisms in order to observe the cell ultrastructure with SEM at normal resolution and show images comparable with those reported with SEM at high resolution, contributing to the development of the ultrastructural cytology, traditionally restricted to the transmission electron microscopy (TEM). These findings reveal an additional aid which will allow to obtain a clearer aspect of the complex cell structure of unicellular organisms.


Acetosyringone treatment duration affects large T-DNA molecule transfer to rice callus.
Large T-DNA fragment transfer has long been a problem for Agrobacterium-mediated transformation. Although vector systems, such as the BIBAC series, were successfully developed for the purpose, low transformation efficiencies were consistently observed. To gain insights of this problem in monocot transformation, we investigated the T-strand accumulation of various size of T-DNA in two kinds of binary vectors (one copy vs. multi-copy) upon acetosyringone (AS) induction and explored ways to improve the efficiency of the large T-DNA fragment transfer in Agrobacterium-mediated rice transformation. By performing immuno-precipitation of VirD2-T-strands and quantitative real-time PCR assays, we monitored the accumulation of the T-strands in Agrobacterium tumeficiens after AS induction. We further demonstrated that extension of AS induction time highly significantly improved large-size T-DNA transfer to rice cells. Our data provide valuable information of the T-strand dynamics and its impact on large T-DNA transfer in monocots, and likely dicots as well.


Angiogenesis and Eye Disease.
The retina consists of organized layers of photoreceptors, interneurons, glia, epithelial cells, and endothelial cells. The economic model of supply and demand used to appropriately determine cost is highly applicable to the retina, in which the extreme metabolic demands of phototransduction are met by precisely localized and designed vascular networks. Proper development and maintenance of these networks is critical to normal visual function; dysregulation is characteristic of several devastating human diseases, including but not limited to age-related macular degeneration and diabetic retinopathy. In this article, we focus on the lessons learned from the study of retinal vascular development and how these lessons can be used to better maintain adult vascular networks and prevent retinal diseases. We then outline the vasculotrophic contributions from neurons, retinal pigment epithelium (RPE) cells, and glia (specifically microglia) before we shift our focus to pathology to provide molecular contexts for neovascular retinal diseases. Finally, we conclude with a discussion that applies what we have learned about how retinal cells interact with the vasculature to identify and validate therapeutic approaches for neurovascular disease of the retina.


Young Adults with High Autistic-Like Traits Displayed Lower Food Variety and Diet Quality in Childhood.
This study explored the association between autistic-like traits in young adults and dietary intake in early childhood in the Gen2 Raine Study cohort. Data were available from 811 participants at years 1, 2 and 3 for the assessment of dietary intake, and at year 20 for measurement of autistic-like traits. Results showed as autistic-like traits increased, total food variety, core food variety and dairy variety decreased (p < 0.05), with a lower consumption of citrus fruits and yoghurt (both p = 0.04). As autistic-like traits increased, diet quality decreased, this trend was significant at 2 years (p = 0.024). Our results suggest that young adults with higher autistic-like traits were more likely to have had lower food variety and diet quality in early childhood.


Gender roles, food system biodiversity, and food security in Indigenous Peoples' communities.
Traditional knowledge and practice of Indigenous Peoples related to their food use and well-being is a wealth of information for academic study and for public health nutrition. Despite unique long-evolved heritages of knowledge of ecosystem resources, Indigenous Peoples comprise 15% of the global poor, but only 5% of the world's population, and they experience poverty, discrimination, and poor nutritional health at far greater rates than mainstream populations in their nations of residence. These disparities are unacceptable in all human rights frameworks, and the call to alleviate them resonates through all human development programmes and the United Nations organizations. The scholars contributing to this special issue of Maternal and Child Nutrition describe how gender roles and the right to food for several cultures of Indigenous Peoples can be fostered to protect their unique foods and traditions, providing food sovereignty and food and nutrition security benefits, especially for women and children. Aspects of societal maternal or paternal lineality and locality, division of labour, spirituality and decision-making are described. These factors structure the impact of gender roles with Indigenous worldviews on the dynamics of family food access, its availability and use, and the use of local food biodiversity. Cultures of Indigenous Peoples in Ecuador, Nigeria, Thailand, India, Canada, Japan, and Morocco are discussed. This publication is a work of the Task Force on Traditional, Indigenous and Cultural Food and Nutrition of the International Union of Nutritional Sciences.


Physical activity and cancer: how may protection be maximized?
A series of meta-analyses have examined relationships between regular physical activity and susceptibility to various forms of cancer. Regular physical activity protects animals against cancer from a variety of sources: subcutaneous, intraperitoneal or intragastric carcinogens, intravenous infusion of tumor cells, or tumor implantation. In humans, regular exercise reduces susceptibility to all-cause cancer, colonic adenomas, colon but not rectal cancers, breast cancers, uterine tumors, prostate and testicular tumors, and possibly lung cancers. At most tumor sites, the average response of women is similar to that of men, but because of a limited number of studies, the effect in women is commonly nonsignificant. The relative effects of occupational and leisure activity are generally similar, an observation that suggests that the optimum response of cancer defense mechanisms is obtained from moderate levels of energy expenditure. In general, the data show a dose-response relationship, the risk of a sedentary lifestyle approximately doubling on passing from a moderate to a low level of habitual physical activity. To date, the findings have not demonstrated the postulated j-shaped relationship, but the cross-sectional comparison of low vs. high levels of leisure activity suggests that the adoption of an active lifestyle could reduce all-cause cancer rates by as much as 46%.


Arms race of temporal partitioning between carnivorous and herbivorous mammals.
Reciprocal coevolutionary changes in predation and anti-predator behaviours have long been hypothesized, but evolutionary-scale evidence is rare. Here, we reconstructed the evolutionary-scale changes in the diel activity patterns of a predator-prey system (carnivorous and herbivorous mammals) based on a molecular phyloecological approach, providing evidence of long-term antagonistic coevolutionary changes in their diel activities. Our molecular reconstruction of diel activity patterns, which is supported by morphological evidence, consistently showed that carnivorous mammals were subjected to a shift from diurnality to nocturnality, while herbivorous mammals experienced a shift from nocturnality to diurnality during their evolutionary histories. A shift in the diel activity of the herbivores as a result of carnivore avoidance is hypothesized based on molecular, morphological and behavioural evidence, and our results suggest an evolutionary-scale arms race of diel activity shifts between carnivorous and herbivorous mammals.


[A statistical analysis of serum sialyl Lewis X-1 (SLX), CEA, SCC and NSE levels in patients with lung cancer].
Serum SLX, CEA, SCC and NSE levels were serially measured in 266 patients with lung cancer and compared with those in 345 patients with benign respiratory disorders (BRD). The positive rate for CEA in lung cancer (44.4%) and the false-positive rate in BRD (15.3%) were the highest among the 4 markers. The positive rate for SLX in lung cancer (32.0%) was lower than that of CEA, while the false-positive rate for SLX in BRD (7.2%) was lower than that of CEA. The positive rate for SLX was highest in adenocarcinoma and correlated better with the clinical stages than did CEA. SCC and NSE were specifically elevated in squamous cell carcinoma and small cell carcinoma, respectively. Using these 4 markers, only 70.2% of patients were correctly diagnosed as having lung cancer or BRD. In monitoring treatment effect, only SLX showed a statistically significant correlation with regression and progression in adenocarcinoma, while NSE and SLX showed such a correlation in small cell carcinoma. Serum tumor markers seem to be less sensitive for the diagnosis of lung cancer than chest X-ray and sputum cytology, indicating that a search for more specific markers is still required. However, in monitoring treatment effect, SLX appeared to be suitable for adenocarcinoma, while NSE and SLX seemed to be useful in small cell carcinoma.


Multiple receptors for the pancreatic polypeptide (PP-fold) family: physiological implications.
The pancreatic polypeptide (PP-fold) family of peptides consists of the endocrine peptides, pancreatic polypeptide (PP) and peptide YY (PYY), and the neuroneally derived peptide, neuropeptide Y (NPY). All three peptides are found in the circulation, with PP found primarily in the pancreas and PYY found principally in the gut. NPY is released into the circulation from neuroneal stores in response to stress. These peptides have broad peripheral actions on a number of organs. Not surprisingly, PYY and PP are believed to play an important role in the function of the gastrointestinal tract while NPY is a potent vasconstrictor and may have effects on the gut through the enteric nervous system. In the brain, NPY has been implicated in anxiety and depression, feeding and obesity, memory retention, neuroneal excitability, endocrine function, and metabolism. Recent advances in the molecular biology of the receptors for these peptides have resulted in the identification of at least six receptor subtypes with varying peptide pharmacology. Compared to other G-protein coupled receptor families, the PP-fold peptide receptors exhibit a relatively low level of sequence identity. Further advances in the development of selective agonists and antagonists for individual receptor subtypes will be needed to understand further their role in physiological function.


NMR relaxation and pulsed-gradient diffusion study of polyethylene nanocomposites.
We performed pulsed-gradient spin-echo nuclear-magnetic-resonance (NMR) experiments on zinc oxide filled polyethylene. The molecular weights of the polyethylene samples ranged between 808 and 33,000 gmol, and four different zinc oxide samples were used: 27-, 33-, 51-, and 2500-nm-diameter particles. The results of these experiments showed that the diffusion coefficients of the polyethylene chains did not change with nanofiller content, but a drastic change is observed in the NMR relaxation spectrum in spin-spin-relaxation experiments. At fixed zinc oxide content and polyethylene molecular weight (close to entanglement), the system with the smallest zinc oxide showed the most rigid environment. At high polyethylene molecular weights, this effect was still observable but the difference between the three investigated systems was very small, suggesting that the system was dominated by entanglements.


Opioid Use Disorder in Patients Undergoing Primary 1- to 2-Level Anterior Cervical Discectomy and Fusion Is Associated With Longer In-Hospital Lengths of Stay and Higher Rates of Readmissions, Complications, and Costs of Care.
Retrospective study. To determine whether opioid use disorder (OUD) patients undergoing 1- to 2-level anterior cervical discectomy and fusion (1-2ACDF) have higher rates of: 1) in-hospital lengths of stay (LOS); 2) readmissions; 3) complications; and 4) costs. OUD patients undergoing primary 1-2ACDF were identified within the Medicare database and matched to a control cohort in a 1:5 ratio by age, sex, and medical comorbidities. The query yielded 80,683 patients who underwent 1-2 ACDF with (n = 13,448) and without (n = 67,235) OUD. Outcomes analyzed included in-hospital LOS, 90-day readmission rates, 90-day medical complications, and costs. Multivariate logistic regression analyses were used to calculate odds-ratios (OR) for medical complications and readmissions. Welch's t-test was used to test for significance for LOS and cost between the cohorts. An alpha value less than 0.002 was considered statistically significant. OUD patients were found to have significantly longer in-hospital LOS compared to their counterparts (3.41 vs. 2.23-days, P < .0001), in addition to higher frequency and odds of requiring readmissions (21.62 vs. 11.57%; OR: 1.38, P < .0001). Study group patients were found to have higher frequency and odds of developing medical complications (0.88 vs. 0.19%, OR: 2.80, P < .0001) and incurred higher episode of care costs ($20,399.62 vs. $16,812.14, P < .0001). The study can help to push orthopaedic surgeons in better managing OUD patients pre-operatively in terms of safe discontinuation and education of opioid drugs and their effects on complications, leading to more satisfactory outcomes.