Blood Lead Levels among Children in Yaoundé Cameroon.
Blood lead levels (BLLs) are a useful indication of a population exposure to lead from environmental sources. No previous published study had reported BLLs in Cameroon. Our objective is to characterize exposure levels in children to inform policymakers of potential lead exposure sources. We tested the BLLs of 147 children aged 12 months to 6 years residing in Yaoundé, Cameroon, and conducted an extensive questionnaire with their parents or guardians to characterize potential exposure sources. The geometric mean BLL among this population was 8.0 μg/dl and arithmetic mean level was 8.7 μg/dl. These levels are more than sixfold higher than the geometric mean BLL reported in the U.S. and more than fivefold higher than those reported in France. In addition, 88% of the children tested had lead levels greater than 5 μg/dl. One limitation of the study is that the selection of the children sampled was not a random survey. The analysis of the responses to the questionnaire failed to uncover any specific exposure patterns. A statistically significant association was noted between the age of the child's home and the duration of exclusive breastfeeding with BLLs. The study points to a need for greater efforts to control sources of lead exposure in Cameroon.


Seventeen years of life support courses for nurses: where are we now?
The Life Support Course for Nurses (LSCN) equips nurses with the resuscitation skills to be first responders in in-hospital cardiac arrests. Seventeen years after the initiation of the LSCN, a confidential cross-sectional Qualtrics™ survey was conducted in May 2016 on LSCN graduands to assess the following: confidence in nurse-initiated resuscitation post-LSCN; defibrillation experience and outcomes; and perceived barriers and usefulness of the LSCN. The majority of respondents reported that the course was useful and enhanced their confidence in resuscitation. Skills retention can be enhanced by organising frequent team-based resuscitation training. Resuscitation successes should be publicised to help overcome perceived barriers.


Prevention and education to decrease patient falls due to syncope.
This article describes a fall reduction program implemented by the University of Wisconsin Medical Foundation in its 50+ clinic sites and departments located across 5 counties in Southern Wisconsin. The fall reduction program specifically targeted falls due to faints in the clinic setting. To reduce the organization's main reason for patient falls, guidelines were developed and mandatory education was given to staff working in high-risk areas.


[The chemical toxicological investigation of gamma-hydroxybutyric acid in biological objects and the interpretation of the results of the analysis].
The authors propose a method for the quantitative determination of gamma-hydroxybutyric acid (GHBA) in biological objects including biological fluids (blood, urine) and tissues with the use of gas chromatography with mass-selective detector. The samples for the analysis were prepared by liquid-liquid extraction by butyl acetate with subsequent derivatization using a N,O-Bis(trimethylsilyl)trifluoroacetamide/Trimethylchlorosilane mixture (BSTFA + 1%TMCS). The graded graphs were linear in the range of GHBA concentrations from 26.4 to 1321.6 mg/l. Coefficients of correlation for all the graphs were higher than 0.999. The threshold of detectability for GHBA in blood, urine, and internal organs was 10 mg/l, the quantification limit concentration 26 mg/l.


Phylogenetic relationships of the Balkan Moitessieriidae (Caenogastropoda: Truncatelloidea).
The family Moitessieriidae includes minute dioecious gastropods exclusively inhabiting subterranean waters, including thermal ones. Only empty shells were collected in most species, the vast majority of them are described from their gross shell morphology alone. Several visits to a site are usually required to obtain at least some living individuals. High variability in shell morphology and the lack of diagnostic features, coupled with anticipated high levels of endemism, has resulted in a long list of nominal moitessierid species. Type specimens stored as empty shells omit unambiguous identification and delimitation of species boundaries. Due to inaccessibility of cave animals and consequent lack of material suitable for molecular analysis, the phylogenetic relationships, as well as the taxonomy of the family at genus/species level, are far from being understood. The anatomy of the family is also poorly known and provided only for a few taxa. The distinctness of the Moitessieriidae has sometimes been questioned, and their monophyly not proved. Twelve species of the Balkan Moitessieriidae are considered: two species of Paladilhiopsis, two species of Bythiospeum, six species of Iglica, Costellina turrita and Lanzaia bosnica. The shell morphology of each species, as well as the reproductive system of Paladilhiopsis and Iglica, were analysed. DNA sequences of nuclear histone H3, ribosomal 18S, ribosomal 28S and mitochondrial cytochrome oxidase subunit I (COI) were applied to infer phylogenetic relationships among the taxa. The sequences of Bythiospeum from GenBank have been used to infer relationships between Bythiospeum and Paladilhiopsis that were recently synonymized. Paladilhiopsis and Iglica are distinct, but closely related genera, as is the genus Bythiospeum, which does not occur in the Balkans. Its relationships with both former taxa remain unresolved. The Moitessieriidae are clearly distinct from all other families of the Truncatelloidea, however, their monophyly remains doubtful.


Scoring and summarising gene product clusters using the Gene Ontology.
We propose an approach for quantifying the biological relatedness between gene products, based on their properties, and measure their similarities using exclusively statistical NLP techniques and Gene Ontology (GO) annotations. We also present a novel similarity figure of merit, based on the vector space model, which assesses gene expression analysis results and scores gene product clusters' biological coherency, making sole use of their annotation terms and textual descriptions. We define query profiles which rapidly detect a gene product cluster's dominant biological properties. Experimental results validate our approach, and illustrate a strong correlation between our coherency score and gene expression patterns.


The pivotal role of the academic health center.
Academic health centers (AHCs) now play major roles in the development, adoption, and evaluation of medical technologies; the provision of advice to other entities involved in medical innovation; and the education of current and future practitioners. However, recent and potential health care reform initiatives could make it increasingly difficult for AHCs to continue to play their historical roles in medical innovation. Policymakers are examining specific options that would explicitly cover the cost of some of these services but could take away some of the autonomy AHCs have enjoyed and could change the role of AHCs in technological innovation.


Ascertaining the role of Taiwan as a source for the Austronesian expansion.
Taiwanese aborigines have been deemed the ancestors of Austronesian speakers which are currently distributed throughout two-thirds of the globe. As such, understanding their genetic distribution and diversity as well as their relationship to mainland Asian groups is important to consolidating the numerous models that have been proposed to explain the dispersal of Austronesian speaking peoples into Oceania. To better understand the role played by the aboriginal Taiwanese in this diaspora, we have analyzed a total of 451 individuals belonging to nine of the tribes currently residing in Taiwan, namely the Ami, Atayal, Bunun, Paiwan, Puyuma, Rukai, Saisiyat, Tsou, and the Yami from Orchid Island off the coast of Taiwan across 15 autosomal short tandem repeat loci. In addition, we have compared the genetic profiles of these tribes to populations from mainland China as well as to collections at key points throughout the Austronesian domain. While our results suggest that Daic populations from Southern China are the likely forefathers of the Taiwanese aborigines, populations within Taiwan show a greater genetic impact on groups at the extremes of the current domain than populations from Indonesia, Mainland, or Southeast Asia lending support to the "Out of Taiwan" hypothesis. We have also observed that specific Taiwanese aboriginal groups (Paiwan, Puyuma, and Saisiyat), and not all tribal populations, have highly influenced genetic distributions of Austronesian populations in the pacific and Madagascar suggesting either an asymmetric migration out of Taiwan or the loss of certain genetic signatures in some of the Taiwanese tribes due to endogamy, isolation, and/or drift.


'Constructing communities for learning in nursing'.
Working in communities is increasingly a feature of UK (United Kingdom) higher education. Within the last decade communities of practice (CoPs) have migrated from organisational development departments and evolved to become tools for practice based learning in educational settings. More recently, in nursing, the literature reports that CoPs have the potential to blend the skills of both academics and clinicians to transform and create new knowledge that is both scholarly and applicable to practice.


Infinite geodesic paths and fibers, new topological invariants in periodic graphs.
Rings are well known invariants of nets. In this work, a generalization of the concepts of cycles and rings is introduced. Infinite paths in periodic graphs are defined as connected, acyclic, regular subgraphs of degree two; geodesics are defined as infinite paths such that the unique path between any pair of vertices is a geodesic path in the whole graph. An infinite path can be thought of as an infinite cycle and a geodesic as an infinite ring. In a further step, a geodesic fiber is defined as a minimal 1-periodic subgraph that contains all geodesic paths between any pair of its vertices. Geodesic fibers are topological invariants of periodic graphs whose labeled quotient graphs are subgraphs of the labeled quotient graph of the whole graph; the paper describes applications of geodesic fibers to the analysis of the automorphisms of minimal nets, crystallographic and non-crystallographic nets.


The effects of compost prepared from waste material of banana plants on the nutrient contents of banana leaves.
In this study, the possible utilization of removed shoots and plant parts of banana as compost after fruit harvest were investigated. Three doses (15-30-45 kg plan(-1)) of the compost prepared from the clone of Dwarf Cavendish banana were compared with Farmyard manure (50 kg plant(-1), Mineral fertilizers (180 g N + 150 g P + 335 g K plant(-1)) and Farmyard manure + Mineral fertilizers (25 kg FM + 180 g N + 150 g P + 335 g K plant(-1)) which determined positive effects on the nutrient contents of banana leaves. The banana plants were grown under a heated glasshouse and in a soil with physical and chemical properties suitable for banana growing. The contents of N, P, K and Mg in compost and in farmyard manure were found to be similar. Nitrogen, phosphorus and potassium contents of leaves in all applications except control, and Ca, Mg, Fe, Zn, Mn, Cu contents in all applications were determined between optimum levels of reference values. There were positive correlations among some nutrient contents of leaves, growth, yield and fruit quality characteristics. Farmyard manure, Farmyard manure + Mineral fertilizers and 45 kg plant(-1) of compost increased the nutrient contents of banana leaves. According to obtained results, 45 kg plant(-1) of compost was determined more suitable in terms of economical production and organic farming than the other fertiliser types.


Gliomatosis cerebri mimicking chemotherapy-induced leukoencephalopathy in a patient with non-Hodgkin's lymphoma.
Patients with hematological malignancies may develop white matter lesions, which are usually associated with chemotherapy. Magnetic resonance imaging (MRI) is the imaging modality of choice for identifying chemotherapy-induced, or "toxic", leukoencephalopathy. Brain biopsy in patients with hematological malignancies suspected of sustaining toxic leukoencephalopathy has rarely been performed, because its characteristic MRI findings are considered pathognomotic. Biopsy may be indicated in atypical cases, however, and it may yield unexpected results. We describe a case with white matter lesions that developed in an elderly man treated for non-Hodgkin's lymphoma. The lesions, initially diagnosed with toxic leukoencephalopathy based on MRI findings, turned out to be gliomatosis cerebri.


Measurement of membrane elasticity by micro-pipette aspiration.
The classical micro-pipette aspiration technique, applied for measuring the membrane bending elasticity, is in the present work reviewed and extended to span the range of pipette aspiration pressures going through the flaccid (low pressures) to tense (high pressures) membrane regime. The quality of the conventional methods for analysing data is evaluated using numerically generated data and a new method for data analysis, based on thermodynamic analysis and detailed statistical mechanical modelling, is introduced. The analysis of the classical method, where the membrane bending modulus is obtained from micro-pipette aspiration data acquired in the low-pressure regime, reveals a significant correction from membrane stretching elasticity. The new description, which includes the full vesicle geometry and both the membrane bending and stretching elasticity, is used for the interpretation of micro-pipette aspiration experiments conducted on SOPC (stearoyl-oleoyl-phosphatidyl-choline) lipid vesicles in the fluid phase. The data analysis, which is extended by detailed image analysis and a fitting procedure based on Monte Carlo integration, gives an estimate of the bending modulus, that agrees with previously published results obtained by the use of shape fluctuation analysis of giant unilamellar vesicles. The obtained estimate of the area expansion modulus, is automatically corrected for contributions from residual thermal undulations and the equilibrium area of the vesicle is resolved.


Anion-π recognition between [M(CN)6]3- complexes and HAT(CN)6: structural matching and electronic charge density modification.
Hexacyanidometalates (M = FeIII, CoIII) and multisite anion receptor HAT(CN)6 (1,4,5,8,9,11-hexaazatriphenylenehexacarbonitrile) recognize each other in acetonitrile solution and self-assemble into the novel molecular networks (PPh4)3[M(CN)6][HAT(CN)6] (M = Fe, 1; Co, 2) and (AsPh4)3[M(CN)6][HAT(CN)6]·2MeCN·H2O (M = Fe, 3; Co, 4). 1-4 contain the stacked columns {[M(CN)6]3-;[HAT(CN)6]}∞ separated by the organic cations. All of the M-C[triple bond, length as m-dash]N vectors point collectively towards the centroids of pyrazine rings on neighboring HAT(CN)6 molecules, with Ncyanidecentroidpyrazine distances that are under 3 Å. The directional character and structural parameters of the new supramolecular synthons correspond to collective triple anion-π interactions between the CN- ligands of the metal complexes and the π-deficient areas of HAT(CN)6. Physicochemical characterisation (IR spectroscopy, UV-Vis spectroscopy, cyclic voltammetry) and dispersion-corrected DFT studies reveal the dominating charge-transfer (CT) and polarisation characters of the interactions. The electronic density flow occurs from the CN- ligands of [M(CN)6]3- to the HAT(CN)6 orbital systems and further, toward the peripheral -CN groups of HAT(CN)6. Solid-state DFT calculations determined the total interaction energy of HAT(CN)6 to be ca. -125 kcal mol-1, which gives ca. -15 kcal mol-1 per one CN-HAT(CN)6 contact after subtraction of the interaction with organic cations. The UV-Vis electronic absorption measurements prove that the intermolecular interactions persist in solution and suggest a 1 : 1 composition of the anion-π {[M(CN)6]3-;[HAT(CN)6]} chromophore, with the formation constant Kadd = (5.8 ± 6) × 102 dm3 mol-1 and the molar absorption coefficient εadd = 180 ± 9 cm-1 dm3 mol-1 at 600 nm, as estimated from concentration-dependent studies.


Road Risk Modeling and Cloud-Aided Safety-Based Route Planning.
This paper presents a safety-based route planner that exploits vehicle-to-cloud-to-vehicle (V2C2V) connectivity. Time and road risk index (RRI) are considered as metrics to be balanced based on user preference. To evaluate road segment risk, a road and accident database from the highway safety information system is mined with a hybrid neural network model to predict RRI. Real-time factors such as time of day, day of the week, and weather are included as correction factors to the static RRI prediction. With real-time RRI and expected travel time, route planning is formulated as a multiobjective network flow problem and further reduced to a mixed-integer programming problem. A V2C2V implementation of our safety-based route planning approach is proposed to facilitate access to real-time information and computing resources. A real-world case study, route planning through the city of Columbus, Ohio, is presented. Several scenarios illustrate how the "best" route can be adjusted to favor time versus safety metrics.


Psychometric properties of the Trauma Assessment for Adults.
The Trauma Assessment for Adults (TAA) was developed to facilitate the assessment of exposure to traumatic events that could result in posttraumatic stress disorder (PTSD). The TAA inquires about numerous potentially traumatic events that an individual may have experienced. Although the TAA has been used extensively for clinical and research purposes, its psychometric properties have never been formally evaluated. The objective of the present investigation was to evaluate the psychometric properties of this frequently used measure. The studies reported here describe the performance of the TAA in two samples-college undergraduates (N=142) and community mental health center clients (N=67). Among undergraduates, 1-week temporal stability was evaluated and, in both samples, item- and scale-level convergence of the TAA with an established trauma exposure measure was assessed. Convergence of the TAA with clinically related constructs was also evaluated. The TAA exhibited adequate temporal stability (r=.80) and satisfactory item-level convergence with existing measures of trauma history among college students. In the clinical sample, the TAA again converged well with an established measure of trauma exposure (r=.65). It was not as strongly predictive, in either sample, of trauma-related distress relative to an alternate trauma exposure measure. Although it performs satisfactorily, the TAA does not appear to be superior to other existing measures of trauma exposure.


Development of databases for use in validation studies of probabilistic models of dietary exposure to food chemicals and nutrients.
The data currently available in the European Union in terms of food consumption and of food chemical and nutrient concentration data present many limitations when used for estimating intake. The most refined techniques currently available were used within the European Union FP5 Monte Carlo project to estimate, as accurately as possible, the intake of food additives, pesticide residues and nutrients. Databases of 'true' intakes of food additives (based on brand level food consumption records and additive concentration data), pesticide residues (based on duplicate diet studies) and nutrients (based on biomarker studies) have thus been generated. These kind of estimates are rarely repeatable because the databases generated and used to calculate them require an extraordinary expenditure of time and resources. The databases created served the purpose of estimating as accurately as possible 'true' chemical intakes for assessing the validity of additive, nutrient and pesticide probabilistic models.


CD4+ T-cell anergy induced by lin- CD117(c-kit)+ stem cell-derived immature dendritic cells loaded with nuclear antigen derived from Trypanosoma equiperdum.
Dendritic cells (DCs) are professional antigen-presenting cells, which have the extraordinary capacity to initiate naïve T-cell-mediated primary immune responses. To investigate the role of DCs in the induction of antigen-specific tolerance, the immature DCs (imDCs) and mature DCs (mDCs) were generated in vitro from lin(-)CD117(c-kit)(+) stem cells isolated from mice bone marrow. Flow cytometry and confocal microscopy were used to characterize the phenotypes of DCs. These cells were loaded with nuclear antigen derived from Trypanosoma equiperdum and then co-cultured with naïve CD4(+) T cells. It was found that imDC-treated T cells had lower proliferation level and cytokine expression of interleukin (IL)-2, IL-4, IL-12, and interferon-γ compared with mDC-treated T cells. These results demonstrated that the maturation status of DCs is critical for preventing the production of autoantibodies.


Intraoral ancient schwannoma: A systematic review of the case reports.
Intraoral ancient schwannoma is a rare type of oral schwannoma, which is encapsulated and well demarcated from the surrounding tissues. Ancient schwannomas are associated with conventional features of neurilemmoma; however, they are distinguished from other types of schwannoma due to factors such as the long history, cellular architecture showing hypocellularity, and hyalinized matrices. This systematic review was performed through searching in databases such as PubMed and Google Scholar using related keywords (intraoral, oral, ancient, schwannoma, and neurilemmoma). Eventually, 26 case reports were systematically reviewed by the researchers. Required data were extracted by one researcher, and all the selected articles were reviewed in full text after screening. This systematic review aimed to determine the most significant influential factors in intraoral ancient schwannoma and evaluate the diagnostic and therapeutic methods in this regard.


In vitro analysis of complement-dependent HIV-1 cell infection using a model system.
Previous studies based on the use of human serum as a source of C have provided evidence for the C-dependent enhancement of cell infection by HIV-1. The present study was undertaken to distinguish C from other serum factors and to identify the proteins and the mechanisms involved in C-dependent cell infection by HIV-1. The classical C activation pathway was reconstituted from the proteins C1q, C1r, C1s, C4, C2, C3, factor H, and factor I; each were purified to homogeneity. A mixture of these proteins at physiological concentrations was shown to reproduce the ability of normal human serum to enhance the infection of MT2 cells by HIV-1 at low doses of virus. This enhancing effect was abolished when heat-inactivated serum and C2- or C3-depleted serum were used, and was restored upon addition of the corresponding purified proteins. A mixture of two synthetic peptides corresponding to positions 10-15 and 90-97 of human C receptor type 2 (CD21) as well as soluble CD4 both inhibited the C-dependent infection process. These data provide unambiguous evidence that HIV-1 triggers a direct activation of the classical C pathway in vitro and thereby facilitates the infection of MT2 cells at low doses of virus. These findings are consistent with a mechanism involving increased interaction between the virus opsonized by C3b-derived fragment(s) and the CD21 cell receptors and subsequent virus entry through CD4 receptors.


Dietary sodium intake and its relation to sleep duration, sleep quality and nocturnal urination in working-aged Korean adults.
Both sodium intake and sleep have an important effect on cardiovascular health. However, few studies have looked at the association between sodium intake and sleep. Therefore, we analysed the association of sodium intake with sleep quality, sleep duration and nocturnal urination. The data for the present study were obtained from the Kangbuk Samsung Health Study. Study participants were 156 696 working-aged Korean adults (average age 38.0 years ±8.0 in men and 36.0 years ±8.1 in women). They were categorised into five groups by quintile of sodium intake, measured by food frequency questionnaire. Poor sleep quality and short sleep duration were determined by Pittsburgh Sleep Quality Index >5, and sleep duration <7 h, respectively. Nocturnal urination was defined as awakening to urinate more than three times a week. Multivariable adjusted logistic regression analysis was used in calculating the odds ratio (OR) and 95% confidence interval (CI) for poor sleep quality, short sleep duration and nocturnal urination (adjusted OR [95% CI]) across five study groups. In all study participants, increased sodium intake was significantly associated with poor sleep quality (quintile 1: reference, quintile 2: 1.07 [1.04-1.11], quintile 3: 1.12 [1.08-1.16], quintile 4: 1.15 [1.11-1.19] and quintile 5: 1.13 [1.09-1.18]). This pattern of relationship was similarly observed in association of sodium intake with short sleep duration (p for trend <0.001) and nocturnal urination (p for trend <0.001). In gender subgroup analysis, increased sodium intake had a significant association with poor sleep quality and short sleep duration in men and with poor sleep quality and nocturnal urination in women. In conclusion, high sodium intake is associated with an increased likelihood of poor sleep quality, short sleep duration and nocturnal urination.


Symptomatic os subfibulare caused by accessory ossification: a case report.
Separated ossicles at the tip of the lateral malleolus, the condition known as os subfibulare, are sometimes a cause of ankle pain. There are two theories regarding the origin of os subfibulare. One theory proposes that it is caused by an avulsion fracture attributable to pull of the anterior talofibular ligament, whereas the other theory proposes that it is the result of an accessory ossification center. However, some authors have reported that os subfibulare is an avulsion fracture and few reports of accessory ossification have been described recently. A patient with os subfibulare that may have been caused by accessory ossification rather than an avulsion fracture was treated by the current authors.


Machine learning algorithms' application to predict childhood vaccination among children aged 12-23 months in Ethiopia: Evidence 2016 Ethiopian Demographic and Health Survey dataset.
Childhood vaccination is a cost-effective public health intervention to reduce child mortality and morbidity. But, vaccination coverage remains low, and previous similar studies have not focused on machine learning algorithms to predict childhood vaccination. Therefore, knowledge extraction, association rule formulation, and discovering insights from hidden patterns in vaccination data are limited. Therefore, this study aimed to predict childhood vaccination among children aged 12-23 months using the best machine learning algorithm. A cross-sectional study design with a two-stage sampling technique was used. A total of 1617 samples of living children aged 12-23 months were used from the 2016 Ethiopian Demographic and Health Survey dataset. The data was pre-processed, and 70% and 30% of the observations were used for training, and evaluating the model, respectively. Eight machine learning algorithms were included for consideration of model building and comparison. All the included algorithms were evaluated using confusion matrix elements. The synthetic minority oversampling technique was used for imbalanced data management. Informational gain value was used to select important attributes to predict childhood vaccination. The If/ then logical association was used to generate rules based on relationships among attributes, and Weka version 3.8.6 software was used to perform all the prediction analyses. PART was the first best machine learning algorithm to predict childhood vaccination with 95.53% accuracy. J48, multilayer perceptron, and random forest models were the consecutively best machine learning algorithms to predict childhood vaccination with 89.24%, 87.20%, and 82.37% accuracy, respectively. ANC visits, institutional delivery, health facility visits, higher education, and being rich were the top five attributes to predict childhood vaccination. A total of seven rules were generated that could jointly determine the magnitude of childhood vaccination. Of these, if wealth status = 3 (Rich), adequate ANC visits = 1 (yes), and residency = 2 (Urban), then the probability of childhood vaccination would be 86.73%. The PART, J48, multilayer perceptron, and random forest algorithms were important algorithms for predicting childhood vaccination. The findings would provide insight into childhood vaccination and serve as a framework for further studies. Strengthening mothers' ANC visits, institutional delivery, improving maternal education, and creating income opportunities for mothers could be important interventions to enhance childhood vaccination.


Interleukin-1alpha protein secretion in breast cancer is associated with poor differentiation and estrogen receptor alpha negativity.
While interleukins (IL)-1alpha and beta are thought to play an important role in malignant disease, little is still known about their expression in breast cancer. We have used reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC) to analyze the expression of IL-1alpha and beta in breast cancer tissues, and compared their expression to estrogen receptor (ER) status and grading. In breast cancer cell lines, we found an inverse correlation between IL-1alpha and beta gene expression and differentiation, and only one highly invasive tumor cell line expressed IL-1alpha protein, while IL-beta was not detectable. Breast cancer tissue expressed variable amounts of IL-1alpha and beta messenger RNA, but consistently high levels of IL-1 type I receptor. IL-1alpha protein was detectable in malignant epithelium and adjacent stroma in 88% of cases. IL-1alpha expression was correlated with poor differentiation (P= 0.002; r= 0.469) and decreasing ERalpha expression (P= 0.004; r=-0.387). Stromal IL-1alpha was confined to areas with low or absent ERalpha protein expression in adjacent tumor epithelium (P= 0.001; r=-0.457). Taken together, we have demonstrated a functional IL-1 system in breast cancer and observed an inverse correlation between IL-1alpha and sex steroid receptor expression. We suggest that the expression of IL-1alpha in poorly differentiated, ERalpha-negative tumors contributes to their malignant phenotype.


Experimental modeling and design optimization of push-pull electret loudspeakers.
A fully experimental modeling technique and a design optimization procedure are presented in this paper for push-pull electret loudspeakers. Conventional electrical impedance-based parameter identification methods are not completely applicable to electret speakers due to the extremely weak electromechanical coupling. This prompts the development of an experimental technique for identifying the electroacoustic parameters of the electret speakers. Mechanical parameters are identified from the membrane velocity measured using a laser vibrometer. The voltage-force conversion factor and the motional impedance are estimated, with the aid of a test-box method. This experimentally identified model serves as the simulation platform for predicting the response of the electret loudspeaker and optimizing the design. Optimal parameters are calculated by using the simulated annealing (SA) algorithm to fulfill various design goals and constraints. Either the comprehensive search for various parameters or the simple search for the optimal gap distance can be conducted by this SA procedure. The results reveal that the optimized design has effectively enhanced the performance of the electret loudspeaker.


An electrostatic backpack sprayer: potential for mosquito control.
A Southwest Electrostatic Sprayers, Inc., nozzle was configured to a Hudson PortaPak backpack. A test was run to compare deposition of BVA no. 13 oil by the electrostatic nozzle to a standard nonelectrostatic nozzle as collected by Teflon slides. Results indicate that 100% greater deposition occurred with the electrostatic nozzle.


Recapitulating kidney development in vitro by priming and differentiating mouse embryonic stem cells in monolayers.
In order to harness the potential of pluripotent stem cells, we need to understand how to differentiate them to our target cell types. Here, we developed a protocol to differentiate mouse embryonic stem cells (ESCs) to renal progenitors in a step-wise manner. Microarrays were used to track the transcriptional changes at each stage of differentiation and we observed that genes associated with metanephros, ureteric bud, and blood vessel development were significantly upregulated as the cells differentiated towards renal progenitors. Priming the ESCs and optimizing seeding cell density and growth factor concentrations helped improve differentiation efficiency. Organoids were used to determine the developmental potential of the renal progenitor cells. Aggregated renal progenitors gave rise to organoids consisting of LTL+/E-cadherin+ proximal tubules, cytokeratin+ ureteric bud-derived tubules, and extracellular matrix proteins secreted by the cells themselves. Over-expression of key kidney developmental genes, Pax2, Six1, Eya1, and Hox11 paralogs, during differentiation did not improve differentiation efficiency. Altogether, we developed a protocol to differentiate mouse ESCs in a manner that recapitulates embryonic kidney development and showed that precise gene regulation is essential for proper differentiation to occur.


Ureteral reconstruction with bowel segments: experience with eight patients in a single institute.
Although replacement of the ureter with a bowel segment is indicated for large ureteral defects, it is still a challenging technique for urologists. We present our experience and outcome of ureteral reconstruction using bowel segments. Ureteral reconstruction with bowel segments was performed in eight patients in our institute between 1969 and 2009. We investigated the position and length of the ureteral defect and methods of reconstruction as well as the patients' backgrounds, postoperative complications, and clinical outcomes. Five patients underwent ureteral replacement with isolated ileal segments alone. In one patient, the ureter was reconstructed by using the Yang-Monti procedure with the ileum. A colon segment was used in two patients who required bladder augmentation for tuberculous contracted bladder at the same time. Metabolic acidosis occurred in three patients having a solitary kidney and the ureter had to be replaced by a relatively long intestinal segment. Two patients who received preoperative radiation therapy were required to undergo additional operations. Long-term cancer-free survival was achieved in one patient who underwent ileal substitution for low-grade renal pelvic cancer. Although ureteral replacement with a bowel segment is a challenging and useful procedure, attention must be paid to the possibility of metabolic acidosis, which is likely to occur in patients having a solitary kidney with renal insufficiency or in patients requiring a long intestinal segment for reconstruction. In addition, preoperative radiation therapy for the pelvic organs may cause postoperative complications.


The era of cultivating smart rice with high light efficiency and heat tolerance has come of age.
How to improve the yield of crops has always been the focus of breeding research. Due to the population growth and global climate change, the demand for food has increased sharply, which has brought great challenges to agricultural production. In order to make up for the limitation of global cultivated land area, it is necessary to further improve the output of crops. Photosynthesis is the main source of plant assimilate accumulation, which has a profound impact on the formation of its yield. This review focuses on the cultivation of high light efficiency plants, introduces the main technical means and research progress in improving the photosynthetic efficiency of plants, and discusses the main problems and difficulties faced by the cultivation of high light efficiency plants. At the same time, in view of the frequent occurrence of high-temperature disasters caused by global warming, which seriously threatened plant normal production, we reviewed the response mechanism of plants to heat stress, introduced the methods and strategies of how to cultivate heat tolerant crops, especially rice, and briefly reviewed the progress of heat tolerant research at present. Given big progress in these area, the era of cultivating smart rice with high light efficiency and heat tolerance has come of age.


Calcium-dependent regulation of phosphatidylserine synthesis in control and activated Jurkat T cells.
Activation of Jurkat T cells with phytohemagglutinin (PHA), CD3 or CD2 monoclonal antibodies (mAbs) results in a marked inhibition of phosphatidylserine (PS) synthesis. Activation of Jurkat T cells with PHA in a Ca(2+)-free medium resulted in an arrest of PS synthesis which was not reversed by the addition of Ca2+. The use of BAPTA to chelate Ca2+ ions released from intracellular stores prevented PHA-induced inhibition of PS synthesis. In addition, it was found that during activation, in the presence of BAPTA, a net Ca2+ influx paralleled an increase in PS synthesis, demonstrating that Ca2+ uptake caused an enhanced PS synthesis rather than an inhibition. The use of a CD2 mAb, D66, able to mobilize exclusively Ca2+ from intracellular stores, resulted in 51% inhibition of PS synthesis. N-Ethylmaleimide (NEM), which inhibits both the release of Ca2+ from internal stores and the influx of Ca2+, totally prevents the inhibition of PS synthesis induced by PHA, anti-CD3 or anti-CD2 mAbs. The presence, in the incubation medium, of either NDGA, TPCK or TPA, three drugs able to markedly inhibit Ca2+ influx without modifying the release of Ca2+ from internal stores, did not modify the inhibition of PS synthesis induced by PHA. Moreover all the drugs known to interact with calmodulin were also found to prevent the PHA-induced inhibition of this phospholipid. Taken together, these results show that the inhibition of PS synthesis induced by T cell activators is regulated by both calmodulin and Ca2+ ions recruited from intracellular compartments.


Anisotropic MoS2 Nanosheets Grown on Self-Organized Nanopatterned Substrates.
Manipulating the anisotropy in 2D nanosheets is a promising way to tune or trigger functional properties at the nanoscale. Here, a novel approach is presented to introduce a one-directional anisotropy in MoS2 nanosheets via chemical vapor deposition (CVD) onto rippled patterns prepared on ion-sputtered SiO2 /Si substrates. The optoelectronic properties of MoS2 are dramatically affected by the rippled MoS2 morphology both at the macro- and the nanoscale. In particular, strongly anisotropic phonon modes are observed depending on the polarization orientation with respect to the ripple axis. Moreover, the rippled morphology induces localization of strain and charge doping at the nanoscale, thus causing substantial redshifts of the phonon mode frequencies and a topography-dependent modulation of the MoS2 workfunction, respectively. This study paves the way to a controllable tuning of the anisotropy via substrate pattern engineering in CVD-grown 2D nanosheets.


Promoting men's awareness, self-examination, and help-seeking for testicular disorders: a systematic review of interventions.
Background: Testicular cancer (TC) is among the most commonly diagnosed cancers in men aged 15-40 years. The incidence of TC is on the rise. Benign testicular disorders, such as testicular torsion and epididymitis, can lead to testicular ischemia, sepsis, and infertility if left untreated. This updated systematic review aims to evaluate the effectiveness of studies promoting men's knowledge and awareness of testicular disorders and/or self-examination, behaviours and/or intentions to examine their testes, and help-seeking behaviours and/or intentions for testicular disorder symptoms. Methods: Academic Search Complete, Medline, CINAHL, PsycINFO, ERIC, the Cochrane Library, the World Health Organisation International Clinical Trials Registry Platform, and Clinicaltrials.gov were searched for studies published between April 2018 and August 2023. Methodological quality was assessed and results were synthesised meta-narratively. Results: Five studies were included. The majority of the reviewed interventions were successful in increasing men's awareness of TC and self-examination, including a PowerPoint presentation, an online educational brochure, video-assisted teaching, a motivational video, and a virtual reality game. Only one study addressed help-seeking for testicular symptoms and promoted men's awareness of benign as well as malignant testicular diseases. Conclusions: This review highlights the importance of evaluating innovative educational interventions aimed at younger men, whilst raising their awareness of testicular disorders and increasing their help-seeking intentions for testicular disorder symptoms. Given the lack of consensus around scheduled testicular self-examination among younger men, clinicians are encouraged to instruct men to familiarise themselves with the look and feel of their own testes and to seek timely medical attention for abnormalities. Registration: The protocol of the previous version of this review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42018093671.


Catch and Release of Cytokines Mediated by Tumor Phosphatidylserine Converts Transient Exposure into Long-Lived Inflammation.
Immune cells constantly survey the host for pathogens or tumors and secrete cytokines to alert surrounding cells of these threats. In vivo, activated immune cells secrete cytokines for several hours, yet an acute immune reaction occurs over days. Given these divergent timescales, we addressed how cytokine-responsive cells translate brief cytokine exposure into phenotypic changes that persist over long timescales. We studied melanoma cell responses to transient exposure to the cytokine interferon γ (IFNγ) by combining a systems-scale analysis of gene expression dynamics with computational modeling and experiments. We discovered that IFNγ is captured by phosphatidylserine (PS) on the surface of viable cells both in vitro and in vivo then slowly released to drive long-term transcription of cytokine-response genes. This mechanism introduces an additional function for PS in dynamically regulating inflammation across diverse cancer and primary cell types and has potential to usher in new immunotherapies targeting PS and inflammatory pathways.


Using quantile regression methodology to evaluate changes in the shape of growth curves in pigs selected for increased feed efficiency based on residual feed intake.
Growth rate is a major component of feed efficiency when estimating residual feed intake (RFI). Quantile regression (QR) methodology can be used to identify animals with different growth trajectories. The objective of this study was to evaluate the use of QR to identify phenotypic and genetic differences in pigs selected for low RFI. Using performance data on 750 Yorkshire pigs selected for low RFI, individual average daily gain (ADG), average daily feed intake (ADFI), RFI and Gompertz growth curve parameters (asymptotic weight (a), inflection point (b) and decay parameter (c)) were estimated for each pig. Using QR methodology, three Gompertz growth curves were estimated for the whole population for three quantiles (0.1, 0.5 and 0.9) of the BW data. Each animal was classified into one of the quantile regression groups (QRG) based on their overall Euclidian distance between each observed and estimated BW from the quantile growth curves. These three curves were also estimated using only part of the data (generations -1 to 3, and -1 to 4) in order to evaluate the agreement classification rate of animals from later generations into QRGs. We evaluated the effect of QRG on growth parameters and performance traits. Genetic parameters were estimated for these traits, as well as for QRG. In addition, genetic trends for each QRG were estimated. Three distinct growth curves were observed for animals classified into either quantiles 0.1 (QRG0.1), 0.5 (QRG0.5) or 0.9 (QRG0.9). When only part of the data was used to estimate quantile growth curves, all animals from QRG0.1 were correctly classified in their group. Animals in QRG0.1 had significantly lower ADFI, ADG and RFI, and greater a, b and c than animals in the other groups. Quantile regression groups analysed as a trait was highly heritable (0.41) and had high (0.8) and moderate (0.46) genetic correlations with ADG and RFI, respectively. Selection for reduced RFI increased the number of animals classified as QRG0.1 in the population. Overall, downward genetic trends were observed for all traits as a function of selection for reduced RFI. However, QRG0.1 was the only group that had a positive genetic trend for ADG. Altogether, these results indicate that selection for reduced RFI changes the shape of growth curves in Yorkshire in pigs, and that QR methodology was able to identify animals having different genetic potential for feed efficiency, bringing a new opportunity to improve selection for reduced RFI.


Integrative proteomics and biochemical analyses define Ptc6p as the Saccharomyces cerevisiae pyruvate dehydrogenase phosphatase.
The pyruvate dehydrogenase complex (PDC) is the primary metabolic checkpoint connecting glycolysis and mitochondrial oxidative phosphorylation and is important for maintaining cellular and organismal glucose homeostasis. Phosphorylation of the PDC E1 subunit was identified as a key inhibitory modification in bovine tissue ∼50 years ago, and this regulatory process is now known to be conserved throughout evolution. Although Saccharomyces cerevisiae is a pervasive model organism for investigating cellular metabolism and its regulation by signaling processes, the phosphatase(s) responsible for activating the PDC in S. cerevisiae has not been conclusively defined. Here, using comparative mitochondrial phosphoproteomics, analyses of protein-protein interactions by affinity enrichment-mass spectrometry, and in vitro biochemistry, we define Ptc6p as the primary PDC phosphatase in S. cerevisiae Our analyses further suggest additional substrates for related S. cerevisiae phosphatases and describe the overall phosphoproteomic changes that accompany mitochondrial respiratory dysfunction. In summary, our quantitative proteomics and biochemical analyses have identified Ptc6p as the primary-and likely sole-S. cerevisiae PDC phosphatase, closing a key knowledge gap about the regulation of yeast mitochondrial metabolism. Our findings highlight the power of integrative omics and biochemical analyses for annotating the functions of poorly characterized signaling proteins.


Design and biological evaluation of new platinum(II) complexes bearing ligands with DNA-targeting ability.
A novel series of platinum(II) complexes bearing aliphatic amines and ligands with DNA-targeting properties was synthesized to achieve more potent and selective metallodrugs. We developed six new platinum-based drugs, which contain methylamine, 1a-c, and isopropylamine, 2a-c, both in the trans position to a selected targeting ligand: naphthalimide. The activity of the complexes has been evaluated in order to confirm the improvements from our proposed approach, and the complexes demonstrate better cytotoxic activity on cancer cell lines when compared with the ligands and, importantly, with cisplatin. Further studies were performed to assess their subcellular localization and binding mode to DNA.


A qualitative investigation of school-aged children's answers to items from a generic quality of life measure.
The development of instruments to measure child self-reported quality of life (QOL) is dependent on whether children can understand the concepts behind items. Researchers need more information on how children are interpreting and answering items. This paper aims to investigate the strategies school-aged children use to answer QOL items. A generic 30-item QOL measure (the TedQL) was administered to 266 healthy children (5-6, 7-9 years old). Children were asked to 'think aloud' while answering a selection of 10 TedQL items (n = 4 ability, n = 4 social, n = 2 mood items), and their responses were recorded verbatim. The strategies children reported using when answering items were coded into five categories: (1) social comparisons; (2) stable character references; (3) concrete examples; (4) other reasons; or (5) no reason given. Concrete examples were used most frequently by children. Strategy type was dependent on age, with 7-9-year-olds reporting social comparisons and concrete examples more frequently than 5-6-year-olds. Five-to-six-year-olds gave no reasons for their response choices more frequently than 7-9-year-olds. Strategy type also differed by item type, with social comparisons used more frequently for ability items, and stable character references for social items. However, concrete examples were used consistently highly across ability and social items. Children aged 5-9 years most commonly report using concrete examples of specific instances when answering QOL items. However, strategy use varies as a function of age and types of items. Our results highlight the importance of keeping in mind children's developmental age when interpreting responses from child QOL instruments.


A quick method for the quantitative analysis of mixtures. 1. Powder X-ray diffraction.
A method of analyzing mixtures of APIs and excipients using X-ray powder diffraction is described. It uses a simple algorithm based on linear regression in which the pure component phases are fitted to the mixture pattern using linear least squares. Unlike many methods that use only the peaks in the powder pattern, this technique uses all the measured data points in the 2theta scan with minimal data processing. In practice, using 33 different samples on three diffractometers, the method can be shown to work well for mixtures with up to three components, giving mean errors between 1.7% and 3.9% for two-phase mixtures, and 4.0% and 8.6% for three-phase mixtures. These results compare favorably to those given by traditional Rietveld refinement. It is also shown that the Bruker GADDS system, which is designed for high throughput crystallization experiments, is capable of giving results of comparable accuracy to those derived from traditional, single sample diffractometers. It is possible to identify those mixtures for which one or more pure phase X-ray powder patterns are not available with a detection limit around 10%. The techniques are implemented in the PolySNAP computer program. The method requires very little computer time or user interaction.


Activating Room-Temperature Phosphorescence of Organic Luminophores via External Heavy-Atom Effect and Rigidity of Ionic Polymer Matrix*.
Pure organic room-temperature phosphorescence (RTP) materials have attracted wide attention for their easy preparation, low toxicity, and applications in various fields like bioimaging and anti-counterfeiting. Developing phosphorescent systems with more universality and less difficulty in synthesis has long been the pursuit of materials scientists. By employing a polymeric quaternary ammonium salt with an ionic bonding matrix and heavy atoms, commercial fluorescent dyes are directly endowed with phosphorescence emission. In a single amorphous polymer, the external heavy-atom effect generates excited triplet states and the rigid polymer matrix stabilizes them. This study put forward a new general strategy to design and develop pure organic RTP materials starting from existing library of organic dyes without complicated chemical synthesis.


Method extension study to validate applicability of AOAC Official Method 996.14 Assurance polyclonal enzyme immunoassay for detection of Listeria monocytogenes and related Listeria spp. from environmental surfaces: collaborative study.
Test portions from 3 environmental surface types, representative of typical surfaces found in a food production facility, were analyzed by the Assurance Listeria Polyclonal Enzyme Immunoassay (EIA) and the U.S. Department of Agriculture/Food Safety and Inspection Service (USDA/FSIS) culture method for Listeria monocytogenes and related Listeria species. In all cases, naturally contaminated environmental test samples were collected from an actual food production facility by sponge or swab. Test samples from concrete surfaces were collected by both swab and sponge; sponge test samples were collected from rubber surfaces, and swabs were used to sample steel surfaces. Test portions from each surface type were simultaneously analyzed by both methods. A total of 23 collaborators, representing government agencies, as well as private industry in both the United States and Canada, participated in the study. During this study, a total of 550 test portions and controls was analyzed and confirmed, of which 207 were positive and 336 were negative by both methods. Six test portions were positive by culture, but negative by the EIA. Three test portions were negative by culture, but positive by the EIA. Two test portions were negative by EIA and by culture, but confirmed positive when EIA enrichment broths were subcultured to selective agars. The data reported here indicate that the Assurance Listeria EIA method and the USDA/FSIS culture method are statistically equivalent for detection of L. monocytogenes and related Listeria species from environmental surfaces taken by sponges or swabs.


Xyloglucan endotransglycosylase activity in pine hypocotyls. Intracellular localization and relationship with endogenous growth.
Since xyloglucan depolymerization has been proposed as one of the biochemical bases for cell wall-loosening in gymnosperms, we characterized xyloglucan endotransglycosylase (XET) activity during pine hypocotyl growth to establish a possible relationship. XET activity was measured as the incorporation of [3 H]XXXGol into partially purified pine hypocotyl xyloglucan. XET specific and total activity was determined in the subapical and basal segments of pine hypocotyls at two different stages of growth in different subcellular fractions. XET activity was found in the apoplastic fluid, the symplastic fluid, and in the fraction of proteins ionically and covalently bound to the cell walls with different distribution profiles. The results showed a relationship between XET activity and hypocotyl growth in all the fractions, suggesting an important role for XET during growth. Consequently, the suggested growth-promoting effect of XET in angiosperms can also be extended to gymnosperms. Also, the results demonstrate that XET bound to the cell wall is able to act on endogenous wall-bound xyloglucan as well as soluble polymeric xyloglucan, using them as substrates for the endotransglycosylation reaction.


Usefulness of Urinoculture to Patients With Dementia and Femoral Neck Fracture at Admission to Hospital: Preliminary Results.
While preoperative urinary tract infection (UTI) has the potential to cause bacteremia and postsurgical acute prosthetic joint infections (APJIs), the influence of asymptomatic bacteriuria (AB) in these infections remains unclear. So the majority of guidelines not recommend the treatment of AB prior to the surgery. However, as patients with dementia usually cannot explain the symptoms of dysuria, the differential diagnosis between AB and UTI may be very difficult in this group of patients. The principal aim of the study was to compare the rate of positive urine culture at admission in patients with femoral neck fracture with and without dementia and secondarily try to assess the connection of positive urinoculture and postoperative acute gram-negative PJI. All patients with a femoral neck fracture underwent a urine culture on hospital admission and were prospectively recorded. Variables such as sex, age, institutionalization, dementia and other comorbidities, PJI rate, and in-hospital death were collected. The results of cultures were retrospectively revised. Patients who received postoperative antibiotics or had been diagnosed with UTI during hospital stay were excluded. Statistical comparisons between patients with and without dementia were performed using SPSS software version 17. A total of 148 patients were included (52 with dementia). The rate of positive urine culture was 32% (n = 16) in patients with dementia and 11.5% in patients without dementia (P = .003). Of these 16 patients with dementia and positive urine culture, 2 (12.5%) developed an acute gram-negative PJI, whereas there were no cases in the group without dementia (P = .011). The only difference between UTI and AB is the expression of symptoms by the patient. However, as patients with dementia have difficulties to explain UTI symptoms, some UTI may be underdiagnosed. Patients with dementia have a statistically higher rate of presurgical positive urine culture compared with patients without dementia.


Evaluation of the Root Canal Anatomy of Maxillary and Mandibular Premolars in a Selected German Population Using Cone-beam Computed Tomographic Data.
The aim of this study was to investigate the number of roots and the morphology of the root canals of maxillary and mandibular premolars in a selected German population. Randomly selected full-size cone-beam computed tomographic images were collected from 700 patients (45% men and 55% women, average age = 50.21 years). This resulted in a total of 644 first and 512 second maxillary premolars as well as 1044 first and 871 second mandibular premolars. The total number of roots and root canals, the frequency and correlations between the left and right sides, and the incidence in men and women were recorded and statistically analyzed using the Fisher exact and chi-square tests. Canal configurations were classified according to the Vertucci classification. First maxillary premolars mainly had 2 roots (1 root: 36.4%, 2 roots: 62.4%, and 3 roots: 1.2%) with predominantly 2 canals (88.4%). The majority of second maxillary premolars had 1 root (82.6%), but 2 root canals (56.3%) occurred more frequently than 1 canal (43.1%). In the first and second mandibular premolars, 1 root was found predominantly (90.76% and 98.16%, respectively) with 1 canal (77.9% and 96.0%), whereas 2 canals were less common (21.9% and 3.6%). Three roots (0%, <0.11%) and 3 canals (0.2%; 0.4%) were rarely found. Vertucci classifications were heterogeneously distributed. Men showed significantly more roots and root canals compared with women (P < .05), with the exception of the second mandibular premolars. This cone-beam computed tomographic study confirmed previous anatomic and morphologic investigations. When treating premolars, the likelihood of additional root canals should be considered.


Performance of two egg parasitoids of brown marmorated stink bug before and after cold storage.
Introduction: The genus Trissolcus includes a number of egg parasitoids that are known to contribute to the control of Halyomorpha halys. The number of progenies, particularly females, is important for the efficient mass rearing of species used in augmentative biological control programs. Cold storage is an important technique for extending the shelf life of natural enemies used in such programs. Methods: We assessed how fecundity, sex ratio, lifespan, and the number of hosts parasitized within 24 h were affected by host density for T. japonicus and T. cultratus when offered fresh H. halys eggs and how these parameters were affected if adult parasitoids were first placed in cold storage (11°C in the dark) for 19 weeks before being used for propagation. Results: The fecundity were 110.2 and 84.2 offspring emerged at 25°C, for parasitoids not placed in cold storage; among the offspring that emerged, 82.6% and 85.6% were female for T. japonicus and T. cultratus, respectively. If first placed in cold storage, T. japonicus and T. cultratus produced 35.1 and 24.6 offspring per female, respectively, although cold storage significantly extended the shelf life. The survival rates of parasitoids that were placed in cold storage were 90.3% and 81.3% for females, and 3.2% and 0.9% for males of T. japonicus and T. cultratus, respectively. The number of hosts parasitized within 24 h was not shown to be density dependent, but it was significantly lower after cold storage. Discussion: This information can be used to estimate the likely production for augmented rearing colonies for use in biological control programs.


Recent trends in aerosol therapy for allergic rhinitis.
By analysing patients who visited our out-patient clinic during 4 years (1980-1983), it was found that 18.1% of total patients were suffering from allergic rhinitis. We also analysed prescriptions for allergic rhinitis and it was found that sodium cromoglycate was administered to about 50% of the patients and was the main therapy not only in aerosol type therapy but also in all therapies used for allergic rhinitis. In particular, sodium cromoglycate was administered to over 50% of pediatric patients. Sodium cromoglycate was administered alone in nearly 50% of the patients who used sodium cromoglycate. Accordingly, it can be said that about 25% of all patients were controlled by sodium cromoglycate alone. Steroid aerosol therapy was given to 30-40% of all allergic rhinitis patients. This was mainly due to a rapid increase of usage of beclomethasone dipropionate after 1982 when this was launched. Beclomethasone dipropionate was mainly used for adults patients and was used about 10% of pediatric patients.


Different Routes to Ampholytic Polydehydroalanine: Orthogonal versus Simultaneous Deprotection.
Polydehydroalanine (PDha) is a polyampholyte featuring both a -NH2 and a -COOH in every repeat unit and with that presents a rather high charge density. The synthesis and polymerization of two monomers, benzyl 2-tert-butoxycarbonylaminoacrylate and methyl 2-benzyloxycarbonylaminoacrylate is herein reported, which feature different protective groups and, after polymerization, the resulting PtBABA and PBOMA can be transformed into PDha using polymer-analogous modification reactions. More important, the current choice of protective groups allows either simultaneous deprotection in one step in both cases, but also the orthogonal deprotection of either -NH2 or -COOH moiety for PtBABA, given that appropriate conditions are chosen. The polymers are prepared using free radical polymerization and all (intermediate) polymeric materials are investigated using a combination of NMR spectroscopy and size exclusion chromatography.


Cloning of a genetic determinant from Clostridium difficile involved in adherence to tissue culture cells and mucus.
Our laboratory has previously shown that Clostridium difficile adherence to Caco-2 cells is greatly enhanced after heat shock at 60 degrees C and that it is mediated by a proteinaceous surface component. The experiments described here show that C. difficile could adhere to several types of tissue culture cells (Vero, HeLa, and KB) after heat shock. The type of culture medium (liquid or solid, with or without blood) had little effect on adhesion. To clone the adhesin gene, polyclonal antibodies against C. difficile heated at 60 degrees C were used to screen a genomic library of C. difficile constructed in lambda ZapII. Ten positive clones were identified in the library, one of which (pCL6) agglutinated several types of erythrocytes in the presence of mannose. In Western blots (immunoblots), this clone expressed in Escherichia coli a 40- and a 27-kDa protein; a 27-kDa protein has been previously identified in the surface extracts of heat-shocked C. difficile as a possible adhesin. The clone adhered to Vero, Caco-2, KB, and HeLa cells; the adherence was blocked by anti-C. difficile antibodies, by a surface extract of C. difficile, and by mucus isolated from axenic mice. Furthermore, the clone could attach ex vivo to intestinal mucus isolated from axenic mice. Preliminary studies on the receptor moieties implicated in C. difficile adhesion revealed that glucose and galactose could partially block adhesion to tissue culture cells, as did di- or trisaccharides containing these sugars, suggesting that the adhesin is a lectin. In addition, N-acetylgalactosamine, a component of mucus, and gelatin partially impeded cell attachment.


Genome-Wide Characterization and Expression Profiling of Sugar Transporter Family in the Whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae).
Sugar transporters (STs) play pivotal roles in the growth, development, and stress responses of phloem-sucking insects, such as the whitefly, Bemisia tabaci. In this study, 137 sugar transporters (STs) were identified based on analysis of the genome and transcriptome of B. tabaci MEAM1. B. tabaci MEAM1 encodes a larger number of STs than other selected insects. Phylogenetic and molecular evolution analysis showed that the 137 STs formed three expanded clades and that the genes in Sternorrhyncha expanded clades had accelerated rates of evolution. B. tabaci sugar transporters (BTSTs) were divided into three groups based on their expression profiles across developmental stages; however, no host-specific BTST was found in B. tabaci fed on different host plants. Feeding of B. tabaci adults with feeding diet containing dsRNA significantly reduced the transcript level of the target genes in B. tabaci and mortality was significantly improved in B. tabaci fed on dsRNA compared to the control, which indicates the sugar transporters may be used as potential RNAi targets for B. tabaci bio-control. These results provide a foundation for further studies of STs in B. tabaci.


Leptin sensitivity in skeletal muscle is modulated by diet and exercise.
Leptin reduces intracellular lipid stores and improves insulin sensitivity. Thus, the development of leptin resistance in obesity may be an early event leading to elevated intramuscular lipids and insulin resistance. Recent data indicate that obesity-causing high-fat diets lead to leptin resistance in muscle, whereas supplementation with dietary fish oil and aerobic training can partially reverse this resistance.


[Pirarubicin (THP-adriamycin)].
Pirarubicin (THP-adriamycin or THP-doxorubicin) was found during a search of new anthracycline antibiotics among 4'-O-substituted compounds having less toxicities than other anthracycline anticancer drugs in 1979 by Umezawa et al. In its preclinical studies, this compound possessed almost similar antitumor efficacies to doxorubicin, but was effective against doxorubicin-resistant P388 and other murine tumor cell lines. This compound was rapidly incorporated into tumor cells, inhibiting DNA polymerase alpha and subsequently DNA synthesis. Inhibition of RNA synthesis was also noted. In the clinical studies, clinical responses were established against head and neck cancer, breast cancer, urogenital cancers, ovarian cancer, uterine cancer, acute leukemia, and malignant lymphoma, showing a wide antitumor spectrum clinically. Among the side effects, cardiac toxicity, alopecia and disturbance of the digestive organs were mild. From these results, THP-adriamycin seems to be a useful clinical drug for human solid tumors.


Is forty the new thirty? Population based study of advanced maternal age.
To compare perinatal outcomes in different advanced maternal age groups. We used a population-based data set to compare perinatal outcomes in three maternal age groups: 30-34.9, 35-39.9, and in women over 40 years. Over a 10-year period there were 23,422 (25.2%) births in the 35-39.9 years group, 3987 (4.3%) in the over 40 years group, and 65,492 births (70.5%) in our reference group (30-34.9 years). A direct significant relationship was found between maternal age and BMI and between pregnancy complications such as diabetes and hypertensive disorders, whereas an inverse relationship was found between older age and nuliparity and spontaneous conceptions. Also, older mothers had a higher incidence of both types of cesareans, and more early as well as late preterm births. Perinatal mortality was similar in all groups. Advanced maternal age is associated with higher, gradually increasing, incidence, of adverse perinatal outcomes.


Biomimetic Mineralization Guided One-Pot Preparation of Gold Clusters Anchored Two-Dimensional MnO2 Nanosheets for Fluorometric/Magnetic Bimodal Sensing.
A novel fluorometric/magnetic bimodal sensor is reported based on gold nanoclusters (Au NCs)-anchored two-dimensional (2D) MnO2 nanosheets (Au NCs-MnO2) that are synthesized through a one-pot biomimetic mineralization process. Bovine serum albumin (BSA) was used as the template to guide the formation and assembly of the Au NCs-MnO2 under physiological conditions and without use of any strong oxidizing agent and toxic surfactants as well as organic solvent. The fluorescence of Au NCs was first quenched by MnO2 nanosheets, while upon H2O2 introduction, the MnO2 nanosheets can be sensitively and selectively reduced to Mn2+ with enhanced magnetic resonance (MR) signal and rapid recovery of Au NCs fluorescence simultaneously. This dual-modal strategy can overcome the weakness of a single-fluorescence detection mode. A linear range of 0.06-2 μM toward H2O2 was obtained for the fluorescence mode, whereas the MR mode also allowed detection of H2O2 at a concentration that ranged from 0.01 to 0.2 mM. Benefiting from the BSA molecule residual on the product surface, the as-prepared Au NCs-MnO2 displays low cytotoxicity and good biocompatibility. Importantly, the successful application of Au NCs-MnO2 for analysis of H2O2 in biological samples and cells indicates that the integration of Au NCs fluorescence with Mn2+ MR response provides a promising bimodal sensing platform for H2O2 in vivo monitoring.


Joseph Towne (1806-1879), master modeller of wax.
Joseph Towne (1806-1879) was a pioneer in the art of wax modelling of anatomical and dermatological material. He began his career at the age of 17, at Guy's Hospital, London, where he spent the whole of his professional life. He was a secretive, self-taught individual, and the finer points of his technique died with him. His brilliant works are on view at the Gordon Museum at Guy's, and are still used for teaching.


The plantaris muscle: anatomy, injury, imaging, and treatment.
The plantaris muscle is often dismissed as a small, vestigial muscle, however an injury to this structure should actually be included in differential considerations of the painful calf. Injury to the plantaris on its own, or in association with concurrent injuries of the knee can present a diagnostic challenge to the manual practitioner. This review discusses the diagnosis, imaging, and evidence based management of this tiny, but important muscle of the lower limb.


Nephrotoxicity of CDDP assessed estimating glomerular filtration rate with 99mTc-DTPA plasma sample method.
To assess early nephrotoxicity of CDDP (Cis-diamminedichloroplatinum) manifested by a decline in the glomerular filtration rate (GFR) estimated by plasma two sample clearance method (PSC 2) after 99mTc-DTPA injection. Descriptive study. Department of Nuclear Medicine, Karachi Institute of Radiotherapy and Nuclear Medicine, Karachi, from September 2004 to January 2005. The renal function was assessed on 36 patients suffering from different types of cancer and receiving CDDP in doses of (3) 50 mg/m(2) before and after in each of six CDDP cycles. The GFR was determined by PSC 2 method after 99mTc-DTPA injection). A paired sample t-test was used for comparison of the mean value with significance at p < 0.01. There were (28 males and 8 females; age range being 16-68 years) The average decline in GFR baseline to the end of sixth cycles was 43.86 ml/min/1.73m(2) (p=0.000) as estimated by PSC 2 method. There was a significant fall of average 9.36 ml/min/1.73m(2) (p < 0.01) in GFR as observed in each cycle of CDDP estimated by the PSC 2 method. In the initial four cycles, CDDP produced a major nephrotoxic effect of average 10.27 ml/min/1.73m(2) (p < 0.01) fall in GFR. This then gradually declined to a plateau of an average decline in GFR of 7.76 and 7.31 ml/min/1.73m(2) (p=0.000) after the 5th and 6th cycle respectively. CDDP produced an early nephrotoxicity which was manifested by a significant decline in GFR in each cycle. Tc-99m PSC 2 method for GFR estimation should be used periodically for the early detection of nephrotoxicity induced by CDDP.


Indoloazepinone-Constrained Oligomers as Cell-Penetrating and Blood-Brain-Barrier-Permeating Compounds.
Non-cationic and amphipathic indoloazepinone-constrained (Aia) oligomers have been synthesized as new vectors for intracellular delivery. The conformational preferences of the [l-Aia-Xxx]n oligomers were investigated by circular dichroism (CD) and NMR spectroscopy. Whereas Boc-[l-Aia-Gly]2,4 -OBn oligomers 12 and 13 and Boc-[l-Aia-β3 -h-l-Ala]2,4 -OBn oligomers 16 and 17 were totally or partially disordered, Boc-[l-Aia-l-Ala]2 -OBn (14) induced a typical turn stabilized by C5 - and C7 -membered H-bond pseudo-cycles and aromatic interactions. Boc-[l-Aia-l-Ala]4 -OBn (15) exhibited a unique structure with remarkable T-shaped π-stacking interactions involving the indole rings of the four l-Aia residues forming a dense hydrophobic cluster. All of the proposed FITC-6-Ahx-[l-Aia-Xxx]4 -NH2 oligomers 19-23, with the exception of FITC-6-Ahx-[l-Aia-Gly]4 -NH2 (18), were internalized by MDA-MB-231 cells with higher efficiency than the positive references penetratin and Arg8 . In parallel, the compounds of this series were successfully explored in an in vitro blood-brain barrier (BBB) permeation assay. Although no passive diffusion permeability was observed for any of the tested Ac-[l-Aia-Xxx]4 -NH2 oligomers in the PAMPA model, Ac-[l-Aia-l-Arg]4 -NH2 (26) showed significant permeation in the in vitro cell-based human model of the BBB, suggesting an active mechanism of cell penetration.


Corrigendum: Effects of a pair programming educational robot-based approach on students' interdisciplinary learning of computational thinking and language learning.
[This corrects the article DOI: 10.3389/fpsyg.2022.888215.].


Plant biodiversity offsets negative effects of metals and metalloids soil multi-contamination on ecosystem multifunctionality.
Despite increasing metals and metalloids (MM) human-driven soil contamination, how it simultaneously alters biodiversity and ecosystem functioning remains unknown. We used a wide gradient of a 170-year-old MM soil multi-contamination in Mediterranean scrublands to assess the effects of soil multi-contamination on multiple plant biodiversity facets, microbial communities and ecosystem multifunctionality (EMF). We found an overall positive effect of plant biodiversity on EMF mediated by microbial communities, and allowing offsetting the negative impacts of MM soil multi-contamination, especially on soil water holding capacity and nitrogen content. The diversity of distant plant lineages was the key facet promoting EMF by enhancing microbial communities, whereas the subordinate species richness altered EMF. By developing a holistic approach of these complex relationships between soil multi-contamination, plant biodiversity, microbial communities and ecosystem functioning, our results reveal the potential of plant biodiversity, and especially the diversity of evolutionary distant species, to offset the alteration of ecosystem functioning by MM soil multi-contamination. In this worldwide decade of ecosystems restoration, our study helps to identify relevant facets of plant biodiversity promoting contaminated ecosystem functioning, which is crucial to guide and optimize management efforts aiming to restore ecosystems and preserve human health.


Catheterization laboratory activations and time intervals for patients with pre-hospital ECGs.
The use of pre-hospital ECGs (PH-ECG) reduces time to reperfusion for patients with ST-segment elevation myocardial infarction (STEMI). The feasibility of reperfusion therapy within 60 minutes for hospitals with 24/7 PCI capability has been questioned, and current guidelines have set time targets to 90 minutes. Our primary objective was to investigate the proportion of false-positive catheterization laboratory activations by PH-ECG. Our secondary objective was to describe the time intervals from first medical contact to reperfusion and to establish the proportion of patients receiving reperfusion within 60 minutes. A retrospective cohort study among 4298 patients for whom a PH-ECG was transmitted to the investigating hospital, mainly due to chest pain, during 2013 were included. Among patients with PH-ECGs, 139 (3.2%) patients had a STEMI. There were 115 pre-hospital catheterization laboratory activations among which 16% (95% confidence interval 10-23) were false-positive for STEMI. The median total time from emergency call to arterial puncture was 76 minutes. The target of PCI within 60 minutes was met in 83% of the cases. The time from EMS arrival to PH-ECG was 20 minutes for female patients and 13 minutes for male patients (p < .001), and only 16% had a PH-ECG within 10 minutes from Emergency Medical Service arrival. The rate of false-positive catheterization laboratory activations based on pre-hospital ECGs was low and the target of PCI within 60 minutes is achievable for a majority of patients. Efforts should be made to reduce the time from ambulance arrival to PH-ECG transmission, especially for female patients.


Fatal Gastrointestinal Disorders Due to COVID-19: A Case Series.
Patients with coronavirus disease 2019 (COVID-19) primarily develop respiratory symptoms, which sometimes can be serious. Respiratory failure is the most common cause of death from COVID-19. This disease also causes gastrointestinal (GI) symptoms. However, there are limited reports that severe GI disorders caused by COVID-19 can be fatal. Herein, we report three cases of fatal GI disorders caused by COVID-19. All patients developed severe pneumonia requiring mechanical ventilation and venovenous extracorporeal membrane oxygenation (V-V ECMO) support. The respiratory status improved, and the patients could be weaned off support. However, severe watery diarrhea (over a few liters per day) developed after the onset of respiratory failure. The CT, endoscopic, and pathological findings were similar to those observed in GI graft-versus-host disease (GI-GVHD). Despite various efforts, the GI disorders did not improve, and all patients died of multiple organ failures associated with sepsis due to intestinal mucosal disruption. COVID-19 can cause fatal GI disorders and may have similar characteristics to GI-GVHD. Further investigation will contribute to a comprehensive understanding of fatal GI disorders due to COVID-19.


dMyc is required in retinal progenitors to prevent JNK-mediated retinal glial activation.
In the nervous system, glial cells provide crucial insulation and trophic support to neurons and are important for neuronal survival. In reaction to a wide variety of insults, glial cells respond with changes in cell morphology and metabolism to allow repair. Additionally, these cells can acquire migratory and proliferative potential. In particular, after axonal damage or pruning the clearance of axonal debris by glial cells is key for a healthy nervous system. Thus, bidirectional neuron-glial interactions are crucial in development, but little is known about the cellular sensors and signalling pathways involved. In here, we show that decreased cellular fitness in retinal progenitors caused by reduced Drosophila Myc expression triggers non cell-autonomous activation of retinal glia proliferation and overmigration. Glia migration occurs beyond its normal limit near the boundary between differentiated photoreceptors and precursor cells, extending into the progenitor domain. This overmigration is stimulated by JNK activation (and the function of its target Mmp1), while proliferative responses are mediated by Dpp/TGF-β signalling activation.


[Orbital decompression by pterional approach in dysthyroid orbitopathies].
The etiology of the endocrine orbitopathy is still unknown and thereby their treatment remains symptomatic. The surgical decompression is achieved in resecting lateral wall, roof and partly bottom of the orbit. We treated 23 eyes in 14 patients and in only one patient the decompression obtained with this method was insufficient. This patient underwent additionally transantral transethmoidal decompression. One patient had a complete loss of vision after surgery probably due to direct lesion of the optic nerve. The decompression of the orbit is indicated in fast progressive endocrine orbitopathies with impairment of the visual function.


Prior surgical uterine evacuation of pregnancy and infertility: protocol for systematic review and meta-analysis.
Prior surgical uterine evacuation is associated with an increased risk of infertility. However, findings are inconsistent, highlighting the need for a clear consensus on the effect of prior surgical uterine evacuation on the risk of infertility. Therefore, the aim of this systematic review and meta-analysis is to summarise the available evidence examining the association between prior surgical uterine evacuation and the risk of infertility. A systematic search of electronic databases (ie, PubMed, Scopus, ClinicalTrials.gov, EMBASE and ScienceDirect) will be conducted since their inception until October 2019 with no limit for language using a detailed prespecified search strategy. Both the authors will independently screen titles and abstracts and select full-text articles, perform data extraction and appraise the quality of included studies using a bias classification tool. Meta-analyses will be performed to calculate the overall pooled estimates using the generic inverse variance method. This systematic review and meta-analysis will follow the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Given that this is a protocol based on published data, there is no requirement for ethics approval. It is anticipated that the dissemination of results will be reported according to the PRISMA statement. The results will be published in peer-reviewed journals and presented at scientific conferences. CRD42019117266.


Retinal ganglion cells and axons survive optic nerve transection.
The effects of optic nerve transection on optic axon and retinal cell survival was studied in C57BL/6J mice. The optic nerve was transected either intracranially or intraorbitally . Data are presented which show that an intracranial transection of the optic nerve may be achieved while maintaining the blood supply to the retina. Intraorbital optic nerve transection, however, necessitates destruction of the retinal blood supply. Cell survival in the retinal ganglion cell layer is compared for both transection methods. In addition, electron microscopic evidence is presented which indicates axonal survival in the optic nerve up to at least 90 days following intracranial transection.


Bipolar Electrode Based Reversible Fluorescence Switch Using Prussian Blue/Au Nanoclusters Nanocomposite Film.
A highly efficient fluorescence switch system based on a closed bipolar electrode (C-BPE) system was proposed for the first time. Here, Au nanoclusters (Au NCs) were premodified on one pole of the BPE and acted as the fluorescent donor. On the basis of the spectral overlap between the absorbance of electrochromic material-Prussian blue (PB) and the fluorescence spectrum of Au NCs, fluorescence quenching ("off" state) induced by the inner filter effect was observed. Due to the electrochemical reversible redox reaction between PB and Prussian white, switching the polarity of driving voltage could easily achieve the fluorescence recovery of the Au NCs, corresponding to the "on" state. Through the reasonable design of C-BPE and optimization of driving voltage, the on-off ratio of the integrated fluorescence switch was up to 2.7 and a good fatigue resistance while performing 10 on-off cycles was obtained owing to the good stability of Au NCs and the reversible redox feature of PB. The introduction of BPE made the fluorescence switch more simple and controllable compared with the traditional three-electrode system, which will provide a new route for the design of the electrical-stimuli responsive fluorescence switch, especially for the integration of the miniaturized device.


Magnification characteristic of a +90-diopter double-aspheric fundus examination lens.
To investigate the magnification characteristic of the +90-D double-aspheric fundus examination lens for biomicroscopic measurement of the optic disc. A calibrated Gullstrand-type model eye adjusted for axial ametropia between -12.5 and +12.6 D was used to measure the change in magnification of the system with refractive error and variation in fundus lens position. A correction factor p (in degrees per millimeter) at different axial ametropias was also calculated. The total change in magnification of the system from myopia to hyperopia was -15.1% to +13.7%. When the fundus lens position was altered with respect to the model eye by +/-2 mm under myopic conditions, the change in magnification of the system was -4.8% to +8.1%. In the hyperopic condition the change was -4.8% to +6.0%. The fundus lens exhibited a linear relationship between p and the degree of ametropia of the model eye and a constant relationship between p and ametropia of -5 to +5 D. Axial ametropia has a significant effect on biomicroscopic measurement of the optic disc with the +90-D lens. Therefore, a correction factor (p) was calculated that can be used in calculations for determining true optic disc size. These findings may be important for improving clinical disc biometry.


Non-equilibrium physics and evolution--adaptation, extinction, and ecology: a key issues review.
Evolutionary dynamics in nature constitute an immensely complex non-equilibrium process. We review the application of physical models of evolution, by focusing on adaptation, extinction, and ecology. In each case, we examine key concepts by working through examples. Adaptation is discussed in the context of bacterial evolution, with a view toward the relationship between growth rates, mutation rates, selection strength, and environmental changes. Extinction dynamics for an isolated population are reviewed, with emphasis on the relation between timescales of extinction, population size, and temporally correlated noise. Ecological models are discussed by focusing on the effect of spatial interspecies interactions on diversity. Connections between physical processes--such as diffusion, turbulence, and localization--and evolutionary phenomena are highlighted.


Granger Causality: A Review and Recent Advances.
Introduced more than a half-century ago, Granger causality has become a popular tool for analyzing time series data in many application domains, from economics and finance to genomics and neuroscience. Despite this popularity, the validity of this framework for inferring causal relationships among time series has remained the topic of continuous debate. Moreover, while the original definition was general, limitations in computational tools have constrained the applications of Granger causality to primarily simple bivariate vector autoregressive processes. Starting with a review of early developments and debates, this article discusses recent advances that address various shortcomings of the earlier approaches, from models for high-dimensional time series to more recent developments that account for nonlinear and non-Gaussian observations and allow for subsampled and mixed-frequency time series.


The duck hepatitis B virus reverse transcriptase functions as a full-length monomer.
Hepadnaviral reverse transcription occurs within cytoplasmic capsid particles and is catalyzed by a virally encoded reverse transcriptase, but the primary structure and multimeric state of the polymerase during reverse transcription are poorly understood. We measured these parameters for the duck hepatitis B virus polymerase employing active enzyme translated in vitro and derived from intracellular core particles and mature virions. In vitro-translated polymerase immunoprecipitated as a monomer, and polymerase molecules with complementary defects in the enzymatic active site and tyrosine 96, which primes DNA synthesis, could not complement or inhibit each other in priming assays. Western analysis using antibodies recognizing epitopes throughout the polymerase combined with nuclease digestion of permeabilized virion-derived capsid particles revealed that only full-length polymerase molecules were in virions and that they were all covalently attached to large DNA molecules. Because DNA synthesis is primed by the polymerase itself and only one copy of the viral DNA is in each capsid, the polymerase must function as an uncleaved monomer. Therefore, a single polymerase monomer is encapsidated, primes DNA synthesis, synthesizes both DNA strands, and participates in the three-strand transfers of DNA synthesis, with all steps after DNA priming performed while the polymerase is covalently coupled to the product DNA. Because the N-terminal domain of the polymerase is displaced from the active site on the same molecule by the viral DNA during reverse transcription, P must be structurally dynamic during DNA synthesis. Therefore, non-nucleoside compounds that interfere with this change may be novel antiviral agents.


Fluorescence-tagged salivary small extracellular vesicles as a nanotool in early diagnosis of Parkinson's disease.
Parkinson's disease is generally asymptomatic at earlier stages. At an early stage, there is an extensive progression in the neuropathological hallmarks, although, at this stage, diagnosis is not possible with currently available diagnostic methods. Therefore, the pressing need is for susceptibility risk biomarkers that can aid in better diagnosis and therapeutics as well can objectively serve to measure the endpoint of disease progression. The role of small extracellular vesicles (sEV) in the progression of neurodegenerative diseases could be potent in playing a revolutionary role in biomarker discovery. In our study, the salivary sEV were efficiently isolated by chemical precipitation combined with ultrafiltration from subjects (PD = 70, healthy controls = 26, and prodromal PD = 08), followed by antibody-based validation with CD63, CD9, GAPDH, Flotillin-1, and L1CAM. Morphological characterization of the isolated sEV through transmission electron microscopy. The quantification of sEV was achieved by fluorescence (lipid-binding dye-labeled) nanoparticle tracking analysis and antibody-based (CD63 Alexa fluor 488 tagged sEV) nanoparticle tracking analysis. The total alpha-synuclein (α-synTotal) in salivary sEVs cargo was quantified by ELISA. The disease severity staging confirmation for n = 18 clinically diagnosed Parkinson's disease patients was done by 99mTc-TRODAT-single-photon emission computed tomography. We observed a significant increase in total sEVs concentration in PD patients than in the healthy control (HC), where fluorescence lipid-binding dye-tagged sEV were observed to be higher in PD (p = 0.0001) than in the HC using NTA with a sensitivity of 94.34%. In the prodromal PD cases, the fluorescence lipid-binding dye-tagged sEV concentration was found to be higher (p = 0.008) than in HC. This result was validated through anti-CD63 tagged sEV (p = 0.0006) with similar sensitivity of 94.12%. We further validated our findings with the ELISA based on α-synTotal concentration in sEV, where it was observed to be higher in PD (p = 0.004) with a sensitivity of 88.24%. The caudate binding ratios in 99mTc-TRODAT-SPECT represent a positive correlation with sEV concentration (r = 0.8117 with p = 0.0112). In this study, for the first time, we have found that the fluorescence-tagged sEV has the potential to screen the progression of disease with clinically acceptable sensitivity and can be a potent early detection method for PD.


Untreated periodontal disease in Indonesian adolescents. Clinical and microbiological baseline data.
At present, several risk factors for the initiation and progression of periodontitis have been identified. In order to investigate the rôle of various potential clinical and microbiological risk factors and indicators, a longitudinal study was initiated in a young population deprived from regular dental care. The present communication describes the baseline cross-sectional data obtained in 1987 in terms of the clinical periodontal condition and prevalence of periodontal bacteria in the oral cavity. All inhabitants in the age range 15-25 years of a village with approximately 2000 inhabitants at a tea estate on Western Java, Indonesia, were examined clinically and microbiologically. In total, 255 adolescents, comprising 130 males and 125 females participated in the study. Samples for bacteriological examination were taken from the gingiva, the dorsum of the tongue, and the saliva. Plaque index, bleeding upon probing, pocket depth, and attachment loss (AL) were scored on the approximal surfaces from the vestibular aspect of all teeth as well as the mid-vestibular and mid-lingual aspects of the Ramfjord teeth. Calculus was scored only on the 4 surfaces of the Ramfjord teeth. Following the clinical measurements, the deepest bleeding pocket with no clinical loss of attachment was sampled for microbiological examination. In addition, in 37 subjects a deep bleeding (> or = 4 mm) with at least 4 mm of attachment loss was sampled. Moderate periodontitis (max. AL 3-4 mm) was found in 26% of the population, advanced periodontitis (max. AL > or = 5 mm) in 8%, whereas 66% of the population showed no or minor periodontitis (max. AL 0-2 mm). Actinobacillus actinomycetemcomitans was found in 57% of the population, Porphyromonas gingivalis in 87%, Prevotella intermedia and motile rods in all cases and spirochetes in 89%. P. gingivalis (66%), A. actinomycetemcomitans (37%) and spirochetes (63%) were, of all the sampled sites of the oral cavity, most frequently detected in pockets without attachment loss. Motile rods were most prevalent on the tongue and in the saliva (92% and 89%, respectively). A high prevalence of the investigated periodontal bacteria was detected both in the pockets without and with attachment loss. No significant association between the clinical periodontal parameters and the prevalence of the microorganisms was observed at a patient level. At a site level, both P. gingivalis and spirochetes were more prevalent in sites with attachment loss. The actual rôle of these putative periodontal pathogens may be elucidated more extensively, when longitudinal data on the present population become available.


Citalopram and escitalopram in the treatment of major depressive disorder: a pooled analysis of 3 clinical trials.
Pooled analysis is a powerful technique that is increasingly used to detect differences in efficacy between pharmacologic agents. Some studies have compared the efficacy and tolerability of citalopram and escitalopram, with contradictory results. The aim of this study was to compare the efficacy and tolerability of citalopram and escitalopram in the treatment of major depressive disorder (MDD) using pooled analyses. Data from 3 randomized, double-blind studies that compared citalopram (20 to 40 mg/d) and escitalopram (10 to 20 mg/d) were pooled and analyzed. The primary efficacy parameter was change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score. Efficacy assessments were made at weeks 0 (baseline), 1, 2, 4, and 6. Based on the mean change from baseline in the HAM-D-17 at weeks 1, 2, 4, and 6, the efficacy of citalopram, 20 to 40 mg/d, was equivalent to escitalopram, 10 to 20 mg/d (P > .05). Similar results were seen for severely depressed patients, with a mean treatment difference of 13.9 (SE = 7.6) vs 15.9 (SE = 7.5). Response and remission rates at week 6 were similar (response, 72.4% for citalopram, compared with 73.5% for escitalopram; remission, 52.6% vs 54.5%, respectively). The pooled analysis showed that over a 6-week treatment period, citalopram, 20 to 40 mg/d, is equivalent to escitalopram, 10 to 20 mg/d, in both efficacy and tolerability.


Mechanistic investigations of the pseudouridine synthase RluA using RNA containing 5-fluorouridine.
The pseuoduridine synthases (psi synthases) isomerize uridine (U) to pseudouridine (psi) in RNA, and they fall into five families that share very limited sequence similarity but have the same overall fold and active-site architecture, including an essential Asp. The mechanism by which the psi synthases operate remains unknown, and mechanistic work has largely made use of RNA containing 5-fluorouridine (f5U) in place of U. The psi synthase TruA forms a covalent adduct with such RNA, and heat disruption of the adduct generates a hydrated product of f5U, which was reasonably concluded to result from the hydrolysis of an ester linkage between the essential Asp and f5U. In contrast, the psi synthase TruB, which is a member of a different family, does not form an adduct with f5U in RNA but catalyzes the rearrangement and hydration of the f5U, which labeling studies with [18O]water showed does not result from ester hydrolysis. To extend the line of mechanistic investigation to another family of psi synthases and an enzyme that makes an adduct with f5U in RNA, the behavior of RluA toward RNA containing f5U was examined. Stem-loop RNAs are shown to be good substrates for RluA. Heat denaturation of the adduct between RluA and RNA containing f5U produces a hydrated nucleoside product, and labeling studies show that hydration does not occur by ester hydrolysis. These results are interpreted in light of a consistent mechanistic scheme for the handling of f5U by psi synthases.