The Johns Hopkins Oncology Clinical Information System.
The Johns Hopkins Oncology Center has developed and maintains a clinical information system to support patient care, education, research, and administrative functions. It operates on a dedicated minicomputer (PDP-11) programmed in MUMPS. Clinical information collected includes patient medical status and laboratory values. Data are used daily in patient care and also in support of retrospective and prospective research. The use of the system to manage a large blood pheresis program and to study and treat infectious disease is described. Administrative functions include patient and personnel scheduling, program evaluation, and projects directed toward control of costs.


A novel gas ionization sensor using Pd nanoparticle-capped ZnO.
A novel gas ionization sensor using Pd nanoparticle-capped ZnO (Pd/ZnO) nanorods as the anode is proposed. The Pd/ZnO nanorod-based sensors, compared with the bare ZnO nanorod, show lower breakdown voltage for the detected gases with good sensitivity and selectivity. Moreover, the sensors exhibit stable performance after more than 200 tests for both inert and active gases. The simple, low-cost, Pd/ZnO nanorod-based field-ionization gas sensors presented in this study have potential applications in the field of gas sensor devices.


Minimal change nephrotic syndrome after stem cell transplantation: a case report and literature review.
Graft-versus-host disease is one of the most frequent complications occurring after haematopoietic stem cell transplantation. Recently, renal involvement has been described as a manifestation of chronic graft-versus-host disease. Immunosuppression seems to play a major role: clinical disease is triggered by its tapering and resolution is achieved with the resumption of the immunosuppressive therapy. Prognosis is apparently favourable, but long term follow up data are lacking.We report a case of a 53-year-old man who developed nephrotic syndrome 142 days after allogeneic stem cell transplantation for acute myeloid leukaemia. Onset of nephrotic syndrome occurred after reduction of immunosuppressants and was accompanied by manifestations of chronic graft-versus-host disease. Histological examination of the kidney was consistent with Minimal Change Disease. After treatment with prednisolone and mycophenolate mofetil he had complete remission of proteinuria and improvement of graft-versus-host disease. Eighteen months after transplantation the patient keeps haematological remission and normal renal function, without proteinuria.Since patients with chronic graft-versus-host disease might be considered at risk for development of nephrotic syndrome, careful monitoring of renal parameters, namely proteinuria, is advisable.


Inner ear anomalies in two cases of trisomy 18.
Two cases of trisomy 18 in which temporal bone defects were limited to the inner ears are described. Several abnormalities were present that have not been described previously in this syndrome. The first case involved a 1-month-old female infant who died of congenital heart defects. Cochlear nerve fibers were absent on the left side, with near-normal innervation on the right. Although the organ of Corti was present bilaterally, some of the outer hair cells were deformed, having small rounded cell bodies unsupported by Deiters' cells. On the right, similar abnormal cells were found in the tunnel of Corti. Vestibular defects in this case included reduced nerve supply of the left saccular macula, cysts in the superior and posterior cristae, and absence of the utriculoendolymphatic valve. The second case involved a newborn male infant with multiple congenital anomalies. The major cochlear defect was a deformity of the stria vascularis. In the lower apical turn, the stria was adherent to Reissner's membrane and extended beneath it into scala media. Large capillaries, which ran freely suspended in scala vestibuli, entered the upper portion of the stria. Severe atresia of the lateral and posterior semicircular ducts was found in the vestibular apparatus.


Preparation of [35S]sulfobromophthalein of high specific activity.
Study of the hepatocyte transport mechanism of organic anions such as bilirubin and sulfobromophthalein has been limited by the relatively low specific activities of these ligands. [3H]Bilirubin and [35S]sulfobromophthalein have been available with specific activities of only approximately 100 mCi/mmol. We now report a relatively simple procedure to prepare [35S]sulfobromophthalein at a specific activity of approximately 3000 mCi/mmol. This compound is radiochemically pure and serves as a tracer for authentic sulfobromophthalein as judged by chromatography, hepatocyte uptake, metabolism, and biliary excretion. Use of this material as a photoaffinity probe and as a transported ligand may permit dissection and understanding of its transport mechanism.


Effect of thiol manipulation on chemopotentiation by nitroimidazoles.
Highly electron affinic compounds such as the nitroimidazole misonidazole (MISO) have been shown both in vitro and in vivo to be effective potentiators of certain conventional chemotherapeutic agents. Mechanistically, the observation that nitroheterocyclics reduce intra-cellular thiols by enhancing the oxidation of glutathione (GSH), has suggested that thiol depletion by MISO may be a key factor in this enhancement. The present investigations were undertaken to determine whether the use of buthionine sulfoximine (BSO) to affect GSH metabolism may lead to more effective potentiation of chemotherapeutic agents by sensitizers. KHT/iv cells were treated in exponential phase under hypoxic conditions with variable doses of the activated form of cyclophosphamide (4-hydroxy-cyclo-phosphamide, 4OH-CY) administered concomitantly with or without MISO (2.5 mM) for an exposure time of 4 hr. Inclusion of the sensitizer in the treatment protocol resulted in a dose modifying factor of approximately 2.4. Exposing cells to 1.0 mM BSO for 2 hr prior to treatment reduced intracellular GSH levels to 70-80% of control and increased the efficacy of 40H-CY approximately 1.2-fold. If BSO was administered prior to the 4OH-CY + MISO combination, severe tumor cell toxicity resulted. For example, when combined with 4OH-CY, similar cell kill could be achieved with 5 to 6-fold lower MISO doses in the presence of BSO as in the absence of BSO. Ultrastructural evaluations revealed that in the three agent combination, membrane damage, as reflected by the formation of surface blebs, may play a key role in the mechanism of the observed enhanced cytotoxicity.


Shared understandings: negotiating the meanings of health via concept mapping.
This paper discusses a project undertaken to explore the effectiveness of concept mapping in assisting students to develop positive concepts of health. Positive concepts of health are central to the notion of health promotion. While strategies for health promotion are included in all nursing education programmes in Australia, to date there have been few strategies that are oriented towards promoting the development of positive concepts of health discussed in the literature. If student nurses are to become health-promoting practitioners, health teaching in nursing education must employ teaching strategies which clarify for students the differences between positive and negative concepts of health. One such strategy is concept mapping, which was developed as an educational tool to foster meaningful learning. Concept maps work to identify misconceptions in relation to a topic by clarifying the essential points, thus opening the way for concept change. This paper discusses the results of using concept mapping within the context of an abstract subject such as health, identifies difficulties in evaluating the strategy and makes recommendations about how these might be overcome.


Lignocellulosic nanofibril aerogel via gas phase coagulation and diisocyanate modification for solvent absorption.
Cellulose-based aerogels are considered to be carriers that can absorb oils and organic solvents owing to the merits of low density and high surface area. However, the natural hydrophility and poor mechanical strength often obstruct their widespread applications. In this work, Miscanthus-based dual cross-linked lignocellulosic nanofibril (LCNF) aerogels were prepared by gas phase coagulation and methylene diphenyl dissocyanate (MDI) modification. Due to physical and chemical cross-linking strategies, the optimally 4 M-LCNF aerogels had high surface area of 157.9 m2/g, water contact angle of 138.1°, and enhanced compression properties. Moreover, the modified aerogels exhibited absorption performance for various organic solvents, and the maximal absorption capacity of chloroform was 42 g/g aerogel. Because LCNF was directly produced from Miscanthus without using bleaching reagents, this research provided a more sustainable methodology to utilize lignocelluloses to design robust aerogels to deal with the leakage of oil and organic solvents in industrial applications.


3D pelvimetry and biometric measurements: a surgical perspective for colorectal resections.
Male sex, high BMI, narrow pelvis, and bulky mesorectum were acknowledged as clinical variables correlated with a difficult pelvic dissection in colorectal surgery. This paper aimed at comparing pelvic biometric measurements in female and male patients and at providing a perspective on how pelvimetry segmentation may help in visualizing mesorectal distribution. A 3D software was used for segmentation of DICOM data of consecutive patients aged 60 years, who underwent elective abdominal CT scan. The following measurements were estimated: pelvic inlet, outlet, and depth; pubic tubercle height; distances from the promontory to the coccyx and to S3/S4; distance from S3/S4 to coccyx's tip; ischial spines distance; pelvic tilt; offset angle; pelvic inlet angle; angle between the inlet/sacral promontory/coccyx; angle between the promontory/coccyx/pelvic outlet; S3 angle; and pelvic inlet to pelvic depth ratio. The measurements were compared in males and females using statistical analyses. Two-hundred patients (M/F 1:1) were analyzed. Out of 21 pelvimetry measurements, 19 of them documented a significant mean difference between groups. Specifically, female patients had a significantly wider pelvic inlet and outlet but a shorter pelvic depth, and promontory/sacral/coccyx distances, resulting in an augmented inlet/depth ratio when comparing with males (p < 0.0001). The sole exceptions were the straight conjugate (p = 0.06) and S3 angle (p = 0.17). 3D segmentation provided a perspective of the mesorectum distribution according to the pelvic shape. Significant differences in the structure of pelvis exist in males and females. Surgeons must be aware of the pelvic shape when approaching the rectum.


IgG:IgM Ratios of Liver Plasma Cells Reveal Similar Phenotypes of Primary Biliary Cholangitis With and Without Features of Autoimmune Hepatitis.
Within the spectrum of autoimmune liver diseases, there are patients who manifest features of more than one disease, which was previously identified as having overlap syndrome1,2 and is now referred to as variant syndromes. The most common variant syndrome is between primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). Typically, AIH presents with elevated serum immunoglobulin (Ig) G, whereas PBC is associated with elevated serum IgM.3,4 Previous studies have suggested that plasma cells in liver biopsies of AIH patients are predominantly IgG+, whereas in PBC, there is an abundance of IgM+ cells.5,6 We wanted to determine the immunostaining pattern for IgG and IgM of liver plasma cells among Hispanic patients in Los Angeles with features of both PBC-AIH compared with those with PBC or AIH alone.


A rare case of follicular thyroid carcinoma in ovarian struma.
Struma ovarii is a form of specialised mature teratoma, with predominantly mature thyroid tissue in an ovarian teratoma as seen in 2% of cases. Its malignant transformation is even rarer and is seen in only 5% of those cases. This 40-year-old female patient had an incidental finding of a pelvic mass during investigation of secondary amenorrhoea. She underwent a staging laparotomy and pelvic clearance. The histopathology revealed a bilateral mature teratoma of the ovary with follicular thyroid carcinoma in the right ovarian struma (malignant struma). A total thyroidectomy was performed followed by a whole body 31I scintigraphy which did not reveal any abnormal uptake of isotope. The patient remains well after four years and is being followed-up with serial serum thyroglobulin surveillance.


High sucrose diet attenuates oxidative stress, inflammation and liver injury in thioacetamide-induced liver cirrhosis.
Liver cirrhosis is the main chronic liver disease and is considered a catabolic disease. Cirrhotic patients have a low energy intake and high energy expenditure at rest, leading to metabolic disorders. Malnutrition is associated with complications of cirrhosis and has been shown that a nutritional intervention with increase of energy intake improves the survival of cirrhotic patients. Therefore, our aim was to evaluate the effect of a high sucrose diet in the liver of animals with cirrhosis induced by thioacetamide and investigate the mechanism involved. Male Wistar rats were divided into three groups: Control; Thioacetamide; and Thioacetamide + high sucrose diet. The thioacetamide was administrated (100 mg kg-1) intraperitoneally and the sucrose was offered in drinking water (300 g L-1). The administration of thioacetamide was associated with fibrosis and inflammatory infiltrate in the liver and increased levels of transaminases enzymes. The high sucrose diet promoted a reduction of theses parameters in cirrhotic rats. The malnutrition observed in cirrhotic rats was attenuated by the high sucrose diet shown by the improvements in weight loss, subcutaneous fat, and caloric intake. The high sucrose diet also attenuated the oxidative stress present in the liver of animals with thioacetamide-induced cirrhosis. The high sucrose diet had anti-inflammatory and anti-oxidant effects in the liver of animals with thioacetamide-induced cirrhosis. In addition, the high sucrose diet also improved malnutrition and catabolism present in cirrhosis. Thus, a high sucrose diet may be a therapeutic option for cirrhotic patients in a catabolic state.


All that glitters is not gold: trustworthy and ethical AI principles.
Ethics of technology systems have become an area of interest in academic research as well as international policy in recent years. Several organisation have consequently published principles of ethical artificial intelligence (AI) in line with this trend. The documents identify principles, values, and other abstract requirements for AI development and deployment. Critics raise concerns about whether these documents are in fact constructive, or if they are produced as a higher form of virtue signalling. A theme that is beginning to become apparent in the academic literature regarding these documents is the inherent lack of effective and practical methods and processes for producing ethical AI. This article attempts a critical analysis which draws upon ethical AI documents from a range of contexts including company, organisational, governmental, and academic perspectives. Both the theoretical and practical components of AI guidelines are explored and analysed, consequently bringing to light the necessity of introducing a measurable component to such documents for the purpose of ensuring a positive outcome of deploying AI systems based on ethical principles. We propose a minimal framework for stakeholders to develop AI in an ethical and human-centred manner.


Positional cloning identifies a novel cyclophilin as a candidate amplified oncogene in 1q21.
Gains of 1q21-q23 have been associated with metastasis and chemotherapy response, particularly in bladder cancer, hepatocellular carcinomas and sarcomas. By positional cloning of amplified genes by yeast artificial chromosome-mediated cDNA capture using magnetic beads, we have identified three candidate genes (COAS1, -2 and -3) in the amplified region in sarcomas. COAS1 and -2 showed higher amplification levels than COAS3. Most notably, amplification was very common in osteosarcomas, where in particular COAS2 was highly expressed. COAS1 has multiple repeats and shows no homology to previously described genes, whereas COAS2 is a novel member of the cyclosporin-binding peptidyl-prolyl isomerase family, very similar to cyclophilin A. COAS2 was overexpressed almost exclusively in aggressive metastatic or chemotherapy resistant tumours. Although COAS2 was generally more amplified than COAS1, it was not expressed in well-differentiated liposarcomas, where amplification of this region is very common. All three genes were found to be amplified and over-expressed also in breast carcinomas. The complex nature of the 1q21-23 amplicons and close proximity of the genes make unequivocal determination of the gene responsible difficult. Quite likely, the different genes may give selective advantages to different subsets of tumours.


CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses.
Alterations in cellular metabolism underpin macrophage activation, yet little is known regarding how key immunological molecules regulate metabolic programs in macrophages. Here we uncover a function for the antigen presenting molecule CD1d in the control of lipid metabolism. We show that CD1d-deficient macrophages exhibit a metabolic reprogramming, with a downregulation of lipid metabolic pathways and an increase in exogenous lipid import. This metabolic rewiring primes macrophages for enhanced responses to innate signals, as CD1d-KO cells show higher signalling and cytokine secretion upon Toll-like receptor stimulation. Mechanistically, CD1d modulates lipid import by controlling the internalization of the lipid transporter CD36, while blocking lipid uptake through CD36 restores metabolic and immune responses in macrophages. Thus, our data reveal CD1d as a key regulator of an inflammatory-metabolic circuit in macrophages, independent of its function in the control of T cell responses.


Function and regulation of cis P-tau in the pathogenesis and treatment of conventional and nonconventional tauopathies.
Conventional tauopathies are a group of disease characterized by tau inclusions in the brains, including Alzheimer's disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and certain types of frontotemporal dementia (FTD), among which AD is the most prevalent. Extensive post-translational modifications, especially hyperphosphorylation, and abnormal aggregation of tau protein underlie tauopathy. Cis-trans isomerization of protein plays an important role in protein folding, function, and degradation, which is regulated by peptidyl-proline isomerases (PPIases). Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1), the only PPIase found to isomerize Pro following phosphorylated Ser or Thr residues, alters phosphorylated tau protein conformation at pT231-P motif. The cis P-tau but not trans P-tau serves as an early driver of multiple neurodegenerative disease, encompassing AD, traumatic brain injury (TBI), chronic traumatic encephalopathy (CTE), and vascular contributions to cognitive impairment and dementia (VCID). Cis but not trans P-tau is resistant to protein dephosphorylation and degradation, and also prone to protein aggregation. Cis P-tau loses its ability to stabilize microtubule, causing and spreading tauopathy mainly in axons, a pathological process called cistauosis. The conformation-specific monoclonal antibody that targets only the cis P-tau serves as a very early diagnosis method and a potential treatment of not only conventional tauopathies but also nonconventional tauopathies such as VCID, with clinical trials ongoing. Notably, cis P-tau antibody is the only clinical-stage Alzheimer's therapeutic that has shown the efficacy in animal models of not only AD but also TBI and stroke, which are very early stages of dementia. Here we review the identification and pathological consequences of cis pt231-tau, the role of its regulator Pin1, as well as the clinical implication of cis pt231-tau conformation-specific antibody in conventional and nonconventional tauopathies.


Abnormal regulation of extracellular matrix and adhesion molecules in corneas of patients with keratoconus.
To identify changes in the expression of genes coding for extracellular matrix (ECM) proteins in patients with non-inflammatory corneal disorder keratoconus (KC), patients with corneal scarring, and normal controls. Total RNA extracted from corneal tissue of 13 KC patients, 2 patients with corneal scaring and 4 normal controls was analyzed using Human Extracellular Matrix & Adhesion Molecules Profiler PCR Array. Statistically significant changes in gene expression were identified using the Data Analysis software. Comparison of KC and control corneas with thresholds of 1.5 or greater fold change and a p-value of 0.05 or lower, revealed 21 differentially expressed genes, 16 genes were downregulated and 5 were upregulated. Among transcripts downregulated in KC patients we identified THBS1, ADAMTS1, SPP1, several collagens and integrins. We found TGFBI (BIGH3) gene was the most significantly upregulated transcript. Development of keratoconus results in deregulation of gene expression of extracellular matrix and adhesion molecules. Downregulation of collagens and upregulation of TGFBI repeatedly identified in KC patients may be used as clinical markers of the disease.


Israeli soldiers' intentions and actions toward seeking mental health help: Barriers and facilitators.
While military settings may increase psychological distress, soldiers frequently avoid seeking professional help. This study aimed to examine barriers and facilitators associated with intentions to seek help and actually seeking help from a mental health officer (MHO) and how these differ among soldiers who had sought help in the past and those who had not. This cross-sectional study included 263 combat and noncombat soldiers. The Health Belief Model and the Help-Seeking Model were the theoretical framework used to map the potential variables associated with soldiers' decision to seek help. Stigma and administrative barriers were found to be significant barriers to both the intention to seek help and actually consulting an MHO. These findings were more definitive among combat soldiers. The belief in the effectiveness of mental health treatment was positively associated with the intention to seek help. Positive associations were found between well-being, perceived seriousness of one's condition, and belief in the effectiveness of mental health care and intention to seek MHO help. Distress and self-concealment were positively associated with actual consultation with an MHO. Public stigma about seeking help was associated with both the intention to seek mental health assistance and actually consulting an MHO. Military commanders should make an effort to make soldiers feel safe to seek mental health assistance by creating a supportive organizational atmosphere to reduce the stigma associated with mental health care.


Characterization of MSlys, the endolysin of Streptococcus pneumoniae phage MS1.
Despite the use of pneumococcal conjugate vaccines, the number of infections related to Streptococcus pneumoniae continues to be alarming. Herein, we identified, characterized the MSlys endolysin encoded in the phage MS1. We further tested its antimicrobial efficacy against planktonic and biofilm cells, assessing the culturability of cells and biofilm structure by scanning electron microscopy, and confocal laser scanning microscopy. The modular MSlys endolysin consists of an amidase catalytic domain and a choline-binding domain. MSlys is active against isolates of children with otitis media, and conditions close to those found in the middle ear. Treatment with MSlys (2 h, 4 μM) reduced planktonic cultures by 3.5 log10 CFU/mL, and 24- and 48-h-old biofilms by 1.5 and 1.8 log10 CFU/mL, respectively. Imaging of the biofilms showed thinner and damaged structures compared to control samples. The recombinantly expressed MSlys may be a suitable candidate for treating pneumococcal infections, including otitis media.


EGFR signaling is required for regenerative proliferation in the cochlea: conservation in birds and mammals.
Proliferation and transdifferentiaton of supporting cells in the damaged auditory organ of birds lead to robust regeneration of sensory hair cells. In contrast, regeneration of lost auditory hair cells does not occur in deafened mammals, resulting in permanent hearing loss. In spite of this failure of regeneration in mammals, we have previously shown that the perinatal mouse supporting cells harbor a latent potential for cell division. Here we show that in a subset of supporting cells marked by p75, EGFR signaling is required for proliferation, and this requirement is conserved between birds and mammals. Purified p75+ mouse supporting cells express receptors and ligands for the EGF signaling pathway, and their proliferation in culture can be blocked with the EGFR inhibitor AG1478. Similarly, in cultured chicken basilar papillae, supporting cell proliferation in response to hair cell ablation requires EGFR signaling. In addition, we show that EGFR signaling in p75+ mouse supporting cells is required for the down-regulation of the cell cycle inhibitor p27(Kip1) (CDKN1b) to enable cell cycle re-entry. Taken together, our data suggest that a conserved mechanism involving EGFR signaling governs proliferation of auditory supporting cells in birds and mammals and may represent a target for future hair cell regeneration strategies.


The Impact of Sequence of Chemotherapy and EGFR-TKI Treatment on Different EGFR Mutation Lung Adenocarcinoma.
Chemotherapy as first-/second-line treatment in different epidermal growth factor receptor (EGFR) mutation lung adenocarcinoma remains controversial. Consecutive patients were collected between 2009 and 2012. Patients were divided into two groups (1st-line chemotherapy: n = 56 and 2nd-line chemotherapy: n = 55). Their outcomes profiles were analyzed. The overall survival (OS) of all patients (390 versus 662 days, p < 0.0001), as well as both progression-free survival (PFS, 151 versus 252 days, p = 0.0001) and OS (308 versus 704 days, p = 0.0001) of patients with L858R mutation (n = 63), who received 2nd-line chemotherapy, was significantly poor. By univariate and multivariate analysis, 2nd-line chemotherapy, and L858R mutation were significantly related to poor PFS and OS. In advanced lung adenocarcinoma, L858R mutation and 2nd-line chemotherapy caused a poor outcome. It is a consideration to choice of 1st-line chemotherapy in these subjects. A prospective design is warranted to confirm this finding.


Evidence for an enhanced adhesion of DC to fibronectin and a role of CCL19 and CCL21 in the accumulation of DC around the pre-diabetic islets in NOD mice.
The non-obese diabetic (NOD) mouse is a widely used animal model for the study of human diabetes. The lymphocytic (peri-)insulitis is preceded by an early accumulation of dendritic cells (DC) around the islets of Langerhans. This DC accumulation is thought to derive from an influx of monocytes attracted by pro-inflammatory chemokines. Besides chemokines, extracellular matrix (ECM) proteins play an important role in the accumulation of leukocytes in tissues. We studied the expression of the chemokines CCL2, CCL5, CXCL10, CCL19 and CCL21 over time in pancreases of NOD and control mice by ELISA on pancreas lysates as well as by immunohistochemistry. In addition, we studied the adhesive capacity of bone marrow-derived DC (BMDC) to ECM components. DC in the NOD pancreas accumulated at sites with an intense expression of fibronectin. In vitro, NOD BMDC showed increased fibronectin adhesion and increased VLA-5 expression. At the time of early DC accumulation (<10 wk), the lymphoid tissue-related chemokines CCL19 and CCL21 were increased. Our findings support the view that the early accumulation of DC around the NOD islets is not the consequence of an enhanced attraction of precursors and immature DC by pro-inflammatory chemokines. It rather might be the consequence of an aberrantly enhanced adhesion and retention of NOD DC.


Enhanced endoscopic detection of occult gastric cancer in carriers of pathogenic CDH1 variants.
Germline inactivating variants in the CDH1 tumor suppressor gene impart an elevated lifetime risk of diffuse gastric cancer. The current endoscopic surveillance method depends upon random gastric biopsies for early cancer detection. Asymptomatic adults with pathogenic or likely pathogenic CDH1 variants referred for endoscopic gastric cancer surveillance were included in this retrospective cohort. Upper gastrointestinal endoscopy was performed according to the consensus Cambridge method, in the early period, or a systematic (Bethesda) protocol as part of an ongoing natural history study. The primary outcome measure was cancer detection. Collectively, 135 endoscopic surveillance procedures were performed in 120 patients. Twenty-six (19%, 26/135) procedures were performed using Cambridge method and 109 (81%) using the Bethesda protocol. Gastric signet ring cell carcinomas were detected in 15% (4/26) using the Cambridge method and 36% (40/109) using the Bethesda protocol (p < 0.05). Almost half (44.2%, 53/120) of patients later elected for prophylactic total gastrectomy, of whom 51 (96%, 51/53) had a signet ring cell carcinoma (T1a) discovered by histopathology. On a per endoscopy basis, the false-negative rates of detection using Cambridge method and Bethesda protocol were 80% (12/15) and 37.7% (17/45), respectively (p < 0.01). Gastric cancer detection was more frequent with implementation of a systematic surveillance protocol in CDH1 variant carriers. Given the decision for prophylactic surgery is often made by patients in the context of family history and pathologic result of surveillance biopsies, we propose the Bethesda protocol offers patients an opportunity to make more informed decisions.


Neostigmine after spontaneous recovery from neuromuscular blockade. Effect on depth of blockade monitored with train-of-four and tetanic stimuli.
The effect of neostigmine on neuromuscular function was examined after spontaneous recovery from an atracurium-induced neuromuscular blockade, which reached a train-of-four ratio of either 0.5 or 0.9. Two doses of neostigmine 2.5 mg were given 5 minutes apart. Neuromuscular recovery was assessed with train-of-four and tetanic stimuli. The first dose of neostigmine antagonised the neuromuscular blockade. The second dose diminished tetanic height and increased tetanic fade. The train-of-four measured mechanically was adversely affected to a small degree, but when measured with the electromyograph no significant change occurred. Neostigmine may adversely affect neuromuscular function after spontaneous recovery from a non-depolarising block. This is unlikely with a single modest dose and any effects are probably short-lived.


The interaction between the clonal herb Trientalis europaea and the host specific smut fungus Urocystis trientalis.
The interaction between the clonal dicotyledonous herb Trientalis europaea and the systemic smut fungus Urocystis trientalis was investigated. By marking individual plants in the field and transplanting plants to the greenhouse, disease transmission and the effect of disease on survival and fecundity of plants were estimated. Field data showed that 50% of the diseased and none of the healthy plants died during summer. Surviving diseased plants produced significantly fewer winter buds than healthy plants (means ±S.E. 1.12±0.05 and 1.88±0.07, respectively). Seed capsule production was low overall and did not differ between diseased and healthy plants. Disease was not seed-transmitted and transmission from infected mother plants to daughter ramets was not total (means 33% and 46%, in two experiments). Disease transmission was also influenced by light conditions.


Magnetic Resonance Imaging-Based Radiomics for the Prediction of Progression-Free Survival in Patients with Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis.
Advanced non-metastatic nasopharyngeal carcinoma (NPC) has variable treatment outcomes. However, there are no prognostic biomarkers for identifying high-risk patients with NPC. The aim of this systematic review and meta-analysis was to comprehensively assess the prognostic value of magnetic resonance imaging (MRI)-based radiomics for untreated NPC. The PubMed-Medline and EMBASE databases were searched for relevant articles published up to 12 August 2021. The Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) checklist was used to determine the qualities of the selected studies. Random-effects modeling was used to calculate the pooled estimates of Harrell's concordance index (C-index) for progression-free survival (PFS). Between-study heterogeneity was evaluated using Higgins' inconsistency index (I2). Among the studies reported in the 57 articles screened, 10 with 3458 patients were eligible for qualitative and quantitative data syntheses. The mean adherence rate to the TRIPOD checklist was 68.6 ± 7.1%. The pooled estimate of the C-index was 0.762 (95% confidence interval, 0.687-0.837). Substantial between-study heterogeneity was observed (I2 = 89.2%). Overall, MRI-based radiomics shows good prognostic performance in predicting the PFS of patients with untreated NPC. However, more consistent and robust study protocols are necessary to validate the prognostic role of radiomics for NPC.


Structural determinants for phosphatidylinositol recognition by Sfh3 and substrate-induced dimer-monomer transition during lipid transfer cycles.
Sec14 family homologs are the major yeast phosphatidylinositol/phosphatidylcholine transfer proteins regulating lipid metabolism and vesicle trafficking. The structure of Saccharomyces cerevisiae Sfh3 displays a conserved Sec14 scaffold and reveals determinants for the specific recognition of phosphatidylinositol ligand. Apo-Sfh3 forms a dimer through the hydrophobic interaction of gating helices. Binding of phosphatidylinositol leads to dissociation of the dimer into monomers in a reversible manner. This study suggests that the substrate induced dimer-monomer transformation is an essential part of lipid transfer cycles by Sfh3.


Efficient detoxication of hydroxylamine and nitrite through heterotrophic nitrification and aerobic denitrification by Acinetobacter johnsonii EN-J1.
The co-existence of hydroxylamine (NH2OH) and nitrite (NO2 --N) can aggravate the difficulty of wastewater treatment. The roles of hydroxylamine (NH2OH) and nitrite (NO2 --N) in accelerating the elimination of multiple nitrogen sources by a novel isolated strain of Acinetobacter johnsonii EN-J1 were investigated in this study. The results demonstrated that strain EN-J1 could eliminate 100.00% of NH2OH (22.73 mg/L) and 90.09% of NO2 --N (55.32 mg/L), with maximum consumption rates of 1.22 and 6.75 mg/L/h, respectively. Prominently, the toxic substances NH2OH and NO2 --N could both facilitate nitrogen removal rates. Compared with the control treatment, the elimination rates of nitrate (NO3 --N) and NO2 --N were enhanced by 3.44 and 2.36 mg/L/h after supplementation with 10.00 mg/L NH2OH, and those of ammonium (NH4 +-N) and NO3 --N were improved by 0.65 and 1.00 mg/L/h after the addition of 50.00 mg/L NO2 --N. Furthermore, the nitrogen balance results indicated that over 55.00% of the initial total nitrogen was transformed into gaseous nitrogen by heterotrophic nitrification and aerobic denitrification (HN-AD). Ammonia monooxygenase (AMO), hydroxylamine oxidoreductase (HAO), nitrate reductase (NR), and nitrite reductase (NIR), which are essential for HN-AD, were detected at levels of 0.54, 0.15, 0.14, and 0.01 U/mg protein, respectively. All findings confirmed that strain EN-J1 could efficiently execute HN-AD, detoxify NH2OH and NO2 --N, and ultimately promote nitrogen removal rates.


Ventricular arrhythmias induced by dynamic and static exercise in relation to coronary artery bypass grafting.
The effect of coronary artery bypass grafting (CABG) on exercise-induced ventricular arrhythmias was examined in 53 patients. A bicycle exercise test and an isometric handgrip exercise test were performed before and 3 months after CABG. Exercise-induced ventricular arrhythmias were detected preoperatively in 14 patients (26%), in 13 during the bicycle test and in 11 during the handgrip test, and in 18 patients (34%) after CABG. Thus, CABG had no significant effect on the occurrence of exercise-induced ventricular arrhythmias. Nine patients had new exercise-induced ventricular arrhythmias after CABG, 8 of whom had evidence of previous myocardial infarction, whereas only 8 of the 35 patients (23%) without postoperative ventricular arrhythmias had had a previous infarction. The rate of graft patency or improvement in exercise tolerance in patients with new postoperative arrhythmias did not differ from that in patients who did not have exercise-induced arrhythmias after CABG. The results confirm that CABG has no influence on the occurrence of ventricular arrhythmias induced by physical exercise. Patients with a previous myocardial infarction appear to be prone to new ventricular arrhythmias despite successful revascularization.


Phase Evolution of Re1-xMoxSe2 Alloy Nanosheets and Their Enhanced Catalytic Activity toward Hydrogen Evolution Reaction.
Two-dimensional ReSe2 has emerged as a promising electrocatalyst for the hydrogen evolution reaction (HER), but its catalytic activity needs to be further improved. Herein, we synthesized Re1-xMoxSe2 alloy nanosheets with the whole range of x (0-100%) using a hydrothermal reaction. The phase evolved in the order of 1T″ (triclinic) → 1T' (monoclinic) → 2H (hexagonal) upon increasing x. In the nanosheets with x = 10%, the substitutional Mo atoms tended to aggregate in the 1T″ ReSe2 phase with Se vacancies. The incorporation of the 1T' phase makes the alloy nanosheets more metallic than the end compositions. The 10% Mo substitution significantly enhanced the electrocatalytic performance toward HER (in 0.5 M H2SO4), with a current of 10 mA cm-2 at an overpotential of 77 mV (vs RHE) and a Tafel slope of 42 mV dec-1. First-principles calculations of the three phases (1T″, 2H, and 1T') predicted a phase transition of 1T″-2H at x ≈ 65% as well as the production of a 1T' phase along the composition tuning, which are consistent with the experiments. At x = 12.5%, two Mo atoms prefer to form a pair along the Re4 chains. Gibbs free energy along the reaction path indicates that the best HER performance of nanosheets with 10% Mo originates from the Mo atoms that form Mo-H when there are adjacent Se vacancies.


Structural organization of the 5' region of the thyroglobulin gene. Evidence for intron loss and "exonization" during evolution.
More than one third of thyroglobulin (1190 residues out of 2750) is made of one peptide motif repeated ten times in tandem. Segments unrelated to the motif interrupt this structure at various places. The corresponding gene region, which extends over 40 x 10(3) bases, was studied in detail. All exon borders and exon/intron junctions were localized precisely and sequenced, and their positions were correlated with the repetitive organization of the protein. When intron positions were compiled on a consensus sequence of all repeats, three categories of introns were observed. Except between repeats numbers 5 and 6, an intron was invariably found within the Cys codon making the limit of each motif. This category of intron most probably reflects the serial duplication events responsible for the evolution of this region of the gene. All other introns, except no. 2, are found at positions were the repetitive structure is disrupted by "inserted" peptides. We present the hypothesis that this second category of introns was already present in the original unit before the first duplication. Thereafter, they would have experienced either complete loss (some units do not contain any intron) or partial or total exonization, resulting in the slipping of intronic material into coding sequence. Intron no. 2, finally, separates motif no. 1 at a position on the boundary between two segments presenting sequence homology. This last type of intron probably reflects an initial duplication event at the origin of a primordial thyroglobulin gene motif. With all these characteristics, the thyroglobulin gene is presented as a paradigm for the analysis of the fate of introns in gene evolution.


Synthesis and biological evaluation of carbohydrate-Coumarin/vanillic acid hybrid as a promising antiparasitic agent.
Leishmaniasis is caused by infection with the protozoan parasites Leishmania. It is classified as one of the most significant neglected tropical diseases. It remains a significant global public health concern. Current treatments include the use of pentavalent antimonial, amphotericin B, pentamidine, miltefosine, and paromomycin. However, several limitations such as toxicity, side effect, and resistance to these drugs of certain species are of concern. To combat this disease, effective chemotherapy is urgently required for its treatment and management. In this study, we synthesized a series of carbohydrate-coumarin/vanillic acid hybrids linked through triazole moiety via CuACC (Copper-catalysed azide-alkyne cycloaddition) reaction. These compounds were evaluated for their in vitro antiparasitic activity using MTT assay against Leishmania donovani whereas, all compounds show IC50 value in the range of 65-74 μM.


Non-enzymatic oligonucleotide ligation in coacervate protocells sustains compartment-content coupling.
Modern cells are complex chemical compartments tightly regulated by an underlying DNA-encoded program. Achieving a form of coupling between molecular content, chemical reactions, and chassis in synthetic compartments represents a key step to the assembly of evolvable protocells but remains challenging. Here, we design coacervate droplets that promote non-enzymatic oligonucleotide polymerization and that restructure as a result of the reaction dynamics. More specifically, we rationally exploit complexation between end-reactive oligonucleotides able to stack into long physical polymers and a cationic azobenzene photoswitch to produce three different phases-soft solids, liquid crystalline or isotropic coacervates droplets-each of them having a different impact on the reaction efficiency. Dynamical modulation of coacervate assembly and dissolution via trans-cis azobenzene photo-isomerization is used to demonstrate cycles of light-actuated oligonucleotide ligation. Remarkably, changes in the population of polynucleotides during polymerization induce phase transitions due to length-based DNA self-sorting to produce multiphase coacervates. Overall, by combining a tight reaction-structure coupling and environmental responsiveness, our reactive coacervates provide a general route to the non-enzymatic synthesis of polynucleotides and pave the way to the emergence of a primitive compartment-content coupling in membrane-free protocells.


Random projection for dimensionality reduction--applied to time-of-flight secondary ion mass spectrometry data.
Random projection (RP) is a simple and fast linear method for dimensionality reduction of high-dimensional multivariate data, independent from the data. The method is briefly described and a new memory-saving algorithm is presented for the generation of random projection vectors. Application of RP to data from scanning experiments with a time-of-flight secondary ion mass spectrometer (TOF-SIMS) showed that data reduced by RP have a satisfying discriminant property for separating target material and minerals without using any knowledge about the composition of the sample. A selection method--based on low dimensional RP data--is described and successfully tested for automatic recognition of characteristic, diverse locations of a sample surface. RP is demonstrated as an unbiased, powerful method, especially for large data sets, severe hardware restrictions (such as in space experiments) or the need for fast data evaluation of hyperspectral data.


More than fear: Contributions of biobehavioral synchrony and infants' reactivity to cooperative care.
We present two challenges to the fearful ape hypothesis: (1) biobehavioral synchrony precedes and moderates the effects of fear on cooperative care, and (2) cooperative care emerges in a more bidirectional manner than Grossmann acknowledges. We present evidence demonstrating how dyadic differences in co-regulation and individual differences in infants' reactivity shape caregivers' responses to infant affect.


Gender differences in career satisfaction, moral distress, and incivility: a national, cross-sectional survey of Canadian critical care physicians.
In a national cross-sectional survey, we aimed to i) characterize work profile, workload, and income, ii) evaluate work satisfaction, work-life integration, burnout, incivility, mentorship, and promotion, iii) gauge future physician resource requirements, and iv) assess for differences by gender and specialty (adult vs pediatric). We developed, tested, and administered an electronic questionnaire. We analyzed 265 fully and 18 partially completed questionnaires. Respondents were predominantly men (192; 72.5%) and adult intensivists (229; 87.7%). Most intensivists (226/272; 83.1%) were somewhat satisfied or strongly satisfied with their career. Over one third of respondents felt that their daily intensive care unit (ICU) clinical work (113/270; 41.9%), yearly non-ICU clinical work (86/248; 34.7%), administrative work (101/264; 38.3%), and in-house call coverage (78/198; 39.4%) were somewhat high or very high. Nearly half (129/273; 47.3%) felt that their work schedule did not leave enough time for personal/family life. Twenty-seven percent (74/272) of respondents were experiencing at least one symptom of burnout when surveyed and 171/272 (63%) experienced burnout symptoms more than once a month. Ten percent planned to retire in the next five years and 17-20% retired each five-year interval thereafter. Compared with men, women felt that their work schedule left significantly less time for personal/family life (χ2 [4] = 11.36, P < 0.05, odds ratio [OR] = 0.55), experienced more frequent and severe burnout symptoms (F [1,120.91] = 8.04, P < 0.01, OR = 2.0; F [1,112.80] = 4.91, P < 0.05, OR = 1.9), and more incivility in their division (χ2 [1] = 13.73, P < 0.001, OR = 2.8), hospital (χ2 [1] = 8.11, P < 0.01, OR = 2.2), and university (χ2 [1] = 4.91, P < 0.05, OR = 2.3). Although most intensivists were satisfied with their careers, many were dissatisfied with their workload, experienced work-life integration challenges, and acknowledged burnout symptoms. Women intensivists were significantly less satisfied with their careers, experienced greater work-life integration challenges, more frequent and severe burnout symptoms, and greater incivility.


Maternal Cortisol Mediates Hypothalamus-Pituitary-Interrenal Axis Development in Zebrafish.
In zebrafish (Danio rerio), de novo synthesis of cortisol in response to stressor exposure commences only after hatch. Maternally deposited cortisol is present during embryogenesis, but a role for this steroid in early development is unclear. We tested the hypothesis that maternal cortisol is essential for the proper development of hypothalamus-pituitary-interrenal (HPI) axis activity and the onset of the stressor-induced cortisol response in larval zebrafish. In this study, zygotic cortisol content was manipulated by microinjecting antibody to sequester this steroid, thereby making it unavailable during embryogenesis. This was compared with embryos containing excess cortisol by microinjection of exogenous steroid. The resulting larval phenotypes revealed distinct treatment effects, including deformed mesoderm structures when maternal cortisol was unavailable and cardiac edema after excess cortisol. Maternal cortisol unavailability heightened the cortisol stress response in post-hatch larvae, whereas excess cortisol abolished the stressor-mediated cortisol elevation. This contrasting hormonal response corresponded with altered expression of key HPI axis genes, including crf, 11B hydroxylase, pomca, and star, which were upregulated in response to reduced cortisol availability and downregulated when embryos had excess cortisol. These findings for the first time underscore a critical role for maternally deposited cortisol in programming HPI axis development and function in zebrafish.


Opioid-prescribing considerations in patients with cancer and substance misuse or substance use disorder: a scoping review protocol.
This scoping review aims to describe factors in the existing literature that may inform opioid-prescribing decisions for patients with a past or present history of cancer and past or present substance misuse or substance use disorder. Opioids and opioid-related decisions are critical components of cancer care. Most individuals with cancer will experience pain during cancer care, and over half of patients will receive an opioid prescription. Opioid-prescribing decisions require weighing the benefits and harms. The presence of substance misuse or substance use disorder may elevate the risk of opioid-related harms, but there is a lack of consensus on managing patients at this intersection. This review will consider studies that include adult patients with a past or present history of cancer who also have pain and current or historical substance misuse or substance use disorder. The pain may be cancer-related or non-cancer-related. Studies of patients with all types of cancer will be eligible for inclusion, with the exception of non-melanoma skin cancers. Eligible studies will explore factors that inform opioid-prescribing decisions in this patient population. The review will be conducted according to JBI methodology for scoping reviews. Studies written in English since database inception will be included. The databases to be searched include MEDLINE (Ovid), CINAHL (EBSCO), Embase, APA PsycINFO, and Google Scholar. Eligible studies will undergo data extraction by 2 independent reviewers using a data extraction tool created by the authors. A narrative summary will describe study characteristics, population details, and strategies used to determine appropriate pain management in the patient population.


An innovative scoring system for predicting an excellent Harris hip score after proximal femoral nail anti-rotation in elderly patients with intertrochanteric fracture.
Typically, intramedullary and extramedullary devices are used to treat elderly with intertrochanteric fractures. The majority of previous research has focused on the association between surgical factors and mechanical failure after internal fixation. There is, however, limited evidence to demonstrate the association between functional outcomes after proximal femoral nail anti-rotation (PFNA) fixation and the non-surgical factors such as patient's comorbidities. The aim of this study is to determine the predictive factors associated with excellent outcome, as well as to develop an integrated scoring system to predict the outcome after PFNA fixation in elderly patients with an intertrochanteric fracture. A retrospective study was conducted between January 2012 and December 2018. Elderly patients with low-energy intertrochanteric fractures who underwent PFNA fixation and at least a year of follow-up were recruited. Demographics, comorbidities, cognitive status, time to operation, and surgical parameters of the patients were all identified. Excellent and non-excellent outcomes were assessed by Harris Hip Score (HHS) after a one-year follow up. Regression analysis was used to determine the predictors for an excellent functional outcome. A new integrated scoring system (ISSI; Integrate Scoring System in elderly patients with Intertrochanteric fracture) was developed and validated. 450 elderly patients were randomly divided into two cohorts: a development (N = 225) and validation cohorts (N = 225). In this study, age < 85 years, normal weight/overweight, Charlson comorbidity index (CCI) < 6, no cognitive impairment, a modified AO/OTA 31A1.3, time to operation < 6 days, and Tip Apex Distance between 20 and 30 mm were significantly associated with an excellent outcome after PFNA fixation. The range of ISSI score was between 0 to 16 and the cut-off score of 13 was found to have the highest discriminatory power to determine the excellent functional outcome where the area of ROC was 0.85. In regards to the validation cohort, the sensitivity and specificity of ISSI score was 69% and 87%, respectively, and the AUC was 0.81. The ISSI score is effortless and practical for orthopedic surgeons for predicting an outcome after PFNA fixation in elderly patients with an intertrochanteric fracture.


Evaluation of AIIMS Modified INCLEN Tool for Diagnosis of Epilepsy.
To evaluate the AIIMS Modified INCLEN tool for the diagnosis of epilepsy. This cross-sectional study enrolled 250 children aged 1 month to 18 years presenting with complaints of abnormal body movements to either the pediatric or neurology outpatient departments in our institution between October 1, 2018 and June 30, 2020. The All India Institute of Medical Sciences (AIIMS) modified International Clinical Epidemiology Network (INCLEN) diagnostic tool for epilepsy (AIIMS modified INDT-EPI) was administered and a diagnosis was made, which was further verified by a pediatrician or a neurologist. Specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. The study tool had a sensitivity of 87.6% and specificity of 84.0%. The PPV and NPV of the study tool were 86.8% and 84.9%, respectively. The study tool has good psychometric properties for physician assessment with regard to diagnosis of epilepsy.


Benign Synthesis of Thiazolo-androstenone Derivatives as Potent Anticancer Agents.
An unprecedented reaction of thiourea derivatives with 6β-bromoandrostenedione has been discovered for the formation of aminothiazolo-androstenones via a simple, safer, cascade protocol that enables the syntheses of novel molecules by using readily available reagents. The reaction mechanism of product formation has been rationalized by density functional theory calculations. This benign methodology accentuates a domino protocol deploying a renewable solvent, ethanol, while generating novel compounds that display potent growth inhibitory effects in in vitro studies for several cancer cell lines at submicromolar concentrations.


Genomic evolution and polymorphism: segmental duplications and haplotypes at 108 regions on 21 chromosomes.
We describe here extensive, previously unknown, genomic polymorphism in 120 regions, covering 19 autosomes and both sex chromosomes. Each contains duplication within multigene clusters. Of these, 108 are extremely polymorphic with multiple haplotypes. We used the genomic matching technique (GMT), previously used to characterise the major histocompatibility complex (MHC) and regulators of complement activation (RCA). This genome-wide extension of this technique enables the examination of many underlying cis, trans and epistatic interactions responsible for phenotypic differences especially in relation to individuality, evolution and disease susceptibility. The extent of the diversity could not have been predicted and suggests a new model of primate evolution based on conservation of polymorphism rather than de novo mutation.


Retention of radiographers in the NHS: Influencing factors across the career trajectory.
In order to meet the rising demands for imaging and radiotherapy services, the chronic workforce deficits experienced in many countries must be addressed. Improving workforce retention is essential; factors influencing radiographer attrition from the NHS have been previously reported as challenging working patterns, lack of flexibility in working patterns and lack of timely career progression and CPD. This article explores how these influencing factors for radiographers to leave the NHS change at different stages of the career trajectory. A qualitative research design using framework analysis explored via semi-structured telephone interviews (n = 44) the perspectives of radiography managers, radiographers who have left the NHS, and those considering leaving. Purposive sampling ensured representation across radiography disciplines, geographical and organisational diversity, and stages of career. The application of Generation Theory revealed how the emphasis on the influencing factors to leave or remain within the NHS changes across the working life of radiographers. Early career radiographers were found to be a more transient workforce leaving for increased career opportunities, mid-career radiographers were more likely to leave due to the lack of progression and CPD and late career radiographers due to the inflexibility of working patterns and conditions. It is imperative managers consider the needs and requirements of each generation of radiographers to improve radiographer retention. The different needs between the generations of radiographers should be viewed in terms of the strengths that they may bring to the workplace, rather than the challenges that they may pose. This generational timeline does not stand still and the learning is a continuous process. Recommendations are presented which will be a catalyst for sharing of best practice between radiology and radiotherapy centres.


Painful lumbosacral sensory distribution patterns: embryogenesis to adulthood.
When the dorsal root ganglion is irritated by any of a variety of mechanisms, pain is referred to the various structures innervated by that root. In many circumstances, this pain is specific and may be used as a diagnostic aid. Unfortunately, emphasis is placed on defining a dermatomal distribution; the existence of a myotomal or sclerotomal origin of referred pain is often overlooked. This review presents the embryologic, anatomic, and neurophysiologic etiology of referred pain from the lumbar spine.


Factors associated with high density lipoprotein cholesterol in a population with high high density lipoprotein cholesterol levels.
A cross-sectional study of a random sample of 976 coloureds (mixed race) of the Cape Peninsula, ages 15 to 64 years old, revealed a population with unexpectedly high levels of high density lipoprotein (HDL) cholesterol. The mean level for men was 55.4 +/- 16.1 mg/dl (SD) and for women, 60.8 +/- 16.0 mg/dl. The ratio of HDL cholesterol to total cholesterol expressed as a percentage was 26.3% +/- 9.5% for men and 28.1% +/- 9.3% for women. The HDL cholesterol levels were apparently lower than those of black and Negro populations, yet higher than those of Caucasian populations. Men with levels of HDL cholesterol above the median reported a personal history and a family history of coronary heart disease less frequently than did men with lower levels, while women with high levels of HDL cholesterol were less likely to have a history of hypertension or diabetes. Stepwise multiple regression analysis of variables significantly associated with HDL cholesterol levels showed that they explained 29.7% and 24.7%, respectively, of the variation in HDL cholesterol in men and women. Those variables independently associated with HDL cholesterol in both men and women were: serum triglyceride (-), cigarette consumption (-), alcohol, body mass index (-), age, and serum low density lipoprotein cholesterol levels (-). The reasons for the relatively high HDL cholesterol levels in this population are unknown. However, it would seem possible that these levels offer some protection against the high risk factors of smoking, hypertension, and hypercholesterolemia.


Optimizing calcium selective fluorimetric nanospheres.
Recently it was shown that optical nanosensors based on alternating polymers e.g. poly(maleic anhydride-alt-1-octadecene) were characterized by a linear dependence of emission intensity on logarithm of concentration over a few of orders of magnitude range. In this work we focus on the material used to prepare calcium selective nanosensors. It is shown that alternating polymer nanosensors offer competitive performance in the absence of calcium ionophore, due to interaction of the nanospheres building blocks with analyte ions. The emission increase corresponds to increase of calcium ions contents in the sample within the range from 10(-4) to 10(-1) M. Further improvement in sensitivity (from 10(-6) to 10(-1) M) and selectivity can be achieved by incorporating calcium ionophore in the nanospheres. The optimal results were obtained for core-shell nanospheres, where the core was prepared from poly(styrene-co-maleic anhydride) and the outer layer from poly(maleic anhydride-alt-1-octadecene). Thus obtained chemosensors were showing linear dependence of emission on logarithm of calcium ions concentration within the range from 10(-7) to 10(-1) M.


Transcriptome analysis of the murine forelimb and hindlimb autopod.
To gain insight into the coordination of gene expression profiles during forelimb and hindlimb differentiation, a transcriptome analysis of mouse embryonic autopod tissues was performed using Affymetrix Murine Gene Chips (MOE-430). Forty-four transcripts with expression differences higher than 2-fold (T test, P < or = 0.05) were detected between forelimb and hindlimb tissues including 38 new transcripts such as Rdh10, Frzb, Tbx18, and Hip that exhibit differential limb expression. A comparison of gene expression profiles in the forelimb, hindlimb, and brain revealed 24 limb-signature genes whose expression was significantly enriched in limb autopod versus brain tissue (fold change >2, P < or = 0.05). Interestingly, the genes exhibiting enrichment in the developing autopod also segregated into significant fore- and hindlimb-specific clusters (P < or = 0.05) suggesting that by E 12.5, unique gene combinations are being used during the differentiation of each autopod type.


Effect of red cyst cell inoculation and iron(II) supplementation on autotrophic astaxanthin production by Haematococcus pluvialis under outdoor summer conditions.
The negative effect of heat stress on the autotrophic astaxanthin production by Haematococcus pluvialis has been observed during outdoor culture in summer. Under the summer conditions, the proliferation of vegetative cells was highly halted in the green stage and the inducibility in the biosynthesis of astaxanthin was partly hindered in the red stage. Herein, under outdoor summer conditions in which variations of the diurnal temperature occur, heat-stress-driven inefficient vegetative growth of H. pluvialis was highly improved by inoculating the red cyst cells; thereby, maintaining relatively moderate intracellular carotenoid levels in the green stage. Subsequently, a remarkably enhanced astaxanthin titer was successfully obtained by supplementing 50 μM iron(II) to induce the heat stress-driven Haber-Weiss reaction in the red stage. As a result, the productivity of astaxanthin in the cells cultured under summer temperature conditions (23.4-33.5 °C) using the two methods of red cell (cyst) inoculation and the iron(Fe(2+)) supplementation was increased by 147% up to 5.53 mg/L day compared with that of the cells cultured under spring temperature conditions (17.5-27.3 °C). Our technical solutions will definitely improve the annual natural astaxanthin productivity in H. pluvialis in locations confronted by hot summer weather, particularly in large-scale closed photobioreactor systems.


Isoperoxidase spectra of single tulip cultivars and their parrot mutants.
The isoperoxidase spectrums of 2 single tulip cultivars and their parrot mutants were analyzed by disc electrophoresis in leaves and tepals i.e. petals plus sepals excised from within the bulbs. It was found that the anodal isoperoxidase pattern of parrot mutant tepals differs distinctly from tepals of their mother cultivars, but no differences were observed in cathodal isoperoxidases. Both the anodal and cathodal isoperoxidase spectra of parrot mutant leaves and leaves of their mother cultivars were similar.


Temporal characteristics of seizures and epileptiform discharges.
The time relations of epileptic events have been studied in 3 sets of data: (I) counts of individual epileptiform discharges in twelve 48 h EEG recordings, (IIa) seizure calendars of 30 therapy-resistant outpatients participating in a drug trial, (IIb) seizure calendars of 10 mentally subnormal epileptic patients resident in a long-stay unit. The EEG data I were characterized most often by a Poisson distribution of intervals between discharges and the occurrence of marked periodicities, particularly at night. The periods of rhythmic nocturnal events ranged from 13 to 142 min and did not appear to correspond to the REM/non-REM cycle. In the seizure data IIa and b a Poisson distribution of intervals between events was found in half the patients. Periodicities occurred only in group IIa and did not correspond to weekly or monthly cycles. A stochastic process is considered to be the model which best fits these data.


A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia.
We report the first identified mutation in the gene encoding human cytochrome c (CYCS). Glycine 41, invariant throughout eukaryotes, is substituted by serine in a family with autosomal dominant thrombocytopenia caused by dysregulated platelet formation. The mutation yields a cytochrome c variant with enhanced apoptotic activity in vitro. Notably, the family has no other phenotypic indication of abnormal apoptosis, implying that cytochrome c activity is not a critical regulator of most physiological apoptosis.


Three photo-cross-linked complexes of yeast phenylalanine specific transfer ribonucleic acid with aminoacyl transfer ribonucleic acid synthetases.
Yeast tRNA-Phe has been cross-linked photochemically to three aminoacyl-tRNA synthetases, yeast phenylalanyl-tRNA synthetase, Escherichia coli isoleucyl-tRNA synthetase, and E. coli valyl-tRNA synthetase. The two non-cognate enzymes are known to interact with tRNA-Phe. In each complex, three regions on the tRNA are found to cross-link. Two of these are common to all of the complexes, while the third is unique to each. Thus, the cognate and non-cognate complexes bear considerable similarity to each other in the way in which the respective enzyme orients on tRNA-Phe, a result which was also established for the complexes of E. coli tRNA-Ile (BUDZIK, G.P., LAM, S.M., SCHOEMAKER, H.J.P., and SCHIMMEL, P.R. (1975) J. Biol. Chem. 250, 4433-4439). The common regions include a piece extending from the 5'-side of the acceptor stem to the beginning of the dihydrouridine helix, and a segment running from the 3' side of the extra loop into the TpsiC helix. These two regions overlap with and include some of the homologous bases found in eight tRNAs aminoacylated by yeast phenylalanyl-tRNA synthetase (ROE, B., SIROVER, M., and DUDOCK, B. (1973) Biochemistry 12, 4146-4153). Although well separated in the primary and secondary structure, these two segments are in close proximity in the crystallographic tertiary structure. In two of the complexes, the third cross-linked fragment is near to the two common ones. The picture which emerges is that the enzymes all interact with the general area in which the two helical branches of the L-shaped tertiary structure fuse together, with additional interactions on other parts of the tRNAas well.


Type I Error Rates For A One Factor Within-Subjects Design With Missing Values.
Missing data are a common problem in educational research. A promising technique, that can be implemented in SAS PROC MIXED and is therefore widely available, is to use maximum likelihood to estimate model parameters and base hypothesis tests on these estimates. However, it is not clear which test statistic in PROC MIXED performs better with missing data. The performance of the Hotelling-Lawley-McKeon and Kenward-Roger omnibus test statistics on the means for a single factor within-subject ANOVA are compared. The results indicate that the Kenward-Roger statistic performed better in terms of keeping the Type I error close to the nominal alpha level.


The Versatility of the Fasciocutaneous Infragluteal (FCI) Flaps for locoregional or free flap reconstruction.
The wide range of reconstructive purposes requires specific demands and considerations for appropriate flap selection. One versatile and reliable option, which is rarely reported in current literature, is the fasciocutaneous infragluteal (FCI) flap. In this study, we present our results of performing the FCI flap for different clinical indications. This retrospectively study was conducted between September 2011 and September 2019. We included 30 patients (21 females and 9 males) who underwent reconstruction with either pedicled or free FCI flap. Indications for performing FCI flap were uni- or bilateral autologous breast reconstruction, perineal reconstruction, congenital thoracic deformity, lower extremity coverage, and vulva reconstruction. Forty-one FCI flaps were performed (34 free and 7 pedicled flaps). The average flap dimension was 7 × 20 cm (range, 7-8 × 19-21) and the mean length of the pedicle was 13.4 cm (range, 10.5-15.5). The mean diameter of the artery was 2.5 mm (range, 2.2-3.2), the mean diameter of the accompanying vein was 3 mm (range, 2.4-3.3). The flap survival rate was 97.6% (one flap loss). The most common minor complications were infragluteal wound healing disorders and hematoma. The FCI flap provides constant and reliable anatomy with a long vascular pedicle as well as enough soft tissue bulk and a well-hidden scar. In our clinical practice, this flap has emerged as a first choice in perineal/vulvar reconstruction and a reliable alternative in breast reconstruction if the gold standard procedure cannot be performed. IV (Therapeutic).


Role of Prognostic Nutritional Index in patients with gastric cancer: a meta-analysis.
The aim of this study was to determine the role of Prognostic Nutritional Index in predicting gastric cancer. Studies were searched in PubMed, EMBASE and ISI Web of Science. The hazard ratios and 95% confidence interval for survival estimate were extracted from the articles and the pooled HR was computed. Nine studies with 3203 participants met the inclusion criteria. Low PNI was associated with poor overall survival (pooled HR 1.92, 95% CI: 1.68-2.19). Prognostic Nutritional Index was an effective indicator for the prognosis of gastric cancer.


Discordance between antibody and T cell responses in recipients of trivalent inactivated influenza vaccine.
Thirty adults were tested for humoral and cellular immune responses following immunization with the trivalent inactivated influenza vaccine. Modest but significant inverse correlations between the baseline and the fold changes in the number of IFNgamma-producing cells and the levels of neutralizing antibodies were observed. Specific increases in proliferative responses in the CD8 CD45RA+ population were noted after vaccination. Minimal correlations between neutralizing antibody titers and the number of IFNgamma-producing cells in terms of prevaccination levels or fold increases were observed. These results show specific increases in a CD8 T cell subset and discordant T and B responses induced by the trivalent inactivated influenza vaccine.


Se-Enriched Cordyceps militaris Inhibits Cell Proliferation, Induces Cell Apoptosis, And Causes G2/M Phase Arrest In Human Non-Small Cell Lung Cancer Cells.
The anticancer effects of cordyceps on various tumors have been reported. However, little is known about the role of selenium (Se)-enriched Cordyceps militaris in non-small cell lung cancer (NSCLC). In this study, the effects of Se-enriched Cordyceps militaris on cell proliferation, cell apoptosis and cell cycle in NSCLC cell line NCI-H292 and A549 were investigated. CCK-8 assay was used to determine the appropriate concentrations of Se-enriched Cordyceps militaris in NSCLC (namely NCI-H292 and A549) cells. Colony formation assay, flow cytometric and Hoechst 33342 staining assays, and flow cytometric analysis were separately employed to assess the effect of increased Se-enriched Cordyceps militaris on NSCLC cell viability, cell apoptosis and cell-cycle distribution. Finally, the qPCR and Western blot assays were, respectively, applied to evaluate the effects of Se-enriched Cordyceps militaris on the expression of pro-apoptotic member BAX and the anti-apoptotic member BCL-2, as well as of G2/M cell cycle regulatory proteins CDK1 and cyclin B1. The concentration of Se-enriched Cordyceps militaris was 0, 4, 8, 12 mg/mL for NCI-H292 cells, and 0, 12.5, 25, 50 mg/mL for A549 cells. NSCLC cells treated with increased Se-enriched Cordyceps militaris showed the inhibited cell viability. Se-enriched Cordyceps militaris induced NSCLC cell apoptosis in concentration-dependent manner. Consistently, Se-enriched Cordyceps militaris diminished the ratio of anti-apoptotic member BCL-2 and pro-apoptotic member BAX at mRNA and protein levels in NSCLC cells. The percentage in G2/M phase was increased in NSCLC cells treated with increased Se-enriched Cordyceps militaris. Downregulation of G2/M cell cycle regulatory proteins CDK1 and cyclin B1 at mRNA and protein levels in NSCLC cells further confirmed the effects of Se-enriched Cordyceps militaris on cell cycle. This study demonstrated the inhibitory role of Se-enriched Cordyceps militaris in cell proliferation and its facilitating role in cell apoptosis and cell cycle in NSCLC cells, suggesting an alternative therapeutic strategy for NSCLC treatment.


Electronic cigarette use and smoking cessation in cohort studies and randomized trials: A systematic review and meta-analysis.
The aim of this systematic review and meta-analysis was to assess the association between e-cigarette use and subsequent smoking cessation in cohort studies and randomized controlled trials (RCT). A systematic literature search was finalized 11 November 2019 using EMBASE, Cochrane Library, Scopus, PubMed Health, NICE evidence search, PROSPERO, CRD, PsycInfo, and PubMed including Medline. Inclusion criteria were: reporting empirical results; longitudinal observational design with a minimum of 3 months of follow-up; including general population samples; and allowing for comparison between users and non-users of e-cigarettes. Studies rated as having high risk of bias were excluded. The procedures described by PRISMA were followed, and the quality of evidence was rated using GRADE. Twenty-eight longitudinal, peer-reviewed publications from 26 cohort studies, and eight publications from seven RCTs assessing the association between e-cigarette use and smoking cessation were included in this review. A random-effects meta-analysis based on 39147 participants in cohort studies showed a pooled unadjusted odds ratio (OR) for smoking cessation among baseline e-cigarette users compared with baseline non-users of 0.97 (95% CI: 0.67-1.40), while the adjusted OR was 0.90 (95% CI: 0.63-1.27). The pooled odds ratio for smoking cessation in RCTs was 1.78 (95% CI: 1.41-2.25). The evidence for cohort studies was graded as very low and for RCTs as low. We did not find quality evidence for an association between e-cigarette use and smoking cessation. Although RCTs tended to support a more positive association between e-cigarette use and smoking cessation than the cohort studies, the grading of evidence was consistently low.


On the population dynamics and ecology of the shrimp species (Crustacea, Decapoda, Natantia) in the Central Amazonian river Tarumã-Mirim.
Collections over four years in the habitat of submerged litter show that shrimps are abundant the year round. Mean densities vary from 5-45 animals/m2 of litter habitat. Finegrained density distribution within litter sites is highly clumped, but coarse-grained distribution in any given month between litter sites along the river is grosso-modo random.Density and species distribution are a function of the annual cycles of inundations. Of the five species (of a total of seven in the area) that were found to be breeding in the litter habitat it could be established that reproduction is restricted to the period of rising and highest water levels. Reproduction is low in all species, namely below 20 eggs per egg batch with essentially a single generation per year.Breeding ecology in relation to the litter habitat is briefly discussed.


Author Correction: CCT α is a novel biomarker for diagnosis of laryngeal squamous cell cancer.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Effect of vitamin D receptor and estrogen receptor gene polymorphism on the relationship between dietary calcium and bone mineral density in Japanese women.
In a longitudinal analysis of the results of bone mineral density (BMD) screenings conducted in local communities, we examined the effect of lifestyle improvements on BMD and investigated the influence of allelic variations of the vitamin D receptor ( VDR) and estrogen receptor ( ER) genes. The subjects were 484 women (age, 24-80 years) who underwent BMD screenings at least twice between 1994 and 2002. We conducted BMD measurements of the lumbar spine by dual-energy X-ray absorptiometry and performed a simple questionnaire survey of lifestyle factors. Women receiving pharmacotherapy, or those with bone fractures, were excluded, leaving 338 women eligible for the study. They were retrospectively divided into three groups: (i) premenopause, women who were at least 5 years preceding menopause; (ii) perimenopause, women who were within 5 years before or after menopause; and (iii) postmenopause, women who were at least 5 years past menopause. There was no correlation at all between improvements of lifestyle factors (i.e., calcium intake from dairy products and time spent walking) and fluctuations in lumbar-spine BMD after 1, 3, or 5 years in the pre-, peri-, and postmenopausal groups. For women in the postmenopausal group, the PP genotype for the ER gene correlated with a significantly higher initial BMD than those with the Pp and pp genotypes ( P = 0.04). After 3 years, presence of the TT genotype of Taq I of VDR gene polymorphism exhibited positive correlations ( r = 0.29, P = 0.03) with the improvements in calcium intake and in lumbar spine BMD for the perimenopausal group, whereas the Tt genotype showed negative correlations ( r = -0.48, P = 0.04). After 1, 3, and 5 years, presence of the Tt genotype showed a tendency toward a negative correlation with the increases in calcium intake and in lumbar spine BMD for the pre- and perimenopausal groups, although almost of these were not significantly different. In this study, we could not prove a positive correlation between the improvement of lifestyle and the fluctuation of BMD within a 5-year timeframe, although the polymorphisms within the VDR gene may have some influence.


Special Section Guest Editorial: Advanced Laser Technologies for Biophotonics
This guest editorial introduces the special section on Advanced Laser Technologies for Biophotonics.


Hookah Smoking: A Potentially Risk Factor for First-Ever Ischemic Stroke.
Hookah consumption, as a common non-cigarette tobacco product, is wrongly considered as less harmful. Moreover, little is known about hookah consumption and risk of ischemic stroke. The current study aimed to assess the association between hookah consumption and first-ever ischemic stroke (FEIS). This case-control study was performed on individuals admitted at a tertiary referral center in Shiraz, Southern Iran between October 1, 2018 and September 20, 2019. We compared FEIS patients with randomly selected stroke-free individuals as a control group. Using a multiple logistic regression analysis, we assessed the association between hookah consumption and FEIS. A total of 208 FEIS patients (mean age 65.2 ± 15.9 years) and 212 age and sex-matched controls (mean age 63.2 ± 14.4) were recruited. The prevalence of vascular risk factors and comorbidities including ischemic heart disease, hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, cigarette smoking, and sleep apnea was higher in patients with FEIS than their control counterparts. After adjusting for a wide range of confounders, including socioeconomic factors, hookah consumption was still an independent risk factor for FEIS (odds ratio: 3.2, 95% CI: 1.7-6.1). Hookah consumption is associated strongly with FEIS. Public awareness about risk of hookah consumption should be raised.


Adverse cutaneous reactions to skin care products on the face vary with age, but not with sex.
Adverse skin reactions to skin care products have been increasing in recent years. However, to date, these reactions have not been well characterized. To describe the symptoms, clinical signs and frequency of adverse cutaneous reactions to skin care products on the face in males vs females of various ages. All outpatients diagnosed with adverse cutaneous reactions to skin care products on the face examined by dermatologists at the Dermatology Hospital of South Medical University between November 1, 2016 and October 31, 2017, employing a questionnaire and an interview, were eligible. The associations of adverse cutaneous reactions with age and sex were analysed. A total of 433 outpatients, accounting for 0.12% of all outpatients, were assessed. Of these, 223 patients, including 204 females and 19 males, aged 4 to 75 years, were eventually diagnosed with adverse reactions to skin care products on the face. Eighty-two per cent of patients experienced pruritus, 80% showed erythema, and 48% showed visible swelling. The incidence rates of both xerosis and oedema correlated positively with age, whereas acne-like lesions were negatively associated with age, but not with sex. Our results indicate that pruritus, xerosis and erythema are common adverse cutaneous reactions to facial skin care products. These reactions vary with age, but not with sex. Vigorous safety testing should precede the marketing of skin care products.


[Effect of gangliosides on Na-K-ATPase activity and the conformation of microsomal membranes].
The effect of gangliosides on the activity of Na, K-ATPase and K-dependent nitrophenyl-phosphatase was studied. Low concentrations of gangliosides proved to activate Na, K-ATPase, and high ones to inhibit it. All the concentrations of gangliosides produced only an inhibitory effect on the K-dependent nitrophenyl-phosphatase. Inhibition of the enzyme by gangliosides is reversible and competitive in respect to K+. Calculation of Hill's coefficient demonstrated that both in case of the activating and of the inhibitory action gangliosides acted allosteric effectors. To ascertain the action mechanism of gangliosides on the enzyme their effect on the microsomal membranes was studied by the fluorescent probe method. Gangliosides were found to produce marked conformation shifts in the membranes of the brain microsomes.


Effects of d-amphetamine and cocaine on repeated acquisition with timeout from avoidance.
The acute effects of d-amphetamine and cocaine on a repeated acquisition baseline with timeout from avoidance were investigated in two rats. Each session the animals acquired one of two different three-member response sequences. Each sequence member was associated with a different response lever. The first two correct responses of each sequence postponed shock for a fixed period of time. The third correct response initiated a signalled timeout (30 sec) from avoidance. Incorrect responses did not postpone shock. The baseline performance was characterized by a decrease in errors within each session, similar to patterns of repeated acquisition maintained by food. In comparison to control sessions, both d-amphetamine and cocaine increased errors and altered the pattern of within-session acquisition. d-Amphetamine increased the rate of sequence completion and the rate of shock delivery in both animals. Cocaine increased the rate of sequence completion in one animal and increased the rate of shock delivery for the other.


Anatomical mapping of the membranous septum in tricuspid and bicuspid aortic valves by cardiac computed tomography.
A higher incidence of conduction disturbances and permanent pacemaker implantation (PPI) has been observed after transcatheter aortic valve implantation (TAVI) in patients with bicuspid aortic valves (BAVs) as compared to those with tricuspid aortic valves (TAVs). This study aimed to provide an anatomical explanation for this observation, supported by an in-depth anatomical mapping of the membranous septum (MS) in a large cohort of BAVs and TAVs using cardiac computed tomography (CT). A total of 300 cardiac CT scans were analysed, revealing a significantly shorter sub-annular length of the MS in BAVs at all measuring points compared to TAVs (p < 0.001). In the current BAV cohort, the MS was found to be at its shortest at the RCC site, measuring less than 1 mm in depth. In addition, the MS was located more anteriorly towards the RCC in BAVs, where the transcatheter aortic valve tends to be implanted deeper, and we observed a trend towards a higher PPI rate in BAVs. Future studies should investigate whether anatomical mapping of the MS in patients undergoing TAVI could be a useful tool for decision-making and potentially mitigate the risk of conduction disturbances.


Social Predictors of Active Life Engagement: A Time-Use Study of Young-Old French Adults.
Active life engagement is important for successful aging of societies and individuals. We tested predictors of engagement in French adults aged 60-74 (the GAZEL cohort). Participants (n = 10,764) reported the previous day's activities in a time-use survey. We modeled concurrent social, demographic, and health predictors of participation incidence and intensity in paid work, volunteering, caregiving, community involvement, and informal social interaction. Men were more active in volunteering/community activities and women in caregiving and informal social interaction. Participation varied inversely with socioeconomic status (SES). Paid work participation declined linearly with age and health status, but this relationship did not hold for other activities. Men and those of higher SES were more likely to participate in certain activities than were women and those of low lifetime SES, potentially limiting the latter groups' future health and well-being benefits from such activities. Findings suggest groups that could benefit from interventions to increase engagement.


Molecular epidemiology of Crimean-Congo hemorrhagic fever in Bulgaria--An update.
Crimean-Congo hemorrhagic fever (CCHF) is endemic in Bulgaria. During 2013-2014, 11 confirmed CCHF cases have been reported in the country (seven in 2013 and four in 2014). The present study provides the CCHF molecular epidemiology in Bulgaria based on all currently available S, M, and L RNA segment nucleotide sequences spanning the years 1978-2014. A relatively low genetic difference (0-6%, the maximum seen in the M RNA segment) was seen among the CCHFV sequences suggesting that a slow evolving CCHFV strain belonging to "Europe 1" clade is present in Bulgaria. Although the virus emerged in new foci during the recent years, it is more active in the established endemic foci which seem to offer the most suitable ecosystem and environment. Understanding the CCHF epidemiology and virus evolution is the basis for public health programs and vaccine design.


Molecular mechanisms of alpha-synuclein neurodegeneration.
alpha-Synuclein is an abundant highly charged protein that is normally predominantly localized around synaptic vesicles in presynaptic terminals. Although the function of this protein is still ill-defined, genetic studies have demonstrated that point mutations or genetic alteration (duplications or triplications) that increase the number of copies of the alpha-synuclein (SCNA) gene can cause Parkinson's disease or the related disorder dementia with Lewy bodies. alpha-Synuclein can aberrantly polymerize into fibrils with typical amyloid properties, and these fibrils are the major component of many types of pathological inclusions, including Lewy bodies, which are associated with neurodegenerative diseases, such as Parkinson's disease. Although there is substantial evidence supporting the toxic nature of alpha-synuclein inclusions, other modes of toxicity such as oligomers have been proposed. In this review, some of the evidence for the different mechanisms of alpha-synuclein toxicity is presented and discussed.


45,X karyotype: may the diagnosis be suspected on ultrasonic examination in the second trimester of pregnancy?
We report three cases of Turner's syndrome with cystic hygromata, which were diagnosed by routine ultrasound scanning before amniocentesis in the second trimester of pregnancy. Maternal and amniotic level of alpha-fetoprotein were normal. Karyotyping carried out afterwards showed a 45,X karyotype. Our data indicate, that cystic hygromata in Turner's syndrome may coexist with a normal amniotic fluid AFP, thus questioning the theory of leakage from the hygroma. It remains to be investigated if all cases of Turner's syndrome present a cystic hygroma in utero.


Multiconfigurational Effects in Theoretical Resonance Raman Spectra.
We analyze resonance Raman spectra of the nucleobase uracil in the short-time approximation calculated with multiconfigurational methods. We discuss the importance of static electron correlation by means of density-matrix renormalization group self-consistent field (DMRG-SCF) calculations. Our DMRG-SCF results reveal that a minimal active orbital space that leads to a qualitatively correct description of the resonance Raman spectrum of uracil should encompass parts of the σ/σ* bonding/anti-bonding orbitals of the pyrimidine ring. We trace these findings back to the considerable entanglement between the σ/σ* bonding/anti-bonding as well as valence π/π* orbitals in the excited-state electronic structure of uracil, which indicates non-negligible non-dynamical correlation effects that are less pronounced in the electronic ground state.


Sudden death due to congenital malformation of coronary arteries.
A case of sudden death of a 12-year-old girl after jogging, due to congenital malformation of coronary arteries, is presented.


Getting the skinny on thick filament regulation in cardiac muscle biology and disease.
Thin (actin) filament accessory proteins are thought to be the regulatory force for muscle contraction in cardiac muscle; however, compelling new evidence suggests that thick (myosin) filament regulatory proteins are emerging as having independent and important roles in regulating cardiac muscle contraction. Key to these new findings is a growing body of evidence that point to an influential and, more recently, direct role for ventricular myosin light chain-2 (MLC2v) phosphorylation in regulating cardiac muscle contraction, function, and disease. This includes the discovery and characterization of a cardiac-specific myosin light chain kinase capable of phosphorylating MLC2v as well as a myosin phosphatase that dephosphorylates MLC2v in the heart, which provides added mechanistic insights on MLC2v regulation within cardiac muscle. Here, we review evidence for an emerging and critical role for MLC2v phosphorylation in regulating cardiac myosin cycling kinetics, function, and disease, based on recent studies performed in genetic mouse models and humans. We further provide new perspectives on future avenues for targeting these pathways as therapies in alleviating cardiac disease.


Cyclooxygenase isoenzyme-2 and vascular endothelial growth factor are associated with poor prognosis in esophageal adenocarcinoma.
Cyclooxygenase isoenzyme-2 (COX-2) and vascular endothelial growth factor (VEGF) contribute to angiogenesis and are overexpressed in various malignancies. The aim of the study was to evaluate expression, prognostic value and correlation between COX-2 and VEGF expression in esophageal adenocarcinoma (EAC). Surgical specimens of 154 patients with EAC were used to construct a tissue micro array (TMA). TMA sections were immunohistochemically stained for COX-2 and VEGF and scored on intensity of staining. Estimated 5-year cancer specific survival was 37%. High COX-2 and VEGF expression was observed in 39 (26.5%) and in 77 (53.8%) tumors, respectively. Both markers were associated with poor cancer specific survival (p = .022 and p = .004, respectively, log rank). No significant correlation was found between VEGF and COX-2 expression (r = 063; p = .455). In multivariate analysis, high COX-2 expression (HR 1.65; 95% CI 1.04-2.61; p = .034) was associated with overall survival. In patients with T3 tumors, COX-2 expression was an independent prognostic factor for cancer specific survival (HR 1.81 95% CI 1.10-2.95; p = .019). This is the first study that evaluated the prognostic value and correlation of COX-2 and VEGF expression in a large and homogenous population of patients with EAC. No correlation between COX-2 and VEGF expression was found. Both markers were expressed in EAC and were associated with poor prognosis. The findings support the use of COX-2 and VEGF inhibitors in future clinical studies.


Lentiviral-mediated BCL2 gene knockdown using comparative microRNA adaptive shRNAs.
B-cell lymphoma 2 (BCL2) family proteins play a critical role in tuning cell death processes. Almost in half of all human cancers, a dysregulation in BCL2 family gene expression has been shown which made it an impressive target for human gene therapy as a novel approach in cancers. In this study we will optimize lentiviral-mediated RNA interference (RNAi), recombinant lentiviruses accommodating anti-BCL2 micro adaptive short hairpin RNAs (shRNAs), to downregulate BCL2 in human embryonic kidney 293T (HEK293T) cells to produce stable cell lines. We tested 4 different Dharmacon™ GIPZ™ shRNAmir lentiviral vectors targeting BCL2 in different positions and a pGIPZ non-silencing shRNAmir lentiviral vector (as a negative control). Lentivirus packaging was performed by the calcium phosphate precipitation method. HEK293T cells were transduced by each type of recombinant lentiviruses individually and selected by puromycin within 10 days. The relative mRNA level and protein expression were assayed by using real-time polymerase chain reaction (PCR) technic and western blotting, respectively. Lentivirus (LV) packaging was performed in high efficiency (transfection rate was > 90%). Recombinant viruses of 4 expression vector addition to a control vector were produced then transduced to HEK293T cells successfully. All the 4 cell groups showed a significant down regulation of BCL2 gene (~90-95%) at mRNA level compared to the control group (p<0.01) but differences between silenced groups were not significant (P > 0.05). We showed that the lentivirus-mediated RNAi technique is an efficient method to establish HEK293 cell lines with stable down-regulation of BCL2 gene.


A comparison of viscoelastic properties of three root canal sealers.
Handling of endodontic sealers is greatly dependent on their elasticity and flow ability. We compared the viscoelastic properties of three root canal sealers. AH Plus (Dentsply, De Trey, Konstanz, Germany), Endofill (Dentsply Hero, Petrópolis, Rio de Janeiro, Brazil) and AH26 (Dentsply, De Trey, Konstanz, Germany) were mixed according to the manufacturers' instructions. The resulted pastes were placed on the plate of a rheometer (MCR 300, Anton-Paar, Graz, Austria). The experiments were performed at 25°C and 37°C. Viscoelastic properties of the sealers including loss modulus (G″), storage modulus (G') and complex viscosity (η*) were studied using dynamic oscillatory shear tests. The shear module versus frequency (from 0.01 to 100 S(-1)) curves were gained using frequency deformation sweep test. Three samples of each material were examined at each temperature. The mean of these three measurements were recorded. The storage modulus of AH plus was higher than its loss modulus at two temperatures. Endofill exhibited a crossover region in which the storage modulus crosses the loss modulus in both temperatures. At 25°C the loss modulus of AH26 was higher than the storage modulus (G″>G'). In contrast, at 37°C G' was greater than G″ (G'>G″). Both shear modules of AH Plus and Endofill decreased as the temperature raised from 25°C to 37°C. On the contrary, the loss modulus and storage modulus of AH26 increased at 37°C. In both test temperatures, AH Plus behaved like viscoelastic solids and Endofill exhibited a gel-like viscoelastic behavior. AH26 at 25°C behaved like liquids, while at 37°C it was an elastic solid-like material.


Focal osteoporosis defect is associated with vertebral compression fracture prevalence in a bone mineral density-independent manner.
Focal osteoporosis defect has shown a high association with the bone fragility and osteoporotic fracture prevalence. However, no routine computed tomography (CT)-based vertebral focal osteoporosis defect measurement and its association with vertebral compression fracture (VCF) were discussed yet. This study aimed to develop a routine CT-based measurement method for focal osteoporosis defect quantification, and to assess its association with the VCF prevalence. A total of 205 cases who underwent routine CT scanning, were retrospectively reviewed and enrolled into either the VCF or the control group. The focal bone mineral content loss (focal BMC loss), measured as the cumulated demineralization within bone void space, was proposed for focal osteoporosis defect quantification. Its scan-rescan reproducibility and its correlation with trabecular bone mineral density (BMD) and apparent microarchitecture parameters were evaluated. The association between focal BMC loss and the prevalence of VCF was studied by logistic regression. The measurement of focal BMC loss showed high reproducibility (RMSSD = 0.011 mm, LSC = 0.030 mm, ICC = 0.97), and good correlation with focal bone volume fraction (r = 0.79, P < 0.001), trabecular bone separation (r = 0.76, P < 0.001), but poor correlation with trabecular BMD (r = 0.37, P < 0.001). The focal BMC loss was significantly higher in the fracture group than the control (1.03 ± 0.13 vs. 0.93 ± 0.11 mm; P < 0.001), and was associated with prevalent VCF (1.87, 95% CI = 1.31-2.65, P < 0.001) independent of trabecular BMD level. As a surrogate measure of focal osteoporosis defect, focal BMC Loss independently associated with the VCF prevalence. It suggests that focal osteoporosis defect is a common manifestation that positively contributed to compression fracture risk and can be quantified with routine CT using focal BMC Loss.