Transdermal permeation of geniposide in the herbal complex liniment in vivo and in vitro.
Zhongtong Caji, a kind of liniment, is a traditional Chinese medicinal formula that is widely used for clinical treatment of inflammation and sprains. In this study, the principal effective compound of this formula, geniposide, was used as a criterion to represent the transdermal permeability of the whole formula. A passive diffusion of Zhongtong Caji through the stratum corneum was discovered by an in vitro experiment. The dosage-content relationship detected in subcutaneous tissue after in vivo drug administration was further evidence of its permeation. Blood analysis after different dosages showed that the geniposide could be absorbed and accumulated by subcutaneous tissue within 1h after drug administration, and it would be eliminated by blood circulation 1h after drug treatment.


Bacterial Cr(VI) reduction concurrently improves sunflower (Helianthus Annuus L.) growth.
Four Cr(VI)-reducing bacterial strains (Ochrobactrum intermedium, CrT-2, CrT-3 and CrT-4) previously isolated from chromium-contaminated sites were inoculated on to seeds of sunflower (Helianthus annuus var SF-187), which were germinated and grown along with non-inoculated controls with chromate salts (300 microg CrCl3 or K2CrO4 ml(-1)). Severe reduction (20%) in seed germination was observed in Cr(VI) stress. Plant height decreased (36%) with Cr(VI) when compared with chromium-free control, while O. intermedium inoculation resulted a 20% increment in this parameter as compared to non-inoculated chromium-free control. CrT-3 inoculation resulted a 69% increment in auxin content as compared to non-inoculated control. O. intermedium caused 30% decrease in chromium uptake in sunflower plant roots under Cr(VI) stress as compared to chromium-free control plants.


Characterization of glycoprotein H and L of human herpesvirus 7.
The genes encoding the glycoproteins H (gH) and L (gL) of human herpesvirus 7 (HHV-7) have been identified. The gH open reading frame (ORF) was 2,070 base pairs in length and encoded a predicted 690 amino-acid protein. The gH contained characteristics of a transmembrane glycoprotein including 10 consensus N-linked glycosylation sites, 12 cysteine residues, a potential amino-terminal signal sequence and a predicted transmembrane segment located near the carboxyl terminus. The gL ORF was 738 base pairs in length and encoded a predicted 246 amino-acid protein. Four possible N-glycosylation sites and 6 cysteine residues existed within gL. The predicted amino-acid sequences of the HHV-7 gH and human herpesvirus 6 variant A (HHV-6A) gH gene products exhibited 23.6% identity to each other; and those of the gL gene products had 26.0% identity. Upon in vitro translation of the gL gene, the addition of microsomal membranes resulted in two modified products with molecular weights of 32 kDa and 35 kDa from the unmodified initial translation product of 26 kDa. An amino-terminal portion of gH and the full length of gL were expressed as glutathione S-transferase fusion proteins, and these proteins were used to raise immune sera in mice. Lysates of cells infected with HHV-7 were subjected to immunoprecipitation analysis. Approximate molecular weights of 33, 37, 80 and 90 kDa polypeptides were immunoprecipitated with antibodies against the gH protein. Antibodies against the gL protein polypeptides with the same molecular weights were also precipitated, and were observed with the antibodies against the gH protein. These results suggest that HHV-7 gH and gL may form a heterodimeric complex with each other in HHV-7 infected cells, as has been reported for other herpesviruses.


'Click chemistry' on polysaccharides: a convenient, general, and monitorable approach to develop (1-->3)-beta-D-glucans with various functional appendages.
(1-->3)-beta-D-Glucans having various functional appendages (lactoside, ferrocene, pyrene, and porphyrin) can be prepared in an convenient, quantitative, and regioselective manner through regioselective bromination-azidation of curdlan to afford 6-azido-6-deoxycurdlan followed by chemoselective [3+2]-cycloadditions with various functional modules bearing a terminal alkyne group. The ability to monitor reaction conversions is an additional advantage of this synthetic approach over the conventional direct modifications on polysaccharides; the reaction can be readily monitored based on the intensity of azido peaks in the in situ attenuated total reflection infrared spectra.


SCENTinel 1.0 : development of a rapid test to screen for smell loss.
Commercially available smell tests are primarily used in research or in-depth clinical evaluations, but are too costly and lengthy for population surveillance in health emergencies like COVID-19. We developed the SCENTinel 1 . 0 test which rapidly evaluates three olfactory functions (detection, intensity, and identification). We tested whether self-administering the SCENTinel 1 . 0 test discriminates between individuals with smell loss or average smell ability (normosmics), and provides comparable performance as the validated and standardized NIH Toolbox ® Odor Identification Test in normosmics. Using Bayesian linear models and prognostic classification algorithms, we compared the SCENTinel 1 . 0 performance of a group of self-reported anosmics (N=111, 47±13yo, F=71%,) and normosmics (N=154, 47±14yo, F=74%), as well as individuals reporting other smell disorders (e.g., hyposmia, parosmia; N=42, 55±10yo, F=67%). Ninety-four percent of normosmics met our SCENTinel 1 . 0 accuracy criteria, while only 10% of anosmics and 64% of individuals with other smell disorders did. Overall performance on SCENTinel 1 . 0 predicted belonging to the normosmic group better than identification or detection alone (vs. anosmic: AUC=0.95, Sensitivity=0.72, Specificity=0.94). Odor intensity provided the best single-feature predictor to classify normosmics. Among normosmics, 92% met the accuracy criteria at both SCENTinel 1 . 0 and the NIH Toolbox ® Odor Identification Test. SCENTinel 1 . 0 is a practical test able to discriminate individuals with smell loss and is likely to be useful in many clinical situations, including COVID-19 symptom screening.


Estimating sexual size dimorphism in fossil species from posterior probability densities.
Accurate characterization of sexual dimorphism is crucial in evolutionary biology because of its significance in understanding present and past adaptations involving reproductive and resource use strategies of species. However, inferring dimorphism in fossil assemblages is difficult, particularly with relatively low dimorphism. Commonly used methods of estimating dimorphism levels in fossils include the mean method, the binomial dimorphism index, and the coefficient of variation method. These methods have been reported to overestimate low levels of dimorphism, which is problematic when investigating issues such as canine size dimorphism in primates and its relation to reproductive strategies. Here, we introduce the posterior density peak (pdPeak) method that utilizes the Bayesian inference to provide posterior probability densities of dimorphism levels and within-sex variance. The highest posterior density point is termed the pdPeak. We investigated performance of the pdPeak method and made comparisons with the above-mentioned conventional methods via 1) computer-generated samples simulating a range of conditions and 2) application to canine crown-diameter datasets of extant known-sex anthropoids. Results showed that the pdPeak method is capable of unbiased estimates in a broader range of dimorphism levels than the other methods and uniquely provides reliable interval estimates. Although attention is required to its underestimation tendency when some of the distributional assumptions are violated, we demonstrate that the pdPeak method enables a more accurate dimorphism estimate at lower dimorphism levels than previously possible, which is important to illuminating human evolution.


A mechanistic model of the aerobic growth of Saccharomyces cerevisiae.
A two-stage deterministic model of the growth of Saccharomyces cerevisiae is presented. The cell cycle of this organism was used to suggest the basic model structure. The model represents the preparatory processes of substrate uptake and conversion separately from replication and division. The regulation of the fraction of the culture devoted to each of these broad areas of metabolism, and the overall growth rate, is related to the nature and availability of the energy substrate. The simulation of respiration and glycolysis is achieved by including two alternative energy producing pathways. The regulation of these pathways is described in terms of the postulated primary regulation of the proportion of the culture required for substrate uptake and conversion, and the overall kinetic constants for each pathway. This regulation is dictated primarily by the growth rate rather than the nature or concentration of the energy substrate. The model successfully describes both batch and continuous growth of S. cerevisiae under conditons of glucose limitation and oxygen excess. A preliminary assessment indicates that adjustment of the relevant parameters will allow the model to describe the growth of S. cerevisiae on other sugars and under oxygen limitation. Similarly the model could be expected to describe the growth characteristics of other yeast species.


Seed and pollen flow and cline discordance among genes with different modes of inheritance.
The relationships between seed and pollen flow and cline discordance/concordance between cytoplasmic and nuclear genes, with the incorporation of the effects of natural selection, are formulated for one locus with two alleles, under assumptions of random mating, no drift and no mutation. Results show that under certain conditions, the relative roles of seed and pollen flow in shaping cline discordance/ concordance are very similar to their roles in influencing population differentiation for selectively neutral markers with different modes of inheritance. Where the disequilibria between cytoplasmic and nuclear genes are of the order similar to selection coefficient, cline discordance/concordance can be predicted from the relative values of the ratio of pollen to seed flow and the ratio of selection coefficients. Where the disequilibria attained by seed and pollen flow are significant, the integrated cytonuclear data are recommended for cline analysis. In both cases, the relative rates of selection coefficients between cytoplasmic and nuclear genes can be roughly estimated according to their characteristic length.


Retention behaviour of peptides in capillary electrochromatography using an embedded ammonium in dodecacyl stationary phase.
The potential of a silica stationary phase bearing an embedded cationic quaternary amine in dodecacyl chain, to separate peptides by capillary electrochromatography (CEC) has been evaluated. The ability of this stationary phase, to generate a consistent anodic electroosmotic flow was first evaluated. This flow was found to be independent of pH over a wide range (2-12), of the acetonitrile percentage in the electrolyte. The stability of the stationary phase evaluated through the electroosmotic flow variations was demonstrated at extreme pH values (2.5 and 9.1). A careful examination of the influence of mobile phase conditions (acetonitrile percentage, salt concentration and nature of buffer) on the electrochromatographic retention and electrophoretic migration behaviour of different standard peptides was carried out. In acidic conditions, the electrokinetic contribution appears to be predominant compared to the chromatographic one. Several types of chromatographic interactions, reversed-phase partitioning and anion exchange, were involved in the CEC of peptides, whereas repulsive electrostatic interaction could be considered as negligible. This stationary phase affords different selectivity compared to that observed on a C18 stationary phase. Finally, the method was applied to the peptide mapping of beta-lactoglobulin and human growth hormone under unpressurized and isocratic elution.


Uniting the divergent Wolfram syndrome-linked proteins WFS1 and CISD2 as modulators of Ca2+ signaling.
Mutations in WFS1 (which encodes Wolframin, WFS1) and CISD2 (which encodes CDGSH iron sulfur domain 2) result in Wolfram syndrome (WS), a rare genetic disorder that starts with juvenile diabetes and progresses to neurological dysfunction. WFS1 and CISD2 belong to different protein families with distinct properties. Despite differences between WFS1 and CISD2, loss-of-function mutations in these proteins result in similar disease phenotypes, suggesting that they have convergent roles. WFS1 and CISD2 both localize at the endoplasmic reticulum (ER), the main intracellular calcium (Ca2+) store, which is implicated in several diseases, including WS. Here, we not only review the roles of WFS1 and CISD2 in Ca2+ signaling modulation but also point out knowledge gaps. Because WFS1 and CISD2 form complexes with Ca2+ transporters and Ca2+ channels, it is thought that they influence the activity of these transport systems in cells. Together, the studies reviewed here provide a better understanding of the pathogenesis and the severe disease burden of WS and may contribute to the development of therapeutics.


Cystic biliary tumors of the liver: diagnostic criteria and common pitfalls.
With major advancements and frequent use of abdominal imaging techniques, hepatic cysts are increasingly encountered in clinical practice. Although the majority of cysts are benign, a small subset represents neoplastic precursors to cholangiocarcinoma. These cystic precursors include intraductal papillary neoplasms of the bile duct (IPNB) and mucinous cystic neoplasms of the liver (MCN-L), and bear striking pathologic resemblance to corresponding cystic neoplastic precursors within the pancreas. This review examines the salient clinical, gross, microscopic and molecular features of IPNBs and MCN-Ls, and, in particular, provides histopathologic comparison to their pancreatic counterparts. Considering these neoplasms may be diagnostically challenging, we also discuss other hepatic lesions within the differential diagnosis, and the potential for molecular methods to improve their preoperative evaluation and the early detection of cholangiocarcinoma.


Involvement of both intrinsic and extrinsic pathways in hepatoprotection of arjunolic acid against cadmium induced acute damage in vitro.
Cadmium (Cd) is one of the ubiquitous environmental pollutants and is responsible for various organ pathophysiology including hepatic disorders. It is extremely toxic even in low concentrations and bioaccumulate in organisms. The present study has been carried out to investigate the cytoprotective role of arjunolic acid (AA), a tri terpenoid saponin, against Cd induced oxidative impairment and cell death in murine hepatocytes. Administration of cadmium (30 μM), in the form of chloride (CdCl(2)) for 2h, significantly enhanced the ALT, ALP and LDH leakage, increased reactive oxygen species (ROS) production, reduced hepatocytes viability and altered the antioxidant status of hepatocytes by reducing intracellular GSH level, anti-oxidant enzymes activity and increasing intracellular GSSG and lipid peroxidation. Evidence for Cd-induced nature of cell death was sought by flow cytometric analysis. Signal transduction studies revealed that Cd markedly increased the levels of caspase-9, -8, -3, Fas and Bid, decreased mitochondrial membrane potential, enhanced cytochrome c release in the cytosol, disturbed the Bcl-2 family protein balance, cleaved PARP protein and ultimately led to apoptotic cell death. Results showed that Cd could trigger both intrinsic and extrinsic apoptotic pathways. In addition, Cd markedly increased NF-κB nuclear translocation in association with IKKα/β phosphorylation and IκBα degradation. Simultaneous treatment with AA (200 μM), however, reduced Cd-induced oxidative stress, attenuated the nuclear translocation of NF-κB and protects the hepatocytes from Cd-induced apoptotic death. Combining, data suggest that Cd-induced hepatic dysfunction and apoptosis might be supported by the ROS formation and mediated via the activation of NF-κB. AA treatment, on the other hand, reduced Cd-induced oxidative stress, attenuated the activation of NF-κB and mitochondrion-dependent and independent apoptotic signaling pathways.


Use of Imaging Endpoints in Clinical Trials.
Cardiovascular imaging is an integral component of many clinical trials beyond those for which the primary goal is to evaluate or validate imaging technologies. The scope of such trials is broad, ranging from those in which a medical, surgical, or interventional cardiovascular device or drug is being evaluated to those in which there is concern about cardiovascular adverse events complicating treatment for noncardiac conditions. This paper discusses study design as it pertains to the incorporation of imaging elements, the important role played by imaging core laboratories, the rationale for and approaches to involvement of imagers in clinical trials, and guidance by the U.S. Food and Drug Administration on imaging endpoints in clinical trials.


Human heart disease: lessons from human pluripotent stem cell-derived cardiomyocytes.
Technical advances in generating and phenotyping cardiomyocytes from human pluripotent stem cells (hPSC-CMs) are now driving their wider acceptance as in vitro models to understand human heart disease and discover therapeutic targets that may lead to new compounds for clinical use. Current literature clearly shows that hPSC-CMs recapitulate many molecular, cellular, and functional aspects of human heart pathophysiology and their responses to cardioactive drugs. Here, we provide a comprehensive overview of hPSC-CMs models that have been described to date and highlight their most recent and remarkable contributions to research on cardiovascular diseases and disorders with cardiac traits. We conclude discussing immediate challenges, limitations, and emerging solutions.


Prophylactic management of radiation-induced mucositis using herbal mouthwash in patients with head and neck cancer: an assessor-blinded randomized controlled trial.
Radiation-induced mucositis (RIOM) is one of the most common side effects from head and neck radiotherapy. Several reagents have been introduced to manage the symptom; however, there is still a limited number of effective reagents. Herbal mouthwashes with payayor (Clinacanthus nutans Lindau) and fingerroot (Boesenbergia rotunda) were tested their efficacies in preventing and reducing severity of RIOM in comparison with normal saline with sodium bicarbonate. One hundred twenty patients with head and neck cancer undergoing radiotherapy participated in the study and were randomly assigned into three treatment groups using block randomization method. The participants were assigned one of the three mouthwashes for use throughout their radiotherapy course and were assessed for their mucositis scores from week one to six into their radiotherapy course as well as at one-month follow-up. Body mass index was also measured for comparison of nutritional status. The two mouthwashes were similarly effective in prophylaxis of RIOM in term of severity. The averaged mucositis scores were less than two for all groups. For the onset of RIOM, both herbal mouthwashes could slightly delay the symptom but not statistically significant. Patients' body mass index across the three treatment groups was also comparable. The patients were largely satisfied with all the mouthwashes with no clear preference on any of them. Prophylactic treatment of RIOM using herbal mouthwashes could substitute the current standard of normal saline with bicarbonate. A different formulation of the two herbs could potentially improve the prophylactic outcome. NCT03359187.


Modelling growth curves of the normal infant's mandible: 3D measurements using computed tomography.
Data on normal mandibular development in the infant is lacking though essential to understand normal growth patterns and to discriminate abnormal growth. The aim of this study was to provide normal linear measurements of the mandible using computed tomography performed in infants from 0 to 2 years of age. 3D voxel software was used to calculate mandibular body length, mandibular ramus length, bicondylar width, bigonial width and the gonial angle. Intra- and inter-rater reliability was assessed for these measurements. They were found to be sufficient for all distances; intra-class correlation coefficients were all above 0.9. Regression analysis for growth modelling was performed. In this multi-centre retrospective study, 109 CT scans were found eligible that were performed for various reasons (e.g. trauma, craniosynostosis, craniofacial abscesses). Craniosynostosis patients had larger mandibular measurements compared to non-craniosynostosis patients and were therefore excluded. Fifty-one CT scans were analysed. Analysis showed that the mandible increases more in size vertically (the mandibular ramus) than horizontally (the mandibular body). Most of the mandibular growth occurs in the first 6 months. These growth models provide insight into normal mandibular development in the first 2 years of life. This reference data facilitates discrimination between normal and abnormal mandibular growth.


Heart Surgery Access Bone: Spectrum of Pathology.
A variety of pathologies may affect the most important bone to cardiac surgeons. In this paper, 3 interesting cases of different pathology and aetiology are presented and discussed.


Gene expression of Pht cluster genes and a putative non-ribosomal peptide synthetase required for phaseolotoxin production is regulated by GacS/GacA in Pseudomonas syringae pv. phaseolicola.
Pseudomonas syringae pv. phaseolicola is the causal agent of halo blight disease of beans (Phaseolus vulgaris L.), which is characterized by watersoaked lesions surrounded by a chlorotic halo resulting from the action of a non-host specific toxin known as phaseolotoxin. This toxin inhibits the enzyme ornithine carbamoyltransferase involved in the arginine biosynthesis pathway. It was previously reported that genes within the Pht cluster were involved in the regulation and synthesis of phaseolotoxin. The GacS/GacA two-component signal transduction system controls important pathogenicity and virulence mechanisms in several Gram-negative bacteria. Tox(-) phenotype gacA(-) and gacS(-) mutants were obtained and gacA(-) transcriptome analysis revealed that this response activator controls expression of genes within the Pht cluster as well as another gene located in a different region in the bacterial chromosome and that has been unambiguously shown to be directly involved in phaseolotoxin biosynthesis. Results presented in this work suggest that phaseolotoxin biosynthesis involve elements within and outside the Pht Cluster, and that the GacS/GacA two-component system exerts control over them.


Adaptive photoacoustic computed tomography.
For many optical imaging modalities, image qualities are inevitably degraded by wavefront distortions caused by varying light speed. In optical microscopy and astronomy, adaptive optics (AO) has long been applied to compensate for such unwanted aberrations. Photoacoustic computed tomography (PACT), despite relying on the ultrasonic wave for image formation, suffers from the acoustic version of the same problem. However, this problem has traditionally been regarded as an inverse problem of jointly reconstructing both the initial pressure and the sound speed distributions. In this work, we proposed a method similar to indirect wavefront sensing in AO. We argued that wavefront distortions can be extracted and corrected by a frequency domain analysis of local images. In addition to an adaptively reconstructed aberration-free image, the speed of sound map can be subsequently estimated. We demonstrated the method by in silico, phantom, and in vivo experiments.


Wells-Dawson Arsenotungstate Porous Derivatives for Electrochemical Supercapacitor Electrodes and Electrocatalytically Active Materials.
Two Wells-Dawson arsenotungstate coordination polymers, [{CuII(bim)2}3(As2W18O62)] (1) and [(CuI10pz10Cl4)(As2W18O62)] (bim = 2,2'-biimidazole; pz = pyrazine), have been assembled via a hydrothermal method and fully characterized. Compound 1 exhibits a 2,6-connected two-dimensional hybrid layer based on asymmetrically modified {As2W18} anions and {Cu(bim)2} linkers, which is extended to a three-dimensional network with a special interlayer structure and a one-dimensional tunnel. Compound 2 is a host-guest framework that consists of a Cu-pz-Cl network with 20-member square rings, 16-member irregular rings, and embedded eight-node {As2W18} guest molecules. Compounds 1 and 2 show uncommon specific capacitance (834.8 and 960.1 F g-1, respectively, at a current density of 2.4 A g-1), enduring cycling stability (capacitance retention rates of 89.3% and 91.9%, respectively, after 5000 cycles), and good electrical conductivity, which are superior to those of the unmodified zero-dimensional Dawson arsenotungstate compound and most reported electrode materials in terms of their stable structure, special layer spacing, and orderly channels. Moreover, the title compounds exhibit excellent electrocatalytic activity for oxidizing ascorbic acid and reducing nitrite.


Repetitive transcranial magnetic stimulation (rTMS) for post-stroke sleep disorders: a systematic review of randomized controlled trials.
Survivors of stroke often experience post-stroke sleep disorders (PSSDs), but pharmacotherapy risks adverse side effects. Transcranial magnetic stimulation (TMS) is potentially a nonpharmacotherapeutic option. This meta-analysis investigated the effects of rTMS to treat PSSD. Databases were searched for randomized controlled trials (RCTs) of rTMS to treat PSSD, conducted in accordance with the PRISMA 2020 guidelines. Risk-of-bias assessments were performed using the Cochrane risk-of-bias tool. A meta-analysis of the following indexes was performed using RevMan 5.4 software: Pittsburgh sleep quality index; effective rate of sleep improvement; Hamilton Anxiety Rating Scale (for mood); and National Institute of Health Stroke Scale (NIHSS, stroke severity). Mean differences (MDs) and confidence intervals (CIs) were calculated. The meta-analysis included 17 RCTs, with 1411 patients overall. The indexes indicated that rTMS could improve the sleep quality, mood, and stroke severity of patients with PSSD: Pittsburgh sleep quality index (12 studies; MD = - 2.51, 95% CI [- 3.24, - 1.79], P < 0.00001); effective rate of sleep improvement (7 studies; MD = 4.03, 95% CI [2.43, 6.68], P < 0.0001); Hamilton Anxiety Rating Scale (2 studies; MD = - 4.05, 95% CI [- 4.77, - 3.32], P < 0.00001); and NIHSS (2 studies; MD = -2.71, 95% CI [- 3.36, - 2.06], P < 0.00001). The results suggest that rTMS may have positive effects on the sleep quality, mood, and stroke severity of patients with PSSD.


What about Alice? Peripheral neuropathy from taxane-containing treatment for advanced nonsmall cell lung cancer.
In this review, we discuss the plight of Alice, a patient with advanced nonsmall cell lung cancer (NSCLC) who struggles with taxane-related peripheral neuropathy (PN). Using this unique point of view helps us to appreciate the implications of PN on daily activities as well as the difficulty in decision-making regarding continuation of treatment. In addition, published reports of phase 3 trials are reviewed to identify the incidence and severity of chemotherapy-induced PN as well as the assessment tools used in these studies. A literature review spanning the years 1998-2012 was performed. Phase 3 studies and a meta-analysis of taxane-based therapy in advanced NSCLC were selected for review for their findings regarding the incidence and severity of chemotherapy-induced PN. In total, 16 phase 3 studies and 1 meta-analysis were reviewed. Use of grading scales and PN assessment tools was inconsistent across the studies, and some studies did not report PN at all. The true incidence and severity of chemotherapy-induced PN in clinical trials may be masked by nonstandardized reporting; thus, a more standardized approach to grading, assessing, and reporting PN in clinical trials is greatly needed to allow for appropriate comparisons across studies. Understanding chemotherapy-induced PN from the patient's perspective as well as the development of PN at the clinical trial level will help health care providers anticipate the development of PN and improve their ability to manage it.


[The health status of children and adolescents with migration background in Germany : Results from KiGGS Wave 2].
Even though 36.5% of children and adolescents living in Germany have a migration background (MB), data on the health of this population is scarce. With population-based data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS Wave 2, 2014-2017), reliable statements can be given. Data from KiGGS Wave 2 is used in order to report on general health status, mental health, and the distribution of allergic diseases among children and adolescents aged 3-17 years (n = 13,568). To determine overweight, standardized measurements of body weight and height (n = 3463) were used. In addition to the MB (none/one-sided/two-sided), the socioeconomic status (SES) is considered. In multivariate analyses among children and adolescents with MB, SES and the parents' duration of stay in Germany were included. Participants with a two-sided MB show lower prevalence of neurodermatitis (3.5% vs. 6.9%) and ADHS (2.0% vs. 5.1%) than those without a migration background and higher prevalence of fair to poor general health status (6.1% vs. 3.9%). Children and adolescents with a two-sided migration background are more often affected by overweight than those without migration background (22.1% vs. 12.2%). After considering SES, the chances of a diagnosed neurodermatitis and ADHS remain higher and the chances for overweight are lower in children and adolescents with a migration background than among those without migration background. If only children with MB are considered, SES and partially the parents' duration of stay in Germany are associated with health outcomes. Differences in the general health status of children and adolescents with and without MB vary depending on the observed indicators. The heterogeneity of children and adolescents with MB, e.g. regarding SES and parents' duration of stay, should be considered when planning and implementing measures of health promotion.


I can read it in your eyes: what eye movements tell us about visuo-attentional processes in developmental dyslexia.
Most studies today agree about the link between visual-attention and oculomotor control during reading: attention seems to affect saccadic programming, that is, the position where the eyes land in a word. Moreover, recent studies show that visuo-attentional processes are strictly linked to normal and impaired reading. In particular, a large body of research has found evidence of defective visuo-attentional processes in dyslexics. What do eye movements tell us about visuo-attentional deficits in developmental dyslexia? The purpose of this paper is to explore the link between oculomotor control and dyslexia, taking into account its heterogeneous manifestation and comorbidity. Clinical perspectives in the use of the eye-movements approach to better explore and understand reading impairments are discussed.


Amount and distribution of collagen in the pancreas have no effect on porcine islet isolation outcome.
Xenotransplantation of porcine islets of Langerhans is considered to be a possible alternative for clinical islet transplantation. However, porcine islet isolation procedures have been shown to produce highly variable yields between pigs with similar backgrounds. One of the variables that could account for this is the collagen substrate within the pancreas. We determined the amount and distribution of collagen within porcine pancreata as they determined islet isolation outcomes. This study involved the histological examination of 140 porcine pancreata (64 juvenile and 76 adult) and islet isolation from 58 adult organs. To quantify the amount of collagen, tissue samples were stained with Sirius Red. Collagen distribution was determined by assessing the presence of collagen in the endocrine-exocrine interface (the "islet capsule"), in tissue samples double-stained with Sirius Red and anti-insulin. Strong variation in total collagen was observed in both adult and juvenile pigs. The mean collagen content in the juvenile group was significantly lower than that in the adult group. Apparently, the pancreas undergoes a process of fibrosis as pigs age. The vast majority of islets from both adult and juvenile pancreata had no or only a limited collagen capsule. However, islet encapsulation was highly variable between pancreata. We observed no significant correlation between total collagen content or the percentage islet encapsulation and islet yield. Although total collagen content and islet encapsulation show great variability between pancreata, neither the amount nor the distribution of collagen affected porcine islet isolation outcome.


The Dammed and the Saved: a Conservation Triage Framework for Wetlands under Climate Change in the Murray-Darling Basin, Australia.
As the impacts of climate change and water demands from irrigation continue to increase in the Murray-Darling Basin, water for the environment is becoming more scarce and the ecological conditions of many wetlands is poor. With water scarcity, conservation triage is becoming an increasingly relevant management option for environmental watering of wetlands. However, triage is controversial; being considered contrary to current conservation objectives and practices. We assessed environmental watering at two Ramsar wetlands, Macquarie Marshes and Gunbower Forest, based on international environmental treaty obligations and domestic policy settings, changes to flow regimes, wetland condition and current management. Triage decision making was found to be in tacit use at Macquarie Marshes, based on 'rules of thumb' and experiential ecohydrological knowledge, whereas formal environmental watering planning formed the basis for triage decision making at Gunbower Forest. We developed a framework for conservation triage of wetlands in the Murray-Darling Basin to stimulate change in the decision context for wetland conservation and adaptation under climate change. Conservation triage entails reframing of relationships between people and nature and values, rules and knowledge used by stakeholders. Because water is the medium by which wetland conservation outcomes eventuate, trade-offs between competing water uses can be realised with the triage framework.


Pitfalls in echocardiographic-based repair of aortic coarctation.
The knowledge of echocardiographic pitfalls, which may impair the correct indication for surgery of aortic coarctation, is of great importance to pediatric cardiologists. We believe that only the suspicion of coronary artery anomalies is a clear indication to perform a cardiac catherization.


Significance of multifocality in papillary thyroid carcinoma.
Although multifocality is often observed in papillary thyroid carcinoma (PTC), the associations with clinicopathologic factors and the prognostic value are still controversial. We aimed to identify the risk factors for multifocality and bilaterality, and investigate the significance of multifocality on prognosis in all PTC, papillary thyroid microcarcinoma (PTMC) and non-PTMC. Data from 635 patients who underwent lobectomy/total thyroidectomy plus cervical lymph node dissection for PTC were retrospectively analyzed. Clinicopathological factors associated with multifocal PTC and bilateral PTC were investigated by univariate analysis. Multivariate Cox regression analyses was used to identify the clinicopathological prognostic factors for recurrence-free survival. Multifocal and bilateral PTC were observed in 157 (24.7%) and 99 (15.6%) patients, respectively. The frequency of large diameter (>1.0 cm), extrathyroidal extension (ETE), vascular invasion and central lymph node metastases (CLNM) was higher in multifocal PTC than that of solitary PTC. Moreover, ETE, vascular invasion, CLNM and lateral lymph node metastasis (LLNM) were more frequent in patients with 3 or more tumor foci compared to those with 2 tumor foci and 1 tumor lesion. Bilateral PTC had higher rates of ETE and CLNM. Multifocality was found to be the predictor of recurrence in all PTC, PTMC, and non-PTMC. In addition, the risk of recurrence increased with increasing number of tumor foci in all multifocal PTC patients and multifocal non-PTMC patients. Although multifocality and bilaterality had more aggressive features in PTC, only multifocality was associated with the increased risk of recurrence. An increase in the number of tumors was associated with an increased risk of ETE, vascular invasion, CLNM and LLNM. The prognostic value of multifocality is particularly significant in non-PTMC patients.


Cloning and characterization of a cDNA encoding Xenopus laevis alpha o1 isoform of the Go protein.
The mammalian gene encoding the alpha subunit of the Go protein generates by alternative splicing two isoforms, alpha o1 and alpha o2, which differ in their carboxy-terminal region. We report here the cloning of a Xenopus cDNA (XG alpha o1) which encodes a protein corresponding to the mammalian alpha o1 isoform. In its 3' untranslated region, the transcript contains a repetitive motif made up of dinucleotide AT repeats. By RT-PCR amplification, we showed that XG alpha o1 transcripts are both maternal and zygotic. As alpha o2 transcripts have been shown to be maternal and devoid of AT repeats, the repetitive motif could play a role in the differential expression of each isoform.


Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential.
Estrogen receptors alpha (ERα) and beta (ERβ) are nuclear transcription factors that are involved in the regulation of many complex physiological processes in humans. Modulation of these receptors by prospective therapeutic agents is currently being considered for prevention and treatment of a wide variety of pathological conditions, such as, cancer, metabolic and cardiovascular diseases, neurodegeneration, inflammation, and osteoporosis. This review provides an overview and update of compounds that have been recently reported as modulators of ERs, with a particular focus on their potential clinical applications.


Small vessel vasculitis.
Vasculitis is a primary inflammatory process of large, medium-sized, and small blood vessels. There are multiple entities particularly among small vessel vasculitides. Some are life threatening and require treatment with toxic agents. Diagnostic challenges are posed by low prevalence, controversial classification, inconsistency of clinical and pathological features, and the existence of clinical and pathological "look-alikes". Also, patients may present to a variety of medical specialists, and the diagnosis is often unexpected. The cause often is unknown. Classification is by vessel size and then on an immunopathologic basis. Generalised and "organ-limited" forms occur. The principal clinical and pathological features are outlined for each of antibasement membrane disease, immune complex disorders including Henoch-Schönlein purpura and cryoglobulinemic vasculitis and the pauci-immune group, which is often associated with antineutrophil cytoplasmic antibody (ANCA), comprising microscopic polyangiitis, Wegener's granulomatosis, and Churg-Strauss syndrome. A brief account is given of "look-alikes" including microthrombotic conditions, which can confound the diagnosis of small vessel vasculitis. Requirements for diagnosis include full disclosure of the past and present medical history with review of laboratory results, especially diagnostic immunology. Histology should be of targeted biopsies of recent active lesions in preference to blind biopsies. Sampling should be extensive using high-quality thin sections. Systematic microscopic evaluation of architectural features and cellular detail is necessary. Tissue immunofluorescence is a useful adjunct. The final opinion must take all available information into account but may ultimately depend on a critical judgement by the pathologist.


Effects of the hydroalcoholic extract of Phyllanthus niruri and its isolated compounds on cyclophosphamide-induced hemorrhagic cystitis in mouse.
The effects of Phyllanthus niruri hydroalcoholic extract and the isolated compounds quercetin, rutin, and gallic acid were examined in the mouse model of cyclophosphamide (CYP)-induced hemorrhagic cystitis (HC). HC was induced by a single CYP injection (300 mg/kg, IP), and the animals were evaluated 4 and 6 h after. Some animals were orally treated with the reference compound 2-mercaptoethane sodium sulfonate (Mesna) 80 mg/kg (30 min before CYP) and 160 mg/kg (2 h after CYP). Other groups were treated with P. niruri extract (30 and 50 mg/kg), or quercetin, rutin, and gallic acid (10 and 20 mg/kg), given orally, at the same intervals described for Mesna. P. niruri extract and its active components produced a significant attenuation of the nociception, edema, and hemorrhage evoked by CYP, which was similar to that seen for Mesna. Gallic acid and rutin displayed greater anti-inflammatory effects, whereas quercetin presented superior antinociceptive activities. Noteworthy is that P. niruri extract and compounds significantly reduced CYP-induced liver lipid peroxidation. Our results shed new light on the beneficial effects of P. niruri extract and its active compounds in attenuating the collateral effects elicited by the chemotherapeutic agent CYP.


Platelet hypersensitivity induced by 1-chloro-2, 4-dinitrobenzene, hydroperoxides and inhibition of lipoxygenase.
Platelets administered 1-chloro-2,4-dinitrobenzene to deplete intracellular glutathione (GSH) and inhibit GSH-peroxidase responded with irreversible aggregation to low doses of arachidonic acid (AA) more rapidly than control cells. This increase in sensitivity was correlated to inhibition of GSH-peroxidase, and not with the depletion of GSH. Addition of hydrogen peroxide, 15-hydroperoxyeicosatetraenoic acid, or inhibition of the lipoxygenase metabolic pathway by 4,7,10,13-eicosatetraynoic acid also induced a hypersensitive aggregation response to AA. These results suggest that the three modes of treatment share a common mechanism of increasing AA metabolism to biologically active prostaglandins and thromboxane A2 through alterations in cyclooxygenase kinetics and available enzyme substrate.


Acid- and base-catalysis in the mononuclear rearrangement of some (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole in toluene: effect of substituents on the course of reaction.
The reaction rates for the rearrangement of eleven (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole 3a-k into the relevant (2-aryl-5-phenyl-2H-1,2,3-triazol-4-yl)ureas 4a-k in the presence of trichloroacetic acid or of piperidine have been determined in toluene at 313.1 K. The results have been related to the effect of the aryl substituent by using Hammett and/or Ingold-Yukawa-Tsuno correlations and have been compared with those previously collected in a protic polar solvent (dioxane/water) as well as with those on the analogous rearrangement of the corresponding (Z)-arylhydrazones of 3-benzoyl-5-phenyl-1,2,4-oxadiazole 1a-k in benzene. Some light can thus be shed on the general differences of chemical reactivity between protic polar (or dipolar aprotic) and apolar solvents.


Use of Real-World Data and Evidence in Drug Development of Medicinal Products Centrally Authorized in Europe in 2018-2019.
Real-world data/real-world evidence (RWD/RWE) are considered to have a great potential to complement, in some cases, replace the evidence generated through randomized controlled trials. By tradition, use of RWD/RWE in the postauthorization phase is well-known, whereas published evidence of use in the pre-authorization phase of medicines development is lacking. The primary aim of this study was to identify and quantify the role of potential use of RWD/RWE (RWE signatures) during the pre-authorization phase, as presented in the initial marketing authorization applications of new medicines centrally evaluated with a positive opinion in 2018-2019 (n = 111) by the European Medicines Agency (EMA). Data for the study was retrieved from the evaluation overviews of the European Public Assessment Reports (EPARs), which reflect the scientific conclusions of the assessment process and are accessible through the EMA website. RWE signatures were extracted into an RWE Data Matrix, including 11 categories divided over 5 stages of the drug development lifecycle. Nearly all EPARs included RWE signatures for the discovery (98.2%) and life-cycle management (100.0%). Half of them included RWE signatures for the full development phase (48.6%) and for supporting regulatory decisions at the registration (46.8%), whereas over a third (35.1%) included RWE signatures for the early development. RWE signatures were more often seen for orphan and conditionally approved medicines. Oncology, hematology, and anti-infectives stood out as therapeutic areas with most RWE signatures in their full development phase. The findings bring unprecedented insights about the vast use of RWD/RWE in drug development supporting the regulatory decision making.


One-stage reconstruction of the scrotum following Fournier's syndrome using a probable arterial flap.
A one-stage procedure is described for restoring the scrotum in a patient who suffered from Fournier's gangrene. The proximal superiomedial-based thigh flaps employed are most likely arterial flaps. These flaps are also well innervated, which makes them ideal for the purpose of scrotal reconstruction.


Photodynamic inactivation of oropharyngeal Candida strains.
Oropharyngeal candidiasis (OPC) is an infection frequent in immunocompromised patients. Photodynamic therapy is an alternative to conventional treatments, based on the utilization of compounds that inhibit or kill microorganisms only under the effect of light, process known as Photodynamic Inactivation (PDI). In the present study, PDI of Candida spp. by the natural product α-terthienyl (α-T) was investigated following the guidelines of CLSI M27-A3, under UV-A light irradiation. The optimal values of two variables, exposure irradiation time (ET) and distance to the irradiation source (DIS) were established by employing Design Expert Software (DES). For this purpose, a panel of Candida strains isolated from OPC (C. albicans, C. tropicalis, C. parapsilosis and C. krusei) was employed and optimal values were 5 min (ET) and between 6.06 and 6.43 cm (DIS) with a desirability factor of 0.989. α-T plus UV-A light in the optimal conditions caused a complete reduction in viable cells in 5 min which was demonstrated by viable cells reduction assays and confocal microscopy after vital staining (propidium iodide/fluorescein diacetate). The germ tube formation of C. albicans was inhibited by α-T at sub-inhibitory concentrations. Results showed that α-T plus UV-A light could constitute an alternative for OPC treatments at the optimal conditions determined here.


Population-based pediatric reference values for serum parathyroid hormone, vitamin D, calcium, and phosphate in Danish/North-European white children and adolescents.
Parathyroid hormone (PTH) and vitamin D are essential hormones in bone metabolism, especially during pediatric growth. Vitamin D insufficiency is often asymptomatic and is prevalent in high-latitude countries. In a Danish population-based cohort of 2211 6-18-year-olds, sex- and age-specific pediatric reference values for fasting concentrations of intact serum PTH, vitamin D (25-hydroxycholecalciferol, 25-OH-D), total calcium, and phosphate were generated in accordance with Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines. The effect of season on these biomarkers of bone metabolism was evaluated. In boys, PTH concentrations increased with age, while the vitamin D and phosphate concentrations decreased (all p < .001). In girls, a peak in PTH concentrations and a nadir in vitamin D concentrations were observed in the 10-14-year-olds (both p < .001). Calcium and phosphate decreased with age for both sexes (girls: both p < .001; boys calcium: p < .05, boys phosphate: p < .001). Vitamin D was 20% lower in winter than summer for both sexes (both p < .001). Individuals with vitamin D sufficiency (25-OH-D > 50 nmol/L) exhibited a 5% lower level of PTH compared to the whole sample population (p < .001). The concentrations of PTH, vitamin D, calcium, and phosphate vary during childhood and adolescence, and is dependent on sex and season. These factors should be considered when screening for and treating imbalances in bone metabolism.


A discrete mathematical model of unlabelled granulocyte kinetics. A preliminary study of feedback control.
The equations used in formulating the continuous model of granulocyte kinetics developed by O'Fallon et al. (1971) were analyzed to see if they could be altered to simulate a feedback mechanism operating on the production and development of granulocytes. After extensive study and modification of the continuous model, it was found that a discrete model based on a Leslie matrix procedure was more effective for simulating the feedback system. This discrete model was used to show experimentally, from a mathematical view point, that a feedback mechanism of some kind must be operating on the production and development of granulocytes. Further, the discrete model was subjected to preliminary tests (simultaneous and cascading feedback) to demonstrate that it has the capability of responding to feedback control.


Cotranslational folding increases GFP folding yield.
Protein sequences evolved to fold in cells, including cotranslational folding of nascent polypeptide chains during their synthesis by the ribosome. The vectorial (N- to C-terminal) nature of cotranslational folding constrains the conformations of the nascent polypeptide chain in a manner not experienced by full-length chains diluted out of denaturant. We are still discovering to what extent these constraints affect later, posttranslational folding events. Here we directly address whether conformational constraints imposed by cotranslational folding affect the partitioning between productive folding to the native structure versus aggregation. We isolated polyribosomes from Escherichia coli cells expressing GFP, analyzed the nascent chain length distribution to determine the number of nascent chains that were long enough to fold to the native fluorescent structure, and calculated the folding yield for these nascent chains upon ribosome release versus the folding yield of an equivalent concentration of full-length, chemically denatured GFP polypeptide chains. We find that the yield of native fluorescent GFP is dramatically higher upon ribosome release of nascent chains versus dilution of full-length chains from denaturant. For kinetically trapped native structures such as GFP, folding correctly the first time, immediately after release from the ribosome, can lead to lifelong population of the native structure, as opposed to aggregation.


Effects of dehydroepiandrosterone (DHEA) supplementation on sexual function in premenopausal infertile women.
To investigate the effects of dehydroepiandrosterone (DHEA) supplementation on female sexual function in premenopausal infertile women of advanced ages. This observational study was conducted in an academically affiliated private fertility center. Patients included 87 premenopausal infertile women, 50 of whom completed the study including the Female Sexual Function Index (FSFI) questionnaires and comprehensive endocrine evaluation before and 4-8 weeks after initiating 25 mg of oral micronized DHEA TID. Age of patients was 41.1 ± 4.2 years, BMI 24.4 ± 6.1 kg/m2, 86% were married, and 42% were parous. Following supplementation with DHEA, all serum androgen levels increased (each P < 0.0001), while FSH levels decreased by 2.6 ± 4.4 from a baseline of 10.3 ± 5.4 mIU/mL (P = 0.009). The FSFI score for the whole study group increased by 7% (from 27.2 ± 6.9 to 29.2 ± 5.6; P = 0.0166). Domain scores for desire increased by 17% (P = 0.0004) and by 12% for arousal (P = 0.0122); lubrication demonstrated an 8% trend towards improvement (P = 0.0551), while no changes in domain scores for orgasm, satisfaction, or pain were observed. Women in the lowest starting FSFI score quartile (<25.7), experienced a 6.1 ± 8.0 (34%) increase in total FSFI score following DHEA supplementation. Among these women, improvements in domain categories were noted for desire (40%), arousal (46%), lubrication (33%), orgasm (54%), satisfaction (24%), and pain (25%). This uncontrolled observational study implies that supplementation with DHEA improves sexual function in older premenopausal women with low baseline FSFI scores.


The complete mitochondrial genome of the ridgetail white prawn Exopalaemon carinicauda Holthuis, 1950 (Crustacean: Decapoda: Palaemonidae) revealed a novel rearrangement of tRNA genes.
The complete mitochondrial (mt) DNA sequence was determined for a ridgetail white prawn, Exopalaemon carinicauda Holthuis, 1950 (Crustacea: Decopoda: Palaemonidae). The mt genome is 15,730 bp in length, encoding a standard set of 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes, which is typical for metazoans. The majority-strand consists of 33.6% A, 23.0% C, 13.4% G, and 30.0% T bases (AT skew=0.057; GC skew=-0.264). A total of 1045 bp of non-coding nucleotides were observed in 16 intergenic regions, including a major A+T rich (79.7%) noncoding region (886 bp). A novel translocation of tRNA(Pro) and tRNA(Thr) was found when comparing this genome with the pancrustacean ground pattern indicating that gene order is not conserved among caridean mitochondria. Furthermore, the rate of Ka/Ks in 13 protein-coding genes between three caridean species is much less than 1, which indicates a strong purifying selection within this group. To investigate the phylogenetic relationship within Malacostraca, phylogenetic trees based on currently available malacostracan complete mitochondrial sequences were built with the maximum likelihood and Bayesian models. All analyses based on nucleotide and amino acid data strongly support the monophyly of Decapoda. The Penaeidae, Reptantia, Caridea, and Meiura clades were also recovered as monophyletic groups with strong statistical support. However, the phylogenetic relationships within Pleocyemata are unstable, as represented by the inclusion or exclusion of Caridea.


Therapeutic targeting of BAP1/ASXL3 sub-complex in ASCL1-dependent small cell lung cancer.
Small cell lung cancer (SCLC) is an aggressive disease, with patients diagnosed with either early-stage, limited stage, or extensive stage of SCLC tumor progression. Discovering and targeting the functional biomarkers for SCLC will be crucial in understanding the molecular basis underlying SCLC tumorigenesis to better assist in improving clinical treatment. Emerging studies have demonstrated that dysregulations in BAP1 histone H2A deubiquitinase complex are collectively associated with pathogenesis in human SCLC. Here, we investigated the function of the oncogenic BAP1/ASXL3/BRD4 epigenetic axis in SCLC by developing a next-generation BAP1 inhibitor, iBAP-II, and focusing on the epigenetic balance established between BAP1 and non-canonical PRC1 complexes in regulating SCLC-specific transcriptional programming. We further demonstrated that pharmacologic inhibition of BAP1's catalytic activity disrupted BAP1/ASXL3/BRD4 epigenetic axis by inducing protein degradation of the ASXL3 scaffold protein, which bridges BRD4 and BAP1 at active enhancers. Furthermore, treatment of iBAP-II represses neuroendocrine lineage-specific ASCL1/MYCL/E2F signaling in SCLC cell lines, and dramatically inhibits SCLC cell viability and tumor growth in vivo. In summary, this study has provided mechanistic insight into the oncogenic function of BAP1 in SCLC and highlighted the potential of targeting BAP1's activity as a novel SCLC therapy.


Fiber contamination of vermiculites: a potential occupational and environmental health hazard.
Vermiculite ores from Montana, Virginia, and South Africa have been analyzed for the presence of amphibole contamination. Fibrous actinolite was found in unexpanded Montana vermiculite ore at a maximum concentration of 2.0%. The fibers persisted in the expanded ore at a maximum concentration of 0.6%. Actinolite was also found in the Virginia vermiculite ore but at a lower concentration and mostly as cleavage fragments with low length-to-width ratios. South African ore contained rare anthophyllite fibers also with low length-to-width ratios. Vermiculite ores have the potential for amphibole contamination and can represent potential health hazards without proper occupational and environmental control measures.


Data reduction for X-ray serial crystallography using machine learning.
Serial crystallography experiments produce massive amounts of experimental data. Yet in spite of these large-scale data sets, only a small percentage of the data are useful for downstream analysis. Thus, it is essential to differentiate reliably between acceptable data (hits) and unacceptable data (misses). To this end, a novel pipeline is proposed to categorize the data, which extracts features from the images, summarizes these features with the 'bag of visual words' method and then classifies the images using machine learning. In addition, a novel study of various feature extractors and machine learning classifiers is presented, with the aim of finding the best feature extractor and machine learning classifier for serial crystallography data. The study reveals that the oriented FAST and rotated BRIEF (ORB) feature extractor with a multilayer perceptron classifier gives the best results. Finally, the ORB feature extractor with multilayer perceptron is evaluated on various data sets including both synthetic and experimental data, demonstrating superior performance compared with other feature extractors and classifiers.


The relationship between ultrasound and densitometric measurements of bone mass at the calcaneus in women.
Broadband ultrasound attenuation (BUA) of the calcaneus predicts axial density in women and is decreased in women who sustain hip fractures. To determine the relationship between ultrasonic and densitometric assessments of bone mass at the same site, BUA and velocity of sound (VOS) were correlated with bone density as measured by dual energy x-ray absorptiometry (DXA) at the calcaneus in 64 Caucasian women aged 35-83 years. BUA, VOS, and bone density in these women decreased annually as a function of age by 1.0%, 0.3%, and 0.9%, respectively. Holding age, years since menopause, height and weight constant, BUA correlated with VOS (r = 0.74, P < 0.001), and calcaneal density correlated with BUA (r = 0.73, P < 0.001) and with VOS (r = 0.66, P < 0.01). The results indicate that both BUA and VOS measurements reflect density at the calcaneus, but suggest that they measure properties of bone other than density and different from each other. The assessment of these additional properties may be useful in the prediction of fracture risk.


Resource consumption and costs in Dutch patients with type 2 diabetes mellitus. Results from 29 general practices.
The aims of this study were to estimate the costs incurred by Dutch patients with Type 2 diabetes, examine which patient and/or treatment characteristics are associated with costs, and estimate the medical and non-medical costs of patients with Type 2 diabetes in The Netherlands. Twenty-nine Dutch general practitioners provided information on all Type 2 diabetes patients in their practice (n = 1371), information on demography, clinical characteristics, treatment type, the presence of complications and the type and amount of medical consumption during the previous 6 months. Medical costs were analysed using multivariate linear regression. Estimates of costs seen in The Netherlands were based on these results plus information from other sources regarding costs of end-stage renal disease, appliances, travel and productivity loss. Although only 9% of patients were hospitalized within the previous 6 months, hospitalization costs represented one-third of the medical costs, drug costs 40% and ambulatory costs 26%. Patients using insulin, patients with macrovascular complications only or in combination with microvascular complications incurred higher medical costs than other patients. Age and hyperlipidaemia were also positively related to medical costs. When these results were combined with other data sources, we estimated that patients with Type 2 diabetes are responsible for pound365 500 000 (1 271 000 000 guilders) or 3.4% of the relevant parts of health care costs in 1998. The non-medical costs (travel costs, productivity costs) are limited: 52 500 000 (183 000 000 guilders). Independent determinants of the medical costs of Type 2 diabetes in The Netherlands include age, complications, insulin use and hyperlipidaemia.


Diagnostic Features of Perianal Fistula in Patients With Crohn's Disease: Analysis of a Japanese Claims Database.
Perianal fistula (PAF) is a disabling complication of Crohn's disease (CD) which greatly impacts the quality of life. To address a scarcity of data in Asian populations, we determined the prevalence of CD-associated PAF in Japan, the order of diagnosis, and medical history of patients. A retrospective, longitudinal, observational cohort study was conducted, using an employer-based health insurance claims database. The study included patients diagnosed with CD and/or PAF from October 2013 to September 2019. The age- and gender-adjusted prevalence rates of CD-associated PAF increased from 10.33 per 100 000 in 2014, to 13.68 per 100 000 in 2019. Among patients with CD-associated PAF, 15.7% were diagnosed with PAF after diagnosis of CD, 68.6% were diagnosed with PAF before diagnosis with CD, and 15.7% were diagnosed with CD and PAF within the same month. Of the patients diagnosed with CD after PAF, approximately 30% were diagnosed with PAF by the age of 20 years, whereas less than 10% of PAF patients without CD were diagnosed with PAF by the age of 20 years. The study reveals the prevalence of CD-associated PAF in Japan and that most individuals were diagnosed with CD after the diagnosis of PAF. Crohn's disease may be underdiagnosed in patients with PAF; patients diagnosed with PAF at a young age should be monitored to allow timely diagnosis of CD.


Clinical features of atlantoaxial involvement in patients with rheumatoid arthritis using 18F-fluorodeoxyglucose-positron emission tomography with computed tomography.
Cervical spine involvement is one of the most serious complications in rheumatoid arthritis (RA). The study aim was to assess the clinical significance of atlantoaxial (AA) joint involvement detected by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) with computed tomography (CT) in patients with RA. A prospective cross-sectional study was conducted to evaluate AA joint involvement detected by FDG-PET/CT in consecutive RA patients from December 2017 to February 2022. We investigated the relationship between AA joint involvement and clinical data, including disease activity and patients' cervical symptoms. Among 48 patients enrolled, abnormal FDG uptake at AA joint was detected in 13 (27%). Rheumatoid factor titre, initial disease activity score 28-erythrocyte sedimentation rate and total standardized uptake value were significantly higher in the 13 patients than in the others (P = 0.004, P < 0.001 and P = 0.001, respectively). All patients with abnormal FDG uptake at AA joint had some cervical symptoms regardless of cervical spine X-ray abnormalities. Neck pain on movement and at rest were more frequent in the 13 patients than in the others (P = 0.001 and P = 0.004, respectively). The most sensitive symptom associated with AA joint involvement was neck pain on movement (sensitivity, 69%), and the most specific symptom was neck pain at rest (specificity, 100%). AA joint involvement was commonly observed by FDG-PET/CT in patients with active RA, independent of radiographic findings. Specific cervical symptoms can be important surrogate markers for detection of potential AA synovitis associated with active RA. Key Points • AA joint involvement was frequently seen in RA with high disease activity independent of radiographic findings. • Neck pain was a hallmark of AA joint involvement reflecting disease activity, and resting pain was highly specific.


Differences between Welsh and Canadian children on parts of the test of motor impairment.
Four subtests, which measured hand function, were taken from the Test of Motor Impairment and given to 53 10-year-old children of normal intelligence. The results showed a wide variation in achievement with one test at a very inappropriate level of difficulty. Girls were consistently faster than boys, achieving a result which was statistically significant in one instance. It is suggested that this test requires restandardization for use among British populations. The provision of separate norms for the sexes would improve the disciminatory value of this instrument.


Brivanib alaninate inhibited dengue virus proliferation through VEGFR2/AMPK pathway.
Dengue virus (DENV) is the most prevalent arthropod-borne viral disease of humans and has a major impact on global public health. There is no clinically approved drugs for DENV infection. Since intracellular VEGFR2 is increased in DENV infected patients, we thus hypothesized that VEGFR2 participated DENV proliferation and its inhibitors could be served as antivirals against DENV. Actually our results showed that VEGFR2 was induced by DENV infection. Also the agonist of VEGFR2, VEGF-A, promoted DENV proliferation. Therefore, we screened the inhibitors of VEGFR2 and found that brivanib alaninate (brivanib) showed the best anti-DENV ability with the lowest cellular cytotoxicity. Mechanically, our results indicated VEGFR2 directly interacted with PTP1B to dephosphorylate AMPK to provide lipid environment for viral replication. However, this effect could be inhibited by brivanib, which significantly reversed the reduction of AMPK phosphorylation caused by DENV infection, thus improving the cellular lipid environment. Moreover, the antiviral effect of brivanib could be reversed by AMPK inhibitor, Compound C. In addition, oral administration of brivianib (20-50 mg/kg/day) clearly improved the survival rate of DENV2 infection, and this effect was abolished in accompanied with Compound C (10mg/kg/day). Collectively, our study disclosed the mechanism of VEGFR2 in DENV2 and evaluated the antiviral ability of brivanib, which deserved more attention for clinical usage in DENV infection.


Spatial and temporal dynamics of base flow in semi-arid montane watersheds and the effects of landscape patterns and topography.
Base flow (BF) is harder to predict than other hydrological signatures. The lack of hydrologically relevant information or adequately broad spectrum of typically selected catchment attributes (particularly landscape and topography) hinders the explanatory power. Our goals were to identify the most influential controls on base flow spatially and temporally and to elucidate the response relationships. Base flow in 19 semi-arid sub-watersheds was separated by digital filtering. One hundred and fourteen sub-watershed attributes were related to base flow using random forest regression. The main results were as follows: (1) Annual BF significantly declined since 1999 due to decreased precipitation, increased air temperature, afforestation, urban expansion, and increasing water consumption. Annual base flow index (BFI), varying between 0.319 and 0.695, showed less noticeable temporal trends. (2) Precipitation (P) and underlying carbonate rocks primarily controlled the spatial variation of annual BF and total flow (TF), with the impacts being positive. Landscape was less influential. After the abrupt runoff decline, landscape composition rather than configuration exerted greater impacts on spatial BF and TF, and the importance of forest increased, whereas landscape configuration was decisive for BFI during the whole observation period. The absence of significant links between landscape configuration and water quantity may result from a scale issue. Concave profile curvatures were found to be topographic variables more important than slopes. The impact of soil was the least. This study would benefit the selection of catchment attributes and spatial extents to quantify these attributes in building BF predicting models in future studies.


Systematic review and meta-analysis of association of polymorphisms in inflammatory cytokine genes with coronary artery disease.
It has comprehensively been acknowledged that a genetic contribution, especially in immune inflammatory players, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, are critically involved in the pathophysiology of coronary artery disease (CAD). This meta-analysis study aimed to reach a conclusive understanding of the role of genetic polymorphisms, including IL6 gene C572G (rs1800796) and G174C (rs1800795) as well as TNFA gene G238A (rs361525) and G308A (rs1800629) in susceptibility to CAD. Two major databases, namely MEDLINE and Scopus, were searched to find the studies surveying the mentioned polymorphisms and CAD susceptibility up to July 2020. Association comparison between the polymorphisms and CAD susceptibility were assessed using pooled odds ratio (OR) and their corresponding 95% confidence interval (CI). This meta-analysis study was conducted on 69 papers (73 population studies), comprising 5062 patients and 8446 controls for IL6 gene rs1800796 (17 studies), 13801 patients and 16215 controls for IL6 gene rs1800795 (38 studies), 1439 patients and 2850 controls for TNFA gene rs361525 (5 studies), and 5051 patients and 3958 controls for TNFA gene rs1800629 (13 studies), according to inclusion and exclusion criteria. There were statistically positive association between all genetic comparisons of IL6 gene rs1800795 polymorphism and the CAD risk. Moreover, the recessive model (CC vs. CG + GG) in IL6 gene rs1800796 polymorphism had marginally significant association with decreased risk of CAD. None of the TNFA gene polymorphisms were associated with CAD risk. The meta-analysis revealed the positive association of IL6 gene rs1800795 polymorphism in susceptibility to CAD.


Influence of tension of the nuchal cord to the developmental output in a one-year-old child.
Influence of nuchal umbilical cord tension in a newborn on the developmental outcome at the end of the first year. and subjects of research: The research is prospective, conducted in northern Bosnia and Herzegovina (Una Sana Canton), for a period of five years. In the research study, we included newborns with a nuchal cord (tight and loose) and newborns without a nuchal cord (control group). We were tracking and recording the Apgar score and the conventional cardiotocography (CTG) findings in both groups. The development of newborns was monitored by the Munich Functional Scale and the development was evaluated at the end of the first year of life. Statistically, there was a significant presence (P < .001) of Apgar score lower than 7 in newborns with nuchal cord concerning the control group. There were significantly lower Apgar score findings in newborns with a tight nuchal cord compared to ones with a loose nuchal cord (P <.001). Pathological cardiotocographic findings were monitored and the statistical significance in neonates with a nuchal cord concerning the control group. Cardiotocographic data in a neonatal group with tight nuchal cord were statistically significantly lower concerning cardiotocographic data in neonates with a loose nuchal cord (P <.001). Infants at the age of 1 year born with tight nuchal cord were found to have a significant developmental delay compared to those born with loose nuchal cord and control group (P <.001). The nuchal cord is the risk factor for later developmental deviation. Early diagnosis of the nuchal cord, especially tight cord around the neck (nuchal cord), is important for the prevention of later morbidity.


Cloning and analysis of the locus for mosquito vitellogenic carboxypeptidase.
Vitellogenic carboxypeptidase is a 53 kDa yolk protein produced by the fat body of the female mosquito, Aedes aegypti, in response to a blood meal. Its expression is sex-, stage- and tissue-specific and is identical to that of the major yolk protein, vitellogenin. The gene is intronless and two alleles have been cloned and sequenced, including more than 1.5 kb on both sides of the coding region. A capsite consensus recently identified as an arthropod initiator is present at the start site of transcription. Upstream of this capsite is a 16 bp imperfect palindrome repeated four times showing strong homology to defined hormone-response elements. In addition, a region that closely resembles the fat body enhancer and double sex binding site from the Drosophila yolk protein genes and several potential fat body-specific regulatory protein binding sites were found.


Rosuvastatin attenuated the existing morphine tolerance in rats with L5 spinal nerve transection through inhibiting activation of astrocytes and phosphorylation of ERK42/44.
Recent studies suggested that statins have anti-inflammatory effects beyond their lipid-lowering properties. In the present study, we sought to investigate whether rosuvastatin could alleviate morphine tolerance by attenuating the glia mediated neuroinflammation in the spinal cord. Using a rat model of L5 spinal nerve transection, on day 8 after surgery morphine (10 mg/kg) was injected subcutaneously twice daily for consecutive 10 days. On day 13, with the establishment of morphine tolerance, rosuvastatin (10 mg/kg) was given o.p. for 5 days. On day 18, lumbar spinal cord was collected immediately after last behavioral testing. The analgesic effect of morphine was determined as the percentage of maximal possible effect (%MPE) after a single morphine (4 mg/kg) injection via tail vein on day 8, 13, and 18. The MPE decreased significantly after administration of morphine to rats with neuropathy for 5 days. Rosuvastatin administration for 5 days could restore morphine antinociceptive effect significantly. Additionally, the activation of astrocytes, the phosphorylation of extracellular signal-regulated kinase 42/44 (ERK(42/44)) and the expressions of TNFα and IL-1β were inhibited significantly by rosuvastatin. Our data suggested that rosuvastatin was a promising choice to treat neuropathic pain in combination with morphine.


High resolution cosmid and P1 maps spanning the 14 Mb genome of the fission yeast S. pombe.
Gridded on high density filters, a P1 genomic library of 17-fold coverage and a cosmid library of 8 genome equivalents, both made from S. pombe strain 972h-, were ordered by hybridizing genetic markers and individual clones from the two libraries. Yeast artificial chromosome (YAC) clones covering the entire genome were used to subdivide the libraries, and hybridization of short oligonucleotides and DNA pools made from randomly selected cosmids provided further mapping information. Restriction digests were generated as an independent confirmation of the clone order. The high resolution clone map was aligned to the genetic map and the physical Notl and YAC maps. The usefulness of the various mapping techniques and cloning procedures could be assessed upon the different data sets.


Oral health conditions in children with idiopathic nephrotic syndrome: a cross-sectional study.
Nephrotic syndrome is one of the chronic illnesses in the pediatric age group. The aim of this study was to assess the oral health of patients with steroid-sensitive idiopathic nephrotic syndrome (iNS). A case-control study was performed on iNS patients and healthy from May 2018 to April 2019. Dental caries was assessed by the World Health Organization criteria, developmental defects of enamel by the mDDE index, oral hygiene by the OHI-S and API, and gingival condition by the GI. Oral health behavior was recorded using a standardized questionnaire including tooth brushing, fluoride prevention, dietary habits and utilization of dental care. Additionally, Streptococcus mutans (SM) and Lactobacillus spp. (LB) bacteria in saliva were assessed using the CRT bacteria test. Statistical analysis comparing oral health parameters was carried by Pearson's chi-squared, Fisher's exact, Shapiro-Wilk verified by Student's t or Mann-Whitney U tests. The study included 94 participants of both sexes at the age of 4 to 17 years (47 cases and 47 controls) who were treated in Clinic of Pediatric Nephrology or outpatients' dental clinic in Wroclaw, Poland. The iNS patients compared to the controls revealed some lower caries experience (83.0% vs 95.7%) and number of caries affected primary and/or permanent teeth (4.6 ± 3.5 vs 6.0 ± 4.1), a significantly lower number of filled primary and/or permanent teeth (1.1 ± 1.6 vs 3.5 ± 3.0, P < 0.001) and higher incidence of enamel hypoplasia (31.9% vs 4.3%, P < 0.001). The numbers of the iNS patients with high level of SM and LB were similar to the controls. The iNS patients had a higher OHI-S score (1.89 ± 1.59 vs 1.05 ± 1.02, P < 0.010) and a higher GI score (0.7 ± 1.0 vs 0.3 ± 0.6, P = 0.050). Moreover, they less frequently brushed their teeth twice a day (78.8% vs 93.6%, P = 0.026) and more frequently consumed three or more snacks daily (53.2% vs 23.4%, P = 0.002). The iNS patients despite the poor oral hygiene revealed lower caries experience but smaller number of restored caries-affected teeth, more severe gingivitis and more frequently teeth affected by enamel hypoplasia.


Free Carriers versus Self-Trapped Excitons at Different Facets of Ruddlesden-Popper Two-Dimensional Lead Halide Perovskite Single Crystals.
The physical origin of sub-band gap photoluminescence in Ruddlesden-Poppers two-dimensional (2D) lead halide perovskites (LHPs) is still under debate. In this paper, we studied the photoluminescence features from two different facets of 2D LHP single crystals: the in-plane facet (IF) containing the 2D inorganic layers and the facet perpendicular to the 2D layers (PF). At the IF, the free carriers (FCs) dominate due to the weak electron-phonon coupling in a symmetric lattice. At the PF, the strain accumulation along the 2D layers enhances the electron-phonon coupling and facilitates self-trapped exciton (STE) formation. The time-resolved PL studies indicate that free carriers (FCs) at the IF can move freely and display the trapping by the intrinsic defects. The STEs at the PF are not likely trapped by the defects due to the reduced mobility. However, with increasing STE density, the STE transport is promoted, enabling the trapping of STE by the intrinsic defects.


Cholesterol and PIP2 Modulation of BKCa Channels.
Ca2+/voltage-gated, large conductance K+ channels (BKCa) are formed by homotetrameric association of α (slo1) subunits. Their activity, however, is suited to tissue-specific physiology largely due to their association with regulatory subunits (β and γ types), chaperone proteins, localized signaling, and the channel's lipid microenvironment. PIP2 and cholesterol can modulate BKCa activity independently of downstream signaling, yet activating Ca2+i levels and regulatory subunits control ligand action. At physiological Ca2+i and voltages, cholesterol and PIP2 reduce and increase slo1 channel activity, respectively. Moreover, slo1 proteins provide sites that seem to recognize cholesterol and PIP2: seven CRAC motifs in the slo1 cytosolic tail and a string of positively charged residues (Arg329, Lys330, Lys331) immediately after S6, respectively. A model that could explain the modulation of BKCa activity by cholesterol and/or PIP2 is hypothesized. The roles of additional sites, whether in slo1 or BKCa regulatory subunits, for PIP2 and/or cholesterol to modulate BKCa function are also discussed.


A knowledge-based clinical toxicology consultant for diagnosing single exposures.
Every year, toxic exposures kill 1200 Americans. To aid in the timely diagnosis and treatment of such exposures, this research investigates the feasibility of a knowledge-based system capable of generating differential diagnoses for human exposures involving unknown toxins. Data mining techniques automatically extract prior probabilities and likelihood ratios from a database managed by the Florida Poison Information Center. Using observed clinical effects, the trained system produces a ranked list of plausible toxic exposures. The resulting system was evaluated using 30,152 single exposure cases. In addition, the effects of two filters for refining diagnosis based on a minimum number of exposure cases and a minimum number of clinical effects were also explored. The system achieved accuracies (calculated as the percentage of exposures correctly identified in top 10% of trained diagnoses) as high as 79.8% when diagnosing by substance and 78.9% when diagnosing by the major and minor categories of toxins. The results of this research are modest, yet promising. At this time, no similar systems are currently in use in the United States and it is hoped that these studies will yield an effective medical decision support system for clinical toxicology.


Nanofibers and Microfibers for Osteochondral Tissue Engineering.
The use of fibers into scaffolds is a way to mimic natural tissues, in which fibrils are embedded in a matrix. The use of fibers can improve the mechanical properties of the scaffolds and may act as structural support for cell growth. Also, as the morphology of fibrous scaffolds is similar to the natural extracellular matrix, cells cultured on these scaffolds tend to maintain their phenotypic shape. Different materials and techniques can be used to produce micrfibers- and nanofibers for scaffolds manufacturing; cells, in general, adhere and proliferate very well on PCL, chitosan, silk fibroin, and other nanofibers. One of the most important techniques to produce microfibers/nanofibers is electrospinning. Nanofibrous scaffolds are receiving increasing attention in bone tissue engineering, because they are able to offer a favorable microenvironment for cell attachment and growth. Different polymers can be electrospun, i.e., polyester, polyurethane, PLA, PCL, collagen, and silk. Other materials such as bioglass fibers, nanocellulose, and even carbon fiber and fabrics have been used to help increase bioactivity, mechanical properties of the scaffold, and cell proliferation. A compilation of mechanical properties and most common biological tests performed on fibrous scaffolds is included in this chapter. The use of microfibers and nanofibers allows for tailoring the scaffold properties. Electrospinning is one of the most important techniques nowadays to produce fibrous scaffolds. Microfibers and nanofibers use in scaffolds is a promising field to improve the behavior of scaffolds in osteochondral applications.


Evaluation framework for automatic privacy auditing tools for hospital data breach detections: A case study.
We aim to 1) design an evaluation framework to examine the accuracy of automatic privacy auditing tools, 2) apply the evaluation method at a hospital to validate the performance of an auditing tool that uses a machine learning algorithm to automate user access auditing, and 3) recommend further improvements in auditing for the hospital. Using the black box method of user acceptance testing, we have designed an evaluation framework consisting of appropriate and inappropriate behaviour scenarios to examine the privacy auditing tools. The scenarios were designed from clinical and non-clinical hospital staff perspective, taking expert opinions from the privacy officers and considering examples from the Information and Privacy Commission (IPC) and were tested using Mackenzie Richmond Hill Hospital's data. The case study using this evaluation framework found that on average 98.09 % of total accesses of the hospital were identified as appropriate and the tool was unable to explain the remaining 1.91 % of accesses. In addition, a statistically significant (P < 0.05) increasing trend on categorizing appropriate accesses by the tool have been observed. Furthermore, an analysis of unexplained accesses revealed the contributing factors and found issues related to hospital workflows and data quality (information was missing about staff roles and departments). Given that adoption of these machine learning tools is increasing in hospitals, this research provides an evaluation framework and an empirical evidence on the effectiveness of automated privacy auditing and detecting anomalies for dynamic hospital workflows.


Concentration-dependent precorneal loss of pilocarpine in rabbit eyes.
Precorneal loss of pilocarpine was studied in pigmented and albino rabbits. We instilled 25 microliter of isotonic pilocarpine solution, pH 6.4, into rabbit eyes and monitored drug concentration in the precorneal tear film. Increased concentration (0.2% - 2.0%) of pilocarpine accelerated precorneal drug loss from the tear film from 0.686 min-1 to 1.064 min-1. This increase was mainly due to induced lacrimation. Polyvinyl alcohol (1.4%) retarded precorneal loss of pilocarpine. The rate of loss was the same in pigmented and albino rabbits. The effects of the changed precorneal loss of pilocarpine on corneal drug absorption are discussed.


Mass spectrometric structure determination of metabolites of 3-[2-(N,N-dimethylaminomethyl)phenylthio]phenol.
Metabolites of 3-[2-(N,N-dimethylaminoethyl)phenylthio]phenol (I) were isolated from the urine of rats, mice, rabbit and dog and from the faeces of rats by extraction and thin-layer chromatography. From the mass spectrum of I and using characteristics mass shifts in the spectra of metabolites, the structures of four metabolites were determined, whereas for two other isomeric metabolites the structures were resolved by means of IR spectra. Conclusions regarding the structures derived from the spectra were confirmed by comparing them with synthetic standards. Generally, metabolic changes of I can be characterized by demethylation, hydroxylation combined with methylation, S-oxidation and by a combination of these metabolic reactions.


Side-Chain Engineering for Enhancing the Molecular Rigidity and Photovoltaic Performance of Noncovalently Fused-Ring Electron Acceptors.
Side-chain engineering is an effective strategy to regulate the solubility and packing behavior of organic materials. Recently, a unique strategy, so-called terminal side-chain (T-SC) engineering, has attracted much attention in the field of organic solar cells (OSCs), but there is a lack of deep understanding of the mechanism. Herein, a new noncovalently fused-ring electron acceptor (NFREA) containing two T-SCs (NoCA-5) was designed and synthesized. Introduction of T-SCs can enhance molecular rigidity and intermolecular π-π stacking, which is confirmed by the smaller Stokes shift value, lower reorganization free energy, and shorter π-π stacking distance in comparison to NoCA-1. Hence, the NoCA-5-based device exhibits a record power conversion efficiency (PCE) of 14.82 % in labs and a certified PCE of 14.5 %, resulting from a high electron mobility, a short charge-extraction time, a small Urbach energy (Eu ), and a favorable phase separation.


Substance use and homelessness: A longitudinal interview study conducted during COVID-19 with implications for policy and practice.
People who are homeless and using substances frequently encounter barriers to accessing support. This paper aims to inform policy and practice by analysing changes in the tobacco, alcohol and illicit drug use of people experiencing homelessness. Data derive from a qualitative longitudinal study (undertaken 2020/2021) and involving telephone interviews (n = 310) conducted with 34 people accommodated in two London hotels provided as part of a UK policy response to COVID-19. The hotels offered various supports, including opioid replacement therapy, prescribed alcohol, licensed nicotine replacement therapy, and e-cigarettes. Participants' substance use data were organised by Iterative Categorization and subjected to a content analysis to identify patterns and themes.. At entry to the hotel, 5/34 participants (14.7%) had never used alcohol nor illicit drugs; 10/34 (29.4%) had only ever used alcohol (mostly without a problem); 11/34 (32.4%) had ever used illicit drugs but without a problem; and 8/34 (23.5%) had ever had a problem with illicit drugs. Sub-groups had different socio-demographic characteristics, particularly regarding being/not being a UK national, sex, and homelessness duration. Tobacco smoking was common across all sub-groups (18/34; 52.9%). Participants were often anxious about living with others who were using substances, and some worried about their own substance use. Substance use was changeable, with more decreases than increases. Changes related to intrapersonal (psychological), interpersonal (social) and structural (resource-based) factors. For example, decreases were precipitated by people feeling motivated to change, separation from others who used drugs, and receiving treatment or support. Findings indicate that various interventions and accommodation models may benefit people who are homeless and using substances. An initiative that combined shelter and basic amenities, pharmacological treatment, psychosocial support, and space where substances were not available and other people using substances could be avoided resulted in an overall reduction in substance use amongst those accommodated.


Collagen Membrane for Guided Bone Regeneration in Dental and Orthopedic Applications.
Treatment of cortical bone defects is a clinical challenge. Guided bone regeneration (GBR), commonly used in oral and maxillofacial dental surgery, may show promise for orthopedic applications in repair of cortical bone defects. However, a limitation in the use of GBR for cortical bone defects is the lack of an ideal scaffold that provides sufficient mechanical support to bridge the cortical bone with minimal interference in the repair process. We have developed a new collagen membrane, CelGro™, for use in GBR. We report the material characterization of CelGro and evaluate the performance of CelGro in translational preclinical and clinical studies. The results show CelGro has a bilayer structure of different fiber alignment and is composed almost exclusively of type I collagen. CelGro was found to be completely acellular and free from xenoantigen, α-gal (galactose-alpha-1,3-galactose). In the preclinical study of a rabbit cortical bone defect model, CelGro demonstrated enhanced bone-remodeling activity and cortical bone healing. Microcomputed tomography evaluation showed early bony bridging over the defect area 30 days postoperatively, and nearly complete restoration of mature cortical bone at the bone defect site 60 days postoperatively. Histological analysis 60 days after surgery further confirmed that CelGro enables bridging of the cortical bone defect by induction of newly formed cortical bone. Compared to a commercially available collagen membrane, Bio-Gide®, CelGro showed much better cortical alignment and reduced porosity at the defect interface. As selection of orthopedic patients with cortical bone defects is complex, we conducted a clinical study evaluating the performance of CelGro in guided bone regeneration around dental implants. CelGro was used in GBR procedures in a total of 16 implants placed in 10 participants. Cone-beam computed tomography images show significantly increased bone formation both horizontally and vertically, which provides sufficient support to stabilize implants within 4 months. Together, the findings of our study demonstrate that CelGro is an ideal membrane for GBR not only in oral and maxillofacial reconstructive surgery but also in orthopedic applications (Clinical Trial ID ACTRN12615000027516).


Are Cu2 Te-Based Compounds Excellent Thermoelectric Materials?
Most of the state-of-the-art thermoelectric (TE) materials exhibit high crystal symmetry, multiple valleys near the Fermi level, heavy constituent elements with small electronegativity differences, or complex crystal structure. Typically, such general features have been well observed in those well-known TE materials such as Bi2 X3 -, SnX-, and PbX-based compounds (X = S, Se, and Te). The performance is usually high in the materials with heavy constituent elements such as Te and Se, but it is low for light constituent elements such as S. However, there is a great abnormality in Cu2 X-based compounds in which Cu2 Te has much lower TE figure of merit (zT) than Cu2 S and Cu2 Se. It is demonstrated that the Cu2 Te-based compounds are also excellent TE materials if Cu deficiency is sufficiently suppressed. By introducing Ag2 Te into Cu2 Te, the carrier concentration is substantially reduced to significantly improve the zT with a record-high value of 1.8, 323% improvement over Cu2 Te and outperforms any other Cu2 Te-based materials. The single parabolic band model is used to further prove that all Cu2 X-based compounds are excellent TE materials. Such finding makes Cu2 X-based compounds the only type of material composed of three sequent main group elements that all possess very high zT s above 1.5.


Correlations between orofacial muscle activity and craniofacial morphology in a sample of control and anterior open-bite subjects.
In order to investigate the correlations between genioglossus, masseter, and orbicularis oris muscle activity and craniofacial morphology, an electromyographic and cephalometric analysis was undertaken on a series of twenty-four human subjects. The activity from the muscles was recorded during voluntary opening movements of the mandible monitored by an electronic transducer. A computer-based method was devised to calculate the threshold incisor-separation position corresponding to a 20 percent increase in base line muscle activity for each of the muscles. In addition, twenty-seven anatmoic points were digitized from lateral head films, and a computer-based cephalometric analysis was completed for each subject. A number of significant correlations were found between the threshold muscle values and the thirty-one linear and angular morphologic variables. Low threshold values for the genioglossus muscle were correlated with negative overbites, undererupted maxillary and mandibular incisors, and low total face heights. Low threshold values for the masseter muscle were also associated with low overbite measurements. In contrast, orbicularis oris muscle thresholds did not appear to be correlated with any of the craniofacial variables measured. This interdependence of tongue and jaw muscle activity and facial morphology suggests a contribution of the musculature to the development and/or maintenance of the dentition.


Endodontic Retreatment Using Dynamic Navigation: A Case Report.
Dynamic navigation systems are used in dental implantology to optimize the accuracy of dental implant placement. A 30-year-old man was seen at the endodontic clinic of the Universidad Autónoma de Yucatán for pain in the left maxillary lateral incisor. A previously treated tooth with symptomatic apical periodontitis was diagnosed. The patient accepted treatment, and after signing an informed consent form, minimally invasive coronal access was performed through a zirconia crown. Then a post removal was performed with an ultrasonic tip to 2 mm before the apical gutta-percha limit, and the removal of material was completed manually with a K-file. This case report demonstrates the use of dynamic navigation to remove a post from under a zirconia crown for the retreatment of a failing root canal procedure. The removal of fiber posts from endodontically treated teeth can present a unique challenge for clinicians. Numerous techniques and instrument kits are recommended for the removal of fiber posts, but the risk of excessive root structure damage is a major concern because the ability to differentiate the color difference between peripheral dentin and a bonded fiber post can complicate the accuracy of the removal. The dynamic navigation system enabled minimally invasive removal of the fiber post with a high degree of accuracy, thus ensuring that there was no unnecessary removal of root structure. Dynamic navigation using real-time monitoring could reduce the attendant risk of iatrogenic errors in complex treatment cases.


Simultaneous quantification of tracheloside and trachelogenin in rat plasma using liquid chromatography/tandem mass spectrometry.
We developed and validated a quantitative method for simultaneously determining the concentrations of tracheloside and trachelogenin in rat plasma. Plasma samples were prepared by liquid-liquid extraction with ethyl acetate. Isocratic chromatographic separation was performed on a reversed-phase Diamonsil C(18) column (4.6×200 mm, 5 μm). The mobile phase consisted of methanol and 10mM aqueous ammonium formate (80:20, v/v). Analyte detection was achieved by positive electrospray ionization (ESI) tandem mass spectrometry. Calibration was performed by internal standardization with glipizide, and regression curves ranging from 0.625 to 625 ng/mL were constructed for both the analytes. The intra- and inter-day precision values were below 8%, and accuracy ranged from -5.33% to 2.53% in all quality control samples. In this study, the validated method was successfully applied to determine the pharmacokinetic profile of tracheloside and trachelogenin in rat plasma after oral and intravenous administration of trachelospermi total lignans.