An instrument for evaluation of performance of heat dissipative coatings.
An instrument is developed to evaluate the performance of heat dissipative coatings. The instrument has features to measure the apparent emissivity of a given surface under different input power settings. The emissivity of aluminum (Al Q-panel) and copper, as measured from 60-135 degrees C, showed a value of 0.15+/-0.03 and 0.42+/-0.05, respectively, consistent with reported values in literature. The relative emissivity of a heat dissipative coating, called as molecular fan carbon nanotube "MF-CNT," was found to be approximately 0.97. A simple mathematical model is built to evaluate the role of different heat transfer mechanisms (convection and radiation) on cooling performance, and it was observed that convection plays a dominant role in cooling, with more than 90% of heat transferred by convection. In presence of MF-CNT coating, radiation heat transfer increases to approximately 30% and lowers the steady state temperature by 10 degrees C. It is illustrated that radiative cooling could be a significant factor in thermal management.


Relationship between Tregitopes Structure and Binding with Major Histocompatibility Complex Class I.
Epitopes of T-cells (tregitopes) are linear sequences of amino acids present in many animal and human proteins. Tregitopes suppress the immunological response and could play a significant regulatory role in the pathogenesis of autoimmune diseases. They modulate T-cell response activated by the antigens of the major histocompatibility complex class I (MHC-I).The aim of this study was an attempt to determine the correlation between physicochemical properties and structures of tregitopes and their binding strength with MHC-I. 21 amino acid sequences of immunoglobulin G with verified or similar to tregitopes function were selected. The analysis of the binding strength with MHC-I was carried out on 41 various alleles since MHC-I can be coded by numerous alleles. The first phase of study attempted to find a correlation between the half minimal inhibitory concentration (LogIC50) calculated for MHC-I and physicochemical properties. From formulated arithmetic statements, only one allowed to determine significant correlation with LogIC50 with reference to alleles A*02:01 and A*02:06. The correlations for the alleles were linear and sigmoid, respectively (p<0.001). The presence of the repeated amino acids was confirmed in the sequences of the studied compounds. These amino acids are connected with stronger binding or lack of the binding with MHC-I expressed by LogIC50. The study shows the translation from the classification (cloud) model to the linear one. The significant linear dependence between chemical structure of tregitopes and their LogIC50 calculated for MHC-I was displayed. The presented method can be used in screening of new sequences that have regulatory properties for regulatory T-cells.


Citric acid cough threshold in patients with gastroesophageal reflux disease rises after laparoscopic fundoplication.
It has been reported that antireflux surgery can diminish chronic cough due to gastroesophageal reflux disease (GERD) that is resistant to pharmacologic therapy. The aim of this study was the assessment of citric acid cough threshold (CACT) in patients with chronic cough due to GERD before and 3 months after laparoscopic Toupet fundoplication. Thirty subjects (20 women and 10 men; median age, 45.3 years) with chronic cough due to GERD and 15 healthy volunteers underwent cough challenge with doubling concentrations of citric acid. Twenty subjects with GERD, a group of 14 women and 6 men (mean age, 45.5 years), underwent the same protocol 3 months after laparoscopic fundoplication. Daytime and nighttime cough score questionnaires (verbal category descriptive score) were completed in all groups. The geometric mean of CACT was significantly lower in GERD patients (9.62 mg/mL) than in healthy volunteers (50.8 mg/mL, p < 0.001). The results of cough score measurement significantly improved within 2 weeks after laparoscopic surgery. In 13 weeks of postoperative follow-up, cough disappeared or was greatly improved in 14 of the 20 patients (70%); in 3 other patients, cough resolved partially. In three patients. there was no improvement in cough. Cough challenge after surgery revealed a significant increase in mean cough threshold, from 8.28 to 19.03 mg/mL (p < 0.05). The results suggest that GERD influences CACT, which was significantly lower in GERD patients compared to healthy subjects. A significant correlation was found between subjective and objective measurements of cough in GERD patients. We found laparoscopic fundoplication to be objectively beneficial in GERD-induced chronic cough, as it reduced the CACT.


Diagnostic Utility of Twist1, Ki-67, and E-Cadherin in Diagnosing Molar Gestations and Hydropic Abortions.
This study aims to assess whether the expression of Twist1, Ki-67, and E-cadherin can guide the differential diagnosis of complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), and hydropic abortion (HA). Differential expression of Twist1, Ki-67, and E-cadherin was analyzed in gestational products from 55 cases of CHM, PHM, and HA using immunohistochemistry. Prior to analysis, the studied cases were confirmed for their diagnosis by flow cytometric assessment of DNA ploidy and p57 immunostaining. Twist1 expression can distinguish CHM from PHM and HA with 100% sensitivity, 100%, specificity, 100% positive predictive value (PPV), and 100% negative predictive value (NPV). Furthermore, combined Ki-67 and E-cadherin expression could differentiate PHM and HA with 100% sensitivity, 93.3% specificity, 92.3% PPV, and 100% NPV. Twist1 expression is a highly reliable marker for the diagnosis of CHM, where combined Ki-67 and E-cadherin immunoreactivity can distinguish PHM from nonmolar pregnancies.


Label-Free Imaging of Membrane Potentials by Intramembrane Field Modulation, Assessed by Second Harmonic Generation Microscopy.
Optical interrogation of cellular electrical activity has proven itself essential for understanding cellular function and communication in complex networks. Voltage-sensitive dyes are important tools for assessing excitability but these highly lipophilic sensors may affect cellular function. Label-free techniques offer a major advantage as they eliminate the need for these external probes. In this work, it is shown that endogenous second-harmonic generation (SHG) from live cells is highly sensitive to changes in transmembrane potential (TMP). Simultaneous electrophysiological control of a living human embryonic kidney (HEK293T) cell, through a whole-cell voltage-clamp reveals a linear relation between the SHG intensity and membrane voltage. The results suggest that due to the high ionic strengths and fast optical response of biofluids, membrane hydration is not the main contributor to the observed field sensitivity. A conceptual framework is further provided that indicates that the SHG voltage sensitivity reflects the electric field within the biological asymmetric lipid bilayer owing to a nonzero χeff(2) tensor. Changing the TMP without surface modifications such as electrolyte screening offers high optical sensitivity to membrane voltage (≈40% per 100 mV), indicating the power of SHG for label-free read-out. These results hold promise for the design of a non-invasive label-free read-out tool for electrogenic cells.


Experimental single controlled study of burned bones: contribution of scanning electron microscopy.
Burned bones were studied using Scanning Electron Microscopy. The samples were cut from a maxillary-mandibular block taken during an autopsy. These fragments were heated in a furnace under controlled temperature conditions for 60 minutes. The temperatures ranged from 150 to 1150 degrees Celsius. The results are as following: (i) there are significant alterations of the bone, more and more obvious as the temperature increases, (ii) it appears to be difficult to establish a precise correlation between the temperature and the scanning electron microscopy patterns.


Protein Extract of a Probiotic Strain of Hafnia alvei and Bacterial ClpB Protein Improve Glucose Tolerance in Mice.
A commercial strain of Hafnia alvei (H. alvei) 4597 bacteria was shown to reduce food intake and promote weight loss, effects possibly induced by the bacterial protein ClpB, an antigen-mimetic of the anorexigenic α-melanocyte-stimulating hormone. A decrease in the basal plasma glucose levels was also observed in overweight fasted humans and mice receiving H. alvei. However, it is not known whether H. alvei influences sweet taste preference and whether its protein extract or ClpB are sufficient to increase glucose tolerance; these are the objectives tested in the present study. C57BL/6J male mice were kept under standard diet and were gavaged daily for 17 days with a suspension of H. alvei (4.5 × 107 CFU/animal) or with H. alvei total protein extract (5 μg/animal) or saline as a control. Sweet taste preference was analyzed via a brief-access licking test with sucrose solution. Glucose tolerance tests (GTT) were performed after the intraperitoneal (IP) or intragastric (IG) glucose administration at the 9th and 15th days of gavage, respectively. The expression of regulatory peptides' mRNA levels was assayed in the hypothalamus. In another experiment performed in non-treated C57BL/6J male mice, effects of acute IP administration of recombinant ClpB protein on glucose tolerance were studied by both IP- and IG-GTT. Mice treated with the H. alvei protein extract showed an improved glucose tolerance in IP-GTT but not in IG-GTT. Both groups treated with H. alvei bacteria or protein extract showed a reduction of pancreatic tissue weight but without significant changes to basal plasma insulin. No significant effects of H. alvei bacteria or its total protein extract administration were observed on the sweet taste preference, insulin tolerance and expression of regulatory peptides' mRNA in the hypothalamus. Acute administration of ClpB in non-treated mice increased glucose tolerance during the IP-GTT but not the IG-GTT, and reduced basal plasma glucose levels. We conclude that both the H. alvei protein extract introduced orally and the ClpB protein administered via IP improve glucose tolerance probably by acting at the glucose postabsorptive level. Moreover, H. alvei probiotic does not seem to influence the sweet taste preference. These results justify future testing of both the H. alvei protein extract and ClpB protein in animal models of diabetes.


Molecular dynamics simulations of the lipid bilayer edge.
Phospholipid bilayers have been intensively studied by molecular dynamics (MD) simulation in recent years. The properties of bilayer edges are important in determining the structure and stability of pores formed in vesicles and biomembranes. In this work, we use molecular dynamics simulation to investigate the structure, dynamics, and line tension of the edges of bilayer ribbons composed of pure dimyristoylphosphatidylcholine (DMPC) or palmitoyl-oleoylphosphatidylethanolamine (POPE). As expected, we observe a significant reorganization of lipids at and near the edges. The treatment of electrostatic effects is shown to have a qualitative impact on the structure and stability of the edge, and significant differences are observed in the dynamics and structure of edges formed by DMPC and palmitoyl-oleoylphosphatidylethanolamine. From the pressure anisotropy in the simulation box, we calculate a line tension of approximately 10-30 pN for the DMPC edge, in qualitative agreement with experimental estimates for similar lipids.


Cell wall regeneration in Chlamydomonas: accumulation of mRNAs encoding cell wall hydroxyproline-rich glycoproteins.
The unicellular alga Chlamydomonas reinhardtii is surrounded by a cell wall composed entirely of hydroxyproline-rich glycoproteins (HRGPs). When the walls of vegetative cells are removed with the enzyme gamete autolysin (g-lysin), they regenerate a matrix within 3-4 hr. In vitro translation of mRNAs isolated from g-lysin-treated cells showed significant increases and decreases in abundance of several mRNAs encoding proline-rich polypeptides. Because the population of up-regulated mRNAs is likely to include species encoding cell wall components, expression of genes for two outer wall HRGPs (GP1 and GP2) was analyzed during wall regeneration by using cDNAs isolated from a C. reinhardtii lambda gt11 library. Transcripts encoding GP1 and GP2 were elevated severalfold within the first hour or regeneration, suggesting that upregulation of HRGP mRNAs is a primary response to cell wall removal by g-lysin. Cell wall regeneration in Chlamydomonas provides an accessible system to study HRGP gene expression during matrix development.


Legitimacy and status groups in financial markets.
Economic sociologists have argued that financial markets should be analysed as uncertainty-processing social networks and intermediary groups. Networks and intermediaries alone cannot confer legitimacy upon financial actors and transactions. Status groups are a solution to this problem. They emphasize reputation, honour and good social behaviour as stabilizers of collective action, as means of social control and as indicators of legitimacy. I examine here the emergence and evolution of status groups of brokers in London, New York and Paris, and show how emphasis on honour was used to legitimize financial transactions. I argue that financial markets should be conceived as networks, intermediary and status groups. In global, automated financial markets status groups like securities analysts are gaining in prominence.


Under nutrition and associated factors among adolescent girls attending school in the rural and urban districts of Debark, Northwest Ethiopia: A community-based comparative cross-sectional study.
Adolescence is the time of puberty in which a substantial changes in physical, mental, and emotional are observed; Nutritional requirements significantly rise as a result. Even though improving adolescent girls' nutritional status helps to break the intergenerational cycle of malnutrition, many studies in Ethiopia focus on determining the nutritional status of under-five and pregnant women and even they don't show disparities between urban and rural adolescent girls. Thus, this study was aimed at comparing the rural and urban prevalence's of stunting and thinness and their associated factors among adolescent girls attending school in Debark district, Northwest Ethiopia, 2020. A community-based comparative cross-sectional study was conducted among 792 adolescent girls from February 25th to March 21st 2020. A multi-stage sampling followed by simple random sampling technique was used. Data were collected through a face-to-face interviewer-based questionnaire. Different anthropometric measurements were taken. The collected data were entered to Epi-data and exported into SPSS for analyses. Variables with p-values < 0.25 in the bivariable analysis were exported to multivariable logistic regression model to control confounders and identify the factor. The strength of association and statistical significance was declared using the adjusted odds ratios with its corresponding 95% CI, and p-value ≤ 0.05 respectively. A total of 757 adolescent girls with a response rate of 95.6% were participated in the study. The overall prevalence of stunting and thinness were 20.1% and 10.3%, respectively. Stunting among rural adolescent girls was 24.2%; whereas it was 16% among urban residents. Likewise, thinness among rural adolescent girls was 8.5%; whereas it was 12.1% among urban dwellers. No latrine [AOR: 1.95 (95% CI: 1.11, 3.43)], lowest media exposure [AOR: 5.14 (95% CI: 1.16, 22.74)], lower wealth class [AOR:2.58 (95% CI: 1.310, 5.091)], and middle wealth class[AOR: 2.37 (95% CI: 1.230, 4.554)] have risen the likelihood of stunting in rural setting while early adolescent age [AOR:3.17 (95% CI:1.445,6.95)] significantly associated with stunting in urban setting. Food insecurity [AOR: 1.95 (95% CI: 1.01, 3.78)] was associated with stunting in overall adolescent girls. Middle adolescent age groups in rural area have more than three times to experience thinness [AOR: 3.67 (95% CI: 1. 21, 11.149)]. Whereas urban resident girls fall in early adolescent age group developed thinness were eight times [AOR: 8.39 (95% CI: 2.48-28.30)]. Stunting was higher among rural adolescent girls as compared to urban. However, thinness was higher among urban dwellers. Lower wealth class, food insecurity, lowest media exposure, and age were significantly associated with stunting and thinness. Hence, increasing latrine coverage, boosting the economic status of the community, and increasing media exposure for adolescent girls should get due attention.


Matrix metalloproteinase-9 (MMP-9), MMP-2, and serum elastase activity are associated with systolic hypertension and arterial stiffness.
Arterial stiffness is an independent determinant of cardiovascular risk, and arterial stiffening is the predominant abnormality in systolic hypertension. Elastin is the main elastic component of the arterial wall and can be degraded by a number of enzymes, including matrix metalloproteinase-9 (MMP-9) and MMP-2. We hypothesized that elastase activity would be related to arterial stiffness and tested this using isolated systolic hypertension (ISH) as a model of stiffening and separately in a large cohort of healthy individuals. A total of 116 subjects with ISH and 114 matched controls, as well as 447 individuals free from cardiovascular disease were studied. Aortic and brachial pulse wave velocity (PWV) and augmentation index were determined. Blood pressure, lipids, C-reactive protein, MMP-9, MMP-2, serum elastase activity (SEA), and tissue-specific inhibitor 2 of metalloproteinases were measured. Aortic and brachial PWV, MMP-9, MMP-2, and SEA levels were increased in ISH subjects compared with controls (P=0.001). MMP-9 levels correlated linearly and significantly with aortic (r=0.45; P=0.001) and brachial PWV (r=0.22; P=0.002), even after adjustments for confounding variables. In the younger, healthy subjects, MMP-9 and SEA were also independently associated with aortic PWV. Aortic stiffness is related to MMP-9 levels and SEA, not only in ISH, but also in younger, apparently healthy individuals. This suggests that elastases including MMP-9 may be involved in the process of arterial stiffening and development of ISH. The relationship between arterial stiffness and elastase activity was examined in isolated systolic hypertension (ISH), and separately in a large cohort of healthy individuals. Aortic stiffness is related to MMP-9, not only in ISH, but also in healthy individuals, suggesting elastases may be involved in the process of arterial stiffening and the development of ISH.


Chemical characterisation, plant remain analysis and radiocarbon dating of the Venetian "Manna di San Nicola".
A sample of oil coming from the case containing the relics of St. Nicholas the Great, preserved in the church of "San Nicolò al Lido" (Venice, Italy), has been characterised by the determination of its chemical composition, its age (radiocarbon dating) and the presence of particles of biological origin. Experimental results show that the sample is a vegetal oil, with a fatty acids composition modified by natural oxidation processes, containing pollen grains of plants from Northern Italy, and dating around 1300 A.D. These results together with an historical and artistic evaluation of the ceramic jar containing the oil, allow us to hypothesise that the jar was introduced into the case after the arrival of the relics in Venice (1100 A.D.) during one of the official inquisitions prior to that documented in 1399 A.D.


Endovascular treatment to boost AV fistula maturation.
Impaired fistula maturation is associated with puncture-related complications, insufficient dialysis and potential permanent access failure. Non-maturation is frequently initiated by stenotic vascular access vessels comprising the outflow veins, the arteriovenous anastomosis and infrequently the inflow artery. Further findings in maturation protraction are central venous stenoses or accessory outflow veins. Depending on the underlying pathology, several endovascular approaches to boost fistula maturation are possible. To date standard balloon angioplasty remains the primary proven treatment option.


Recurrent chronic histiocytic intervillositis with intrauterine growth restriction, osteopenia, and fractures.
Chronic histiocytic intervillositis (CHI) is characterized by the presence of histiocytes within the intervillous space of the placenta. The pathogenesis is unclear but available evidence supports an alloimmune mechanism on the basis of the presence in maternal blood of HLA antibodies directed against paternal HLA antigens. CHI has a high risk of recurrence and of abnormal perinatal outcomes. Little is known about the effects of CHI on the developing fetus, in particular on the growth and development of the skeleton. We have studied a woman whose third pregnancy was terminated after ultrasonography showed severe intrauterine growth restriction, raising the possibility of a lethal skeletal dysplasia. Postmortem radiographs showed multiple fractures and other signs of osteogenesis imperfecta (OI). However, bone histology was not typical of OI and no abnormalities were identified by sequencing OI genes. The subsequent pregnancy was also severely growth restricted and was terminated. The placenta showed chronic histiocytic intervillositis, which, on retrospective review, had also been present in her second and third pregnancies. Her fifth pregnancy was again associated with intrauterine growth restriction and CHI but resulted in a premature birth. CHI can be associated with radiographic features that mimic OI and should be considered when fetal fractures occur in the context of recurrent miscarriage, fetal death in utero, and intrauterine growth restriction. The correct diagnosis can be made by histopathology of the placenta, supported by bone histology and normal results of molecular studies for OI. © 2016 Wiley Periodicals, Inc.


Role of carnitine and its derivatives in the development and management of type 2 diabetes.
Type 2 diabetes is a highly prevalent chronic metabolic disorder characterized by hyperglycemia and associated with several complications such as retinopathy, hyperlipidemia and polyneuropathy. The dysregulated fatty acid metabolism along with tissue lipid accumulation is generally assumed to be associated in the development of insulin resistance and T2D. Moreover, several studies suggest a central role for oxidative stress in the pathogenesis of the disease. Since L-carnitine (LC) has an indispensable role in lipid metabolism via its involvement in the β-oxidation of long-chain fatty acids and it has antioxidant properties as well, carnitine supplementation may prove to be an effective tool in the management of the clinical course of T2D. In this review we summarize the results from animal and clinical studies demonstrating the effects of supplementation with LC or LC derivatives (acetyl-LC, propionyl-LC) on various metabolic and clinical parameters associated with T2D.


Concomitant stromal tumor and early cancer of the stomach: What should be done?
Concomitant gastric stromal tumor (GST) and gastric cancer (GC) is uncommon; even more uncommon is a concomitant GST and early stage GC (EGC). Tumor resection by endoscopic submucosal dissection (ESD) for concomitant GST and EGC has not been reported. We sought to define the clinical importance of detection of concomitant GST and EGC during the first esophagogastroduodenoscopy (EGD), and compare the clinical outcomes of ESD versus radical surgery for the treatment of concomitant GST and EGC. Our investigation was a retrospective cohort study. Patients with concomitant GST and EGC who underwent ESD or radical surgery were enrolled at the university-affiliated hospital from January 2005 to January 2015. The detection rate of concomitant GST and EGC during the first EGD was 3/25 (12%). Among 25 patients, 14 underwent ESD and 11 underwent surgery. Mean operation time and hospital stay were significantly shorter in the ESD group than the surgery group. There were no significant differences in terms of rates of en bloc resection, complete resection, and early complications. Late complications were more common in the surgery group than in the ESD group. The median follow-up duration was 58.9 months. Three- or 5-year overall survival rates were 100% for both groups and no patient died of EGC and GST. There was no local recurrence in the 2 groups; however, 3 metachronous EGC lesions were found during the follow-up period in the ESD group as follows: the simultaneous occurrence of GST and EGC was uncommon; the detection rate of concomitant GST and EGC was very low at the first EGD; and ESD appeared to be a safe, efficient, and popular treatment option for concomitant GST and EGC, that met the ESD absolute indication, and the outcomes were comparable to those achieved with surgery.


Mediated electron transfer in glucose oxidising enzyme electrodes for application to biofuel cells: recent progress and perspectives.
Glucose oxidising enzyme electrodes have long been studied for their application to biosensors and, more recently, anodes in biofuel cells. At a fundamental level, insight into enzyme electron transfer and oxidation current generation at enzyme electrodes can be gained by systematic studies on integration of surfaces, biocatalysts, and artificial substrates (mediators). In this perspective, we present an overview of methods to aid the development of glucose oxidising enzyme electrodes based on mediated electron transfer for application to continuous-use anodes in a biofuel cell. Focus is placed on the rational design of mediators, based on osmium redox complexes, and screening of the activity of such complexes as mediators for glucose oxidising enzymes. An overview of the performance of enzyme electrodes, focused predominantly on crosslinked films of redox polymers and glucose oxidase, for glucose oxidation, is presented and approaches to improve both current output and stability of such enzyme electrodes are discussed.


Protective serum effects in tumor immunity.
Administration of serum presumed to contain tumor-specific antibodies supported the rejection in immunized mice of syngeneic fibrosarcoma implants which receded after an initial period of s.c. growth. Passive transfer of immune serum to unsensitized mice, sublethally radiated and injected with normal lymph node cells, protected the recipients against i.v. but not against s.c. implantation of syngeneic mammary carcinoma cells. Injection of immune serum assisted the recovery of mice in a state of tumor-induced specific immune depression induced by a large. s.c. mammary carcinoma implant and maintained after surgical cure by injections of serum presumed to contain soluble tumor antigen.


Acute Severe Ulcerative Colitis Is Associated With an Increased Risk of Acute Pouchitis.
Pouchitis occurs in up to 80% of patients after total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA) and has been associated with microbial and host-related immunological factors. We hypothesized that a more robust immune response at the time of colectomy, manifested by acute severe ulcerative colitis (ASUC), may be associated with subsequent acute pouchitis. This was a retrospective cohort analysis of all patients with UC or indeterminate colitis complicated by medically refractory disease or dysplasia who underwent TPC with IPAA at Mount Sinai Hospital between 2008 and 2017 and at least 1 subsequent pouchoscopy. Acute pouchitis was defined according to the Pouchitis Disease Activity Index. Cox regression was used to assess unadjusted relationships between hypothesized risk factors and acute pouchitis. A total of 416 patients met inclusion criteria. Of the 165 (39.7%) patients who underwent urgent colectomy, 77 (46.7%) were admitted with ASUC. Acute pouchitis occurred in 228 (54.8%) patients a median of 1.3 (interquartile range, 0.6-3.1) years after the final surgical stage. On multivariable analysis, ASUC (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.04-2.17) and a greater number of biologics precolectomy (HR, 1.57; 95% CI, 1.06-2.31) were associated with an increased probability of acute pouchitis, while older age at colectomy (HR, 0.98; 95% CI, 0.97-0.99) was associated with a decreased probability. Time to pouchitis was significantly less in patients admitted with ASUC compared with those not (P = .002). A severe UC disease phenotype at the time of colectomy was associated with an increased probability of acute pouchitis.


A new insight into the pathogenesis of filarial disease.
Filariasis is a major public health problem throughout many regions of the tropics. The disease is caused by several species of filarial nematode including Wuchereria bancrofti and Brugia malayi, the agents of lymphatic filariasis, and Onchocerca volvulus, the cause of 'riverblindness'. Disease caused by these worms varies depending on the tissue location of the parasite, and is associated with episodes of acute and chronic inflammation. These pathologies, including elephantiasis and blindness, rank among the most disabling in the world. Studies aimed at characterizing the molecular nature of the inflammatory stimuli derived from filarial nematodes uncovered a long forgotten secret, their symbiont Wolbachia. LPS-like molecules from these intracellular bacteria are responsible for potent inflammatory responses from macrophages and in animal models of filarial disease. Wolbachia has also been associated with severe inflammatory reactions to filarial chemotherapy, being released into the blood following the death of the parasite. Recent studies in animal models even implicate Wolbachia in the onset of lymphodema and blindness. Taken together these studies suggest a major role for Wolbachia in the pathogenesis of filarial disease. It may be possible, through the use of antibiotic therapy, to clear worms of their bacteria, in the hope that this will prevent the onset and development of filarial pathology.


A stepwise approach to fine needle aspiration cytology of lymph nodes.
The cytological diagnosis of lymph node lesions is extremely challenging because of the diverse diseases that cause lymph node enlargement, including both benign and malignant or metastatic lymphoid lesions. Furthermore, the cytological findings of different lesions often resemble one another. A stepwise diagnostic approach is essential for a comprehensive diagnosis that combines: clinical findings, including age, sex, site, multiplicity, and ultrasonography findings; low-power reactive, metastatic, and lymphoma patterns; high-power population patterns, including two populations of continuous range, small monotonous pattern and large monotonous pattern; and disease-specific diagnostic clues including granulomas and lymphoglandular granules. It is also important to remember the histological features of each diagnostic category that are common in lymph node cytology and to compare them with cytological findings. It is also essential to identify a few categories of diagnostic pitfalls that often resemble lymphomas and easily lead to misdiagnosis, particularly in malignant small round cell tumors, poorly differentiated squamous cell carcinomas, and nasopharyngeal undifferentiated carcinoma. Herein, we review a stepwise approach for fine needle aspiration cytology of lymphoid diseases and suggest a diagnostic algorithm that uses this approach and the Sydney classification system.


Inhibitory effect of dietary perilla oil rich in the n-3 polyunsaturated fatty acid alpha-linolenic acid on colon carcinogenesis in rats.
The inhibitory effect of dietary perilla oil rich in the n-3 polyunsaturated fatty acid alpha-linolenic acid against colon carcinogenesis was investigated in rats. Four groups of 26 F344 rats each received an intrarectal dose of 2 mg of N-methyl-N-nitrosourea 3 times a week for 2 weeks, and received a diet containing 12% perilla oil, 6% or 12% safflower oil (rich in the n-6 polyunsaturated fatty acid linoleic acid), or 12% palm oil (rich in saturated and monounsaturated fatty acids). At week 35, the incidence of colon cancer was significantly lower in perilla oil-fed rats than in other dietary groups; 19% vs. 46%, 56% and 58%. When examined at week 10, the concentration of fecal bile acids, known to be tumor promoters, was not significantly different among the dietary groups, and the intrarectal deoxycholic acid-induced colonic mucosal ornithine decarboxylase activity, a marker of tumor promotion, was significantly lower in perilla oil-fed group than in other groups. The serum and colonic mucosal fatty acid compositions and the blood plasma prostaglandin E2 level directly reflected the fatty acid composition of each dietary fat. The results suggest that the anti-tumor-promoting effect of dietary perilla oil was a result of a decreased sensitivity of colonic mucosa to tumor promoters arising from the altered fatty acid composition in membrane phospholipid of colonic epithelial cells, and was not a consequence of a decrease of promoters such as bile acids.


[The 48,XXXX syndrome: study of psychomotor development from birth to 11 years of age and review of the literature].
A child with four X chromosomes is described. This case and the literature review allow to underline the mental retardation and some other "major" but inconstant signs that are extremely helpful for the early clinical diagnosis. They are hypertelorism, epicanthal fold and genital anomalies. The mental evolution is assessed on an eleven year period. The bad results concern particularly the child's use of language and the complicated works. They become worse with time. The additional X chromosomes Mary Lyon inactivation, perhaps incomplete, is discussed because its determinism. Enzymatic measuring out is our approach to this problem.


Ovarian cancer in older women.
Advancing age is considered a risk factor for survival in ovarian cancer. Several groups reported at least a twofold increased risk of death in women older than 65 years of age. In this review, we will focus on several aspects of the management of ovarian cancer in the elderly, including the prognostic implications of advanced age, surgical considerations in the frail, chemotherapy options such as intraperitoneal (IP) treatment, and geriatric assessment in predicting toxicity.


Automobile injury: a common familiar risk for presenting and comparing risks in dermatology.
Highly effective treatments exist in dermatology, yet fears regarding rare potential adverse events lead to poor adherence and treatment refusal. The use of a common identifiable risk, such as the risk of automobile injury warranting a visit to the emergency department, could provide a helpful tool for putting risks into perspective. PubMed and US Department of Transportation data were searched to quantify lifetime risk (LTR) of different dermatologic interventions and compare them to an automobile injury risk unit (RU). The LTR of automobile injury was 32%, defined as 1.0 RU. Herein, we review the dermatologic interventions that are less common and much safer than the risk of automobile injury. The use of a visual tool, using an automobile injury RU as comparator, might help alleviate fears and improve patient outcomes.


[Protocol for the combination of neurohistological techniques on vibratome obtained sections].
The histological study of the nervous system requires the use of special techniques. Currently, no methods are available to visualize simultaneously all the cellular constituents of nervous tissue. A protocol was adapted for staining nervous tissue by modification of a formerly difficult procedure. Slices of brain and spinal cord, 4 mm thick, were taken from adult mice, previously fixed by intracardiac perfusion with 4% paraformaldehyde. Vibratome sections were obtained with thickness of 15-25 µm. These were mounted on glass slides prepared with gelatin as an adhesive. The preparations were subjected to staining protocol Luxol Fast Blue-PAS-hematoxylin (LPH) combined with silver staining method (LPH-Holmes). LPH technique yielded an excellent differentiation of gray and white matter in all regions of the nervous system. A panoramic view of the gray matter was colored pink in contrast to the myelinated nerve fibers and tracts which were light blue. The combination LPH-Holmes retained the staining characteristics but significantly improved the demarcation of axons and tracts. A protocol was standardized for the LPH and LPH-Holmes nervous tissue stains applied in combination to tissue slices obtained with a vibratome. The method was shorter, less wasteful and less expensive than the original and also better preserved the integrity of nervous tissue.


Using an Integrated Clinical and Functional Assessment Tool to Describe the Use of Social and Medical Care in an Urban Community-Dwelling Swedish Older Population.
To describe the use of social and medical care services in a community-dwelling older population from Stockholm, Sweden, using an integrated clinical and functional assessment tool. Study based on data from the longitudinal community-based Swedish National Study on Aging and Care in Kungsholmen. Random sample of people >65 years of age living in the community in central Stockholm between March 2001 and June 2004 (N = 2368). Health status was measured with a health assessment tool (HAT), which combines 5 indicators (gait speed, cognitive function, chronic multimorbidity, mild disability, severe disability) collected during Swedish National Study on Aging and Care in Kungsholmen clinical examinations. The amount of formal and informal social care was self-reported in hours per month and recorded by trained nurses at baseline and the 3-year follow-up for those ≥78 years of age at baseline. Data on hospital admissions, 30-day readmissions, days spent in the hospital, primary care visits, and specialist visits were obtained from Stockholm County Council registers (2001-2007). At baseline, 10% of the sample received formal social care and 11% received informal care. Annually between baseline and the 3-year follow-up, 15% were admitted to the hospital, 5% were readmitted, 78% visited a specialist, and 89% visited primary care. Those with the best HAT scores received 0.02 hours/month of formal care; those with the worst, 34 h/mo. The corresponding numbers for other variables were 0.02 vs 73 h/mo of informal care, 2 vs 11 hospital admissions per 10 persons/year, 44 vs 226 hospital days per 10 persons/y, 0.4 vs 2 30-day readmissions per 10 persons/y, 37 vs 78 specialist visits per 10 persons/y, and 50 vs 327 primary care visits per 10 persons/y. Because of its high discriminative power, the easy-to-use HAT index could help decision makers to plan medical and social care services.


Immune regulation by CD40-CD40-L interactions.
CD40 is a cell surface receptor, which belongs to the TNF-R family, and which was first identified and functionally characterized on B lymphocytes. However, in recent years it has become clear that CD40 is expressed much broader, including expression on monocytes, dendritic cells, endothelial cells and epithelial cells. Therefore it is now thought that CD40 plays a more general role in immune regulation. The present paper reviews recent developments in this field of research, with main emphasis on 1) structure and expression of CD40 and its ligand; 2) CD40 signal transduction; 3) in vitro function of CD40 on different cell types; 4) in vivo functions of CD40/CD40-L interactions.


A rapid expansion of hospitals: the adaptation of multi-campus hospitals under the Chinese healthcare system.
In recent years, China's healthcare system has undergone significant changes to meet the increasing demands of its growing population. One notable development is the rapid expansion of hospitals, particularly the adaptation of multi-campus hospitals. These multi-campus hospitals have become increasingly popular due to the many advantages that single-campus hospitals lack, including the ability to; improve medical service quality, reduce operating costs, and facilitate the development of healthcare services in rural areas. In this study, we discuss the advantages that this type of medical facility offers and identify existing and potential problems that could hinder the development of multi-campus hospitals. Additionally, we propose appropriate solutions to mitigate these problems. Overall, we propose that there should be more communication between multi-campus hospitals and other healthcare providers.


Cerebral blood flow and vasoreactivity in aging: an arterial spin labeling study.
Regional cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) in young and elderly participants were assessed using pulsed arterial spin labeling (ASL) and blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) techniques in combination with inhalation of CO2. Pulsed ASL and BOLD-MRI were acquired in seventeen asymptomatic volunteers (10 young adults, age: 30±7 years; 7 elderly adults, age: 64±8 years) with no history of diabetes, hypertension, and neurological diseases. Data from one elderly participant was excluded due to the incorrigible head motion. Average baseline CBF in gray matter was significantly reduced in elderly (46±9 mL·100 g-1·min-1) compared to young adults (57±8 mL·100 g-1·min-1; P=0.02). Decreased pulsed ASL-CVR and BOLD-CVR in gray matter were also observed in elderly (2.12±1.30 and 0.13±0.06 %/mmHg, respectively) compared to young adults (3.28±1.43 and 0.28±0.11 %/mmHg, respectively; P<0.05), suggesting some degree of vascular impairment with aging. Moreover, age-related decrease in baseline CBF was observed in different brain regions (inferior, middle and superior frontal gyri; precentral and postcentral gyri; superior temporal gyrus; cingulate gyri; insula, putamen, caudate, and supramarginal gyrus). In conclusion, CBF and CVR were successfully investigated using a protocol that causes minimal or no discomfort for the participants. Age-related decreases in baseline CBF and CVR were observed in the cerebral cortex, which may be related to the vulnerability for neurological disorders in aging.


Endoscopic Treatment of Greater Trochanteric Pain Syndrome - A Case Series of 11 Patients.
Greater trochanteric pain syndrome (GTPS) includes patients with symptoms of peritrochanteric pain, gluteus medius/minimus tendinopathy, and external snapping hip. Non-operative treatment includes iliotibial band (ITB) stretching, gluteal exercises and cortisone injections. When surgery is indicated due to the failure of non-operative strategies, open Z-plasty at the level of the greater trochanter has been the traditional procedure. Endoscopic release of the ITB and bursectomy at the level of the greater trochanter has over the last decades evolved and is established as an alternative method of surgery. We here present a case series with 11 consecutive patients who have undergone endoscopic release of the ITB and bursectomy at the level of the greater trochanter due to GTPS. The patients were all Caucasians, 43-years of age, and six were female. The patients retrospectively scored their pre-operative function and pain during follow-up at 28 months (range 15-42). Post-operative pain and function were scored at follow-up. In this paper, we discuss investigation, differential diagnoses, surgical options, and outcomes in the treatment of GTPS. All patients reported significant reduction of pain, and 10 of 11 patients reported an improvement in function. We observed no complications. Endoscopic release of the ITB and bursectomy at the level of the greater trochanter appears to be an effective and safe procedure when conservative treatment options for GTPS have failed.


Effects of PACAP-38 and an analog, acetyl-[Ala15, Ala20] PACAP-38-propylamide, on memory consolidation in the detection of spatial novelty task in rats.
PACAP-38 (P38) is a pleiotropic peptide that exerts multiple peripheral and central actions, including neurotrophic, neuroprotective and anti-inflammatory actions. Previous studies have suggested an improvement of memory in rats that have received a single systemic injection of P38. In a therapeutic perspective, we used an analog, acetyl-[Ala15, Ala20]PACAP-38-propylamide (ALG), to improve both stability and affinity for PAC1 receptors vs. endogen PACAP. We investigated the effect of P38 and ALG on memory consolidation using a spatial novelty detection (SND) task in which rats had to memorize a configuration of objects to identify that, during a test session, a familiar object has been moved to a new location. Rats received an intravenous injection of P38 or ALG after the last training session. In Experiment 1, P38 (30 µg/kg) improved spatial memory consolidation allowing detection of novelty vs. saline injection. In Experiment 2, we confirmed this effect and showed that P38 restored the performance similar to what was found using non-injected rats. This suggests that, contrary to ALG, P38 exerted a promesiant rather than an anxiety-related effect whereas ALG did not show similar action. We also examined whether P38 effect involved an interaction with NR2B-containing NMDA receptors (NMDARs) by administrating ifenprodil (IFE; a selective NR2B-containing NMDAR antagonist) alone or in combination with P38 or ALG. The results suggested that P38 action on memory involved NR2B-containing NMDARs. Lastly, brain-derived neutrophic factor (BDNF) modulation appeared to be not related to the behavioral performance in the SND task. Overall, the results indicate that P38 exerted a beneficial effect on memory consolidation in a non-associative task, whereas ALG did not have this action.


GSK3β inhibitor promotes myelination and mitigates muscle atrophy after peripheral nerve injury.
Delay of axon regeneration after peripheral nerve injury usually leads to progressive muscle atrophy and poor functional recovery. The Wnt/β-catenin signaling pathway is considered to be one of the main molecular mechanisms that lead to skeletal muscle atrophy in the elderly. We hold the hypothesis that the innervation of target muscle can be promoted by accelerating axon regeneration and decelerating muscle cell degeneration so as to improve functional recovery of skeletal muscle following peripheral nerve injury. This process may be associated with the Wnt/β-catenin signaling pathway. Our study designed in vitro cell models to simulate myelin regeneration and muscle atrophy. We investigated the effects of SB216763, a glycogen synthase kinase 3 beta inhibitor, on the two major murine cell lines RSC96 and C2C12 derived from Schwann cells and muscle satellite cells. The results showed that SB216763 stimulated the Schwann cell migration and myotube contraction. Quantitative polymerase chain reaction results demonstrated that myelin related genes, myelin associated glycoprotein and cyclin-D1, muscle related gene myogenin and endplate-associated gene nicotinic acetylcholine receptors levels were stimulated by SB216763. Immunocytochemical staining revealed that the expressions of β-catenin in the RSC96 and C2C12 cytosolic and nuclear compartments were increased in the SB216763-treated cells. These findings confirm that the glycogen synthase kinase 3 beta inhibitor, SB216763, promoted the myelination and myotube differentiation through the Wnt/β-catenin signaling pathway and contributed to nerve remyelination and reduced denervated muscle atrophy after peripheral nerve injury.


Patients' views regarding choice of dialysis modality.
Increasing patient numbers have resulted in pressure on dialysis centres and a need to reorganize dialysis treatment. This study explored patients' experiences with different dialysis modalities and investigated issues related to the patient's choice of modality, especially 'out-of-centre' dialysis (i.e. modalities other than CHD). Six focus group interviews were conducted with 24 dialysis patients, 3 pre-dialysis patients and 18 relatives. Each focus group comprised patients on one type of dialysis, i.e. CHD, self-care CHD, HHD, CAPD/APD, aAPD or pre-dialysis patients. Based on a semi-structured interview guide, the group discussions centred on advantages and disadvantages of dialysis modalities, problems experienced and their (possible) solutions and patient involvement in choice of modality. The focus groups participants considered that each dialysis modality has its advantages and disadvantages. Flexibility, independence and feelings of security were key factors in determining choice of modality, with maintenance of a normal life being a major goal. Patients and their relatives want to participate in choice of modality, but a genuine offer of out-of-centre dialysis including professional support and appropriate and timely education is needed to encourage a greater use of modalities other than CHD. No single dialysis modality emerged as offering the best solution for patients with end-stage renal disease. In the absence of absolute clinical contraindications, the treatment of choice should be the modality that best accommodates the patients' preferences for their daily activities and lifestyle. A move towards more patients on out-of-centre dialysis requires a greater focus on pre-dialysis patients and closer consideration of patients' preferences and current lifestyle.


Effects of initial eye position on saccade-related behavior of abducens nucleus neurons in the primate.
Previous work suggests that when the eye starts at different orbital initial positions (IPs), the saccade control system is faced with significant nonlinearities. Here we studied the effects of IP on saccade-related firing of monkey abducens neurons by either isolating saccade variables behaviorally or applying a multiple linear regression analysis. Over a 50 degrees range of IPs, we could select 10 degrees horizontal saccades with identical velocity profiles, which would require identical control signals in a linear system. The bursts accompanying ipsiversive saccades for IPs above the threshold for steady firing were quite similar. The excess burst rate above steady firing was either constant or decreased with ipsiversive IP, and both the number of excess spikes in the burst and burst duration were nearly constant. However, for ipsiversive saccades from IPs below threshold, both peak burst rate (6.82 +/- 1.38 spikes.s(-1).deg(-1)) and burst duration (0.67 +/- 0.28 ms/deg) increased substantially with ipsiversive IPs. Moreover, the pause associated with contraversive saccades shortened considerably with ipsiversive IPs (mean 1.2 ms/deg). This pattern of results for pauses and for bursts below threshold suggests the presence of a significant nonlinearity. Abducting saccades are produced by the net force of agonist lateral rectus (LR) and antagonist medial rectus (MR) muscles. We suggest that the decreasing force in the MR muscle with IPs in the abducting direction requires a more vigorous burst in LR motoneurons, which appears to be generated by a combination of saturating and nonsaturating burst commands and the recruitment of additional abducens neurons.


Topology-defined units in numerosity perception.
What is a number? The number sense hypothesis suggests that numerosity is "a primary visual property" like color, contrast, or orientation. However, exactly what attribute of a stimulus is the primary visual property and determines numbers in the number sense? To verify the invariant nature of numerosity perception, we manipulated the numbers of items connected/enclosed in arbitrary and irregular forms while controlling for low-level features (e.g., orientation, color, and size). Subjects performed discrimination, estimation, and equality judgment tasks in a wide range of presentation durations and across small and large numbers. Results consistently show that connecting/enclosing items led to robust numerosity underestimation, with the extent of underestimation increasing monotonically with the number of connected/enclosed items. In contrast, grouping based on color similarity had no effect on numerosity judgment. We propose that numbers or the primitive units counted in numerosity perception are influenced by topological invariants, such as connectivity and the inside/outside relationship. Beyond the behavioral measures, neural tuning curves to numerosity in the intraparietal sulcus were obtained using functional MRI adaptation, and the tuning curves showed that numbers represented in the intraparietal sulcus were strongly influenced by topology.


No prolongation of skin allograft survival by immunoproteasome inhibition in mice.
The immunoproteasome, a distinct class of proteasomes, which is inducible under inflammatory conditions and constitutively expressed in monocytes and lymphocytes, is known to shape the antigenic repertoire presented on major histocompatibility complex (MHC) class I molecules. Moreover, inhibition of the immunoproteasome subunit LMP7 ameliorates clinical symptoms of autoimmune diseases in vivo and was shown to suppress the development of T helper cell (Th) 1 and Th17 cells and to promote regulatory T-cell (Treg) generation independently of its function in antigen processing. Since Th1 and Th17 cells are detrimental and Treg cells are critical for transplant acceptance, we investigated the influence of the LMP7-selective inhibitor ONX 0914 in a mixed lymphocyte reaction (MLR) in vitro as well as on allograft rejection in a MHC-disparate (C57BL/6 to BALB/c) and a multiple minor histocompatibility antigen (miHA)-disparate (B10.Br to C3H) model of skin transplantation in vivo. Although we observed reduced allo-specific IL-17 production of T cells in vitro, we found that selective inhibition of LMP7 had neither an influence on allograft survival in an MHC-mismatch model nor in a multiple minor mismatch skin transplantation model. We conclude that inhibition of the immunoproteasome is not effective in prolonging skin allograft survival in skin allotransplantation.


Perforin-dependent CD4+ T-cell cytotoxicity contributes to control a murine poxvirus infection.
CD4(+) T cells are generally regarded as helpers and regulators of the immune response. Although cytolytic CD4(+) T cells have been described, whether those generated during the course of a viral infection play a role in virus control remains unknown. Here we show that during acute infection with ectromelia virus, the mouse homolog of the human virus of smallpox, large numbers of CD4(+) T cells in the draining lymph node and liver of resistant mice have a cytotoxic phenotype. We also show that these cells kill targets in vivo in a perforin-dependent manner and that mice with specific deficiency of perforin in CD4(+) T cells have impaired virus control. Thus, perforin-dependent CD4(+) T-cell killing of infected cells is an important mechanism of antiviral defense.


Effects of subcortical cerebrovascular lesions on cortical hemodynamic parameters assessed by perfusion magnetic resonance imaging.
A simultaneous decrease of cerebral blood volume (CBV) and cerebral blood flow (CBF) has been described after subcortical stroke with positron emission tomography. However, this imaging modality cannot be applied routinely to stroke patients. Dynamic susceptibility contrast-enhanced MRI techniques (DSC-MRI) might be interesting in the assessment of these effects. Dynamic T2-weighted echo planar imaging was used to produce DSC-MR images during an intravenous bolus injection of gadopentetate dimeglumine in 9 patients who experienced a subcortical stroke involving thalamus or basal ganglia and in 8 control subjects. A series of 50 consecutive images at 1-second intervals was acquired at the anatomic level of the centrum semiovale quite distant from the subcortical lesion, rCBF and rCBV were determined over frontal and parietal regions of interest and through the entire cortical mantle. DSC-MRI enabled the detection of hemodynamic changes induced by subcortical stroke. Analysis of rCBV and rCBF values showed that the hemodynamic parameters were significantly decreased on the affected side. In controls mean rCBF and rCBV values recorded over the whole cortical mantle of each hemisphere showed no significant interhemispheric asymmetry.


Self-Assembled Zinc/Cystine-Based Chloroplast Mimics Capable of Photoenzymatic Reactions for Sustainable Fuel Synthesis.
Prototypes of biosystems provide good blueprints for the design and creation of biomimetic systems. However, mimicking both the sophisticated natural structures and their complex biological functions still remains a great challenge. Herein, chloroplast mimics have been fabricated by one-step bioinspired amino acid mineralization and simultaneous integration of catalytically active units. Hierarchically structured crystals were obtained by the metal-ion-directed self-assembly of cystine (the oxidized dimer of the amino acid cysteine), with a porous structure and stacks of nanorods, which show similar architectural principles to chloroplasts. Porphyrins and enzymes can both be encapsulated inside the crystal during mineralization, rendering the crystal photocatalytically and enzymatically active for an efficient and sustainable synthesis of hydrogen and acetaldehyde in a coupled photoenzymatic reaction.


English-speaking and Spanish-speaking domestic violence perpetrators: an MMPI-2 assessment.
The use of assessments to characterize domestic violence perpetrators continues to develop with an emphasis on increasing the effectiveness of domestic violence interventions. The present study examines and compares Minnesota Multiphasic Personality Inventory (MMPI)-2 responses from 41 English-speaking and 48 Spanish-speaking men who were in court-mandated domestic violence treatment programs. Data are analyzed on all validity, clinical, supplementary, and content scales using composite means and cluster analyses. Although there are significant differences between the 2 groups on 12 scales, no scale shows significant clinical elevations (T > 65) for either language cohort. Three perpetrator subgroups are identified using a methodology similar to that used in previous MMPI-2 studies: nonpathological, antisocial, and otherwise psychologically disturbed. The proportion of participants falling into each of the 3 groups, for both English and Spanish speakers, is similar to that found in other studies. The results are discussed in terms of cultural influences and the need for treatment approaches tailored to characteristics of each personality type.


Shallow Whole Genome Sequencing on Circulating Cell-Free DNA Allows Reliable Noninvasive Copy-Number Profiling in Neuroblastoma Patients.
Purpose: Neuroblastoma (NB) is a heterogeneous disease characterized by distinct clinical features and by the presence of typical copy-number alterations (CNAs). Given the strong association of these CNA profiles with prognosis, analysis of the CNA profile at diagnosis is mandatory. Therefore, we tested whether the analysis of circulating cell-free DNA (cfDNA) present in plasma samples of patients with NB could offer a valuable alternative to primary tumor DNA for CNA profiling.Experimental Design: In 37 patients with NB, cfDNA analysis using shallow whole genome sequencing (sWGS) was compared with arrayCGH analysis of primary tumor tissue.Results: Comparison of CNA profiles on cfDNA showed highly concordant patterns, particularly in high-stage patients. Numerical chromosome imbalances as well as large and focal structural aberrations including MYCN and LIN28B amplification and ATRX deletion could be readily detected with sWGS using a low input of cfDNA.Conclusions: In conclusion, sWGS analysis on cfDNA offers a cost-effective, noninvasive, rapid, robust and sensitive alternative for tumor DNA copy-number profiling in most patients with NB. Clin Cancer Res; 23(20); 6305-14. ©2017 AACR.


Association Between Hospital Participation in Medicare Shared Savings Program Accountable Care Organizations and Readmission Following Major Surgery.
To evaluate the effect of Medicare Shared Savings Program accountable care organizations (ACOs) on hospital readmission after common surgical procedures. Hospital readmissions following surgery lead to worse patient outcomes and wasteful spending. ACOs, and their associated hospitals, have strong incentives to reduce readmissions from 2 distinct Centers for Medicare and Medicaid Services policies. We performed a retrospective cohort study using a 20% national Medicare sample to identify beneficiaries undergoing 1 of 7 common surgical procedures-abdominal aortic aneurysm repair, colectomy, cystectomy, prostatectomy, lung resection, total knee arthroplasty, and total hip arthroplasty-between 2010 and 2014. The primary outcome was 30-day risk-adjusted readmission rate. We performed difference-in-differences analyses using multilevel logistic regression models to quantify the effect of hospital ACO affiliation on readmissions following these procedures. Patients underwent a procedure at one of 2974 hospitals, of which 389 were ACO affiliated. The 30-day risk-adjusted readmission rate decreased from 8.4% (95% CI, 8.1-8.7%) to 7.0% (95% CI, 6.7-7.3%) for ACO affiliated hospitals (P < 0.001) and from 7.9% (95% CI, 7.8-8.0%) to 7.1% (95% CI, 6.9-7.2%) for non-ACO hospitals (P < 0.001). The difference-in-differences of the 2 trends demonstrated an additional 0.52% (95% CI, 0.97-0.078%) absolute reduction in readmissions at ACO hospitals (P = 0.021), which would translate to 4410 hospitalizations avoided. Readmissions following common procedures decreased significantly from 2010 to 2014. Hospital affiliation with Shared Savings ACOs was associated with significant additional reductions in readmissions. This emphasis on readmission reduction is 1 mechanism through which ACOs improve value in a surgical population.


Low plasma N-3 fatty acids and dementia in older persons: the InCHIANTI study.
N-3 fatty acids (FA) have an important role in brain development and function. However, there is conflicting evidence concerning the relationship between n-3 FA and dementia in older persons. In the Invecchiare in Chianti (InCHIANTI) study, we measured plasma FA by gas chromatography in 935 community-dwelling older persons randomly extracted from the population of two towns near Florence, Italy. Cognitive impairment was measured using the Mini-Mental Status Examination. Participants who scored </=26 underwent a detailed clinical and neuropsychological evaluation. The diagnosis of dementia was based on Diagnostic and Statistical Manual of Mental Disorders, Third Revision (DSM-III-R) criteria. The population was divided in three groups: persons with normal cognitive function, persons with cognitive impairment not demented, and persons with dementia. After adjustment for age, gender, education, body mass index, weight loss, smoking status, cholesterol and triglycerides levels, daily intake of alcohol, FA and total energy, cardiovascular disease, depression and other FA levels, participants with dementia had significantly lower n-3 FA levels (2.9% vs 3.2%; p <.05), particularly alpha-linolenic acid levels (0.34% vs 0.39%; p <.05), than did participants with normal cognitive function. Dementia is associated with low plasma n-3 FA relative concentrations. The possibility that higher n-3 FA intake is associated with a lower risk of cognitive impairment should be further investigated in prospective studies.


Aminode: Identification of Evolutionary Constraints in the Human Proteome.
Evolutionarily constrained regions (ECRs) are a hallmark for sites of critical importance for a protein's structure or function. ECRs can be inferred by comparing the amino acid sequences from multiple protein homologs in the context of the evolutionary relationships that link the analyzed proteins. The compilation and analysis of the datasets required to infer ECRs, however, are time consuming and require skills in coding and bioinformatics, which can limit the use of ECR analysis in the biomedical community. Here, we developed Aminode, a user-friendly webtool for the routine and rapid inference of ECRs. Aminode is pre-loaded with the results of the analysis of the whole human proteome compared with proteomes from 62 additional vertebrate species. Profiles of the relative rates of amino acid substitution and ECR maps of human proteins are available for immediate search and download on the Aminode website. Aminode can also be used for custom analyses of protein families of interest. Interestingly, mapping of known missense variants shows great enrichment of pathogenic variants and depletion of non-pathogenic variants in Aminode-generated ECRs, suggesting that ECR analysis may help evaluate the potential pathogenicity of variants of unknown significance. Aminode is freely available at http://www.aminode.org .


Identification and characterization of a Saccharomyces cerevisiae gene, RSB1, involved in sphingoid long-chain base release.
Sphingoid long-chain bases (LCBs) and long-chain base phosphates (LCBPs) act as signaling molecules in eukaryotic cells. Accumulation of LCBPs results in cell growth inhibition in yeast, although the mechanism is unknown. Here, we identified a novel yeast gene, RSB1 (resistance to sphingoid long-chain base), by screening a multicopy suppressor of the LCB-sensitive phenotype of the LCBP lyase mutant. RSB1 encodes a polypeptide of 354 amino acids with a molecular mass of 40.4 kDa. Rsb1p is predicted to be an integral membrane protein with seven transmembrane-spanning domains. We demonstrated that cells overproducing Rsb1p showed a decrease in accumulation of exogenously added sphingosine and dihydrosphingosine because of their increased release. This release was ATP-dependent, and a mutant of the predicted ATP binding motif had no activity. Substrate specificity analysis of Rsb1p demonstrated that it is active on LCBs but not on LCBPs or other hydrophobic compounds. These results suggest that Rsb1p is a transporter or flippase that translocates LCBs from the cytoplasmic side toward the extracytoplasmic side of the membrane.


Multifocal diffusion of a KPC-3 producing ST512 K. pneumoniae clone in Northern Italy.
Sequence Type 258 (ST258) together with its allelic single- and double-locus variants have mostly been associated with the dissemination of KPC-producing Klebsiella pneumoniae in Europe. A total of 56 nonreplicate K. pneumoniae isolates with decreased carbapenem-susceptibility, collected at 7 different hospitals located in Northern Italy were investigated for the occurrence of blaKPC-type genes. PCR and sequencing results highlighted the presence of blaKPC2 or blaKPC-3 determinants in 10/56 and 5/56 cases respectively. Here we describe the intra- and inter-hospital spread in Northern Italy of a K. pneumoniae ST512 clone harboring the blaKPC-3 gene.


A dichotomy in the lipophilicity of natural estrogens, xenoestrogens, and phytoestrogens.
Using two independent analyses, it is demonstrated that natural (e.g., estradiol) and some xenoestrogens (e.g., methoxychlor metabolite) are characterized by a lipophilic region that is absent in nonestrogens as well as in phytoestrogens. It is suggested that this lipophilic region affects binding to specific receptors and may, in fact, differentiate harmful from beneficial estrogens.


Sensitivity and Specificity of Plasma ALT, ALP, and Bile Acids for Hepatitis in Labrador Retrievers.
Biochemical indicators for diagnosing liver disease are plasma alanine aminotransferase activity (ALT), alkaline phosphatase activity (ALP), and bile acid concentration (BA). To determine the sensitivity and specificity of ALT, ALP, and BA for detecting primary hepatitis (PH) in clinically healthy Labrador retrievers and investigate whether ALT and ALP can discriminate between dogs with PH and nonspecific reactive hepatitis (RH). 191 clinically healthy and 51 clinically ill Labrador retrievers with hepatic histopathology. Retrospective study. Medical records were reviewed for ALT, ALP, preprandial BA, liver histopathology, and hepatic copper concentrations. In 64% (122/191) of the clinically healthy Labrador retrievers, hepatic histology revealed inflammatory infiltrates. This frequency might be biased because part of them was included as first-line relatives of dogs with copper-associated hepatitis. Sensitivity of ALT, ALP, and BA in this population for detecting acute hepatitis was 45, 15, and 15%, respectively. For chronic hepatitis, sensitivity was 71, 35, and 13%, respectively. Specificity of ALT, ALP, and BA was >90% for AH, CH, and RH. When increased liver enzymes were present, median ALT was significantly higher in PH cases (312 U/L, range 38-1,369) compared to RH cases (91 U/L, range 39-139) (P < .001). There was no difference in ALP between dogs with a PH and a RH (P = .361). Histopathologic abnormalities in the liver were present in the majority of apparent clinically healthy Labrador retrievers. The sensitivity of ALT, ALP, and BA for detecting acute and chronic hepatitis in this population was low. More sensitive biomarkers are needed for early detection of liver disease in apparent clinically healthy dogs.


Precision and Safety of an Intravascular Temperature Management System for Postcardiac Arrest Syndrome Patients: A Multicenter Clinical Trial (COOL-ARREST JP).
Rapid induction and maintaining a target temperature of 32.0-36.0°C within a narrow range for <24 hours are essential, but those are very hard to perform in postcardiac arrest syndrome (PCAS) patients. We investigated the usability of an intravascular temperature management (IVTM) system with neurolept-anesthesia (NLA; droperidol and fentanyl). Single-arm, prospective multicenter trial was carried out in the seven university and the three affiliated hospitals. In the 24 comatose PCAS patients, the target temperature (33.0°C) was rapidly induced and maintained for 24 hours using an IVTM system with NLA. The rewarming speed was 0.1°C/h until 36.5°C and was maintained for 24 hours. The primary end point was the ability to achieve ≤34.0°C for <3 hours after starting cooling, and the secondary end points were the cooling rate, deviation from the target temperature, and adverse events. Cerebral Performance Category (CPC) score at 14 days was also evaluated. Statistical analyses were performed by SPSS software, using the intention-to-treat data sets. The target temperature of ≤34.0°C was reached by 45 minutes (35-73 minutes) and was within 3 hours in all patients. The cooling rate from 36.4°C to 33.0°C was 2.7°C/h (2.4-3.6°C/h). The temperature of 33.1°C (33.1-33.1°C) and 36.7°C (36.6-36.9°C) for 24 hours each was held during the maintenance and the after rewarming phases, respectively. Temperature deviations >0.2°C from 33.0°C in the maintenance phase occurred once each in two patients. The favorable neurological outcomes (CPC1, 2) were relatively good (50%). Five patients experienced serious adverse events; none was device related. We rapidly achieved therapeutic hypothermia within a narrow temperature range without major complications using the IVTM system with NLA in PCAS patients.


Unsupervised Analysis of Big ToF-SIMS Data Sets: a Statistical Pattern Recognition Approach.
We present a new method, fast and low demanding in terms of CPU performances, which is able to extract latent chemical information from ToF-SIMS big data sets, such as those arising from chemical imaging, by working on the unbinned raw data files. The method is able to evaluate the similarity/dissimilarity of very low intensity spectra, such as those arising from a single pixel, in terms of symmetry and asymmetry relationships of the count distribution in the Fourier transform domain. The tests performed so far on model samples show that the method supplies results that, without sacrificing mass or spatial resolution, are equivalent, at least, to those achievable by an experienced ToF-SIMS user by applying PCA techniques.


Probabilistic fecal pollution source profiling and microbial source tracking for an urban river catchment.
We developed an innovative approach to estimate the occurrence and extent of fecal pollution sources for urban river catchments. The methodology consists of 1) catchment surveys complemented by literature data where needed for probabilistic estimates of daily produced fecal indicator (FIBs, E. coli, enterococci) and zoonotic reference pathogen numbers (Campylobacter, Cryptosporidium and Giardia) excreted by human and animal sources in a river catchment, 2) generating a hypothesis about the dominant sources of fecal pollution and selecting a source targeted monitoring design, and 3) verifying the results by comparing measured concentrations of the informed choice of parameters (i.e. chemical tracers, C. perfringensspores, and host-associated genetic microbial source tracking (MST) markers) in the river, and by multi-parametric correlation analysis. We tested the approach at a study area in Vienna, Austria. The daily produced microbial particle numbers according to the probabilistic estimates indicated that, for the dry weather scenario, the discharge of treated wastewater (WWTP) was the primary contributor to fecal pollution. For the wet weather scenario, 80-99 % of the daily produced FIBs and pathogens resulted from combined sewer overflows (CSOs) according to the probabilistic estimates. When testing our hypothesis in the river, the measured concentrations of the human genetic fecal marker were log10 4 higher than for selected animal genetic fecal markers. Our analyses showed for the first-time statistical relationships between C. perfringens spores (used as conservative microbial tracer for communal sewage) and a human genetic fecal marker (i.e. HF183/BacR287) with the reference pathogen Giardia in river water (Spearman rank correlation: 0.78-0.83, p < 0.05. The developed approach facilitates urban water safety management and provides a robust basis for microbial fate and transport models and microbial infection risk assessment.


Molecular defects in alkaptonuria.
At the dawn of human genetics Sir Archibald Garrod used alkaptonuria as a paradigm to demonstrate the applicability of the Mendelian laws to men and to develop the concept of inborn errors of metabolism. The human cDNA for homogentisate 1,2 dioxygenase was identified due to its homology to the corresponding mouse enzyme and was screened for mutations in alkaptonuric patients from Slovakia. Homozygous mutations were found in four unrelated families and their segregation with the disease was demonstrated. One of the mutations, observed in two families, leads to a frame-shift and thus is unlikely to produce functional protein. The data formally establish the homogentisate 1,2 dioxygenase gene (HGD) as the molecular cause of alkaptonuria and allow for the development of molecular carrier tests in populations at risk.


A faster running speed is associated with a greater body weight loss in 100-km ultra-marathoners.
In 219 recreational male runners, we investigated changes in body mass, total body water, haematocrit, plasma sodium concentration ([Na(+)]), and urine specific gravity as well as fluid intake during a 100-km ultra-marathon. The athletes lost 1.9 kg (s = 1.4) of body mass, equal to 2.5% (s = 1.8) of body mass (P < 0.001), 0.7 kg (s = 1.0) of predicted skeletal muscle mass (P < 0.001), 0.2 kg (s = 1.3) of predicted fat mass (P < 0.05), and 0.9 L (s = 1.6) of predicted total body water (P < 0.001). Haematocrit decreased (P < 0.001), urine specific gravity (P < 0.001), plasma volume (P < 0.05), and plasma [Na(+)] (P < 0.05) all increased. Change in body mass was related to running speed (r = -0.16, P < 0.05), change in plasma volume was associated with change in plasma [Na(+)] (r = -0.28, P < 0.0001), and change in body mass was related to both change in plasma [Na(+)] (r = -0.36) and change in plasma volume (r = 0.31) (P < 0.0001). The athletes consumed 0.65 L (s = 0.27) fluid per hour. Fluid intake was related to both running speed (r = 0.42, P < 0.0001) and change in body mass (r = 0.23, P = 0.0006), but not post-race plasma [Na(+)] or change in plasma [Na(+)] (P > 0.05). In conclusion, faster runners lost more body mass, runners lost more body mass when they drank less fluid, and faster runners drank more fluid than slower runners.


An ESR study of spin-labeled silk fibroin membranes and spin-labeled glucose oxidase immobilized in silk fibroin membranes.
This article describes the characteristics of silk fibroin membranes and glucose oxidase, immobilized in membranes as determined by a variety of physical methods, mainly the spin-label electron spin resonance (ESR) method. The properties of membranes insolubilized by different methods, i. e., immersion in 80% methanol aqueous solution, uniaxially drawing by placing on a stretcher, and hydration by placing in a desiccator of 96% relative humidity (RH) for 17 h, are compared. The results are also analyzed in relation to ESR spectra of spin-labeled immobilized glucose oxidase and 4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy as a model of the substrate. It is concluded that the heterogeneous structures of the swollen membranes in water differ locally among membranes insolubilized by different methods, but the immobilized state of the enzyme in such membranes is mostly similar. This is correlated to the fact that the thermal or pH stabilities are essentially same among glucose-oxidase-immobilized silk fibroin membranes insolubilized by different methods.


Washed microbiota transplantation reduces glycemic variability in unstable diabetes.
Dysbiosis of gut microbiota is causally linked to impaired host glucose metabolism. We aimed to study effects of the new method of fecal microbiota transplantation, washed microbiota transplantation (WMT), on reducing glycemic variability (GV) in unstable diabetes. Fourteen eligible patients received three allogenic WMTs and were followed up at 1 week, 1 month, and 3 months. Primary outcomes were daily insulin dose, glucose excursions during meal tests, and GV indices calculated from continuous monitoring or self-monitoring glucose values. Secondary outcomes were multiomics data, including 16S rRNA gene sequencing, metagenomics, and metabolomics to explore underlying mechanisms. Daily insulin dose and glucose excursions markedly dropped, whereas GV indices significantly improved up to 1 month. WMT increased gut microbial alpha diversity, beta diversity, and network complexity. Taxonomic changes featured lower abundance of genera Bacteroides and Escherichia-Shigella, and higher abundance of genus Prevotella. Metagenomics functional annotations revealed enrichment of distinct microbial metabolic pathways, including methane biosynthesis, citrate cycle, amino acid degradation, and butyrate production. Derived metabolites correlated significantly with improved GV indices. WMT did not change circulating inflammatory cytokines, enteroendocrine hormones, or C-peptide. WMT showed strong ameliorating effect on GV, raising the possibility of targeting gut microbiota as an effective regimen to reduce GV in diabetes.


Pretreatment methods of lignocellulosic biomass for anaerobic digestion.
Agricultural residues, such as lignocellulosic materials (LM), are the most attractive renewable bioenergy sources and are abundantly found in nature. Anaerobic digestion has been extensively studied for the effective utilization of LM for biogas production. Experimental investigation of physiochemical changes that occur during pretreatment is needed for developing mechanistic and effective models that can be employed for the rational design of pretreatment processes. Various-cutting edge pretreatment technologies (physical, chemical and biological) are being tested on the pilot scale. These different pretreatment methods are widely described in this paper, among them, microaerobic pretreatment (MP) has gained attention as a potential pretreatment method for the degradation of LM, which just requires a limited amount of oxygen (or air) supplied directly during the pretreatment step. MP involves microbial communities under mild conditions (temperature and pressure), uses fewer enzymes and less energy for methane production, and is probably the most promising and environmentally friendly technique in the long run. Moreover, it is technically and economically feasible to use microorganisms instead of expensive chemicals, biological enzymes or mechanical equipment. The information provided in this paper, will endow readers with the background knowledge necessary for finding a promising solution to methane production.


A cohort study of stomach cancer risk in men after gastric surgery for benign disease.
For the past 40 years, investigators have suggested that there exists an increased risk of stomach cancer following gastric surgery for benign disease. Recent cohort studies have consistently identified an increased risk of stomach cancer beginning 20 years or more following gastric surgery. Validation of this association and elucidation of risk factors related to gastric cancer have been complicated by variability in study designs. This cohort study was designed to investigate the risk of stomach cancer following gastric surgery and to identify patient and treatment characteristics that may alter this risk. Medical admission records of 17077 male military veterans hospitalized during 1970-1971 in U.S. Department of Veterans Affairs (VA) hospitals were examined. From this initial cohort, 1094 patients who died within the 1st year following gastric surgery were excluded. Data analysis was performed on the final cohort consisting of 15,983 patients divided into the following two groups: 1) an exposed group (gastric surgery group) that included 7609 patients receiving gastric surgery for a documented benign disorder and 2) an unexposed group (comparison group) that included 8374 male patients randomly selected from all other hospitalized male patients in the patient database. The comparison group was matched to the gastric surgery group by age (within 10 years), race, hospital, and year of admission. Mortality follow-up utilized the following three sources to identify vital status: 1) the VA Patient Treatment File (1970-1988), 2) the VA Beneficiary Identification Record Linkage System (1970-1989), and 3) the National Death Index (1979-1988). Death certificates were obtained for 99% of the deceased patients. Analyses included estimations of risk using standardized rate ratios (SRRs) and proportional hazards techniques. A statistically significant increase in risk of stomach cancer was demonstrated among males during the 20 years following gastric surgery (SRR = 1.9; 95% confidence interval [CI] = 1.3-2.4; P = .0001). The risk of developing gastric cancer was greatest during the 2nd to 5th postoperative years (SRR = 2.8; 95% CI = 1.6-4.5; P < .01) and during years 11-15 (SRR = 2.5; 95% CI = 1.2-4.8; P < .01). Also, the risk of developing gastric cancer was greatest among those treated by gastrectomy for any type of ulcer (SRR = 2.6; 95% CI = 1.2-4.9; P < .01) and those having any type of gastric surgery when the primary diagnosis was gastric ulcer (SRR = 2.9, 95% CI = 1.4-5.3; P < .01). This study confirms that men undergoing gastrectomy for benign disease and men receiving any gastric surgery for gastric ulcer are at increased risk for developing gastric cancer. Unlike earlier studies, we find that the increased risk is not delayed for 20 years.


Full Recovery of Sensorineural Hearing Loss in a Patient with Congenital Hypothyroidism.
Congenital hypothyroidism (CH) is one of the most preventable causes of intellectual disability in the world. Screening programs have led to earlier detection of CH, and children with adequate thyroid supplementation can have minor long-term differences in overall neuropsychological testing compared to baseline. However up to one- fourth of children born with CH suffer from hearing loss even with early and adequate thyroid hormone supplementation. We report a rare case of a patient with hearing loss attributed to congenital hypothyroidism who had complete recovery of hearing after early thyroid hormone replacement.


A review of kala-azar in China from 1949 to 1959.
This is the first account of China as an important area of kala-azar to appear in the west for nearly 50 years. The review is divided into four main sections. The epidemiological aspects which are described include the geographical distribution and endemicity (under the sub-headings natural conditions of the epidemic area, age distribution, sex differences, seasonal changes in incidence) and research on reservoirs (under the sub-headings survey of canine leishmaniasis and survey of other wild and domestic animals). The section on clinical aspects covers symptoms and signs, post kala-azar dermal leishmaniasis, laboratory diagnosis (puncture, serum tests, complement fixation test, intradermal test) and treatment (medication and the effects of treatment). The possibility that two different types of kala-azar occur in China is discussed and the paper concludes with an appraisal of the present position.


Age-related prognosis of syncope associated with a preexcitation syndrome.
Syncope in Wolff-Parkinson-White syndrome (WPW) is without relationship with WPW or reveals a poorly tolerated arrhythmia. Electrophysiologic study (EPS) is recommended. The purpose of the study was to evaluate the influence of the patient's age on the causes and prognosis of syncope. A total of 98 patients, mean age 35 ± 18 years, with WPW were admitted for syncope. Note that 29 were aged between 9 and 19 years (mean 15 ± 3) (children and teenagers/group I), 45 between 20 and 49 years (mean 34 ± 8) (adults/group II), and 24 between 50 and 70 years (mean 60 ± 8) (elderly/group III). EPS consisted of atrial pacing and programmed atrial stimulation in control state and after isoproterenol. Potentially malignant form (rapid conduction in accessory pathway >240 beats/min in control state or >300 beats/min after isoproterenol and atrial fibrillation [AF] induction) was more frequent in group I (34%) than in groups II (7%) (P < 0.002) and III (0%) (P < 0.001). Orthodromic atrioventricular reentrant tachycardia (AVRT) and AF were induced as frequently in groups I (59, 34%), II (47, 15.5%), and III (54, 17%). AVRT was induced in all but one patient with malignant form. EPS was as frequently negative in groups I (27.5%), II (44%), and III (37.5%). Natural follow-up (mean 8 ± 6 years) indicated a favorable prognosis, only related to AVRT induction. Induced AF was without significance. Data in syncope and WPW syndrome depended on age: electrophysiological malignant form was frequent in children/teenagers, rare in adults, and absent in elderly. AVRT, the main cause of syncope, was as frequent in all ranges of age. AF's induction alone had no significance. Final prognosis was favorable.


A Microphysiological Cell-Culturing System for Pharmacokinetic Drug Exposure and High-Resolution Imaging of Arrays of 3D Microtissues.
Understanding the pharmacokinetic/pharmacodynamic (PK/PD)-relationship of a drug candidate is key to determine effective, yet safe treatment regimens for patients. However, current testing strategies are inefficient in characterizing in vivo responses to fluctuating drug concentrations during multi-day treatment cycles. Methods based on animal models are resource-intensive and require time, while traditional in vitro cell-culturing methods usually do not provide temporally-resolved information on the effects of in vivo-like drug exposure scenarios. To address this issue, we developed a microfluidic system to 1) culture arrays of three-dimensional spheroids in vitro, to 2) apply specific dynamic drug exposure profiles, and to 3) in-situ analyze spheroid growth and the invoked drug effects in 3D by means of 2-photon microscopy at tissue and single-cell level. Spheroids of fluorescently-labeled T-47D breast cancer cells were monitored under perfusion-culture conditions at short time intervals over three days and exposed to either three 24 h-PK-cycles or a dose-matched constant concentration of the phosphatidylinositol 3-kinase inhibitor BYL719. While the overall efficacy of the two treatment regimens was similar, spheroids exposed to the PK profile displayed cycle-dependent oscillations between regression and regrowth. Spheroids treated with a constant BYL719 concentration regressed at a steady, albeit slower rate. At a single-cell level, the cell density in BYL719-treated spheroids oscillated in a concentration-dependent manner. Our system represents a versatile tool for in-depth preclinical characterization of PK/PD parameters, as it enables an evaluation of drug efficacy and/or toxicity under realistic exposure conditions.


Ischaemia and neovascularization.
Varied clinical situations associated with ocular neovascularization are described and categorized according to whether they are initially venous, capillary, or arterial obstructive in origin. Common to many of these entities is the presence of retinal ischaemia, as evidenced by retinal capillary non-perfusion with intravenous fluorescein angiography. The similarities between an experimental angiogenesis model and clinical vasoproliferative disease states are also noted.


Carrying Skills From One C-Suite to Another: An Interview With Dr Maureen Swick.
This interview of Dr Maureen Swick chronicles career development and preparation for a transition into the role of CEO of the American Organization of Nurse Executives. While there are an estimated 400 000 nurses in middle management roles in the United States and 5700 in the most senior nursing positions in US hospitals, Dr Swick has assumed a role leading the leaders and highlights those experiences that have influenced her and provides insights into her vision for nursing leadership.


Implementation of a mental health consultation model and its impact on early childhood teachers' efficacy and competence.
Early childhood mental health (MH) consultants work closely with childcare teachers onsite to serve as a resource for childcare providers as they foster and enhance children's early development. The increase in the quality of care that can be supported through an early childhood MH consultation program makes this type of consultation an optimal tool for enhancing the childcare environment and overall child development. This article details the initial launch of the MH consultation program to childcare centers in the state of Louisiana. Analyses support the assertions that (a) a model of MH consultation can be implemented successfully at a statewide level, (b) MH consultation is associated with an increase in teacher self-efficacy, and (c) teachers' report that the MH consultation increased their competence in specific areas related to children's socioemotional development. Analyses indicate that there is a differential impact on teachers based on their age and level of experience. The clinical implications of these findings are discussed.


Brazil Patient Knowledge Questionnaire (PKQ) and evaluation of disease-specific knowledge in patients with rheumatoid arthritis.
To create a Brazilian version of the Patient Knowledge Questionnaire--PKQ, an instrument for measuring the knowledge of patients with rheumatoid arthritis (RA) as regards their disease, and through the use of this instrument, also measure the knowledge of RA patients from reference hospitals in the city of São Paulo. Two teachers of English translated the PKQ into Portuguese in order to obtain a single version, which was then translated back into English to evaluate its equivalence to the original version (back translation). The final version in Portuguese was applied to 20 patients with RA for adaptation to cultural issues, and questions not understood by 20% or more patients were subsequently modified. Inter- and intraobserver reliability and the constructive validity of the PKQ were tested. The questionnaire was then applied to 100 RA patients, selected in four outpatient clinics at reference hospitals in the city of São Paulo. Three of the PKQ questions were modified to adapt to cultural issues. Intraclass correlation coefficients used for the reliability and validity of the PKQ were between were between 0.62 and 0.94, therefore, statistically significant (p< 0.05). The mean PKQ score was 12.96 and the mean test application time was 10.3 minutes, for the 100 patients assessed. The lowest scores were observed in the domains of medications and joint protection/energy conservation. PKQ scores showed a positive correlation with the level of education (r=0.40) and a negative correlation with the patients' age (r= -0.32) and with HAQ (r= -0.28). The Brazilian version of the PKQ that was created and proved to be a reliable and valid instrument. Patients' knowledge of RA is poor, particularly in the domains regarding medications and joint protection/energy conservation.


Scintigraphic determination of the effect of metoclopramide and morphine on small intestinal transit time.
To determine if a scintigraphic method could detect pharmacologic changes in small intestinal transit time (SITT), 10 male volunteers were studied at baseline and after intravenously administered metoclopramide (10 mg) and morphine (8 mg). Five of these volunteers were studied with the hydrogen breath test method for comparison. For each of the scintigraphic studies, the volunteers were positioned supine under a large-field-of-view gamma camera after ingesting an isosmotic lactulose solution containing 99mtechnetium-diethylenetriaminepentaacetic acid (DTPA). Data were collected and stored in a computer. Both gastric emptying and SITT were determined. SITT was 81 +/- 11 min (mean +/- S.E.M.; N = 10) during baseline studies, was decreased significantly to 50 +/- 6 min (N = 10; P less than 0.01) after metoclopramide, and was increased significantly to 161 +/- 15 min (N = 8; P less than 0.01) after morphine. Baseline mean values were 86.3 +/- 15 min (N = 15) for the hydrogen breath tests, 47 +/- 8 min (N = 5) for metoclopramide, and 183 +/- 16 min (N = 5) for morphine. For gastric emptying, there was no significant difference in percentage emptying at 1 hr for baseline and metochopramide (82 +/- 5% vs. 88 +/- 4%). Morphine prolonged gastric emptying at 1 hr to 63 +/- 8%. We conclude that the scintigraphic method for measuring SITT permits accurate investigation of the pharmacologic effects on intestinal motility and, in addition, may be a useful research and clinical method for SITT determination.


The Development of Bilateral Mastoiditis Following Acute Otitis Media in a Pediatric Patient with Limited Access to Health Care.
Infection of the mastoid cells, known as mastoiditis, can develop due to untreated otitis media, in which bacteria colonize the mastoid air cells that line the inner and middle ear. Antibiotic therapy for otitis media has made the development of mastoiditis a very rare occurrence. However, despite its low prevalence, it is important to keep this complication in mind when treating otitis media in the pediatric population due to the increased susceptibility of mastoiditis in this demographic. Furthermore, pediatric patients of lower socioeconomic status who have limited access to health care may be at an even greater risk for the development of mastoiditis. We report a case of a pediatric patient with significant barriers to health care who developed bilateral mastoiditis as a complication of otitis media, requiring hospitalization and intravenous antibiotic therapy. The patient also experienced hearing loss as a sequela of the infection. Improved access to medical care, parent or guardian education on how to recognize primary otitis media infections, and the use of adequate antibiotic therapy when indicated can effectively prevent the development of mastoiditis following otitis media infections among patients.


Six-Electron-Redox Iodine Electrodes for High-Energy Aqueous Batteries.
Iodine (I2 ) shows great promising as the active material in aqueous batteries due to its distinctive merits of high abundance in ocean and low cost. However, in conventional aqueous I2 -based batteries, the energy storage mechanism of I- /I2 conversion is only two-electron redox reaction, limiting their energy density. Herein, six-electron redox chemistry of I2 electrodes is achieved via the synergistic effect of redox-ion charge-carriers and halide ions in electrolytes. The redox-active Cu2+ ions in electrolytes induce the conversion between Cu2+ ions and I2 to CuI at low potential. Simultaneously, the Cl- ions in electrolytes activate the I2 /ICl redox couple at high potential. As a result, in our case, I2 -based battery system with six-electron redox is developed. Such energy storage mechanism with six-electron redox leads to high discharge potential and capacity, excellent rate capability, as well as stable cycling behavior of I2 electrodes. Impressively, six-electron-redox I2 cathodes can match various aqueous metal (e.g. Zn, Mn and Fe) anodes to construct metal||I2 hybrid batteries. These hybrid batteries not only deliver enhanced capacities, but also exhibit higher operate voltages, which contributes to superior energy densities. Therefore, this work broadens the horizon for the design of high-energy aqueous I2 -based batteries.


Ettringite-induced heave in chromite ore processing residue (COPR) upon ferrous sulfate treatment.
A pilot-scale treatment study was implemented at a deposition site of chromite ore processing residue (COPR) in New Jersey. Ferrous sulfate heptahydrate (FeSO4 x 7H2O) was employed to reduce hexavalent chromium in two dosages with three types of soil mixing equipment. XANES analyses of treated samples cured for 240 days indicated that all treatment combinations failed to meet the Cr(VI) regulatory limit of 240 mg/kg. More importantly, the discrepancy between XANES and alkaline digestion results renders the latter unreliable for regulatory purposes when applied to ferrous-treated COPR. Regardless of Cr-(VI), the introduction of reductant containing sulfate, mechanical mixing, water, acidity, and the resulting temperature increase in treated COPR promoted dissolution of brownmillerite (Ca2FeAlO5), releasing alumina and alkalinity. The pH increase caused initially precipitated gypsum (CaSO4 x 2H2O) to progressively convert to ettringite (Ca6Al2(SO4)3 x 32H2O) and its associated volume expansion under both in situ and ex situ conditions, with a maximum of 0.8 m vertical swell within 40 days of curing. While Cr-(VI) treatment remains a challenge, the intentional exhaustion of the heave potential of COPR by transforming all Al sources to ettringite emerges as a possible solution to delayed ettringite formation, which would hamper site redevelopment.