Related risk factors associated with post-stroke fatigue: a systematic review and meta-analysis.
Post-stroke fatigue (PSF) is one of the most common complications of stroke and has a negative impact on quality of life over time. Although several therapeutic approaches have been explored in the last decade, the risk factors responsible for the occurrence of PSF are still largely unknown. The aim of this meta-analysis was to identify the risk factors contributing to PSF, especially clinical and social risk factors, which may help to prevent PSF. A systematic literature search was performed with PubMed, EMBASE, Cochrane Library, and Web of Science databases from inception until April 2019. Only original studies measuring the association between potential risk factors and PSF were included. All relevant data the included studies were extracted by two independent reviewers using predefined data fields. Fourteen studies (n = 3933) were included in this meta-analysis. Female (OR = 1.39; p < 0.01), thalamus (OR = 1.76; p = 0.02), leucoaraiosis (OR = 1.73; p < 0.01), NIHSS score (OR = 1.16; p < 0.01), modified Rankin Scale (OR = 1.63; p < 0.01), depression (OR = 1.75; p < 0.01), and sleeping disturbances (OR = 2.01; p < 0.01) were all significantly associated with PSF. In the subgroup analysis, depression (OR = 2.75; p < 0.01) tended to be associated with Asian patients with PSF. For patients who had a stroke survive for more than half a year, PSF was more likely to occur in stroke survivors with depression (OR = 1.46; p < 0.01), anxiety (OR = 1.13; p < 0.01), or sleeping disturbances (OR = 1.98; p < 0.01). Despite some limitations, this study first identified that female and depression conferred an increased susceptibility to PSF, regardless of whether in European or Asian populations. Risk factors associated with PSF included female, thalamic, leucoaraiosis, depression, sleeping disturbances, diabetes mellitus, and anxiety. This meta-analysis shows that chronic PSF appears to be largely attributable to patients with multiple comorbidities. It is necessary to strengthen the treatment for stroke-related complications and improve stroke patient care, which could help to reduce the incidence of PSF. CRD42019128751.


Nitrate bioreduction in redox-variable low permeability sediments.
Lowpermeability zone (LPZ) can play an important role as a sink or secondary source in contaminant transport in groundwater system. This study investigated the rate and end product of nitrate bioreduction in LPZ sediments. The sedimentswere fromthe U.S. Department of Energy's Hanford Site,where nitrate is a groundwater contaminant as a by-product of radionuclide waste discharges. The LPZ at the Hanford site consists of two layerswith an oxidized layer on top and reduced layer below. The oxidized layer is directly in contact with the overlying contaminated aquifer, while the reduced layer is in contact with an uncontaminated aquifer below. The experimental results showed that nitrate bioreduction rate and end-product differed significantly in the sediments. The bioreduction rate in the oxidized sediment was significantly faster than that in the reduced one. A significant amount of N2O was accumulated in the reduced sediment; while in the oxidized sediment, N2O was further reduced to N2. RT-PCR analysis revealed that nosZ, the gene that codes for N2O reductase, was below detection limit in the reduced sediment. Batch experiments and kinetic modeling were performed to provide insights into the role of organic carbon bioavailability, biomass growth, and competition between nitrate and its reducing products for electrons fromelectron donors. The results revealed that it is important to consider sediment redox conditions and functional genes in understanding and modeling nitrate bioreduction in subsurface sediments. The results also implied that LPZ sediments can be important sink of nitrate and a potential secondary source of N2O as a nitrate bioreduction product in groundwater.


[Distribution of livers from deceased donors : current allocation rules and algorithms].
Eurotransplant is responsible for the allocation of organs from deceased donors in Germany. The guidelines governing this allocation process have been developed and are continuously updated by the German Medical Association and are based on urgency and outcome of the planned transplantation. The allocation sequence for donor livers is based on the model of end-stage liver disease (MELD) score, which is calculated using three laboratory values, bilirubin, creatinine and the international normalized ratio (INR) and allows an objective and transparent evaluation of the urgency of the transplantation. For patients with liver diseases where the MELD score does not allow an estimation of the urgency of the transplantation, special rules apply. The international cooperation among the Eurotransplant member countries especially increases the probability of finding a suitable donor organ in time for highly urgent patients and patients with special difficulties in matching characteristics.


Expression of ricin A chain and ricin A chain-KDEL in Escherichia coli.
Ricin and its A chains can be used to conjugate with monoclonal antibodies to prepare immunotoxins. Ricin A chain (RTA) and its modification RTA-KDEL (ER-retrieval signal) were expressed with the pKK223.3 system in Escherichia coli under control of a tac promoter. The recombinant proteins can be purified by one-step affinity chromatography on a column of Blue-Sepharose 6B. The toxicities of RTA and its mutant RTA-KDEL were evaluated by the MTT assay in HeLa, MCF, and ECV-304 cells following fluid-phase endocytosis. RTA-KDEL was somewhat more cytotoxic than RTA itself in the different cell lines. The results suggest that rRTA-KDEL may be useful for the synthesis of more potent immunotoxins.


Use of surgery and postoperative radiation in the treatment of advanced squamous cell carcinoma of the pyriform sinus.
Forty-seven patients with very advanced cancer of the pyriform sinus were treated with surgery and immediate postoperative radiation in a planned sequential manner. Eradication of the cancer above the clavicles was obtained in 81% of the patients, with a treatment mortality of 8%. Most of the patients' tumors were resected with primary closure, which obviated the need for complicated reconstructive procedures. The survival rate of 23% at 2 years and the high rate of distant metastasis reflect the aggressive biologic behavior of this cancer. The need to find an adjuvant treatment that will act upon the systemic spread of this cancer is obvious.


The emerging field of lipidomics.
The crucial role of lipids in cell, tissue and organ physiology is demonstrated by a large number of genetic studies and by many human diseases that involve the disruption of lipid metabolic enzymes and pathways. Examples of such diseases include cancer, diabetes, as well as neurodegenerative and infectious diseases. So far, the explosion of information in the fields of genomics and proteomics has not been matched by a corresponding advancement of knowledge in the field of lipids, which is largely due to the complexity of lipids and the lack of powerful tools for their analysis. Novel analytical approaches--in particular, liquid chromatography and mass spectrometry--for systems-level analysis of lipids and their interacting partners (lipidomics) now make this field a promising area of biomedical research, with a variety of applications in drug and biomarker development.


Unraveling the metabolism of HEK-293 cells using lactate isotopomer analysis.
HEK-293 is the most extensively used human cell line for the production of viral vectors and is gaining increasing attention for the production of recombinant proteins by transient transfection. To further improve the metabolic characterization of this cell line, we have performed cultures using ¹³C-labeled substrates and measured the resulting mass isotopomer distributions in lactate by LC/MS. Simultaneous metabolite and isotopomer balancing allowed improvement and validation of the metabolic model and quantification of key intracellular pathways. We have determined the amounts of glucose carbon channeled through the PPP, incorporated into the TCA cycle for energy production and lipids biosynthesis, as well as the cytosolic and mitochondrial malic enzyme fluxes. Our analysis also revealed that glutamine did not significantly contribute to lactate formation. An improved and quantitative understanding of the central carbon metabolism is greatly needed to pursue the rational development of engineering approaches at both the cellular and process levels.


Down-regulation of HECTD3 by HER2 inhibition makes serous ovarian cancer cells sensitive to platinum treatment.
Resistance to platinum-based chemotherapy is a major cause of treatment failure in patients with epithelial ovarian cancer and predicts a poor prognosis. Previously, we found that HECTD3 confers cancer cell resistance to apoptosis. However, the significance of HECTD3 expression in ovarian cancer and its regulatory mechanisms were unknown. Here, we found that HECTD3 depletion promotes carboplatin-induced apoptosis in both an ovarian cancer cell model and a xenograft mouse model. Moreover, high HECTD3 expression is significantly associated with poor platinum response and prognosis in ovarian cancer patients. We further demonstrated that HER2 can up-regulate HECTD3 expression through activating STAT3. Furthermore, HER2 inhibitors, such as lapatinib, down-regulate HECTD3 expression and thus promote the chemosensitivity of ovarian cancer cells to carboplatin. Lapatinib combined with carboplatin also significantly inhibits serous ovarian carcinoma growth compared with each drug alone in a xenograft mouse model. HECTD3 may be considered a promising molecular predictor of platinum chemosensitivity and prognosis for serous ovarian cancer. Through decreasing HECTD3, lapatinib possesses significantly increased anti-tumor activity when combined with carboplatin compared with each agent alone, which provides an optional therapeutic regimen for serous ovarian cancer.


Prognostic Value of Radiotracer-Based Perfusion Imaging in Critical Limb Ischemia Patients Undergoing Lower Extremity Revascularization.
The purpose of this study was to evaluate the prognostic value of single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of angiosome foot perfusion for predicting amputation outcomes in patients with critical limb ischemia (CLI) and diabetes mellitus (DM). Radiotracer imaging can assess microvascular foot perfusion and identify regional perfusion abnormalities in patients with critical limb ischemia CLI and DM, but the relationship between perfusion response to revascularization and subsequent clinical outcomes has not been evaluated. Patients with CLI, DM, and nonhealing foot ulcers (n = 25) were prospectively enrolled for SPECT/CT perfusion imaging of the feet before and after revascularization. CT images were used to segment angiosomes (i.e., 3-dimensional vascular territories) of the foot. Relative changes in radiotracer uptake after revascularization were evaluated within the ulcerated angiosome. Incidence of amputation was assessed at 3 and 12 months after revascularization. SPECT/CT detected a significantly lower microvascular perfusion response for patients who underwent amputation compared with those who remained amputation free at 3 (p = 0.01) and 12 (p = 0.01) months after revascularization. The cutoff percent change in perfusion for predicting amputation at 3 months was 7.55%, and 11.56% at 12 months. The area under the curve based on the amputation outcome was 0.799 at 3 months and 0.833 at 12 months. The probability of amputation-free survival was significantly higher at 3 (p = 0.002) and 12 months (p = 0.03) for high-perfusion responders than low-perfusion responders to revascularization. SPECT/CT imaging detects regional perfusion responses to lower extremity revascularization and provides prognostic value in patients with CLI (Radiotracer-Based Perfusion Imaging of Patients With Peripheral Arterial Disease; NCT03622359).


Divergent consequences of different biochar amendments on carbon dioxide (CO2) and nitrous oxide (N2O) emissions from the red soil.
Climate change due to greenhouse gas (GHG) emissions is one of the global environmental matters of the 21st century. Biochar (BC) amendments have been proposed as a potential solution for improving soil quality and to mitigate GHGs emissions. Therefore, we evaluated the influence of different BCs on soil CO2 and N2O emissions in an outdoor pot experiment. The soil was mixed with three different types of BCs; bamboo, hardwood, and rice straw BCs as BB, BH, and BR, respectively, and control as B0 with four levels (0, 5, 20, and 80 g kg-1 of soil). Gas samples were collected on a bi-monthly basis for six months. A polyvinyl chloride (PVC) static chamber was placed on each replicate to collect the gas samples at 15, 30, 45, and 60 min, respectively. Compared to B0, the lowest cumulative N2O emissions were observed in BH80 (11%) followed by BH20, BH5, and BR80. However, for cumulative CO2 emissions, B0 and BC treatments showed no significant differences except for BB80 (>11%) and BB5 (<2%). BC type and level both had a significant (P < 0.001) impact on the cumulative N2O emissions with a significant interaction (P < 0.001). However, cumulative CO2 emissions were unaffected by BC type but BC level showed a significant influence on cumulative CO2 emissions (P < 0.05) and there was a significant (P < 0.001) interaction between the BC type and level on cumulative CO2 emissions. Overall, higher doses of BR and BB showed a pronounced effect on soil pH over BH. The soil pH and moisture showed a negative correlation with N2O emissions whereas soil temperature showed a positive correlation with the cumulative fluxes of N2O. Our results demonstrate that BC incorporation to soil may help to mitigate GHGs emissions but its influence may vary with BC type and level under different conditions and soil type.


Simultaneous measurement of cytosolic free calcium concentration and cell circumference during contraction, both in a single rat cardiomuscular cell, by digital imaging microscopy with indo-1.
We have developed a novel system using digital imaging microscopy with indo-1 to measure the cytosolic free calcium concentration [( Ca2+]i). The method is particularly suitable for measuring the rapid change in [Ca2+]i in relation to the cell motion. With this system, we made the first successful simultaneous measurement of [Ca2+]i and cell circumference during contraction in an electrically stimulated single rat ventricular myocyte. It was found that the level of [Ca2+]i was elevated during contraction, and that the onset and peak time of the calcium transient preceded that of the decrease in circumference.


Combination of C-reactive protein, procalcitonin and sepsis-related organ failure score for the diagnosis of sepsis in critical patients.
To measure the ability of a new bioscore to diagnose sepsis in a general critical care population. The study was done at an intensive care unit (ICU) from April to December 2012. Demographic and clinical patient information were recorded on admission to the ICU with blood samples taken for C-reactive protein (CRP), procalcitonin (PCT), interleukin-6, white blood cell count, as well as body temperature, age and the sepsis-related organ failure (SOFA) score. These parameters were used to create a scoring system. The scoring system then underwent analysis by univariate analysis and multivariate logistic regression analysis to identify which of these clinical parameters were statistically different in septic versus non-septic patients. The bioscore was then tested in a receiver operator characteristic curve to determine statistical significance of the scoring systems ability to predict sepsis. Finally, a bioscore cutoff value was defined to provide a level for sepsis diagnosis. Three hundred patients were enrolled, of which 107 patients were septic and 193 patients were non-septic. Univariate logistic regression showed that age, gender, CRP, PCT and SOFA were risk factors for occurrence of sepsis. Multivariate analysis revealed CRP (AUC 0.729, 95 % CI 0.671-0.787, P < 0.001), PCT (AUC 0.711, 95 % CI 0.652-0.770, P < 0.001) and SOFA (AUC 0.670, 95 % CI 0.607-0.733, P < 0.001) to be statistically significant. The combination of these values in the bioscore had an AUC of 0.790 (95 % CI 0.739-0.834, P < 0.001). A bioscore of ≥2.65 was considered to be statistically significant in making a positive diagnosis of sepsis. This bioscore using CRP, PCT and SOFA score may potentially be used in the future to help identify septic patients earlier, improving their access to timely treatment modalities.


The fa(c)ts that matter: Bumble bees differentially allocate and oxidate three common fatty acids in pollen.
Pollen serves as a crucial source of protein and lipids for numerous insects. Despite the importance of pollen lipids for nutrient regulation in bees, the digestibility and absorption of different fatty acids (FAs) by bees remain poorly understood. We used 13C labeled fatty acids (FAs) to investigate the absorption and allocation of three common dietary FAs in pollen by bumble bees. Palmitic acid, the most common saturated FA in pollen, was poorly absorbed, even when supplied as tripalmitate, emulsified, or mixed in vegetable oil. In contrast, the essential linoleic acid was absorbed and allocated at the highest rate among the three FAs tested. Oleic acid, a non-essential monounsaturated FA, was absorbed and oxidized at lower rates than linoleic acid. Notably, a feeding rate experiment revealed that different fatty acids did not affect the consumption rate of pollen. This results suggests that the specific FA's absorption efficiency and allocation differ in bumble bees, impacting their utilization. These findings demonstrate the importance of considering the digestibility and absorption of different FAs. Furthermore, the study highlights the influence of pollen lipid composition on the nutritional content for pollinators and raises questions about the utilization of polyunsaturated FAs in insect metabolism.


Predictors of segmental lumbar lordosis following midline posterior (transforaminal) lumbar interbody fusion: Does interbody device type matter?
Controversy exists regarding the ability of posterior (transforaminal) lumbar interbody fusion (PLIF/TLIF) to achieve lordosis. We hypothesized that an interbody device (IBD) designed for positioning in the anterior disc space produces greater lordosis than IBDs designed for straight-in positioning. The purpose of this study is to determine if using either an anterior-position or straight-in position IBD design were associated with successful achievement of postoperative lordosis. A consecutive series of patients undergoing a undergoing a single-level, posterior open midline (transforaminal) lumbar interbody fusion procedure for degenerative spine conditions during a time period when the two types of interbody devices were being used at surgeon discretion were identified from a multi-surgeon academic training center. Patient demographics and radiographic measures including surgical level lordosis (SLL), anterior disc height, middle disc height, posterior disc height, IBD height, and IBD insertion depth were measured on preop, immediate postop, and one-year postop standing radiographs using PACS. Group comparison and regression analysis were performed using SPSS. Sixty-one patients were included (n=37 anterior, n=34 straight-in). Mean age was 59.8±8.7 years, 32 (52%) were female. There was no difference between IBD type (anterior vs. straight-in) for mean Pre-op SLL (19±7° vs. 20±6°, p=0.7), Post-op SLL (21±5° vs 21±6°, p=0.5), or Change in SLL (2±4° vs. 1±5°, p=0.2). Regression analysis showed that Pre-op SLL was the only variable associated with Change in SLL (Beta = negative 0.48, p=0.000). While the mean Change in SLL could be considered clinically insignificant, there was wide variability: from a loss of 9° to a gain of 13°. Gain of lordosis >5° only occurred when Pre-op SLL was <21°, and loss of lordosis >5° only occurred when Pre-op SLL was >21°. While group averages showed an insignificant change in segmental lordosis following a posterior (transforaminal) interbody fusion regardless of interbody device type, pre-operative lordosis was correlated with a clinically significant change in segmental lordosis. Preoperative hypolordotic discs were more likely to gain significant lordosis, while preoperative hyperlordotic discs were more likely to lose significant lordosis. Surgeon awareness of this tendency can help guide surgical planning and technique.


High-dose-rate interstitial brachytherapy in oral cancer-Its impact on quality of life.
The aim of the study was to assess the impact of high-dose-rate (HDR) interstitial brachytherapy on quality of life (QOL) in oral cancer. Thirty-two patients of oral cancer treated at our institute from January 2010 to December 2014 with radical radiotherapy (external beam radiotherapy + brachytherapy) were included for analysis; 30 patients received external beam radiotherapy (50-54 Gy) and HDR brachytherapy boost (18-24.5 Gy); 2 patients received radical HDR brachytherapy (31.5 Gy). Quality of life (QOL) was assessed by Telugu, Hindi, and English versions of EORTC Quality of Life Core-30 and EORTC Quality of Life Head and Neck Module (QLQ H&N35) before treatment, at 3 months, 6 months, 1 year, and 2 years after treatment. Of the 32 patients, 2 patients died and 1 patient progressed on followup; 2 patients were re-irradiation cases. On excluding these cases, 27 patients were available for analysis. The followup duration was 6-55 months. At the time of analysis, 91% (29) patients were disease free, 3% (1) progressed, and 6% (2) died. At the end of 2 years, none of the QLQ-C30 functional scores fell below the baseline. Pain, swallowing, sensory, speech, social contact, and social eating worsened at 3 months but improved over 2 years (p < 0.001). Sexuality and financial status showed delayed improvement (p < 0.001). Among the head and neck parameters, dry mouth and sticky saliva were significant determinants of QOL with delayed improvement (p < 0.001). The impact of age, sex, and tumor stage and on QOL was analyzed. Women reported a poorer QOL for physical and emotional parameters, social eating, weight loss, and fatigue. Tumor stage significantly affected QOL, with early stages showing a better QOL. Almost all patients regained normal function after treatment and reported an excellent QOL at 2 years. However, tumor stage significantly affected the QOL.


Antinuclear antibodies as indicators for the procainamide-induced systemic lupus erythematosus-like syndrome and its clinical presentations.
Fifty patients on a regimen of procainamide were studied in regard to the association between antinuclear antibodies (ANA) and the development of drug-induced systemic lupus erythematosus (SLE)-like syndrome. Four groups were identified: Group 1 was ANA-positive, with clinical manifestations (serologic and clinical findings); Group 2 was ANA-positive, without clinical manifestations (serologic findings only); Group 3 was ANA negative (no patients with clinical manifestations); and Group 4 had SLE persisting after discontinuance of procainamide. The leukocyte-specific ANA (LSANA) patterns were predominant, with peripheral LSANA confined to Groups 1 and 4. Furthermore, the titer of the homogeneous LSANA, to which peripheral LSANA converts on dilution, was clinically significant. A homogeneous LSANA titer of 160 or greater was seen essentially only in patients with clinical manifestations of the SLE-like syndrome. Serial ANA determinations are therefore necessary to monitor patients receiving procainamide.


An experimental investigation of enhanced harpacticoid (Copepoda) abundances around isolated seagrass shoots.
At a site in the Gulf of Mexico (29°54.6'N, 81°31.4'W) off the coast of northern Florida, harpacticoid copepod abundance is significantly enhanced around isolated "plants" (technically short shoots) of the seagrass Syringodium filiforme. Using inanimate mimics of seagrass short shoots, we demonstrate, in the field, that the enhanced abundance does not results from the presence of the plant as a living entity. Our experiments reveal a two-fold increase in bacterial biomass around both short shoots and mimics; the harpacticoids appear to be responding to a local increase in their resources. We suggest that the flow field around a short shoot improves the rate of supply of oxygen and other materials to sedimentary bacteria, thereby driving the effect. Given the ubiquity of structures that have similar flow effects, localized bacterial enhancement may be common and should be considered in studies of the effects of surface structures on soft-bottom community organization.


Long-term results of 28 esthesioneuroblastomas managed over 35 years.
The purpose of our study was to assess the long-term results in the management of patients with esthesioneuroblastoma. A total of 28 patients were retrospectively reviewed to analyze their clinical features, treatment outcomes, pattern of failures, and course of the disease. The patients were classified as 2 patients with T1, 10 patients with T2, 10 patients with T3, and 6 patients with T4; the results of all were included in this study. Twenty-six patients underwent surgery and 23 had postoperative radiotherapy over the tumor bed, only 9 had radiotherapy over the nodes. The average follow-up was 99.11 months. Fifteen-year and 20-year disease-specific and disease-free survival rates were 88.6% to 66.4% and 59.6% to 29.8%, respectively. Six patients had recurrences and 60% of them occurred more than 10 years after treatment. In the first decade, nodal recurrences appeared earlier than local ones when patients with N0 did not undergo neck irradiation. Surgery on patients with T presentations and adjuvant radiotherapy on T and N0 neck presentations seem to be essential to treat esthesioneuroblastoma. A follow-up for a minimum of 20 years is necessary to ensure complete cure.


Intraindividual variability and the effect of acute illness on immune senescence markers.
To determine the intraindividual variability and effect of acute illness on two markers of immune senescence. Cohort study with repeated measures. Clinical research center and emergency department at two academic medical centers. Seventy-three subjects aged 65 and older enrolled in three groups: chronic underlying conditions but no acute illness, acutely ill with infection (community-acquired pneumonia), and acutely ill without infection. CD16 density on polymorphonuclear neutrophils (PMNs) and the proportion of CD8+ T cells that express CD28 determined twice in the nonacutely ill group and three times (Days 0, 30, and 60) in the acute illness groups. In the nonacutely ill group, PMN CD16 density demonstrated wide intraindividual variation, but there was a strong correlation for repeated measures of the percentage of CD8+ T cells expressing CD28 (correlation coefficient (r)=0.77, P<.001). Acute illness markedly affected both measures, regardless of whether the illness was due to infection; there was no correlation between measures obtained on Day 0 versus Day 30 for either immune marker. In contrast, a strong correlation existed between Day 30 and Day 60 values, particularly for CD8+/CD28+ percentage (r=0.58-0.86; P=.006 to <.001). The percentage of CD8+ T cells that express CD28 is a highly reproducible marker of immune senescence. Although acute illness affects this marker, 30 to 60 days of convalescence appears adequate for it to return to baseline.


Health related quality of life in immigrants and native school aged adolescents in Spain.
To compare health related quality of life (HRQL) between native and immigrant adolescents aged 12 to 18 years, and to analyse psychosocial factors associated with HRQL. A cross sectional study of adolescents (12-18 years old) who answered a self administered questionnaire. All the secondary schools from Lloret de Mar (Girona, Spain). 1246 participants (88.9% of the eligible students). Main outcome was the Spanish version of the Vecu et Sante Percue de l'Adolescent (VSP-A), a HRQL measure addressed to adolescents. Mean scores of the VSP-A index of natives and immigrants were compared, as well as their sociodemographic and health related factors. Multiple regression examined the relation between HRQL and psychosocial factors, controlling for the effect of socioeconomic variables. Half of the sample were boys, in the middle socioeconomic status, and 18.2% were immigrants (n = 226). HRQL score was higher in native Spanish adolescents than immigrants (p<0.01). Multiple regression model explaining 48.1% of the VSP-A variance showed that migration in itself has no statistically significant impact on HRQL, and age, socioeconomic status, social support, discrimination, and psychological distress do play a part. Migrants have worse HRQL than natives but it seems to be mediated by their disadvantage in socioeconomic status, social support, and psychological distress.


Transplacental carcinogenesis and chemical determination of 1-butyl-1-nitrosourea in stomach content after simultaneous oral administration of 1-butylurea and sodium nitrite to ACI/N rats.
Solutions of 100 mg/kg 1-butylurea and 50 mg/kg sodium nitrite were administered daily by a stomach tube to pregnant ACI/N rats from the 13th to 21st day of gestation. Neurogenous tumors were induced in their offspring. The incidence of tumours and mean survival time of rats with nervous tumours were 64% (23/36) and 309 (189672) days respectively. Localization and histological findings of the nervous tumors were similar to those observed previously in rats whose mothers received 1-butyl-1-nitrosourea (BNU) during pregnancy. Neurogenous tumors did not develop in the offspring of the mothers that received 100 mg/kg of 1-butylurea alone in the same manner. In several rats of both group, a few spontaneous tumors of the testis, pituitary gland, urinary bladder, uterus, and colon were detected. In vivo formation BNU in stomach content after intubation of 1-butylurea and sodium nitrite was determined. BNU was detected in the stomach content at levels of 25 ppm at 30 min and 23 ppm at 60 min after administration. The concentration of BNU in the stomach content corresponded to 48.3 and 29.2 microng/rat, respectively.


Simultaneous aortic and mitral valve replacement for lupus endocarditis: report of a case and review of the literature.
Severe aortic and mitral valvular insufficiency developed in a 52-year-old woman with systemic lupus erythematosis after previous treatment with corticosteroids, splenectomy, and cyclophosphamide for immune thrombocytopenia and hemolytic anemia. After aggressive management of the thrombocytopenia, simultaneous prosthetic replacement of both valves was satisfactorily performed; pathologic examination revealed myxoid degeneration. The patient was doing well with excellent valve function 26 months after the operation. The relationship of steroid therapy to lupus valvulitis is reviewed.


An extended phenotype of RP1L1 maculopathy - case report.
To report the ophthalmological findings of a new phenotypical variant of RP1L1 maculopathy in an Indian patient with a homozygous variant in the RP1L1 gene. A 39-year-old male presented with complaints of disturbance in the central field of vision in both eyes (BE) for a duration of 6 months. He underwent ophthalmic examinations and diagnostic imaging. A complete retinal degeneration panel consisting of 228 genes was evaluated for pathologic variations using next-generation sequencing (NGS), which showed a variant in the RP1L1 gene. On fundus examination, he was found to have ill-defined foveal mottling in BE. Spectral domain optical coherence tomography (SD-OCT) showed sub-foveal hyper-reflective deposits and outer retinal layer disruption. A provisional diagnosis of the atypical variant of adult-onset foveomacular vitelliform dystrophy (AOFVD) was made on the basis of clinical, OCT, Fundus autofluorescence (FAF) and electrophysiological features. Genetic assessment of the proband revealed the presence of a homozygous base pair deletion in exon 4 of RP1L1 gene (chr8:g.10468194_10468195del), which results in frameshift and premature truncation of the protein 24 amino acids downstream to codon 1138 (p.Lys1138SerfsTer24). This variant was confirmed in the proband's parents by Sanger sequencing. The diagnosis was revised to RP1L1 maculopathy, as the RP1L1 gene variant is most commonly associated with this entity. This report presents the multimodal imaging of a previously unreported phenotype of RP1L1 maculopathy associated with a genetic variant of RP1L1 gene, thereby expanding the spectrum associated with RP1L1 maculopathy.


Adenosine A1 and A2 receptors modulate extracellular dopamine levels in rat striatum.
To clarify differences in the operating mechanisms of adenosine receptor subtypes (A1 and A2), striatal extracellular dopamine levels under various conditions were determined by in vivo microdialysis. Adenosine (50 microM) as well as the selective A1 agonist, 2-chloro-N6-cyclopentyladenosine (CCPA; 1 microM) decreased striatal extracellular dopamine levels, while the selective adenosine A1 antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT; 50 microM) and caffeine (100 microM) increased striatal extracellular dopamine levels. A selective A2a agonist, 2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamideadeno sine (CGS21680; 10 microM), a selective A2 agonist, N6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl)ethyl]adenosine (DPMA; 5 microM) and a selective A2 antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX; 10 microM), did not affect extracellular dopamine levels. When the A1 receptor was blocked by CPT, extracellular dopamine levels were increased by adenosine and DPMA, decreased by caffeine as well as DMPX, and unaffected by CGS21680. These results indicate that the stimulatory effects of the A2 receptor on striatal extracellular dopamine levels are masked by the inhibitory effects of the A1 receptor.


CD56-negative extranodal NK/T cell lymphoma should be regarded as a distinct subtype with poor prognosis.
Previous results about the clinical and prognostic significance concerning CD56 expression status in extranodal NK/T cell lymphoma (ENKTL) are controversial due to a small sample size and the heterogeneity nature of this disease. The complete data of 288 patients with early-stage upper aerodigestive tract ENKTL were retrospectively reviewed. One hundred eighty-three patients (63.5 %) had stage I disease, and the primary tumor site of 204 patients (70.8 %) was in the nasal cavity. Sixty patients (20.8 %) were categorized to CD56-negative ENKTL group. The complete remission rate in CD56-positive ENKTL group was 80.6 %, significantly higher than that in CD56-negative ENKTL group (60.8 %, P = 0.005). At a median follow-up time of 69 months, the 5-year and 10-year progression-free survival (PFS) rate were 52 and 41 %, respectively, and the 5-year and 10-year overall survival (OS) rate were 69 % and 68 %, respectively. Patients with primary tumor site located in the nasal cavity or CD56-positive expression had significantly superior PFS and OS (P < 0.05). In multivariate Cox regression model that included age, Ann Arbor stage, lactate dehydrogenase (LDH) level, primary tumor site, chemotherapy regimens, and CD56 expression status, all these six factors remained to be independent prognostic factors for PFS, and the first five factors were independent prognostic factors for OS, while CD56 expression status had a trend to be independently correlated with OS (P = 0.084). In a subgroup analysis according to primary tumor site location, CD56 expression status significantly correlated with survival outcomes in patients with primary nasal cavity involvement (P < 0.05). In conclusion, in this large cohort of patients with early-stage ENKTL, we found that CD56-negative ENKTL had significantly inferior survival outcomes, indicating CD56-negative ENKTL should be regarded as a distinct phenotype, and optimal treatment strategies need to be evaluated further for this entity.


Prevalence of biologics monotherapy in a cohort of patients with Rheumatoid Arthritis in daily clinical practice.
Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy, in spite that combination therapy with Disease Modifying Drugs is more efficacious than monotherapy. The aim of our study was to assess the prevalence of biologics monotherapy in a cohort of patients with RA followed at a single center, and to analyze the reasons for monotherapy, including patients with prescriptions that do not take the medication. All patients with Rheumatoid Arthritis, with biologic therapy followed at our Rheumatology Unit were included. Prevalence and reasons for biologics monotherapy was calculated in general, for each biologic course and for each biologic. Prescription data was obtained from the Electronic Medical Record, and drugs acquisition was obtained from the Hospital Administrative database. Drug survival was also calculated and compared between monotherapy and combination therapy. Seventy nine patients with 115 courses of biologic treatments were included. In 40 (35 %, 95 % CI: 26-44 %) of all biologics courses, biologics were initiated as monotherapy. In 27 courses (23 %, 95 % CI: 16-32 %) biologic monotherapy was prescribed by the treating rheumatologists, and in the other 13 (11 %, 95 % CI: 6-18 %) it was initiated as such by decision of the patient regardless of the physician indication. Reasons for prescription of biologic monotherapy by the treating rheumatologists were adverse events with previous DMARDs in 55.5 %, and was not specified in the remaining courses. Only 25 % of biologics' courses were monotherapy from the beginning to the end of the biologic therapy. The overall survival on biologics was 45 % (95 % CI: 35-55 %) at 3 years. There were no statistically differences in biologics survival by modality (monotherapy vs combination) (p = 0.543), course (p = 0.4454), or by biologic drug (p = 0.9612). Almost 1/3 of patients on biologics use them as monotherapy. This is due to physician's preferences in 60 % of the cases, and to patients not compliance with the indication in around 40 % of the cases. Better communications is needed to assure that physicians and patients agree on the prescribed and used medication.


L-glutamine: an amino acid required for maintenance of the tegumental membrane potential of Schistosoma mansoni.
The tegumental membrane potential (-63 +/- 2.9 mV) of adult male Schistosoma mansoni in RPMI-1640 is significantly depolarized (-26 +/- 7.3 mV) when the parasite is incubated in inorganic media (Hank's Balanced Saline or RPMI-1640 without organic constituents). Of 9 amino acids (L-glutamine, D-glutamine, L-arginine, L-proline, L-aspartate, L-glutamate, L-asparagine, L-isoleucine and L-methionine) L-glutamine alone is sufficient to repolarize the membrane potential to a value (-56 +/- 4.5 mV) not significantly different from that found in RPMI-1640. Repolarization by glutamine is dose-dependent, with significant effects obtained as low as 0.10 mM. The concentration of phosphate in the medium also significantly alters the membrane potential. Physiological levels of phosphate (5.6 mM) are necessary in conjunction with L-glutamine to obtain the full repolarization of the membrane potential. In the absence of organic constituents, the membrane potential is strongly dependent on the external medium pH. When L-glutamine is present in the medium, the membrane potential becomes virtually independent of the external pH.


Variable column length method development strategy for amino acid analysis in serum samples of neonates with metabolic disorders.
Accurate quantitative analysis of amino acids forms an important part of targeted metabolic profiling as deviations from normal amino acid profiles can be indicative of several inborn metabolic disorders. A variable-length method development strategy for HPLC analysis on superficially porous particle columns using UV detection is proposed for the separation of 21 primary amino acids. This strategy consists of the evaluation of a large set of gradient and mobile phase compositions on short columns with different stationary phase properties to rapidly determine the best separation conditions leading to the highest number of separated peaks. These conditions are subsequently used to optimize the separation on a longer column length benefitting from its higher separation performance. A minimum critical resolution of 2.0 and a maximum analysis time of 10min were imposed to allow for accurate, robust and rapid quantitation of all amino acids over a large linear range. For amino acids playing a key role in commonly encountered amino acid and urea cycle disorders, a minimum critical resolution of 2.5 was pursued. Mass spectrometry was used for fast peak tracking during the method development procedure. It was demonstrated that the retention behavior of the studied amino acids is more pressure than temperature dependent. This allowed performing the entire method development strategy at the same maximum pressure on all column lengths, while preserving the retention profile, resulting in a significant time profit for the initial scouting runs. The applicability of the method was demonstrated by analyzing serum samples of several neonates diagnosed with metabolic disorders such as maple syrup urine disorder, phenylketonuria and citrullinemia.


Muscle strength, physical fitness, and weight but not age predict femoral neck bone mass.
Hip fractures are the most serious complication of osteoporosis. Although low proximal femoral bone mineral density (BMD) does not cause hip fractures directly, it is clearly a prerequisite for the increased risk associated with aging. To investigate the mechanism of the age-related decline in proximal femoral bone mineral density, we have examined the relative importance of muscle strength, physical fitness, and body mass index (BMI) in addition to age in the determination of proximal femoral BMD in 73 healthy female volunteers age 20-75 years. Muscle strength was an independent predictor of BMD at all three sites in the proximal femur as well as in the lumbar spine and forearm; proximal femur BMD was also predicted by physical fitness. BMI was a positive predictor of bone mass at all sites. In the proximal femur, age was not an independent predictor of BMD at any site. In postmenopausal women muscle strength was a significant predictor of bone mass in the femur and forearm, but not in the spine. However, BMI remained predictive of bone mineral at all sites. Muscle strength, physical fitness, and weight appear to exert independent effects upon bone mass. Age effects may be mediated indirectly through associated changes in these factors. The integrated physical load on the skeleton may be a final common pathway.


Tracking of systolic blood pressure during childhood: a 15-year follow-up population-based family study in eastern Finland.
To investigate the tracking of systolic arterial blood pressure (SBP) during childhood. All children born during 1981-82 in a rural community of eastern Finland were followed at the ages of 6 months, 7 and 15 years (SBP-6m, SBP-7y, SBP-15y). One hundred and thirty-eight out of 205 children completed the full follow-up period, of which 100 (45 girls) were included in the analysis with complete data. SBP (mmHg). SBP-6m was associated with SBP-7y (r = 0.715; P < 0.001) and with SBP-15y (r = 0.238; P = 0.017) and SBP-7y was associated with SBP-15y (r = 0.348; P < 0.001). Adjustment for confounders did not change these results. Children at the highest tertile of SBP-6m had a higher probability of being at the highest tertile of SBP-7y [relative risk (RR) = 4.3; 95% confidence interval (CI), (2.4-7.6)] and SBP-15y [RR = 1.9; 95% CI, (1.1-3.3)]. Children at the highest tertile of SBP-7y had a higher probability of being at the highest tertile of SBP-15y [RR = 2.6 (1.5-4.6)]. The regression analysis showed a significant main effect on SBP-15y for birth weight (negative association), male gender, current body mass index (BMI), change of BMI between the ages of 7 years and 15 years, SBP-6m, SBP-7y and the mean SBP between the ages of 6 months and 7 years (all with positive association). Children with family history of hypertension appear to have a higher SBP during childhood; however, this association did not reach a significant level. The study confirmed the tracking of SBP during childhood. Birth weight was inversely associated with SBP-15y. Family history of hypertension was not significantly associated with SBP during childhood.


Ethnobotanical inventory of medicinal plants used by the Guaymi Indians in western Panama. Part I.
Plants used by Guaymi "Curanderos" in Western Panama (Bocas del Toro and Chiriquí) are listed. Results of a literature survey are also reported, including medical use, known constituents and pharmacological effects.


A proximal E-box modulates NGF effects on rat PPT-A promoter activity in cultured dorsal root ganglia neurones.
The rat preprotachykinin A (rtPPTA) promoter fragment spanning -865+92, relative to the major transcriptional start, has previously been demonstrated to be nerve growth factor (NGF) responsive in primary cultures of rat dorsal root ganglion (DRG) neurones [Harrison, P.T., Dalziel, R.G., Ditchfield, N.A., Quinn, J.P., 1999. Neuronal-specific and nerve growth factor-inducible expression directed by the preprotachykinin-A promoter delivered by an adeno-associated virus vector. Neuroscience 94, 997-1003]. In this communication, we demonstrate that an E box element at -60, in part, regulates the activity of this rtPPT-A promoter fragment in DRG neurones in response to NGF. Differential regulation of the promoter is observed in the presence or absence of NGF when the E Box site is present. Under basal conditions binding of proteins to this -60 element may antagonise promoter activity. Hence, in the absence of NGF, mutation of the -60 E box increased reporter gene expression. Further, comparison of levels of reporter gene expression supported by both WT and mutated promoter indicate that in the presence of NGF the -60 E box element also plays a role as an activator domain. This represents a novel mechanism for NGF regulation of rtPPT-A. Similarly, an important role for this signalling pathway was observed in neonate rat DRG neuronal cultures, which require NGF for their survival, namely mutation of the -60 element resulted in higher levels of reporter gene expression.


Walch B0 glenoid: pre-osteoarthritic posterior subluxation of the humeral head.
The management of primary osteoarthritis of the shoulder has been well investigated. However, the etiology and management of posterior humeral head subluxation in the context of primary glenohumeral osteoarthritis remain controversial. The finding of static posterior subluxation of the humeral head before the development of posterior bone erosion of the glenoid in young men with radiographic findings of primary osteoarthritis has been described as arthrogenic posterior subluxation of the humeral head. It demonstrates the earliest form of the osteoarthritic evolution, and an excessive glenoid retroversion is the only probable cause of this static subluxation, although this is controversial. The clinical relevance of these findings is important in allowing the identification of patients at risk for development of glenohumeral osteoarthritis and in developing an early treatment for the subluxation to try to alter the natural course of this disease. The aim of our summary paper was to review the current literature on this matter in an attempt to better understand the pathophysiologic mechanism of this condition, which we named pre-osteoarthritic posterior subluxation of the humeral head, or Walch B-zero (B0) glenoid. It appears that Walch B0 glenoid is a pathologic condition (initially dynamic, eventually evolving into a static condition) that may lead to posterior erosion of the glenoid, taking place once there is asymmetric increased posterior glenohumeral contact forces and possibly associated with increased glenoid retroversion.


The influence of physical activity and fractures on ultrasound parameters in elderly people.
In this cross-sectional study we investigated the relationship between ultrasound measurements in the calcaneus versus daily physical activity and fractures sustained in the past in elderly subjects. Ultrasound measurements were performed at both heels, which enabled us to examine determinants of differences between contralateral heels. Participants were 132 men and 578 women, aged 70 years and over (mean age and standard deviation (SD): 83 +/- 6 years), living in homes for the elderly (n = 343) or apartment houses for the elderly (n = 367). Broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured in the right and left calcaneus. The median difference (and interquartile range) between the two heels for BUA and SOS, expressed as a percentage of the mean value for each individual, was 9.6% (4.2-15.7%) and 1.0% (0.4-1.7%), corresponding to 25% and 40% of the study population SD, respectively. Greater differences in BUA between the two heels were associated with variables indicating poorer functional status, such as past fractures at the lower extremities. The level of daily physical activity was obtained by means of a questionnaire regarding household and leisure activities. Subsequently sumscores were calculated for daily physical activity and a subscore indicating weight-bearing physical activity. After adjustment for age, gender, residence, and body weight, physical activity scores were positively linearly related to both BUA and SOS. Each 5 point increase on the weight-bearing physical activity score, corresponding to, for example, walking for 2.5 h per week, was associated with a difference in BUA of 4.7 dB/MHz and in SOS of 5.1 m/s, which is similar to the differences associated with 10 kg higher body weight, or 10 years younger age. After the age of 50 years, 47 subjects had fractured a hip, 61 subjects had sustained another lower extremity fracture, 104 subjects a wrist fracture, and 62 subjects another upper extremity fracture. After adjusting for age, gender and residence, odds ratios for all fracture types in the lowest terciles of BUA and SOS versus the highest terciles ranged from 1.9 to 3.8. This study showed significant differences in ultrasound measurements between the left and the right heel, indicating that measurements at both sides are necessary for optimal evaluation of bone strength. Furthermore, after careful adjustments, ultrasound parameters had higher values with higher daily physical activity in elderly subjects and discriminated subjects with a history of fracture from those without.


Humic substances failed to prevent the systemic absorption of deoxynivalenol (DON) and its adverse effects on piglets.
The aim of this study was to examine the effects of a control diet (CON, 0.25 mg DON/kg diet) or a Fusarium toxin-contaminated diet (FUS, 4.49 mg DON/kg diet) without and with humic substances (HS) (CON-HS and FUS-HS, 0.23 and 4.56 mg DON/kg diet, respectively) on piglets during a 5-week growth trial starting after weaning (6.7 ± 0.9 kg live weight, n = 20/group). Feed intake was significantly reduced by feeding the FUS containing diets by approximately 21% compared with the CON diet irrespective of HS supplementation. The decrease in live weight gain paralleled the feed intake depression and amounted to approximately 26%. Feeding the FUS diet was clearly reflected by the DON levels in blood. While only traces of DON with median concentrations of 3 ng/ml (2-5 ng/ml) and 2 ng/ml (0-3 ng/ml) were detected in piglets fed the CON and CON-HS diets, respectively, significantly higher levels of 22.5 ng/ml (7-30 ng/ml) and 23.5 ng/ml (15-32 ng/ml) were found in piglets fed the FUS and FUS-HS diet, respectively. The urinary excretion of DON and its metabolite de-epoxy-DON as percentage of DON intake was not significantly influenced by HS supplementation and amounted to 24.1 and 20.2% for groups FUS and FUS-HS, respectively. In conclusion, the tested HS preparation cannot be recommended as a DON inactivating feed supplement for pigs.


VEGF signaling inside vascular endothelial cells and beyond.
Vascular endothelial growth factor-A (VEGF-A) has long been recognized as the key regulator of vascular development and function in health and disease. VEGF is a secreted polypeptide that binds to transmembrane tyrosine kinase VEGF receptors on the plasma membrane, inducing their dimerization, activation and assembly of a membrane-proximal signaling complex. Recent studies have revealed that many key events of VEGFR signaling occur inside the endothelial cell and are regulated by endosomal receptor trafficking. Plasma membrane VEGFR interacting molecules, including vascular guidance receptors Neuropilins and Ephrins also regulate VEGFR endocytosis and trafficking. VEGF signaling is increasingly recognized for its roles outside of the vascular system, notably during neural development, and blood vessels regulate epithelial branching morphogenesis. We review here recent advances in our understanding of VEGF signaling and its biological roles.


Polyphasic characterization of benthic, moderately halophilic, moderately thermophilic cyanobacteria with very thin trichomes and the proposal of Halomicronema excentricum gen. nov., sp. nov.
A new genus of moderately halophilic, moderately halotolerant and moderately thermophilic cyanobacteria with very thin trichomes is described. The four strains included in this genus were isolated from benthic microbial mats in a man-made hypersaline pond. Trichomes were around 1 microm thick, with small constrictions at the cross-walls and diffluent colorless sheaths. Thylakoids were parallel to the cell wall, but thylakoids and nucleoid were often excentrically arranged within the cytoplasm with respect to the main trichome axis. Strains grew at between 3.2 and 12-15% (w/v) salinity with optima between 3.2 and 12%. They showed lower temperature limits around 20 degrees C and upper limits between 45 and 50 degrees C, with optima between 28 and 45-50 degrees C. Carotenoid and mycosporine amino-acid complements were identical among strains. Phylogenetic analyses based on 16S rRNA gene sequence showed that all strains were closely related (99% or higher similarity) and distantly related to other cyanobacteria (91% or lower similarity). We propose the new genus and species Halomicronema excentricum for these strains. The type strain is TFEP1.


A multicenter audit of the use of bronchoscopy during open and thoracoscopic repair of esophageal atresia with tracheoesophageal fistula.
Esophageal atresia (EA) with tracheoesophageal fistula is usually repaired in the neonatal period. Preferential ventilation through the fistula can lead to gastric distension. Bronchoscopy has a role in defining the site and size of the fistula, and may be carried out by the surgeon or the anesthetist. The use of bronchoscopy varies across different institutions. This is a multicenter case note review of infants with EA with tracheoesophageal fistula who underwent surgery between January 2010 and December 2015. This retrospective audit aims primarily to document the use of bronchoscopy during open and thoracoscopic repair at a selection of United Kingdom centers. Respiratory complications, that is relating to airway management, the respiratory system, and difficulty with ventilation, at induction and during surgery, are recorded. The range of techniques for anesthesia and analgesia in these centers is noted. Bronchoscopy was carried out in 52% of cases. The incidence of respiratory complications was 7% at induction and 21% during surgery. Thoracoscopic repair usually took longer. One center used high-frequency oscillatory ventilation, on an elective basis during thoracoscopic repair, to facilitate surgical access and address concerns about hypoxemia and hypercarbia. The use of bronchoscopy varies considerably between institutions. Infants undergoing tracheoesophageal fistula repair are at risk of perioperative respiratory morbidity. The advent of thoracoscopic repair has introduced further variation.


Managing depression in the community.
Community and practice nurses have a vital role to play in depressive illness. Depression is a very treatable illness; early detection requires a knowledge of symptoms. Patient education and monitoring of drug side-effects are essential aspects of the management of depression.


Acute changes in passive stiffness of the individual hamstring muscles induced by resistance exercise: effects of muscle length and exercise duration.
A previous study revealed that resistance exercise with eccentric contraction and a wide range of motion (ROM) can acutely decrease muscle stiffness of a specific muscle. To explore further approaches to decrease the stiffness, we examined the acute changes in passive stiffness of the individual hamstring muscles after eccentric-only resistance exercise with different combinations of muscle lengths and exercise durations. Thirteen healthy young male participants performed three sessions of eccentric-only exercises that comprised stiff-leg deadlift with different muscle lengths and exercise durations (duration per repetition × the total number of repetitions) on separate days as follows: (1) short muscle lengths with a short duration (SS); (2) long muscle lengths with a short duration (LS); and (3) long muscle lengths with a long duration (LL). Maximal joint ROM, passive torque, shear modulus of each hamstring muscle, and maximal isometric torque of knee flexion were measured before, and at 3, 30, and 60 min after each session. The shear modulus of the semimembranosus was significantly lower at 3 min post-exercise (129.8 ± 22.7 kPa) than at pre-exercise (140.5 ± 19.1 kPa, p < 0.01) in LL, but not in SS or LS. No significant differences were observed in the shear moduli of the biceps femoris long head or semitendinosus between pre-exercise and 3 min post-exercise in any session. The combination of long muscle lengths and a long duration during eccentric-only resistance exercise is important to immediately decrease the stiffness (shear modulus) of a specific muscle.


Mechanism of action of buckwheat quercetin in regulating lipid metabolism and intestinal flora via Toll-like receptor 4 or nuclear factor κB pathway in rats on a high-fat diet.
Buckwheat quercetin (QUE) was used as a dietary supplement to investigate the mechanism of QUE on the regulation of lipid metabolism and intestinal flora in hyperlipidemic rats. Here, using a high-fat diet-induced hyperlipidemia model, the intervention was carried out by gavage of QUE at doses of 50, 100, and 200 mg/kg. Serum lipid levels, liver biochemical parameters, and histopathologic changes in the liver and intestinal microorganisms were measured in rats by enzyme-linked immunosorbent assay, hematoxylin-eosin, and high-throughput sequencing, respectively. Our results found that QUE, at a dose of 200 mg/kg, significantly reduced body weight, liver index, and lipid levels in rats (P < 0.05); improved hepatic oxidative stress; and repaired liver injury. In addition, the upregulation of beneficial bacteria, such as christensenellaceae and Bifidobacterium, in the organism increased the content of short-chain fatty acids, thus interfering with intestinal pH and improving the intestinal environment, while downregulating the relative abundance of Proteobacteria and Eubacterium_coprostanoligenes_group, and regulating the overproduction of butyrate. The real-time fluorescence quantitative polymerase chain reaction results found that QUE inhibited the expression of Toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) mRNA content and blocked the activation of the TLR4/NF-κB signaling pathway, thus affecting the downregulation of lipid levels and restoring intestinal homeostasis. A QUE dose of 200 mg/kg may improve lipid levels and the composition of intestinal flora through the TLR4/NF-κB pathway, suggesting that proteobacteria and christensenellaceae abundance changes may be biomarkers of potential diseases.


Agricultural production and CO2 emissions from two sources in the ECOWAS region: New insights from quantile regression and decomposition analysis.
Agriculture being the dominant economic activity of the West African economies is responsible for the most greenhouse gasses emitted in the region. Are there heterogeneous determinants of environmental degradation across low, intermediate, and high CO2 emitters in West Africa? Considering the significance of agriculture, industrial activities, renewable energy consumption and economic growth in West-Africa, this paper investigates the conditional determinants of environmental degradation from two sources (per-capita CO2 emission and CO2 emission from liquid sources) using panel data from 15 ECOWAS countries for the period 1990-2015. The study adopts a panel quantile regression technique with non-additive fixed effects as well as quintile decomposition techniques to explore if the relationship between agricultural and economic factors differs across low, intermediate, and high CO2 emitters and the extent of CO2 emission gap between Low Income Group (LIG) and Lower-Middle Income Groups (LmIG). Results from the mean estimators show that while agricultural production impedes CO2 emissions from liquid sources, it however increases total emissions implying a shift from mechanized farming to more traditional farming methods and the burning and use of biomass from agricultural produce as an energy source. Estimates of the conditional determinants of environmental degradation vary along the quantiles signifying heterogeneity of the determinants of environmental degradation across, low, intermediate, and high CO2 emitters. Additionally, results emanating from the quantile decomposition procedure show that lower-income West African economies have superseded their lower-middle income counterparts at higher quantiles of CO2 emissions.


Encapsulation of CO2 into amorphous alpha-cyclodextrin powder at different moisture contents - Part 1: Encapsulation capacity and stability of inclusion complexes.
This study investigated the effects of water-induced crystallization of amorphous alpha-cyclodextrin (α-CD) powder on CO2 encapsulation at 0.4-1.6 MPa pressure for 1-72 h through the addition of water (to reach to 13, 15 and 17% wet basis, w.b.) into amorphous α-CD powder prior to the encapsulation. The results showed that the α-CD encapsulation capacity was over 1 mol CO2/mol α-CD after pressurizing for longer than 48 h. The encapsulated CO2 concentration by the addition of water was considerably higher (p<0.05) than that of amorphous α-CD powder (5.51% MC, w.b.) without an addition of water and that of crystalline α-CD powders under the same MC and encapsulation conditions. A comparison of CO2 release properties (75% relative humidity, 25 °C) from complexed powders prepared from amorphous and crystalline α-CD powders under the same conditions is also presented.


Neonatal and early-onset diabetes in Ukraine: Atypical features and mortality.
The aim of this study is to elucidate the aetiology and clinical features of neonatal and early-onset diabetes in a large database for pediatric diabetes patients in Ukraine. We established a Pediatric Diabetes Register to identify patients diagnosed with diabetes before 9 months of age. Genetic testing was undertaken for 66 patients from 65 unrelated families with diabetes diagnosed within the first 6 months of life (neonatal diabetes, n = 36) or between 6 and 9 months (early-onset diabetes, n = 30). We determined the genetic aetiology in 86.1% of patients (31/36) diagnosed before 6 months and in 20% (6/30) diagnosed between 6 and 9 months. Fourteen individuals (37.8% of those with a genetic cause identified) had activating heterozygous variants in ABCC8 or KCNJ11. An additional 10 individuals had pathogenic variants in the INS or GCK genes, while 4 had 6q24 transient neonatal diabetes. Rare genetic subtypes (including pathogenic variants in EIF2AK3, GLIS3, INSR, PDX1, LRBA, RFX6 and FOXP3) were identified in nine probands (24.3% of solved cases), 6 of whom died. In total, eight individuals died between infancy and childhood, all of them were diagnosed before 6 months and had received a genetic diagnosis. In the last decade, the increased availability of comprehensive genetic testing has resulted in increased recognition of the contribution of rare genetic subtypes within pediatric diabetes cohorts. In our study, we identified a high mortality rate among these patients.


Acute cyanide poisoning from laetrile ingestion.
A case of cyanide poisoning from laetrile ingestion is presented as an illustration of the recognition and treatment of cyanide intoxication. The pharmacology of laetrile, of cyanide, and of antidotes to cyanide intoxication are discussed as they relate to the acute management and successful treatment of this patient after this highly lethal ingestion.


The brain-specific gene for rat aldolase C possesses an unusual housekeeping-type promoter.
A DNA fragment encompassing the first exon and about 750 bp of the 5'-flanking sequence has been isolated and sequenced. The gene has multiple start sites of transcription which are dispersed over about 200 bp. The promoter lacks TATA and CAAT boxes and is very G + C-rich, with putative binding sites for the transcriptional factors Sp1 and AP2. Similar features are shared with two other brain-specific genes encoding thy-1 antigen and gamma-enolase. The existence of a conserved block of similarity upstream of the human and rat aldolase C genes suggests that this region could be involved in tissue-specific expression whose mechanism seem to be, at least in part, transcriptional.


Effects of low-dose long-term sodium fluoride preventive treatment on rat bone mass and biomechanical properties.
Effects of fluoride on bone strength and cortical bone mass remain controversial. We compared 9-month, low-dose sodium fluoride (NaF) treatment with estrogen replacement therapy. Female Wistar rats 4.5 months old were divided into baseline, sham-operated (sham), sham-treated with NaF at 0.5 mg NaF/kg/day in drinking water, and ovariectomy (OVX), OVX treated with NaF and with estrogen. Bone mass was measured by dual X-ray absorptiometry (DXA) in vitro. Dimensions of the first lumbar vertebral body (L1) were determined by radiogrammetry. The right femur was processed undecalcified to obtain a midshaft cross-section to determine cross-sectional moments of inertia (CSMIs). L1 compressive test and left femoral torsional test were performed. OVX induced significant bone loss in L1 and femoral midshaft. Bone mass was increased to a greater extent in NaF-treated rats than in rats receiving estrogen replacement therapy. Femoral CSMIs in OVX rats, both L1 sizes and femoral CSMIs in NaF-treated rats, were significantly increased. Estrogen treatment had the least dimension expansion. OVX significantly decreased L1 compressive variables. There was no statistical difference in compressive parameters between NaF-treated groups and controls. OVX significantly increased femoral torsional strength but NaF treatment did not. Bone fluoride content was significantly increased after treatment with NaF. No significant difference in bone mineralization degree (ash and calcium) was found between treated and control rats. The discrepancy that an increase in bone mass and geometric properties in both trabecular and cortical bones by low-dose, long-term NaF treatment did not increase vertebral strength nor proportionally improve femoral strength indicated that the bone intrinsic biomechanical properties could be changed by NaF treatment.


Results of a specific and structured program in the transition of young patients with type 1 diabetes from the paediatric center to an adult hospital. The experience of a decade.
Evaluate the results of a healthcare and therapeutic education programme (TEP) aimed at young patients with type 1 diabetes (T1D) transferred from a paediatric centre. This was a prospective, pre-postest in young T1D patients transferred from 2005-2015. The programme has four phases: coordinated transfer, evaluation and objective pacting, knowledge (DKQ2) adherence (SCI-R.es) and quality of life (DQoL and SF12). Results were compared according to Multiple Daily Injections (MDI) vs. Continuous Subcutaneous Insulin Infusión (CSII) and adherence (SCI-R.es < 65 vs. > 65%). A total of 330 patients were transferred (age 18.19 ± 0.82 years, 49% females, glycated haemoglobin [HbA1c] 8.6 ± 1.4%). The programme was completed by 68%, and 61% did a group course. While no changes in HbA1c were observed at one year (8.3 ± 1.4 vs. 8.2 ± 1.4%), there were changes in severe hypoglycaemias/patient/year (0.23 ± 0.64 to 0.05 ± 0.34 p < 0.001) and mild > 5 hypoglycaemias/patient/week (6.9% vs. 3.9% p = 0.09). DQK2 knowledge increased (25.7 ± 3.6 vs. 27.8 ± 3.8 p < 0.001), with no changes in quality of life or grade of adherence. Patients with CSII (n = 21) performed more blood glucose controls and showed greater programme adherence with no changes in metabolic control. Patients with the best initial adherence presented the best control (p < 0.0001). A lower initial HbA1c and receiving the group course were associated with better clinical HbA1c results ≥ 0.5% (p < 0.05) CONCLUSIONS: The TEP improved some parameters of metabolic control without modifying the quality of life in young T1D patients. When comparing patients on MDI vs. CSII, there were no differences in metabolic control but there were when differences were evaluated considering treatment adherence.


Changes in floral nectar are unlikely adaptive responses to pollinator flight sound.
Under noiseless experimental conditions, sugar concentration of secreted floral nectar may increase after flower exposure to nearby sounds of pollinator flight (Veits et al. 2019). However, we reject the argument that this represents adaptive plant behaviour, and consider that the appealing analogy between a flower and human ear is unjustified.


Wavelength dependence of mycosporine-like amino acid synthesis in Gyrodinium dorsum.
The synthesis or accumulation of mycosporine-like amino acids (MAAs) is an important UV tolerance mechanism in aquatic organisms. To investigate the wavelength dependence of MAA synthesis in the marine dinoflagellate Gyrodinium dorsum, the organism was exposed to polychromatic radiation (PAR and UV) from a solar simulator for up to 72 h. Different irradiance spectra were produced by inserting various cut-off filters between lamp and samples. A polychromatic action spectrum for the synthesis of MAA synthesis was constructed. PAR and long wavelength UV-A radiation showed almost no effect while the most effective wavelength range was around 310 nm. Shorter wavelengths where less effective in the induction of MAA synthesis. Wavelengths below 300 nm damaged the organisms severely as indicated by a decrease in chlorophyll a absorption.


Can green structure reduce the mortality of cardiovascular diseases?
Previous studies have shown that green spaces are beneficial to health; however, few studies have analyzed the relationship between green structure and mortality of cardiovascular disease. Green structure may mediate the effects of air pollution and temperature on health. This work applies partial least squares (PLS) modeling to analyze the degree to which green structure reduces mortality of cardiovascular disease, using Taipei Metropolitan Area as an empirical case. In addition to clarifying the complex relationships and effects of green structure, air pollution, temperature, and mortality of cardiovascular disease, this study demonstrates that green structure has a significant influence on mortality of cardiovascular disease because it reduces the effects of air pollution and heat. The most crucial elements for planning a healthy living environment are the maximization of the largest green patch proportion and the minimization of green space fragmentation. Moreover, to enhance the benefits of greening city spaces on health, this work proposes several strategies for connecting fragmentary green spaces, expanding green patches to the largest possible proportion, and managing green spaces. The proposed strategies may serve as a reference for other metropolitan areas with features similar to those of the study area.


Association between the presence of anti-HLA antibodies with acute rejection and chronic allograft nephropathy in the first year after kidney transplantation.
The clinical relevance of anti-HLA antibodies following kidney transplantation has been a recent focus of research. Patients who present anti-HLA antibodies in the posttransplantation period have shown higher incidences of acute rejection episodes (ARE) and chronic allograft nephropathy (CAN). The objective of this study was to evaluate the presence of anti-HLA antibodies during the first year after kidney transplantation and their association with the occurrence of ARE and CAN. Eighty-eight kidney transplant recipients were evaluated for the presence of IgG anti-HLA antibodies using an enzyme-linked immunosorbent assay (LAT-M and LAT-1240, One Lambda Inc, Calif, United States). Protocol kidney biopsies were performed in consenting patients. ARE and CAN were diagnosed by clinical, laboratory, and histopathological criteria. Anti-HLA antibodies were observed in 20 (22.7%) patients. At 1 year follow-up, 26.1% presented ARE and 51.2% developed CAN. Nine patients (45%) with antibodies developed ARE as opposed to 20.6% without antibodies and 64.7% developed CAN as opposed to 47.8% of those without antibodies. In the histological analysis, the anti-HLA antibodies were associated with Banff IIA ARE (P = .001) and Banff grade II CAN (P = .012). Routine posttransplantation search for antibodies may identify cases at higher risk for acute and chronic rejection, and perhaps help to tailor the immunosuppressive regimen.


Social workers in primary prevention: action and ideology in mental health.
Primary prevention and a public health model have been among the distinguishing innovations of the community mental health movement. Social work practice, however, has historically been involved in community intervention and environmental manipulation to offset social and psychological jeopardy. Given a long tradition of commitment to activity and techniques which are now hailed as mental health's "third revolution," this study explores the role of social work in primary prevention. Data are from a survey of three community mental health centers in which professional staff completed the Gottesfeld Critical Issues of Community Mental Health questionnaire, a time-distribution form, and a prevention questionnaire. In addition, all staff working in primary prevention were interviewed in depth. The total sample of this study of mental health professionals was 84. This study points to some interesting contradictions found between social work action and ideology in primary prevention. Also, social workers are compared with other professionals in order to isolate some primary prevention tasks and attitudes that appear unique to each.


Compulsive Digital Gaming: An Emerging Mental Health Disorder in Children.
Excessive digital gaming is emerging as a mental health disorder because youngsters are losing control of their lives by wasting their time by indulging in online multiplayer games. The popularity of the games can be gauged by the fact that India's online gaming market of US $360 million is expected to grow to $ 1 billion by 2021. Video gaming is an obsessive compulsive disorder. The players enjoy creating and building relationships with other online characters, which provides a virtual community feeling at the expense of one-to-one social interactions and real life bonding. In due course of time, the players are preoccupied or "hooked" to the games and display mood swings like irritability, restlessness, and aggressive behavior when they are denied the playing gadgets. Realizing the multifarious health hazards of digital gaming, WHO has recently classified it as a mental health disorder in the 11th revision of its International Classification of Diseases (ICD-11) so that it is accorded the state health benefits for its prevention and treatment. The technology is both a boon as well as a bane, the option is with us. It is important to avoid all obsessions or compulsions in life in order to follow the philosophy of "middle path".


Arthritis accompanying ileal pouchitis or undifferentiated HLA B27-related spondyloarthropathy?
The case of an HLA B27(+) patient who developed inflammatory arthritis accompanying ileal pouchitis, following total proctocolectomy for familial adenomatous polyposis is presented for the first time in the literature. Based on its clinical presentation and serology, it can be classified either as arthritis accompanying ileal pouchitis, or as an undifferentiated spondyloarthropathy.


Anti-hepatitis C virus antibody detection in oral fluid: influence of human immunodeficiency virus co-infection.
Saliva sampling may provide an easier access to hepatitis C virus (HCV) screening test. HIV infection influence on specific salivary antibody detection has not been extensively studied. An anti-HCV antibodies (HCV-Ab) test was adapted for saliva specimens and its performances were analysed according to the patients' HIV status and related factors such as CD4 cell counts and HIV viral load. Four patients groups were selected: (i) HCV and HIV negative volunteers (n=28); (ii) HCV positive and HIV negative patients (n=30); (iii) HCV negative and HIV positive patients (n=30); (iv) HCV and HIV co-infected patients (n=30). Saliva samples were collected (Salivette system, Sarstedt) and an in-house adapted HCV-Ab detection assay was performed (MONOLISA anti-HCV PLUS Version 2, Biorad). HIV viral load, CD4 cells counts and HCV viremic status were reported. Sensitivity and specificity of saliva anti-HCV antibody tests in the HIV negative groups were 90% and 100%, respectively, compared to 73% and 93%, respectively in the HIV infected population. Compared to the HIV negative population, HIV mono-infected patients presented higher absorbance values (p=0.01) and HIV/HCV co-infected population presented lower HCV-Ab absorbance values (p<0.001). Sensitivity decline was associated with HIV replication (p=0.02), HCV replication (p=0.16) but not with CD4 cell counts (p=0.64). Performances of salivary HCV antibodies testing are strongly deteriorated in the HIV positive population, especially for patients with residual HIV replication. This serious limitation should prompt careful testing of non-invasive screening tests for hepatitis C in HIV-infected patients before use in real screening conditions.


Hoarseness after laryngeal blunt trauma: a differential diagnosis between an injury to the external branch of the superior laryngeal nerve and an arytenoid subluxation. A case report and literature review.
Arytenoid subluxation is a well-known cause of hoarseness due to incomplete glottic closure with intact inferior laryngeal nerves after severe laryngeal trauma. We report the case of a young man presenting after laryngeal blunt trauma with hoarseness, easy fatigue during phonation, marked difficulty with his high-pitch and singing voice and decreased phonation time, but intact function of both inferior laryngeal nerves, intact endolaryngeal mucosa sensibility and normal CT scans of the larynx and the neck. Due to the asymmetric anteromedial position of the right arytenoid with incomplete glottic closure, the primary diagnosis was arytenoid subluxation, and the patient was referred for instantaneous relocation therapy. The stroboscopic and electromyographic diagnosis of a unilateral paresis of the external branch of the right superior laryngeal nerve caused the therapy to be changed. Without repositioning, the patient had a total recovery of voice quality when the paresis receded 2 months later. In conclusion, the unilateral paresis of the external branch of the superior laryngeal nerve after laryngeal blunt trauma is reported here for the first time. Although the clinical findings are familiar sequelae of thyroid surgery, they may be misdiagnosed as arytenoid subluxation after laryngeal blunt trauma. Stroboscopy and electromyography permitted the correct diagnosis.


External radiotherapy prior to thyroid cancer: a case-control study.
The aim of this investigation was to study previous radiotherapy of malignant diseases as a risk factor for thyroid cancer. By using the Swedish Cancer Registry all cases of thyroid cancer with another malignant disease at least one year previously and living within the catchment area of our hospital were traced. During 1959-1989 a total of 1056 cases of thyroid cancer were identified. Of these 37 had had another previous malignant disease and they constituted the cases in this study. As controls four persons with at least two malignant diseases, thyroid cancer excluded, were selected for each case from the same cancer registry. Ten (27.0%) of the 37 patients with thyroid cancer as a second tumor had earlier been irradiated with the treatment dose including the thyroid gland as compared with 34 (24.5%) of the 139 control patients. Eight of the ten cases with previous irradiation of the thyroid gland had papillary cancer. The median latency was 13 years. The estimated radiation dose in the thyroid varied between 3 and 40 Gy. External radiotherapy gave a crude odds ratio of 1.1 with 95% confidence interval = 0.5-2.8 for thyroid cancer. The weighted odds ratio was calculated to 2.3 with confidence interval = 0.5-8.9. This case-control study gave a non significantly increased odds ratio for thyroid cancer in patients with external radiotherapy including the thyroid gland.


Effect of treatment with a JAK2-selective inhibitor, fedratinib, on bone marrow fibrosis in patients with myelofibrosis.
Progressive bone marrow fibrosis (BMF) is a cardinal feature of many myeloproliferative neoplasms (MPNs) and there is a documented association between the severity of BMF and overall prognosis. We conducted an exploratory analysis of sequential BMF data from two phase I studies of long-term treatment with the Janus kinase 2 (JAK2) inhibitor fedratinib in patients with myelofibrosis. Bone marrow samples were obtained at baseline and after every six cycles (24 weeks) of daily fedratinib treatment. Fibrosis was centrally assessed by three independent haematopathologists, who were blinded to the patients' data, and graded according to European Consensus Myelofibrosis Grading Criteria. The analysis population comprised patients with a baseline BMF grade ≥1, and at least one post-baseline BMF grade assessment. Changes in BMF grade compared with baseline were classified as improvement (≥1 grade reduction), stabilisation (no change in any baseline BMF grade <3) or worsening (≥1 grade increase). Twenty-one patients were included in the analysis. A total of 153 bone marrow samples were analysed. Improvement or stabilisation of BMF from baseline was recorded in 15 of 18 (83%) evaluable patients at cycle 6 and in four of nine (44%) evaluable patients at cycle 30. Two patients achieved resolution of their BMF (grade = 0) by cycle 12. This exploratory analysis indicates that improvement or even resolution of BMF may be achievable with JAK2 inhibitor therapy in some patients with MPNs and myelofibrosis.


[Surgical anatomy of the nose. I].
Since a few years, more and more papers are published in the international literature about nasal anatomy, probably because of the growing popularity of the open rhinoplasty. So, new concepts, new anatomic entities have been established without equivalent in the French literature. The authors review the most recent notions of the surgical anatomy of the nose and propose a french terminology for several concepts developed in the international literature (e.g. supratip breakpoint). The surgical anatomy of the external nose is described.


Probing aggregation and fibril formation of insulin in polyelectrolyte multilayers.
Ultrathin films are useful for coating materials and controlling drug delivery processes. Here, we explore the use of polyelectrolyte multilayers as templates for the formation of two-dimensional protein networks, which represent biocompatible and biodegradable ultrathin films. In a first step, we have studied the lateral aggregation and amyloid fibril formation of bovine insulin that is adsorbed at and confined within planar polyelectrolyte multilayers, assembled with poly(diallyldimethylammonium chloride) (PDDA), poly(styrenesulfonic acid) (PSS), and hyaluronic acid (HA). Si-PDDA-PSS-(insulin-PSS)(x) and Si-PDDA-PSS-(insulin-HA)(x) multilayers (x=1-4) have been prepared and characterized in the fully hydrated state by using X-ray reflectometry, attenuated total reflection-Fourier transform infrared spectroscopy and confocal fluorescence microscopy. The obtained data demonstrate a successful build-up of the insulin-polyelectrolyte multilayers on silicon wafers that grow strongly in thickness upon insulin adsorption on PSS and HA layers. The secondary structure analysis of insulin, based on the vibrational amide I'-band, indicates an enhanced intermolecular β-sheet formation within the multilayers at 70°C and pD=2, i.e. at conditions that promote insulin amyloid fibrils rich in β-sheet contents. However, insulin that is confined between two polyelectrolyte layers rather forms amorphous aggregates as can be inferred from confocal fluorescence images. Remarkably, when insulin is deposited as the top-layer, a partial conversion into a two-dimensional fibrillar network can be induced by adding amyloid seeds to the solution. Thus, the results of this study illustrate the capability of polyelectrolyte multilayers as templates for the growth of protein networks.


Mesenchymal Neoplasms of the Liver.
Mesenchymal neoplasms of the liver can be diagnostically challenging, particularly on core needle biopsies. Here, I discuss recent updates in neoplasms that are specific to the liver (mesenchymal hamartoma, undifferentiated embryonal sarcoma, calcifying nested stromal-epithelial tumor), vascular tumors of the liver (anastomosing hemangioma, hepatic small vessel neoplasm, epithelioid hemangioendothelioma, angiosarcoma), and other tumor types that can occur primarily in the liver (PEComa/angiomyolipoma, inflammatory pseudotumor-like follicular dendritic cell sarcoma, EBV-associated smooth muscle tumor, inflammatory myofibroblastic tumor, malignant rhabdoid tumor). Lastly, I discuss metastatic sarcomas to the liver, as well as pitfalls presented by metastatic melanoma and sarcomatoid carcinoma.


Comparative leaf proteomics of drought-tolerant and -susceptible peanut in response to water stress.
Water stress (WS) predisposes peanut plants to fungal infection resulting in pre-harvest aflatoxin contamination. Major changes during water stress including oxidative stress, lead to destruction of photosynthetic apparatus and other macromolecules within cells. Two peanut cultivars with diverse drought tolerance characteristics were subjected to WS, and their leaf proteome was compared using two-dimensional electrophoresis complemented with MALDI-TOF/TOF mass spectrometry. Ninety-six protein spots were differentially abundant to water stress in both cultivars that corresponded to 60 non-redundant proteins. Protein interaction prediction analysis suggests that 42 unique proteins showed interactions in tolerant cultivar while 20 showed interactions in the susceptible cultivar, activating other proteins in directed system response networks. Four proteins: glutamine ammonia ligase, chitin class II, actin isoform B, and beta tubulin, involved in metabolism, defense and cellular biogenesis, are unique in tolerant cultivar and showed positive interactions with other proteins. In addition, four proteins: serine/threonine protein phosphate PP1, choline monooxygenase, peroxidase 43, and SNF1-related protein kinase regulatory subunit beta-2, that play a role as cryoprotectants through signal transduction, were induced in drought tolerant cultivar following WS. Eleven interologs of these proteins were found in Arabidopsis interacting with several proteins and it is believed that similar mechanisms/pathways exist in peanut. Peanuts (Arachis hypogaea L.) are a major source of plant protein grown in subtropical and tropical regions of the world. Pre-harvest aflatoxin contamination is a major problem that affects peanut crop yield and food safety. Poor understanding of molecular and cellular mechanisms associated with aflatoxin resistance is largely responsible for the lack of progress in elucidating a process/methodology for reducing aflatoxin contamination in peanuts. Drought perturbs the invasion of the aflatoxin producing fungus and thus affects the quality and yield of peanut. Therefore, more studies involving the effects of drought stress to determine the molecular changes will enhance our understanding of the key metabolic pathways involved in the combined stresses. The changes associated with the biotic and abiotic interactions within the peanut will be used to determine the metabolic pathways involved in the stress tolerance. This research would be beneficial in identifying the tolerant molecular signatures and promoting food safety and consumer health through breeding superior quality peanut cultivars.


Modality-specific effects on crosstalk in task switching: evidence from modality compatibility using bimodal stimulation.
The present study was aimed at examining modality-specific influences in task switching. To this end, participants switched either between modality compatible tasks (auditory-vocal and visual-manual) or incompatible spatial discrimination tasks (auditory-manual and visual-vocal). In addition, auditory and visual stimuli were presented simultaneously (i.e., bimodally) in each trial, so that selective attention was required to process the task-relevant stimulus. The inclusion of bimodal stimuli enabled us to assess congruence effects as a converging measure of increased between-task interference. The tasks followed a pre-instructed sequence of double alternations (AABB), so that no explicit task cues were required. The results show that switching between two modality incompatible tasks increases both switch costs and congruence effects compared to switching between two modality compatible tasks. The finding of increased congruence effects in modality incompatible tasks supports our explanation in terms of ideomotor "backward" linkages between anticipated response effects and the stimuli that called for this response in the first place. According to this generalized ideomotor idea, the modality match between response effects and stimuli would prime selection of a response in the compatible modality. This priming would cause increased difficulties to ignore the competing stimulus and hence increases the congruence effect. Moreover, performance would be hindered when switching between modality incompatible tasks and facilitated when switching between modality compatible tasks.


LncRNA FIRRE promotes the proliferation and metastasis of hepatocellular carcinoma by regulating the expression of PXN through interacting with MBNL3.
Hepatocellular carcinoma (HCC) has been a long-time public health problem impacting people's heath and challenging healthcare professions because of its poor prognosis and high lethality. More and more evidence indicated the important role of long non-coding RNAs (lncRNAs) in carcinogenesis and cancer metabolism in a variety of cancer types. In this study, we found that FIRRE, a recently identified cancer-associated lncRNA located on chromosome X, is highly expressed in HCC cell lines and tissue samples, and its expression is positively correlated with poor HCC prognosis. In vitro and in vivo functional analyses showed that FIRRE could promote the proliferation, migration, and invasion of HCC. As for the potential mechanism, FIRRE specifically binds to the splicing factor MBNL3 to affect the expression of PXN to regulate the pathological characteristics of HCC cells. In summary, our study showed that the lncRNA FIRRE is a cancer promoting factor and may be a potential biomarker for the prognosis and drug target for the treatment of HCC.


Pulmonary involvement in brucellosis.
Pulmonary involvement is a rare manifestation of brucellosis. The aim of this study was to determine the incidence and forms of pulmonary involvement in the course of brucellosis. A prospective study was carried out in 110 patients with brucellosis. All the patients were evaluated with their pulmonary symptoms, physical examination and chest radiography. If pulmonary pathologic findings were present, patients underwent additional diagnostic evaluations including computerized tomography of the thorax and pulmonary function tests. From 110 patients, 11 (six females and five males) were diagnosed as pulmonary brucellosis. Eight of 11 patients had pulmonary symptoms including cough, sputum and dyspnoea. Radiologic findings were parenchymal nodules, lobar pneumonia, paratracheal lymphadenopathy and pleural effusion. At the end of the treatment of brucellosis, clinical findings of pulmonary involvement were recovered in all patients except four dyspnoeic patients who had coexisting COPD. Radiological findings were normal in three and improved in four patients after 6 months of the treatment. Pulmonary involvement is a rare event in the course of brucellosis. But especially in endemic regions, brucellosis should never be forgotten as a causative agent in patients with pulmonary symptoms.


Nitrosylhemoglobin in photodynamically stressed human tumors growing in nude mice.
The role of nitric oxide in human tumor biology and therapy has been the subject of extensive studies. However, there is only limited knowledge about the mechanisms of NO production and its metabolism, and about the role NO can play in modern therapeutic procedures, such as photodynamic therapy. Here, for the first time, we report the presence of nitrosylhemoglobin, a stable complex of NO, in human lung adenocarcinoma A549 tumors growing in situ in nude mice. Using electron paramagnetic resonance spectroscopy we show that the level of nitrosylhemoglobin increases in the course of photodynamic therapy and that the phenomenon is local. Even the destruction of strongly vascularized normal liver tissue did not induce the paramagnetic signal, despite bringing about tissue necrosis. We conclude that photodynamic stress substantiates NO production and blood extravasation in situ, both processes on-going even in non-treated tumors, although at a lower intensity.


Anatomic regurgitant orifice area obtained using 3D-echocardiography as an indicator of severity of mitral regurgitation in dogs with myxomatous mitral valve disease.
To determine feasibility and repeatability of measuring the anatomic regurgitant orifice area (AROA) using real-time three-dimensional transthoracic echocardiography (RT3DE) in dogs with myxomatous mitral valve disease (MMVD), and to investigate differences in the AROA of dogs with different disease severity and in different American College of Veterinary Internal Medicine (ACVIM) stages. Sixty privately-owned dogs diagnosed with MMVD. The echocardiographic database of our institution was retrospectively searched for dogs diagnosed with MMVD and RT3DE data set acquisition. Dogs were classified into mild, moderate, or severe MMVD according to a Mitral Regurgitation Severity Score (MRSS), and into stage B1, B2 or C according to ACVIM staging. The RT3DE data sets were imported into dedicated software and a short axis plane crossing the regurgitant orifice was used to measure the AROA. Feasibility, inter- and intra-observer variability of measuring the AROA was calculated. Differences in the AROA between dogs in different MRSS and ACVIM stages were investigated. The AROA was measurable in 60 data sets of 81 selected to be included in the study (74%). The inter- and intra-observer coefficients of variation were 26% and 21%, respectively. The AROA was significantly greater in dogs with a severe MRSS compared with dogs with mild MRSS (p=0.045). There was no difference between the AROA of dogs in different ACVIM clinical stages. Obtaining the AROA using RT3DE is feasible and might provide additional information to stratify mitral regurgitation severity in dogs with MMVD. Diagnostic and prognostic utility of the AROA deserves further investigation.


Differentiation of EBV-induced post-transplant Hodgkin lymphoma from Hodgkin-like post-transplant lymphoproliferative disease.
The development of lymphomas after SOT is a well-known complication of the immunosuppressive therapy necessary to prevent graft rejection. Epstein-Barr virus plays a central role in the pathogenesis of lymphomas because of its ability to transform infected cells. Differentiating PTLD from malignant lymphomas, especially HL can be challenging. We report on two patients, who developed EBV-associated lymphomas several years after SOT. A histological examination of lymph nodes led to a diagnosis of HL in both patients, who were started on chemotherapy according to current treatment protocols. A rapid and complete remission in one patient prompted us to analyze the expression pattern of EBV-latency genes. In this patient, the EBV expression profile revealed a latency type III suggesting the diagnosis of Hodgkin-like PTLD. The other patient required six courses of chemotherapy plus radiotherapy to reach a complete remission. In his tumor cells, a restricted EBV-latency type II pattern was found, suggesting a diagnosis of classical HL. These two cases demonstrate that in post-transplant lymphomas with histological features of HL, an analysis of the expression pattern of EBV proteins might aid in the differentiation between PTLD and HL.