Efficiency of Soybean Products in Broiler Chicken Nutrition.
The study aimed to determine the overall effect of replacing soybean meal completely with soybean expeller cake or extruded full-fat soybean in feed rations for broiler chickens on their carcass composition and meat quality. The experiment involved one hundred and twenty Ross 308 broiler chickens randomly allocated to three equinumerous groups (SBM, SEC, EFS). Each group was divided into five subgroups-each consisting of eight birds of both sexes (1:1). From Day 1 to Day 21 of life the birds were fed with loose starter rations, and from Day 22 to Day 42 they were fed grower rations based on a wheat meal, protein products and mineral and vitamin admixtures. The experimental factor was a protein raw material comprising: SBM group-soybean meal from GM (genetically modified) seeds, SEC-soybean expeller cake from n-GM seeds, and EFS-extruded full-fat soybean from n-GM seeds. The experimental diets were isocaloric and isonitrogenous. It was demonstrated that replacing soybean meal with SEC or EFS in feed rations for broiler chickens led to a significant (p < 0.05) weight gain on Day 42 of rearing by 4.57% and 2.88%, respectively. The chickens fed diets with EFS had worse (more than 4.14%) feed conversion rate (FCR) in comparison to the others (p < 0.05). Broiler chickens from the SBM and SEC groups showed a higher share of breast and leg muscles (by 4.74% and 7.54%) and a lower share of abdominal fat (by 31.1%) and skin with subcutaneous fat (by 18.8% and 13.4%) in comparison with birds from the EFS group (p < 0.05). The highest content of intramuscular fat with the best fatty acids profile was determined in the muscles of birds fed with diets containing EFS, while the muscles of chickens receiving SEC scored the highest. The results provide grounds for recommending SEC in broiler chicken nutrition as it allowed for obtaining the best production and slaughter results, whereas-from the point of view of the human diet-EFS should be recommended since it best modified the lipid fraction of muscles.


Atmospheric iodine, selenium and caesium depositions in France: II. Influence of forest canopies.
Estimation of the canopy influence on atmospheric inputs of iodine (I), selenium (Se) and caesium (Cs) in terrestrial ecosystems is an essential condition for appropriate biogeochemical models. However, the processes involved in rain composition modifications after its passage through forest canopy have been barely studied for these elements. We monitored I, Se and Cs concentrations in both rainfall and throughfall of fourteen French forested sites throughout one year, and estimated dry deposition and canopy exchange fluxes for these elements, as well as speciation of I and Se. Comparison of rainfall and throughfall elemental composition highlighted an important impact of forest canopy on both (i) concentrations and fluxes of I, Se and Cs, and (ii) I and Se species. For the three elements, most of their throughfall concentrations were higher than corresponding rainfall. The increase of throughfall elemental fluxes was mostly due to dry deposition for I and Se although the canopy exchange model revealed some sorption within the canopy in most cases; for Cs, foliage leaching was most influencing. Regarding speciation, iodine species in rainfall were highly modified by forest canopy with an important increase of unidentified I proportion in throughfall (on average 49 and 82% in rainfall and throughfall, respectively), possibly due to washoff of dry deposition and/or to transformation into organic forms. Similarly, while rainfall was composed of 26-54% of inorganic Se, inorganic species were undetectable in throughfall. This dataset represents key information to improve modelling of I, Se and Cs cycling within forest ecosystems.


Cutaneous verrucous xanthoma in a bone marrow transplant recipient with recessive dystrophic epidermolysis bullosa.
Verrucous xanthomas (VXs) typically arise on the oral mucosa but have been reported on glabrous skin in patients with graft-versus-host disease or recessive dystrophic epidermolysis bullosa (RDEB). The inciting cause of these tumors is unclear but may result from cutaneous inflammation and trauma. We describe a patient with RDEB who had previously undergone a bone marrow transplant for her condition and subsequently developed an VX on her neck.


New mutation in the β1 propeller domain of LRP4 responsible for congenital myasthenic syndrome associated with Cenani-Lenz syndrome.
Congenital myasthenic syndromes (CMS) are a clinically and genetically heterogeneous group of rare diseases due to mutations in neuromuscular junction (NMJ) protein-coding genes. Until now, many mutations encoding postsynaptic proteins as Agrin, MuSK and LRP4 have been identified as responsible for increasingly complex CMS phenotypes. The majority of mutations identified in LRP4 gene causes bone diseases including CLS and sclerosteosis-2 and rare cases of CMS with mutations in LRP4 gene has been described so far. In the French cohort of CMS patients, we identified a novel LRP4 homozygous missense mutation (c.1820A > G; p.Thy607Cys) within the β1 propeller domain in a patient presenting CMS symptoms, including muscle weakness, fluctuating fatigability and a decrement in compound muscle action potential in spinal accessory nerves, associated with congenital agenesis of the hands and feet and renal malformation. Mechanistic expression studies show a significant decrease of AChR aggregation in cultured patient myotubes, as well as altered in vitro binding of agrin and Wnt11 ligands to the mutated β1 propeller domain of LRP4 explaining the dual phenotype characterized clinically and electoneuromyographically in the patient. These results expand the LRP4 mutations spectrum associated with a previously undescribed clinical association involving impaired neuromuscular transmission and limb deformities and highlighting the critical role of a yet poorly described domain of LRP4 at the NMJ. This study raises the question of the frequency of this rare neuromuscular form and the future diagnosis and management of these cases.


68Ga-prostate-specific membrane antigen PETCT-based response to androgen deprivation therapy in patients with prostate cancer.
To assess the response of castration-naïve prostate cancer to androgen deprivation therapy (ADT) in Ga-PSMA PETCT, and test the hypothesis of differential response in primary, nodal and metastatic lesions. Patients with adenocarcinoma prostate with baseline Ga-prostate-specific membrane antigen (PSMA) PETCT scan, and response scan after 3-12 months of ADT from 2014 to 2017 were analyzed. Change in radiotracer uptake in the prostate, involved regional nodes and distant metastasis was semiquantitatively assessed in paired scans using maximum standardized uptake value (SUVmax). Response was categorized into complete or partial response (CR, PR) or stable disease or progressive disease (SD, PD), and correlated with known prognostic factors. Total 86 scans of 43 patients (17 metastatic, M+) were analyzed. After median 6 months of ADT, 0% primary, 23.3% nodes and 17.6% metastases showed CR; 18.6% primary, 8.3% nodes and 35% metastases showed PD. Prostate response was not significantly associated with any prognostic factor. Nodal response was higher in M0 than in M+ disease (CR 37 vs 4%, P = 0.003). Oligometastases responded better than polymetastases (CR/PR 62.5 vs 11.1%, P = 0.05). Decline in SUVmax of primary tumor correlated with decline in serum prostate-specific antigen (PSA) (90% of partial responders showed >80% decline in serum PSA vs 50% with PD, P = 0.06). Primary prostatic tumor seems less likely to respond to ADT than nodal or metastatic lesions. Residual primary uptake may guide patient selection for local therapy in (oligo) metastatic prostate cancer.


Same-day repeatability and Between-Sequence reproducibility of Mean ADC in PI-RADS lesions.
This study aimed to assess repeatability after repositioning (inter-scan), intra-rater, inter-rater and inter-sequence variability of mean apparent diffusion coefficient (ADC) measurements in MRI-detected prostate lesions. Forty-three patients with suspicion for prostate cancer were included and received a clinical prostate bi-/multiparametric MRI examination with repeat scans of the T2-weighted and two DWI-weighted sequences (ssEPI and rsEPI). Two raters (R1 and R2) performed single-slice, 2D regions of interest (2D-ROIs) and 3D-segmentation-ROIs (3D-ROIs). Mean bias, corresponding limits of agreement (LoA), mean absolute difference, within-subject coefficient of variation (CoV) and repeatability/reproducibility coefficient (RC/RDC) were calculated. Bradley & Blackwood test was used for variance comparison. Linear mixed models (LMM) were used to account for multiple lesions per patient. Inter-scan repeatability, intra-rater and inter-sequence reproducibility analysis of ADC showed no significant bias. 3D-ROIs demonstrated significantly less variability than 2D-ROIs (p < 0.01). Inter-rater comparison demonstrated small significant systematic bias of 57 × 10-6 mm2/s for 3D-ROIs (p < 0.001). Intra-rater RC, with the lowest variation, was 145 and 189 × 10-6 mm2/s for 3D- and 2D-ROIs, respectively. For 3D-ROIs of ssEPI, RCs and RDCs were 190-198 × 10-6 mm2/s for inter-scan, inter-rater and inter-sequence variation. No significant differences were found for inter-scan, inter-rater and inter-sequence variability. In a single-scanner setting, single-slice ADC measurements showed considerable variation, which may be lowered using 3D-ROIs. For 3D-ROIs, we propose a cut-off of ∼ 200 × 10-6 mm2/s for differences introduced by repositioning, rater or sequence effects. The results suggest that follow-up measurements should be possible by different raters or sequences.


Elevated plasma human urotensin-II-like immunoreactivity in ischemic cardiomyopathy.
The recently discovered, vasoactive, cyclic undecapeptide human urotensin-II (hU-II), and its G-protein coupled receptor (GPR14) are both expressed in the human cardiovascular system. Little is known about the pathophysiological relevance of hU-II. We hypothesised that circulating hU-II is elevated in patients with coronary artery disease (CAD) corresponding to the degree of cardiac dysfunction. 38 patients were diagnosed with coronary artery disease by left heart catheterization, and their functional status was classified according to the New York Heart Association (NYHA). hU-II-like immunoreactivity (hU-II-LI) was measured using a novel specific and sensitive enzyme-linked immunoassay. Calculations were performed with log-transformed hU-II-LI values. hU-II-LI correlated positively with left ventricular end diastolic pressure (LVEDP) (r=0.32, P=0.05) and tended to correlate inversely with left ventricular ejection fraction (LV-EF) (r=-0.31, P=0.061). There was a positive correlation between hU-II-LI and NYHA class (r=0.53, P=0.001). Circulating hU-II-LI was significantly higher in patients with NYHA class III (4822+/-723 pg/ml, N=13) than in patients with class I (1884+/-642 pg/ml, N=9, P=0.007) or class II (2294+/-426 pg/ml, N=15, P=0.046). There was no difference between classes I and II (P=0.83). Furthermore, hU-II-LI correlated significantly with B-type natriuretic peptide, a marker for heart failure (r=0.40, P=0.025). In a linear regression analysis, NYHA class was the only significant independent predictor of hU-II-LI. The present study demonstrates that plasma hU-II-LI rises significantly in proportion to parameters of cardiac dysfunction and functional impairment in patients with coronary artery disease. These results suggest a pathophysiological role for hU-II in cardiac disease and warrant further investigation.


Re-operation for Hirschsprung's disease: experience in 24 patients from China.
The aim of this study is to review the authors' 12-year experience with re-operative surgery for Hirschsprung's disease (HD) including indications of re-operation and surgical technique. We retrospectively reviewed the data of 24 patients who underwent re-operation from 1998 to 2010. The type of initial procedure, clinical presentations, indications and details of redo surgery, and the functional results were analyzed. The primary operations performed on these patients included Duhamel (nine cases), Soave (12 cases), Swenson (one case) and Rehbein (two cases). The indications for re-operation were recurrent constipation due to severe anastomotic stricture (five cases), residual aganglionic segments (five cases) and gate syndrome after Duhamel procedure (five cases); fistula formation including rectocutaneous fistula (six cases), rectovaginal fistula (one case), complex fistula (two cases). The redo procedure ranged from posterior sagittal approach combined with laparotomy (seven cases), Soave procedure (seven cases, six conventional Soave + one transanal Soave), Duhamel procedure (one case), Rehbein procedure (three cases), re-using the stapling device (five cases), repairing the rectovaginal fistula via laparotomy (one case). We have followed up the patients for 7 months to 6 years (mean 2.5 years). After re-operation, in 22 patients older than 3 years, 19 (86.4%) have normal or near normal bowel habits with a stool frequency of 1-5 times per day, two have voluntary bowel movements but occasional soiling (once or twice per week) and without significant incontinence, one presented rectosacral fistula due to careless dilatation. There were no deaths. Re-operation can work out the anatomical or pathological problems resulted from failed initial procedure and improve the patient's quality of life. Posterior sagittal approach, Soave and Duhamel are all safe and effective, but we still need to try our best to diminish the necessity of re-operation.


Executive control development in Tourette syndrome and its role in tic reduction.
Tourette syndrome (TS) is a childhood-onset disorder characterized by motor and vocal tics. Recent findings point to a possible role of executive functions system development in the tic reduction observed with age. The goal of the present work was to track the development of executive functions system measured by well-established cognitive tasks and its correlation with diminished tic severity over time in order to understand the role of executive functions in the remission process observed in most adults. The first study followed 25 young TS patients, measuring their executive functions and clinical condition at three time- points. In the second study we compared executive functions performance of 19 adult TS patients with 19 healthy controls and 12 remitted TS patients. The first study showed that tic reduction is related to the development of the executive functions components associated with response inhibition. The second study similarly showed impaired inhibition ability in TS patients but not in controls or the remitted TS patients. The remitted group performed at normal or even higher levels on certain measures. We conclude that inhibition, an important executive function, is impaired in subjects suffering from TS and that intact executive function development is related to remission processes.


A delayed, unusual non-cardiogenic pulmonary edema after intravascular administration of non-ionic, low osmolar radiocontrast media for coronary angiography.
Non-cardiogenic pulmonary edema (NCPE) is a rare adverse reaction to iodinated radiocontrast media (RCM), in which all previous cases were immediate reactions. A 56-year-old male was given iopamidol, a non-ionic, low osmolar RCM, during coronary artery angiography. He developed pulmonary edema and fever a day after the procedure. Despite diuretic therapy, the patient's pulmonary edema worsened and his high fever persisted. The patient's pulmonary edema was eventually resolved with intravenous steroid treatment. We interpreted the patient's condition as NCPE manifesting as a delayed reaction to RCM. To our knowledge, our case is the first to show NCPE as a delayed hypersensitivity reaction.


Contribution to the Chinese subfamily Rhaphidophorinae Walker, 1869 (Orthoptera: Rhaphidophoridae) V: Two new species of Eurhaphidophora.
This paper describes two new species of Eurhaphidophora, namely: Eurhaphidophora curvata sp. nov. (Chinese name: ) and Eurhaphidophora fossa sp. nov. (Chinese name: ) based on the specimens from Yunnan Province, China. The type specimens are deposited in the Guangxi Normal University, Guilin, China.


Acute upper extremity flaccid paralysis in a 5year old child secondary to enterovirus infection.
The incidence of acute flaccid paralysis has been on a declining trend with the global efforts on eradication of polio virus. A few scattered clusters of acute flaccid paralysis associated with pathogens like enterovirus other than polio virus and flaviviruses have recently come to limelight. This is a case of acute onset flaccid paralysis of left upper extremity in a fully immunized 5 year old child in New York.


Service evaluation of weight outcomes as a function of initial BMI in 34,271 adults referred to a primary care/commercial weight management partnership scheme.
It is not clear if behaviour change programmes are more or less effective for weight management in people with high BMIs than for those who are moderately overweight. An earlier service evaluation reported on the rate and extent of weight loss in a primary care/commercial weight management organisation partnership scheme, in 34,271 patients were referred by their health care professionals to a UK commercial weight management organisation, Slimming World for 12 weekly sessions. This project updated that service evaluation by examining weight loss outcomes as a function of initial BMI in the same 34,271 patients. Patients referred to the scheme (n = 34,271) were categorised by BMI groups <30 kg/m(2), 30-34.9 kg/m(2), 35-39.9 kg/m(2) and to ≥ 40 kg/m(2). Mean weight losses after 12 weekly sessions were 2.9, 3.6, 4.1, and 4.8 kg for each BMI category respectively. Regression analysis showed that after adjusting for age and gender, relative to the <30 kg/m(2) group, absolute weight losses were 0.8, 1.4 and 2.4 kg more for the 30-34.9 kg/m(2), 35-39.9 kg/m(2) and to ≥ 40 kg/m(2) groups, respectively (all p<0.001). Percent weight loss was similar in each BMI category: 3.7%, 4.0%, 4.0% and 3.9%, respectively (p<0.001). This service evaluation demonstrates that 12 week referral to a commercial organisation is as effective for people with high BMIs as for those who are moderately overweight.


When it does hurt to try: adult age differences in the effects of instructions on implicit pattern learning.
Trying to learn sometimes impairs implicit learning of artificial grammars and of control systems. We asked whether such negative effects of trying also occur in implicit learning of subtle sequential regularities and whether such effects vary with adult age. Young (n = 12, age = 20-23) and older (n = 24, age = 60-80) adults completed an alternating serial response time task in which predictable pattern events alternated with random ones in a visual/spatial display. Half of the participants were informed about the pattern and were instructed to try to discover it (intentional instructions), and half were not (incidental instructions). Age-related deficits in implicit learning occurred for both conditions. In addition, for the older group, but not for the younger one, intentional instructions impaired implicit pattern learning. This negative effect of trying to learn demonstrates another similarity among implicit learning tasks, supporting the view that some common processes underlie different forms of implicit learning.


Sensitivity to delay is affected by magnitude of reinforcement in rats.
Previous research has provided discrepant results about how reinforcement delay and magnitude are combined to determine the value of the alternatives in concurrent-chains schedules. In the present experiment, we analyzed a possible interaction between these characteristics of reinforcement, employing a two component concurrent-chains schedule, with rats as experimental subjects. Non-independent VI schedules were presented in the initial links of each component. In the terminal links, the following pairs of delays to reinforcement were presented in 4 conditions: 2-28, 6-24, 24-6, 28-2s (fixed time schedules for a group, fixed interval schedules for the other). Magnitude of reinforcement was maintained constant within components: one pellet for one component, and four pellets for the other. The results indicated that in both groups, the sensitivity to delay - calculated according to the generalized matching law - was higher in the component with the larger reinforcer. This result is in contrast with those reported in the literature of temporal discounting with human participants.


Impaired fibrinolytic capacity in patients with inflammatory bowel disease.
The venous occlusion test was applied to 17 patients with inflammatory bowel disease (IBD; 7 cases of Crohn's disease, 10 cases of ulcerative colitis). Results were compared to those obtained in 20 healthy matched control subjects. Patients with IBD had significantly decreased t-PA Ag release (p less than 0.001) and had no significant vWF Ag release. Residual PAI activity was evidenced after venous stasis in the IBD group but not in the control group. Hypofibrinolysis was more important in patients with an evolutive IBD than in patients with IBD in remission. Impaired systemic fibrinolytic capacity might contribute to an increased risk for thromboembolic complications and to the pathogenesis of inflammatory bowel disease.


Early transmural healing and its predictors assessed by magnetic resonance enterography in patients with Crohn's disease receiving ustekinumab.
Transmural healing (TH) is a potential therapeutic goal of Crohn's disease (CD) and is associated with better clinical outcomes. However, few studies have described early TH and its predictors. We aimed to evaluate early TH and its predictors using magnetic resonance enterography (MRE) in patients with CD receiving ustekinumab (UST). This was a retrospective observational study. Patients with active CD treated with UST and their intestinal segments with bowel wall thickness (BWT) ⩽ 3 mm at baseline were included. Clinical characteristics, laboratory indicators, endoscopic manifestations, and MRE indices were evaluated at baseline and week 26 (W26) of the therapy. The following MRE parameters were assessed: BWT, edema, apparent diffusion coefficient (ADC), Clermont score, Magnetic Resonance Index of Activity score, fat stranding, comb sign, and stricture. TH was defined as BWT ⩽ 3 mm without any signs of inflammation (i.e., ulceration, edema, diffusion-weighted hyperintensity, and increased contrast enhancement) at W26. The study included 37 patients with 106 intestinal segments (including 15 proximal small intestines, 33 terminal ilea, and 58 colons). Clinical features, laboratory indicators, endoscopic results, and MRE parameters at W26 were significantly improved after UST treatment in both patient-based and intestinal segment-based analysis. Seven (18.9%) patients and 26 (24.5%) intestinal segments achieved TH at W26. Baseline BWT [odds ratio (OR) = 0.287, 95% confidence interval (CI), 0.090-0.918, p = 0.035] and ADC (OR = 2.997, 95% CI, 1.009-8.908, p = 0.048) predict TH of patients at W26. Baseline ADC (OR = 2.857, 95% CI, 1.285-6.349, p = 0.010) and presence of stenosis (OR = 0.196, 95% CI, 0.052-0.735, p = 0.016) were associated with TH of segments at W26. Early TH assessed by MRE was observed in nearly one-fifth of patients with CD and intestinal segments after UST treatment for 26 weeks. Baseline MRE indices such as BWT and presence of stenosis might negatively predict TH, while ADC might positively predict early TH.


Rhodopsin levels and retinal function in cats during recovery from vitamin A deficiency.
Extended vitamin A deficiency in the cat led to an abnormal appearance in the tapetal fundus with the formation of a dark brown streak centered on the area centralis. At this time rod sensitivity, as measured by the b-wave of the electroretinogram, was reduced by more than two log units; the level of rod visual pigment was reduced by about 90% throughout the paracentral retinal region and was essentially absent from the area centralis. Following oral supplementation with vitamin A there was a rapid partial recovery of both rhodopsin levels and rod sensitivity. Further recovery continued over more than 18 days to levels that were not substantially below normal. This recovery was absent from the area centralis, in which measured visual pigment levels remained very low. In supplemented cats, the brown color in the fundus faded but there remained a small hyper-reflective zone at the area centralis. Morphological examination of the central retina in a supplemented cat showed an outer nuclear layer reduced to one or two rows in the small zone with low rhodopsin levels. Cone but not rod photoreceptors were present in this zone and they appeared to lack outer segments. During recovery, the increase in rod sensitivity was approximately linearly related to the recovery of rhodopsin levels. Thus, in these conditions reduction in sensitivity resulting from previous vitamin A deficiency was limited by the ability of the photoreceptors to absorb incident quanta. The time course of the recovery of rhodopsin and sensitivity suggests that at least two processes were involved. The faster of these may be the regeneration of rhodopsin from existing opsin molecules in the outer segments, while the slower may depend on the renewal of the outer segments themselves.


Maternal anxiety during pregnancy and children's asthma in preschool age: The Ma'anshan birth cohort study.
The fetal immune system and consequent elevated risk of asthma in childhood may be impacted by maternal anxiety during pregnancy. Limited studies have evaluated whether there was a sensitive period and cumulative effect of the relationship between prenatal anxiety and children's asthma. 3131 mother-child pairs made up the study's sample from the Ma'anshan Birth Cohort Study in China. Maternal anxiety status was repeated three times using the pregnancy-related anxiety questionnaire in the 1st, 2nd and 3rd trimesters of pregnancy. Diagnostic information on asthma was collected three times at 24, 36, and 48 months of age. After adjusting for confounders, children born to mothers with anxiety in the 1st, 2nd and 3rd trimesters of pregnancy all had an elevated risk of total asthma from 12 to 48 months of age. After further adjusting prenatal anxiety in the other trimesters, no association was observed between prenatal anxiety in any trimester and preschoolers' asthma. Children of mothers with persistently high anxiety score trajectory during pregnancy had an elevated risk of total asthma and high prevalence trajectory of asthma. Cumulative effects analysis showed that the more frequent the mother's anxiety, the higher the risk of her offspring developing a high prevalence trajectory of asthma from 12 to 48 months of age. The results of the subgroup analysis by age showed similar associations overall. Maternal antenatal anxiety was associated with an elevated risk of preschool children's asthma, and a possible cumulative effect was observed. Maternal mental health conditions during pregnancy should receive constant attention throughout pregnancy, not just during one period.


An automated approach for conditioning and testing the hearing of gerbils.
A simple, inexpensive hardware and software protocol is described for conditioning and testing hearing of gerbils with minimal experimenter involvement. Behavioral thresholds correspond closely with data which employ nonautomated procedures. Partial source listings of the programs written in the 'C' programming language are provided.


Circ-HIPK3 plays an active role in regulating myoblast differentiation.
The development of skeletal muscle is a complex biological process involving a variety of regulatory pathways. A deeper understanding of the developmental mechanisms of skeletal muscle is of great significance for the treatment of muscular lesions. In recent years, studies have shown that circRNAs, as a new class of post-transcriptional regulators, play an important regulatory role in a variety of biological processes, but their function in skeletal muscle development remains unclear. Here, we used C2C12 myoblasts to study circ-HIPK3, which has significant differences in the developmental stages of skeletal muscle and is highly expressed. We found that the expression level of circ-HIPK3 was significantly up-regulated (p < .05) with the persistence of C2C12 cell differentiation. Combining the results of bioinformatics analysis and dual luciferase reporter experiments, we found that circ-HIPK3 is a sponge of miR-124 and miR-379 that regulate muscle differentiation. Our study shows that circ-HIPK3 can promote the differentiation of C2C12 myoblasts, providing a scientific basis for further research on the development of skeletal muscle at the level of circRNAs.


Antifungal agents in current pediatric practice.
Invasive fungal infections are an important cause of morbidity and mortality in immunocompromised children. Increases in the incidence of systemic mycoses have been observed during the last 2 decades. Treatment of invasive fungal infections has improved through a better knowledge and application of current treatment strategies and through the development of new antifungal compounds. The purpose of this review is to provide antifungal treatment recommendations for pediatric patients that can help clinicians find the most suitable treatment for each specific case.


A fluorescent photoimmunoconjugate for imaging of cholesteatoma.
Cholesteatoma is a potentially serious complication of chronic ear infections and requires surgical intervention for definitive management. Long-term complications include a frequent need for repeat surgical intervention for disease recurrence, and techniques to improve efficacy of single-stage surgery are an important area of continued research. This study investigates a novel application of the photosensitizer immune conjugate (PIC) cetuximab-benzoporphyrin derivative (Cet-BPD) for in vitro localization of human cholesteatoma tissue, coupled with an in vivo safety study for middle ear application of Cet-BPD in a murine model. In fresh human cholesteatoma tissues, Cet-BPD demonstrates selective localization to the hyperplastic squamous cell tissue associated with cholesteatoma, without localizing to other tissues such as middle ear mucosa. Applied to the murine middle ear, Cet-BPD does not demonstrate any deleterious effect on murine hearing when assessed by any of auditory brainstem response (ABR) thresholds, distortion product otoacoustic emission thresholds, or ABR wave I amplitudes. These findings demonstrate the technical promise and encouraging safety profile for the use of PICs for intraoperative localization and treatment of cholesteatoma.


Effect of doping an organic molecule ligand on TGS single crystals.
Good quality single crystals of thiourea-doped triglycinesulphate (TuTGS) a new semiorganic nonlinear optical (NLO) crystal has been successfully grown from aqueous solution by slow evaporation method. The solubilities under various solvents in different proportions have been studied. The structural characterization of the grown crystals was carried out by X-ray diffraction. The grown crystals were subjected to FTIR and Raman analyses for vibrational assignments. The optical absorption coefficient alpha was analysed and interpreted to be allowed in the direct transition. The values of allowed direct energy gap (Eg) for undoped and doped crystals were calculated. It was found that Eg values were decreased with organic molecule doping. The powder technique of Kurtz and Perry confirm the NLO property of the grown crystal.


[Research progression in tumor-infiltration lymphocytic cells in colorectal cancer].
With the development of tumor immunology research, it has been recognized that the anti-tumor immune system function is better to predict the prognosis. Relationship between the tumor-infiltrating lymphocytes (TIL) and colorectal cancer has become one of the hot topics in research. Here we summarize the latest studies about the relationship between the TIL and clinicopathological factors, prognosis and microsatellite instability (MSI).


Radiosurgery: its role in brain metastasis management.
Stereotactic radiosurgery is effective in controlling brain metastasis at presentation and those that recur after radiotherapy. It is the treatment of choice for most patients with small solitary brain metastasis by virtue of its low morbidity, high-effectiveness, and cost.


The effects of ArginMax, a natural dietary supplement for enhancement of male sexual function.
This study examines the role of ArginMax, a natural daily dietary supplement, on male sexual function. 25 subjects diagnosed with mild to moderate erectile dysfunction were evaluated over a 4-week period while on ArginMax. Of the 21 subjects that completed the study, 88.9% improved in ability to maintain erection during sexual intercourse and 75.0% improved in satisfaction with their overall sex life. No significant side effects were noted.


Carvedilol improves ethanol-induced liver injury via modifying the interaction between oxidative stress and sympathetic hyperactivity in rats.
Oxidative stress is a major pathway mediating ethanol hepatotoxicity and liver injury. We previously found that carvedilol, which can block the sympathetic nervous system via β1-, β2- and α1-adrenoreceptors, modifies ethanol-induced production of lipogenesis- and fibrogenesis-related mediators from hepatic stellate cells (HSC). In the present study, we assessed the effects of carvedilol on ethanol-induced liver injury, hepatic insulin resistance, and the interaction between oxidative stress and sympathetic hyperactivity in rats with alcoholic fatty liver disease (AFLD). Male Wistar rats were pair-fed for 49 days and divided into four groups: control and ethanol liquid-diet-fed rats with and without 7-day carvedilol treatment. Rats' sympathetic activity, hepatic oxidative stress, hepatic insulin resistance and liver injury were evaluated based on biochemical analysis, enzyme-linked immunosorbent assay, fluorescence immunohistochemistry, western blot and reverse transcriptase polymerase chain reaction. Forty-nine days of ethanol consumption induced the increases in circulating noradrenaline metabolite (3-methoxy-4-hydroxyphenylglycol), hepatic noradrenaline and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, the downregulation of hepatic insulin receptor substrate-1 gene expression, and the accumulation of fatty droplets within hepatocytes with the increased hepatic triglyceride and blood alanine aminotransferase levels. All of these changes were modified by carvedilol treatment. 8-OHdG was detected in activated HSC and suppressed by carvedilol treatment based on fluorescence immunohistochemical double-staining analysis. Carvedilol may modify the interaction between the oxidative stress and the sympathetic hyperactivity, and then contribute to attenuating the development of AFLD in rats. Additionally, oxidative stress may be responsible for the activation of HSC during the early stage of alcoholic liver disease.


Antimicrobial activity of Elytropappus rhinocerotis (Asteraceae) against micro-organisms associated with foot odour and skin ailments.
The twigs of Elytropappus rhinocerotis are widely used in the Cape region of South Africa to treat foot odour, perspiration and also itchy, chilblained and burning feet. However, no antimicrobial studies have hitherto been published on this popular Cape herbal medicine, which is also used for a wide range of ailments. To determine the antimicrobial activity of the extracts, essential oil and two major labdane diterpenes isolated from E. rhinocerotis against micro-organisms associated with foot odour and other conditions associated with skin infections. Leafy stems were harvested from three individual plants at three separate geographical localities, giving a total of nine plant samples. The samples were air-dried, powdered and extracted with a 1:1 mixture of methanol and dichloromethane, and also with sterile distilled water. A portion of each sample was also hydrodistilled to obtain nine samples of essential oil. Isolation of the major labdane diterpenes was performed using silica and ethyl acetate in hexane (3:7 v/v) as the mobile phase. Minimum inhibitory concentrations (MIC) were determined for nine crude extracts, as well as three essential oil samples and two labdane diterpenes obtained from a bulk sample. The test organisms used in this study were from Deutsche Sammlung von Mikrooganismen (DSM) and American type culture collection (ATCC) strains and included five bacterial species (Brevibacterium agri ATCC 51663, B. epidermidis DSM 20660, B. linens DSM 20425, Staphylococcus aureus ATCC 25923, S. epidermidis ATCC 12228) and one fungal species (Trichophyton mentagrophytes ATCC 9533) associated with the skin. The presence of essential oil is reported for the first time. Organic extracts and essential oil samples showed moderate to noteworthy activity against selected test organisms. For the Brevibacteria, the lowest MIC values for phenolic extracts were several times lower than the corresponding values for the positive control zinc (shown in brackets): 0.0031 mg/mL against Brevibacterium agri (0.33 mg/mL), 0.17 mg/mL against B. epidermidis (3.91 mg/mL) - both for sample 2 of Vanwyksdorp; 0.13 mg/mL against B. linens (2.28 mg/mL) - for sample 3 of Vanwyksdorp. Two isolated labdane diterpenoids (one of which is here first reported) were also antimicrobially tested and showed moderate activity but had high abundance in the extracts. Two major monoterpenes and four sesquiterpenes in the essential oil were identified as 1,8-cineole (4.6-12.3%), terpinen-4-ol (9.2-24.3%), germacrene A (3.9-15.6%), (-)-spathulenol (1.7-37.8%), viridiflorol (0.3-100%), and silphiperfol-6-en-5-one (4.5-26.8%). The antimicrobial results particularly for the essential oils and against the Brevibacteria support the traditional topical use of Elytropappus rhinocerotis twigs to treat foot perspiration, foot odour and other related skin conditions.


Optimization of a Vaginal Suppository Formulation to Deliver SHetA2 as a Novel Treatment for Cervical Dysplasia.
Cervical dysplasia induced by the human papilloma virus unpredictably progresses to cervical cancer. Therapeutic options are invasive and affect the patient's quality of life. SHetA2 has demonstrated therapeutic efficacy against human and murine human papilloma virus-induced tumors, but its oral bioavailability is <1%. An optimized vaginal suppository formulation can deliver SHetA2 in sufficient doses to prevent cervical dysplasia. The quality by design approach was employed to optimize the suppository formulation consisting of cocoa butter as base with 5% Kolliphor and 40% SHetA2. The suppository had a content uniformity of 105.44 ± 0.42%, melted in <8 min, and had a complete release of SHetA2 in water. Administration of the suppository to mice-achieved cervix concentrations that were significantly higher than the SHetA2 therapeutic concentration, with the maximum concentration (Cmax-cervix = 336.78 μg/g) being more than 100-fold the therapeutic SHetA2 concentration. Furthermore, the levels of cyclin D1 protein decreased 9-fold indicating a correlation of drug concentrations with the pharmacodynamic endpoint. These proof-of-concept studies suggest that the SHetA2 optimized vaginal suppository formulation may have a potential use in the prevention of cervical dysplasia, but detailed efficacy studies are required to confirm this assumption.


Hypotonic duodenography--too often performed but of too little value? A comparison with conventional spot films.
Hypotonic duodenography was compared with conventional barium examination in 68 patients (70 examinations) with clinically suggested or verified disease of the pancreas or duodenum. In 13 cases (18.5%) conventional examination demonstrated the duodenal anatomy better than hypotonic duodenography. In nine cases (13%) hypotonic duodenography was superior and in 48 cases (68.5%) both techniques were diagnostically equal. It is concluded that, in only a few cases, does hypotonic duodenography add any diagnostic information to that which can be obtained with properly performed conventional examination of the duodenum.


Effects of redox oscillations on the phosphogypsum waste in an estuarine salt-marsh system.
Salt marshes are natural deposits of heavy metals in estuarine systems, where sulphide precipitation associated with redox changes often results in a natural attenuation of contamination. In the present study, we focus on the effects of variable redox conditions imposed to a highly-polluted phosphogypsum stack that is directly piled over the salt marsh soil in the Tinto River estuary (Huelva, Spain). The behaviour of contaminants is evaluated in the phosphogypsum waste and in the marsh basement, separately, in controlled, experimentally-induced oscillating redox conditions. The results revealed that Fe, and to a lesser extent S, control most precipitation/dissolution processes. Ferric iron precipitates in the form of phosphates and oxyhydroxides, while metal sulphide precipitation is insignificant and appears to be prevented by the abundant formation of Fe phosphates. An antagonistic evolution with changing redox conditions was observed for the remaining contaminants such as Zn, As, Cd and U, which remained mobile in solution during most of experimental run. Therefore, these findings revealed that high concentrations of phosphates inhibit the typical processes of immobilisation of pollutants in salt-marshes which highlights the elevated contaminant potential of phosphogypsum wastes on coastal environments.


14-3-3ε acts as a proviral factor in highly pathogenic porcine reproductive and respiratory syndrome virus infection.
The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) emerged in 2006 in China and caused great economic losses for the swine industry because of the lack of an effective vaccine. 14-3-3 proteins are generating significant interest as potential drug targets by allowing the targeting of specific pathways to elicit therapeutic effects in human diseases. In a previous study, 14-3-3s were identified to interact with non-structural protein 2 (NSP2) of PRRSV. In the present study, the specific subtype 14-3-3ε was confirmed to interact with NSP2 and play a role in the replication of the HP-PRRSV TA-12 strain. Knockdown of 14-3-3ε in Marc-145 cells and porcine alveolar macrophages (PAMs) caused a significant decrease in TA-12 replication, while stable overexpression of 14-3-3ε caused a significant increase in the replication of TA-12 and low pathogenic PRRSV (LP-PRRSV) CH-1R. The 14-3-3 inhibitor difopein also decreased TA-12 and CH-1R replication in Marc-145 cells and PAMs. These findings are consistent with 14-3-3ε acting as a proviral factor and suggest that 14-3-3ε siRNA and difopein are therapeutic candidates against PRRSV infection.


Frontotemporal dementia: change of familial caregiver burden and partner relation in a Dutch cohort of 63 patients.
The current study examined the change of caregiver burden and the development of the quality of the partner relation in frontotemporal dementia (FTD). During a 2-year period, deterioration, behavioural problems, caregiver burden, general psychopathology, quality of life, social support, coping strategies and relationship quality were inspected in 63 FTD caregiver-care recipient dyads. After 2 years patients reached maximum dementia severity with stable Neuropsychiatric Inventory levels. Contrary to expectations, caregiver burden decreased and psychological well-being remained stable. Coping style and social support changed unfavourably. Relationship closeness and getting along were preserved, whereas communication and sharing viewpoint on life were dramatically reduced. FTD caregivers need support in coping with the increasingly hopeless situation of their patients. Future research methods into caregiver burden should address response shift as a means for psychological adjustment.


The effect of different agitation modes on platelet metabolism, thromboxane formation, and alpha-granular release during platelet storage.
Platelet concentrates (PCs), prepared by plateletpheresis, were stored in aliquots in polyvinylchloride blood bags for 5 days at 22 degrees C under rapid, slow, or no agitation. Nonagitated PCs were also stored in a 98-percent oxygen atmosphere. In nonagitated PCs, pO2, lactate production, and platelet factor 4 (PF 4) concentration increased, whereas the ATP level and pH dropped rapidly. These changes were somewhat minimized in nonagitated PCs stored in oxygen. There was no significant difference between the two agitated groups. The increase in PF 4 correlated inversely to the decrease in ATP: r = -0.91, p less than 0.001, n = 24. The formation of thromboxane B2 (TxB2) after stimulation with arachidonic acid or collagen was significantly higher in slowly agitated PCs on Day 5 than on Day 0 (p less than 0.01). Nonagitated PCs produced lower levels of TxB2 (collagen stimulation) on Day 5 (p less than 0.05). In unstimulated PCs, the levels of TxB2 and ATP were inversely correlated on Day 5 (r = -0.70, p less than 0.001, n = 20). In vivo survival was performed after 72 hours of storage; mean survival (+/- SD) was 6.5 (+/- 0.3) days for nonagitated oxygenated PCs and 6.8 (+/- 0.7) days for agitated PCs. In nonagitated PCs, anaerobic metabolism increased, although oxygen diffusion through the container wall was sufficient. Agitation seems to facilitate the diffusion of oxygen through the storage medium. Nonagitated PCs were stored safely for 24 hours; this period can be extended to at least 72 hours when aerobic metabolism is maintained.


Postintubation Multisegmental Tracheal Stenosis: A 24-Year Experience.
Management of multisegmental tracheal stenosis is challenging. In this 24-year longitudinal single-center study, we present an algorithmic treatment approach. A retrospective analysis of 2167 patients with postintubation tracheal stenosis indicated 83 (3.83%) patients with multisegmental tracheal stenosis. Patients were assigned to 4 management groups according to the length, location, and severity of stenoses; tracheal infection/mucositis; laryngeal function; symptoms; general condition; and comorbid diseases. Type 1 (n = 13): 1-stage resection of both strictures, Type 2 (n = 6): 2-stage resection of both strictures, Type 3 (n = 40): resection of 1 stricture and nonresectional management of the other, Type 4 (n = 24): nonresectional management of both strictures. Outcomes were categorized as Good, Acceptable, or Poor. Univariate analyses for factors predictive of recurrence and outcome were performed. Follow-ups were completed in 70 (84.34%) patients (median, 22.5 months). Outcome was assessed as Good in 56 (82.35%), Acceptable in 10 (14.71%), Poor in 2 (2.94%), and mortality in 2 (2.94%) patients. The median length of airway resection was 46, 67.5, and 40 mm in Types 1-3, respectively. Only 11 (13.25%) patients had no history of tracheostomy or tracheal surgery. By univariate analysis, a shorter intubation period was associated with Good outcome (P = .017). No factors predictive of recurrence or outcome were ascertained. Multisegmental tracheal stenosis, generally caused by performing an inappropriate tracheostomy, is an iatrogenic disease that can be prevented. Although resection of both strictures may be feasible and is associated with Good results, in the majority of cases, a combination of surgical resection and non-resectional methods are sufficient to achieve Good results.


[Functional examination findings after parietal pleurectomy in patients with recurrent of spontaneous pneumothorax (author's transl)].
Eight patients with recurrent of spontaneous pneumothorax were re-examined sixteen months or more after a total parietal pleurectomy had been carried out. This re-examination included: 1. Detailed case history with emphasis on physical performance; 2. clinical findings; 3. Thorax x-ray at two planes; 4. Lungscintigraphy; 5. Spirometry. Following parietal pleurectomy, none of the patients exhibited any functional disturbance worthy of mention. This operative technique, perhaps modified as a partial parietal pleurectomy, can be recommended at this time as the method of choice for treating recurrent spontaneous pneumothorax.


Cancer risks derived from alcohol.
Most cancers of the upper aero-digestive tract are related to alcohol consumption. For the mouth, oesophagus and larynx a positive dose-response relationship has been observed, as well as a combination effect with tobacco smoking--according to a multiplicative model in the case of the oesophagus. Nutritional factors also play a role. For other cancer sites, the role of alcohol is controversial, except for primary liver cancer which often develops on a cirrhotic liver. The mechanisms by which alcohol increases cancer risk are still obscure. It is not considered to be a carcinogen by itself but rather as a co-carcinogen, facilitating or enhancing the role of other carcinogens. Another mechanism might be the induction of microsomal enzymes activating pro-carcinogens. As in the case for smoking, prevention can be achieved by abstention or reduction of consumption. This has to be considered seriously in countries where alcohol consumption is increasing.


Competing ligand exchange-solid phase extraction method for the determination of the complexation of dissolved inorganic mercury (II) in natural waters.
A method employing dual competitive ligand exchange followed by solid phase extraction (CLE-SPE) for characterizing the complexation of inorganic Hg(II) in natural waters is described. This method employs parallel use of two competing ligands: diethyldithiolcarbamate (DEDC), which forms hydrophobic complexes with Hg(II), and thiosalicylic acid (TSA), which forms hydrophilic complexes with Hg(II). Inorganic mercury complexed by natural and competing ligands are separated based on hydrophobicity using C18 solid phase extraction columns. Data modeling allows for the calculation of the concentration and conditional stability constants of natural ligands capable of complexing Hg(II) in both the operationally defined hydrophilic and hydrophobic fractions. The use of multiple ligand concentrations, and thus multiple analytical windows, to characterize different ligand classes within both of these two fractions is described. Studies of the kinetics of the ligand exchange involved, potential for changes in the stability of natural ligands during freezing and thawing, potential breakthrough during solid phase extraction, as well as the method's precision and estimation of error, are presented and discussed. Results from the application of the method to natural freshwaters demonstrated that in the limited samples collected over 99.99% of the ambient inorganic mercury is strongly complexed by ligands with conditional stability constants (K(HgL)(cond), Hg2+) on the order of 10(30), values similar to that of reduced sulfur ligands. At ambient conditions 85-90% of the mercury exists in hydrophobic complexes in these freshwaters, but strong Hg-binding ligands exist in both the hydrophobic and hydrophilic fractions.


Adolescents' Involvement in Cyber Bullying and Perceptions of School: The Importance of Perceived Peer Acceptance for Female Adolescents.
Young people are spending increasing amounts of time using digital technology and, as such, are at great risk of being involved in cyber bullying as a victim, bully, or bully/victim. Despite cyber bullying typically occurring outside the school environment, the impact of being involved in cyber bullying is likely to spill over to school. Fully 285 11- to 15-year-olds (125 male and 160 female, Mage = 12.19 years, SD = 1.03) completed measures of cyber bullying involvement, self-esteem, trust, perceived peer acceptance, and perceptions of the value of learning and the importance of school. For young women, involvement in cyber bullying as a victim, bully, or bully/victim negatively predicted perceptions of learning and school, and perceived peer acceptance mediated this relationship. The results indicated that involvement in cyber bullying negatively predicted perceived peer acceptance which, in turn, positively predicted perceptions of learning and school. For young men, fulfilling the bully/victim role negatively predicted perceptions of learning and school. Consequently, for young women in particular, involvement in cyber bullying spills over to impact perceptions of learning. The findings of the current study highlight how stressors external to the school environment can adversely impact young women's perceptions of school and also have implications for the development of interventions designed to ameliorate the effects of cyber bullying.


The association between albuminuria and thyroid antibodies in newly diagnosed type 2 diabetes mellitus patients with Hashimoto's thyroiditis and euthyroidism.
Microalbuminuria is a prognostic marker of diabetes kidney disease. It is generally diagnosed as the ratio of urinary albumin to creatinine (UACR) of 30-300 mg/g. Hashimoto's thyroiditis is a common disease in the endocrinology and the thyroid antibodies may associated with kidney disease. We investigated the UACR in the newly diagnosed T2DM with Hashimoto's thyroiditis and tried to detect the relationship between the UACR and thyroid antibodies. One hundred twenty newly diagnosed T2DM patients with Hashimoto's thyroiditis and euthyroidism and 50 sex and age-matched T2DM with non-Hashimoto's and other thyroid disease were recruited. T2DM patients were divided into 2 groups by the titer of TPOAb: (1). TPOAb (+) group: T2DM with positive TPOAb (n = 105); (2). TPOAb (-) group: T2DM with negative TPOAb (n = 65). T2DM with positive TPOAb group had higher UACR than T2DM with negative TPOAb group (21.55 ± 7.28 vs 15.13 ± 5.69 mg/g, P < 0.01). UACR were positively related to BMI (r = 0.255, P < 0.05), FPG (r = 0.285, P < 0.05), HbA1c (r = 0.260, P < 0.05) and TPOAb (r = 0.349, P < 0.05). HbA1c (β = 0.793, P < 0.05), BMI (β = 0.342, P < 0.05) and lnTPOAb (β = 1.207, P < 0.05) were independently associated with UACR. In the newly diagnosed T2DM patients, Hashimoto's thyroiditis with TPOAb positive had higher UACR levels. TPOAb titer, BMI and HbA1c were independent associated with UACR in these patients.


Homomeric interaction of the mouse Rad52 protein.
The Rad52 protein plays a crucial role in repairing DNA damage and homologous recombination, possibly by virtue of its ability to catalyze annealing of single-stranded DNA. In agreement with recent genetic data, we here present results based on the two-hybrid system, demonstrating that mouse Rad52p is able to form homomeric complexes. A small domain necessary and sufficient for the self-interaction is located in the conserved N-terminus of the protein. These data contribute to the important insights into the architecture of the multi-protein complex involved in recombinational DNA repair.


Seborrheic Dermatitis in Older Adults: Pathogenesis and Treatment Options.
Seborrheic dermatitis is a common and chronic skin disease, which is particularly prevalent in older adults. While a specific cause of seborrheic dermatitis remains largely unelucidated, the currently understood pathogenesis of seborrheic dermatitis revolves around the presence of Malassezia yeast colonies and an inflammatory response in the affected individual. Keratinocyte proliferation resulting from inflammasome response in the host skin leads to the clinically relevant symptoms of seborrheic dermatitis. The increasing number of older adults as a percentage of the population in the USA will lead to an even higher prevalence of the disease in the ensuing decades. Fortunately, there are multiple treatment options based on individual patient situations and preferences. Topical treatment is the gold standard, but oral therapy may be required in certain cases. In order to maximize effectiveness and minimize adverse pharmacologic effects, effective treatment for older adults must take into account changes in lifestyle and metabolism that occur with aging.


Static and dynamic components of Debye-Waller coefficients in the novel cubic polymorph of low-temperature disordered Cu2ZnSnS4.
Cu2ZnSnS4 (CZTS) is an attractive material for sustainable photovoltaics and thermoelectrics, and several properties originate from its marked polymorphism. High-energy mechanical alloying is found to lead to a disordered phase that possesses a sphalerite-like cubic structure. This is investigated in detail with the aid of laboratory and synchrotron radiation X-ray diffraction, Raman spectroscopy, electron microscopy and ab initio molecular dynamics. The disordered cubic polymorph is preserved below 663 K. With thermal treatments above 663 K, the tetragonal kesterite phase forms, used here as a reference for structural and microstructural features. Particular attention is paid to the stacking arrangement: a significant fraction of twin faults was found in the disordered cubic samples, which then progressively annealed with domain growth and with the transition to the ordered tetragonal phase. This study also focuses on Debye-Waller coefficients, which were found to be considerably larger for the disordered cubic than the tetragonal sample. Indeed, disorder leads to an ∼1 Å2 upward shift through the temperature range 100-700 K, a feature confirmed by ab initio calculations, which points to a particularly high contribution from disordered Sn cations. This supports the general understanding that structural disorder introduces a temperature-independent static contribution to the atomic mean-square displacement. Debye-Waller coefficients are found to be a good measure of this disorder, known to have a critical effect on transport properties.


Spectral signature and heterodyne efficiency for different wavelengths in laser Doppler flowmetry.
Laser Doppler perfusion monitoring and imaging technologies generate time traces and two-dimensional flow maps of the microcirculation. With the goal of reaching different tissue depths, these technologies are equipped with lasers operating at different wavelengths lambda. The fact that the average scattering angle, at a single scattering event, between a photon and a red blood cell increases with lambda is compensated for by a 1/lambda effect in the scattering vector, rendering the average frequency shift virtually independent of the choice of wavelength. Monte Carlo simulations showed that the corresponding spectral signature of the Doppler signals for lambda = 632.8 nm and 780 nm were close to identical. The theoretical predictions were verified by calculating the centre-of-gravity (COG) frequency of the laser Doppler power spectral density for the two wavelengths from forearm and finger skin, representing a low and high perfusion area, respectively (forearm COG= 123 against 121 Hz, finger COG = 220 against 212 Hz). When the wavelength changes from 632.8 nm to 780 nm, the heterodyne efficiency of the detector and, thereby, the inherent system amplification increase. For tissues with identical microvascular flow conditions, the output signal therefore tends to increase in magnitude when shifting to longer wavelengths.


Newborn screening by DNA analysis of dried blood spots.
Amplification of DNA recovered from a dried blood spot was used to genotype individuals with sickle cell disease, sickle cell carriers, and controls. A single 200-microliters blood spot applied to a filter paper provides sufficient material for more than 20 genetic analyses. In addition, the stability of the DNA is such that adequate material for amplification can be isolated from dried blood spots up to a year following collection. The DNA analysis methods described in this study could be applied to large-scale screening of newborns for genetic disorders.


Evaluation of mechanical properties of different polyetheretherketone endodontic post systems: an in vitro study.
Survival of endodontically treated teeth depends on an efficient restoration of the missing tooth structure. This study aimed to investigate the mechanical properties of different endodontic post systems. Human permanent maxillary central incisors (no.=58) were decoronated and root-filled. The specimens with prepared root canals were randomly divided into Group P: Polyether Ether Ketone (PEEK) post and composite core and Group C: custom-made post-core of PEEK. The cementation of the posts was carried out using self-adhesive resin cement. Nano-hybrid composite resin was used for core fabrication. After cementation, the specimens from each group were randomly divided into two subgroups according to the types of tests utilized: 14 from each group were for the fracture strength test, which was restored with IPS e-max CAD crown, and 15 from each group for the pullout resistance test. A universal testing machine was used for the test performance. The fracture resistance test showed that the values significantly differed among tested posts (P = 0.013). Group P showed the highest fracture resistance. Group C exhibited higher mean pullout resistance values than the other group (P) (P = 0.059). In the two-piece PEEK post and composite core, the predominant type of failure was a core fracture, while in the one-piece PEEK post-core, most types of failures were either in the crown or in the post. The prefabricated posts are more resistant to fracture than the custom-made posts, with fracture and displacement mainly of the core. In contrast, both showed similar pullout resistance.


Ischemic heart disease and regional left ventricular wall motion: a study comparing radial, centerline and a video intensity based slope technique.
Left ventricular regional wall motion in ischemic heart disease was evaluated and compared using three different methods based on radiographic ventriculograms. Radial method uses an internal reference system, and centerline method employs an external reference system, both methods are based on two frame analysis. The last method, an automated video intensity technique, analyzes on a frame by frame basis utilizing an external reference system. A total of 42 patients were included in the study, of these 12 had a history of myocardial infarction. Significant coronary artery stenosis was defined as 50% measured diameter reduction. Right coronary artery (29/42) was most commonly involved. Single vessel disease was present in 18 patients, two vessel disease in 15 and three vessel disease in eight patients. The radial method detected abnormal wall motion in 16/42 patients, centerline method yielded a detection accuracy of 22/42 and with the new technique, asynchrony was noted in 39/42 patients. All three methods detected regional wall motion abnormalities with a higher sensitivity in patients with prior myocardial infarction. The centerline method had highest sensitivity for the right coronary artery bed (55%). The radial method (45%) and the video intensity based technique (95%) had the highest sensitivity for regions supplied by the left anterior descending artery.


2-{1-[(2-Nitro-benzene-sulfonamido)-meth-yl]cyclo-hexyl}acetic acid.
In the title compound, C(15)H(20)N(2)O(6)S, the C-SO(2)-NH-C torsion angle is 64.54 (14)°. In the mol-ecule, there is a bifurcated N-H⋯(O,O) hydrogen bond, forming S(7) rings. In the crystal, inversion dimers are formed via O-H⋯O hydrogen bonds involving the carboxyl group, so forming R(2) (2)(8) rings. These dimers are further linked via pairs of C-H⋯O hydrogen bonds, forming a C(6) chain propagating along the c-axis direction.


Responses to amrinone in isolated cardiac muscles from cat, rabbit, and guinea pig.
Amrinone (10(-5)-10(-2) M) produced a positive inotropic response in several electrically stimulated, isolated cardiac muscle preparations. The order of potencies for amrinone in the tissues studied was: cat papillary muscle greater than rabbit papillary muscle greater than muscle strips from rabbit left atria = guinea pig papillary muscle greater than guinea pig left atria. Amrinone also restored contractility to cat and rabbit papillary muscles which had been partially depolarized with 20 mM K+. The beta-adrenergic antagonists timolol and propranolol partially inhibited these responses in rabbit but not cat papillary muscles. Reserpine pretreatment did not influence the responses to amrinone in any of the preparations studied. In conclusion, (a) the cat papillary muscle was the most sensitive preparation to the inotropic effect of amrinone, and (b) in the rabbit papillary muscle, beta-adrenoceptors contribute to the amrinone response but are not solely responsible for the enhanced inotropy.


Draft Genome Sequence of a vanA-Type Vancomycin-Resistant Reference Strain, Enterococcus faecium ATCC 51559.
Vancomycin-resistant Enterococcus faecium has emerged as a multidrug-resistant pathogen in hospital settings. Here, we present the draft genome sequence of a high-level vancomycin-resistant strain, E. faecium ATCC 51559, which is employed as a standard laboratory vanA genotype-positive control strain for clinical and laboratory studies.


Mortality from liver cirrhosis in Italy: proportion associated with consumption of alcohol.
A descriptive analysis of the features of mortality from cirrhosis in Italy suggests that it is made up of two components which are characterized by different age trends. On the basis of this hypothesis, a model has been postulated and applied to the data for the 94 Italian provinces in order to identify the two components. When considering alcoholic drinking data, it appears that only one of these components is associated with the consumption of alcohol, both for men and for women. In this way an estimate can be made of the proportion of mortality in Italy which can be linked to alcohol consumption. For males, this is 40.4% (47.1% for the North, 29.7% for Central Italy, and 33% for the South/Islands). For females, the average is 24.6% (36.6% for the North, 16.2% for Central Italy, and 12.3% for the South/Islands). In absolute terms, these figures represent approx 5000 of the 13,000 deaths per year among males and around 1200 of the 5000 deaths from cirrhosis among females.


Whole lung irradiation as a novel treatment for COVID-19: Final results of the prospective randomized trial (WINCOVID trial).
The ability of low dose radiotherapy (LDRT) to control the unprecedented cytokine release associated with COVID-19 pathogenesis has been an area of widespread research since the COVID pandemic. It has not been studied adequately whether the anti-inflammatory effect of LDRT provides additional benefit when used concurrently with steroids amongst other standard pharmacologic therapy. 51 RT-PCR positive COVID-19 patients were recruited between November 2020 and July 2021. 34 patients were allotted to receive 0.5 Gy single session LDRT along with standard pharmacologic therapy while 17 patients received standard pharmacologic therapy alone. All had SpO2 <94% on room air, respiratory frequency >24/min and SpO2/FiO2 (SF) ratio between >89 but <357. All patients underwent a baseline CT scan. They were followed up for 28 days during when serial SF ratio, blood biomarkers (CRP, Serum ferritin, IL-6), Absolute lymphocyte count (ALC), repeat CT scan were performed at pre-defined time points. LDRT showed a statistically significant early improvement in oxygenation, an early time to clinical recovery, early hospital discharge and better radiological resolution compared to control group. There was no statistically significant difference between the two groups with respect to ALC or blood biomarkers at any of the measured time points. The 28-day mortality rate did not show statistically significant difference between the two groups. LDRT can be considered for selected oxygen-dependent moderate to severe COVID-19 patients for rapid relief of respiratory distress. It can be safely combined with standard pharmacologic treatment in such patients for added clinical benefit.


Analysis of micro-shear bond strength of self-etch adhesive systems with dentine: An in vitro study.
Success or failure of a composite restoration largely depends on its bonding to enamel/dentine. Several better adhesive systems have been developed during the last few years due to rapid advancement in the technology. Recent self-etched adhesives have fewer clinical steps and are less technique sensitive. Ninety extracted human permanent molars were collected, grounded and finished to prepare flat dentine-bonding surfaces on their occlusal surface. All specimens were divided into three groups (n = 30) on the basis of three adhesive systems Adper Easy Bond (AE), Beautibond (BB) and Xeno IV (XE). These adhesive systems were applied on prepared mid-dentine-bonding surface. A restorative resin was added with the help of a transparent tube of 2 mm height and 1.7 mm internal diameter and cured. Fifteen specimens in each group were loaded to failure in an Instron Universal Testing Machine after storage for 24 h at 37 °C to check micro-shear bond strength. Another fifteen specimens from each group were thermocycled 500 times at 5 °C and 55 °C with dwell time of 1 min in each bath followed by loading to failure. The data obtained was analyzed with SPSS version 21 at significance level of <05. After 24 h, micro-shear bond strength of BB was higher (26.04 MPa) than XE (23.69 MPa) and AE (21.50 MPa). After thermocycling, micro-shear bond strength decreased significantly in BB (P = .001) and XE (P = .03). The micro-shear bond strength of BB was highest among three groups, which decreased after thermocycling.


Joint modelling and simulation of M-protein dynamics and progression-free survival for alternative isatuximab dosing with pomalidomide/dexamethasone.
Addition of isatuximab (Isa) to pomalidomide/dexamethasone (Pd) significantly improved progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma (RRMM). We aimed to characterize the relationship between serum M-protein kinetics and PFS in the phase 3 ICARIA-MM trial (NCT02990338), and to evaluate an alternative dosing regimen of Isa by simulation. Data from the ICARIA-MM trial comparing Isa 10 mg/kg weekly for 4 weeks then every 2 weeks (QW-Q2W) in combination with Pd versus Pd in 256 evaluable RRMM patients were used. A joint model of serum M-protein dynamics and PFS was developed. Trial simulations were then performed to evaluate whether efficacy is maintained after switching to a monthly dosing regimen. The model identified instantaneous changes (slope) in serum M-protein as the best on-treatment predictor for PFS and baseline patient characteristics impacting serum M-protein kinetics (albumin and β2-microglobulin on baseline levels, non-IgG type on growth rate) and PFS (presence of plasmacytomas). Trial simulations demonstrated that switching to a monthly Isa regimen at 6 months would shorten median PFS by 2.3 weeks and induce 42.3% patients to progress earlier. Trial simulations supported selection of the approved Isa 10 mg/kg QW-Q2W regimen and showed that switching to a monthly regimen after 6 months may reduce clinical benefit in the overall population. However, patients with good prognostic characteristics and with a stable, very good partial response may switch to a monthly regimen after 6 months without compromising the risk of disease progression. This hypothesis will be tested in a prospective clinical trial.


Host plant utilization in the comma butterfly: sources of variation and evolutionary implications.
A major challenge in the study of insect-host plant interactions is to understand how the different aspects of offspring performance interact to produce a preference hierarchy in the ovipositing females. In this paper we investigate host plant preference of the polyphagous butterfly Polygonia c-album (Lepidoptera: Nymphalidae) and compare it with several aspects of the life history of its offspring (growth rate, development time, adult size, survival and female fecundity). Females and offspring were tested on four naturally used host plants (Urtica dioica, Ulmus glabra, Salix caprea, and Betula pubescens). There was substantial individual variation in host plant preference, including reversals in rank order, but the differences were largely confined to differences in the ranking of Urtica dioica and S. caprea. Different aspects of performance on these two plants gave conflicting and complementary results, implying a trade-off between short development time on U. dioica, and larger size and higher fecundity on S. caprea. As all performance components showed low individual variation the large variation in host plant preference was interpreted as due to alternative oviposition strategies on the basis of similar 'performance hierarchies'. This indicates that the larval performance component of host-plant utilization may be more conservative to evolutionary change than the preference of ovipositing females. Possible macro-evolutionary implications of this are discussed.


Evaluation and comparison of the accuracy of transvaginal ultrasound and MRI for the diagnosis of deep rectal endometriosis: A cross-sectional study.
To determine and compare the value of magnetic resonance imaging (MRI) and transvaginal sonography (TVS) in the diagnosis of rectal endometriosis. In this cross-sectional study, 555 patients with rectal endometriosis, who had undergone MRI and TVS before laparoscopic operation, were included. The sensitivity, specificity, and accuracy of these two imaging modalities were evaluated and compared based on histopathologic reports and three different kinds of rectal endometriosis surgeries (shaving as a first group and disk and segmental resection methods combined as a second group). Sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of ultrasound in the diagnosis of rectal endometriosis were, respectively, 69.55% (65.4%-73.4%), 91.30% (72%-98.9%), 70.4% (66.4%-74.17%), 11.48% (9.77%-13.43%), 99.46% (98%-99.86%), 8.0 (2.12-30.1), and 0.3 (0.28-0.4). These values were 51.37% (47.1%-55.6%), 79.17% (57.8%-92.9%), 52.53% (48.3%-56.6%), 6.64% (5.39%-8.16%), 98.26% (96.26%-99.2%), 2.47 (1.13-5.4), and 0.6 (0.49-077) for MRI. Even though ultrasound had better accuracy for detection of superficial rectal endometriosis (Group 1) (P < 0.001), the sensitivity, specificity, and accuracy of both imaging modalities in diagnosis of deep rectal lesions (Group 2) were almost identical. TVS should be considered as a first-line modality for diagnosis of rectal endometriosis, mainly because of its greater availability, lower cost, and higher accuracy.


Magnitude and determinants of neonatal and postneonatal mortality in Goiânia, Goiás, Brazil: a retrospective cohort study, 2012.
To estimate magnitude and determinants of neonatal and postneonatal mortality rates in Goiânia, Brazil, 2012. This was a retrospective cohort study based on data linkage of the Live Birth Information System and the Mortality Information System. Logistic regression was used to evaluate factors associated with neonatal and postneonatal death. Neonatal mortality (0-27 days of life) was 9.4 deaths per 1,000 live births; while postneonatal mortality (28-364 days of life) was 3.0 deaths per 1,000 live births. Neonatal mortality associated factors were: 0-3 prenatal care visits (OR=13.10 - 95%CI 7.48;22.96), 19-34-week pregnancy (OR=6.25 - 95%CI 2.26;17.29), birth weight <1,500g (OR=62.42 - 95%CI 22.72;171.48) and cesarean delivery (OR=0.54 - 95%CI 0.37;0.79). Postneonatal mortality associated factors were: 0-3 prenatal care visits (OR=4.16 - 95%CI 1.51;11.43) and birth weight <1.500g (OR=18.74 - 95%CI 4.04;87.00). A low number of prenatal care visits, premature childbirth and low birth weight were the main risk factors for neonatal and postneonatal mortality.


Clinically relevant patch test reactions in children--a United States based study.
Allergic contact dermatitis in the pediatric population is more common than previously recognized, with recent prevalence estimates of positive patch test reactions in the range of 14-70% of children patch tested. The aim of this study was to confirm the prevalence of clinically relevant allergic contact dermatitis in children at two referral centers and determine the most common contact allergens. We performed a retrospective case series analysis of 65 symptomatic children (35 girls and 30 boys) aged 1-18 years old who were patch tested over a 5-year period for recalcitrant dermatitis. Positive patch test reactions were noted in 54 of the 65 children (prevalence rate of 83%) to 80 different allergens. Fifty children (77%) had positive reactions which were determined to be of "definite" or "probable" current clinical relevance. We conclude that the diagnosis of allergic contact dermatitis to specific relevant allergens is common in children referred for patch testing and that contact allergy should be considered in all children with recalcitrant dermatitis. With this article, we review the literature and present a US based study regarding the clinical relevance of positive patch test reactions in children.


Replication of the association between CHRNA4 rs1044396 and harm avoidance in a large population-based sample.
Harm avoidance is a personality trait characterized by excessive worrying and fear of uncertainty, which has repeatedly been related to anxiety disorders. Converging lines of research in rodents and humans point towards an involvement of the nicotinic cholinergic system in the modulation of anxiety. Most notably, the rs1044396 polymorphism in the CHRNA4 gene, which codes for the α4 subunit of the nicotinic acetylcholine receptor, has been linked to negative emotionality traits including harm avoidance in a recent study. Against this background, we investigated the association between harm avoidance and the rs1044396 polymorphism using data from N=1673 healthy subjects, which were collected in the context of the German multi-centre study ׳Genetics of Nicotine Dependence and Neurobiological Phenotypes׳. Homozygous carriers of the C-allele showed significantly higher levels of harm avoidance than homozygous T-allele carriers, with heterozygous subjects exhibiting intermediate scores. The effect was neither modulated by age or gender nor by smoking status. By replicating previous findings in a large population-based sample for the first time, the present study adds to the growing evidence suggesting an involvement of nicotinic cholinergic mechanism in anxiety and negative emotionality, which may pose an effective target for medical treatment.


NEUROCYSTICERCOSIS - A CLINICOPATHOLOGICAL APPRAISAL.
Neurocysticercosis is the most common parasitic disease affecting the human central nervous system, with protean clinical manifestations. During the last 17 years, 153 cases of neurocysticercosis were histopathologically diagnosed on surgically resected and autopsied material. Variable number of cysts, from a solitary one to multiple were found invading different parts of the neuraxis (118 cases). These cestode larval forms had a prediliction for locating in the cerebral grey matter (98 cases), followed by subcortical nuclear area (12), cerebral ventricles and subarachnoid cisterns (26 cases). Patients harbouring parenchymal cysts manifested predominantly with seizures and encephalitis (113 cases) whereas those with ventricular and/or cisternal cysts presented with features of chronic meningitis and hydrocephalus. The unusual clinical presentations were psychiatric symptoms with behavioural abnormalities and stroke in the young as a result of cysticercal meningitis with associated arteritis. Primary cysticercal abscess in the brain parenchyma was an interesting pathological feature noted in 3 cases. In the endemic areas, the co-existence of neurocysticercosis appears to enhance the morbidity and mortality due to Japanese encephalitis (31 cases). The surface glycoprotein of the cysticercal cyst has been identified to be the antigenic component to which the host immune system responds by forming antibody in the CSF.


Physiologic correlates of the heart rate response to upright isotonic exercise: relevance to rate-responsive pacemakers.
Rate-responsive cardiac pacing requires a sensitive physiologic variable that is closely correlated with the heart rate-oxygen uptake relation, particularly in patients with heart failure whose cardiac output response to exercise is more dependent on heart rate. Accordingly, the heart rate response to upright exercise was measured in 81 patients with heart failure or hypertension, or both, and in 27 normal subjects. Oxygen uptake (VO2), minute ventilation (VE), cardiac output, right heart pressures and the mixed venous temperature, oxygen saturation (SvO2) and pH were analyzed throughout exercise. Linear regression analysis of these variables with heart rate revealed the following: 1) There was a highly linear heart rate-VO2 relation in each subject (the average slope of this relation was greater [p less than 0.05] in patients with more severe failure). 2) VE was highly correlated with exercise heart rate, and its slope was not different between normal subjects and patients. 3) Mixed venous temperature and pH were poor predictors of exercise heart rate, particularly at low or moderate levels of work; however, SvO2 was highly correlated with heart rate for all levels of work. Thus, in normal subjects and patients with heart failure or hypertension, or both, heart rate increases linearly with isotonic leg exercise. Minute ventilation and mixed venous oxygen saturation are highly correlated with this response and may serve as potential sensors for rate-responsive pacemakers.


Integrative medicine outcomes: what should we measure?
The outcomes of Integrative medicine (IM) that combine biomedicine with traditional, complementary and alternative medicine (TCAM) are broad, reflecting the integration. IM is concerned with acute and chronic diseases, holistic approaches, and health promotion and wellness. Before commencing a research program in a primary care IM clinic, stakeholders were interviewed about IM outcomes. Everyone thought Physical Health and Mental Health were important. Those with a more holistic view of health thought a broader range of topics should be measured. Less important topics were lifestyle; health-related aspects of life satisfaction and quality of life; and healthcare evaluation. However, no one thought these should be excluded. Spirituality was the most contentious. Some commended its inclusion. For others, once religiousness and God were removed, the remaining elements should be relocated to the domains of mental health and life satisfaction. The results highlight the importance of consulting stakeholders before measuring outcomes.


Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function.
Positional cloning of hereditary deafness genes is a direct approach to identify molecules and mechanisms underlying auditory function. Here we report a locus for dominant deafness, DFNA36, which maps to human chromosome 9q13-21 in a region overlapping the DFNB7/B11 locus for recessive deafness. We identified eight mutations in a new gene, transmembrane cochlear-expressed gene 1 (TMC1), in a DFNA36 family and eleven DFNB7/B11 families. We detected a 1.6-kb genomic deletion encompassing exon 14 of Tmc1 in the recessive deafness (dn) mouse mutant, which lacks auditory responses and has hair-cell degeneration. TMC1 and TMC2 on chromosome 20p13 are members of a gene family predicted to encode transmembrane proteins. Tmc1 mRNA is expressed in hair cells of the postnatal mouse cochlea and vestibular end organs and is required for normal function of cochlear hair cells.


Adverse reactions to practolol in hospitalized patients: a report from the Boston Collaborative Drug Surveillance Program.
Adverse reactions to practolol were studied in 198 prospectively monitored hospitalized medical patients. The mean age of the practolol recipients was 57 years; angina and cardiac arrhythmias were the most common indications for therapy. Adverse reactions were attributed to practolol in 20 patients (10%). Fifteen of these twenty reactions involved impairment of cardiac function (bradyarrhythmias, heart block, congestive heart failure, hypotension), and in three instances the reaction was considered life-threatening. Three additional patients had cutaneous reactions attributed to the drug. Adverse reactions to practolol were not dose-related, but toxicity appeared to be more frequent among patients concurrently receiving quinidine. The frequency of cardiovascular complications of propranolol in a similar series of patients was nearly identical. However, no skin reactions were attributed to propranolol. The findings suggest that practolol and propranolol produce unwanted cardiovascular effects with nearly equal frequency among hospitalized patients. Cutaneous reactions to practolol are evident even during short-term use.


Patterns of Relative Telomere Length is Associated With hTERT Gene Expression in the Tissue of Patients With Breast Cancer.
Homeostasis of telomere in breast cancer might be altered as a result of cumulative effects of various factors causing genomic instability and affecting prognosis. This study aimed to compare the relative telomere length (RTL) and hTERT mRNA expression in the tissue of patients with breast cancer along with the clinicopathologic parameters. Frozen tumor tissues and adjacent normal breast tissue from 98 patients with invasive ductal breast cancer were used for the analysis. RTL and hTERT mRNA expression were measured using quantitative real time polymerase chain reaction. Among the 98 cases, 51% had an early-stage carcinoma, 66% were tumor size < 5 cm, 30% were node-negative, and 20% were low-grade tumors. In this study, 63% of cases showed higher hTERT gene expression with an odds ratio of 2.77 (P = .02). The median RTL for elongated telomere was 3.49, and the value was significantly elevated when compared with the shorter telomere. Shortened RTL was present in 60% of early-stage cancer cases, 55% where the tumor size was < 5 cm, 72% of the lymph node-negative cases, and 68% of low-grade carcinoma. Significantly elongated RTL, with median 4.22, 3.19, 3.17, and 3.28 was observed (P < .05) in the advanced stage, larger tumor size, node-positive, and high-grade cases respectively. In this study, shortened telomere was observed in early-stage cancer, and elongated telomere was found in advanced diseases. However, 13% of patients with lower hTERT gene expression showed elongated telomeres, indicating relative telomere length measurement in tissue is different from blood leukocyte, showing the dynamic process of tumorigenesis in tissue.


The foraging behavior of the central mudminnow and yellow perch: the influence of foraging site, intraspecific and interspecific competition.
The central mudminnow (Umbra limi) and yellow perch (Perca flavescens) are two species of fishes that commonly co-occur in small bog lakes in the Great Lakes region of North America. Both species are dietary generalists with a high degree of dietary overlap, and perch populations have been shown to have a strong negative effect on mudminnow populations. I compared the foraging rates of the two species in a series of laboratory experiments in which four foraging sites were simulated (open bottom substrate, water column, submerged aquatic macrophytes, and water surface). Fish were observed as they foraged singly, in monospecific pairs, and in mixed species pairs to evaluate the effects of intra- and interspecific competition on foraging success and the potential for resource partitioning based on foraging site. Single species trials showed that each species had similar foraging rates at each of the four sites. Across all sites combined, interspecific competition had a greater negative effect on the foraging success of mudminnows than did intraspecific competition. Conversely, intraspecific competition had a greater negative effect on the foraging success of perch than did interspecific competition. In mixed species trials perch took more food items from each of the four foraging sites than did mudminnows and caused shifts in site-use patterns of mudminnows. Differences in the foraging success of the two species reflected the superior ability of perch to discover the presence of food and to search rapidly for additional items, but were unrelated to handling times. These differences were linked to the species' foraging modes. The competitive superiority of perch, demonstrated in these experiments, could contribute to the negative impact of perch on mudminnow populations under natural conditions.


Detection of Modified Bases in Bacteriophage Genomic DNA.
Collectively, the dsDNA tailed bacteriophages (Caudovirales) contain the largest chemical diversity of naturally occurring deoxynucleotides in DNA observed to date. The continuing discovery of new modifications in phages suggest many more are waiting to be found. Thus, methods for the observation and characterization of noncanonical nucleosides are timely. We present here protocols for extraction of genomic DNA from bacteriophage particles, enzymatic hydrolysis of DNA to free nucleosides, and examination of nucleoside composition by HPLC and mass spectrometry.


Instrumental Swallowing Assessments in the Neonatal and Pediatric Populations: A Systematic Review.
The scientific scope of swallowing disorders in the neonatal and pediatric populations is growing exponentially; however, the preponderance of evidence for evaluation protocols has been concentrated in non-instrumental evaluations creating a lack of research about protocols for instrumental swallowing assessment. Thus, the purpose of this study was to systematically review the literature to identify and to report protocols used in instrumental assessments through videofluoroscopic swallow study (VFSS) and fiberoptic endoscopic evaluation of swallowing (FEES) in the neonatal and pediatric populations to support clinical decision making. The search strategy was applied in five online databases, no filters were applied to restrict languages or publication dates and the gray literature was reviewed. PRISMA statement was used to guide the construction of this review. The studies included validated and unvalidated protocols, the validated protocols had their risk of bias estimated using the QUADAS-2. In total, 13 studies were included in the final review, of these eleven assessed through QUADAS-2, and two classified with low risk of bias. One study is in the process of standardization and validation of an instrumental assessment protocol for swallowing in bottle-fed infants through VFSS. Information about validity and reliability of published protocols for instrumental evaluation in the neonatal and pediatric populations is limited. Therefore, further research is needs to development studies aiming to standardize and validate protocols for instrumental assessments in these populations.


[Cutaneous side effects associated with epidermal growth factor receptor and tyrosine kinase inhibitors].
Basic knowledge in oncogenesis has dramatically improved in the last decade providing more recently new drugs for cancer treatment. These new targeted compounds usually act by inhibiting tyrosine kinase activity of one or more than one proteins involved in tumor growth and cancer progression. This pharmacological effect is the result of monoclonal or small molecule action. Many of these new compounds have cutaneus secondary effects. Cancer patients are now facing new toxicity, essentially skin toxicity. The cutaneous side effects observed in the patients depend on the drug. For example, EGFR inhibitors induce acneiform rash whereas multitarget tyrosine kinase inhibitors induce different more complex effects which physiopatholgy is not yet completely understood. The secondary effects that are frequently observed are described is this article. A better clinical long term management of these effects is a clear medical need as of these effects could be surrogate markers of drug efficacy.


Modified Estrogen-Progesterone Induction Method of Mammary Gland Hyperplasia in Rats.
In female Wistar rats, mammary gland hyperplasia (MGH) was modeled according to a modified protocol involving estrogen-progesterone induction and taking into account the duration of the estrous cycle of this animal species. MGH was induced over four 7-day cycles; each cycle included subcutaneous administration of 17β-estradiol (0.5 mg/kg) for 4 days, injection of progesterone (5 mg/kg) on day 5, then 2 days without injections. In females with MGH, a significant increase in the height and diameter of the nipples of the mammary glands was recorded, two types of changes were observed in the gland tissue: tubuloalveolar and lobuloalveolar hyperplasia. The study confirmed the development of MGH in rats by a modified method.


Bcl-x(L)-mediated changes in metabolic pathways of breast cancer cells: from survival in the blood stream to organ-specific metastasis.
Bcl-x(L) protein plays a role in breast cancer dormancy, promoting survival of cells in metastatic foci by counteracting the proapoptotic signals in the microenvironment. The aim of this study was to identify phenotypes mediated by Bcl-x(L) in breast cancer cells that enhance in vivo survival of clinical metastases. 435/Bcl-x(L) or 435/Neo human breast cancer cells were injected into the inguinal mammary gland of nude mice, and tumors, metastases in lymph node, lung, and bone, and bloodstream surviving cells were examined. Proteomic analysis identified 17 proteins that were overexpressed (more than twofold) or underexpressed (less than twofold) in metastases. A protein interaction program allowed us to functionally associate peroxiredoxin 3, peroxiredoxin 2, carbonyl reductase 3, and enolase 1, suggesting a role for cellular responses to oxidative stress in metastasis organ selection. The prediction included proteins involved in redox systems, kinase pathways, and the ATP synthase complex. Furthermore, the interaction of redox proteins with enolase 1 suggests a connection between glycolysis and antioxidant pathways, enabling achievement of a high metastatic activity. In conclusion, Bcl-x(L) mediates a phenotype in which redox pathways and glycolysis are coupled to protect breast cancer metastatic cells during transit from the primary tumor to the metastatic state.


Capnocytophaga spp. DF-1 pneumonia in an immune-competent 56-year old man post-CABG.
We report a case of a nosocomial Capnocytophaga spp. DF-1 pneumonia in an intubated 56-year-old man following coronary artery bypass grafting. We review Capnocytophaga spp., including the infections they produce and antibiotic susceptibilities.


A cost analysis study of the implementation of fixed-dosing of monoclonal antibodies in the Netherlands Cancer Institute.
Background There is a strong rationale for fixed-dosing of monoclonal antibodies in oncology. Although fixed-dosing of recently introduced monoclonal antibodies is well accepted, the rationale is also applicable for other monoclonal antibodies that already have been used for years, but are still body-size-based dosed in many hospitals. In the Netherlands Cancer Institute, Antoni van Leeuwenhoek (NKI-AVL), fixed-dosing has been implemented now for all monoclonal antibodies and, therefore, this site offers an ideal opportunity for a cost analysis study. Objective To investigate the financial impact of switching to fixed-dosing in the NKI-AVL. Setting The NKI-AVL. Method Information on the preparations of monoclonal antibodies was collected from August 2017 to February 2020. We compared the number of vials needed during preparation for fixed-dosing and body-size -based dosing strategies. The economic impact was calculated for 2 scenarios: scenario 1 assumed clustering of all preparations per day and scenario 2 assumed no clustering of preparations. Main outcome measure Number of saved vials and the correlating savings in health care costs. Results The implementation of fixed-dosing resulted in a substantial reduction in vials used for almost all monoclonal antibodies. The economic savings were calculated to be €0,8 and €3,1 million per year for scenario 1 and 2, respectively. Conclusion Fixed-dosing resulted in substantial savings in health care costs.


What to do, or how to do it?
In this issue of Neuron, Ajemian et al. present a computational model of the activity of neurons in primary motor cortex (M1) during isometric movements in different postures. By modeling the output of M1 neurons in terms of their influence on muscles, they find each M1 neuron maps its output into a particular pattern of muscle actions.


Breast cancer progression: insights into multifaceted matrix metalloproteinases.
The restricted view of matrix metalloproteinases (MMPs) as simple destroyers of extracellular matrix components has largely ignored their substantial contribution in many aspects of cancer development and metastatic dissemination. Over the last few years, the relevance of MMPs in the processing of a large array of extracellular and cell surface-associated proteins has grown considerably. Our knowledge about the complex functions of MMPs and how their contribution may differ throughout cancer progression is rapidly expanding. These new findings provide several explanations for the lack of success of MMP inhibition in clinical trials. A complete understanding of MMP biology is needed before considering them, their substrates or their products as therapeutic targets. In this review, we explore the different faces of MMP implication in breast cancer progression by considering both clinical and fundamental aspects.