Bacterial biofilm formation after nasal packing in nasal mucosa-wounded mice.
Bacterial biofilm plays an important role in recalcitrant chronic rhinosinusitis. Staphylococcus aureus is a crucial pathogen in chronic rhinosinusitis and S. aureus biofilm is related to unfavorable postoperative outcomes. Although S. aureus is known to be the most common bacteria leading to postoperative infection, whether biofilm forms on the wound surface after functional endoscopic sinus surgery and the relationship between biofilm formation and surgery are still not clear. This study was designed to observe whether S. aureus biofilm forms in mice with wounded nasal mucosa mice after bacteria inoculation. Three hundred twenty-four wild-type male C57BL/6 mice were recruited for the experiment. Except for the four used in the preliminary experiment, the mice were randomly divided into four groups: a wound plus packing group (group A), a wound group (group B), a packing group (group C), and a control group (group D). After treatment, groups A, B, and C were inoculated with S. aureus suspension at 1 × 10(9) CFU/mL in the right nasal cavity; sterile physiological saline was used instead of bacteria suspension for group D. Confocal laser scanning microscopy was used to detect the biofilm. A nasal lavage culture was also completed. Biofilm formation was found in group A on the 3rd, 7th, and 15th days after inoculation with growth rates of 10, 25, and 40%, respectively. Three cases of biofilm were also detected in group B on the 15th day postinoculation. There was no biofilm observed on the nasal mucosa in group C or D. The nasal lavage culture showed that the inoculated bacteria stayed on the nasal mucosa temporarily after inoculation. Our results indicate that a nasal wound, nasal packing, and the existence of pathogenic bacteria are all essential elements for biofilm formation in healthy mice. This result indicated that biofilm formation may be avoided by shortening the duration of nasal packing and reducing the nasal wound.


Simultaneous polysubstance use among Danish 3,4-methylenedioxymethamphetamine and hallucinogen users: combination patterns and proposed biological bases.
To describe patterns of simultaneous polysubstance use (SPU) among Danish 3,4-methylenedioxymethamphetamine (MDMA) ("Ecstasy") and hallucinogen users. A cross-sectional survey of 98 active MDMA and/or hallucinogen users recruited through homepage advertisements, flyers, and word of mouth in Denmark. Lifetime and recent substance use and SPU at last recalled use was described by structured interviews. Hair samples from a subset of participants were analyzed for MDMA. The participants had used an average of 12.6 (95% confidence interval: 11.7-13.4) psychoactive substances during their lifetime. SPU was prevalent among MDMA, d-lysergic acid diethylamide (LSD), and psilocybin users, in particular with alcohol and cannabis. Among MDMA users, 69% had combined MDMA with amphetamines, 56% with hallucinogens, and 47% with cocaine. At last recalled use, MDMA was taken with 2.1 ± 1.2 substances in 32 different combinations. The participants preferred specific drug combinations and named several, which in their experience enhanced or counteracted each other. Alcohol and cannabis were typically used before, during, and after MDMA, LSD, and psilocybin, whereas amphetamines were predominantly taken before these substances. When LSD was combined with MDMA, the majority took MDMA after LSD. Simultaneous polysubstance use was common among Danish MDMA and hallucinogen users, and patterns of preferred substance combinations were evident.


Acute myeloblastic leukaemia with marrow fibrosis (malignant myelosclerosis): acute leukaemia or malignant myelosclerosis?
Malignant myelosclerosis has been described as a rare form of acute myeloproliferative disorder characterised by minimal or absent splenomegaly, cytopenias, circulating myeloblasts and diffuse marrow fibrosis, but distinction between this entity and acute myeloblastic leukaemia with marrow fibrosis is difficult. This report describes a 50-year-old man who presented with features similar to those of malignant myelosclerosis but ther terminal stage was characterised by generalised lymphadenopathy, bone tenderness, marked leucocytosis and myeloblastaemia. Post mortem examination showed multiple chloromata consisting of myeloblasts. These findings suggest that malignant myelosclerosis may be but a variant of acute myeloblastic leukaemia and probably should be treated similarly. A possible association between diagnostic medical irradiation and this acute myeloproliferative disorder is discussed.


Anthracene derivative covalently immobilized on sensing membrane as a fluorescent carrier for water assay.
This article describes an optical chemical sensor based on a fluorescent dye 1-allyloxy-4-hydroxyanthracene-9, 10-dione (AHD) with terminal double bond, which is covalently bonded to quartz glass plate surface treated with a silanizing agent to prevent its leakage. The purpose of this work was to characterize and optimize the sensor for determining the water content in the acetone organic solvent. The sensor is resistant to swelling; the membrane possesses relatively long lifetime, short response and recovering time. The reversibility and reproducibility of the sensor are adequate for practical measurements.


A comparison of principal component analysis and factor analysis strategies for uncovering pleiotropic factors.
Principal component analysis (PCA) and factor analysis (FA) are often used to uncover genetic factors that contribute to complex disease phenotypes. The purpose of such an analysis is to distill a genetic signal from a large number of correlated phenotype measurements. That signal can then be used in genetic analyses (e.g. linkage analysis), presumably leading to greater success at finding genes than one would achieve with any one raw trait. Although both PCA and FA have been used this way, there has been no comparison of their performance in the literature. We compared the ability of these two procedures to extract unobserved underlying genetic components from complex simulated data on nuclear families. We first simulated seven underlying genetic and environmentally determined traits. Then we derived two sets of 50 complex (observed) traits using algebraic combinations of the underlying components. We next performed PCA and FA on the complex traits. We assessed two aspects of the performance of the methods: (1) ability to detect the underlying genetic components; (2) whether the methods worked better when applied to raw traits or to residuals (after regressing out significant environmental covariates). Our results indicate that both the methods behave similarly in most cases, although FA generally produced factors that had stronger correlations with the underlying traits. We also found that using residuals in PCA or FA analyses greatly increased the probability that the PCs or factors detected common genetic components instead of common environmental factors, except if there was statistical interaction between genetic and environmental factors.


[Diagnostic modalities and treatment of cancer of the pancreas. Evolution in the population in the department of Côte d'Or from 1976 to 1988].
There is no study establishing time trends for the diagnostic and therapeutic approaches to pancreatic cancer based on population data. The data of the Registry of Digestive Tumors of Côte-d'Or (France) were used to this end in 544 cancers diagnosed between 1976 and 1988. The proportion of the histologically confirmed cases increased annually by 13.4% (P < 0.001). This was mainly due to progress in percutaneous biopsy (+25.7% per year between 1983 and 1988, P < 0.001). As regards the diagnosis, ultrasonography was used more frequently (+21.9% per year, P < 0.001) as well as CT scan since its introduction in 1983 (+19.6% per year, P < 0.001). Pancreatic cancer was diagnosed by sonography in 16.7% of the cases in 1976 and 70.6% in 1988 (mean annual variation: +5.7%, P < 0.001). The proportions for CT scan were 12.8% in 1983 and 23.5% in 1988 (mean annual variation: +3.5%, NS). There was no significant change in the use of retrograde cholangiopancreatography over time. Other diagnosis criteria were less frequently used: laparoscopy was no longer used after 1983 and intraoperative diagnosis was made less frequently (-2.5% per year, P < 0.001). Endoscopy or radiographic data were rarely used as a diagnosis criterion. These changes in approaches to the diagnosis of pancreatic cancer were not accompanied by any progress in diagnosis stage, therapeutic approach or survival suggesting that when clinical symptoms become evident, pancreatic cancer is already advanced. Therapeutic advances, early diagnosis in patient at risk or identification or reasons for pancreatic cancer are the only means of progress in this problem.


The Cobas AmpliPrep/Cobas TaqMan HCV test, version 2.0, real-time PCR assay accurately quantifies hepatitis C virus genotype 4 RNA.
Accurate hepatitis C virus (HCV) RNA quantification is mandatory for the management of chronic hepatitis C therapy. The first-generation Cobas AmpliPrep/Cobas TaqMan HCV test (CAP/CTM HCV) underestimated HCV RNA levels by >1-log10 international units/ml in a number of patients infected with HCV genotype 4 and occasionally failed to detect it. The aim of this study was to evaluate the ability of the Cobas AmpliPrep/Cobas TaqMan HCV test, version 2.0 (CAP/CTM HCV v2.0), to accurately quantify HCV RNA in a large series of patients infected with different subtypes of HCV genotype 4. Group A comprised 122 patients with chronic HCV genotype 4 infection, and group B comprised 4 patients with HCV genotype 4 in whom HCV RNA was undetectable using the CAP/CTM HCV. Each specimen was tested with the third-generation branched DNA (bDNA) assay, CAP/CTM HCV, and CAP/CTM HCV v2.0. The HCV RNA level was lower in CAP/CTM HCV than in bDNA in 76.2% of cases, regardless of the HCV genotype 4 subtype. In contrast, the correlation between bDNA and CAP/CTM HCV v2.0 values was excellent. CAP/CTM HCV v2.0 accurately quantified HCV RNA levels in the presence of an A-to-T substitution at position 165 alone or combined with a G-to-A substitution at position 145 of the 5' untranslated region of HCV genome. In conclusion, CAP/CTM HCV v2.0 accurately quantifies HCV RNA in genotype 4 clinical specimens, regardless of the subtype, and can be confidently used in clinical trials and clinical practice with this genotype.


Electrocardiographic changes in elderly patients during endoscopic retrograde cholangiopancreatography.
Cardiorespiratory complications may occur during gastrointestinal endoscopy, and elderly people seem to be more vulnerable to these complications during endoscopic procedures involving the manipulation of abdominal viscera. To determine the incidence of cardiac arrhythmias, changes in oxygen saturation, heart rate and blood pressure during endoscopic retrograde cholangiopancreatography (ERCP) via Holter monitoring in elderly patients older than 70 years of age. Holter monitoring and 12-lead electrocardiograms were performed in 30 elderly patients undergoing ERCP and in 30 control subjects undergoing routine chest, abdomen, bone and upper gastrointestinal small bowel follow-through studies. A computerized nontriggered template system was used to analyze the electrocardiograms qualitatively and quantitatively. Arrhythmias, cardiac axis, conduction defects, pauses, ST segment changes, ectopic beats, oxygen desaturation and changes in blood pressure and rate-pressure product were evaluated. Increased heart rate, ST segment changes resulting from myocardial ischemia, oxygen desaturation and transient atrial and ventricular ectopic beats were frequent during ERCP compared with the control group. In one patient, transient left bundle branch block developed and this was attributed to pre-existing hypertension with cardiomegaly. One patient developed ventricular tachycardia and one other sinus bradycardia, but this was attributed to sick sinus syndrome. Transient myocardial ischemia and various cardiac arrhythmias are frequent in elderly patients undergoing ERCP. Appropriate noninvasive monitoring seems to be justified during this procedure.


The impact of "ancient pathogen" studies on the practice of public health.
A new field of "ancient pathogens" is making an impact on our concepts of the evolution of infectious diseases, and it will eventually alter the practice of public health in their control. It has begun to answer important questions regarding past epidemics of influenza and tuberculosis by recovering the genetic sequences of the ancient causative agents. Vaccination strategics will have to study these microbial variants in order to develop tomorrow's vaccines. It may also be possible to examine the role of past and present reservoirs in the dynamics of emerging diseases. In unraveling the evolution of pathogens, insights into the mechanisms of drug and antibiotic resistance are possible. As "genome projects" of more and more pathogens are being completed. Targets for chemotherapy are being revealed which are totally different from the metabolic processes of the mammalian host. Signal molecules are being identified which alter the virulence of the microbe. Focussing on these mechanisms without attempting to kill the pathogen may in some cases drive it into a benign state. These and other aspects of the evolution of pathogens are discussed which may lead to innovative approaches to the control of infectious diseases.


Etoposide and adriamycin containing combination chemotherapy (HOPE-Bleo) for relapsed Hodgkin's disease.
Forty-four patients with relapsed or resistant Hodgkin's disease were treated with adriamycin 40 mg m-2 i.v. on day 1, vincristine 1.4 mg m-2 i.v. on days 1 and 8, prednisolone 40 mg m-2 orally daily for 8 days, etoposide 200 mg m-2 orally daily for 4 days according to the nadir white cell count, and bleomycin 10 mg m-2 i.v. days 1 and 8 (HOPE-Bleo). Median age was 27 (range 12-71). When stage was considered according to all sites currently or previously involved by Hodgkin's disease (cumulative stage) 26 patients (59%) had stage IV, 13 (29%) stage III and five (11%) stage II disease; 33 (75%) had B symptoms. All patients had received previous chemotherapy and 18 (41%) had received two or more regimens. Twenty-six patients (59%) achieved CR and 10 (23%) PR; the median duration of CR was 22 months and median survival for all patients was 48 months. Eight patients remain in continuous CR; none of these had received extensive previous chemotherapy. Among the 19 patients who had relapsed from CR achieved by a single previous chemotherapy regimen, six (32%) achieved long CR on HOPE-Bleo. The regimen was generally well tolerated but the principal toxicity was myelosuppression. There were two toxic deaths, one due to neutropenic sepsis and the other due to acute peritonitis. The HOPE-Bleo regimen is an effective treatment for relapsed or resistant Hodgkin's disease, with a low probability of carcinogenesis and infertility. These factors suggest that HOPE-Bleo deserves further evaluation as primary treatment for Hodgkin's disease and very careful selection of relapsed patients for high dose salvage chemotherapy with bone marrow transplants must be exercised.


Gastric residual volume in critically ill patients: a dead marker or still alive?
Early enteral nutrition (EN) is consistently recommended as first-line nutrition therapy in critically ill patients since it favorably alters outcome, providing both nutrition and nonnutrition benefits. However, critically ill patients receiving mechanical ventilation are at risk for regurgitation, pulmonary aspiration, and eventually ventilator-associated pneumonia (VAP). EN may increase these risks when gastrointestinal (GI) dysfunction is present. Gastric residual volume (GRV) is considered a surrogate parameter of GI dysfunction during the progression of enteral feeding in the early phase of critical illness and beyond. By monitoring GRV, clinicians may detect patients with delayed gastric emptying earlier and intervene with strategies that minimize or prevent VAP as one of the major risks of EN. The value of periodic GRV measurements with regard to risk reduction of VAP incidence has frequently been questioned in the past years. Increasing the GRV threshold before interrupting gastric feeding results in marginal increases in EN delivery. More recently, a large randomized clinical trial revealed that abandoning GRV monitoring did not negatively affect clinical outcomes (including VAP) in mechanically ventilated patients. The results have revived the discussion on the role of GRV monitoring in critically ill, mechanically ventilated patients receiving early EN. This review summarizes the most recent clinical evidence on the use of GRV monitoring in critically ill patients. Based on the clinical evidence, it discusses the pros and cons and further addresses whether GRV is a dead marker or still alive for the nutrition management of critically ill patients.


Stroke awareness among Dubai emergency medical service staff and impact of an educational intervention.
Emergency medical services (EMS) play a vital role in expediting hospital arrival in stroke patients. The objective of our study was to assess the level of awareness regarding pre-hospital identification and management of acute stroke among EMS Staff in Dubai and to evaluate the impact of an educational lecture on their knowledge. Ours was a cross-sectional study with a pre-test and post-test design. The intervention was an educational lecture, based on the updated guidelines in pre-hospital care of acute stroke. Participants were assessed before and after the intervention on various aspects of stroke care. Paired t test were used to compare the impact of the intervention. A total of 274 EMS workers participated in our study. The baseline knowledge of participants regarding stroke types was inadequate with only 68% correctly identifying these. 79% were able to name the cardinal stroke symptoms. Knowledge of stroke mimics was poor with only 6.6% identifying stroke mimics correctly. With respect to management, most participants were unable to correctly identify the points to illicit in the history of an acute stroke patient (25.2%) and also the steps in pre-hospital management (40%). All these aspects showed remarkable improvement post intervention. The baseline awareness of most aspects of acute stroke identification and management was poor in our EMS participants. Our educational lecture proved effective in improving this knowledge when tested immediately post intervention. However, there is a need to re-assess this at periodic intervals to identify the need for refresher courses on pre-hospital stroke management.


Industry economics in the United States.
Demand for medical equipment in the United States (US) is projected to grow by 8% between 2001 and 2006, to reach 105 billion dollars. In 2001,the market was valued at 71.4 billion dollars, based on an annual growth of 7.5% between 1996 and 2001, according to The Freedonia Group. Product innovation and the growing ageing population is driving the industry, despite health-care cost containment measures. Medical and surgical instruments continue to be the largest sector, which is expected to grow to 30.5 billion dollars in 2006. However, electromedical/electrotherapeutic apparatus will remain the fastest growing sector, with annual gains of 10.8% predicted for this period.


Effectiveness of Enzyme Dentifrices on Oral Health in Orthodontic Patients: A Randomized Controlled Trial.
Plaque accumulation and white spot lesions are common adverse effects of fixed orthodontic appliance use. This study compared the effects between enzyme-containing and conventional dentifrices on orthodontic patients. This double-blind randomized controlled trial included 42 orthodontic patients (25 women and 17 men: 22.7 ± 4.2 years) from Taipei Medical University Hospital between 2017 and 2018. The patients were randomly divided into three groups and assigned to dentifrice use during the first 3 months of the orthodontic treatment: group 1 used dentifrices containing enzymes including amyloglucosidase and glucose oxidase, group 2 used dentifrices containing 1450 ppm fluoride, and group 3 used natural dentifrices containing no chemical agent. White spot lesion index (WSL), gingival bleeding index (GBI), and visible plaque index (VPI) were recorded and analyzed. WSL, GBI, and VPI values exhibited no significant difference among the three groups. WSL increased significantly in group 3, GBI decreased significantly in all groups, and VPI decreased significantly in groups 1 and 2. No significant difference was observed between the use of enzyme-containing and conventional dentifrices after fixed orthodontic appliance placement.


Chorea-acanthocytosis: neuropathology of brain and peripheral nerve.
We report the neuropathological data from a familial case of chorea-acanthocytosis with central and peripheral nervous system involvement. At the age of 34, the patient underwent a peripheral nerve biopsy which was analyzed by light- and electron microscopy. These studies showed a selective reduction in the large diameter myelinated fibre population, with several clusters of regeneration. Remyelinating fibers surrounded by flattened Schwann cell processes were also present. The patient died at the age of 44, and post-mortem macroscopic examination of the brain showed marked atrophy of the caudate. Histological examination of paraffin sections showed almost complete depletion of neurons in the caudate, with severe astrocytic gliosis. The putamen and pallidum were slightly less severely depleted of neurons, but with marked astrocytic gliosis. Diffuse mild gliosis was also evidenced, by immunohistochemistry with anti-GFAP, in the thalamus and subcortical white matter.


Efficacy and Safety of Daprodustat Vs rhEPO for Anemia in Patients With Chronic Kidney Disease: A Meta-Analysis and Trial Sequential Analysis.
Introduction: Daprodustat, a novel hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI), its efficacy and safety remain unclear. Thus, we conducted this meta-analysis aiming at investigating its efficacy and safety on the treatment of patients with chronic kidney disease (CKD)-related anemia. Methods: We systematically searched for relevant studies in PubMed, Embase, Cochrane Library and Clinical Trial Registries databases from inception until December 2021. We selected randomized controlled trials comparing daprodustat with recombinant human erythropoietin (rhEPO) in anemia patients with CKD with or without dialysis. Results: Seven studies including 7933 patients met the inclusion criteria. For both nondialysis-dependent (NDD-) CKD and dialysis-dependent (DD-) CKD patients, the pooled results showed that there was no significant difference in the changes in hemoglobin levels between the daprodustat and rhEPO groups (mean difference (MD) = -0.01, 95% confidence interval (CI) = -0.38, 0.35, p = 0.95; MD = 0.15, 95% CI = -0.29, 0.60, p = 0.50; respectively). In addition, a significant increase in transferrin saturation (TSAT), total iron binding capacity (TIBC) and total iron was observed in daprodustat groups compared with rhEPO groups in DD-CKD patients (p < 0.05). As for safety, the overall frequency of adverse events was similar between the daprodustat and rhEPO groups in DD-CKD patients (relative risk (RR) = 0.99, 95%CI = 0.92, 1.06, p = 0.76), and the trial sequential analysis (TSA) confirmed this result. But for NDD-CKD patients, the incidence of adverse events in the daprodustat groups was significantly higher than that of rhEPO groups (RR = 1.04, 95%CI = 1.01,1.07, p = 0.02), while the TSA corrected this result. No trend of increasing incidence of serious adverse events was found in all daprodustat treated patients, but the TSA could not confirm this result. Conclusion: Although daprodustat was noninferior to rhEPO in correcting anemia in both NDD-CKD and DD-CKD patients, it seemed to have a better effect on optimizing iron metabolism in DD-CKD patients. Daprodustat may be a promising alternative for the treatment of anemia in patients with CKD. However, due to the lack of included studies, future researches are needed to further evaluate the therapeutic effect of daprodustat. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021229636.


Scalp Dermatitis in Patients Sensitized to Components of Hair Products.
Allergic contact dermatitis is an inflammatory condition that less commonly presents with scalp involvement. Recently, T regulatory cells have been documented to be residents of hair follicles, illuminating why contact allergens are less likely to elicit dermatitis in the scalp. The aims of the study were to determine the prevalence of scalp symptoms, with and without other affected areas, in patients presenting for evaluation of allergic contact dermatitis and to determine the allergens most likely to be associated with scalp dermatitis. We examined allergens commonly found in hair products and stratified positive patch test results by the following affected areas: face, eyelid, neck, or hands, where exposure by runoff is common, versus scalp. Para-phenylenediamine (PPD) is the most common allergen in patients with scalp dermatitis. The rate of PPD sensitization is higher in nonwhite compared with white patients. In the small number of patients with isolated scalp involvement, positive patch tests to PPD were documented in a minority. Other allergens found in hair products may present without scalp symptoms. Patients with dermatitis affecting areas other than the scalp should provide their hair product ingredients to guide patch test selection.


Synthesis, High-Resolution Infrared Spectroscopy, and Vibrational Structure of Cubane, C8H8.
Carbon-cage molecules have generated a considerable interest from both experimental and theoretical points of view. We recently performed a high-resolution study of adamantane (C10H16), the smallest hydrocarbon cage belonging to the diamandoid family ( Pirali , O. ; et al. J. Chem. Phys. 2012 , 136 , 024310 ). There exist another family of hydrocarbon cages with additional interesting chemical properties: the so-called platonic hydrocarbons that comprise dodecahedrane (C20H20) and cubane (C8H8). Both possess C-C bond angles that deviate from the tetrahedral angle (109.8°) of the sp(3) hybridized form of carbon. This generates a considerable strain in the molecule. We report a new wide-range high-resolution study of the infrared spectrum of cubane. The sample was synthesized in Bari upon decarboxylation of 1,4-cubanedicarboxylic acid thanks to the improved synthesis of literature. Several spectra have been recorded at the AILES beamline of the SOLEIL synchrotron facility. They cover the 600-3200 cm(-1) region. Besides the three infrared-active fundamentals (ν10, ν11, and ν12), we could record many combination bands, all of them displaying a well-resolved octahedral rotational structure. We present here a preliminary analysis of some of the recorded bands, performed thanks the SPVIEW and XTDS software, based on the tensorial formalism developed in the Dijon group. A comparison with ab initio calculations, allowing to identify some combination bands, is also presented.


Electrochemical performance of amorphous carbon nanotube as anode materials for lithium ion battery.
Amorphous carbon nanotubes (ACNTs) showed the different structure with crystal carbon nanotubes, such as single-walled and multi-walled carbon nanotubes due to their unique tube walls. The tube wall of ACNTs is comprised of many single layer graphene sheets which present long-distance disorder and short-distance order. Herein, we mainly studied the electrochemical property of ACNTs as anode materials for lithium ion secondary batteries and the mechanism of intercalation lithium. The electrochemical performances of as-grown and oxidized ACNTs were tested by two-electrode cell. The results indicate that the reversible capacity of ACNTs oxidized at 300 degrees C reaches 530 mAh/g and after the first 5 cycles the capacity remains 93%. The intercalation Li of ACNT include the inner wall and the side wall between graphene sheets. ACNTs offer a new exciting alternative to the traditional materials used for fabrication of lithium ion secondary batteries.


Two forms of the basic fibroblast growth factor receptor-like mRNA are expressed in the developing mouse brain.
The embryonic neuroepithelium gives rise to the components of the central nervous system in the mature animal. To study the early development of the murine central nervous system we have sought to isolate growth factor receptors from the neuroepithelium of the neural tube of 10-day-old mouse embryos. Because many growth factor receptors are members of the protein-tyrosine kinase family, we have used the polymerase chain reaction to amplify mRNA sequences from 10-day-old mouse embryo neuroepithelium; these sequences lie between the nucleotide sequences of two highly conserved amino acid motifs from the catalytic domain of protein-tyrosine kinases. By using this technique we have isolated a clone encoding the murine basic fibroblast growth factor receptor (bFGF-R), as well as a shorter form of this mRNA. This latter cDNA comprised 75% of the bFGF-R cDNA clones isolated from the immortalized neuroepithelial cell lines. This variant mRNA, designated here as N-bFGF-R, appears to be expressed at higher levels in neuronal cells in early stages of development. The bFGF-R is a member of a multigene family, as demonstrated by Southern blot analysis and the cloning of two other members of this family.


[THE ROLE OF HYDROGEN SULFIDE IN REGULATION OF CIRCULATION BLOOD LIVER].
It was shown in acute experiments on laboratory rats that intraportalinjectionof hydrogen sulfide's precursor L-cysteine (15 mg/kg)caused dilatation of the intrahepatic vessels. As a result, systemic blood pressure (SBP) and blood pressure in the portal vein (PVP) significantly decreased on 17,6 and 24,5%, respectively, and the rate of local blood flow in the liver (LF) and its blood filling (BF) increased on 28,2 and 24,4% respectively. Application of hydrogen sulfide donor NaHS (7 mg/kg) resulted in similarly directed changes: SBP and PVP decreased on 20,8% i 26,2% respectively,LF and BF increased on 16,4% and 30,9% respectively. Application of L-cysteine in the conditions of tsystationin-gamma-lyase blockade by LD-proparhilhlitsyn led to an increase in SBP on 20,4 % and PVP on 26,6% and a decrease of BF on 21,5% and LF in the liver on 11,7% comparing with baseline values of these parameters. So, blockade of tsystationin-gamma-lyase not only completely removed the effects of L-cysteine, but also inhibited synthesis of H2S from its endogenous predecessors,which led to vasoconstriction of liver's blood vessels and, consequently, to an increase of blood pressure and a decrease of liver blood flow rat's and volume of blood deposited in liver.


Proteomic characterization of the site-dependent functional difference in the rat small intestine.
To investigate the site-dependent functional difference in the small intestine, proteomic analysis was carried out on the three distinct parts of the rat small intestine. Male Wistar rats (7 weeks old) were fed a semi-purified diet ad libitum for 1 week. Intestinal tissues from the proximal, middle and distal regions of the small intestine were subjected to two-dimensional polyacrylamide gel electrophoresis, and the abundance of each spot was determined fluorometrically. MALDI-TOF/MS and LC-MS/MS analysis of the tryptic peptides were performed to identify the proteins. Many of the 180 identified proteins showed a distinctive distribution pattern along the small intestine. Glutathione S-transferase, Catechol O-methyltransferase and Villin 2 decreased gradually from the jejunum to the ileum, in contrast, non-specific dipeptidase and Keratin 19 increased gradually toward the ileum. The voltage-dependent anion channel 2 was most abundant in the duodenum while the L- and I-Fatty acid binding protein (FABP) and Cellular retinol binding protein (CRBP-II) were in the jejunum, and the Bile acid binding protein (BABP) was only observed in the ileum. The findings of these and of another proteins identified in this study may contribute to further understanding of the small intestinal function, and to clinical applications of small intestinal diseases.


Comparison of different methods for combining phase-contrast images obtained with multiple coils.
The ability to determine coil sensitivities implies that a method optimized in terms of maximized signal-to-noise ratio (SNR) can be applied to the combination of multiple coil images. An optimization of SNR subsequently results in a minimized variance in quantitative velocity measurements using phase-contrast imaging. When coil sensitivities are unknown, the weighted mean method, utilizing the square of the signal magnitude as weights, is suitable for combination of multiple phase images. In this study, the optimized method using estimated coil sensitivities was compared to the weighted mean method both theoretically and experimentally. It is shown that absence of noise correlation between the different coil images implies no difference between the methods regarding the variance of the phase. In the practical situation, noise correlation does exist, implying an opportunity for further reduction of phase variance using the optimized method. In vitro and in vivo studies showed, however, no significant difference between the two methods studied.


Passive broadband source localization based on a Riemannian distance with a short vertical array in the deep ocean.
A passive broadband source localization approach in the deep ocean is proposed based on the coherent matched-field processing combined with a Riemannian distance. The spatial coherence between hydrophones over frequency bandwidth is utilized for eliminating the unknown source spectrum. Three Riemannian distances are introduced for the measurement of the similarity between the data and replica matrices. The experimental results indicate that the proposed processors with a short array can effectively suppress the sidelobe and improve the localization performance. The source localization influenced by the factors such as the aperture, number of hydrophones, and desired bandwidth is also demonstrated.


Selection of controls in clinical trials: introduction and conference summary.
Understanding the strengths and weaknesses of the control group used in a randomized clinical trial is essential because comparisons of outcomes between the investigational and control groups form the basis of inferences regarding the safety and efficacy of the investigational treatment. For its 2007 International Conference, the American Thoracic Society (ATS) sponsored a scientific symposium in which the strengths and limitations of different types of control groups in clinical trials of pharmacotherapy, procedures, devices, and behavioral interventions were discussed. In this section, the co-chairs of this ATS symposium provide an overview of the presentations, including a brief historical perspective on the use of control groups in clinical trials.


A New Formulation of Calcitriol (DN-101) for High-Dose Pulse Administration in Prostate Cancer Therapy.
Although the antineoplastic activity of calcitriol in prostate cancer has been known for many years, the agent's use in oncology has been prevented because of the occurrence of hypercalcemia with daily administration. High-dose pulse administration of calcitriol has the potential to improve the therapeutic index of calcitriol. Results of a phase II study of calcitriol and docetaxel (Taxotere(R)) suggest that this combination may have utility in androgen-independent prostate cancer (AIPC). DN-101, a high-dose (15 mug) formulation of calcitriol suitable for use in oncology, is now being tested in a randomized trial (AIPC Study of Calcitriol Enhancing Taxotere). This formulation of calcitriol could become an important new tool for improving the efficacy of docetaxel in the treatment of AIPC and would join the ranks of other nuclear receptor ligands in cancer treatment. Investigations of DN-101 in the treatment of a broad range of tumor types and in combination with a variety of agents are an exciting new area of research.


Study of the Huntington's disease IT-15 gene in different ethnic groups in Ecuador.
This study aims to establish the current state of the IT-15 (HTT) gene in different Ecuadorian ethnic groups and patients by determining CAG triplet repeats, compared with the ethnicity of individuals. A total of 412 individuals were studied using nested polymerase chain reaction and Sanger sequencing: 75 individuals were indigenous (Kichwas), 211 mestizos, and 65 Afro-Ecuadorians. We included 31 patients who were clinically diagnosed with Huntington's disease (HD) and relatives of the affected patients (n = 30). Moreover, we correlated the presence of HD in Ecuadorian patients with 46 genetic ancestry-informative insertion-deletion polymorphic markers. We found that 77.20% had <28 CAG repetitions, 18.80% had mutable alleles, 2.27% had incomplete penetrance, and 1.70% reflected >39 repetitions. The average of CAG repetitions was 24 ± 3 for indigenous people; 28 ± 2 for mestizos; and 24 ± 3.2 repetitions for the Afro-Ecuadorians. The ancestral component showed that the main ancestry corresponded to Native Americans (0.873) and European ascendants (0.145), Africans were less represented in the evaluated population (0.018). There was a significant difference between the number of CAG repeats in mestizos and indigenous people (P < .01), suggesting that the Ecuadorian mestizo population has a risk factor for the gene mutation.


Incorporating perspective analysis into critical thinking performance assessments.
The International Performance Assessments of Learning (iPAL) project developed a framework for the construction of performance assessments for testing critical thinking, which proposes structuring them around a problem situation that sets an authentic (i.e., real-life-like) problem-solving task for the test-taker. Its critical thinking construct - which reflects the dominant conception of critical thinking - focuses on assessment and use of information, of arguments, and of consequences, and on communication. However, it fails to acknowledge that perspectives on a problem situation are systemically articulated in networks and derive from worldviews, which should also be critically examined. We aim to elaborate on the iPAL framework and enhance its critical thinking construct, incorporating a new facet of perspective analysis. We also intend to show what design considerations the construction of a performance assessment appropriate for this task entails. Based on Werner Ulrich's Critical Systems Heuristics, which provides a systemic way of analysing perspectives about a problem situation, we argue the need to introduce perspective analysis in the critical thinking construct, and we discuss the considerations necessary for designing critical thinking performance assessments that test perspective analysis skills: about the kind of problem situation the test-taker will face and about the expectations she may have about her task or role in that problem situation. We illustrate how performance assessments of this kind can be constructed by means of an example of an actual test.


Signal transduction-dependent small regulatory RNA is involved in glutamate metabolism of the human pathogen Bordetella pertussis.
Bordetella pertussis is the causative agent of human whooping cough, a highly contagious respiratory disease which despite vaccination programs remains the major cause of infant morbidity and mortality. The requirement of the RNA chaperone Hfq for virulence of B. pertussis suggested that Hfq-dependent small regulatory RNAs are involved in the modulation of gene expression. High-throughput RNA sequencing revealed hundreds of putative noncoding RNAs including the RgtA sRNA. Abundance of RgtA is strongly decreased in the absence of the Hfq protein and its expression is modulated by the activities of the two-component regulatory system BvgAS and another response regulator RisA. Whereas RgtA levels were elevated under modulatory conditions or in the absence of bvg genes, deletion of the risA gene completely abolished RgtA expression. Profiling of the ΔrgtA mutant in the ΔbvgA genetic background identified the BP3831 gene encoding a periplasmic amino acid-binding protein of an ABC transporter as a possible target gene. The results of site-directed mutagenesis and in silico analysis indicate that RgtA base-pairs with the region upstream of the start codon of the BP3831 mRNA and thereby weakens the BP3831 protein production. Furthermore, our data suggest that the function of the BP3831 protein is related to transport of glutamate, an important metabolite in the B. pertussis physiology. We propose that the BvgAS/RisA interplay regulates the expression of RgtA which upon infection, when glutamate might be scarce, attenuates translation of the glutamate transporter and thereby assists in adaptation of the pathogen to other sources of energy.


A review of studies looking at quality of life and psychological impact in people with photodermatoses - skin diseases triggered by sunlight.
Photodermatoses, or photosensitivity conditions, are a group of skin disorders caused by exposure to sunlight, overall affecting a large number of people. They cause a range of distressing symptoms including pain and burn, and can make the skin blister, flake and scar. The conditions themselves and the need for patients to avoid and protect themselves from sunlight may affect quality of life and psychological health. This study, from the U.K., aimed to find out what methods of assessment (tools) have been used to evaluate quality of life and psychological health in photodermatoses, and report what the impact is for patients. The authors reviewed relevant published English-language studies and summarised their findings. 20 studies were included: 19 assessing quality of life and three assessing psychological function. Six different tools had been used to assess quality of life, and four different tools to assess psychological health. It was shown that 31-39% of patients with photodermatoses experienced a very large impact on their quality of life. There was a particular impact on issues related to employment, social/leisure activities and clothing choices. Patients had around double the rates of anxiety and depression found in the general population, although few studies focussed on psychological health. The authors also noted that most available tools were not designed to address the unique impact of intermittent sunlight-induced skin conditions and suggested that development of more specific tools could be beneficial. In conclusion, this study confirmed that patients with photodermatoses experience substantial impact on their quality of life and that more research is needed. This is a summary of the study: Quality of life and psychological impact in the photodermatoses: a systematic review.


Cereal Leaf Beetle (Coleoptera: Chrysomelidae) Regional Dispersion and Relationship With Wheat Stand Denseness.
Cereal leaf beetle, Oulema melanopus L., is a pest of small grains and the literature conflicts on whether it is more abundant in sparse or dense stands of wheat. Our objectives were to determine the impact of stand denseness on cereal leaf beetle abundance and to investigate the regional dispersion of cereal leaf beetles across North Carolina and Virginia. One-hundred twenty fields were sampled across North Carolina and Virginia during 2011 for stand denseness, and cereal leaf beetle eggs, larvae, and adults. Two small-plot wheat experiments were planted in North Carolina using a low and a high seeding rate. Main plots were split, with one receiving a single nitrogen application and one receiving two. Egg density, but not larva or adult density, was positively correlated with stand denseness in the regional survey. Furthermore, regional spatial patterns of aggregation were noted for both stand denseness and egg number. In the small-plot experiments, seeding rate influenced stand denseness, but not nitrogen application. In one experiment, egg densities per unit area were higher in denser wheat, while in the other experiment, egg densities per tiller were lower in denser wheat. Larvae were not influenced by any factor. Overall, there were more cereal leaf beetle eggs in denser wheat stands. Previous observations that sparse stands of wheat are more prone to cereal leaf beetle infestation can be attributed to the fact that sparser stands have fewer tillers, which increases the cereal leaf beetle to tiller ratio compared with denser stands.


Connexin 43 is localized with actin in tenocytes.
Varieties of cell-matrix or cell-cell adhesions are associated with the actin cytoskeleton. However, for gap junctions, which are both channels and adhesions, there has been little evidence for such an association. The purpose of this study was to determine if connexin 43 (Cx43) associates with actin and to determine if this association is altered under mechanical load in tenocytes, a mechanically sensitive cell. Avian tenocytes were subjected to multiple cyclic strain regimens and then fixed and examined immunohistochemically at various times poststrain to determine where Cx43 protein was localized within the cells in relation to actin filaments. Four percent of tenocytes had colocalization of actin filaments and Cx43, which was significantly increased with 5% cyclic strain. To confirm this phenomenon, human tenocytes and COS-7 cells were also subjected to cyclic strain and then fixed at the same times after strain. As with avian tenocytes, Cx43 was colocalized with actin in human tenocytes and COS-7 cells. The colocalization increased significantly after cyclic strain in human tenocytes but not in COS-7 cells. The lack of detectable changes in COS-7 cells may indicate that they are less mechanosensitive than tenocytes perhaps due to the less robust actin cytoskeleton seen in the COS-7 cells when compared to the tenocytes. Furthermore, inhibiting myosin II activity greatly reduced the immunohistochemically-detectable Cx43 on actin filaments. Connexins may associate with actin to stabilize gap junctions at the plasma membrane, ensuring that tenocytes remain coupled during periods of prolonged or intense mechanical loading.


Determination of the optimum mixing time for a mixture of lactose and colloidal silicon dioxide.
The homogeneity of a mixture of colloidal silicon dioxide (CSD) and lactose is examined by quantifying the dependence of the CSD content on the mixing time. CSD concentration is determined photometrically as a blue silica-molybdic complex. Its deviation from the expected content is taken to characterize the mixture quality and the optimum mixing time. The conformity of this result with the flow properties of the same mixture is studied by measuring the dependence of the angle of repose on the mixing time.


Metastatic adrenocortical carcinoma displays higher mutation rate and tumor heterogeneity than primary tumors.
Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and high mortality due to metastatic disease. All reported genetic alterations have been in primary ACC, and it is unknown if there is molecular heterogeneity in ACC. Here, we report the genetic changes associated with metastatic ACC compared to primary ACCs and tumor heterogeneity. We performed whole-exome sequencing of 33 metastatic tumors. The overall mutation rate (per megabase) in metastatic tumors was 2.8-fold higher than primary ACC tumor samples. We found tumor heterogeneity among different metastatic sites in ACC and discovered recurrent mutations in several novel genes. We observed 37-57% overlap in genes that are mutated among different metastatic sites within the same patient. We also identified new therapeutic targets in recurrent and metastatic ACC not previously described in primary ACCs.


Can mHealth Revolutionize the Way We Manage Adult Obesity?
Obesity is the largest driver of chronic preventable diseases, accounting for an estimated $147 billion or 10 percent of total US healthcare costs in 2008. It has been forecasted that 42 percent of Americans will be obese by 2030. Mobile health (mHealth) technologies target and may modify the behavioral factors that lead to obesity to promote a healthy lifestyle. These technologies could potentially reduce the cost and the morbidity and mortality burden of obesity because of their inexpensive and portable nature. This study aimed to analyze the efficacy and cost-effectiveness of mHealth interventions for adult obesity in the United States. The methodology used in this study was a literature review of 54 articles. Weight, body mass index (BMI), waist circumference reductions, and favorable lifestyle behavior changes were noted across most studies. Existing data and research on efficacy and linked costs indicated that mHealth technologies were more effective than other methods and could be inexpensively delivered remotely to manage adult obesity, offering significant benefits over conventional care. Further studies on the costs and benefits of adapting such mHealth interventions in clinical settings are needed.


[Calcified masses of the kidney. Apropos of 58 cases].
Case reports were analyzed of patients with calcified renal masses observed in the department since 1968. Of the 65 radiologic reports reviewed, 7 were rejected since the course since diagnosis was unknown. Of the 58 case reports studied, 34 were of masses of certain diagnosis, 12 undetermined, 7 of masses in polycystic kidneys, 3 in tuberculous kidneys and 3 probably calcified hematomas. Analysis involved only those masses of proven diagnosis. Results confirmed the absence of specificity in favor of the cyst of peripheral character of calcifications: 33% of these masses were cancers. The existence of tissue calcification is synonymous of a solid mass, nearly always malignant (92% of cases). For peripherally calcified masses, arteriography was not sufficient to affirm benign nature of lesions, most of these masses having a particularly poorly vascularized or even avascular appearance. In these cases angiotensin was of special interest. Ultrasound imaging proved to be a reliable and perfectly sensitive examination. The presence of calcifications rarely interfered with study of tumoral contents. CT scan imaging and puncture biopsy were also perfectly sensitive and reliable examinations. Because of the high frequency of cancers in masses with peripheral calcification, all these masses should be surgically explored or at least punctured. Although a "benign" CT scan image appears sufficient to affirm the benign nature, this still requires more ample confirmation.


Strengthening Health Research and Ethics Systems in Timor-Leste.
Meaningful health research should lead to evidence-based decision-making that can be translated into policy and practice. Every country needs to have a well-functioning and resourced ethics review and clearance system to ensure health and medical research is conducted in line with ethical standards, preventing harm to research participants, and contributing to better health outcomes and national priorities. The purpose of this study is to describe the origins of the system for managing health research and ethics in Timor-Leste and how it has evolved over time; to identify the strengths and limitations of the current system; and to recommend areas for improvement. A narrative review of the literature (published papers, gray literature, and unpublished data) was conducted alongside key informant interviews with 15 Ministry of Health (MOH) policymakers and National Institute of Health staff between October 2020 and March 2021. The system for managing health research and ethics in Timor-Leste has remained largely the same since it was first established in 2009, with some adaptations to cope with a progressively increasing workload. Main findings include: the Department of Research and Studies (DRS) oversees complex ethics approval process in addition to other responsibilities; the DRS lacks the legal authority, policies, and procedures to help implement its full range of functions and responsibilities; national research priorities should be identified; MOH experiences difficulties in securing funding to support health research; training in health research, ethics and governance is an important priority for DRS. It is timely and important to invest in strengthening key components of health research and ethics systems in Timor-Leste. Despite limited resources, improvements can be achieved in key areas with focused assistance and collaboration with local, national, and international partners.


[Antiviral activity of murine interferons produced by bacterial and animal cell translation of messenger RNA].
Interferon was produced by E. Coli bacteria and animal cell messenger-RNA--interferon translation (mRNA--IF). The activity of the interferon produced by simultaneous mRNA--IF translation in these two cellular systems was, approximately, similar. The interferons translated by bacteria and animal cells inhibited the cytopathic effect, reproduction and plaque-formation of vesicular stomatitis virus, and, to a greater extent, of mouse encephalomyocarditis virus. The virus titration was carried out by the dye-uptake method. The bacteria-translated interferon (BTIF) was more susceptible to the indicator-virus dose variation and had antiviral effect of shorter duration than the virus-induced and animal cell-translated interferon. The BTIF, probably, due to the action of bacterial proteolytic enzymes proved nonstable on storage.


USP28 Deficiency Promotes Breast and Liver Carcinogenesis as well as Tumor Angiogenesis in a HIF-independent Manner.
Recent studies suggest that the ubiquitin-specific protease USP28 plays an important role in cellular repair and tissue remodeling, which implies that it has a direct role in carcinogenesis. The carcinogenic potential of USP28 was investigated in a comprehensive manner using patients, animal models, and cell culture. The findings demonstrate that overexpression of USP28 correlates with a better survival in patients with invasive ductal breast carcinoma. Mouse xenograft experiments with USP28-deficient breast cancer cells also support this view. Furthermore, lack of USP28 promotes a more malignant state of breast cancer cells, indicated by an epithelial-to-mesenchymal (EMT) transition, elevated proliferation, migration, and angiogenesis as well as a decreased adhesion. In addition to breast cancer, lack of USP28 in mice promoted an earlier onset and a more severe tumor formation in a chemical-induced liver cancer model. Mechanistically, the angio- and carcinogenic processes driven by the lack of USP28 appeared to be independent of HIF-1α, p53, and 53BP1.Implications: The findings of this study are not limited to one particular type of cancer but are rather applicable for carcinogenesis in a more general manner. The obtained data support the view that USP28 is involved in tumor suppression and has the potential to be a prognostic marker. Mol Cancer Res; 16(6); 1000-12. ©2018 AACR.


Sustained pharmacological blockade of NK1 substance P receptors causes functional desensitization of dorsal raphe 5-HT 1A autoreceptors in mice.
Antagonists at NK1 substance P receptors have demonstrated similar antidepressant properties in both animal paradigms and in human as selective serotonin reuptake inhibitors (SSRIs) that induce desensitization of 5-HT 1A autoreceptors within the dorsal raphe nucleus (DRN). We investigated whether this receptor adaptation also occurs upon NK1 receptor blockade. C57B/L6J mice were treated for 21 days with the selective NK1 receptor antagonist GR 205171 (10 mg/kg daily) through subcutaneously implanted osmotic mini pumps, and DRN 5-HT 1A autoreceptor functioning was assessed using various approaches. Recording of DRN serotonergic neurons in brainstem slices showed that GR 205171 treatment reduced (by approximately 1.5 fold) the potency of the 5-HT 1A receptor agonist, ipsapirone, to inhibit cell firing. In parallel, the 5-HT 1A autoreceptor-mediated [35S]GTP-gamma-S binding induced by 5-carboxamidotryptamine onto the DRN in brainstem sections was significantly decreased in GR 205171-treated mice. In vivo microdialysis showed that the cortical 5-HT overflow caused by acute injection of the SSRI paroxetine (1 mg/kg) was twice as high in GR 205171-treated as in vehicle-treated controls. In the DRN, basal 5-HT outflow was significantly enhanced by GR 205171 treatment. These data supported the hypothesis that chronic NK1 receptor blockade induces a functional desensitization of 5-HT 1A autoreceptors similar to that observed with SSRIs.


Delivering End-of-Life Cancer Care: Perspectives of Providers.
Persistent gaps in end-of-life cancer care delivery and growing associated expenditures remain imminent US public health issues. The objective of this study was to understand clinical providers' experiences delivering cancer care for patients at the end of life and their perspectives on potential solutions to improve quality of care. Semistructured interviews were conducted with 75 cancer care providers across the United States. The interviews were recorded, transcribed, and analyzed using constant comparative method of qualitative analysis. Providers identified 3 major cancer care delivery challenges including lack of time to educate patients and caregivers due to clinical volume and administrative burdens, ambiguity in determining both prognosis and timing of palliative care at the end-of-life, and lack of adequate systems to support non-face-to-face communication with patients. To address these challenges, providers endorsed several options for clinical practice redesign in their settings. These include use of a lay health worker to assist in addressing early advance care planning, proactive non-face-to-face communication with patients specifically regarding symptom management, and community and in-home delivery of cancer care services. Specific strategies for cancer care redesign endorsed by health-care providers may be used to create interventions that can more efficiently and effectively address gaps in end-of-life cancer care.


Pelvic lymph node dissection in the context of radical cystectomy: a thorough insight into the connection between patient, surgeon, pathologist and treating institution.
Pelvic lymph node dissection (PLND) in patients with bladder cancer varies widely in extent, technique employed, and pathological workup of specimens. The present paper provides an overview of the existing evidence regarding the effectiveness of PLND and elucidates the interactions between patient, surgeon, pathologist, and treating institution as well as their cumulative impact on the final postoperative lymph node (LN) staging. Bladder cancer patients undergoing radical cystectomy with extended PLND appear to have better oncologic outcomes compared to patients undergoing radical cystectomy and limited PLND. Attempts have been made to define and assess the quality of PLND according to the number of lymph nodes identified. However, lymph node counts depend on multiple factors such as patient characteristics, surgical template, pathological workup, and institutional policies; hence, meticulous PLND within a defined and uniformly applied extended template appears to be a better assurance of quality than absolute lymph node counts. Nevertheless, the prognosis of the patients can be partially predicted with findings from the histopathological evaluation of the PLND specimen, such as the number of positive lymph nodes, extracapsular extension, and size of the largest LN metastases. Therefore, particular prognostic parameters should be addressed within the pathological report to guide the urologist in terms of patient counseling.


Energy expenditure in myelofibrosis patients treated with a JAK1/2 inhibitor.
Weight gain is a known adverse effect of ruxolitinib, a JAK1/2 inhibitor that is the mainstay of treatment for many patients with myelofibrosis. The mechanisms behind weight increase with ruxolitinib is incompletely understood, although decreased adipose tissue lipolysis and increased appetite due to blocking the effects of leptin in the hypothalamus have been proposed. In order to explore the metabolic changes in ruxolitinib-treated patients with myelofibrosis, we performed a pilot study to assess the feasibility of using a portable indirect calorimeter to quantify energy expenditure before and during ruxolitinib treatment and report the results of two patients. Waist circumference increased during ruxolitinib treatment in both patients. Energy expenditure initially increased followed by a decrease and then increase again, but to levels below baseline. These results suggest that weight gain secondary to ruxolitinib may be related to changes in whole body energy expenditure.


Minimising compassion fatigue in obstetrics/gynaecology doctors: exploring an intervention for an occupational hazard.
To explore the indicators of occupational stress in a group of obstetrics and gynaecology doctors and to investigate the impact of work-focused discussion groups over a 6 month period. The ProQOL questionnaire was used to measure the efficacy of monthly psychiatrist-led Balint style discussion groups on minimising Compassion Fatigue (consisting of Secondary Traumatic Stress and Burnout). The 25 doctors were given the given the ProQOL questionnaire to complete: (a) at the initiation of the intervention in July 2015, (b) in October 2015, and (c) in December 2015. Significantly decreased levels of Secondary Traumatic Stress ( p=0.008), Burnout ( p=0.010), as well as significantly increased rates of Compassion Satisfaction ( p=0.035) were recorded. Participants requested that the groups be continued. Psychiatrist-led work focused discussion groups were associated with improved rates of Secondary Traumatic Stress, Burnout, and Compassion Satisfaction in this sample group.


Morphology of Sigmoid Colon in South Indian Population: A Cadaveric Study.
Sigmoid volvulus is a common etiological factor in acute large bowel obstruction. The increased length of sigmoid colon is attributed as one of the causes of sigmoid volvulus. The aim of this study was to find the morphology of sigmoid colon in South Indian population using cadavers. The present study was performed with 31 cadavers used for teaching purpose. The sigmoid colon was classified into classical, long-narrow and long- broad types by their disposition in the abdominal cavity. The sigmoid loop's relation to pelvic brim was also observed and grouped as pelvic and suprapelvic in position. The length of sigmoid colon along the mesenteric and antimesenteric border, height and width of sigmoid mesocolon in relation to the pelvic brim and the root of mesentery were measured in the study. The study showed that the majority of the sigmoid colons fell into the classical type (47.6%). The sigmoid colon in pelvic position was significantly more prevalent. The mean length of sigmoid colon was 15.2 ± 4.4cm and 19.2 ± 6cm considering the pelvic brim and root of mesentery as reference points of measurement respectively. The mean length along antimesenteric border was 22.3 ± 7.9cm and 25 ± 8.7cm along the same reference points. The mean length of mesocolon height was 6.5 ± 3cm with reference to pelvic brim and 7.3 ± 3cm with reference to root of Sigmoid mesocolon respectively. The mean width of mesocolon was 7.4 ± 3cm (pelvic brim) and 8 ± 2cm (root of Sigmoid mesocolon) There was a positive correlation of sigmoid colon length with the height of the mesocolon. The gender analysis showed that males had statistically significant longer sigmoid colon and mesocolon. This study documents that the South Indian population has a more classical type of sigmoid colon and that the anatomical dimensions of sigmoid colon and its mesocolon is significantly longer in males.


Songbirds and humans apply different strategies in a sound sequence discrimination task.
The abilities of animals and humans to extract rules from sound sequences have previously been compared using observation of spontaneous responses and conditioning techniques. However, the results were inconsistently interpreted across studies possibly due to methodological and/or species differences. Therefore, we examined the strategies for discrimination of sound sequences in Bengalese finches and humans using the same protocol. Birds were trained on a GO/NOGO task to discriminate between two categories of sound stimulus generated based on an "AAB" or "ABB" rule. The sound elements used were taken from a variety of male (M) and female (F) calls, such that the sequences could be represented as MMF and MFF. In test sessions, FFM and FMM sequences, which were never presented in the training sessions but conformed to the rule, were presented as probe stimuli. The results suggested two discriminative strategies were being applied: (1) memorizing sound patterns of either GO or NOGO stimuli and generating the appropriate responses for only those sounds; and (2) using the repeated element as a cue. There was no evidence that the birds successfully extracted the abstract rule (i.e., AAB and ABB); MMF-GO subjects did not produce a GO response for FFM and vice versa. Next we examined whether those strategies were also applicable for human participants on the same task. The results and questionnaires revealed that participants extracted the abstract rule, and most of them employed it to discriminate the sequences. This strategy was never observed in bird subjects, although some participants used strategies similar to the birds when responding to the probe stimuli. Our results showed that the human participants applied the abstract rule in the task even without instruction but Bengalese finches did not, thereby reconfirming that humans have to extract abstract rules from sound sequences that is distinct from non-human animals.


Multifaceted anticancer activity of BH3 mimetics: Current evidence and future prospects.
BH3 mimetics are a novel class of anticancer agents designed to specifically target pro-survival proteins of the Bcl-2 family. Like endogenous BH3-only proteins, BH3 mimetics competitively bind to surface hydrophobic grooves of pro-survival Bcl-2 family members, counteracting their protective effects and thus facilitating apoptosis in cancer cells. Among the small-molecule BH3 mimetics identified, ABT-737 and its analogs, obatoclax as well as gossypol derivatives are the best characterized. The anticancer potential of these compounds applied as a single agent or in combination with chemotherapeutic drugs is currently being evaluated in preclinical studies and in clinical trials. In spite of promising results, the actual mechanisms of their anticancer action remain to be identified. Findings from preclinical studies point to additional activities of BH3 mimetics in cancer cells that are not connected with apoptosis induction. These off-target effects involve induction of autophagy and necrotic cell death as well as modulation of the cell cycle and multiple cell signaling pathways. For the optimization and clinical implementation of BH3 mimetics, a detailed understanding of their role as inhibitors of the pro-survival Bcl-2 proteins, but also of their possible additional effects is required. This review summarizes the most representative BH3 mimetic compounds with emphasis on their off-target effects. Based on the present knowledge on the multifaceted effects of BH3 mimetics on cancer cells, the commentary outlines the potential pitfalls and highlights the considerable promise for cancer treatment with BH3 mimetics.


Correlating the accuracy of colposcopy with practitioner experience when diagnosing cervical pathology using the dynamic spectral imaging system.
To assess the performance of colposcopists and correlate it with their experience when diagnosing cervical pathology by reviewing conventional colposcopy (CC) digital images and the Dynamic Spectral Imaging System (DySIS) cervical map. Images from 50 women with normal and abnormal cervix collected during CC and the corresponding DySIS maps were projected consecutively to 63 participating colposcopists. Participants were asked for their diagnosis (normal, abnormal findings or cancer). The clinical experience of the participants was divided into low (n = 27), medium (n = 18) and high (n = 18), considering the number of colposcopies each one performed routinely. The mean of overall correct diagnoses was significantly higher with DySIS than CC for the low and medium experience group (20.4 vs. 24.4, and 21.9 vs. 26.0, respectively; p < 0.001), but not in the high experience group. The correct diagnosis was significantly higher with DySIS than CC for all experience groups in cases with a normal cervix and cervical intraepithelial neoplasia 2+ (CIN2+), but not for those with CIN1. All groups agreed that DySIS guides biopsies better, offers more information and allows performing colposcopy even without extensive experience. The results of evaluating projected colposcopy images were more successful with DySIS than with CC in the diagnosis of cervical pathology, especially among less experienced colposcopists.


Novel mannose binding natterin-like protein in the skin mucus of Atlantic cod (Gadus morhua).
This study presents the first report of purification of natterin-like protein (Nlp) in a non-venomous fish. The peptide identities of purified cod Nlp were confirmed through LC-MSMS and matched to a cod expressed sequence tag (EST). A partial cod nlp nucleotide sequence was amplified and sequenced based on this EST. Multiple sequence alignment of cod Nlp showed considerable homology with other teleost Nlps and the presence of an N-terminal jacalin-like lectin domain coupled with a C-terminal toxin domain. nlp expression was higher in skin, head kidney, liver and spleen than in other tissues studied. Hemaggluttination of horse red blood cells by Nlp was calcium dependent and inhibited by mannose. A Vibrio anguillarum bath challenge however, did not alter the expression of cod nlp transcripts in the skin and gills. Further functional characterization is required to establish the significance of this unique protein in Atlantic cod and other teleosts.


Stabilization of beef meat by a new active packaging containing natural antioxidants.
A new antioxidant active packaging material for food has been designed and developed, consisting of a polypropylene film in which some natural antioxidants have been immobilized. The antioxidant properties of the new material have been tested by using both pure myoglobin and fresh beef steaks. Two different cell configurations (glass vial and Petri dish) and four different myoglobin concentrations-according to the common content of this compound in fresh meat and meat derivatives (1080, 1995, 3332, and 4414 microg g(-1), respectively)-have been evaluated in oxidation studies. Furthermore, three different concentrations of natural antioxidants in the film (designated as PR1, PR2, and PR3) were evaluated. Once myoglobin samples and the active films were introduced in the cell, they were exposed to cool white fluorescent light to accelerate oxidation for a period of time ranging from 5 to 30 days. Remaining myoglobin concentration was measured by molecular absorption UV-vis spectrophotometry at 409 nm. Organoleptic properties and color, texture, and physical characteristics of fresh meat packaged with the new active film have also been measured to evaluate the shelf life of the packaged meat. Results showed that, compared to normal polypropylene, the active film containing natural antioxidants efficiently enhanced the stability of both myoglobin and fresh meat against oxidation processes, thus being a promising way to extend the shelf life of fresh meat.


Cervical metastasis of esophagogastric junction cancer.
As cervical metastases in esophagogastric junction cancer are extremely rare, the authors herein report a case. A 63-year-old woman presented with dysphagia since 6 months. Diagnostic endoscopy showed that the tumor was located at the esophagogastric junction and histopathological diagnosis of adenocarcinoma was offered. A subtotal gastrectomy was performed. Histopathological diagnosis was moderately differentiated adenocarcinoma, invading upto the serosa with metastases to perigastric nodes. The patient received chemotherapy of cisplatin and fluorouracil for one cycle and oral capecitabine for two cycles. Two years later, the patient presented with vaginal bleeding and magnetic resonance imaging of pelvis revealed a tumor of the cervix. Histopathological impression of the tumor was metastatic cervical adenocarcinoma and immunohistochemistry showed the tumor was cytokeratin, villin, and CDX2 were positive and cytokeratin 20, CA125, and CA199 were negative. The immunohistochemical profile was the same as that of primary.


Neuro-ophthalmic Manifestations of Coronavirus Disease 2019 and Its Vaccination: A Narrative Review.
Coronavirus disease 2019 (COVID-19) is a current pandemic caused by SARS-CoV-2 that has vastly affected the whole world. Although respiratory disease is the most common manifestation of COVID-19, the virus can affect multiple organs. Neurotropic aspects of the virus are increasingly unfolding, in so far as some respiratory failures are attributed to brainstem involvement. The neuro-ophthalmic manifestations of COVID-19 and the neuro-ophthalmic side effects of vaccination were reviewed. The major findings are that the SARS-CoV-2 infection commonly causes headaches and ocular pain. It can affect the afferent and efferent visual pathways by ischemic or inflammatory mechanisms. Optic nerve may be the origin of transient or permanent visual loss from papillophlebitis, idiopathic intracranial hypertension, or optic neuritis. Cerebrovascular strokes are not uncommon and may lead to cortical visual impairment or optic nerve infarction. SARS-CoV-2 may affect the pupillomotor pathways, resulting in tonic pupil (Adie's syndrome) or Horner's syndrome. Cranial neuropathies including third, fourth, sixth, and seventh nerve palsies have all been reported. Rhino-orbital mucormycosis superinfections in COVID-19 patients receiving steroids or other immunosuppressive therapies may result in unilateral or bilateral visual loss and ophthalmoplegia. Autoimmune conditions such as Guillain-Barré, Miller-Fisher syndrome, and ocular myasthenia have been reported.


Entrapping Digestive Enzymes with Engineered Mesoporous Silica Particles Reduces Metabolic Risk Factors in Humans.
Engineered mesoporous silica particles (MSP) are thermally and chemically stable porous materials composed of pure silica and have attracted attention for their potential biomedical applications. Oral intake of engineered MSP is shown to reduce body weight and adipose tissue in mice. Here, clinical data from a first-in-humans study in ten healthy individuals with obesity are reported, demonstrating a reduction in glycated hemoglobin (HbA1c) and low-density lipoprotein cholesterol, which are well-established metabolic and cardiovascular risk factors. In vitro investigations demonstrate sequestration of pancreatic α-amylase and lipase in an MSP pore-size dependent manner. Subsequent ex vivo experiments in conditions mimicking intestinal conditions and in vivo experiments in mice show a decrease in enzyme activity upon exposure to the engineered MSP, presumably by the same mechanism. Therefore, it is suggested that tailored MSP act by lowering the digestive enzyme availability in the small intestine, resulting in decreased digestion of macronutrient and leading to reduced caloric uptake. This novel MSP based mechanism-of-action, combined with its excellent safety in man, makes it a promising future agent for prevention and treatment of metabolic diseases.


A survey of parent satisfaction with pediatric neuropsychological evaluations.
Satisfaction with pediatric neuropsychological evaluations was surveyed by asking parents or guardians of children who completed pediatric neuropsychological evaluations at a large children's hospital over a 2-year period to complete a 30-item rating scale. The scale included items drawn from published measures of consumer satisfaction, and incorporated a well-validated measure of general satisfaction. A total of 338 surveys were distributed, with 117 completed, for a return rate of 35%. Respondents were generally similar to non-respondents, except that respondents had a higher average level of maternal education and were more likely to have been referred for neuropsychological evaluations by sources outside the hospital. Parents were generally satisfied with pediatric neuropsychological evaluations, although some parents indicated that the evaluations did not provide as much help as expected. A factor analysis of the survey instrument revealed four dimensions of satisfaction: General Satisfaction, Clinician Acceptance/Empathy, Provision of Help, and Facilities/Administrative Assistance. Maternal education was negatively correlated with all four factors, but no other demographic, patient, or clinician variables were significantly related to satisfaction. Future studies could survey physicians and educators to provide a more complete understanding of satisfaction with pediatric neuropsychological evaluations.


Ecotoxicology of phenylphosphonothioates.
The phenylphosphonothioate insecticides EPN and leptophos, and several analogs, were evaluated with respect to their delayed neurotoxic effects in hens and their environmental behavior in a terrestrial-aquatic model ecosystem. Acute toxicity to insects was highly correlated with sigma sigma of the substituted phenyl group (regression coefficient r = -0.91) while acute toxicity to mammals was slightly less well correlated (regression coefficient r = -0.71), and neurotoxicity was poorly correlated with sigma sigma (regression coefficient r = -0.35). Both EPN and leptophos were markedly more persistent and bioaccumulative in the model ecosystem than parathion. Desbromoleptophos, a contaminant and metabolite of leptophos, was seen to be a highly stable and persistent terminal residue of leptophos.


Delayed sexual maturity in males of Vespa velutina.
Vespa velutina var nigrithorax (Lepelletier, 1835) is an invasive predator of bees accidentally introduced in France in 2004, and it is having a serious impact on apiculture and ecosystems. Studying the reproduction of an invasive species is key to assess its population dynamic. This study explores the sexual maturation of V. velutina males and the evolution of their fertility. The main studied parameters were physiologic (spermiogenesis, spermatogenesis) and anatomic (testes size and structure, head width). Two populations of males were described based on their emergence period: early males in early summer or classic males in autumn. Each testis has an average of 108 testicular follicles. Spermatogenesis is synchronous, with only 1 sperm production wave, and completed, on average, at 10.3 d after emergence with the degeneration of the testes. The sperm counts in seminal vesicles of mature males are 3 × 106 in October/November and 0.8 × 106 in June. In comparison, females store 0.1 × 106 sperm in their spermathecae. The early males emerged from colonies made by fertilized queens. The reproductive potential of these early males seemed limited, and their function in the colony is discussed. The sperm stock evolution in autumn males suggests the occurrence of a reproductive pattern of male competition for the access to females and a single copulation per male. The synchronicity of male and foundress emergences and sexual maturation is of primary importance for the mating success and the future colony development.


Regulation of invertase synthesis by glucose in Saccharomyces cerevisiae.
Saccharomyces cerevisiae growing under repressible conditions (1% of glucose or more) produces a burst of external invertase when shifted to higher temperatures. The secretion of this invertase requires protein synthesis, but was found to be independent of RNA formation. The level of mRNA accumulated and translated was inversely proportional to the glucose present in the growth medium. These results are consistent with the hypothesis that invertase is continuously synthesized both in the presence and absence of glucose, but under repressible conditions is degraded before secretion takes place.


Cartilage proteoglycan depletion in acute and chronic antigen-induced arthritis.
We examined the kinetics of proteoglycan (PG) depletion in rabbits with antigen-induced arthritis. There was a rapid loss of PG from arthritic cartilage, reaching 35-40% at day 7. Thereafter, the rate of PG depletion declined, and by day 42, the maximum loss was 55-60%. The initial loss of PG was accompanied by the appearance of large amounts of sulfated glycosaminoglycans (GAGs) in the joint fluid (measured as total sulfated GAGs by dye binding and as keratan sulfate by radioimmunoassay). However, by day 14, the levels of sulfated GAGs in arthritic joint fluid declined to control levels, even though the cartilage demonstrated a sustained depletion of PG. The cartilage PG degradation observed in antigen-induced arthritis could also be produced in normal animals by a single intraarticular injection of recombinant interleukin-1. The acute loss of cartilage PG occurred independently of neutrophil accumulation, both in the case of antigen-induced arthritis and after injection of interleukin-1.


Screening of Chlorinated Paraffins and Unsaturated Analogues in Commercial Mixtures: Confirmation of Their Occurrences in the Atmosphere.
Characterizing the detailed compositions of chlorinated paraffins (CPs) commercial mixtures is crucial to understand their environmental sources, fates, and potential risks. In this study, dichloromethane (DCM)-enhanced UPLC-ESI-QTOFMS analysis combined with characteristic isotope chlorine peaks is applied to screen all CPs and their structural analogues in the three most commonly produced CP commercial mixtures (CP-42, CP-52, and CP-70). Mass fractions of total short-chain CPs (SCCPs), medium-chain CPs (MCCPs) and long-chain CPs (LCCPs) ranged from 0.64 to 31.9%, 0.64 to 21.8%, and 0.04 to 43.9%, respectively, in the three commercial mixtures. 113 unsaturated SCCPs, MCCPs, and LCCPs were identified in the commercial mixtures. The detailed mass percentages of saturated and unsaturated CPs with carbon numbers of 10-30, chlorine numbers of 5-28, and unsaturated degrees of 0-7 were characterized in all commercial mixtures. Occurrences of the predominant saturated and unsaturated CPs were further confirmed in air samples collected in Guangdong Province, one of the major CP production areas in China, over one year. The profiles of the detected compounds indicated that LCCPs in air samples might come mainly from the production and usage of CP-52, and unsaturated C24-29-LCCPs were specifically originated from CP-70 used in the area.


CACNA1C hypermethylation is associated with bipolar disorder.
The CACNA1C gene, encoding a subunit of the L-type voltage-gated calcium channel is one of the best-supported susceptibility genes for bipolar disorder (BD). Genome-wide association studies have identified a cluster of non-coding single-nucleotide polymorphisms (SNPs) in intron 3 to be highly associated with BD and schizophrenia. The mechanism by which these SNPs confer risk of BD appears to be through an altered regulation of CACNA1C expression. The role of CACNA1C DNA methylation in BD has not yet been addressed. The aim of this study was to investigate if CACNA1C DNA methylation is altered in BD. First, the methylation status of five CpG islands (CGIs) across CACNA1C in blood from BD subjects (n=40) and healthy controls (n=38) was determined. Four islands were almost completely methylated or completely unmethylated, while one island (CGI 3) in intron 3 displayed intermediate methylation levels. In the main analysis, the methylation status of CGI 3 was analyzed in a larger sample of BD subjects (n=582) and control individuals (n=319). Out of six CpG sites that were investigated, five sites showed significant hypermethylation in cases (lowest P=1.16 × 10(-7) for CpG35). Nearby SNPs were found to influence the methylation level, and we identified rs2238056 in intron 3 as the strongest methylation quantitative trait locus (P=2.6 × 10(-7)) for CpG35. In addition, we found an increased methylation in females, and no difference between bipolar I and II. In conclusion, we find that CACNA1C methylation is associated with BD and suggest that the regulatory effect of the non-coding risk variants involves a shift in DNA methylation.


Changing in lipid profile induced by the mutation of Foxn1 gene: A lipidomic analysis of Nude mice skin.
Nude mice carry a spontaneous mutation affecting the gene Foxn1 mainly expressed in the epidermis. This gene is involved in several skin functions, especially in the proliferation and the differentiation of keratinocytes which are key cells of epithelial barrier. The skin, a protective barrier for the body, is essentially composed of lipids. Taking into account these factors, we conducted a lipidomic study to search for any changes in lipid composition of skin possibly related to Foxn1 mutation. Lipids were extracted from skin biopsies of Nude and BALB/c mice to be analyzed by liquid chromatography coupled to a high resolution mass spectrometer (HRMS). Multivariate and univariate data analyses were carried out to compare lipid extracts. Identification was performed using HRMS data, retention time and mass spectrometry fragmentation study. These results indicate that mutation of Foxn1 leads to significant modifications in the lipidome in Nude mice skin. An increase in cholesterol sulfate, phospholipids, sphingolipids and fatty acids associated with a decrease in glycerolipids suggest that the lipidome in mice skin is regulated by the Foxn1 gene.


Transformation of common warts into squamous cell carcinoma on sun-exposed areas in an immunosuppressed patient.
We report one case of renal transplant recipient who developed widespread multiple verrucous skin lesions. Histologic examination revealed typical warts and, only from several sites exposed to sun (hands and face), a development of dysplasia within the warts and a transformation of some of them toward infiltrating squamous cell carcinoma (SCC). Human papillomavirus (HPV) testing for DNA by polymerase chain reaction DNA amplification identified HPV type 1 in both warts and SCC. Our findings suggest that classic warts may progress to high-grade lesions and that, in addition to the oncogenic potential of the virus alone, other factors including the host's immunosuppressed state and ultraviolet radiation seem to be essential to malignant transformation.


Symptomatology and etiology of chronic pediatric rhinosinusitis.
This study aims to define symptoms and etiology and determine how to prevent chronic rhinosinusitis in children. Between February 2003 and February 2005, 50 pediatric patients (25 girls and 25 boys; mean age 8.22 years; range 4 to 14 years) with chronic rhinosinusitis were included in the study. The patients were questioned about anterior/posterior nasal dripping, night cough, headache, nausea, vomiting and nasal obstruction for symptomatology; about school condition, smoking behavior of parents and history of asthma for etiology. Hemogram, serum biochemistry, allergy test, nasal smear, chest and lateral neck radiography and sweat test were performed. Symptomatologic examination revealed that 48% had anterior nasal dripping, 62% with postnasal dripping, 70% with headache and 90% with nasal obstruction. Evaluation of etiological factors revealed that 68% were going to school, 48% of the parents had the history of smoking, 42% with allergy test-positivity and 60% with adenoid vegetation. Our study results indicated that environmental factors are important as etiological factors in rhinosinusitis. For prevention, we recommend restriction of close relationship at school, not to smoke at home and vaccination in each year with influenza and S. pneumonia vaccine.


PEG-fibrin conjugates: the PEG impact on the polymerization dynamics.
Fibrin and its modifications, particularly those with functionalized polyethylene glycol (PEG), remain highly attractive as a biomaterial in drug delivery and regenerative medicine. Despite the extensive knowledge of fibrinogenesis, there is little information on the processes occurring after its modification. Previously, we found structural differences between native fibrin and its conjugates with PEG that allows us to hypothesize that a combination of methods such as terahertz (THz) pulsed spectroscopy and rheology may contribute to the characterization of gelation and reveal the effect of PEG on the polymerization dynamics. Compared to native fibrin, PEGylated fibrins had a homogenously soft surface; PEGylation also led to a significant decrease in the gelation time: from 42.75 min for native fibrin to 31.26 min and 35.09 min for 5 : 1 and 10 : 1 PEGylated fibrin, respectively. It is worth noting that THz pulsed spectroscopy makes it possible to reliably investigate only the polymerization process itself, while it does not allow us to observe statistically significant differences between the distinct PEGylated fibrin gels. The polymerization time constant of native fibrin measured by THz pulsed spectroscopy was 14.4 ± 2.8 min. However, it could not be calculated for PEGylated fibrin because the structural changes were too rapid. These results, together with those previously reported, led us to speculate that PEG-fibrin conjugates formed homogenously distributed highly water-shelled aggregates without bundling compared to native fibrin, ensuring rapid gelation and stabilization of the system without increasing its complexity.


The effect of asymmetric external reorganization energy on electron and hole transport in organic semiconductors.
Understanding the relationship between charge mobilities and the molecular stacking structures of π-conjugated organic semiconducting materials is essential for their development. In this study, a quantum mechanics (QM)-derived state-specific polarizable force field (SS-PFF) is applied to explicitly estimate the external reorganization energies (λext) during electron transfer (ET) or hole transfer (HT) processes using our recently proposed two-point model (J. Phys. Chem. A, 2018, 122, 8957-8964). Different from the Marcus two-sphere model, the application of the explicit two-point model produces a notably asymmetric λext for ET and HT processes in oligoacene crystals. For the same charge transfer channels, the λext of ET is 7-10 times higher than that of HT, which results in a larger intrinsic hole mobility. This successfully rationalizes why acenes are prone to be p-type conducting materials. Perfluorination can change the polarity of the molecular surface electrostatic potential (ESP). Thus, perfluorination is a possible approach to reduce the external reorganization energies for ET reactions, which can be used to tune the order of λext of ET and HT processes. The two-point model with the SS-PFF, therefore, opens the door to revisit the intrinsic mobilities of electrons and holes in organic semiconductors.


Immunocytochemical localization of macrophage migration inhibitory factor in human hypophysis and pituitary adenomas.
To establish the presence of macrophage migration inhibitory factor (MIF) in human nontumorous and adenomatous pituitaries. Macrophage migration inhibitory factor was demonstrated by immunocytochemistry on paraffin sections with a polyclonal antirecombinant murine MIF using the streptavidin-biotin-peroxidase complex method. Nontumorous hypophyses (14 cases) obtained from autopsy and 54 surgically removed pituitary adenomas were studied. In nontumorous pituitaries, serial sections were immunostained for both pituitary hormones and MIF. Macrophage migration inhibitory factor was localized in all corticotrophs, including basophils extending into the posterior lobe, Crooke's cells, and a few thyrotrophs. The posterior lobe was immunonegative for MIF. Densely (five cases) and sparsely (six cases) granulated somatotroph and lactotroph (six cases) adenomas lacked MIF immunostaining. Macrophage migration inhibitory factor was found in 3 of 4 thyrotroph adenomas, 3 of 6 gonadotroph adenomas, 10 of 11 functioning corticotroph and 8 of 10 silent corticotroph adenomas, 3 of 3 null cell adenomas, and 3 of 3 oncocytic adenomas. The immunopositivity was diffuse or focal, and the intensity was variable. This study is the first to demonstrate the presence of MIF in human nontumorous and adenomatous pituitaries using an immunocytochemical staining technique.


Limnological effects of wood ash application to the subcatchments of boreal, humic lakes.
To assess environmental risks of wood ash, limnological effects of ash application to the drainage basins of two small, humic lakes and one reference lake in southern Finland were examined in this three-year study. Treated areas corresponded to 12 and 19% of the total catchment and the amount of wood ash added was 6400 kg ha(-1). Immediate effects of wood ash on lake water were investigated in three tank experiments each lasting 1.5 wk. In tank experiments, addition of wood ash increased pH, alkalinity, conductivity, and Ca and P concentrations of humic lake water, while growth of phytoplankton decreased. After wood ash application to the subcatchments, pH, alkalinity, conductivity, and concentrations of K+, SO4(2-), and Cl- slightly increased, both in inflowing waters and in the lakes, but no increased leaching of Ca, N, or P from the treated subcatchments occurred. Phytoplankton biomass increased in both experimental lakes in comparison with the reference lake. In the lake with 19% application rate to the catchment, zooplankton biomass also increased. The results indicate that, over the short term, a small-scale ash treatment to a forested drainage basin will not necessarily cause significant changes in the water quality of boreal humic lakes, but at higher application rates, changes in water chemistry and biology are more evident.


Alterations of resting state networks and structural connectivity in relation to the prefrontal and anterior cingulate cortices in late prematurity.
Late preterm birth is increasingly recognized as a risk factor for cognitive and social deficits. The prefrontal cortex is particularly vulnerable to injury in late prematurity because of its protracted development and extensive cortical connections. Our study examined children born late preterm without access to advanced postnatal care to assess structural and functional connectivity related to the prefrontal cortex. Thirty-eight preadolescents [19 born late preterm (34-36 /7 weeks gestational age) and 19 at term] were recruited from a developing community in Brazil. Participants underwent neuropsychological testing. Individuals underwent three-dimensional T1-weighted, diffusion-weighted, and resting state functional MRI. Probabilistic tractography and functional connectivity analyses were carried out using unilateral seeds combining the medial prefrontal cortex and the anterior cingulate cortex. Late preterm children showed increased functional connectivity within regions of the default mode, salience, and central-executive networks from both right and left frontal cortex seeds. Decreased functional connectivity was observed within the right parahippocampal region from left frontal seeding. Probabilistic tractography showed a pattern of decreased streamlines in frontal white matter pathways and the corpus callosum, but also increased streamlines in the left orbitofrontal white matter and the right frontal white matter when seeded from the right. Late preterm children and term control children scored similarly on neuropsychological testing. Prefrontal cortical connectivity is altered in late prematurity, with hyperconnectivity observed in key resting state networks in the absence of neuropsychological deficits. Abnormal structural connectivity indicated by probabilistic tractography suggests subtle changes in white matter development, implying disruption of normal maturation during the late gestational period.


Dynamic Context-Aware Event Recognition Based on Markov Logic Networks.
Event recognition in smart spaces is an important and challenging task. Most existing approaches for event recognition purely employ either logical methods that do not handle uncertainty, or probabilistic methods that can hardly manage the representation of structured information. To overcome these limitations, especially in the situation where the uncertainty of sensing data is dynamically changing over the time, we propose a multi-level information fusion model for sensing data and contextual information, and also present a corresponding method to handle uncertainty for event recognition based on Markov logic networks (MLNs) which combine the expressivity of first order logic (FOL) and the uncertainty disposal of probabilistic graphical models (PGMs). Then we put forward an algorithm for updating formula weights in MLNs to deal with data dynamics. Experiments on two datasets from different scenarios are conducted to evaluate the proposed approach. The results show that our approach (i) provides an effective way to recognize events by using the fusion of uncertain data and contextual information based on MLNs and (ii) outperforms the original MLNs-based method in dealing with dynamic data.


A Window into the World of Nephrology Nursing: Nephrology Nurses' Views of the Health and Safety of Their Work Environments, the Impact on Patient Care, and Opportunities for Improvement.
In January 2018, the American Nephrology Nurses Association and Nephrology News and Issues conducted a national study, The Health and Safety of Nephrology Nurses and the Environments in Which They Work. This article presents initial qualitative results from that study - in the words of nephrology nurses. Based on responses of participants, themes and subthemes were identified: staffing, nursing practice (time to provide nursing care, nursing work hours, level of practice, nurses responsibility for the practice of others), work environment conditions (physical environments, psychological environments, civility/ incivility, environmental health, and work spaces), respect, recognition, interprofessional collaboration and support, and career and job satisfaction. Results of the study provide insight into what it is like to work on the frontlines of nephrology nursing.