Cytochrome b5 reductase and the control of lipid metabolism and healthspan.
Cytochrome b5 reductases (CYB5R) are required for the elongation and desaturation of fatty acids, cholesterol synthesis and mono-oxygenation of cytochrome P450 enzymes, all of which are associated with protection against metabolic disorders. However, the physiological role of CYB5R in the context of metabolism, healthspan and aging remains ill-defined. We generated CYB5R-overexpressing flies (CYB5R-OE) and created a transgenic mouse line overexpressing CYB5R3 (CYB5R3-Tg) in the C57BL/6J background to investigate the function of this class of enzymes as regulators of metabolism and age-associated pathologies. Gender- and/or stage-specific induction of CYB5R, and pharmacological activation of CYB5R with tetrahydroindenoindole extended fly lifespan. Increased expression of CYB5R3 was associated with significant improvements in several metabolic parameters that resulted in modest lifespan extension in mice. Diethylnitrosamine-induced liver carcinogenesis was reduced in CYB5R3-Tg mice. Accumulation of high levels of long-chain polyunsaturated fatty acids, improvement in mitochondrial function, decrease in oxidative damage and inhibition of chronic pro-inflammatory pathways occurred in the transgenic animals. These results indicate that CYB5R represents a new target in the study of genes that regulate lipid metabolism and healthspan.


The future of mathematics education since COVID-19: humans-with-media or humans-with-non-living-things.
The COVID-19 pandemic has changed the agenda of mathematics education. This change will be analyzed by looking at three trends in mathematics education: the use of digital technology, philosophy of mathematics education, and critical mathematics education. Digital technology became a trend in mathematics education in response to the arrival of a different kind of artifact to the mathematics classroom. It was thrust into the spotlight as the pandemic suddenly moved classrooms online around the world. Challenges specific to mathematics education in this context must be addressed. The link between the COVID-19 pandemic and digital technology in education also raises epistemological issues highlighted by philosophy of mathematics education and critical mathematics education. Using the notion that the basic unit of knowledge production throughout history is humans-with-media, I discuss how humans are connected to the virus, how it has laid bare social inequality, and how it will change the agendas of these three trends in mathematics education. I highlight the urgent need to study how mathematics education happens online for children when the home environment and inequalities in access to digital technologies assume such significant roles as classes move on-line. We need to understand the political role of agency of artifacts such as home in collectives of humans-with-media-things, and finally we need to learn how to implement curricula that address social inequalities. This discussion is intertwined with examples.


Assessing the prevalence, products, and pathways of dissolved organic matter partial photo-oxidation in arctic surface waters.
In sunlit waters, photodegradation of dissolved organic matter (DOM) yields completely oxidized carbon (i.e., CO2) as well as a suite of partially oxidized compounds formed from oxygen incorporation (i.e., partial photo-oxidation). Of these two groups of DOM photo-products, more studies focus on CO2 (a greenhouse gas) than on partially oxidized DOM, which is likely a diverse group of compounds with poorly constrained roles in aquatic carbon cycling or biogeochemistry. The objective of this study is to address knowledge gaps on the prevalence, products, and pathways of DOM partial photo-oxidation. Here we traced the photochemical incorporation of isotopically labelled 18O2 into DOM isolated from Alaskan Arctic surface waters using high-resolution mass spectrometry. Complete and partial photo-oxidation of DOM was also quantified as CO2 production and O2 consumption. The majority of 18O-containing partial oxidation photo-products were classified as carboxylic rich alicyclic molecules (CRAM) and overlapped in composition with previously reported photo-products known to result from the oxidation of DOM by singlet oxygen. These results support a previously proposed hypothesis that photo-oxidation by singlet oxygen may contribute to the formation of CRAM, a compound class of DOM ubiquitously observed in surface waters. The novel application of an isotopic tracer for oxygen incorporation with a mass balance approach to quantify complete and partial photo-oxidation of DOM revealed that less than one mol of O2 is required to produce one mol of CO2. A sensitivity analysis based on this new knowledge demonstrated that the magnitude of DOM partial photo-oxidation may be underestimated by up to four-fold. Consequently, partial photo-oxidation likely plays a more prominent role in shaping DOM composition in sunlit waters of the Arctic than previously understood. Therefore, partial photo-oxidation should be increasingly incorporated into the experimental framework of studies focused on DOM composition in surface waters.


FABP4 induces vascular smooth muscle cell proliferation and migration through a MAPK-dependent pathway.
The migration and proliferation of vascular smooth muscle cells play crucial roles in the development of atherosclerotic lesions. This study examined the effects of fatty acid binding protein 4 (FABP4), an adipokine that is associated with cardiovascular risk, endothelial dysfunction and proinflammatory effects, on the migration and proliferation of human coronary artery smooth muscle cells (HCASMCs). A DNA 5-bromo-2'-deoxy-uridine (BrdU) incorporation assay indicated that FABP4 significantly induced the dose-dependent proliferation of HCASMCs with a maximum stimulatory effect at 120 ng/ml (13% vs. unstimulated cells, p<0.05). An anti-FABP4 antibody (40 ng/ml) significantly inhibited the induced cell proliferation, demonstrating the specificity of the FABP4 proliferative effect. FABP4 significantly induced HCASMC migration in a dose-dependent manner with an initial effect at 60 ng/ml (12% vs. unstimulated cells, p<0.05). Time-course studies demonstrated that FABP4 significantly increased cell migration compared with unstimulated cells from 4 h (23%vs. 17%, p<0.05) to 12 h (74%vs. 59%, p<0.05). Pretreatment with LY-294002 (5 µM) and PD98059 (10 µM) blocked the FABP4-induced proliferation and migration of HCASMCs, suggesting the activation of a kinase pathway. On a molecular level, we observed an up-regulation of the MAPK pathway without activation of Akt. We found that FABP4 induced the active forms of the nuclear transcription factors c-jun and c-myc, which are regulated by MAPK cascades, and increased the expression of the downstream genes cyclin D1 and MMP2, CCL2, and fibulin 4 and 5, which are involved in cell cycle regulation and cell migration. These findings indicate a direct effect of FABP4 on the migration and proliferation of HCASMCs, suggesting a role for this adipokine in vascular remodelling. Taken together, these results demonstrate that the FABP4-induced DNA synthesis and cell migration are mediated primarily through a MAPK-dependent pathway that activates the transcription factors c-jun and c-myc in HCASMCs.


Incidence of antiviral drug resistance markers among human influenza A viruses in the Eastern Mediterranean Region, 2005-2016.
Two classes of antiviral drugs are available for influenza antiviral therapy: the adamantanes and the neuraminidase inhibitors (NAIs). Due to the emergence of adamantane-resistant variants, the use of these drugs has been largely limited in the world. The NAIs became the drugs of choice for treatment of influenza A infections. However, amino acid substitutions in the NA protein might lead to reduced sensitivity to NAIs. The frequency and distribution of matrix protein 2 (M2) and neuraminidase (NA) variants which confer resistance to antiviral drugs was investigated in the Eastern Mediterranean Region (EMR) between 2005 and 2016. A total of 314 M2 and 1209 NA protein sequences from influenza A/H1N1, A/H1N1pdm09, A/H3N2, and A/H5N1 available in the public database were analyzed. Eighty-six percent of the influenza A viruses detected in the EMR were resistant to adamantanes, among which, H3 strains exhibited the highest (95.32%) level of adamantane resistance. Approximately 98.51% (265/269) of influenza A/H1N1 and H3N2 resistant viruses had the S31N substitution in their M2 sequences. The V27A mutation was the only resistance marker found in A/H5N1 viruses and was detected at a frequency of 7.40% among the investigated viruses. Other resistant mutations L26F, A30T, G34E, and L38F were not detected in any of the variants. We found that 2.81% (n = 34) of the detected NA sequences from influenza A viruses possessed at least one NAI-resistant mutation and the vast majority of resistant viruses 79.41% (27/34) bear the H274Y mutation. The frequency of NAI-resistant viruses was 3.29% (24/729) for the H1N1pdm09, 10.64% (5/47) for the seasonal H1N1, and 4.06% (5/123) for H5N1 viruses. None of the H3N2 viruses analyzed during the study period were resistant to NAIs. Our study reveals the emergence and spread of antiviral drug resistant influenza A viruses in the EMR and emphasizes the importance of continuous surveillance to maintain the effective use of the current antivirals.


Characterization in Micromonospora inyoensis of aminoglycoside acetyltransferase activity not previously encountered among actinomycetes.
Extracts of Micromonospora inyoensis contain aminoglycoside acetyltransferase activity not previously encountered among actinomycetes. Neomycin and its derivatives (excluding butirosin) are good substrates as is the novel aminoglycoside apramycin, whereas the gentamicins and kanamycins are utilized poorly if at all. Sisomicin, which is produced by M. inyoensis, is not acetylated. When neomycin was modified by extracts of M. inyoensis the product, most probably 3-N-acetylneomycin, was inactive against cell-free protein synthesis.


Physiological and physiopathological aspects of connexins and communicating gap junctions in spermatogenesis.
Spermatogenesis is a highly regulated process of germ cell proliferation and differentiation, starting from spermatogonia to spermatocytes and giving rise to spermatids, the future spermatozoa. In addition to endocrine regulation, testicular cell-cell interactions are essential for spermatogenesis. This precise control is mediated through paracrine/autocrine pathways, direct intercellular contacts and through intercellular communication channels, consisting of gap junctions and their constitutive proteins, the connexins. Gap junctions are localized between adjacent Leydig cells, between Sertoli cells and between Sertoli cells and specific germ cells. This review focuses on the distribution of connexins within the seminiferous epithelium, their participation in gap junction channel formation, the control of their expression and the physiological relevance of these junctions in both the Sertoli-Sertoli cell functional synchronization and the Sertoli-germ cell dialogue. In this review, we also discuss the potential implication of disrupted connexin in testis cancer, since impaired expression of connexin has been described as a typical feature of tumoral proliferation.


Comparative aquatic toxicity evaluation of 2-(thiocyanomethylthio)benzothiazole and selected degradation products using Ceriodaphnia dubia.
2-(Thiocyanomethylthio)benzothiazole (TCMTB) is a biocide used in the leather, pulp and paper, and water-treatment industries. TCMTB may enter aquatic ecosystems during its manufacture and use. TCMTB is environmentally unstable; therefore, it is important to evaluate the toxicity of the more persistent degradation products. This study compared the toxicity of TCMTB with its degradation products 2-mercaptobenzothiazole (2-MBT), 2-(methylthio)benzothiazole (MTBT), benzothiazole (BT), and 2-hydroxybenzothiazole (HOBT). Toxicity was determined using Ceriodaphnia dubia 48-hour acute and 7-day chronic test protocols. TCMTB was the most toxic compound evaluated in both the acute and chronic tests with EC50s of 15.3 and 9.64 microg/L, respectively. 2-MBT, the first degradation product, was the second most toxic compound with acute and chronic EC50s of 4.19 and 1.25 mg/L, respectively. The toxicity of MTBT and HOBT were similar with acute EC50s of 12.7 and 15.1 mg/L and chronic EC50s of 6.36 and 8.31 mg/L, respectively. The least toxic compound was BT with acute and chronic EC50s of 24.6 and 54.9 mg/L, respectively. TCMTB was orders of magnitude more toxic than its degradation products. Toxicity data on these benzothiazole degradation products is important because of concerns regarding their release, degradation, persistence, and non-target organism effects in aquatic ecosystems.


In vitro metabolism and stability of the actinide chelating agent 3,4,3-LI(1,2-HOPO).
The hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. The preclinical characterization of this highly promising ligand comprised the evaluation of its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, and intestinal absorption using the Caco-2 cell line. When mixed with active human liver microsomes, no loss of parent compound was observed after 60 min, indicating compound stability in the presence of liver microsomal P450. At the tested concentrations, 3,4,3-LI(1,2-HOPO) did not significantly influence the activities of any of the cytochromal isoforms screened. Thus, 3,4,3-LI(1,2-HOPO) is unlikely to cause drug-drug interactions by inhibiting the metabolic clearance of coadministered drugs metabolized by these enzymes. Plasma protein-binding assays revealed that the compound is protein-bound in dogs and less extensively in rats and humans. In the plasma stability study, the compound was stable after 1 h at 37°C in mouse, rat, dog, and human plasma samples. Finally, a bidirectional permeability assay demonstrated that 3,4,3-LI(1,2-HOPO) is not permeable across the Caco-2 monolayer, highlighting the need to further evaluate the effects of various compounds with known permeability enhancement properties on the permeability of the ligand in future studies.


The Features of Comorbidity of Childhood ADHD in Patients With Obsessive Compulsive Disorder.
Objective: Our aim is to investigate the impact of childhood ADHD comorbidity on the clinical features of obsessive compulsive disorder (OCD). Method: Ninety-five adult outpatients with a diagnosis of OCD were assessed by using the Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version, ADHD module, and the Yale-Brown Obsessive Compulsive Scale. Patients with or without childhood ADHD were compared in terms of the sociodemographic and clinical features, psychiatric comorbidities, and rating scales. Results: The rate of episodic course of OCD (p < .001), religious and sexual obsessions (p = .009, p = .020, respectively), lifetime comorbidity of bipolar disorder (BD), social anxiety disorder (SAD; p = .001, p = .009, respectively), and tic disorder (TD) comorbidity (p < .001) were higher in the OCD + ADHD group than in the OCD without ADHD group. Conclusion: Childhood ADHD may be associated with higher rates of BD, SAD, and TD comorbidity and episodic course of OCD as well as higher frequency of certain types of obsessions.


Detuned slow light in the Doppler broadened multi-level D2 line of Rubidium.
We observed a detuned slow light phenomenon based on electromagnetically induced transparency in (87)Rb D2 line composed of multiple excited-hyperfine states within a Doppler-broadened linewidth. The results show that the maximum group delay of a probe occurs at off-detuned two-photon resonance frequency. The observed detuned group delay is analyzed with numerical calculations for a probe pulse interacting with the neighboring excited-states-modified Doppler broadening atoms for a fixed coupling field. The experimental results are in good agreement with the numerical calculations.


Bilateral macular thickening in mild unilateral anterior uveitis: is HLA-B27 involved?
Macular thickening (MT) without clinically recognized macular edema has been described in anterior uveitis (AU). Although fellow-eyes of patients have been used as controls in several studies, little is known about macular thickness in these eyes. We studied the rate and extent of MT in both AU-affected and quiescent fellow-eyes of phakic AU patients with good visual acuity (VA). We also assessed macular thickness related to HLA-B27 presence and to recurrence, since these issues have been almost unexplored by previous optical coherence tomography (OCT) studies. Patients with AU were prospectively included and macular thickness was measured with OCT initially and on follow up. Macular thickness in patients' affected eyes (n = 30) as well as in their quiet fellow-eyes (n = 28) was compared with eyes of age- and gender matched controls. Inter-ocular differences in macular thickness between AU affected eyes and their fellow-eyes were assessed in patients (n = 28), also in a subgroup with visual acuity ≥ 0.8 (n = 23) by one-sample Student's t-tests. Inter-ocular differences were also assessed related to HLA-B27 presence and related to the status of current AU episode (initial or relapse). Subclinical MT is present in both quiet fellow-eyes and AU-affected eyes of patients. MT was found in most cases of AU, even in phakic eyes with good VA. There was a larger increase in macular thickness in HLA-B27-positive than in HLA-B27-negative patients. No differences in macular thickness were found between patients with their first AU episode and patients with recurrent episodes. MT probably reflects systemic immune-mediated response to the inflammatory disorder in AU, and it is possible that HLA-B27-related factors are involved in the pathogenesis of AU. These observations are in line with and extend the current understanding of the mechanisms behind MT in AU.


Geographical distribution of two haplotypes of chloroplast DNA in four oak species (Quercus) in Japan.
Chloroplast DNA polymorphism in four oak species (Quercus serrata, Q. mongolica var. crispula, Q. dentata and Q. aliena) was studied using collections from a total of 127 localities in Japan and South Korea on the basis of five intergenic spacers (trnD-trnT, trnT-trnL, rps14-psaB, trnS-trnT and trnQ-trnS). Although no variation existed in sequences among the four species, a single nucleotide (T/C) substitution in the trnQ-trnS intergenic spacer was found in all the four species, resulting in two haplotypes (T- and C-type). Phylogenetic analyses of the four species and related species showed that the C-type is derived and even likely of monophyletic origin, while the T-type is ancestral. Geographically, the T-type is widespread from South Korea to Japan, whereas the C-type is restricted to eastern Japan with rare exceptions. "Eastern Japan" approximately coincides with the distribution range of the boreal conifer forest during the last glacial maximum. Overall evidence suggests that the mutation from T- to C-type occurred in an individual of one of the four oak species and then was transferred to all the species by hybridization in eastern Japan, and that the Kanto District provided individuals with the C-type with a refugium during the last glacial maximum.


Cerebrovascular Complications of Pediatric Blunt Trauma.
Ischemic and hemorrhagic stroke can occur in the setting of pediatric trauma, particularly those with head or neck injuries. The risk of stroke appears highest within the first two weeks after trauma. Stroke diagnosis may be challenging due to lack of awareness or concurrent injuries limiting detailed neurological assessment. Other injuries may also complicate stroke management, with competing priorities for blood pressure, ventilator management, or antithrombotic timing. Here we review epidemiology, clinical presentation, and diagnostic approach to blunt arterial injuries including dissection, cerebral sinovenous thrombosis, mineralizing angiopathy, stroke from abusive head trauma, and traumatic hemorrhagic stroke. Owing to the complexities and heterogeneity of concomitant injuries in stroke related to trauma, a single pathway for stroke management is impractical. Therefore providers must understand the goals and possible costs or consequences of stroke management decisions to individualize patient care. We discuss the physiological principles of cerebral perfusion and oxygen delivery, considerations for ventilator strategy when stroke and lung injury are present, and current available evidence of the risks and benefits of anticoagulation to provide a framework for multidisciplinary discussions of cerebrovascular injury management in pediatric patients with trauma.


Biomechanical properties of off-axis screw in Pauwels III femoral neck fracture fixation: Bicortical screw construct is superior to unicortical screw construct.
The purpose of this study is to determine the biomechanical properties of the bicortical off-axis screw fixation for stabilizing of Pauwels III femoral neck fractures compared with other fixation methods. Eighteen synthetic femurs (Sawbones Pacific Research Laboratories, Vashon, WA) were divided into three groups. The osteotomy was made vertically to mimic the Pauwels type III femoral neck fracture. Group A (n = 6) was fixed with traditional inverted triangle cannulated screws. Group B (n = 6) was fixed with a unicortical off-axis screw and two parallel cannulated screws. Group C (n = 6) was fixed with a bicortical off-axis screw and two parallel cannulated screws. Each group was tested with a nondestructive axial compression test at a 7° of valgus followed with 1000 cycles of cyclic loading test from 100 N to 1000 N. Finally, a destructive axial compression test was applied until catastrophic failure. The average axial stiffness from group A to group C was 856.5, 934, and 1340 N/mm, respectively. The average ultimate failure load from group A to group C was 2612.7, 2508.8, and 3706 N, respectively. Group C exhibited significantly greater axial stiffness and a higher ultimate failure load than the other two groups (P < 0.05). Regarding the interfragmental displacement, the values from group A to group C were 0.41, 0.83, 0.36, respectively, and group B exhibited significantly larger fracture gap formation after the cyclic loading test. The results of this biomechanical study show statistically significant increases in axial stiffness and ultimate failure load for the off-axis screw placed in bicortical fashion. Once the off-axis screw was positioned unicortically, the largest fracture diastasis was observed as compared to the other two methods.


Differential gene expression in Arabidopsis following infection by plant-parasitic nematodes Meloidogyne incognita and Heterodera schachtii.
SUMMARY Whole genome microarrays were used to study plant gene expression in mature Meloidogyne incognita-induced galls in Arabidopsis. We found 959 genes to be significantly differentially expressed, and two-thirds of these were down-regulated. Microarray results were confirmed by qRT-PCR. The temporal and spatial responses of four differentially expressed genes were analysed using GUS reporter plants following infection with M. incognita and the cyst nematode Heterodera schachtii. The ammonium transporter gene AtAMT1;2 was consistently and locally repressed in response to both nematodes at all developmental stages. The lateral organ boundary domain gene LBD41 showed up-regulation in the feeding sites of both nematode species, although there was variation in expression in saccate H. schachtii female feeding sites. Expression of an actin depolymerizing factor ADF3 and a lipid transfer protein was induced in feeding sites of both nematodes at the fusiform stage and this persisted in feeding sites of saccate M. incognita. These results contribute to the knowledge of how plant gene expression responds to parasitism by these nematodes as well as highlighting further differences in the mechanisms of development and maintenance of these feeding site structures.


Oxidative Processes in Muscle Systems and Fresh Meat: Sources, Markers, and Remedies.
Oxidation of meat occurs under postmortem conditions and is inevitable. This oxidation includes the biochemical changes in meat leading to changes in color pigments and lipids. As a consequence, color deteriorates, and undesirable flavors and rancidity develop in meat thereby impacting on consumer appeal and satisfaction. Across carcasses, there is variation in the rate at which muscle undergoes chemical reactions under postmortem conditions that reflect inherent variation at the biochemical level. It is expected that this underlying biochemical variation will be reflected in living muscle through oxidative processes. The oxidative process of muscle tissues will vary according to an animal's immunity status, temperament, and ability to cope with stress, with all these affected by nutrition, genetics, management practices, and environmental conditions (hot and cold seasons). Identification of biomarkers that indicate the oxidative status levels of animals or muscle tissues in vivo could provide insight as to how the muscle will respond to the anoxic conditions that produce undesirable results in meat. This review outlines the potential use of 1 group of biomarkers, the isoprostanes, in the context of complex biochemical reactions relating to oxidative processes that take place in the biological systems of live animals (in vivo) and subsequently in meat (in vitro).


Association of Chinese visceral adiposity index with clinical outcome in patients after endovascular thrombectomy.
The Chinese Visceral Adiposity Index (CVAI) is a reliable indicator of visceral adiposity dysfunction in the Chinese population. We aimed to evaluate the association between CVAI and clinical outcome in Chinese ischemic stroke patients who received endovascular thrombectomy (EVT). This study retrospectively included patients with large vessel occlusive stroke receiving EVT treatment in 2 China stroke centers. Baseline CVAI was calculated after admission. Patients with a modified Rankin scale score ≥ 3 at 3 months after ischemic stroke were defined as poor outcome. Binary multivariate logistic regression models were utilized to explore the association between CVAI and the risk of 90-day unfavorable outcome. A total of 453 patients (mean age, 70.4 ± 12.1 years; 280 male) were included. During the 90-day follow-up, 236 (52.1 %) patients experienced poor outcome. After multivariable adjustment for potential confounders, increasing CVAI was associated with an increased risk of 90-day poor outcome (odds ratios, per-standard deviation increase: 1.521; 95 % confidence interval, 1.127-2.052; P = 0.006). Similar significant results were observed when the CVAI was analyzed as a categorical variable. Furthermore, the multiple-adjusted spline regression model showed an inverted J-shape association between CVAI and risk of unfavorable outcome (P = 0.048 for non-linearity). This study demonstrated that CVAI is positively correlated with 90-day poor outcome in Chinese ischemic stroke patients after EVT.


Assessment of concentration of polycyclic aromatic hydrocarbons (PAHs) in vegetables from farms in Accra, Ghana.
Ingestion of leafy vegetables is an important dietary component of most Africans due to its health benefits. High levels of polycyclic aromatic hydrocarbons (PAHs) in the leafy vegetables may pose a significant health hazard to the consumers. Rose/Hibiscus, Chinese cabbage, lettuce, and garden egg leaves from farms along the Nima Creek, Accra, were selected. At each sampling site, the vegetable was uprooted and cut into leaves, stem, and root and analyzed differently. The GC-MS method was employed in the identification and quantification of 16 PAHs in the samples. The analysis was done at CSIR - Water Research Institute Organic Laboratory. The results obtained show concentrations of acenapththylene, acenapthene, benzo[a]anthracene, benzo[b]fluoranthene, and benzo[a]pyrene (except chrysene and pyrene which were found in garden egg leaves and Chinese cabbage respectively), while naphthalene was detected in all the vegetables. The mean concentration of phenanthrene in leaves, stem, and roots of Chinese cabbage vegetable varies according to the following order: roots (0.744 ± 0.16 μg/kg) ≥ leaves (0.598 ± 1.21 μg/kg) ≥ stem (0.327 ± 1.01 μg/kg). From the results of the isomeric ratios, the source of the PAHs in the leafy vegetables are from mixed sources, i.e., either pyrogenic and petrogenic origins. This calls for the formulation of stringent policies on the importation of over-age vehicles into the countries as well as on the indiscriminate burning of materials containing PAHs.


Mhealth tools for community-based infectious disease surveillance in Africa: a scoping review protocol.
Countries in the WHO's African region have found community-based surveillance useful in ensuring the effectiveness of the Integrated Disease Surveillance and Response strategy. This approach encourages community participation in the surveillance system, in addition to early detection of outbreaks and other health threats. Thus, advancements in mobile health have the potential to improve community-based surveillance in Africa. The purpose of this review is to map evidence on available mhealth tools for community-based infectious disease surveillance in Africa. The scoping review will follow a mixed-methods approach in line with the framework of Arksey and O'Malley amended by Levac and colleagues and the Joanna Briggs Institute. To retrieve published literature, PubMed, Scopus, Web of Science, Google Scholar and Google databases will be explored. Websites of organisations involved in surveillance activities across the African region will also be explored. Authors will be interested in published literature between 2000 and 2022 in any language. The primary investigator and a second author will independently review the retrieved titles according to the inclusion criteria, while a third reviewer will resolve conflicts that may arise. The review will map evidence according to the key concepts (mhealth, community-based surveillance and Africa) to inform stakeholders and mhealth designers on best practices to adopt involving mhealth approaches at the community level and mhealth tool designs, respectively. Results following the review will be presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: Extension for Scoping Review Guidelines. Ethical approval is not required for scoping reviews as it does not involve the use of human subjects. This review is the first phase in an overall project on digital health. The findings of the review will be published in a peer-reviewed journal and disseminated at suitable forums and conferences.


Coronal approach for rejuvenation of the eyes and forehead.
Aesthetic surgeons are using the coronal forehead lift to achieve more consistent and enduring results due to a better understanding of the anatomy, dynamics, and aging process of the forehead. The varied indications for the procedure, such as soft-tissue ptosis and facial wrinkles, are discussed. The surgical technique is described, including the many controversial methods of managing the frontalis muscle. Eyeglasses and precise photography are employed to more objectively evaluate the amount of eyebrow elevation. Very gratifying results have been achieved with only minimal complications. The coronal forehead lift enhances the effects of the standard blepharoplasty and the orbicularis oculi muscle flap suspension techniques, and can be done in conjunction with a facial-cervical rhytidectomy. Presently, this is the procedure of choice in most women for rejuvenating the upper third of the face.


PREDICTING RECIDIVISM FOR RELEASED STATE PRISON OFFENDERS: Examining the Influence of Individual and Neighborhood Characteristics and Spatial Contagion on the Likelihood of Reincarceration.
We examined the influence of individual and neighborhood characteristics and spatial contagion in predicting reincarceration on a sample of 5,354 released Pennsylvania state prisoners. Independent variables included demographic characteristics, offense type, drug involvement, various neighborhood variables (e.g., concentrated disadvantage, residential mobility), and spatial contagion (i.e., proximity to others who become reincarcerated). Using geographic information systems (GIS) and logistic regression modeling, our results showed that the likelihood of reincarceration was increased with male gender, drug involvement, offense type, and living in areas with high rates of recidivism. Older offenders and those convicted of violent or drug offenses were less likely to be reincarcerated. For violent offenders, drug involvement, age, and spatial contagion were particular risk factors for reincarceration. None of the neighborhood environment variables were associated with increased risk of reincarceration. Reentry programs need to particularly address substance abuse issues of ex-offenders as well as take into consideration their residential locations.


Victimization Disparities Between Heterosexual and Sexual Minority Youth From Ages 9 to 15.
Mental health disparities between heterosexual and sexual minority youth are partly explained by the higher rates of victimization experienced by sexual minority youth. The onset and progression of these victimization disparities, however, are poorly understood. Using multirater longitudinal data, trajectories of victimization starting at age 9 were compared among youth who did and did not report same-sex attraction at age 15 (N = 310). Self and teacher, but not primary caregivers, reported victimization was significantly higher among sexual minority youth starting at age 9, but did not vary across time. The findings underscore the importance of understanding homophobic experiences of sexual minority youth during late childhood and early adolescence in order to inform prevention programs.


Apolipoprotein A1 regulates coenzyme Q10 absorption, mitochondrial function, and infarct size in a mouse model of myocardial infarction.
HDL and apolipoprotein A1 (apoA1) concentrations inversely correlate with risk of death from ischemic heart disease; however, the role of apoA1 in the myocardial response to ischemia has not been well defined. To test whether apoA1, the primary HDL apolipoprotein, has an acute anti-inflammatory role in ischemic heart disease, we induced myocardial infarction via direct left anterior descending coronary artery ligation in apoA1 null (apoA1(-/-)) and apoA1 heterozygous (apoA1(+/-)) mice. We observed that apoA1(+/-) and apoA1(-/-) mice had a 52% and 125% increase in infarct size as a percentage of area at risk, respectively, compared with wild-type (WT) C57BL/6 mice. Mitochondrial oxidation contributes to tissue damage in ischemia-reperfusion injury. A substantial defect was present at baseline in the electron transport chain of cardiac myocytes from apoA1(-/-) mice localized to the coenzyme Q (CoQ) pool with impaired electron transfer (67% decrease) from complex II to complex III. Administration of coenzyme Q10 (CoQ10) to apoA1 null mice normalized the cardiac mitochondrial CoQ pool and reduced infarct size to that observed in WT mice. CoQ10 administration did not significantly alter infarct size in WT mice. These data identify CoQ pool content leading to impaired mitochondrial function as major contributors to infarct size in the setting of low HDL/apoA1. These data suggest a previously unappreciated mechanism for myocardial stunning, cardiac dysfunction, and muscle pain associated with low HDL and low apoA1 concentrations that can be corrected by CoQ10 supplementation and suggest populations of patients that may benefit particularly from CoQ10 supplementation.


[Order as a task: the construction of nursing diagnoses].
Classifying means segregating. It means seeing the world as something that can be made up of different entities that could be sorted and make what has been organized into something real. Thus, the Nursing Diagnoses (ND) aims at being an archive that allows a knowledge framework to be drawn about the individuals. In this paper we intend to learn how nurses have built this documental device. So, we analysed articles published on the Revista Brasileira de Enfermagem and found out that some meanings have been attributed to ND, which allowed us to group them into five classes. We also observed that the journal's discourses assign powers to such classification, because they make this knowledge stronger by publicising it.


Molecular cloning and functional characterization of a novel delayed rectifier potassium channel from channel catfish (Ictalurus punctatus): expression in taste buds.
The gustatory system of channel catfish is widely studied for its sensitivity to amino acids. As a first step in identifying the molecular components that play a role in taste transduction in catfish, we cloned the full-length cDNA for Kv2-catfish, a novel K(+) channel that is expressed in taste buds. The deduced amino acid sequence is 816 residues, and shares a 56-59% sequence identity with Kv2.1 and Kv2.2, the other members of the vertebrate Kv2 subfamily of voltage-gated K(+) channels. The Kv2-catfish RNA was expressed in taste buds, brain, skeletal muscle, kidney, intestine and gills, and its gene is represented as a single copy in the catfish genome. Recombinant channels expressed in Xenopus oocytes were selective for K(+), and were inhibited by tetraethylammonium applied to the extracellular side of the membrane during two-electrode voltage clamp analysis with a 50% inhibitory constant of 6.1 mM. The channels showed voltage-dependent activation, and did not inactivate within 200 ms. Functionally, Kv2-catfish is a voltage-gated, delayed rectifier K(+) channel, and its primary structure is the most divergent sequence identified among the vertebrate members of the Kv2 subfamily of K(+) channels, being related equally well to Kv2.1 and Kv2.2.


The effect of intravenous administration of variable-dose flumazenil after fixed-dose ketamine and midazolam in healthy cats.
The effects of intravenous administration of variable-dose flumazenil (0, 0.001, 0.005, 0.01, and 0.1 mg/kg) after ketamine (3 mg/kg) and midazolam (0.0 and 0.5 mg/kg) were studied in 18 healthy unmedicated cats from time of administration until full recovery. End-points were chosen to determine whether flumazenil shortened the recovery period and/or modified behaviors previously identified and attributed to midazolam. Overall, flumazenil administration had little effect on recovery or behaviors. One minute after flumazenil administration, all cats were recumbent but a greater proportion of cats which received the highest dose assumed sternal recumbency with head up than any other group. Although not significant, those cats that received the highest flumazenil dose also had shorter mean times for each of the initial recovery stages (lateral recumbency with head up, sternal recumbency with head up and walking with ataxia) than any of the other treatment groups that received midazolam. For complete recovery, flumazenil did decrease the proportion of the cats that was sedated, but did not shorten the time to walking without ataxia. Based on this study, the administration of flumazenil in veterinary practice, at the doses studied, to shorten and/or improve the recovery from ketamine and midazolam in healthy cats cannot be recommended.


Experimental W values of low-energy protons in the alkane series from methane to pentane.
Accurate measurements of the mean energy expended in a gas per ion pair formed (W value) for protons slowed down in alkanes are needed (i) in the fields of neutron metrology and microdosimetry, and (ii) in the field of basic radiation research to check the validity of theoretical models describing the degradation of protons in matter. Here, data for protons at energies of less than 100 keV are of particular interest because W increases strongly with decreasing proton energy in the very low-energy region and shows some structure between 10 keV and 100 keV. For these reasons, the energy dependence of W was studied for completely slowed down monoenergetic protons in the alkane series from methane to pentane at energies 1 keV < or = T < or = 100 keV, by measuring the positive ionization yield produced in a plane-parallel ionization chamber. The final results, which have uncertainties of less than 1.5%, are given in tabular form and also in an analytical representation. They were used to determine the differential value omega of the mean energy expended in a gas per ion pair formed and to analyse differences in proton degradation in the alkanes as a function of the number of carbon atoms.


Will the war for the Croatian Homeland War veterans ever end?
The aim of this paper is to show the psychological consequences of participation in the Homeland War and experienced trauma which can indirectly be seen through drawing even after more than 15 years after the war had ended. The research was conducted on a sample of 125 patients of both genders treated in the Daily Hospital program of University Hospital Dubrava, Psychiatry Clinics. All the tested had trauma in their medical history and all of them met the PTSD diagnostic criteria, 75 examinees participated in the Homeland War and they represent the veteran group, and 50 examinees went through a stressful situation during peacetime and they represent the civilian group. All the examinees had to make two individual drawings, and the task was to portray feelings of term "love" (first drawing) and term "hate" (second drawing). They could choose motifs and colors freely. When portraying the term love, choice of motifs between the civilian and the veteran group wasn't considerably different, and only a small number of male veteran population (6.6%) drawings hinted at the connection with the Homeland War. The results between two groups are completely different in portraying the term hate. As much as 76% examinees from the veteran group have unequivocally and directly decided to portray wartime motifs, unlike the civilian group whose use of wartime motifs was just 10%. When choosing color, nearly 90% of the veteran group used neutral and cool colors to portray the term hate.


Molecular mechanisms of pyrimidine dimer excision in Saccharomyces cerevisiae: incision of ultraviolet-irradiated deoxyribonucleic acid in vivo.
A group of genetically related ultraviolet (UV)-sensitive mutants of Saccharomyces cerevisiae has been examined in terms of their survival after exposure to UV radiation, their ability to carry out excision repair of pyrimidine dimers as measured by the loss of sites (pyrimidine dimers) sensitive to a dimer-specific enzyme probe, and in terms of their ability to effect incision of their deoxyribonucleic acid (DNA) during post-UV incubation in vivo (as measured by the detection of single-strand breaks in nuclear DNA). In addition to a haploid RAD(+) strain (S288C), 11 different mutants representing six RAD loci (RAD1, RAD2, RAD3, RAD4, RAD14, and RAD18) were examined. Quantitative analysis of excision repair capacity, as determined by the loss of sites in DNA sensitive to an enzyme preparation from M. luteus which is specific for pyrimidine dimers, revealed a profound defect in this parameter in all but three of the strains examined. The rad14-1 mutant showed reduced but significant residual capacity to remove enzyme-sensitive sites as did the rad2-4 mutant. The latter was the only one of three different rad2 alleles examined which was leaky in this respect. The UV-sensitive strain carrying the mutant allele rad18-1 exhibited normal loss of enzyme-sensitive sites consistent with its assignment to the RAD6 rather than the RAD3 epistatic group. All strains having mutant alleles of the RAD1, RAD2, RAD3, RAD4, and RAD14 loci showed no detectable incubation-dependent strand breaks in nuclear DNA after exposure to UV radiation. These experiments suggest that the RAD1, RAD2, RAD3, RAD4 (and probably RAD14) genes are all required for the incision of UV-irradiated DNA during pyrimidine dimer excision in vivo.


Examining Contributors to Intent to Continue Exercising in Patients With Cancer in Rehabilitation.
Exercise is physiologically and psychologically beneficial to cancer survivors, leading to an increase in supervised exercise programs targeting this population. However, more than half of survivors who are offered a supervised exercise program do not complete it. The purpose of this study was to determine which factors influence survivors' decisions to continue exercising in or outside of a supervised exercise program using the theory of planned behavior (TPB). Survivors who graduated from an oncology rehabilitation program at a community hospital in the Midwest within a six-month period completed a survey on the TPB items of intention, perceived behavior control, attitude, and subjective norm, as well as demographic information. Participation in the oncology rehabilitation program demonstrated significant improvements in health and well-being. Bivariate analysis revealed that attitude and subjective norm were significantly related to and more important than perceived behavior control in survivors' intention to exercise. Oncology rehabilitation programs can foster more positive attitudes toward exercise and encourage participant renewal.


DREF is critical for Drosophila bristle development by regulating endoreplication in shaft cells.
DREF (DNA replication-related element-binding factor) plays important roles in replication and proliferation in vivo by regulating transcription of various genes. However, due to a lack of appropriate cell biological studies in vivo, roles of DREF during a single cell development are poorly understood. To address this question, we focused our attention on macrochaetes bristle development system. Utilizing cell lineage analysis focusing on a single posterior scutellar (PSC) macrochaete sensory organ precursor (SOP) lineages in combination with GAL4/UAS targeted expression system for DREF double strand RNA, we revealed that DREF plays no apparent role in differentiation process during SOP formation. Rather, DREF regulates the timing of asymmetric cell division but perhaps plays no direct role in differentiation during asymmetric cell division. Most importantly, DREF affected replication and growth in shaft cells and/or socket cells. Further analysis revealed that DREF is necessary but not sufficient for nuclear growth and protein synthesis in shaft cells. Finally, it could be demonstrated that DREF plays a critical role in regulating pcna transcription in endocycling shaft cells. All these results provide evidence that DREF plays critical roles, especially in endoreplication process of bristle development, at least in part by regulating the pcna gene expression.


Novel analytic tools for the study of porcine reproductive and respiratory syndrome virus (PRRSv) in endemic settings: lessons learned in the U.S.
Since its emergence in the late 1980's, the porcine reproductive and respiratory syndrome virus (PRRSv) has posed a significant challenge to the pig industry worldwide. Since then, a number of epidemiological tools have been created to support control and eventual elimination of the disease at the farm and regional levels. Still, many aspects of the disease dynamics are yet-to-be elucidated, such as what are the economically optimal control strategies at the farm and regional level, what is the role that the voluntary regional control programs may play, how to optimize the use of molecular tools for surveillance and monitoring in infected settings, what is the full impact of the disease in a farm, or what is the relative contribution of alternative transmission routes on the occurrence of PRRSv outbreaks. Here, we summarize a number of projects demonstrating the use of novel analytical tools in the assessment of PRRSv epidemiology in the United States. Results presented demonstrate how quantitative analysis of routinely collected data may help in understanding regional epidemiology of PRRSv and to quantify its full impact, and how the integration of phylodynamic methods as a standard tool for molecular surveillance of PRRSv might help to inform control and prevention strategies in high-risk epidemiological situations. Ultimately, these tools will help to support PRRSv control at farm and regional levels in endemically infected settings.


Outcome and risk factors for death of elderly burn patients: a case series in Vietnam.
The aim of this study is to investigate characteristics, outcome and risk factors for death among elderly burn patients. A retrospective study was conducted on 416 elderly (≥ 65 years old) burn patients admitted to the National Burn Hospital, Hanoi, Vietnam from 1/1/2016 to 31/12/2018. Data on demographics, comorbidity, burn severity, complications and mortality were recorded. Bivariate and multivariate analyses were conducted to determine independent risk factors for death. Results indicated that elderly burn patients accounted for 4.2% of total admitted patients with an average age of 74.7 ± 8.1 years old. Significantly higher burn surface area (12.4% vs. 7.3%; p < .001) and deep burn area (5.5% vs. 2.5%; p < .001) were seen in the female group when compared to the male group. Pre-existing medical conditions were recorded in 20.9% of patients, the highest proportion (13.2%) represented by cardiovascular disease followed by neurological and diabetic disease (8.7% and 7% respectively). Over half (51.5%) of the patients had suffered deep burn and 6.3% developed complications, the most common being multiple organ failure and pneumonia. Overall mortality rate was 9.9%. However, death rate was extremely high in patients with inhalation injury (92.9%), burn extent > 40% total body surface area (TBSA) and deep burn > 10% TBSA (61.2% and 62.5% respectively). Comorbidity was not an independent risk factor for death, unlike increased age, burn extent and presence of inhalation injury. In conclusion, we show that despite advances in management, severe burn and inhalation injury in the elderly remains a big challenge in Vietnam.


Predicting women at risk for developing obstetric fistula: a fistula index? An observational study comparison of two cohorts.
To ascertain if a predictor of obstructed labour and obstetric fistula (OF) occurrence could be devised. Observational study of two cohorts. Selian Lutheran Mission Hospital, Arusha, Tanzania and Aberdeen Women's Centre, Freetown, Sierra Leone. All women presenting with OF caused by obstructed labour and all women having a normal vaginal delivery (NVD) at both institutions were eligible for the study. All women with OF and those delivering normally had their height in centimetres measured and their intertuberous space measured by the number of examiner's knuckles admitted. The dimensions for OF and normal delivery were examined individually and multiplied to gain a 'fistula index'. Dimensions and index were compared statistically between OF and NVD women using t tests. Sensitivity, specificity and predictive values from receiver operating characteristic curves were obtained for predicting OF. There were statistical differences between the groups with OF women being significantly shorter, having a smaller intertuberous space and lower fistula index than those undergoing NVD (each P < 0.001). Sensitivity was high for fistula index ≤ 507.5 (94.9%, 95% confidence interval 83.1-98.6%) and for intertuberous space of at least three knuckles (92.3%, 95% CI 79.7-97.3%) alone. A simple antenatal measurement of intertuberous space could screen those women at higher risk of needing medical intervention to prevent OF.


Neurohormonal modulation of the Limulus heart: amine actions on neuromuscular transmission and cardiac muscle.
The responses of Limulus cardiac neuromuscular junctions and cardiac muscle cells to four endogenous amines were determined in order to identify the cellular targets underlying amine modulation of heartbeat amplitude. The amines increased the amplitude of the Limulus heartbeat, with dopamine (DA) being more potent than octopamine, epinephrine or norepinephrine. The effect of DA on heartbeat amplitude was not blocked by phentolamine. DA enhanced the contractility of deganglionated heart muscle, with time course and dose-dependence similar to its effect on the intact heart. The amines also enhanced neuromuscular transmission, with time course and dose-dependence similar to their effects upon the intact heart. The amplitude of unitary excitatory junction potentials (EJPs) and frequency of miniature excitatory junction potentials (mEJPs) were increased by DA, while mEJP amplitude was unchanged. Thus DA, and probably the other amines, had a presynaptic effect. Combined actions upon cardiac muscle and cardiac neuromuscular transmission account for the ability of these amines to increase the amplitude of the Limulus heartbeat.


[Evaluation of vascular surgery with digital subtraction angiography. A study of 127 patients].
We have performed digital subtraction angiography (DSA) on 127 patients treated by vascular surgery. This technique was easily and safely performed in outpatients, without any complication. Our experience indicates that DSA is accurate for post operative evaluation in 96% of cases. In digestive arterial surgery, some examinations (3.3%) are insufficient. Distal run off is usually well seen, everywhere, except in kidneys. There is a good correlation between angiographic results and clinical status. However, significant abnormalities were discovered in 5% of cases without any clinical signs. Digital intravenous angiography is a safe and mildly invasive procedure for postoperative evaluation of vascular surgery.


Public reporting and case selection for percutaneous coronary interventions: an analysis from two large multicenter percutaneous coronary intervention databases.
The purpose of this research was to determine the potential effect of public reporting on case selection for percutaneous coronary intervention (PCI). Previous studies have suggested that public reporting of coronary artery bypass graft surgery (CABG) mortality might result in case selection bias and in denial of care to or out migration of high-risk patients. The potential effect of public reporting on case selection for PCI is unknown. We compared demographics, indications, and outcomes of 11,374 patients included in a multicenter (eight hospitals) PCI database in Michigan where no public reporting is present, with 69,048 patients in a statewide (34 hospitals) PCI database in New York, where public reporting is present. The primary end point was in-hospital mortality. Patients in Michigan more frequently underwent PCI for acute myocardial infarction (14.4% vs. 8.7%, p < 0.0001) and cardiogenic shock (2.56% vs. 0.38%, p < 0.0001) than those in New York. The Michigan cohort also had a higher prevalence of congestive heart failure and extracardiac vascular disease. The unadjusted in-hospital mortality rate was significantly lower in New York than in Michigan (0.83% vs. 1.54%, p < 0.0001; odds ratio [OR] 0.54, 95% confidence interval [CI] 0.45 to 0.63). However, after adjustment for comorbidities, there was no significant difference in mortality between the two groups (adjusted OR 1.05, 95% CI 0.84 to 1.31, p = 0.70, c-statistic 0.88). There are significant differences in case mix between patients undergoing PCI in Michigan and New York that result in marked differences in unadjusted mortality rates. A propensity in New York toward not intervening on higher-risk patients because of fear of public reporting of high mortality rates is a possible explanation for these differences.


[The in-vitro effects of arbidol hydrochloride against 2009 new influenza virus A (H1N1)].
To detect the in-vitro effects of arbidol hydrochloride against 2009 new influenza virus A (H1N1). The activity of arbidol hydrochloride against 2009 new influenza virus A (H1N1) was determined in MDCK cell cultures. Hemagglutination assay, observation of cytopathic effects, RT-PCR and quantitative RT-PCR tests were performed for determination of virus titers. Inhibition concentration 50% and cytotoxic concentration 50% were calculated with Chou's Menu of Dose-Effect Program. Arbidol hydrochloride showed low cytotoxicity (cytotoxic concentration 50%>100 μmol/L)and significant anti-2009 new influenza virus A (H1N1) activity in cell cultures. Inhibition concentration 50% were (5.5 ± 0.9), (3.4 ± 0.8), and (1.5 ± 0.2) μmol/L in hemagglutination assay, cytopathic effect test, and quantitative RT-PCR assay, respectively. Arbidol has low cytotoxicity and high anti-virus activity and can effectively trigger the activities of interferon and immune response, and therefore can be a valuable anti-influenza virus drug.


Peptide Adjuvant to Invigorate Cytolytic Activity of NK Cells in an Obese Mouse Cancer Model.
Cancer patients who are overweight compared to those with normal body weight have obesity-associated alterations of natural killer (NK) cells, characterized by poor cytotoxicity, slow proliferation, and inadequate anti-cancer activity. Concomitantly, prohibitin overexpressed by cancer cells elevates glucose metabolism, rendering the tumor microenvironment (TME) more tumor-favorable, and leading to malfunction of immune cells present in the TME. These changes cause vicious cycles of tumor growth. Adoptive immunotherapy has emerged as a promising option for cancer patients; however, obesity-related alterations in the TME allow the tumor to bypass immune surveillance and to down-regulate the activity of adoptively transferred NK cells. We hypothesized that inhibiting the prohibitin signaling pathway in an obese model would reduce glucose metabolism of cancer cells, thereby changing the TME to a pro-immune microenvironment and restoring the cytolytic activity of NK cells. Priming tumor cells with an inhibitory the prohibitin-binding peptide (PBP) enhances cytokine secretion and augments the cytolytic activity of adoptively transferred NK cells. NK cells harvested from the PBP-primed tumors exhibit multiple markers associated with the effector function of active NK cells. Our findings suggest that PBP has the potential as an adjuvant to enhance the cytolytic activity of adoptively transferred NK cells in cancer patients with obesity.


Review on Nanoparticles and Nanostructured Materials: Bioimaging, Biosensing, Drug Delivery, Tissue Engineering, Antimicrobial, and Agro-Food Applications.
In the last few decades, the vast potential of nanomaterials for biomedical and healthcare applications has been extensively investigated. Several case studies demonstrated that nanomaterials can offer solutions to the current challenges of raw materials in the biomedical and healthcare fields. This review describes the different nanoparticles and nanostructured material synthesis approaches and presents some emerging biomedical, healthcare, and agro-food applications. This review focuses on various nanomaterial types (e.g., spherical, nanorods, nanotubes, nanosheets, nanofibers, core-shell, and mesoporous) that can be synthesized from different raw materials and their emerging applications in bioimaging, biosensing, drug delivery, tissue engineering, antimicrobial, and agro-foods. Depending on their morphology (e.g., size, aspect ratio, geometry, porosity), nanomaterials can be used as formulation modifiers, moisturizers, nanofillers, additives, membranes, and films. As toxicological assessment depends on sizes and morphologies, stringent regulation is needed from the testing of efficient nanomaterials dosages. The challenges and perspectives for an industrial breakthrough of nanomaterials are related to the optimization of production and processing conditions.


[Systematic review and meta-analysis of epidemiology, prophylaxis and therapy of infections with viral hepatitis B and C in Polish paediatric oncology centres].
Summary of published data on epidemiology, prophylaxis and therapy of HBV and HCV infections in Polish paediatric oncology centres. Metaanalysis of available data from 1985-2008. 1. Epidemiology of HBV/HCV infections in 2070 patients. HBV infections in 716/1735 (41.3%), HCV in 497/1557 (31.9%), dual HBV+HCV in 76/707 (10.7%) patients. 2. Documented vaccinations against HBV infections before introduction of neonate vaccination in 1995 were carried out in 1056 children. In 614/985 (62.3%) patients seroconversion was detected, but 62/792 (7.8%) patients became infected. 3. Therapy with interferon was introduced in 188 patients; 89 with HBV, 41 with HCV and 58 with HBV+HCV. Response to interferon therapy defined as inhibition or decrease of viral replication or elimination of viral markers was documented in 37/188 (19.6%) patients. Alanine transaminase normalization occurred in 127/168 (75.6%) patients. 4. Protective effect against HBV infection after neonates/infants vaccination in 1995 was analyzed in 392 patients. Protective effect was obtained in 339/392 (86.5%) children, while infection with HBV occurred in 28/392 (7.1%) patients. During this period HCV infection was detected in 1/159 patients. No dual infections were found. Introduction of active immunoprophylaxis against HBV infections in haematology/oncology wards in 1989-1992, has led to 10-fold (p<0.00001), decrease of risk of HBV infection, and obligatory vaccination of infants/neonates in l995 additionally decreased the risk by 4-fold (p<0.00001). After introducing all prophylaxis measures, the risk of HBV infection decreased 38-fold (p<0.00001). Vaccination of neonates/infants has decreased 8-fold (p<0.00001), the risk of lack of anti-HBV. The risk of HCV infection decreased 74-fold (p<0.00001) in the same period. No risk of dual HBV+HCV infections was found currently.


[Body image and eating disorders].
Assessing the association of age and weight with internalisation of the ideal of being thin, bodily dissatisfaction and eating disorder symptoms amongst three groups of females: teenage, young and adult women. 145 females participated, ranging in age from 12 to 46, who answered four self-reporting questionnaires aimed at measuring symptoms of anorexia nervosa, bulimia nervosa, the ideal of being thin and bodily dissatisfaction. The participants' weight and height were also recorded for calculating their body mass index. Data analysis included descriptive and inferential statistics, specifically Spearman correlation and Kruskal-Wallis test. Being an older woman was associated with high internalisation of ideally being thin and bodily dissatisfaction; however, it was not correlated with eating disorder symptoms. Comparisons between groups showed that adult females were more dissatisfied with their bodies and their attitudes towards being thin; however, their attitudes and behaviour concerning abnormal eating were just as inappropriate as that amongst teenagers. These findings show the need for research into attitudes towards eating amongst adult women because they use extreme methods for controlling weight which may result in higher health risks.


Residential mobility in the UK during pregnancy and infancy: are pregnant women, new mothers and infants 'unhealthy migrants'?
People that move home within developed countries report, on average, better health than non-movers. Pregnant women, new mothers and infants are particularly mobile, but the limited evidence regarding the relationship between their mobility and health suggests they may not conform to the 'healthy migrant' effect. This paper examines the relationship between mobility and health among these groups in the UK, using logistic regression to analyse cross-sectional data for 18,197 families in the Millennium Cohort Study wave one. It compares health status variables among mobile and non-mobile families; describes mobile families' socio-demographic characteristics; explores associations between health outcomes, reasons for residential moves, and experiences of homelessness; and assesses the association between mobility and health care utilisation, social support and residential satisfaction. The paper concludes that mobile pregnant women, new mothers and infants do have poor health outcomes in comparison to non-movers, but this is primarily explained by their socio-demographic characteristics and the negative circumstances associated with a minority of their moves. Families that moved during pregnancy and infancy had worse self-rated health and depression among mothers, and lower birth weight and higher risk of accidents among infants, than non-movers. Mothers in mobile families were younger and had lower levels of education and owner-occupation than non-movers. After adjustment for socio-demographic characteristics mobility was weakly and non-significantly associated with most health variables with the exception of self-rated health and depression among mothers who moved for negative reasons (such as relationship breakdown or problems with neighbours), or had been homeless since birth. After adjustment mobile families had lower levels of most measures of health care utilisation compared to non-movers, but mothers did not report less frequent social contacts, and those that moved during infancy for positive reasons (such as wanting a better home or neighbourhood) had greater satisfaction with home and area.


Functional dissection of nebulette demonstrates actin binding of nebulin-like repeats and Z-line targeting of SH3 and linker domains.
Nebulette, a 107 kDa protein associated with the I-Z-I complex of cardiac myofibrils, may play an important role in the assembly of the Z-line. Determination of the complete primary structure of 1011 residue human fetal nebulette reveals a four-domain layout similar to skeletal muscle nebulin: a short N-terminal domain, followed by 22 nebulin-like repeats that are linked to a C-terminal Src homology 3 (SH3) domain via a short linker domain. To elucidate the mechanisms of assembly for nebulette in the Z-line, the complete coding sequence or fusions of nebulette domains with green fluorescent protein (GFP) were expressed in cardiomyocytes and fibroblasts. The complete protein localized to Z-lines in cardiac cells and to dense bodies in nonmuscle cells. The GFP-repeat domain forms bundles that are associated with actin filaments in both cell types and disrupts the microfilament network. In contrast, the GFP-repeat plus linker shows limited interaction with dense bodies in nonmuscle cells and the Z-lines of cardiomyocytes. Interestingly, the tagged linker or SH3 is diffusely distributed in nonmuscle cells, but localizes to the Z-lines in cardiomyocytes. Supporting the cellular localization work, recombinant nebulette fragments bind to actin, tropomyosin, and alpha-actinin in in vitro binding assays. These results suggest the repeat domain contains actin binding functions and that the linker domain may target this interaction to Z-lines and dense bodies. Our data also indicate that the linker and SH3 domains can distinguish between dense bodies and Z-lines, suggesting that the ligands for their interactions are specific to these muscular substructures.


Citicoline decreases phospholipase A2 stimulation and hydroxyl radical generation in transient cerebral ischemia.
Neuroprotection by citicoline (CDP-choline) in transient cerebral ischemia has been demonstrated previously. Citicoline has undergone several Phase III clinical trials for stroke, and is being evaluated for treatment of Alzheimer's and Parkinson's diseases. Phospholipid degradation and generation of reactive oxygen species (ROS) are major factors causing neuronal injury in CNS trauma and neurodegenerative diseases. Oxidative metabolism of arachidonic acid (released by the action of phospholipases) contributes to ROS generation. We examined the effect of citicoline on phospholipase A(2) (PLA(2)) activity in relation to the attenuation of hydroxyl radical (OH.) generation after transient forebrain ischemia of gerbil. PLA(2) activity (requires mM Ca(2+)) increased significantly (P < 0.05) in both membrane (50.2 +/- 2.2 pmol/min/mg protein compared to sham 35.9 +/- 3.2) and mitochondrial fractions (77.0 +/- 1.2 pmol/min/mg protein compared to sham 33.9 +/- 1.2) after cerebral ischemia and 2 hr reperfusion in gerbil, which was significantly attenuated (P < 0.01) by citicoline (membrane, 39.9. +/- 2.2 and mitochondria, 41.9 +/- 3.2 pmol/min/mg protein). In vitro, citicoline and its components cytidine and choline had no effect on PLA(2) activity, and thus citicoline as such is not a PLA(2) inhibitor. Ischemia/reperfusion resulted in significant OH. generation (P < 0.01) and citicoline significantly (P < 0.01) attenuated their formation (expressed as 2,3-dihydroxybenzoic acid/salicylate ratio; ischemia/24 hr reperfusion, 6.30 +/- 0.23; sham, 2.56 +/- 0.27; ischemia/24 hr reperfusion + citicoline, 4.85 +/- 0.35). These results suggest that citicoline affects PLA(2) stimulation and decreases OH. generation after transient cerebral ischemia.


Role of bone marrow transplantation in the disease pathway of myeloma.
In multiple myeloma, autologous stem cell transplantation (ASCT) has been considered a standard of care in younger patients. The introduction of novel agents (i.e., thalidomide, lenalidomide, and bortezomib) may change this scenario. These agents can be administered before or after ASCT with the goal of increasing the complete remission (CR) rate and prolonging remission. For instance, thalidomide given as maintenance therapy after double ASCT increases CR rate, event-free survival (EFS), and overall survival. Moreover, combinations of conventional chemotherapy with novel agents such as thalidomide or bortezomib yield CR rates and EFS comparable to those achieved with standard single ASCT. Prospective randomized studies are needed to evaluate the impact of novel agents versus or in combination with ASCT. Myeloablative conditioning regimens before allogeneic stem cell transplantation are being replaced with concurrent autologous-transplantation and reduced-intensity conditioning allogeneic stem cell transplantation. Transplant-related mortality associated with this procedure is lower, but more follow-up is needed before definite conclusions can be drawn.


The relation between impairments and functional outcomes poststroke.
To assess the influence of initial stroke impairments on the severity of basic and higher level functional deficits over time and to determine the cumulative impact on functional deficits beyond severity of motor deficits alone. Observational study. Twelve participating hospitals in the Greater Kansas City area, as part of the Kansas City Stroke Study (October 1995-March 1998). Individuals (n = 459) who sustained an eligible stroke were evaluated prospectively using standardized assessments at enrollment (within 14 days of stroke onset, 8.8 +/- 3.5 days). Mobility and activities of daily living (ADLs) were assessed at 1, 3, and 6 months poststroke using the Functional Independence Measure, Barthel index, Lawton Instrumental Activities of Daily Living (IADL), and the Medical Outcomes Study Short-Form Health Survey instruments. The cumulative probability of achieving independence with walking, a Barthel index of 60 or greater or 90 or greater, and independence in 3 or more IADL was significantly different for the following 4 impairment groups in descending order: motor; motor and somatosensory; motor and hemianopia; and motor, sensory, and hemianopia. Although motor severity was a strong predictor of outcome (p < .0001), the additional somatosensory and hemianopia deficits significantly (p < .05) affected time and likelihood of achieving these levels of function. Cumulative deficits poststroke affect patients' functional outcome in the first 6 months poststroke beyond the effect of motor severity alone.


Varicella zoster virus infections in immunocompromised hosts. A review of the natural history and management.
Varicella is relatively mild in otherwise normal children, in whom new lesions form for a mean of four days after onset and heal 50 percent of their lesions in eight days. New lesions form in most immunocompromised children for longer than five days and those not treated with antiviral drugs have a 28 percent incidence of pneumonitis and a 7 percent mortality rate. Untreated immunocompromised adults with herpes zoster shed virus for longer (7.0 days) than otherwise normal adults (5.3 days). Herpes zoster is much more likely to disseminate cutaneously in immunocompromised than in immunocompetent hosts. Visceral dissemination, which is a rare event in immunocompetent patients, occurred in 8 percent of prospectively followed untreated immunocompromised hosts with herpes zoster. Acyclovir has been found to be superior to vidarabine for treatment of both chickenpox and herpes zoster. Whether or not steroids should be used to treat herpes zoster remains controversial. Concerns about the use of intravenous acyclovir include the side effects of renal and central nervous system dysfunction and the possibility of emergence of resistant viral strains. None of these concerns has proved to be an impediment to successful treatment of immunocompromised patients. The major future challenge is to find an optimal way to treat varicella zoster virus infections with oral formulations of acyclovir or its congeners.


Ultraviolet Patterned Calixarene-Derived Supramolecular Gels and Films with Spatially Resolved Mechanical and Fluorescent Properties.
Supramolecular assemblies have in the past been considered mechanically weak and in most cases unable to withstand their own weight. Calixarene-derived networks can, however, provide robust supramolecular gels. Incorporating a photoreactive stilbene moiety, we show that the aggregation state of the material can be tuned by heating and UV exposure in order to control the mechanical as well as the fluorescent properties. Regulating the extent of heating to control the proportion of H-aggregates and J-aggregates and further cross-linking of H-aggregates by control over UV exposure allows for adjustable photopatterning of the fluorescence as well as the material stiffness in the range from ∼100 to 450 kPa. We expect this straightforward supramolecular system will be suitable for advanced prototyping in applications where modulus and shape are important design criteria.


Intracellular negative feedback mechanisms in blubber and muscle moderate acute stress responses in fasting seals.
Animals may limit the cost of stress responses during key life history stages such as breeding and molting by reducing tissue sensitivity to energy-mobilizing stress hormones (e.g., cortisol). We measured expression of genes encoding glucocorticoid receptor (GR, NR3C1), GR inhibitor (FKBP5), and cortisol-inactivating enzyme (HSD11B2) in blubber and muscle of northern elephant seals before and after stress axis stimulation by adrenocorticotropic hormone (ACTH) early and late in a fasting period associated with molting. ACTH elevated cortisol levels for >24 hours and increased FKBP5 and HSD11B2 expression while downregulating NR3C1 in blubber and muscle, suggesting robust intracellular negative feedback in peripheral tissues. This feedback was maintained over prolonged fasting, despite differences in baseline cortisol and gene expression levels between early and late molt, suggesting that fasting-adapted animals use tissue-specific, intracellular negative feedback mechanisms to modulate downstream impacts of acute stress responses during key life history stages.


A participatory, farmer-led approach to changing practices around antimicrobial use on UK farms.
Farmer-led, participatory approaches are being increasingly employed in agricultural research, with promising results. This study aimed to understand how a participatory approach based on the Danish stable schools could help to achieve practical, farmer-led changes that reduced reliance on antimicrobials in the UK. Five facilitated farmer action groups comprising 30 dairy farms across South West England met on farm at regular intervals between 2016 and 2018, and worked collaboratively within their groups to discuss how to reduce antimicrobial use. Qualitative data from group discussions and individual semi-structured interviews were collected and analyzed using thematic analysis to explore how the approach helped farmers address and deal with changes to their on-farm practices. Facilitator-guided reviews of antimicrobial use and benchmarking were carried out on each farm to assess any change in usage and help farmers review their practices. The pattern of antimicrobial use changed over the 2 yr of the study, with 21 participating farms reducing their use of highest-priority critically important antibiotics (6 farms were not using any of these critical medicines from the outset). Thirty practical action plans were co-developed by the groups with an average implementation rate of 54.3% within a year. All assessed farms implemented 1 recommendation, and many were still ongoing at the end of the study. Farmers particularly valued the peer-to-peer learning during farm walks. Farmers reported how facilitated discussions and action planning as a peer group had empowered them to change practices. Participants identified knowledge gaps during the project, particularly on highest-priority critically important antibiotics, where they were not getting information from their veterinarians. The study demonstrated that facilitation has a valuable role to play in participatory approaches beyond moderating discussion; facilitators encouraged knowledge mobilization within the groups and were participants in the research as well. Facilitated, farmer-led, participatory approaches that mobilize different forms of knowledge and encourage peer learning are a promising way of helping farmers to adapt and develop responsible practices.


[Clinical and histopathological characteristics of malignant melanoma cases seen at "Dr. Manuel Gea González" General Hospital].
Melanoma is a type of tumor that arises from melanocytes generally located in the dermoepidermal junction. Although melanoma is found in less than 10% of cases, mortality is high representing 75% of deaths attributed to cutaneous cancer. There are four major subtypes: Superficial spreading melanoma, lentigo malignant melanoma, acral lentiginous melanoma and nodular melanoma. Superficial spreading melanoma is the most common type among Caucasians. In a Mexican case series, the nodular type is the most common type reported. The aim of this study was to determine the most common type seen at our medical facility. We analyzed patient's medical records from March 1981 to December 2006. Demographic data included sex, age, place of residence, occupation, tumor progression, location and clinical description. Histologically we evaluated tumor thickness using the Breslow scale; invasion was measured using the Clark scale. This is a descriptive, cross-sectional and retrospective study. 165 patients were studied, 112 were females and 53 males. The most common location was the lower limb. Acral lentiginous melanoma was the most common subtype. Our findings differ from the other series where they report nodular and superficial spreading melanoma as the most common types. The most common subtypes in our study were acral lentiginous melanoma and lentigo malignant melanoma among females, with a ratio of female-male of 2.1:1.


Mediterranean diet and risk of heart failure: results from the PREDIMED randomized controlled trial.
The aim of this study was to evaluate the effect of the Mediterranean diet (MedDiet) on the incidence of heart failure (HF), a pre-specified secondary outcome in the PREDIMED (PREvención con DIeta MEDiterránea) primary nutrition-intervention prevention trial. Participants at high risk of cardiovascular disease were randomly assigned to one of three diets: MedDiet supplemented with extra-virgin olive oil (EVOO), MedDiet supplemented with nuts, or a low-fat control diet. Incident HF was ascertained by a Committee for Adjudication of events blinded to group allocation. Among 7403 participants without prevalent HF followed for a median of 4.8 years, we observed 29 new HF cases in the MedDiet with EVOO group, 33 in the MedDiet with nuts group, and 32 in the control group. No significant association with HF incidence was found for the MedDiet with EVOO and MedDiet with nuts, compared with the control group [hazard ratio (HR) 0.68; 95% confidence interval (CI) 0.41-1.13, and HR 0.92; 95% CI 0.56-1.49, respectively]. In this sample of adults at high cardiovascular risk, the MedDiet did not result in lower HF incidence. However, this pre-specified secondary analysis may have been underpowered to provide valid conclusions. Further randomized controlled trials with HF as a primary outcome are needed to better assess the effect of the MedDiet on HF risk. ISRCTN35739639.


Neurotrophins 3 and 4 differentially regulate NCAM, L1 and N-cadherin expression during peripheral nerve regeneration.
The addition of NT-3 (neurotrophin 3) or NT-4 to injured nerves improves their regeneration potential and may aid axon guidance. It is not well defined whether NTs (neurotrophins) influence other elements, such as the cell-adhesion molecules, which promote nerve guidance and regeneration. Using poly-3-hydroxybutyrate conduits, we applied either NT-3 or NT-4 to axotomized rat sciatic nerves and monitored nerve regeneration and cell-adhesion molecule expression. Regenerating nerves were stained with antibodies against NCAM (neural cell-adhesion molecule) and N-cadherin 2 weeks after injury and staining intensity was quantified. NCAM, N-cadherin and L1 (L1 cell-adhesion molecule) transcription was measured in the proximal and distal stumps and ipsilateral DRG (dorsal root ganglia) (fourth and fifth DRG) using RT (reverse transcriptase)-PCR. Both NT-3 and NT-4 increased NCAM and L1 transcript levels in the DRG of axotomized nerves. This is reflected in the increased NCAM expression at the proximal stump and regeneration front. Increased levels of NCAM were also observed in the distal stump. NT-4 administration increased N-cadherin levels proximal to the injury, but not distally. Following NT-3 administration, N-cadherin expression decreased in proximal and distal stumps compared with the control. In conclusion, NTs differentially alter adhesion molecule expression in regenerating nerves and transcription in the corresponding DRG, although these changes in expression do not alter NT-enhanced regeneration. Thus we propose that retrograde transport of the NTs to the DRG affects adhesion molecule transcription, reflected by protein expression in peripheral nerve axons.


Electrocatalytic Oxygen Reduction to Produce Hydrogen Peroxide: Rational Design from Single-Atom Catalysts to Devices.
Electrocatalytic production of hydrogen peroxide (H2O2) via the 2e- transfer route of the oxygen reduction reaction (ORR) offers a promising alternative to the energy-intensive anthraquinone process, which dominates current industrial-scale production of H2O2. The availability of cost-effective electrocatalysts exhibiting high activity, selectivity, and stability is imperative for the practical deployment of this process. Single-atom catalysts (SACs) featuring the characteristics of both homogeneous and heterogeneous catalysts are particularly well suited for H2O2 synthesis and thus, have been intensively investigated in the last few years. Herein, we present an in-depth review of the current trends for designing SACs for H2O2 production via the 2e- ORR route. We start from the electronic and geometric structures of SACs. Then, strategies for regulating these isolated metal sites and their coordination environments are presented in detail, since these fundamentally determine electrocatalytic performance. Subsequently, correlations between electronic structures and electrocatalytic performance of the materials are discussed. Furthermore, the factors that potentially impact the performance of SACs in H2O2 production are summarized. Finally, the challenges and opportunities for rational design of more targeted H2O2-producing SACs are highlighted. We hope this review will present the latest developments in this area and shed light on the design of advanced materials for electrochemical energy conversion.


The vascular disrupting agent STA-9584 exhibits potent antitumor activity by selectively targeting microvasculature at both the center and periphery of tumors.
Vascular disrupting agents (VDAs) are an emerging class of therapeutics targeting the existing vascular network of solid tumors. However, their clinical progression has been hampered because of limited single-agent efficacy, primarily caused by the persistence of surviving cells at the well perfused "viable rim" of tumors, which allows rapid tumor regrowth to occur. In addition, off-target adverse events, including cardiovascular toxicities, underscore a need for compounds with improved safety profiles. Here, we characterize the mechanism of action, antitumor efficacy, and cardiovascular safety profile of (S)-2-amino-N-(2-methoxy-5-(5-(3,4,5-trimethoxyphenyl)isoxazol-4-yl)phenyl)-3-phenylpropanamide hydrochloride (STA-9584), a novel tubulin-binding VDA. In vitro, 2-methoxy-5-(5-(3,4,5-trimethoxyphenyl)isoxazol-4-yl)aniline (STA-9122) (active metabolite of STA-9584) displayed increased potency relative to other tubulin-binding agents and was highly cytotoxic to tumor cells. STA-9584 induced significant tumor regressions in prostate and breast xenograft models in vivo and, in an aggressive syngeneic model, demonstrated superior tumor growth inhibition and a positive therapeutic index relative to combretastatin A-4 phosphate (CA4P). It is noteworthy that histological analysis revealed that STA-9584 disrupted microvasculature at both the center and periphery of tumors. Compared with CA4P, STA-9584 induced a 73% increase in central necrotic area, 77% decrease in microvasculature, and 7-fold increase in tumor cell apoptosis in the remaining viable rim 24 h post-treatment. Ultrasound imaging confirmed that STA-9584 rapidly and efficiently blocked blood flow in highly perfused tumor regions. Moreover, cardiovascular effects were evaluated in the Langendorff assay and telemetered dogs, and cardiovascular toxicity was not predicted to be dose-limiting. This bioactivity profile distinguishes STA-9584 from the combretastatin class and identifies the compound as a promising new therapeutic VDA candidate.


Intensive Care Nurses' Views and Practices for Eye Care: An International Comparison.
Eye care is an important area of critical care. However, lack of eye care studies is a common issue across the globe. The aim of this study is to determine the views and practices of intensive care unit (ICU) nurses on eye care in Turkey and Palestine. This descriptive study was conducted using a self-administrated questionnaire. The data were collected from 111 nurses in nine kinds of ICUs in two education hospital. Normal saline (75.9%) was the most commonly reported solution for eye hygiene among the Palestinian nurses, and gauze soaked in normal saline or sterile water (64.3%) were the most frequently used supplies by the Turkish nurses. Although both Palestinian and Turkish ICU nurses took some precautions to prevent eye complications in critical patients, there were some gaps and insufficiencies in the eye care of ICU patients. There is a need for continuing training in this area.


Spatial coding of word-initial letters: evidence from a Simon-like task.
In this study, we investigated whether the processing of written words leads to a preferential coding of word beginnings and whether this coding occurs in the context of word representations that are spatial in nature and depend on the orientation of the actual stimuli. Two experiments were carried out wherein participants were asked to press a left or right key, in accordance with a nonspatial feature of standard-oriented or mirror-reversed wordlike stimuli (words and pronounceable nonwords). Both experiments showed an effect of correspondence between position of the beginning part of the stimuli and position of the required response (i.e., a Simon-like effect): Responses to standard-oriented stimuli were faster with the left key, whereas responses to mirror-reversed stimuli were faster with the right key. The present findings indicate for the first time that, in reading, the direction of script is automatically processed and the position of the word beginning is coded before the orthographic lexicon is accessed.


Effects of exenatide on coronary stent's endothelialization in subjects with type 2 diabetes: a randomized controlled trial. The Rebuild study.
Subjects with type 2 diabetes (T2D) have a higher risk of in-stent restenosis and stent thrombosis. The activation of the glucagon-like peptide-1 receptor (GLP-1R) has been suggested to induce several effects on the vasculature that may reduce the risk of stent failure following an angioplasty. The aim of this study is to evaluate the effect of the GLP-1R agonist exenatide on endothelialization of a modern drug-eluting stent (DES) in subjects with T2D. 38 subjects with T2D who were eligible for revascularization with implantation of DES were randomized to treatment with exenatide (once weekly) plus standard treatment, or to standard treatment alone. After 12 weeks, a new coronary angiography was performed to evaluate the percentage of strut coverage (primary endpoint) and the presence of neo-atherosclerosis by optical coherence tomography. This study was approved by the Stockholm's Ethical Review Board. The two groups were well balanced regarding baseline clinical characteristics. Strut coverage was 95% (88.7-98.5%) in the exenatide group and 91.4% (88.8-98.5%) in the control group (p = 0.692). There were no significant differences between groups neither in the thickness of neo-intima (0.2 mm in both groups, p = 0.471), nor the maximal in-stent obstruction by neo-intima (15.5% in exenatide group vs 14.7% in control group, p = 0.801). No significant differences were detected in the rate of target lesion revascularization between groups (p = 0.224). Twelve weeks treatment with exenatide did not lead to a significantly better stent coverage in people with T2D. No significant differences in the occurrence of neo-atherosclerosis were detected between groups. The study was registered at www. gov (Rebuild Study, NCT02621489).


Distribution and evolution of circular miniproteins in flowering plants.
Cyclotides are disulfide-rich miniproteins with the unique structural features of a circular backbone and knotted arrangement of three conserved disulfide bonds. Cyclotides have been found only in two plant families: in every analyzed species of the violet family (Violaceae) and in few species of the coffee family (Rubiaceae). In this study, we analyzed >200 Rubiaceae species and confirmed the presence of cyclotides in 22 species. Additionally, we analyzed >140 species in related plant families to Rubiaceae and Violaceae and report the occurrence of cyclotides in the Apocynaceae. We further report new cyclotide sequences that provide insights into the mechanistic basis of cyclotide evolution. On the basis of the phylogeny of cyclotide-bearing plants and the analysis of cyclotide precursor gene sequences, we hypothesize that cyclotide evolution occurred independently in various plant families after the divergence of Asterids and Rosids ( approximately 125 million years ago). This is strongly supported by recent findings on the in planta biosynthesis of cyclotides, which involves the serendipitous recruitment of ubiquitous proteolytic enzymes for cyclization. We further predict that the number of cyclotides within the Rubiaceae may exceed tens of thousands, potentially making cyclotides one of the largest protein families in the plant kingdom.


Measurement of total risk of spontaneous abortion: the virtue of conditional risk estimation.
The concepts, methods, and problems of measuring spontaneous abortion risk are reviewed. The problems touched on include the process of pregnancy verification, the changes in risk by gestational age and maternal age, and the presence of induced abortions. Methods used in studies of spontaneous abortion risk include biochemical assays as well as life table technique, although the latter appears in two different forms. The consequences of using either of these are discussed. It is concluded that no study design so far is appropriate for measuring the total risk of spontaneous abortion from early conception to the end of the 27th week. It is proposed that pregnancy may be considered to consist of two or three specific periods and that different study designs should concentrate on measuring the conditional risk within each period. A careful estimate using this principle leads to an estimate of total risk of spontaneous abortion of 0.33.


Initial pioneer venus magnetic field results: nightside observations.
Initial observations by the Pioneer Venus magnetometer on the nightside of Venus frequently reveal moderately strong fields from 20 to 30 nanoteslas. However, there is little evidence that thesefields arise from an internal dynamo since they are mainly horizontal and vary from orbit to orbit. Determining a precise upper limit to the intrinsic moment awaits further processing. This limit is expected to be much less than 10(22) gauss-cubic centimeters.


Survey of Trichinella in American minks (Neovison vison Schreber, 1777) and wild rodents (Muridae and Cricetidae) in Chile.
Trichinellosis is a zoonosis with worldwide distribution. Several hosts have been recognized around the world; however, there is a lack of knowledge of the role of feral mammals in Chile in its transmission. Herein, we tested muscle samples from 555 individuals among American minks (Neovison vison Schreber, 1777. n = 100) and several myomorph rodent species (Muridae and Cricetidae. n = 455) from southern Chile by artificial digestion to detect Trichinella larvae and identified the larvae at the species level through molecular analyses. Rodents were captured in agricultural and wild protected areas of several administrative regions (hereafter: region), while minks were captured in agricultural areas of the Los Ríos region. Trichinella spiralis larvae were detected in a synanthropic black rat (0.24%) of the Ñuble region and in seven minks (7%) trapped in agricultural areas of the Los Ríos region. The present results suggest that T. spiralis circulation is restricted to synanthropic rodents and minks living in agricultural areas where the parasite circulates among domesticated pigs. This study represents the first record of T. spiralis in a mustelid mammal in South America, increasing the number of feral species that could participate in the reservoir.


Pioglitazone improves the phenotype and molecular defects of a targeted Pkd1 mutant.
Mutations of either PKD1 or PKD2 are associated with autosomal dominant polycystic kidney disease (ADPKD). The molecular function of the gene product of PKD1, polycystin-1, in vitro has been elucidated recently, but the molecular pathological consequences of the loss of polycystin-1 in vivo have remained unclear. We have generated a mouse with a targeted deletion of exons 2-6 of Pkd1 to study the molecular defects in Pkd1 mutants. Homozygote embryos (Pkd1(-/-)) developed hydrops, cardiac conotruncal defects and renal cystogenesis. Total protein levels of beta-catenin in heart and kidney and c-MYC in heart were decreased in Pkd1(-/-) embryos. In the kidneys of Pkd1(-/-), the expression of E-cadherin and PECAM in basolateral membranes of renal tubules was attenuated, and tyrosine phosphorylation of epidermal growth factor receptor and Gab1 were constitutively enhanced when cystogenesis started on embryonic day (E) 15.5-16.5. Maternally administered pioglitazone, a thiazolidinedione compound, resolved these molecular defects of Pkd1(-/-). Treatment with pioglitazone improved survival of Pkd1(-/-) embryos and ameliorated the cardiac defects and the degree of renal cystogenesis. Long-term treatment with pioglitazone improved the endothelial function of adult Pkd1(+/-). These data indicated that molecular defects observed in Pkd1(-/-) embryos contributed to the pathogenesis of ADPKD and that thiazolidinediones had a compensatory effect on the pathway affected by the loss of polycystin-1. Pathways activated by thiazolidinediones may provide new therapeutic targets in ADPKD.


NNP/MM: Accelerating Molecular Dynamics Simulations with Machine Learning Potentials and Molecular Mechanics.
Machine learning potentials have emerged as a means to enhance the accuracy of biomolecular simulations. However, their application is constrained by the significant computational cost arising from the vast number of parameters compared with traditional molecular mechanics. To tackle this issue, we introduce an optimized implementation of the hybrid method (NNP/MM), which combines a neural network potential (NNP) and molecular mechanics (MM). This approach models a portion of the system, such as a small molecule, using NNP while employing MM for the remaining system to boost efficiency. By conducting molecular dynamics (MD) simulations on various protein-ligand complexes and metadynamics (MTD) simulations on a ligand, we showcase the capabilities of our implementation of NNP/MM. It has enabled us to increase the simulation speed by ∼5 times and achieve a combined sampling of 1 μs for each complex, marking the longest simulations ever reported for this class of simulations.