Machine Learning Algorithms to Predict Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis.
Delayed cerebral ischemia (DCI) is a common and severe complication after subarachnoid hemorrhage (SAH). Logistic regression (LR) is the primary method to predict DCI, but it has low accuracy. This study assessed whether other machine learning (ML) models can predict DCI after SAH more accurately than conventional LR. PubMed, Embase, and Web of Science were systematically searched for studies directly comparing LR and other ML algorithms to forecast DCI in patients with SAH. Our main outcome was the accuracy measurement, represented by sensitivity, specificity, and area under the receiver operating characteristic. In the six studies included, comprising 1828 patients, about 28% (519) developed DCI. For LR models, the pooled sensitivity was 0.71 (95% confidence interval [CI] 0.57-0.84; p < 0.01) and the pooled specificity was 0.63 (95% CI 0.42-0.85; p < 0.01). For ML models, the pooled sensitivity was 0.74 (95% CI 0.61-0.86; p < 0.01) and the pooled specificity was 0.78 (95% CI 0.71-0.86; p = 0.02). Our results suggest that ML algorithms performed better than conventional LR at predicting DCI.Trial Registration: PROSPERO (International Prospective Register of Systematic Reviews) CRD42023441586; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=441586.


Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways.
Metastasis is a major cause of death in human colorectal cancer patients. However, the contribution of chemokines in the tumor microenvironment to tumor metastasis is not fully understood. Herein, we examinined several chemokines in colorectal cancer patients using chemokine ELISA array. Immunohistochemistry was used to detect expression of CXCL5 in colorectal cancer patients tissues. Human HCT116 and SW480 cell lines stably transfected with CXCL5, shCXCL5 and shCXCR2 lentivirus plasmids were used in our in vitro study. Immunoblot, immunofluorescence and transwell assay were used to examine the molecular biology and morphological changes in these cells. In addition, we used nude mice to detect the influence of CXCL5 on tumor metastasis in vivo. We found that CXCL5 was overexpressed in tumor tissues and associated with advanced tumor stage as well as poor prognosis in colorectal cancer patients. We also demonstrated that CXCL5 was primarily expressed in the tumor cell cytoplasm and cell membranes, which may indicate that the CXCL5 was predominantly produced by cancer epithelial cells instead of fibroblasts in the tumor mesenchyme. Additionally, overexpression of CXCL5 enhanced the migration and invasion of colorectal cancer cells by inducing the epithelial-mesenchymal transition (EMT) through activation of the ERK/Elk-1/Snail pathway and the AKT/GSK3β/β-catenin pathway in a CXCR2-dependent manner. The silencing of Snail and β-catenin attenuated CXCL5/CXCR2-enhanced cell migration and invasion in vitro. The elevated expression of CXCL5 can also potentiate the metastasis of colorectal cancer cells to the liver in vivo in nude mice intrasplenic injection model. In conclusion, our findings support CXCL5 as a promoter of colorectal cancer metastasis and a predictor of poor clinical outcomes in colorectal cancer patients.


[Corneal sensitivity after photocoagulation for diabetic retinopathy].
Corneal sensitivity was determined with the Draeger aesthesiometer in 39 patients with proliferative diabetic retinopathy who underwent treatment with a xenon photocoagulator or argon laser. In 29 patients measurements were performed before and after photocoagulation; in 10 patients the unaffected eye was used for comparison. Statistical evaluation showed a significant difference between the mean values for corneal touch threshold before and after argon laser coagulation. After xenon photocoagulation, corneal sensitivity was reduced in all patients (n = 7). It was shown that corneal sensitivity was significant lower after xenon photo coagulation than with argon laser coagulation.


P2Y2 Receptor Promotes High-Fat Diet-Induced Obesity.
P2Y2, a G protein-coupled receptor (R), is expressed in all organs involved in the development of obesity and insulin resistance. To explore the role of it in diet-induced obesity, we fed male P2Y2-R whole body knockout (KO) and wild type (WT) mice (B6D2 genetic background) with regular diet (CNT; 10% calories as fat) or high-fat diet (HFD; 60% calories as fat) with free access to food and water for 16 weeks, and euthanized them. Adjusted for body weights (BW), KO mice consumed modestly, but significantly more HFD vs. WT mice, and excreted well-formed feces with no taint of fat or oil. Starting from the 2nd week, HFD-WT mice displayed significantly higher BW with terminal mean difference of 22% vs. HFD-KO mice. Terminal weights of white adipose tissue (WAT) were significantly lower in the HFD-KO vs. HFD-WT mice. The expression of P2Y2-R mRNA in WAT was increased by 2-fold in HFD-fed WT mice. Serum insulin, leptin and adiponectin levels were significantly elevated in the HFD-WT mice, but not in the HFD-KO mice. When induced in vitro, preadipocytes derived from KO mice fed regular diet did not differentiate and mature as robustly as those from the WT mice, as assessed by cellular expansion and accumulation of lipid droplets. Blockade of P2Y2-R by AR-C118925 in preadipocytes derived from WT mice prevented differentiation and maturation. Under basal conditions, KO mice had significantly higher serum triglycerides and showed slightly impaired lipid tolerance as compared to the WT mice. HFD-fed KO mice had significantly better glucose tolerance (GTT) as compared to HFD-fed WT mice. Whole body insulin sensitivity and mRNA expression of insulin receptor, IRS-1 and GLUT4 in WAT was significantly higher in HFD-fed KO mice vs. HFD-fed WT mice. On the contrary, the expression of pro-inflammatory molecules MCP-1, CCR2, CD68, and F4/80 were significantly higher in the WAT of HFD-fed WT vs. HFD-fed KO mice. These data suggest that P2Y2-R plays a significant role in the development of diet-induced obesity by promoting adipogenesis and inflammation, and altering the production of adipokines and lipids and their metabolism in adipose tissue, and thereby facilitates HFD-induced insulin resistance.


Potential chemoprevention activity of pterostilbene by enhancing the detoxifying enzymes in the HT-29 cell line.
Detoxifying enzymes are present in most epithelial cells of the human gastrointestinal tract where they protect against xenobiotics which may cause cancer. Induction of examples such as glutathione S-transferase (GST) and its thiol conjugate, glutathione (GSH) as well as NAD(P)H: quinoneoxidoreductase (NQO1) facilitate the excretion of carcinogens and thus preventing colon carcinogenesis. Pterostilbene, an analogue of resveratrol, has demonstrated numerous pharmacological activities linked with chemoprevention. This study was conducted to investigate the potential of pterostilbene as a chemopreventive agent using the HT-29 colon cancer cell line to study the modulation of GST and NQO1 activities as well as the GSH level. Initially, our group, established the optimum dose of 24 hours pterostilbene treatment using MTT assays. Then, effects of pterostilbene (0-50 μM) on GST and NQO1 activity and GSH levels were determined using GST, NQO1 and Ellman assays, respectively. MTT assay of pterostilbene (0-100 μM) showed no cytotoxicity toward the HT-29 cell line. Treatment increased GST activity in the cell line significantly (p<0.05) at 12.5 and 25.0 μM. In addition, treatment at 50 μM increased the GSH level significantly (p<0.05). Pterostilbene also enhanced NQO1 activity significantly (p<0.05) at 12.5 μM and 50 μM. Hence, pterostilbene is a potential chemopreventive agent capable of modulation of detoxifiying enzyme levels in HT-29 cells.


Coupled elasticity-diffusion model for the effects of cytoskeleton deformation on cellular uptake of cylindrical nanoparticles.
Molecular dynamic simulations and experiments have recently demonstrated how cylindrical nanoparticles (CNPs) with large aspect ratios penetrate animal cells and inevitably deform cytoskeletons. Thus, a coupled elasticity-diffusion model was adopted to elucidate this interesting biological phenomenon by considering the effects of elastic deformations of cytoskeleton and membrane, ligand-receptor binding and receptor diffusion. The mechanism by which the binding energy drives the CNPs with different orientations to enter host cells was explored. This mechanism involved overcoming the resistance caused by cytoskeleton and membrane deformations and the change in configurational entropy of the ligand-receptor bonds and free receptors. Results showed that deformation of the cytoskeleton significantly influenced the engulfing process by effectively slowing down and even hindering the entry of the CNPs. Additionally, the engulfing depth was determined quantitatively. CNPs preferred or tended to vertically attack target cells until they were stuck in the cytoskeleton as implied by the speed of vertically oriented CNPs that showed much faster initial engulfing speeds than horizontally oriented CNPs. These results elucidated the most recent molecular dynamics simulations and experimental observations on the cellular uptake of carbon nanotubes and phagocytosis of filamentous Escherichia coli bacteria. The most efficient engulfment showed the stiffness-dependent optimal radius of the CNPs. Cytoskeleton stiffness exhibited more significant influence on the optimal sizes of the vertical uptake than the horizontal uptake.


[A case of breast cancer with multiple bone metastases that responded remarkably to doxifluridine (5'-DFUR), cyclophosphamide (CPA), medroxyprogesterone acetate (MPA) and pamidronate disodium therapy].
A 49-year-old female underwent bilateral breast preserving surgery for heterochronic breast cancers. She later developed a sternal metastasis and was recommended for intravenous chemotherapy. However, she refused such an intensive therapy and opted for immunotherapy. Afterward, she came to our hospital because of spinal metastases with back pain. She was treated with oral administration of 5'-DFUR and MPA 1,200 mg/day for 3 weeks, respectively, CPA 100 mg/day for 2 weeks, and pamidronate disodium 30 mg intravenously every 4 weeks. This combined chemotherapy relieved her pain after one course. After 5 courses, tumor markers were reduced to the normal range. After 14 courses, bone X-P revealed that the osteolytic bone showed sclerotic changes and bone scintigraphy showed a complete remission (CR). The adverse effects were not remarkable. This regimen is possible on an outpatient basis, and it may play an important role from the standpoint of treatment effectiveness and the quality of life of the patient.


Total Synthesis of the Proposed Structure of Maltepolide C.
The first total synthesis of the proposed structure of cytotoxic macrolide maltepolide C has been achieved via an E-selective intramolecular Heck cyclization as a key step. Other key features of the synthesis are Z-selective Wittig olefination, Sharpless asymmetric dihydroxylation followed by Williamson-type cyclo-etherification, Brown asymmetric allylation, and Noyori reduction of an alkynone. Detailed NMR study confirms the structure and stereochemistry of the synthetic maltepolide C unambiguously. However, the deviation of the spectra of the synthetic maltepolide C from those of the natural maltepolide C indicates a possible error in the original structural assignment.


[Dangerous, illegal captivities].
On the 21st of August 1997 the Polish legislature introduced the first animal protection law nr 724. This act however failed to specify in a clear and proper manner the problem of possession and maintenance of dangerous animals, which allows its multiple interpretations. Poland ratified the Washington Convention in 1990 restricting the trade of animals classified as endangered species. The present regulations enable illegal purchase and trade of those animals. According to the available data illegal trade of such animals, as well as the trade of products obtained from them, ranks in the third position in terms of crime generated income, only after the trade of drugs and weapons. In our country the sales of such animals have been growing at an alarming rate. The animals often get out of the control of their owners, or are abandoned by them. The presented work describes cases of reptiles being found in public places in our region. It also mentions the problem of possible dangers associated with intentional letting out of such animals in public places. The aim of the following paper is the analysis of the problem of raising of exotic animals, in particular venomous snakes and other animals, the possession of which may be dangerous not only for the owner but also for the people around. The existing laws and executive procedures have been discussed. Both, the family doctors as well as toxicologists have little knowledge as far as diagnosis and treatment of cases of stinging and biting by exotic animals is concerned. The authors suggest providing medical emergency doctors, family doctors and surgeons, with clinic toxicology programs, as well as introduction of special courses for middle medical personnel. Establishment of a central database and a database concerned with basic polyvalent serums are crucial in our country in order have the Toxicology Centers ready to face possible dangers associated with dangerous animals, and to prepare emergency solutions in cases of criminal actions involving the use of dangerous animals.


The University of the National Football League: How Technology, Injury Surveillance, and Health Care Have Improved the Safety of America's Game.
American football has become one of the most popular sports in the United States. Despite the millions of players at all levels of competition who gain the physical, social, and psychological rewards that football provides, many interested stakeholders continue to ask, "Is football safe?" Although there are only approximately 1,700 players on National Football League (NFL) rosters, the injuries they sustain have garnered the most attention-and criticism-from the national media. Increased public awareness of the injury potential football possesses has led to an open debate and a major shift in public sentiment over the past 5 years. Although no sport is perfectly safe, the question is whether it can be made relatively safe and if the long-term consequences are worth the risk. This article reviews the methods by which one sports league-the NFL-has used advances in medical technology and injury surveillance to improve the health and safety of its players.


Regulatory elements in the promoter of the vitelline membrane gene VM32E of Drosophila melanogaster direct gene expression in distinct domains of the follicular epithelium.
The Drosophila vitelline membrane protein gene VM32E is expressed according to a precise temporal and spatial program in the follicle cells. Results from germ line transformation experiments using different fragments of the -465/-39 VM32E region fused to the hsp/lacZ reporter gene revealed that the region -348/-39 is sufficient to confer the wild-type expression pattern. Within this segment, distinct cis-regulatory elements control VM32E expression in ventral and dorsal follicle cells. The region between -135/-113 is essential for expression of the VM32E gene in the ventral columnar follicle cells. Expression in the dorsal domain requires the two regions -348/-254 and -118/-39. Furthermore, the region -253/-119 appears to contain a negative element that represses gene activity in anterior centripetal cells. We suggest that the expression of the VM32E gene throughout the follicular epithelium is controlled by specific cis-regulatory elements acting in distinct spatial domains and following a precise developmental program.


Socioeconomic disparities in indoor air, breath, and blood perchloroethylene level among adult and child residents of buildings with or without a dry cleaner.
In many cities, dry cleaners using perchloroethylene are frequently located in multifamily residential buildings and often cause elevated indoor air levels of perchloroethylene throughout the building. To assess individual perchloroethylene exposures associated with co-located dry cleaners, we measured perchloroethylene in residential indoor air, and in blood and breath of adults and children residing in buildings with a dry cleaner as part of the New York City (NYC) Perc Project. We also measured perchloroethylene in indoor air, and in blood and breath of residents of buildings without a dry cleaner for comparison. Here, we evaluate whether an environmental disparity in perchloroethylene exposures is present. Study participants are stratified by residential building type (dry cleaner or reference) and socioeconomic characteristics (race/ethnicity and income); measures of perchloroethylene exposure are examined; and, the influence of stratified variables and other factors on perchloroethylene exposure is assessed using multivariate regression. All measures of perchloroethylene exposure for residents of buildings with a dry cleaner indicated a socioeconomic disparity. Mean indoor air perchloroethylene levels were about five times higher in minority (82.5 ug/m(3)) than in non-minority (16.5 ug/m(3)) households, and about six times higher in low-income (105.5 ug/m(3)) than in high income (17.8 ug/m(3)) households. Mean blood perchloroethylene levels in minority children (0.27 ng/mL) and adults (0.46 ng/mL) were about two and three times higher than in non-minority children (0.12 ng/mL) and adults (0.15 ng/mL), respectively. Mean blood perchloroethylene levels in low income children (0.34 ng/mL) and adults (0.62 ng/mL) were about three and four times higher than in high income children (0.11 ng/mL) and adults (0.14 ng/mL), respectively. A less marked socioeconomic disparity was observed in perchloroethylene breath levels with minority and low income residents having slightly higher levels than non-minority and high income residents. Multivariate regression affirmed that indoor air perchloroethylene level in dry cleaner buildings was the single most important factor determining perchloroethylene in blood and breath. Neither age, gender, nor socioeconomic status significantly influenced perchloroethylene levels in breath or blood. We previously reported that increased indoor air, breath, and blood perchloroethylene levels among NYC Perc Project child participants were associated with an increased risk for slightly altered vision. Thus, the disproportionately elevated perchloroethylene exposures of minority and low-income child residents of buildings with a dry cleaner shown here constitutes an environmental exposure disparity with potential public health consequences. Among residents of buildings without a dry cleaner, we observed some small increases in perchloroethylene breath and blood levels among non-minority or high income residents compared to minority or low income residents. These differences were not attributable to differences in indoor air levels of perchloroethylene which did not differ across socioeconomic categories, but appear to be associated with more frequent exposures dry cleaned garments.


Stereospecificity of citrate synthetase in relation to glutamate biosynthesis by extracts of Chloropseudomonas ethylicum.
The synthesis of citric and glutamic acids by extracts of Chloropseudomonas ethylicum was studied with labeled precursors. When acetyl-coenzyme A-1-(14)C was used as substrate, only 0.1% of the total radioactivity was found in the C-5 position of citric acid; whereas, with oxalacetate-4-(14)C as substrate, 100% of the total radioactivity was found in C-5. These results demonstrated that the Chloropseudomonas citrate synthetase had an absolute stereospecificity, identical to that of the pig heart synthetase. The distribution of radioactivity in the glutamic acid synthesized from acetyl-coenzyme A-1-(14)C was 0% in C-1 and 94.0% in C-5; whereas the glutamic acid formed from oxalacetate-4-(14)C contained 89.6% in C-1 and 0.5% in C-5. This distribution is entirely consistent with the biosynthesis of glutamic acid from citric acid via aconitase, d(s)-isocitrate, and l-glutamate dehydrogenases. The presence of l-glutamate dehydrogenase in extracts was demonstrated. The stereospecificity of the citrate synthetase and the pattern of glutamate labeling further establish that the aconitase of Chloropseudomonas is completely stereospecific.


Extranodal NK/T Cell Lymphoma, Nasal Type with Palatal Involvement: A Rare Case Report and Literature Review.
T-cell lymphomas are infrequently encountered in the head and neck area, with the most common subtype being Extranodal NK/T cell lymphoma, nasal type (ENKTL-NT). ENKTL-NT shows a predilection for midline facial structures presenting with ulcerative destructive lesions, whereas palatal involvement is one of the most prominent signs from the oral cavity. Herein, we describe a case of a 76-year-old Greek man with nasal obstruction and an extensive painful necrotic ulcer with ragged borders on the left distal portion of the soft palate and palatine tonsil of 4-months duration. After an initial non-diagnostic biopsy from the nasopharynx, a second incisional biopsy from the palatal lesions was performed. Histopathology was suggestive of an angiocentric lymphoproliferative neoplasm and immunohistochemical examination and in situ hybridization for EBV RNA led to a final diagnosis of ENKTL-NT. The patient was placed under combined chemotherapy and radiotherapy and no recurrence has been noted. Additionally, a retrospective review of the cases in the English literature with an established diagnosis of ENTKL-NT between 2000 and 2019, based on the latest WHO classification of Head and Neck tumors, is performed.


Characterisation of phosphorylated nucleotides by collisional and electron-based tandem mass spectrometry.
Tandem mass spectrometry of phosphorylated ions can often yield a limited number of product ions owing to the labile nature of phosphate groups. Developing techniques to improve dissociation for this type of ion has implications for the structural characterisation of many different phosphorylated ions, such as those from nucleotides, pharmaceutical compounds, peptides and polymers. Solutions of adenosine monophosphate, diphosphate and triphosphate (AMP, ADP and ATP) were studied in a hybrid linear ion trap-Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Precursor ions with an overall single positive charge, including protonated nucleotides or nucleotide cations containing one, two or three sodium atoms, were isolated for tandem mass spectrometry. Collision-induced dissociation (CID) was performed in the linear ion trap, with electron-induced dissociation (EID) being conducted in the FTICR cell. EID resulted in many product ions not seen in CID. EID product ion spectra were seen to vary for AMP, ADP and ATP when the nucleotide cation contained zero, one, two or three sodiums. Precursor cations that contain two or three sodiums mainly formed product ions derived from the phosphate group. Conversely, when a precursor ion containing no sodium underwent EID, product ions mainly relating to the non-phosphate end of the ion were observed. The number of phosphate groups was not seen to greatly affect either CID or EID product ion spectra. The presence of sodium in a precursor ion directs electron-induced bond dissociation, thus enabling targeted, and therefore tuneable, fragmentation of groups within that precursor ion. For all precursor ions, the most useful product ion spectra were obtained by EID for a precursor ion containing one sodium, with bond dissociation occurring across the entire nucleotide cation. The findings of this study can be used to improve the structural elucidation of many phosphorylated molecules by broadening the range of product ions achievable. © 2016 The Authors. Rapid Communications in Mass Spectrometry Published by John Wiley & Sons Ltd.


Onset of Tuberculosis from a Pulmonary Latent Tuberculosis Infection during Antiviral Triple Therapy for Chronic Hepatitis C.
A 62-year-old man was diagnosed with the onset of tuberculosis (Tb) from a pulmonary latent tuberculosis infection (LTBI) during triple therapy with pegylated interferon α2a, ribavirin, and telaprevir for a chronic hepatitis C infection in 2013 before interferon (IFN)-free anti-viral therapy was introduced in Japan. A liver biopsy before IFN treatment revealed the presence of epithelioid cell granulomas (ECGs). IFN may also be employed for chronic hepatitis B infection and malignant tumors, thus, special attention must be paid to the development of Tb from a LTBI when ECGs are observed before treatment. It is also necessary to review the significance of the liver biopsy.


Accuracy of diagnostic methods and surveillance sensitivity for human enterovirus, South Korea, 1999-2011.
The epidemiology of enteroviral infection in South Korea during 1999-2011 chronicles nationwide outbreaks and changing detection and subtyping methods used over the 13-year period. Of 14,657 patients whose samples were tested, 4,762 (32.5%) samples were positive for human enterovirus (human EV); as diagnostic methods improved, the rate of positive results increased. A seasonal trend of outbreaks was documented. Genotypes enterovirus 71, echovirus 30, coxsackievirus B5, enterovirus 6, and coxsackievirus B2 were the most common genotypes identified. Accurate test results correlated clinical syndromes to enterovirus genotypes: aseptic meningitis to echovirus 30, enterovirus 6, and coxsackievirus B5; hand, foot and mouth disease to coxsackievirus A16; and hand, foot and mouth disease with neurologic complications to enterovirus 71. There are currently no treatments specific to human EV infections; surveillance of enterovirus infections such as this study provides may assist with evaluating the need to research and develop treatments for infections caused by virulent human EV genotypes.


Pseudotumor cerebri secondary to minocycline intake.
Pseudotumor cerebri, or idiopathic intracranial hypertension, is a condition most commonly affecting women of childbearing age who are obese or who have experienced recent weight gain. Frequently the patient complains of headache accompanied by dizziness, nausea, or visual defects, and it is characterized by elevated intracranial pressure in the absence of a space-occupying lesion or infection A patient had been prescribed minocycline and subsequently developed symptoms 6 weeks after an increase in the original dosage. She was initially examined by an ophthalmologist, then was sent to the Emergency Department, and finally admitted under the family practice service. Articles were searched through MEDLINE, MD Consult, and Google. Key words included "pseudotumor cerebri," benign intracranial hypertension," idiopathic intracranial hypertension," and "minocycline." Although the pathogenesis of pseudotumor cerebri is not completely understood, an association has been observed with minocycline use. This report describes a 16-year-old girl who developed idiopathic intracranial hypertension while taking minocycline for acne. Symptoms of blurred vision and severe headache unrelated to position or activity; an absence of fever, bilateral disk edema, and focalizing neurologic signs; negative neuroradiographic findings; increased cerebrospinal fluid pressure with a normal cell count; and exclusion of systemic or structural cause of increased intracranial pressure satisfy the criteria for the diagnosis of idiopathic intracranial hypertension. Minocycline is often used by family physicians for the treatment of acne, and this complication requires vigilance to protect against potential vision loss.


Towards an Understanding of the Adsorption of Vaporized Hydrogen Peroxide (VHP) Residues on Glass Vials After a VHP Decontamination Process Using a Miniaturized Tool.
Isolators for aseptic filling of biopharmaceuticals and vaccine products are commonly sanitized by vaporized hydrogen peroxide (VHP). However, remaining traces of H2O2 may contaminate the solution and cause oxidative degradation of the pharmaceutical products. The present report aims to establish a thorough understanding of the factors influencing H2O2 adsorption on empty glass intended for pharmaceutical product filling. A lab-scale miniaturized set-up that mimics the VHP- based isolator decontamination process was used. A fractional factorial design of experiment (DoE) was performed including relative humidity (RH), VHP concentration and exposure time as variables. The results revealed that VHP concentration and RH both impacts significantly the extent of H2O2 adsorption on the surface of glass vials and rubber stoppers. The lower extent of H2O2 adsorption at elevated RH implies the existence of competitive co-adsorption. Thus, adsorbed H2O2 may be removed more efficiently from the isolator after the decontamination phase by insufflating air with a high %RH rate during the isolator's aeration phase. The understanding gained from the present set-up can be applied to optimize the design of isolator decontamination cycles and evaluate the trade-off between process performance and the resulting product quality.


Clinical management of women at high risk of breast cancer.
This article reviews the evidence that underpins breast cancer screening and prevention strategies for women at high risk of the disease, with a particular focus on evidence published in the last 18 months. The review is timely because the US National Comprehensive Cancer Network, the UK National Institute for Health and Care Excellence and the American Society of Clinical Oncology have recently updated relevant guidelines that inform practice. In the recently published literature, there have been several important findings. A meta-analysis of randomized trials of selective oestrogen receptor modulators (SERMs), along with the first results from the International Breast Cancer Intervention Study II trial, further support the use of SERMs and aromatase inhibitors in the primary prevention of breast cancer. A large observational study has provided evidence that the SERM tamoxifen may be efficacious for breast cancer prevention in women who carry mutations in the breast cancer predisposition genes, BRCA1 and BRCA2. Several observational studies have suggested that contralateral risk-reducing mastectomy, following a diagnosis of breast cancer, may reduce mortality. Evidence regarding the optimal management of women at high risk of breast cancer continues to evolve and needs to be rapidly implemented into clinical practice.


Evolutional conservation of molecular structure and antiviral function of a type I interferon, IFN-kappa, in poultry.
IFN-kappa (IFN-κ) is a type I IFN expressed by keratinocytes, monocytes and dendritic cells with important roles during the innate immune response period. This research was conducted to elaborate the evolution and characteristics of IFN-κ in poultry. Chicken IFN-κ is located on the sex-determining Z chromosome, which is greatly different from mammals. Poultry IFN-κ cluster together in a species-specific manner through positive selection pressure and share only 19-33% homology with mammalian IFN-κ and poultry other type I IFN. Both chicken and duck IFN-κ was constitutively expressed in spleen, skin, lung, and peripheral blood mononuclear cells (PBMC), as well as being significantly induced after treatment with virus in PBMC. Biologically, poultry IFN-κ has antiviral activity against VSV in chicken embryonic fibroblasts and duck embryonic fibroblasts (CEF and DEF) cells, and induces the expression of IFN stimulated genes (ISGs). After treatment with JAK1 inhibitor, the ISGs expression can be down-regulated. Overall, our research on poultry IFN-κ not only enriches the knowledge about IFN-κ but also facilitates further research on the role of type I IFNs in antiviral defense responses in poultry.


Effects of a rostral motor cortex lesion on primary motor cortex hand representation topography in primates.
Small lesions to rostral versus caudal portions of the hand representation in the primary motor cortex (M1) produce different behavioral deficits. The goal of the present study was to determine if rehabilitative training has similar effects on functional topography of the spared M1 after rostral versus previously reported caudal M1 lesions. Following a lesion to the rostral M1 hand area, monkeys were trained for 1 h/day for 30 days to retrieve food pellets from small wells using their impaired hand. Electrophysiological maps of the M1 were derived in anesthetized monkeys before infarct and after rehabilitative training using intracortical microstimulation. After a lesion to the rostral M1 and rehabilitative training, the size of the spared hand representation decreased 1.2%. This change is not statistically different from the 9% increase seen after caudal M1 lesion and rehabilitative training (P > 0.2). Postlesion training spares peri-infarct hand area regardless of whether the lesion is in the rostral or caudal M1.


ExPlanes: exploring planes in triplet data.
Many methods for the analysis of gene expression-, protein- or metabolite-data focus on the investigation of binary relationships, while the underlying biological processes creating this data may generate relations of higher than bivariate complexity. We give a novel method ExPlanes that helps to explore certain types of ternary relationships in a statistically robust, Bayesian framework. To arrive at an characterization of the data structure contained in triplet data we investigate 2-dimensional planes being the only linear structures that cannot be inferred from projections of the data. The key part of our methodology is the definition of a robust, Bayesian plane posterior under the assumption of an invariant prior and a Gaussian error model. A numerical representation of the plane posterior can be explored interactively. Beyond this purely Bayesian approach we can use the plane posterior to construct a family of posterior-based test statistics that allow testing the data for different plane related hypotheses. To demonstrate practicability we queried triplets of metabolic data from a plant crossing experiment for the presence of plane-, line- and point-structures by using posterior-based test statistics and were able to show their distinctiveness.


Molecular insights into MYO3A kinase domain variants explain variability in both severity and progression of DFNB30 hearing impairment.
Hereditary hearing impairment (HI) is a common disease with the highest incidence among sensory defects. Several genes have been identified to affect stereocilia structure causing HI, including the unconventional myosin3A. Interestingly, we noticed that variants in MYO3A gene have been previously found to cause variable HI onset and severity. Using clinical exome sequencing, we identified a novel pathogenic variant p.(Lys50Arg) in the MYO3A kinase domain (MYO3A-KD). Previous in vitro studies supported its damaging effect as a 'kinase-dead' mutant. We further analyzed this variation through molecular dynamics which predicts that changes in flexibility of MYO3A structure would influence the protein-ATP binding properties. This Lys50Arg mutation segregated with congenital profound non-syndromic HI. To better investigate this variability, we collected previously identified MYO3A-KDs variants, p.(Tyr129Cys), p.(His142Gln) and p.(Pro189Thr), and built both wild type and mutant 3 D MYO3A-KD models to assess their impact on the protein structure and function. Our results suggest that KD mutations could either cause a congenital profound form of HI, when particularly affecting the kinase activity and preventing the auto-phosphorylation of the motor, or a late onset and progressive form, when partially or completely inactivating the MYO3A protein. In conclusion, we report a novel pathogenic variant affecting the ATP-binding site within the MYO3A-KD causing congenital profound HI. Through computational approaches we provide a deeper understanding on the correlation between the effects of MYO3A-KD mutations and the variable hearing phenotypes. To the best of our knowledge this is the first study to correlate mutations' genotypes with the variable phenotypes of DFNB30.Communicated by Ramaswamy H. Sarma.


Mg(5.23)Sm(0.77)Sb4: an ordered superstructure derived from the Mg3Sb2 structure type.
The ternary polar intermetallic phase Mg(5.231(8))Sm(0.769(8))Sb4 has been obtained from solid-state reactions at 700-850 degrees C in sealed Ta or Nb containers when the synthetic conditions took into account its characteristic incongruent melting point. The compound crystallizes in the trigonal space group P3 (Z = 1) with a = 4.618(1) A and c = 14.902(6) A in a structure that derives from that of Mg3Sb2 (anti-La2O3 type). This composition appears to be near the lower limit of Sm content, and solutions with appreciably higher Sm contents are also stable [Mg(6-x)SmxSb4, x <or= 1]. The result provides the first example of a superstructure of a Mg3Sb2-like structure with a doubled c axis induced by ordering a mixture of the larger divalent Sm and Mg ions separately within alternate layers of octahedral sites. Still larger proportions of Sm also give rise to a second solid solution region in the parent Mg3Sb2 type structure (P3m1), Mg(3-y)SmySb4, 0 <or= y <or= 1. Retention of the same 3e- valence electron counts per antimony in all of these phases suggests that the compounds remain electron precise and Zintl phases. Analogous compounds with Ca, Sr, or Ba substitution have evidently not been investigated.


Medium- to Long-term Results of Strut Allografts Treating Periprosthetic Bone Defects.
We evaluated the medium- to long-term outcomes of cortical strut allografts used to treat periprosthetic bone defects to better understand the correlation between radiological and clinical outcomes. We retrospectively reviewed outcomes from 19 patients undergoing cortical strut allografts to treat periproshtetic bone defects from 2001 to 2015. The mean age at index operation was 59.4 years and the average follow-up period was 8.6 years. Surgeries were performed because of aseptic loosening (n=9), periprosthetic fractures (n=5), and infections (n=5). Each case was characterized and described in detail including the length of allograft and the union period; possible correlations between allograft length and detailed classification and union period was analyzed. Clinical evaluations included the Harris hip score and Kaplan-Meier survivorship. In revision total hip arthroplasty (THA), the average length of allografts used in patients experiencing fractures was significantly longer than those with aseptic loosening or infection. Of the 19 cases, incorporation was observed in 18 cases (94.7%). The average time to incorporation was 21.2 months and the time to incorporation was not significantly different among the two groups (fracture vs. aseptic loosening or infection). No positive correlation was identified between the length of allograft and incorporation period or in the time to cortical strut allograft incorporation among Paprosky or Vancouver subgroups. Results of cortical strut allografts show excellent incorporation rates based on medium- to long-term follow-up. Cortical strut allografts may be considered useful for the treatment of femoral bone defects experienced during revision THA and following periprosthetic fracture.


Power law diffusion coefficient and anomalous diffusion: analysis of solutions and first passage time.
We investigate one-dimensional equations for the diffusion with a nonconstant diffusion coefficient inside the second derivative and between the derivatives. In particular, we employ the diffusion coefficient D(x) proportional to /x/(-theta)(theta in R) and a quartic potential. These diffusion equations present a rich variety of behaviors associated with different regimes. Results of two approaches are analyzed and compared. We also investigate the mean first passage time of these systems. We show that the system with the coefficient D(x) between the derivatives can produce different behaviors for the mean first passage time in comparison with those obtained by the system with the coefficient inside the derivatives.


Effects of hypoxia and reoxygenation on tissue ATP level and electrical and mechanical function of isolated guinea pig ventricular muscles.
The myocardial ATP level in guinea pig ventricular muscles was determined during hypoxia and reoxygenation and compared with the cardiac electrical and mechanical function. The action potential duration (APD), contractile force (CF) and tissue ATP level were depressed gradually depending on the N2 concentration in the medium. Time course studies revealed that the membrane electrical activity and the ATP content did not show parallel evolution, although changes in CF coincided with changes in ATP level.


Blood pressure lowering medication initiation and fracture risk: a SWAN pharmacoepidemiology study.
We examined the fracture risk after initiation of blood pressure-lowering drugs compared with initiation of antidepressants. Multivariable regression models demonstrated an increased risk of fracture among women initiating a blood pressure-lowering medication (HR 1.73, 95% CI 1.02-2.95). This is likely related to an increased risk of falls. Initiation of blood pressure-lowering drugs has been associated with fractures in several studies, presumably due to an increase in the risk of falls. However, these studies used self-controlled designs without active comparators. We examined the risk of fractures after initiation of blood pressure lowering drugs compared with initiation of antidepressants. Women participants in the Study of Women Across the Nation (SWAN) were potentially eligible if they initiated blood pressure-lowering or antidepressant drugs during follow-up. To reduce the risk of confounding, we estimated a propensity score that included potential confounders including age, menopausal status, osteoporosis, and osteoporosis medication use. The propensity score was used to match subjects in both groups and we then constructed multivariable logistic regression models comparing the risk of any fracture. Sensitivity analyses assessed a limited range of fractures less likely related to trauma. Among the 3302 potentially eligible women participating in the SWAN cohort, we were able to propensity-score match 289 women who initiated a blood pressure-lowering medication with 289 who initiated an antidepressant. Multivariable logistic regression models demonstrated an increased risk of fracture among women initiating a blood pressure lowering medication (OR 1.74, 95% CI 1.02-2.95). After excluding fractures of the digits and face, the results were similar (OR 1.57, 95% CI 0.88-2.81). There was evidence of an increased risk in fractures among women initiating blood pressure-lowering medications compared to those initiating antidepressants. This is likely related to an increased risk of falling.


Ecological monitoring of physical activity, emotions and daily life activities in schizophrenia: the DiAPAson study.
Schizophrenia spectrum disorders (SSD) compromise psychosocial functioning, including daily time use, emotional expression and physical activity (PA). We performed a cohort study aimed at investigating: (1) the differences in PA, daily activities and emotions between patients with SSD and healthy controls (HC); (2) the strength of the association between these variables and clinical features among patients with SSD. Ninety-nine patients with SSD (53 residential patients, 46 outpatients) and 111 matched HC were assessed for several clinical variables, and levels of functioning by means of standardised clinical measures. Self-reported daily activities and emotions were assessed with a smartphone application for ecological momentary assessment (EMA), and PA levels were assessed with a wearable accelerometer for 7 consecutive days.FindingsPatients with SSD, especially those living in residential facilities, spent more time being sedentary, and self-reported more sedentary and self-care activities, experiencing higher levels of negative emotions compared with HC. Moreover, higher functioning levels among patients were associated with more time spent in moderate-to-vigorous activity. Sedentary behaviour and negative emotions are particularly critical among patients with SSD and are associated with more impaired clinical outcomes. Mobile-EMA and wearable sensors are useful for monitoring the daily life of patients with SSD and the level of PA. This population needs to be targeted with specific rehabilitative programmes aimed at improving their commitment to structured daily activities.


Leptin up-regulates microRNA-27a/b-3p level in hepatic stellate cells.
Obese patients, often accompanied by hyperleptinemia, are prone to liver fibrogenesis. Leptin is an adipocyte-derived hormone and plays a promotion role in liver fibrosis. Sterol regulatory element binding protein-1c (SREBP1c) exerts a crucial role in inhibiting hepatic stellate cell (HSC) activation, a key step in liver fibrogenesis. Our previous studies indicated that leptin inhibited SREBP1c expression, contributing to leptin-induced HSC activation and liver fibrosis. microRNAs (miR) have emerged as important layers of regulatory control and regulate gene expression, and are implicated in numerous diseases. The present study revealed leptin up-regulation of miR-27a/b-3p levels in HSCs in vitro and in vivo. Three signaling pathways were required for leptin regulation of miR-27a/b-3p levels. miR-27a/b-3p could reduce SREBP1c and liver x receptor α (LXRα) levels, increased α-smooth muscle actin (α-SMA, a marker for HSC activation) and α1(I)collagen levels in cultured HSCs. miR-27a/b-3p regulation of SREBP1c and LXRα were independent of 3'-untranslated region of SREBP1c and LXRα mRNA. In vivo experiments further demonstrated the miR-27a/b-3p involved in leptin-associated decrease in SREBP1 level in HSCs, HSC activation, and liver fibrosis. These data might have potential implications for our understanding of molecular mechanisms underlying leptin roles in liver fibrogenesis of obese patients with hyperleptinaemia.


Thoracic endometriosis: a report of two cases.
We describe two patients with recurrent hemopneumothorax associated with pelvic endometriosis. The first patient a 37-year-old nulliparous lady with recurrent bilateral hemopneumothorax. She had a past history endometriosis years earlier. Laparoscopy and biopsy confirmed widespread endometriosis including in the omentum. Recurrence of the hemopneumothorax stopped after danazol therapy suggesting thoracic endometriosis as the cause of hemopneumothorax. The second lady is 47-years old with 2 children. She first presented with hemopneumothorax associated with menstrual period but ultrasound of pelvis did not reveal evidence of endometriosis. However, when she presented with a second episode of hemopneumothorax one year later, she was confirmed to have endometriosis and no further recurrence after treatment with Gonadotropin-releasing hormone analogue.


Estrogen and enalapril attenuate the development of right ventricular hypertrophy induced by monocrotaline in ovariectomized rats.
The present study evaluated the importance of ovarian functions and the renin-angiotensin system in the progression of the right ventricular (RV) hypertrophy. Female Sprague-Dawley rats were bilaterally ovariectomized (Ovx) and injected with monocrotaline (MCT, 60 mg/kg, sc). Four weeks after MCT-treatment, only the male and Ovx female rats showed marked RV hypertrophy. The hypertrophied RV of the male-MCT and Ovx-MCT rats exhibited remarkably elevated renin mRNA levels. Gene expression levels of angiotensinogen, TGF-beta1, and endothelin-1 in the hypertrophied RV also increased, but to the less degree than did the renin mRNA. To investigate beneficial effects of estrogen or enalapril on progression of the pulmonary hypertension and RV hypertrophy, histological changes of the lung and heart were examined. Sham-MCT female rats showed histological changes indicating pulmonary hypertension without RV hypertrophy. In contrast, Ovx-MCT rats showed marked RV hypertrophy with pathological changes, denoting severe pulmonary and myocardial injuries. Estrogen-or enalapril-treated Ovx-MCT rats did not show RV hypertrophy, and showed remarkably ameliorated ultrastructural changes in the lung and RV. These results from this rat model suggest that both estrogen and inhibition of the renin-angiotensin system have protective functions against the development of the pulmonary hypertension and cardiac remodeling.


Neuroinflammation and Microglial Activation at Rostral Ventrolateral Medulla Underpin Cadmium-Induced Cardiovascular Dysregulation in Rats.
Cadmium is a heavy metal and environmental toxicant known to act on the central cardiovascular regulatory mechanisms, and one of its brain targets is the rostral ventrolateral medulla (RVLM), a brainstem site that maintains blood pressure and sympathetic vasomotor tone. The present study assessed the hypothesis that cadmium elicits cardiovascular dysregulation by inducing neuroinflammation and microglial activation, two potential cellular mechanisms, in RVLM. Adult male Sprague-Dawley rats were used for measuring cardiovascular responses after intravenous administration of cadmium. We further conducted real-time PCR, immunofluorescence staining, in situ determination of mitochondrial superoxide, hematoxylin and eosin staining, and enzyme-linked immunosorbent assay (ELISA) to identify cytokine and chemokine mRNA expression, microglia activation, superoxide production, and necrotic and apoptotic cell death in RVLM. We found animals maintained under propofol anesthesia, intravenous administration of cadmium acetate (4 mg/kg) resulted in an increase, followed by a rebound and a secondary decrease in spontaneous baroreflex-mediated sympathetic vasomotor tone, a progressive reduction in mean arterial pressure and heart rate, alongside augmentation of pro-inflammatory cytokine and chemokine in RVLM. All those cardiovascular and neuroinflammatory events were reversed by pretreatment with an anti-inflammatory drug, pentoxifylline (50 mg/kg, i.p.). There were also concurrent microglial activation, reactive oxygen species production, hypoxia, reduced blood flow, and necrotic and apoptotic cell death in RVLM. Based on these biochemical, pharmacological and morphological observations, we conclude that neuroinflammation and microglial activation at RVLM, and their downstream cellular mechanisms, causally underpin cadmium-induced cardiovascular dysregulation.


[Efficacy of dietetic treatment in a case of galactosemia diagnosed late].
The authors describe a six months old girl affected by galactosemia, due to Galacto-1-phosphate Uridyl Transferase deficiency. The patient presented with hepatosplenomegaly and failure to thrive, without neurological impairment or cataracts. In this case removal of galactose from diet, although lately performed, resulted in normal growth and development. The authors emphasize the importance of ruling out galactosemia, even if clinical picture is unusual.


Association of eosinophilic fasciitis, multiple morphea and antiphospholipid antibody.
The occurrence of morphea-like changes during the course of eosinophilic fasciitis is considered to be rare. We observed such a case with simultaneous occurrence of both types of lesions. Histologically, fibrosis and inflammatory infiltrate were seen in the entire dermis, the subcutis and the fascia, suggesting that the same process might account for all skin changes. In addition, our patient had an antiphospholipid antibody, neurologic symptoms and livedo-like cutaneous lesions. However, whether the antiphospholipid antibody played a pathogenic role or not remains unclear. Corticosteroid treatment was successful.


Detecting Underspecification in SNOMED CT concept definitions through natural language processing.
Quality assurance and audit issues play a major role in maintening large biomedical terminology, such as SNOMED CT. Several automatized techniques have been proposed to facilitate the identification of weak spots and suggest adequate improvements.In this study, we address a well-known issue within SNOMED CT: Albeit the wording of many free-text concept descriptions suggests a connection to other concepts, they are often not referred to in the logical concept definition.To detect such inconsistencies, we use a semantic indexing approach which maps free text onto a sequence of semantic identifiers. Applied to SNOMED CT concepts without attributes, our technique spots refinable concepts and suggests appropriate attributes, i.e., connections to other concepts. Based on a manual analysis of random samples, we estimate that approximately 18,000 refinable concepts can be found.


Effects of a Communication Intervention Randomized Controlled Trial to Enable Goals-of-Care Discussions.
Patients with advanced cancer often have a poor understanding of cancer incurability, which correlates with more aggressive treatment near the end of life (EOL). We sought to determine whether training oncologists to elicit patient values for goals-of-care (GoC) discussions will increase and improve these discussions. We explored its impact on use of aggressive care at EOL. We enrolled and used block randomization to assign 92% of solid tumor oncologists to 2-hour communication skills training and four coaching sessions. We surveyed 265 patient with newly diagnosed advanced cancer with < 2-year life expectancy at baseline and 6 months. We assessed prevalence and quality of GoC communication, change in communication skills, and use of aggressive care in the last month of life. Intervention (INT) oncologists' (n = 11) skill to elicit patient values increased (27%-55%), while usual care (UC) oncologists' (n = 11) skill did not (9%-0%; P = .01). Forty-eight percent (n = 74) INT v 51% (n = 56) UC patients reported a GoC discussion (P = .61). There was no difference in the prevalence or quality of GoC communication between groups (global odds ratio, 0.84; 95% CI, 0.57 to 1.23). Within 6 months, there was no difference in deaths (18 INT v 16 UC; P = .51), mean hospitalizations (0.47 INT v 0.42 UC; P = .63), intensive care unit admissions (5% INT v 9% UC; P = .65), or chemotherapy (26% INT v 16% UC; P = .39). Use of a coaching model focused on teaching oncologists to elicit patient values improved that skill but did not increase prevalence or quality of GoC discussions among patients with advanced cancer. There was no impact on high care utilization at EOL.


circRNA_101277 Influences Cisplatin Resistance of Colorectal Cancer Cells by Modulating the miR-370/IL-6 Axis.
Colorectal cancer (CRC) is among the most prevalent malignancies globally. Early detection of precancerous lesions through routine colonoscopy has led to a dramatic reduction in CRC-related incidence and mortality among those between the ages of 50 and 70. However, in those where the disease progresses to an advanced stage, chemotherapy remains the primary available treatment option, and the associated 5-year survival rate remains low. The identification of genes associated with CRC chemoresistance would thus be a beneficial approach to identifying novel treatments for this deadly disease. The expression of circRNA_101277, miR-370, and IL-6 was assessed via qRT-PCR. IL-6 levels were measured with a human IL-6 ELISA kit based on the provided protocols. CRC cellular proliferation and cisplatin IC50 values were quantified via MTT assays. Luciferase assays were used to detect circRNA_101277 and miR-370 binding sites or miR-370 and IL-6 binding sites. circRNA_101277 was increased in CRC tissues compared with control samples. circRNA_101277 overexpression was evident in CRC cells, and knockdown of this circRNA suppressed cellular proliferation and cisplatin resistance in these cancer cells. At a mechanistic level, circRNA_101277 was found to function by sequestering miR-370, thereby upregulating the miR-370 target gene IL-6 and promoting cisplatin resistance via this miR-370/IL-6 axis. In summary, our data highlight circRNA_101277 as a novel driver of CRC cell cisplatin resistance that functions by sequestering miR-370 and thereby enhancing IL-6 expression. These findings suggest that this circRNA_101277/miR-370/IL-6 axis may represent a critical axis of chemoresistance in CRC that can be targeted to diagnose and/or treat this cancer.


Protease-activated receptor (PAR)1, PAR2 and PAR4 expressions in esophageal squamous cell carcinoma.
Here, we used reverse transcription-PCR (RT-PCR) and western blot to detect protease-activated receptor (PAR) 1, PAR 2 and PAR 4 expression in cancer tissues and cell lines of esophageal squamous cell carcinoma, and investigated the co-relationship between PAR expression and clinic-pathological data for esophageal cancer. The methylation of PAR4 gene promoter involved in esophageal carcinoma was also analyzed. By comparing the mRNA expressions of normal esophageal tissue and human esophageal epithelial cells (HEEpiC), we found that among the 28 cases of esophageal squamous cell carcinoma, PAR1 (60%) and PAR2 (71%) were elevated in 17 and 20 cases, respectively, and PAR4 (68%) expression was lowered in 19 cases. Whereas, in human esophageal squamous cells (TE-1 and TE-10), PAR1 and PAR2 expression was increased but PAR4 was decreased. Combined with clinical data, the expression of PAR1 in poorly differentiated (P=0.016) and middle and lower parts of the esophagus (P=0.016) was higher; expression of PAR4 in poorly differentiated carcinoma was lower (P=0.049). Regarding TE-1 and TE-10 protein expression, we found that in randomized esophageal carcinoma, PAR1 (P=0.027) and PAR2 (P=0.039) expressions were increased, but lowered for PAR4 (P=0.0001). In HEEpiC, TE-1, TE-10, esophageal and normal esophagus tissue samples (case No. 7), the frequency of methylation at the 19 CpG loci of PAR4 was 35.4%, 95.2%, 83.8%, 62.6% and 48.2%, respectively. Our results indicate that the expression of PAR1 and PAR2 in esophageal squamous cell carcinoma is increased but PAR4 is decreased. Hypermethylation of the promoter of the PAR4 gene may contribute to reduced expression of PAR4 in esophageal squamous cell carcinoma.


Giant abdominal lipofibroma - case presentation.
Abdominal lipomas are benign mesenchymal tumors of mature fatty tissue that may appear at any age. We present the case of a 58-year-old patient with a cardiovascular pathology, who presented with diffuse abdominal pains, asthenia, anterior thorax pains and palpitations, abdomen increase, symptoms that had an insidious onset. The clinical and imagistic examinations suggested the diagnosis of giant abdominal lipoma. The surgical intervention allowed the excision of an encapsulated tumor, of 250÷220÷230 mm, relatively well encapsulated, with a macroscopic aspect of section adipose tissue, with hard whitish areas, with a 12.3 kg weight. The histopathological examination confirmed the diagnosis of lipofibroma.


Cytochemical profile of megakaryoblastic leukaemia: a study with cytochemical methods, monoclonal antibodies, and ultrastructural cytochemistry.
A cytochemical study using: Sudan black B; alpha-naphthyl acetate (ANAE) staining; estimation of alpha-naphthyl butyrate (ANBE) esterase activity; acid phosphatase activity; and 5' nucleotidase activity was carried out in 15 cases of megakaryoblastic leukaemia. These included cases of M7 acute myeloid leukaemia and blast crises of chronic granulocytic leukaemia. The megakaryoblastic nature of the blasts was first established using two monoclonal antibodies against platelet glycoproteins, and by estimating the platelet/peroxidase reaction at ultrastructural level. Our findings suggest that megakaryoblasts have a typical cytochemical profile comprising positive ANAE staining and acid phosphatase activity with a predominant localisation in the Golgi zone and negative or weak ANBE activity. A similar positive cytochemical pattern was also found in five cases of erythroleukaemia (M6). The specificity of the 5'nucleotidase activity for megakaryoblasts was not confirmed. In most cases of megakaryoblastic leukaemia there was no 5'nucleotidase activity only two cases showed positive reactions--reactions were positive in several cases of myeloblastic and lymphoblastic leukaemia. We suggest that cytochemical methods may be useful in diagnosing M6 and M7 acute leukaemia because less than 40% of leukaemic cells react with specific monoclonal antibodies.


Knowledge and Prevention of Vertical Transmission of Hepatitis B Infection: A Cross-Sectional Study among Pregnant Females in Varanasi, India.
300 million individuals worldwide suffer from chronic HBV infection. India, an intermediate endemicity zone, has a 3-4% HBsAg prevalence in the general population and 0.9-11.2% among pregnant women. As 95% of infantile infections progress to chronicity, vertical transmission is a vital intervention area. To assess the knowledge of pregnant women and post-natal mothers concerning Hepatitis-B infection transmission and prevention. A cross-sectional study was conducted with 143 participants (124 pregnant females and 19 postnatal mothers) attending the antenatal clinic at the rural block primary health center. A semi-structured questionnaire was used. Blood samples were evaluated for HBsAg using RAPIKIT. SPSS-22 was utilized for descriptive statistical analysis. 91.6% of respondents had heard of Hepatitis. 1.4% stated that it can be caused by a virus, whereas 40% identified consumption of oily, spicy, and unhygienic food as causative. 67.1% of respondents underwent blood tests but could not specify what they were screened for. 5.2% were HBsAg positive. ~40% were aware of vertical transmission. 59.4% of respondents were unaware of any preventive modality, and 7.7% said vaccination is preventive. 97.9% had never been counseled during their antenatal period by health workers. 41.1% said that their newborns were vaccinated within 24 hours of birth. Findings emphasize the paucity of knowledge possessed by pregnant women and post-natal mothers concerning Hepatitis B causation, transmission, and prevention regardless of age, education, or socioeconomic status. Misconceptions were prevalent, and counseling was inadequate.


Effects of cyproheptadine on plasma superoxide dismutase activity and malondialdehyde content in rabbits with hemorrhagic shock.
Profound hemorrhagic shock was produced in thirty rabbits by exsanguination via the carotid artery until blood pressure (BP) reached 5.3 kPa (40 mmHg) and was sustained for a period of 90 minutes. The rabbits were equally divided into cyproheptadine (Cyp) treated group and control group. Blood samples 30 minutes after liquid and blood infusion and administration of Cyp (10 mg/kg) were collected from the carotid artery, and the plasma superoxide dismutase (SOD) activity and malondialdehyde (MDA) content measured. The results showed that Cyp remarkably enhanced the plasma SOD activity (2462 +/- 338 vs 1955 +/- 596, P < 0.01) and reduced MDA content (2.68 +/- 0.24 vs 3.20 +/- 0.49, P < 0.01). We believe that the increase of O2 production plays an important role in the development of shock, the single blood and liquid infusion can not significantly improve the shock conditions. Scavenging oxygen free radicals and alleviating cellular damage and multiple organ failure are the possible mechanisms of cyproheptadine anti-shock effect.


[From heparin to synthetic antithrombotic oligosaccharides].
In the early eighties, following breakthroughs in oligosaccharide chemistry, we achieved the total chemical synthesis of pentasaccharides related to the antithrombin-binding domain in heparin. Selective inhibitors of coagulation factor Xa, thus obtained, represent a new class of efficient antithrombotic drugs. In a further step, we have designed and synthesised oligosaccharides (pentadeca--to eicosasaccharides), comprising an antithrombin binding domain prolonged by a thrombin binding domain. These compounds inhibit both factor Xa and thrombin, in the presence of antithrombin, while they are devoid of undesirable non-specific interactions, particularly with platelet factor 4 (PF4). The efficacy of these new synthetic antithrombotics, with a unique biological profile, will be evaluated in clinical trials.


Geographic Variation in Mentally Unhealthy Days: Air Pollution and Altitude Perspectives.
Ha, Hoehun. Geographic variation in mentally unhealthy days: air pollution and altitude perspectives. High Alt Med Biol. 18:258-266, 2017. Mental health incorporates our emotional, psychological, and social well-being and it is critical at each phase of life, from youth and preadulthood through adulthood. We assessed the association between mentally unhealthy days (MUDs), air pollutant concentrations, and altitude on the basis of cross-county studies. Data on poor mental health days for the United States were based on health-related telephone surveys conducted by the Behavioral Risk Factor Surveillance System (BRFSS). Average annual regional air pollution data were obtained from Center for Disease Control and Prevention (CDC) WONDER Environmental data, and altitude data were collected from the U.S. Geological Survey (USGS). In the data set (across 2589 U.S. counties for 2011), even after accounting for potential confounding variables and multicollinearity, a significant association between altitude, air pollution, and poor mental health days was found, explaining that poor mental health days increase with increasing air pollution concentrations and with decreasing altitude (R2 = 0.663, p < 0.001). Controlling for socioeconomic (e.g., education and employment) and social (including social relationship and crime) factors did not change these findings. In this study, we found that counties with lower air pollution and higher altitude had significantly lower average number of MUDs reported within the past 30 days. This association has not been reported before in the literature. These findings suggest a need for further investigation into the extent that air quality and altitude may serve as significant factors for mental health and have major implications in our understanding of the etiology of mental health by medical professionals.


Age-period-cohort analysis of colorectal cancer, service members aged 20-59 years, active component, U.S. Armed Forces, 1997-2016.
In the U.S. general population, incidence of colorectal cancer appears to be increasing in younger age groups since the mid-1980s. The objective of this report was to better understand the time-varying elements (age, period, and birth cohort effects) in the epidemiology of colorectal cancer among the active component of the U.S. Armed Forces. During 1997-2016, there were 1,108 incident cases of colorectal cancer among service members aged 20-59 years, corresponding to an overall incidence rate of 4.3 per 100,000 person-years (p-yrs). Rates were particularly high among men (4.4 per 100,000 p-yrs) and non- Hispanic black service members (5.3 per 100,000 p-yrs). Overall crude incidence of colorectal cancer increased in an exponential fashion with increasing age groups until the oldest age group (55-59 years), in which the increase was attenuated. No birth cohort or period effects were identified in the age-period-cohort analysis. This finding could be due to limited power, selection bias, better screening practices in the Military Health System (MHS) compared with the general population, or true lack of effects. Continued population-based screening for colorectal cancer in the MHS is recommended to maintain low and decreasing incidence in the U.S. Armed Forces.


[Functional deficiency of bone marrow mesenchymal stem cells in patients with immune thrombocytopenia: An update].
Immune thrombocytopenia (ITP) is an acquired autoimmune hemorrhagic disorder characterized by persistent thrombocytopenia. It may be induced by different pathogenesis due to its heterogeneity, and the therapeutic effects vary on different patients. Bone marrow derived mesenchymal stem cells (BMMSCs) can modulate innate and adaptive immunity, thus resulting in a tolerant microenvironment. Functional defects and immunomodulatory disorders of BMMSCs are significant causes of ITP. Functional effects associated with the activation of the P53 pathway include decreased activity of the phosphatidylinositol 3 kinase/AKT pathway and activation of the TNFAIP3/NF-κB/SMAD7 pathway. Immune dysfunction appears to be correlated with an impaired ability of BMMSCs to induce various types of immune cells in ITP. An in-depth investigation into the pathogenesis of ITP facilitates the treatment of ITP, but larger-scale clinical trials are needed to verify the efficacy of exogenous BMMSCs in the clinical treatment of ITP.


An evaluation of emergency sclerotherapy of varices in randomized trials: looking the needle in the eye.
The role of sclerotherapy for acute variceal bleeding is challenged by vasoactive drugs and by ligation. A meta-analysis was performed to evaluate whether sclerotherapy remains a gold standard in acute variceal bleeding. Sclerotherapy was evaluated across four randomized trial groups: (a) combined with vasoconstrictors vs. vasoconstrictors alone (five trials, with 400 patients); (b) vs. vasoconstrictors alone (15 trials, with 1296 patients); (c) vs. combination of vasoconstrictors and sclerotherapy (eight trials, with 1026 patients); (d) vs. ligation (12 trials, with 1309 patients). We used the risk difference (absolute risk reduction) as our main effect measure. The efficacy of acute sclerotherapy was highest vs. ligation at 95 %, with a small advantage for ligation (an overtube was used in eight trials) of 2.5 % (95 % CI 0.4 % to 4.6 %) ( P = 0.018), but no survival difference. Efficacy of sclerotherapy combined with vasoconstrictors vs. vasoconstrictors alone was 86 %, whereas it was 83 % for sclerotherapy vs. vasoconstrictors alone. In both these groups sclerotherapy was superior for control of bleeding at, respectively, 16.3 % (95 % CI 8.7 % to 23.9 % ( P = 0.0001) and 5.9 % (95 % CI, 1.5 % to 10.3 %) ( P = 0.008), with increased survival in the latter. In the combination group of sclerotherapy with vasoconstrictors, the efficacy of sclerotherapy alone was 69 %, with the combination superior in controlling bleeding, at 13.2 % (95 % CI, 8.4 % to 18.1 %) ( P < 0.0001) but with no survival difference. This comparison of sclerotherapy across trials demonstrates a problem in defining its real efficacy. The conclusive evidence for substituting banding ligation or the combination of vasoconstrictors with sclerotherapy as better therapeutic approaches has not been provided in randomized trials. Sclerotherapy can remain a gold standard in variceal bleeding but there is scope for further studies of ligation and vasoactive drugs.


MRI vs CT for diagnosing brain disorders in the elderly.
Following a very brief, simplified explanation of magnetic resonance imaging principles, the general advantages inherent in such a system, as compared to CT, are explored. Clinical exploitation of MRI's attributes are then specifically discussed and illustrated in multiple types of intracranial pathology.


Fifth Annual Stem Cell Summit.
The Fifth Annual Stem Cell Summit, held in New York, included topics covering new commercial developments in the research field of stem cell-based therapies. This conference report highlights selected presentations on embryonic and adult stem cells, stem cell-based therapies for the treatment of orthopedic and cardiovascular indications and inflammatory diseases, as well as technologies for processing and storing stem cells. Investigational therapies discussed include placental expanded (PLX) cells (Pluristem Therapeutics Inc), StemEx (Gamida-Teva Joint Venture/Teva Pharmaceutical Industries Ltd) and remestemcel-L (Osiris Therapeutics Inc/Genzyme Corp/JCR Pharmaceuticals Co Ltd/ Mochida Pharmaceutical Co Ltd).


Pharyngeal electrical stimulation device for the treatment of neurogenic dysphagia: technology update.
Neurogenic dysphagia (ND) can occur in patients with nervous system diseases of varying etiologies. Moreover, recovery from ND is not guaranteed. The therapeutic approaches for oropharyngeal ND have drastically changed over the last decade, mainly due to a better knowledge of the neurophysiology of swallowing along with the progress of neuroimaging and neurophysiological studies. For this reason, it is a priority to develop a treatment that is repeatable, safe, and can be carried out at the bedside as well as for outpatients. Pharyngeal electrical stimulation (PES) is a novel rehabilitation treatment for ND. PES is carried out via location-specific intraluminal catheters that are introduced transnasally and enable clinicians to stimulate the pharynx directly. This technique has demonstrated increasingly promising evidence in improving swallowing performance in patients with ND associated with stroke and multiple sclerosis, probably by increasing the corticobulbar excitability and inducing cortical reorganization of swallowing motor cortex. In this article, we update the reader as to both the physiologic background and past and current studies of PES in an effort to highlight the clinical progress of this important technique.


The Reciprocal Relationship between Climate and Environmental Changes and Food Systems and Its Impact on Food/Nutrition Security and Health.
Changes in our climate and physical environments are having profound effects on all aspects of human existence, and the ability to develop sustainable and resilient food systems is critical not just to the environment but to all aspects of human health. The Pediatric Growth and Nutrition Branch (PGNB) of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the US National Institutes of Health has adopted a new paradigm to undergird the study of nutrition that recognizes the complex and reciprocal nature of the relationships between nutrition and health outcomes. This conceptual framework, termed the "nutritional ecology," views humans as complex biological systems interacting with both their internal and external environments. Herein, we focus on: (i) the reciprocal relationship between climate and environmental changes and food systems and their impact on food/nutrition security and health; and (ii) how PGNB is utilizing the "nutritional ecology" framework to support science addressing the interactions among health, nutrition, food systems, climate, and the environment.


Compensation for nucleotide bias in a genome by representation as a discrete channel with noise.
Calculation of the information content of motifs in genomes highly biased in nucleotide composition is likely to lead to overestimates of the amount of useful information in the motif. Calculating relative information can compensate for biases, however the resulting information content is the amount seen by an observer and not by a macromolecule binding to the motif. The latter is needed to calculate the discriminatory power of the motif and to compare motifs between species. By treating a biased genome as a discrete channel with noise, in accordance with Shannon Information Theory, we were able to remove both 'Distortion' and 'Noise' from the motif and recover a more instructive biological 'signal.' A Java application, LogoPaint, was developed to remove nucleotide bias distortion and triplet frequency noise from motifs, calculate information content and present the motif as a logo. We demonstrate how this technique can 'unmask' motifs in the translation initiation regions of bacteria that are obscured by strong sequence biases. LogoPaint is available to all users from the authors as an executable JAR file. Source code is available by arrangement.


Semiochemicals Produced by Microbes in Mealybug Honeydew Attract Fire Ants.
Semiochemicals produced by microbes in hemipteran honeydew play an important role in mediating the ant-hemipteran interaction. However, the specific volatile compounds and their origins remain unclear. Here, we found that honeydew produced by Phenacoccus solenopsis exhibited strong attractiveness to fire ant workers, but sterilized honeydew was much less attractive. Four compounds were identified from the honeydew volatiles, including 1-octen-3-ol, limonene, phenylethyl alcohol, and 2,4-ditert-butylphenol. All the identified compounds triggered strong electroantennography response of fire ants and showed repellence at relatively high concentrations while attractiveness at low concentrations to fire ant workers. Furthermore, six bacterial isolates were identified based on 16S rRNA sequencing, namely, Bacillus, Brachybacterium, Kocuria, Microbacterium, Pseudomonas, and Staphylococcus. Fire ants exhibited a strong preference for Brachybacterium, Kocuria, and Microbacterium, suggesting that these bacterial isolates are involved in the attracting effect of honeydew. Both limonene and phenylethyl alcohol were detected from Brachybacterium, while limonene was only detected from Kocuria, and phenylethyl alcohol was exclusively detected from Microbacterium. Reinoculation of these bacteria restored the attractiveness of honeydew to fire ants, and the active compounds, limonene and phenylethyl alcohol, were detectable in bacteria-reinoculated honeydew. Collectively, our results reveal the active compounds in hemipteran honeydew and their association with honeydew bacteria. The findings will contribute to the development of novel attractants for efficient monitoring of fire ants.


Targeting PI3K Signaling in Acute Lymphoblastic Leukemia.
Adhesion of acute lymphoblastic leukemia (ALL) cells to bone marrow stroma cells triggers intracellular signals regulating cell-adhesion-mediated drug resistance (CAM-DR). Stromal cell protection of ALL cells has been shown to require active AKT. In chronic lymphocytic leukemia (CLL), adhesion-mediated activation of the PI3K/AKT pathway is reported. A novel FDA-approved PI3Kδ inhibitor, CAL-101/idelalisib, leads to downregulation of p-AKT and increased apoptosis of CLL cells. Recently, two additional PI3K inhibitors have received FDA approval. As the PI3K/AKT pathway is also implicated in adhesion-mediated survival of ALL cells, PI3K inhibitors have been evaluated preclinically in ALL. However, PI3K inhibition has yet to be approved for clinical use in ALL. Here, we review the role of PI3K in normal hematopoietic cells, and in ALL. We focus on summarizing targeting strategies of PI3K in ALL.


Native Valve Infective Endocarditis Caused by Histoplasma capsulatum in an Immunocompetent Host: The First Case in Asia and Literature Review in Asia and Australia.
Infective endocarditis caused by the dimorphic fungus Histoplasma capsulatum is extremely rare, occurring predominantly in individuals with prosthetic heart valves and HIV infection. To our knowledge, no case of H. capsulatum native valve endocarditis has been reported in Asia. Methodology. A descriptive study was carried out at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, in 2020. A previously healthy 34-year-old man developed fever, umbilicated skin lesions, oral ulcers, hoarseness of voice, severe weight loss, and progressive dyspnea over the course of one week. Facial umbilicated papules, nodular ulcers in his tongue and palate, a diastolic rumbling murmur at the mitral valve, diffuse fine crackles in both lungs, and engorged neck veins were detected during the examination. Skin scraping of the facial lesion revealed both extracellular and intracellular yeasts with buddings, 2-4 μm in size on Wright's stain. Transthoracic echocardiography demonstrated a left ventricular ejection fraction of 54 percent, severe rheumatic mitral stenosis, and multiple oscillating masses in the anterior mitral valve leaflet ranging in dimension from 1.5 to 2.4 cm. The HIV antibody test was negative. H. capsulatum endocarditis was diagnosed, and liposomal amphotericin B was administered. Due to cardiogenic shock, emergency open-heart surgery was conducted one day after admission. However, he died of multiorgan failure four days after the operation. The skin and vegetation cultures finally grew H. capsulatum after 1 week of incubation. To date, there has been handful of cases of H. capsulatum native valve endocarditis in non-HIV-infected patients. We report herein the first case in Thailand. Umbilicated skin lesions, especially combined with oral mucosal lesions, are a clinical clue that leads to the correct diagnosis of the causative organism.


Mechanism of phase separation generation in Ge-based solar cell tunnel junctions.
Enhanced performance, reduced cost and compact dimensions are a prerequisite for novel products in the solar industry. III-V based multi-junction heterostructures are promising devices to give an answer to make a substancial step in the photovoltaic technology. However, such heterostructures need tunnel junctions to connect the different active layers and so ternary alloys are needed to tune the energy gap. In the present contribution, artefacts generated by ternary alloying are investigated by transmission electron microscopy (TEM). Composition modulation in In0.015Ga0.985As/In0.3Ga0.7P/Al0.3Ga0.7As/In0.3Ga0.6Al0.1P/In0.3Al0.7P/In0.015Ga0.985As heterostructures grown on Ge subtrates is observed. This should affect the spectral sensitivity of the active layer. But, as a probably more important consequence, this observed modulation is shown to also generate modulation in the Al0.3Ga0.7As tunnel junction. This behaviour is anomalous in standard AIGaAs thick epilayers grown on GaAs substrates. In the present case, it could strongly affect the carrier transport imposing an important handicap to their potential application within electro-optical components.


Canadian multicenter randomized trial comparing sequential and alternating administration of two non-cross-resistant chemotherapy combinations in patients with limited small-cell carcinoma of the lung.
In order to assess the effect of scheduling of chemotherapy on the outcome of patients with limited small-cell lung cancer (SCLC), the Clinical Trials Group of the National Cancer Institute of Canada carried out a randomized trial comparing the alternation of cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, OH; doxorubicin) and vincristine (CAV) with etoposide (VP-16) and cisplatin for six cycles to the administration of these two combinations in a sequential fashion (three cycles of CAV followed by three of VP-16/cisplatin). Three hundred eligible patients were enrolled on the trial from September 1981 to October 1984. All responding patients were also treated after completion of chemotherapy with thoracic irradiation in randomly allocated doses of 2,000 and 3,750 cGy. The complete response (CR) rate to chemotherapy was slightly, but not significantly, higher on the alternating arm (52% v 44%, P = .20). However, there was no difference in disease-free or overall survival on the alternating and sequential arms, respectively (47.3 weeks v 45.1 weeks, P = .26; 61.7 weeks v 59.5 weeks, P = .56). Data on the effect of radiotherapy dose on survival are not yet mature, but it does not appear the results of this portion of the trial will alter the interpretation of the chemotherapy comparison. Patient characteristics favorably influencing survival were female sex, good performance status, younger age, and absence of supraclavicular node involvement. Two interpretations of these and other results in SCLC are suggested: (1) the difference between the schedules used is too small for the predictions of the Goldie-Coldman model to be realized in a trial of this size, or (2) VP-16/cisplatin is actually a superior regimen and any schedule that exposes patients to these drugs early in treatment will produce improved results.


Efficient expression of stable recombinant human insulin-like growth factor-1 fusion with human serum albumin in Chinese hamster ovary cells.
Insulin-like growth factor-1 (IGF-1) plays a crucial role in cell development, differentiation, and metabolism, and has been a potential therapeutic agent for many diseases. Chinese hamster ovary (CHO) cells are widely used for production of recombinant therapeutic proteins, but the expression level of IGF-1 in CHO cells is very low (1,500 µg/L) and the half-life of IGF-1 in blood circulation is only 4.5 min according to previous studies. Therefore, IGF-1 was fused to long-circulating serum protein human serum albumin (HSA) and expressed in CHO cells. After 8-day fed-batch culture, the expression level of HSA-IGF-1 reached 100 mg/L. The fusion protein HSA-IGF-1 was purified with a recovery of 35% using a two-step chromatographic procedure. According to bioactivity assay, the purified HSA-IGF-1 could stimulate the proliferation of NIH3T3 cells in a dose-dependent fashion and promote the cell-cycle progression. Besides this, HSA-IGF-1 could bind to IGF-1 receptor on cell membrane and activate the intracellular PI3K/AKT signaling pathway. Our study suggested that HSA fusion technology carried out in CHO cells not only provided bioactivity in HSA-IGF-1 for further research but also offered a beneficial strategy to produce other similar cytokines in CHO cells.


Aqp5 is a new transcriptional target of Dot1a and a regulator of Aqp2.
Dot1l encodes histone H3 K79 methyltransferase Dot1a. Mice with Dot1l deficiency in renal Aqp2-expressing cells (Dot1l(AC)) develop polyuria by unknown mechanisms. Here, we report that Aqp5 links Dot1l deletion to polyuria through Aqp2. cDNA array analysis revealed and real-time RT-qPCR validated Aqp5 as the most upregulated gene in Dot1l(AC) vs. control mice. Aqp5 protein is barely detectable in controls, but robustly expressed in the Dot1l(AC) kidneys, where it colocalizes with Aqp2. The upregulation of Aqp5 is coupled with reduced association of Dot1a and H3 dimethyl K79 with specific subregions in Aqp5 5' flanking region in Dot1l(AC) vs. control mice. In vitro studies in IMCD3, MLE-15 and 293Tcells using multiple approaches including real-time RT-qPCR, luciferase reporter assay, cell surface biotinylation assay, colocalization, and co-immunoprecipitation uncovered that Dot1a represses Aqp5. Human AQP5 interacts with AQP2 and impairs its cell surface localization. The AQP5/AQP2 complex partially resides in the ER/Golgi. Consistently, AQP5 is expressed in none of 15 normal controls, but in all of 17 kidney biopsies from patients with diabetic nephropathy. In the patients with diabetic nephropathy, AQP5 colocalizes with AQP2 in the perinuclear region and AQP5 expression is associated with impaired cellular H3 dimethyl K79. Taken together, these data for the first time identify Aqp5 as a Dot1a potential transcriptional target, and an Aqp2 binding partner and regulator, and suggest that the upregulated Aqp5 may contribute to polyuria, possibly by impairing Aqp2 membrane localization, in Dot1l(AC) mice and in patients with diabetic nephropathy.


Influence of hyperglycaemia on maximal gastric secretion in healthy subjects.
The influence of a single intravenous glucose load on maximal gastric acid secretion in 25 healthy men when stimulated with pentagastrin was studied. Under the influence of hyperglycaemia, a highly significant decrease of maximal acid output was found. Moreover, in the gastric juice an increase of chloride and calcium concentrations was noted. On the other hand, the output of potassium, chloride and magnesium was lowered. The above differences were statistically significant.


Crystallization of a (1-butene)-ethylene copolymer in phase I directly from the melt in nanocomposites with montmorillonite.
Nanocomposites based on a copolymer of 1-butene and ethylene filled with montmorillonite (Cloisite 15A) were studied, obtaining for the first time crystallization from the melt directly into phase I. The polymorphism of the polymer and the dispersion of the filler in the matrix were investigated. The effect of the compatibilizer (PB-g-MA) on these properties was also singled out. The dramatic increase in the rate of the II --> I phase transition due to montmorillonite was attributed to the alteration in the phase stability diagram of the matrix, due to the introduction of defects and to induction of local pressure on the crystalline domains.


Picture-Word Interference Effects Are Robust With Covert Retrieval, With and Without Gamification.
The picture-word interference (PWI) paradigm has been used to investigate the time course of processes involved in word retrieval, but is challenging to implement online due to dependence on measurements of vocal reaction time. We performed a series of four experiments to examine picture-word interference and facilitation effects in a form of covert picture naming, with and without gamification. A target picture was accompanied by an audio word distractor that was either unrelated, phonologically-related, associatively-related, or categorically-related to the picture. Participants were instructed to judge whether the name of the target picture ended in the phoneme assigned to the block by pressing corresponding keys as quickly and accurately as possible. Experiments 1 and 2 successfully replicated categorical interference and phonological facilitation effects at different optimal stimulus-onset-asynchronies (SOAs) between words and pictures. Experiment 3 demonstrated that a key gamification feature (collecting coins) motivated faster speed at the expense of accuracy in the gamified vs. experimental format of the task. Experiment 4 adopted the optimal SOAs and verified that the gamification reveals expected interference and facilitation effects despite the speed-accuracy tradeoff. These studies confirmed that categorical interference occurs earlier than phonological facilitation, while both processes are independent from articulation and inherent to word retrieval itself. The covert PWI paradigm and its gamification have methodological value for neuroimaging studies in which articulatory artifacts obscure word retrieval processes, and may be developed into potential online word-finding assessments that can reveal word retrieval difficulties with greater sensitivity.


Alpha-fetoprotein and modified response evaluation criteria in solid tumors progression after locoregional therapy as predictors of hepatocellular cancer recurrence and death after transplantation.
Locoregional therapy (LRT) is being increasingly used for the management of hepatocellular cancer (HCC) in patients listed for liver transplantation (LT). Although several selection criteria have been developed, stratifications of survival according to the pathology of explanted livers and pre-LT LRT are lacking. Radiological progression according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and alpha-fetoprotein (AFP) behavior was reviewed for 306 patients within the Milan criteria (MC-IN) and 116 patients outside the Milan criteria (MC-OUT) who underwent LRT and LT between January 1999 and March 2010. A prospectively collected database originating from 6 collaborating European centers was used for the study. Sixty-one patients (14.5%) developed HCC recurrence. For both MC-IN and MC-OUT patients, an AFP slope > 15 ng/mL/month and mRECIST progression were unique independent risk factors for HCC recurrence and patient death. When the radiological Milan criteria (MC) status was combined with radiological and biological progression, MC-IN and MC-OUT patients without risk factors had similarly excellent 5-year tumor-free and patient survival rates. MC-IN patients with at least 1 risk factor had worse outcomes, and MC-OUT patients with at least 1 risk factor had the poorest survival (P < 0.001). In conclusion, both radiological and biological modifications permit documentation of the response to LRT in patients waiting for LT. According to these 2 parameters, tumor progression significantly increases the risk of recurrence and patient death not only for MC-OUT patients but also for MC-IN patients. The monitoring of both parameters in combination with the initial radiological MC status is an essential element for further refining the selection criteria for potential liver recipients with HCC.


Electrochemical Field-Effect Transistor Utilization to Study the Coupling Success Rate of Photosynthetic Protein Complexes to Cytochrome c.
Due to the high internal quantum efficiency, reaction center (RC) proteins from photosynthetic organisms have been studied in various bio-photoelectrochemical devices for solar energy harvesting. In vivo, RC and cytochrome c (cyt c; a component of the biological electron transport chain) can form a cocomplex via interprotein docking. This mechanism can be used in vitro for efficient electron transfer from an electrode to the RC in a bio-photoelectrochemical device. Hence, the success rate in coupling RCs to cyt c is of great importance for practical applications in the future. In this work, we use an electrochemical transistor to study the binding of the RC to cytochrome. The shift in the transistor threshold voltage was measured in the dark and under illumination to estimate the density of cytochrome and coupled RCs on the gate of the transistor. The results show that ~33% of the cyt cs on the transistor gate were able to effectively couple with RCs. Due to the high sensitivity of the transistor, the approach can be used to make photosensors for detecting low light intensities.


Specific antibodies and heterologous antigensin monofactor sera.
A concentrated monofactor serum 9 (Wellcome lot K 8028) precipitated against proteins from 2 different strains of Salmonella enteritidis and from a strain of S. dublin, as well as against the proteinic moiety of the somatic antigen from S. typhi 0 901; no polysaccharide from the strains, sharing factor 9, precipitated against this serum. A concentrated monofactor serum 20 (Wellcome lot K 6733) precipitated against the proteins from S. emek (8, 20), but not against its polysaccharide. A monofactor serum 8 (Wellcome lot K 7801), different from a lot previously analysed (Wellcome lot K 6860), precipitated against the same proteins as the previous lot, but, in addition, precipitated strongly against the polysaccharide of S, newport (6.8) and weakly with the polysaccharide of S. emek too. According to these and previous results, it is not clear what sort of antibodies responsible for cross-agglutination are absorbed by the heterologous strains used in the operations. Since more often than not antipolysaccharide antibodies were not found in concentrated monofactor sera, it may be that just the antipolysaccharides. All the monofactor sera so far analysed (Wellcome) 1,2,4,5,8,9,20 are full of proteins left by the bacteria used for absorptions; due to these proteins, the presence of which may be meaningless for the agglutinations, strong precipitations in agar-gel were obtained between monofactor sera and different antibacterial and anti-protein sera containing antibodies induced against the corresponding free proteins.


Inventory development for perfluorooctane sulfonic acid (PFOS) in Turkey: challenges to control chemicals in articles and products.
Perfluorooctane sulfonic acid (PFOS) and related substances have been listed as persistent organic pollutants (POPs) in the Stockholm Convention. Countries which have ratified the Convention need to take appropriate actions to control PFOS use and release. This study compiles and enhances the findings of the first inventory of PFOS and related substances use in Turkey conducted within the frame of the Stockholm Convention National Implementation Plan (NIP) update. The specific Harmonized Commodity Description and Coding System (Harmonized System (HS)) codes of imported and exported goods that possibly contain PFOS and 165 of Chemical Abstracts Service (CAS) numbers of PFOS-related substances were assessed for acquiring information from customs and other authorities. However, with the current approaches available, no useful information could be compiled since HS codes are not specific enough and CAS numbers are not used by customs. Furthermore, the cut-off volume in chemical databases in Turkey and the reporting limit in the HS system (0.1 %) are too high for controlling PFOS. The attempt of modeling imported volumes by a Monte Carlo simulation did not also result in a satisfactory estimate, giving an upper-bound estimate above the global production volumes. The replies to questionnaires were not satisfactory, highlighting that an elaborated approach is needed in the communication with potentially PFOS-using stakeholders. The experience of the challenges of gathering information on PFOS in articles and products revealed the gaps of controlling highly hazardous substances in products and articles and the need of improvements.


The net contribution of rehabilitation to improvement in performance in patients with spinal cord lesions in five countries.
Change in ability realization reflects the main contribution of rehabilitation to improvement in the performance of daily activities in patients with spinal cord lesions (SCL). To assess the net effect of rehabilitation of patients with SCL and compare it between countries. We calculated the Spinal Cord Ability Realization Measurement Index (SCI-ARMI) and its change from admission to rehabilitation to discharge, for inpatients admitted to SCL units in five countries, between 2016 and 2019. We used chi-square tests, analysis of variance (ANOVA), McNemar's test, Pearson's correlations, and analysis of covariance (ANCOVA) to compare countries and patient groups and assess the relationships of various factors with SCI-ARMI gain during rehabilitation. The study included 218 inpatients (67% males, age 52 ± 17). In Brazil, Israel, Italy, Portugal, and Turkiye, respectively, SCI-ARMI gain was 2 (SD = 15), 19 (SD = 17), 31 (SD = 23), 13 (SD = 15), and 16 (SD = 12). Yet, after controlling for admission SCI-ARMI and the time from SCL onset to the examination, the effect of the country on ability realization gain was found non-significant (P = 0.086). The study confirmed that rehabilitation makes a net contribution to improvement in performance in patients with SCL, beyond the contribution of neurological recovery. After controlling for affecting factors, this contribution was quite similar in the participating units from different countries.