Computerized physician order entry and electronic medical record systems in Korean teaching and general hospitals: results of a 2004 survey.
To determine the availability of computerized physician order entry (CPOE) and electronic medical record (EMR) systems in teaching and general hospitals in the Republic of Korea. A combined mail and telephone survey of 283 hospitals. The surveys assessed the availability of CPOE and EMRs in the hospitals, as well as inducement, participation, and saturation regarding CPOE use by physicians. A total of 122 (43.1%) hospitals responded to the survey. The complete form of CPOE was available in 98 (80.3%) hospitals. The use of CPOE was mandatory in 92 (86.0%) of the 107 hospitals that responded to the questions regarding the requirement of CPOE use. In 85 (79.4%) of the hospitals in which CPOE was in use, more than 90% of physicians used the system. In addition, physicians entered more than 90% of their total orders through CPOE in 87 (81.3%) hospitals. In contrast, a complete EMR system was available in only 11 (9.0%) of the hospitals. Of the teaching and general hospitals in the Republic of Korea that responded to the survey, the majority (80.3%) have CPOE systems, and a complete EMR system is available in only 9%.


Treatment strategy of hilar and intraglandular stones in wharton's duct: A 12-year experience.
To suggest a strategy for transoral removal of hilar and intraparenchymal submandibular stones. Retrospective case series. Retrospective evaluation was performed for 514 consecutive patients with hilar and intraparenchymal submandibular stones treated via endoscopy-assisted surgery from January 2006 to June 2018. Three patients had bilateral stones. The stones were classified as: hilar (type I), posthilar (type II), intraparenchymal (type III), and multiple stones (type IV). The affected glands included 311 with type I, 84 with type II, 65 with type III, and 57 with type IV stones. Stones were successfully removed in 478 glands (92.5%, 478/517). Main treatment techniques included hilum ductotomy in 311 glands, intraparenchymal ductotomy in 68, submandibulotomy in 14, intraductal retrieval in 74, and hilum ductotomy accompanied by intraductal retrieval in 11. At a mean 40-months follow-up of 478 successful cases, clinical outcomes were good in 425, fair in 27, and poor in 26 glands. Postoperative sialograms in 75 stone-free patients were categorized as: type I, normal (n = 6); type II, ectasia or stenosis in the main duct and no persistent contrast on functional films (n = 44); type III, ectasia or stenosis in the main duct and mild contrast retention (n = 15); and type IV, poor shape of the main duct and evident contrast retention (n = 10). Postoperative sialometry of 32 patients revealed no significant differences of the gland function between the two sides. Appropriate use of various endoscopy-assisted approaches helps preserve the gland and facilitates recovery of gland function in patients with different depths of hilo-parenchymal submandibular stones. 4 Laryngoscope, 130:2360-2365, 2020.


Biomimetic affinity ligands for immunoglobulins based on the multicomponent Ugi reaction.
Affinity chromatography is the method of choice for biomolecule separation and isolation with highly specific target recognition; it is ideally suited to the purification of immunotherapeutic proteins (i.e., mAbs). Conventional affinity purification protocols are based on natural immunoglobulin (Ig)-binding proteins, which are expensive to produce, labile, unstable, and exhibit lot-to-lot variability. Biological ligands are now being replaced by cost-effective, synthetic ligands, derived from the concepts of rational design and combinatorial chemistry, aided by in silico approaches. In this chapter, we describe a new synthetic procedure for the development of affinity ligands for immunoglobulins based on the multicomponent Ugi reaction. The lead ligand developed herein is specific for the IgG-Fab fragment and mimics Protein L (PpL), an IgG-binding protein isolated from Peptostreptococcus magnus strains and usually used for the purification of antibodies and their fragments.


Spectrum of Thrombotic Complications in Fatal Cases of COVID-19: Focus on Pulmonary Artery Thrombosis In Situ.
COVID-19-related thrombosis affects the venous and arterial systems. Data from 156 autopsies of COVID-19 patients were retrospectively analyzed to investigate the pattern of thrombotic complications and factors associated with pulmonary artery thrombosis and thromboembolism. Thrombotic complications were observed in a significant proportion (n = 68, 44%), with pulmonary artery thrombosis the most frequently identified thrombotic event (42, 27%). Multivariate analysis revealed that the length of hospital stay (OR 1.1, p = 0.004), neutrophil infiltration in the alveolar spaces (OR 3.6, p = 0.002), and the absence of hyaline membranes (OR 0.1, p = 0.01) were associated with thrombotic complications. Neutrophil infiltration in the alveolar spaces (OR 8, p < 0.001) and the absence of hyaline membranes (OR 0.1, p = 0.003) were also independent predictors of pulmonary artery thrombosis. The association of pulmonary artery thrombosis with an absence of hyaline membranes suggests it occurs later in the course of COVID-19 infection. As neutrophil infiltration in the alveolar spaces may indicate bacterial infection, our studies suggest the consideration of bacterial infections in these critically ill patients.


Advances in understanding the molecular mechanisms of cytoplasmic male sterility and restoration in rice.
Cytoplasmic male sterility (CMS) in plants is a male reproductive defect determined by mitochondrial genes and inherited maternally. CMS can be suppressed by nuclear restorer of fertility (Rf) genes. Therefore, CMS/Rf systems provide a classic model for the study of mitochondrial-nuclear interactions in plants. Moreover, CMS/Rf systems are economical, effective tools for the production of hybrid seeds. For example, CMS/Rf systems have been applied in over forty countries to breed hybrid rice (Oryza sativa L.) with improved yields due to hybrid vigor. The production of hybrid rice mainly depends on three types of CMS systems, namely Wild-Abortive type CMS (CMS-WA), Hong-Lian type CMS (CMS-HL) and Boro II type CMS (CMS-BT). Understanding the molecular mechanisms underlying these CMS/Rf systems will help us to understand mitochondrial-nuclear interactions, and accelerate the utilization of heterosis for improvement in yield. In the past decades, research benefitting from the availability of the high-quality, annotated mitochondrial and nuclear genome sequences of rice has isolated many CMS genes, identified the cognate nuclear Rf genes and studied the molecular mechanisms underlying CMS and restoration in rice. Here, we focus on recent advances in studies of the three major CMS/Rf systems in rice and discuss the key issues facing basic research and application of CMS/Rf systems in the future.


SPP1 rs4754 and its epistatic interactions with SPARC polymorphisms in gastric cancer susceptibility.
The matricellular glycoprotein products of the SPP1 and SPARC genes play critical roles in many aggressive tumor phenotypes including gastric cancer. We sought to test whether the polymorphisms of these two genes, individually or jointly, influence gastric cancer susceptibility. Nine potentially functional, tagging single nucleotide polymorphisms (tagSNPs) of SPP1 and SPARC were selected and detected using the Kompetitive Allele Specific PCR method in 301 gastric cancer cases and 1441 healthy control subjects. We found that the genotype frequencies of SPP1 rs4754 in gastric cancer were significantly different from those in controls. The rs4754 TT genotype conferred an increased risk of gastric cancer, with unadjusted and adjusted ORs ranging from 1.75 to 1.95 (all P<0.05). The assessment of the effect modifications of sex and age on the genetic effects also confirmed the statistically significant association of the rs4754 TT genotype with increased gastric cancer risk. Epistatic interactions were found between SPP1 rs4754 and SPARC rs1054204, rs3210714 and rs3549 (all P values for interaction<0.05). During the assessment of the epistatic effects between pairs of interacting factors, increased gastric cancer risk was observed in the combined presence of the SPP1 rs4754 TT genotype and the common genotypes of interacting SPARC SNPs, with ORs ranging from 3.94 to 4.41. When the genetic influence of SPP1 rs4754 TT was excluded, the genetic effects of the SPARC rs1054204, rs3210714 and rs3549 common genotypes on gastric cancer susceptibility switched from being risky to beneficial. These data reveal an association between the SPP1 rs4754 polymorphism and altered risk of gastric cancer and highlight an important role of the epistatic effects of SPP rs4754 with SPARC polymorphisms in gastric carcinogenesis. Additional functional experiments and independent large-scale studies, especially in other ethnic populations, are needed to confirm our results.


Emerging biomarkers in urothelial carcinoma: Challenges and opportunities.
Advanced urothelial carcinoma (UC) is a very important cause of cancer-related morbidity and mortality with, until recently, only a few available therapeutic options. The treatment landscape has dramatically changed in recent years with the introduction of immune checkpoint inhibitors and the development of novel targeted agents, such as erdafitinib, and antibody-drug conjugates, such as enfortumab vedotin. Cost-effective utilization of this rapidly expanding therapeutic armamentarium can be further optimized via the identification and validation of reliable prognostic and predictive biomarkers that inform prognostication and patient selection. In this review, we aim to summarize examples of recent developments in the rapidly expanding field of emerging biomarkers in UC, outlining challenges and opportunities.


Cirrhotomimetic type hepatocellular carcinoma diagnosed after liver transplantation--eighteen months of follow-up: a case report.
Diffuse-type hepatocellular carcinoma (HCC) is a contraindication to liver transplantation (OLT). However, cirrhotomimetic HCC, which is a form of the diffuse type, is difficult to diagnose preoperatively, there are no published reports about its prognosis after OLT. We performed an OLT for a case of cirrhotomimetic HCC diagnosed postoperatively. This 41-years-old man was on the waiting list for OLT owing to hepatitis B virus-related liver cirrhosis and esophageal variceal bleeding. Three months before transplantation, newly developed small nodules were detected on computed tomography (CT); there were no interval changes on CT after 2 months. His serum value of alpha-fetoprotein (alpha-FP) was 327 ng/mL. The patient received a deceased donor liver transplantation and his postoperative course was uneventful. However, on pathologic findings, the explanted liver showed malignant cells in most cirrhotic nodules. So, the patient's pathologic diagnosis was cirrhotomimetic HCC. Triple immunosuppression was administered and steroid stopped at about 2 weeks after transplantation. Eighteen months after transplantation, alpha-FP was 1.5 ng/mL and there was no evidence of recurrence on follow-up CT. In conclusion, cirrhotomimetic HCC is rare and difficult to detect, preoperatively. Despite the short-term follow-up, we did not detect recurrence of HCC.


Trajectories of Older Adults' Leisure Time Activity and Functional Disability: a 12-Year Follow-Up.
This study explored how changes in leisure time activities interplayed with changes in functional disability among Taiwanese older adults. A parallel process and multiple-indicator latent growth curve modeling was adopted for analysis of the data. Longitudinal data from four waves of the Taiwan Longitudinal Study on Aging, collected between 1996 and 2007, were used for analysis. Data included responses of 5451 older adults with a mean age of 67.16 years (SD = 2.51) in 1996. Compared to baseline level of leisure time activities, increasing the rate of change in leisure time activities has more than three times the effect on slowing down the progression of functional disabilities. The baseline functional disabilities did not significantly predict the changes in leisure time activity participation. Engagement in leisure time activity in later life is associated with a slower speed of progression toward functional disability. Early functional disability may not inhibit leisure time activity participation in later life.


Sexual debut and college entrance among South Korean adolescents.
For the past few decades, numerous theoretical perspectives have predicted a negative association between adolescent sexual debut and the probability of college entrance. The present article extends the literature by using nationally representative longitudinal data from South Korea to assess these perspectives. Drawing on longitudinal data from South Korea, this article examined the impact of becoming sexually active between 8th and 12th grades on the probability of college entrance. We controlled for a wide array of confounding variables by using logit models that account for longitudinal attrition and school-based sampling design. Analytical results showed that the initiation of sexual intercourse during adolescence predicted a statistically significant decrease in the probability of college entrance for both boys and girls. Gender-specific analyses suggested that, on average, sexual debut in adolescence was associated with a decrease of 10.3 percentage points in the probability of college entrance for boys and a decrease of 14.7 percentage points for girls. These findings strongly support the theoretical perspectives of age norm theory and sexual double standards in South Korea, where strictly conservative attitudes toward sexuality and sexual behaviors are dominant.


Does training practice nurses to carry out physical health checks for people with severe mental illness increase the level of screening for cardiovascular risk?
Compared to the general population, people with severe mental illness (SMI) have a higher risk of developing cardiovascular disease (CVD). Authors of clinical guidelines advise annual screening for CVD risk factors with appropriate lifestyle counselling. There are seven recommended elements of this health check: blood pressure, body mass index (or waist circumference), blood glucose, serum cholesterol, diet advice, exercise recommendations and smoking cessation guidance. To establish whether training practice nurses increases the proportion of patients with SMI who are screened for CVD risk factors and given lifestyle advice in primary care. A before-and-after audit of 400 patients on the SMI registers in five primary care centres in Northampton, England. Following the training, the proportion of patients with SMI who received all elements of the health check significantly increased (pre-training: n = 33, 8%, 95% CI = 6-11; post-training: n = 60, 15%, 95% CI = 12-19; RR = 1.82, 95% CI = 1.22-2.72, p = .01). Training practice nurses about CVD prevention in people with SMI may be effective in increasing the proportion of patients in this group who receive a comprehensive health check.


Inhibition of the voltage-dependent calcium currents in isolated frog sensory neurons by GABA-related agonistic compounds.
Effects of GABAA-, barbiturate- and benzodiazepine receptor agonists and GABAB agonist, baclofen, on voltage-dependent Ca2+ current (ICa) were studied in isolated frog sensory neurons after suppression of Na+ and K+ currents using single-electrode voltage-clamp. GABA, muscimol, taurine and pentobarbital (PB) dose-dependently induced a transient Cl- current (ICl), while baclofen and diazepam (DZP) did not elicit any currents. With GABAA agonists such as GABA, muscimol and taurine, ICa was suppressed transiently, and the maximum inhibition of ICa occurred within 1 min. The suppression of ICa by all GABAA agonists was neither voltage dependent nor attenuated in the presence of either bicuculline or picrotoxin. In addition, there was no correlation between GABA- and baclofen-induced suppressions of ICa. The results suggest that the inhibition of ICa by GABAA receptor agonists is not due to either GABAA or GABAB receptor activation at least. The inhibition of ICa by baclofen, PB and DZP was persistent. PB suppressed the amplitude of ICa and also facilitated the inactivation process, suggesting that PB behaves as a Ca channel blocker. However, the mechanisms of ICa suppression by baclofen and DZP are the subject for a future study. The potency order of the drugs in reducing ICa was muscimol greater than GABA = DZP greater than baclofen greater than PB greater than taurine.


Unusual arteriovenous communications presenting as cardiac murmurs in infancy. Report of three cases.
Three cases are decribed of infants presenting with murmurs in, or adjacent to, the thorax and considered to be cardiac. Later full investigations established that the murmurs were due to aorto-azygos fistula, vertebral arterio-venous fistula and intercostal angioma, respectively. While such lesions are extremely rare, the possibility of systemic arteriovenous communication should be considered in infants with atypical murmurs.


Prenatal exposure to phthalates and emotional/behavioral development in young children.
Endocrine disrupting chemicals (EDCs) such as phthalates, found in our daily environment, are nowadays suggested to be associated with adverse outcomes. Prenatal exposure was found associated with neurodevelopmental complications such as behavioral difficulties in school age children. To explore the association between intrauterine exposure to phthalates and emotional/behavioral development of 24 months old toddlers. Women were recruited at 11-18 weeks of gestation and provided spot urine samples, analyzed for phthalate metabolites (DEHP, DiNP, MBzBP). Offspring were examined at 24 months of age, using standard maternal report, regarding developmental and behavioral problems (CBCL, ASQ-3, HOME questionnaires) (N = 158). To explore the associations between metabolite levels and developmental outcomes, multivariate GLM analysis (General Linear Model) was used according to tertiles and developmental scores on each developmental outcome. Associations of Di-(2-ethylhexyl) phthalate (DEHP) maternal exposure with behavioral-developmental outcomes were found only in boys. Compared with boys with lower DEHP maternal exposure, boys with high DEHP maternal exposure had lower developmental score in personal social abilities in the ASQ-3 questionnaire (50.68 + 8.06 and 44.14 + 11.02, high and low DEHP, respectively, p = 0.03), and more internalizing problems (for example, emotionally reactive score in high and low DEHP: 53.77 + 7.41 and 50.50 + 1.19, respectively, p = 0.029; anxious or depressed score: 53.38 + 5.01 and 50.75 + 1.34, respectively, p = 0.009; and somatic complaints scores 64.03 + 10.1 and 55.84 + 7.84, respectively, p = 0.003), and externalizing problems (49.28 + 8.59 and 43.33 + 9.11, respectively, p = 0.039). No differences were found in the development and behavior problems between high and low DEHP maternal exposure level in girls. Maternal DEHP metabolite concentrations measured in first trimester urine was associated with children's emotional/behavioral developmental problems in 24-months old boys, supporting accumulating evidence of DEHP as a potentially harming chemical and call for environmental attention.


Subtemporal approach to basilar bifurcation aneurysms: advanced technique and clinical experience.
The surgical treatment of basilar bifurcation aneurysms is challenging, and many of these aneurysms are currently treated by endovascular means. However, the complete closure of the aneurysm by surgical clipping still remains the best and most permanent cure for the aneurysm. The "gold standard", subtemporal approach was established and introduced by Drake and it has been adapted by the senior author Hernesniemi. We describe our present modified technique of this approach based on clinical experience. The subtemporal approach to basilar bifurcation aneurysms has been regularly used by the senior author Hernesniemi in recent 15 years in over 200 operations in Kuopio and Helsinki, Finland. This approach is suitable in most basilar bifurcation aneurysms except for those high above the posterior clinoid process. To avoid temporal lobe damage, cerebrospinal fluid drainage is necessary. Benefits of subtemporal approach are short operative and retraction times, and no need for skull base resection. The subtemporal approach is simple and safe in experienced hands, and should be considered the standard method to approach most basilar bifurcation aneurysms.


Adropin decreases endothelial monolayer permeability after cell-free hemoglobin exposure and reduces MCP-1-induced macrophage transmigration.
Cell-free heme-containing proteins mediate endothelial injury in a variety of disease states including subarachnoid hemorrhage and sepsis by increasing endothelial permeability. Inflammatory cells are also attracted to sites of vascular injury by monocyte chemotactic protein 1 (MCP-1) and other chemokines. We have identified a novel peptide hormone, adropin, that protects against hemoglobin-induced endothelial permeability and MCP-1-induced macrophage migration. Human microvascular endothelial cells were exposed to cell-free hemoglobin (CFH) with and without adropin treatment before measuring monolayer permeability using a FITC-dextran tracer assay. mRNA and culture media were collected for molecular studies. We also assessed the effect of adropin on macrophage movement across the endothelial monolayer using an MCP-1-induced migration assay. CFH exposure decreases adropin expression and increases paracellular permeability of human endothelial cells. Treating cells with synthetic adropin protects against the increased permeability observed during the natural injury progression. Cell viability was similar in all groups and Hmox1 expression was not affected by adropin treatment. MCP-1 potently induced macrophage migration across the endothelial monolayer and adropin treatment effectively reduced this phenomenon. Endothelial injury is a hallmark of many disease states. Our results suggest that adropin treatment could be a valuable strategy in preventing heme-mediated endothelial injury and macrophage infiltration. Further investigation of adropin therapy in animal models and human tissue specimens is needed.


Optimal use of anthracycline-free perioperative chemotherapy in HER2-positive breast cancer patients.
In adjuvant settings of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, anthracycline-based chemotherapy followed by taxane and trastuzumab is a standard regimen. Recent studies have reported the use of anthracycline-free adjuvant chemotherapy in selected HER2-positive breast cancer patients. We conducted a single-center retrospective study to identify the characteristics of HER2-positive breast cancer patients for whom anthracyclines can be safely omitted. A total of 238 women were diagnosed with HER2-positive breast cancer and treated with neoadjuvant and/or adjuvant chemotherapy between January 1, 2008 and December 31, 2015 at Keio University Hospital. They were divided in two cohorts: an "anthracycline" cohort of 112 anthracycline-treated women and a "no anthracycline" cohort of 126 anthracycline-untreated women. Survival outcomes were estimated by Kaplan-Meier method. The 3-year disease-free survival rates in the no-anthracycline and anthracycline cohorts were 91.3% and 93.1%, respectively (P = 0.692). After using a statistical method with inverse probability of treatment weighting to minimize the selection bias, no significant differences were observed between the two cohorts (adjusted hazard ratio for disease-free survival: 1.042; P = 0.909). Stratified by tumor size, no significant differences were observed between the two cohorts in the cT1N0 and cT2N0 subsets (P = 0.516 and P = 0.579, respectively). The recurrence rate was low among patients who achieved pathological complete response after receiving neoadjuvant chemotherapy with or without anthracyclines. Our study suggests that anthracyclines can be safely omitted in selected patients with HER2-positive breast cancer, who have cT1N0 or cT2N0 and achieved pathological complete response after receiving neoadjuvant chemotherapy.


Alteration of GABA transporter expression in the rat cerebral cortex following needle puncture and colchicine injection.
In the adult cerebral cortex, GABA transporters (GATs) are expressed by both neurons and astrocytes. GAT-1 immunoreactivity is found in axon terminals of GABAergic neurons and astrocytes, while GAT-3 immunolabeling occurs only in the latter. The present study was designed to determine whether the expression of GAT-1 and GAT-3 in the adult rat cerebrum changes after needle lesion and colchicine infusion. Following a needle puncture or a saline injection, immunolabeling for GAT-1 and GAT-3 was slightly increased in an area around the needle track. Not only was the neuropil labeling for both GATs increased, but also a few neuronal somata were found to be immunoreactive for GAT-1. Colchicine injections induced a striking increase in immunolabeling for both GATs in the neuropil in an area adjacent to the needle path and surrounding it. A homologous region of the contralateral hemisphere also showed a moderate increase of immunoreactivity in the neuropil for both GATs. Furthermore, this contralateral site showed many neuronal somata immunolabeled for GAT-1. These changes were mainly detected during the first 5 days following intracortical lesions. These results indicate that (1) the upregulation of GAT-1 and GAT-3 in cortical interneurons and astrocytes is caused by both mechanical and chemical factors associated with the injections; (2) increased GAT-1 and GAT-3 expression contralateral to the site of colchicine injection is mediated by transcellular signaling across the corpus callosum; and (3) the lesion-induced GAT expression may play a protective role by helping to balance excitatory and inhibitory neuronal activities.


Retraction: Successful management of massive intraoperative pulmonary fat embolism with percutaneous cardiopulmonary support.
[This retracts the article on p. 136 in vol. 12, PMID: 19742250.].


Cost-effectiveness of latanoprost and timolol maleate for the treatment of glaucoma in Scandinavia and the United Kingdom, using a decision-analytic health economic model.
To assess the cost-effectiveness of latanoprost or timolol in glaucoma treatment in Norway, Sweden, Denmark (Scandinavia) and the United Kingdom (UK). A Markov model was constructed to perform a cost-effectiveness analysis. Health states were 'stable' and 'progressed' glaucoma, and transition probabilities for both primary open-angle and exfoliation glaucoma were derived from the medical literature. Practice patterns were obtained from surveys completed by 54 ophthalmologists geographically dispersed throughout each country. Country specific unit costs were used for medications, patient visits, diagnostics, and therapeutic procedures. Over the life of the model latanoprost was less expensive than timolol by 5.3-7.6% (Scandinavia) and 2.1% (UK). Following adjustments, therapy in the original timolol-treated cohort was slightly more effective in each country with a difference in 0.003-0.015 years to progression of glaucoma existing between latanoprost. This may have resulted from the model design, which reflected that physicians ultimately control most patients' glaucoma over 5 years by adding or changing therapy. The associated incremental cost-effectiveness ratios for latanoprost vs timolol generated by the Scandinavian and the UK models, respectively, were: Norway 351,396 NOK; Sweden 988,985 SEK; Denmark 351,641; and the UK 4751 GBP. Over 5 years, in the UK timolol is the cost-effective option, whereas in Scandinavia latanoprost may be the cost-effective alternative to timolol.


Therapeutic potency of Poly I:C in HSV-induced inflammation through up-regulation of IL-15 receptor alpha.
Interleukin-15 receptor alpha (IL-15Rα) forms stable complex with IL-15 on the cell surface of activated monocytes and mediates the proliferation of memory CD8+ T cells. Recent studies informed that polyinosinic:polycytidylic acid (Poly I:C) is an immunostimulant which boosts the generation of memory T cells through induction of IL-15Rα. The aim of this study is to evaluate the relevance of IL-15Rα in Herpes simplex virus (HSV)-induced Behçet's disease (BD) mouse model and BD patients. The frequencies of IL-15Rα expression in PBMCs of BD patients and BD-like symptomatic mice were analyzed by flow cytometry. In addition, Poly I:C supplementation could reduce inflammation through the up-regulation of memory T cells and IL-15Rα+ cells accompany with down-regulation of pro-inflammatory cytokine, IL-17A in BD mice. In BD patients, the frequencies of IL-15Rα expression in PBMCs were also significantly different between the inactive and active disease states. These results suggest that IL-15Rα is a relevant factor in BD.


Metabolic profiling of cold adaptation of a deep-sea psychrotolerant Microbacterium sediminis to prolonged low temperature under high hydrostatic pressure.
The most wide-spread "hostile" environmental factor for marine microorganisms is low temperature, which is usually accompanied by high hydrostatic pressure (HHP). Metabolic mechanisms of marine microorganisms adapting to prolonged low temperature under HHP remain to be clarified. To reveal the underlying metabolic mechanisms, we performed NMR-based metabolomic analysis of aqueous extracts derived from a psychrotolerant Microbacterium sediminis YLB-01, which was isolated from deep-sea sediment and possess great biotechnology potentials. The YLB-01 cells were firstly cultivated at the optimal condition (28 °C, 0.1 MPa) for either 18 h (logarithmic phase) or 24 h (stationary phase), then continually cultivated at either 28 °C or 4 °C under HHP (30 MPa) for 7 days. The cells cultivated at low temperature, which experienced cold stress, were distinctly distinguished from those at normal temperature. Cold stress primarily induced metabolic changes in amino acid metabolism and carbohydrate metabolism. Furthermore, the logarithmic and stationary phase cells cultivated at low temperature exhibited distinct metabolic discrimination, which was mostly reflected in the significantly disturbed carbohydrate metabolism. The logarithmic phase cells displayed suppressed TCA cycle, while the stationary phase cells showed decreased pyruvate and increased lactate. In addition, we performed transcriptome analysis for the stationary phase cells to support the metabolomic analysis. Our results suggest that the cold adaptation of the psychrotroph YLB-01 is closely associated with profoundly altered amino acid metabolism and carbohydrate metabolism. Our work provides a mechanistic understanding of the metabolic adaptation of marine psychrotrophs to prolonged low temperature under HHP.


Are rotating tourniquets useful for left ventricular preload reduction in patients with acute myocardial infarction and heart failure?
We examined the hemodynamic effects of congesting cuffs (rotating tourniquets) in 12 patients with first acute myocardial infarction and new onset of congestive heart failure 24 to 48 hours after admission. Congesting cuffs were applied for two periods of 15 minutes each, 15 minutes apart, and inflated to 30 mm Hg and 60 mm Hg consecutively. No change was noticed in mean pulmonary artery wedge pressure, which was 20 +/- 3 mm Hg at the beginning of the study and 19 +/- 3 mm Hg at the completion (P greater than .05, NS), nor in other hemodynamic and blood gases parameters. Patients' clinical conditions remained unchanged. We conclude that application of congesting cuffs at pressures of 30 mm Hg and 60 mm Hg does not result in any change in clinical or hemodynamic data in patients with acute myocardial infarction and new onset of congestive heart failure.


Nitrogen-doped carbon and high-content alumina containing bi-active cobalt oxides for efficient storage of lithium.
Low-content ultrathin coating of non-active alumina (Al2O3) has been extensively utilized as one of the most effective strategies to improve electrochemical performances of electrodes for lithium-ion batteries (LIBs), however, typically by employing expensive atomic layer deposition equipment. We herein demonstrate a simple preparation of high-content and well-dispersed Al2O3 (24.33wt.%)-containing multi-component composite (CoO/Co3O4/N-C/Al2O3) by calcination of melamine/CoAl-layered double hydroxide (CoAl-LDH) mixture. The resulting composite bundles the advantages expected to improve electrochemical performances: (i) bi-active CoO/Co3O4, (ii) highly conductive N-doped carbon, and (iii) N-doped carbon and high-content non-active Al2O3 as buffering reagents, as well as (iv) good distribution of bi- and non-active components resulted from the lattice orientation and confinement effect of the LDH layers. Electrochemical evaluation shows that the composite electrode delivers a highly enhanced reversible capacity of 1078mAhg(-1) after 50cycles at 100mAg(-1), compared with the bi-active CoO/Co3O4 mixtures with and without non-active Al2O3. Transmission electron microscopy/scanning electron microscopy observations and electrochemical impedance spectra experimentally provide the information on the good distributions of multiple components and the improved conductivity underlying the enhancements, respectively. Our LDH precursor-based preparation route may be extended to design and prepare various multi-component transition metal oxides for efficient lithium storage.


Intra-articular injection of anti-inflammatory peptide-loaded glycol chitosan/fucoidan nanogels to inhibit inflammation and attenuate osteoarthritis progression.
Glycol chitosan/fucoidan nanogels loaded with anti-inflammatory peptide KAFAK (GC/Fu@KAFAK NGs) were fabricated based on the electrostatic interaction and genipin cross-linking methods. The prepared NGs had an average size of 286.3 ± 5.0 nm and positive surface charge of 14.0 ± 0.2 mV. The anti-inflammatory and chondro-protective effects of GC/Fu@KAFAK NGs were evaluated on interlecukin-1β (IL-1β)-stimulated rat chondrocytes. We found that GC/Fu@KAFAK NGs not only inhibited the expression of inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), but also enhanced the expression of chondrogenic markers type II collagen, aggrecan, and Sox9. More importantly, in rat osteoarthritis (OA) model, the intra-articular (IA) injection of GC/Fu@KAFAK NGs reduced glycosaminoglycan loss and diminished inflammatory cytokine release. In addition, GC/Fu@KAFAK NGs showed good biocompatibility both in vitro and in vivo. In conclusion, IA inject-able GC/Fu@KAFAK NGs might have great potential in OA treatment.


MicroRNA-17/20a functions to inhibit cell migration and can be used a prognostic marker in oral squamous cell carcinoma.
Oral squamous cell carcinoma (OSCC) accounts for>90% oral cancer which is a leading cause of cancer death worldwide. Early diagnosis may well offer an opportunity to increase survival to this neoplasm. Micro(mi)RNA-interfered cancer progression is crucial, yet its migration machinery of OSCC is still unknown. To access whether the possible miRNA prognostic markers and underlying mechanisms, we developed a highly migratory TW2.6 MS-10 cells from TW2.6 cells to investigate the issue. miRNA profiling was performed on TW2.6 and TW2.6 MS-10. Target miRNA was correlated to pathological status in OSCC patients by real-time RT-PCR. A downstream effector was identified using a bioinformatics analysis, and a 3'-untranslated region (UTR) reporter assay was used. An miRNA cluster, miR-17-92, including miR-17, miR-19b, miR-20a, and miR-92a, was found to be significantly down-regulated in TW2.6 MS-10 compared to TW2.6 cells. Overexpression of this cluster decreased the migratory ability of OSCC cell lines. We further demonstrated that miR-17 and miR-20a are the main miRNAs of miR-17-92 cluster which modulate OSCC migration. Clinically, miR-17/20a showed negative correlation with TNM stage and lymphatic metastasis. Through a bioinformatics screening analysis and 3'UTR reporter assay, we confirmed the integrin (ITG) β8 as a direct target of miR-17/20a, and knockdown of ITGβ8 reduced cell migratory capability of OSCC. miR-17/20a acts as a prognostic predictor of OSCC patients' outcome and a tumor migration suppressor miRNA.


Percutaneous or mini-invasive surgical radiofrequency re-ablation of atrial fibrillation: Impact on atrial function and echocardiographic predictors of short and long-term success.
The aim of this study was to compare percutaneous catheter ablation vs. minimally invasive surgical ablation, evaluating the impact of repeated ablation on atrial function, and evaluating predictors of atrial fibrillation (AF) recurrence. When AF ablation fails, re-ablations are required in up to 40% of patients to treat recurrent arrhythmia; surgical ablation is more effective than catheter ablation. Thirty-two patients with failed prior catheter ablation and referred for a second ablation (18 catheter and 14 surgical) were included in a descriptive observational study. Left atrial volumes, strain, and strain rate were measured with 2D speckle tracking echocardiography at baseline and 6 months after the procedures to assess left atrial functions. Patients received up to 1 year of clinical and Holter follow-up. At the 12-month follow-up, catheter ablation was effective in 56% and surgical ablation in 72% of patients (OR 2 (CI 0.45-8.84), p 0.36). Left atrial booster function was similar in all patients, but left atrial reservoir function was more impaired in those patients who underwent surgical ablation. Left atrial booster function was predictive of arrhythmia recurrence after both catheter and surgical ablation: late diastolic strain rate (LASRa) cut-off ≤ -0.89 s-1 (sensitivity 88%, specificity 70%, AUC 0.82) and ≤ -0.85 s-1 (sensitivity 60%, specificity 100%, AUC 0.82), respectively. Surgical ablation has a more negative impact on LA reservoir function despite being slightly more effective in arrhythmia suppression. LA booster function is not significantly impaired by either procedure. LA booster function predicts arrhythmia elimination after a re-ablation (catheter or surgical).


Data on cell spread area and directional contraction in human umbilical vein endothelial cells on fibronectin and on collagen type I-coated micro-posts.
Fibronectin and collagen type I are abundant extracellular matrix proteins that modulate cell mechanics and they regulate angiogenic sprouting. In this data article, fibronectin- or collagen type I-coated micro-posts were used to examine the traction force, cell spread area and directional contraction of human umbilical vein endothelial cells (HUVECs).


[Patient with diabetes and chronic ischemic heart disease. Myocardial revascularization, how to do it?].
Diabetes is one of the reasons for major concerns when managing patients with acute or chronic ischemic heart disease. The presence of diabetes poses specific issues with respect to outcome and treatment options, leading to worse prognosis. The role of myocardial revascularization in the management of chronic ischemic heart disease is a matter of debate, largely due to some clinical studies that failed to demonstrate it's superiority. Following the BARI-2D trial, coronary artery bypass surgery has gained some advantage over coronary angioplasty in diabetic patients with multivessel disease. This advantage was recently consolidated in the FREEDOM trial, which showed significantly better outcomes at five year follow up.


Radiomic signature: a non-invasive biomarker for discriminating invasive and non-invasive cases of lung adenocarcinoma.
We aimed to assess the classification performance of a computed tomography (CT)-based radiomic signature for discriminating invasive and non-invasive lung adenocarcinoma. A total of 192 patients (training cohort, n=116; validation cohort, n=76) with pathologically confirmed lung adenocarcinoma were retrospectively enrolled in the present study. Radiomic features were extracted from preoperative unenhanced chest CT images to build a radiomic signature. Predictive performance of the radiomic signature were evaluated using an intra-cross validation cohort. Diagnostic performance of the radiomic signature was assessed via receiver operating characteristic (ROC) analysis. The radiomic signature consisted of 14 selected features and demonstrated good discrimination performance between invasive and non-invasive adenocarcinoma. The area under the ROC curve (AUC) for the training cohort was 0.83 (sensitivity, 0.84 ; specificity, 0.78; accuracy, 0.82), while that for the validation cohort was 0.77 (sensitivity, 0.94; specificity, 0.52 ; accuracy, 0.82). The CT-based radiomic signature exhibited good classification performance for discriminating invasive and non-invasive lung adenocarcinoma, and may represent a valuable biomarker for determining therapeutic strategies in this patient population.


Regulatory role of cyclic adenosine 3',5'-monophosphate on the platelet cyclooxygenase and platelet function.
Thromboxane A2 plays an important role in arachidonic acid- and prostaglandin H2-induced platelet aggregation. Agents that stimulate platelet adenylate cyclase (prostaglandin I2, prostaglandin I1 and prostaglandin E1) and dibutyryl cyclic AMP inhibit both thromboxane A2 formation and arachidonate-induced aggregation in platelet-rich plasma. Despite complete suppression of aggregation with agents that elevate cyclic AMP, considerable thromboxane A2 is still formed. Prostaglandin H2-induced aggregations which bypass the cyclooxygenase regulatory step are also inhibited by agents that elevate cyclic AMP without any measurable effect on thromboxane A2 production. These data demonstrate that cyclic AMP can inhibit platelet aggregation by a mechanism independent of its ability to suppress the cyclooxygenase enzyme. Parallel experiments with washed platelet preparations suggest that they may be an inadequate model for studying the relationship between the platelet cyclooxygenase and platelet function.


Role of keratan sulphate (sulphated poly -N-acetyllactosamine repeats) in keratoconic cornea, histochemical, and ultrastructural analysis.
Keratan sulphate (KS) is the predominant glycosaminoglycan (GAG) present in the corneal stroma where it is thought to regulate collagen fibril diameter. In this study we investigated the distribution of KS in normal and keratoconic corneas. Four normal, one mild, and four severe keratoconic corneas were used for the study. Distribution of keratan sulphate proteoglycans (KS-PG) was investigated using a primary monoclonal antibody (5-D-4) that recognizes disulphated disaccharides in the poly-N-acetyllactosamine repeats of KS. The immuno-reactivity of 5-D-4 was analyzed by immunohistochemistry and immuno-electron microscopy. Immuno-histochemistry showed diffuse 5-D-4 staining in keratoconic cornea compared to the punctuate staining in normal corneas. In the single cornea with mild keratoconus, immunogold microscopy revealed a very high density of KS-PG staining, especially in the posterior stroma, compared to severe keratoconic and normal cornea. The amount of KS-PG in the stroma in severe keratoconus was slightly less compared to the normal cornea. In the mild keratoconic cornea, a higher quantity of KS-PG was present around the keratocytes. In severe keratoconic corneas, a higher quantity of KS-PG was present within the keratocytes compared to normal cornea. The finding of an altered expression of KS in our keratoconic corneas, in particular the strong expression of KS in keratocytes, is in keeping with reports of an altered expression of proteoglycan metabolism in keratoconus. KS-PG plays an important role in stromal collagen fibril assembly and a dysregulation of KS-PG synthesis or catabolism could explain changes in collagen fibril spacing and diameter, which we have reported elsewhere.


Multi-gene technical assessment of qPCR and NanoString n-Counter analysis platforms in cynomolgus monkey cardiac allograft recipients.
Quantitative gene expression profiling of cardiac allografts characterizes the phenotype of the alloimmune response, yields information regarding differential effects that may be associated with various anti-rejection drug regimens, and generates testable hypotheses regarding the pathogenesis of the chronic rejection lesions typically observed in non-human primate heart transplant models. The goal of this study was to assess interplatform performance and variability between the relatively novel NanoString nCounter Analysis System, ΔΔCT (relative) RT-qPCR, and standard curve (absolute) RT-qPCR utilizing cynomolgus monkey cardiac allografts. Methods for RNA isolation and preamplification were also systematically evaluated and effective methods are proposed. In this study, we demonstrate strong correlation between the two RT-qPCR methods, but variable and, at times, weak correlation between RT-qPCR and NanoString. NanoString fold change results demonstrate less sensitivity to small changes in gene expression than RT-qPCR. These findings appear to be driven by technical aspects of each platform that influence the conditions under which each technique is ideal. Collectively, our data contribute to the general effort to optimally utilize gene expression profiling techniques, not only for transplanted tissues, but for many other applications where accurate rank-order of gene expression versus precise quantification of absolute gene transcript number may be relatively valuable.


A benign form of thalassaemia intermedia may be determined by the interaction of triplicated alpha locus and heterozygous beta-thalassaemia.
In this paper we report that the combination of a triplicated alpha globin locus with heterozygous beta-thalassaemia produces a clinical phenotype of thalassaemia intermedia in five Italian subjects from four unrelated families, while in two other cases the phenotype was thalassaemia minor. The haematological findings of the five patients were uniform, producing a benign form of thalassaemia intermedia, transfusion independent, with a long life expectancy. The pattern of inheritance of the two genetic determinants and the more pronounced beta/alpha globin chain imbalance, demonstrates that the genetic combination is indeed the cause of the phenotype. The pattern of restriction enzyme site polymorphisms suggests the presence of the beta IVS I 110 G----A mutation at least in three of these cases.


TARC: Turkish aripiprazole consensus report- Aripiprazole use and switching from other antipsychotics to aripiprazole- consensus recommendations by a Turkish multidisciplinary panel.
In this review, we have attempted to share our 10 years' clinical experience with aripiprazole use and switching from other antipsychotics to aripiprazole. There are various reasons for switching, including a partial or complete lack of efficacy, adverse side effects, and partial or noncompliance with medication. Aripiprazole has some unique receptor-binding qualities that provides some advantages over other antipsychotics in certain clinical situations. We have covered potential clinical scenarios for aripiprazole use as a single agent and switching from other agents in inpatient and outpatient settings. Patients switched from other antipsychotics to aripiprazole have been shown to benefit from significant improvements in clinical response and tolerability. This review examines the strategies for switching patients from antipsychotic drugs to aripiprazole.


Development of Enantioselective Palladium-Catalyzed Alkene Carboalkoxylation Reactions for the Synthesis of Tetrahydrofurans.
The Pd-catalyzed coupling of γ-hydroxyalkenes with aryl bromides affords enantiomerically enriched 2-(arylmethyl)tetrahydrofuran derivatives in good yield and up to 96:4 e.r. This transformation was achieved through the development of a new TADDOL/2-arylcyclohexanol-derived chiral phosphite ligand. The transformations are effective with an array of different aryl bromides, and can be used for the preparation of products bearing quaternary stereocenters.


Management Strategies for COVID-19 in the General Ward of Cardiovascular Surgery: Experience From a Single Tertiary Hospital in China.
Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease that threatens global health. During the pandemic period of COVID-19, the task for prevention in the general ward of cardiovascular surgery is fairly arduous. The present study intends to summarize our experience with infection control, including ward setting, admission procedures, personnel management, health education, and so on, to provide references for clinical management.


Comparative uptake and translocation of pharmaceutical and personal care products (PPCPs) by common vegetables.
Reuse of treated wastewater to irrigate agricultural crops is increasing in many arid and semi-arid areas around the world. The presence of numerous pharmaceutical and personal care products (PPCPs) in treated wastewater and their potential transfer into food produce such as vegetables poses an unknown human health risk. The goal of this study was to identify PPCPs that have a comparatively high potential for plant uptake and translocation. A total of 20 frequently-occurring PPCPs were compared for their accumulation into four staple vegetables (lettuce, spinach, cucumber, and pepper) grown in nutrient solutions containing PPCPs at 0.5 or 5μgL(-1). Triclocarban, fluoxetine, triclosan, and diazepam were found at high levels in roots, while meprobamate, primidone, carbamazepine, dilantin, and diuron exhibited more active translocation from roots to leaves. Root uptake of neutral PPCPs was positively correlated with the pH adjusted log Kow(i.e., log Dow), and was likely driven by chemical adsorption onto the root surfaces. In contrast, translocation from roots to leaves was negatively related to log Dow, suggesting hydrophilicity-regulated transport via xylems. Compounds preferentially sorbed to roots should be further evaluated for their uptake in tuber vegetables (e.g., carrot, radish) under field conditions, while those easily translocated into leaves (e.g., carbamazepine, dilantin) merit focused consideration for leafy and other vegetables (e.g., lettuce, cucumber). However, estimation of dietary intake by humans suggested the implied risks from exposure to PPCPs via wastewater irrigation to be negligible.


Formerly bile-farmed bears as a model of accelerated ageing.
Bear bile-farming is common in East and Southeast Asia and this farming practice often results in irreversible health outcomes for the animals. We studied long-term effects of chronic bacterial and sterile hepatobiliary inflammation in 42 Asiatic black bears (Ursus thibetanus) rescued from Vietnamese bile farms. The bears were examined under anesthesia at least twice as part of essential medical interventions. All bears were diagnosed with chronic low-grade sterile or bacterial hepatobiliary inflammation along with pathologies from other systems. Our main finding was that the chronic low-grade inflammatory environment associated with bile extraction in conjunction with the suboptimal living conditions on the farms promoted and accelerated the development of age-related pathologies such as chronic kidney disease, obese sarcopenia, cardiovascular remodeling, and degenerative joint disease. Through a biomimetic approach, we identified similarities with inflammation related to premature aging in humans and found significant deviations from the healthy ursid phenotype. The pathological parallels with inflammageing and immuno-senescence induced conditions in humans suggest that bile-farmed bears may serve as animal models to investigate pathophysiology and deleterious effects of lifestyle-related diseases.


Myocardial perfusion imaging in stable symptomatic patients with extensive coronary atherosclerosis.
High coronary artery calcium (CAC) scores are associated with a high likelihood of ischaemia and obstructive coronary disease. Myocardial perfusion imaging (MPI) is a key investigation to determine the need for revascularization. However, the value of MPI in presence of extensive CAC has so far only been demonstrated in asymptomatic patients, whereas its value in symptomatic patients remains largely unclear. Therefore, we studied the impact of MPI in symptomatic patients with a CAC score ≥ 1,000. We included 282 patients (mean age 69 ± 9 years, 63% men) without a history of coronary disease with suspected stable angina referred for MPI and with a CAC score ≥ 1,000. On follow-up at 18 months invasive angiography, coronary revascularization, nonfatal myocardial infarction and death were recorded. MPI was normal in 54 %, equivocal in 10 % and abnormal in 37 % (fixed defect 9 % and ischaemia 28 %) of patients. More abnormal MPI findings were observed in men, smokers and those with even higher CAC scores. During follow-up, 1 patient (with nonischaemic MPI) died from a cardiac cause, 1 patient (with ischaemic MPI) suffered a myocardial infarction and 92 patients (33 %) underwent revascularization. Ischaemia on MPI was a strong predictor of coronary revascularization (odds ratio 13.1; 95 % CI 7.1-24.3; p < 0.001). Ischaemia on MPI is observed in approximately 30 % of patients with a CAC score ≥ 1,000, and is a strong predictor of coronary revascularization. However, nonischaemic MPI does not exclude revascularization, and patients with persisting complaints should be considered for invasive angiography.


Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections detected by real-time PCR among individuals reporting sexual assaults in the Paris, France area.
Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) are the most common bacteria involved in sexually transmitted infections (STIs). In France, combined screening for CT and NG using nucleic acid amplification tests is recommended in populations that are considered at risk. However, no data have been published about victims of sexual assaults. The aim of this retrospective study was to assess the usefulness of real-time PCR for the rapid detection of CT and NG genomic DNA, and the prevalence of CT/NG infections in a sample of sexual assault victims examined at a department of forensic medicine. Between July 2012 and July 2013, 326 adults and adolescents aged over 12 years reported a sexual assault and they were referred to the Department of Forensic Medicine for a medical and forensic examination. Secretions from urogenital (cervix or vagina), anorectal, or pharyngeal sites were collected for CT/NG assays. CT and NG were detected in 48/326 (15%) and 16/326 patients (5%), respectively, where 10 (3%) had a CT/NG co-infection. Among 48 patients with CT infection, 13 (27.1%) patients had co-occurring genital and anorectal infections. For the pharyngeal sites, 3/21 men (14.3%) were NG-positive. Given the high prevalence of CT and NG infections, systematic screening of both pathogens at the time of forensic examination should provide an opportunity for the early treatment of diagnosed STIs.


Biosynthesis of sialosyllactotetraosylceramide in human colorectal carcinoma cells.
A monosialoganglioside, IV3-NeuNAcLcOse4Cer, has recently been detected in colorectal carcinoma cells, small cell lung carcinoma cells, embryonal carcinoma cells and in human brain extracts. We report here the presence of a CMP-sialic: LcOse4Cer sialyl transferase activity in subcellular membrane fractions of the human colorectal carcinoma. SW1116, which recognizes the non-reducing terminal galactosyl moiety of lactotetraosylceramide. A convenient method for structural analysis of picomolar quantities of the radioactive enzymatic product(s) using bacterial endoglycoceramidase, sialidase and a viral sialidase is presented.


Overexpression of BIRC6 Is a Predictor of Prognosis for Colorectal Cancer.
Inhibitors of apoptosis proteins (IAPs) have been well investigated in human cancers, where they are frequently overexpressed and associated with poor prognosis. Here we explored the role of baculoviral IAP repeat containing 6 (BIRC6), a member of IAPs, in human colorectal cancer (CRC). We used Western blotting and immunohistochemistry to examine BIRC6 expression in 7 CRC cell lines and 126 CRC clinical samples. We determined the biological significance of BIRC6 in CRC cell lines by a lentivirus-mediated silencing method. We reported that BIRC6 was overexpressed in CRC cell lines and clinical CRC tissues. BIRC6 overexpression was correlated with tumor size and invasion depth of CRC. BIRC6 overexpression is associated with worse overall survival (OS) (P = 0.001) and shorter disease-free survival (DFS) (P = 0.010). BIRC6 knockdown inhibited cell proliferation, arrested cell cycle at S phase, downregulated cyclin A2, B1, D1 and E1 levels, and sensitized CRC cells to chemotherapy in vitro and in vivo. Taken together, these data suggests that BIRC6 overexpression is a predictor of poor prognosis in colorectal cancer and BIRC6 could be a potential target of CRC therapy.


Fibrous meningeal tumours with extensive non-calcifying collagenous whorls and glial fibrillary acidic protein expression: the whorling-sclerosing variant of meningioma.
Meningiomas comprise a wide range of morphological patterns. We describe unusual fibrous meningeal tumours in two patients, composed of extensive non-calcifying collagenous whorls of varying size, resembling non-calcified psammoma bodies, while interposed tumour cells are sparse. Immunohistochemistry showed expression of S-100, vimentin and glial fibrillary acidic protein, whereas only single tumour cells stained for epithelial membrane antigen. Electron microscopy detected desmosomes or desmosome-like structures in both specimens. We conclude that these tumours represent a peculiar whorling-sclerosing variant of fibrous meningioma. Recognition of this meningioma variant is important in the differential diagnosis of meningioma versus other fibrous tumours of the meninges, including solitary fibrous tumours of the meninges, unusual forms of desmoplastic gliomas or chondroid tumours.


People behavioral during health information searching in COVID-19 era: a review.
The COVID-19 pandemic has led to an increase in health information-seeking behavior (HISB) on the Internet. This review aims to identify and synthesize the available evidence on health information-seeking behavior on the Internet during and after the COVID-19 pandemic. Electronic search of databases was conducted on PubMed, ScienceDirect, Scopus, and Taylor and Francis Online to identify relevant articles. Studies that examined health information-seeking behavior on the Internet during or after the COVID-19 pandemic were included. Data from the included studies were subjected to a thematic analysis. A total of 355 articles were identified in the initial database search. After screening, 15 articles were included in this review paper, with a population of 33,326. Search engines, social media, and news portals were the most commonly used information sources. The primary motivators for seeking health information online were curiosity, catching up with updated information, and paying attention to the COVID-19 transmission. Participants' satisfaction with the information obtained online was positive in most studies. The online query for all items related to COVID-19 and health increased during the pandemic. The most searched topics were symptoms of COVID-19, restrictions, current prevalence/spread of COVID-19, and preventive measures. Higher scores in digital health literacy (DHL) were associated with a well-established and effective health information-seeking behavior. The findings of this review provide insight into the patterns and trends of health information-seeking behavior on the Internet during and after the COVID-19 pandemic. The results suggest that search engines, social media, and news portals remain key sources of information during the pandemic. It also assessed the relationship between the DHL and the HISB and found that having a good DHL generally meant a good HISB.


From the Occipital Condyle to the Sphenoid Sinus: Extradural Extension of the Far Lateral Transcondylar Approach with Endoscopic Assistance.
Surgical management of extensive skull base tumors, such as chordoma and chondrosarcoma, remains very challenging. The need for gross total removal to improve survival must be weighed against the risk of injury to neurovascular structures and the loss of stability at the craniovertebral junction. In cases of tumors that are already compromising craniovertebral junction stability, the occipital condyle can be exploited as a deep keyhole to reach the clivus, petrous apex, and sphenoid sinus. We performed an anatomic study on 7 cadaveric specimens to describe the main landmarks and boundaries of the corridor. We also provide a clinical case to demonstrate the feasibility of the approach. In all specimens, using the space provided by the condyle, it was possible to drill the petrous bone up to the posterior wall of the sphenoid sinus following the direction of the inferior petrosal sinus. To successfully complete the approach, after the hypoglossal canal was exposed, endoscopic assistance was needed to overcome the narrowing of the visual field provided by the microscope. In cases of invasive skull base tumor involving the craniovertebral junction and affecting its stability, the occipital condyle can be exploited as a deep keyhole to the homolateral and contralateral petrous apex, clivus, and sphenoid sinus.


Speciation of inorganic arsenic in aqueous samples using a novel hydride generation microfluidic paper-based analytical device (µPAD).
The development of the first microfluidic paper-based analytical device (µPAD) for the speciation of inorganic arsenic in environmental aqueous samples as arsenite (As(III)) and arsenate (As(V)) which implements hydride generation on a paper platform is described. The newly developed µPAD has a 3D configuration and uses Au(III) chloride as the detection reagent. Sodium borohydride is used to generate arsine in the device's sample zone by reducing As(III) in the presence of hydrochloric acid or both As(III) and As(V) (total inorganic As) in the presence of sulfuric acid. Arsine then diffuses across a hydrophobic porous polytetrafluoroethylene membrane into the device's detection zone where it reduces Au(III) to Au nanoparticles. This results in a color change which can be related to the concentration of As(III) or total inorganic As (i.e., As(III) and As(V)) concentration. Under optimal conditions, the µPAD is characterized by a limit of detection of 0.43 mg L-1 for total inorganic As (As(III) + As(V)) and 0.41 mg L-1 for As(III) and a linear calibration range in both cases of 1.2-8.0 mg As L-1. The newly developed µPAD-based method was validated by applying it to groundwater and freshwater samples and comparing the results with those obtained by conventional atomic spectrometric techniques.


Retrievability of the Günther Tulip vena cava filter after dwell times longer than 180 days in patients with multiple trauma.
To evaluate the retrieval feasibility of the Günther Tulip inferior vena cava filter (IVCF) after dwell times >180 days in patients with multiple trauma. A retrospective study was conducted of 117 multiple-trauma patients (70 men; mean age 36 years, range 17 to 64) who underwent prophylactic placement of Günther Tulip retrievable IVCFs between December 1, 2003 and October 1, 2006. Prior to IVCF retrieval, all patients had vena cavography to identify possible IVCF thrombus entrapment. Filter retrieval was performed in the catheterization laboratory under sterile conditions from a right internal jugular vein approach. After IVCF retrieval, repeat vena cavography was performed to evaluate the IVC for contrast extravasation, intraluminal defects, or IVC narrowing. Twelve (10.3%) filters were not retrieved as the patients died of their injuries (no deaths related to IVCF placement or retrieval). Forty-one (35.0%) filters had dwell times >180 days (mean 261.5 days, range 182-403). Of these, 31 (76%) were uneventfully retrieved; 10 were left in place permanently. Pre-retrieval vena cavography identified filter tilting in 13 filters: 9 had a mild tilt < or =10 degrees, and 4 had severe tilting > or =25 degrees. All of the 10 filters that could not be retrieved were tilted (4 severe and 6 mild). In comparison to the 64 (54.7%) filters in place for <180 days (mean 51 days, range 42-180), 4 (6.2%) could not be retrieved (p = 0.367). No filter had trapped thrombus identified by vena cavography at the time of retrieval. None of the retrieved filters had structural fracture or collapse, and none had migrated. Post-retrieval vena cavograms demonstrated no contrast extravasation, intraluminal defects, or impingement on adjacent organs. If retrieval of a Gunther Tulip filter with an dwell time >180 days is considered, the patient should be ambulatory and a candidate for anticoagulation if indicated; notably, the filter should have a <25 degrees tilt. Under these circumstances, retrieval of the Günther Tulip filter after 180 days of dwell time appears justified and safe.


T follicular helper cells in cancer, tertiary lymphoid structures, and beyond.
With the emergence and success of checkpoint blockade immunotherapy, immuno-oncology has primarily focused on CD8 T cells, whose cytotoxic programs directly target tumor cells. However, the limited response rate of current immunotherapy regimens has prompted investigation into other types of tumor-infiltrating immune cells, such as CD4 T cells and B cells, and how they interact with CD8 T cells in a coordinated network. Recent studies have demonstrated the potential therapeutic benefits of CD4 T follicular helper (TFH) cells and B cells in cancer, highlighting the important role of their crosstalk and interactions with other immune cell components in the tumor microenvironment. These interactions also occur in tumor-associated tertiary lymphoid structures (TLS), which resemble secondary lymphoid organs (SLOs) with orchestrated vascular, chemokine, and cellular infrastructures that support the developmental pathways of functional immune cells. In this review, we discuss recent breakthroughs on TFH biology and T cell-B cell interactions in tumor immunology, and their potential as novel therapeutic targets to advance cancer treatment.


Phenoloxidase, a marker enzyme for differentiation of the neural ectoderm and the epidermal ectoderm during embryonic development of amphioxus Branchiostoma belcheri tsingtaunese.
The development of phenoloxidase during amphioxus embryogenesis was spectrophotometrically and histochemically studied for the first time in the present study. It was found that (1) PO activity initially appeared in the general ectoderm including the neural ectoderm and the epidermal ectoderm at the early neurula stage but not in the mesoderm or the endoderm, and (2) PO activity disappeared in the neural plate cells but remained unchanged in the epidermal cells when the neural plate was morphologically quite distinct from the rest of the ectoderm. It is apparent that PO could serve as a marker enzyme for differentiation of the neural ectoderm from the epidermal ectoderm during embryonic development of amphioxus.


Microbial disinfection of water with endotoxin degradation by photocatalysis using Ag@TiO2 core shell nanoparticles.
The studies on photocatalytic disinfection of water contaminated with Escherichia coli using Ag core and TiO2 shell (Ag@TiO2) nanoparticles under UV irradiation showed that these nanoparticles are very efficient in water disinfection both in their free and immobilised form. Complete disinfection of 40 × 10(8) CFU/mL could be achieved in 60 min with 0.4 g/L catalyst loading and in 35 min with 1 g/L catalyst loading. Ag@TiO2 nanoparticles were found to be superior to TiO2 nanoparticles in photocatalytic disinfection of water. Kinetics of disinfection followed Chick's law, and the pseudo-first-order rate constant was 0.0168 min(-1) for a catalyst loading of 0.1 g/L. Disinfection of water and degradation of endotoxins (harmful disinfection residual) occurred simultaneously during photocatalysis thereby making the treated water safe for use. Endotoxin degradation showed a shifting order of kinetics. The rate of photocatalysis with nanoparticles immobilised in cellulose acetate film was marginally lower as compared to that of free nanoparticles. Negligible Ag ion leakage and re-growth of cells post-photo-catalytic treatment of water confirmed that complete disintegration of E. coli occurred during photocatalysis making the treated water safe for use. Therefore, Ag@TiO2 nanoparticles have a potential for large-scale application in drinking water treatment plants and household purification units.


The accuracy of presepsin (sCD14-ST) for the diagnosis of sepsis in adults: a meta-analysis.
The early diagnosis of sepsis remains a challenge. Recently, soluble cluster of differentiation 14 subtype (sCD14-ST), also known as presepsin, has been identified as a potential biomarker of sepsis. We performed a meta-analysis to assess the diagnostic accuracy of presepsin for sepsis in patients with systemic inflammation. We systematically searched the PubMed, Embase, Web of Knowledge and Cochrane databases. Studies were included if they assessed the diagnostic accuracy of presepsin for sepsis in adult patients with systemic inflammatory response syndrome (SIRS). Furthermore, a 2 × 2 contingency table was constructed based on these results. Two authors independently judged the studies and extracted the data. The diagnostic accuracy of presepsin in sepsis was calculated using a bivariate meta-analysis model. The Q-test and I (2) index were used to test the heterogeneity. Eight studies involving a total of 1,815 patients were included in the present study. The pooled sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio and negative likelihood ratio were 0.86 (95% CI: 0.79-0.91), 0.78 (95% CI: 0.68-0.85), 22 (95% CI: 10-48), 3.8 (95% CI: 2.6-5.7), and 0.18 (95% CI: 0.11-0.28), respectively. The area under the summary receiver operator characteristic curve was 0.89 (95% CI: 0.86-0.92). Meta-regression analysis revealed that consecutive patient selection, sample size and setting significantly accounted for the heterogeneity of sensitivity. Our findings suggest that presepsin exhibits very good diagnostic accuracy (AUC=0.89) for the diagnosis for sepsis. Nevertheless, an overall assessment of all the clinical indexes for sepsis diagnosis and continual re-evaluation of presepsin during the course of the disease are needed.


MALAT1: A regulator of inflammatory cytokines in diabetic complications.
In this study, we examined the role of MALAT1, a highly conserved nuclear long non-coding RNA molecule, in chronic diabetic complications affecting the heart and kidneys using both in vitro and in vivo models: human endothelial cell culture and a Malat1 knockout mice model. Findings from our in vitro experiments demonstrated that MALAT1 was predominantly localized to nuclear speckles in endothelial cells and MALAT1 expression was significantly increased following incubation with high glucose in association with increased expression of inflammatory cytokines. As for our in vivo experiments, we used Malat1 knockout mice and wild-type controls with or without streptozotocin-induced diabetes over 2 months of follow-up, where all of our diabetic animals showed hyperglycaemia and polyuria. Examination of cardiac and renal tissues demonstrated altered MALAT1 RNA expression in wild-type diabetic animals. Such changes were associated with augmented production of downstream inflammatory molecules at the mRNA and protein levels. Diabetes-induced elevations of inflammatory markers were significantly decreased in Malat1 knockout diabetic animals. In addition to transcript and protein analyses, we examined functional changes in the heart and kidneys. Organ functions were affected in the wild-type diabetic mice but were rescued in Malat1 knockout mice. Taken together, findings from this study will provide direct evidence and insight into the importance of MALAT1 in the pathogenesis of chronic diabetic complications involving the heart and kidneys.


Carbohydrate specificities of the murine DC-SIGN homologue mSIGNR1.
C-type lectins are important receptors expressed by antigen presenting cells that are involved in cellular communications as well as in pathogen uptake. An important C-type lectin family is represented by DC-SIGN and its homologues in human and mouse. Here we have investigated the carbohydrate specificity of cellular mSIGNR1 and compared it with DC-SIGN and L-SIGN. mSIGNR1 has a similar specificity as human DC-SIGN for high mannose-containing ligands present on both cellular and pathogen ligands. However, the DC-SIGN molecules differ in their recognition of Lewis antigens; mSIGNR1 interacts not only with Le(x/y) and Le(a/b) antigens similar to DC-SIGN, but also with sialylated Lex, a ligand for selectins. The differential recognition of Lewis antigens suggests differences between mSIGNR1 and DC-SIGN in the recognition of cellular ligands and pathogens that express Lewis epitopes.


[Experimental research of PDE5 activity in corpora cavernosa of ganyu qizhi rat model].
To study the PDE5 activity in corpora cavernosa of the Ganyu Qizhi model penis and the effect of the Chinese herbal medicine Shugan Liqi Huoxue (SLH) ointment on it. Non-injury stress stimulus method similar to human spirit stress was used to extablish the Ganyu Qizhi animal(rat) model, and the PDE5 activity in corpora cavernosa of the rat penis was measured by the method of immunohistochemistry and computer image analysis. The PDE5 activity in corpora cavernosa of the high-dosage SLH group was significantly different from that of the model group (P < 0.01). Ganyu Qizhi may increase the PDE5 activity in corpora cavernosa of the penis while SLH can reduce such activity.


The hydrodynamics of water strider locomotion.
Water striders Gerridae are insects of characteristic length 1 cm and weight 10 dynes that reside on the surface of ponds, rivers, and the open ocean. Their weight is supported by the surface tension force generated by curvature of the free surface, and they propel themselves by driving their central pair of hydrophobic legs in a sculling motion. Previous investigators have assumed that the hydrodynamic propulsion of the water strider relies on momentum transfer by surface waves. This assumption leads to Denny's paradox: infant water striders, whose legs are too slow to generate waves, should be incapable of propelling themselves along the surface. We here resolve this paradox through reporting the results of high-speed video and particle-tracking studies. Experiments reveal that the strider transfers momentum to the underlying fluid not primarily through capillary waves, but rather through hemispherical vortices shed by its driving legs. This insight guided us in constructing a self-contained mechanical water strider whose means of propulsion is analogous to that of its natural counterpart.


Pathologic fracture of the femur neck as first manifestation of a minute columnar cell carcinoma of the thyroid gland.
This case report concerns a 64 year-old woman who presented a pathologic fracture of the femur neck. Histologic examination of the performed bone biopsy disclosed the presence of a carcinomatous metastasis with unusual microscopic features. The site of the primary tumor could be unequivocally determined as being the thyroid gland, as immunostaining of the tumor cells showed positivity with anti-thyroglobulin. The thyroidectomy specimen weighed 149 g, was nodular and partially calcified. Exhaustive microscopic examination finally revealed the presence of a minute columnar cell carcinoma, 0.6 cm in diameter, with obvious vascular invasion. This case illustrates well 1) the usefulness of immunostaining with anti-thyroglobulin in cases of bone metastasis with unusual microscopic features and unknown primary, as well as 2) the aggressiveness of this rare type of carcinoma of the thyroid.


TGF-β1 re-programs TLR4 signaling in L. donovani infection: enhancement of SHP-1 and ubiquitin-editing enzyme A20.
Visceral leishmaniasis (VL), caused by Leishmania donovani, is a major health concern in India. It represents T-helper type 2 (Th2) bias of cytokines in active state and Th1 bias at cure. However, the role of the parasite in regulating Toll-like receptor (TLR)-mediated macrophage activation in VL patients remains elusive. In this report, we demonstrated that later stages of L. donovani infection rendered tolerance to macrophages, leading to incapability for the production of inflammatory cytokines like tumor necrosis factor (TNF)-α and interleukin (IL)-1β in response to TLR stimulation. Overexpression of transforming growth factor (TGF)-β(1), but not IL-10, resulted in suppressed lipopolysaccharide (LPS)-induced production of TNF-α and downregulation of TLR4 expression in L. donovani-infected macrophages. Recombinant human (rh)TGF-β(1) markedly enhanced tyrosine phosphatase (Src homology region 2 domain-containing phosphatase-1) activity, but inhibited IL-1 receptor-activated kinase (IRAK)-1 activation. Addition of neutralizing TGF-β(1) antibody reversed these effects, and thus suggesting the pivotal role of TGF-β(1) in promoting refractoriness for LPS in macrophages. Surprisingly, the use of a tyrosine phosphatase inhibitor (sodium orthovanadate, Na(3)VO(4)) promoted IRAK-1 activation, confirming the negative inhibitory role of tyrosine phosphatase in macrophage activation. Furthermore, rhTGF-β(1) induced tolerance in infected macrophages by reducing inhibitory protein (IκBα) degradation in a time-dependent manner. In addition, short interfering RNA studies proved that overexpression of A20 ubiquitin-editing protein complex induced inhibitory activity of TGF-β(1) on LPS-mediated nuclear factor-κB activation. Thus, these findings suggest that TGF-β(1) promotes overexpression of A20 through tyrosine phosphatase activity that ensures transient activation of inflammatory signaling pathways in macrophages in active L. donovani infection.


The association of hemoglobin A1c and high risk plaque and plaque extent assessed by coronary computed tomography angiography.
The objective of this study was to investigate the relationship of Hemoglobin A1c (HbA1c) and plaque characteristics including high risk plaque and plaque extent. We retrospectively examined 1079 consecutive coronary computed tomography (CT) angiography scans and the HbA1c results. We divided the patients into four groups by the HbA1c status: non-diabetic, ≤6.0; borderline, 6.1-6.4; diabetic low, 6.5-7.1; diabetic high, >7.1. We determined segment involvement score >4 as extensive disease. High risk plaque was defined as two feature positive (FP) plaque which consists of positive remodeling (remodeling index >1.1) and low attenuation (<30 HU). Univariate and multivariate analysis including conventional cardiovascular risk factors, symptoms and medication was performed. Univariate analysis showed that diabetic patients as well as borderline patients were significantly related with 2FP plaque and extensive disease. Although the relationship of borderline patients and 2FP plaque was marginal in multivariate analysis [odds ratio (OR) 1.53, 95% confidence interval (CI) 0.95-2.40, p = 0.07], the elevation of HbA1c was strongly associated with 2FP plaque (diabetic low, OR 2.19, 95% CI 1.37-3.45, p < 0.005; diabetic high, OR 4.14, 95% CI 2.57-6.67, p < 0.0005). The association of HbA1c elevation and extensive disease was quite similar between borderline and diabetic patients (borderline, OR 1.96, 95% CI 1.29-2.95, p < 0.005; diabetic low, OR 1.94, 95% CI 1.25-3.01, p < 0.005; diabetic high, OR 2.19, 95% CI 1.39-3.43, p < 0.005). Patients with elevated HbA1c of >6.0 are potentially at risk for future cardiovascular events due to increased high risk plaque and extensive disease, even below the diabetic level of 6.5. Coronary CT could be used for risk stratification of these patients.


Incivility Toward Nursing Students in Clinical Rotations: Measuring the Incidence and Testing Interventions.
The purpose of this study was to measure nursing student perceptions of incivility in the clinical learning environment and test interventions that improve these perceptions. The secondary aim was to further test the reliability of the Nursing Student Perception of Civil and Uncivil Behaviors (NSPCUB) tool. Incidence of incivility in nursing is well documented in the literature; however, there are few evidence-based interventions to combat this phenomenon. NSPCUB was administered to 314 nursing students. Data were used to develop hospital-wide and unit-specific interventions. After implementation of the interventions, the survey was administered to 410 students. There was a statistically significant mean increase for 7 of the 12 survey items, hospital-wide, and the findings reenforced NSPCUB as a highly reliable tool. This instrument can be used by nurse executives to measure perceptions of incivility, identify areas for improvement, and implement interventions.


Efficacy of particle repositioning manoeuvres in benign positional paroxysmal vertigo: A revision of 176 cases treated in a tertiary care centre.
Benign paroxysmal positional vertigo is the most common peripheral vertigo disease. The aim of this paper is to review the results obtained with the different specific particle repositioning manoeuvres, evaluating the possible risk factors linked to a poorer prognosis. One hundred and seventy-six patients with a diagnosis of benign paroxysmal positional vertigo were reviewed retrospectively, of whom 150 had vertigo of the posterior canal, 20 had vertigo of the horizontal canal, 3 had vertigo of the superior canal, and 3 had a double vertigo. The Epley manoeuvre was used to treat the posterior and superior canals, and Lempert manoeuvre was used to treat the horizontal canal. An imaging study by nuclear magnetic resonance with gadolin was always used in refractory cases. The Epley manoeuvre showed an efficacy of 74.6 and 100% at first attempt for posterior and superior canals respectively. The efficacy of the Lempert manoeuvre for the horizontal canal was 72.72% in the patients with canalolithiasis, and 58.33% in the patients with cupulolithiasis. The treatment of patients with more than one affected canal and a history of surgery in the previous month was more difficult. Particle repositioning manoeuvres show a very high success rate, allowing better results in the treatment of the posterior canal. We need more studies to confirm the suspicion that surgery may be a factor of poorer prognosis.


Estimating the amount and distribution of radon flux density from the soil surface in China.
Based on an idealized model, both the annual and the seasonal radon ((222)Rn) flux densities from the soil surface at 1099 sites in China were estimated by linking a database of soil (226)Ra content and a global ecosystems database. Digital maps of the (222)Rn flux density in China were constructed in a spatial resolution of 25 km x 25 km by interpolation among the estimated data. An area-weighted annual average (222)Rn flux density from the soil surface across China was estimated to be 29.7+/-9.4 mBq m(-2)s(-1). Both regional and seasonal variations in the (222)Rn flux densities are significant in China. Annual average flux densities in the southeastern and northwestern China are generally higher than those in other regions of China, because of high soil (226)Ra content in the southeastern area and high soil aridity in the northwestern one. The seasonal average flux density is generally higher in summer/spring than winter, since relatively higher soil temperature and lower soil water saturation in summer/spring than other seasons are common in China.


Prediction models for evaluating the impacts of ambient air pollutants on the biochemical response of selected tree species of Haridwar, India.
This study aimed to assess the spatio-temporal impact of selected ambient air pollutants (SO2, NO2, PM10, and PM2.5) on the biochemical response of four tree species including Neem (Azadirachta indica), Mountain cedar (Toona ciliate), Bottlebrush (Callistemon citrinus), and Guava (Psidium guajava) in the province of Haridwar City, Uttarakhand, India. The study was performed in 2020 and 2021 over three selected sites (S1: institutional; S2: industrial; and S3: urban). Purposely, seasonal data of ambient air pollutants and biochemical parameters (ascorbic acid, carotenoid, chlorophyll, pH, relative water content, and dust load) of selected tree species were collected and analyzed using multiple linear regression (MLR) tool to develop prediction models. The results indicated that biochemical parameters of all tree species were negatively impacted by the polluted ambient air quality in the industrial and urban (S2 and S3) sites as compared to the non-polluted institutional (S1) site. The models were characterized by high prediction performance as indicated by the coefficient of determination (R2) values greater than 0.80. Moreover, A. indica was found to be more 'tolerant' based on the air pollution tolerance index (APTI) followed by T. ciliate, P. guajava, and C. citrinus. Similarly, the anticipated performance index (API) was reported higher for A. indica (75 to 81.25%) followed by T. ciliate (68.75 to 75.00%), P. guajava (56.25%), and C. citrinus (37.50%), respectively. This study revealed that the selected tree species are being negatively impacted by the induced pollutant exposure in the urban and industrial region of Haridwar, India which needs sufficient mitigation measures to conserve their diversities.


Effects of paraprobiotics on bile acid metabolism and liver health in largemouth bass (Micropterus salmoides) fed a cottonseed protein concentrate-based diet.
Cottonseed protein concentrate is a sustainable fishmeal alternative in aquafeed. A 10-week experiment was conducted to investigate the effects of a cottonseed protein concentrate-based diet with and without multi-strain yeast fractions (MsYF) on growth, bile acid metabolism, and health in largemouth bass. Four hundred fish (54.0 ± 0.0 g) were casually distributed into 16 tanks (4 replicates/diet). Fish were fed with 4 iso-nitrogen and iso-energetic diets 3 times daily, including a fishmeal diet (FM), a soy protein concentrate-based diet (SPC; replacing 81% fishmeal protein), a cottonseed protein concentrate-based diet (CPC; replacing 81% fishmeal protein), and a CPC diet supplemented with 800 mg/kg MsYF (CPCY). Results showed that the survival of SPC was the lowest, i.e., 48%, with no apparent diet effect among other treatments; we omitted the SPC in additional analyses. Fish fed cottonseed protein concentrate-based diets showed lower growth than FM (P < 0.05). Fish fed CPC showed the highest nuclear dense hepatic phenotypes ratio (50%), followed by CPCY (33%) and FM (17%). Further, dietary CPC increased hepatic total cholesterol and triglyceride levels with concurrently increased cholesterol synthesis but decreased triglyceride synthesis-associated transcription levels (P < 0.05). Furthermore, dietary CPC increased bile acid synthesis but decreased bile acid transport-associated transcription levels (P < 0.05), and then induced an increment of plasma cholic acid and hepatic chenodeoxycholic acid content and the decrement of genus Romboustia (P < 0.05). Regarding the effect of MsYF, fish fed CPCY reduced hepatic lipid accumulation and total plasma bile acid content (P < 0.05) compared to CPC, suggesting an improvement in liver health. Also, dietary MsYF could reverse the microbiota community structure showing a similar gut microbial composition to FM. In conclusion, 81% of fishmeal protein replaced by cottonseed protein concentrate suppressed growth and liver health, while dietary MsYF might mitigate the negative impact of a high cottonseed protein concentrate level diet on liver functions via gut microbiota regulation.


Incidence of hospital-acquired infections associated with caesarean section.
A retrospective cohort study was conducted to determine the incidence of post-caesarean infections in a Canadian community teaching hospital using computer algorithms designed for the diagnosis of nosocomial infections. Inferential chart review was done on 1335 women delivered by lower-segment caesarean section (793 primary and 542 secondary) at the Calgary General Hospital between January 1985 and April 1988. The overall infection rates were 42.1 and 46.1% for women delivered by primary and secondary caesarean section, respectively. Incisional surgical wound infection accounted for the largest proportion of post-caesarean infections found. Women delivered by primary caesarean section had significantly higher rates of endometritis, deep surgical wound infection and bacteraemia than those delivered by secondary section. All types of post-caesarean infection, except asymptomatic bacteriuria, caused the duration of the post-partum hospital stay to be significantly increased.


Globalizing Genomics: The Origins of the International Nucleotide Sequence Database Collaboration.
Genomics is increasingly considered a global enterprise - the fact that biological information can flow rapidly around the planet is taken to be important to what genomics is and what it can achieve. However, the large-scale international circulation of nucleotide sequence information did not begin with the Human Genome Project. Efforts to formalize and institutionalize the circulation of sequence information emerged concurrently with the development of centralized facilities for collecting that information. That is, the very first databases build for collecting and sharing DNA sequence information were, from their outset, international collaborative enterprises. This paper describes the origins of the International Nucleotide Sequence Database Collaboration between GenBank in the United States, the European Molecular Biology Laboratory Databank, and the DNA Database of Japan. The technical and social groundwork for the international exchange of nucleotide sequences created the conditions of possibility for imagining nucleotide sequences (and subsequently genomes) as a "global" objects. The "transnationalism" of nucleotide sequence was critical to their ontology - what DNA sequences came to be during the Human Genome Project was deeply influenced by international exchange.


Effect of Culture Supernatant Derived from Trichophyton Rubrum Grown in the Nail Medium on the Innate Immunity-related Molecules of HaCaT.
Trichophyton rubrum is superficial fungi characteristically confined to dead keratinized tissues. These observations suggest that the soluble components released by the fungus could influence the host immune response in a cell in contact-free manner. Therefore, this research aimed to analyze whether the culture supernatant derived from T. rubrum grown in the nail medium could elicit the immune response of keratinocyte effectively. The culture supernatants of two strains (T1a, T XHB ) were compared for the β-glucan concentrations and their capacity to impact the innate immunity of keratinocytes. The β-glucan concentrations in the supernatants were determined with the fungal G-test kit and protein concentrations with bicinchoninic acid protein quantitative method, then HaCaT was stimulated with different concentrations of culture supernatants by adopting morphological method to select a suitable dosage. Expressions of host defense genes were assessed by quantitative polymerase chain reaction after the HaCaT was stimulated with the culture supernatants. Data were analyzed with one-way analysis of variance, followed by the least significant difference test. The T. rubrum strains (T1a and T XHB ) released β-glucan of 87.530 ± 37.581 pg/ml and 15.747 ± 6.453 pg/ml, respectively into the media. The messenger RNA (mRNA) expressions of toll-like receptor-2 (TLR2), TLR4, and CARD9 were moderately up-regulated in HaCaT within 6-h applications of both supernatants. HaCaT cells were more responsive to T1a than T XHB . The slight increase of dendritic cells-specific intercellular adhesion molecule 3-grabbing nonintegrin expression was faster and stronger, induced by T1a supernatant than T XHB . The moderate decreases of RNase 7, the slight up-regulations of Dectin-1 and interleukin-8 at the mRNA level were detected only in response to T1a rather than T XHB . After a long-time contact, all the elevated defense genes decreased after 24 h. The culture supernatant of T. rubrum could directly and transiently activate the innate immune response of keratinocytes.


The Anatomic Distribution of Skin Involvement in Patients with Incident Chronic Graft-versus-Host Disease.
Little is known about the anatomic distribution of cutaneous chronic graft-versus-host disease (cGVHD). Using data from the cGVHD Consortium Improving Outcomes Assessment Study, we describe the frequency and extent of erythema and superficial and deep sclerosis in 8 anatomic sites in patients with incident disease (ie, new cGVHD diagnosis within 3 months of study entry) receiving systemic therapy. Of 339 patients with incident disease, 182 (54%) had skin involvement. When an extremity was involved, the same type of disease was present contralaterally in 92% of cases, revealing a high level of symmetry. As anticipated, erythema was the most common incident feature; however, sclerotic skin involvement at the time of cGVHD diagnosis was more common than has been suggested by previous studies. Erythema occurred in 155 (85%) and sclerosis in 53 (29%) of the patients with skin involvement (46% and 16%, respectively, of the entire cohort of 339 incident cGVHD cases). Erythema was least common on the lower extremities (n = 71; 39% of patients with skin involvement). Moveable sclerosis was rare on the head, neck, and scalp (n = 4; 2%). Deep sclerosis did not occur in this region, and instead was most likely to occur on the upper extremities (n = 14; 8%) and lower extremities (n = 14; 8%). More than one-half of patients with erythema (n = 107; 58.7%) had diffuse involvement (4 or more of 8 sites involved), compared with less than one-third of those with sclerosis (n = 16; 30.2%).


Advances in management of severe head injuries in childhood.
An analysis of the clinical courses of 205 children with severe head injuries is given. In addition to the use of modern intensive care methods, advances are due to monitoring intracranial pressure directly, steroid therapy in very high doses, and early activation in the subacute stage after injury. By this it is possible to lower mortality and to achieve better clinical results.


Resolution of spinal epidural vascular pseudotumor following balloon occlusion of a postoperative vertebral arteriovenous fistula.
We describe a case of a vascular mass arising secondary to a postoperative vertebral arteriovenous fistula mimicking recurrent cervical neurofibroma on CT in a patient with neurofibromatosis. Angiography was required for diagnosis. The "recurrent tumor" resolved following balloon embolization of the fistula.


[Characteristics of the mutagenic and toxic effects of ethylene imine and its oligomers. Comparative study in the automated SOS-chromotest system and in standard bacterial test systems].
Raising total positive charge of a chemical mutagen does increase its local concentration in the area of biological target-DNA, and, as a consequence, causes increase in the rate of interaction of a mutagen with the target. Experimental evidence of this idea has been obtained in three test systems: the Ames test, Trp+ reversions in Escherichia coli WP2 and in the automated "SOS-chromotest" system with E. coli PQ 37 ("Labsystems", Finland).


Modification of MRI criteria for multiple sclerosis in patients with clinically isolated syndromes.
The McDonald criteria include MRI evidence for dissemination in space and dissemination in time for the diagnosis of multiple sclerosis in young adult patients who present with clinically isolated syndromes (CIS) typical of the disease. Although a major advance, the criteria have limited sensitivity for making an early diagnosis. To compare the performance of McDonald criteria and modified McDonald criteria for dissemination in space and time for assessing the development of clinically definite multiple sclerosis. McDonald criteria were modified using the combination of a less stringent definition for dissemination in space and allowing a new T2 lesion per se after three months as evidence for dissemination in time. Modified and McDonald criteria were applied in 90 CIS patients at baseline and at three month follow up scans. Both criteria were highly specific (>90%) but the modified criteria were more sensitive (77% v 46%) and more accurate (86% v 73%). These modified criteria should be evaluated in other CIS cohorts.


Emergency contraception in the emergency department.
On June 24, 2022, the Supreme Court overturned Roe v. Wade, which will limit legal abortion in many areas of the U.S., making the need for effective emergency contraception even more critical. This narrative review focuses on the approach to providing safe and effective emergency contraception in the emergency department (ED) with a focus on agents that are used in the U. S.; however, many of the agents discussed are also available and utilized in other countries. Emergency contraception methods included in this review are, ulipristal, levonorgestrel, combined oral contraceptive pills, and copper intrauterine devices (IUDs). The efficacy of products used for emergency contraception depend on patient and temporal factors. Emergency physicians must have an understanding of the optimal use of these agents to prevent unwanted pregnancy, particularly in the setting of restricted abortion access.