Good Medical Practice: what are we trying to say? Textual analysis using tag clouds.
Good Medical Practice, produced by the General Medical Council (GMC), represents the professional code of practice for doctors in the UK. It is regularly updated to reflect the changing relationships of the profession with both patients and society in general. The discourse within this guidance appears to have shifted over time to a stance that aligns itself more closely with the protection of patients, rather than with the traditional professional provision of guidance and support to doctors. Tag clouds are a feature of the latest applications of the World Wide Web, commonly known as Web 2.0. They can be used to rapidly analyse textual data, revealing textual messages in a pictorial form. Tag cloud-generating software was used to produce tag clouds of four texts illustrating GMC guidance produced between 1963 and 2006 to aid textual analysis and to determine whether this methodology could pick up this change in tenor. This analysis supports the view that there has been a shift from a doctor-centred regulatory discourse to a patient-centred health improvement agenda over the period of time examined. Whether this documentation voices a deprofessionalisation agenda or simply mirrors a period of societal change in general is discussed. The changing discourse around professionalism highlights the need to avoid adopting 'nostalgic' notions of professionalism in educating doctors and reinforces where the GMC sees we should focus our education efforts: in patient-centred care and team-working. The demands on, and responsibilities of students and juniors entering the profession have been fundamentally altered and our teaching, particularly in the domain of professionalism, needs to reflect this. Tag clouds provide an interesting and innovative way of analysing text and revealing obscured discourses, and their potential in education and research is worthy of further exploration.


cis-9,cis-15-octadecadienoic acid: a novel fatty acid found in higher plants.
An unusual fatty acid, cis-9,cis-15-octadecadienoic acid, has been identified in the pulp lipids of mango (Mangifera indica L.) grown in the Philippines. To our knowledge, the occurrence of cis-9,cis-15-octadecadienoic acid in higher plant lipids has not been previously reported. The structure confirmation was based on the results of chromatographic (capillary GC, argentation thin-layer) and spectrometric (GC-MS, infrared, ultraviolet) analysis and chemical treatment. This butylene-interrupted dienoic fatty acid is concentrated in the pulp part of mango fruit and occupies 5.4% of total acyl groups in the pulp lipids; whereas a common octadecadienoic acid, linoleic acid, is a minor component (1.1%) in the same lipids. If a trivial name is desired, it is suggested that cis-9,cis-15-octadecadienoic acid be called "mangiferic" acid.


Differential serum interferon-β levels in autoimmune thyroid diseases.
Interferon (IFN)-β is known as an environmental trigger for the occurrence of autoimmune thyroid disease (AITD). However, the association of another type-1 IFN, IFN-β, with AITD is unknown. In the study, we explored the association of serum IFN-β levels with AITD in an ethnic Chinese (i.e., Taiwanese) population. We enrolled 160 patients with Graves' disease (GD), 47 patients with Hashimoto's thyroiditis (HT), and 119 healthy controls. Serum IFN-β and B-cell activating factor (BAFF) levels were quantified in healthy controls at the baseline and in patients with AITD either prior to receiving medication or while under medication. Thyroid function and thyroid-stimulating hormone receptor antibody (TSHRAb) levels were measured at the time of serum collection. Serum IFN-β levels were lower in the HT group than in the control group (p = 0.031). A significant inverse correlation was observed between IFN-β and TSHRAb levels in men with GD (r = -0.433, p = 0.044). Serum IFN-β levels were also negatively associated with BAFF levels in men with GD, HT, and AITD (r = -0.320, p = 0.032; r = -0.817, p = 0.047; and r = -0.354, p = 0.011, respectively), but not in women with GD, HT, or AITD. Serum IFN-β levels were lower in HT patients. Correlations of serum IFN-β with TSHRAb and BAFF levels were found to be gender-specific. Further well-designed studies with larger sample sizes are required to confirm our findings.


Pulsed radio frequency energy in the treatment of painful chronic cutaneous wounds: a report of two cases.
Chronic cutaneous wounds may cause considerable pain, often affecting patient compliance with necessary treatment protocols. Two patients are presented who were unable to comply with compression therapy because of severe wound pain. Adjunctive pulsed radio frequency energy was administered for 30 minutes twice daily through an applicator pad placed directly on the dressing over the wound area. Both patients reported immediate, marked pain reduction, allowing compression therapy. The ulcers healed completely within 3 weeks for patient 1 and 28 weeks for patient 2. Further investigation into the efficacy of pulsed radio frequency energy for the treatment of painful wounds is warranted.


Cryptic chromosomal rearrangements in children with idiopathic mental retardation in the Czech population.
The aim of our study was to scan for cryptic rearrangements using the multiplex ligation probe amplification method in a cohort of 64 probands with mental retardation or developmental delays in combination with at least one of the following symptoms: hypotonia after birth, congenital anomalies, or face dysmorphisms; but without a positive cytogenetic finding. The study contributes to the knowledge of microdeletion syndromes and helps disclose their natural phenotypic variability. In total, 10 positives (16%) were detected, particularly 3 duplications (Xpter-p22.32; 17p11.2; 22q11) and 6 different deletions (1p36; 7q11.23; 10p15; 15q11-q13; 17p11.2; 17p13.3), 1 of these in 2 probands. Besides the well-characterized syndromes, less-often described rearrangements with ambiguous phenotype associations were also detected. Some rearrangements, particularly duplications, are associated with vague phenotypes; and their frequency could be underestimated.


To Find a Better Dosimetric Parameter in the Predicting of Radiation-Induced Lung Toxicity Individually: Ventilation, Perfusion or CT based.
This study aimed to find a better dosimetric parameter in predicting of radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC) individually: ventilation(V), perfusion (Q) or computerized tomography (CT) based. V/Q single-photon emission computerized tomography (SPECT) was performed within 1 week prior to radiotherapy (RT). All V/Q imaging data was integrated into RT planning system, generating functional parameters based on V/Q SPECT. Fifty-seven NSCLC patients were enrolled in this prospective study. Fifteen (26.3%) patients underwent grade ≥2 RILT, the remaining forty-two (73.7%) patients didn't. Q-MLD, Q-V20, V-MLD, V-V20 of functional parameters correlated more significantly with the occurrence of RILT compared to V20, MLD of anatomical parameters (r = 0.630; r = 0.644; r = 0.617; r = 0.651 vs. r = 0.424; r = 0.520 p < 0.05, respectively). In patients with chronic obstructive pulmonary diseases (COPD), V functional parameters reflected significant advantage in predicting RILT; while in patients without COPD, Q functional parameters reflected significant advantage. Analogous results were existed in fractimal analysis of global pulmonary function test (PFT). In patients with central-type NSCLC, V parameters were better than Q parameters; while in patients with peripheral-type NSCLC, the results were inverse. Therefore, this study demonstrated that choosing a suitable dosimetric parameter individually can help us predict RILT accurately.


Cytotoxicity and activation of CB1954 in a human tumour cell line.
CB1954 (5-aziridin-1-yl-2,4-dinitrobenzamide) is a monofunctional alkylating agent, to which Walker 256 cells are very sensitive. These cells express a nitroreductase which reduces CB1954 to a bifunctional crosslinking agent 5-(aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide. In vitro testing on the human colon line LS174T showed that the differential cytotoxicities between the monofunctional agent (CB1954), and the active species (generated in situ by the addition of NADH and the Walker rat nitroreductase) were smaller than anticipated due to the unexpected toxicity of CB1954 (IC50 value for CB1954 on LS174T cells of 78 microM). The toxicity of the chemically synthesised active form was less than if it had been generated in situ (on LS174T cells). Further experiments showed that NADH was toxic at the levels used to generate the active species (500 microM). Gel filtration and electrophoresis experiments demonstrated that the human colon carcinoma and choriocarcinoma cell lines MAWI and JAR, as well as LS174T express an enzyme of similar molecular weight to that of the 33 kD Walker cell nitroreductase, which is capable of reducing CB1954 to its toxic metabolite, and reducing MTT to its insoluble formazan salt. The expression of this enzyme presumably accounts for the unexpected toxicity of CB1954.


Non-invasive biomarkers of Fontan-associated liver disease.
Fontan-associated liver disease (FALD) has emerged as an important morbidity following surgical palliation of single ventricle congenital heart disease. In this study, non-invasive biomarkers that may be associated with severity of FALD were explored. A retrospective cohort of paediatric patients post-Fontan who underwent liver biopsy at a high volume at a paediatric congenital heart disease centre was reviewed. Among 106 patients, 66% were male and 69% were Hispanic. The mean age was 14.4 ± 3.5 years, and biopsy was performed 10.8 ± 3.6 years post-Fontan. The mean BMI was 20.8 ± 5 kg/m2, with 27.4% meeting obesity criteria. Bridging fibrosis was observed in 35% of patients, and 10.4% of all patients had superimposed steatosis. Bridging fibrosis was associated with lower platelet counts (168.3 ± 58.4 vs. 203.9 ± 65.8 K/μl for congestive hepatic fibrosis score [CHFS] 0-2b, p = 0.009), higher bilirubin (1.7 ± 2.2 vs. 0.9 ± 0.7 mg/dl, p = 0.0090), higher aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 [FIB-4] scores (APRI: 0.5 ± 0.3 vs. 0.4 ± 0.1, p <0.01 [AUC: 0.69] and FIB-4: 0.6 ± 0.4 vs. 0.4 ± 0.2, p <0.01 [AUC: 0.69]), and worse overall survival (median 2 years follow-up post-biopsy, p = 0.027). Regression modelling of temporal changes in platelet counts before and after biopsy correlated with fibrosis severity (p = 0.005). In this large, relatively homogeneous adolescent population in terms of age, ethnicity, and Fontan duration, bridging fibrosis was observed in 35% of patients within the first decade post-Fontan. Bridging fibrosis was associated with worse survival. Changes in platelet counts, even years before biopsy, and APRI/FIB-4 scores had modest discriminatory power in identifying patients with advanced fibrosis. Steatosis may represent an additional risk factor for disease progression in obese patients. Further prospective studies are necessary to develop strategies to screen for FALD in the adolescent population. In this study, the prevalence of Fontan-associated liver disease (FALD) in the young adult population and clinical variables that may be predictive of fibrosis severity or adverse outcomes were explored. Several lab-based, non-invasive markers of bridging fibrosis in FALD were identified, suggesting that these values may be followed as a prognostic biomarker for FALD progression in the adolescent population.


The genetic system of kinetoplasts in trypanosomatides.
In the present report, the genetic system of Crithidia oncopelti kinetoplast is used as a model for investigation of kinetoplast DNA (kDNA) structure, its transcription, protein synthesizing apparatus of the kinetoplast and the protein synthesis controlled genetically by kDNA. It was shown that kDNA of C. oncopelti can be isolated from cells or from kinetoplast fraction in the form of a network complex structure consisting of a lot of circular molecules. These minicircles have a contour length of about 0.83 micronm and molecular weight of 1.6 X 10(6). The kDNA was demonstrated to be of higher AT content type than nuclear DNA. Besides, kDNA is characterized by a lesser degree of clustering of pyrimidines as compared with the nuclear one. The isolated kinetoplasts of C. oncopelti were shown to exhibit activity of DNA dependent RNA polymerase. The effect of some antibiotics and intercalating substances on RNA synthesis in kinetoplasts and mitochondria appears to be identical. Kinetoplasts of C. oncopelti have their own protein synthesizing system, whose components (ribosomes, rRNA, proteins, factors of incorporation) differ from those of the cytoplasm. Inhibition of translation by some antibiotics and of transcription by acriflavin allowed the suggestion that several proteins of kinetoplast ribosomes may be synthesized within this organoid. It was shown then that kDNA may be involved in the formation of the protein synthesizing apparatus in the kinetoplast.


Meanings of "the existential" in a Secular Country: A Survey Study.
"The existential" is a concept that many people use albeit associated with different meanings. In order to increase research-based insight into the meaning of "the existential," we conducted a questionnaire study in Denmark in 2018 in which we asked 1.106 Danes of various age, gender, educational and geographical background about personal associations linked to "the existential." Factor analysis of the answers resulted in three different groups of meaning: (1) essential meanings of life, (2) spirituality/religiosity and (3) existential thinking. The findings show that "the existential" serves well as an overarching construct potentially including secular, spiritual and religious meaning domains, at least within the European context.


Variability in the COMT gene and modification of the risk of schizophrenia conferred by cannabis consumption.
The risk of schizophrenia conferred by cannabis has recently been proposed to be modulated by the Val158Met polymorphism (rs4680) at the COMT gene. To date, these findings have not been replicated in independent samples. We tested the potential gene-by-environment interaction between Val158Met genotype at the COMT gene and previous use of cannabis in schizophrenia in 192 healthy controls and 91 inpatients with DSM-IV schizophrenia. The functional COMT Val158Met polymorphism was analyzed using TaqMan technology. Cannabis use was measured by taking into account the frequency of intake during the previous month. Logistic regression models were used to test the interaction between genetic and environment factors. Cannabis use was strongly associated with the case condition (p<0.0001). The Val158Met polymorphism at the COMT gene was not associated with schizophrenia, although Val/Val homozygosity tended to be more frequent in the case group than in the control group (34% vs 27%; OR=1.39; 95% CI, 0.78-2.47). Finally, in women we found a non-significant trend toward the association when we tested for the interaction between cannabis use, the number of Val alleles and susceptibility to schizophrenia (p=0.152). Our results tend to support recent findings suggesting that the Val158Met polymorphism at the COMT gene modifies the risk of schizophrenia conferred by cannabis use. In our study, this possible effect was only detected in women.


Effect of stabilization on biomass activity.
The study aimed to compare aerobic and aerobic/anoxic stabilization processes in terms of organic matter and the biomass removal efficiencies using a municipal sludge sample. The efficiency of stabilization process was assessed monitoring suspended solids (SS), volatile suspended solids (VSS), total and dissolved organic carbon (TOC, DOC), nitrate, nitrite, and phosphate parameters. The oxygen uptake rate (OUR) measurements were conducted to determine active biomass concentration. On the 30th day of the aerobic stabilization, the SS, VSS and TOC removal efficiencies were 22%, 28% and 55%, respectively. Under aerobic/anoxic conditions, removal efficiencies for SS, VSS and TOC were 25%, 27% and 67%. On the 17th day of the stabilization, SS and VSS removal rates were 60 mg SS/L day and 47 mg VSS/L day for aerobic and 102 mg SS/L day and 63 mg VSS/L day for aerobic/anoxic conditions, respectively. These findings reflected the higher stabilization performance of the aerobic/anoxic conditions. Based on respirometric results, the ratios of the active biomass were decreased to 30% and 24% for the 17th and 30th day of the aerobic stabilization, respectively. Such results have significant implications relative to the activity decrease quantification of the biomass as well as its further application potentials after aerobic or aerobic/anoxic sludge stabilization.


Simultaneous determination of mercury, lead and cadmium ions in water using near-infrared spectroscopy with preconcentration by thiol-functionalized magnesium phyllosilicate clay.
Analysis of metal ions in environment is of great importance for evaluating the risk of heavy metal to public health and ecological safety. A method for simultaneous determination of metal ions in water samples was developed by using adsorption preconcentration and near-infrared diffuse reflectance spectroscopy (NIRDRS). A high capacity adsorbent of thiol-functionalized magnesium phyllosilicate, named Mg-MTMS, was prepared by co-condensation for preconcentration of Hg(2+), Pb(2+) and Cd(2+) in aqueous solutions. After adsorbing the analytes onto the adsorbent, NIRDRS was measured and PLS models were established for fast and simultaneous quantitative prediction. Because the interaction of the ions with the functional group of the adsorbent can be reflected in the spectra, the models built with the samples prepared by river water were proven to be efficient enough for precise prediction. The determination coefficients (R(2)) of the validation samples for the three ions were found as high as 0.9197, 0.9599 and 0.9861, respectively. Furthermore, because the high adsorption efficiency of Mg-MTMS, the detected concentrations are as low as milligrams per liter for the three ions, and the concentration can be further reduced. Therefore, the feasibility of quantitative analysis metal ions in river water by NIRDRS is proven and this may provide a new way for fast simultaneous determination of trace metals in environmental waters.


Resin-process methods for improved isolation of organisms from blood and other body fluids.
Two resin-based processes and conventional culturing methods were compared in isolating organisms from blood specimens of patients given antimicrobial agents. Of 20 patients whose specimens were found to contain clinically relevant organisms, one or both of the resin-process methods isolated organisms in eight after conventional culturing was unsuccessful. Conventional cultures were successful in five cases in which the resin-process methods did not work, and both resin-process and conventional culturing were successful in seven cases. In eight cases in which other body fluids were cultured, only a resin-process method was successful in four, although they are intended for use only with blood specimens. Data indicate that resin-process methods should be used along with conventional culturing methods when patients have already been given an antimicrobial. A review of the literature shows that the devices improve the recovery of organisms but does not establish that detection time is decreased.


Soil fertility, chemical properties, and pollutant removal efficiency of Salicornia europaea in response to different times and duration of wastewater irrigation.
Halophytes are the good candidates in coastal saline areas which could be irrigated with wastewater. The purpose of this study was to evaluate the soil-water-plant system under control and wastewater irrigation (containing toxic elements and organic matter) at three durations (vegetative, flowering, and reproductive stages) and two exposure times (2 and 4 days in each stage). The results obtained in the experimental tests for wastewater irrigation indicated that the Salicornia is efficient for the removal of chemical oxygen demand (61%), biochemical oxygen demand (74%), total suspended solids (47.6%), and ammoniacal nitrogen (64%) at the reproductive stage. At the same time, the average nitrate concentration increased to 51.3 mg L-1 with more solids. Regardless of wastewater irrigation duration, irrigation with wastewater significantly increased organic matter, nitrogen, phosphorus, and potassium of the soil. The Mg2+ and Ca2+ contents in the aboveground biomass of the plants were also high ranged from 0.58 to 1%, and 0.43 to 0.68 mg g-1 DW, respectively. All the exchangeable cations other than Na+ were higher for wastewater irrigation at the flowering stage. Plants maintained noticeably higher Ca2+/Na+ and K+/Na+ ratios in the roots than those in the shoots except for 4 days after the reproductive stage. S. europaea is well adapted to grow in wastewater irrigation and can tolerate hypoxic conditions through improving water and soil quality.


Immunopeptidome Analysis of HLA-DPB1 Allelic Variants Reveals New Functional Hierarchies.
HLA-DP alleles can be classified into functional T cell epitope (TCE) groups. TCE-1 and TCE-2 are clearly defined, but TCE-3 still represents an heterogeneous group. Because polymorphisms in HLA-DP influence the presented peptidome, we investigated whether the composition of peptides binding in HLA-DP may be used to refine the HLA-DP group classification. Peptidomes of human HLA-DP-typed B cell lines were analyzed with mass spectrometry after immunoaffinity chromatography and peptide elution. Gibbs clustering was performed to identify motifs of binding peptides. HLA-DP peptide-binding motifs showed a clear association with the HLA-DP allele-specific sequences of the binding groove. Hierarchical clustering of HLA-DP immunopeptidomes was performed to investigate the similarities and differences in peptidomes of different HLA-DP molecules, and this clustering resulted in the categorization of HLA-DP alleles into 3-DP peptidome clusters (DPC). The peptidomes of HLA-DPB1*09:01, -10:01, and -17:01 (TCE-1 alleles) and HLA-DPB1*04:01, -04:02, and -02:01 (TCE-3 alleles) were separated in two maximal distinct clusters, DPC-1 and DPC-3, respectively, reflecting their previous TCE classification. HLA-DP alleles categorized in DPC-2 shared certain similar peptide-binding motifs with DPC-1 or DPC-3 alleles, but significant differences were observed for other positions. Within DPC-2, divergence between the alleles was observed based on the preference for different peptide residues at position 9. In summary, immunopeptidome analysis was used to unravel functional hierarchies among HLA-DP alleles, providing new molecular insights into HLA-DP classification.


Compatibility between the endoparasitoid Hyposoter didymator and the entomopathogenic fungus Metarhizium brunneum: a laboratory simulation for the simultaneous use to control Spodoptera littoralis.
The cotton leafworm, Spodoptera littoralis, is one of the most destructive pests in the Mediterranean basin, being predominantly controlled using synthetic chemical pesticides. Strain EAMa 01/58-Su of the fungus Metarhizium brunneum and the parasitoid Hyposoter didymator are promising biological control agents for this pest. In this study, we assessed the compatibility between these two agents to control S. littoralis under joint attack scenarios. Firstly, the direct and indirect effects of the fungus towards parasitoid adults were studied. The fungus significantly decreased life expectancy of the parasitoid (mortality = 62.5%; mean lethal concentration = 1.85 × 106 conidia ml-1 ; average survival time = 92.2 h) when applied at high concentrations (108 conidia ml-1 ), whereas it did not affect the reproductive potential of the parasitoid females during the 3 days after treatment. Secondly, the combinations between the two agents to control S. littoralis under different simultaneous use scenarios (inoculation of S. littoralis larvae with the fungus before being exposed to parasitoid females and vice versa) were investigated, with additive effect in all cases. A significant effect on fitness (preimaginal development time and reproductive potential) of the F1 parasitoid generation were detected. Moreover, parasitization significantly reduced the total hemocytes in S. littoralis hemolymph compared with the control, promoting fungal infection. Finally, parasitoids showed a significant preference for non-inoculated S. littoralis larvae. We demonstrated compatibility (additive effect) between fungus and parasitoid under different joint attack scenarios to control S. littoralis in laboratory conditions. However, this will be supported by our ongoing greenhouse and field studies. © 2019 Society of Chemical Industry.


Mitochondrial bioenergetics in leukocytes and oxidative stress in blood serum of mild to moderately depressed women.
Major depressive disorder (MDD) has been associated with lower mitochondrial energy production and higher oxidative stress. We investigated whether these alterations manifest in patients with current mild to moderate MDD severity. We observed no differences in mitochondrial respiration and density (i.e., citrate-synthase activity) in peripheral blood mononuclear cells and oxidative stress markers (i.e., 8-hydroxy-2'-deoxyguanosine, 8-isoprostane) in blood serum of 20 female MDD patients compared to 24 non-depressed women. Alterations in mitochondrial energy production and oxidative stress did not linearly depend on the current severity of MDD. However, biological alterations might rather manifest with higher MDD severity/chronicity and at higher age.


[Hearing and cognition: neurocognitive test batteries in otorhinolaryngology].
Hearing and cognition are closely related to each other. Particularly in suboptimal listening situations, cognitive abilities become important to enable speech comprehension. Besides, studies have indicated that hearing impairment is associated with a more rapid mental decline compared to persons with normal hearing. However, hearing loss also has an impact on neurocognitive testing, which is generally based on auditive stimuli. With increasing age, the risk of sensory but also of cognitive impairments increases. So far this comorbidity receives little consideration in otorhinolaryngology. The paper presents an overview and evaluation of widely used German neurocognitive test batteries for older patients, with regard to the different test modalities and their focus. A multitude of different neurocognitive screening tests and detailed test batteries are available, particularly in the field of dementia. So far, sensory deficits have not been considered in neurocognitive testing, neither concerning application nor interpretation. Normative data adapted to the hearing impaired are still missing. With regard to demographic changes and the well-known bias between hearing and cognition, screening of neurocognitive functions should be implemented in basic otorhinolaryngologic diagnostics. More comprehensive test batteries might be useful for research purposes or speech therapy.


Impact of patient education videos on genetic counseling outcomes after exome sequencing.
Growing use of clinical exome sequencing (CES) has led to an increased burden of genomic education. Self-guided educational tools can minimize the educational burden for genetic counselors (GCs). The effectiveness of these tools must be evaluated. Parents of patients offered CES were randomized to watch educational videos before their visit or to receive routine care. Parents and GCs were surveyed about their experiences following the sessions. The responses of the video (n = 102) and no-video (n = 105) groups were compared. GCs reported no significant differences between parents in the video and no-video groups on genetics knowledge or CES knowledge. In contrast, parents' scores on genetics knowledge questions were lower in the video than no-video group (p = 0.007). Most parents reported the videos were informative, and the groups did not differ in satisfaction with GCs or decisions to have CES. GCs and parents perceived the videos to be beneficial. However, lower scores on genetics knowledge questions highlight the need for careful development of educational tools. Educational tools should be developed and assessed for effectiveness with the input of all stakeholders before widespread implementation. Better measures of the effectiveness of these educational tools are needed.


Synthesis of 4-methylcoumarin derivatives containing 4,5-dihydropyrazole moiety to scavenge radicals and to protect DNA.
A series of 4-methylcoumarin derivatives containing 4,5-dihydropyrazole moiety were synthesized and their antioxidant activities were evaluated in AAPH (2,2'-azobis(2-amidinopropane hydrochloride))-induced oxidation of DNA, and in trapping DPPH (2,2'-diphenyl-1-picrylhydrazyl) and ABTS(+•) (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical), respectively. Among coumarin derivatives, 3a-d and 4a-c exhibited the termination of radical propagation-chains in AAPH-induced oxidation of DNA. The ortho dihydroxyphenyl substitution at 5 position and 1-unsubstitution of the 4,5-dihydroxylpyrazole was found enhancing the antioxidant activities of these coumarin derivatives.


An in vivo study of a custom-made high-frequency irreversible electroporation generator on different tissues for clinically relevant ablation zones.
To examine the ablation zone, muscle contractions, and temperature increases in both rabbit liver and kidney models in vivo for a custom-made high-frequency irreversible electroporation (H-FIRE) generator. A total of 18 New Zealand white rabbits were used to investigate five H-FIRE protocols (n = 3 for each protocol) and an IRE protocol (n = 3) for the performance of the designed H-FIRE device in both liver and kidney tissues. The ablation zone was determined by using histological analysis 72 h after treatment. The extent of muscle contractions and temperature change during the application of pulse energy were measured by a commercial accelerometer attached to animals and fiber optic temperature probe inserted into organs with IRE electrodes, respectively. All H-FIRE protocols were able to generate visible ablation zones without muscle contractions, for both liver and kidney tissues. The area of ablation zone generated in H-FIRE pulse protocols (e.g., 0.3-1 μs, 2000 V, and 90-195 bursts) appears similar to that of IRE protocol (100 μs, 1000 V, and 90 pulses) in both liver and kidney tissues. No significant temperature increase was noticed except for the protocol with the highest pulse energy (e.g., 1 μs, 2000 V, and 180 bursts). Our work serves to complement the current H-FIRE pulse waveforms, which can be optimized to significantly improve the quality of ablation zone in terms of precision for liver and kidney tumors in clinical setting.


Mycorrhizal symbioses: how to be seen as a good fungus.
Plants continually encounter many microorganisms. Some are good, but many are bad. Two studies show how beneficial fungi tell the plant to let them in and how the fungus avoids setting off the plant's defense reaction.


Down-regulation of B2R contributes to preeclampsia by inhibiting human trophoblast cell invasion and angiogenesis.
Bradykinin B2 receptor (B2R) was decreased in early chorionic villi of pregnancies who progressed to severe preeclampsia (PE), suggesting downregulation of B2R may be involved in the pathogenesis of PE. The aim of this study was to investigate the possible roles of B2R in the pathophysiology of PE and its function in trophoblastic cells. The expression of B2R in placentas from patients with early-onset severe PE (sPE) and LPS induced PE-like rats were detected. The roles of B2R in HTR-8/SVneo cells migration and invasion were analyzed through transfecting B2R overexpressing plasmid vector or B2R-specific siRNA. The effect of HTR-8/SVneo cells culture supernatant with high and low expressing B2R on human umbilical vein endothelial cells (HUVEC) capillary formation ability was also investigated. We found that B2R expression was significantly decreased in placentas of patients with sPE and PE-like rats. In addition, siRNA-mediated down-regulation of B2R markedly inhibited the migration and invasion of HTR-8/SVneo cells. Conversely, over-expression of B2R significantly promoted the migration and invasion of HTR-8/SVneo cells. Furthermore, the culture supernatant from B2R-overexpressed-HTR-8/SVneo cells promoted the capillary formation of HUVEC through increasing placental growth factor (PlGF) levels, while the culture supernatant from si-B2R-HTR-8/SVneo cells had the opposite effects. The decrease of B2R in placentas leads to the dysfunction of invasion, migration and angiogenesis of trophoblasts, which may be involved in the pathogenesis of PE.


Development and validation of a nomogram predicting the risk of recurrent lumbar disk herniation within 6 months after percutaneous endoscopic lumbar discectomy.
To develop and validate a nomogram useful in predicting recurrent lumbar disk herniation (rLDH) within 6 months after percutaneous endoscopic lumbar discectomy (PELD). Information on patients' lumbar disk herniation (LDH) between January 2018 and May 2019 in addition to 26 other features was collected from the authors' hospital. The least absolute shrinkage and selection operator (LASSO) method was used to select the most important risk factors. Moreover, a nomogram was used to build a prediction model using the risk factors selected from LASSO regression. The concordance index (C-index), the receiver operating characteristic (ROC) curve, and calibration curve were used to assess the performance of the model. Finally, clinical usefulness of the nomogram was analyzed using the decision curve and bootstrapping used for internal validation. Totally, 352 LDH patients were included into this study. Thirty-two patients had recurrence within 6 months while 320 showed no recurrence. Four potential factors, the course of disease, Pfirrmann grade, Modic change, and migration grade, were selected according to the LASSO regression model. Additionally, the C-index of the prediction nomogram was 0.813 (95% CI, 0.726-0.900) and the area under receiver operating characteristic curve (AUC) value was 0.798 while the interval bootstrapping validation C-index was 0.743. Hence, the nomogram might be a good predictive model. Each variable, the course of disease, Pfirrmann grade, Modic change, and migration grade in the nomogram had a quantitatively corresponding risk score, which can be used in predicting the overall recurrence rate of rLDH within 6 months.


Anaesthetic uptake and washout characteristics of patient circuit tubing with special regard to current decontamination techniques.
The amounts of halothane and isoflurane trapped after exposure for up to 3 h at 2 MAC in commonly used anaesthesia circuit tubing were quantitated by gas chromatography. The decontaminating effects of procedures such as flushing with oxygen, thermal disinfection and/or routine storage were assessed in a similar way. After halothane exposure, anaesthetic content was highest in silicone (398 +/- 55 mg 100 g-1). Lower quantities were found in all other tubings investigated (electrically conductive latex: 64 +/- 4, conductive rubber: 62 +/- 4, polyethylene-vinyl-acetate (PEVA): 293 +/- 10 and 149 +/- 17 for non-conductive corrugated and spiral tubes, respectively, polysulfone (Hytrel): 155 +/- 10 mg 100 g-1). The isoflurane contents were substantially lower (silicone: 278 +/- 23; others: 55 +/- 7, 61 +/- 6, 163 +/- 9 and 86 +/- 8, 74 +/- 4 mg 100 g-1). The tubings' content did not correlate with the material's partition coefficient as full saturation was not achieved during exposure. Decontamination procedures reduced the content of volatile anaesthetics to a variable extent. Conductive latex and rubber showed the highest residual content, even after thermal disinfection and subsequent storage. Twenty-minute flushing with oxygen (8 l min-1) decreased effluent gas concentrations below 5 p.p.m. in all tubings. With silicone, after 1 h flushing, halothane concentrations still exceeded 10 p.p.m. (isoflurane: 8 p.p.m.). It is concluded that urgent decontamination by a 20-min flush warrants the safe re-use of previously 'contaminated' conductive rubber and latex as well as polysulfone tubings in critical situations, e.g. in malignant hyperthermia patients if disposable tubing is not immediately available.(ABSTRACT TRUNCATED AT 250 WORDS)


Cadmium neurotoxicity.
The Cd has been recognized as one of the most toxic environmental and industrial pollutants due to its ability to induce disturbances in several organs and tissues following either acute or chronic exposure. This review accounts for the recent evidence on its mechanisms to induce neurotoxicity, the role of the blood-brain barrier, oxidative stress, interference with calcium, and zinc-dependent processes and apoptosis induction as well as the modulatory effect of metallothionein. Discussion about cadmium neurotoxicity is centered on mechanisms of induction of cellular disfunctions. Future investigations must address those neuronal mechanisms in detail in order to understand cadmium-induced neurotoxicity.


Hypospadias: results of surgical treatment and perspectives in management.
An institutional experience with the repair of hypospadias over a fifteen-year period is reviewed. The 119 patients treated surigcally serve as the substance of this report. Recommendations concerning options in surgical treatment are predicated on this experience and the contemporary literature.


Polypeptide-metal cluster connectivities in Cd(II) GAL4.
Two-dimensional 1H-113Cd correlation NMR spectra have been used to determine the polypeptide/metal cluster connectivities in Cd(II) GAL4. The results show that the protein contains a two metal ion cluster where Cys-11 and Cys-28 are the bridging ligands.


About hysteresis in Shaker: Response to note by Villalba-Galea.
In this issue, Villalba-Galea (2023. J. Gen. Physiol.https://doi.org/10.1085/jgp.202313371) expresses interest in our recently published work (Cowgill and Chanda. 2023. J. Gen. Physiol.https://doi.org/10.1085/jgp.202112883). Our response points out the deficiencies in the alternative explanation proposed by Villalba-Galea to account for our findings on hysteresis (or lack thereof) in steady state charge-voltage curves of Shaker potassium channel.


Enhanced social interactions in rats following chronic, centrally infused oxytocin.
Most studies investigating the behavioral effects of centrally administered oxytocin (OT) have been confined to single acute injections followed by brief behavioral observations lasting up to 90 min. The present study examines the behavioral effects of chronic, centrally administered OT in male rats observed continuously for prolonged periods of time. Either artificial cerebrospinal fluid or OT was centrally infused (via osmotic minipump) to gonadally intact male rats. Behavioral observations were made on males paired with either ovariectomized or estrous females during a 6-h time period. Most striking was the observation that durations of physical contact were doubled in pairs containing OT-infused males, even in the absence of sexual interactions. Also, OT-infused males showed significantly higher levels of anogenital sniffing of females and autogrooming; however, sexual interactions were unaffected by chronic OT. Chronic OT had no effect on body temperature, analgesia, or exploratory behavior in an open field. These findings suggest that chronic OT in male rats has behavioral effects that may significantly enhance adult social (nonsexual) interactions, possibly through alterations in olfactory and somatosensory information processing.


A prospective population-based study of triggers of symptomatic flares in IBD.
We aimed to determine whether any of the nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, infections, and stress trigger symptomatic flares of inflammatory bowel diseases (IBDs). Participants drawn from a population-based IBD research registry were surveyed every 3 months for 1 year. They simultaneously tracked the use of NSAIDs, antibiotics, infections, major life events, mood, and perceived stress. Social networks, childhood socioeconomic status, and smoking were assessed at baseline. Disease flare was identified using the Manitoba Inflammatory Bowel Disease Index, a validated disease activity index. Across any two consecutive survey periods, participants were categorized as having a flare (inactive/active), having no flare (inactive/inactive), or remaining active (active/active). Potential triggers were evaluated for the first 3-month period to determine predictive rather than concurrent relationships. Data from only one pair of 3-month periods from an individual were analyzed. A total of 704 participants completed the baseline survey; 552 (78.3%) returned all 5 surveys. In all, 174 participants who had a flare were compared with 209 who had no flare. Perceived stress, negative affect (mood), and major life events were the only trigger variables significantly associated with flares. There were no differences between those who flared and those who did not, in the use of NSAIDs, antibiotics, or in the presence of infections. Multivariate logistic regression analyses indicated that only high-perceived stress (adjusted odds ratio=2.40 (1.35, 4.26)) was associated with an increased risk of flare. This study adds to the growing evidence that psychological factors contribute to IBD symptom flares. There was no support for differential rates of use of NSAIDS, antibiotics, or for the occurrence of (non-enteric) infections related to IBD flares.


Amyloid-beta is present in human lymph nodes and greatly enriched in those of the cervical region.
Degradation and clearance of amyloid beta (Aβ) peptide are likely critical for brain health. Animal studies have demonstrated the role of the glial-lymphatic (glymphatic) system in the clearance of Aβ and other brain metabolites, but no such information has been available in humans. Here we ask whether this system contributes to the clearance of Aβ from the human brain. In the absence of an applicable imaging method, we examined cervical and inguinal lymph nodes resected for cancer therapy or staging using immunohistochemistry. Aβ-labeled cells were present in lymph nodes, and cervical lymph nodes showed labeled cells in far greater abundance than did inguinal nodes. This observation supports the hypothesis that the glymphatic system contributes to the clearance of Aβ from the human brain.


Fine-needle aspiration cytology of pleomorphic lobular carcinoma of the breast. Comparison with the classic type.
The pleomorphic variant of invasive lobular carcinoma shares the typical infiltrating histologic pattern of classic invasive lobular carcinoma, but differs from it in its nuclear pleomorphism and aggressive behavior. The purpose of this study was to describe the fine-needle aspiration (FNA) cytologic findings of the pleomorphic variant of lobular carcinoma and to compare them with those of classic lobular carcinoma. Among 405 breast FNA performed in 1995, 7 examples of classic infiltrating lobular carcinoma and 4 cases of this neoplasm's pleomorphic variant were identified; all were histologically confirmed. The FNA from three of the four pleomorphic variant cases and from two of the seven classic lobular carcinoma cases were diagnostic of malignancy; these were evaluated for a variety of cytologic criteria, which were graded from 0 to 3. Although exhibiting many cytologic features in common with the classic type, such as indian files and cytoplasmic vacuoles, the FNA of the pleomorphic variant differed in their tendency to yield greater cellularity, larger cell size, and, particularly, more pleomorphic nuclei. The FNA cytologic findings of the pleomorphic variant of lobular carcinoma are characteristically hybrid between those of classic lobular carcinoma and ductal carcinoma.


Neurogenesis in colorectal cancer is a marker of aggressive tumor behavior and poor outcomes.
Colorectal cancer staging criteria do not rely on examination of neuronal tissue. The authors previously demonstrated that perineural invasion is an independent prognostic factor of outcomes in colorectal cancer. For the current study, they hypothesized that neurogenesis occurs in colorectal cancer and portends an aggressive tumor phenotype. In total, samples from 236 patients with colorectal cancer were used to create a tissue array and database. Tissue array slides were immunostained for protein gene product 9.5 (PGP9.5) to identify nerve tissue. The correlation between markers of neurogenesis and oncologic outcomes was determined. The effect of colorectal cancer cells on stimulating neurogenesis in vitro was evaluated using a dorsal root ganglia coculture model. Patients whose tumors exhibited high degrees of neurogenesis had 50% reductions in 5-year overall survival and disease-free survival compared with patients whose tumors contained no detectable neurogenesis (P = .002 and P = .006, respectively). Patients with stage II disease and high degrees of neurogenesis had greater reductions in 5-year overall survival and disease-free survival compared with lymph node-negative patients with no neurogenesis (P = .002 and P = .008, respectively). Patients with stage II disease and high degrees of neurogenesis had lower 5-year overall survival and disease-free survival compared with patients who had stage III disease with no neurogenesis (P = .01 and P = .008, respectively). Colorectal cancer cells stimulated neurogenesis and exhibited evidence of neuroepithelial interactions between nerves and tumor cells in vitro. Neurogenesis in colorectal cancer appeared to play a critical role in colorectal cancer progression. Furthermore, the current results indicated that neurogenesis functions as an independent predictor of outcomes and may play a role in therapy stratification for patients with lymph node-negative disease.


Paul of Aegina (ca 625-690 ad): Byzantine Surgeon and Pioneer of Surgical Management of Congenital Atresia of the External Auditory Canal.
Diseases of the ear have been recorded and treated since ancient times. Ex-votos have been offered to heal deafness. Noninvasive treatments have evolved into minor, and later more advanced, surgical techniques to treat head and neck issues. Paul of Aegina (ca 625-690 ad) perfected his medical skills in the School of Alexandria in Egypt. His medical encyclopedia, Medical Compendium, described a broad series of surgical operations, including a chapter "On the atresia of the auditory canal," which vividly described a surgical technique to open the ear canal. This surgery is particularly interesting, as it exceeds the limits of resection and amputation known at that time and describes a novel surgical technique. His innovative methods paved the way for future surgeons.


Low doses of methylnaltrexone inhibits head and neck squamous cell carcinoma growth in vitro and in vivo by acting on the mu-opioid receptor.
The Mu-opioid receptor (MOR) has been implicated in tumorigenesis and metastasis. Methylnaltrexone (MNTX), an antagonist of MOR, has shown to inhibit tumor growth and metastasis in lung cancer cell lines. The effect of MNTX on other cell lines such as head and neck squamous cell carcinoma (HNSCC) has not been investigated. We measured the expression and activity of the receptor in different HNSCC cell lines. Then, we evaluated the impact of modulating the expression MOR and the effect of MNTX on the proliferation, clonogenic activity, invasion, and migration of two HNSCC (FaDu and MDA686Tu) cell lines expressing MOR and one cell line (UMSCC47) not expressing the receptor. We also evaluated the impact of MNTX on tumor growth and metastasis formation in vivo. Activation of the receptor with [d-Ala2,N-Me-Phe4, Gly5-ol] (DAMGO) caused a significant reduction in cyclic adenosine monophosphate levels in FaDu cells. Knockdown of MOR inhibited in vitro aggressive cell behaviors on FaDu and MDA686Tu cells and correlated with a reduction in markers of epithelial-mesenchymal transition. In vitro studies showed that MNTX strongly inhibited the proliferation, clonogenic activity, invasion, and migration of FaDu and MDA686Tu cells but has no effect on UMSCC47 cells. In vivo experiments demonstrated that MNTX suppresses tumor growth in HNSCC cell tumor-bearing mice. Our studies indicate that MOR could be considered as a therapeutic target to treat HNSCC.


Infants' eyewitness testimony: effects of postevent information on a prior memory representation.
In eyewitness testimony research, postevent information impairs retention of the original event and increases the probability that interpolated information will be identified as part of the original event. The present experiments studied these effects with 3-month-olds. Infants learned to kick to move a particular crib mobile and then were briefly exposed to information about a novel mobile. The novel postevent information impaired recognition of the original mobile when it immediately followed training but not when it was delayed by 1 day. Like adults, infants treated the postevent information as part of the original training event, continuing to do so for at least 2 weeks. We propose that postevent information displaces conflicting information coactive with it in primary memory and creates a new, updated memory token of the event. Once the new token leaves primary memory, however, it is protected; only a copy can be retrieved and modified in the future.


Sex differences in the hypothalamic-pituitary-adrenal axis in patients with burning mouth syndrome.
To investigate the sex differences in clinical features, including salivary flow rate, psychological distress and hypothalamic-pituitary-adrenal axis response and their inter-relationships in patients with burning mouth syndrome. Eighteen men and 37 postmenopausal women with burning mouth syndrome underwent a comprehensive questionnaire evaluation, psychological evaluation and salivary flow rate measurement. Laboratory tests were performed to investigate the function and integrity of the hypothalamic-pituitary-adrenal axis. Both unstimulated and stimulated salivary flow rates were higher in men than in women (unstimulated: 0.58 ± 0.32 vs. 0.37 ± 0.15 ml/min, p < .01; stimulated: 1.83 ± 0.63 vs. 1.22 ± 0.31, p < .001). Symptom severity scored on a visual analogue scale negatively correlated with anti-diuretic hormone levels in both sexes. The visual analogue scale scores negatively correlated with unstimulated (r = -.652, p < .01) and stimulated (r = -.376, p < .05) salivary flow rates in men and women, respectively. Unstimulated salivary flow rates positively correlated with anti-diuretic hormone (r = .453, p < .05) and progesterone (r = .402, p < .05) levels only in women. Our results suggest that clinicians should consider hypothalamic-pituitary-adrenal axis response, as well as sex and salivary flow rates, when identifying the aetiology of patients with burning mouth syndrome, as it may enable more accurate and effective treatment.


Lutropin receptors from male and female tissues: different responses to a lutropin receptor binding inhibitor.
An inhibitor for lutropin receptor site binding (LH-RBI), which strongly inhibited the binding of 125I-labeled ovine lutropin ([125I]oLH) to ovarian LH receptors, did not inhibit the [125I]oLH binding to testicular LH receptors. Preincubation of the LH-RBI with [125I]oLH did not affect the binding of preincubated ]125I]oLH to ovarian LH receptors. No inhibition of [125I]oLH binding to testicular LH receptors was observed even uhen the concentration of LH-RBI was significantly increased or when the testicular LH receptors uere first incubated with LH-RBI prior to the addition of [125I]oLH and a second incubation. Scatchard analysis revealed that the dissociation constant of [125I]oLH binding was essentially the same in the presence or absence of LH-RBI. The results suggest that: (i) the lutropin receptor of ovaries, but not of testes, has a specific LH-RBI binding site in addition to the lutropin binding site, and (ii) the binding of the LH-RBI produces an "allosteric" type of inhibition to the binding of lutropin at the lutropin binding site.


[Effect of diabetes-psychosomatic group education on metabolic control and coping with disease by insulin-dependent diabetic patients].
Even though cognitive education programs are essential for the treatment of diabetics, long term efficacy often seems to be poor. Problems of coping with illness could be the reason for a lack of transfer of knowledge into daily practice. Small discussion groups with the aim of modifying attitudes towards illness might be a good possibility to face this problem. 54 IDDM, HbA1 10.7 +/- 2.3% (median +/- SD) absolved our 5-day education program for outpatients, in which daily group sessions (90 min), supervised by a group-therapist, were integrated. Follow-up sessions took place after 1, 4 and 8 months. The efficacy was measured by HbA1 and different questionnaires on diabetologic knowledge, life satisfaction (FLZ) and complaints (BL). 4 months after the education program HbA1 had decreased to 9.0 (median +/- SD) and remained stable within small range during the rest of the study-period. Diabetologic knowledge increased from 70% (median +/- SD) to 87% (median +/- SD) 1 month after the education and remained stable during the rest of the study-period. Complaints decreased within one month from a level above average somatic illness to the normal level for healthy subjects. However, in regard to their life satisfaction our patients were significantly less satisfied concerning their health, whereas family life and friendship were declared to be more satisfying (after 8 months). We believe that more intensive communication in the family (encouraged by the group-therapy) and parallel more critical attitudes towards illness lead to this results. As basic elements for long term modification of illness behaviour these emotional aspects seem to be essential.


A minimally invasive periacetabular osteotomy improves the radiographic parameters and functional outcomes in the treatment of developmental dysplasia of the hip in adolescents and adults: surgical technique and early results.
To introduce West China Hospital periacetabular osteotomy (WCH PAO) for acetabular dysplasia in adolescent and young adult patients and evaluate the early clinical results of WCH PAO. A retrospective analysis of 34 patients with developmental dysplasia of the hip was performed from October 2019 to April 2021. Baseline data with surgical time and perioperative blood-loss volume were retrieved from medical record systems. The lateral center-to-edge angle (LCEA), acetabular inclination (AI), hip disability and osteoarthritis outcome score (HOOS), University of California Los Angeles (UCLA), and modified Harris hip score (mHHS) were compared preoperatively and postoperatively. All patients had significant postoperative radiology improvements, including LCEA and AI. The LCEA was improved from 12.9 to 33.2°, and the AI was decreased from 27.2 to 8.5°. In addition, hip functional outcomes, including HOOS, UCLA and mHHS, were improved. The UCLA was improved from 3.9 to 6.3, and the HOOS was decreased from 71.0 to 10.5. The Harris hip score improved from 50.8 before surgery to 87.4 after surgery. The mean operative time was 155 min (range 120 to 190 min), and the mean intra-operative blood loss was 580.2 ± 285.5 ml. Furthermore, no major complications, including nerve injury or bone nonunion, occurred in the cohort study. WCH PAO is a minimally invasive surgical method for acetabular dysplasia in adolescent and young adult patients who that simplifies the surgical procedure and decreases the incidence of complications related to osteotomy.


3D-based buccal augmentation for ideal prosthetic implant alignment-an optimized method and report on 7 cases with pronounced buccal concavities.
Screw-retained restoration of implants is advantageous for biological and esthetic reasons. Due to buccal concavities, however, this preferred type of restoration can only be used in about half of the anterior indications. Based on case series, an optimized method for the treatment of such indications is to be described; the clinical reliability is to be ascertained by means of measurements (before and after augmentation) and assigned to the current literature. A case series of seven cases with buccal concavities of the anterior alveolar ridge were treated with optimized method, which is presented step-by-step until the prosthetic restoration. The depths of the bone concavities were measured and related to the bone gain after augmentation procedure respectively after implantation. Linear measurements of the buccal concavities showed an average undercut of 4 mm [SD ± 1.13]. After healing period of six months, the buccal concavities could be compensated bony to such an extent that implants could be inserted in correct position and angulation. On average, there was a horizontal bone gain of 3.7 mm [SD ± 0.59]. Even after implantation and another six months of healing, stable bone dimensions could be assumed with an average of 4.3 [SD ± 0.83] mm of bone gain compared to baseline. In six of the seven cases, the favorite screw-retained, one-piece full-ceramic restoration could be fixed on the implants. Due to the implant axis, one case had to be treated with a cemented two-part full-ceramic system. With the described optimized method the most favorable screw-retained restoration can also be used in situations with unfavorable concavities of buccal bone. Especially for this indication, a special form of the horizontal deficit, the customized bone regeneration with titanium meshes is highly reliable in terms of healing and extent of augmentation. However, long-term results and a study/control group are required to evaluate the effectiveness of the presented protocol. Since these situations require an augmentation that is up to 5 mm thick and a procedure that is as minimally invasive as possible appears to be necessary in the visible area, an optimized method is described in this publication.


Defensive responses by a social caterpillar are tailored to different predators and change with larval instar and group size.
Gregariousness in animals is widely accepted as a behavioral adaptation for protection from predation. However, predation risk and the effectiveness of a prey's defense can be a function of several other factors, including predator species and prey size or age. The objective of this study was to determine if the gregarious habit of Malacosoma disstria caterpillars is advantageous against invertebrate natural enemies, and whether it is through dilution or cooperative defenses. We also examined the effects of larval growth and group size on the rate and success of attacks. Caterpillars of M. disstria responded with predator-specific behaviors, which led to increased survival. Evasive behaviors were used against stinkbugs, while thrashing by fourth instar caterpillars and holding on to the silk mat by second instar caterpillars was most efficient against spider attacks. Collective head flicking and biting by groups of both second and fourth instar caterpillars were observed when attacked by parasitoids. Increased larval size decreased the average number of attacks by spiders but increased the number of attacks by both stinkbugs and parasitoids. However, increased body size decreased the success rate of attacks by all three natural enemies and increased handling time for both predators. Larger group sizes did not influence the number of attacks from predators but increased the number of attacks and the number of successful attacks from parasitoids. In all cases, individual risk was lower in larger groups. Caterpillars showed collective defenses against parasitoids but not against the walking predators. These results show that caterpillars use different tactics against different natural enemies. Overall, these tactics are both more diverse and more effective in fourth instar than in second instar caterpillars, confirming that growth reduces predation risk. We also show that grouping benefits caterpillars through dilution of risk, and, in the case of parasitoids, through group defenses. The decreased tendency to aggregate in the last larval instar may therefore be linked to decreasing predation risk.


WITHDRAWN: Detection of digital and interdigital dermatitis in Holstein Frisian dairy cows by means of infrared thermography.
Ahead of Print article withdrawn by publisher.


Biomedical applications of green synthesized Nobel metal nanoparticles.
Synthesis of Nobel metal nanoparticles, play a key role in the field of medicine. Plants contain a substantial number of organic constituents, like phenolic compounds and various types of glycosides that help in synthesis of metal nanoparticles. Synthesis of metal nanoparticles by green method is one of the best and environment friendly methods. The major significance of the green synthesis is lack of toxic by-products produced during metal nanoparticle synthesis. The nanoparticles, synthesized by green method show various significant biological activities. Most of the research articles report the synthesized nanoparticles to be active against gram positive and gram negative bacteria. Some of these bacteria include Escherichia coli, Bacillus subtilis, Klebsiella pneumonia and Pseudomonas fluorescens. The synthesized nanoparticles also show significant antifungal activity against Trichophyton simii, Trichophyton mentagrophytes and Trichophyton rubrum as well as different types of cancer cells such as breast cancer cell line. They also exhibit significant antioxidant activity. The activities of these Nobel metal nano-particles mainly depend on the size and shape. The particles of small size with large surface area show good activity in the field of medicine. The synthesized nanoparticles are also active against leishmanial diseases. This research article explores in detail the green synthesis of the nanoparticles and their uses thereof.


Sucrose accelerates flower opening and delays senescence through a hormonal effect in cut lily flowers.
Sugars are generally used to extend the vase life of cut flowers. Such beneficial effects have been associated with an improvement of water relations and an increase in available energy for respiration by floral tissues. In this study we aimed at evaluating to what extent (i) endogenous levels of sugars in outer and inner tepals, androecium and gynoecium are altered during opening and senescence of lily flowers; (ii) sugar levels increase in various floral tissues after sucrose addition to the vase solution; and (iii) sucrose addition alters the hormonal balance of floral tissues. Results showed that endogenous glucose levels increased during flower opening and decreased during senescence in all floral organs, while sucrose levels increased in outer and inner tepals and the androecium during senescence. Sucrose treatment accelerated flower opening, and delayed senescence, but did not affect tepal abscission. Such effects appeared to be exerted through a specific increase in the endogenous levels of sucrose in the gynoecium and of glucose in all floral tissues. The hormonal balance was altered in the gynoecium as well as in other floral tissues. Aside from cytokinin and auxin increases in the gynoecium; cytokinins, gibberellins, abscisic acid and salicylic acid levels increased in the androecium, while abscisic acid decreased in outer tepals. It is concluded that sucrose addition to the vase solution exerts an effect on flower opening and senescence by, among other factors, altering the hormonal balance of several floral tissues.


Progesterone receptor expression is a marker for early stage breast cancer: implications for progesterone receptor as a therapeutic tool and target.
We determined the association of estrogen receptor (ER) and progesterone receptor (PR) expression in invasive breast cancer with stage at diagnosis. Univariate analyses indicated that although ER and PR expression were inversely associated with grade (P<0.0001), only PR expression (P<0.01) was inversely associated with stage. Multivariate analyses, adjusted for covariates, including HER-2/neu expression, indicated that PR (odds ratio (OR), 0.88; confidence interval (CI), 0.77-0.99; P=0.03) and not ER expression (OR, 1.04; CI, 0.94-1.16; P=0.45) was inversely associated with stage. PR and not ER expression is a marker for early stage breast cancer.


Enhanced lipid degradation in an upflow anaerobic sludge blanket reactor by integration with an acidogenic reactor.
Lipids inhibition and their degradation in dairy wastewater treatment were investigated in this study. A two-phase system, composed of an acidogenic continuously stirred tank reactor (CSTR) and a methanogenic upflow anaerobic sludge blanket (UASB) reactor, was compared with the single-phase system of a conventional UASB reactor. The systems were operated up to an organic loading rate of 8.09 g chemical oxygen demand (COD)/L x d at a lipid loading rate of 2.94 g COD/L x d. The two-phase system showed better performance in COD removal (1.19 times), lipids removal (1.92 times), and methane production (1.42 times) compared with the single-phase system. The degradation of lipids and the saturation of the double-bonded lipids in the CSTR enhanced the performance of the system. In serum bottle tests at different lipids concentrations, a high lipids concentration resulted in a long lag-phase time for methane production. However, 69.5% of COD eventually was converted to methane within 50 days at 6.1 g lipid-COD/L.


The effects of short time hyperoxia on glutamate concentration and glutamate transporters expressions in brain of neonatal rats.
Preterm infants often suffer from impaired postnatal brain development, and glutamate excitotoxicity is identified as a pivotal mechanism of hyperoxia-induced neurological abnormality. We aimed to investigate the effect of short time hyperoxia on glutamate homeostasis and glutamate transporters expressions in immature brain. Six-day-old (P6) rat pups were exposed to 80% oxygen for 24 h (the hyperoxia group) or placed in atmospheric air (the control group). The concentrations of glutamate and γ-aminobutyric acid (GABA) in immature cerebrum and cerebellum at P7, P14 and P21 were determined by ELISA. The mRNA levels of glutamate transporters including excitatory amino acid transporter 1 (EAAT1), EAAT2, EAAT3, vesicular glutamate transporter 1 (VGLUT1) and VGLUT2 in brain were determined by qPCR. Glutamate accumulation was induced by hyperoxia both in immature cerebrum and cerebellum at P7 but got gradually attenuated at P14 and P21, as evidenced by the changes of glutamate and GABA concentrations. Hyperoxia also induced sustained glutamatic oxidative stress in both cerebrum and cerebellum, as GSH (reduced glutathione) levels in the hyperoxia group were constantly higher than the control group at three examined time-points. Furthermore, at P7, the expressions of all glutamate transporters decreased in both cerebrum and cerebellum except that of EAAT1. At P21, VGLUT2 in cerebrum and EAAT1, EAAT3 and VGLUT2 in cerebellum still displayed significant decrease in expression levels upon hyperoxia stimulation. Taken together, our results indicate that hyperoxia induces glutamate accumulation in brain of rat pups, which is associated with increased oxidative stress and decreased expressions of glutamate transporters.


Successful intraosseous adenosine administration in a newborn infant with supraventricular tachycardia.
Supraventricular tachycardia (SVT) is the most common type of tachycardia in childhood. The incidence is 1-4/1000 in childhood and 0.6/1000 in newborns. Here we report a 28-day-old male newborn who was diagnosed SVT, admitted to the Pediatric Emergency Department after restlessness that had started three hours before admission and measurement of the heart rate was above 250 beats/min. This case is presented in order to emphasize that SVT is rare in the neonatal period and SVT is successfully terminated with the administration of intraosseous adenosine.


Effect of depletion of bicarbonate or phosphate ions on insulin action in rat adipocytes. Further characterization of the receptor-effector system.
In the preceding paper (Shechter, Y., and Ron, A. (1986) J. Biol. Chem. 261, 14945-14950) we have shown that in fat cells, prepared and maintained in an isotonic buffer (pH 7.4) containing neither phosphate nor bicarbonate anions (Buffer A), the dose-response curve to insulin shifted to the right by about 2 logarithms and insulin binding affinity or capacity was only slightly decreased. In the current paper we demonstrate that progressive loss of insulin binding, either by treatment with trypsin or preincubating the cells with isoproterenol, correlates well with the reduced ability of the cells to elicit maximal lipogenesis in response to insulin. We further demonstrate in the "new" system that: the dissociation of labeled insulin from fat cells is not accelerated by the inclusion of unlabeled insulin in the medium; termination of lipogenesis in Buffer A occurs immediately; ligand-induced receptor internalization is grossly defective; and insulin is unable to stimulate lipogenesis at 15 degrees C. The data support the hypothesis that in the new experimental system all measurable binding sites are linked to a coupling mechanism. Each site behaves as an independent, separate entity and there are no site to site interactions. This leads to a linear relationship between binding and bioactivation, lack of negative or positive cooperatively, accelerated rate of termination, defective internalization, a shift to the right in the dose-response curve to insulin, and a lack of insulin response at a lower temperature. In more general terms, the study indicates that all measurable insulin receptors are chemically homogeneous in their potential capability to be coupled to an insulin effector (biologically relevant) system, and they do so under particular experimental conditions.


The association of hemoglobin drop with in-hospital outcomes in COVID-19 patients.
Bleeding events can be critical in hospitalized patients with COVID-19, especially those with aggressive anticoagulation therapy. We aimed to investigate whether hemoglobin drop was associated with increased risk of acute kidney injury (AKI) and in-hospital mortality among patients with COVID-19. Retrospective cohort study. This retrospective study was conducted by review of the medical records of 6683 patients with laboratory-confirmed COVID-19 hospitalized in the Mount Sinai Health system between 1st March 2020 and 30th March 2021. We compared patients with and without hemoglobin drop >3 g/dl during hospitalization within a week after admissions, using inverse probability treatment weighted analysis (IPTW). Outcomes of interest were in-hospital mortality and AKI which was defined as serum creatine change of 0.3 mg/dl increase or 1.5 times baseline. Of the 6683 patients admitted due to COVID-19, 750 (11.2%) patients presented with a marked hemoglobin drop. Patients with hemoglobin drop were more likely to receive therapeutic anticoagulation within 2 days after admissions. Patients with hemoglobin drop had higher crude in-hospital mortality (40.8% vs. 20.0%, P < 0.001) as well as AKI (51.4% vs. 23.9%, P < 0.001) compared to those without. IPTW analysis showed that hemoglobin drop was associated with higher in-hospital mortality compared to those without (odds ratio (OR) [95% confidential interval (CI)]: 2.21 [1.54-2.88], P < 0.001) as well as AKI (OR [95% CI]: 2.79 [2.08-3.73], P < 0.001). Hemoglobin drop during COVID-19 related hospitalizations was associated with a higher risk of AKI and in-hospital mortality.


Cognitive behavioral intervention for improving emotion recognition among individuals with substance use disorders: A randomized-controlled pilot study in a naturalistic setting.
Individuals with substance use disorders (SUD) experience impaired facial emotion recognition. This pilot study explored the efficacy of a cognitive behavioral therapy (CBT) intervention to improve facial cues interpretation. Twenty-four men with SUD were randomized into an equal-size experimental and control groups and were evaluated by a cognitive-assessment battery at baseline and post-intervention. Post-intervention individuals in the experimental group recognized happy expressions with higher accuracy, and their response times were slower in sadness/disgust/neutral expressions. Interventions focused at improving social cues interpretation may facilitate social interactions and treatment outcomes for SUD population.


The combined effect of short foot exercises and orthosis in symptomatic flexible flatfoot: a randomized controlled trial.
Flatfoot is a musculoskeletal problem associated with dysfunctional active and passive supporting structures of the normal foot curvature. Strengthening of the intrinsic foot muscles or using shoe orthosis are recommend treatment approaches. However, investigating the effect of combining both approaches is still warranted. To examine the effect of applying short foot exercises (SFE) combined with shoe insole versus shoe insole alone on foot pressure measures, pain, function and navicular drop in individuals with symptomatic flexible flatfoot. Prospective, active control, parallel-group, assessor-blinded, randomized controlled trial and intention-to-treat analysis. Outpatient physical therapy clinic of a university teaching hospital. Forty participants with symptomatic flexible flatfoot. A six-week treatment protocol of SFE (three sets of 10 repetitions a day) in addition to shoe insole (eight hours a day) (experimental group, N.=20) or shoe insole only (eight hours a day) (control group, N.=20). Clinic visits were made at baseline and every two weeks for monitoring and follow-up. The static and dynamic foot area, force and pressure measures, pain, lower extremity function, and navicular drop were assessed at baseline and postintervention. Forty participants joined the study and 37 (92.5%) completed the six-week intervention period. Foot pressure, pain and function showed a significant interaction (P=0.02 - <0.001) and time (P<0.001) effects with a non-significant group effect in favor of the experimental group. Post-hoc analysis revealed that the experimental group had lesser pain (P=0.002) and better function (P=0.03) than the control group at six weeks. Navicular drop decreased equally in both groups. Implementation of shoe insole and SFE for six weeks improved pain and function and altered foot pressure distribution greater than shoe insole alone in patients with symptomatic flatfoot. Wearing shoe insole is an easy, but passive, treatment approach for a flatfoot problem. This study provided evidence regarding the added benefit of SFE. It is recommended that rehabilitation practitioners implement a comprehensive treatment protocol including both shoe insole and SFE for at least six weeks to achieve better results for their flatfoot patients.


[Effect of phenformin on fat-carbohydrate metabolism in pregnant rats].
Rats given phenphormin, an antidiabetic biguanide, from the 1st (8th) day of pregnancy displayed a fall of cholesterol, phospholipids and free fatty acids in the blood; no maldevelopment of the fetus or placenta was seen. Permissibility of prescription of biguanides during pregnancy is discussed.


Assessment of trifloxystrobin uptake kinetics, developmental toxicity and mRNA expression in rare minnow embryos.
Trifloxystrobin (TFS) is the widely used strobilurin fungicide. However, little information is so far available regarding the uptake kinetics and developmental toxicity of TFS to fish. The present study was conducted to investigate the uptake kinetics, potential environment risk and toxicity of TFS on Gobiocypris rarus embryos. Results revealed that increased malformation, decreased body length and heart rate, affected spontaneous movement and swimming speed provide a gradual concentration-dependent manner; values of 144 h LC50 (median lethal concentration) and EC50 (median effective concentration) were 1.11 and 0.86 μg L(-1). Continuous exposure to TFS resulted in a steady accumulation with no evidence of elimination. Enzyme activities were significantly changed; reactive oxygen species and DNA damage were significantly induced after TFS treatment. Certain genes related to cell apoptosis (p53), metabolism (cyp1a), stress response (hsp70) and blood vessels (vezf1) development were all significantly up-regulated. This is the first study to define uptake kinetics and to focus on behavioral consequences, physiological changes and mRNA expression following TFS exposure in the early life stages of fish. Our results suggest that TFS is highly toxic to fish embryos.


Hydrogen generation via anaerobic fermentation of paper mill wastes.
The objective of this work was to determine the hydrogen production from paper mill wastes using microbial consortia of solid substrate anaerobic digesters. Inocula from mesophilic, continuous solid substrate anaerobic digestion (SSAD) reactors were transferred to small lab scale, batch reactors. Milled paper (used as a surrogate paper waste) was added as substrate and acetylene or 2-bromoethanesulfonate (BES) was spiked for methanogenesis inhibition. In the first phase of experiments it was found that acetylene at 1% v/v in the headspace was as effective as BES in inhibiting methanogenic activity. Hydrogen gas accumulated in the headspace of the bottles, reaching a plateau. Similar final hydrogen concentrations were obtained for reactors spiked with acetylene and BES. In the second phase of tests the headspace of the batch reactors was flushed with nitrogen gas after the first plateau of hydrogen was reached, and subsequently incubated, with no further addition of inhibitor nor substrate. It was found that hydrogen production resumed and reached a second plateau, although somewhat lower than the first one. This procedure was repeated a third time and an additional amount of hydrogen was obtained. The plateaux and initial rates of hydrogen accumulation decreased in each subsequent incubation cycle. The total cumulative hydrogen harvested in the three cycles was much higher (approx. double) than in the first cycle alone. We coined this procedure as IV-SSAH (intermittently vented solid substrate anaerobic hydrogen generation). Our results point out to a feasible strategy for obtaining higher hydrogen yields from the fermentation of industrial solid wastes, and a possible combination of waste treatment processes consisting of a first stage IV-SSAH followed by a second SSAD stage. Useful products of this approach would be hydrogen, organic acids or methane, and anaerobic digestates that could be used as soil amenders after post-treatment.


The masking role of the sodium pump and chloride ions on the effect of carbachol in- and outside the endplate region of rat diaphragm muscle.
The effect of carbachol (10(-3)M) on the membrane potential of rat diaphragm muscle fibres near and remote from the endplate has been investigated by means of a microelectrode technique. In the endplate region a rather slow depolarization was observed followed by spontaneous repolarization. Outside the endplate region similar, but smaller, responses could be measured. In a muscle part separated from the endplate zone, carbachol had no depolarizing effect. Inhibition of the sodium pump by ouabain (10(-4)M) or potassium-free medium not changing the membrane potential itself, allowed carbachol to exert a depolarizing effect on this endplate-free membrane, while in endplate-free regions continuous with the endplate-zone the depolarizations already observed were enhanced. In low chloride solutions carbachol also had a depolarizing effect on endplate-free muscle membrane. It is concluded from these experiments that a direct effect of cholinergic drugs on endplate-free muscle membrane of rat diaphragm is counteracted by the sodium pump in combination with passive chloride movements. The results are discussed in the context of known receptor densities and chloride effects.


Secondary intrachoroidal cavitation in a case of iridofundal coloboma.
Intrachoroidal cavitation is a morphological entity usually described in high myopic eyes. It is usually seen in peripapillary location, though macular location has also been reported. It has been associated with optic disc tilting and posterior staphyloma. We report a case of a 27 year old female who presented to us with recent onset scotoma in her visual field. On examination she had a fundal coloboma with intercalary membrane detachment with intrachoroidal cavitation at the edge of the coloboma. We hypothetise that this intrachoroidal cavitation is a secondary phenomenon and is responsible for recent onset scotoma in her visual field.


Risk rating in the tea planting industry: The employees' opinion.
Workers in the tea planting industry are exposed to a variety of occupational health and safety hazards. Whether the workers perceive the risks involved and to what degree is an interesting point in question. To identify occupational health and safety risks involved in the tea planting sector and to rate these risks from the workers' perspective. Permanent workers from four estates belonging to one tea planting company in southern India were enlisted in this descriptive study The sample was randomly and then proportionately selected to give a total number equal to the calculated sample size of 341. Data were collected by reviewing medical records, conducting focus group discussions with field officers and supervisors, worker interviews and key informant interviews with the management in these four estates. Proportions were used to describe occurrence and distribution of work-related injuries. The risks as perceived by the workers were rated on their severity and frequency, using a Risk Rating Matrix. The incidence of injuries was greater among male workers, those working both in the field and factory and those handling multiple tasks. The most common morbidities suffered were "small cuts and abrasions" in about 53%of the workers. Backache and insect bites were assigned the highest risk rating scores. Continued monitoring of the risk assessment by the workers could help in a planned reduction of commonly occurring injuries by agreeing on a specified risk limit.


A high environmental composite quality factor score was associated with the risk of sick building syndrome among adults in northeast China.
Epidemiological evidence regarding the association between the combination of indoor and outdoor neighborhood pollution and sick building syndrome (SBS) among adults is limited and inconsistent. A cross-sectional study was conducted to investigate the association between the environmental composite quality factor score and SBS among adults. This study included 2594 females and 666 males aged 18-77 years enrolled from the Northeast China. The environmental composite quality factor score was computed based on factors potentially associated with SBS risk, including the outdoor neighborhood pollution sources (the housing on the street, the presence of pollutants within 100 m of the house (gutters, garbage stations, noise, chemical pollution, and dust pollution), and the presence of arterial roads, factories, and chimneys) and indoor pollution sources (redecoration, clean fuel used for heating/cooking, cooking oil fume (COF) outside kitchen, using of mosquito coil or repellent, and using of incense). We performed multivariate logistic regression analysis to calculate the odds ratios (ORs) and 95% confidence intervals (95%CIs) between environmental composite quality factor score, indoor pollution composite factor score, outdoor neighborhood pollution composite factor score, and SBS adjustment for covariates. Further, we also did the stratified analysis and constructed a weighted score to verify the results. Compared with the lowest environmental composite quality factor score, the ORs of the highest scores were: 1.58 (95% CI, 1.20-2.27, Ptrend = 0.001) for general symptoms; 1.73 (95% CI, 1.35-2.23, Ptrend < 0.001) for mucosal symptoms and 1.75 (95% CI, 1.34-2.29, Ptrend < 0.001) for dermal symptoms and 1.81 (95% CI, 1.36-2.42, Ptrend < 0.001) for all of the three symptoms. We also observed similar patterns with the using of weighted scores and stratified analysis. Higher exposure to indoor pollution sources and outdoor pollution sources near the residence may be associated with a higher risk of SBS in adults in northeast China.


Does noise stress modulate effects of smoking/nicotine? Mood, vigilance, and EEG responses.
Effects of smoking multiple cigarettes on EEG, vigilance, and subjective state were assessed in a repeated measures design where noise level (high versus minimal) was crossed with nicotine dose (quasi-ad lib own versus 1.0 mg FTC nicotine machine-delivered dose versus 0.05 mg FTC nicotine machine-delivered dose). Vigilance was increased by nicotine, but not by noise and there was no noise by dose interaction. Effects of nicotine on EEG varied as a function of dose, noise, hemisphere, time, and eyes-open versus eyes-closed condition. Smoking normal nicotine delivery (0.9-1.1 mg FTC-estimated) cigarettes resulted in decreases in percentages of delta and theta EEG magnitude and increased percentage beta-1 EEG magnitude across conditions and time. Changes in alpha and theta magnitude were dependent on eyes being open versus closed. Hemispheric asymmetries varied as a function of noise and time. Consistent with inverted "U" models, effects of nicotine on EEG were clearly stimulant during the quiet conditions while there were minimal to no differences between nicotine doses during the high-noise conditions. The failure of nicotine to modify mood is interpreted in terms of bioinformational models of nicotine's subjective effects.


A cross-sectional study of United States Academic-clinical research collaborations: Characteristics, resources, benefits and outcomes.
The aims of the study were to compare characteristics, resources, benefits and outcomes of academic-clinical collaborations of nursing researcher leaders from academic, clinical and joint-employer sites. Few research-based publications addressed academic-clinical research collaborations. New knowledge could increase nursing and multidisciplinary research productivity, including implementation science. An anonymous survey using a 40-item questionnaire. Information letters with a link to the questionnaire were emailed to United States nursing research leaders. Data were grouped by institution type: academic, clinical or joint-employer. Analyses included Kruskal-Wallis tests for ordered responses, Pearson's chi-square test or Fisher's exact test for categorical responses and Cohen's Kappa agreement statistic for expected and actual time devoted to research. STROBE guidelines were followed. Of 120 respondents from academic (n = 60; 50.0%), clinical (n = 53; 41.2%) and joint-employer (n = 7; 5.8%) sites, 78.3%, 92.3% and 100%, respectively, were from metropolitan areas. Mean (SD) priority for active collaborations was higher at joint-employer sites; p = .002. Clinical sites were more likely to have directors of evidence-based practice (p = .031) and informatics (p = .008) and librarians (p = .029). Sites with collaborations were more likely to have access to research subjects (p = .008) and post-award research account management (p = .045). By collaboration status, there were no differences in the number of ethics board-approved studies. Collaborating site benefits were perceived to be executive leadership support (p = .003), greater research engagement by clinical nurses (p = .048), more co-authored publications (p = .048) and more abstracts accepted at national meetings (p = .044). Despite more resources and perceived benefits, outcomes did not differ by collaboration status. Sites with and without academic-clinical research collaborations differed; however, outcomes were similar. Future efforts should focus on nurse scientist collaboration to address important clinical questions aimed at improving clinical outcomes. Despite some successful outcomes, potential benefits of academic-clinical research collaborations have not been fully actualised.


Quality of life in Danish children and adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion or multiple daily injections.
The aims of the study were to compare health-related quality of life (HRQoL) in a National Danish population of children and adolescents with type 1 diabetes (T1D) treated with either continuous subcutaneous insulin injection (CSII) or multiple daily insulin injections (MDI), and to investigate whether HRQoL assessments were influenced by treatment duration. Participants were recruited through the Danish Registry for Diabetes in Childhood and Adolescence. A total of 700 children and adolescents (360 girls), 8-17 years, were included. Of these, 295 were treated with CSII (160 for more than one year) and 405 with MDI (238 for more than one year). Participants and their parents completed the Pediatric Quality of Life Inventory Diabetes and Generic Module. HbA1c was analyzed centrally. Parents reported children and adolescents on CSII for more than one year to have less diabetes-related symptoms and worry, less problems in communicating diabetes, and better generic functioning compared with those on MDI. Children and adolescents on CSII for more than one year reported less diabetes-related symptoms, but more treatment problems, and better generic functioning in all subscales except social functioning compared with those on MDI for more than one year. Comparing those on CSII and MDI for less than one year, no differences in HRQoL ratings were found, apart from better rating of treatment barriers in the MDI group. This Danish national study on HRQoL in children and adolescents on CSII or MDI showed better HRQoL in children and adolescents on long time CSII, particularly concerning generic HRQoL.


Unraveling the pros and cons of interferon-gamma gene regulation.
Although transforming growth factor-beta (TGF-beta) inhibition of interferon-gamma (IFN-gamma) expression has been known for some time, in this issue of Immunity, the crosstalk between proinflammatory cytokine and TGF-beta signaling that regulates IFN-gamma expression is detailed for the first time.


Reliability and validity of the Cancer Health Literacy Test - Chinese versions: CHLT-30-Chinese and CHLT-6-Chinese.
The Cancer Health Literacy - 30 (CHLT-30) and Cancer Health Literacy - 6 (CHLT-6) are widely used instruments to measure cancer health literacy and to identify individuals with limited cancer health literacy, respectively. This study evaluated the psychometric performance of both instruments in Chinese cancer patient population. The back-translation method was used in cross-cultural adaptation. Chinese versions, labeled as CHLT-30-Chinese and CHLT-6-Chinese, were administered to a diverse cross-sectional sample of 602 cancer patients. Of these, 30 patients retook the instruments over a 2-week interval to estimate test-retest reliability. Classical and modern psychometric methods were used to estimate the item and test properties. Model fit statistics confirmed the original measurement structures of CHLT-30-Chinese (one-factor model) and CHLT-6-Chinese (latent class model with limited and adequate cancer health literacy classes) providing construct validity evidence. The CHLT-30-Chinese showed high internal consistency (Cronbach's α = 0.83; McDonald's Ω = 0.93) and 2-week test-retest reliability (r = 0.78). The CHLT-6-Chinese separated limited and adequate cancer health literacy classes well (entropy = 0.77) with the estimated prevalence rates of 19% and 81%, respectively. The CHLT-6-Chinese was highly precise in assigning cancer patients into two categories: limited and adequate cancer health literacy classes with probability of 0.95 and 0.90, respectively. Invariant measurement properties of both instruments were supported between male and female patients as well as patients with and without high school diploma. The findings support the psychometric properties of the CHLT-30-Chinese for measuring cancer health literacy as a continuous trait and CHLT-6-Chinese for identifying patients with limited cancer health literacy with high precision. The two tools are recommended for use in both daily practice and clinical trials.


Image-based profiling for drug discovery: due for a machine-learning upgrade?
Image-based profiling is a maturing strategy by which the rich information present in biological images is reduced to a multidimensional profile, a collection of extracted image-based features. These profiles can be mined for relevant patterns, revealing unexpected biological activity that is useful for many steps in the drug discovery process. Such applications include identifying disease-associated screenable phenotypes, understanding disease mechanisms and predicting a drug's activity, toxicity or mechanism of action. Several of these applications have been recently validated and have moved into production mode within academia and the pharmaceutical industry. Some of these have yielded disappointing results in practice but are now of renewed interest due to improved machine-learning strategies that better leverage image-based information. Although challenges remain, novel computational technologies such as deep learning and single-cell methods that better capture the biological information in images hold promise for accelerating drug discovery.


MELD-accelerated molecular dynamics help determine amyloid fibril structures.
It is challenging to determine the structures of protein fibrils such as amyloids. In principle, Molecular Dynamics (MD) modeling can aid experiments, but normal MD has been impractical for these large multi-molecules. Here, we show that MELD accelerated MD (MELD x MD) can give amyloid structures from limited data. Five long-chain fibril structures are accurately predicted from NMR and Solid State NMR (SSNMR) data. Ten short-chain fibril structures are accurately predicted from more limited restraints information derived from the knowledge of strand directions. Although the present study only tests against structure predictions - which are the most detailed form of validation currently available - the main promise of this physical approach is ultimately in going beyond structures to also give mechanical properties, conformational ensembles, and relative stabilities.


Identification of a potential third component of the male-produced pheromone of Anoplophora glabripennis and its effect on behavior.
The Asian longhorned beetle, Anoplophora glabripennis, is considered to be one of the most serious invasive pests of deciduous trees in North America. An efficient monitoring trap is needed to detect and delimit new introductions and assess population densities of established infestations. Previous studies on A. glabripennis have shown that males produce a two-component aggregation pheromone that consists of a 1:1 blend of 4-(n-heptyloxy)butan-1-ol and 4-(n-heptyloxy)butanal. Moderate attraction in field trapping studies suggested that there may be additional chemical cues missing. Volatiles from male A. glabripennis were examined to identify other potential pheromone components. Gas chromatographic / electroantennographic (GC/EAD) analyses of male aerations detected a consistent EAD-active response to a previously unidentified compound. This compound was identified as (3E,6E)-α-farnesene. Both male and female beetles were antennally responsive to this sesquiterpene, and both sexes were attracted to it in olfactometer bioassays at different doses. When (3E,6E)-α-farnesene was combined with 4-(n-heptyloxy)butan-1-ol and 4-(n-heptyloxy)butanal, attraction of both sexes increased compared to assays using 4-(n-heptyloxy)butan-1-ol and 4-(n-heptyloxy)butanal alone.


Immobilization and encapsulation during vitrification of incineration ashes in a coke bed furnace.
A real-scale coke bed furnace system has been successfully applied to vitrify the incineration ashes into glassy slags. The object of this research was to evaluate the effect of the system on the immobilization of metal species in the slag. Ashes and slag specimens were tested to identify their metal phase distribution following a sequential extraction procedure. The mobility of Al, Ca, Cd, Cr, Mg, Mn and Pb was noticeably reduced by vitrification. An important implication is the reduction of Cr(6+) to Cr(3+) along with its immobilization with this coke bed furnace. The Ni and Zn contents were relatively low in slag, indicating that their availability of mobile phases in ashes was reduced during vitrification. The XRD analyses identified the major crystalline phase in slag as åkermanite, which is inert and helpful in metal immobilization. The phase distribution analysis also contributed to verify that the incorporation of Ca and Mg enhanced the encapsulation in the slag matrix. The low oxygen content in slag made the structure of silicate resistant to the proton-promoted attack and also enhanced the mobility reduction of matrix elements (Ca, Mg and Al) in the moderately reducible phase and also contributed to the immobilization of other metal species. However, the properties of slag also deserve further studies to ensure its long-term stability and safety.


Preventive prosthodontics: maxillary denture fracture.
Factors that contribute to the fracture and failure of the single maxillary denture have been discussed. Recognition of these factors and their prevention or correction will result in a single maxillary denture that is physiologically and functionally acceptable for the patient for an extended period without chronic denture failure.