Linking Species Functional Traits to Specific Biogeochemical Processes under Trawling Pressure.
The impact of otter trawling on the relationship between functional traits of benthic invertebrates and specific biogeochemical processes were investigated in the oligotrophic Cretan Sea. The fishery is managed through a seasonal closure during the summer. During two seasons (winter and summer) replicate samples were taken from the field from a commercial trawl ground and an adjacent control area. Environmental parameters related to sediment biogeochemistry were measured including particulate organic carbon, sedimentary organic carbon, bottom water and sedimentary chlorophyll a and phaeopigment concentrations as well as benthic oxygen consumption. A significant impact of trawling was recorded only for bottom water chlorophyll and sedimentary organic carbon. Furthermore, the links between species traits and specific ecosystem processes were affected by trawling, highlighting the importance of unique functional modalities on ecosystem functioning. The traits that mostly influenced benthic biogeochemistry in the control sites were related to bioturbation and burrowing activities. In contrast, in the trawled sites, the associated traits were related to more opportunistic lifestyles and deposit feeding species that do not act as bioturbators. Thus, under trawling disturbance, this shift can decouple the species-sediment relations and affect nutrient cycling.


High-resolution oesophageal manometry and 24-hour impedance-pH study in systemic sclerosis patients: association with clinical features, symptoms and severity.
To evaluate the associations between objectively measured gastroesophageal involvement using high-resolution manometry and 24- hour impedance-pH study, and clinical presentations in systemic sclerosis (SSc) patients. This cross-sectional study was conducted in University of Malaya Medical Centre (UMMC) with 31 consecutive SSc patients recruited into this study. Clinical symptoms of gastroesophageal involvement, high-resolution impedance-manometry and 24-hour impedance-pH monitoring were assessed. Their associations with serological features and other organ involvement were evaluated. Twenty-five (80.6%) patients had gastroesophageal reflux disease (GORD) symptoms, mainly heartburn (45.1%), regurgitation (32.2%) and dysphagia (29%). Using manometry, oesophageal dysmotility was detected in 24 (88.9%) patients, while hypotensive lower oesophageal sphincter (LOS) was observed in 17 (63%) patients. 21 (84%) patients had GORD based on pH study. Hypotensive LOS was significantly associated with presence of digital ulcers. The main gastroesophageal symptoms were absent in majority of the SSc patients including in those with severe gastroesophageal manifestations demonstrating failed peristalsis >75%, hypotensive LOS, Demeester score >200 and acid reflux >200 per day. Demeester score >200 is associated with severity of GORD symptoms. Demeester score >200 was also associated with restrictive lung pattern (p=0.001). Significant association between GORD severity (daily number of acid reflux episodes >200) and pulmonary fibrosis was seen (p=0.030). The presence and severity of gastroesophageal symptoms may not accurately reflect the seriousness of oesophageal involvement. GORD severity is associated with presence of restrictive lung pattern and pulmonary fibrosis. Oesophageal manometry and 24-hour pH study should be considered more frequently in the assessment of SSc patients.


Altered axonal targeting and short-term plasticity in the hippocampus of Disc1 mutant mice.
Carefully designed animal models of genetic risk factors are likely to aid our understanding of the pathogenesis of schizophrenia. Here, we study a mouse strain with a truncating lesion in the endogenous Disc1 ortholog designed to model the effects of a schizophrenia-predisposing mutation and offer a detailed account of the consequences that this mutation has on the development and function of a hippocampal circuit. We uncover widespread and cumulative cytoarchitectural alterations in the dentate gyrus during neonatal and adult neurogenesis, which include errors in axonal targeting and are accompanied by changes in short-term plasticity at the mossy fiber/CA3 circuit. We also provide evidence that cAMP levels are elevated as a result of the Disc1 mutation, leading to altered axonal targeting and dendritic growth. The identified structural alterations are, for the most part, not consistent with the growth-promoting and premature maturation effects inferred from previous RNAi-based Disc1 knockdown. Our results provide support to the notion that modest disturbances of neuronal connectivity and accompanying deficits in short-term synaptic dynamics is a general feature of schizophrenia-predisposing mutations.


Crystal structures of cisplatin bound to a human copper chaperone.
Copper trafficking proteins, including the chaperone Atox1 and the P(1B)-type ATPase ATP7B, have been implicated in cellular resistance to the anticancer drug cisplatin. We have determined two crystal structures of cisplatin-Atox1 adducts that reveal platinum coordination by the conserved CXXC copper-binding motif. Direct interaction of cisplatin with this functionally relevant site has significant implications for understanding the molecular basis for resistance mediated by copper transport pathways.


Ocean acidification alters foraging behaviour in Dungeness crab through impairment of the olfactory pathway.
Crustacean olfaction is fundamental to most aspects of living and communicating in aquatic environments and more broadly, for individual- and population-level success. Accelerated ocean acidification from elevated CO2 threatens the ability of crabs to detect and respond to important olfactory-related cues. Here, we demonstrate that the ecologically and economically important Dungeness crab (Metacarcinus magister) exhibits reduced olfactory-related antennular flicking responses to a food cue when exposed to near-future CO2 levels, adding to the growing body of evidence of impaired crab behaviour. Underlying this altered behaviour, we find that crabs have lower olfactory nerve sensitivities (twofold reduction in antennular nerve activity) in response to a food cue when exposed to elevated CO2 . This suggests that near-future CO2 levels will impact the threshold of detection of food by crabs. We also show that lower olfactory nerve sensitivity in elevated CO2 is accompanied by a decrease in the olfactory sensory neuron (OSN) expression of a principal chemosensory receptor protein, ionotropic receptor 25a (IR25a) which is fundamental for odorant coding and olfactory signalling cascades. The OSNs also exhibit morphological changes in the form of decreased surface areas of their somata. This study provides the first evidence of the effects of high CO2 levels at multiple levels of biological organization in marine crabs, linking physiological and cellular changes with whole animal behavioural responses.


Improving effectiveness of online learning for higher education students during the COVID-19 pandemic.
During the COVID-19 pandemic, online learning has become one of the important ways of higher education because it is not confined by time and place. How to ensure the effectiveness of online learning has become the focus of education research, and the role of the "online learning community" cannot be ignored. In the context of the Internet of Things (IoT), we try to build up a new online learning community model: (1) First, we introduce the Kolb learning style theory to identify different online learning styles; (2) Second, we use a clustering algorithm to identify the nature of different learning style groups; and (3) Third, we introduce the group dynamics theory to design the dimensions of the questionnaire and combine the Analytic Hierarchy Process (AHP) method to identify the key influencing factors of the online learning community. We take business administration majors and students in universities as an example. The results show that (1) as a machine learning method, the clustering algorithm method is superior to the random construction method in identifying different learning style groups, and (2) our method can well judge the importance of each factor based on hierarchical analysis and clarify the different roles of factors in the process of knowledge transfer. This study can provide a useful reference for the sustainable development of online learning in higher education.


Sleep, Workload, and Stress in Aerial Firefighting Crews.
BACKGROUND:The challenges of climate change and increasing frequency of severe weather conditions has demanded innovative approaches to wildfire suppression. Australia's wildfire management includes an expanding aviation program, providing both fixed and rotary wing aerial platforms for reconnaissance, incident management, and quick response aerial fire suppression. These operations have typically been limited to day visual flight rules operations, but recently trials have been undertaken extending the window of operations into the night, with the assistance of night vision systems. Already a demanding job, night aerial firefighting operations have the potential to place even greater physical and mental demands on crewmembers. This study was designed to investigate sleep, fatigue, and performance outcomes in Australian aerial firefighting crews.METHODS:A total of nine subjects undertook a 21-d protocol, completing a sleep and duty diary including ratings of fatigue and workload. Salivary cortisol was collected daily, with additional samples provided before and after each flight, and heart rate variability was monitored during flight. Actigraphy was also used to objectively measure sleep during the data collection period.RESULTS:Descriptive findings suggest that subjects generally obtained >7 h sleep prior to flights, but cortisol levels and self-reported fatigue increased postflight. Furthermore, the greatest reported workload was associated with the domains of 'performance' and 'mental demand' during flights.DISCUSSION:Future research is necessary to understand the impact of active wildfire response on sleep, stress, and workload on aerial firefighting crews.Sprajcer M, Roberts S, Aisbett B, Ferguson S, Demasi D, Shriane A, Thomas MJW. Sleep, workload, and stress in aerial firefighting crews. Aerosp Med Hum Perform. 2022; 93(10):749-754.


[Cardiovascular reactivity to emotional texts in subjects with low and high level of psychoticism].
The article presents the results of comparative study of groups of subjects with low and high level of psychoticism. Heart rate, heart rate responses to inspiratory and expiratory Valsalva maneuvers, and blood pressure were measured before and after presentation of the texts with validated negative content in groups of subjects with low and high psychoticism scores. It was hypothesized that subjects with high level of psychoticism would be less engaged in the processing of negative contents of the texts and their physiological reactivity (physiological resources submitted for support of cognitive processing) would be less pronounced compared to subjects with low level of psychoticism. Significant main effect of psychoticism was obtained for changes in heart rate to expiratory Valsalva maneuver after presentations of the texts. Significant interaction effects of gender and psychoticism were obtained for systolic blood pressure. Other cardiovascular variables were not sensitive to the level of psychoticism. These effects of psychoticism were independent of other individual traits, such as neuroticism, extraversion, lie (social desirability), anger, trait anxiety and depression.


Prediction of secondary structural elements in glycerol-3-phosphate dehydrogenase by comparison with other dehydrogenases.
The secondary structure of glycerol-3-phosphate dehydrogenase was predicted from its amino acid sequence. The pattern of helices and sheets within the first half of the polypeptide as well as specific marker residues were consistent with the properties of the NAD binding domain in other dehydrogenases. The second half of the sequence shows similarities with the catalytic domain of glyceraldehyde-3-phosphate dehydrogenase. The resulting two-domain structure of glycerol-3-phosphate dehydrogenase allows the correct environment for the B specificity of the nicotinamide ring and the L-glycerol 3-phosphate substrate.


The role of barren stalk1 in the architecture of maize.
The architecture of higher plants is established through the activity of lateral meristems--small groups of stem cells formed during vegetative and reproductive development. Lateral meristems generate branches and inflorescence structures, which define the overall form of a plant, and are largely responsible for the evolution of different plant architectures. Here, we report the isolation of the barren stalk1 gene, which encodes a non-canonical basic helix-loop-helix protein required for the initiation of all aerial lateral meristems in maize. barren stalk1 represents one of the earliest genes involved in the patterning of maize inflorescences, and, together with the teosinte branched1 gene, it regulates vegetative lateral meristem development. The architecture of maize has been a major target of selection for early agriculturalists and modern farmers, because it influences harvesting, breeding strategies and mechanization. By sampling nucleotide diversity in the barren stalk1 region, we show that two haplotypes entered the maize gene pool from its wild progenitor, teosinte, and that only one was incorporated throughout modern inbreds, suggesting that barren stalk1 was selected for agronomic purposes.


Anemia in general practice.
Among 4928 consecutive consultations in urban general practice in Mid-Norway anemia was found in 106 patients. Eighty-nine patients had their anemia worked out and treated by their general practitioner, 11 patients were referred to hospital or specialist, and in 6 patients no clear-cut reason for the anemia could be found. The patients could be broadly divided into four groups: iron deficiency in pregnancy (48%), iron deficiency secondary to bleeding (21%) anemia of chronic diseases (17%) and miscellaneous (7%).


Production of Arachidonic Acid and Eicosapentaenoic Acid by Mortierella alpina CBS 528.72 on Date Waste.
Arachidonic acid (ARA) and eicosapentaenoic acid (EPA) are important for human health and are produced by the fungus Mortierella alpina. Fermentation conditions may affect fatty acid profile of produced oil. Substrates in solid-state fermentation are usually renewable and low-cost agro-industrial waste. The aim of this research is to study simultaneous production of ARA and EPA by M. alpina CBS 528.72 in solid-state fermentation. Date waste and soybean meal served as carbon and nitrogen sources, respectively. Plackett-Burman design was used to evaluate the impact of eleven process variables on ARA and EPA production. Analysis of the results showed that the main variables with significant impact on production include seed age, and supplementation of linseed oil and nitrogen. These three variables were then studied in a central composite design for the optimization of production of both fatty acids. Finally, reconfirmation test was conducted to obtain experimental results from predicted optimum conditions. This report showed that simultaneous optimization of the production of ARA and EPA by M. alpina CBS 528.72 on date waste can be achieved by modification of process variables in solid-state fermentation.


Highly efficient extraction of lead ions from smelting wastewater, slag and contaminated soil by two-dimensional montmorillonite-based surface ion imprinted polymer absorbent.
The rapid, efficient and selective extraction of heavy metal ions is significant for wastewater pretreatment and metal ion recycle. Using montmorillonite as the template substrate and Pb2+ as template ions, a novel two-dimensional montmorillonite-based surface ion imprinted polymer (IIP-MMT) adsorbent is successfully synthesized via activators generated by electron transfer for atom transfer radical polymerization (AGET-ATRP). Batch adsorption experiments are performed to assess the properties of the imprinted polymer sorbent, along with its selectivity and reusability in practical extraction of Pb2+. It is interesting that the crosslinking density of the imprinted polymer has impact on the sorption property, where suitable density is coupled with the highest adsorption capacity and the best selectivity. Benefiting from the surface-imprinting technique and AGET-ATRP, IIP2-MMT is proved to own a highly effective Pb2+ adsorption capacity to reach 158.68 mg/g within 30 min, where the corresponding maximum adsorption capacity is 201.84 mg/g. Moreover, this material exhibits satisfactory stability and reusability that the high adsorptive capability of IIP-MMT retains more than 95% after six cycles. Thus, it is expected to reduce the wastewater disposal expenses. Besides, owing to the characteristics of PHEMA brushes and SHA chelating ligand, IIP-MMT has strong anti-interference and anti-blockage abilities to extract Pb2+ from smelting wastewater, slag and contaminated soil. Considering the low cost, excellent stability, high extraction efficiency, environmental friendliness, it is expected that the proposed material is very promising for treatment of heavy metals-contaminated wastewaters and soil, or ion recycle.


[Comparison of antibody responses to hepatitis B surface antigen among four recipient groups of hepatitis B vaccines that have been approved in Japan: evaluation using passive hemagglutination assay and chemiluminescent immunoassay].
In hepatitis B virus (HBV) infection-preventing programs, serum or plasma levels of antibody to hepatitis B surface antigen (anti-HBs) are important to determine whether individuals are protective or not. We compared anti-HBs responses using passive hemagglutination assay (Mycell) and chemiluminescent immunoassay (Architect) among four recipient groups of HB vaccines, Meinyu, HBY, Bimmugen and Heptavax II, that have been approved in Japan. Overall, in a total of 1875 vaccinees Mycell results showed recipient groups of Meinyu and HBY acquired higher anti-HBs levels than those of Bimmugen and Heptavax II. Comparison of anti-HBs responses by both Mycell and Architect in recipient groups of Meinyu (n=150), HBY (n=218), Bimmugen (n=260), and Heptavax II (n=47) demonstrated the order of vaccinees' responses, such as geometric mean titers, ratios of acquiring high antibody levels (Mycell titers over 1024, Architect measurements over 1000 mIU/mL), and ratios of having unsuccessful antibody responses (Mycell titers under 8, Architect measurements under 10 mIU/mL), were somewhat different between the two assays. Comparison of Architect measurements at given Mycell titers revealed Bimmugen-recipients showed significantly lower values than HBY- or Heptavax II-recipients. Around critical protective levels, 5 of 22 Bimmugen-recipients with Mycell titers 16 or 32 showed Architect measurements under 10 mIU/mL, while 8 of 11 Heptavax II-recipients with Mycell titers below 8 demonstrated Architect measurements over 10 mIU/mL. Thus, discrepancies in anti-HBs evaluation between Mycell and Architect seemed to partly depend on administered vaccines. These results indicate anti-HBs concentration should be evaluated carefully so that we could completely prevent HBV infection.


Limited Metabolic Effect of the CREBRFR457Q Obesity Variant in Mice.
The Arg457Gln missense variant in the CREBRF gene has previously been identified as driving excess body weight in Pacific/Oceanic populations. Intriguingly, Arg457Gln variant carriers also demonstrate paradoxical reductions in diabetes risk, indicating that the gene has a critical role in whole-body metabolism. To study the function of this variant in more detail, we generated mice on an FVB/N background with the Crebrf Arg458Gln variant knocked in to replace the endogenous Crebrf. The whole-body metabolic phenotype was characterized for male and female mice on a regular chow diet or an 8-week high-fat challenge. Regular assessment of body composition found that the Crebrf variant had no influence on total body weight or fat mass at any time point. Glucose tolerance tests demonstrated no obvious genotype effect on glucose homeostasis, with indirect calorimetry measures of whole-body energy expenditure likewise unaffected. Male chow-fed variant carriers displayed a trend towards increased lean mass and significantly reduced sensitivity to insulin administration. Overall, this novel mouse model showed only limited phenotypic effects associated with the Crebrf missense variant. The inability to recapitulate results of human association studies may invite reconsideration of the precise mechanistic link between CREBRF function and the risks of obesity and diabetes in variant allele carriers.


Respiratory Involvement in Children with Inflammatory Bowel Disease.
Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are systemic diseases with a variety of extra-intestinal manifestations. Respiratory involvement, whether clinically symptomatic or latent, may be more common than previously thought. As opposed to adults, most of the cases in children involve Crohn's disease. The pathogeneses of the pulmonary manifestations are obscure. The inflammatory process is not restricted to the bowel as has been suggested by findings of high levels of fractional exhaled nitric oxide (FeNO) in the airways. Increased FeNO has been reported even during clinical remission, while increasing further during exacerbations. Pulmonary manifestations develop usually after the onset of the bowel disease; however, they may emerge after colectomy and cessation of therapy. Pulmonary lesions in children usually involve the lung parenchyma with granulomatous infiltrates. Other less common injuries involve the airways and the pleura. The most prevalent pathologies in adults are bronchiectasis, cryptogenic organizing pneumonia, and small airway disease. Pulmonary involvement in IBD is often latent or sub-clinical and may be detected solely by laboratory or imaging techniques. Abnormalities in pulmonary function tests (PFTs) are not consistent except for low-diffusion capacity for carbon monoxide, which was found in both children and adults. High-resolution computed tomography (CT) is a sensitive tool for detecting lung involvement and may reveal abnormalities even when PFTs are normal and the patient is asymptomatic. Medications used for IBD, especially nonsteroidal anti-inflammatory drugs, are also a risk factor for lung injury. Treatment of pulmonary involvement often includes systemic corticosteroids with subsequent prolonged treatment of inhaled steroids in appropriate selected cases. Other immune-modulators have been tried. Pediatricians, especially those treating children with IBD, pediatric gastroenterologists, and pediatric pulmonologists should have a high index of suspicion and be aware of tools to be used in the assessment and treatment of pulmonary complications in IBD.


Beyond the Quality Illusion: The Learning Era.
By highlighting the intangible, personal, contextual, and illusory nature of "quality," the authors reconceptualize quality improvement as a pluralistic and moral journey. They imagine a new era of quality improvement in which patients and health care providers work together to understand and achieve quality. The authors recommend, for the path forward, a "travel kit" of 10 crucial elements-compassion, deliberation, flexible goals, ownership, the engagement of patients, the inclusion of payers, the involvement of learners, feedback loops, the fostering of learning, and the application of different sources of knowledge-to reframe quality improvement in a new era of learning.


Agreement Between International Radiologists on the Appropriateness and Urgency in Lumbar Spine MRI Referrals.
To determine how radiologists across health-care jurisdictions internationally assess the appropriateness and urgency levels of lumbar spine Magnetic Resonance Imaging MRI referrals. Clinical information was extracted from 203 lumbar spine MRI referrals. Texts were divided into 10 datasets and embedded into a software to facilitate the classification process. Participant radiologists were recruited at the Image Perception Lab, at the Radiological Society of North America Congress, 2019 and through the institution radiology network. Radiologists were asked if they use referral guidelines in their practices. Radiologists assigned appropriateness and urgency levels based on the referral text. Appropriateness level descriptors were: indicated, indicated but needs more information or not indicated. Urgency levels were categorized: urgent, semi-urgent, or not urgent. All cases containing neurological symptoms with/without red flags were extracted and exact agreement between radiologists' responses on the indication status was calculated. Seventy radiologists from 25 countries participated; 42% of participants indicated non-use of referral guidelines. Poor-moderate radiology agreements were recorded for appropriateness and referral urgency level decisions. 79.6% of responses indicated that cases containing neurological symptoms with/without red flags were indicated for scanning. Despite referral guidelines promotion, nearly half of participants stated non-usage. Subsequently, a varied agreement levels were found in assigning the appropriateness of the referrals. Appropriateness of referrals with neurological symptoms (with/without red flags) recorded good agreement.


Integrated annotation and analysis of genetic variants from next-generation sequencing studies with variant tools.
Storing, annotating and analyzing variants from next-generation sequencing projects can be difficult due to the availability of a wide array of data formats, tools and annotation sources, as well as the sheer size of the data files. Useful tools, including the GATK, ANNOVAR and BEDTools can be integrated into custom pipelines for annotating and analyzing sequence variants. However, building flexible pipelines that support the tracking of variants alongside their samples, while enabling updated annotation and reanalyses, is not a simple task. We have developed variant tools, a flexible annotation and analysis toolset that greatly simplifies the storage, annotation and filtering of variants and the analysis of the underlying samples. variant tools can be used to manage and analyze genetic variants obtained from sequence alignments, and the command-line driven toolset could be used as a foundation for building more sophisticated analytical methods. variant tools consists of two command-line driven programs vtools and vtools_report. It is freely available at http://varianttools.sourceforge.net, distributed under a GPL license. firstname.lastname@example.com.


Chronic intermittent but not constant hypoxia decreases NAA/Cr ratios in neonatal mouse hippocampus and thalamus.
Chronic constant hypoxia (CCH) and chronic intermittent hypoxia (CIH) are known to have deleterious effects on the central nervous system. Because of the difference in the pattern of hypoxic exposure, it is possible that the pathological outcome would vary. The N-acetyl aspartate/creatine (NAA/Cr) ratio is a reliable marker of neuronal integrity, and this can be noninvasively measured by proton nuclear magnetic resonance spectroscopy. P2 CD1 mouse pups with their dams were exposed to either CCH, where the Fi(O(2)) was maintained at 11% continuously or to CIH, where the Fi(O(2)) was varied between 21 and 11% every 4 min. P30 mice exposed to intermittent hypoxia for 4 wk demonstrated a significant decrease in the NAA/Cr ratio in the hippocampus and thalamus, which was reversed by a subsequent exposure to 4 wk of normoxia. Meanwhile, mice exposed to 4 wk of constant hypoxia did not demonstrate any differences in their NAA/Cr ratios from controls in these brain regions. These results indicate that an intermittent pattern of hypoxic exposure may have a more adverse effect on neuronal function and integrity than a continuous one. The reversal of NAA/Cr levels to baseline during the return to normoxia indicates that therapeutic strategies targeted at alleviating the intermittent hypoxic stress in diseases, such as obstructive sleep apnea, have the potential for inducing significant neurocognitive recovery in these patients.


First Report of Blood Parasites in Black-Capped Sparrow (Arremon abeillei) from Neotropical Dry Deciduous Forest.
Avian haemosporidian parasites (Order: Haemosporida) are a diverse group of microorganisms that spend part of their life cycle in the erythrocytes of avian hosts. Parasite presence has been confirmed in all Ecuadorian regions, but some ecosystems, such as the deciduous dry forest of the Coastal region, have not been evaluated for parasite presence. Data on presence or absence, and prevalence, of haemosporidian blood parasites were obtained from avian blood samples collected in two different dry deciduous forests in Guayaquil, Ecuador: Bosque Protector Prosperina and Área Nacional de Recreación Parque Lago. Mist netting was performed between December 2018 and September 2019; blood smears were prepared from blood taken from 35 individuals of 20 bird species and all samples were analyzed by optical microscope observation. Most species showed no evidence of parasite infection, but haemosporidia were found on a blood smear obtained from a Black-capped Sparrow, Arremon abeillei (Passerelleidae), confirming this species as a newly discovered host of blood parasites.


Sugared soda consumption and dental caries in the United States.
Because of the complexity of the caries process, the potential cariogenicity of specific food items is difficult to assess. The purpose of this study was to investigate the associations between sugared soda consumption and caries. Dietary and dental examination data from the 1988-94 Third National Health and Nutrition Examination Survey (NHANES III) were used. From the food frequency questionnaire and 24-hour recall data, significant associations between DMFS and soda consumption were generally seen in persons over age 25. No differences in DMFS, relative to soda consumption, were seen in persons under age 25, or in analyses of dfs for children under age 12. The observed associations could be due to the cumulative effects of the long-term consumption of sugared soda. The absence of apparent effects of sugared soda consumption in younger people may also be related to the increased use of fluorides since the 1960s.


Use of Ferrule Rings as Stress Dissipators in Temporomandibular Joint Intramedullary Implants: A Finite Element Analysis Study.
The use of temporomandibular joint (TMJ) implants is considered to be a reliable treatment for some TMJ disorders when TMJ anatomical integrity is compromised. Among all of the designs proposed for these devices, intramedullary approaches are relatively new, and they may offer several advantages compared to those of past models with a lateral approach. In this report, we use finite element analysis (FEA) to calculate stress forces of a TMJ implant featuring a ferrule ring, which is frequently used in engineering as a stress distractor to reduce the splinter effect. Our analysis suggests that the addition of a ferrule ring in the TMJ implant helps to reduce von Mises stresses in the device and displacement forces in the volume and surface of the implant. These results suggest that including a ferrule ring in a TMJ implant may contribute to the stability and outcome of a TMJ implant by reducing component stress and displacement forces.


Structural complexity in the rare earth metallocene hydride complexes, [(C₅Me₅)₂LnH]₂.
X-ray crystallographic data obtained on the metallocene hydrides, [(C5Me5)2LnH]2 (Ln = Gd, Tb, and Dy), of interest for their magnetic properties, have revealed unexpected structural variability in a closely related series of rare earth complexes that can complicate magnetic analysis. Crystals of the two larger metals, Gd and Tb, were structurally straightforward and isomorphous with crystals of [(C5Me5)2SmH]2. However, only for Tb were the locations of the hydride ligands in this structural type identified for the first time and found to be consistent with a (C5Me5)2Ln(μ-H)2Ln(C5Me5)2 structure. In contrast, for Ln = Dy, the [(C5Me5)2H](3-) ligand set does not appear to have one optimum crystal structure. Two different types of crystals and one other solid form of [(C5Me5)2DyH]2 were repeatedly isolated upon crystallization and demonstrated that the structure of any particular crystalline sample selected for magnetic analysis could be variable. Asymmetric structures with a single hydride bridge, (C5Me5)2Dy(μ-H)DyH(C5Me5)2, were identifiable for the two crystalline forms. This demonstrated uncertainty in structure and highlights the importance of having a coordination environment with one preferred form for magnetically interesting complexes.


Diffusion of aniline blue injected into the thyroarytenoid muscle as a proxy for botulinum toxin injection: an experimental study in cadaver larynges.
Endolaryngeal injection of botulinum toxin into the thyroarytenoid (TA) muscle is one of the methods for treatment of focal laryngeal dystonia. However, after treatment, there is variation in laryngeal configuration as well as the side effects reported by patients. As a consequence of the functional variability of results, it was hypothesized that botulinum toxin diffuses beyond the limits of the muscle into which it is injected. After injection of botulinum toxin into the TA muscle for the treatment of focal laryngeal dystonia, patients differ in terms of laryngeal configuration and side effects. We hypothesized that this toxin diffuses from the target muscle to adjacent muscles. The TA muscles of 18 cadaver larynges were injected with aniline blue (0.2 mL). After fixation in formaldehyde and nitric acid decalcification, the larynges were sectioned in the coronal plane and the intrinsic muscles were analyzed. We found diffusion of aniline blue to the lateral cricoarytenoid muscle, cricothyroid muscle, and posterior cricoarytenoid muscle in 94.3%, 42.9%, and 8.6% of the cases, respectively. In terms of the degree of diffusion to adjacent muscles, we found no differences related to the size (height and width) of the TA muscle or to gender. Our findings suggest that diffusion of botulinum toxin from its injection site in the TA muscle to the lateral cricoarytenoid muscle is likely in most cases. On the other hand, diffusion to the cricothyroid muscle occurs in approximately half of cases and diffusion to the posterior cricoarytenoid muscle occurs in very few cases.


Successful treatment of fulminant community-acquired Pseudomonas aeruginosa necrotizing pneumonia in a previously healthy young man.
This report presents a case of fulminant community-acquired Pseudomonas aeruginosa necrotizing pneumonia in a previously healthy young man, including an analysis of the virulence of the P.aeruginosa isolated from the patient. The patient was successfully treated with intensive care and antibiotic treatment. This study analyzed the pathogenicity of the isolated strain both in vivo (using a mouse pneumonia model) and in vitro (using biofilm production), but could not explain how an otherwise healthy young man developed such severe community-acquired P.aeruginosa pneumonia. Although rare in community-acquired pneumonia, P.aeruginosa infection should be considered in patients with severe rapidly progressive pneumonia.


Solar optics-based active panel for solar energy storage and disinfection of greywater.
Smart city and innovative building strategies are becoming increasingly more necessary because advancing a sustainable building system is regarded as a promising solution to overcome the depleting water and energy. However, current sustainable building systems mainly focus on energy saving and miss a holistic integration of water regeneration and energy generation. Here, we present a theoretical study of a solar optics-based active panel (SOAP) that enables both solar energy storage and photothermal disinfection of greywater simultaneously. Solar collector efficiency of energy storage and disinfection rate of greywater have been investigated. Due to the light focusing by microlens, the solar collector efficiency is enhanced from 25% to 65%, compared to that without the microlens. The simulation of greywater sterilization shows that 100% disinfection can be accomplished by our SOAP for different types of bacteria including Escherichia coli. Numerical simulation reveals that our SOAP as a lab-on-a-wall system can resolve the water and energy problem in future sustainable building systems.


Factors and complications affecting catheter and technique survival with permanent single-lumen dialysis catheters.
This long-term study on the outcome of permanent silicone single-lumen dialysis catheters consisted of 43 surgically inserted catheters in 33 patients. All catheters were attached to a pressure-pressure single-cannula dialysis system. Technique and catheter survival were 80 and 59% at 1 year, and 63 and 50% at the 3rd year respectively. These parameters were not different in older patients (> or = 70 years, n = 12). Factors corresponding to a less successful outcome were placement in the left jugular vein (3-month actuarial survival of 44%) and absence of distal side holes (1-year actuarial survival of 44%). Insertion in both subclavian veins was not different to the classical right jugular vein. Infectious complications (incidence of 0.72 per 1000 catheter days) often caused simultaneous catheter and technique failure (14 versus 15%), whereas inadequate flow (incidence of 2 per 1000 catheter days) caused catheter rather than technique failure (30 versus 12%). The incidence of both complications declined significantly with time after insertion during the follow-up period. The first 3 months after insertion were more predisposed to the occurrence of inadequate flow than catheter-related infections. The general performance of these permanent single-lumen catheter devices justifies their long-term application in haemodialysis, even as a first choice of vascular access, especially in the elderly. Insertion in the left jugular vein and use of catheters without side holes should be avoided, providing a better catheter survival.


Energy and muscular contraction.
In this paper, a model of the chemical energy conversion into mechanical energy is presented. According to this model, for each stage, the transfer of the energy is produced in the framework of a polymolecular system composed by a donor molecule, an enzyme and an acceptor molecular couple. The energy is released in the form of two quanta of electronic excitation. The transfer of the energy determines the change of the orbital directions, as well as the ionic constellations previously fixed at the level of the donor molecule and at the level of the acceptor molecular couple. Subsequently, an allosteric modification of the enzyme which connects the donor with the acceptor molecular couple is produced. The conversion of the chemical energy into mechanical energy is explained by means of the ions movement and by the conformational changes of the enzymes involved in the processes of the energy transfer.


Cell-based detection of electrochemical oxidative stress by a fluorescent tryptophan intermediate.
The present study suggests a sensitive and rapid cell analysis method to evaluate the oxidative stress produced in a physiological culture medium, by anodic electrochemical products. The detection of these oxidizing agents, probably involving hypochlorite, is carried out by measuring the presence of an oxidized tryptophan intermediate, entrapped and stabilized in the cell cytoplasm. The formation of this tryptophan intermediate depends solely on the presence of a free tryptophan in the extracellular medium near the anode. This intermediate possesses a characteristic emission maximum at λ~560 nm, which can be abolished by the presence of anti-oxidants in the media during the cells' exposure to electric current. However, this intermediate's emission is unaffected by increased concentrations of intracellular anti-oxidants. This suggests that the anodic produced unstable tryptophan intermediate permeates the cell plasma membrane and becomes stabilized by cytoplasmic proteins. Tryptophan oxidative intermediates with similar spectra could also be formed by the chemical reaction of hypochlorite with tryptophan in solution. The analysis of the intracellularly stabilized tryptophan intermediate by flow cytometry can be used for measuring external oxidation stress without the disturbance of intracellular anti-oxidative capacity.


Imido Analogues of Common Oxo Anions: A New Episode in the Chemistry of Cluster Compounds.
Oxo anions of p- and d-block elements, for example, SiO(4)(4-), PO(4)(3-), SO(4)(2-), and CrO(4)(2-), are commonly encountered species. The full or partial replacement of the oxo ligands by isoelectronic imido (NR) groups generates homoleptic polyimido anions of the type [E(NR)(x)](z-) or heteroleptic imidooxo anions with the general formula [O(y)E(NR)(x-y)](z-) (where E=main group element or transition metal). The alkali metal derivatives of this new class of anions form ternary or quaternary cluster systems, respectively. The structures of these clusters can be rationalized in terms of the self-assembly of fundamental building blocks. An understanding of the factors that control this process may allow the design of functional materials with specific properties. In addition, these anions are attracting attention as multidentate ligands with unique electronic and stereochemical properties that may engender novel metal-centered chemistry.


Prunella vulgaris aqueous extract attenuates IL-1β-induced apoptosis and NF-κB activation in INS-1 cells.
We previously reported that Prunella vulgaris aqueous extract (PVAE) promotes hepatic glycogen synthesis and decreases postprandial hyperglycemia in ICR mice. Inflammatory cytokines play a critical role in the pathogenesis of diabetes. This study was designed to examine whether PVAE has a protective effect on IL-1β-induced apoptosis in INS-1 cells. INS-1 pancreatic β cells were plated at 2×10(6)/ml and treated with PVAE (100 µg/ml) 30 min before the cells were challenged with IL-1β (10 ng/ml). Untreated INS-1 cells served as control. INS-1 cell cytotoxicity was examined by MTT and lactate dehydrogenase (LDH) activity assays. Caspase-3 activity and activation of the apoptotic signaling pathway were analyzed by western blotting. NF-κB binding activity was examined by EMSA. The levels of inflammatory cytokines in the supernatant were measured by ELISA. IL-1β treatment significantly induced INS-1 cell death by 49.2%, increased LDH activity by 1.5-fold and caspase-3 activity by 7.6-fold, respectively, compared with control cells. However, PVAE administration significantly prevented IL-1β-increased INS-1 cell death and LDH activity and attenuated IL-1β-increased caspase-3 activity. Western blot data showed that PVAE also significantly attenuated IL-1β-increased Fas, FasL and phospho-JNK levels in the INS-1 cells. In addition, PVAE treatment significantly attenuated IL-1β-increased NF-κB binding activity and prevented IL-1β-increased TNF-α and IL-6 expression in INS-1 cells. Our data suggest that PVAE has a protective effect on IL-1β-induced INS-1 cell apoptosis. PVAE also attenuates IL-1β-increased NF-κB binding activity and inflammatory cytokine expression in INS-1 cells. PVAE may have a benefit for type I diabetic patients.


Three new constituents, latifolinal, latifolidin and cordicinol, from the fruits and leaves of Cordia latifolia.
Isolation and structure elucidation of three new natural constituents are reported. These include a new substituted furfuryl ester of stearic acid, latifolinal (1), and two aromatic compounds, latifolidin (2) and cordicinol (3). Compounds 1 and 2 were obtained from the dried fruits and compound 3 from the leaves of Cordia latifolia.


Karyotype variation of CHO host cell lines over time in culture characterized by chromosome counting and chromosome painting.
Genomic rearrangements are a common phenomenon in rapidly growing cell lines such as Chinese hamster ovary (CHO) cells, a feature that in the context of production of biologics may lead to cell line and product instability. Few methods exist to assess such genome wide instability. Here, we use the population distribution of chromosome numbers per cell as well as chromosome painting to quantify the karyotypic variation in several CHO host cell lines. CHO-S, CHO-K1 8 mM glutamine, and CHO-K1 cells adapted to grow in media containing no glutamine were analyzed over up to 6 months in culture. All three cell lines were clearly distinguishable by their chromosome number distribution and by the specific chromosome rearrangements that were present in each population. Chromosome Painting revealed a predominant karyotype for each cell line at the start of the experiment, completed by a large number of variants present in each population. Over time in culture, the predominant karyotype changed for CHO-S and CHO-K1, with the diversity increasing and new variants appearing, while CHO-K1 0 mM Gln preferred chromosome pattern increased in percent of the population over time. As control, Chinese hamster lung fibroblasts were shown to also contain an increasing number of variants over time in culture.


Conformational analysis of alternative protein structures.
Alternative structural models determined experimentally are available for an increasing number of proteins. Structural and functional studies of these proteins need to take these models into consideration as they can present considerable structural differences. The characterization of the structural differences and similarities between these models is a fundamental task in structural biology requiring appropriate methods. We propose a method for characterizing sets of alternative structural models. Three types of analysis are performed: grouping according to structural similarity, visualization and detection of structural variation and comparison of subsets for identifying and locating distinct conformational states. The alpha carbon atoms are used in order to analyse the backbone conformations. Alternatively, side-chain atoms are used for detailed conformational analysis of specific sites. The method takes into account estimates of atom coordinate uncertainty. The invariant regions are used to generate optimal superpositions of these models. We present the results obtained for three proteins showing different degrees of conformational variability: relative motion of two structurally conserved subdomains, a disordered subdomain and flexibility in the functional site associated with ligand binding. The method has been applied in the analysis of the alternative models available in SCOP. Considerable structural variability can be observed for most proteins. The results of the analysis of the SCOP alternative models, the estimates of coordinate uncertainty as well as the source code of the implementation are available in the STRuster web site: http://struster.bioinf.mpi-inf.mpg.de.


Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo.
Piwi-associated RNAs (piRNAs), a specific class of 24- to 30-nucleotide-long RNAs produced by the Piwi-type of Argonaute proteins, have a specific germline function in repressing transposable elements. This repression is thought to involve heterochromatin formation and transcriptional and post-transcriptional silencing. The piRNA pathway has other essential functions in germline stem cell maintenance and in maintaining germline DNA integrity. Here we uncover an unexpected function of the piRNA pathway in the decay of maternal messenger RNAs and in translational repression in the early embryo. A subset of maternal mRNAs is degraded in the embryo at the maternal-to-zygotic transition. In Drosophila, maternal mRNA degradation depends on the RNA-binding protein Smaug and the deadenylase CCR4, as well as the zygotic expression of a microRNA cluster. Using mRNA encoding the embryonic posterior morphogen Nanos (Nos) as a paradigm to study maternal mRNA decay, we found that CCR4-mediated deadenylation of nos depends on components of the piRNA pathway including piRNAs complementary to a specific region in the nos 3' untranslated region. Reduced deadenylation when piRNA-induced regulation is impaired correlates with nos mRNA stabilization and translational derepression in the embryo, resulting in head development defects. Aubergine, one of the Argonaute proteins in the piRNA pathway, is present in a complex with Smaug, CCR4, nos mRNA and piRNAs that target the nos 3' untranslated region, in the bulk of the embryo. We propose that piRNAs and their associated proteins act together with Smaug to recruit the CCR4 deadenylation complex to specific mRNAs, thus promoting their decay. Because the piRNAs involved in this regulation are produced from transposable elements, this identifies a direct developmental function for transposable elements in the regulation of gene expression.


Self-consistent density functional calculation of the image potential at a metal surface.
It is well known that the exchange-correlation (XC) potential at a metal surface has an image-like asymptotic behaviour given by -1/4(z-z(0)), where z is the coordinate perpendicular to the surface. Using a suitable fully non-local functional prescription, we evaluate self-consistently the XC potential with the correct image behaviour for simple jellium surfaces in the range of metallic densities. This allows a proper comparison between the corresponding image-plane position, z(0), and other related quantities such as the centroid of an induced charge by an external perturbation. As a by-product, we assess the routinely used local density approximation when evaluating electron density profiles, work functions, and surface energies by focusing on the XC effects included in the fully non-local description.


The olivocochlear efferent bundle and susceptibility of the inner ear to acoustic injury.
1. The role of the efferent olivocochlear bundle (OCB) in protecting the inner ear from acoustic injury was studied in the anesthetized cat. Middle-ear muscles (MEM) were cut to eliminate possible effects of this feedback system on the auditory periphery. In each of a series of animals, the OCB was unilaterally transected. The animal was then exposed binaurally to an intense pure tone, and the resultant damage to the two sides compared by measuring threshold shifts in the compound action potential from each ear. Data from each animal provide one control measurement (threshold shift with an intact OCB) and one experimental measurement (threshold shift without a functional OCB). 2. Two experimental series were analyzed. In one the OCB was electrically stimulated, providing maximal firing rates in the efferents projecting to the control ear. In another series the OCB was not electrically stimulated: thus any OCB activity to the control ear was only that evoked by the acoustic stimulation itself. 3. In neither experimental series was there evidence that activity in the OCB provides protection from acoustic injury. These results are in disagreement with conclusions drawn from experiments with acoustic overstimulation of guinea pigs. 4. Interpretations for the discrepancy between the present study and those on guinea pigs include interspecies differences and the possible contribution of the MEM reflex or cochlear blood-flow changes to previously observed effects.


Prognosis and Risk Factors of Radiation-Induced Lymphopenia in Early-Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy.
Background: To investigate the role of stereotactic body RT (SBRT) in decreased total peripheral lymphocyte count (TLC) in patients with early-stage lung cancer and to explore possible risk factors for RT-induced lymphopenia. Materials and Methods: We analyzed the TLCs and lymphocyte subsets of 76 patients in our prospective clinical database who received SBRT for early-stage lung cancer treatment. Relationships between clinical factors or dosimetric parameters and TLC were evaluated using Spearman's correlation analysis and Chi-square tests for continuous and categorical variables, respectively. Multivariate linear regression analysis was used to control for confounding factors. Kaplan-Meier analysis with a log-rank test and a multivariate Cox regression model were used for survival analysis. Results: Most patients (64/76, 84.2%) experienced decreased absolute lymphocyte counts following SBRT, as well as shifts in lymphocyte subset distributions. Spearman's correlation coefficients between post-SBRT TLC and the percentage of the lung and heart receiving 5 to 50 Gy (in 5 Gy increments) shown that most lung DVH parameters [V(10)-V(50)] were significantly negatively correlated with post-SBRT TLC, while only heart V(5), V(20), V(25), V(30), and V(45) were significant. Univariate analyses revealed that a lower Pre-SBRT TLC level, higher mean lung dose, longer treatment duration, and longer TBT were significantly associated with a lower Post-SBRT TLC level (all P < 0.05). Stepwise multivariate linear regression, which incorporated all of the significantly clinical variables and SBRT-related parameters in univariate analysis, revealed that lower pre -SBRT TLC (P < 0.001), higher heart V5 (P = 0.002), and longer total beam-on time (TBT) (P = 0.001) were the independent risk factors for decrease in post-SBRT TLC. Patients with lower post-SBRT TLC and longer TBT exhibited significantly inferior progression-free survival (PFS) (P < 0.001 and P = 0.013) and overall survival (P = 0.006 and P = 0.043). Conclusions: G2 and more severe lymphopenia after SBRT might be an independent prognostic factor for poorer outcome in early-stage lung cancer. Lowering heart V5 and TBT when designing SBRT plans may spare circulating lymphocytes and have the potential to further improve survival outcomes.


EFFECT OF COLLA CORNUS CERVI COMBINED WITH LV-MEDIATED BMP7 TRANSFECTED BMSCs ON ANFH IN RATS.
In the present study, we investigated the combined effect of Colla Comus Cervi (CCC) and BMP7-overexpressing bone marrow-derived mesenchymal stem cells (BMSCs) on osteogenic induction and the treatment of avascular necrosis of the femoral head (ANFH). BMSCs were isolated from rats. BMP7-overexpressing BMSCs were generated by lentiviral-mediated gene transduction. Cell proliferation, alkaline phosphatase (ALP) activity, osteogenesis related gene expression, osteocalcin levels, and calcified nodules were quantified and compared between four groups: untreated controls, BMSCs cultured with CCC complex medium, BMP7-overexpressing BMSCs, and BMP7-overexpressing BMSCs cultured with CCC complex medium (CCC+BMP7). CCC+BMP7 BMSCs showed higher proliferation rate. ALP activity and osteaocalcin content were significantly increased in CCC+BMP7 BMSCs. The osteogenesis related genes, COLI, and integrin-α2, -α5, and -β1, were expressed significantly higher in CCC+BMP7 BMSCs. The number of calcified nodules in the CCC+BMP7 group was significantly higher than that in other groups. For in vivo assays, ANFH was induced in rats, and BMSCs were injected into the femoral head of the lower left extremity. In rats with induced ANFH, general observation scores of the CCC+BMP7 injected group were significantly higher than the model group. X-ray and microscopic observations revealed that ANFH was significantly improved and femoral head cells gradually recovered in rats treated with CCC+BMP7 BMSCs. Our results suggest that CCC+BMP7 significantly promote the proliferation and osteogenic differentiation of BMSCs in vitm. CCC+BMP7 BMSCs promote the ability of repairing ANFH in rats, providing a new therapeutic paradigm for the treatment of ANFH.


TSH crosslinks to the TSH receptor through the beta subunit.
TSH binds specifically to the TSH receptor present on the surface of thyroid follicular cells and consequently activates adenylate cyclase. It was not known, however, which of the two subunits of the TSH bound to the receptor. By covalently crosslinking TSH to its receptor and characterizing the product with antisera specific for either the alpha or beta subunit of TSH, we have shown that the TSH beta subunit but not the TSH alpha subunit crosslinks to the TSH receptor.


SLHSD: hybrid scaffolding method based on short and long reads.
In genome assembly, scaffolding can obtain more complete and continuous scaffolds. Current scaffolding methods usually adopt one type of read to construct a scaffold graph and then orient and order contigs. However, scaffolding with the strengths of two or more types of reads seems to be a better solution to some tricky problems. Combining the advantages of different types of data is significant for scaffolding. Here, a hybrid scaffolding method (SLHSD) is present that simultaneously leverages the precision of short reads and the length advantage of long reads. Building an optimal scaffold graph is an important foundation for getting scaffolds. SLHSD uses a new algorithm that combines long and short read alignment information to determine whether to add an edge and how to calculate the edge weight in a scaffold graph. In addition, SLHSD develops a strategy to ensure that edges with high confidence can be added to the graph with priority. Then, a linear programming model is used to detect and remove remaining false edges in the graph. We compared SLHSD with other scaffolding methods on five datasets. Experimental results show that SLHSD outperforms other methods. The open-source code of SLHSD is available at https://github.com/luojunwei/SLHSD.


Effect of Shading on Red Colour and Fruit Quality in Blush Pears "ANP-0118" and "ANP-0131".
Some cultivars of Pyrus communis develop mature fruit with a distinctive red blush. Investigating the patterns of pear colour development in response to sunlight has implications for orchard management of these pears. The objectives of these experiments are to study the seasonal patterns of colour development and investigate the influence of shade and sunlight exposure on the red colour and harvest quality of blush pears "ANP-0118" and "ANP-0131". Several long, medium and short shading treatments were applied at different stages of fruit development from 28 ("ANP-0131") and 29 ("ANP-0118") days after full bloom (DAFB) until harvests at 119 DAFB ("ANP-0118") and 175 DAFB ("ANP-0131"). Fruits were measured every three weeks for colour parameters (a*, hue angle, chroma) and at harvest for quality parameters (fresh weight, visual assessments of percentage blush coverage and blush intensity, flesh firmness and soluble solids concentration). In the unshaded control, red colour increased during the growing season (increase in a* value and decrease in hue angle), as well as increasing in chroma value. Periods of shading during the season negatively affected red colour in both cultivars, as evidenced by significant decreases in a* value and increases in hue angle. Shaded fruits that were subsequently re-exposed to sunlight reacted with a dynamic increase in a* value and decrease in hue angle. Fruit shaded for the length of the experiment or prior to harvest had significantly lower a* values than the control at harvest. Visual assessment at harvest of percentage blush coverage and blush intensity were significantly affected by shading in both cultivars. Shading treatments applied early in the experiment had a negative effect on the fresh fruit weight of "ANP-0118".


Novel Amoxicillin-Loaded Sericin Biopolymeric Nanoparticles: Synthesis, Optimization, Antibacterial and Wound Healing Activities.
Infected wounds are a major threat among diabetic patients. Technological advancements are currently increasing the number of new adjunctive therapies that may be potent agents for speeding recovery, lowering the amputation rate and limiting infection recurrences. A novel formula with promising antibacterial activity, namely sericin/propolis/Amoxicillin nanoparticles, was assessed as a potent treatment of infected wounds in normal and diabetic rats. Skin wound healing efficiency was assessed through wound healing scorings, bacterial load assessment and histological examinations. It was revealed that upon using sericin/propolis/Amoxicillin nanoparticles, complete wound healing was successfully achieved after 10 and 15 days postinjury for nondiabetic and diabetic rats, respectively. However, the bacterial load in the induced infected wounds was extremely low (0-10 CFU/mL) after 15 days post-treatment. The histological studies revealed that the dermis was more organized with new matrix deposition, and mature collagen fibers were observed among the treated animal groups. The present study is the first preclinical study which reported the importance of silk sericin in the form of nano-sericin/propolis loaded with Amoxicillin as an effective treatment against bacterial wound infections.


Analysis of the RNA helicase A gene in human lung cancer.
In this study we investigated the RNA helicase A (RHA) gene localized on chromosome 1q25 in 15 lung cancer cell lines, 54 primary carcinomas, bronchial epithelial cells and normal lung. Both RT-PCR and real-time RT-PCR showed that RHA is over-expressed in tumour samples compared to normal lung tissues (p=0.01). There was a tendency for higher expression levels in small cell lung cancer compared to non-small cell carcinomas. Over-expression of Y-162 correlated with high grade tumours (p=0.023). However, there was no correlation with tumour stage and survival. Our observations are compatible with the role of RHA in lung cancer development.


Personal use of hair dyes--increased risk of non-Hodgkin's lymphoma in Thailand.
The use of hair dyes has been inconsistently associated with an increased risk of lymphomas. To further evaluate this possibility, we examined hair dye use and lymphoma risk in a case-control study in the Thai population. A total of 390 histologically confirmed incident non-Hodgkin's lymphoma (NHL) cases and 422 controls were included. Information on hair dye use was obtained through a personal interview together with information on other known risk factors of lymphoma. Analysis was performed using logistic regression; odds ratios (ORs) estimates and 95% confidence intervals (CI) were calculated. Ever use of hair dyes was not associated with an increase risk of NHL both overall (OR=1.1, 95%CI 0.8-1.5) and in women (OR=1.4, 95%CI 0.9-2.3). However, NHL was significantly higher among persons who began using hair dyes before 1980 (OR=2.1, 95%CI 1.0-4.1). An increased risk was also observed among women who reported use of permanent hair dye product (OR=1.8, 95% CI 1.0-3.1). Analyses by NHL subtype showed an increased risk for diffuse large B-cell lymphoma among users of permanent hair dyes (OR=1.6, 95%CI 1.0-2.5) while follicular lymphoma was associated with the use of dark-colored dyes (OR=3.7, 95%CI 1.1-12.8). No association was observed with duration of use, nor total lifetime applications. These results indicate that personal hair dye use may play role in risks of NHL among person who used hair dyes before 1980.


Why did the strepsirhine tooth comb evolve.
The hypothesis that the original strepsirhine tooth comb evolved for scraping gum is examined. The comparative morphology of the anterior dentition does not corroborate this view, and our study suggests that the primitive tooth comb, which was 6-toothed, evolved for the maintenance of the five, evenly distributed narrow spaces in between them. Unlike the incisors of other groups, platyrrhines or catarrhines, for example, the apical extremities in the primitive condition are not closer to one another than the basal portions of these teeth. The biological role responsible for the evolution of the function of the original tooth comb is believed to be fur-combing. Subsequent modifications in numerous lineages altered both morphology and function as a result of new roles, and this tended to obscure the cause of origin of this character complex.


Body condition scoring (BCS) in corn snakes (Pantherophis guttatus) and comparison to pre-existing body condition index (BCI) for snakes.
In the veterinary profession, the body condition score (BCS) plays an important role in the assessment of patients. It is a subjective, tactile method of evaluating body fat and muscle mass and is used in numerous species. Recognizing obesity (or the contrary, emaciation) is important for veterinarians treating reptiles and could be facilitated by a BCS. An existing form of body condition assessment already used is the body condition index (BCI), where the residuals from a regression of body mass on body length are calculated. Therefore, the goal of this study was to provide practitioners with a BCS system for corn snakes (Pantherophis guttatus) and to test it against the BCI. A total of 22 corn snakes (Pantherophis guttatus), stationed at the "Auffangstation für Reptilien" in Munich (reptile rescue centre, RRC), were subject of this study. Each had the following measurements taken: body weight (BW), snout-tail tip length (STL), snout-vent length (SVL) and circumference in the middle (C). Manual palpation of spine, area between vertebral spinous and transverse process, ribs and neck of each snake was performed by three veterinarians and assigned to specific scores by each examiner. A BCS (mean of examiners' scores) was given to each snake according to manual palpation. The BCS system was chosen to be out of 5 in 0.5-point steps with 2.5 considered as ideal BCS. In the studied snakes, the BCS ranged from 1.5 to 3.5, with a median of 2.5. The median BW was 309 g (75-967 g), the median STL was 123 cm (79-153 cm), the median SVL was 104 cm (73-133 cm) and the median C was 7.5 cm (4.3-11 cm). BCS and BCI were positively correlated. A BCS includes a manual palpation of the animal and thus gives the examiner additional information to the objectively measured/calculated index.


Radon and lung cancer in the pooled uranium miners analysis (PUMA): highly exposed early miners and all miners.
Radon is a ubiquitous occupational and environmental lung carcinogen. We aim to quantify the association between radon progeny and lung cancer mortality in the largest and most up-to-date pooled study of uranium miners. The pooled uranium miners analysis combines 7 cohorts of male uranium miners with 7754 lung cancer deaths and 4.3 million person-years of follow-up. Vital status and lung cancer deaths were ascertained between 1946 and 2014. The association between cumulative radon exposure in working level months (WLM) and lung cancer was modelled as the excess relative rate (ERR) per 100 WLM using Poisson regression; variation in the association by temporal and exposure factors was examined. We also examined analyses restricted to miners first hired before 1960 and with <100 WLM cumulative exposure. In a model that allows for variation by attained age, time since exposure and annual exposure rate, the ERR/100 WLM was 4.68 (95% CI 2.88 to 6.96) among miners who were less than 55 years of age and were exposed in the prior 5 to <15 years at annual exposure rates of <0.5 WL. This association decreased with older attained age, longer time since exposure and higher annual exposure rate. In analyses restricted to men first hired before 1960, we observed similar patterns of association but a slightly lower estimate of the ERR/100 WLM. This new large, pooled study confirms and supports a linear exposure-response relationship between cumulative radon exposure and lung cancer mortality which is jointly modified by temporal and exposure factors.


The paraureteric diverticulum in childhood.
The clinical features and the results of surgical treatment in 27 children with a paraureteric diverticulum treated between 1969 and 1979 were reviewed. The condition is commoner in males. Vesicoureteric reflux and double ureters were associated findings and together with the diverticulum accounted for the high incidence of urinary infection as a presenting feature. In only 2 patients with the diverticulum seen on excretion urography, but micturating cystography confirmed the diagnosis in 24 patients. Conservative treatment with continuous chemotherapy is satisfactory when the diverticulum is small and prior to the development of vesicoureteric reflux. In the later stages, excision of the diverticulum and reimplantation of the contiguous ureter is the surgical treatment of choice.


Flax Fibre Yarn Coated with Lignin from Renewable Sources for Composites.
The present experimental work analyses the potential of lignin as a matrix for materials made from renewable resources for composite components and the production of hybrid semi-finished products by coating a flax fibre yarn. Natural fibres, due to their low density, in combination with lignin can be a new renewable source for lightweight products. For this purpose, the extrusion process was adapted to lignin as a matrix material for bio-based composites and coating of natural fibre yarns. A commercial flax yarn is the basis for the lignin coating by extrusion. Subsequently, the coated flax yarn was characterised with regard to selected yarn properties. In order to produce composite plates, the lignin-coated flax yarn was used as warp yarn in a bidirectional fabric due to its insufficient flexibility transversely to the yarn axis. The commercial flax yarn was used as weft yarn to increase the fibre volume content. The tensile and flexural properties of the bio-based composite material were determined. There was a significant difference in the mechanical properties between the warp and weft directions. The results show that lignin can be used as matrix material for bio-based natural fibre composites and the coating of natural fibre yarns is an alternative to spun hybrid yarns.


Enhanced renal function in bradykinin B(2) receptor transgenic mice.
The tissue kallikrein-kinin system has been recognized as a paracrine and/or autocrine hormonal system that regulates arterial pressure, renal hemodynamics, and electrolyte excretion. We have created a transgenic mouse model overexpressing human bradykinin B(2) receptor, and the mice developed lifetime hypotension. With this animal model, we further analyzed the potential role of B(2) receptors in regulation of renal function. Baseline urinary excretion, urinary potassium excretion, and pH were significantly increased in transgenic mice, whereas urinary sodium excretion and serum sodium concentration were unaltered. Transgenic mice exhibited increased renal blood flow, glomerular filtration rate, and urine flow. Enhanced renal function was accompanied by significant increases in urinary nitrate/nitrite, cGMP, and cAMP levels with unaltered urinary kinin levels in transgenic mice compared with control siblings. Renal cGMP and cAMP content was also significantly increased in transgenic mice. Because the renin-angiotensin system exerts vasoconstriction buffering vasodilation of the kallikrein-kinin system, expression of renin-angiotensin components was examined by Northern blot analysis. We found a significant increase in hepatic angiotensinogen expression with no changes in renal renin and pulmonary angiotensin-converting enzyme mRNA levels in B(2) receptor transgenic mice. These studies showed that overexpression of B(2) receptors in transgenic mice resulted in hypotension and enhanced renal function through activation of nitric oxide-cGMP and cAMP signal transduction pathways.


Altered serotonin 2A receptor activity in women who have recovered from bulimia nervosa.
The authors' goal was to confirm that brain serotonin (5-HT) alterations are present in patients who have recovered from bulimia nervosa. Positron emission tomography imaging with [(18)F]altanserin was used to characterize binding of the 5-HT(2A) receptor, which might contribute to altered feeding, mood, or impulse control. Nine women who had recovered from bulimia nervosa (they had no episodes of binge eating or purging, were at normal weight, and had regular menstrual cycles for more than 1 year) were compared with 12 female volunteers who had never had bulimia. The healthy volunteers, but not the women who had recovered from bulimia nervosa, had an age-related decline in 5-HT(2A) binding. Women who had recovered from bulimia nervosa had a reduction of medial orbital frontal cortex 5-HT(2A) binding. The lack of age-related changes in 5-HT activity is further evidence of 5-HT alterations in subjects who have recovered from bulimia nervosa. In addition, vulnerabilities for eating disorders, impulse dyscontrol, and mood disturbances may involve 5-HT and frontal lobe activity.


Observations of isolated enterocytes and of their subcellular components using transmission and scanning electron microscopy.
Isolated epithelial cells and their subcellular organelles were examined both by transmission and by scanning electron microscopy. It was shown that scanning electron microscopy is particularly useful for displaying the three-dimensional structure of the brush border. Furthermore, it has been possible to observe the basal aspect of separated epithelium for the first time. Studies on the scanning electron microscopic appearance of isolated nuclei, mitochondria, and lysosomes did not reveal any evidence of surface structure.


Silver Nitrate Grade and Its Effect on Physical Developer Performance-A Validation Study.
Silver nitrate is a critical component of the physical developer (PD) reagent. Significant increases in the cost of silver nitrate in recent years have caused the United States Secret Service's Forensic Laboratory to look for a more economical way to produce physical developer. One possible solution to this dilemma is to use a lower grade of silver nitrate, which typically has a lower cost. This study compared the quality of fingerprints produced on various paper substrates by three physical developer working solutions, each prepared using either the American Chemical Society (ACS), U.S. Pharmacopeia (USP), or technical grade of silver nitrate. It was determined that the less pure grades of silver nitrate produced approximately the same quality of fingerprints as the ACS grade, which is currently used in the authors' laboratory for making PD working solutions. In the experiments comparing PD prepared using the ACS and USP grades of silver nitrate, the ACS grade was superior only 5% of the time, whereas the USP grade was chosen 27% of the time. In the experiments comparing PD prepared using the ACS and technical grades of silver nitrate, the ACS grade was superior only 10% of the time, whereas the technical grade was selected 17% of the time. For the majority of the sample comparisons, no difference in fingerprint quality was observed. The overall conclusion was that either USP or technical grade silver nitrate can be used in place of the current, and more expensive, ACS grade of silver nitrate.


Interplay between the structural and magnetic probes in the elucidation of the structure of a novel 2D layered [V4O4(OH)2(O2CC6H4CO2)4]·DMF.
The title compound has been synthesized under solvothermal conditions by reacting vanadium(V) oxytriisopropoxide with terephthalic acid in N,N-dimethylformamide. A combination of synchrotron powder diffraction, infrared spectroscopy, scanning and transmission electron microscopy, and thermal and chemical analysis elucidated the chemical, structural and microstructural features of a new 2D layered inorganic-organic framework. Due to the low-crystallinity of the final material, its crystal structure has been solved from synchrotron X-ray powder diffraction data using a direct space global optimization technique and subsequent constraint Rietveld refinement. [V(4)O(4)(OH)(2)(O(2)CC(6)H(4)CO(2))(4)]·DMF crystallizes in the monoclinic system (space group P2/m (No. 10)); cell parameters: a = 20.923(4) Å, b = 5.963(4) Å, c = 20.425(1) Å, β = 123.70(6)°, V = 2120.1(9) Å(3), Z = 2. The overall structure can be described as an array of parallel 2D layers running along [-101] direction, consisting of two types of vanadium oxidation states and coordination polyhedra: face-shared trigonal prisms (V(4+)) and distorted corner-shared square pyramids (V(5+)). Both configurations form independent parallel chains oriented along the 2-fold symmetry crystallographic b-axis mutually interlinked with terephthalate ligands in a monodentate mode perpendicular to it. The morphology of the compound exhibits long nanofibers, with the growth direction along the layered [-101] axis. The magnetic susceptibility measurements show that the magnetic properties of [V(4)O(4)(OH)(2)(O(2)CC(6)H(4)CO(2))(4)]·DMF can be described by a linear antiferromagnetic chain model, with the isotropic exchange interaction of J = -75 K between the nearest V(4+) neighbours of S = 1/2.


Using concept mapping principles in PowerPoint.
The use of linear PowerPoint templates to support lectures may inadvertently encourage dental students to adopt a passive approach to learning and a narrow appreciation of the field of study. Such presentations may support short-term learning gains and validate assessment regimes that promote surface learning approaches at the expense of developing a wider appreciation of the field that is necessary for development of clinical expertise. Exploitation of concept mapping principles can provide a balance for the negative learning behaviour that is promoted by the unreflective use of PowerPoint. This increases the opportunities for students to access holistic knowledge structures that are indicators of expertise. We illustrate this using the example of partial denture design and show that undergraduates' grasp of learning and teaching issues is sufficiently sophisticated for them to appreciate the implications of varying the mode of presentation. Our findings indicate that students understand the strategic value of bullet-pointed presentations for short-term assessment goals and the benefits of deep learning mediated by concept mapping that may support longer term professional development. Students are aware of the tension between these competing agendas.


[An immunohistochemical study on neovascularization in TMJ during mandibular advancement].
Neovascularization is proved to be closely correlated with ossification. This study was designed to determine the biochemical path through which the new bone formation is enhanced in TMJ during mandibular protrusion. SD Rats were fitted with bite-jumping appliances to allow for an adequate advancement of the mandible. The animals were sacrificed 3, 7, 14, 21 and 30 days, respectively, after placement of the appliances. Slides with TMJ tissue were prepared for biochemical procedure. Immunohistochemical approaches were adopted to examine neovascularization in TMJ by immuno-localizing the newly formed endothelial cells. Computer-assisted image analysis system was applied to quantify the positive immunoreaction. Neovascularization in connective tissue close to the condyle was 200% higher in the experimental groups than that in the control, and, within the bony tissue of the condyle, neovascularization in experimental animals was found to be 103% higher than that of the control. Increased neovascularization triggered by mandibular protrusion might intensify new bone formation in condyle and glenoid fossa and finally lead to a growth adaptation of TMJ to bite-jumping therapy.


Repression of CENP-A assembly in metaphase requires HJURP phosphorylation and inhibition by M18BP1.
Centromeres are the foundation for mitotic kinetochore assembly and thus are essential for chromosome segregation. Centromeres are epigenetically defined by nucleosomes containing the histone H3 variant CENP-A. CENP-A nucleosome assembly is uncoupled from replication and occurs in G1, but how cells control this timing is incompletely understood. The formation of CENP-A nucleosomes in vertebrates requires CENP-C and the Mis18 complex which recruit the CENP-A chaperone HJURP to centromeres. Using a cell-free system for centromere assembly in X. laevis egg extracts, we discover two activities that inhibit CENP-A assembly in metaphase. HJURP phosphorylation prevents the interaction between HJURP and CENP-C in metaphase, blocking the delivery of soluble CENP-A to centromeres. Non-phosphorylatable mutants of HJURP constitutively bind CENP-C in metaphase but are not sufficient for new CENP-A assembly. We find that the M18BP1.S subunit of the Mis18 complex also binds to CENP-C to competitively inhibit HJURP's access to centromeres. Removal of these two inhibitory activities causes CENP-A assembly in metaphase.


Patterned Trichoteiromania in Androgenetic Alopecia.
Trichotillomania is the most frequent reported cause of self-inflicted hair disorders, within which are included trichoteiromania, trichotemnomania, and trichocryptomania, also known as trichorrexomania. These conditions are commonly described in the context of psychiatric disorders. Nevertheless, there exists reports in otherwise healthy patients that suffer a form of no cicatricial alopecia, such as alopecia areata. We communicate 3 cases of male androgenetic alopecia with patterned miniaturization that coexisted with trichoscopic findings of trichoteiromania. The presence of brush-like ends or broom hairs is a highly suggestive feature of this entity. To the best of our knowledge, this association was not previously reported in the medical literature. The possibility of self-induced hair loss should be kept in mind during every follow-up visit in all types of alopecia, remembering that hair loss itself is already a distressing condition.


The Collaborative IPD of Sleep and Stillbirth (Cribss): is maternal going-to-sleep position a risk factor for late stillbirth and does maternal sleep position interact with fetal vulnerability? An individual participant data meta-analysis study protocol.
Accumulating evidence has shown an association between maternal supine going-to-sleep position and stillbirth in late pregnancy. Advising women not to go-to-sleep on their back can potentially reduce late stillbirth rate by 9%. However, the association between maternal right-sided going-to-sleep position and stillbirth is inconsistent across studies. Furthermore, individual studies are underpowered to investigate interactions between maternal going-to-sleep position and fetal vulnerability, which is potentially important for producing clear and tailored public health messages on safe going-to-sleep position. We will use individual participant data (IPD) from existing studies to assess whether right-side and supine going-to-sleep positions are independent risk factors for late stillbirth and to test the interaction between going-to-sleep position and fetal vulnerability. An IPD meta-analysis approach will be used using the Cochrane Collaboration-endorsed methodology. We will identify case-control and prospective cohort studies and randomised trials which collected maternal going-to-sleep position data and pregnancy outcome data that included stillbirth. The primary outcome is stillbirth. A one stage procedure meta-analysis, stratified by study with adjustment of a priori confounders will be carried out. The IPD meta-analysis has obtained central ethics approval from the New Zealand Health and Disability Ethics Committee, ref: NTX/06/05/054/AM06. Individual studies should also have ethical approval from relevant local ethics committees. Interpretation of the results will be discussed with consumer representatives. Results of the study will be published in peer-reviewed journals and presented at international conferences. CRD42017047703.


Overactive, aggressive, disruptive and agitated behavior associated with the use of psychotropic medications in schizophrenia.
Evidence is limited for the associations between use of psychotropic medications and overactive, aggressive, disruptive or agitated behavior (OADA)1 in clinical practice. To investigate the associations between risk of readmission with OADA and use of antipsychotics, antidepressants, mood stabilizers and benzodiazepines in patients with schizophrenia. A consecutive total cohort diagnosed with schizophrenia (N = 663) after admission to the Haukeland University Hospital psychiatric acute unit in Bergen, Norway, was followed from discharge over a 10-year period. At every following readmission, the level of OADA was assessed using the first item of the Health of the Nation Outcome Scale (HoNOS). Periods of use versus non-use of antipsychotics, antidepressants, mood stabilizers and benzodiazepines were recorded as time-dependent variables in each patient and compared using Cox multiple regression analyses. A total of 161 (24.3 %) patients were readmitted with OADA, and the mean (SD) and median times in years to readmission with OADA were 2.8 (2.6) and 2.1, respectively. We found that the risk of readmission with OADA was negatively associated with use of antipsychotics (adjusted hazard ratio (AHR) = 0.33, p < 0.01, CI: 0.24-0.46) and antidepressants (AHR = 0.57, p = 0.03, CI: 0.34-0.95), positively associated with use of benzodiazepines (AHR = 1.95, p < 0.01, CI: 1.31-2.90) and not significantly associated with use of mood stabilizers. Use of antipsychotics and antidepressants is associated with reduced risk of readmission with OADA whereas benzodiazepines are associated with an increased risk of readmission with OADA in patients with schizophrenia.


[Comparative analysis of metastatic variants from the colorectal tumor cell line HT-29]
OBJECTIVE: To analyze the relationship between metastatic potential and related facters of colorectal tumor cell lines. METHODS: The variants HT-29c and HT-29d cell lines derived from the selection of HT-29 cells were injected into nude rats and the metastatic potential of the two tumor cell variants was analyzed. Expression of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) were measured with ELISA in vitro in colorectal carcinoma cell lines WiDr, HT-29 and HT-29d. Expression of carcinoembryonic antigen (CEA) and phosphoinositide 3-kinase (PI3-Kinase) were determined with immunohistochemistry, (IHC) in vitro and in vivo in WiDr, HT-29 and HT-29d cell lines. In addition, CEA expression was demonstrated with fluorescence activated cell sorter (FACS) in vitro. RESULTS: The liver metastasis rate of the variant HT-29d (with 4 cycles of selection), increased as compared with that of parental HT-29 cells and that of variant HT-29b cells (with 2 cycle of selection). The uPA concentration of variant HT-29d cell line was significantly higher than that of the non metastatic WiDr and the low metastatic HT-29 cells (P<0.05). The variant HT-29d cells produced stronger PI3-kinase expression as compared with the non-anetastatic WiDr cells and the low metastatic HT-29 cells in vivo. CONCLUSION: The selected variant cell lines can exhibit an enhanced metastatic potential. The level of uPA and PAI-1 are positively correlated with the metastatic capacity of tumor cells. The expression of PI3 kinasecorrelates with tumor development and metastasis.


Effects of melengestrol acetate on the inflammatory response in heifers challenged with Mannheimia haemolytica.
Previous research from our laboratory has indicated that melengestrol acetate (MGA) added to the diet during the first 35 d after arrival in the feedlot improves growth rates and tends to reduce chronic respiratory disease in heifers naturally challenged with bovine respiratory disease. The current study was conducted to provide further insight into the possible immunomodulatory effects of MGA. Crossbred heifers (n = 48; 232 +/- 5.5 kg of BW) were used in a randomized complete block design to determine the effects of MGA on lung pathology and markers of inflammation after Mannheimia haemolytica challenge. On d 0, cattle were blocked by BW and randomly assigned, within block, to diets (54% concentrate) that provided 0 or 0.5 mg of MGA per heifer daily for the duration of the experiment. Inoculum containing from 1.3 x 10(9) to 1.7 x 10(9) cfu of M. haemolytica (20 mL) was instilled at the bifurcation of the trachea on d 14. Blood samples were collected, clinical observations were made, and rectal temperatures were recorded for each animal at 0, 12, 24, 48, 72, 96, 120, and 138 h after inoculation. Heifers fed MGA had greater circulating concentrations of eosinophils and postchallenge concentrations of segmented neutrophils and white blood cells (P < 0.01) than controls, as well as elevated plasma protein, serum haptoglobin, and fibrinogen after M. haemolytica challenge (P < 0.01). Heifers fed MGA had lower plasma glucose (P < 0.01), greater plasma urea N (P = 0.02), and elevated respiratory indices (P < 0.01) compared with controls. Necropsies performed on d 6 after inoculation suggested that M. haemolytica challenge was relatively mild, because lesions were confined to a small portion of the lungs. On a 0 to 100 scale, average lung lesion scores were 3 and 1 for MGA-fed and control groups, respectively (P < 0.06). Heifers fed MGA before mild M. haemolytica challenge were more susceptible to infection, as evidenced by a greater number of heifers fed MGA exhibiting pulmonary lesions 138 h after inoculation than controls (14 out of 23 vs. 6 out of 24 for MGA and controls, respectively; P < 0.02).


Hypopituitarism: a difficult diagnosis in elderly people but worth a search.
Hypopituitarism is uncommon in elderly people. We report 12 cases of hypopituitarism diagnosed after the age of 60 (range 63-89, mean 74.9) years over a 10-year period. Aetiology was evident in eight cases, viz. pituitary tumour in six and previous post-partum haemorrhage and giant aneurysm of carotid artery in one each. The presentation was often non-specific with symptoms such as lethargy, pallor, falls, urinary incontinence, confusion, fever and flexion contractures. Subtle clues to the condition were missed in four cases resulting in delayed diagnosis. Although levels of pituitary trophic hormones are generally low in this condition, the thyrotrophin (TSH) was normal in seven cases in the present series. Normal levels of serum sodium and potassium did not exclude cortisol deficiency. Hormone replacement therapy resulted in improved quality of life. Physicians dealing with elderly patients should bear this easily treated condition in mind.


Long-term patient survival in a pediatric renal transplantation program.
In adult renal transplant recipients, reports have shown continuing mortality beyond 5 years after transplantation with the majority of deaths due to myocardial infarctions, malignancies, and liver failure. Little information is available on the long-term survival of children following renal transplantation. Children with end-stage renal disease have fewer systemic complications than adults and should have better long-term survival. Furthermore, analysis of mortality in the pediatric population should be more informative of the risks of renal transplantation, separate from underlying pretransplant diseases and the inherent complications of aging. We analyzed, therefore, the long-term mortality of renal transplant recipients in a single pediatric center. A total of 299 renal transplants were performed in 251 patients from 1971 through 1990. No patient was excluded from the evaluation. Over all, actuarial survival was 91% at 1 year, 83% at 10 years, and 81% at 15 years. Patient's age at transplantation, donor source, and number of previous allografts were not correlated with patient survival. There were 35 deaths with 51% attributable to infections. The majority of deaths (71%) occurred within the first 6 months after renal transplantation during the period of greatest immunosuppression. Mortality within the first 12 months following renal transplantation was higher during the period 1971-1974 when compared to subsequent years. These data demonstrate that in a pediatric renal transplant center, long-term patient survival is excellent. Most deaths occur within the first 6 months following renal transplantation and are caused by infections. As expected, long-term survival in children is better than reports in adult renal transplant recipients and may more accurately reflect true renal-transplant-related mortality.


Treatment options for infections caused by multidrug-resistant Gram-negative bacteria: a guide to good clinical practice.
The rapid emergence of multidrug-resistant Gram-negative bacterial infections necessitates the development of new treatments or the repurposing of available antibiotics. Here, treatment options for treatment of these infections, recent guidelines and evidence are reviewed. Studies that included treatment options for infections caused by multidrug-resistant Gram-negative bacteria (Enterobacterales and nonfermenters), as well as extended-spectrum β-lactamase-producing and carbapenem-resistant bacteria, were considered. Potential agents for the treatment of these infections, considering type of microorganism, mechanism of resistant, source and severity of infection as well as pharmacotherapy considerations, are summarized.


Association between diastolic dysfunction by color tissue Doppler imaging and vascular calcification on plain radiographs in dialysis patients.
Diastolic dysfunction is frequently associated with left ventricular hypertrophy, which is indicative of future cardiovascular events. Vascular calcification (VC) is known to be associated with coronary artery disease in dialysis patients. The present study was to determine the interrelationship between LV diastolic dysfunction by tissue Doppler imaging and VC on plain radiographs in dialysis patients. Fifty-six dialysis patients were recruited and VC scores were evaluated by plain radiographic film. The ratio of early diastolic transmitral inflow velocity (E) to early diastolic mitral annular velocity (E') was measured by tissue Doppler imaging. We defined diastolic dysfunction as an E/E' ratio >15 on tissue Doppler imaging. Patients with diastolic dysfunction showed a higher percentage of coronary artery disease history, abdominal aortic calcification (AAC) scores ≥5, high LV mass index, and high left atrium volume compared to patients without diastolic dysfunction. The E/E' ratio was significantly higher in patients with significant VC, VC scores of the pelvis and hands ≥3, and AAC scores ≥5 on plain radiographs. AAC scores ≥5 were considered an independent predictor of diastolic dysfunction. VC on plain radiographs is associated with the E/E' ratio and AAC scores ≥5 are important clues for LV diastolic dysfunction in dialysis patients.


Three Homology Models of PAR2 Derived from Different Templates: Application to Antagonist Discovery.
Protease activated receptor 2 (PAR2) is an unusual G-protein coupled receptor (GPCR) involved in inflammation and metabolism. It is activated through cleavage of its N-terminus by proteases. The new N-terminus functions as a tethered ligand that folds back and intramolecularly activates PAR2, initiating multiple downstream signaling pathways. The only compounds reported to date to inhibit PAR2 activation are of moderate potency. Three structural models for PAR2 have been constructed based on sequence homology with known crystal structures for bovine rhodopsin, human ORL-1 (also called nociceptin/orphanin FQ receptor), and human PAR1. The three PAR2 model structures were compared and used to predict potential interactions with ligands. Virtual screening for ligands using the Chembridge database, and either ORL-1 or PAR1 derived PAR2 models led to identification of eight new small molecule PAR2 antagonists (IC50 10-100 μM). Notably, the most potent compound 1 (IC50 11 μM) was derived from the less homologous template protein, human ORL-1. The results suggest that virtual screening against multiple homology models of the same GPCR can produce structurally diverse antagonists and that this may be desirable even when some models have less sequence homology with the target protein.


Nandrolone induces a stem cell-like phenotype in human hepatocarcinoma-derived cell line inhibiting mitochondrial respiratory activity.
Nandrolone is a testosterone analogue with anabolic properties commonly abused worldwide, recently utilized also as therapeutic agent in chronic diseases, cancer included. Here we investigated the impact of nandrolone on the metabolic phenotype in HepG2 cell line. The results attained show that pharmacological dosage of nandrolone, slowing cell growth, repressed mitochondrial respiration, inhibited the respiratory chain complexes I and III and enhanced mitochondrial reactive oxygen species (ROS) production. Intriguingly, nandrolone caused a significant increase of stemness-markers in both 2D and 3D cultures, which resulted to be CxIII-ROS dependent. Notably, nandrolone negatively affected differentiation both in healthy hematopoietic and mesenchymal stem cells. Finally, nandrolone administration in mice confirmed the up-regulation of stemness-markers in liver, spleen and kidney. Our observations show, for the first time, that chronic administration of nandrolone, favoring maintenance of stem cells in different tissues would represent a precondition that, in addition to multiple hits, might enhance risk of carcinogenesis raising warnings about its abuse and therapeutic utilization.


Multiorgan resection (including the pancreas) for metastasis of cutaneous malignant melanoma.
Several studies have demonstrated improved survival after complete resection of hollow viscus gastrointestinal metastases of malignant melanoma. Patients with metastatic disease of intra-abdominal solid organs might also benefit from complete surgical resection. The authors report the case of a 22-year-old female patient with multiorgan abdominal metastases of cutaneous malignant melanoma, including the ovarium, jejunum, stomach and pancreas. All metastases were resected successfully. In highly selected patients with melanoma metastatic to intra-abdominal solid organs and hollow viscus gastrointestinal organs, aggressive attempts and complete surgical resection may improve survival.