A novel approach for estimating ingested dose associated with paracetamol overdose.
In cases of paracetamol (acetaminophen, APAP) overdose, an accurate estimate of tissue-specific paracetamol pharmacokinetics (PK) and ingested dose can offer health care providers important information for the individualized treatment and follow-up of affected patients. Here a novel methodology is presented to make such estimates using a standard serum paracetamol measurement and a computational framework. The core component of the computational framework was a physiologically-based pharmacokinetic (PBPK) model developed and evaluated using an extensive set of human PK data. Bayesian inference was used for parameter and dose estimation, allowing the incorporation of inter-study variability, and facilitating the calculation of uncertainty in model outputs. Simulations of paracetamol time course concentrations in the blood were in close agreement with experimental data under a wide range of dosing conditions. Also, predictions of administered dose showed good agreement with a large collection of clinical and emergency setting PK data over a broad dose range. In addition to dose estimation, the platform was applied for the determination of optimal blood sampling times for dose reconstruction and quantitation of the potential role of paracetamol conjugate measurement on dose estimation. Current therapies for paracetamol overdose rely on a generic methodology involving the use of a clinical nomogram. By using the computational framework developed in this study, serum sample data, and the individual patient's anthropometric and physiological information, personalized serum and liver pharmacokinetic profiles and dose estimate could be generated to help inform an individualized overdose treatment and follow-up plan.


Expression of Osteoprotegrin Is Enhanced in Lung Cancer Tissues and Promotes Aggressive Cellular Traits in H3122 Lung Cancer Cells.
Osteoprotegrin (OPG), a secreted protein and a member of the tumor necrosis factor receptor superfamily has been well-characterized and is an important regulator of bone remodeling by blocking osteoclast maturation thus preventing osteolysis. In recent years, OPG has been reported to have an association with the malignant capacity of various cancer types and cancer-associated bone metastasis, although the mechanisms of this are not clearly understood. In this study, OPG expression was analyzed in human lung cancer tissue and normal tissue based on the dataset of The Cancer Genome Atlas and Oncomine. The in vitro effect of OPG on H3122 lung cancer cells was also assessed by characterizing cell function following knock-down and forced overexpression in this cell line. The expression of OPG was significantly increased in lung cancer tissues compared to the normal control group and OPG promoted the malignant phenotypes of H3122 cells in in vitro models. OPG may be a potential driver of lung cancer cells and therefore might have potential in therapy and diagnostics.


The cross-cultural adaptation, validity, and reliability of the Spanish version of the Fremantle Back Awareness Questionnaire.
In chronic low back pain (CLBP), disturbed body image has been highlighted as a contributor to the condition and a potential target for treatment. The Fremantle Back Awareness Questionnaire (FreBAQ) allows its assessment. Following international guidelines for the cross-cultural translation of questionnaires, we aimed to translate the FreBAQ into Spanish (FreBAQ-S) and validate the new questionnaire in a sample of Spanish-speaking people with CLBP. Two hundred and sixty-four adults with CLBP (91 males) and 128 healthy controls (34 males) completed an online form including the FreBAQ-S and questionnaires related to the pain experience. All participants were Spanish and no gender identities differing from biological sex were reported. A week later, 113 CLBP participants and 45 healthy controls (41 and 13 males, respectively), re-answered the FreBAQ-S to evaluate test-retest reliability. Confirmatory factor and multigroup analysis assessed the scale consistency on the patient sample. Discriminant and convergent validity were explored by between-group differences and the relationship with clinical characteristics. Reliability relied on Cronbach's alpha estimates and test-retest (intraclass correlation coefficient, standard error of measurement, minimal detectable change). Confirmatory factor analysis showed a one-factor structure of the questionnaire, without supporting evidence for item deletion (CFI = 0.97; TLI = 0.96; RMSEA = 0.06; SRMR = 0.07; SRMRu = 0.064). Multigroup analyses do not support mean invariance between groups regarding health condition or sex. The FreBAQ-S demonstrated good discriminant and convergent validity, internal consistency (α = 0.82), and test-retest reliability (ICC = 0.78; SE = 3.41; MDC = 5.12). The FreBAQ-S is a valid and reliable tool to assess back awareness in clinical and non-clinical samples.


Normalisation theory: Does it accurately describe temporal changes in adolescent drunkenness and smoking?
The multiple risk model postulates that accumulating risk factors increase adolescent drunkenness and smoking. The normalisation theory adds to this by arguing that the relation between accumulative risk and drunkenness and smoking is dependent on the distribution of these behaviours in the larger population. More concretely, normalisation theory predicts that: (i) when population level use increases, low risk adolescents will be more likely to use alcohol and cigarettes; and (ii) adolescents facing multiple risk factors will be equally likely to use alcohol and cigarettes, regardless of trends in population level use. The current study empirically tests these assumptions on five waves of nationally representative samples of Israeli Jewish youth. Five cross-sectional waves of data from the Israeli Health Behaviour in School-aged Children survey for Jewish 10th graders were used. Logistic regression models measured the impact of changes in population level use across waves on drunkenness and smoking, and their association with differing levels of risk factors. Between zero and two risk factors, the risk of drunkenness and smoking increases for each additional risk factor. When reaching two risk factors, added risk does not significantly increase the likelihood of smoking and drunkenness. Changes in population level drunkenness and smoking did not systematically relate to changes in the individual level relationship between risk factors and smoking and drunkenness. The pattern of results in this study provides strong evidence for the multiple risk factor model and inconsistent evidence for the normalisation theory. [Sznitman SR, Zlotnick C, Harel-Fisch Y. Normalisation theory: Does it accurately describe temporal changes in adolescent drunkenness and smoking? Drug Alcohol Rev 2016;35:424-432].


Multicomponent Cascade Reaction of 3-Formylchromones: Highly Selective Synthesis of Functionalized 9-Azabicyclo[3.3.1]nonane Derivatives.
A novel protocol for the preparation of functionalized 9-azabicyclo[3.3.1]nonane (ABCN) derivatives from 3-formylchromones, enaminones, and heterocyclic ketene aminals (HKAs) through an unprecedented cascade reaction has been developed by simply refluxing the mixture of the substrates 1-3. As a result, a series of ABCNs were produced through a very complex cascade reaction. This protocol can be used in the synthesis of ABCNs that are suitable for combinatorial and parallel syntheses of ABCN natural-like products in a one-pot reaction.


Preparation of frozen reference sera and examples of applications.
We describe procedures for preparation of human serum from ACD bank blood and bovine serum from slaughter house blood. Preparation techniques including filtration and dialysis are described in detail as well as how to obtain desired concentrations. Special attention has been drawn to procedures yielding low lactate dehydrogenase activity. Long-term storage should take place at -75 degrees C. Different frozen reference sera have been used for calibration purposes, internal quality control and external quality assessment.


MicroRNA-145 Increases the Apoptosis of Activated Hepatic Stellate Cells Induced by TRAIL through NF-κB Signaling Pathway.
During the liver fibrosis recovery stage tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can effectively induce apoptosis of activated hepatic stellate cells (HSCs). Normal hepatic stellate cells are resistant to TRAIL cytotoxicity. Therefore, enhancing the sensitivity of TRAIL-induced apoptosis of HSCs may be useful to treat hepatic fibrogenesis. Here, we demonstrated that miR-145 and TRAIL were down-regulated in both liver fibrosis tissue samples and transforming growth factor-β1 induced HSCs, concomitant with increased the expression of ZEB2. In addition, we found that mimics-mediated over-expression of miR-145 led to resistance to the ZEB2 expression and up-regulation of the TRAIL-induced apoptosis after treatment of LX-2 cells with TRAIL. Furthermore, ZEB2-siRNA transfected LX-2 cells showed the increased sensitivity to TRAIL-induced apoptosis. Whereas, opposite results were obtained in miR-145-inhibitor group or ZEB2 plasmid group. Moreover, miR-145 regulated ZEB2 gene expression by specifically interacting with the 3'-UTR of ZEB2 mRNA to inhibit the expression of ZEB2. Further studies showed that the over-expression of ZEB2 could inhibit TRAIL-induced apoptosis via inhibiting nuclear factor-κB (NF-κB) signaling pathway in LX-2 cells. Collectively, our data suggest that up-regulation of miR-145 can down-regulate ZEB2 expression, consequently promoting TRAIL-induced apoptosis in LX-2 cells through NF-κB signaling pathway, which facilitates the resolution of liver fibrosis.


The prognostic significance of trisomy 8 in patients with acute myeloid leukemia.
Recent therapeutic outcomes for patients with acute myeloid leukemia and trisomy 8 (+8) who were seen at our institution were investigated. Complete remission was achieved in 85% with isolated +8, 100% with +8 and chromosomal abnormalities predictive of a favorable outcome, and 47% of patients with +8 and other, mostly complex chromosomal abnormalities. Median relapse-free and overall survivals in months were 5.5 and 12 (isolated +8), 20 and 25 (+8 and favorable karyotype), and 7.5 and 6 (+8 and unfavorable karyotype). Despite an encouraging rate of complete remission, the relapse-free and overall survivals for patients with isolated +8 were not significantly different from those of patients with +8 and unfavorable karyotypes. The presence of +8 did not appear to adversely affect the outcome of patients with favorable karyotypes.


[Enzootic nasal adenocarcinoma in a dairy sheep flock].
In a herd of dairy sheep several losses occurred due to a respiratory syndrome in combination with progressive wasting. Clinical and pathomorphological diagnostics of 3 sheep revealed the presence of cancerous masses in the nasal cavities. These neoplasms were identified as adenocarcinomas originating from the nasal mucosa. Etiologically, they were attributed to JRSV (Jaagsiekte Sheep Retrovirus) by detection of capsid protein 24 in western blot. The significance of the disease in Switzerland is discussed, also in the context of lung adenomatosis.


Genomic potential for polysaccharide deconstruction in bacteria.
Glycoside hydrolases are important enzymes that support bacterial growth by enabling the degradation of polysaccharides (e.g., starch, cellulose, xylan, and chitin) in the environment. Presently, little is known about the overall phylogenetic distribution of the genomic potential to degrade these polysaccharides in bacteria. However, knowing the phylogenetic breadth of these traits may help us predict the overall polysaccharide processing in environmental microbial communities. In order to address this, we identified and analyzed the distribution of 392,166 enzyme genes derived from 53 glycoside hydrolase families in 8,133 sequenced bacterial genomes. Enzymes for oligosaccharides and starch/glycogen were observed in most taxonomic groups, whereas glycoside hydrolases for structural polymers (i.e., cellulose, xylan, and chitin) were observed in clusters of relatives at taxonomic levels ranging from species to genus as determined by consenTRAIT. The potential for starch and glycogen processing, as well as oligosaccharide processing, was observed in 85% of the strains, whereas 65% possessed enzymes to degrade some structural polysaccharides (i.e., cellulose, xylan, or chitin). Potential degraders targeting one, two, and three structural polysaccharides accounted for 22.6, 32.9, and 9.3% of genomes analyzed, respectively. Finally, potential degraders targeting multiple structural polysaccharides displayed increased potential for oligosaccharide deconstruction. This study provides a framework for linking the potential for polymer deconstruction with phylogeny in complex microbial assemblages.


Congruence of Holland's theory of vocational and work environments with GPA of college students in the United Arab Emirates.
Holland's theory of vocational personalities and work environment, extended to educational environments, was used as a theoretical framework for the study of the relation of congruence and sex on self-reported GPA. 617 students at Ajman University of Science and Technology responded to the Vocational Preference Inventory. Analysis of variance indicated that students' congruence and sex were significant predictors of GPA and the interaction of GPA and sex. Associations of sex with congruence and with Academic Environment were significant, represented by choice of major. Implications of the findings were discussed.


Orthologues of Bacillus subtilis Spore Crust Proteins Have a Structural Role in the Bacillus megaterium QM B1551 Spore Exosporium.
The exosporium of Bacillus megaterium QM B1551 spores is morphologically distinct from exosporia observed for the spores of many other species. Previous work has demonstrated that unidentified genes carried on one of the large indigenous plasmids are required for the assembly of the Bacillus megaterium exosporium. Here, we provide evidence that pBM600-encoded orthologues of the Bacillus subtilis CotW and CotX proteins, which form the crust layer in spores of that species, are structural components of the Bacillus megaterium QM B1551 spore exosporium. The introduction of plasmid-borne cotW and orthologous cotX genes to the PV361 strain, which lacks all indigenous plasmids and produces spores that are devoid of an exosporium, results in the development of spores with a rudimentary exosporium-type structure. Additionally, purified recombinant CotW protein is shown to assemble at the air-water interface to form thin sheets of material, which is consistent with the idea that this protein may form a basal layer in the Bacillus megaterium QM B1551 exosporium.IMPORTANCE When starved of nutrients, some bacterial species develop metabolically dormant spores that can persist in a viable state in the environment for several years. The outermost layers of spores are of particular interest since (i) these represent the primary site for interaction with the environment and (ii) the protein constituents may have biotechnological applications. The outermost layer, or exosporium, in Bacillus megaterium QM B1551 spores is of interest, as it is morphologically distinct from the exosporia of spores of the pathogenic Bacillus cereus family. In this work, we provide evidence that structurally important protein constituents of the Bacillus megaterium exosporium are different from those in the Bacillus cereus family. We also show that one of these proteins, when purified, can assemble to form sheets of exosporium-like material. This is significant, as it indicates that spore-forming bacteria employ different proteins and mechanisms of assembly to construct their external layers.


[Ruptured aneurysm at the anomalous arterial wall of the distal anterior inferior cerebellar artery: a case report].
Distal anterior inferior cerebellar artery(AICA)aneurysms are rare, so its pathogenesis and treatment remain controversial. Here, we report the unique pathogenesis of a ruptured aneurysm in this area that was based on anomalous components as well as partial dissection of the arterial wall. A 61-year-old woman presented to our hospital with sudden headache and nausea. On admission, neurological examination revealed slight consciousness disturbance. Computed tomography(CT)of the head showed a clotted subarachnoid hemorrhage(SAH)that was dominant in the right cerebellopontine and prepontine cistern. Three-dimensional CT angiography detected an irregular fusiform aneurysm 4.5×3.2mm in size in the distal portion of the AICA. The patient underwent trapping without distal vascular reconstruction by the lateral suboccipital approach. After surgery, she experienced right hearing disturbance and ipsilateral facial palsy that were considered to be caused by vasogenic edema at the cerebellar peduncle that resulted from the initial SAH damage. Pathology revealed an aneurysmal wall with anomalous components and arterial dissection in the arterial wall. To our knowledge, only one article has reported the histological findings of a distal AICA aneurysm. Based on the pathology of this case, these findings may suggest a useful treatment strategy for this rare aneurysm.


Evaluation of efficacy and safety of lubiprostone in patients with chronic constipation.
Lubiprostone is an apical type 2 chloride channel activator approved for the treatment of chronic constipation (CC), and nausea is the most common adverse symptom. However, the associated factors with the efficacy and the precise mechanism of nausea remain unclear. The aim of this study is to characterize clinical backgrounds related with the efficacy and the adverse symptoms of lubiprostone. Subjects were patients with CC who were prescribed lubiprostone from April 2017 to October 2019. The efficacy and safety of lubiprostone were retrospectively examined using the electronic medical record. Hundred and fifty-five patients (76 men, and mean age 69) were evaluated. Lubiprostone was effective in 74 patients (47.8%), and the discontinuation due to adverse in 34 patients (21.9%). including nausea, diarrhea and abdominal pain in 16, 12 and 3 patients, respectively. The efficacy was significantly associated with gender, age, body mass index (BMI), diabetes mellitus, hypertension, calcium channel blockers and antipsychotics. In multivariate analysis, the efficacy was significantly associated with men (odds ratio [OR], 3.21; 95% confidence interval (CI), 1.42-7.27) and BMI (OR, 1.14; 95% CI, 1.02-1.28). The incidence of nausea was higher in patients under 65 years old, and hypertension was the significant protective factor for nausea. Lubiprostone was effective for men patients with CC, and hypertension seems to be the protective factor for nausea.


Long-term outcomes after percutaneous patent foramen ovale closure.
Percutaneous patent foramen ovale (PFO) closure is a treatment for cryptogenic stroke and migraine headache. The goal of this study was to assess long-term outcomes of patients treated with percutaneous PFO closure. Records of patients with percutaneous PFO closure at Emory University Hospital from February 2002 to July 2009 were reviewed. Follow-up telephone questionnaire and chart review assessed recurrent stroke, migraine, and complications. Data was reviewed on 414 consecutive patients. Long-term follow-up was obtained in 207 of patients, and mean follow up was 4.6 ± 2.0 years. Cryptogenic stroke was the primary indication for intervention in 193 (93%) patients. Thirteen (7%) patients had a recurrent neurologic event post closure. In patients with multiple neurological events at baseline, 17% (n = 11) had a recurrent event, compared with 2% (n = 2) of patients with a single neurological event prior to PFO-closure (P < 0.002). Post closure, migraine frequency and severity declined from 4.5 to 1.1 migraine/month (P < 0.01) and 7.2 to 3.6 out of 10 (P < 0.01) in patients with history of migraine (n = 60). Thirty-day mortality was 1% (n = 2). One patient had device erosion 5 years post-procedure requiring emergent surgery. Atrial fibrillation was newly diagnosed in 8 (4%) patients within 6 months. In conclusion, the long-term rate of recurrent stroke after PFO closure is low in patients with a single neurological event at baseline. Serious long-term complications after PFO closure are rare. PFO closure may decrease the frequency and severity of migraine.


Method for Classifying Schizophrenia Patients Based on Machine Learning.
Schizophrenia is a chronic and severe mental disorder that affects individuals in various ways, particularly in their ability to perceive, process, and respond to stimuli. This condition has a significant impact on a considerable number of individuals. Consequently, the study, analysis, and characterization of this pathology are of paramount importance. Electroencephalography (EEG) is frequently utilized in the diagnostic assessment of various brain disorders due to its non-intrusiveness, excellent resolution and ease of placement. However, the manual analysis of electroencephalogram (EEG) recordings can be a complex and time-consuming task for healthcare professionals. Therefore, the automated analysis of EEG recordings can help alleviate the burden on doctors and provide valuable insights to support clinical diagnosis. Many studies are working along these lines. In this research paper, the authors propose a machine learning (ML) method based on the eXtreme Gradient Boosting (XGB) algorithm for analyzing EEG signals. The study compares the performance of the proposed XGB-based approach with four other supervised ML systems. According to the results, the proposed XGB-based method demonstrates superior performance, with an AUC value of 0.94 and an accuracy value of 0.94, surpassing the other compared methods. The implemented system exhibits high accuracy and robustness in accurately classifying schizophrenia patients based on EEG recordings. This method holds the potential to be implemented as a valuable complementary tool for clinical use in hospitals, supporting clinicians in their clinical diagnosis of schizophrenia.


Comparison of different fluorescence spectrum analysis techniques to characterize humification levels of waste-derived dissolved organic matter.
In the present work, the humification level of waste-derived dissolved organic matter (DOM) at different waste biostability was investigated, by using fluorescent excitation-emission matrix (EEM) scanning. Different fluorescence spectrum analysis techniques were applied and compared. Experimental results demonstrate that parallel factor (PARAFAC) analysis was sensitive to reflect DOM humification, and the most reasonable to deconstruct DOM compositions, when compared with other spectrum analysis techniques. It suggests applying the DOM-EEM-PARAFAC pipeline for rapid estimation of waste biostability.


Ultrafast and Cost-Effective Pathogen Identification and Resistance Gene Detection in a Clinical Setting Using Nanopore Flongle Sequencing.
Rapid bacterial identification and antimicrobial resistance gene (ARG) detection are crucial for fast optimization of antibiotic treatment, especially for septic patients where each hour of delayed antibiotic prescription might have lethal consequences. This work investigates whether the Oxford Nanopore Technology's (ONT) Flongle sequencing platform is suitable for real-time sequencing directly from blood cultures to identify bacteria and detect resistance-encoding genes. For the analysis, we used pure bacterial cultures of four clinical isolates of Escherichia coli and Klebsiella pneumoniae and two blood samples spiked with either E. coli or K. pneumoniae that had been cultured overnight. We sequenced both the whole genome and plasmids isolated from these bacteria using two different sequencing kits. Generally, Flongle data allow rapid bacterial ID and resistome detection based on the first 1,000-3,000 generated sequences (10 min to 3 h from the sequencing start), albeit ARG variant identification did not always correspond to ONT MinION and Illumina sequencing-based data. Flongle data are sufficient for 99.9% genome coverage within at most 20,000 (clinical isolates) or 50,000 (positive blood cultures) sequences generated. The SQK-LSK110 Ligation kit resulted in higher genome coverage and more accurate bacterial identification than the SQK-RBK004 Rapid Barcode kit.


Nosocomial Infection Agents of Şişli Hamidiye Etfal Training and Research Hospital: Comparison of 1995 and 2017 Data.
Healthcare-associated infections (HCAI), which are important causes of mortality and morbidity, are high cost but preventable infections. This study aimed to determine hospital infections and isolates in Şişli Hamidiye Etfal Training and Hospital and to determine our local data. The changes in the distribution of the isolates in this process were evaluated by comparing the data of 1995 and today. Materials sent to the microbiology laboratory of our hospital in 1995 and 2017 from the patients hospitalized in the period between June 1-December 31 were evaluated concerning hospital infection. The standard manual methods were used in 1995, while in 2017, MALDI-TOF MS was used for identification and BD Phoenix automated system for antibiotic susceptibility. In 1995, in total, 100 bacteria were isolated from pediatric and adult patients, of which 48 Pseudomonas aeruginosa (48/100), 37 Klebsiella spp (37/100). In 2017, Acinetobacter baumannii causing an important resistance problem was found to be increased in number. The main hospital infection causes were Acinetobacter baumannii (37/179), Klebsiella spp (41/179). In 2017, bacterial diversity was also increased. Isolated strains, as in the past, are gram-negative bacteria, Pseudomonas spp decreased in 2017, and Acinetobacter spp increased. The findings suggest that the automated systems used in microbiology laboratories may have a role in the detection of bacterial diversity.


Expression of osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) in HCC70 breast cancer cells and effects of treatment with gonadotropin-releasing hormone on RANKL expression.
The majority of human breast cancers and in addition most breast-cancer cell lines express gonadotropin-releasing hormone (GnRH) receptors. Their proliferation and in addition their bone-directed invasion is time- and dose-dependently reduced by GnRH. Osteolytic metastases are characteristic for breast cancer-derived metastasis. Since the osteolytic activity depends on the receptor activator of nuclear factor-kappaB (NFkappaB) ligand (RANKL)/osteoprotegerin (OPG) ratio, we analyzed RANKL and OPG expression in different breast-cancer cell lines. Different human breast-cancer cell lines were tested for expression of GnRH receptor, OPG and RANKL. Using a co-culture system of breast-cancer cell lines and human primary osteoblasts (hOB), we analyzed the expression of OPG and RANKL in the GnRH receptor-positive breast-cancer cell line HCC70 co-cultured with or without hOB. In addition, we assessed the effects of GnRH analog treatment on OPG and RANKL mRNA and protein levels. All tested breast-cancer cell lines were GnRH receptor-positive. The majority of these cell lines expressed OPG but not RANKL. The HCC70 breast-cancer cell line derived from an invasive ductal carcinoma with metastases was positive for both OPG and RANKL. The expression of RANKL by HCC70 cells was increased when co-cultured with hOB. Treatment with GnRH analogs reduced the expression of RANKL by HCC70 cells co-cultured with hOB. No effects were observed on breast cancer OPG expression. These data show that the majority of human breast-cancer cell lines express OPG but not RANKL. The HCC70 breast-cancer cell line is RANKL-positive. Co-culture of HCC70 breast cancer cells with hOB increases RANKL expression. Activation of tumor GnRH receptors reduces RANKL expression. These experiments demonstrate that HCC70 breast cancer cells are able to activate osteoclasts directly via RANKL. The interaction between HCC70 breast cancer cells and osteoblasts induces osteoclastogenesis through an increase of RANKL expression. GnRH seems to play an important role by modulating the RANKL expression in HCC70 breast cancer cells.


Sphingosine-1-phosphate receptor 2 modulates pain sensitivity by suppressing the ROS-RUNX3 pathway in a rat model of neuropathy.
Neuropathic pain correlates with a lesion or other dysfunction in the nervous system. Sphingosine-1-phosphate receptor 2 (S1P2) is expressed in the central nervous system and modulates synaptic plasticity. The present study aimed to investigate the role of S1P2 in neuropathic pain caused by chronic constriction injury (CCI). Sprague-Dawley rats were allocated into eight groups (n = 15 for each group): sham, CCI, CCI + green fluorescent protein, CCI + S1P2, CCI + Ctrl-short hairpin RNA (shRNA), CCI + S1P2 shRNA, CCI + S1P2 + CYM-5442, and CCI + S1P2 shRNA + CYM-5442. The CCI model was established via sciatic nerve ligation. S1P2 was overexpressed or knocked down by intrathecal injection of adeno-associated virus-S1P2 (AAV-S1P2) or AAV-S1P2 shRNA. The S1P1 agonist, CYM-5442 (1 mg/kg), was injected intraperitoneally after surgery. S1P2 expression, pain thresholds, apoptosis signaling, inflammation, and oxidative stress in rats were then examined. We found that sciatic nerve injury downregulated S1P2 expression in the spinal cords of rats. S1P2 overexpression enhanced pain thresholds. In contrast, S1P2 knockdown decreased pain thresholds in rats exposed to CCI. CCI and S1P2 silencing increased secretion of interleukin-1β (IL-1β), IL-6, and CCL2, whereas S1P2 overexpression decreased. S1P2 impeded CCI-induced reactive oxygen species (ROS) production and runt-related transcription factors 3 (RUNX3) downregulation, and S1P2 knockdown had the opposite effect. S1P2 overexpression suppressed Bax and active caspase 3 expression and promoted Bcl-2 expression, whereas loss of S1P2 reversed their expression. Additionally, S1P1 activation counteracted the effect of S1P2 on pain sensitivity. In conclusion, S1P2 is downregulated in CCI rats and may help modulate neuropathic pain via the ROS/RUNX3 pathway.


Cerebral Oximetry Use For Cardiac Surgery.
Studies have shown maintaining good cerebral perfusion during Cardiac Surgeries is very important in terms of patient outcomes and reducing the hospital stay, which may have its financial and clinical implications. The aim of this review study was to determine the effectiveness of Cerebral Oximetry (Transcranial Near-Infrared Spectroscopy-NIRS to monitor cerebral oxygenation) for Cardiac Surgery and to propose a possible concluding remark about its potential applications, overall clinical value and whether to keep using it or not. Medical database and archives including Pubmed, Embase, index medicus, index copernicus and Medline were searched. Different papers were looked upon and each had an argument, scientific evidence and background. Fifteen research papers were selected and brought under review after carefully consideration. The papers were carefully reviewed and findings were given in favour of not using NIRS technique for Cerebral Oximetry in Cardiac Surgery. This can rightly be concluded from this study that NIRS Cerebral Oximetry does not carry the clinical significance and relevance which was previously thought. The subject under observation needs further studies and research to evaluate the effectiveness of the Cerebral Oximetry Use for Cardiac Surgery.


Knowledge, attitude, and practices among Iranian neurologists toward evidence-based medicine.
Background: Evidence-based medicine (EBM) is a current practice in medicine to produce clinical practice guidelines from well-designed, randomized, controlled trials. We studied knowledge, attitude, and practice of EBM of neurologists who participated in the Iranian congress of neurology. Methods: A self-administered anonymous questionnaire was distributed and filled by neurologists. Results: A total of 200 neurologists were randomly sampled and with response rate of 56%. 33.9% of responder had previously participated in EBM courses. The average total knowledge score was 4.05 ± 0.80 out of a maximum possible score of 5.0. Textbooks were still the most favorite source of knowledge for our neurologists. A lack of time was the highest, and motivation the least mentioned barrier in using EBM. Conclusion: Overall, the Iranian neurologist had acceptable knowledge and attitude toward EBM and had same similar as found in other studies.


Mesoporous zeolite-chitosan composite for enhanced capture and catalytic activity in chemical fixation of CO2.
Carbon dioxide is one of the greenhouse gases whose increasing concentration in the atmosphere can cause severe problems to both human health and wildlife. A simple ecofriendly procedure was developed to prepare zeolite-chitosan (ZY-CS) composite using solvent exchange followed by calcination for adsorption and chemical fixation of CO2. The as synthesized ZY-CS composite along with zeolite and chitosan were characterized by attenuated total reflection infrared, X-ray diffraction, thermogravimetric, scanning electron microscopy, high-resolution transmission electron microscopy and nitrogen adsorption-desorption isotherms studies. The ZY-CS composite showed enhanced CO2 adsorption capacity compared with pure zeolite and chitosan. The composites also exhibited significant catalytic activity in the chemical fixation of CO2 into cyclic carbonates. This work is foreshadowing the prospect of ZY-CS composite in enhanced capture and catalytic activity in chemical fixation of CO2 for environmental applications.


Distribution and Activity of Mitochondrial Proteins in Vascular and Avascular Retinas: Implications for Retinal Metabolism.
Understanding the energetics of retinal neurons and glia is crucial for developing therapies for diseases that feature deficits in nutrient or oxygen availability. Herein, we performed a detailed characterization of the distribution and activity of mitochondrial proteins in the vascularized retinas of rat and marmoset, and the avascular retinas of rabbit and guinea pig. Further, we delineated expression of ubiquitous mitochondrial creatine kinase (uMtCK). Expression of eight mitochondrial proteins was investigated using Western blotting, single- and double-labeling immunohistochemistry. Activities of cytochrome c oxidase, succinate dehydrgogenase, and isocitrate dehydrogenase were determined by enzyme histochemistry using unfixed tissue sections. In vascularized retinas, immunoreactivities were characterized by strong, punctate labeling in the plexiform layers, photoreceptor inner segments, somas of various cell types, notably retinal ganglion cells (RGCs), and the basolateral surface of the retinal pigment epithelium. In avascular retinas, immunoreactivities featured intense labeling of inner segments, together with weak, but unambiguous, staining of both plexiform layers. RGCs were relatively enriched. In Müller cells of avascular retinas, mitochondria were restricted to scleral-end processes. For each species, enzyme activity assays yielded similar results to the protein distributions. Labeling for uMtCK in vascular and avascular retinas was fundamentally similar, being restricted to neuronal populations, most notably inner segments and RGCs. Of all of the mitochondrial proteins, uMtCK displayed the strongest labeling in avascular retinas. uMtCK was not detectable in Müller cells in any species. The current findings advance our understanding of the metabolic similarities and differences between vascular and avascular retinas.


Acoustic Möbius Insulators from Projective Symmetry.
In the presence of gauge symmetry, common but not limited to artificial crystals, the algebraic structure of crystalline symmetries needs to be projectively represented, giving rise to unprecedented topological physics. Here, we demonstrate this novel idea by exploiting a projective translation symmetry and constructing a variety of Möbius-twisted topological phases. Experimentally, we realize two Möbius insulators in acoustic crystals for the first time: a two-dimensional one of first-order band topology and a three-dimensional one of higher-order band topology. We observe unambiguously the peculiar Möbius edge and hinge states via real-space visualization of their localiztions, momentum-space spectroscopy of their 4π periodicity, and phase-space winding of their projective translation eigenvalues. Not only does our work open a new avenue for artificial systems under the interplay between gauge and crystalline symmetries, but it also initializes a new framework for topological physics from projective symmetry.


A Federated Learning Latency Minimization Method for UAV Swarms Aided by Communication Compression and Energy Allocation.
Unmanned aerial vehicle swarms (UAVSs) can carry out numerous tasks such as detection and mapping when outfitted with machine learning (ML) models. However, due to the flying height and mobility of UAVs, it is very difficult to ensure a continuous and stable connection between ground base stations and UAVs, as a result of which distributed machine learning approaches, such as federated learning (FL), perform better than centralized machine learning approaches in some circumstances when utilized by UAVs. However, in practice, functions that UAVs must perform often, such as emergency obstacle avoidance, require a high sensitivity to latency. This work attempts to provide a comprehensive analysis of energy consumption and latency sensitivity of FL in UAVs and present a set of solutions based on an efficient asynchronous federated learning mechanism for edge network computing (EAFLM) combined with ant colony optimization (ACO) for the cases where UAVs execute such latency-sensitive jobs. Specifically, UAVs participating in each round of communication are screened, and only the UAVs that meet the conditions will participate in the regular round of communication so as to compress the communication times. At the same time, the transmit power and CPU frequency of the UAV are adjusted to obtain the shortest time of an individual iteration round. This method is verified using the MNIST dataset and numerical results are provided to support the usefulness of our proposed method. It greatly reduces the communication times between UAVs with a relatively low influence on accuracy and optimizes the allocation of UAVs' communication resources.


Influence of changes in insulin receptor binding during insulin infusions on the shape of the insulin dose-response curve for glucose disposal in man.
To determine the influence of insulin infusions used in dose-response studies on monocyte insulin binding, monocyte insulin binding and glucose disposal were measured in six normal subjects before and at the end of each of four sequential 2-h insulin infusions (0.4, 1.0, 2.0, and 10 mU kg-1 min-1). Monocyte insulin binding was unaltered at the end of the first three infusions (plasma insulin, 31 +/- 2 (SEM), 77 +/- 3, and 184 +/- 10 microU/ml) but was decreased after the last infusion (plasma insulin, 1730 +/- 125 microU/ml) at 0.2 through 10.2 ng/ml insulin concentrations in the binding assay (P less than 0.01). Using a one-site model, this could be ascribed to a decrease in insulin receptor affinity (1.54 +/- 0.26 vs. 2.27 +/- 0.48 X 10(8) M-1, P less than 0.05), whereas in a two-site model this appeared to be due to a decrease in high affinity binding sites (1,868 +/- 228 vs. 2,387 +/- 207, P less than 0.02). Nevertheless, insulin receptor occupancies estimated to occur during the insulin infusions were virtually identical whether preinsulin infusion binding data (745 +/- 72, 1,383 +/- 117, 2,572 +/- 302, and 10,092 +/- 1,708) or binding data at the end of each infusion (702 +/- 56, 1,367 +/- 150, 2,383 +/- 318, and 9,158 +/- 2,023) were used to calculate occupancy. These results indicate that although monocyte insulin binding decreased during dose-response experiments using sequential infusions of insulin, due to the concentrations of insulin at which this occurs this decrease did not alter the shape of the dose-response curve relating glucose disposal to monocyte insulin receptor occupancy.


In situ measurements of thin films in bovine serum lubricated contacts using optical interferometry.
The aim of this study is to consider the relevance of in situ measurements of bovine serum film thickness in the optical test device that could be related to the function of the artificial hip joint. It is mainly focussed on the effect of the hydrophobicity or hydrophilicity of the transparent surface and the effect of its geometry. Film thickness measurements were performed using ball-on-disc and lens-on-disc configurations of optical test device as a function of time. Chromatic interferograms were recorded with a high-speed complementary metal-oxide semiconductor digital camera and evaluated with thin film colorimetric interferometry. It was clarified that a chromium layer covering the glass disc has a hydrophobic behaviour which supports the adsorption of proteins contained in the bovine serum solution, thereby a thicker lubricating film is formed. On the contrary, the protein film formation was not observed when the disc was covered with a silica layer having a hydrophilic behaviour. In this case, a very thin lubricating film was formed only due to the hydrodynamic effect. Metal and ceramic balls have no substantial effect on lubricant film formation although their contact surfaces have relatively different wettability. It was confirmed that conformity of contacting surfaces and kinematic conditions has fundamental effect on bovine serum film formation. In the ball-on-disc configuration, the lubricant film is formed predominantly due to protein aggregations, which pass through the contact zone and increase the film thickness. In the more conformal ball-on-lens configuration, the lubricant film is formed predominantly due to hydrodynamic effect, thereby the film thickness is kept constant during measurement.


Quality of life of adults with intellectual disabilities who live with families in Taiwan.
Little research has been conducted about the quality of life (QOL) of people with intellectual disabilities (ID) in Taiwan, particularly their subjective QOL. This study examined the personal perceptions of these individuals as measured on internationally recognized core QOL domains and indicators. A census interview survey was conducted in Hsin-Chu City in Taiwan; 233 adults aged over 16 years with mild ID and living with their families participated in the study. Data were collected using the Cross-Cultural QOL Indicators (CCQOLI) together with socio-demographic data that included 'activities of daily living' and 'instrumental activities of daily living' (IADL). The CCQOLI were based on the three most commonly reported indicators of each of the eight QOL domains: emotional well-being, interpersonal relations, material well-being, personal development, physical well-being, self-determination, social inclusion and rights. Each indicator has two sets of questions related to the indicator's 'importance' and 'use'. These are answered by the respondent using a 4-point Likert scale. The importance and use of the QOL indicators were evaluated positively by the respondents. The adults' individual characteristics, namely IADL and educational level, were significant predictors for the 'importance' while the adults' perceptions of 'use' for overall QOL were significantly affected by his/her socio-economic data, that is, residence location and father's educational level. The present study addressed the issue of self-reported QOL in people with ID in Taiwanese society, becoming a possible benchmark for similar measurements carried out by disability movements there. These results contribute to current advocacy efforts towards creating a supportive environment for people with ID.


Atypical presentation of Parsonage-Turner syndrome confounded by surgical rotator cuff injury.
Parsonage-Turner syndrome (PTS) is a rare neuropathy that commonly presents as unexpected severe shoulder and arm pain that eventually subsides while weakness or paralysis ensues. During exceptions to this classic presentation, confirming PTS can be challenging. Alternative causes of upper extremity pain may confound the diagnostic algorithm. Moreover, objective findings from necessary diagnostic tests depend on when those tests are performed. We present an atypical onset of PTS, whereby the initial presentation of severe neuropathic pain was preceded by mild shoulder pain that should decrease one's clinical suspicion for PTS. This milder pain coincided with the presence of a rotator cuff injury, whereby surgical intervention preceded impending paralysis and hindered postoperative rehabilitation. Physicians should be aware of the possibility of atypical presentations of PTS in hopes of avoiding either untimely surgery or delays in diagnosis.


Chemistry of Sputter-Deposited Lithium Sulfide Films.
Lithium sulfide (Li2S) is under intense study because it is the insulating discharge product of ultrahigh energy density lithium-sulfur (Li-S) batteries and a candidate cathode material for lithium-metal-free Li-S cells. In this work, we report the fabrication of an apparatus for sputter deposition of Li2S films ranging in thickness from a few nanometers to several micrometers at rates over 2 nm min-1. High-temperature annealing of the films is shown to produce crystalline films of high chemical purity Li2S for the first time. We provide evidence via complementary X-ray photoelectron and Raman spectroscopy that sputter deposition produces a unique sulfide structure composed of polymer-like chains of Li2S units. The electrochemistry of these films is markedly different from annealed crystalline Li2S, which is shown to be electrochemically inactive. The full theoretical capacity of the as-deposited sulfide structure could be realized during galvanostatic charge, suggesting a facile, solid-state charge process. Finally, we explore trends in the plasma chemistry that lead to nonstoichiometry and depth inhomogeneity during Li2S sputter deposition.


Food poisoning, listeriosis, and febrile gastroenteritis.
Outbreaks of foodborne disease owing to contamination with Listeria monocytogenes bacteria have usually been associated with the development of severe invasive disease. A recent report has provided clear documentation showing that outbreaks of L. monocytogenes also present as gastroenteritis and fever. Further studies of this foodborne organism are needed to determine its infectious dose and the characteristics of the host that are associated with noninvasive febrile gastroenteritis.


Gastric squamous papilloma in a 52-year-old female patient.
A papilloma is a benign epithelial lesion characterized by finger-like projections of tissue lined by an overgrowth of squamous cells and a core of connective tissue. We report a case of squamous papilloma on the cardia in a 52-year-old asymptomatic female. Endoscopy showed a 1-cm sized is polyp with hyperemic change originating from the cardia adjacent to the esophagogastric junction, the biopsy of which suggested a diagnosis of squamous papilloma. Endoscopic mucosal resection was performed to obtain a definite diagnosis and the polyp was completely removed. The histological result was compatible with squamous papilloma, and its surrounding tissues showed foveolar epithelium, which suggested a stomach origin. This is the first report of endoscopic resection of a gastric squamous papilloma. Squamous papilloma should be considered in the differential diagnosis of a gastric polyp, especially one in the cardia. As the prognostic value of a squamous papilloma is not well known, we recommend endoscopic resection to treat a gastric squamous papilloma, when possible.


Comparison between arthroscopic suture anchor fixation and open plate fixation in the greater tuberosity fracture of the proximal humerus.
The purpose of this study is to compare the clinical and radiological outcomes of patients undergoing open reduction and internal fixation (OR/IF) using a plate or patients undergoing an arthroscopic suture anchor fixation for the greater tuberosity (GT) fracture of the proximal humerus. The purpose of this study is to compare the clinical and radiological outcomes of patients undergoing OR/IF or an arthroscopic suture anchor fixation for the GT fracture. Between January, 2010 and December, 2020, 122 patients with GT fracture underwent operative fixation. Either OR/IF using proximal humeral locking plate (50 patients) or arthroscopic suture anchor (72 patients) fixation was performed. Fourteen patients were lost to follow-up and finally, 108 patients were enrolled in this study. We divided these patients into two groups: (1) OR/IF group (Group I: 44 patients) and arthroscopic anchor fixation group (Group II: 64 patients). The primary outcome was subjective shoulder function (shoulder functional scale). Secondary outcomes were range of motion, and complications including GT fixation failure, fracture migration, or neurologic complication. Also, age, sex, BMI, operation time, shoulder dislocation, fracture comminution, AP (anteroposterior), SI (superoinferior) size and displacement were evaluated and compared between two groups. Both groups showed satisfactory clinical and radiological outcomes at mid-term follow-up. Between 2 groups, there were no significant differences in age, sex, BMI, presence of shoulder dislocation or comminution. Group II showed higher clinical scores except VAS score (p < 0.05) and longer surgical times (95.3 vs. 61.5 min). Largest fracture displacement (Group I vs. II: SI displacement: 40 vs. 13 mm, and AP displacement: 49 vs. 11 mm) and higher complication rate (p = 0.049) was found in Group I. Both arthroscopic anchor fixation and open plate fixation methods showed satisfactory outcomes at mid-term follow-up. Among them, OR/IF is preferred for larger fracture displacement (> 5 mm) and shorter operation time However, arthroscopic anchor fixation group showed better clinical outcomes and less complications than the OR/IF group. Level 4, Case series with subgroup analysis.


COVID-19: Special Precautions in Ophthalmic Practice and FAQs on Personal Protection and Mask Selection.
The Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory coronavirus-2, was first reported in December 2019. The World Health Organization declared COVID-19 a pandemic on March 11, 2020 and as of April 17, 2020, 210 countries are affected with >2,000,000 infected and 140,000 deaths. The estimated case fatality rate is around 6.7%. We need to step up our infection control measures immediately or else it may be too late to contain or control the spread of COVID-19. In case of local outbreaks, the risk of infection to healthcare workers and patients is high. Ophthalmic practice carries some unique risks and therefore high vigilance and special precautions are needed. We share our protocols and experiences in the prevention of infection in the current COVID-19 outbreak and the previous severe acute respiratory syndrome epidemic in Hong Kong. We also endeavor to answer the key frequently asked questions in areas of the coronaviruses, COVID-19, disease transmission, personal protection, mask selection, and special measures in ophthalmic practices. COVID-19 is highly infectious and could be life-threatening. Using our protocol and measures, we have achieved zero infection in our ophthalmic practices in Hong Kong and China. Preventing spread of COVID-19 is possible and achievable.


The Role of BDNF on Neural Plasticity in Depression.
Using behavioral, pharmacological, and molecular methods, lots of studies reveal that depression is closely related to the abnormal neural plasticity processes occurring in the prefrontal cortex and limbic system such as the hippocampus and amygdala. Meanwhile, functions of the brain-derived neurotrophic factor (BDNF) and the other neurotrophins in the pathogenesis of depression are well known. The maladaptive neuroplastic in depression may be related to alterations in the levels of neurotrophic factors, which play a central role in plasticity. Enhancement of neurotrophic factors signaling has great potential in therapy for depression. This review highlights the relevance of neurotrophic factors mediated neural plasticity and pathophysiology of depression. These studies reviewed here may suggest new possible targets for antidepressant drugs such as neurotrophins, their receptors, and relevant signaling pathways, and agents facilitating the activation of gene expression and increasing the transcription of neurotrophic factors in the brain.


Psychrophilic versus psychrotolerant bacteria--occurrence and significance in polar and temperate marine habitats.
The numerical dominance and ecological role of psychrophilic bacteria in bottom sediments, sea ice, surface water and melt pools of the polar oceans were investigated using isolates, colony forming units (CFU) and metabolic activities. All sediment samples of the Southern Ocean studied showed a clear numerical dominance of cold-loving bacteria. In Arctic sediments underlying the influence of cold polar water bodies psychrophiles prevailed also but they were less dominant in sediments influenced by the warm Atlantic Water. A predominance of psychrophiles was further found in consolidated Antarctic sea ice as well as in multiyear Arctic sea ice and in melt pools on top of Arctic ice floes. A less uniform adaptation response was, however, met in polar surface waters. In the very northern part of the Fram Strait (Arctic Ocean) we found bacterial counts and activities at 1 degree C exceeding those at 22 degrees C. In surface water of the Weddell Sea (Southern Ocean) psychrophiles also dominated numerically in early autumn but the dominance declined obviously with the onset of winter-water and a decrease of chlorphyll a. Otherwise in surface water of the Southern Ocean CFUs were higher at 22 degrees C than at 1 degree C while activities were vice versa indicating at least a functional dominance of psychrophiles. Even in the temperate sediments of the German Bight true psychrophiles were present and a clear shift towards cold adapted communities in winter observed. Among the polar bacteria a more pronounced cold adaptation of Antarctic in comparison with Arctic isolates was obtained. The results and literature data indicate that stenothermic cold adapted bacteria play a significant role in the global marine environment. On the basis of the temperature response of our isolates from different habitats it is suggested to expand the definition of Morita in order to meet the cold adaptation strategies of the bacteria in the various cold habitats.


Unsymmetrical and Symmetrical Push-Pull Phenothiazines.
A series of unsymmetrical and symmetrical push-pull phenothiazines (3-7) were designed and synthesized by the Pd-catalyzed Sonogashira cross-coupling reaction and subsequent [2 + 2] cycloaddition-retroelectrocyclization reaction with tetracyanoethylene (TCNE) and 7,7,8,8-tetracyanoquinodimethane (TCNQ). The effect of systematic variation of the number and nature of cyano-based acceptor TCNE and TCNQ units on the photophysical, electrochemical, and computational studies was investigated. The single-photon absorption on phenothiazines 3-7 reveals that substitution of 1,1,4,4-tetracyanobutadiene (TCBD) and a cyclohexa-2,5-diene-1,4-diylidene-expanded TCBD unit results in strong intramolecular charge transfer and lowering of the LUMO energy level. The TCBD-linked and cyclohexa-2,5-diene-1,4-diylidene-expanded TCBD-linked phenothiazines 3-7 exhibit multiredox waves. The computational studies on phenothiazines 3-7 exhibit substantial stabilization of the LUMO with the increase in acceptor strength, which results in lowering of the HOMO-LUMO gap.


Predictors of tobacco smoking and smokeless tobacco use among adults in Bangladesh.
To examine predictors of current tobacco smoking and smokeless tobacco use among the adult population in Bangladesh. We used data from the 2009 Global Adult Tobacco Survey (GATS) in Bangladesh consisting of 9,629 adults aged ≥15 years. Differences in and predictors of prevalence for both smoking and smokeless tobacco use were analyzed using selected socioeconomic and demographic characteristics that included gender, age, place of residence, education, occupation, and an index of wealth. The prevalence of smoking is high among males (44.7%, 95% confidence interval [CI]: 42.5-47.0) as compared to females (1.5%, 95% CI: 1.1-2.1), whereas the prevalence of smokeless tobacco is almost similar among both males (26.4%, 95% CI: 24.2-28.6) and females (27.9%, 95% CI: 25.9-30.0). Correlates of current smoking are male gender (odds ratio [OR] = 41.46, CI = 23.8-73.4), and adults in older age (ORs range from 1.99 in 24-35 years age to 5.49 in 55-64 years age), less education (ORs range from 1.47 in less than secondary to 3.25 in no formal education), and lower socioeconomic status (ORs range from 1.56 in high wealth index to 2.48 in lowest wealth index. Predictors of smokeless tobacco use are older age (ORs range from 2.54in 24-35 years age to 12.31 in 55-64 years age), less education (ORs range from 1.44 in less than secondary to 2.70 in no formal education), and the low (OR = 1.34, CI = 1.0-1.7) or lowest (OR = 1.43, CI = 1.1-1.9) socioeconomic status. Implementation of tobacco control strategies needs to bring special attention on disadvantaged group and cover all types of tobacco product as outlined in the WHO Framework Convention on Tobacco Control (FCTC) and WHO MPOWER to protect people's health and prevent premature death.


High-order orbital angular momentum generation in a helically twisted pig-nose-shaped core microstructured optical fibers.
We propose a helically twisted pig-nose-shaped core microstructured optical fiber (HPC-MOF) for orbital angular momentum (OAM) mode generation. It comprises seven air-hole rings hexagonally arranged with two air holes and one air-hole ring replaced, forming two cores in a line 3 µm from the fiber center and one ring-shaped core. The fiber is helically twisted along the rotation axis. In this fiber, supermodes in inner dual-core can be coupled to high-order modes in outer ring-core, yielding OAM ring-shaped modes at different certain wavelengths, and various OAM modes at different twist rates were investigated in this paper. We demonstrate the distinct coupling differences of symmetric and antisymmetric supermodes in inner dual-core when the supermode coupled to ring-core mode. A modal matching rule is presented to characterize the coupling differences, which is suitable for describing supermode coupling characteristics in HPC-MOFs. Compared to conventional methods, these properties indicate that the fiber can generate higher-order OAM modes and more easily integrate into all-fiber optical communication systems, with potential in OAM generators, light-controlling devices, and integrated optics applications.


One-Step Protein Conjugation to Upconversion Nanoparticles.
The emerging upconversion nanoparticles offer a fascinating library of ultrasensitive luminescent probes for a range of biotechnology applications from biomarker discovery to single molecule tracking, early disease diagnosis, deep tissue imaging, and drug delivery and therapies. The effective bioconjugation of inorganic nanoparticles to the molecule-specific proteins, free of agglomeration, nonspecific binding, or biomolecule deactivation, is crucial for molecular recognition of target molecules or cells. The current available protocols require multiple steps which can lead to low probe stability, specificity, and reproducibility. Here we report a simple and rapid protein bioconjugation method based on a one-step ligand exchange using the DNAs as the linker. Our method benefits from the robust DNA-protein conjugates as well as from multiple ions binding capability. Protein can be preconjugated via an amino group at the 3' end of a synthetic DNA molecule, so that the 5' end phosphoric acid group and multiple phosphate oxygen atoms in the phosphodiester bonds are exposed to replace the oleic acid ligands on the surface of upconversion nanoparticles due to their stronger chelating capability to lanthanides. We demonstrated that our method can efficiently pull out the upconversion nanoparticles from organic solvent into an aqueous phase. The upconversion nanoparticles then become hydrophilic, stable, and specific biomolecules recognition. This allows us to successfully functionalize the upconversion nanoparticles with horseradish peroxidise (HRP) for catalytic colorimetric assay and for streptavidin (SA)-biotin immunoassays.


Tools, Strains, and Strategies To Effectively Conduct Anaerobic and Aerobic Transcriptional Reporter Screens and Assays in Staphylococcus aureus.
Transcriptional reporters are reliable and time-tested tools to study gene regulation. In Staphylococcus aureus, β-galactosidase (lacZ)-based genetic screens are not widely used because of the necessity of selectable markers for strain construction and the production of staphyloxanthin pigment, which obfuscates results. We describe a series of vectors that allow for markerless insertion of codon-optimized lacZ-based transcriptional reporters. The vectors code for different ribosomal binding sites, allowing for tailored lacZ expression. A ΔcrtM::kanR deletion insertion mutant was constructed that prevents the synthesis of staphyloxanthin, thereby permitting blue-white screening without the interference of carotenoid production. We demonstrate the utility of these vectors to monitor aerobic and anaerobic transcriptional activities. For the latter, we describe the use of a ferrocyanide-ferricyanide redox system [Fe(CN)63-/4-] permitting blue-white screening in the absence of oxygen. We also describe additional reporter systems and methods for monitoring transcriptional activity during anaerobic culture, including an FAD-binding fluorescent protein (EcFbFP), alpha-hemolysin (hla), or lipase (geh). The systems and methods described are compatible with vectors utilized to create and screen high-density transposon mutant libraries. IMPORTANCE Staphylococcus aureus is a human pathogen and a leading cause of infectious disease-related illness and death worldwide. For S. aureus to successfully colonize and invade host tissues, it must tightly control the expression of genes encoding virulence factors. Oxygen tension varies greatly at infection sites, and many abscesses are devoid of oxygen. In this study, we have developed novel tools and methods to study how and when S. aureus alters transcription of genes. A key advantage of these methods and tools is that they can be utilized in the presence and absence of oxygen. A better understanding of anaerobic gene expression in S. aureus will provide important insights into the regulation of genes in low-oxygen environments.


Evaluating the Frequency and Characteristics of Unexpected Ovarian Malignancy in Postmenopausal Women Who Have Undergone Laparoscopic Surgery for Adnexal Masses - A Review of Five Years.
Aim The aim of this study was to estimate the frequent existence of unexpected ovarian malignant lesions after laparoscopic surgery for an apparent benign adnexal mass and assess its clinical and ultrasound characteristics in postmenopausal women. Methods We re-examined the hospital records of 96 cases of postmenopausal women who underwent laparoscopic surgery for benign adnexal mass over five years. The age of the patient, parity, ultrasound findings, tumor markers level, intraoperative findings, and histopathological report were collected. Pearson's Chi-squared test and Fisher's exact test were used for statistical analysis, and a p-value of <0.05 was accepted as statistically significant. Results Of a total of 96, benign adnexal mass was in 93 (96.83%), an unexpected ovarian malignancy was observed in two (2.08%) cases, and one (1.04%) had a borderline ovarian tumor. Tumor marker CA-125 was done for all those cases of adnexal mass in postmenopausal women, and not a single case was found to have above 35 IU/ml, defined as the cut-off value for CA-125. Statistically significant differences were observed between the benign and malignant groups in relation to symptoms (p<0.05), ultrasound score (p=0.001), and bilaterality (p=0.013) of the tumor mass. Conclusion In postmenopausal women, the critical concern for laparoscopic surgery of benign adnexal mass is unexpected malignancy. So it is essential to select patients carefully for laparoscopic surgery. If a benign-looking adnexal mass turned out to be malignant on the histopathological report, we should try to post the patient for subsequent staging laparotomy as soon as possible.


Lactase genetic polymorphisms and coeliac disease in children: a cohort study.
Lactase activity declines during childhood in the majority of human populations leading to adult-type hypolactasia (AtH). C/T-13910 and G/A-22018 single nucleotide polymorphisms (SNPs) have been suggested to be associated with AtH in different human populations. Coeliac disease (CD) is an autoimmune condition characterized by damage to intestinal cells leading to ultimate deterioration. This study investigated the association between coeliac disease (CD) and SNPs leading to AtH in children from North India. Intestinal biopsies and saliva samples were obtained from 52 children with CD diagnosis and 102 control subjects. Biopsies were assayed for disaccharidase activities and samples were genotyped for given SNPs. Prevalence of C/C and G/G genotypes of AtH was almost equal in the CD and control group. The CD group had low lactase activity compared to the control group, irrespective of genotype at C/T -13910 and G/A -22018 SNPs (p < 0.05). For the control group, lactase activity was high in children with C/T + G/A genotypes compared to C/C + G/G (p < 0.05). There appears to be no significant correlation between C/T -13910 or G/A -22018 SNPs of AtH and CD. Children with C/C or G/G genotype of AtH may not be at greater risk of CD.


Unveiling the Evolutions of Nanotube Diameter Distribution during the Growth of Single-Walled Carbon Nanotubes.
In situ and ex situ Raman measurements were used to study the dynamics of the populations of single-walled carbon nanotubes (SWCNTs) during their catalytic growth by chemical vapor deposition. Our study reveals that the nanotube diameter distribution strongly evolves during SWCNT growth but in dissimilar ways depending on the growth conditions. We notably show that high selectivity can be obtained using short or moderate growth times. High-resolution transmission electron microscopy observations support that Ostwald ripening is the key process driving these seemingly contradictory results by regulating the size distribution and lifetime of the active catalyst particles. Ostwald ripening appears as the main termination mechanism for the smallest diameter tubes, whereas carbon poisoning dominates for the largest ones. By unveiling the key concept of dynamic competition between nanotube growth and catalyst ripening, we show that time can be used as an active parameter to control the growth selectivity of carbon nanotubes and other 1D systems.


[Imaging aspects of sphenoid during development].
To show the different steps of ossification and pneumatization of the sphenoid bone in children in order to emphasize normal anatomic variations. CT scanners and MRI studies of children up to 15 year old performed for various craniofacial conditions, without suspected involvement on cranial growth, are presented. The normal process of the ossification, of the closure of the synchondroses and of the pneumatization is demonstrated. Some examples of congenital abnormalities are also shown. The knowledge of these normal steps and variations is essential, in order to properly evaluate traumatic or congenital situations, but is also helpful for the diagnosis of bone dysplasias and bone marrow diseases (tumor or hematologic disorders).


Murine fetal development enhanced by dietary vitamin A, corn oil, and inositol.
Previous work on the effects of dietary vitamin A on craniofacial anomalies in mice revealed that 18-day-old fetuses from dams given 200 IU of vitamin A in corn oil daily in their diet weighed approximately 10% more than fetuses from mothers fed the unsupplemented standard mouse diet, Purina 5001. In the experiments reported here, it has been found that water-soluble vitamin A (200 IU/day) and myo-inositol (5 mg/day) added separately to the diets of pregnant mice increased the weight of 11-day gestations by approximately 25% and enhanced development of the eyes by the equivalent of 0.5-1.0 day without significantly affecting development of the liver or hind limbs. Corn oil alone (0.2 ml/day) had a similar effect on weight and eye development of 11-day fetuses and, in addition, growth of the hind limbs was enhanced modestly. The addition to the diet of vitamin A (200 IU/day) dissolved in corn oil (0.2 ml/day) resulted in a 25% increase in the weight of the 11-day fetuses and enhanced development of the eyes and hind limbs by the equivalent of about 1 day of gestation, suggesting that corn oil contains a factor(s) that interacts with vitamin A to accelerate limb development. Corn oil contains very small quantities of beta-carotene or retinol (< 1.0 IU vitamin A/ml); however, it is a rich source of the essential growth factors linoleic and linolenic acids and of inositol esters. The data suggest that the growth-promoting actions of dietary corn oil are due in part to the inositol esters.


Development of fast cooling pulsed magnets at the Wuhan National High Magnetic Field Center.
Pulsed magnets with fast cooling channels have been developed at the Wuhan National High Magnetic Field Center. Between the inner and outer sections of a coil wound with a continuous length of CuNb wire, G10 rods with cross section 4 mm × 5 mm were inserted as spacers around the entire circumference, parallel to the coil axis. The free space between adjacent rods is 6 mm. The liquid nitrogen flows freely in the channels between these rods, and in the direction perpendicular to the rods through grooves provided in the rods. For a typical 60 T pulsed magnetic field with pulse duration of 40 ms, the cooling time between subsequent pulses is reduced from 160 min to 35 min. Subsequently, the same technology was applied to a 50 T magnet with 300 ms pulse duration. The cooling time of this magnet was reduced from 480 min to 65 min.


[Computer-assisted vaccine design].
With the modern molecular biology techniques, it has been possible to detect, isolate and clone biological macromolecules, which could be used as immunogenes in artificial vaccine constructs. In the post-genomic era, the prospective immunogenic components are searched using bionformatic tools and proteomic technologies. Today it is quite realistic to combine the artificial vaccine constructs from the preselected molecular components. Existing computational methods are able to detect the potential immunogenes in genomic sequences, predict their characteristics and subcellular location. The set of methods is designed to predict the T- and B-epitopes that can be used as components of minimal vaccine constructs. The variety of systems for production and delivery of vaccines are developed and tested. These include transgenic plants, bacterial and viral vectors, DNA molecules etc. Several informational resources provide free access to molecular immunology data and deliver services on prediction of antigenic features. Several artificial vaccines have already been launched, but much more preparations are under preclinical and clinical trials. Computer-aided design of vaccines may significantly decrease time and costs required for their development. Modern bioinformatic technologies are now employed for discovery of more effective and potent vaccine.


A humanizing gaze for transcultural nursing research will tell the story of health disparities.
If we limit our gaze to epidemiologic or medicalized discourse about health disparities, we risk losing sight of the person living in a health disparity context. We may erase or make invisible the person from a health disparity group; pathologize difference at the population level and, by extension, stigmatize the individual; eliminate the upstream context or causes of disparities; and obscure the human story. For the continued viability of our ideas about health disparities, it is crucial that we maintain cognitive flexibility. The unconscious bedrock of trusted ideas about "culture" and "disparities" can be enriched through a humanized view of the person in the health disparities story. Transcultural nursing research complements the biomedical gaze, placing the patient at the center of a cultural context where health problems are embodied, place based, and socially constituted. Humanizing our practice depends on dialogues with those who experience health disparity conditions.


Identification of posttranslational modifications and cDNA sequencing errors in the rat S100 proteins MRP8 and 14 using electrospray ionization mass spectrometry.
MRP8 and 14 are S100 proteins expressed by myeloid cells and are predicted to have important functions in inflammation. The proteins were isolated from spleens from three rat strains. Electrospray ionization mass spectrometry indicated masses of 10,149 +/- 2 Da for MRP8 and 13,069 +/- 2 Da for MRP14 compared to masses calculated from proteins derived from their cDNA sequences of 10,211 and 13,214 Da, respectively, indicating posttranslational modifications and/or errors in the derived protein sequences. Several endoprotease digest peptides did not correspond to any theoretical digest products after comparison of ESI masses with those derived from the theoretical digest. Both proteins were N-terminally acetylated after deletion of the initiator Met, reducing the theoretical masses by 89 Da. A peptide with mass 28 Da greater than the theoretical was isolated from the Asp N digestion of MRP8. N-terminal sequencing indicated translated Val instead of the predicted Ala at position 72 of MRP8. A peptide 56 Da less than the theoretical was isolated from the chymotryptic digestion of MRP14, and the carboxyamidomethylated form was N-terminally sequenced and found to have translated Ser instead of the predicted Arg at position 105. In addition, His106 was methylated. The corrected theoretical masses, incorporating the posttranslational modifications and sequencing errors, are 10,149.4 and 13,069.9 Da for MRP8 and 14, respectively, in good agreement with the experimental masses.


Principles of hospital disaster management: an integrated and multidisciplinary approach.
Principles of hospital disaster management: an integrated and multidisciplinary approach. Hospitals play an important role during a disaster response, and are also at risk for internal incidents. We propose an integrated and multidisciplinary approach towards hospital disaster management and preparedness. In addition to response strategies, much attention is given to risk assessment and preparedness in the pre-incident phase and to business continuity planning (BCP) in the post-incident phase. It is essential to train key players and all personnel to understand the Hospital Incident Management System (HIMS) and to perform specific emergency procedures. All emergency procedures should be grounded in evidence-based practice resulting from essential disaster response research.


Fatal overdose from synthetic cannabinoids and cathinones in Japan: demographics and autopsy findings.
Sixty-one autopsy cases involving cathinones and/or cannabinoids (synthetic cathinones/cannabinoids) use have been reported. However, little is known about the demographics and autopsy findings in fatal synthetic cathinones/cannabinoids users. To elucidate demographic and autopsy findings (i.e. major organ pathology and causes of death) in synthetic cathinones/cannabinoids cases. We reviewed forensic autopsy reports in Department of Legal Medicine of Tokyo Women's Medical University (Tokyo, Japan) between 2011 and 2015 (a total of 359). We compared demographic and autopsy findings between synthetic cathinones/cannabinoids and methamphetamine cases (as control subjects). There were 12 synthetic cathinones/cannabinoids cases and 10 methamphetamine cases. Synthetic cathinones/cannabinoids users were significantly younger than methamphetamine users (p < 0.01), and there were no cases that used both synthetic cathinones/cannabinoids and methamphetamine. Acute intoxication and cardiac ischemia were the two most prominent causes of death in both synthetic cathinones/cannabinoids users and methamphetamine users. Excited delirium syndrome and pulmonary aspiration were found only in synthetic cathinones/cannabinoids cases. The populations of synthetic cathinones/cannabinoids and methamphetamine users who died of an overdose are different in Japan. Acute intoxication, cardiac ischemia, excited delirium syndrome, pulmonary aspiration, and drowning are the major autopsy findings in synthetic cathinones/cannabinoids-related death. Clinicians shuld be aware of these potentially fatal complications in the medical management of synthetic cathinones/cannabinoids users.


Deformation-Compensated Learning for Image Reconstruction Without Ground Truth.
Deep neural networks for medical image reconstruction are traditionally trained using high-quality ground-truth images as training targets. Recent work on Noise2Noise (N2N) has shown the potential of using multiple noisy measurements of the same object as an alternative to having a ground-truth. However, existing N2N-based methods are not suitable for learning from the measurements of an object undergoing nonrigid deformation. This paper addresses this issue by proposing the deformation-compensated learning (DeCoLearn) method for training deep reconstruction networks by compensating for object deformations. A key component of DeCoLearn is a deep registration module, which is jointly trained with the deep reconstruction network without any ground-truth supervision. We validate DeCoLearn on both simulated and experimentally collected magnetic resonance imaging (MRI) data and show that it significantly improves imaging quality.


Three Weeks of Treatment Induced Long-term Remission in a Patient with Micrococcus luteus-related Peritonitis.
Micrococcus luteus can cause relapsing and refractory peritoneal dialysis infection because it leads to strong biofilm formation. A 69-year-old woman who had undergone peritoneal dialysis (PD) visited the emergency department complaining of cloudy peritoneal dialysate. She was initially given intraperitoneal cefazolin (1 g/day) and ceftazidime (1 g/day). Micrococcus luteus was detected in a culture test. Thus, ceftazidime was discontinued. She remained disease-free for 22 months until she developed PD-related peritonitis. We administered antibiotics for 21 days and thereafter identified 2 important clinical issues. Micrococcus species-related peritonitis can sometimes be cured without vancomycin. Furthermore, the provision of three weeks of sufficient treatment may be important.


Comparative conformational studies on cyclic hexapeptides corresponding to message sequence His-Phe-Arg-Trp of alpha-melanotropin by NMR.
Solution conformation of cyclo(Gly1-His2-Phe3-Arg4-Trp5-Gly6) and its D-Phe analog corresponding to the message sequence [Gly-alpha-MSH5-10] of alpha-MSH has been studied by 1D and 2D proton magnetic resonance spectroscopy in dimethyl sulfoxide (DMSO)-d6 solution and in a DMSO-d6/H2O cryoprotective mixture. The NMR data for both the analogs in solution at 300 K cannot be interpreted based on a single ordered conformation, as evidenced by the broadening of only -NH resonances as well as the temperature coefficients of the amide protons. An analysis of the nuclear Overhauser effect (NOE) cross-peaks in conjunction with temperature coefficient data indicates an equilibrium of multiple conformers with a substantial population of particular conformational states at least in the D-analog. The molecular dynamics simulations without and with NOE constraints also reveal numerous low-energy conformers with two gamma-turns, a gamma-turn and a beta-turn, two beta-turns, etc. for both the analogs. The observed NMR spectra can be rationalized by a dynamic equilibrium of conformers characterized by a gamma-bend at Gly6, two gamma-bends at Phe3 and Gly6 and a conformer with a single beta-turn and a gamma-bend for the L-Phe analog. On the other hand, a conformation with two fused beta-turns around the two tetrads His2-D-Phe3-Arg4-Trp5 and Trp5-Gly6-Gly1-His2 dominates the equilibrium mixture for the D-Phe analog. For the D-Phe analog, the experimentally observed average conformation is corroborated by molecular dynamics simulations as well as by studies in cryoprotective solvent.


A sorbicillinoid urea from an intertidal Paecilomyces marquandii.
A ureido Diels-Alder adduct of sorbicillinol 3 has been isolated from an intertidal marine Paecilomyces marquandii strain, in a screening for new natural products. The structure was determined by spectroscopic methods, and the relative stereochemistry was confirmed by molecular modeling. The absolute stereochemistry was deduced by comparison of the CD curves with those of known members of the bisorbicillinol family. This is the first report of the isolation of a ureido sorbicillinol derivative.


HAM-5 functions as a MAP kinase scaffold during cell fusion in Neurospora crassa.
Cell fusion in genetically identical Neurospora crassa germlings and in hyphae is a highly regulated process involving the activation of a conserved MAP kinase cascade that includes NRC-1, MEK-2 and MAK-2. During chemotrophic growth in germlings, the MAP kinase cascade members localize to conidial anastomosis tube (CAT) tips every ∼8 minutes, perfectly out of phase with another protein that is recruited to the tip: SOFT, a recently identified scaffold for the MAK-1 MAP kinase pathway in Sordaria macrospora. How the MAK-2 oscillation process is initiated, maintained and what proteins regulate the MAP kinase cascade is currently unclear. A global phosphoproteomics approach using an allele of mak-2 (mak-2Q100G) that can be specifically inhibited by the ATP analog 1NM-PP1 was utilized to identify MAK-2 kinase targets in germlings that were potentially involved in this process. One such putative target was HAM-5, a protein of unknown biochemical function. Previously, Δham-5 mutants were shown to be deficient for hyphal fusion. Here we show that HAM-5-GFP co-localized with NRC-1, MEK-2 and MAK-2 and oscillated with identical dynamics from the cytoplasm to CAT tips during chemotropic interactions. In the Δmak-2 strain, HAM-5-GFP localized to punctate complexes that did not oscillate, but still localized to the germling tip, suggesting that MAK-2 activity influences HAM-5 function/localization. However, MAK-2-GFP showed cytoplasmic and nuclear localization in a Δham-5 strain and did not localize to puncta. Via co-immunoprecipitation experiments, HAM-5 was shown to physically interact with NRC-1, MEK-2 and MAK-2, suggesting that it functions as a scaffold/transport hub for the MAP kinase cascade members for oscillation and chemotropic interactions during germling and hyphal fusion in N. crassa. The identification of HAM-5 as a scaffold-like protein will help to link the activation of MAK-2 cascade to upstream factors and proteins involved in this intriguing process of fungal communication.


[gammadelta T cells stimulated by zoledronate kill osteosarcoma cells].
To investigate the cytotoxicity of human γδT cells from PBMCs stimulated by zoledronate against osteosarcoma cell line HOS in vitro and in vivo and evaluate the relavent pathways. The peripheral blood mononuclear cells (PBMCs)of healthy donors were stimulated by single dose zoledronate and cultured in the present of IL-2 for two weeks, analysising the percentage of γδT cells on a FACSCalibur cytometer.Study the cytotoxicity of γδT cells against the osteosarcoma line HOS using LDH release assay kit. Pre-treatment of γδT cells with anti-human γδTCR antibody, anti-human NKG2D antibody and concanamycin A to bolck the relavent pathways for evaluating the mechenisms of its cytotoxicity. In vivo, BALB/c mice were inoculated subcutaneously osteosarcoma cell HOS for developing hypodermal tumors. And they were randomized into two groups: unteated group, γδT cell therapy group. Tumor volume and weight of the two groups were compared. After two weeks of culture, γδT cells from zoledronate-stimulated PBMCs could reach (95±3)%. When the E:T as 6:1, 12:1, 25:1, 50:1, the percentage of osteosarcoma cell HOS killed by γδT cells was 26.8%, 31.5%, 37.8%, 40.9%, respectively.When anti-huma γδTCR antibody, anti-human NKG2D antibody and concanamycin A blocked the relavent pathways, the percentage was 32.3%, 4.7%, 16.7% ( E:T as 25:1), respectively. In vivo, the tumor inhibition rate of the group of γδT cell therapy was 42.78%. γδT cells derived from PBMCs stimulated by zoledronate can acquired pure γδT cells. And they show strong cytoxicity against osteosarcoma cell line HOS in vitro and in vivo.


[The free forearm flap in covering defects of the pharynx and oral cavity].
The radial forearm flap is a versatile method for reconstruction of the pharynx and the oral cavity after tumour resection. We prefer the distal volar forearm since the flap is thin, with little subcutaneous fat. The vascular pedicle is rather long. Twenty patients with carcinoma of the oropharynx and the oral cavity have been operated on. Thirteen patients had carcinomas of the oropharynx, 7 of the oral cavity. In all cases the distal flap was used. The size varied from 3 x 5 cm to 10 x 7 cm. Twelve patients underwent radiotherapy which did not do any damage to the flap. Fifteen patients had a good functional result. Two patients suffered recurrences after a few months. One patient died from respiratory problems. One flap underwent a partial necrosis due to venous congestion. The donor defect was closed with split skin from the thigh.


Impact of Resilience on the Association Between Amyloid-β and Longitudinal Cognitive Decline in Cognitively Healthy Older Adults.
The present study aims at investigating if the association between amyloid-β and longitudinal cognitive decline in cognitively healthy elderly is modulated by resilience capacity. Resilience capacity was quantified by education, which is a common proxy of resilience and has been shown to be related to a wide range of behaviors promoting resilience. Analyses were conducted with longitudinal cognitive data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). 276 cognitively healthy older individuals (≥56 years) were included in the study. Baseline amyloid pathology was quantified using CSF amyloid-β 1-42 measurements. Longitudinal cognitive decline was assessed using ADAS13, Clinical Dementia Rating - Sum of Boxes, and ADNI-Memory composite scores. Duration of follow-up was 10 years (mean follow-up: 2.6 years). Linear mixed effects models demonstrated stronger cognitive decline over time with increasing baseline amyloid. Subsequent mixed-effects analyses showed that this amyloid-related cognitive decline is stronger in individuals with lower resilience capacity (i.e., lower levels of education). Of note, this effect was not an artifact of differences in neurodegeneration patterns between individuals with lower and higher resilience. Results suggest that resilience capacity has high potential to counteract early amyloid pathology and to significantly slow cognitive decline.


Intermittent lead-induced stress on antioxidant enzyme activity and subcellular distribution of Pb in Pogonatherum crinitum seedlings.
Pogonatherum crinitum is a promising lead (Pb) hyperaccumulator due to its high Pb tolerance and accumulation ability. However, the mechanisms that support Pb accumulation and tolerance in P. crinitum are not yet clearly understood. An indoor hydroponic experiment was conducted by cultivating P. crinitum seedlings exposed to intermittent Pb stress for 60 days, divided into four stages (T1, T2, T3 and T4), with a 15-day duration per stage. The following concentrations of Pb were used: 0, 500, 0, 500 mg·l-1 and 0, 1000, 0, 1000 mg·l-1 ). Antioxidant enzyme activity, Pb concentration and subcellular distribution of Pb were measured at each of the above stages. The results showed that superoxide dismutase (SOD) activity in shoots, and SOD, peroxidase (POD) and malondialdehyde (MDA) activity in shoots and roots significantly increased from T1 (no Pb stress) to T2 (Pb stress) in both 500 mg·l-1 and 1000 mg·l-1 treatments; however, no significant difference was noted between stages T3 (no Pb stress) and T4 (Pb stress). There was no obvious effect of Pb stress on catalase (CAT) activity in shoots and roots among different stages. The Pb concentration in shoots was up to 5090.90 mg·kg-1 and 7573.57 mg·kg-1 , and the bioconcentration factor (BFC) was 10.18 and 7.57 for the 500 mg·l-1 and 1000 mg·l-1 treatments, respectively, which confirmed the Pb hyperaccumulator characteristics of P. crinitum. For plants under Pb stress, most of the Pb was fixed in the cell walls, with a smaller amount in leaves and root vacuoles. Both SOD and POD scavenging of reactive oxygen radicals and fixing and compartmentalisation of Pb in the cell wall might play important roles in detoxification of P. crinitum seedlings in response to Pb stress. There was no phased response of P. crinitum to intermittent Pb stress and the physiological response to Pb stress may be contiguous.


De novo urothelial carcinoma in a pediatric recipient of living donor kidney graft.
De novo urothelial carcinoma is relatively rare among post-transplant malignancies and never reported in pediatric kidney transplant recipients. In this paper, we reported one 12-yr-old male case with painless gross hematuria as the initial manifestation of de novo urothelial carcinoma in living donor graft pelvis. We emphasize the importance that cystoscopy and retrograde pyelography of native and transplant kidneys should be performed in all kidney transplant recipients with painless gross hematuria.


Endogenous insulin and insulin sensitivity. An important determinant of skeletal muscle blood flow in chronic heart failure?
Patients with heart failure have a reduced sensitivity to insulin's actions on glucose metabolism and a compensatory increase in endogenous plasma insulin levels. As insulin has a selective vasodilatory action in skeletal muscle, we have studied the association between insulin sensitivity and central and regional haemodynamics in patients with heart failure. Ten patients with stable symptomatic heart failure were studied. We used non-invasive techniques to measure cardiac output, forearm blood flow, superior mesenteric artery blood flow and right renal artery blood flow. Blood samples were assayed for noradrenaline, renin and atrial natriuretic peptide levels. Insulin sensitivity was assessed using the low dose short insulin tolerance test. There was a significant inverse correlation between forearm blood flow and insulin sensitivity (r = -0.67, P = 0.03), patients with lesser degrees of insulin sensitivity having the greater forearm blood flows. There was no correlation with the other haemodynamic or neurohumoral parameters. Patients with greater insulin resistance tended to have higher circulating endogenous insulin levels, although this relationship did not reach statistical significance (r = -0.53, P = 0.12). Insulin sensitivity appears to be an important determinant of skeletal muscle blood flow in heart failure. We speculate that this is secondary to the increased circulating endogenous insulin levels, and suggest that the therapeutic potential of exogenous insulin merits further investigation.


Role of Intrinsic Factors in the Growth of Transplanted Organs Following Transplantation.
Shortages in the availability of transplantable organs have forced the transplant community to seek alternative methods to increase the supply of available organs. In our recent study following α-1,3-galactocyltransferase knockout (GalT-KO) pig-to-baboon kidney xenotransplantation, we found that certain recipients developed increased serum creatinine, possibly due to the rapid growth of orthotopic pig grafts in smaller baboon recipients. To test our hypothesis, we assessed whether the growth of outbred (Yorkshire) organ transplants (kidney and lung) in miniature swine was regulated by intrinsic (graft) factors. Yorkshire kidneys reached 3.7× their initial volume over 3 months vs. 1.2× for miniature swine kidneys over a similar time period. A similar pattern was seen in porcine lung allografts as well. Following xenotransplantation, a review of our results suggests that there is a threshold for kidney graft volume of 25 cm3/kg of recipient body weight at which cortical ischemia is induced in transplanted GalT-KO kidneys in baboons. These results suggest that intrinsic factors are in part responsible for the growth of donor organs and this should be taken into consideration for growth-curve-mismatched transplants.


The fractal nature of human gastro-oesophageal reflux.
We are unaware of the analyses of time series data resulting from 24 h recordings of human gastric or oesophageal pH. As a result, we have no understanding of the quantitative changes in gastric or oesophageal acidity over time, the patterns that might characterize these changes, or the physiological significance of gastro-oesophageal reflux. To examine the time series for gastric and oesophageal pH. Detrended fluctuation analysis and lag analysis were used to analyse data from 24 h recordings of oesophageal and gastric pH in five normal subjects and five subjects with gastro-oesophageal reflux disease. Analyses of the patterns of gastric and oesophageal pH over time in normal subjects and subjects with gastro-oesophageal reflux disease indicate that the fluctuations in pH are self-similar across different time scales and are consistent with an underlying fractal process. Furthermore, there is a significant statistical association between sequential pH values separated by as much as 2.2 h. We hypothesize that the self-similar, fractal pattern encodes information about gastric acidity and that the oesophagus decodes this information and, when appropriate, may signal the stomach to reduce gastric acidity. Subjects with gastro-oesophageal reflux disease might have an impaired oesophageal-gastric feedback mechanism that results in increased gastric acid, which reflux from the stomach into the oesophagus.


Estimation of the Wing-Kristofferson model for discrete motor responses.
A number of estimation methods for the variance components in the Wing-Kristofferson model for inter-response times are examined and compared by means of a simulation study. The estimation methods studied are the method of moments, maximum likelihood, and an alternative approach in which the Wing-Kristofferson model is recognized as a moving average model.


[Study on the Correlation between Elevated Serum Free Light Chain and Inferior Clinical Features or Hematological Parameters of Lymphoma Patients in Chengdu Area].
To analyze the correlation of the serum free light chain elevated (sFLC) and clinical characteristics and hematological parameters of lymphoma in Chengdu area. 249 cases of non-Hodgkin lymphoma (NHL) out of 274 patients with lymphoma diagnosed in Sichuan People's Hospital from April 2019 to July 2021 were selected, the sFLC, clinical features and hematological parameters of the patients were analyzed retrospectively. The difference of clinical features between the patients with normal sFLC and elevated sFLC was examined by chi-square test. The difference of hematological parameters between patients with normal sFLC and elevated sFLC were examined by chi-square test and nonparametric Mann-Whitney U test. Among the 249 NHL patients, 55.42% (138/249) patients had an elevated sFLC, of which 9.24% (23/138) were being monoclonal and 46.18% (115/138) were polyclonal. The sFLC elevation was common in NHL, but varied according to the types of sFLC secretion (monoclonal or polyclonal), and types of lymphoma. Furthermore, there were no significant statistical differences in clinical characteristics, including age, sex, stage disease, International Prognostic Index (IPI), B symptoms, and bone marrow invasion between elevated sFLC and normal sFLC of the NHL patients (P>0.05). However, the patients with elevated sFLC had adverse hematological parameters more frequently, including higher WBC, ANC, AMC, hsCRP, Cr, Glb, LDH, and lower Hb, Alb. Elevated sFLC is associated with inferior hematological parameters, revealing the uniqueness of the diagnostic and prognostic value of sFLC in lymphoma in chengdu area.


Fracture Resistance of Tilted Premolars Restored with Different Post-Core Systems.
To assess the effect of root tilt on the fracture resistance and failure pattern of endodontically-treated premolars restored with different post-core systems. Ninety endodontically-treated premolars were mounted in acrylic blocks with 0°, 12°, and 24° axial root tilt. Teeth in each group were restored in three subgroups with cast post-core, readymade metal posts and composite cores, and fiber post and composite cores. Crowns of all teeth were prepared coinciding with the long axis of the acrylic blocks to receive all-ceramic crowns. All restored teeth were stressed to record the maximum load at failure and the associated failure pattern. The collected data were statistically analyzed using two-way ANOVA, Tukey's, and Kruskal-Wallis tests at α = 0.05 on past software to detect any differences between subgroups. Analysis of the collected data indicated significant differences between the tested subgroups (ANOVA, P = 3.86). Further analysis showed significant difference between all test subgroups and the control (Tukey's, P < 0.05). In general, teeth with 0° tilt seemed more resistant to fracture than the tilted ones. For all groups, teeth restored with fiber post and composite cores (SG3) were more resistant to fracture compared to other post-core systems (SG1 and SG2) (Tukey's, P < 0.05). The root fracture was the most commonly seen mode of failure. Root tilting usually affects the fracture resistance of teeth restored with post-core systems. The fiber post and composite cores seemed to be the best choice to restore teeth with different root tilting possibilities.