DNA methylation profile of genes involved in inflammation and autoimmunity in inflammatory bowel disease.
The contribution of epigenetic alterations to disease pathogenesis is emerging as a research priority. In this study, we aimed to seek DNA methylation changes in peripheral blood and tissue biopsies from patients with inflammatory bowel disease. The promoter methylation status of genes involved in inflammation and autoimmunity was profiled using the Human Inflammatory Response and Autoimmunity EpiTect Methyl II Signature PCR Array profiles. Methylation was considered to be hypermethylated if >20% according to the instructions of the manufacturer. The microarrays were validated with Quantitative Real-time PCR. Regarding Crohn disease (CD) no gene appeared hypermethylated compared to healthy controls. In ulcerative colitis (UC) 5 genes (CXCL14, CXCL5, GATA3, IL17C, and IL4R) were hypermethylated compared to healthy controls. Some of the examined genes show different methylation patterns between CD and UC. Concerning tissue samples we found that all hypermethylated genes appear the same methylation pattern and confirmed a moderate-strong correlation between methylation levels in colon biopsies and peripheral blood (Pearson coefficients r=0.089-0.779, and r=0.023-0.353, respectively). The epigenetic changes observed in this study indicate that CD and UC exhibit specific DNA methylation signatures with potential clinical applications in IBD non-invasive diagnosis and prognosis.


The development and validation of the assessment engagement scale.
The quality of student engagement in assessment within higher education affects learning outcomes. However, variations in conceptions of what quality in engagement looks like impacts assessment design and the way that students and lecturers engage with each other in the assessment process. Given that assessment is an important driver of student engagement in higher education, it is surprising that no specific measures to support understanding of this measure exist. To address this significant gap, we outline the evolution of an assessment engagement scale derived from a research-informed conceptual framework utilizing best practice in assessment and feedback. We consider the validity and utility of the assessment engagement scale in supporting students' understanding of assessment and their role within it using exploratory and confirmatory factor analyses. The resultant nine-item assessment engagement scale's underpinning two factors included: (i) Understanding of the Assessment Context (UAC) including one's role within it, and confidence in navigating assessment requirement, and (ii) Realising Engagement Opportunities (REO) (i.e., willingness to engage and ability to utilise the assessment context effectively to support one's understanding). Construct, criterion, and convergent validity of the scale were established. The AES is a powerful tool in promoting dialogue between lecturers and students about what high quality engagement in assessment looks like, and the respective roles of all parties in realising this. Implications for assessment practices are discussed along with the potential of the scale as a predictive and developmental tool to support enhancements in assessment design and student learning outcomes in higher education.


Immune dysregulation and tumor-associated gene changes in recurrent respiratory papillomatosis: a paired microarray analysis.
Recurrent respiratory papillomas (RRP) are benign airway tumors, caused primarily by human papillomaviruses (HPV) types 6 and 11. The disease is characterized by multiple recurrences after surgical removal, with limited effective therapy. To identify novel targets for future therapy, we established transcriptional profiles for actively growing papillomas compared with autologous, clinically normal, laryngeal epithelia (adjacent tissue). Total ribonucleic acid (RNA) from 12 papillomas and 12 adjacent tissues were analyzed by microarray, and the matched sets of tissues compared by paired t test, to identify differentially expressed genes in papilloma tissues while minimizing variations intrinsic to individual patients. Quantitative polymerase chain reaction (PCR) was used to confirm the relative expression levels for a subset of genes. Within the 109 differentially expressed transcripts whose expression varied at least three-fold were two large groups of genes with related functions. The first group consisted of 18 genes related to host defense, including both innate and adaptive immunity. The second group contained 37 genes that likely contribute to growth of papillomas as benign tumors, since the altered pattern of expression also had been reported previously in many cancers. Our results support our previous studies that document a systemic T(H)2-like adaptive immune response in RRP, and suggest that there is a role for altered innate immunity in RRP as well. We propose that HPV 6 and 11 infection establishes a tumorigenic microenvironment characterized by alteration of both innate inflammatory signals and adaptive immune responses that prevent effective T(H)1-like response, in conjunction with altered expression of numerous genes that regulate cellular growth and differentiation.


The economic burden of informal care.
The great interest focused on home care technologies during the last decade resulted from its potential to cut costs. However, the reallocation of costs between healthcare providers and social welfare providers, and the indirect costs of informal care, are not as frequent topics of discussion. The aim of this paper is to discuss different models for estimating the costs of informal care in the home care setting in economic appraisals. The outcome of using different models for estimating indirect costs was illustrated using empirical data regarding the time spent by informal caregivers in providing care in a group of home care patients (n = 59). The models used comprise different interpretations of the traditional human capital approach and the friction cost model. Informal care is an important component in home care. The inclusion of indirect costs of informal care in economic appraisals will have implications for the cost-effectiveness of home care, since it will raise costs depending on the model used for estimating indirect costs. In this study we have shown that indirect costs estimated by the friction cost model only amount to 18% to 44% of the cost when the human capital approach is used. The results indicate that, regardless of the method used to estimate indirect costs, the cost of informal care in evaluations of home care programs is often underestimated due to the exclusion of indirect costs.


Surgical Repair of Neglected Bucket-Handle Meniscal Tears Displaced into the Intercondylar Notch: Clinical and Radiological Results.
The literature contains very limited articles wherein the treatment results of bucket-handle meniscal tears according to various types are evaluated and wherein results for repair of chronic tears are discussed. The objective of this study is a clinical and radiologic evaluation of arthroscopic repair for patients suffering flipped, neglected chronic bucket-handle meniscal tear in the intercondylar notch. A total of 26 patients were evaluated retrospectively. The mean age at the time of surgery was 27 years (range, 16-44). Mean period from meniscal injury to surgery was 28 months (range, 4-96). The mean follow-up period was 31 months (range, 11-67). During the follow-up, the patients were evaluated clinically, functional scores from the International Knee Documentation Committee (IKDC), Lysholm, and Tegner as well as magnetic resonance imaging (MRI). The mean preoperative Lysholm score of 24 increased to 85 postoperatively. Mean IKDC score was 56.3 preoperatively and 84.5 postoperatively. The mean Tegner score of 3.4 increased to 5.6 postoperatively. Mean Lysholm, IKDC, and Tegner scores in the first group were 84, 74, and 5.1, respectively, and in the anterior cruciate ligament (ACL) reconstruction group; 86, 85.9, and 5.8. While 20 (77%) out of 26 patients had none of the clinical findings, 6 patients (23%) presented with these findings. Postoperative MRI assessment revealed meniscal healing in 21 patients (27% complete, 54% partial healing) and no healing in 5 patients (19%). A clinical healing rate of 77% and a radiological healing rate of 81% along with statistically significant increases in Lysholm, IKDC, and Tegner scores prove that the repair option is effective for neglected, chronic bucket-handle meniscal tears flipping to the intercondylar notch. This study showed that good results could be achieved with the repair of neglected, chronic period bucket-handle meniscal tears flipping to the intercondylar notch, whether with an accompanying ACL tear or not.


A case of greater occipital nerve schwannoma causing neuralgia.
Schwannomas are common tumors of the head and neck region, but they rarely develop in the suboccipital region. A 34-year-old woman presented with a left suboccipital mass causing local pain and neck stiffness. Following physical examination, fine needle aspiration biopsy was performed, which revealed benign cytology. In the light of preoperative radiologic examination and intraoperative observations, the lesion was thought to originate from the greater occipital nerve. Following complete excision of the lesion, histopathological diagnosis was made as schwannoma. Apart from mild neck stiffness and transient local paresthesia in the early postoperative period, no complications were seen during a two-year follow-up period.


Validation of the shoulder36 for the activities of daily living with shoulder disorders.
[Purpose] The Shoulder36 (V 1. 3) is a regional questionnaire in Japan that has not been validated as a functional evaluation of the shoulder via a thorough comparison with other questionnaires (e.g., QuickDASH). The purpose of this study was to test the reliability, validity, and responsiveness of the Shoulder36 (V 1. 3). [Subjects and Methods] A series of 46 patients with upper extremity disorders completed the Shoulder36 (V 1. 3) and the QuickDASH Japanese version (QuickDASH-JSSH). The reliability of the Shoulder36 was assessed for consistency and validity. The correlation coefficients between the Shoulder36 (V 1. 3) and the QuickDASH-JSSH were obtained. [Results] The total of the Cronbach's alpha coefficients for the Shoulder36 (V 1. 3) was 0.98. The intraclass correlation coefficients for the six domains of the Shoulder36 (V 1. 3) were similarly high, ranging from 0.81 to 0.94. The correlations between the six domains of the Shoulder36 (V 1. 3) and the three domains of the QuickDASH subscales ranged from -0.43 to -0.78. [Conclusion] The Shoulder36 (V 1. 3) was able to evaluate the relationship between activities of daily living and shoulder joint function with the same degree of accuracy but in more detail than QuickDASH-JSSH. Therefore, it should prove to be a valuable asset in physiotherapy plans and have multiple research applications.


Multi-domain conformational selection underlies pre-mRNA splicing regulation by U2AF.
Many cellular functions involve multi-domain proteins, which are composed of structurally independent modules connected by flexible linkers. Although it is often well understood how a given domain recognizes a cognate oligonucleotide or peptide motif, the dynamic interaction of multiple domains in the recognition of these ligands remains to be characterized. Here we have studied the molecular mechanisms of the recognition of the 3'-splice-site-associated polypyrimidine tract RNA by the large subunit of the human U2 snRNP auxiliary factor (U2AF65) as a key early step in pre-mRNA splicing. We show that the tandem RNA recognition motif domains of U2AF65 adopt two remarkably distinct domain arrangements in the absence or presence of a strong (that is, high affinity) polypyrimidine tract. Recognition of sequence variations in the polypyrimidine tract RNA involves a population shift between these closed and open conformations. The equilibrium between the two conformations functions as a molecular rheostat that quantitatively correlates the natural variations in polypyrimidine tract nucleotide composition, length and functional strength to the efficiency to recruit U2 snRNP to the intron during spliceosome assembly. Mutations that shift the conformational equilibrium without directly affecting RNA binding modulate splicing activity accordingly. Similar mechanisms of cooperative multi-domain conformational selection may operate more generally in the recognition of degenerate nucleotide or amino acid motifs by multi-domain proteins.


[The effectiveness of endoscopic variceal ligation in patients with different grades of liver function].
To evaluate the effectiveness of endoscopic variceal ligation (EVL) in patients with different grades of liver function. MELD scores were determined for 156 patients before their EVL operations. After the EVL these patients were followed-up and their survival rates were analyzed. Fifty percent of the patients whose MELDs were less than or equal to 7 survived longer than 45 months after the EVL; in those with MELDs between 7 and 9, 50% of the patients survived 47.34 months; however, the figure for those whose MELD were more than 9 survived only 24.89 months. In the first two groups, 50% of the patient' survival duration was significantly longer than that of the third group. The difference was statistically significant. EVL becomes an effective clinical way to treat hemorrhage of esophagus varicose veins. The survival rate for this procedure is directly correlated with the liver function of the patient before the EVL.


Application of quantum machine learning using quantum kernel algorithms on multiclass neuron M-type classification.
The functional characterization of different neuronal types has been a longstanding and crucial challenge. With the advent of physical quantum computers, it has become possible to apply quantum machine learning algorithms to translate theoretical research into practical solutions. Previous studies have shown the advantages of quantum algorithms on artificially generated datasets, and initial experiments with small binary classification problems have yielded comparable outcomes to classical algorithms. However, it is essential to investigate the potential quantum advantage using real-world data. To the best of our knowledge, this study is the first to propose the utilization of quantum systems to classify neuron morphologies, thereby enhancing our understanding of the performance of automatic multiclass neuron classification using quantum kernel methods. We examined the influence of feature engineering on classification accuracy and found that quantum kernel methods achieved similar performance to classical methods, with certain advantages observed in various configurations.


Stillbirth rates and their determinants in a national maternity hospital in Phnom Penh, Cambodia in 2017-2020: a cross-sectional assessment with a nested case-control study.
In Cambodia, stillbirths and their underlying factors have not been systematically studied. This study aimed to assess the proportion and trends in stillbirths between 2017 and 2020 in a large maternity referral hospital in the country and identify their key determinants to inform future prevention efforts. This was a retrospective cross-sectional analysis with a nested case-control study of women giving birth at the National Maternal and Child Health Centre (NMCHC) in Phnom Penh, 2017-2020. We calculated percentages of singleton births at ≥ 22 weeks' gestation resulting in stillbirth and annual stillbirth rates by timing: intrapartum (fresh) or antepartum (macerated). Multivariable logistic regression was used to explore factors associated with stillbirth, where cases were all women who gave birth to a singleton stillborn baby in the 4-year period. One singleton live birth immediately following each case served as an unmatched control. Multiple imputation was used to handle missing data for gestational age. Between 2017 and 2020, 3.2% of singleton births ended in stillbirth (938/29,742). The stillbirth rate increased from 24.8 per 1000 births in 2017 to 38.1 per 1000 births in 2020, largely due to an increase in intrapartum stillbirth rates which rose from 18.8 to 27.4 per 1000 births in the same period. The case-control study included 938 cases (stillbirth) and 938 controls (livebirths). Factors independently associated with stillbirth were maternal age ≥ 35 years compared to < 20 years (aOR: 1.82, 95%CI: 1.39, 2.38), extreme (aOR: 3.29, 95%CI: 2.37, 4.55) or moderate (aOR: 2.45, 95%CI: 1.74, 3.46) prematurity compared with full term, and small-for-gestational age (SGA) (aOR: 2.32, 1.71, 3.14) compared to average size-for-age. Breech/transverse births had nearly four times greater odds of stillbirth (aOR: 3.84, 95%CI: 2.78, 5.29), while caesarean section reduced the odds by half compared with vaginal birth (aOR: 0.50, 95%CI: 0.39, 0.64). A history of abnormal vaginal discharge increased odds of stillbirth (aOR: 1.42, 95%CI: 1.11, 1.81) as did a history of stillbirth (aOR: 3.08, 95%CI: 1.5, 6.5). Stillbirth prevention in this maternity referral hospital in Cambodia requires strengthening preterm birth detection and management of SGA, intrapartum care, monitoring women with stillbirth history, management of breech births, and further investigation of high-risk referral cases.


Allocation of freshly assimilated carbon into primary and secondary metabolites after in situ ¹³C pulse labelling of Norway spruce (Picea abies).
Plants allocate carbon (C) to sink tissues depending on phenological, physiological or environmental factors. We still have little knowledge on C partitioning into various cellular compounds and metabolic pathways at various ecophysiological stages. We used compound-specific stable isotope analysis to investigate C partitioning of freshly assimilated C into tree compartments (needles, branches and stem) as well as into needle water-soluble organic C (WSOC), non-hydrolysable structural organic C (stOC) and individual chemical compound classes (amino acids, hemicellulose sugars, fatty acids and alkanes) of Norway spruce (Picea abies) following in situ (13)C pulse labelling 15 days after bud break. The (13)C allocation within the above-ground tree biomass demonstrated needles as a major C sink, accounting for 86% of the freshly assimilated C 6 h after labelling. In needles, the highest allocation occurred not only into the WSOC pool (44.1% of recovered needle (13)C) but also into stOC (33.9%). Needle growth, however, also caused high (13)C allocation into pathways not involved in the formation of structural compounds: (i) pathways in secondary metabolism, (ii) C-1 metabolism and (iii) amino acid synthesis from photorespiration. These pathways could be identified by a high (13)C enrichment of their key amino acids. In addition, (13)C was strongly allocated into the n-alkyl lipid fraction (0.3% of recovered (13)C), whereby (13)C allocation into cellular and cuticular exceeded that of epicuticular fatty acids. (13)C allocation decreased along the lipid transformation and translocation pathways: the allocation was highest for precursor fatty acids, lower for elongated fatty acids and lowest for the decarbonylated n-alkanes. The combination of (13)C pulse labelling with compound-specific (13)C analysis of key metabolites enabled tracing relevant C allocation pathways under field conditions. Besides the primary metabolism synthesizing structural cell compounds, a complex network of pathways consumed the assimilated (13)C and kept most of the assimilated C in the growing needles.


Cleavage of metal-ion-induced DNAzymes released from nanolabels for highly sensitive and specific immunoassay.
This work reports a novel electrochemical immunoassay protocol with signal amplification for determination of low-abundance protein (free prostate-specific antigen, PSA, used as a model) with high sensitivity and high selectivity by coupling metal sulfide (PbS)-based nanolabels with cleavage of the corresponding lead ion-induced DNAzymes. The assay mainly consists of an antigen-antibody immunoreaction with metal nanolabel in a transparent 96-well polystyrene microplate, the release of metal ions from the nanolabel, and cleavage of metal ion-induced DNAzyme. The signal is amplified by the labeled redox tag (ferrocene) on the DNAzyme-based sensor. In the presence of target analyte, the sandwiched immunocomplex can be formed between the primary antibody on the microplate and the corresponding metal sulfide nanolabel. The carried nanolabel can release numerous metal ions by acid, and induce the cleavage of the corresponding DNAzyme, thus resulting in the change of electrochemical signal. Under optimal conditions, the DNAzyme-based immunoassay presents an obvious electrochemical response for the detection of PSA, and allows detection of PSA at a concentration as low as 0.1 pg mL(-1). Intra-assay and interassay coefficients of variation (CV) were less than 9.5% and 10%, respectively. No significant differences at the 0.05 significance level were encountered in the analysis of 12 clinical serum specimens between the developed immunoassay and a commercially available enzyme-linked immunosorbent assay (ELISA).


4,5-Bis(4-fluoro-phen-yl)-5-hy-droxy-3-(2-methyl-propano-yl)-1-phenyl-pyrrolidin-2-one.
The title compound, C(26)H(23)F(2)NO(3), was synthesized by the reaction of 2-(4-fluoro-benzyl-idene)-4-methyl-3-oxo-N-phenyl-penta-namide and 4-fluoro-benzaldehyde. The dihedral angles between the mean plane through the pyrrolidine ring (nearly planar; maximum deviation of 0.145 Å for the C atom bearing the hydroxy group) with the phenyl and benzene rings are 37.22 (7), 51.88 (7) and 87.64 (9)°, respectively. The pyyolidine ring is near coplaner, with max offset of 0.145 A for C19 atom.\uff09 In the crystal, mol-ecules are linked by pairs of O-H⋯O hydrogen bonds into inversion dimers, which are further assembled into chains parallel to the b axis by weak C-H⋯O hydrogen bonds.


Death Receptor 3 Signaling Controls the Balance between Regulatory and Effector Lymphocytes in SAMP1/YitFc Mice with Crohn's Disease-Like Ileitis.
Death receptor 3 (DR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, has been implicated in regulating T-helper type-1 (TH1), type-2 (TH2), and type-17 (TH17) responses as well as regulatory T cell (Treg) and innate lymphoid cell (ILC) functions during immune-mediated diseases. However, the role of DR3 in controlling lymphocyte functions in inflammatory bowel disease (IBD) is not fully understood. Recent studies have shown that activation of DR3 signaling modulates Treg expansion suggesting that stimulation of DR3 represents a potential therapeutic target in human inflammatory diseases, including Crohn's disease (CD). In this study, we tested a specific DR3 agonistic antibody (4C12) in SAMP1/YitFc (SAMP) mice with CD-like ileitis. Interestingly, treatment with 4C12 prior to disease manifestation markedly worsened the severity of ileitis in SAMP mice despite an increase in FoxP3+ lymphocytes in mesenteric lymph node (MLN) and small-intestinal lamina propria (LP) cells. Disease exacerbation was dominated by overproduction of both TH1 and TH2 cytokines and associated with expansion of dysfunctional CD25-FoxP3+ and ILC group 1 (ILC1) cells. These effects were accompanied by a reduction in CD25+FoxP3+ and ILC group 3 (ILC3) cells. By comparison, genetic deletion of DR3 effectively reversed the inflammatory phenotype in SAMP mice by promoting the expansion of CD25+FoxP3+ over CD25-FoxP3+ cells and the production of IL-10 protein. Collectively, our data demonstrate that DR3 signaling modulates a multicellular network, encompassing Tregs, T effectors, and ILCs, governing disease development and progression in SAMP mice with CD-like ileitis. Manipulating DR3 signaling toward the restoration of the balance between protective and inflammatory lymphocytes may represent a novel and targeted therapeutic modality for patients with CD.


Using Hematuria as Detection of Post-kidney Transplantation Upper Urinary Tract Urothelial Carcinoma Is Associated With Delayed Diagnosis of Cancer Occurrence.
Kidney transplantation (KT) is an important renal replacement therapy for end-stage renal disease (ESRD). The incidence of upper urinary tract urothelial carcinoma (UTUC) is relatively higher in Taiwan. According to our institutional database, early onset of post-KT UTUC is not uncommon. Early detection of post-KT UTUC is an important issue to improve oncologic outcome. Because painless hematuria is a common symptom for UTUC, this study analyzes whether using hematuria as post-KT UTUC screening delayed cancer diagnosis or not. From 2005 to 2012, 128 ESRD patients were found to have UTUCs. There were 28 patients who underwent KT and were regularly followed up at our institution. All the patients underwent standard nephroureterectomy. In ESRD patients with UTUC, the post-KT group revealed significantly less gross hematuria and microscopic hematuria at presentation compared with the non-KT group (43% versus 76%, P = .001 and 64% versus 86%, P = .011). For those patients with gross hematuria, non-organ-confined UTUC occurred more in the post-KT group compared with the non-KT group (42% versus 12%, P = .009). For those patients with microscopic hematuria, non-organ-confined UTUC occurred more in the post-KT group compared with the non-KT group with borderline significance (33% versus 16%, P = .085). According to our observation, using gross or microscopic hematuria as detection of post-KT UTUC is associated with delayed diagnosis of cancer occurrence. Closer upper urinary tract image study such as sonography may help earlier cancer screening.


Long-range correlations in pinned athermal networks.
We derive exact results for displacement fields that develop as a response to external pinning forces in two-dimensional athermal networks. For a triangular lattice arrangement of particles interacting through soft potentials, we develop a Green's function formalism which we use to derive exact results for displacement fields produced by localized external forces. We show that in the continuum limit the displacement fields decay as 1/r at large distances r away from a force dipole. Finally, we extend our formulation to study correlations in the displacement fields produced by the external pinning forces. We show that uncorrelated pinned forces at each vertex give rise to long-range correlations in displacements in athermal systems, with a nontrivial system size dependence. We verify our predictions with numerical simulations of athermal networks in two dimensions.


Natural history of severe left ventricular dysfunction after myocardial infarction.
The prevalence and prognosis of severe left ventricular dysfunction after infarction was prospectively analyzed in a series of 259 male patients aged 60 years or less surviving an acute myocardial infarction. All patients underwent coronary angiography 30 days after the acute event and were followed up for a mean period of 34 months (range, 15 to 55 months). Forty-five patients (17 percent) were found to have severe left ventricular dysfunction (ejection fraction less than or equal to 30 percent). Comparison of patients with and without severe impairment of left ventricular function showed the former to have a lower cardiac index (p less than 0.001), higher left ventricular end-diastolic volume index (p less than 0.001), and a higher prevalence of three-vessel disease (p less than 0.025) and of total or subtotal occlusion of at least one coronary artery (p less than 0.025). While the occurrence of congestive heart failure was higher in patients with severe left ventricular dysfunction (p less than 0.001), the probability of developing angina was similar in both groups. Cox's regression analysis showed ejection fraction to be the only independent predictor of survival in patients with severe impairment of left ventricular function. An ejection fraction of 20 percent or less identified a subset of patients with the highest mortality (62 percent at four years), significantly different from that of patients whose ejection fraction was between 21 and 30 percent (28 percent) (p less than 0.001).


Complication of hybrid treatment in type B aortic dissection diagnosed by echocardiography.
This case illustrates an unusual and fatal complication after endovascular treatment of type B aortic dissection and highlights the role of echocardiography in the early diagnosis of complications. In this case, a patient with previous diagnosis of chronic type B aortic dissection and moderate aortic regurgitation underwent endovascular repair of the proximal descending aorta and conservative surgical correction of the aortic valve. On early postoperative, a transesophageal echocardiogram and aortic angiotomography demonstrated proximal endoleak by contrast extravasation around the proximal graft attachment site, causing compression of the stent in its middle portion, resulting in narrowing with reduced cross-sectional area.


New Anticoagulants for the Prevention and Treatment of Venous Thromboembolism.
Anticoagulant drugs, like vitamin K antagonists and heparin, have been the mainstay for the treatment and prevention of venous thromboembolic disease for many years. Although effective if appropriately used, traditional anticoagulants have several limitations such as unpredictable pharmacologic and pharmacokinetic responses and various adverse effects including serious bleeding complications. New oral anticoagulants have recently emerged as an alternative because of their rapid onset/offset of action, predictable linear dose-response relationships and fewer drug interactions. However, they are still associated with problems such as bleeding, lack of reversal agents and standard laboratory monitoring. In an attempt to overcome these drawbacks, key steps of the hemostatic pathway are investigated as targets for anticoagulation. Here we reviewed the traditional and new anticoagulants with respect to their targets in the coagulation cascade, along with their therapeutic advantages and disadvantages. In addition, investigational anticoagulant drugs currently in the development stages were introduced.


Cardiomyocyte production in mass suspension culture: embryonic stem cells as a source for great amounts of functional cardiomyocytes.
Exploiting embryonic stem cell (ESC)-derived cardiomyocytes as a vital source for cell therapies and tissue engineering will depend on robust, large-scale production processes. Recently, we have reported stirring-controlled formation of embryoid bodies, enabling the generation of pure cardiomyocytes in 2-L scale. Expansion and differentiation of genetically engineered mouse ESCs was followed by antibiotic-based cardiomyocyte enrichment. Here we have investigated modification of various parameters aiming at process optimization in a 250-mL spinner flask system. Duration of the differentiation phase, timing of retinoic acid addition, and a slower medium exchange rate were found to be crucial to enhancing cardiomyocyte yield. Improved process conditions were consequently transferred to a 2-L controlled bioreactor. Employing a manual fill-and-draw medium change resulted in the formation of 0.86 x 10(9) cardiomyocytes in a single 2-L batch, thereby reproducing our previous findings. In contrast, an automated perfusion-based strategy enabled the production of 4.6 x 10(9) cardiomyocytes in a single run. This is significantly higher than previously reported and highlights the enormous process optimization potential in the scalable generation of ESC-derived cell lineages.


Light field quality assessment based on aggregation learning of multiple visual features.
Light field imaging is a way to represent human vision from a computational perspective. It contains more visual information than traditional imaging systems. As a basic problem of light field imaging, light field quality assessment has received extensive attention in recent years. In this study, we explore the characteristics of light field data for different visual domains (spatial, angular, coupled, projection, and depth), study the multiple visual features of a light field, and propose a non-reference light field quality assessment method based on aggregation learning of multiple visual features. The proposed method has four key modules: multi-visual representation of a light field, feature extraction, feature aggregation, and quality assessment. It first extracts the natural scene statistics (NSS) features from the central view image in the spatial domain. It extracts gray-level co-occurrence matrix (GLCM) features both in the angular domain and in the spatial-angular coupled domain. Then, it extracts the rotation-invariant uniform local binary pattern (LBP) features of depth map in the depth domain, and the statistical characteristics of the local entropy (SDLE) features of refocused images in the projection domain. Finally, the multiple visual features are aggregated to form a visual feature vector for the light field. A prediction model is trained by support vector machines (SVM) to establish a light field quality assessment method based on aggregation learning of multiple visual features.


Probiotic monotherapy and Helicobacter pylori eradication: A systematic review with pooled-data analysis.
To define probiotic monotherapy effect on Helicobacter pylori (H. pylori) status by performing a systematic review. Methods of analysis and inclusion criteria were based on PRISMA recommendations. Relevant publications were identified by searching PubMed, MEDLINE, Science Direct, and EMBASE. The end-point was to estimate eradication rate and urea breath test delta value before and after probiotic monotherapy across all studies and, overall, with a pooled data analysis. Adverse events of probiotic therapy were evaluated. The data were expressed as proportions/percentages, and 95%CIs were calculated. For continuous variables, we evaluated the weighted mean difference. Odd ratios (ORs) were calculated according to the Peto method for the comparison of eradication rates between probiotics and placebo. Eleven studies were selected. Probiotics eradicated H. pylori in 50 out of 403 cases. The mean weighted eradication rate was 14% (95%CI: 2%-25%, P = 0.02). Lactobacilli eradicated the bacterium in 30 out of 235 patients, with a mean weighted rate of 16% (95%CI: 1%-31%). Saccharomyces boulardii achieved eradication in 6 out of 63 patients, with a pooled eradication rate of 12% (95%CI: 0%-29%). Multistrain combinations were effective in 14 out of 105 patients, with a pooled eradication rate of 14% (95%CI: 0%-43%). In the comparison of probiotics vs placebo, we found an OR of 7.91 in favor of probiotics (95%CI: 2.97-21.05, P < 0.001). Probiotics induced a mean reduction in delta values higher than placebo (8.61% with a 95%CI: 5.88-11.34, vs 0.19% for placebo, P < 0.001). Finally, no significant difference in adverse events was found between probiotics and placebo (OR = 1, 95%CI: 0.06-18.08). Probiotics alone show a minimal effect on H. pylori clearance, thus suggesting a likely direct role.


How to approach and treat viral infections in ICU patients.
Patients with severe viral infections are often hospitalized in intensive care units (ICUs) and recent studies underline the frequency of viral detection in ICU patients. Viral infections in the ICU often involve the respiratory or the central nervous system and can cause significant morbidity and mortality especially in immunocompromised patients. The mainstay of therapy of viral infections is supportive care and antiviral therapy when available. Increased understanding of the molecular mechanisms of viral infection has provided great potential for the discovery of new antiviral agents that target viral proteins or host proteins that regulate immunity and are involved in the viral life cycle. These novel treatments need to be further validated in animal and human randomized controlled studies.


Influence of Wolbachia infection on mitochondrial DNA variation in the genus Polytremis (Lepidoptera: Hesperiidae).
The maternally inherited obligate bacteria Wolbachia is known for infecting the reproductive tissues of a wide range of arthropods and can contribute to phylogenetically discordant patterns between mtDNA and nDNA. In this study, we tested for an association between mito-nuclear discordance in Polytremis and Wolbachia infection. Six of the 17 species of Polytremis were found to be infected with Wolbachia. Overall, 34% (70/204) of Polytremis specimens were Wolbachia positive and three strains of Wolbachia identified using a wsp marker were further characterized as six strains based on MLST markers. Wolbachia acquisition in Polytremis appears to occur mainly through horizontal transmission rather than codivergence based on comparison of the divergence times of Wolbachia and Polytremis species. At the intraspecific level, one of the Wolbachia infections (wNas1) is associated with reduced mtDNA polymorphism in the infected Polytremis population. At the interspecific level, there is one case of mito-nuclear discordance likely caused by introgression of P. fukia mtDNA into P. nascens driven by another Wolbachia strain (wNas3). Based on an absence of infected males, we suspect that one Wolbachia strain (wNas2) affects sex ratio, but the phenotypic effects of the other strains are unclear. These data reveal a dynamic interaction between Polytremis and Wolbachia endosymbionts affecting patterns of mtDNA variation.


The genes for schizophrenia: finally a breakthrough?
A number of susceptibility genes for schizophrenia have recently been identified. They have engendered excitement because replicate studies have attained greater consistency than in the past. In this review, we outline gene mapping methods, and briefly review their strengths and challenges. We also evaluate peer-reviewed genetic association studies that have implicated six selected genes: catechol-O-methyl transferase (COMT), neuregulin 1 (NRG1), dysbindin (DTNBP1), regulator of G-protein signaling 4 (RGS4), and G72 and D-amino-acid oxidase (DAAO). The available supporting evidence is variable. Though credible evidence is available for all of these genes, it is strongest for NRG1 and DTNBP1. Further studies, particularly exhaustive analyses of all polymorphisms at each locus, meta-analyses, and investigations of the likely function of risk alleles (variants) are desirable.


Reports of anaphylaxis after coronavirus disease 2019 vaccination, South Korea, 26 February to 30 April 2021.
The South Korea mass vaccination programme administered 3.8 million doses of COVID-19 vaccinations between 26 February and 30 April 2021. After 173 suspected anaphylaxis reports to the nationwide monitoring system for adverse events following immunisation, 44 anaphylaxis cases were confirmed using Brighton Collaboration case definitions. The rates per million doses were 18.2 cases and 6.2 cases for Vaxzevria and Comirnaty, respectively. Median time of onset was 14 min after vaccination and most cases had recovered at the time of review.


Can young preschool children be trained to perform percept deprivation tasks?
Young preschool children aged 2 and 3 years were exposed to a novel paradigm designed to train visual perception skills. The results indicate that children of this age can be trained to perform a percept deprivation task that requires a sophisticated understanding of attention not normally mastered until 3.5-4 years. Results are discussed with reference to engagement, a precursor to an adult-like understanding of perception.


The Use of Polyvinyl Alcohol Sponge and Cyanoacrylate Glue in the Treatment of Large and Chronic Bronchopleural Fistulae following Lung Cancer Resection.
Bronchopleural fistulae represent a relatively rare complication of pulmonary resection. For inoperable patients, several endoscopic procedures have been described. In the presence of large and chronic bronchopleural fistulae, persistent air leaks require a surgical therapy, while endoscopic airway stent represents a useful palliative treatment. We describe the successful closure of large and chronic bronchopleural fistulae using an expandable polyvinyl alcohol (PVA) sponge and cyanoacrylate glue. In all patients, a rigid bronchoscope was used to insert a small cylinder of PVA sponge within the fistula. After releasing the patch, cyanoacrylate glue was applied directly on the PVA sponge using a channel catheter. This methodology induces an expansion of the clot and the closure of the air leak. The long-term outcome of treatment was checked by flexible bronchoscopy once every month for 3 months and every 6 months until 5 years. We performed endoscopic treatment in 7 consecutive patients with bronchopleural fistula ranging from 4 to 8 mm. In 6 of 7 patients, the bronchial stump was the site of the fistula. In 1 patient, the fistula was visualized on the right wall of the distal trachea. A temporary complete occlusion of the fistula was achieved in 7 of 7 patients and a definitive result in 5 of 7 patients. The use of an expandable PVA sponge and cyanoacrylate glue is an available strategy for endobronchial closure of bronchopleural fistulae.


Therapeutic bispecific antibody formats: a patent applications review (1994-2017).
Bispecific antibodies have become increasingly of interest by enabling new therapeutic applications such as retargeting cellular immunity towards tumor cells. About 23 bispecific antibody platforms have therefore been developed, generating about 62 molecules which are currently being evaluated for potential treatment of a variety of indications, such as cancer and inflammatory diseases, among which three molecules were approved. This class of drugs will represent a multi-million-dollar market over the coming years. Many companies have consequently invested in the development of bispecific antibody platforms, creating an important patent activity in this field. The present review gives an overview of the patent literature over the period 1994-2017 of different immunoglobulin gamma-based bispecific antibody platforms and the molecules approved or in clinical trials. Bispecific antibodies are progressively accepted as potentially superior therapeutic molecules in a broad range of diseases. This frantic activity creates a maze of hundreds of patents that pose considerable legal risks for both newcomers and established companies. It can consecutively be anticipated that the number of patent conflicts will increase. Nevertheless, it can be expected that patents related to the use of a bispecific antibody will have tremendous commercial value.


Collision-induced dissociation of sodiated glucose and identification of anomeric configuration.
Collision-induced dissociation (CID) of sodiated glucose was investigated using electronic structure calculations and resonance excitation in a low-pressure linear ion trap. The major dissociation channels in addition to desodiation are dehydration and C2H4O2 elimination reactions which the barrier heights are near to or lower than the sodiation energy of glucose. Dehydration reaction involves the transfer of the H atom from the O2 atom to the O1 atom, followed by the cleavage of the C1-O1 bond. Notably, α-glucose has a dehydration barrier lower than that of β-glucose. This difference results in the larger branching ratio of dehydration reactions involving α-glucose, which provides a simple and fast method for identifying the anomeric configurations of glucose. The C2H4O2 elimination starts from the H atom transfer from the O1 atom to the O0 atom, followed by the cleavage of the C1-O0 bond. These results were further confirmed by experimental study using 18O-isotope-labeled compounds. Both the experimental data and theoretical calculations suggest that the dehydration reaction and cross-ring dissociation of sodiated carbohydrates mainly occur at the reducing end during low-energy CID.


Nutritional and reproductive signaling revealed by comparative gene expression analysis in Chrysopa pallens (Rambur) at different nutritional statuses.
The green lacewing, Chrysopa pallens Rambur, is one of the most important natural predators because of its extensive spectrum of prey and wide distribution. However, what we know about the nutritional and reproductive physiology of this species is very scarce. By cDNA amplification and Illumina short-read sequencing, we analyzed transcriptomes of C. pallens female adult under starved and fed conditions. In total, 71236 unigenes were obtained with an average length of 833 bp. Four vitellogenins, three insulin-like peptides and two insulin receptors were annotated. Comparison of gene expression profiles suggested that totally 1501 genes were differentially expressed between the two nutritional statuses. KEGG orthology classification showed that these differentially expression genes (DEGs) were mapped to 241 pathways. In turn, the top 4 are ribosome, protein processing in endoplasmic reticulum, biosynthesis of amino acids and carbon metabolism, indicating a distinct difference in nutritional and reproductive signaling between the two feeding conditions. Our study yielded large-scale molecular information relevant to C. pallens nutritional and reproductive signaling, which will contribute to mass rearing and commercial use of this predaceous insect species.


Hospital admissions during the first five years of life: a report from the Dunedin Multidisciplinary Child Development Study.
Admissions to hospital experienced by 991 Dunedin children in the first five years of life are described. Changes in behaviour reported by the mothers as following these admissions were related to the age of the child, circumstances of admission, and extent of contact with parents. Twenty-seven percent of the children had been in hospital and 7% more than once. The majority of admissions were short, particularly for the older children, and parent contact was usual. The majority of admissions were not followed by reported changes in behaviour. Children between 13 and 36 months had the highest incidence of reported behaviour deterioration (25%). Children between 36 and 60 months had the highest incidence of improved behaviour (22%). These results are discussed in relationship to other research on the effects of admission to hospital on young children.


The magnitude, the kinetics and the metabolic efficiency of first-phase insulin response to intravenous glucose are related.
We investigated the relationship between the kinetics, the magnitude and the metabolic efficiency of first-phase insulin response (FPIR) to intravenous glucose. Twenty healthy control subjects and fifty first degree relatives of Type 1 diabetic patients were studied using a standardized protocol for the intravenous glucose tolerance test (IVGTT). The first significant increase in plasma insulin concentrations above baseline appeared as early as the 2nd min (1 min before the end of glucose injection, fast response) in 80% of controls and 70% of relatives, and at the 3rd min or later (delayed response) in the remaining subjects. The greatest delay in insulin release (5th min) was observed in 4 of 6 relatives of Type 1 diabetic patients with impaired FPIR. In the controls and the relatives, the subjects with a fast insulin response had a significantly higher FPIR (controls 215.4 +/- 93.5 vs 59.7 +/- 5.6 microU/ml, p < 0.001 and relatives 143.5 +/- 61.8 vs 55.9 +/- 27.7 microU/ml, p < 0.001) and showed better glucose assimilation (controls 3.05 +/- 1.05 vs 1.64 +/- 0.16%/min, p < 0.05 and relatives 2.6 +/- 0.96 vs 1.6 +/- 0.85%/min, p < 0.01) during IVGTT than the subjects with a delayed response. Moreover, for normal FPIR values in the group of relatives of Type 1 diabetic patients, a fast response was associated with a significantly better glucose assimilation as assessed by the incremental area under the glucose curve (358.6 +/- 64.7 vs 539.2 +/- 67.7 mmol/l per 90 min, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


A wide spectrum of dengue IgM and PCR positivity post-onset of illness found in a large dengue 3 outbreak in Pakistan.
During a large outbreak of dengue serotype 3 in Pakistan in 2006, multiple serum samples were routinely collected for laboratory testing. Two hundred ninety-seven samples were collected between August and November 2006. Serological testing for dengue IgM was performed in Pakistan and polymerase chain reaction (PCR) testing for dengue RNA detection and serotyping were performed in Hong Kong. Dengue-specific IgM was detectable as early as 1 day, and dengue RNA remained detectable for up to 14 days, post-onset of illness. Further statistical analysis found that IgM status (positive, negative, or equivocal) was significantly correlated to clinical (duration of illness, severity of patient-reported arthralgia pain, the presence of any evidence of bleeding, a positive tourniquet test, shock), and other laboratory (platelet and total white cell counts) parameters. In contrast, the qualitative dengue RNA status (PCR positive or negative) was not statistically significantly correlated with any of these other parameters. The results for this population during this outbreak, obtained from single acute samples, demonstrate a wide range of intervals post-onset of illness during which dengue IgM and dengue RNA may be detected. Interestingly, in this study, the dengue IgM positivity correlates more closely with significant clinical illness than the dengue RNA positivity, which may be a feature specific to this particular outbreak.


Quantitative EEG and neurochemical aspects of memory and learning.
Different, established or putative animal models of learning were studied by electrophysiological (EEG) and neurochemical methodologies. The training of rats to new behavioral patterns proved to result in the stimulation of total RNA synthesis rate in specific brain structures, as well as in modifications of the EEG organization of hippocampus. This two-fold approach to the assessment of modifications in learning-involved brain structures was extended to the study of mirror focus and kindling, to verify the suitability of these phenomena as experimental models of learning. Reduced (3H) uridine incorporation and proportion of poly (A)-associated RNA were found in mirror focus in comparison with control regions. These variations seem related to brain damage rather than be congruent with learning-related modifications. Further studies are necessary to verify whether the kindling phenomena are to be equated to learning models.


[Relationship between imaging and pathological features and clinical factors in surgical cases of temporal lobe epilepsy].
The relationships between imaging, pathology and presumed causes in surgical cases of temporal lobe epilepsy (TLE) was studied. The subject was 62 patients (33 males and 29 females) who had had no attacks for more than one year after surgery. Average age at surgery was 28.2 +/- 9.9 years. Obvious neurological abnormalities were not found in these cases. MRI, PET and SPECT were performed. Hematoxylin and eosin was used for pathological judgement. Their medical charts were used to investigate their clinical factors. Although patients suspected of having encephalitis/meningitis had been hospitalized for 2 days to three months during childhood due to disturbance of consciousness with high fever and convulsion for several days; they were not diagnosed with encephalitis/meningitis at that time, and they suffered almost no handicaps other than epilepsy for several years following their comatose episodes. [Result] (1) On MRI, mesial temporal sclerosis (MTS) was detected in 48 of 52 patients (92%); 32 (62%) had high-signal intensity on T 2-weighted images; 31 (60%) had atrophy ¿23 (44%) had high-signal intensity on T 2 + atrophy¿; 5 (10%) had calcified lesions; and 2 (4%) had cystic lesions. On PET and SPECT, abnormal cerebral blood flow was noted in 33 of 36 (92%). (2) On pathological findings (61 cases), Ammon's horn sclerosis (AHS), tumors, gliosis in lateral temporal and meningeal inflammatory finding were detected in 42 (69%), 10 (23%) and 8 (13%) cases, respectively, whereas 2 showed no abnormalities. The 2 patients with normal pathology showed both high-signal intensity and atrophy on MRI. (3) The presumed causes of TLE were encephalitis/meningitis and/or suspected of these diseases in 15 patients (24%), injuries at birth in 5 (8%), and none in 42 (68%). The presumed causes in the 43 patients with AHS were encephalitis/meningitis in 11, injuries at birth in 3, and none in 29. Of the 15 patients in whom encephalitis/meningitis was estimated as the causes of TLE, only 6 (40%) had pathological evidence of meningeal inflammatory finding. Of the 42 patients in whom cause could not be determined, 2 had pathological evidence of meningeal inflammatory finding.


Evidence of non-Maxwellian ion velocity distributions in spherical shock-driven implosions.
The ion velocity distribution functions of thermonuclear plasmas generated by spherical laser direct drive implosions are studied using deuterium-tritium (DT) and deuterium-deuterium (DD) fusion neutron energy spectrum measurements. A hydrodynamic Maxwellian plasma model accurately describes measurements made from lower temperature (<10 keV), hydrodynamiclike plasmas, but is insufficient to describe measurements made from higher temperature more kineticlike plasmas. The high temperature measurements are more consistent with Vlasov-Fokker-Planck (VFP) simulation results which predict the presence of a bimodal plasma ion velocity distribution near peak neutron production. These measurements provide direct experimental evidence of non-Maxwellian ion velocity distributions in spherical shock driven implosions and provide useful data for benchmarking kinetic VFP simulations.


An unusual case of congenital dermal melanocytosis.
Dermal melanocytosis is characterized by the presence of ectopic melanocytes in the dermis. The most common forms include the Mongolian spot, blue nevus, nevus of Ota, and nevus of Ito. Some types of dermal melanocytosis do not fit into any of these morphologic categories, however. Our case demonstrated an extensive amount of uniform deep blue patches of nevi with unilateral distribution on the left face, neck, chest, shoulder, and back. On histopathologic examination, a number of elongated melanocytes scattered throughout the dermis were found. We herein report a case of congenital unilateral dermal melanocytosis.


IgE elevation and anti-plasmodium falciparum IgE antibodies: association of high level with malaria resistance.
The total IgE and anti-Plasmodium falciparum IgE antibodies were determined by enzyme linked immunosorbent assay (ELISA) in 480 children and adults living in malaria endemic area along Thai-Myanmar border, Kanchanaburi Province, western Thailand. Approximately 73.13% of tested individuals had elevated levels of total IgE with a range of 160-998 ng/ml. 20.5% of these IgE were specific to P falciparum blood stage antigens, with a range of 78-353 microg/ml. However, the levels of total IgE were not significantly correlated with those of specific IgE (r = 0.083). The elevation of anti-P falciparum IgE antibodies seems to be age dependent. The prolonged or repeated exposure to malaria parasites is necessary for the induction of specific IgE response as indicated by the finding of a significant correlation between the levels of P falciparum specific IgE and the number of malaria attacks (r = 0.551, p = 0.01). Interestingly, among the specific IgE responders, 20 individuals naturally exposed to malaria but without clinical malaria reported had high levels of both total IgE and anti- P. falciparum IgE antibodies, with mean values of 418.67 mg/ml and 146.25 ng/ml, respectively. It is likely that the antibodies from such specific IgE responders could mediate phagocytosis in vitro.


A meta-analysis of the published research on the affective, cognitive, and behavioral effects of corporal punishment.
The present study is a meta-analysis of the published research on the effects of corporal punishment on affective, cognitive, and behavioral outcomes. The authors included 70 studies published between 1961 and 2000 and involving 47,751 people. Most of the studies were published between 1990 and 2000 (i.e., 53 or 68%) and were conducted in the United States (65 or 83.3%). Each of the dependent variables was coded, and effect sizes (ds) were computed. Average unweighted and weighted ds for each of the outcome variables were .35 and .20 for affective outcomes, .33 and .06 for cognitive outcomes, and .25 and .21 for behavioral outcomes, respectively. The analyses suggested small negative behavioral and emotional effects of corporal punishment and almost no effect of such punishment on cognition. Analyses of several potentially moderating variables, such as gender or socioeconomic status, and the frequency or age of first experience of corporal punishment, the relationship of the person administering the discipline, and the technique of the discipline all had no affect on effect size outcome. There was insufficient data about a number of the moderator variables to conduct meaningful analyses. The results of the present meta-analysis suggest that exposure to corporal punishment does not substantially increase the risk to youth of developing affective, cognitive, or behavioral pathologies.


The serum ferritin levels and liver iron concentrations in patients with alpha-thalassemia: is there a good correlation?
Liver iron overload is common in patients with thalassemia. In patients with beta-thalassemia, the correlation between serum ferritin and liver iron concentration is well established. The correlation between serum ferritin levels and liver iron concentrations in patients with alpha-thalassemia remains limited. This is a cross-sectional study in patients with alpha-thalassemia aged ≥ 18 years old at Srinagarind Hospital, Khon Kaen University, Thailand. Liver iron concentration (LIC) was evaluated by the MRI-T2* technique. Linear logistic regression analysis was used to determine the correlation between serum ferritin levels and liver iron concentrations. One hundred and thirty-one of the MRI-T2* measurements from 65 patients with alpha-thalassemia were evaluated. Patients with non-deletional alpha-thalassemia had higher LIC compared to patients with deletional alpha-thalassemia. The serum ferritin levels were relatively low at the same levels of LIC in patients with non-deletional alpha-thalassemia compared to deletional alpha-thalassemia. The correlation of serum ferritin levels and LIC was modest and different among alpha-thalassemia genotypes. A different serum ferritin threshold is needed to guide iron chelation therapy in patients with alpha-thalassemia. Evaluation of liver iron concentration is necessary for patients with alpha-thalassemia, especially in patients with non-deletional alpha-thalassemia.


Relationships between urbanization and CO2 emissions in China: An empirical analysis of population migration.
China's announcement of its goal of carbon neutrality has increased the practical significance of research on carbon dioxide (CO2) emissions that result from urbanization. With a comprehensive consideration of population migration in China, this study examines the impact of urbanization on CO2 emissions based on provincial panel data from 2000 to 2012. Two indicators (resident population and household registration population) are used to measure urbanization rate. The results reveal that the impact of urbanization on CO2 emissions in China is closely correlated with the structure of urban resident population and interregional population migration. The estimation results are still robust by using generalized method of moments (GMM) estimator and two-stage least squares (2SLS) estimator. The proportion of temporary residents is introduced as a proxy variable for population migration. The panel threshold model regression results show that the proportion of temporary residents has a marginal effect on the relationship between urbanization and CO2 emissions. In regions with a higher proportion of temporary residents, the positive effects of resident population urbanization on CO2 emissions tend to be weaker. These findings are consistent with the theories of ecological modernization and urban environmental transition. This paper makes suggestions on China's urbanization development model and countermeasures are proposed to minimize the CO2 emissions caused by urbanization.


Angiotensin II Type 1 Receptor-Mediated Electrical Remodeling in Mouse Cardiac Myocytes.
We recently characterized an autocrine renin angiotensin system (RAS) in canine heart. Activation of Angiotensin II Type 1 Receptors (AT1Rs) induced electrical remodeling, including inhibition of the transient outward potassium current Ito, prolongation of the action potential (AP), increased calcium entry and increased contractility. Electrical properties of the mouse heart are very different from those of dog heart, but if a similar system existed in mouse, it could be uniquely studied through genetic manipulations. To investigate the presence of a RAS in mouse, we measured APs and Ito in isolated myocytes. Application of angiotensin II (A2) for 2 or more hours reduced Ito magnitude, without affecting voltage dependence, and prolonged APs in a dose-dependent manner. Based on dose-inhibition curves, the fast and slow components of Ito (Ito,fast and IK,slow) appeared to be coherently regulated by [A2], with 50% inhibition at an A2 concentration of about 400 nM. This very high K0.5 is inconsistent with systemic A2 effects, but is consistent with an autocrine RAS in mouse heart. Pre-application of the microtubule destabilizing agent colchicine eliminated A2 effects on Ito and AP duration, suggesting these effects depend on intracellular trafficking. Application of the biased agonist SII ([Sar1-Ile4-Ile8]A2), which stimulates receptor internalization without G protein activation, caused Ito reduction and AP prolongation similar to A2-induced changes. These data demonstrate AT1R mediated regulation of Ito in mouse heart. Moreover, all measured properties parallel those measured in dog heart, suggesting an autocrine RAS may be a fundamental feedback system that is present across species.


Comanagement of Rashes by Primary Care Providers and Dermatologists: A Retrospective Study.
There is a high demand for managing skin disease, and dermatologists are in short supply. To better understand how rashes and other specific skin conditions are co-managed by primary care providers (PCPs) and dermatologists, we estimated the frequency with which PCPs sought consultation with or referral to dermatology and the proportion of patients who had a follow-up dermatology office visit in the following 90 days. The retrospective longitudinal study included 106,459 patients with a skin condition diagnosed by 3,830 PCPs, from January 2017 to March 2017. Comprehensive electronic medical record data with generalized linear mixed modeling accounted for patient factors including diagnosis and clustering by medical center and PCP. PCPs escalated 9% of patients to dermatology through consultation or referral, while 5% required a follow-up dermatology office visit within 90 days. Patients with bullous, hair, or pigment conditions or psoriasis were most likely to be escalated. Clustering of escalation and follow-up visits was minimal in relation to medical center (intraclass correlation, 0.04 for both outcomes) or PCP (escalation, intraclass correlation, 0.16; follow-up visits, 0.09). Improving primary care education in skin disease and, for certain skin conditions, standardizing approaches to workup, treatment, and escalation may further streamline care and reduce pressure on the dermatologist workforce. PCPs managed 91% of rashes without consultation or referral to dermatology, and the frequency of patients scheduled for dermatology office visits after primary care was similar from one PCP to another.


[Omental pedicle flap for chronic empyema].
We have used the omental pedicle flap (OPF) method to treat 10 patients with chronic empyema secondary to pulmonary tuberculosis. Since 1987 they included 9 men and one woman ranging from 48 to 70 years in age. Two patients were required re-operation because of residual bronchopleural fistulas, and the additional procedures (muscle plombage and thoracoplasty) performed in order to close residual dead space produced more severe thoracic deformity and pulmonary dysfunction. In our first successful case, complete thoracoplasty combined with the OPF method also produced pulmonary dysfunction. On the other hand, thoracic deformity was avoided in 3 other patients and 4 patients without thoracoplasty showed better pulmonary function postoperatively. A comparison of the re-operated patients with the successful cases highlighted two important points regarding the OPF method. One is the need for firm fixation of the OPF to a fistula. We usually place a muscular pedicle flap over the OPF, and add limited thoracoplasty as necessary. The other important point is the control of infection. Open window thoracostomy before the OPF method is effective in patients with active infection. The OPF method is an effective radical operation for severe empyema even when residual dead space is present, and it can also be applied to patients with poor pulmonary function.


The problems of increasing transparency on uncertainty.
Public regulators (such as European Food Safety Authority, European Medicines Agency, and European Centre for Disease Prevention and Control) are placing increasing demands on scientists to make uncertainties about their evidence transparent to the public. The stated goal is utilitarian, to inform and empower the public and ensure the accountability of policy and decision-making around the use of scientific evidence. However, it is questionable what constitutes uncertainty around the evidence on any given topic, and, while the goal is laudable, we argue the drive to increase transparency on uncertainty of the scientific process specifically does more harm than good, and may not serve the interests of those intended. While highlighting some of the practical implications of making uncertainties transparent using current guidelines, the aim is to discuss what could be done to make it worthwhile for both public and scientists.


Celochalcoside, a new quinochalcone C-glycoside from Celosia trigyna.
A new quinochalcone C-glycoside featuring a unique quinonoid moiety, named celochalcoside (1), was isolated from the n-butanol extract of the aerial parts of Celosia trigyna L. The structure was determined by extensive spectroscopic analysis as well as mass spectrometric data. Compound 1 showed moderate cytotoxic activities against breast cancer cell lines (MCF-7), colon cancer cell lines (HT-29) and hepatocellular carcinoma cell lines (HepG2) with IC50 values of 23.16, 37.05 and 18.35 μg/ml, respectively.


Thermally Induced Crystallization of High Quality CH3 NH3 PbI3 Film with Large Grains for Highly Efficient Perovskite Solar Cells.
Recently, fully covered and smooth perovskite films could be fabricated by optimized coating methods; however, it is still hard to prepare perovskite films with large grain sizes and high crystallinity. Given the fact that thermal energy can promote crystallization, we combine high-temperature crystallization with the application of a solvent featuring a high boiling point, in order to produce high quality perovskite films with micrometer-sized grains. We further investigated the temperature dependence of the thermally induced synthetic strategy, whereby the grains become larger as the temperature is elevated. After solar cell device fabrication, the efficiency of the best cell can attain a high value of 15.53 % with reduced hysteresis behavior.


Spontaneous plasma exchange by gravity.
Lysagth et al have reported a semplified model of spontaneous plasmapheresis by placing between an A-V shunt a conventional plasmafilter. On the basis of this experience we tried to make a further semplification of this apparatus using a single venous puncture, obtaining by gravity sufficient transmembrane pressure for plasma separation. By alternatively lowering and elevating the system, plasma is separated from the blood and packed red cells are reinfused after a new pass through the filter with FFP or plasma substitutes.


Induction of NO synthesis by lipoteichoic acid from Staphylococcus aureus in J774 macrophages: involvement of a CD14-dependent pathway.
Lipoteichoic acid (LTA), a wall fragment of gram-positive bacteria, induces an isoform of NO synthase (iNOS) in vascular smooth muscle cells and macrophages which produces large quantities of NO and profound vasodilation in rats; this process may be involved in the cause of gram-positive septic shock. This study investigates the effect of LTA from Staphylococcus aureus on NO synthesis and iNOS mRNA induction in a mouse macrophage cell line (J774). LTA caused a time- and dose-dependent increase in NO production and a marked induction of iNOS mRNA. The induction of NO synthesis and iNOS gene expression in response to LTA was significantly inhibited by an anti-mouse CD14 monoclonal antibody. Studies utilizing a mutant cell line (J7.DEF3), which is defective in the expression of a CD14 antigen, showed that the increase in NO and iNOS mRNA caused by LTA is profoundly depressed in J7.DEF3 cells compared to that in parent J774 cells. In contrast, interferon-gamma produced a similar concentration-dependent increase in NO formation in both cell types. Thus, CD14 is involved in the signal transduction events leading to the enhanced expression of iNOS mRNA and activity elicited by LTA in murine macrophages. We propose that agents which block CD14-dependent events may be useful therapeutics in gram-positive shock.


Long-term results of hyperfractionated radiation and high-dose intraarterial cisplatin for unresectable oropharyngeal carcinoma.
In this report, the authors present the results from a study of patients with unresectable oropharyngeal squamous cell carcinomas who were treated on a protocol of hyperfractionated radiation and high-dose intraarterial cisplatin (HYPERRADPLAT) at the University of Kentucky. The study was designed as a prospective, single-armed case series that was conducted in the setting of a single, academic, tertiary referral center. The patient cohort consisted of 24 previously untreated patients who were diagnosed with unresectable oropharyngeal carcinoma and were treated on the HYPERRADPLAT regimen, which included hyperfractionated external beam radiotherapy (1.2 grays [Gy] twice daily) was given for 5 weeks (60 Gy) followed by high-dose intraarterial cisplatin (150 mg/m2) and sodium thiosulfate. Shrinking "large-field" portals were started on Week 6 and finished on Week 7 with a cumulative dose of 76.8-81.6 Gy. The main outcome measures of the study were the primary and neck response rates, the 2-year and 5-year overall survival and disease-specific survival rates, and acute and late treatment morbidity. The median follow-up was 77 months. Complete response rates at the primary and regional lymph nodes were both 88%. The 2-year overall survival and disease-specific survival rates were 57% and 68%, respectively; whereas the 5-year overall survival and disease-specific survival rates were 33% and 42%, respectively. Two patients had Grade 4 mucosal toxicity, and no patient experienced neurologic or significant hematologic toxicities. Within 1 year of treatment, 58% of patients had used a feeding tube. The HYPERRADPLAT regimen produced excellent response rates and overall survival rates comparable to those achieved by patients who had unresectable oropharyngeal carcinomas. Tolerance of the therapy was good, and further studies using HYPERRADPLAT with induction therapy may improve outcomes further in this subset of patients with unfavorable disease.


Reduced racial disparity in receipt of optimal locoregional treatment for women with early-stage breast cancer.
Racial disparities in breast cancer treatment contribute to Black women having the worst breast cancer survival rates in the U.S. We investigated whether differences in receipt of optimal locoregional treatment (OLT), defined as receipt of mastectomy, breast-conserving surgery, or no surgery when contraindicated, existed between Black and White women with early-stage breast cancer from 2008-2018. In this retrospective cohort study, data from the Surveillance, Epidemiology, and End Results (SEER) Program Incidence Database was utilized to identify tumor cases from Black and White women aged 20-64 years old with stage I-II breast cancer. Logistic regression analyses were used to evaluate the associations between race and receipt of OLT as well as potential effect modification by tumor characteristics, and year of diagnosis. Among 177,234 women diagnosed with early-stage breast tumors, disparities in OLT between Black and White women were present from 2008-2010 (2008: 82.1% Black vs. 85.7% White, p<0.001; 2009: 82.1% Black vs. 85.8% White, p<0.001; 2010: 82.2% Black vs. 87.2% White, p<0.001). This disparity was eliminated between 2010-2011 (86.3% Black vs. 87.5% White, p = 0.15), and did not reoccur during the remainder of the study period. From 2010-2011, more Black women received radiation therapy following breast-conserving surgery (43.4% to 48.9%; p = 0.001), which accounted for an overall increased receipt of OLT. Increased receipt of radiation therapy with breast-conserving surgery appeared to drive a substantial increase in OLT for Black women from 2010-2011 that lasted throughout the study period. Further research on the underlying mechanisms that reduced this disparity is warranted.


Emotion in Painting and Art Installations.
Paintings are static 2-dimensional images with limited narrative means. On the basis of a critical analysis of the relevant laboratory scaling studies, museum studies, and neuroaesthetic work, the article reaches a negative conclusion about most paintings' ability to engage sufficiently with general viewers' associative-memory systems, so as to lead to identification and empathy, and induce fundamental psychobiological emotions. In contrast, designers of art installations can draw on subtle combinations of several classes of stimulus properties with psychological significance subsumable under the classical concept of the sublime (physical grandeur, rarity, an association with beauty and with biologically significant outcomes), so that some installations may induce the peak aesthetic emotional response, aesthetic awe--as defined in Aesthetic Trinity Theory (Konečni, 2005, 2011), along with the states of being moved and physiological thrills. The approach also involves an analytical skepticism about emotivism, defined as a culturological proclivity for unnecessary insertion of emotion into accounts of mental life and behavior, especially in the arts. Implications for the role of emotion theory in empirical aesthetics are examined.


Design and performance of an atmospheric pressure inlet system for lithium ion attachment mass spectrometry.
We designed a simple and efficient inlet system to act as an interface between samples at atmospheric pressure and the high vacuum inside a mass spectrometer. The newly designed stainless steel orifice leak sample inlet system is simple and rugged and fulfills all the basic requirements. With this inlet system coupled with a lithium ion attachment mass spectrometer, it is possible to detect any chemical species at atmospheric pressure, including radical intermediates, on a real-time basis. For illustrative purposes, the sampling efficiency of the inlet probe coupled with a lithium ion attachment mass spectrometer is discussed for laboratory air and polyethylene pyrolysis.


Gene structure and expression of a novel Euglena gracilis chloroplast operon encoding cytochrome b6 and the beta and epsilon subunits of the H(+)-ATP synthase complex.
The genes encoding cytochrome b6 of the chloroplast cytochrome b6/f complex (petB) and the ATP synthase CF1-beta subunit (atpB) and epsilon-subunit (atpE) were identified on the EcoD fragment of the Euglena gracilis chloroplast genome. The complete nucleotide sequence of these three genes was determined. The petB-atpB-atpE genes are cotranscribed as a tricistronic operon. This gene organization differs from that of land plants in which atpB-atpE form a discistronic operon, and petB is within the psbB-ycf8-psbH-petB-petD operon. Euglena cytochrome b6 and the beta-subunit of the chloroplast ATP synthase are very similar in derived amino acid sequence to the corresponding gene products from other organisms. The epsilon-subunit of the chloroplast ATP synthase complex is more divergent. In Euglena, the petB-atpB-atpE genes contain introns, including two twintrons, at eight different positions. All of the intron positions were confirmed by analysis of cDNAs. Two independent intercistronic RNA processing events and 11 splicing reactions lead to the accumulation of the mature petB, atpB and atpE monocistronic mRNAs.


Analysis of the toll-like receptor 2-2 (TLR2-2) and TLR4 mRNA expression in the intestinal mucosal immunity of broilers fed on diets supplemented with nickel chloride.
Toll-like receptor (TLRs) are important innate immune receptors, and TLR2 and TLR4 play an important role in intestinal mucosal innate immunity. It has been found that nickel (Ni) can affect the immune system in broilers. The purpose of this study was to analyze changes in TLR2-2 and TLR4 mRNA expression levels in the intestinal mucosal immunity system of broilers induced by dietary nickel chloride (NiCl2) using quantitative real-time polymerase chain reaction (qRT-PCR) assays. Two hundred and forty one-day-old avian broilers were divided into four groups and fed on a corn-soybean basal diet as control diet or the same basal diet supplemented with 300, 600 and 900 mg/kg of NiCl2 for 42 days. Results showed that the TLR2-2 and TLR4 mRNA expression levels in the intestinal mucosa and the cecal tonsil were lower (p < 0.05 or p < 0.01) in the 300, 600 and 900 mg/kg groups than those in the control group. It was concluded that dietary NiCl2 in excess of 300 mg/kg could reduce TLR2-2 and TLR4 mRNA expression levels in the intestinal mucosa and cecal tonsil in broilers, implying that the innate immunity in intestinal mucosal immune system could be impaired by pathways involving injured surface epithelium cells or/and the inhibition of the TLR signal transduction.


The Critical Role of Long Noncoding RNA in Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells.
Objective. Long noncoding RNAs (lncRNAs) have been demonstrated to regulate many biological processes including differentiation. However, their role in osteogenic differentiation was poorly known. Materials and Methods. In this study, we first globally profiled the differentially expressed lncRNAs and mRNAs during osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMMSCs). Bioinformatics analysis was performed to further analyze these significantly changed molecules. Then the role of lncRNA ENST00000502125.2 in the osteogenic differentiation was determined. Results. A number of lncRNAs and mRNAs were significantly differentially expressed during hBMMSC osteogenic differentiation. Among them, 433 lncRNAs and 956 mRNAs were continuously upregulated, while 232 lncRNAs and 229 mRNAs were continuously downregulated. Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that carbohydrate derivative binding and complement and coagulation cascades were most correlated molecular function and pathway, respectively. Downregulation of lncRNA ENST00000502125.2 promoted the osteogenic differentiation of hBMMSCs, and opposite results were found when lncRNA ENST00000502125.2 was upregulated. Conclusions. lncRNAs play a critical role in the osteogenic differentiation of hBMMSCs and targeting lncRNA ENST00000502125.2 might be a promising strategy to promote osteogenic differentiation.


Non-invasive imaging in cardiology for the generalist.
In contrast to invasive techniques, the goal of non-invasive cardiac imaging is to identify or exclude heart disease in response to a patient's clinical history of cardiac localizing symptoms. Imaging also aims to establish the risk of an individual developing future heart disease with a view to preventing major cardiovascular events such as myocardial infarction. As well as a role in risk stratification, non-invasive cardiac imaging also helps with decision making for future medical and procedural interventions. This review outlines the non-invasive imaging modalities available to physicians to identify and risk stratify cardiovascular disease. It discusses the strengths of each imaging technique, in which circumstances it is most useful and its diagnostic accuracy.


Adverse drug reactions and death. A review of 827 cases.
A study of 827 cases of adverse drug reactions (ADRs) in which autopsies were done was carried out to determine the relative frequency of drugs that caused adverse reactions, their sites of action, and the variety of pathologic processes induced by them. Because a variety of nondrug factors played critical roles in generating many of the ADRs, these 827 cases were divided into seven groups. Only one of these groups (25% of the total) met the criteria of ADRs in the usual definitional sense and were also lethal. The validity of the diagnoses of both the ADRs and the basic diseases being treated was strengthened by the addition of morphologic findings to the data base and by the use of an analytic algorithm that was specifically developed for and directed to the evaluation of ADRs.


Investigating the Effects of Tactile Masking and Surface Texture on the Velvet Hand Illusion.
When we hold thin metallic bars between the palms of our hands and rub the palms against each other, the feeling of touching smooth velvet occurs. Previous studies have shown that tactile motion and pressure on the palms are important for this velvet hand illusion. Interestingly, when we experience this illusion, we cannot feel the texture of our palms as we usually do. In the present study, we investigated the possibility that tactile masking contributes to the occurrence of the velvet hand illusion. We measured vibrotactile detection performance on the palms of the hands during the occurrence of the velvet hand illusion. The detection performance was worse when the illusion occurred than when it did not. Moreover, the degradation of the detection performance correlated positively with the subjective magnitude of the illusion. We also examined whether additional surface texture could affect the occurrence of the illusion and found that the illusion became weaker as the roughness of the surface increased. These findings suggest that tactile motion and pressure information delivered by the bars of smooth surface mask tactile sensations on the palms of the hands, resulting in an illusory smooth, frictionless feeling on the palms.


Motility disturbances in the tube versus trabeculectomy study during the first year of follow-up.
To describe the preoperative and postoperative motility disturbances encountered in the Tube Versus Trabeculectomy (TVT) Study during the first year of follow-up. Multicenter randomized clinical trial. settings: Seventeen clinical centers. population: Patients 18 to 85 years old who had previous trabeculectomy and/or cataract surgery and uncontrolled glaucoma with intraocular pressure > or =18 mm Hg and < or =40 mm Hg on maximum tolerated medical therapy. interventions: 350-mm(2) Baerveldt glaucoma implant or trabeculectomy with mitomycin C (MMC). main outcome measures: Preoperative and postoperative evaluation of ocular motility and diplopia. Motility disturbances were detected in 55 patients (28%) at baseline. New-onset persistent diplopia was reported in 5 patients (5%) in the tube group and no patients in the trabeculectomy group at 1 year (P = .06). A new postoperative motility disturbance developed or worsened in 7 patients (9.9%) in the tube group and no patients in the trabeculectomy group during the first year of follow-up (P = .005). Postoperative motility disturbances were also associated with increasing age (P < .001) and right eye surgery (P = .044). Preoperative motility disturbances were common among patients in the TVT Study. New postoperative motility disturbances were more frequent following tube shunt surgery than trabeculectomy with MMC after 1 year of follow-up.


Reagentless impedimetric immunosensor for monitoring of methotrexate in human blood serum using multiwalled carbon nanotube@polypyrrole/polytyramine film electrode.
Ensuring effective monitoring of methotrexate (MTX) levels in the bloodstream of cancer patients undergoing high-dose methotrexate chemotherapy is crucial to prevent potentially harmful side effects. However, the absence of portable analytical devices suitable for point-of-care bedside monitoring has presented a significant obstacle to achieving real-time MTX monitoring. In this study, we developed an impedimetric immunosensor that doesn't require reagents for measuring MTX levels in undiluted human blood serum. This reagentless approach simplifies the assay process, enabling rapid and straightforward MTX quantification. The immunosensor transducer was fabricated by electrodepositing conductive network of porous multiwalled carbon nanotube@polypyrrole/polytyramine on screen-printed gold microchip electrode (SP-Au/MWCNT70@PPy-PTA). Polyclonal anti-MTX antibodies were immobilized on the film, acting as the immunorecognition element. Non-specific binding was prevented by blocking the transducer interface with denatured bovine serum albumin (dBSA) fibrils, resulting in SP-Au/MWCNT70@PPy-PTA/anti-MTXAb|dBSA film electrode. When MTX binds to the SP-Au/MWCNT70@PPy-PTA/anti-MTXAb|dBSA interface, the film conductance and electron transfer resistance changes. This conductivity attenuation allows for electrochemical impedimetric signal transduction without a redox-probe solution. The electrochemical impedance spectroscopy (EIS) results showed increased charge transfer resistance and phase angle as MTX concentrations increased. The SP-Au/MWCNT70@PPy-PTA/anti-MTXAb|dBSA demonstrated high sensitivity, with a linear response from 0.02 to 20.0 μM and a detection limit of 1.93 nM. The detection limit was 50 times lower than the intended safe level of MTX in human serum. The immunosensor exhibited minimal cross-reactivity with endogenous MTX analogs and serum proteins. The SP-Au/MWCNT70@PPy-PTA/anti-MTXAb|dBSA immunosensor presents a simple and rapid method for therapeutic drug monitoring compared to traditional immunoassay systems.


[Concept of the Pain Rehabilitation].
Pain causes physical disability and psychosocial issues and consequently reduces quality of life. Pain rehabilitation with exercise, cognitive-behavioral therapy, interdisciplinary rehabilitation and patient education improves not only subjective pain perception but also pain-associated dysfunction. The pain rehabilitation is characterized by enabling self-management based on patient-centered perspective and decision-making by the patient.


Systemic release of high mobility group box 1 protein during severe murine influenza.
Hypercytokinemia is gaining recognition as the mechanism of fatality from influenza. No work to date has addressed the role of high mobility group box 1 protein (HMGB1) in influenza, the parallel being that in other severe proinflammatory cytokine syndromes (e.g., sepsis and malaria) levels of circulating HMGB1 are elevated and may correlate with death. Using a commercially available ELISA for HMGB1, we found that HMGB1 was not increased in the plasma of influenza virus-infected mice (A/Japan/305/57) on day 7 post infection, about the time of peak mortality, and peak levels of HMGB1 in the plasma did not occur until relatively late in infection, on day 9 post infection. In keeping with the late peak of HMGB1 being unassociated with mortality, administration of ethyl pyruvate, which inhibits active secretion but not passive release of HMGB1, to influenza virus-infected mice, did not affect their survival. Further work is required to determine whether influenza virus infection induces passive release of HMGB1, and whether HMGB1 neutralization with a specific Ab would improve survival.


A prospective study of hip fracture patients.
This prospective study of 85 femoral neck fracture patients has shown that these patients are older than other 65 + orthopaedic admissions and match the age of geriatric admissions. A disproportionately high number of the patients fall into the disabled, less mobile, not married and institutionalised categories. Disuse is suggested as one aetiological factor in the generation of osteoporosis. Rehabilitation is compromised by the significant delays in discharge which occur when patients are not able to return to their original environment, particularly where placement is required in a geriatric unit or in a private hospital.


Stent fracture and occlusion after treatment of symptomatic vertebral artery ostium stenosis with a self-expanding device. A case report.
Endovascular stenting with a balloon expandable device is currently the preferred treatment modality for symptomatic proximal vertebral artery stenosis, but high rates of in-stent restenosis remain a major problem, for which stent fracture might be a contributing factor. Limited reports showed that placement of self-expanding stents in the proximal vertebral artery might reduce restenosis; no stent fracture has been reported to date. We describe here a new case of fracture and occlusion of a self-expanding stent after endovascular treatment of symptomatic vertebral artery ostium stenosis.


Role of arginase in sciatectomized muscle.
Substrate kinetics of arginase were investigated in normal and sciatectomized gastrocnemius muscle of frog. Sciatectomized muscle arginase showed 47% elevation in V while Km showed no change. Sciatectomic activation of muscle arginase accounted for the stepped up urea levels which may be of significant use in combating ammonia toxicity and maintaining chemohomeostasis.


Proteomics as a tool for the modelling of biological processes and biomarker development in nutrition research.
Nutrition research has slowly started to adopt the proteomics techniques to measure changes in the protein complement of a biological system. This enables modelling of biological processes in response to dietary interventions, as well as the elucidation of novel biomarkers for health or disease that are sensitive to such interventions. There are limited studies on the effect of micronutrients on the proteome, so this review concentrates rather more on dietary intervention studies that have used proteomics (mainly classical 2D gel electrophoresis combined with mass spectrometry) to elucidate changes in pathways that relate to glucose and fatty acid metabolism, oxidative stress, anti-oxidant defence mechanisms and redox status. The ability to measure regulation of more low abundant proteins, such as those involved in inflammatory pathways, as well as the evaluation and validation of newly discovered candidate biomarkers in human biofluids, may depend on the introduction of more quantitative and sensitive methods like multiple reaction monitoring (MRM) and multiplexed immunoassays in nutrition research.


Intrapersonal Variation in Goal Setting and Achievement in Health Coaching: Cross-Sectional Retrospective Analysis.
Chronic conditions in the United States are among the most costly and preventable of all health problems. Research suggests health coaching is an effective strategy for reducing health risks including decreases in weight, blood pressure, lipids, and blood glucose. Much less is known about how and when coaching works. The aim of this study was to conduct an analysis of intrapersonal variations in participants' progression in health coaching, examining gender and age-related differences. This was a cross-sectional, retrospective analysis of 35,333 health coaching participants between 2012 and 2016. Differences in number of goals and activities set and completed, and number of interactions were assessed using negative binomial models. Differences in goal type were assessed using logistic regression for gender and using the Welch test for age to account for unequal variances. Participants choosing online coaching were more likely to be younger and female (P<.001). Gender and age differences were found for the types of goals set by participants. Regarding program activity, women set and completed 12% more action steps than men (P<.001), averaging 21% more interactions than men (P<.001); no gender differences were found in number of goals completed (P=.12), although the percentage of males and females completing goals was significantly different at 60 and 120 days postenrollment (P<.001). Results indicated significant age-related differences in all aspects of program activity: number of interactions, goals set and completed, action steps set and completed (all P values <.01), as well as significant differences in percentage of individuals completing initial goals within 30 days, with older individuals completing more than younger individuals did (all P values <.001). This study found significant intrapersonal variation in how people participate in and progress through a coaching program. Age-related variations were found in all aspects of coaching activity, from modality preference and initial choice of goal type (eg, weight management, tobacco cessation) to goal completion, whereas gender-related differences were demonstrated for all program activities except number of goals set and completed. These findings indicate that to maximize behavior change, coaches need to personalize the coaching experience to the individual.


The effect of positions on spirometric values in obese asthmatic patients.
Obesity as a common health risk is increasing all over the world. The aim of this study was evaluation of standing and sitting positions on spirometric values in obese asthmatic patients, in comparison with normal obese subjects. The study included 49 obese asthmatic patients with mean age of 42.63 years and body mass index of 36.06 kg/m2, and 51 control obese normal subjects with mean age of 39.86 years and body mass index of 36.69 kg/m2. Subjects with body mass index of (BMI) > or =30 kg/m2 were enrolled in the study. Spirometric values were measured according to American Thoracic Society (ATS) recommendation. In both groups forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were measured in sitting and standing positions, and the results were compared. The mean+/-SD of FVC in sitting and standing positions in obese asthmatic patients were: 3.04+/-0.93 lit and 3.03+/-0.96 lit, p=0.37; and in control group: 3.68+/-1.12 lit and 3.72+/- 1.11 lit, p=0.39, respectively. The mean+/-SD of FEV1 in the sitting position and standing positions in obese asthmatic patients were: 2.38+/- 0.75 lit and 2.40+/- 0.81 lit, p=0.20; and in control subjects: 3.17+/- 0.92 lit and 3.21+/- 0.93 lit, p=0.07. This study showed that spirometric values in obese asthmatic patients with BMI> or =30 are not affected by the standing and sitting positions.


The DNA damage response: implications for tumor responses to radiation and chemotherapy.
Cellular responses to DNA damage are important determinants of both cancer development and cancer outcome following radiation therapy and chemotherapy. Identification of molecular pathways governing DNA damage signaling and DNA repair in response to different types of DNA lesions allows for a better understanding of the effects of radiation and chemotherapy on normal and tumor cells. Although dysregulation of the DNA damage response (DDR) is associated with predisposition to cancer development, it can also result in hypersensitivity or resistance of tumors to therapy and can be exploited for improvement of cancer treatment. We highlight the DDR pathways that are activated after treatment with radiation and different classes of chemotherapeutic drugs and describe mechanisms determining tumor sensitivity and resistance to these agents. Further, we discuss approaches to enhance tumor sensitivity to radiation and chemotherapy by modulating the DDR with a goal of enhancing the effectiveness of cancer therapies.


Recent topics on podocytes and aldosterone.
Podocyte injury is a major cause of proteinuria, a core component of chronic kidney disease. We reported that podocyte impairment underlied the early glomerulopathy in animal models of lifestyle-related diseases, such as hypertension and metabolic syndrome. Accumulating evidence suggests that overactivation of the aldosterone-mineralocorticoid receptor (MR) system has harmful effects on podocytes. We found that MR signaling was enhanced in such lifestyle-related diseases with podocyte injury and proteinuria, which were ameliorated by MR antagonist. Subsequent studies revealed that plasma aldosterone concentrations are not always increased in proteinuric conditions with renal MR activation, and the mechanisms of MR overactivation remained elusive. We recently identified a novel mechanism of Rac1-mediated podocyte impairment using RhoGDIα knockout mice; Rac1 potentiates the activity of MR in a ligand-independent manner, thereby accelerating podocyte injury. We demonstrated that the Rac1-MR pathway contributes to the ligand-independent aberrant MR activation in salt-sensitive hypertension and renal injury models. The importance of the RhoGDIα-Rac1-MR pathway in human glomerular disease is underscored by the findings that mutations in RhoGDIαgene cause nephrotic syndrome. Our results provide evidence that the Rac1-MR signal cascade as a novel therapeutic target for chronic kidney disease.


An integrated chronic disease management model: a diagonal approach to health system strengthening in South Africa.
The integrated chronic disease management model provides a systematic framework for creating a fundamental change in the orientation of the health system. This model adopts a diagonal approach to health system strengthening by establishing a service-linked base to training, supervision, and the opportunity to try out, assess, and implement integrated interventions.