Prolonged mild hypothermia after experimental hypothermic circulatory arrest in a chronic porcine model.
We sought to evaluate the potential efficacy of prolonged mild hypothermia after hypothermic circulatory arrest. Twenty pigs, after a 75-minute period of hypothermic circulatory arrest, were randomly assigned to be rewarmed to 37 degrees C (normothermia group) or to 32 degrees C and kept at that temperature for 14 hours from the start of rewarming (hypothermia group). The 7-day survival was 30% in the hypothermia group and 70% in the normothermia group (P =.08). The hypothermia group had poorer postoperative behavioral scores than the normothermia group. Prolonged hypothermia was associated with lower oxygen extraction and consumption rates and higher mixed venous oxygen saturation levels during the first hours after hypothermic circulatory arrest. Decreased cardiac index, lower pH, and higher partial pressure of carbon dioxide were observed in the hypothermia group. There was a trend for beneficial effect of prolonged hypothermia in terms of lower brain lactate levels until the 4-hour interval and of intracranial pressure until the 10-hour interval. Postoperatively, total leukocyte and neutrophil counts were lower, and creatine kinase BB was significantly increased in the hypothermia group. At extubation, the hypothermia group had higher oxygen extraction rates and lower brain tissue oxygen tension. A 14-hour period of mild hypothermia after 75-minute hypothermic circulatory arrest seems to be associated with poor outcome. However, the results of this study suggest that mild hypothermia may preserve its efficacy when it is used for no longer than 4 hours, but the potentials of a shorter period of postoperative mild hypothermia still require further investigation.


Changes in relative histone abundance and heterochromatin in αA-crystallin and αB-crystallin knock-in mutant mouse lenses.
Understanding the mechanisms of cataract formation is important for age-related and hereditary cataracts caused by mutations in lens protein genes. Lens proteins of the crystallin gene families α-, β-, and γ-crystallin are the most abundant proteins in the lens. Single point mutations in crystallin genes cause autosomal dominant cataracts in multigenerational families. Our previous proteomic and RNAseq studies identified genes and proteins altered in the early stages of cataract formation in mouse models. Histones H2A, H2B, and H4 increase in abundance in αA- and αB-crystallin mutant mouse lenses and in cultured cells expressing the mutant form of αA-crystallin linked with hereditary cataracts. In this study of histones in mutant lenses, we extracted histones from adult mouse lenses from cryaa-R49C and cryab-R120G mutant knock-in mice. We characterized the histones using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF)-mass spectrometric analysis and gel electrophoresis and characterized the lens nucleus morphology using electron microscopy (EM). The relative abundance of histone H3 protein decreased in lenses from cryaa-R49C mutant mice and the relative abundance of histone H2 increased in these lenses. Electron microscopy of nuclei from cryaa-R49C-homozygous mutant mouse lenses revealed a pronounced alteration in the distribution of heterochromatin.


Dairy product consumption and its association with metabolic disturbance in a prospective study of urban adults.
The role of dairy foods and related nutrients in cardiometabolic health aetiology is poorly understood. We investigated longitudinal associations between the metabolic syndrome (MetS) and its components with key dairy product exposures. We used prospective data from a bi-racial cohort of urban adults (30-64 years at baseline (n 1371)), the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS), in Baltimore City, MD (2004-2013). The average of two 24-h dietary recalls measured 4-10 d apart was computed at baseline (V1) and follow-up (V2) waves. Annual rates of change (Δ) in dairy foods and key nutrients were estimated. Incident obesity, central obesity and the MetS were determined. Among key findings, in the overall urban adult population, both cheese and yogurt (V1 and Δ) were associated with an increased risk of central obesity (hazard ratio (HR) 1·13; 95 % CI 1·05, 1·23 per oz equivalent of cheese (V1); HR 1·21; 95 % CI 1·01, 1·44 per fl oz equivalent of yogurt (V1)]. Baseline fluid milk intake (V1 in cup equivalents) was inversely related to the MetS (HR 0·86; 95 % CI 0·78, 0·94), specifically to dyslipidaemia-TAG (HR 0·89; 95 % CI 0·81, 0·99), although it was directly associated with dyslipidaemia-HDL-cholesterol (HR 1·10; 95 % CI 1·01, 1·21). Furthermore, ΔCa and ΔP were inversely related to dyslipidaemia-HDL and MetS incidence, respectively, whereas Δdairy product fat was positively associated with incident TAG-dyslipidaemia and HDL-cholesterol-dyslipidaemia and the MetS. A few of those associations were sex and race specific. In sum, various dairy product exposures had differential associations with metabolic disturbances. Future intervention studies should uncover how changes in dairy product components over time may affect metabolic disorders.


Stretchable Piezoelectric Substrate Providing Pulsatile Mechanoelectric Cues for Cardiomyogenic Differentiation of Mesenchymal Stem Cells.
Ex vivo induction of cardiomyogenic differentiation of mesenchymal stem cells (MSCs) before implantation would potentiate therapeutic efficacy of stem cell therapies for ischemic heart diseases because MSCs rarely undergo cardiomyogenic differentiation following implantation. In cardiac microenvironments, electric pulse and cyclic mechanical strain are sequentially produced. However, no study has applied the pulsatile mechanoelectric cues (PMEC) to stimulate cardiomyogenic differentiation of MSCs ex vivo. In this study, we developed a stretchable piezoelectric substrate (SPS) that can provide PMEC to human MSCs (hMSCs) for cardiomyogenic differentiation ex vivo. Our data showed that hMSCs subjected to PMEC by SPS underwent promoted cardiac phenotype development: cell alignment and the expression of cardiac markers (i.e., cardiac transcription factors, structural proteins, ion channel proteins, and gap junction proteins). The enhanced cardiac phenotype development was mediated by the upregulation of cardiomyogenic differentiation-related autocrine factor expression, focal adhesion kinase, and extracellular signal-regulated kinases signaling pathways. Thus, SPS providing electrical and mechanical regulation of stem cells may be utilized to potentiate hMSC therapies for myocardial infarction and provide a tool for the study of stem cell biology.


Residential tap water contamination following the Freedom Industries chemical spill: perceptions, water quality, and health impacts.
During January 2014, an industrial solvent contaminated West Virginia's Elk River and 15% of the state population's tap water. A rapid in-home survey and water testing was conducted 2 weeks following the spill to understand resident perceptions, tap water chemical levels, and premise plumbing flushing effectiveness. Water odors were detected in all 10 homes sampled before and after premise plumbing flushing. Survey and medical data indicated flushing caused adverse health impacts. Bench-scale experiments and physiochemical property predictions showed flushing promoted chemical volatilization, and contaminants did not appreciably sorb into cross-linked polyethylene (PEX) pipe. Flushing reduced tap water 4-methylcyclohexanemethanol (4-MCHM) concentrations within some but not all homes. 4-MCHM was detected at unflushed (<10 to 420 μg/L) and flushed plumbing systems (<10 to 96 μg/L) and sometimes concentrations differed among faucets within each home. All waters contained less 4-MCHM than the 1000 μg/L Centers for Disease Control drinking water limit, but one home exceeded the 120 μg/L drinking water limit established by independent toxicologists. Nearly all households refused to resume water use activities after flushing because of water safety concerns. Science based flushing protocols should be developed to expedite recovery, minimize health impacts, and reduce concentrations in homes when future events occur.


PKCzeta regulates TNF-alpha-induced activation of NADPH oxidase in endothelial cells.
Although oxidant generation by NADPH oxidase is known to play an important role in signaling in endothelial cells, the basis of activation of NADPH oxidase is incompletely understood. The atypical isoform of protein kinase C, PKCzeta, has been implicated in the mechanism of tumor necrosis factor-alpha (TNF-alpha)-induced oxidant generation in endothelial cells; thus, in the present study, we have addressed the role of PKCzeta in regulating NADPH oxidase function. We showed by immunoblotting and confocal microscopy the presence of the major cytosolic NADPH oxidase subunits, p47(phox) and membrane-bound gp91(phox) in human pulmonary artery endothelial (HPAE) cells. TNF-alpha failed to activate oxidant generation in lung vascular endothelial cells derived from p47(phox-/-) and gp91(phox-/-) mice, indicating the requirement of NADPH oxidase in mediating the oxidant generation in endothelial cells. Stimulation of HPAE cells with TNF-alpha resulted in the phosphorylation of p47(phox) and its association with gp91(phox). Inhibition of PKCzeta by multiple pharmacological and genetic approaches prevented the TNF-alpha-induced phosphorylation of p47(phox), and its translocation to the membrane. PKCzeta was shown to colocalize with p47(phox), and inhibition of PKCzeta activation prevented the interaction of p47(phox) with gp91(phox) induced by TNF-alpha. Furthermore, inhibition of association of p47(phox) with gp91(phox) prevented the oxidant generation in endothelial cells. These data demonstrate a novel function of PKCzeta in signaling oxidant generation in endothelial cells by the activation of NADPH oxidase, which may be important in mediating endothelial activation responses.


Beneficial effects of ginkgetin on improving nonalcoholic steatohepatitis characterized by bulk and single-cell RNA sequencing analysis.
Background and aims: Nonalcoholic steatohepatitis (NASH) has become one of the major causes of cirrhosis and liver failure. However, there are currently no approved medications for managing NASH. Our study was designed to assess the effects of ginkgetin on NASH and the involved mechanisms. Methods: We constructed a mouse model of NASH by high-fat diet for 24 weeks. The effects of ginkgetin on NASH were evaluated by histological study, Western blot, and biochemical analysis. RNA Sequencing (RNA-Seq) analysis was used to investigate the alteration in gene expression and signaling pathways at bulk and single-cell levels. Results: Administration of ginkgetin resulted in a marked improvement in hepatic lipid accumulation, inflammation, and fibrosis in the NASH model. And these results were supported by bulk RNA-Seq analysis, in which the related signaling pathways and gene expression were markedly downregulated. Furthermore, single-cell RNA-Seq (scRNA-Seq) analysis revealed that the effects of ginkgetin on NASH were associated with the reprogramming of macrophages, hepatic stellate cells, and endothelial cells. Especially, ginkgetin induced a marked decrease in macrophages and a shift from pro-inflammatory to anti-inflammatory phenotype in NASH mice. And the NASH-associated macrophages (NAMs), which emerge during NASH, were also significantly downregulated by ginkgetin. Conclusion: Ginkgetin exhibits beneficial effects on improving NASH, supported by bulk and single-cell RNA-Seq. Our study may promote pharmacological therapy for NASH and raise the existent understanding of NASH.


Studies with bromocriptine. Part 1. "On-off" phenomena.
A dopaminergic agonist, bromocriptine, has been studied in patients with idiopathic parkinsonism complicated by severe "on-off" phenomena induced by levodopa. In a "blind" self-evaluating within-patient comparison, fluctuations in clinical state still occurred when levodopa (with or without carbidopa) was replaced with bromocriptine, but they were significantly reduced in frequency. The observation that on-off phenomena can be induced by bromocriptine complicates interpretation of these episodes in terms of pharmacokinetics of levodopa. There may be variations in receptor sensitivity or alterations in the influence of unidentified neurophysiologic mechanisms that modulate striatal output.


Stratified response to environmental stress in a polar lichen characterized with FT-Raman microscopic analysis.
The role of Antarctic epilithic lichens in the primary colonization of rocks and in the formation of soils is receiving attention because of the production of the stress-protective biochemicals needed to combat radiation, desiccation and extremes of temperature. Raman microscopy has been used here to study the encrustations produced at the interface between the rock substratum and Buellia spp. lichen thalli; in addition to whewellite, calcium oxalate monohydrate, the presence of weddellite, the metastable dihydrate form, was confirmed in the encrustations. An unusual pigmentation of the rock surface found on detachment of the lichen growths is identified as beta-carotene from its characteristic Raman bands at 1525, 1191, 1157 and 1003 cm(-1); normally, beta-carotene, which has been identified as a UV-radiation protectant, is found at the exposed upper surface of the biological organism. The interface between the detached lichen thalli and the rock also contains whewellite as the sole biomineralization product--which suggests a possible strategy for the formulation of weddelite in the growing Buellia spp. colony as an anti-desiccant.


[Head measurements of 153 2-year-old and 3-year-old children from Trnava and its surrounding region].
In the years 1990-1991 the authors performed an antropometric examination in children (total 153) from the district of Trnava. The antropometric examination consisted of the cefalometric minimum composed of 10 parameters of neurocranium and splanchnocranium. The acquired results were compared with dates which originated in the period preceding the last two decades. In the group of children from the Trnava district it was discovered that the cephalic index had been reduced. The authors supposed that the positioning of infants during the first month of life to affect the configuration of the head. (Tab. 8, Fig. 1, Ref. 14.)


Evaluation of single liquid primers with organic sulfur compound for bonding between indirect composite material and silver-palladium-copper-gold alloy.
The purpose of this study was to evaluate the effect of primers on bonding between a silver-palladium-copper-gold alloy and an indirect composite material. Cast disks were air-abraded with alumina, conditioned with one of five primers (Alloy Primer, Luna-Wing Primer, Metal Primer II, Metaltite, M.L. Primer), and bonded with a light-activated indirect composite. Shear bond strengths were determined after 20,000 times of thermocycling. The results showed that four of the primers, except the Luna-Wing Primer, were effective in enhancing the bond strength as compared with the unprimed control group. Of these four primers, Alloy Primer, Metal Primer II, and M.L. Primer exhibited significantly greater bond strengths. It can be concluded that the effectiveness of primers varies considerably according to the organic sulfur compounds added to the solvent, and that care must be taken in selecting priming agents for bonding the composite material and the silver-palladium-copper-gold alloy.


Synthesis of Sr2Si5N8:Ce3+ phosphors for white LEDs via an efficient chemical vapor deposition [corrected].
Novel chemical vapor deposition (CVD) process was successfully developed for the growth of Sr2Si5N8:Ce3+ phosphors with elevated luminescent properties. Metallic strontium was used as a vapor source for producing Sr3N2 vapor to react with Si3N4 powder via a homogeneous gas-solid reaction. The phosphors prepared via the CVD process showed high crystallinity, homogeneous particle size ranging from 8 to 10 μm, and high luminescence properties. In contrast, the phosphors prepared via the conventional solid-state reaction process exhibited relative low crystallinity, non-uniform particle size in the range of 0.5-5 μm and relatively lower luminescent properties than the phosphors synthesized via the CVD process. Upon the blue light excitation, Sr2-xCexSi5N8 phosphors exhibited a broad yellow band. A red shift of the emission band from 535 to 556 nm was observed with the increment in the doping amount of Ce3+ ions from x = 0.02 to x = 0.10. The maximum emission was observed at x = 0.06, and the external and internal quantum efficiencies were calculated to be 51% and 71%, respectively. Furthermore, the CVD derived optimum Sr1.94Ce0.06Si5N8 phosphor exhibited sufficient thermal stability for blue-LEDs and the activation energy was calculated to be 0.33 eV. The results demonstrate a potential synthesis process for nitride phosphors suitable for light emitting diodes.


The effect of vibration frequency and amplitude on biofouling deterrence.
The use of vibration is proposed as a means of controlling the settlement of marine fouling organisms. In this study, panels with embedded lead zirconate titanate, known as PZT, were placed in the field over 3 months. The panels were vibrated at different velocity levels at frequencies between 70 and 445 Hz. It was found that barnacles (Amphibalanus variegatus Darwin and Elminius sp.) were the only fouling organisms affected by the applied vibration, and these organisms settled in significantly lower numbers when the plates were excited at specific frequencies and amplitudes. Panels vibrating at relatively higher frequencies, greater than 260 Hz, exhibited reduced barnacle settlement, whilst lower frequencies in the 70-100 Hz range had little or no effect. The settlement of other fouling organisms such as tubeworms, bryozoans, ascidians and algae did not appear to be affected by the applied excitation. The experimental results showed that increasing the velocity amplitude of vibration was a contributing factor in inhibiting barnacle settlement.


Type I Non-ST Segment Elevation Myocardial Infarction (NSTEMI) Followed by Type II in a Young Patient With Fibromuscular Dysplasia (FMD) Presented With Hypertensive Emergency: A Case Report.
This article presents a case report highlighting the association between fibromuscular dysplasia (FMD) and acute myocardial infarction in a 25-year-old female patient with multiple cardiovascular comorbidities. Initially presenting with a hypertensive emergency, the patient subsequently developed acute coronary syndrome. MRI revealed irregular narrowing of the bilateral renal arteries, consistent with a diagnosis of FMD. Further evaluation through cardiac catheterization confirmed 95% stenosis of the mid-circumflex artery, necessitating percutaneous coronary intervention (PCI). Fibromuscular dysplasia has been frequently reported in conjunction with coronary artery dissection leading to acute coronary syndrome, especially in young females. Here, we describe the case of FMD without any coronary artery dissection. The presence of FMD highlights the need for comprehensive evaluation and management in patients with multiple cardiovascular risk factors. The recognition of FMD as an underlying pathology in acute myocardial infarction is crucial for appropriate intervention strategies. In this particular case, PCI was successfully performed to address the significant stenosis of the mid-circumflex artery. These findings emphasize the importance of considering FMD as a potential contributing factor in young patients presenting with acute coronary syndrome, particularly in the context of renal artery involvement. Increased awareness among healthcare providers regarding the association between FMD and acute myocardial infarction can aid in prompt diagnosis, appropriate management, and improved patient outcomes.


CEACAM1 in Liver Injury, Metabolic and Immune Regulation.
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a transmembrane glycoprotein that is expressed on epithelial, endothelial and immune cells. CEACAM1 is a differentiation antigen involved in the maintenance of epithelial polarity that is induced during hepatocyte differentiation and liver regeneration. CEACAM1 regulates insulin sensitivity by promoting hepatic insulin clearance, and controls liver tolerance and mucosal immunity. Obese insulin-resistant humans with non-alcoholic fatty liver disease manifest loss of hepatic CEACAM1. In mice, deletion or functional inactivation of CEACAM1 impairs insulin clearance and compromises metabolic homeostasis which initiates the development of obesity and hepatic steatosis and fibrosis with other features of non-alcoholic steatohepatitis, and adipogenesis in white adipose depot. This is followed by inflammation and endothelial and cardiovascular dysfunctions. In obstructive and inflammatory liver diseases, soluble CEACAM1 is shed into human bile where it can serve as an indicator of liver disease. On immune cells, CEACAM1 acts as an immune checkpoint regulator, and deletion of Ceacam1 gene in mice causes exacerbation of inflammation and hyperactivation of myeloid cells and lymphocytes. Hence, hepatic CEACAM1 resides at the central hub of immune and metabolic homeostasis in both humans and mice. This review focuses on the regulatory role of CEACAM1 in liver and biliary tract architecture in health and disease, and on its metabolic role and function as an immune checkpoint regulator of hepatic inflammation.


[The effect of immunotherapy and hyperthermia on patients with advanced or recurrent breast cancer].
We treated 172 patients with advanced or recurrent breast cancer using hyperthermia or immunotherapy between July 2005 and September 2012. In these patients, standard therapy showed no results, or it was refused. Clinical benefit( complete response [CR], partial response[PR], and long stable disease [SD] for more than 6 months) was observed in 30 patients( 17.4%), including CR in 5 patients. The effective rate of immunotherapy increased from 7.7% to 26.0% using hyperthermia. The effective rate of hyperthermia was only 5.1%. The standard therapy had not been altered in 23 of the 30 patients in whom clinical benefit was observed. Thus, immunotherapy or hyperthermia had benefited these 23 patients. Of the 23 effectively treated patients, skin or regional lymph node metastases disappeared in 3 patients treated with hyperthermia alone, and lung metastases disappeared and carcinomatous pleuritis improved in 1 patient treated with immunotherapy alone. In the remaining 19 effectively treated patients, multiple metastases were observed in important solid organs such as the liver, lung, bone, and brain. Combined hyperthermia and immunotherapy was used to treat these 19 patients to good effect.


Aharonov-Bohm interference in neutral excitons: effects of built-in electric fields.
We report a comprehensive discussion of quantum interference effects due to the finite structure of neutral excitons in quantum rings and their first experimental corroboration observed in the optical recombinations. The signatures of built-in electric fields and temperature on quantum interference are demonstrated by theoretical models that describe the modulation of the interference pattern and confirmed by complementary experimental procedures.


Recommendations for the anticoagulation of pregnant patients with mechanical heart valves.
The management of pregnant patients with mechanical heart valves remains challenging because there are no large randomised studies to provide guidelines for effective anticoagulant therapy. Both vitamin K antagonists and heparins may be associated with maternal and foetal adverse events. The Southern African Society of Thrombosis and Haemostasis reviewed available literature and comprehensive evidence-based guidelines for the anticoagulation of pregnant patients with mechanical heart valves. A draft document was produced and revised by consensus agreement. The guidelines were adjudicated by independent international experts to avoid local bias. We present concise, practical guidelines for the clinical management of pregnant patients with mechanical heart valves. Recommendations reflect current best practice which will hopefully lead to improved anticoagulation practice in this select group of high risk patients.


Benign epithelial inclusions in axillary lymph nodes: report of 18 cases and review of the literature.
The occurrence of various types of heterotopic epithelial structures in lymph nodes is a well-documented phenomenon. Here, we report on the presence of such inclusions in axillary lymph nodes. A total of 18 cases were identified. All patients were women, their ages ranging from 32 to 79 years (median, 57 y). Thirteen patients had concomitant or antecedent breast abnormalities, and 12 of them had undergone nodal sampling for staging purposes. The other 5 patients had noted enlarging axillary masses, with no clinical evidence of previous or concomitant breast or genital tract pathology. We classified the nodal inclusions on morphologic grounds into 3 main categories: those composed exclusively of glandular structures (glandular-type inclusions; 10 cases, 56%); those made up only of squamous cysts (squamous-type inclusions; 2 cases, 11%); and those containing both glandular and squamous epithelia (mixed glandular-squamous-type inclusions; 6 cases, 33%). We speculate about the possible mechanism for the migration of the epithelial cells into the lymph nodes, discuss the modifications that they may later undergo as a result of local and systemic factors, and consider the differential diagnosis with other conditions, particularly with metastatic well-differentiated breast carcinoma.


Treatment of diarrhea.
Diarrheal diseases remain a leading cause of morbidity and mortality in the developing countries and represent at least a nuisance in the industrialized world. Fluid and electrolyte replacement, particularly via oral rehydration, is the mainstay of therapy for the prevention and treatment of dehydration associated with these illnesses. Antibiotics are not indicated for the majority of enteric infections, and their promiscuous use can contribute to the escalating prevalence of bacterial resistance worldwide. Used judiciously, however, antimicrobial agents can ameliorate illness or curtail pathogen excretion and spread of disease, or both, in some diarrheal infections. Antimicrobial agents are indicated for shigellosis, cholera, traveler's diarrhea, amebiasis, and giardiasis. They are indicated in some specific circumstances to treat infections caused by Campylobacter, some categories of diarrheagenic E. coli, C. difficile, nontyphoidal Salmonella, and certain Vibrionaceae. Few adjunctive treatments provide proven benefit without risk of adverse reactions; most offer no advantage over placebo, and their general use is not encouraged.


The ultimate in facial rejuvenation: the mid-facelift.
Facial rejuvenation in 2001 encompasses a plethora of areas. Facial rejuvenation begins with excellent skin health, incorporating appropriate surgical procedures and an overall holistic approach to facial surgery. Appearance is important. Aesthetic surgery, particularly of the face, offers women the chance to turn back the hands of time.


Designing a physical activity intervention for children with asthma: a qualitative study of the views of healthcare professionals, parents and children with asthma.
Qualitative methods were used to examine: (1) the attitudes of health professionals to promoting physical activity for children with asthma; (2) reasons why children with asthma are less active and (3) how a physical activity programme for children with asthma could be designed. Semistructured interviews were conducted with health professionals, children with asthma and their parents between October 2015 and March 2016. Interviews were transcribed verbatim and thematically analysed. Primary and secondary care in Bristol (UK). Interviews were held with 8 primary care practitioners (5 general practitioners, 2 nurse practitioners and 1 practice nurse), 9 parent-child dyads (2 fathers, 7 mothers, 6 sons, 3 daughters) of children aged 6-7 who had asthma and 4 secondary care professionals (2 respiratory consultants, 2 specialist nurses). Health professionals reported that physical activity was beneficial for children with asthma and if managed appropriately, children with asthma could be as active as children without asthma. Current promotion of physical activity for children with asthma was limited and restricted by NHS staff time, access to inhalers at school and a lack of parental knowledge. Potentially important components of a new programme include parental education on the possibilities of activity for children with asthma and the difference between exercise-induced breathlessness and asthma symptoms. Other important elements include how to use inhalers as a preventive measure, coping with exacerbations and practical solutions (such as clearing sputum), managing transitions from warm to cold climates and general symptom control. There is a need to build on current asthma programmes to increase the support for children with asthma to be physically active. Future programmes could consider working more closely with schools, increasing parental knowledge and providing children with practical support to help be physically active.


[Challenges of long-term follow up for Hodgkin lymphoma survivors].
CHALLENGES OF LONG-TERM FOLLOW UP FOR HODGKIN LYMPHOMA SURVIVORS. Challenge of Hodgkin lymphoma care is to obtain a high level of curability and minimize acute toxicities and long-term complications of chemotherapy and radiotherapy. A specific long-term multi-disciplinary follow-up should be organize with an important place of general practitioners. The follow-up concerns the risk of second cancer especially breast cancer and treatment-related cardiovascular diseases. In addition, a careful attention concerns some possible negative effects of the disease and treatments on psychosocial status and quality of life of Hodgkin lymphoma survivors.


Perioperative management in children with sickle cell disease undergoing laparoscopic surgery.
The aim of this study was to evaluate our experience with laparoscopic surgery in children with sickle cell disease. A retrospective chart review was performed to analyze the indication for surgery, perioperative management, surgical technique, complications, duration of hospitalization, and outcome. One pediatric surgeon performed all procedures. Thirteen children underwent laparoscopic surgery for the following indications: symptomatic cholelithiasis/cholecystitis in 9; recurrent splenic sequestration in 3; and hypersplenism/symptomatic cholelithiasis in 1. The 7 boys and 6 girls had a median age of 7.8 years. Patients undergoing splenectomy only were younger than those undergoing cholecystectomy (median age, 3.6 years versus 11.5 years, respectively). Four children underwent endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy because of common bile duct dilatation and stones. Twelve patients received packed red blood cell transfusions prior to surgery. The median operative time was 150 minutes, and the median hospitalization was 3 days. Four patients suffered postoperative complications (2 with acute chest syndrome, 1 with recurrent abdominal pain, and 1 with priapism). The patient with abdominal pain was found to have a retained stone in the common bile duct, which was retrieved via endoscopic retrograde cholangiopancreatography and sphincterotomy. All complications resolved with medical management. Laparoscopic surgery is safe in children with sickle cell disease. Meticulous attention to perioperative management, transfusion guidelines, and pulmonary care may decrease the incidence of acute chest syndrome.


Scaling Up Nature: Large Area Flexible Biomimetic Surfaces.
The fabrication and advanced function of large area biomimetic superhydrophobic surfaces (SHS) and slippery lubricant-infused porous surfaces (SLIPS) are reported. The use of roll-to-roll nanoimprinting techniques enabled the continuous fabrication of SHS and SLIPS based on hierarchically wrinkled surfaces. Perfluoropolyether hybrid molds were used as flexible molds for roll-to-roll imprinting into a newly designed thiol-ene based photopolymer resin coated on flexible polyethylene terephthalate films. The patterned surfaces exhibit feasible superhydrophobicity with a water contact angle around 160° without any further surface modification. The SHS can be easily converted into SLIPS by roll-to-roll coating of a fluorinated lubricant, and these surfaces have outstanding repellence to a variety of liquids. Furthermore, both SHS and SLIPS display antibiofouling properties when challenged with Escherichia coli K12 MG1655. The current article describes the transformation of artificial biomimetic structures from small, lab-scale coupons to low-cost, large area platforms.


S100A9 is indispensable for survival of pneumococcal pneumonia in mice.
S100A8/A9 has important immunomodulatory roles in antibacterial defense, but its relevance in focal pneumonia caused by Streptococcus pneumoniae (S. pneumoniae) is understudied. We show that S100A9 was significantly increased in BAL fluids of patients with bacterial but not viral pneumonia and correlated with procalcitonin and sequential organ failure assessment scores. Mice deficient in S100A9 exhibited drastically elevated Zn2+ levels in lungs, which led to bacterial outgrowth and significantly reduced survival. In addition, reduced survival of S100A9 KO mice was characterized by excessive release of neutrophil elastase, which resulted in degradation of opsonophagocytically important collectins surfactant proteins A and D. All of these features were attenuated in S. pneumoniae-challenged chimeric WT→S100A9 KO mice. Similarly, therapy of S. pneumoniae-infected S100A9 KO mice with a mutant S100A8/A9 protein showing increased half-life significantly decreased lung bacterial loads and lung injury. Collectively, S100A9 controls central antibacterial immune mechanisms of the lung with essential relevance to survival of pneumococcal pneumonia. Moreover, S100A9 appears to be a promising biomarker to distinguish patients with bacterial from those with viral pneumonia. Trial registration: Clinical Trials register (DRKS00000620).


A frequency-modulated continuous-wave reflectometer for the Lithium Tokamak Experiment.
The frequency-modulated continuous-wave reflectometer on LTX (Lithium Tokamak Experiment) and the data analysis methods used for determining electron density profiles are described. The diagnostic uses a frequency range of 13.1-33.5 GHz, for covering a density range of 0.21-1.4×1013 cm-3 (in O-mode polarization) with a time resolution down to 8 μs. The design of the diagnostic incorporates the concept of an "optimized" source frequency sweep, which minimizes the large variation in the intermediate frequency signal due to a long dispersive transmission line. The quality of the raw data is dictated by the tuning characteristics of the microwave sources, as well as the group delay ripple in the transmission lines, which can generate higher-order nonlinearities in the frequency sweep. Both effects are evaluated for our diagnostic and best practices are presented for minimizing "artifacts" generated in the signals. The quality of the reconstructed profiles is also improved using two additional data analysis methods. First, the reflectometer data are processed as a radar image, where clutter due to echoes from the wall and backscattering from density fluctuations can be easily identified and removed. Second, a weighed least-squares lamination algorithm POLAN (POLynomial ANalysis) is used to reconstruct the electron density profile. Examples of density profiles in LTX are presented, along with comparisons to measurements from the Thomson scattering and the λ = 1 mm interferometer diagnostics.


Vascularized adipose tissue grafts from human mesenchymal stem cells with bioactive cues and microchannel conduits.
Vascularization is critical to the survival of engineered tissues. This study combined biophysical and bioactive approaches to induce neovascularization in vivo. Further, we tested the effects of engineered vascularization on adipose tissue grafts. Hydrogel cylinders were fabricated from poly(ethylene glycol) diacrylate (PEG) in four configurations: PEG alone, PEG with basic fibroblast growth factor (bFGF), microchanneled PEG, or both bFGF-adsorbed and microchanneled PEG. In vivo implantation revealed no neovascularization in PEG, but substantial angiogenesis in bFGF-adsorbed and/or microchanneled PEG. The infiltrating host tissue consisted of erythrocyte-filled blood vessels lined by endothelial cells, and immunolocalized to vascular endothelial growth factor (VEGF). Human mesenchymal stem cells were differentiated into adipogenic cells, and encapsulated in PEG with both microchanneled and adsorbed bFGF. Upon in vivo implantation subcutaneously in immunodeficient mice, oil red O positive adipose tissue was present and interspersed with interstitial fibrous (IF) capsules. VEGF was immunolocalized in the IF capsules surrounding the engineered adipose tissue. These findings suggest that bioactive cues and/or microchannels promote the genesis of vascularized tissue phenotypes such as the tested adipose tissue grafts. Especially, engineered microchannels may provide a generic approach for modifying existing biomaterials by providing conduits for vascularization and/or diffusion.


An automated method for gridding and clustering-based segmentation of cDNA microarray images.
Microarrays are widely used to quantify gene expression levels. Microarray image analysis is one of the tools, which are necessary when dealing with vast amounts of biological data. In this work we propose a new method for the automated analysis of microarray images. The proposed method consists of two stages: gridding and segmentation. Initially, the microarray images are preprocessed using template matching, and block and spot finding takes place. Then, the non-expressed spots are detected and a grid is fit on the image using a Voronoi diagram. In the segmentation stage, K-means and Fuzzy C means (FCM) clustering are employed. The proposed method was evaluated using images from the Stanford Microarray Database (SMD). The results that are presented in the segmentation stage show the efficiency of our Fuzzy C means-based work compared to the two already developed K-means-based methods. The proposed method can handle images with artefacts and it is fully automated.


Perceived difficulty in the theory of planned behaviour: perceived behavioural control or affective attitude?
A study was conducted to explore (a) the dimensional structure of perceived behavioural control (PBC), (b) the conceptual basis of perceived difficulty items, and (c) how PBC components and instrumental and affective attitudes, respectively, relate to intention and behaviour. The material stemmed from a two-wave study of Norwegian graduate students (N = 227 for the prediction of intention and N = 110 for the prediction of behaviour). Data were analysed using confirmatory factor analysis (CFA) and multiple regression by the application of structural equation modelling (SEM). CFA suggested that PBC could be conceived of as consisting of three separate but interrelated factors (perceived control, perceived confidence and perceived difficulty), or as two separate but interrelated factors representing self-efficacy (measured by perceived difficulty and perceived confidence or by just perceived confidence) and perceived control. However, the perceived difficulty items also overlapped substantially with affective attitude. Perceived confidence was a strong predictor of exercise intention but not of recycling intention. Perceived control, however, was a strong predictor of recycling intention but not exercise intention. Affective attitudes but not instrumental attitudes were identified as substantial predictors of intentions. The findings suggest that at least under some circumstances it may be inadequate to measure PBC by means of perceived difficulty. One possible consequence may be that the role of PBC as a predictor of intention is somewhat overestimated, whereas the role of (affective) attitude may be similarly underestimated.


[Role of master transcriptional factor Prox-1 in lymphatic endothelial differentiation of Kaposiform hemangioendothelioma].
Objective: To analyze the clinical and pathological features of Kaposiform hemangioendothelioma (KHE), and to investigate the role of master transcriptional factor Prox-1 in the regulation of lymphatic differentiation. Methods: Nine cases of KHE (during the period from October 2009 to June 2016) were collected with clinical and pathological data. H&E stained section review and immunohistochemietry using the Dako EnVision method were performed. Results: There were 6 female and 3 male patients with age ranging from 2 months to 8 years (median 3 years and 4 months). The patients presented with either single subcutaneous soft tissue mass, or bone tumors, with the duration of disease onset ranging from 1 month to 1 year. The sites of involvement included the skins of neck (2 cases), nose root (1 case), inguinal (1 case), thigh root (1 case), humerus (2 cases), lumbar vertebrae(1 case), and mesentery (1 case). These tumors were histologically composed of nodules of densely packed spindle or ovoid cells and deformed small blood vessels in an invasive growth pattern. The tumor cells were immunohistochemically positive for both blood vessels and lymphatic endothelial markers, including Prox-1, the master transcriptional factor, and VEGFR-3. With followed-up from 1 to 60 months (median 26 months), two patients died of the disease, while the remaining patients were alive without recurrence. Conclusions: KHE is a rare vascular tumor with at least partial lymphatic endothelial differentiation, in which Prox-1 may act as a master regulator for such differentiation. KHE is an aggressive tumor of intermediate malignant potential, with local invasion and recurrence tendency, and long term follow-up is required.


Sweetener augmentation of serum triacylglycerol during a fat challenge test in humans.
High concentrations of fructose enhance postprandial lipemia following lipid loading whereas glucose exerts a negative or minimal effect. This study evaluated the effect of lower sweetener concentrations and the contribution of their sweetness level and palatability. At each of four test sessions, twelve male and ten female healthy adults ingested one of four milkshakes containing 108 g dairy cream alone or supplemented with 30 g fructose, 17.5 g glucose or 1 g aspartame. Blood samples were collected at baseline, two, four, six and eight hours after ingestion. Sensory discrimination tests were conducted after the last two sessions. Fructose and glucose led to 37% (p = 0.03) and 59% (p = 0.08) rises in triacylglycerol area under the curve (TG AUC) when compared to the plain milkshake, respectively. Although the sweetened shakes were equisweet and were more palatable than the plain shake, the TG rise after the aspartame milkshake did not differ from the plain milkshake. These data indicate that low levels of glucose and fructose consumed with lipid enhance postprandial lipemia. Sweetness and palatability did not account for the effect.


Microbial availability of mercury: effective detection and organic ligand effect using a whole-cell bioluminescent bioreporter.
A luxCDABE-based genetically engineered bacterial bioreporter (Escherichia coli ARL1) was used to detect bioavailable ionic mercury (Hg(II)) and investigate the effects of humic acids and ethylenediaminetetraacetic acid (EDTA) on the bioavailability of mercury in E. c oli. Results showed that the E. c oli ARL1 bioreporter was sensitive to mercury, with a detection limit of Hg(II) of 0.5 µg/L and a linear dose/response relationship up to 2000 µg Hg(II)/L. Humic acids and EDTA decreased the Hg(II)-induced bioluminescent response of strain ARL1, suggesting that the two organic ligands reduced the bioavailability of Hg(II) via complexation with Hg(II). Compared with traditional chemical methods, the use of E. c oli ARL1 is a cost-effective, rapid, and reliable approach for measuring aqueous mercury at very low concentrations and thus has potential for applications in field in situ monitoring.


Virus-induced double-membrane vesicles.
Many viruses that replicate in the cytoplasm compartmentalize their genome replication and transcription in specific subcellular microenvironments or organelle-like structures, to increase replication efficiency and protect against host cell defences. Recent studies have investigated the complex membrane rearrangements induced by diverse positive-strand RNA viruses, which are of two morphotypes : membrane invagination towards the lumen of the endoplasmic reticulum (ER) or other specifically targeted organelles and double-membrane vesicles (DMVs) formed by extrusion of the ER membrane. DMVs resemble small autophagosomes and the viruses inducing these intriguing organelles are known to promote autophagy, suggesting a potential link between DMVs and the autophagic pathway. In this review, we summarize recent findings concerning the biogenesis, architecture and role of DMVs in the life cycle of viruses from different families and discuss their possible connection to autophagy or other related pathways.


Insights from shotgun metagenomics into bacterial species and metabolic pathways associated with NAFLD in obese youth.
Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease and is often the precursor for more serious liver conditions such as nonalcoholic steatohepatitis and cirrhosis. Although the gut microbiome has been implicated in the development of NAFLD, the strong association of obesity with NAFLD and its effect on microbiome structure has made interpreting study outcomes difficult. In the present study, we examined the taxonomic and functional differences between the microbiomes of youth with obesity and with and without NAFLD. Shotgun metagenome sequencing was performed to profile the microbiomes of 36 subjects, half of whom were diagnosed with NAFLD using abdominal magnetic resonance imaging. Beta diversity analysis showed community-wide differences between the groups (p = 0.002). Specific taxonomic differences included increased relative abundances of the species Fusicatenibacter saccharivorans (p = 0.042), Romboutsia ilealis (p = 0.046), and Actinomyces sp. ICM47 (p = 0.0009), and a decrease of Bacteroides thetaiotamicron (p = 0.0002), in the NAFLD group as compared with the non-NAFLD group. At the phylum level, Bacteroidetes (p < 0.0001) was decreased in the NAFLD group. Functionally, branched-chain amino acid (p = 0.01343) and aromatic amino acid (p = 0.01343) synthesis pathways had increased relative abundances in the NAFLD group along with numerous energy use pathways, including pyruvate fermentation to acetate (p = 0.01318). Conclusion: Community-wide differences were noted based on NAFLD status, and individual bacterial species along with specific metabolic pathways were identified as potential drivers of these differences. The results of the present study support the idea that the NAFLD phenotype displays a differentiated microbial and functional signature from the obesity phenotype.


Mediators and mechanisms of immune checkpoint inhibitor-associated myocarditis: Insights from mouse and human.
The broad application of immune checkpoint inhibitors (ICIs) has led to significant gains in cancer outcomes. By abrogating inhibitory signals, ICIs promote T cell targeting of cancer cells but can frequently trigger autoimmune manifestations, termed immune-related adverse events (irAEs), affecting essentially any organ system. Among cardiovascular irAEs, immune-related myocarditis (irMyocarditis) is the most described and carries the highest morbidity. The currently recommended treatment for irMyocarditis is potent immunosuppression with corticosteroids and other agents, but this has limited evidence basis. The cellular pathophysiology of irMyocarditis remains poorly understood, though mouse models and human data have both implicated effector CD8+ T cells, some of which are specific for the cardiomyocyte protein α-myosin. While the driving molecular signals and transcriptional programs are not well defined, the involvement of chemokine receptors such as CCR5 and CXCR3 has been proposed. Fundamental questions regarding why only approximately 1% of ICI recipients develop irMyocarditis and why irMyocarditis carries a much worse prognosis than other forms of lymphocytic myocarditis remain unanswered. Further work in both murine systems and with human samples are needed to identify better tools for diagnosis, risk-stratification, and treatment.


Effects of eccentrically and concentrically biased training on mouse muscle phenotype.
The molecular adaptations specifically induced by different muscle contraction types have only been partially elucidated. We previously demonstrated that eccentric contractions in human quadriceps elicited proteome modifications that suggest a muscle fiber typology adaptation. We address this question in a more systematic way by examining here the effects of different running modes on the mouse muscle proteome and the muscle fiber typology. Male adult mice (C57BL6) were randomly divided into downhill running (DHR) (quadricipital eccentrically biased contractions), uphill running (UHR) (quadricipital concentrically biased contractions), and untrained control (CONT) groups. Running groups performed five training sessions on an inclined treadmill for 75 to 135 min · d(-1), and the quadriceps muscles were dissected 96 h after the last session. Muscle protein extracts of DHR and UHR groups (n = 4/group) were subjected to a two-dimensional difference in gel electrophoresis (2D-DIGE) analysis coupled with mass spectrometry. The assessment of fiber type, size, and number was performed on the rectus femoris of the three groups (n = 6/group) using myosin heavy chain immunohistochemistry. In the proteomic analysis, eight spots identified as the fast myosin heavy chain isoforms exhibited a lower abundance in DHR compared with UHR (P < 0.05, t-test). In contrast, adenosine triphosphate (ATP) synthase subunit α and tubulin β were more expressed in DHR (P < 0.05). A significant higher proportion of Type I and IIa fibers was found for DHR compared with UHR or CONT groups (P < 0.05, one-way ANOVA). Our data suggest that the eccentrically biased contractions in mice induced specific adaptations in protein expression and muscle fiber composition, which may reflect a more oxidative muscle phenotype. The differences in stress placed on the muscle between both trainings may be responsible for some unique adaptations resulting from the eccentrically biased training.


Epidermal fatty-acid-binding protein: a new circulating biomarker associated with cardio-metabolic risk factors and carotid atherosclerosis.
Epidermal fatty-acid-binding protein (E-FABP) is highly homologous to adipocyte FABP (A-FABP), which mediates obesity-related metabolic syndrome (MetS), diabetes and atherosclerosis in animals. Combined deficiency of E-FABP and A-FABP protects against the MetS and atherosclerosis in mice. This study investigated the association of serum E-FABP with cardio-metabolic risk factors and carotid atherosclerosis in humans. The presence of E-FABP in human plasma was detected by tandem mass spectrometry. Serum E-FABP levels, determined by an enzyme-linked immunosorbent assay in 479 Chinese subjects (age: 55.4 ± 13.5 years; M/F: 232/247), correlated positively (P < 0.05 to <0.001, age-adjusted) with parameters of adiposity, adverse lipid profiles, serum insulin, A-FABP, and C-reactive protein levels and were higher in subjects with the MetS (P < 0.001 vs. no MetS). The association of E-FABP with the MetS was independent of A-FABP. Furthermore, serum E-FABP correlated with carotid intima-media thickness (IMT; P < 0.001) and was independently associated with carotid IMT in men (adjusted P = 0.03). E-FABP is a new circulating biomarker associated with increased cardio-metabolic risk. It may contribute to the development of the MetS and carotid atherosclerosis in humans, independent of the effect of A-FABP.


Using fragment cocktail crystallography to assist inhibitor design of Trypanosoma brucei nucleoside 2-deoxyribosyltransferase.
The 1.8 A resolution de novo structure of nucleoside 2-deoxyribosyltransferase (EC 188.8.131.52) from Trypanosoma brucei (TbNDRT) has been determined by SADa phasing in an unliganded state and several ligand-bound states. This enzyme is important in the salvage pathway of nucleoside recycling. To identify novel lead compounds, we exploited "fragment cocktail soaks". Out of 304 compounds tried in 31 cocktails, four compounds could be identified crystallographically in the active site. In addition, we demonstrated that very short soaks of approximately 10 s are sufficient even for rather hydrophobic ligands to bind in the active site groove, which is promising for the application of similar soaking experiments to less robust crystals of other proteins.


Addressing the psychosocial and communication challenges posed by radiological/nuclear terrorism: key developments since NCRP Report No. 138.
One of the most innovative aspects of NCRP Report No. 138 (Management of Terrorist Incidents Involving Radioactive Material) was the high priority it accorded to psychosocial and communication issues. While previous discussions of radiological and nuclear terrorism had occasionally referred to these topics, NCRP Report No. 138 was the first report of its kind to recognize the profound challenges posed by these issues and to place them at the heart of preparedness and response efforts. In the years since the report's release, a host of important developments have taken place in relation to psychosocial and communication issues. This paper reviews key changes and advances in five broad areas: (1) training exercises, (2) policy and guidance development, (3) findings on hospital and clinician needs, (4) survey research on public perceptions of radiological terrorism, and (5) risk communication for radiological and nuclear terrorism situations. The article concludes with a discussion of continuing psychosocial and communication challenges, including critical areas needing further attention as the nation moves to meet the threat of terrorism involving radioactive materials.


Tableting Properties and Compression Models of Labisia pumila Tablets.
The tableting properties of Labisia pumila herbal powder, which is well known for its therapeutic benefits was investigated. The herbal powder was compressed into tablets using a stainless steel cylindrical uniaxial die of 13-mm- diameter with compaction pressures ranging from 7 to 25 MPa. Two feed weights, 0.5 and 1.0 g were used to form tablets. Some empirical models were used to describe the compressibility behavior of Labisia pumila tablets. The strength and density of tablets increased with increase in compaction pressure and resulted in reduction in porosity of the tablets. Smaller feeds, higher forces and increase in compaction pressure, contributed to more coherent tablets. These findings can be used to enhance the approach and understanding of tableting properties of Labisia pumila herbal powder tablets.


Management strategies for neoplastic and vascular brain lesions presenting during pregnancy: A series of 29 patients.
The occurrence of a brain tumor or intracranial vascular lesion during pregnancy is a rare event, but when it happens, it jeopardizes the lives of both the mother and infant. It also creates challenges of a neurosurgical, obstetric, and ethical nature. A multidisciplinary approach should be used for their care. Between 1986 and 2015, 12 pregnant women diagnosed with brain tumors and 17 women with intracranial vascular lesion underwent treatment at the Neurosurgery Department of the Servidores do Estado Hospital and Rede D'Or/São Luis. The Neurosurgery Department teamed up with Obstetrics Anesthesiology Departments in establishing the procedures. The patients' records, surgical descriptions, imaging studies, and histopathological material were reviewed. Among 12 patients presenting with brain tumors, there were neither operative mortality nor fetal deaths. Among the vascular lesions, aneurysm rupture was responsible for bleeding in 6 instances. Arteriovenous malformation was diagnosed in 7 patients. In this subgroup, the maternal and fetal mortality rates were 11.7% and 23.7%, respectively. We can assert that the association between a brain tumor and vascular lesions with pregnancy is a very unusual event, which jeopardizes both the lives of the mother and infant. It remains incompletely characterized due to the rare nature of these potentially devastating events. Knowing the exact mechanism responsible for the interaction of pregnancy and with these lesions will improve the treatment of these patients.


Case report of subacute presentation of tricuspid valve thrombus complicated by widespread bilateral pulmonary emboli: a multifactorial aetiology.
Right heart thrombus (RHTh) complicated by pulmonary embolism (PE) usually presents as a medical emergency with significant haemodynamic instability. However, less is known about subacute presentations. We present a 74-year-old haemodynamically stable gentleman with a 3-week history of mild pleuritic chest pain and exertional dyspnoea preceded by lower respiratory tract infection. Early trans-thoracic echocardiogram (TTE) revealed a 3 cm elongated tricuspid valve thrombus with right ventricular dysfunction, new-onset atrial fibrillation, and new-onset severe left ventricular impairment. Subsequent computed tomography pulmonary angiogram showed widespread bilateral pulmonary emboli with retrograde opacification of the hepatic veins. The RHTh successfully resolved with warfarin therapy with no further complications, and the patient was discharged on Day 8 of hospitalization. An early TTE is crucial in detecting the RHTh in patients suspected of PE and can significantly change the management compared with uncomplicated PE. The index of suspicion for PE and RHTh should remain high even in subacute cases.


Sensitivity analysis of stabilization pond system design parameters.
Two stabilization pond systems are examined. A sensitivity analysis is undertaken, aimed at investigating the influence of the pond depths on stabilization pond surface area and pond volume for the specific combination of temperature, wastewater characteristics and effluent requirements. The dependencies are presented in a functional form, allowing for the graphical solution of the unit pond volume, area, and hydraulic residence time as a function of the respective pond depths. Based on these graphs, designers can determine the most appropriate depth value for each type of pond that minimizes the required area or volume, or balances excavation versus land acquisition and floor lining costs, taking under consideration the topographic and other local characteristics of the site area.


Abdominal DCE-MRI reconstruction with deformable motion correction for liver perfusion quantification.
Abdominal dynamic contrast-enhanced (DCE) MRI suffers from motion-induced artifacts that can blur images and distort contrast-agent uptake curves. For liver perfusion analysis, image reconstruction with rigid-body motion correction (RMC) can restore distorted portal-venous input functions (PVIF) to higher peak amplitudes. However, RMC cannot correct for liver deformation during breathing. We present a reconstruction algorithm with deformable motion correction (DMC) that enables correction of breathing-induced deformation in the whole abdomen. Raw data from a golden-angle stack-of-stars gradient-echo sequence were collected for 54 DCE-MRI examinations of 31 patients. For each examination, a respiratory motion signal was extracted from the data and used to reconstruct 21 breathing states from inhale to exhale. The states were aligned with deformable image registration to the end-exhale state. Resulting deformation fields were used to correct back-projection images before reconstruction with view sharing. Images with DMC were compared to uncorrected images and images with RMC. DMC significantly increased the PVIF peak amplitude compared to uncorrected images (P << 0.01, mean increase: 8%) but not compared to RMC. The increased PVIF peak amplitude significantly decreased estimated portal-venous perfusion in the liver (P << 0.01, mean decrease: 8 ml/(100 ml·min)). DMC also removed artifacts in perfusion maps at the liver edge and reduced blurring of liver tumors for some patients. DCE-MRI reconstruction with DMC can restore motion-distorted uptake curves in the abdomen and remove motion artifacts from reconstructed images and parameter maps but does not significantly improve perfusion quantification in the liver compared to RMC.


Who makes alcohol policy? Science and policy networks 1950-2000.
This chapter examines the interaction between alcohol policy networks, ideological "frames" of understanding of the alcohol problem and the production and use of research evidence. The emergence and growth of policy networks and the production of research based "evidence" as the rationale for change is traced from the mid-nineteenth century over major shifts in understanding of the problem, from a "moral" model to a "disease" model to a "public health" approach and, finally, to an approach which brings together health and criminal justice perspectives. The chapter challenges policy discourse which presents a rational model of policy making supported by "scientific" research.


Tumor progression and angiogenesis: cathepsin B & Co.
Experimental and clinical evidence reveals that the growth of solid tumors is dependent on angiogenesis. Proteolytic enzymes such as plasminogen activators and matrix metalloproteinases have been implicated in this neovascularization. The role of lysosomal proteases in this process has yet to be explored. Increased expression of the lysosomal cysteine protease cathepsin B has been observed in many etiologically different tumors, including human brain, prostate, breast, and gastrointestinal cancers. Immunohistochemical and in situ histochemical studies have demonstrated expression of cathepsin B in neovessels induced during malignant progression of human glioblastoma and prostate carcinomas. In these two tumor types, neovessels stain strongly for cathepsin B compared with the normal microvasculature. As an initial point to elucidate whether cathepsin B is an important component of the angiogenic response in tumours, we analyzed expression of cathepsin B in endothelial cells during neovessel formation. We present evidence for strong immunostaining of cathepsin B in rat brain microvascular endothelial cells as they form capillary tubes in vitro. This finding is discussed within the general framework of the role of proteolytic enzymes in tumor invasion and angiogenesis.


[Current status of castration resistant prostate cancer basic research].
Recently, novel anti-androgen and CYP-17 inhibitor have been introduced in clinical practice and significance of androgen mediated pathway is re-acknowledged in basic research of castration resistant prostate cancer (CRPC). Generations of AR splicing variant and/or AR mutation, which result in ligand independent activation of AR, are still primary mechanism of acquiring castration resistance in addition to classical AR amplification. Chromosomal rearrangement through FOXA emerged as novel AR regulating mechanism. TMPRSS2-ERG gene fusion is one of the most prevalent signatures in CRPC. Regulation through non-coding miRNA also play critical role in AR mediated oncogenic pathways. Here we describe the classical and recent topics in basic research of CRPC.


Preventive role of exercise training in autonomic, hemodynamic, and metabolic parameters in rats under high risk of metabolic syndrome development.
High fructose consumption contributes to metabolic syndrome incidence, whereas exercise training promotes several beneficial adaptations. In this study, we demonstrated the preventive role of exercise training in the metabolic syndrome derangements in a rat model. Wistar rats receiving fructose overload in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) or kept sedentary (F) for 10 wk. Control rats treated with normal water were also submitted to exercise training (CT) or sedentarism (C). Metabolic evaluations consisted of the Lee index and glycemia and insulin tolerance test (kITT). Blood pressure (BP) was directly measured, whereas heart rate (HR) and BP variabilities were evaluated in time and frequency domains. Renal sympathetic nerve activity was also recorded. F rats presented significant alterations compared with all the other groups in insulin resistance (in mg · dl(-1) · min(-1): F: 3.4 ± 0.2; C: 4.7 ± 0.2; CT: 5.0 ± 0.5 FT: 4.6 ± 0.4), mean BP (in mmHG: F: 117 ± 2; C: 100 ± 2; CT: 98 ± 2; FT: 105 ± 2), and Lee index (in g/mm: F = 0.31 ± 0.001; C = 0.29 ± 0.001; CT = 0.27 ± 0.002; FT = 0.28 ± 0.002), confirming the metabolic syndrome diagnosis. Exercise training blunted all these derangements. Additionally, FS group presented autonomic dysfunction in relation to the others, as seen by an ≈ 50% decrease in baroreflex sensitivity and 24% in HR variability, and increases in sympathovagal balance (140%) and in renal sympathetic nerve activity (45%). These impairments were not observed in FT group, as well as in C and CT. Correlation analysis showed that both Lee index and kITT were associated with vagal impairment caused by fructose. Therefore, exercise training plays a preventive role in both autonomic and hemodynamic alterations related to the excessive fructose consumption.


Development and in-house validation of the event-specific qualitative and quantitative PCR detection methods for genetically modified cotton MON15985.
To implement genetically modified organism (GMO) labeling regulations, an event-specific analysis method based on the junction sequence between exogenous integration and host genomic DNA has become the preferential approach for GMO identification and quantification. In this study, specific primers and TaqMan probes based on the revealed 5'-end junction sequence of GM cotton MON15985 were designed, and qualitative and quantitative polymerase chain reaction (PCR) assays were established employing the designed primers and probes. In the qualitative PCR assay, the limit of detection (LOD) was 0.5 g kg(-1) in 100 ng total cotton genomic DNA, corresponding to about 17 copies of haploid cotton genomic DNA, and the LOD and limit of quantification (LOQ) for quantitative PCR assay were 10 and 17 copies of haploid cotton genomic DNA, respectively. Furthermore, the developed quantitative PCR assays were validated in-house by five different researchers. Also, five practical samples with known GM contents were quantified using the developed PCR assay in in-house validation, and the bias between the true and quantification values ranged from 2.06% to 12.59%. This study shows that the developed qualitative and quantitative PCR methods are applicable for the identification and quantification of GM cotton MON15985 and its derivates.


Enhanced plasma IL-6 and IL-1ra responses to repeated vs. single bouts of prolonged cycling in elite athletes.
The impact of repeated bouts of exercise on plasma levels of interleukin (IL)-6 and IL-1 receptor antagonist (IL-1ra) was examined. Nine well-trained men participated in four different 24-h trials: Long [two bouts of exercise, at 0800-0915 and afternoon exercise (Ex-A), separated by 6 h]; Short (two bouts, at 1100-1215 and Ex-A, separated by 3 h); One (single bout performed at the same Ex-A as second bout in prior trials); and Rest (no exercise). All exercise bouts were performed on a cycle ergometer at 75% of maximal O(2) uptake and lasted 75 min. Peak IL-6 observed at the end of Ex-A was significantly higher in Short (8.8 +/- 1.3 pg/ml) than One (5.2 +/- 0.7 pg/ml) but not compared with Long (5.9 +/- 1.2 pg/ml). Peak IL-1ra observed 1 h postexercise was significantly higher in Short (1,774 +/- 373 pg/ml) than One (302 +/- 53 pg/ml) but not compared with Long (1,276 +/- 451 pg/ml). We conclude that, when a second bout of endurance exercise is performed after only 3 h of recovery, IL-6 and IL-1ra responses are elevated. This may be linked to muscle glycogen depletion.


Double staining of ginsenosides by Western blotting using anti-ginsenoside Rb1 and Rg1 monoclonal antibodies.
Ginsenosides separated by silica gel TLC blotted to a polyvinylidene difluoride (PVDF) membrane was treated with a NaIO4 solution followed by bovine serum albumin (BSA), resulting in a ginsenoside-BSA conjugate on a PVDF membrane. The blotted bands were stained with anti-ginsenoside Rg1 and Rb1 monoclonal antibodies (MAbs). The newly established double staining with the Western blotting methods was applied for the determination of ginsenosides possessing protopanaxadiol or protopanaxatriol and the number of sugar depending on the stained color and their Rf values in the Panax plants.


Design method of an ultra-thin two-dimensional geometrical waveguide near-eye display based on forward-ray-tracing and maximum FOV analysis.
A two-dimensional geometrical waveguide enables ultra-thin augmented reality (AR) near-eye display (NED) with wide field of view (FOV) and large exit-pupil diameter (EPD). A conventional design method can efficiently design waveguides that meet the requirements, but is unable to fully utilize the potential display performance of the waveguide. A forward-ray-tracing waveguide design method with maximum FOV analysis is proposed, enabling two-dimensional geometrical waveguides to achieve their maximum FOV while maintaining minimum dimensions. Finally, the designed stray-light-suppressed waveguide NED has a thickness of 1.7 mm, a FOV of 50.00°H × 29.92°V, and an eye-box of 12 mm × 12 mm at an eye-relief of 18 mm.


Sotos syndrome: two cases with severe scoliosis.
Two patients with Sotos syndrome who developed a severe scoliosis are described. These cases illustrate the potential to develop significant spinal curvature in Sotos syndrome.


Philadelphia chromosome and terminal transferase-positive acute leukemia: similarity of terminal phase of chronic myelogenous leukemia and de novo acute presentation.
Twenty-eight patients with Philadelphia chromosome (Ph1)--positive and terminal transferase (TdT)--positive acute leukemia (AL) were treated with intensive chemotherapy used for adult acute lymphoblastic leukemia (L-10 and L-10M protocols). Fifteen patients had a documented chronic phase of Ph1-positive chronic myelogenous leukemia preceding the acute transformation (TdT + BLCML) while the remaining 13 patients did not (TdT + Ph1 + AL). An overall complete remission (CR) rate of 71% was obtained with a median survival of 13 months in the responders. Clinical presentation, laboratory data, cytogenetics, response to treatment, and survivals of the two groups of patients are compared. These results appear to be similar, suggesting a common or closely related origin. Since the overall survival of those receiving chemotherapy maintenance is poor, three patients underwent allogeneic bone marrow transplantation (BMT) from histocompatibility leukocyte antigen--matched siblings after they achieved CR. One of them is a long-term survivor (35 + months) with a Ph1-negative bone marrow. New techniques such as BMT should be considered in young patients with a histocompatibility leukocyte antigen--compatible sibling once a CR has been achieved.


Tips for a physician in getting the right job, part XIX: introduction to employment contracts.
It is very helpful for physicians searching for a job to know a little about employment contracts. This article summarizes some important principles about contracts and some of their clauses. The article also emphasizes the importance of having the understandings regarding employment put in a formal written contract. This article may help the candidate avoid certain difficulties and may help in contract negotiations. However, this article is not a substitute for legal advice, and all physicians should consult a lawyer before signing an employment contract.


Late removal of dense posthemorrhagic vitreous membranes following cataract extraction.
Severe, seemingly permanent intraocular hemorrhages caused by ocular trauma, Eales' disease and retinal vein thrombosis, lead to late formation of a dense retrolental membrane, vitreous liquefaction and intumescent cataract with faulty light perception. In the absence of ultrasound, the diagnosis was made possible only after removal of the cataract. Lens extraction and excision of the vitreal membrane led to surprisingly good recovery of vision. Three cases are presented and the pathological study of a posthemorrhagic membrane.


A survey of animal welfare needs in Soweto.
The diagnostic phase of an interactive research evaluation model was used in the investigation of the animal welfare needs of a low-income urban community in South Africa. Data were gathered by means of a structured interview and direct observations by animal welfare officers. During the survey of 871 animal owners in Soweto, it was found that dogs were owned by 778 households and cats by 88 households. The dog to human ratio was estimated at 1:12.4. Respondents were asked whether they enjoyed owning animals and 96.1% said that they did. Only 26.3% mentioned that they had problems with their own animals and 16.6% had problems with other people's animals. Treatment of sick animals (29.7%) was seen as a priority. However, less than 1% (n = 6) used the services of private veterinarians. Others took their animals to welfare organisations or did not have them treated. Perceptions of affordable costs of veterinary treatments were also recorded. In addition to treatment, respondents indicated a need for vaccination (22.5%), sterilisation (16.5%), control of internal (3.7%) and external (8.8%) parasites, education and extension (6.6%), prevention of cruelty to animals (3.2%) and expansion of veterinary clinics to other parts of Soweto (1.3%).


Detection of spinal cord compression in dogs with cervical intervertebral disc disease by magnetic resonance imaging.
The medical records and magnetic resonance images of 33 dogs with surgically confirmed Hansen type I cervical intervertebral disc disease were reviewed. Fourteen of the dogs were chondrodystrophic and 19 were not chondrodystrophic. The most common clinical sign was neck pain, which affected 28 of the dogs, and 23 of the dogs were able to walk. Fifteen of the dogs had developed clinical signs acutely, within the previous 24 hours. On cross-sectional images the median area of spinal cord compression was 26 per cent (range 11 to 71 per cent) of the normal spinal cord area. The degree of spinal cord compression was significantly associated with the dogs' presurgical neurological status but not with their postsurgical neurological status. The dogs with an acute onset of clinical signs had more severe neurological dysfunction before surgery, but their condition improved more as a result of surgery.


Regulation of serum insulin-like growth factor-I (IGF-I) and IGF binding proteins during rat pregnancy.
Serum concentrations of insulin-like growth factor-I (IGF-I) in rats are reduced dramatically in the latter half of pregnancy, decreasing from 1758 +/- 356 ng/ml at 12 days of pregnancy (mean +/- SD) to 761 +/- 192 ng/ml at 15 days. After parturition, IGF-I increases to nonpregnant values in 4 days. Using ligand blotting, we have demonstrated that most of the serum IGF binding proteins (IGFBPs) are concurrently reduced during pregnancy. IGFBP-3, the predominant IGFBP in nonpregnant serum, is reduced to 1.3% of nonpregnant values by 21 days of pregnancy and begins to rise within 1 h postpartum (PP). The sera of 21-day pregnant (but not nonpregnant) rats degrade IGFBP-3 in vitro, and this degradation is prevented by the protease inhibitor antipain. Decreased serum IGF-I concentrations during pregnancy, therefore, may result from reduced IGFBP-3 concentrations causing increased IGF-I clearance. In addition, steady state IGF-I mRNA and peptide levels in liver are decreased in 21-day pregnant rats (37% and 42% of 4 day PP levels, respectively), suggesting that decreased synthesis of IGF-I may also lead to lower serum IGF-I concentrations. After bolus injection, [125I]IGF-I is cleared from the serum of pregnant rats nearly 5 times faster than that of 4 day PP rats (1.21 vs. 0.25 ml/min/kg, respectively). Urinary clearance is relatively insignificant (less than 4%), and [125I]IGF-I does not cross the placenta. The intermediate distribution phase of IGF-I is slower in pregnant rats than in PP rats (t1/2 alpha, 17.1 vs. 5.4 min), whereas the terminal elimination of IGF-I is twice as fast (t1/2 beta, 228.1 vs. 106.4 min). The prolonged IGF-I distribution phase in the pregnant rats may result from decreased concentrations of 34,000 and 30,000 mol wt IGFBPs, which may transport IGF-I to tissues. The faster serum elimination half-life may result from diminished IGFBP-3, leading to greater IGF-I availability to tissues in pregnancy.


Effects of unilateral strength training and detraining on bone mineral density and content in young women: a study of mechanical loading and deloading on human bones.
This study assessed the effect of unilateral strength training at 80% one repetition maximum and of detraining on bone mineral density (BMD, g/cm-2) and bone mineral content (sigma BMC, g) in young women. Twelve female physiotherapy students trained their left limb by leg press an average of four times per week for 1 year followed by 3 months of detraining. Twelve students served as controls. Repeated bone measurements were performed by dual energy X-ray absorptiometry of the lumbar spine, femoral neck, distal femur, patella, proximal tibia, and calcaneus. The training increased the muscle strength of the trained limb, and the BMD of the same limb showed a nonsignificant but systematic increase in distal femur, patella, and proximal tibia, and in sigma BMC of the five measured limb sites (considered an index of the total osteogenic effectiveness of the training). Simultaneously, the muscle strength increased in the untrained limb as an evidence of cross-training effect. A corresponding small but systematic increase was also seen in BMD of this limb as well as in sigma BMC. After the cessation of training, leg extension strength was retained but BMD and sigma BMC of the trained and untrained limbs declined towards baseline values in 3 months. The BMD and sigma BMC values in the control group showed an increasing tendency during the follow-up but the changes were less than 1%. The differences of the changes in BMD and sigma BMC between the left and right limb in the control group, as well as between the same limb in the training and control groups were nonsignificant.(ABSTRACT TRUNCATED AT 250 WORDS)


Multiple comparisons of repeatedly measured response: issues of validation testing in thorough QT/QTc clinical trials.
In order to validate the results of a thorough QT/QTc clinical trial, ICH E14 recommended that a concurrent positive control treatment be included in the trial. Zhang (2008) recommended that the study results are validated if the positive control establishes assay sensitivity, i.e., has an effect on the mean QT/QTc interval of 5 ms or more. Zhang (2008) and Tsong et al. (2008) discussed the intersection-union test approach and an alternative global average test approach for testing assay sensitivity during the validation process. In this article, we further discuss the multiple comparison issues of the repeatedly measured QT difference between positive control treatment and placebo in the validation test. We describe and discuss several approaches for type I error rate adjustment that are applicable to the situation.


Synthesis of Lipophilic Antioxidants by a Lipase-B-Catalyzed Addition of Peracids to the Double Bond of 4-Vinyl-2-methoxyphenol.
4-Vinyl guaiacol (2) was lipophilized through the electrophilic addition of peracids to its vinylic double bond. Those peracids were formed in situ, by the Candida antarctica lipase-B-assisted perhydrolysis of carboxylic acids ranging from C2 to C18, in hydrogen peroxide solution. The addition of peracids with 4-8 carbons in their alkyl chains led to the formation of two regioisomers, with the prevalence of hydroxyesters bearing a primary free hydroxyl (4c-4e). This prevalence became more pronounced when peracids with longer alkyl chains (C10-C18) were used. In this case, only isomers 4f-4h were formed. The antioxidant activity of the resulting hydroxyesters was assessed by means of the conjugated autoxidizable triene (CAT) assay, and it was found out that the 4-vinyl guaiacol antioxidant activity was significantly increased by grafting alkyl chains with 2-8 carbons.


Screening of enzymatic activities within different enological non-Saccharomyces yeasts.
Ninety-seven non-Saccharomyces wine yeast strains belonging to ten different genera and species (Candida spp. and Criptococcus spp.; Debaryomyces hansenii, Lachancea thermotolerans, Metschnikowia pulcherrima, Pichia kluyveri, Sporidiobolus salmonicolor, Torulaspora delbrueckii, Williopsis pratensis and Zygosaccharomyces bailii) were screened for 13 enzymes related to wine aroma, color and clarity. Understanding the yeasts' influence in these wine characteristics provides a platform for selecting strains for their development as starter cultures and for the management of alcoholic fermentation. Most of the strains showed the presence of one or more enzymes of biotechnological interest. Our screening demonstrated several intraspecific differences within the yeast species investigated, indicating that strain selection is of great importance for their enological application, and also that some non-Saccharomyces that have not been thoroughly explored, may deserve further consideration. This research represents the first stage for selecting non-Saccharomyces strains to be used as a starter along with Saccharomyces cerevisiae to enhance some particular characteristics of wines.


Evaluation of carotenoids and reactive oxygen species in human skin after UV irradiation: a critical comparison between in vivo and ex vivo investigations.
UV irradiation is one of the most harmful exogenous factors for the human skin. In addition to the development of erythema, free radicals, that is reactive oxygen species (ROS), are induced under its influence and promote the development of oxidative stress in the skin. Several techniques are available for determining the effect of UV irradiation. Resonance Raman spectroscopy (RRS) measures the reduction of the carotenoid concentration, while electron paramagnetic resonance (EPR) spectroscopy enables the analysis of the production of free radicals. Depending on the method, the skin parameters are analysed in vivo or ex vivo. This study provides a critical comparison between in vivo and ex vivo investigations on the ROS formation and carotenoid depletion caused by UV irradiation in human skin. The oxygen content of tissue was also determined. It was shown that the antioxidant status measured in the skin samples in vivo and ex vivo was different. The depletion in the carotenoid concentration in vivo exceeded the value determined ex vivo by a factor of about 1.5, and the radical formation after UV irradiation was significantly greater in vivo by a factor of 3.5 than that measured in excised human skin, which can be explained by the lack of oxygen ex vivo.


Noninvasive prenatal testing: impact on genetic counseling, invasive prenatal diagnosis, and trisomy 21 detection.
The aim of this study was to compare rates of genetic counseling, invasive prenatal diagnosis, and trisomy 21 detection among women at increased risk for aneuploidy, before versus after the availability of noninvasive prenatal testing (NIPT). This institutional review board-exempt retrospective study included all women who had an ultrasound (US) examination between 10 0/7 and 21 6/7 weeks' gestation and were eligible for NIPT (ie, age ≥35 years, US findings suggestive of increased aneuploidy risk, positive aneuploidy screen, prior trisomic fetus, parental balanced translocation with increased risk for trisomy 13 or 21) between June 1, 2012 and February 1, 2013. NIPT was performed by a single laboratory after patients received genetic counseling. We also identified a comparison group of women evaluated between December 1, 2010 and November 30, 2011, who would have been eligible for NIPT had it been available. The two groups were compared for maternal demographics, aneuploidy risk factors, rates of genetic counseling, invasive diagnostic procedures, and trisomy 21 detection. The before-NIPT and after-NIPT groups contained 1,464 and 1,046 subjects, respectively. All 33 fetuses with trisomy 21 in the two groups were identified by positive aneuploidy screening. After the introduction of NIPT, genetic counseling for aneuploidy risk increased (adjusted odds ratio [aOR], 1.77 [1.49-2.11]; p < 0.0001) and the overall invasive diagnosis (aOR, 0.42 [0.32-0.55]; p < 0.0001), including amniocentesis (aOR, 0.37 [0.27-0.52], p < 0.0001), decreased, whereas the prenatal diagnosis of trisomy 21 remained similar (88% versus 100%; p = 0.86). NIPT in clinical practice uses more genetic counseling resources but requires significantly fewer invasive procedures to maintain the detection rates of trisomy 21.


A Novel Prognostic Model Based on Ferroptosis-Related Gene Signature for Bladder Cancer.
Bladder cancer (BC) is a molecular heterogeneous malignant tumor; the treatment strategies for advanced-stage patients were limited. Therefore, it is vital for improving the clinical outcome of BC patients to identify key biomarkers affecting prognosis. Ferroptosis is a newly discovered programmed cell death and plays a crucial role in the occurrence and progression of tumors. Ferroptosis-related genes (FRGs) can be promising candidate biomarkers in BC. The objective of our study was to construct a prognostic model to improve the prognosis prediction of BC. The mRNA expression profiles and corresponding clinical data of bladder urothelial carcinoma (BLCA) patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. FRGs were identified by downloading data from FerrDb. Differential analysis was performed to identify differentially expressed genes (DEGs) related to ferroptosis. Univariate and multivariate Cox regression analyses were conducted to establish a prognostic model in the TCGA cohort. BLCA patients from the GEO cohort were used for validation. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-sample gene set enrichment analysis (ssGSEA) were used to explore underlying mechanisms. Nine genes (ALB, BID, FADS2, FANCD2, IFNG, MIOX, PLIN4, SCD, and SLC2A3) were identified to construct a prognostic model. Patients were classified into high-risk and low-risk groups according to the signature-based risk score. Receiver operating characteristic (ROC) and Kaplan-Meier (K-M) survival analysis confirmed the superior predictive performance of the novel survival model based on the nine-FRG signature. Multivariate Cox regression analyses showed that risk score was an independent risk factor associated with overall survival (OS). GO and KEGG enrichment analysis indicated that apart from ferroptosis-related pathways, immune-related pathways were significantly enriched. ssGSEA analysis indicated that the immune status was different between the two risk groups. The results of our study indicated that a novel prognostic model based on the nine-FRG signature can be used for prognostic prediction in BC patients. FRGs are potential prognostic biomarkers and therapeutic targets.


Assessing and Interpreting Real-World Evidence Studies: Introductory Points for New Reviewers.
Nonrandomized real-world evidence (RWE) studies are conducted using healthcare data collected as part of clinical practice. As RWE studies are increasingly considered for regulatory, coverage, and other clinical decision making, nonspecialists will find themselves in the position of assessing the validity of RWE studies, a field that may be less familiar to them. This introductory guide provides conceptual guidance for reviewing RWE studies and is particularly directed at professionals for whom this is new or whose prior experience has primarily been in reviewing randomized controlled trial evidence. We focus on RWE studies that make causal inference, evaluating whether one treatment option is better, worse, or neutral compared to another. Although we provide citations to direct the reader to resources with more details on complex issues, this guide cannot substitute for years of training and expertise in the field.


Sunscreens: A Review of UV Filters and Their Allergic Potential.
Abstract Active ingredients of sunscreens, or UV filters, have increased in use because public awareness of sun safety has risen. In addition to this intentional use, unintentional exposures to UV filters also occur through application of personal care products, where the filters are incorporated into the product. There are 2 main types of UV filters: organic (chemical) filters and the 2 inorganic (mineral) filters, titanium dioxide and zinc oxide. Both allergic contact dermatitis (ACD) and photoallergic contact dermatitis (PACD) have been caused by organic filters; oxybenzone (benzophenone-3) is the most frequently reported contact and photocontact allergen compared with all other UV filters. There are no reports of ACD or PACD to the inorganic (physical) UV filters. Here, we review the categories of sunscreens available, currently marketed UV filters, and their corresponding ACD and PACD.


High dose rate brachytherapy for nonmalignant airway obstruction: new treatment option.
High dose rate (HDR) endobronchial brachytherapy is widely used as a palliative treatment for symptomatic airway obstruction by primary or secondary malignant tumors. We report on a successful use of HDR brachytherapy in patients with nonmalignant airway obstruction. Case series Six patients received HDR brachytherapy for airway obstruction caused by granulation tissue around a metal stent placed for restoration of the airway patency for nonmalignant causes. In four patients, brachytherapy was performed following recurrent occlusion of the airway by granulation tissue formation; in two patients, it was done as a prophylactic procedure. HDR brachytherapy catheters were passed through the metal stents under direct fluoroscopic guidance. Simulation and computerized treatment planning were done, and a single dose of 10 Gy was administered using a brachytherapy remote afterloader with a (192)Ir source. The dose was prescribed to a distance of 1 cm from the center of the source, with a margin of 1 cm from the proximal and distal ends of the stent. At a median follow-up of 15 months, moderate granulation tissue formation was observed in only one patient; in four others, it was categorized as minimal, 5 to 30 months from the procedure. Restoration of the lumen was complete in four patients, near complete in one patient, and partial in one patient. In one patient, previously treated by external radiotherapy, local tissue necrosis was evident. HDR brachytherapy can be used safely for nonmalignant airway obstruction. Further studies including more patients and longer follow-up are needed.


Evans Calcaneal Osteotomy: Assessment of Multiplanar Correction.
Flatfoot deformity consists of collapse of the medial arch, forefoot abduction, increased talonavicular uncoverage, and hindfoot valgus. Although numerous soft tissue and bony procedures have been proposed to correct each plane of deformity, there is a lack of objective data in the literature quantifying the amount of structural correction. The purpose of this study was to quantify the multiplanar deformity correction of the lateral column lengthening osteotomy (Evans) on hindfoot alignment through objective, reproducible, radiographic measurements. We retrospectively reviewed 45 Evans calcaneal osteotomy procedures in 24 female (53%) and 21 male (47%) feet performed on 40 patients (5 bilateral). The mean follow-up was 53 weeks (range, 32-116). The mean age at the time of surgery was 35 years (range, 11-73). Statistically significant improvement in radiographic alignment was found in the calcaneal inclination angle, tibial-calcaneal angle, tibial-calcaneal position, and the anteroposterior talo-first metatarsal angle (p < .0001 for all). Although a direct correlation between graft size and degree of angular correction was not observed, it should be noted the calcaneal graft size (mean, 11.8 mm) and the amount of hindfoot valgus correction (mean, 12.6°) appear to be clinically related. The results of this study support that the Evans calcaneal osteotomy corrects the hindfoot alignment in 3 planes as evidenced by our multiplanar radiographic measurements.


Unveiling new sequestrate Cortinarius species from northern Patagonian Nothofagaceae forests based on molecular and morphological data.
Because of systematic sampling campaigns in the northern Patagonian Nothofagaceae forests of Argentina, several specimens of sequestrate fungi were collected. Some of those collections showed phylogenetic affinities and morphological similarities to members of the formerly recognized sequestrate genus Thaxterogaster, currently a synonym of Cortinarius on the basis of molecular data. Comparisons of macro- and micromorphological features and sequences of nuc rDNA internal transcribed spacer (ITS) regions have revealed that these collections belong to formerly undescribed species. The sequences of the four new taxa presented here, Cortinarius flavopurpureus, C. translucidus, C. nahuelhuapensis, and C. infrequens, were combined into a data set including additional sequences generated from herbarium collections and retrieved from public gene databases and analyzed by maximum likelihood and Bayesian inference methods. The four new species were resolved as distinct clades with strong support; at the same time, they showed unique morphological characteristics (hypogeous to subhypogeous habit, complete gasteromycetation, and spore shape and ornamentation) that separate them from previously described Cortinarius species. In addition, several undescribed and/or not previously sequenced species from these forests were detected through phylogenetic analysis of ectomycorrhizal root tip sequences. A key of characters to identify the sequestrate Cortinarius from Patagonia is provided.


Household income and risk-of-poverty of parents of long-term childhood cancer survivors.
Taking care of children diagnosed with cancer affects parents' professional life and may place the family at risk-of-poverty. We aimed to (i) compare the household income and risk-of-poverty of parents of childhood cancer survivors (CCS) to parents of the general population, and (ii) identify sociodemographic and cancer-related factors associated with risk-of-poverty. As part of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to parents of CCS aged 5-15 years, who survived ≥5 years after diagnosis. Information on parents of the general population came from the Swiss Household Panel (parents with ≥1 child aged 5-15 years). Risk-of-poverty was defined as having a monthly household income of <4,500 Swiss Francs (CHF) for single parents and <6,000 CHF for parent-couples. We used logistic regression to identify factors associated with risk-of-poverty. We included parents of 383 CCS and 769 control parent households. Parent-couples of CCS had a lower household income (Ptrend < 0.001) and were at higher risk-of-poverty (30.4% vs. 19.3%, P = 0.001) compared to control parent-couples. Household income and risk-of-poverty of single parents of CCS was similar to control single parents. Parents of CCS were at higher risk-of-poverty if they had only standard education (ORmother = 3.77 [where OR is odds ratio], confidence interval [CI]: 1.61-8.82; ORfather = 8.59, CI: 4.16-17.72) and were from the German language region (OR = 1.99, CI: 1.13-3.50). We found no cancer-related risk factors. Parents of long-term CCS reported lower household income and higher risk-of-poverty than control parents. Support strategies may be developed to mitigate parents' risk-of-poverty in the long term, particularly among parents with lower education.


Rapid PCR amplification of minimal enediyne polyketide synthase cassettes leads to a predictive familial classification model.
A universal PCR method for the rapid amplification of minimal enediyne polyketide synthase (PKS) genes and the application of this methodology to clone remaining prototypical genes from producers of structurally determined enediynes in both family types are presented. A phylogenetic analysis of the new pool of bona fide enediyne PKS genes, consisting of three from 9-membered producers (neocarzinostatin, C1027, and maduropeptin) and three from 10-membered producers (calicheamicin, dynemicin, and esperamicin), reveals a clear genotypic distinction between the two structural families from which to form a predictive model. The results from this study support the postulation that the minimal enediyne PKS helps define the structural divergence of the enediyne core and provides the key tools for generating enediyne hybrid genes/molecular scaffolds; by using the model, a classification is also provided for the unknown enediyne PKS genes previously identified via genome scanning.