Fluorotelomer alcohols are efficiently biotransformed by Cunninghamella elegans.
Cunninghamella elegans is a well-studied fungus that biotransforms a range of xenobiotics owing to impressive cytochrome P450 (CYP) activity. In this paper, we report the biotransformation of 6:2 fluorotelomer alcohol (6:2 FTOH) by the fungus, yielding a range of fluorinated products that were detectable by fluorine-19 nuclear magnetic resonance spectroscopy (19F NMR), gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). Upon incubation with the pre-grown cultures, the substrate (100 mg/L) was completely consumed within 48 h, which is faster biotransformation than other fungi that have hitherto been studied. The main metabolite formed was the 5:3 fluorotelomer carboxylic acid (5:3 FTCA), which accumulated in the culture supernatant. When the cytochrome P450 inhibitor 1-aminobenzotriazole was included in the culture flasks, there was no biotransformation of 6:2 FTOH, indicating that these enzymes are key to the catalysis. Furthermore, when exogenous 5:3 FTCA was added to the fungus, the standard biotransformation of the drug flurbiprofen was inhibited, strongly suggesting that the main fluorotelomer alcohol biotransformation product inhibits CYP activity and accounts for its accumulation.


Lipophagy: A potential therapeutic target for nonalcoholic and alcoholic fatty liver disease.
Lipid droplets are unique lipid storage organelles in hepatocytes. Lipophagy is a key mechanism of selective degradation of lipid droplets through lysosomes. It plays a crucial role in the prevention of metabolic liver disease, including nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD), and is a potential therapeutic target for treating these dysfunctions. In this review, we highlighted recent research and discussed advances in key proteins and molecular mechanisms related to lipophagy in liver disease. Reactive oxygen species (ROS) is an inevitable product of metabolism in alcohol-treated or high-fat-treated cells. Under this light, the potential role of ROS in autophagy in lipid droplet removal was initially explored to provide insights into the link between oxidative stress and metabolic liver disease. Subsequently, the current measures and drugs that treat NAFLD and AFLD through lipophagy regulation were summarized. The complexity of molecular mechanisms underlying lipophagy in hepatocytes and the need for further studies for their elucidation, as well as the status and limitations of current therapeutic measures and drugs, were also discussed.


Colony size and initial conditions combine to shape colony reunification dynamics.
Group cohesion and collective decision-making are important for many social animals, like social insects, whose societies depend on the coordinated action of individuals to complete collective tasks. A useful model for understanding collective, consensus-driven decision-making is the fluid nest selection dynamics of ant colonies. Certain ant species oscillate between occupying multiple nests simultaneously (polydomy) and reuniting at a single location (monodomy), but little is known about how colonies achieve a consensus around these dynamics. To investigate the factors underpinning the splitting-reunification dynamics of ants, we manipulated the availability and quality of nest sites for the ant Temnothorax rugatulus and measured the likelihood and speed of reunification from contrasting starting conditions. We found that pursuing reunification was more likely for smaller colonies, that rates of initial splitting were lower when colonies could coordinate their activity from a central hub, and that diluting colonies among additional sites did not impair reaching consensus on a single nest. We further found mixed support for a specific threshold of social density that prevents reunification (i.e., prolonged polydomy) and no evidence that nest quality influences reunification behavior. Together our data reveal that consensus driven decisions can be influenced by both external and intrinsic group-level factors and are in no way simple stereotyped processes.


"Central Road" cystoscopic finding: The road to worsened incontinence following laparoscopic sacrocolpopexy.
This paper presents the "Central Road" cystoscopic finding accompanied by magnified mixed urinary incontinence following laparoscopic sacrocolopopexy. A 70-year-old female experienced severe mixed urinary incontinence upon completing laparoscopic sacrocolopopexy. The cystoscopy showed a cord-like appearance in the center of the bladder trigon and posterior wall. Videourodynamics confirmed stress urinary incontinence, and chain cystourethrography indicated that the proximal urethra was open and the posterior vesicourethral angle was atypically widened. After implanting a midurethral sling, mixed urinary incontinence was cured subjectively and objectively without medication. The "Central Road" cystoscopic finding can be a signpost pointing to laparoscopic sacrocolopopexy mesh overtensioning, which can cause dekinking of the bladder neck, exacerbate stress urinary incontinence, and possibly lead to stress-induced instability. A midurethral sling successfully relieved mixed urinary incontinence in this case, but it might be necessary to loosen the laparoscopic sacrocolopopexy mesh in some other cases.


Effects of high- and low-yield moso bamboo (Phyllostachys edulis) forests on bacterial community structure.
To study the characteristics of bacterial community structure in high-yield and low-yield moso bamboo (Phyllostachys edulis) forests, we collected bamboo rhizome, rhizome root, stem, leaf, rhizosphere soil, and non-rhizosphere soil from high- and low-yield forests in Yong'an City and Jiangle County of Fujian Province, China. The genomic DNA of the samples was extracted, sequenced and analyzed. The results show that: the common differences between the high-yield and low-yield P. edulis forest samples in the two regions were mainly in bacterial community compositions in the bamboo rhizome, rhizome root, and soil samples. Differences in the bacterial community compositions in the stem and leaf samples were insignificant. The bacterial species and diversity in rhizome root and rhizosphere soil of high-yield P. edulis forests were less than those of low-yield forests. The relative abundance of Actinobacteria and Acidobacteria in rhizome root samples of high-yield forests was higher than that in low-yield forests. The relative abundance of Rhizobiales and Burkholderiales in bamboo rhizome samples in high-yield forests was higher than that in low-yield forests. The relative abundance of Bradyrhizobium in bamboo rhizome samples in high-yield forests was higher than that in low-yield forests in the two regions. The change of bacterial community composition in P. edulis stems and leaves showed little correlation with high- or low-yields of P. edulis forests. Notably, the bacterial community composition of the rhizome root system was correlated with the high yield of bamboo. This study provides a theoretical basis for using of microbes to enhance the yields of P. edulis forests.


Systematic review and meta-analysis of the effect of North American working hours restrictions on mortality and morbidity in surgical patients.
Short duty hours, imposed by the Accreditation Council of Graduate Medical Education (ACGME) regulations, have been claimed to be associated with loss of continuity of care among surgical patients, leading to a potentially increased risk of adverse surgical outcomes. This systematic review and meta-analysis assessed the strength of associations between duty hour restrictions and morbidity and mortality of various surgical procedures. MEDLINE, Embase, BIOSIS Previews(®), the Education Resources Information Center and the Cochrane Central Register of Controlled Trials (January 2000 to September 2009) were searched, and reports screened to identify comparative studies of mortality and morbidity before and after the introduction of ACGME regulation periods. Random-effects (RE) and quality-effects (QE) meta-analyses were performed to determine the risk of morbidity or death associated with long duty hours compared with shorter duty hours. Results are presented as odds ratio (OR) with 95 per cent confidence interval. A total of 19 data sets (10 articles), including 730,648 subjects in the mortality studies and 64,346 in the morbidity studies, were analysed. Long duty hours were associated with a non-significantly increased risk of death compared with shorter duty hours (OR 1·28, 0·94 to 1·73). There was no difference in morbidity between the two groups (OR 1·03, 0·67 to 1·57). Mortality associations were generally stronger for general surgery, more recent studies and higher-quality studies. Heterogeneity was evident among the studies included. The reduction in working hours has not affected patient care negatively in terms of demonstrable differences in morbidity and mortality. However, it cannot be distinguished whether this effect is actually due to a non-detrimental effect of the reduction in working hours or whether any such detriment is offset by continually improving patient care and increased surgical supervision.


DNA nanofilm thickness measurement on microarray in air and in liquid using an atomic force microscope.
The measurement of the thickness of DNA films on microarray as a function of the medium (liquid, air) is gaining importance for understanding the signal response of biosensors. Thiol group has been used to attach DNA strands to gold micropads deposited on silicon surface. Atomic force microscopy (AFM) was employed in its height mode to measure the change in the pad thickness and in its force mode to measure the indentation depth of the nanofilm. A good coherence between the height and force modes is observed for the film thickness in air. The adhesion force was found to be an alternative way to measure the surface coverage of the biolayer at nanoscopic scale. However the force analysis (compression, steric and electrostatic) provides baseline information necessary to interpret the AFM height image in liquid. Analysis of the film thickness distribution shows that the height of the DNA strands depends on both the DNA strand length (15-35 base pairs) and the environment (air, liquid). In air, longer strands lay down onto gold surface whereas the charge reversal of gold in liquid causes a repulsion of longer strands, which stand up.


High resolution microscopic survey of third metacarpal articular calcified cartilage and subchondral bone in the juvenile horse: possible implications in chondro-osseous disease.
The aim was to survey articular calcified cartilage (ACC) and subchondral bone in the palmar and dorsal regions of the condyles of the third metacarpal bone (Mc3) of young horses with minimal or no signs of musculo-skeletal abnormality. Back-scattered electron scanning electron microscopy (BSE SEM) was conducted on polymethyl methacrylate-embedded mediolateral slices and macerated wedges of the right distal Mc3 from seven each of trained and untrained 2-year-old Thoroughbred horses. Furrows or grooves visible to the naked eye in the mineralizing front (MF) of ACC are the commonest "lesion" and are most common in the palmar portions of the medial and lateral condylar grooves. Cracks running predominantly in the parasagittal plane that infill with hypercalcified matrix are found in the same domain. Common to all these defects are deficiencies or absence of the ACC MF. Other anomalies include local excrescences or depressed areas of the MF. More important condylar lesions show displaced fragmented hypermineralized ACC with underlying excess resorption in the bone domain, leaving a thin ACC layer with cavernous space beneath it. The fragments may dislodge and displace to the joint space. Obvious although small lesions are present in horses that have undertaken little or no training. The nature and sites of the lesions indicate that they are possibly the earliest morphological evidence of changes that may lead to specific joint abnormalities. The lesions appear unlikely to be solely due to functional traumatic forces, and developmental influences are likely to be important in their initiation.


Urinary calculi and primary hyperparathyroidism: simultaneous surgical treatment.
We report 8 cases in which simultaneous surgical treatment of primary hyperparathyroidism and renal stone disease was performed. Treatment of a parathyroid tumor and urinary calculus under the same anesthetic is practical and should be considered in appropriate patients.


Goretex graft replacement of left and right main stem coronary arteries in dissecting aortic aneurysm.
A dissecting aneurysm of the ascending aorta was replaced by a valved conduit. As both coronary ostia could not be used for implantation into the conduit and the patient had undergone vein stripping on both legs, 2 Goretex-grafts (5 mm) were used for reconstruction of the right and left main stem coronary arteries.


Cingulate subregions in posttraumatic stress disorder, chronic stress, and treatment.
Decades of research have revealed that the cingulate cortex is important in posttraumatic stress disorder (PTSD). Initially inspired by basic rodent research examining the mechanisms of fear learning, researchers have attempted to determine the respective roles of the anterior cingulate cortex (ACC), anterior midcingulate cortex (aMCC), and posterior cingulate cortex (PCC) in PTSD. Various neuroimaging techniques have shown the ACC is both functionally hypoactive and structurally diminished in PTSD, while the aMCC is functionally hyperactive and structurally diminished. Relatedly, chronic stress has been shown to be a significant vulnerability factor in the development of PTSD after a traumatic event, inspiring research into the effect of chronic stress on brain activation and structure. Similar to patterns in PTSD, perceived work-related stress, outgroup membership, and lower socioeconomic status appear to negatively affect cingulate function and morphology. While great strides have been made to understand better the ACC, aMCC, and PCC in both PTSD and chronic stress, additional studies are needed to determine the origin of these cingulate abnormalities and whether they can be used as biomarkers in assessing and predicting treatment response in PTSD.


Inflammatory dentigerous cysts of children treated by tooth extraction and decompression--report of four cases.
Inflammatory dentigerous cysts are only found in the mixed dentition. The four cases presented here illustrate the uncomplicated behavior of these cysts when properly treated. By extracting the infected primary teeth, opening the cyst and ensuring continuous drainage, it is possible to achieve spontaneous eruption of the involved permanent teeth into the dental arch even if they are badly dislocated. Simultaneous with the eruption of the permanent teeth, ossification of the bony defect can take place. The reparatory process is completed in one to two years.


The descending limb of the sarcomere length-force relation in single muscle fibres of the frog.
Single muscle fibres, isolated from the tibialis anterior muscle of the frog, were used to study intersarcomere dynamics during muscle-isometric (fixed-end) tetani at long sarcomere lengths. Sarcomere length was measured by an online laser diffraction technique. On the descending limb of the length-force relation, the slow rise of force (creep) was always associated with changes in sarcomere length. Sarcomeres at the ends of the fibres shortened, while those of the central 90% of the fibre length were stretched. Fibres were found to have a range of passive length-force curves, those with high resting forces developed little creep force, while low resting force fibres developed substantial creep, resulting in a fixed-end sarcomere length-force relation which deviated greatly from that expected from crossbridge theory. These differences in creep force can be qualitatively accounted for by differences in sarcomere dynamics. The simultaneous measurement of force and sarcomere length during force development allows the construction of a 'sarcomere-isometric' length-force curve from minima in the sarcomere length record. Force declined linearly from a plateau at 2.2 microns to zero at a sarcomere length close to 3.65 microns. The online, diffraction-derived sarcomere length was used in a feedback loop to clamp sarcomere length in short (100-200 microns) segments of fibres. A length-force curve constructed from sarcomere length-clamped tetani shows a linear decline in force from a plateau at 2.2 microns to zero at a sarcomere length of 3.65 microns.


The Perils of Not Being Attractive or Athletic: Pathways to Adolescent Adjustment Difficulties Through Escalating Unpopularity.
Adolescents who lack traits valued by peers are at risk for adjustment difficulties but the mechanisms responsible for deteriorating well-being have yet to be identified. The present study examines processes whereby low athleticism and low attractiveness give rise to adolescent adjustment difficulties. Participants were public middle school students (ages 10 to 13 years, Mage = 11.54, SDage = 1.00) in the USA and Lithuania (300 girls, 280 boys; 52.7% girls). Self-reports of alcohol misuse and loneliness were collected three times during an academic year (M = 12.3 week intervals). Athleticism, attractiveness, unpopularity, and peer rejection were assessed through peer nominations. Full longitudinal mediation analyses examined direct and indirect pathways from stigmatized traits (i.e., low athleticism, low attractiveness) to adjustment difficulties (i.e., alcohol misuse, loneliness) through two indices of low peer status: unpopularity and rejection. The results indicated that the possession of stigmatized traits predicted escalating unpopularity, which, in turn, predicted increasing adjustment difficulties. Similar indirect associations did not emerge with rejection as a mediator, underscoring the unique role of power and prominence (and the lack thereof) in socioemotional development. The findings underscore the adjustment risks and interpersonal challenges that confront children and adolescents who lack traits valued by peers.


Is lower incisor inclination a good parameter to estimate alveolar bone level? A cone-beam CT evaluation.
This study verified whether an IMPA above the normative value could be a sign of reduced lower incisor labial bone height. Such association, which could improve the quality of treatment planning, was not confirmed. A cone-beam CT is still recommended when a more precise diagnosis is needed.


Traumatic cerebral aneurysms caused by shell fragments. Report of four cases and review of the literature.
Traumatic aneurysms of the cerebral arteries of penetrating origin are rare but a well recognized entity and their development in military practice have not been adequately discribed. In the review of the literature we encountered only 24 cases of traumatic aneurysms after penetrating brain wounds. In view of their rarity, we are adding four new cases. The need for routine angiography in the evaluation of the vascular state in penetrating brain wounds as well as the necessity of their prompt surgical intervention is emphasized.


Age-dependent change in the ability of protein synthesis by rat liver microsomes-significance of 2 associated factors.
An activator and an inhibitor of polypeptide synthesis were isolated from microsomes of rat liver. The young rat contained a higher level of the activator but a lower level of the inhibitor than the aged rat. The significantly higher ratio of the specific activity of the activator to inhibitor in the young microsomes helps explain the higher capacity for protein synthesis of these microsomes as compared to the microsomes of the aged animal.


A visual representation of cattle movement in Ireland during 2016.
The aim of this study was to create a clear visual representation of the live movements of cattle in the Republic of Ireland over the course of the year 2016. The animation created can be viewed online: https://youtu.be/PTCdPMnenBw This animation was created to be a communication tool to enable stakeholders to appreciate the extent of high risk cattle movements (farm to farm, farm to market to farm) in the Republic of Ireland and to highlight the potential role that these movements may play in the spread of infectious diseases of cattle in Ireland from one farm to another.


Peptide mapping of basic proteins by proteolysis in acetic acid/urea-minislab polyacrylamide gels.
A method to obtain peptide maps of basic proteins on acetic acid/urea (AU) -polyacrylamide minislab gels is presented. Basic proteins such as the histones are digested with Staphylococcus aureus V8 protease in the stacking gel (pH 4) of an AU-polyacrylamide minislab gel. As the peptides are resolved in the AU minislab gel on the basis of charge and size, it is possible to separate peptides containing modified amino acids from the unmodified, parent peptide. The peptide(s) containing the modified residue may be identified following electrophoresis on a second-dimension sodium dodecyl sulfate-polyacrylamide minislab gel. This procedure will be useful for comparing histone variants and for the study of histone modifications.


The proliferative and anti-apoptosis functions of KGF/KGFR contributes to bronchial epithelial repair in asthma.
This study aimed to investigate the effect of keratinocyte growth factor (KGF) on the apoptosis, proliferation, damage repair, intercellular adhesion, and inflammatory cytokine release of cultured 16HBE 14o-bronchial ECs in vitro. Bronchial epithelial cells (ECs) from all subjects were obtained by bronchoscopic brushing. The expression levels of KGF and its receptor KGFR in collected cells were determined using RT-qPCR and Western blotting. The apoptosis and adhesion molecules expression by KGF administration were determined using flow cytometry and Western blotting. This occurred when 16HBE 14o-cell lines cultured and were exposed to interferon-γ (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in vitro. The role of KGF on proliferation and damage repair were analyzed using CCK-8, EdU and wound closure assays after 16HBE 14o-cells were scraped. The effect of KGF on the release of inflammation related cytokines by damaged ECs was measured using ELISA kits. Compared with healthy controls, the KGF and KGFR expression and apoptosis significantly increased in collected cells from asthma patients. In vitro, treatment of KGF may limit IFN-γ and TNF-α induced apoptosis by inhibiting apoptosis-associated markers in the TNF signaling pathway. Besides, KGF could limit the release of TSLP, IL-25 and IL-33 by damaged 16HBE 14o-cells. On the contrary, KGF could promote the intercellular adhesion and wound closure of cultured 16HBE 14o-cells via the increased expression level of intercellular junction proteins ICAM-1, β-catenin, E-cad, and Dsc3. In conclusion, KGF and KGFR may help bronchial ECs repair in asthma via the inhibition apoptosis of ECs while the promotion of proliferation and migration of ECs.


Different effects of metformin on hypothalamic-pituitary-thyroid axis activity in levothyroxine-treated and levothyroxine-naïve women with non-autoimmune hypothyroidism.
Metformin was found to reduce thyrotrophin levels in subjects with hypothyroidism. This case-control study was aimed at comparing metformin action on hypothalamic-pituitary-thyroid axis activity between levothyroxine-treated and levothyroxine-naïve women with non-autoimmune thyroid hypofunction. The study included two groups of thyroid antibody-negative women with thyrotrophin levels in the range between 4.5 and 10 mIU/L and untreated prediabetes, matched for age, body mass index, thyrotrophin levels and glucose homeostasis markers. The first group had been treated for at least 6 months with levothyroxine, whereas the second group had not received thyroid hormones. All these women were then managed with metformin (3 g daily). Circulating levels of glucose, insulin, glycated haemoglobin, thyrotrophin, total and free thyroid hormones and prolactin were assessed at baseline and 6 months later. Thirty-two women (16 in each treatment arm) completed the study. At baseline, both groups differed only in free and total thyroxine levels. Metformin reduced glucose levels and glycated haemoglobin, improved insulin sensitivity and decreased thyrotrophin levels. The impact on insulin sensitivity and thyrotrophin was stronger in women simultaneously treated with levothyroxine than in women not receiving this hormone. In levothyroxine-treated patients, metformin slightly reduced prolactin levels. In both study groups, metformin treatment exerted a neutral effect on free and total thyroxine and triiodothyronine. The thyrotrophin-lowering effect of metformin correlated with the improvement in insulin sensitivity and in levothyroxine-treated women with the changes in prolactin levels. The obtained results suggest that metformin/levothyroxine combination therapy may be an interesting treatment option in women with non-autoimmune hypothyroidism poorly tolerating high-dose levothyroxine treatment.


Feature-based attention influences later temporal perception.
We investigated the influence of feature-based visual attention on later temporal perception. Although there is ample evidence that space-based attention modulates temporal perception, it is not known whether feature-based attention also serves this function. The present study combined a visual selection task with a temporal interval production task to determine whether feature-based attention interacted with temporal perception. The results indicated that temporal perception of visual stimuli depended on whether the same stimulus had been attended to or ignored in a previous visual selection task. The temporal production of previously ignored stimuli was longer than the temporal production of either previously attended to or novel stimuli. This is the first demonstration of the effect of feature-based attention on later temporal perception. We concluded that temporal perception is affected by previously ignored stimuli.


The distribution of dorsal root axons to laminae IV, V, and VI of the Macaque spinal cord: a quantitative electron microscopic study.
The projections of dorsal root axons to the deeper laminae (IV, V, and VI) of the Macaque spinal cord were examined by the use of experimentally induced degeneration following dorsal rhizotomy or by injection of dorsal root ganglia with tritiated amino acids followed by light and electron microscopic autoradiography. Following dorsal rhizotomy, neurofilamentous degeneration of synaptic profiles occurs in each of the three deep laminae, more commonly in laminae IV and V than in lamina VI. The neurofilamentous degeneration is seen both in central glomerular (C) profiles and in many of the round vesicle (R) profiles. Neurofilamentous degeneration occurs as early as 18 hours following rhizotomy and the degenerating terminals are most numerous at 3-4 days postrhizotomy. None are seen after 7 days survival. The neurofilamentous profiles form axodendritic and, occasionally, axosomatic synapses with neurons of the dorsal horn. They are also seen to be postsynaptic to flat vesicle (F) profiles in axoaxonal synapses. A second type of degeneration, electron-lucent degeneration, is seen in laminae V and VI, and only occasionally in lamina IV. The lucent degeneration occurs somewhat later after rhizotomy than does the neurofilamentous degeneration and reaches its peak at 5 days postrhizotomy. No lucent terminals are seen after 7 days survival. Electron-dense degeneration, so common in lamina II, is not seen in the deeper dorsal horn. Autoradiographic techniques show that both C and R terminals are labelled in the deeper dorsal horn. Both of these terminals form axodendritic synapses and a significant number are found to be postsynaptic in axoaxonal synapses. Most of the C terminals degenerate following rhizotomy or are labelled following injection of the parent dorsal root ganglia with tritiated amino acids. Approximately one-fifth of the R profiles are derived from dorsal roots. F profiles do not appear to be of dorsal root origin in any case. It is concluded that neurofilamentous alterations represent the degeneration of larger-diameter (A beta) axons which distribute to the deeper dorsal horn and that electron-lucent degeneration represents the termination of A delta fibers. Electron-dense degeneration thought to represent the termination of nonmyelinated axons (C fibers) in the superficial dorsal horn is not seen in the deeper dorsal and it is concluded that C fibers do not project to the deeper laminae.


Induction of a regulatory T cell type 1 response reduces the development of atherosclerosis in apolipoprotein E-knockout mice.
T helper type 1 (Th1) response plays a permissive role in atherosclerosis. We hypothesized that adoptive transfer of a novel subtype of T lymphocytes called regulatory T cells type 1 (Tr1) would inhibit Th1 responses by inducing a bystander immune suppression and therefore limit the development of atherosclerosis. Clones of ovalbumin (OVA)-specific Tr1 cells expanded in vitro were administered intraperitoneally (106 cells per mouse) with their cognate antigen (50 microg of OVA subcutaneously in complete Freund's adjuvant [CFA]) to female apolipoprotein E-knockout mice. A group of mice received only (OVA/CFA) immunization without Tr1 cells. Two other control groups received no immunization and were injected with either Tr1 cells or saline. After 9 weeks of treatment, mice injected with (OVA/CFA)+OVA-specific Tr1 cells showed a significant decrease in Th1 responses, as revealed by a decrease in OVA-specific IgG2a serum levels (P<0.0001), a decrease in the production of interferon-gamma (P<0.001), and an increase in interleukin-10 production (P<0.001) by cultured spleen and lymph T cells compared with controls. In addition, cytokine production by concanavalin A-stimulated spleen cells showed a clear switch to a regulatory immune response in mice treated with (OVA/CFA)+Tr1. This was associated with a significant reduction in atherosclerotic lesion size in both the thoracic aorta and aortic sinus of mice treated with (OVA/CFA)+Tr1 compared with controls (P=0.002 to P<0.0001). Plaques of mice injected with (OVA/CFA)+Tr1 showed significantly lower accumulation of macrophages and T cells than plaques of control mice. Tr1-type regulatory immune response reduces the development of experimental atherosclerosis.


Teaching the patient with a chronic wound.
To provide the physician and registered professional nurse with an overview of education strategies for patients with wounds. This continuing education activity is intended for physicians and nurses with an interest in learning more about strategies for educating patients with wounds. After reading the article and taking the test, the participant should be able to: 1. Describe the educational needs of the adult learner. 2. Discuss strategies for educating the adult learner in wound care.


Cutaneous Complications in Recipients of Lung Transplants: A Pictorial Review.
Lung transplant is now an established modality for a broad spectrum of end-stage pulmonary diseases. According to the International Society for Heart and Lung Transplantation Registry, more than 50,000 lung transplants have been performed worldwide, with nearly 11,000 recipients of lung transplants alive in the United States. With the increasing use of lung transplant, pulmonologists must be cognizant of the common as well as the unique posttransplant dermatologic complications. Immunosuppression, infections, and a variety of medications and environmental exposures can contribute to these complications. This review aims to provide representative pictures and describe the pathogenesis, epidemiologic characteristics, and clinical manifestations of dermatologic complications encountered among recipients of lung transplants.


[NGAL, biomarker of acute kidney injury in 2012].
Neutrophil Gelatinase Associated Lipocalin (NGAL) is one of the most promising biomarkers for acute kidney injury (AKI). Although urinary NGAL is intuitively more appropriate to apprehend renal injury, clinical data have accumulated on the potential interest of NGAL measured indifferently in serum or urine. Diagnostic performance of NGAL greatly varies across studies according to different factors such as the type of patients (pediatric versus adult) and the clinical situations (surgery versus intensive care). Overall, NGAL is presented as a useful tool to diagnose and predict AKI outcome but several issues (the absence of a unique pertinent threshold value, the incomplete analytical validation of its measurement and, its apparent limited clinical added value as compared to traditional AKI markers) remain to be addressed in order to definitely recommend its use in clinical practice.


Malignant triton tumor (MTT) of the neck.
Malignant Triton Tumor (MTT) is a rare, malignant periphere nerve sheath tumor with rhabdomyoblastic differentiation. One third of described MTT's were located at the head and neck region. One third of these are associated with neurofibromatosis type 1. MTT most often appears in the third decade. MTT's are very aggressive tumors with early metastases and the overall survival is poor (26%). Therefore, early diagnosis and correct treatment is of utmost importance. We report a case of MTT of the left supraclavicular region in a 41-year-old man. We present the pathological findings, both light and immunohistochemically.


Protective factors associated with American Indian adolescents' safer sexual patterns.
This paper presents findings from a research partnership with rural American Indian communities to identify protective factors associated with their adolescents' health-related behaviors including 1) delay of sexual debut; 2) not having had intercourse in the past 3 months; 3) birth control use among sexually active adolescents in the past 3 months; 4) condom use in the past 3 months. Our goal was to identify salient characteristics of students and their perceptions of family, school, and friends which could be incorporated or supported in future program planning for adolescents. A written survey was administered to 484 Indian students in Grades 6-12 from five rural schools. The survey measured several potential protective factors identified by Problem Behavior Theory, along with self-efficacy and cultural interest and knowledge. Logistic regression assessed the relationship of the protective factors and positive sexual behaviors. Factors significantly associated with abstention from intercourse and/or consistent use of birth control included perceived lower health-risk behavior of friends, higher perceived parental support, higher perceived parental knowledge and monitoring of the adolescent's activities and friends, a higher value on scholastic achievement, higher reported academic performance, and higher self-efficacy for safer sexual behaviors. This research suggests that Indian adolescents have several protective factors indigenous to their communities which are modifiable. Building on the unique cultural heritage of Indian communities, many of these factors may be addressed through community planned prevention programs.


Determining the burden of infectious diseases caused by carbapenem-resistant gram-negative bacteria in Spain.
To estimate the burden of nosocomial infections induced by carbapenem resistant Gram-negative (CRGN) pathogens in Spain, focusing on both the clinical and economic impact. The burden of disease was estimated using data from 2017 according to the availability of data sources. The impact, both clinical and economic, of the most frequent CRGN nosocomial infections (those produced by Klebsiella pneumoniae, Pseudomonasaeruginosa and Acinetobacter baumannii) was analysed. Incidence and mortality of CRGN nosocomial infections were estimated, as well as the direct and indirect costs produced by this health problem. Approximately 376,346 patients are believed to have suffered a nosocomial infection in Spain in 2017; 3.2% of them due to CRGN bacilli. Infections by carbapenem-resistant P. aeruginosa produced the highest mortality rates (2578 deaths) when compared with A. baumannii (1571) and K. pneumoniae (415). Total economic costs of CRGN nosocomial infections in Spain were estimated to be €472 million in 2017, with 83% of the total cost caused by direct costs. CRGN nosocomial infections have a high clinical impact on patients' lives, high mortality rates, and represent one of the hospitalisation episodes with the most associated costs. Efforts should be focussed to implement preventive policies in order to avoid infections due to CRGN pathogens and the resulting burden, and to reduce direct costs due to morbimortality, specifically in those infections produced by P. aeruginosa.


Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure. The Q10 Study Group.
Seventy-nine patients with stable chronic congestive heart failure were randomized into a double-blind, crossover placebo controlled study with 3-month treatment periods, where either 100 mg coenzyme Q10 (CoQ10) or placebo was added to conventional therapy. Mean patient age was 61 +/- 10 years, ejection fraction at rest was 22% +/- 10%, and maximal exercise tolerance was 91 +/- 30 W. The follow-up examinations included ejection fraction (primary objective), exercise test, and quality of life questions. Ejection fraction at rest, during a slight volume load, and during a submaximal supine exercise increased slightly compared with placebo: 24% +/- 12% versus 23% +/- 12% (NS), 25% +/- 13% versus 23% +/- 12% (P < .05), and 23% +/- 11% versus 22% +/- 11% (NS). Maximal exercise capacity increased from 94 +/- 31 W during the placebo period to 100 +/- 34 W during the CoQ10 period (P < .05). Total score for the quality of life assessment increased significantly from 107 +/- 23 during the placebo period to 113 +/- 22 during the CoQ10 period (P < .05). The results indicate that oral long-term treatment with 100 mg CoQ10 in patients with congestive heart failure only slightly improves maximal exercise capacity and the quality of life and that the clinical importance of this needs to be further evaluated.


Women's sexual empowerment and utilization of long-acting reversible contraceptives in Ghana: evidence from the 2014 demographic and health survey.
Long-Acting Reversible Contraceptives (LARC) contribute significantly to a decline in unintended pregnancies globally. However, not much is known about women's sexual empowerment and their utilization of Long-Acting Reversible Contraceptives in Ghana. The main objective of this study was to examine the association between women's sexual empowerment and LARC utilization in Ghana. We used data from 5116 sexually active women who participated in the 2014 Ghana Demographic and Health Survey. Women's sexual empowerment was defined as women's perception of their right to self-determination and equity in sexual relations, and their ability to express themselves in sexual decision-making. A sum of scores was created with four dichotomous items as sexual empowerment score (0 = low sexual empowerment; 1, 2, and 3 = medium sexual empowerment; and 4 = high sexual empowerment). Multivariable binary logistic regression analyses were performed to establish the association between women's sexual empowerment and the use of LARC. Pearson Chi-square test was used in data analysis. The results are presented as adjusted odds ratios (aOR), with their respective confidence intervals (CIs) at a statistical significance of p < 0.05. The prevalence of LARC utilization among sexually active women in Ghana was 6%. Majority of the women had medium sexual empowerment (91%). Although not statistically significant, the likelihood of utilizing LARC was lowest among women with high level of sexual empowerment (aOR = 0.62; CI = 0.27-1.43). On the other hand, Utilization of LARC increased with an increase in age. Women with parity four or more had higher odds of utilizing LARC as compared to women with zero birth (aOR = 9.31; CI = 3.55-24.39). Across religion, women who belong to the Traditional religion (aOR = 0.17; CI = 0.04-0.71) and Islam religion (aOR = 0.52; CI = 0.36-0.76) had lower odds of LARC utilisation as compared to Christian women. Women who make health decisions with someone else (aOR = 1.52; CI = 1.12-2.09) had higher odds of LARC utilisation as compared to women who make health decision alone. Age, health decision maker, parity and religion were found to have a significant relationship with LARC utilization. Specifically, uneducated women, unemployed women and women who practice traditional religion were less likely to utilise LARC. However, women's sexual empowerment did not have a significant relationship with LARC. There is therefore the need for planning interventions for LARC utilization in line with educating women on the benefits and potential side effects of LARC. Also, there is a need for interventions targeted at increasing access to LARC among sexually active women.


Direct visualizations of air flow in the human upper airway using in-vitro models.
A better understanding of airflow characteristics in the upper airway (UA) is crucial in investigating obstructive sleep apnea (OSA), particle sedimentation, drug delivery, and many biomedical problems. Direct visualization of air flow patterns in in-vitro models with realistic anatomical structures is a big challenge. In this study, we constructed unique half-side transparent physical models of normal UA based on realistic anatomical structures. A smoke-wire method was developed to visualize the air flow in UA models directly. The results revealed that the airflow through the pharynx was laminar but not turbulent under normal inspiration, which suggested that compared with turbulent models, a laminar model should be more suitable in numerical simulations. The flow predicted numerically using the laminar model was consistent with the observations in the physical models. The comparison of the velocity fields predicted numerically using the half-side and complete models confirmed that it was reasonable to investigate the flow behaviors in UA using the half-side model. Using the laminar model, we simulated the flow and evaluated the effects of UA narrowing caused by rostral fluid shift on pharyngeal resistance. The results suggested that fluid shift could play an important role in the formation of hypopnea or OSA during sleep.


GH overexpression decreases spermatic parameters and reproductive success in two-years-old transgenic zebrafish males.
Growth hormone (GH) transgenesis has been postulated as a biotechnological tool for improving growth performance in fish aquaculture. However, GH is implied in several other physiological processes, and transgenesis-induced GH excess could lead to unpredictable collateral effects, especially on reproductive traits. Here, we have used two-years-old transgenic zebrafish males to evaluate the effects of GH-transgenesis on spermatic parameters and reproductive success. Transgenic spermatozoa were analyzed in terms of motility, motility period, membrane integrity, mitochondrial functionality, DNA integrity, fertility and hatching rate. We have also performed histological analyses in gonad, in order to verify the presence of characteristic cell types from mature testes. The results obtained have shown that, even in transgenic testes present in all cells in normal mature gonads, a significant general decrease was observed in all spermatic and reproductive parameters analyzed. These outcomes raise concerns about the viability of GH-transgenesis appliance to aquaculture and the environmental risks at the light of Trojan gene hypothesis.


Neuromusculoskeletal models based on the muscle synergy hypothesis for the investigation of adaptive motor control in locomotion via sensory-motor coordination.
Humans and animals walk adaptively in diverse situations by skillfully manipulating their complicated and redundant musculoskeletal systems. From an analysis of measured electromyographic (EMG) data, it appears that despite complicated spatiotemporal properties, muscle activation patterns can be explained by a low dimensional spatiotemporal structure. More specifically, they can be accounted for by the combination of a small number of basic activation patterns. The basic patterns and distribution weights indicate temporal and spatial structures, respectively, and the weights show the muscle sets that are activated synchronously. In addition, various locomotor behaviors have similar low dimensional structures and major differences appear in the basic patterns. These analysis results suggest that neural systems use muscle group combinations to solve motor control redundancy problems (muscle synergy hypothesis) and manipulate those basic patterns to create various locomotor functions. However, it remains unclear how the neural system controls such muscle groups and basic patterns through neuromechanical interactions in order to achieve adaptive locomotor behavior. This paper reviews simulation studies that explored adaptive motor control in locomotion via sensory-motor coordination using neuromusculoskeletal models based on the muscle synergy hypothesis. Herein, the neural mechanism in motor control related to the muscle synergy for adaptive locomotion and a potential muscle synergy analysis method including neuromusculoskeletal modeling for motor impairments and rehabilitation are discussed.


Cricoarytenoid arthritis in a patient with ankylosing spondylitis.
A 50-year-old woman with a 27-year history of ankylosing spondylitis developed cricoarytenoid joint arthritis that was indicated by hoarseness, sore throat, and vocal cord fixation. This unusual manifestation of ankylosing spondylitis responded to treatment with moderate doses of prednisone, but it recurred when the cortiocosteroid therapy was discontinued.


Bile duct injuries in laparoscopic era.
The article describes the problem of bile duct injuries after laparoscopic cholecystectomy. Epidemiology, diagnostic and therapeutic management were presented based on the current literature review.


Beyond arousal and valence: the importance of the biological versus social relevance of emotional stimuli.
The present study addressed the hypothesis that emotional stimuli relevant to survival or reproduction (biologically emotional stimuli) automatically affect cognitive processing (e.g., attention, memory), while those relevant to social life (socially emotional stimuli) require elaborative processing to modulate attention and memory. Results of our behavioral studies showed that (1) biologically emotional images hold attention more strongly than do socially emotional images, (2) memory for biologically emotional images was enhanced even with limited cognitive resources, but (3) memory for socially emotional images was enhanced only when people had sufficient cognitive resources at encoding. Neither images' subjective arousal nor their valence modulated these patterns. A subsequent functional magnetic resonance imaging study revealed that biologically emotional images induced stronger activity in the visual cortex and greater functional connectivity between the amygdala and visual cortex than did socially emotional images. These results suggest that the interconnection between the amygdala and visual cortex supports enhanced attention allocation to biological stimuli. In contrast, socially emotional images evoked greater activity in the medial prefrontal cortex (MPFC) and yielded stronger functional connectivity between the amygdala and MPFC than did biological images. Thus, it appears that emotional processing of social stimuli involves elaborative processing requiring frontal lobe activity.


Aspect elucidation of a physicochemical pretreatment for continuous decrystallization.
The purpose of this study is to understand the operating conditions of a physicochemical pretreatment process for lignocellulosic biomass using homogeneous acid catalysts. Four parameters were studied: moisture content, acid catalyst, type of biomass and reactor morphology. The different types of biomass (perennial grasses: sugarcane bagasse, corn stover; flowering plants: cannabis (stalks and leaves); hardwoods (pulp and bark): poplar, sugar maple; softwood bark) were processed in a meat grinder with sulfuric acid. Furthermore, softwood bark was used to change the moisture content, acid catalyst and reactor morphology. Biomass moisture above 17 wt% yielded less than 50 wt% glucose. Sulfuric acid, by far, had the best performance with a 74.5 wt% glucose yield in the meat grinder. The glucose yield showed a direct relationship with the non-carbohydrate components of biomass (lignin, ash, etc).


Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis.
Systemic infusion of bone marrow mesenchymal stem cells (BMMSCs) yields therapeutic benefit for a variety of autoimmune diseases, but the underlying mechanisms are poorly understood. Here we show that in mice systemic infusion of BMMSCs induced transient T cell apoptosis via the FAS ligand (FASL)-dependent FAS pathway and could ameliorate disease phenotypes in fibrillin-1 mutated systemic sclerosis (SS) and dextran-sulfate-sodium-induced experimental colitis. FASL(-/-) BMMSCs did not induce T cell apoptosis in recipients, and could not ameliorate SS and colitis. Mechanistic analysis revealed that FAS-regulated monocyte chemotactic protein 1 (MCP-1) secretion by BMMSCs recruited T cells for FASL-mediated apoptosis. The apoptotic T cells subsequently triggered macrophages to produce high levels of TGFβ, which in turn led to the upregulation of CD4(+)CD25(+)Foxp3(+) regulatory T cells and, ultimately, immune tolerance. These data therefore demonstrate a previously unrecognized mechanism underlying BMMSC-based immunotherapy involving coupling via FAS/FASL to induce T cell apoptosis.


Liquid scintillation based quantitative measurement of dual radioisotopes (3H and 45Ca) in biological samples for bone remodeling studies.
Acute and prolonged bone complications associated with radiation and chemotherapy in cancer survivors underscore the importance of establishing a laboratory-based complementary dual-isotope tool to evaluate short- as well as long-term bone remodeling in an in vivo model. To address this need, a liquid scintillation dual-label method was investigated using different scintillation cocktails for quantitative measurement of (3)H-tetracycline ((3)H-TC) and (45)Ca as markers of bone turnover in mice. Individual samples were prepared over a wide range of known (45)Ca/(3)H activity ratios. Results showed that (45)Ca/(3)H activity ratios determined experimentally by the dual-label method were comparable to the known activity ratios (percentage difference ∼2%), but large variations were found in samples with (45)Ca/(3)H activity ratios in range of 2-10 (percentage difference ∼20-30%). Urine and fecal samples from mice administered with both (3)H-TC and (45)Ca were analyzed with the dual-label method. Positive correlations between (3)H and (45)Ca in urine (R=0.93) and feces (R=0.83) indicate that (3)H-TC and (45)Ca can be interchangeably used to monitor longitudinal in vivo skeletal remodeling.


Glatiramer acetate attenuates the pro-migratory profile of adhesion molecules on various immune cell subsets in multiple sclerosis.
An altered expression pattern of adhesion molecules (AM) on the surface of immune cells is a premise for their extravasation into the central nervous system (CNS) and the formation of acute brain lesions in multiple sclerosis (MS). We evaluated the impact of glatiramer acetate (GA) on cell-bound and soluble AM in the peripheral blood of patients with relapsing-remitting MS (RRMS). Fifteen patients treated de novo with GA were studied on four occasions over a period of 12 months. Surface levels of intracellular cell adhesion molecule (ICAM)-1, ICAM-3, lymphocyte function-associated antigen (LFA)-1 and very late activation antigen (VLA)-4 were assessed in T cells (CD3(+) CD8(+) , CD3(+) CD4(+) ), B cells, natural killer (NK) cells, natural killer T cells (NK T) and monocytes by five-colour flow cytometry. Soluble E-selectin, ICAM-1, ICAM-3, platelet endothelial cell adhesion molecule (PECAM)-1, P-selectin and vascular cell adhesion molecule (VCAM)-1 were determined with a fluorescent bead-based immunoassay. The pro-migratory pattern in RRMS was verified by comparison with healthy controls and was characterized by up-regulation of LFA-1 (CD3(+) CD4(+) T cells, B cells), VLA-4 (CD3(+) CD8(+) T cells, NK cells), ICAM-1 (B cells) and ICAM-3 (NK cells). Effects of GA treatment were most pronounced after 6 months and included attenuated levels of LFA-1 (CD3(+) CD4(+) ) and VLA-4 (CD3(+) CD4(+) , CD3(+) CD8(+) , NK, NK T, monocytes). Further effects included lowering of ICAM-1 and ICAM-3 levels in almost all immune cell subsets. Soluble AM levels in RRMS did not differ from healthy controls and remained unaltered after GA treatment. The deregulated pro-migratory expression profile of cell-bound AM is altered by GA treatment. While this alteration may contribute to the beneficial action of the drug, the protracted development and unselective changes indicate more secondary immune regulatory phenomena related to these effects.


Trypanosoma cruzi surface molecule gp90 downregulates invasion of gastric mucosal epithelium in orally infected mice.
Experiments were performed to elucidate why Trypanosoma cruzi isolates 573 and 587 differ widely in their efficiency to infect gastric mucosal epithelium when administered orally to mice. These isolates have the same surface profile and a similar capacity to enter host cells in vitro. Metacyclic forms of isolates 573 and 587 and the control CL isolate expressed similar levels of gp82, which is a cell invasion-promoting molecule. Expression of gp90, a molecule that downregulates cell invasion, was lower in the CL isolate. Consistent with this profile, approximately threefold fewer parasites of isolates 573 and 587 entered epithelial HeLa cells, as compared to the CL isolate. No difference in the rate of intracellular parasite replication was observed between isolates. When given orally to mice, metacyclic forms of isolate 573, like the CL isolate, produced high parasitemia (>10(6) parasites per ml at the peak), killing approximately 40% of animals, whereas infection with isolate 587 resulted in low parasitemia (<10(5) parasites per ml), with zero mortality. On the fourth day post-inoculation, tissue sections of the mouse stomach stained with hematoxylin and eosin showed a four to sixfold higher number of epithelial cells infected with isolate 573 or CL than with isolate 587. The rate of intracellular parasite development was similar in all isolates. Mimicking in vivo infection, parasites were treated with pepsin at acidic pH and then assayed for their ability to enter HeLa cells or explanted gastric epithelial cells. Pepsin extensively digested gp90 from isolate 573 and significantly increased invasion of both cells, but had minor effect on gp90 or infectivity of isolates 587 and CL. The profile of g82 digestion was similar in isolates 573 and 587, with partial degradation to a approximately 70 kDa fragment, which preserved the target cell binding domain as well as the region involved in gastric mucin adhesion. Gp82 from CL isolate was resistant to pepsin. Assays with parasites recovered from the mouse stomach 2 h after oral infection showed an extensive digestion of gp90 and increased infectivity of isolate 573, but not of isolate 587 or CL. Our data indicate that T. cruzi infection in vitro does not always correlate with in vivo infection because host factors may act on parasites, modulating their infectivity, as is the case of pepsin digestion of isolate 573 gp90.


Some considerations on the current debate about typing resolution in solid organ transplantation.
The shortage of suitable organs and achieved tolerance are uncontested main concerns in transplantation. Long waiting lists for deceased donors and limited numbers of living donors are the current scenarios. Kidney grafts from living donors have better overall survival compared to cadaveric and require less aggressive immunosuppressive regimens. The human leukocyte antigen (HLA) labs have the key role to test the recipient and donors compatibility based on typing and antibody profile. The current standard molecular procedure in solid organ transplantation is low-resolution typing, at the antigen level. In this commentary, the merits of high versus low degree of typing resolution in solid organ transplantation are discussed. Critical questions and reasons to bring high-resolution typing as a routine test in health system are considered. Specifically, with the introduction of the next-generation sequencing (NGS) in HLA, the pros and cons in living donation and benefits after deceased donation are critically evaluated. NGS has the potential to improve the transplant rates and the overall graft survival. Alternative strategies to increase in demanding the number of transplants are briefly highlighted.


Transcriptional responses of the marine diatom Chaetoceros tenuissimus to phosphate deficiency.
The planktonic diatom Chaetoceros tenuissimus sometimes forms blooms in coastal surface waters where dissolved inorganic phosphorus (P) is typically deficient. To understand the molecular mechanisms for survival under P-deficient conditions, we compared whole transcripts and metabolites with P-sufficient conditions using stationary growth cells. Under P-deficient conditions, cell numbers and photosynthetic activities decreased as cells entered the stationary growth phase, with downregulation of transcripts related to the Calvin cycle and glycolysis/gluconeogenesis. Therefore, metabolites varied across nutritional conditions. Alkaline phosphatase, phosphodiesterase, phytase, phosphate transporter, and transcription factor genes were drastically upregulated under dissolved inorganic P deficiency. Genes related to phospholipid degradation and nonphospholipid synthesis were also upregulated. These results indicate that C. tenuissimus rearranges its membrane composition from phospholipids to nonphospholipids to conserve phosphate. To endure in P-deficient conditions, C. tenuissimus modifies its gene responses, suggesting a potential survival strategy in nature.


Hepatic and renal tolerability of long-term naproxen treatment in patients with rheumatoid arthritis.
Clinical and laboratory assessments of hepatic and renal function in rheumatoid arthritis (RA) patients who received naproxen for up to 6 months during two randomized, double-blind studies comparing naproxen 375 mg twice daily (n = 286) with naproxen 750 mg twice daily (n = 300) were analyzed. Patient groups were segregated by dosage, duration of treatment, and age at entry (less than 65 years v greater than or equal to 65 years), and laboratory measurements of SGOT, SGPT, serum creatinine (Scr), and BUN were examined. Records of individual patients with clinically meaningful abnormalities in laboratory tests or adverse events of hepatic or renal origin were examined in detail. Over the duration of these studies, there were no clinically meaningful changes in mean laboratory values or differences in occurrences of abnormal values among the different patient groups. In both dosage groups, pretreatment incidences of clinically meaningful abnormalities in laboratory tests were similar to those in serial observations during treatment. Six patients who received naproxen 375 mg twice daily and four patients who received naproxen 750 mg twice daily had a hepatic or renal clinical event or distinctly abnormal laboratory value, but only three of these withdrew because of these problems. Occasional transient abnormalities of conventional laboratory tests of hepatic and renal function occurred in some patients during naproxen treatment. Such abnormalities called for careful patient monitoring but generally did not warrant immediate drug withdrawal.


Professional Burnout of Advanced Practice Providers Based on 2019 American Urological Association Census Data.
Burnout has been recognized as an occupational hazard among health care professionals. The objective of this study was to assess the extent and pattern of burnout in advanced practice providers (APPs) in urology by analyzing American Urological Association Census data. The American Urological Association conducts an annual census survey to all providers in the urological care community, including APPs. In the 2019 Census, the Maslach Burnout Inventory questionnaire was included to measure burnout among APPs. Demographic and practice variables were assessed to establish correlating factors to burnout. A total of 199 APPs (83 physician assistants and 116 nurse practitioners) completed the 2019 Census. Slightly more than 1 in 4 APPs experienced professional burnout (25.3% in physician assistants and 26.7% in nurse practitioners). Observed higher burnout rates were seen in APPs who were aged 45 to 54 (34.3%), women (29.6% vs 10.8% in men, p value <0.05), non-White (33.3% vs 24.9% in White), those who had 4-9 years of practice (32.4%) and those who practiced in academic medical centers (31.7%). Except for gender, none of the above observed differences were statistically significant. Using a multivariate logistic regression model, gender remained the only significant factor associated with burnout (women vs men with an odds ratio of 3.2 [95% confidence interval: 1.1-9.6]). Overall, APPs in urological care reported lower levels of burnout than urologists; however, there was a higher chance of female APPs experiencing higher professional burnout in comparison to their male counterparts. Future studies are needed to investigate possible reasons for this finding.


Bottled mineral water as a potential source of antibiotic resistant bacteria.
The antibiotic resistance phenotypes of the cultivable bacteria present in nine batches of two Portuguese and one French brands of commercially available mineral waters were examined. Most of the 238 isolates recovered on R2A, Pseudomonas Isolation agar or on these culture media supplemented with amoxicillin or ciprofloxacin, were identified (based on 16S rRNA gene sequence analysis) as Proteobacteria of the divisions Beta, Gamma and Alpha. Bacteria resistant to more than three distinct classes of antibiotics were detected in all the batches of the three water brands in counts up to 10² CFU/ml. In the whole set of isolates, it was observed resistance against all the 22 antimicrobials tested (ATB, bioMérieux and disc diffusion), with most of the bacteria showing resistance to three or more classes of antibiotics. Bacteria with the highest multi-resistance indices were members of the genera Variovorax, Bosea, Ralstonia, Curvibacter, Afipia and Pedobacter. Some of these bacteria are related with confirmed or suspected nosocomial agents. Presumable acquired resistance may be suggested by the observation of bacteria taxonomically related but isolated from different brands, exhibiting distinct antibiotic resistance profiles. Bottled mineral water was confirmed as a possible source of antibiotic resistant bacteria, with the potential to be transmitted to humans.


Acute aortic occlusion.
Acute aortic occlusion is a rare and emergent vascular event. Patients who present with this disorder have a classical history and physical examination consistent with occlusion of the distal aorta and resultant ischemia to the distal tissues. Time is of the essence in dealing with these patients. Aortography proved to be important in determining renal artery involvement in our patients. Based on this finding, we suggest that preoperative arteriograms be obtained. The method of treating these patients after arteriography should be to move quickly to the operating room. Patients with renal artery occlusion must be seriously considered for primary revascularization with either aortofemoral or aortoiliac reconstruction and thrombectomy or bypass of the occluded renal artery. If no renal artery involvement is revealed on arteriography, the initial operation should include an attempt to reestablish inflow by retrograde femoral thromboembolectomy under local anesthesia. If that fails, a decision must be made based on the patient's clinical status, whether a major vascular procedure would be tolerated. If so, primary revascularization or transabdominal thrombectomy should be attempted. If the patient is deemed unable to tolerate a major vascular procedure, then axillobifemoral bypass under local anesthesia should be performed. Postoperatively, the patient should be aggressively managed to prevent pulmonary and renal complications. Even with aggressive surgical management and postoperative care, these patients have an uncertain postoperative course. It is of primary importance that physicians realize that time is a critical factor and these patients must be referred to the appropriate care center promptly. Only by ensuring prompt surgical management can a mortality rate of less than 50 percent be expected.


A dipteran larva-pitcher plant digestive mutualism is dependent on prey resource digestibility.
Positive species interactions tend to be context dependent. However, it is difficult to predict how benefit in a mutualism changes in response to changing contexts. Nepenthes pitcher plants trap animal prey using leaf pitfall traps known as pitchers. Many specialized inquiline organisms inhibit these pitchers, and are known to facilitate the digestion of prey carcasses in them. Nepenthes gracilis traps diverse arthropod prey taxa, which are likely to differ greatly in the ease with which they may be digested, independently of inquilines, by plant enzymes. In this study, we used in vitro experiments to compare the nutritional benefit provided by phorid (scuttle fly) and culicid (mosquito) dipteran larvae to their host, N. gracilis, and to each other. The effects of phorids on N. gracilis nutrient sequestration were very variable, being positive for large prey which have low digestibility, but negative for small prey which are highly digestible. However, the effect of culicids on N. gracilis and the effects of culicids and phorids on each other were not significantly altered by prey type. These results show that a digestive mutualism is highly dependent on the digestibility of the resource-a context dependency that conforms well to the predictions of the stress-gradient hypothesis in facilitation research. Our findings have significant implications for many other digestive mutualisms, and also suggest that greater insights may be gained from the synthesis of concepts between the fields of mutualism and facilitation research.


Doppler ultrasound and supraorbital photoplethysmography for noninvasive screening of carotid occlusive disease.
Doppler ultrasound and supraorbital photoplethysmography were 95 per cent accurate in identifying or excluding significant carotid obstruction in 156 vessels of seventy-six consecutive patients undergoing arteriography. Plethysmography was more sensitive but less specific than Doppler ultrasound. These technics provide simple, rapid, and accurate detection of significant carotid occlusive disease.


N-terminal pro-B-type natriuretic peptide in the circulation of fetuses with cardiac malformations.
Cardiac malformations with impact on loading patterns have the potential to progress to irreversible loss of ventricular function during human fetal life. N-terminal pro-B-type natriuretic peptide (nt-proBNP) is a marker of cardiac dysfunction and involved in cardiac remodeling and fibrosis. We evaluated nt-proBNP levels in the circulation of human fetuses with cardiac defects. A total of 45 cases and 75 controls during the second half of gestation were recruited. Nt-proBNP concentrations were determined in venous specimens obtained by fetal blood sampling. Results were correlated to echocardiography and Doppler studies. Mean gestational age was 26.9 weeks (range 21.0-33.4 weeks). Levels of circulating nt-proBNP were elevated in fetuses with cardiac defects (mean 6,896 ng/L (range 595-42,479 ng/L) vs. 1,867 ng/L (73-3,751 ng/L), p < 0.001). In the presence of abnormal Doppler indices a further increase was detected (mean 11,287 ng/L (range 1,403-42,479 ng/L) vs. 4,659 ng/L (595-30,848 ng/L), p = 0.021). No difference was found in fetuses with co-existing growth restriction. Malformations were classified according to their hemodynamic effect. Compared to shunt defects nt-proBNP concentrations were significantly higher in left or right ventricular outflow tract obstruction with intact ventricular septum (mean 15,639 ng/L (range 2,301-42,479 ng/L) vs. 3,891 ng/L (595-13,752 ng/L), p = 0.013), and corresponded to the degree of ventricular dysfunction. In the circulation of human fetuses with cardiac defects levels of circulating nt-proBNP are elevated. Concentrations correlate with the type of myocardial wall stress. This finding supports a role for nt-proBNP as early indicator of intrauterine cardiovascular dysfunction and cardiac remodeling.


Prostate specific antigen versus prostate specific antigen density as a prognosticator of pathological characteristics and biochemical recurrence following radical prostatectomy.
The usefulness of prostate specific antigen density for predicting pathological stage and biochemical recurrence after radical prostatectomy has not been well defined. We investigated whether prostate specific antigen density yielded an advantage over total prostate specific antigen for predicting adverse pathological characteristics and disease recurrence following radical prostatectomy. A total of 13,434 men who underwent radical prostatectomy for clinically localized prostate cancer between 1984 and 2006 were included in this study. The study population was stratified by Gleason score (6 or less, 7, and 8 or greater), and the clinical and pathological characteristics of each group were compared. We constructed ROC curves and determined the ROC AUC and concordance index to specifically investigate the accuracy of prostate specific antigen and prostate specific antigen density for predicting pathological stage and biochemical recurrence. Prostate specific antigen density was better than prostate specific antigen for predicting extraprostatic extension and biochemical-free recurrence in patients with a biopsy Gleason score of 6 or less (each p <0.001). In patients with a biopsy Gleason score of 7 prostate specific antigen was more predictive than prostate specific antigen density for seminal vesicle involvement (p <0.001), lymph node involvement (p = 0.017) and biochemical-free recurrence (p <0.001). In men with a biopsy Gleason score of 8 or greater there was no statistical difference between prostate specific antigen and prostate specific antigen density in terms of prognostic value for pathological or clinical outcomes. Prostate specific antigen density is highly associated with pathological stage and biochemical-free survival following radical prostatectomy. In lower grade prostate cancers prostate specific antigen density is significantly more accurate for predicting extraprostatic extension and biochemical-free recurrence compared to total prostate specific antigen. It should be considered when counseling patients on outcomes following radical prostatectomy.


Nitrogen-rich based conjugated microporous polymers for highly efficient adsorption and removal of COVID-19 antiviral drug chloroquine phosphate from environmental waters.
Chloroquine phosphate (CQP) has been suggested as an important and effective clinical reliever medication for the 2019 coronavirus (COVID-19). Nevertheless, its excessive use will inevitably cause irreparable damage to the entire ecosystem, thereby posing a considerable environmental safety concern. Hence, the development of highly-efficient methods of removing CQP from water pollution sources, e.g., effluents from hospitals and pharmaceutical factories is significant. This study reported the fabrication of novel C-N bond linked conjugated microporous polymers (CMPs) (BPT-DMB-CMP) with multiple nitrogen-rich anchoring sites for the quick and efficient removal of CQP from aqueous solutions. The irreversible covalent C-N bond linked in the internal framework of BPT-DMB-CMP endowed it with good chemical stability and excellent adsorbent regeneration. With its predesigned functional groups (i.e., rich N-H bonds, triazine rings, and benzene rings) and large area surface (1,019.89 m2·g-1), BPT-DMB-CMP demonstrated rapid adsorption kinetics (25 min) and an extraordinary adsorption capacity (334.70 mg·g-1) for CQP, which is relatively higher than that of other adsorbents. The adsorption behavior of CQP on BPT-DMB-CMP corresponded with Liu model and mixed-order model. Based on the density functional theory (DFT) calculations, X-ray photoelectron spectroscopy (XPS), and adsorption comparisons test, the halogen bonding, and hydrogen bonding cooperates with π - π, C - H···π interactions and size-matching effect in the CQP adsorption system on BPT-DMB-CMP. The excellent practicability for the removal of CQP from real wastewater samples verified the prospect of practical application of BPT-DMB-CMP. BPT-DMB-CMP exhibited the application potentials for the adsorption of other antiviral drugs. This work opens up an efficient, simple, and high adsorption capacity way for removal CQP.


Systemic and cardiac neuroendocrine activation and severity of myocardial ischemia in humans.
The purpose of this study was to assess the effect of different degrees of ischemia on circulating and cardiac neurohormones and vasotone. Neuroendocrine activation and subsequent systemic vasoconstriction may complicate ischemia. Whether this relates to severity of ischemia and subsequent cardiac dysfunction, and whether neurohormonal balance in the ischemic area changes, is unknown. Fifty-six normotensive patients with coronary artery disease were evaluated during incremental atrial pacing. On the basis of ST segment changes, patients were classified in a nonischemic (n = 11) or ischemic group (n = 45), the latter patients were subsequently classified as lactate (n = 28) or nonlactate (n = 17) producing, to identify neurohormonal changes in the effluent of the ischemic myocardium. Angina occurred in 55%, 82% and 82% of patients in the nonischemic, lactate- and nonlactate-producing groups, respectively. Baseline hemodynamic variables and neurohormones were comparable in all groups, as were heart rate, rate-pressure product and coronary hemodynamic variables during pacing. In lactate producers, contractility did not improve, relaxation deteriorated, left ventricular filling pressure increased and cardiac output decreased during pacing, indicating more severe ischemia compared with that in nonlactate producers. Neurohormones did not change in the nonischemic group. In contrast, arterial and coronary venous catecholamines increased significantly more in lactate producers than in nonlactate producers (arterial norepinephrine by 68% vs. 36%, respectively). Moreover, arterial angiotensin II increased in lactate producers from a baseline mean +/- SEM of 6.8 +/- 0.9 to 9.7 +/- 1.6 pmol/liter (p < 0.05), accompanied by a sustained 23% increase in systemic resistance and arterial pressures. In lactate producers, baseline net cardiac norepinephrine release changed to net uptake during pacing (-0.05 +/- 0.02 vs. 0.06 +/- 0.05 nmol/min, p < 0.05). Epinephrine uptake increased in all patients with ischemia, albeit more in lactate producers. Circulating catecholamines and renin-angiotensin levels are activated, and systemic vasotone is increased in relation to the degree of ischemia. Cardiac epinephrine uptake increases, whereas net baseline norepinephrine release from the ischemic myocardium changes to net uptake. Modulation of this neurohormonal activation may provide an alternative mode to limit ischemia.


Effects of serotonin 5-HT(3) receptor antagonists on CRF-induced abnormal colonic water transport and defecation in rats.
The effects of corticotropin releasing factor (CRF) and serotonin (5-HT)(3) receptor antagonists on intestinal water transport are not well understood. Hence, we established a CRF-induced abnormal water transport model in rat colon, and evaluated the effects of 5-HT(3) receptor antagonists including ramosetron, alosetron, and cilansetron, and the antidiarrheal agent loperamide, in this model. In addition, the effects of 5-HT(3) receptor antagonists and loperamide on abnormal defecation induced by CRF in rats were examined. Colonic water transport was measured in colonic loops in conscious rats. Centrally administered CRF (3-30 microg/kg) markedly decreased colonic fluid loss, whereas oral administration of ramosetron (3, 30 microg/kg), alosetron (300 microg/kg), cilansetron (300 microg/kg), or loperamide (3 mg/kg) significantly inhibited it. Ramosetron (1-10 microg/kg), alosetron (10-100 microg/kg), cilansetron (10-100 microg/kg), or loperamide (0.3-3 mg/kg) also showed dose-dependent inhibition of CRF-induced defecation in rats. These results suggest that 5-HT(3) receptors are involved in both abnormal colonic water transport and defecation induced by CRF, and that the inhibitory effects of 5-HT(3) receptor antagonists on CRF-induced abnormal defecation partly result from their ameliorating action on colonic water transport.


Barbell velocity: a practical and precise method for predicting bench press strength in sedentary women.
Bench press one-repetition maximum (BP1RM) prediction models offer a timely approach to predict BP1RM while avoiding the limitations with traditional BP1RM testing. Interestingly, no models have determined the ability for a traditional weight, the 20.5 kg barbell, to predict BP1RM strength. Few models have exclusively examined females and sedentary individuals, leaving the accuracy of these models unknown for these populations. Therefore, this investigation sought to examine the ability for 20.5 kg barbell velocity to predict BP1RM in sedentary females. Nineteen sedentary females (21.79±1.43 years, 166.08±7.76 cm, 63.98±7.54 kg, 31.57±4.72 BP1RM) completed BP1RM testing and completed two additional visits to determine 20.5 kg barbell velocity from a single repetition separated by 7-10 days. Nineteen additional females (21.39±1.09 years, 164.31±7.37 cm, 67.34±9.32 kg, 32.75±5.09 BP1RM) served as a cross-validating group completing identical testing procedures. Regression analyses revealed that 20.5 kg barbell velocity accounted for 95% of the variance in BP1RM strength while presenting marginal standard error (1.34 kg) and mean absolute error (0.97 kg), with similar values observed in the cross-validating group (SEE: 2.13 kg, MAE: 1.56 kg). Predicted BP1RM values were not significantly different from actual BP1RM (P=0.43) nor were measures in barbell velocity between trials 1 and 2 (P=0.57), while displaying high reliability (ICC: 0.81). Measure bias between BP1RM methods was 0.449±1.651kg and the agreement between methods varied between -2.78 kg less and 0.3686 kg greater for 95% of the participants. The present data provides an accurate prediction model regarding BP1RM for sedentary females. These findings can reduce the limitations associated with traditional BP1RM testing while providing a practical and accurate BP1RM approximation with marginal error.


Elastic propagation of fast electron vortices through amorphous materials.
This work studies the elastic scattering behavior of electron vortices when propagating through amorphous samples. A formulation of the multislice approach in cylindrical coordinates is used to theoretically investigate the redistribution of intensity between different angular momentum components due to scattering. To corroborate and elaborate on our theoretical results, extensive numerical simulations are performed on three model systems (Si3N4, Fe0.8B0.2, Pt) for a wide variety of experimental parameters to quantify the purity of the vortices, the net angular momentum transfer, and the variability of the results with respect to the random relative position between the electron beam and the scattering atoms. These results will help scientists to further improve the creation of electron vortices and enhance applications involving them.


The factors present in regenerating muscles impact bone marrow-derived mesenchymal stromal/stem cell fusion with myoblasts.
Satellite cells, a population of unipotent stem cells attached to muscle fibers, determine the excellent regenerative capability of injured skeletal muscles. Myogenic potential is also exhibited by other cell populations, which exist in the skeletal muscles or come from other niches. Mesenchymal stromal/stem cells inhabiting the bone marrow do not spontaneously differentiate into muscle cells, but there is some evidence that they are capable to follow the myogenic program and/or fuse with myoblasts. In the present study we analyzed whether IGF-1, IL-4, IL-6, and SDF-1 could impact human and porcine bone marrow-derived mesenchymal stromal/stem cells (hBM-MSCs and pBM-MSCs) and induce expression of myogenic regulatory factors, skeletal muscle-specific structural, and adhesion proteins. Moreover, we investigated whether these factors could induce both types of BM-MSCs to fuse with myoblasts. IGF-1, IL-4, IL-6, and SDF-1 were selected on the basis of their role in embryonic myogenesis as well as skeletal muscle regeneration. We found that hBM-MSCs and pBM-MSCs cultured in vitro in the presence of IGF-1, IL-4, IL-6, or SDF-1 did not upregulate myogenic regulatory factors. Consequently, we confirmed the lack of their naïve myogenic potential. However, we noticed that IL-4 and IL-6 impacted proliferation and IL-4, IL-6, and SDF-1 improved migration of hBM-MSCs. IL-4 treatment resulted in the significant increase in the level of mRNA encoding CD9, NCAM, VCAM, and m-cadherin, i.e., proteins engaged in cell fusion during myotube formation. Additionally, the CD9 expression level was also driven by IGF-1 treatment. Furthermore, the pre-treatment of hBM-MSCs either with IGF-1, IL-4, or SDF-1 and treatment of pBM-MSCs either with IGF-1 or IL-4 increased the efficacy of hybrid myotube formation between these cells and C2C12 myoblasts. To conclude, our study revealed that treatment with IGF-1, IL-4, IL-6, or SDF-1 affects BM-MSC interaction with myoblasts; however, it does not directly promote myogenic differentiation of these cells.


A sensitive acetylcholinesterase biosensor based on gold nanorods modified electrode for detection of organophosphate pesticide.
A sensitive amperometric acetylcholinesterase (AChE) biosensor, based on gold nanorods (AuNRs), was developed for the detection of organophosphate pesticide. Compared with Au@Ag heterogeneous NRs, AuNRs exhibited excellent electrocatalytic properties, which can electrocatalytically oxidize thiocholine, the hydrolysate of acetylthiocholine chloride (ATCl) by AChE at +0.55V (vs. SCE). The AChE/AuNRs/GCE biosensor was fabricated on basis of the inhibition of AChE activity by organophosphate pesticide. The biosensor could detect paraoxon in the linear range from 1nM to 5μM and dimethoate in the linear range from 5nM to 1μM, respectively. The detection limits of paraoxon and dimethoate were 0.7nM and 3.9nM, which were lower than the reported AChE biosensor. The proposed biosensor could restore to over 95% of its original current, which demonstrated the good reactivation. Moreover, the biosensor can be applicable to real water sample measurement. Thus, the biosensor exhibited low applied potential, high sensitivity and good stability, providing a promising tool for analysis of pesticides.


Third ventriculostomy in shunt malfunction.
Endoscopic third ventriculostomy (ETV) is the treatment of choice for noncommunicating hydrocephalus. In the last decade, its routine use also has taken place in patients who have previously undergone shunt placement (secondary ETV). This study reviews the specific anatomy of the ventricular system in patients presenting with shunt malfunction, the criteria for patient selection, and the results of ETV performed as an alternative to shunt revision in cases of shunt malfunction or infection. The success rate of secondary ETV in well-selected cases is not different from that of primary ETV; it should be reasonable to offer all patients with blocked shunts and suitable anatomy indicating an obstructive cause the opportunity for shunt independence regardless of the original cause of the hydrocephalus. Shunt infection should not be considered a contraindication to ETV, even if the success rate may be lower. Considering the higher complication rate and higher risk of intraoperative failure, secondary ETV should be performed by expert neuroendoscopists.


Bridge Carbon Emissions and Driving Factors Based on a Life-Cycle Assessment Case Study: Cable-Stayed Bridge over Hun He River in Liaoning, China.
Due to the rapid growth of the construction industry's global environmental impact, especially the environmental impact contribution of bridge structures, it is necessary to study the detailed environmental impact of bridges at each stage of the full life cycle, which can provide optimal data support for sustainable development analysis. In this work, the environmental impact case of a three-tower cable-stayed bridge was analyzed through openLCA software, and more than 23,680 groups of data were analyzed using Markov chain and other research methods. It was concluded that the cable-stayed bridge contributed the most to the global warming potential value, which was mainly concentrated in the operation and maintenance phases. The conclusion shows that controlling the exhaust pollution of passing vehicles and improving the durability of building materials were the key to reducing carbon contribution and are also important directions for future research.


Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation.
Exposure to ionizing radiation induces complex stress responses in cells, which can lead to adverse health effects such as cancer. Although a variety of studies investigated gene expression and affected pathways in human fibroblasts after exposure to ionizing radiation, the understanding of underlying mechanisms and biological effects is still incomplete due to different experimental settings and small sample sizes. Therefore, this study aims to identify the time point with the highest number of differentially expressed genes and corresponding pathways in primary human fibroblasts after irradiation at two preselected time points. Fibroblasts from skin biopsies of 15 cell donors were exposed to a high (2Gy) and a low (0.05Gy) dose of X-rays. RNA was extracted and sequenced 2 h and 4 h after exposure. Differentially expressed genes with an adjusted p-value < 0.05 were flagged and used for pathway analyses including prediction of upstream and downstream effects. Principal component analyses were used to examine the effect of two different sequencing runs on quality metrics and variation in expression and alignment and for explorative analysis of the radiation dose and time point of analysis. More genes were differentially expressed 4 h after exposure to low and high doses of radiation than after 2 h. In experiments with high dose irradiation and RNA sequencing after 4 h, inactivation of the FAT10 cancer signaling pathway and activation of gluconeogenesis I, glycolysis I, and prostanoid biosynthesis was observed taking p-value (< 0.05) and (in) activating z-score (≥2.00 or ≤ - 2.00) into account. Two hours after high dose irradiation, inactivation of small cell lung cancer signaling was observed. For low dose irradiation experiments, we did not detect any significant (p < 0.05 and z-score ≥ 2.00 or ≤ - 2.00) activated or inactivated pathways for both time points. Compared to 2 h after irradiation, a higher number of differentially expressed genes were found 4 h after exposure to low and high dose ionizing radiation. Differences in gene expression were related to signal transduction pathways of the DNA damage response after 2 h and to metabolic pathways, that might implicate cellular senescence, after 4 h. The time point 4 h will be used to conduct further irradiation experiments in a larger sample.


Ochratoxin A and fumonisins (B1 and B 2) in maize from Balkan nephropathy endemic and non endemic areas of Croatia.
The occurrence of ochratoxin A, fumonisin B1 and B2 has been investigated in maize samples collected in 1996 (105 samples) and 1997 (104 samples) in 14 counties of Croatia, including Brodsko-Posavska county, the main area of Balkan endemic nephropathy in Croatia. Ochratoxin A and fumonisins co-occurred in 21% of the examined samples. In particular, ochratoxin A (OTA) was found in 10 samples (10%) of the 1996 and 36 samples (35%) of the 1997 crops with mean concentrations of positive samples of 37.9 ng/g and 57.1 ng/g, and highest concentrations at 223.6 ng/g and 613.7 ng/g, respectively. Similar incidence of OTA contamination was observed in 1996 samples from both endemic and non endemic areas of Balkan nephropathy, whereas a significant difference (P<0.01) was found between the two areas in 1997, with 50% and 20% incidence of contamination in the endemic and non endemic area, respectively, and relevant OTA mean concentration of positive samples of 73.4 ng/g and 20.2 ng/g. High incidence of infection byPenicillium spp. (potential OTA producers) was found in all tested samples, with mean values of 88% and 93% in samples of 1996 and 1997, respectively. With respect to fumonisin B1 (FB1) and B2 (FB2) all but one of the 1996 samples were contaminated, with highest and mean concentrations of positive samples (FB1+FB2) at 11661 ng/g and 645 ng/g, respectively. Similar incidence of positive samples (93%), but lower contamination levels (mean 134 ng/g, maximum 2524 ng/g) were found in 1997 samples. The results of fumonisin analysis were in agreement with the mycological analysis showing higher incidence of Fusarium infection in samples of 1996 with respect to those of 1997.These data provide additional information on the occurrence of ochratoxin A in Balkan endemic nephropathy areas and, for the first time, its co-occurrence with other nephrotoxic compounds, such as fumonisins, that may contribute to the disease development. However the finding of these mycotoxins in the non-endemic areas, also at high levels, do not allow to draw a conclusion about their role in the etiology of the disease.


Mycotoxins biosynthesized by plant-derived Fusarium isolates.
There is little information on secondary metabolites produced by Fusaria infecting crop plants other than cereals. Many members of Fusarium genus have the ability to colonise perennial crops with only scarce infection or disease symptoms or with no symptoms at all while still being detectable. Even in case of such asymptomatic infection, significant mycotoxin contamination of the plant tissues is possible. The aim of this study was to characterise the spectrum of Fusarium species isolates obtained from different plant hosts (like asparagus, garlic, pineapple, banana, rhubarb, peppers, rice, maize, wheat, and oncidium) and evaluate their ability to biosynthesize the most common mycotoxins in vitro. Among the F.proliferatum isolates, up to 57 % of them biosynthesized fumonisins at very high mass fractions, amounting to above 1000 μg g(-1), while other Fusarium species such as F. verticillioides, F. lactis, F. polyphialydicum, F. concentricum, F. temperatum, and F. fujikuroi formed fumonisins mostly at much lower level. Only F. ananatum and F. oxysporum did not produce these toxins. Co-occurrence of FBs with other mycotoxins [moniliformin (MON) and beauvericin (BEA)] was often observed and it was mainly F. proliferatum species that formed both mycotoxins (0.4 μg g(-1) to 41.1 μg g(-1) BEA and 0.1 μg g(-1) to 158.5 μg g(-1) MON).


Dynamics, outcomes and prerequisites of the first SARS-CoV-2 superspreading event in Germany in February 2020: a cross-sectional epidemiological study.
The first German SARS-CoV-2 outbreak was a superspreading event in Gangelt, North Rhine-Westphalia, during indoor carnival festivities called 'Kappensitzung' (15 February 2020). We determined SARS-CoV-2 RT-PCR positivity rate, SARS-CoV-2-specific antibodies, and analysed the conditions and dynamics of superspreading, including ventilation, setting dimensions, distance from infected persons and behavioural patterns. In a cross-sectional epidemiological study (51 days postevent), participants were asked to give blood, pharyngeal swabs and complete self-administered questionnaires. The SARS-CoV-2 superspreading event took place during festivities in the small community of Gangelt in February 2020. This 5-hour event included 450 people (6-79 years of age) in a building of 27 m × 13.20 m × 4.20 m. Out of 450 event participants, 411 volunteered to participate in this study. Primary outcome: infection status (determined by IgG ELISA). symptoms (determined by questionnaire). Overall, 46% (n=186/404) of participants had been infected, and their spatial distribution was associated with proximity to the ventilation system (OR 1.39, 95% CI 0.86 to 2.25). Risk of infection was highly associated with age: children (OR 0.33, 95% CI 0.267 to 0.414) and young adults (age 18-25 years) had a lower risk of infection than older participants (average risk increase of 28% per 10 years). Behavioural differences were also risk associated including time spent outside (OR 0.55, (95% CI 0.33 to 0.91) or smoking (OR 0.32, 95% CI 0.124 to 0.81). Our findings underline the importance of proper indoor ventilation for future events. Lower susceptibility of children/young adults indicates their limited involvement in superspreading.


[Research on method in avoiding the interference of poloxamer in determination of polysaccharides in thermosensitive gel].
To study a method in avoiding the interference of poloxamer in determination of polysaccharides in thermosensitive gel and develop an assay correspondingly. After extracting the freeze dried gel with acetic ether, detected it in colorimetric method. The interference of poloxamer was removed thoroughly, while the retention rate of the polysacchrarides showed to be 100.11% (n = 3). The average recovery was 102.6% (n = 6). The method shows to be simple, maneuverable, stable and well reproducible.


The Role of TRAIL in Apoptosis and Immunosurveillance in Cancer.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that selectively induces apoptosis in tumor cells without harming normal cells, making it an attractive agent for cancer therapy. TRAIL induces apoptosis by binding to and activating its death receptors DR4 and DR5. Several TRAIL-based treatments have been developed, including recombinant forms of TRAIL and its death receptor agonist antibodies, but the efficacy of TRAIL-based therapies in clinical trials is modest. In addition to inducing cancer cell apoptosis, TRAIL is expressed in immune cells and plays a critical role in tumor surveillance. Emerging evidence indicates that the TRAIL pathway may interact with immune checkpoint proteins, including programmed death-ligand 1 (PD-L1), to modulate PD-L1-based tumor immunotherapies. Therefore, understanding the interaction between TRAIL and the immune checkpoint PD-L1 will lead to the development of new strategies to improve TRAIL- and PD-L1-based therapies. This review discusses recent findings on TRAIL-based therapy, resistance, and its involvement in tumor immunosurveillance.


Detection of antibodies to strain-specific and cross-reactive antigenic determinants on the haemagglutinin of influenza viruses A/Texas/1/77 and A/Bangkok/1/79 in human sera. Brief report.
The antibody response to antigenic determinants on the haemagglutinin molecule of A/Texas/77 and A/Bangkok/79 strains was analysed by SRH of virus-absorbed sera, in human sera collected from persons of different ages following natural infection or immunization. The results have shown, as expected, low and high frequencies of strain-specific antibodies in sera of adults and young children respectively. However, in the latter group antibodies to cross-reactive antigens were also detected.


Telomeres and NextGen CO-FISH: Directional Genomic Hybridization (Telo-dGH™).
The cytogenomics-based methodology of Directional Genomic Hybridization (dGH™) emerged from the concept of strand-specific hybridization, first made possible by Chromosome Orientation FISH (CO-FISH), the utility of which was demonstrated in a variety of early applications, often involving telomeres. Similar to standard whole chromosome painting (FISH), dGH™ is capable of identifying inter-chromosomal rearrangements (translocations between chromosomes), but its distinctive strength stems from its ability to detect intra-chromosomal rearrangements (inversions within chromosomes), and to do so at higher resolution than previously possible. dGH™ brings together the strand specificity and directionality of CO-FISH with sophisticated bioinformatics-based oligonucleotide probe design to unique sequences. dGH™ serves not only as a powerful discovery tool-capable of interrogating the entire genome at the megabase level-it can also be used for high-resolution targeted detection of known inversions, a valuable attribute in both research and clinical settings. Detection of chromosomal inversions, particularly small ones, poses a formidable challenge for more traditional cytogenetic approaches, especially when they occur near the ends or telomeric regions. Here, we describe Telo-dGH™, a strand-specific scheme that utilizes dGH™ in combination with telomere CO-FISH to differentiate between terminal exchange events, specifically terminal inversions, and an altogether different form of genetic recombination that often occurs near the telomere, namely sister chromatid exchange (SCE).