The simplified tailor-made workflows for a 3D slicer-based craniofacial implant design.
A specific design of craniofacial implant model is vital and urgent for patients with traumatic head injury. The mirror technique is commonly used for modeling these implants, but it requires the presence of a healthy skull region opposite to the defect. To address this limitation, we propose three processing workflows for modeling craniofacial implants: the mirror method, the baffle planner, and the baffle-based mirror guideline. These workflows are based on extension modules on the 3D Slicer platform and were developed to simplify the modeling process for a variety of craniofacial scenarios. To evaluate the effectiveness of these proposed workflows, we investigated craniofacial CT datasets collected from four accidental cases. The designed implant models were created using the three proposed workflows and compared to reference models created by an experienced neurosurgeon. The spatial properties of the models were evaluated using performance metrics. Our results show that the mirror method is suitable for cases where a healthy skull region can be completely reflected to the defect region. The baffle planner module offers a flexible prototype model that can be fit independently to any defect location, but it requires customized refinement of contour and thickness to fill the missing region seamlessly and relies on the user's experience and expertise. The proposed baffle-based mirror guideline method strengthens the baffle planner method by tracing the mirrored surface. Overall, our study suggests that the three proposed workflows for craniofacial implant modeling simplify the process and can be practically applied to a variety of craniofacial scenarios. These findings have the potential to improve the care of patients with traumatic head injuries and could be used by neurosurgeons and other medical professionals.


Epidemiology of Helicobacter pylori in an asymptomatic population in the United States. Effect of age, race, and socioeconomic status.
A causative role is now accepted for Helicobacter (formerly Campylobacter) pylori in type B gastritis, and evidence is accumulating that H. pylori infection plays a major contributory role in peptic ulcer disease. Preliminary studies have reported that the prevalence of H. pylori infection increases with age, but detailed information on the prevalence of the bacteria in any defined population and on the factors that may influence the pattern of distribution remains scanty. In the present study, a sensitive enzyme-linked immunosorbent assay and a [13C] urea breath test were used to investigate the prevalence of H. pylori infection among 485 healthy asymptomatic volunteers between the ages of 15 and 80 residing in the Houston metropolitan area. H. pylori infection was present in 52%. The prevalence of H. pylori infection increased rapidly with age at 1%/yr for the overall population. The frequency of H. pylori infection was higher in blacks (70%) than whites (34%) (P less than 0.001); this difference remained after adjustments were made for age, gender, educational level, income, and use of tobacco or alcohol. H. pylori infection was independent of gender but was closely correlated with socioeconomic class. There were significant inverse correlations between age-adjusted frequency of H. pylori infection and income and between educational level and H. pylori infection. There was no association between H. pylori infection and consumption of alcohol or nonsteroidal antiinflammatory drug use or smoking. Having pets was associated with a lower frequency of H. pylori infection, but this was highly associated with higher socioeconomic status. The mode(s) of transmission of H. pylori is unknown, but the social patterns of H. pylori infection are consistent with fecal-oral transmission as one important pathway. Socioeconomic factors seem to determine the age of acquisition.


Characterization of the complete chloroplast genome sequence of Impatiens pritzelii (Balsaminaceae): an endemic species from China.
This study was the first report about complete chloroplast genome of Impatiens pritzelii (Balsaminaceae). The plastome of I. pritzelii was found to possess a total length 152,487 bp with the typical quadripartite structure of angiosperms, containing two inverted repeats (IRs) of 25,684 bp separated by a large single-copy (LSC) region and a small single-copy (SSC) region of 83,290 and 17,829 bp, respectively. The plastid genome of I. pritzelii contains 113 genes, including 79 protein-coding genes, 4 ribosomal RNA genes, and 30 transfer RNA genes. The overall GC content of I. pritzelii plastid genome is 37.0% and the corresponding values in LSC, SSC, and IR regions are 34.9%, 29.8%, and 43.1%, respectively.


Endobronchial ALK+ anaplastic large-cell lymphoma resembling asthma in a 13-year-old girl.
Anaplastic large-cell lymphoma is a rare disease in children, and endobronchial localization is extremely rare in any age group. We report the case of a 13-year-old girl with endobronchial anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma presenting as asthma, and discuss the diagnostic, therapeutic, and clinical implications.


N-terminal amino acid sequences of the heavy and light chains of chicken liver cathepsin L.
Avian cathepsin L (EC 220.127.116.11) was first purified from chicken liver. The enzyme was composed of two polypeptides with Mr values of 28,000 (heavy chain) and 5000 (light chain). The two polypeptide chains of the enzyme were separated by gel filtration after cleavage of disulfide bonds. The N-terminal amino acid sequences of the heavy and light chains were (sequence in text) and (sequence in text) respectively. These sequences show high homologies with those of the N-terminal and C-terminal portions of papain, respectively. The residues of the surrounding area of cysteine-25 in the heavy chain were quite similar to those in the region around the active-site cysteine of papain.


CTLA-4 gene A-G polymorphism and childhood Graves' disease.
Graves' disease is associated with a polymorphism at position 49 in exon 1 of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene in Caucasians and Japanese. A high incidence of childhood Graves' disease has been documented in Hong Kong Chinese. The aims of this study were to investigate the CTLA-4 gene A-G polymorphism association in Chinese children with Graves' disease. One hundred and twenty-three Chinese children with Graves' disease (104 girls and 19 boys) and 158 racially matched healthy controls were recruited for the study. Genomic DNA was extracted from venous blood samples. The dimorphism at position 49 A-G was analysed by polymerase chain reaction, single-strand conformation polymorphism and restriction fragment-length polymorphism analysis. The genotype distribution and allele frequencies of children with Graves' disease differed significantly from those of the controls (P = 0.0023 and P = 0.022, respectively). The presence of at least one G allele (GG or AG) was associated with an increased risk of Graves' disease (OR = 6.8, 95% CI = 2.0-36.1; P = 0.001). This study confirms that CTLA-4 49 A-G polymorphism is associated with Graves' disease in Chinese children. The CTLA-4 49 G allele confers an increased risk of childhood Graves' disease.


Post-column fluorescence derivatization of peptides. Problems and potential in high-performance liquid chromatography.
Some critical parameters such as the pumping system, mixing devices and detector design in instrumentation for post-column derivatization in high-performance liquid chromatography are discussed. The derivatization was studied with pharmaceutically important nona-peptides containing primary amino groups which react with Fluram and reaction parameters such as pH, solvent and reagent concentration were investigated. Both adsorption systems and reversed-phase systems were used to separate the peptides prior to the post-column reaction. Reversed-phase chromatography has the advantage of simpler sample preparation, better reaction control and optimization of solvent conditions. As a result, detection limits of between 5 and 10 ng per injection can be obtained and the reproducibility of the results is better than +/- 2% (relative standard deviation). The method has been applied to the analysis of injection solutions (ampoules).


Intramolecular 1,5- versus 1,6-hydrogen abstraction reaction promoted by alkoxy radicals in carbohydrate models.
[reaction: see text] The alkoxy radical generated by reaction of 3,7-anhydro-2-deoxyoctitols with (diacetoxyiodo)benzene (DIB) and iodine abstracts regioselectively either the proton at C7 or that at C4 depending on the electronegativity of the substituent at C4. The correct election of this substituent can switch the reaction to give 2,9-dioxabicyclo[3.3.1]nonane or hexahydro-2H-furo[3,2-b]pyran ring systems.


CT angiography for differentiation between intracerebral and intra-sylvian hematoma in patients with ruptured middle cerebral artery aneurysms.
ISHs and ICHs from ruptured MCA aneurysms can be difficult to distinguish on NCE-CT but may have a different impact on admission status and outcome. The presence of IHCEV on CTA may differentiate ISHs and ICHs. Two observers independently reviewed non-contrast-enhanced CT scans and CTAs of 71 patients with MCA aneurysm hematomas for the site of the hematoma, according to predefined characteristics, and for the presence of IHCEV. We compared CTAs with NCE-CT scans in which both observers were confident about hematoma localization. We calculated κ statistics for interobserver agreement, and RRs for poor clinical condition and poor outcome. Agreement for IHCEV was almost perfect (κ, 0.87; 95% CI, 0.74-0.99). After consensus reading, 30 of 71 patients had IHCEV. In 28 of the 71 NCE-CT scans, both observers were confident as to the the site of the hematoma (κ, 0.55; 95% CI, 37%-73%). IHCEV were present in 10 of these 28 patients, of whom 9 had an ISH based on NCE-CT (positive predictive value, 90%; 95% CI, 55%-100%). In all 18 of 28 patients without IHCEV, the hematoma was not intra-Sylvian (negative predictive value, 100%; 95% CI, 82%-100%). Poor admission status occurred in 50% of patients with IHCEV and in 60% without IHCEV (RR, 1.2; 95% CI, 0.8-1.9). Poor outcome occurred in 63% of patients with IHCEV and in 65% without IHCEV (RR, 1.0; 95% CI, 0.7-1.5). Although CTA could reliably and accurately differentiate the hematoma types, admission status and outcome were similar for both groups.


Transcriptional regulation of a myeloid-lineage specific gene lysozyme C during zebrafish myelopoiesis.
lysozyme C (lyz), a glycoside hydrolase expressed exclusively in myeloid cells, is involved in the host defense against bacterial infection. We isolated a 2.4kb zebrafish lyz promoter region and established transgenic lines that drive enhanced green fluorescent protein (EGFP) to examine how lyz expression is regulated during myelopoiesis. We found that the 2.4kb lyz promoter is sufficient to drive myeloid-specific expression of EGFP in zebrafish. We identified potential transcriptional regulatory elements including a Runx element (TGTGGT at -1.70kb) and a C/ebp element (TTTGGCAAT at -1.46kb) in the lyz promoter, and showed that they are required for myeloid-specific expression of EGFP. We found that the myeloid-lineage transcription factors C/ebp1, Runx1 and Pu.1 can bind to the 2.4kb lyz promoter. Forced expression of runx1, c/ebp1 and pu.1 together induced ectopic lyz expression in the intermediated cell mass (ICM). Thus, we propose that c/ebp1 and runx1 presumably cooperated with pu.1 in the transcriptional regulation of lyz during zebrafish myelopoiesis.


In situ measurement of synthetic musks in wastewaters using diffusive gradients in thin film technique.
Synthetic musks (SMs) are used extensively in household and personal care products and have acted significant concerns due to their environmental impacts and potential health effects. Here, we present a passive sampling approach based on diffusive gradients in thin films (DGT) for in situ measurement of SMs in urban wastewaters. XAD-2 binding gel, which has a rapid binding rate and high elution efficiency, was used in DGT device for the accumulation of six polycyclic musks and three nitro musks. The diffusion coefficients (D and DNL) of the SMs through agarose gel without and with a nylon filter membrane were 3.37-4.49 and 1.48-4.41 ×10-6cm2 s-1. The filter membrane caused an ~3 h lag phase and slowed the diffusion rates of the SMs through the diffusive phase. Solution pH (4.30-8.92), ionic strength (0.0001-0.5 M) and dissolved organic matter (0-20 mg L-1) showed no obvious influence on uptake of the SMs in DGT. The measured average SM concentrations in the effluent of wastewater treatment plants ranged from 0.45-696 ng/L for DGT deployment, without obvious membrane biofouling, and they were comparable to the concentrations determined by grab sampling. These results confirmed that the present method is reliable and convenient for in situ measurement of semivolatile hydrophobic SMs in complicated waters and is an available tool to investigate the environmental behaviors of SMs in the environment.


An analysis of protein folding type prediction by seed-propagated sampling and jackknife test.
In the development of methodology for statistical prediction of protein folding types, how to test the predicted results is a crucial problem. In addition to the resubstitution test in which the folding type of each protein from a training set is predicted based on the rules derived from the same set, cross-validation tests are needed. Among them, the single-test-set method seems to be least reliable due to the arbitrariness in selecting the test set. Although the leaving-one-out (or jackknife) test is more objective and hence more reliable, it may cause a severe information loss by leaving a protein in turn out of the training set when its size is not large enough. In order to overcome the above drawback, a seed-propagated sampling approach is proposed that can be used to generate any number of simulated proteins with a desired type based on a given training set database. There is no need to make any predetermined assumption about the statistical distribution function of the amino acid frequencies. Combined with the existing cross-validation methods, the new technique may provide a more objective estimation for various protein-folding-type prediction methods.


Flavored waters: influence of ingredients on antioxidant capacity and terpenoid profile by HS-SPME/GC-MS.
The antioxidant profiles of 39 water samples (29 flavored waters based on 10 natural waters) and 6 flavors used in their formulation (furnished by producers) were determined. Total phenol and flavonoid contents, reducing power, and DPPH radical scavenging activity were the optical techniques implemented and included in the referred profile. Flavor extracts were analyzed by HS-SPME/GC-MS to obtain the qualitative and quantitative profiles of the volatile fraction of essential oils. Results pointed out a higher reducing power (0.14-11.8 mg of gallic acid/L) and radical scavenging activity (0.29-211.5 mg Trolox/L) of flavored waters compared with the corresponding natural ones, an interesting fact concerning human health. Bioactive compounds, such as polyphenols, were present in all samples (0.5-359 mg of gallic acid/L), whereas flavonoids were not present either in flavored waters or in flavors. The major components of flavor extracts were monoterpenes, such as citral, α-limonene, carveol, and α-terpineol.


Latent tuberculosis: interaction of virulence factors in Mycobacterium tuberculosis.
Tuberculosis (TB) remains a prominent health concern worldwide. Besides extensive research and vaccinations available, attempts to control the pandemic are cumbersome due to the complex physiology of Mycobacterium tuberculosis (Mtb). Alongside the emergence of drug-resistant TB, latent TB has worsened the condition. The tubercle bacilli are unusually behaved and successful with its strategies to modulate genes to evade host immune system and persist within macrophages. Under latent/unfavorable conditions, Mtb conceals itself from immune system and modulates its genes. Among many intracellular modulated genes, important are those involved in cell entry, fatty acid degradation, mycolic acid synthesis, phagosome acidification inhibition, inhibition of phagosome-lysosome complex and chaperon protein modulation. Though the study on these genes date back to early times of TB, an insight on their inter-relation within and to newly evolved genes are still required. This review focuses on the findings and discussions on these genes, possible mechanism, credibility as target for novel drugs and repurposed drugs and their interaction that enables Mtb in survival, pathogenesis, resistance and latency.


Early bronchial airflow impairment in patients with persistent allergic rhinitis and bronchial hyperreactivity.
Allergic rhinitis and its impact on asthma (ARIA) document underlines the link between upper and lower airways. Patients suffering from allergic rhinitis frequently (up to 80%) show bronchial hyperreactivity (BHR). This study aimed at evaluating a group of subjects suffering from persistent allergic rhinitis, with BHR but with nasal symptoms only, to investigate the type and intensity of nasal symptoms, nasal and bronchial airflow, and BHR grade during the pollen season. One hundred and twenty one polysensitized rhinitics were investigated. Total symptom score (TSS) was assessed in all patients. Rhinomanometry, spirometry and methacholine bronchial challenge were performed in all patients. 65 (53.7%) patients had impaired FEF 25-75 values. TSS correlated with nasal airflow (P<0.001) and BHR grade (P<0.001). Nasal airflow correlated with FEF 25-75 values (P<0.05) and BHR (P<0.001). FEF 25-75 values correlated with FEV(1) levels (P<0.003), BHR grade (P<0.001), and nasal obstruction symptom (P<0.05). Severe BHR correlated with FEV(1) (P<0.05) and FEF 25-75 (P<0.03) values, nasal airflow (P<0.05) and nasal symptoms (P<0.001). This study evidences that early bronchial impairment is frequently detectable in patients with persistent allergic rhinitis and BHR. Moreover, nasal function is strictly related with bronchial calibre and BHR grade. Therefore, careful evaluation of lower airways should be investigated in all rhinitics as suggested by the ARIA document.


Novel therapies for coeliac disease.
Coeliac disease is a widespread, lifelong disorder for which dietary control represents the only accepted form of therapy. There is an unmet need for nondietary therapies to treat this condition. Most ongoing and emerging drug-discovery programmes are based on the understanding that coeliac disease is caused by an inappropriate T-cell-mediated immune response to dietary gluten proteins. Recent genome-wide association studies lend further support to this pathogenic model. The central role of human leucocyte antigen genes has been validated, and a number of new risk loci have been identified, most of which are related to the biology of T cells and antigen-presenting cells. Here, we review the status of potential nondietary therapies under consideration for coeliac disease. We conclude that future development of novel therapies will be aided considerably by the identification of new, preferably noninvasive, surrogate markers for coeliac disease activity.


Fractionation and speciation of arsenic in three tea gardens soil profiles and distribution of As in different parts of tea plant (Camellia sinensis L.).
The distribution pattern and fractionation of arsenic (As) in three soil profiles from tea (Camellia sinensis L.) gardens located in Karbi-Anglong (KA), Cachar (CA) and Karimganj (KG) districts in the state of Assam, India, were investigated depth-wise (0-10, 10-30, 30-60 and 60-100 cm). DTPA-extractable As was primarily restricted to surface horizons. Arsenic speciation study showed the presence of higher As(V) concentrations in the upper horizon and its gradual decrease with the increase in soil depths, following a decrease of Eh. As fractionation by sequential extraction in all the soil profiles showed that arsenic concentrations in the three most labile fractions (i.e., water-soluble, exchangeable and carbonate-bound fractions) were generally low. Most arsenic in soils was nominally associated with the organic and Fe-Mn oxide fractions, being extractable in oxidizing or reducing conditions. DTPA-extractable As (assumed to represent plant-available As) was found to be strongly correlated to the labile pool of As (i.e. the sum of the first three fractions). The statistical comparison of means (two-sample t-test) showed the presence of significant differences between the concentrations of As(III) and As(V) for different soil locations, depths and fractions. The risk assessment code (RAC) was found to be below the pollution level for all soils. The measurement of arsenic uptake by different parts of tea plants corroborated the hypothesis that roots act as a buffer and hold back contamination from the aerial parts.


Electrical activity of the diaphragm during progressive cycling exercise in endurance-trained men.
The study aimed to investigate diaphragm respiratory drive modulation through electrical activity of the diaphragm (EADi) during progressive cycling in endurance-trained men (N=7) and to test day-to-day measurement reliability. Normalized EADi increased at exercise intensities from 40% workload (WL) to 70% and 85%WL but plateaued from 70% to 85% (p<0.05). V˙O2, V˙CO2, V˙E, increased at all exercise intensities, where Vt and BF increased from 40% to 55% WL and from 70% to 85% and RER increased at 70% and 85% (p<0.05). Bland-Altman plots of normalized EADi showed bias of 0.9% and -6.4% and limits of agreement of ±36.0% and ±30.4% for absolute measurements and relative changes from 40% WL, respectively. Within-day variability appeared constant indicating that measurements within a trial are reliable. Results suggest that diaphragm respiratory drive increases at moderate exercise intensities, but plateaus at high intensities where other respiratory muscles might contribute significantly to the breathing effort, perhaps to "protect" against diaphragm fatigue.


Exercise-induced left bundle branch block: prevalence and prognosis.
Exercise-induced left bundle branch block (EI-LBBB) is an infrequent finding. Its prevalence and prognostic significance are not clear. To evaluate, in a longitudinal study, the prevalence and prognostic significance of EI-LBBB in American war veterans. We evaluated 9,623 patients submitted to an exercise test (ET) in treadmill between 1987 and 2007. The outcomes were compared between those with normal TE, the ones with EI-LBBB and the ones with down-sloping ST-segment. Mortality and causes of death were identified while blinded to the ET results. In this prospective cohort, 6,922 individuals had normal ET results (57.2 ± 11.4 years), 1,739 had abnormal ST-segment depression (62.7 ± 9.8 years), and 38 had EI-LBBB (65.2 ± 11.9 years). The prevalence of EI-LBBB was 0.38%. After 8.8 years, there were 1,699 deaths due to all-cause mortality and 610 cardiovascular (CV) deaths; coronary artery disease and heart failure were more prevalent in patients with EI-LBBB. Patients with EI-BCRE had a hazard ratio of 2.37 (p = 0.002) for all-cause mortality, but it was not significant when adjusted for age or when the CV death was the assessed outcome. EI-LBBB is a rare clinical finding. Individuals with BCRE-EI have higher all-cause mortality when compared to those with normal ET results. However, this fact is explained by the fact that these patients are significantly older and have more associated cardiovascular diseases.


The Z-plasty contributes to the coalescence of a chronic non-healing wound.
This study aimed to explore the treatment effect of Z-plasty on a non-healing wound. A total of 72 patients diagnosed with a chronic non-healing wound in Peking University Third Hospital from November 2009 to August 2019 were retrospectively analysed. Among them, 27 patients were treated with Z-plasty, and 45 patients were treated with the general method. Detailed patient information was retrieved from medical records, including age, gender, body mass index (BMI), alcohol, smoking, and comorbidities (diabetes mellitus, hypertension, heart disease). Surgical parameters included operation time and intraoperative blood loss. Wound swelling, epidermal blisters, wound edge colour, and skin temperature at 1 day after surgery were assessed to evaluate the blood supply of the wound. Surgical complications included infection, haematoma, dehiscence, and non-healing within 2 weeks postoperatively. Student t test (for continuous data) and Chi-square test (for categorical data) were conducted to determine the statistical difference. We found no significant differences in age, gender, BMI, alcohol, smoking, and comorbidities between the two groups. Z-plasty did not show any advantages in the surgical time, invasive blood loss, hospital days, and hospitalisation expenses. The incidence of abnormal wound edge colour with Z-plasty was significantly lower than that with the general treatment (P < .05), and the Z-plasty enables better healing of the patient's wound (P < .05). Z-plasty promoted better recovery of chronic non-healing wounds than direct suturing.


The response of midfacial bone in sheep to loaded osteosynthesis screws in pretapped and nontapped implant sites.
This study compared the functional retention of pretapped and self-tapping 2-mm AO miniscrews (Stratec Medical, Waldenburg, Switzerland) in an animal experimental model. Histologic evaluation of the bone surrounding the loaded screws showed significantly more remodeling when pretapped screws were used than when self-tapping screws were used. Although the experimental situation may not be directly comparable with the clinical situation, this study does lend credibility to the assumption that pretapping is not advisable in the thin bone of the midface.


Oral mucosal graft with amniotic membrane transplantation for total limbal stem cell deficiency.
To report the results of oral mucosal graft for reconstruction of corneas with total limbal stem cell deficiency. Retrospective, interventional case series. Seven patients (7 eyes) with total limbal stem cell deficiency caused by chemical burn (4 eyes), Stevens-Johnson syndrome / toxic epidermal necrolysis (1 eye), ocular cicatricial pemphigoid (1 eye), and multiple cryotherapies and application of mitomycin C for conjunctival melanoma (1 eye) were enrolled in this study. Oral mucosal graft was transplanted as a surrogate limbus together with amniotic membrane transplantation with a follow-up of at least 8 months. Symptomatic relief, restoration of a stable epithelium, corneal clarity, and the best-corrected visual acuity were assessed. Limbal stem cell deficiency was confirmed by impression cytology in all eyes, among which 6 were bilateral while 1 was unilateral. All 7 patients presented with severe loss of vision, photophobia, pain, chronic inflammation, and corneal vascularization and scarring. For 30 ± 19.8 months, pain and photophobia were resolved in all 7 eyes; 6 eyes exhibited a stable epithelium with regressed corneal vascularization and reduced chronic inflammation. Visual acuity was improved in all 7 eyes. One eye developed partial limbal stem cell deficiency due to exposure at 47 months follow-up and was reoperated. Five eyes had peripheral corneal vascularization. Oral mucosal graft is a viable alternative for treating total limbal stem cell deficiency in eyes where transplantation of allogeneic limbal stem cells has failed or is not feasible.


High Blood Pressure States in Children, Adolescents, and Young Adults Associate Accelerated Vascular Aging, with a Higher Impact in Females' Arterial Properties.
The aims of the study were to determine (1) whether the presence of High blood pressure (HBP) states in the youth associate a steeper rate of age-related change in arterial geometrical and wall properties with respect to subjects with no previous cardiovascular risk factor (CRF) exposure, (2) in which parameters and in what magnitude, and (3) the existence of a gender-related difference in the impact of this condition on arterial properties. 300 individuals (mean/range: 15/4-29 years; 133 females) were included. Two groups were assembled: (1) Reference: nonprevious exposure to traditional CRF and (2) HBP: subjects with arterial hypertension and/or elevated blood pressure (BP) levels during the study. Additionally, HBP subjects were separated in BP-related subgroups. Measured parameters were (1) central (aortic) arterial BP and aortic pulse wave analysis parameters, (2) carotid and femoral artery local (pressure-strain elastic modulus) and regional (pulse wave velocity; PWV) stiffness, and (3) arterial diameters and carotid intima-media thickness (CIMT). Age-related changes in these parameters (absolute values and z-scores) were explored by obtaining simple linear regression models for each group. HBP presented a steeper rate of change (accelerated vascular aging; VA) for most of the parameters assessed, mainly in central (aortic) hemodynamics. VA increased as the HBP level got higher. Both males' and females' aging rates were affected by this condition, but females presented a more marked relative age-related increase with HBP exposure. HBP states in the youth gradually associate accelerated VA, with a progressive hemodynamic-structural-functional onset of damage, with females presenting a more marked relative HBP-associated arterial repercussion.


Identification and Validation of Plasma Metabolomic Signatures in Precancerous Gastric Lesions That Progress to Cancer.
Metabolic deregulation plays an important role in gastric cancer (GC) development. To date, no studies have comprehensively explored the metabolomic profiles along the cascade of gastric lesions toward GC. To draw a metabolic landscape and define metabolomic signatures associated with the progression of gastric lesions and risk of early GC. A 2-stage, population-based cohort study was initiated in 2017 in Linqu County, Shandong Province, China, a high-risk area for GC. Prospective follow-up was conducted during the validation stage (June 20, 2017, to May 27, 2020). A total of 400 individuals were included based on the National Upper Gastrointestinal Cancer Early Detection Program in China. The discovery stage involved 200 individuals with different gastric lesions or GC (high-grade intraepithelial neoplasia or invasive GC). The validation stage prospectively enrolled 152 individuals with gastric lesions who were followed up for 118 to 1063 days and 48 individuals with GC. Metabolomic profiles and metabolite signatures were examined based on untargeted plasma metabolomics assay. The risk of GC overall and early GC (high-grade intraepithelial neoplasia), and progression of gastric lesions. Of the 400 participants, 124 of 200 (62.0%) in the discovery set were men; mean (SD) age was 56.8 (7.5) years. In the validation set, 136 of 200 (68.0%) were men; mean (SD) age was 57.5 (8.1) years. Distinct metabolomic profiles were noted for gastric lesions and GC. Six metabolites, including α-linolenic acid, linoleic acid, palmitic acid, arachidonic acid, sn-1 lysophosphatidylcholine (LysoPC)(18:3), and sn-2 LysoPC(20:3) were significantly inversely associated with risk of GC overall and early GC (high-grade intraepithelial neoplasia). Among these metabolites, the first 3 were significantly inversely associated with gastric lesion progression, especially for the progression of intestinal metaplasia (α-linolenic acid: OR, 0.42; 95% CI, 0.18-0.98; linoleic acid: OR, 0.43; 95% CI, 0.19-1.00; and palmitic acid: OR, 0.32; 95% CI, 0.13-0.78). Compared with models including only age, sex, Helicobacter pylori infection, and gastric histopathologic findings, integrating these metabolites significantly improved the performance for predicting the progression of gastric lesions (area under the curve [AUC], 0.86; 95% CI, 0.70-1.00 vs AUC, 0.69; 95% CI, 0.50-0.88; P = .02) and risk of early GC (AUC, 0.83; 95% CI, 0.58-1.00 vs AUC, 0.61; 95% CI, 0.31-0.91; P = .03). This study defined metabolite signatures that might serve as meaningful biomarkers for assessing high-risk populations and early diagnosis of GC, possibly advancing targeted GC prevention and control.


Spread of influenza virus A (H5N1) clade 188.8.131.52 to Bulgaria in common buzzards.
On March 15, 2010, a highly pathogenic avian influenza virus was isolated from the carcass of a common buzzard (Buteo buteo) in Bulgaria. Phylogenetic analyses of the virus showed a close genetic relationship with influenza virus A (H5N1) clade 18.104.22.168 viruses isolated from wild birds in the Tyva Republic and Mongolia during 2009-2010. Designated A/common buzzard/Bulgaria/38WB/2010, this strain was highly pathogenic in chickens but had low pathogenicity in mice and ferrets and no molecular markers of increased pathogenicity in mammals. The establishment of clade 188.8.131.52 highly pathogenic avian influenza viruses of the H5N1 subtype in wild birds in Europe would increase the likelihood of health threats to humans and poultry in the region.


MTM1 displays a new function in the regulation of nickel resistance in Saccharomyces cerevisiae.
Nickel (Ni) is an essential yet toxic trace element. Although a cofactor for many metalloenzymes, nickel function and metabolism is not fully explored in eukaryotes. Molecular biology and metallomic methods were utilized to explore the new physiological functions of nickel in Saccharomyces cerevisiae. Here we showed that MTM1 knockout cells displayed much stronger nickel tolerance than wild-type cells and mitochondrial accumulations of Ni and Fe of mtm1Δ cells dramatically decreased compared to wild-type cells when exposed to excess nickel. Superoxide dismutase 2 (Sod2p) activity in mtm1Δ cells was severely attenuated and restored through Ni supplementation in media or total protein. SOD2 mRNA level of mtm1Δ cells was significantly higher than that in the wild-type strain but was decreased by Ni supplementation. MTM1 knockout afforded resistance to excess nickel mediated through reactive oxygen species levels. Meanwhile, additional Ni showed no significant effect on the localization of Mtm1p. Our study reveals the MTM1 gene plays an important role in nickel homeostasis and identifies a novel function of nickel in promoting Sod2p activity in yeast cells.


The minipig in dermatotoxicology: methods and challenges.
In view of more morphological and physiological similarities between human and porcine skin than for other laboratory animal species, the minipig is a preferred model to evaluate the safety profile of dermally applied xenobiotics. Different methods of dermal administration and examples of non-invasive and invasive investigations during the in-life phase of the studies are described. Routine and special post-mortem examinations in dermal studies are presented to assess responses to the topical treatment of minipig skin. Challenges in dermal minipig studies are discussed with respect to animal welfare and husbandry, test formulations, application methods and different types of investigations. One of the most significant issues for dermal minipig studies is the extensive measures required to prevent cross-contamination of blood and tissue samples taken to monitor local and systemic exposure to the test item.


[Microbial nitrogen fixation in the gastro-intestinal tract of Kalmykia gerbils (Meriones. tamariscinus and Meriones meridianus)].
The nitrogen-fixing activity, nitrogen (N) and carbon (C) contents, and the number of microorganisms in the forestomach, cecum, and segmented intestine were detected in two gerbil species, granivorous Meriones meridianus and M. tamariscinus, which consume a large amount of green parts of the plants. M. meridianus had higher levels of nitrogen-fixation activity in all investigated parts of the gastro-intestinal tract compared with M. tamariscinus. The highest levels were detected in the colon of M. meridianus. The C/N ratios in the forestomach of M. tamariscinus were higher than in M. meridianus, which is consistent with the greater role of the green parts of plants in its diet. A gradual increase in the nitrogen content from the forestomach to the colon of M. tamariscinus was noted. The amount of microorganisms in the forestomach and intestine of the studied gerbil species was similar.


Incrementing non-matching- but not matching-to-sample is rapidly learned in an automated version of the odor span task.
The odor span task (OST) is frequently used to assess memory capacity in rodents. Odor stimuli are presented in a large arena and choices of session-novel odors produce food reward. The procedure can be described as an incrementing non-matching-to-sample contingency because on each trial one new stimulus is presented along with one or more previously presented (non-reinforced) comparison odors. An automated version of this task has recently been developed in which odors are presented with an olfactometer in an operant chamber using a successive conditional discrimination procedure. The present study compared the acquisition of matching- vs. non-matching-to-sample versions of the task with six rats tested under each procedure. All six rats trained on the non-matching variation showed rapid acquisition of the discrimination with high rates of responding to odor stimuli when they were session-novel and low rates of responding to subsequent presentations of those odors. However, only three of the six rats trained on the matching variation met acquisition criteria, and two of the three that did acquire the task required extensive training to do so. These results support findings from the OST that rats can differentiate between stimuli that are session-novel and those previously encountered, but also that a matching contingency is more difficult to learn than a non-matching arrangement. These findings parallel differences observed between acquisition of simple matching- and non-matching-to-sample tasks, but accounts such as novelty preference or the oddity preference effect may not be sufficient to explain the present results.


A phase I/II study of neoadjuvant chemotherapy with Pemetrexed (Alimta) in rectal cancer.
The aim was to assess the feasibility of preoperative chemotherapy and possible tumour response using Pemetrexed (Alimta) in rectal cancer. The study was a prospective, non-randomized, single-centre phase I/II feasibility trial. 37 patients with resectable rectal cancer were recruited and given three 3-week cycles of preoperative Pemetrexed therapy. Tumour size and stage were assessed by MRI scans before and after chemotherapy. Treatment tolerability and response such as changes in tumour size and symptoms were assessed. All patients completed the chemotherapy. Whilst mild side effects were frequent (grade 1, 34/37), the risk of severe effects was limited (grade 3 or 4, 4/37). Overall, there was a significant reduction in tumour size (p < 0.001). By RECIST criteria, one patient had tumour progression, 23/36 had stable disease and 12 patients had a response of up to 65%. There was also a significant decrease in the number of pre-treatment symptoms (p < 0.018) including reduction of bleeding and diarrhoea/constipation. Preoperative (Neoadjuvant) treatment with Pemetrexed was feasible in studied patients. Serious side effects were limited and a radiological tumour response or stable disease was seen in a majority of patients.


Accounting for past patient composition in evaluations of quality reporting.
To investigate whether accounting for past patient composition in evaluations of the association between public quality reports and patient selectivity changes findings and conclusions. Secondary data analysis of public reports of Assisted Reproductive Technology Clinic success rates between 2011 and 2018. Two sets of fixed effects models, (1) a standard fixed-effects model (FE) and (2) a dynamic panel model using structural equation modeling estimated with maximum-likelihood (ML-SEM) with one- and two-year lagged patient characteristics, are compared. The outcome variables are patient composition features associated with success rates, including two age categories and eight diagnoses of infertility. Two-year lagged success rates for any live birth and a singleton live birth are central predictor variables. Clinics with complete records for the 2011-2018 period were included (N = 303). For live birth success rates, the two models show increases in the two-year lagged success rate is associated with a reduction in (1) the transformed percentage of patients with endometriosis (FE: β = -0.006, SE = 0.002, p < 0.01; ML-SEM: β = -0.005, SE = 0.002, p < 0.01) and (2) the percentage of patients with tubal diagnoses (FE: β = -0.090, SE = 0.017, p < 0.001; ML-SEM: β = -0.064, SE = 0.027, p < 0.05). For singleton birth success rates, the models show positive associations between the two-year lagged success rate and the percent of patients over 35 years old (FE: β = 0.219, SE = 0.033, p < 0.001; ML-SEM: β = 0.095, SE = 0.047, p < 0.05). Overall, the FE models show numerous significant associations with the two-year lagged success rate not observed in the ML-SEM models. Thus, the preferred and theoretically appropriate model (ML-SEM) and the more commonly used model (FE) yield different results. Researchers and policymakers should use models that account for past patient composition when evaluating the associations between quality reports and patient selectivity.


Development of cancer after bariatric surgery.
Although bariatric surgery has been associated with a reduction in risk of obesity-related cancer, data on the effect of bariatric interventions on other cancers are limited. This study aimed to examine the relationship between bariatric interventions and the incidence of various cancers after bariatric surgery. Administrative statewide database. The New York Statewide Planning and Research Cooperative System database was used to identify all adult patients diagnosed with obesity between 2006 and 2012 and patients who underwent bariatric procedures without preexisting cancer diagnosis and alcohol or tobacco use. Subsequent cancer diagnoses were captured up to 2016. Multivariable proportional subdistribution hazard regression analysis was performed to compare the risk of having cancer among obese patients with and without bariatric interventions. We identified 71,000 patients who underwent bariatric surgery and 323,197 patients without a bariatric intervention. Patients undergoing bariatric surgery were less likely to develop both obesity-related cancer (hazard ratio.91; 95% confidence interval, .85-.98; P = .013) and other cancers (hazard ratio .81; 95% confidence interval, .74-.89; P < .0001). Patients undergoing Roux-en-Y gastric bypass had a lower risk of developing cancers that are considered nonobesity related (hazard ratio .59; 95% confidence interval, .42-.83; P = .0029) compared with laparoscopic sleeve gastrectomy. Bariatric surgery is associated with a decreased risk of obesity-related cancers. More significantly, we demonstrated the relationship between bariatric surgery and the reduction of the risk of some previously designated nonobesity-related cancers, as well. Reclassification of nonobesity-related cancers and expansion of bariatric indications for reducing the risk of cancer may be warranted.


Education and cancer risk.
Socioeconomic factors have been associated, to a variable degree, with the risk of serious cancers. The relationship between education and cancer risk was analyzed using data from a series of case-control studies conducted in northern Italy between 1983 and 1990, including 119 histologically confirmed cancers of the oral cavity and pharynx, 294 of the esophagus, 564 of the stomach, 673 of the colon, 406 of the rectum, 258 of the liver, 41 of the gallbladder, 303 of the pancreas, 149 of the larynx, 2860 of the breast, 692 of the cervix, 567 of the corpus uteri, 742 of the ovary, 107 of the prostate, 365 of the bladder, 147 of the kidney, and 120 of the thyroid, 72 Hodgkin diseases, 173 non-Hodgkin lymphomas, 117 myelomas, and a total of 6147 control subjects admitted to the same network of hospitals for acute, non-neoplastic conditions. Nine types of cancer were inversely related to education. Those were oral cavity and pharynx, with a relative risk (RR) of 0.3 for the highest versus the lowest level; esophagus, RR = 0.6; stomach, RR = 0.5; liver, RR = 0.7; gallbladder, RR = 0.5; larynx, RR = 0.3; cervix, RR = 0.7; endometrium, RR = 0.5; and non-Hodgkin lymphomas, RR = 0.6. Five cancer sites were directly related to education: colon, RR = 1.3; pancreas, RR = 1.3; breast, RR = 1.5; kidney, RR = 1.3; and thyroid, RR = 1.5. No consistent gradient in risk with education was observed for the six other neoplasms considered, including rectum, prostate, bladder, Hodgkin disease, and multiple myeloma. The patterns of risk for education were consistent in men and women for most cancer sites except colon, for which the direct relationship was stronger in males. This study confirms the existence of and quantifies a number of strong socioeconomic correlates of cancer risk and indicates a few points open to additional investigation, such as the different pattern of risk for rectal and colon cancer, the strong negative gradient for endometrial cancer, and the absence of any clear association with education for cancers of the ovary, prostate, urinary tract, lymphomas, and myeloma.


A novel cytotoxic ternary copper(II) complex of 1,10-phenanthroline and L-threonine with DNA nuclease activity.
A novel ternary copper(II) complex, [Cu(phen)(L-Thr)(H2O)](ClO4) (phen=1,10-phenanthroline, L-Thr=L-threonine), has been synthesized and structurally characterized. The complex crystallized in a triclinic system with space group P1 , a=7.526(15) A, b=11.651(2) A, c=12.127(2) A, alpha=115.41(3) degrees , beta=102.34(3) degrees and gamma=91.33(3) degrees . The copper(II) center is situated in a distorted square-pyramidal geometry. At a concentration of 10(-6) mol L(-1), the complex exhibited potent cytotoxic effects against human leukemia cell line HL-60 and human stomach cancer cell line SGC-7901 with inhibition rates of over 90%, however, less pronounced effects were observed for human liver carcinoma cell line BEL-7402 and human non-small-cell lung cancer cell line A-549. The complex was shown to bind DNA by intercalation and cleave pBR322 DNA in the presence of ascorbate.


Does theory of mind predict specific domains of social functioning in individuals following a first episode psychosis?
Social functioning is a central aspect in the treatment of people with psychosis, even more so with the recovery movement promoting an optimal life in one's environment. A good ability to function socially is, among other things, associated with fewer future complications and a better overall quality of life. However, prognostic markers currently in use (i.e., cognitive functioning) to predict an individual's subsequent functioning do not always produce conclusive results in individuals who have recently experienced a first episode of psychosis (FEP). The objective of this study was to evaluate the prognostic value of theory of mind in FEP individuals. Thirty-seven individuals who were followed in a FEP clinic were recruited for the study. Multiple linear regressions were performed for data analysis. The results suggest that theory of mind may be, for specific domains of social functioning in this sub-population, a more important predictor than cognitive functioning variables; though studies with larger samples are needed to support these results.


Probing the role of HDACs and mechanisms of chromatin-mediated neuroplasticity.
Advancing our understanding of neuroplasticity and the development of novel therapeutics based upon this knowledge is critical in order to improve the treatment and prevention of a myriad of nervous system disorders. Epigenetic mechanisms of neuroplasticity involve the post-translational modification of chromatin and the recruitment or loss of macromolecular complexes that control neuronal activity-dependent gene expression. While over a century after Ramón y Cajal first described nuclear subcompartments and foci that we now know correspond to sites of active transcription with acetylated histones that are under epigenetic control, the rate and extent to which epigenetic processes act in a dynamic and combinatorial fashion to shape experience-dependent phenotypic and behavioral plasticity in response to various types of neuronal stimuli over a range of time scales is only now coming into focus. With growing recognition that a subset of human diseases involving cognitive dysfunction can be classified as 'chromatinopathies', in which aberrant chromatin-mediated neuroplasticity plays a causal role in the underlying disease pathophysiology, understanding the molecular nature of epigenetic mechanisms in the nervous system may provide important new avenues for the development of novel therapeutics. In this review, we discuss the chemistry and neurobiology of the histone deacetylase (HDAC) family of chromatin-modifying enzymes, outline the role of HDACs in the epigenetic control of neuronal function, and discuss the potential relevance of these epigenetic mechanisms to the development of therapeutics aiming to enhance memory and neuroplasticity. Finally, open questions, challenges, and critical needs for the field of 'neuroepigenetics' in the years to come will be summarized.


Caveolae and caveolin-1 in reptilian liver.
Caveolae are plasma-membrane invaginations that, by interacting with membrane-associated molecules such as endothelial nitric oxide synthase and tyrosine kinases, precisely regulate cell-signalling pathways responsible for cell structure and cell function. Indeed, there is widespread evidence that caveolae associate, structurally and functionally, with proteins, lipids and solutes to facilitate transcellular transport of these macromolecules. Caveolin-1, one of the family of membrane proteins that form caveolae, is most prominently expressed in endothelial cells of the vascular bed. Therefore, we have applied advanced electron microscopy as well as molecular biology techniques to study the presence of caveolae and caveolin-1 in the liver sinusoidal endothelium of reptiles. Reptiles are known to store excess lipid in the liver as an energy source for hibernation, and so offer a useful animal model in which to assess the structural and functional implications these subcellular compartments might have on liver sinusoidal endothelial transport. This study demonstrates that caveolae are indeed conserved across vertebrate species, whether mammalian or reptilian. It also presents as first novel data on the presence of caveolin-1-associated, tubular structures located within the cytoplasm of the lizard liver sinusoidal endothelium.


Effect of morphine and ibuprofen on nociceptive behavior, preening and motor activity following tonic chemical pain in the Japanese quail (Coturnix japonica).
To establish a tonic chemical model of pain in quail and evaluate the efficacy of opioid and non-steroidal anti-inflammatory drugs. A randomized, blinded, experimental study design. A total of 120 male Japanese quail, aged 7 weeks. A formalin solution (0.3%, 0.6% and 0.9%; total volume of 40 μL) was injected subcutaneously (SC) into the medial aspect of the right metatarsus (shank). Foot lift and preening activities were recorded for 45 minutes following injection of formalin and scored by an investigator blinded to the treatment. An open field test was used to evaluate motor activity. Treatments included SC saline, SC morphine (1.25, 2.5 and 5 mg kg-1) and oral ibuprofen (5 and 10 mg kg-1). The treatment effect was analyzed by one-way anova and the time course effect analyzed using repeated measures anova, both followed by Dunnett's post hoc test (p < 0.05). All formalin concentrations induced significant foot lifting activity in the first phase (0-5 minutes), whereas only 0.6% and 0.9% formalin elicited responses in both the first and second (25-45 minutes) phases. Neither morphine nor ibuprofen affected phase 1 of the formalin test. Morphine (2.5 and 5 mg kg-1) and ibuprofen (5 and 10 mg kg-1) significantly reduced foot lift responses. Preening activity was significantly decreased following injection of 0.6% and 0.9% formalin. Preening was normalized with ibuprofen, but not with morphine. Morphine, but not ibuprofen, reduced quail activity. These results suggest that the formalin test was a reliable method for assessing tonic pain behavior in quail. The acute phase of the formalin test was not affected by morphine or ibuprofen. Although ibuprofen reduced the pain response in phase 2, the analgesic effects of morphine were not conclusive because morphine appeared to induce sedation.


Synergism of irbesartan and amlodipine on hemodynamic amelioration and organ protection in spontaneously hypertensive rats.
To investigate the synergism of low-doses of amlodipine and irbesartan on reduction of blood pressure variability (BPV), amelioration of baroreflex sensitivity (BRS) and organ protection in spontaneously hypertensive rats (SHR). The rats were administered amlodipine (1 mg·kg(-1)·d(-1)) alone, irbesartan (10 mg·kg(-1)·d(-1)) alone, or the combination of the two drugs for 4 months. The drugs were mixed into the rat chow. Blood pressure (BP) was continuously monitored in conscious animals. After the determination of BRS, the rats were killed for morphological evaluation of organ damages. The combination of low-dose irbesartan and amlodipine had statistically significant synergism on reduction of BP and BPV, amelioration of BRS and organ protection in SHR. Multiple regression analysis showed that the decrease in left ventricular hypertrophy was associated with the decrease in systolic BPV (r=0.665, P<0.01); the decrease in aortic hypertrophy was associated with the increase in BRS (r=0.656, P<0.01); and the amelioration in renal lesion was associated with the increase in BRS (r=0.763, P<0.01) and the decrease in systolic BPV (r=0.706, P<0.01). Long-term treatment with a combination of low-doses of amlodipine and irbesartan showed significant synergism on reduction of BP and BPV, restoration of BRS and organ protection in SHR. Besides BP reduction, the enhancement of BRS and reduction of BPV might contribute to the organ protection.


Photocatalytic degradation and reactor modeling of 17α-ethynylestradiol employing titanium dioxide-incorporated foam concrete.
Photocatalytic degradation of 17α-ethynylestradiol (EE2) using TiO2 photocatalysts incorporated with foam concrete (TiO2/FC) was investigated for the first time. Scanning electron microscopy (SEM) study of the samples revealed a narrow air void size distribution on the surface of FC cubes on with 5 wt% addition of P25 TiO2, and TiO2 particles were distributed heterogeneously on the surface of TiO2/FC samples. The sorption and photocatalytic degradation of EE2 with UV-light irradiation by TiO2/FC cubes were investigated. Adsorption capacity of EE2 by the TiO2/FC and blank foam concrete (FC) samples were similar, while the degradation rates showed a great difference. More than 50 % of EE2 was removed by TiO2/FC within 3.5 h, compared with 5 % by blank FC. The EE2 removal process was then studied in a photoreactor modified from ultraviolet disinfection pool and constructed with TiO2/FC materials. An integrated model including a plate adsorption-scattering model and a modified flow diffusion model was established to simulate the photocatalytic degradation process with different radiation fields, contaminant load, and flow velocity. A satisfactory agreement was observed between the model simulations and experimental results, showing a potential for the design and scale-up of the modified photocatalytic reactor.


Application of a user-friendly Brucella-specific IgM and IgG antibody assay for the rapid confirmation of Rose Bengal-positive patients in a hospital in Iran.
The Brucella IgM/IgG flow assay was used for the confirmation of brucellosis in patients from an area endemic for brucellosis and who had a Rose Bengal (RB)-positive serum sample collected at the time of first presentation for diagnosis. The flow assay confirmed the result of the RB test in 46.6% of the positive admission sera, with the majority (62.5%) of the flow assay-positive samples staining moderately strong to very strong (> or =2+). In comparison, Wright and 2-ME at the routinely used cut-off titre values of 1:320 for Wright and 1:160 for 2-ME tested positive in 37.7% of the RB-positive samples. A relatively large number of RB-positive samples agglutinated at or around the cut-off value in the Wright and 2-ME tests and 66.7% of the RB-positive samples tested positive in these confirmatory tests when using one titre step lower threshold values. The relatively high number of samples with low antibody levels supports the argument for testing follow-up samples from patients with an RB-positive sample in order to confirm the diagnosis by showing seroconversion or a rise in antibody levels.


Coomera: a new genus of Fellodistomidae (Digenea) from Monodactylus argenteus (Monodactylidae) of southern Queensland, Australia.
A new genus, Coomera, is erected to accommodate C. brayi new species, here described from the intestine and rectum of Monodactylus argenteus from southern Queensland, Australia. The species is characterised by a single gut caecum, conical pharynx, oblique testes, pars prostatica lined with anucleate vesicles, a large genital atrium, and a large muscular cirrus. Despite the single caecum, C. brayi is not assigned to the Monascinae for the following reasons: the sub-terminal oral sucker opens in a round aperture rather than a medial slit, the ventral sucker is larger than the oral sucker, a pre-pharynx is present, the pharynx is conical rather than elongate and the testes are symmetrical rather than tandem. These character states are shared with the Fellodistominae to which we assign this genus, suggesting that possession of a single caecum is homoplasious within the Fellodistomidae.


Adjuvant whole abdominal radiotherapy in epithelial cancer of the ovary.
To reexamine the use of adjuvant radiotherapy in optimally debulked patients. Between January 1985 and April 1998, 60 patients were treated with adjuvant whole abdominal radiotherapy (A-WART). The stage distribution was Stage IC in 17 patients, Stage II in 9, and Stage III in 34. The grade distribution was Grade 1 in 9 patients, Grade 2 in 27, and Grade 3 in 24; thus, 60% of the patients had Stage III disease and 40% had Grade 3 tumors. After surgery, no residuum was left in 42 (70%), <or=2 cm in 13 (22%), and >2 cm in 5 (8%) of 60 patients. Of the 60 patients, 19 also received platinum-based chemotherapy; in 12 of the 19, the chemotherapy was before A-WART. Thirty-seven of the patients had undergone previous abdominal procedures and a second-look operation was performed in 25% of them. A-WART consisted of 22 Gy in 22 fractions, at 5 fractions weekly in 90% of the patients. The remaining 10% received 25 Gy in 25 fractions within 5 weeks. The A-WART was delivered using a 4-MV linear accelerator. After abdominal irradiation, a boost to the pelvis was given to reach 45 Gy at 1.8 cGy/fraction, using a 4-15-MV linear accelerator. Treatment was delivered in a median of 50 days (range 48-70). In 12 (20%) of the 60 patients, a transient treatment interruption occurred because of acute toxicity, mainly vomiting and diarrhea. The overall survival rate was 55% at 5 years (median follow-up 96.5 months). Patients with low-histologic grade tumors (Grade 1-2) had a better 5-year survival rate (66%) than those with Grade 3 tumors (35%; p <0.03). A tendency for better survival was found for those with Stage I-II than for those with Stage III (69% vs. 43%). Nonetheless, this difference did not reach statistical significance (p = 0.17). For patients receiving chemotherapy, the 5-year survival rate was 51%, not statistically different from the 58% 5-year survival rate observed among those patients without adjuvant chemotherapy (p = 0.9). The abdominal control rate was 83%. Thirty-five percent of the patients sustained acute Grade 2-3 complications. Late complications were observed in 6 of 60 patients, 4 had Grade 3 (7%) and 2 had Grade 4 (3%). Two patients died of intestinal occlusion, both had undergone previous abdominal procedures and in 1, no tumor was found in the abdomen at the postmortem examination. A-WART achieves a quite favorable 5-year survival rate with a low complication rate in properly selected patients. A-WART should be included in the elective postoperative treatment of ovarian cancer patients who are at risk of abdominal failure, and this should be explored in a randomized trial.


Serology-based criteria for adult coeliac disease have excellent accuracy across the range of pre-test probabilities.
The revised paediatric criteria for coeliac disease allow omission of duodenal biopsies in symptomatic children who have specific serology and coeliac disease-associated genetics. It remains unclear whether this approach is also applicable for adults with various clinical presentations. To evaluate the accuracy of serology-based criteria in adults with variable pre-test probabilities for coeliac disease. Three study cohorts comprised adults with high-risk clinical coeliac disease suspicion (n = 421), moderate-risk family members of coeliac disease patients (n = 2357), and low-risk subjects from the general population (n = 2722). Serological and clinical data were collected, and "triple criteria" for coeliac disease comprised transglutaminase 2 antibodies >10× the upper limit of normal, positive endomysium antibodies, and appropriate genetics without requirement of symptoms. The diagnosis was based on intestinal biopsy. The diagnosis of coeliac disease was established in 274 subjects. Of these, 59 high-risk subjects, 17 moderate-risk subjects, and 14 low-risk subjects fulfilled the "triple criteria". All had histologically proven coeliac disease, giving the criteria a positive predictive value of 100%. Altogether, 90 (33%) of all 274 newly diagnosed patients could have avoided biopsy, including 37% among high-risk, 20% among moderate-risk, and 48% among low-risk patients. No histological findings other than coeliac disease were found in the biopsies of "triple positive" subjects. Coeliac disease can reliably and safely be diagnosed without biopsy in adults fulfilling the "triple criteria" regardless of the pre-test probability. Revised criteria would enable the number of endoscopies to be reduced by one-third.


Reduced norepinephrine turnover in interscapular brown adipose tissue of obese rats after ovariectomy.
Norepinephrine (NE) turnover, which is a reliable indicator of sympathetic nervous system (SNS) activity, was measured in the interscapular brown adipose tissue (IBAT), heart, and pancreas of ovariectomized (OVX), sham-operated rats receiving injections of estradiol benzoate (EB). Ovariectomized rats (OVX rats) ate much more than controls and became obese, whereas the administration of EB to obese OVX rats decreased their food intake to the level below that of sham-operated animals and body weight to the level of sham controls. The results from studies using the inhibition of NE biosynthesis with alpha-methyl-p-tyrosine or radiolabeled NE to measure NE turnover significantly demonstrated reductions in SNS activity in IBAT of OVX rats than in sham controls, whereas the injections of EB to OVX rats significantly restored the decrease of NE turnover in IBAT. NE turnover in heart and pancreas were similar in these three groups. It is suggested that reduced NE turnover in IBAT may be a major factor in the development of obesity after ovariectomy (OVX).


Effect of MT1 melatonin receptor deletion on melatonin-mediated phase shift of circadian rhythms in the C57BL/6 mouse.
In the mouse suprachiasmatic nucleus (SCN), melatonin activates MT1 and MT2 G-protein coupled receptors, which are involved primarily in inhibition of neuronal firing and phase shift of circadian rhythms. This study investigated the ability of melatonin to phase shift circadian rhythms in wild type (WT) and MT1 melatonin receptor knockout (KO) C57BL/6 mice. In WT mice, melatonin (90 microg/mouse, s.c.) administered at circadian time 10 (CT10; CT12 onset of activity) significantly phase advanced the onset of the circadian activity rhythm (0.60 +/- 0.09 hr, n = 41) when compared with vehicle treated controls (-0.02 +/- 0.07 hr, n = 28) (P < 0.001). In contrast, C57 MT1KO mice treated with melatonin did not phase shift circadian activity rhythms (-0.10 +/- 0.12 hr, n = 42) when compared with vehicle treated mice (-0.12 +/- 0.07 hr, n = 43). Similarly, in the C57 MT1KO mouse melatonin did not accelerate re-entrainment to a new dark onset after an abrupt advance of the dark cycle. In contrast, melatonin (3 and 10 pm) significantly phase advanced circadian rhythm of neuronal firing in SCN brain slices independent of genotype with an identical maximal shift at 10 pm (C57 WT: 3.61 +/- 0.38 hr, n = 3; C57 MT(1)KO: 3.45 +/- 0.11 hr, n = 4). Taken together, these results suggest that melatonin-mediated phase advances of circadian rhythms of neuronal firing in the SCN in vitro may involve activation of the MT2 receptor while in vivo activation of the MT1 and possibly the MT2 receptor may be necessary for the expression of melatonin-mediated phase shifts of overt circadian activity rhythms.


Ex vivo purging with NK-92 prior to autografting for chronic myelogenous leukemia.
Although controversial, purging of the autograft may be necessary to optimize transplant outcome, especially if better treatments become available to eliminate or control residual disease that may be left after the conditioning regimen. The intent of this study was to show that immunological purging with the cytotoxic cell line NK-92 effectively reduces the number of clonogenic cells and that the method can be performed in compliance with GMP. Owing to the easy quantification of bcr-abl transcripts, chronic myelogenous leukemia (CML) was used as a model disease for proof of principle. A detection level of 10(-7) bcr-abl+ cells and purging efficiency of four logs were achievable for the bcr-abl+ cell line, K562. Leukapheresis products collected from CML patients after stem cell mobilization were then tested. For all patients tested, residual CML cells were highly sensitive to purging by NK-92 with a purging efficacy of several logs. No adverse effect on hematopoietic progenitor cell function was noted. These results demonstrate the efficacy of NK-92 as a purging agent to decrease or eliminate malignant contamination of autologous stem cell grafts and establish proof of principle for ex vivo purging of CML autografts using cytotoxic effector cells.


[The importance of the surgical treatment method in cancer of the oral mucosa with the primary tumor 4 cm in size and larger].
The authors analyze the results of surgical treatment of patients with local disseminated squamous-cell carcinoma of the buccal mucosa. The data on the survival rate of patients treated with different surgical methods are presented and variants of combined operations described.


Age-dependent alterations in mitochondrial enzymes in cortex, striatum and hippocampus of rat brain -- potential role of L-Carnitine.
Mitochondria link the energy -- releasing activities of electron transport and proton pumping with the energy conserving process of oxidative phosphorylation to form ATP. A declined mitochondrial performance has been generally observed during aging. In the present investigation, the activities of tricarboxylic acid cycle enzymes such as isocitrate, alpha-ketoglutarate, succinate and malate dehydrogenases and electron transport complexes I-IV were measured in mitochondria isolated from brain regions like cortex, striatum and hippocampus of young and aged rats before and after L-Carnitine supplementation. All the three brain regions of aged rats showed decreased activities of isocitrate, alpha-ketoglutarate and succinate dehydrogenases, complexes I and IV when compared to control young rats. Striatum seems to be the most susceptible region when compared to hippocampus and cortex. L-Carnitine supplementation to aged rats reversed the activities of these enzymes to near normal whereas treatment to young rats did not show any significant alterations. These results confirm that L-Carnitine can alleviate the age-associated decline in the metabolic efficiency of mitochondria in all three brain regions under investigation.


Degradation of antibiotics, organic matters and ammonia during secondary wastewater treatment using boron-doped diamond electro-oxidation combined with ceramic ultrafiltration.
In this study, a BDD electrolytic oxidation-ceramic membrane ultrafiltration (EO-CM) system for the removals of antibiotics, organic matters and ammonia in wastewater was evaluated. Sulfamethazine (SMZ) was degraded following a pseudo first-order kinetics. The removal rate of SMZ improved with the increase of electro-oxidation time (0-60 min) and current density (5-30 mA/cm2). During the BDD electro-oxidation process, H2O2 and hydroxyl radicals (•OH) were generated which were detected by N, N-diethyl-p-phenylenediamine (DPD) method and electron paramagnetic resonance spectroscopy (EPR), respectively. Chemical oxygen demand (COD) was able to be removed by EO and CM processes, in which proteins and humic acids were regarded as the main removed components measured using excitation-emission matrix (EEM) technique. Moreover, BDD electro-oxidation pretreatment could make the CM process maintain a high water flux and significantly control the membrane fouling and relieve transmembrane pollution. In addition, the removal of ammonia was enhanced with the increase of chloride ions (Cl-) in wastewater during EO process due to the generation of active chlorine (i.e., ClO-, HClO, or Cl2) from the oxidation of Cl-. Chloramine and nitrogen were produced in the oxidation of ammonia by active chlorine. Overall, the results of this study suggest that BDD EO-CM system is a promising process for removing antibiotics, organic matters and ammonia.


ZNF37A promotes tumor metastasis through transcriptional control of THSD4/TGF-β axis in colorectal cancer.
Poorly differentiated colorectal cancer (CRC) is characterized by aggressive invasion and stromal fibroblast activation, which results in rapid progression and poor therapeutic consequences. However, the regulatory mechanism involved remains unclear. Here, we showed that ZNF37A, a member of KRAB-ZFP family, was upregulated in poorly differentiated CRCs and associated with tumor metastasis. ZNF37A enhanced the metastatic potential of multiple CRC cell lines and promoted distant metastasis in an orthotopic CRC model. Further investigation attributed the ZNF37A-exacerbated metastasis to increased extracellular TGF-β and the consequent activation of cancer-associated fibroblasts (CAFs) in tumor microenvironment (TME). Mechanistically, ZNF37A formed a complex with KAP1 and bound to the promoter of THSD4, a TME modulator, to suppress its transcription, which is required for ZNF37A-mediated TGF-β activation and CRC metastasis. Collectively, our study indicates that ZNF37A promotes TGF-β signaling in CRC cells and activates CAFs by transcriptionally repressing THSD4 to drive CRC metastasis, implicating ZNF37A as a potential biomarker for CRC differentiation and progression.


Giant bladder uric acid stone with a history of prolonged sun exposure and high protein diet in North Moluccas: Case series.
Giant bladder uric acid stone cases that have more than 4 cm in diameters and weighing more than 100 g are considered rare. At the end of 2019, two men presented with chronic lower abdominal pain since five years ago. Abdominal radiography found a giant opaque mass inside the bladder. Open suprapubic cystolithotomy was performed by a general surgeon. Both giant bladder stones were extracted and measured approximately 11 × 7 × 6 cm and 500 g in weight. More than 80 % of stone composition was uric acid. Neither of the patients developed severe complications after the procedure. Our patients had a history of prolonged sun exposure related to occupation and high protein intake. Benign prostatic hyperplasia as a major underlying cause for stone formation was not found in the digital rectal examination. Prostatectomy was not performed. Uric acid stone is common in Southeast Asia, with a multifactorial pathogenesis. Open suprapubic cystolithotomy is the best method to extract giant bladder stones in limited settings in the rural areas of Indonesia. It was likely that the most important factors associated with the stone formation were the climate and dietary habits. The findings showed that pathogenesis of bladder stone formation and particularly, uric acid bladder stone is still not clearly understood.


Local feature descriptors based ECG beat classification.
ECG beat type analysis is important in the detection of various heart diseases. The ECG beats give useful information about the status of the monitored heart condition. Up to now, various artificial intelligence-based methods have been proposed for ECG based heart failure detection. These methods were generally based on either time or frequency domain signal processing routines. In this study, we propose a different approach for ECG beat classification. The proposed approach is based on image processing. Thus, the initial step of the proposed work is converting the ECG beat signals to the ECG beat images. To do that, the ECG beat snapshots are initially saved as ECG beat images and then local feature descriptors are considered for feature extraction from ECG beat images. Eight local feature descriptors namely Local Binary Patterns, Frequency Decoded LBP, Quaternionic Local Ranking Binary Pattern, Binary Gabor Pattern, Local Phase Quantization, Binarized Statistical Image Features, CENsus TRansform hISTogram and Pyramid Histogram of Oriented Gradients are considered for feature extraction. The Support Vector Machines (SVM) classifier is used in the classification stage of the study. Linear, Quadratic, Cubic and Gaussian kernel functions are used in the SVM classifier. Five types of ECG beats from the MIT-BIH arrhythmia dataset are considered in experiments and the classification accuracy is used for performance measure. To construct a balanced training and test sets, 5000 and 10,000 ECG beat samples are randomly selected and are used in experiments in tenfold cross-validation fashion. The obtained results show that the proposed method is quite efficient where the calculated accuracy score is 99.9% and the comparisons with the state-of-the-art method show that the proposed method outperforms other methods.


Oxidative DNA damage and antioxidant vitamin level: comparison among lung cancer patients, healthy smokers and nonsmokers.
In the present study, we examined whether the level of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in leukocyte DNA is higher in lung cancer patients compared to controls. Factors that may influence oxidative stress, such as antioxidant vitamins, were also determined. These parameters were analyzed in 4 groups of subjects: smokers with lung cancer, ex-smokers with lung cancer, healthy smokers with comparable smoking status and healthy nonsmokers. The 8-oxodGuo mean level in leukocytes of lung cancer patients reached values of 9.22/10(6) dGuo molecules (smokers) and 11.16/10(6) dGuo molecules (ex-smokers). These values were significantly higher than in DNA of healthy smokers and nonsmokers, where mean levels reached 6.99/10(6) dGuo molecules and 5.98/10(6) dGuo molecules, respectively. Mean levels of vitamin C in the plasma of controls and lung cancer patients were 56.17 microM (nonsmokers), 26.34 microM (healthy smokers), 23.83 microM (cancer patients, smokers) and 29.19 microM (cancer patients, ex-smokers). The difference between nonsmokers and the 3 other groups was statistically significant. Vitamin E level was significantly reduced in the plasma of cancer patients (smokers 19.94 microM, ex-smokers 19.59 microM) compared to healthy smokers (28.93 microM). No changes in vitamin A concentration were found. Our results suggest that a high level of 8-oxodGuo in leukocyte DNA and a low concentration of vitamin E in the blood may predict lung cancer risk. However, it is also possible that these phenomena may simply result from disease development.


Advances in anti-EV-A71 drug development research.
Enterovirus A71 (EV-A71) is capable of causing hand, foot and mouth disease (HFMD), which may lead to neurological sequelae and even death. As EV-A71 is resistant to environmental changes and mutates easily, there is still a lack of effective treatments or globally available vaccines. For more than 50 years since the HFMD epidemic, related drug research has been conducted. Progress in this area can promote the further application of existing potential drugs and develop more efficient and safe antiviral drugs, and provide useful reference for protecting the younger generation and maintaining public health security. At present, researchers have identified hundreds of EV-A71 inhibitors based on screening repurposed drugs, targeted structural design, and rational modification of previously effective drugs as the main development strategies. This review systematically introduces the current potential drugs to inhibit EV-A71 infection, including viral inhibitors targeting key sites such as the viral capsid, RNA-dependent RNA polymerase (RdRp), 2C protein, internal ribosome entry site (IRES), 3C proteinase (3Cpro), and 2A proteinase (2Apro), starting from each stage of the viral life cycle. Meanwhile, the progress of host-targeting antiviral drugs and their development are summarized in terms of regulating host immunity, inhibiting autophagy or apoptosis, and regulating the cellular redox environment. In addition, the current clinical methods for the prevention and treatment of HFMD are summarized and discussed with the aim of providing support and recommendations for the treatment of enterovirus infections including EV-A71.


HIV in Adolescents.
Adolescence is a time of dramatic physical, emotional, cognitive, and social change that brings new vulnerabilities. Youth represent half of all new HIV infections in the United States and the rest of the world. The number of newly infected adolescents who acquire the disease behaviorally and the number of perinatally infected children surviving into adolescence have both contributed to this growth. This article reviews the most recent epidemiology of HIV/AIDS in adolescents, gives guidance on clinical practice, including medical and psychosocial care, and examines prevention issues, including counseling and testing, which are needed to make programs effective for youth.


Mechanism of assembly of G protein betagamma subunits by protein kinase CK2-phosphorylated phosducin-like protein and the cytosolic chaperonin complex.
Phosducin-like protein (PhLP) is a widely expressed binding partner of the G protein betagamma subunit complex (Gbetagamma) that has been recently shown to catalyze the formation of the Gbetagamma dimer from its nascent polypeptides. Phosphorylation of PhLP at one or more of three consecutive serines (Ser-18, Ser-19, and Ser-20) is necessary for Gbetagamma dimer formation and is believed to be mediated by the protein kinase CK2. Moreover, several lines of evidence suggest that the cytosolic chaperonin complex (CCT) may work in concert with PhLP in the Gbetagamma-assembly process. The results reported here delineate a mechanism for Gbetagamma assembly in which a stable ternary complex is formed between PhLP, the nascent Gbeta subunit, and CCT that does not include Ggamma. PhLP phosphorylation permits the release of a PhLP x Gbeta intermediate from CCT, allowing Ggamma to associate with Gbeta in this intermediate complex. Subsequent interaction of Gbetagamma with membranes releases PhLP for another round of assembly.


Liquiritin exhibits anti-acute lung injury activities through suppressing the JNK/Nur77/c-Jun pathway.
Licorice (Glycyrrhiza uralensis Fisch.), a well-known traditional medicine, is traditionally used for the treatment of respiratory disorders, such as cough, sore throat, asthma and bronchitis. We aim to investigate the effects of liquiritin (LQ), the main bioactive compound in licorice against acute lung injury (ALI) and explore the potential mechanism. Lipopolysaccharide (LPS) was used to induce inflammation in RAW264.7 cells and zebrafish. Intratracheal instillation of 3 mg/kg of LPS was used for induction an ALI mice model. The concentrations of IL-6 and TNF-α were tested using the enzyme linked immunosorbent assay. Western blot analysis was used to detect the expression of JNK/Nur77/c-Jun related proteins. Protein levels in bronchoalveolar lavage fluid (BALF) was measured by BCA protein assay. The effect of JNK on Nur77 transcriptional activity was determined by luciferase reporter assay, while electrophoretic mobility shift assay was used to examine the c-Jun DNA binding activity. LQ has significant anti-inflammatory effects in zebrafish and RAW264.7 cells. LQ inhibited the expression levels of p-JNK (Thr183/Tyr185), p-Nur77 (Ser351) and p-c-Jun (Ser63), while elevated the Nur77 expression level. Inhibition of JNK by a specific inhibitor or small interfering RNA enhanced the regulatory effect of LQ on Nur77/c-Jun, while JNK agonist abrogated LQ-mediated effects. Moreover, Nur77-luciferase reporter activity was suppressed after JNK overexpression. The effects of LQ on the expression level of c-Jun and the binding activity of c-Jun with DNA were attenuated after Nur77 siRNA treatment. LQ significantly ameliorated LPS-induced ALI with the reduction of lung water content and BALF protein content, the downregulation of TNF-α and IL-6 levels in lung BALF and the suppression of JNK/Nur77/c-Jun signaling, which can be reversed by a specific JNK agonist. Our results indicated that LQ exerts significant protective effects against LPS-induced inflammation both in vivo and in vitro via suppressing the activation of JNK, and consequently inhibiting the Nur77/c-Jun signaling pathway. Our study suggests that LQ may be a potential therapeutic candidate for ALI and inflammatory disorders.


The cerebellum as a predictor of neural messages--II. Role in motor control and motion sickness.
The hypothesis of a "stable estimator" was proposed in the preceding article as a circuit computing an internal estimate of a body movement variable and endowed with regulating properties. Such a circuit would exist for each variable, and would be embedded in a particular folium of the cerebellar cortex and the related paths of the brainstem nuclei and the inferior olive. In this article, the action of the premotor orders on the stable estimator circuit is studied, at initiation and during execution of voluntary movements. A feedback loop via the cerebellar cortex would control on-going movements and maintain the efficacy of the stabilizing sensorimotor reaction, while preventing its interfering with the movement. The regulating loop via the inferior olive would have a short-term role in initiating movements and would boost insufficient stabilizing reactions. The discrepancy between internal estimates of the same variable would be reflected in motion sickness.


The "Microbiome": A Protagonist in COVID-19 Era.
Respiratory infections are among the main causes of hospitalization and mortality, particularly in elderly patients [...].


DNA barcoding of morphologically characterized mosquitoes belonging to the subfamily Culicinae from Sri Lanka.
Vectors of mosquito-borne diseases in Sri Lanka, except for malaria, belong to the subfamily Culicinae, which includes nearly 84% of the mosquito fauna of the country. Hence, accurate and precise species identification of culicine mosquitoes is a crucial factor in implementing effective vector control strategies. During the present study, a combined effort using morphology and DNA barcoding was made to characterize mosquitoes of the subfamily Culicinae for the first time from nine districts of Sri Lanka. Cytochrome c oxidase subunit 1 (cox1) gene from the mitochondrial genome and the internal transcribed spacer 2 (ITS2) region from the nuclear ribosomal DNA were used for molecular characterization. According to morphological identification, the field collected adult mosquitoes belonged to 5 genera and 14 species, i.e. Aedes aegypti, Ae. albopictus, Ae. pallidostriatus, Aedes sp. 1, Armigeres sp. 1, Culex bitaeniorhynchus, Cx. fuscocephala, Cx. gelidus, Cx. pseudovishnui, Cx. quinquefasciatus, Cx. tritaeniorhynchus, Cx. whitmorei, Mansonia uniformis and Mimomyia chamberlaini. Molecular analyses of 62 cox1 and 36 ITS2 sequences were exclusively comparable with the morphological identifications of all the species except for Ae. pallidostriatus and Aedes sp. 1. Although the species identification of Armigeres sp. 1 specimens using morphological features was not possible during this study, DNA barcodes of the specimens matched 100% with the publicly available Ar. subalbatus sequences, giving their species status. Analysis of all the cox1 sequences (14 clades supported by strong bootstrap value in the Neighbor-Joining tree and interspecific distances of > 3%) showed the presence of 14 different species. This is the first available DNA sequence in the GenBank records for morphologically identified Ae. pallidostriatus. Aedes sp. 1 could not be identified morphologically or by publicly available sequences. Aedes aegypti, Ae. albopictus and all Culex species reported during the current study are vectors of human diseases. All these vector species showed comparatively high diversity. The current study reflects the significance of integrated systematic approach and use of cox1 and ITS genetic markers in mosquito taxonomy. Results of DNA barcoding were comparable with morphological identifications and, more importantly, DNA barcoding could accurately identify the species in the instances where the traditional morphological identification failed due to indistinguishable characters of damaged specimens and the presence of subspecies.


Spontaneous dewetting transitions of droplets during icing & melting cycle.
Anti-icing superhydrophobic surfaces have been a key research topic due to their potential application value in aviation, telecommunication, energy, etc. However, superhydrophobicity is easily lost during icing & melting cycles, where the water-repellent Cassie-Baxter state turns to the sticky Wenzel state. The reversible transition during icing & melting cycle without external assistance is challenging but vital for reliable anti-icing superhydrophobic performance, such a topic has rarely been reported. Here we demonstrate a spontaneous Wenzel to Cassie-Baxter dewetting transition during icing & melting cycle on well-designed superhydrophobic surfaces. Bubbles in ice droplets rapidly impact the micro-nano valleys under Marangoni force, prompting the continuous recovery of air pockets during melting processes. We establish models to confirm the bubbles movement broadens the dewetting conditions greatly and present three criteria for the dewetting transitions. This research deepens the understanding of wettability theory and extends the design of anti-icing superhydrophobic surfaces.


Pediatric teratoma and dermoid cysts.
Teratomas and dermoid cysts are germ cell neoplasms. This article focuses on cervical and craniofacial teratomas. Presentation of these neoplasms varies in degree of severity, from cosmetic deformities to airway distress requiring emergent intervention. Nasal lesions (particularly if suspicious for a nasal dermoid) require imaging before biopsy to assess for intracranial extension. Treatment consists of airway management if respiratory distress is present, and early surgical intervention. Postoperative follow-up is required to monitor for recurrence.


Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB₁ receptor ligand.
To investigate the possible interactions between kavalactone-based molecules and proteins of the endocannabinoid system and provide novel and synthetically accessible structural scaffolds for the design of cannabinoid receptor ligands sharing pharmacological properties with kavapyrones, a preliminary SAR analysis was performed on five commercially available natural kavalactones and nine kavalactone-analogues properly synthesized. These compounds were investigated for assessing their cannabinoid receptor binding affinity and capability of inhibiting the activity of the two major metabolic enzymes of the endocannabinoid system, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Among the molecules tested, only yangonin exhibited affinity for the human recombinant CB₁ receptor with a K(i)=0.72 μM and selectivity vs. the CB₂ receptor (K(i)>10 μM). None of the compounds exhibited strong inhibitory effects on the two enzymes analyzed. The CB₁ receptor affinity of yangonin suggests that the endocannabinoid system might contribute to the complex human psychopharmacology of the traditional kava drink and the anxiolytic preparations obtained from the kava plant.


[Changes in the morphofunctional status of the capillary system of the cerebral cortex in cats exposed to adrenergic stimulation while prostaglandin biosynthesis is inhibited].
Experiments were made in cats to study the morphological and functional state of the capillary system of the brain in response to adrenaline administration and stimulation of the sympathetic cervical nerve under conditions of prostaglandin biosynthesis inhibition. In the presence of indomethacin administration there occurs potentiation of the vasoconstrictor effect of noradrenaline as well as of stimulation of the sympathetic nerve although to a less extent. It is assumed that the effect of exo- and endogenous noradrenaline on cerebral microcirculation is related to a definite measure to prostaglandin endogenous biosynthesis whose inhibition may lead to potentiation of the adrenergic effects thereby creating a risk of cerebrovascular spasms. Evidence for adrenergic control at the level of the capillary system of the cerebral cortex is discussed.


Tissue characterization using R1rho dispersion imaging at low locking fields.
Measurements of the variations of spin-locking relaxation rates (R1ρ) with locking field amplitude allow the derivation of quantitative parameters that describe different dynamic processes, such as slow molecular motions, chemical exchange and diffusion. In some samples, changes in R1ρ values between locking frequency 0 and 200 Hz may be dominated mainly by diffusion of water in intrinsic field gradients, while those at higher locking fields are due to exchange processes. The exchange and diffusion effects act independently of each other, as confirmed by simulation and experimentally. In tissues, the relevant intrinsic field gradients may arise from the magnetic inhomogeneities caused by microvascular blood so that R1ρ dispersion over weak locking field amplitudes (≤ 200 Hz) is affected by changes in capillary density and geometry. Here we first review the theoretical and experimental background to the interpretation of R1ρ dispersions caused by intrinsic magnetic susceptibility variations within the tissue. We then provide new empirical results of R1ρ dispersion imaging of the human brain and skeletal muscle at low locking field amplitudes for the first time and identify potential applications of R1ρ dispersion imaging in clinical studies.


Expression of neurofibromin, the neurofibromatosis 1 gene product: studies in human neuroblastoma cells and rat brain.
Neurofibromatosis type 1 (NF1) is one of the most frequent Mendelian disorders in man and one of the most common autosomal dominant disorders affecting the nervous system. The NF1 gene has recently been cloned, and shows homology to the GTPase activating protein. In order to characterize the NF1 gene product, now called neurofibromin, we raised polyclonal antibodies against C- and N-terminal regions of neurofibromin and analyzed the protein by Western blot analysis and immunohistochemical studies of rat brain.


Aortic stiffness in systemic sclerosis is increased independently of the extent of skin involvement.
To study the stiffness of large arteries in relation to the extent of skin and lung fibrosis, aortic distensibility was examined in patients with diffuse and limited systemic sclerosis (SSc). Consecutive patients (55 with diffuse and 51 with limited SSc) without signs and symptoms of heart failure or a previous history of arterial hypertension underwent echocardiography and lung function tests. Aortic stiffness was determined non-invasively by aortic distensibility and aortic strain measurements in all patients and in 50 healthy subjects, matched for age and gender. Aortic distensibility in patients with either diffuse (2.03 +/- 0.26 x 10(-6) cm(2) dyn(-1)) or limited SSc (2.12 +/- 0.33) was similarly decreased compared with controls (2.49 +/- 0.36, P<0.001). Moreover, aortic strain was significantly reduced in both patient groups compared with controls, confirming that aortic stiffness is increased in SSc independently of the extent of skin involvement. Left ventricular performance was similar between patients and controls, while left ventricular mass and tricuspid systolic gradient were significantly increased in both SSc groups, the latter being associated with aortic stiffness in multivariate analysis. No association with serum levels of C-reactive protein or lung function abnormalities indicative of pulmonary fibrosis were found. Stiffness of the aorta is increased in patients with established SSc regardless of the extent of the inflammatory fibrotic process in the skin and lungs, suggesting that additional pathogenetic mechanisms contribute to the compromise of large arteries.


Education can reassure people with rotator cuff-related shoulder pain: a 3-arm, randomised, online experiment.
We aimed to investigate the immediate effect of best practice education (with and without pain science messages) and structure-focused education on reassurance among people with rotator cuff-related shoulder pain. We conducted a 3-arm, parallel-group, randomised experiment. People with rotator cuff-related shoulder pain were randomised (1:1:1) to (1) best practice education (highlights that most shoulder pain is not serious or a good indicator of tissue damage and recommends simple self-management strategies); (2) best practice education plus pain science messages (which attempt to improve understanding of pain); and (3) structure-focused education (highlighting that structural changes are responsible for pain and should be targeted with treatment). Coprimary outcomes were self-reported reassurance that no serious condition is causing their pain and continuing with daily activities is safe. Secondary outcomes measured management intentions, credibility and relevance of the education, and similarity to previous education. Two thousand two hundred thirty-seven participants were randomised and provided primary outcome data. Best practice education increased reassurance that no serious condition is causing their pain (estimated mean effect 0.5 on a 0-10 scale, 95% confidence interval [CI] 0.2-0.7) and continuing with daily activities is safe (0.6, 95% CI 0.3-0.8) compared with structure-focused education. Adding pain science messages to best practice education slightly increased both measures of reassurance (0.2, 95% CI 0.0-0.4). Clinicians treating patients with rotator cuff-related shoulder pain should highlight that most shoulder pain is not serious or a good indicator of tissue damage and recommend simple self-management strategies. The benefit of adding pain science messages is small.


Predicting factors for progression of the myopia in the MiSight assessment study Spain (MASS).
To investigate which baseline factors are predictive for success in controlling myopia progression in a group of children wearing MiSight Contact Lens (CLs). Myopic patients (n=41) fitted with MiSight CLs and followed up two years were included in this study. Bivariate analysis, a logistic regression analysis (LG) and a decision tree (DT) approach were used to screen for the factors influencing the success of the treatment. To assess the response, axial length (AL) changes were considered as main variable. Patients were classified based on a specific range of change of axial length at the end of each year of treatment as "responders" (R) (AL change <0.11mm/per year) and "non-responders" (NR) (AL change ≥0.11mm/per year). Of a total of forty-one Caucasian patients treated with MiSight CLs, 21 and 16 were considered responders in the first and the second year of follow-up, respectively. LG analysis showed that the only factor associated with smaller axial length growth was more time spent outdoors (p=0.0079) in the first year of treatment. The decision tree analysis showed that in the responding group spending more than 3 and 4h outdoors per week was associated with the best response in the first year and in the second year of treatment respectively. The LR and the DT approach of this pilot study identifies time spent outdoors as a main factor in controlling axial eye growth in children treated with MiSight CLs.


Recent advances in pre-clinical diagnosis of Alzheimer's disease.
Alzheimer's disease (AD) is the most common dementia with currently no known cures or disease modifying treatments (DMTs), despite much time and effort from the field. Diagnosis and intervention of AD during the early pre-symptomatic phase of the disease is thought to be a more effective strategy. Therefore, the detection of biomarkers has emerged as a critical tool for monitoring the effect of new AD therapies, as well as identifying patients most likely to respond to treatment. The establishment of the amyloid/tau/neurodegeneration (A/T/N) framework in 2018 has codified the contexts of use of AD biomarkers in neuroimaging and bodily fluids for research and diagnostic purposes. Furthermore, a renewed drive for novel AD biomarkers and innovative methods of detection has emerged with the goals of adding additional insight to disease progression and discovery of new therapeutic targets. The use of biomarkers has accelerated the development of AD drugs and will bring new therapies to patients in need. This review highlights recent methods utilized to diagnose antemortem AD.