Experimental and modeling study of proton and copper binding properties onto fulvic acid fractions using spectroscopic techniques combined with two-dimensional correlation analysis.
Fulvic acid (FA) significantly influences the bioavailability and fate of heavy metals in environments, while its acid-base characters and metal binding processes are still unclear. Here, spectroscopic techniques combined with multiple models (e.g., NICA-Donnan model) and two-dimensional correlation spectroscopy (2D COS) were applied to explore the proton and copper binding properties of FA sub-fractions (FA3-FA13). The charge densities, average contents of carboxylic and phenolic groups, average dissociation constants pKa1 and pKa2 of sub-fractions ranged 0-16 meq∙g∙C-1, 5.03-9.58 meq∙g∙C-1, 2.52-4.67 meq∙g∙C-1, 4.15-4.33 and 8.52-9.72, respectively. FA sub-fractions had a relatively narrow distribution of carboxyl group and a broad distribution of phenolic group. FA sub-fractions also exhibited roughly two phenolic hydroxyl groups per every 1-3 phenyl rings. Differential absorbance spectra (DAS) derived Gaussian bands were associated to the inter-chromophore interactions, the changes of molecular conformations and functional groups with copper addition. Differential spectra slopes (DSlope275-295&325-375) were more significant with higher copper concentration and copper amounts bonded to carboxylic groups. UV-Vis and fluorescence spectra with 2D heterospectral COS revealed the copper binding heterogeneities and sequential orders of chromophores and fluorophores, quantitatively confirming by the order of conditional stability constants (log KCu: 4.64-5.56). Salicylic-/polyhydroxyphenolic, hydroxyl and amino groups were strongly associated to the basic units for fluorophores. Sequential changes followed the order of humic-like→fulvic-like materials for FA3/FA5, humic-like→fulvic-like→tryptophan-like materials for FA7, and humic-like→tryptophan-like→fulvic-like→tyrosine-like materials for FA9/FA13. Spectroscopic techniques combined with various models (especially for 2D COS) are beneficial to elucidate the binding heterogeneity and sensitivity for metal-organic matters at the functional group level.


Influence of season and site location on European cultured sea bass parasites in Corsican fish farms using indicator species analysis (IndVal).
The parasites of 536 European sea bass, Dicentrarchus labrax, were studied between January 2012 and December 2013 in six Corsican fish farms. The indicator value (IndVal) method, which combines measures of fidelity and specificity, has been used in this study. Because of its resilience to changes in abundance, IndVal is a particularly effective tool for ecological bioindicator. The IndVal method showed how season can influence the occurrence of parasite species in cultured sea bass and also identified parasites as bioindicators relative to fish farm location. The combination of specificity and fidelity highlighted several parasite species as significant indicators. A randomization test identified five parasite species as having a significant indicator value for season (the monogenean Diplectanum aequans; the copepods Lernanthropus kroyeri and Caligus minimus; the isopod Ceratothoa oestroides, and the myxosporidian Ceratomyxa labracis). If gills parasites are compared, they can be seen to be indicator species for two different seasons. The only Monogenea species D. aequans had fidelity and specificity more pronounced in winter, whereas both copepod species and the Isopoda revealed highest rates of infestation corresponding with an increase of water temperature. Four species have a significant indicator value for site location (D. aequans, L. kroyeri, C. minimus, and C. oestroides). The fact that the farm 6 was isolated on the east coast of Corsica may not have allowed the parasite to infect other farms. The presence of copepods on a single farm can also be explained according to salinity variations. Data for species composition and infection levels should help to improve the monitoring and management of parasitism in cultured sea bass populations.


Transvenous Fogarty balloon catheter occlusion of an iatrogenic innominate artery to innominate vein fistula.
Transvenous embolization therapy is reported in a patient who developed a fistula from the innominate artery to the innominate vein as a complication of permanent cardiac pacemaker insertion. A transarterial approach at occlusion was unfavorable due to previous difficult catheterizations, and the patient's poor clinical condition precluded alternative operative intervention. The fistula was successfully closed by transvenous placement of a Fogarty nondetachable balloon catheter after coil and detectable balloon placement attempts were unsuccessful.


The first steps towards professional distance: A sequential analysis of students' interactions with patients expressing emotional issues in medical interviews.
Explore sequential patterns in students' interactions with patients expressing emotional concerns in a medical interview. Concepts and principles from conversation analysis (CA) were used to examine the turn-by-turn sequential organization of student actions in eleven video-taped medical interviews. We used results from an earlier coding with an interaction analysis system (VR-CoDES) in a previously published paper as a point of reference. By using CA instead of VR-CoDES as our primary investigative method we observed that student turns previously coded as elicitations to simulated patients' expressions of emotion were often preceded by subtle patient initiatives. Students encouraged further elaboration by displaying their understanding of the emotional issue as a story telling still in progress. Students' expressions of understanding however, gave little room for further elaboration. Finally, students often addressed emotional issues as a medical issue and offered professional advice. Students' actions seemed specifically designed to display interest in the patients' initiatives to talk about emotional experiences without departing from their initial interview task or violating norms for professional conduct. Educators and practitioners should reconsider how the medical interview may shape expectations for professional conduct and can thereby unintentionally restrict students' empathy development.


Intracranial hypertension secondary to a skull lesion without mass effect.
We report and discuss five patients with intracranial hypertension due to a skull lesion reducing cerebral sinus patency with a compressive, non-thrombotic mechanism. We illustrate the importance of a high level of suspicion for this condition in patients presenting with headache, papilledema and increased intracranial pressure in the absence of focal signs or radiological evidence of mass effect.


Adolescent and Young Adult Preventive Care: Comparing National Survey Rates.
The Affordable Care Act's preventive healthcare provisions have the potential to increase adolescents' and young adults' receipt of recommended preventive services. Assessing whether this potential is realized requires valid monitoring data in several areas, including receipt of an annual preventive visit. The purpose of this study is to describe and compare preventive visit rates across national surveys for adolescents and young adults. This study, conducted in 2014: (1) identified national surveys with past-year preventive visit measures; (2) compared survey features, including mode of administration, respondent, response rate, demographic profile (univariate analysis), preventive visit measure wording, and method of construction; and (3) compared preventive visit rates, including rates among sociodemographic subgroups (bivariate analyses). Four 2011 surveys were identified: National Health Interview Survey, National Survey of Children's Health (2011-2012), and Medical Expenditure Panel Survey (MEPS) for adolescents, and MEPS and Behavioral Risk Factor Surveillance System for young adults. Surveys varied by most assessed features; demographic profiles were similar. Preventive visit rates varied significantly across adolescents (43%-81%) and young adults (26%-58%). The largest differences in visit rates were in comparisons of subjective assessments to a more detailed assessment coded from specific records of visits kept by respondents. Sociodemographic differences in visit rates were consistent across surveys. Further research is needed to assess reasons for the different estimates of preventive visits across national surveys. Those who monitor trends in receipt of recommended care for adolescents and young adults should take survey differences into account. Monitoring content of care is also needed.


Visual acuity development in normal and abnormal preterm human infants.
The grating acuity of preterm infants was determined by measurements of the visual evoked potential (VEP) produced by phase alternation of sinusoidal luminance gratings. The development of visual acuity in healthy preterm infants appears to be accelerated when compared with full term infants of the same post-conceptual age. Cortical insults and the more advanced stages of retinopathy of prematurity may adversely affect acuity development as indexed by the VEP. Preterm twins also appear to have lower acuity than preterm monoparous infants.


Racial differences in melanoma incidence.
The incidences of malignant melanoma recorded by 59 population-based cancer registries were investigated to determine the effects of racial and skin-colour differences. White populations exhibited a wide range of melanoma incidences and females commonly, though not invariably, had a higher incidence than males. Non-white populations experienced in general a much lower incidence of melanoma although there was some overlap of white and non-white rates. No predominant sex difference emerged among non-whites. Populations of African descent were found to have a higher incidence than those of Asiatic origin, but it was concluded that this was due largely to the high frequency of tumours among Africans on the sole of the foot. A clear negative correlation between degree of skin pigmentation and melanoma incidence emerged for the exposed body sites. These data provide strong support for the hypotheses that UV radiation is a major cause of malignant melanoma and that melanin pigmentation protects against it. Further research is required to elucidate the aetiology of melanoma of the sole of the foot.


Gremlin: a novel mediator of epithelial mesenchymal transition and fibrosis in chronic allograft nephropathy.
Chronic allograft nephropathy (CAN) is the most frequent cause of chronic dysfunction and late loss of renal allografts. Epithelial mesenchymal transition (EMT) has been identified as responsible for the presence of activated interstitial fibroblasts (myofibroblasts) and transforming growth factor beta (TGF-beta)/Smad is the key signaling mediator. It has been proposed that the bone morphogenetic protein 7 (BMP-7) antagonist, Gremlin, could participate in EMT, as a downstream mediator of TGF-beta. We evaluated 33 renal allograft biopsies, 16 of which showed CAN, versus 17 controls. By in situ hybridization we studied the expression of TGF-beta and Gremlin mRNA. Gremlin, BMP-7, E-cadherin, and alpha-smooth muscle actin (alpha-SMA) proteins were evaluated by immunohistochemistry and Smad3 activation by Southwestern. In cultured human tubuloepithelial cells (HK2 cell line), Gremlin induction by TGF-beta was studied by confocal microscopy. Among renal biopsies of transplanted patients with CAN, we detected up-regulation of TGF-beta in colocalization with Gremlin (RNA and protein), mainly in areas of tubulointerstitial fibrosis. In the same tubules, we observed decreased expression of E-cadherin and induction of vimentin and alpha-SMA. BMP-7 was significantly decreased in the CAN biopsies. In addition, HK2 stimulated with TGF-beta (1 ng/mL) induced Gremlin production at 72 hours. We postulated that Gremlin is a downstream mediator of TGF-beta, suggesting a role for Gremlin in EMT observed in CAN.


Time and energy constraints on the brood size of swallows, Hirundo rustica, and sand martins, Riparia riparia.
The daily energy requirements of swallow Hirundo rustica and sand martin Riparia riparia adults with broods of different sizes were compared with the energy (food) gain rates of adults. Energy requirements of broods were obtained from food delivery rates, growth rates and from published data. The energy requirements of adults were obtained from D2O18 measurements and from time budgets. Energy gain rates were measured from food delivery rates to collared nestlings. These energy gain rates were reduced in bad weather when food abundance was low. In good weather, energy gain rates were theoretically high enough to supply the energy needs of larger than normal broods. In bad weather, however, the adults would only be able to collect sufficient energy for a normal brood of four to six. I suggest that this effect of weather and feeding conditions on energy gain rates and, hence, on reproductive effort is an important factor in limiting the upper level of brood size in these species.


[Immunohistochemical markers for cytoplasmic antigens in acquired melanosis, malignant melanomas, and nevi of the conjunctiva].
Benign and malignant melanocytic lesions of the conjunctiva are difficult to differentiate histologically. At present in the ophthalmologic literature there is not known a high specific and simply applicable histological feature (tumor marker) of differentiation to identify melanocytic lesions of the conjunctiva. In this study 55 nevi, 15 primary acquired melanoses (stage Ia) and 54 melanomas of the conjunctiva were examined retrospectively immunhistochemically by antibodies vs. S-100 protein, and the melanoma-associated antigens HMB-45 and NKI/C3 using the labelled avidin-biotin method. 45 patients (25 female, 20 male) with malignant melanomas of the conjunctiva have been followed up clinically. S-100, HMB-45 and NKI/C3 are highly significant markers to identify malignant melanomas of the conjunctiva (sensitivity: S-100: 96.4%, HMB-45: 96.3%, NKI/C3: 98.1%), whereas markers in acquired melanoses (sensitivity: 93.3%, 78.6% and 92.9%), and nevi (sensitivity: 92.9% 40.7%, 98.2%) are not. Positive tumor markers do not correlate with local recurrences or metastasis. The localization of malignant melanomas and the lymphocytic infiltration are not prognostically significant. The only significant risk factor (p = 0.0485) predicting the development of recurrence or metastasis is tumor thickness > 1.5 mm. The tumor markers S-100, HMB-45 and NKI/C3 cannot differentiate reliably between benign and malignant melanocytic lesions of the conjunctiva, and positive tumor markers do not correlate with local recurrences or metastasis. The only significant risk factor (p = 0.0485) predicting the development of metastasis is tumor thickness (> 1.5 mm).


NR2 antibody is associated with quality of life in aortic valve replacement.
The relationship between the potential brain injury biomarker N-methyl-D-aspartate receptor antibody and quality of life has never been assessed. We measured serum N-methyl-D-aspartate receptor antibody levels preoperatively in patients undergoing aortic valve replacement. Quality of life was scored using the Short Form-36 and European Quality of Life 5-Dimensions questionnaires pre- and postoperatively. We analyzed the antibody levels as a continuous variable and as a dichotomous variable with 1.8 ng mL(-1) as the cutoff. Fifty-two patients (15 females) with a mean age of 71 ± 8.4 years were recruited for this study. Forty-eight (92%) patients attended the follow-up visit (405 ± 161 days). No mortality or severe neurological event was recorded. In both quality-of-life instruments, the low antibody level group (n = 35) had significantly better scores than the high antibody level group (n = 17) preoperatively. Postoperatively, the scores for both groups improved; however, the low antibody level group continued to score significantly better in most of the physical and mental health domains (p = 0.04 to <0.001). Multiple regression analyses revealed that antibody level and the 1.8 ng mL(-1) cutoff were independently related to quality of life (pre- and postoperatively). Higher N-methyl-D-aspartate receptor antibody levels in aortic valve replacement patients are independently related to poorer quality of life pre- and postoperatively.


Parallel imaging reconstruction using automatic regularization.
Increased spatiotemporal resolution in MRI can be achieved by the use of parallel acquisition strategies, which simultaneously sample reduced k-space data using the information from multiple receivers to reconstruct full-FOV images. The price for the increased spatiotemporal resolution in parallel MRI is the degradation of the signal-to-noise ratio (SNR) in the final reconstructed images. Part of the SNR reduction results when the spatially correlated nature of the information from the multiple receivers destabilizes the matrix inversion used in the reconstruction of the full-FOV image. In this work, a reconstruction algorithm based on Tikhonov regularization is presented that reduces the SNR loss due to geometric correlations in the spatial information from the array coil elements. Reference scans are utilized as a priori information about the final reconstructed image to provide regularized estimates for the reconstruction using the L-curve technique. This automatic regularization method reduces the average g-factors in phantom images from a two-channel array from 1.47 to 0.80 in twofold sensitivity encoding (SENSE) acceleration. In vivo anatomical images from an eight-channel system show an averaged g-factor reduction of 1.22 to 0.84 in 2.67-fold acceleration.


Radiation management of primary carcinoma of the vagina.
This 15-year retrospective study includes 71 patients with diagnosis of primary carcinoma of the vagina treated at the University of Maryland Hospital, Radiation Therapy section from 1957 to 1970. The lesions were staged according to the system advocated by International Federation of Gynecology and Obstetrics (FIGO) with a minor modification (Perez et al.11). With the exception of Stage O, histologic diagnosis was 94% (60/64) invasive squamous cell carcinoma and 6.0% (4/64) adenocarcinoma. Of 71 cases who are eligible for a minimum five-year follow-up, the absolute five-year cure rate for various clinical stages is as follows: Stage O 100% (7/7), Stage 1 83.2% (5/6), Stage 11A 65% (13/20), Stage 11B 63.5% (7/11), Stage 111 40% (8/20), Stage IV 0% (0/7). The overall absolute five-year cure-rate for all stages combined was 56.3% (40/71). A comparable result and even better in some stages (II and III) as compared to several previous reports are thought to be due to the proper intergrated irradiation combining interstitial and intracavitary radium with external super-voltage beam. Furthermore, an aggressive radium implant to the vagina, paracolpium, and specifically to parametrium and pelvic wall in Stage II and III appears to be one of the keys to our good results. The technique of treatment, stage by stage, are being fully discussed along with a few complications and failures.


Transferring a naso-gallbladder drainage tube to the mouth for re-examination of a gallbladder lesion.
Conventional gallbladder re-intervention along the naso-gallbladder drainage tube may result in dislocation of the tube during scope insertion or failure of guidewire insertion into the gallbladder. Mandai et al report a simple method for transferring a transpapillary naso-gallbladder drainage tube to the mouth that facilitates reliable re-intervention for gallbladder lesions.


Interactions of the serotonin and circadian systems: nature and nurture in rhythms and blues.
The serotonin and circadian systems are principal regulatory networks of the brain. Each consists of a unique set of neurons that make widespread neural connections and a defined gene network of transcriptional regulators and signaling genes that subserve serotonergic and circadian function at the genetic level. These master regulatory networks of the brain are extensively intertwined, with reciprocal circuit connections, expression of key genetic elements for serotonin signaling in clock neurons and expression of key clock genes in serotonergic neurons. The reciprocal connections of the serotonin and circadian systems likely have importance for neurobehavioral disorders, as suggested by their convergent contribution to a similar range of mood disorders including seasonal affective disorder (SAD), bipolar disorder, and major depression, and as suggested by their overlapping relationship with the developmental disorder, autism spectrum disorder. Here we review the neuroanatomical and genetic basis for serotonin-circadian interactions in the brain, their potential relationship with neurobehavioral disorders, and recent work examining the effects on the circadian system of genetic perturbation of the serotonergic system as well as the molecular and behavioral effects of developmental imprinting of the circadian system with perinatal seasonal light cycles.


Should gamete donors be tested for spinal muscular atrophy?
To report two cases of spinal muscular atrophy (SMA) after artificial insemination and to discuss why genetic screening of the disease may be justified in gamete donors. Case report. Academic departments of genetics and obstetrics. A 32-year-old woman with two successive assisted pregnancies. Molecular studies of the SMN1 (survival motor neuron), the determining gene of the disease. MAIN OUTCOME MEASURE(S); Prenatal testing to detect a homozygous deletion of the SMN1 gene; carrier diagnosis by quantitative analysis to detect a single or double dose of exon 7 in the SMN1 gene. After a first assisted pregnancy, an SMA child with a homozygous deletion of the SMN1 gene was born. In the second assisted pregnancy, using sperm from a different donor, a fetus with a homozygous deletion of SMN1 was detected. Carrier status in the donor was confirmed by a single dose of SMN1 in the quantitative analysis. Genetic screening of SMA carrier status by quantitative analysis of the SMN1 gene should be performed in gamete donors when the recipient is a known carrier. Cost-benefit analysis should be made to consider the inclusion of the test in prospective gamete donor programs.


Current uses of ultrasound in the evaluation of the breast.
Ultrasound is an important imaging modality in evaluating the breast. One of the most common uses of ultrasound is to help distinguish benign from malignant breast disease, primarily with gray-scale ultrasound but also with Doppler ultrasound. Another common use is to provide guidance for interventional procedures. Less common uses include assisting in staging of breast cancer and evaluating patients with implants. Recently there has been an interest in using ultrasound to screen asymptomatic women for breast cancer, as is done with mammography. Further studies must be performed to assess if this reduces mortality from breast cancer. Although primarily used to image the female breast, ultrasound also can be used to evaluate breast-related concerns in men. Uses of contrast-enhanced ultrasound are still experimental and would add an invasive component to an otherwise noninvasive study.


Histological findings, genotype distribution and percentage of patients fulfilling the treatment criteria among patients with chronic hepatitis C virus infection in a single Swedish centre.
Genotype distribution of chronic hepatitis C in Sweden has shown a predominance of genotype non-1. With recent improvements in therapy, genotypes 2 and 3 infections can, according to consensus, be treated without histological assessment. The aim of this study was to evaluate the genotype distribution, histological stage and grade, and the percentage of patients fulfilling the histological treatment criteria. A total of 323 patients with chronic hepatitis C were tested for genotype, histological findings and the percentage fulfilling the histological treatment criteria as stated by Swedish consensus; i.e. having fibrosis stage II or more, or fibrosis stage I with inflammation grade II or more. The patients had a mean age of 45 years (range 16-71 years) and 62% were males. Genotypes were determined in 79% of patients and genotype 2b or 3a was found to predominate, comprising 56%. Former intravenous drug use was found to be the predominant mode of acquisition, noted in 60%. The mean disease duration was 21 years (range 3-40) after which time 14% of patients had developed cirrhosis (stage IV). In the total material, 77% fulfilled the histological treatment criteria, 76% and 86%, respectively, among genotype I and genotype non-1 (2b and 3a) patients. Genotype non-1 (2b or 3a) predominated among Swedish patients, 14% of whom developed cirrhosis after a mean follow-up time of 21 years. Furthermore, an absolute majority fulfilled the histological criteria used to judge patients' eligibility for antiviral therapy, supporting the recent Swedish consensus decision to treat genotypes 2 and 3 infected patients without a previous biopsy.


Segregating the effects of ferric citrate-mediated iron utilization and FGF23 in a mouse model of CKD.
Ferric citrate (FC) is an approved therapy for chronic kidney disease (CKD) patients as a phosphate (Pi) binder for dialysis-dependent CKD, and for iron deficiency anemia (IDA) in non-dialysis CKD. Elevated Pi and IDA both lead to increased FGF23, however, the roles of iron and FGF23 during CKD remain unclear. To this end, iron and Pi metabolism were tested in a mouse model of CKD (0.2% adenine) ± 0.5% FC for 6 weeks, with and without osteocyte deletion of Fgf23 (flox-Fgf23/Dmp1-Cre). Intact FGF23 (iFGF23) increased in all CKD mice but was lower in Cre+ mice with or without FC, thus the Dmp1-Cre effectively reduced FGF23. Cre+ mice fed AD-only had higher serum Pi than Cre- pre- and post-diet, and the Cre+ mice had higher BUN regardless of FC treatment. Total serum iron was higher in all mice receiving FC, and liver Tfrc, Bmp6, and hepcidin mRNAs were increased regardless of genotype; liver IL-6 showed decreased mRNA in FC-fed mice. The renal 1,25-dihydroxyvitamin D (1,25D) anabolic enzyme Cyp27b1 had higher mRNA and the catabolic Cyp24a1 showed lower mRNA in FC-fed mice. Finally, mice with loss of FGF23 had higher bone cortical porosity, whereas Raman spectroscopy showed no changes in matrix mineral parameters. Thus, FC- and FGF23-dependent and -independent actions were identified in CKD; loss of FGF23 was associated with higher serum Pi and BUN, demonstrating that FGF23 was protective of mineral metabolism. In contrast, FC maintained serum iron and corrected inflammation mediators, potentially providing ancillary benefit.


Analgesic efficacy of etoricoxib in primary dysmenorrhea: results of a randomized, controlled trial.
To determine the efficacy of etoricoxib in the treatment of primary dysmenorrhea. Seventy-three women were randomly assigned to receive single oral doses of etoricoxib 120 mg, placebo, or naproxen sodium 550 mg at the onset of moderate to severe pain associated with menses. During 3 consecutive menstrual cycles in this double-blind, 3-period, crossover study, pain intensity and pain relief were assessed over the 24-hour period following dosing, and global ratings of therapy were made at 8 and 24 h after dosing. Tolerability was assessed by spontaneous reports of adverse experiences. Etoricoxib 120 mg provided analgesic efficacy superior to placebo for the primary endpoint, total pain relief over 8 h (TOPAR8, p<0.001), and for all secondary endpoints (p<0.050). The analgesic effect of etoricoxib 120 mg over the first 8 h was similar to that of naproxen sodium 550 mg. All treatments were well tolerated. Etoricoxib 120 mg provided rapid and sustained analgesia that was superior to placebo and similar to that of naproxen sodium 550 mg.


Germinal peptide eye drops promote corneal wound healing and decrease inflammation after alkali injury.
Germinal peptide is being developed to treat corneal injuries. The purpose of this study was to investigate its effect on corneal epithelial cells in vitro and its ability to promote healing in an alkali injury model in vivo. Cultured rabbit corneal epithelial cells were treated with germinal peptide at three concentrations. Cell proliferation and migration were assessed and compared with the effect of recombinant human epidermal growth factor (rh-EGF). In vivo, the corneas of New Zealand albino rabbits were chemically burned with 1 mol/l NaOH for 30 s. The injured eyes were topically treated with germinal peptide (10, 20, and 40 μg/ml), rh-EGF, or phosphate-buffered saline thrice daily. At fixed time points post injury, the healing of the cornea and its histopathology were evaluated. There was no difference in the effect of germinal peptide on cultured cell proliferation. However, cell migration was significantly higher than that in the control groups, with germinal peptide at concentrations of 20 and 40 μg/ml being the most efficacious. In vivo, 20 and 40 μg/ml germinal peptide significantly alleviated corneal opacity and edema. By day 21, the areas of corneal neovascularization in the germinal peptide-treated groups were smaller than those in the rh-EGF and control groups. The repaired corneas in the germinal peptide- and rh-EGF-treated groups also had more corneal epithelial layers and fewer inflammatory cells than the controls. Germinal peptide may be developed as a novel topical treatment agent for corneal wound healing in clinical settings.


An alternative phototherapy light combination.
Combinations of fluorescent lamps for phototherapy were evaluated in order to select one that maximizes blue light content (400 to 500 nanometers) for most effective photodegradation of bilirubin, maintains acceptable color balance for observing infant skin color, and requires minimal lamp replacement for low maintenance cost. The combination that best achieves these objectives consists of four special blue (Westinghouse F20T12-BB) and four broad spectrum (Verd-A-Ray F20T12-CC) lamps that produce blue radiation in excess of an array of eight conventional blue lamps, a spectrum closely approximating that of natural light, and at least 80% of the original blue radiation after 2,100 hours of use.


Production and characterization of monoclonal antibodies against the H-Y antigen.
Monoclonal antibodies against the H-Y antigen were produced using spleen cells from female C57BL/6 mice hyperimmunized with cells from syngeneic males. Anti-H-Y positive clones were detected by enzyme immunoassays. Supernatant fluids from Daudi cell cultures and testicular cell preparations taken from mice, rabbits or calves served as presumptive sources of H-Y antigen. In addition, testis supernatant from genetically sterile mice was used. Male specificity was ascertained by the fact that the antibodies could be absorbed with spleen cells from male but not from female mice. Binding of the antibodies to H-Y antigen on the surface of male and female cells, obtained from a number of tissues and species, was confirmed by an indirect immunofluorescence assay. Several monoclonal antibodies appeared to be positive in all assays tested, suggesting that the molecule conferring the H-Y antigenicity lacks species-specificity and appears to be identical for soluble and membrane-bound H-Y antigen.


Prognostic Significance of Percutaneous Coronary Intervention for First Acute Myocardial Infarction with Heart Failure: Five-Year Follow-Up Results.
The study aimed to investigate the incidence and influencing factors of heart failure after 5 years of percutaneous coronary intervention (PCI) for first acute myocardial infarction. A total of 1235 patients, diagnosed as acute myocardial infarction and treated with PCI in Beijing Anzhen Hospital, Capital Medical University, from January 1, 2014, to December 31, 2014, were enrolled. Based on the exclusion criteria, 671 patients were followed up to obtain echocardiographic results 5 years after the onset of myocardial infarction (from January 1, 2019, to December 31, 2019). Of 671 patients, 62 were lost to follow-up. Finally, 609 patients were recruited in this study. According to the results of the echocardiographic examination, patients were divided into a heart failure group (n = 97) (LVEF < 50%) and a nonheart failure group (n = 512) (LVEF ≥ 50%). The clinical characteristics were compared between the two groups, and the influencing factors of heart failure after 5 years of PCI in patients with acute myocardial infarction were analyzed using logistic regression and receiver-operating characteristic (ROC) analyses. Of 609 patients, 97 had heart failure within 5 years after PCI for first myocardial infarction, with an incidence of 15.9%. Multivariate regression analysis finally examined the predictors related to the occurrence of heart failure, including age (aOR, 1.008; 95% confidence interval (CI), 1.054-1.123; P ≤ 0.001), peak troponin I level (aOR, 1.020; 95% CI, 1.006-1.034; P = 0.004), left ventricular ejection fraction (LVEF) (during admission) (aOR, 0.908; 95% CI, 0.862-0.956; P ≤ 0.001), and left ventricular end-diastolic dimension (LVEDD) (at admission) (aOR, 1.136; 95% CI, 1.016-1.271; P = 0.025). In this study, the incidence of heart failure (LVEF < 50%) in patients with acute myocardial infarction who underwent PCI was 15.9% at a five-year follow up. Age, peak troponin I level, and LVEDD (at admission) were risk factors for heart failure, while LVEF (at admission) of patients during hospitalization was a protective factor for heart failure.


Respiration-Averaged CT for Attenuation Correction of PET Images - Impact on PET Texture Features in Non-Small Cell Lung Cancer Patients.
We compared attenuation correction of PET images with helical CT (PET/HCT) and respiration-averaged CT (PET/ACT) in patients with non-small-cell lung cancer (NSCLC) with the goal of investigating the impact of respiration-averaged CT on 18F FDG PET texture parameters. A total of 56 patients were enrolled. Tumors were segmented on pretreatment PET images using the adaptive threshold. Twelve different texture parameters were computed: standard uptake value (SUV) entropy, uniformity, entropy, dissimilarity, homogeneity, coarseness, busyness, contrast, complexity, grey-level nonuniformity, zone-size nonuniformity, and high grey-level large zone emphasis. Comparisons of PET/HCT and PET/ACT were performed using Wilcoxon signed-rank tests, intraclass correlation coefficients, and Bland-Altman analysis. Receiver operating characteristic (ROC) curves as well as univariate and multivariate Cox regression analyses were used to identify the parameters significantly associated with disease-specific survival (DSS). A fixed threshold at 45% of the maximum SUV (T45) was used for validation. SUV maximum and total lesion glycolysis (TLG) were significantly higher in PET/ACT. However, texture parameters obtained with PET/ACT and PET/HCT showed a high degree of agreement. The lowest levels of variation between the two modalities were observed for SUV entropy (9.7%) and entropy (9.8%). SUV entropy, entropy, and coarseness from both PET/ACT and PET/HCT were significantly associated with DSS. Validation analyses using T45 confirmed the usefulness of SUV entropy and entropy in both PET/HCT and PET/ACT for the prediction of DSS, but only coarseness from PET/ACT achieved the statistical significance threshold. Our results indicate that 1) texture parameters from PET/ACT are clinically useful in the prediction of survival in NSCLC patients and 2) SUV entropy and entropy are robust to attenuation correction methods.


Reticulate evolution in the Pteris fauriei group (Pteridaceae).
The Pteris fauriei group (Pteridaceae) has a wide distribution in Eastern Asia and includes 18 species with similar but varied morphology. We collected more than 300 specimens of the P. fauriei group and determined ploidy by flow cytometry and inferred phylogenies by molecular analyses of chloroplast and nuclear DNA markers. Our results reveal a complicated reticulate evolution, consisting of seven parental taxa and 58 hybrids. The large number of hybrid taxa have added significant morphological complexity to the group leading to difficult taxonomic issues. The hybrids generally had broader ranges and more populations than their parental taxa. Genetic combination of different pairs of parental species created divergent phenotypes of hybrids, exhibited by both morphological characteristics and ecological fidelities. Niche novelty could facilitate hybrid speciation. Apogamy is common in this group and potentially contributes to the sustainability of the whole group. We propose that frequent hybridizations among members of the P. fauriei group generate and maintain genetic diversity, via novel genetic combinations, niche differentiation, and apogamy.


William E. Bradley and his contributions to urology.
We review the myriad contributions to urological science by neurologist and engineer, William E. Bradley. Remembrances and personal interviews were collated for this article. Doctor Bradley was a pioneer in neurourology. He described a neurophysiological paradigm for micturition, devised urodynamic and electrophysiological techniques, and contributed to the development of genitourinary prosthetic devices. Doctor Bradley made notable and groundbreaking contributions to urology, many of which are still in use today.


Single-nucleotide polymorphism and mutation identification by the nanogen microelectronic chip technology.
The present chapter describes a microarray technology developed by Nanogen Inc., for the identification of DNA variations based on the use of microelectronics. The NMW 1000 NanoChip Molecular Biology Workstation allows the active deposition and concentration of charged biotinylated molecules on designated test sites. The DNA at each pad is then hybridized with specific oligonucleotide probes, complementary to normal or mutant sequences, that labeled with Cy3 or Cy5 dyes, respectively. The array is imaged, and fluorescence signals are scanned, monitored, and quantified by highly developed, digital image-processing procedures. The experimental steps to be performed for the development and execution of a microchip assay are described. Attention is focused on the fundamental aspects of probe design, and guidelines and useful suggestions are given. Protocols for sample preparation, addressing, reporting, and data analysis are also detailed.


Untargeted and targeted LC-MS and data processing workflow for the comprehensive analysis of oligopeptides from cyanobacteria.
Cyanobacteria produce a plethora of structurally diverse bioactive secondary metabolites, including cyanotoxins which pose a serious threat to humans and other living organisms worldwide. Currently, a wide variety of mass spectrometry-based methods for determination of microcystins (MCs), the most commonly occurring and studied class of cyanotoxins, have been developed and employed for research and monitoring purposes. The scarcity of commercially available reference materials, together with the ever-growing range of mass spectrometers and analytical approaches, make the accuracy of quantitative analyses a critical point to be carefully investigated in view of a reliable risk evaluation. This study reports, a comparative investigation of the qualitative and quantitative MCs profile obtained using targeted and untargeted liquid chromatography-mass spectrometry approaches for the analyses of cyanobacterial biomass from Lake Kastoria, Greece. Comparison of the total MCs content measured by the two approaches showed good correlation, with variations in the range of 3.8-13.2%. In addition, the implementation of an analytical workflow on a hybrid linear ion trap/orbitrap mass spectrometer is described, based on combining data-dependent acquisition and a powerful database of cyanobacterial metabolites (CyanoMetDB) for the annotation of known and discovery of new cyanopeptides. This untargeted strategy proved highly effective for the identification of MCs, microginins, anabaenopeptins, and micropeptins. The systematic interpretation of the acquired fragmentation patterns allowed the elucidation of two new MC structural variants, MC-PrhcysR and MC-Prhcys(O)R, and proposal of structures for two new microginins, isomeric cyanostatin B and MG 821A, and three isomeric micropeptins at m/z 846.4715, 846.4711 and 846.4723.


Estrogen-mediated induction of a vitellogenin-specific nonhistone chromatin protein in the male chicken liver.
Non-histone chromatin proteins prepared from the livers of estrogen-treated and nontreated male chickens were compared by reverse-phase high performance liquid chromatography (RP-HPLC), followed by sodium dodecyl-sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The results revealed that the hormone-treated male liver chromatin contained a specific protein corresponding to the vitellogenin-specific protein previously purified from the liver of egg-laying hens (Nakayama 1985). The chicken protein, purified further by gel-filtration high performance liquid chromatography (GF-HPLC), showed specific binding activity to DNA fragments carrying a part of the vitellogenin gene. On the basis of similarities in the elution patterns from GF-HPLC and RP-HPLC as well as in the mobility on SDS-PAGE, we concluded that this hormone-induced protein in the male chicken liver was identical to the vitellogenin-specific protein identified in the hen liver, and assumed it to be a specific regulatory protein for the vitellogenin gene expression. The amino acid composition of this chicken protein has been determined.


Advances in approaches to DNA-based diagnostics.
The most tangible advances in DNA diagnostics during the past year have been in enhancing existing techniques to simplify their use and improve throughput. This has led to simplified genotyping methods using homogeneous analysis coupled with spectral data output. Miniaturisation and increased throughput have also been achieved through improvements in DNA chip technology.


Receptive field types of area 18 neurones in the cat.
In cats, 131 area 18 units with receptive fields 10-50 degrees from the visual axis, were recorded and tested with moving stimuli. These stimuli included light slits, dark bars, single edges, gratings and a random square pattern. 94% of the units were responsive to visual motion. 106 neurones could be classified by a screening procedure based on responses to a moving standard grating and a moving random square pattern. When testing with moving stimuli, the criteria for distinguishing between simple and complex cells in area 17 (Pettigrew et al., 1968; Bishopel al., 1971a,b, 1973 Goodwin and Henry, 1975, Sherman et al., 1976) also apply to area 18 neurones. No tests with stationary stimuli were made in distinguishing simple from complex cells. In addition to simple (50%) and complex (18%) cells, area 18 contains other cell types as hypercomplex cells (11%), cells with a radially symmetric RF (6%) and amplitude specific cells (10%). Six cells (5%) were unclassified. A special battery of tests was designed to study the RF of the very sophisticated amplitude specific cells. Their RF appears to consist of a discharge region preceded by a trigger area and of two flanking inhibitory regions.


The signal intensity ratio of the optic nerve to ipsilateral frontal white matter is of value in the diagnosis of acute optic neuritis.
To evaluate the usefulness of the signal intensity ratio (SIR) of the optic nerve to the white matter (WM) on short tau inversion recovery (STIR) images to diagnose acute optic neuritis (AON). The 405 consecutive patients with suspected orbital diseases underwent orbital magnetic resonance imaging (MRI) using a 3-T scanner between June 2008 and August 2011. Among them, 108 optic nerves (33 AON and 75 control) were retrospectively analysed. The averaged SIR (SIRave) and maximum SIR (SIRmax) were defined as the averaged signal intensity (SI) of the optic nerve divided by that of WM, and the maximum SI of the optic nerve divided by averaged SI of WM, respectively. These values were compared between AON and control using the Mann-Whitney U test. A P < 0.05 was considered statistically significant. SIRave and SIRmax were significantly (P < 0.001) higher in the AON compared to the control. At a cut-off SIRave value of 1.119, the sensitivity, specificity and accuracy were 0.939, 0.840, and 0.870; and at a cut-off SIRmax value of 1.281, these were 1.000, 0.720 and 0.806, respectively. The SIR of the optic nerve to WM on STIR images is of value in diagnosing AON. • We propose a method of diagnosing acute optic neuritis using 3-T MRI. • Our method is simple and objective and requires no novel imaging techniques. • Our method shows high diagnostic accuracy.


Evaluation of a Dog Population Management Intervention: Measuring Indicators of Impact.
Dogs are important companions to people but can also present challenges to health and safety of communities if their populations are not effectively managed. Dog population management (DPM) is often undertaken by individual dog owners; however, some communities require additional DPM interventions, especially when veterinary services are unavailable or underutilised. This study evaluated the effectiveness of a DPM intervention conducted in 13 communities between September 2016 and November 2019 and assessed the utility of routinely collected data-program metrics and secondary data collected by local governments-to measure indicators of impacts. The intervention resulted in significant increases in the proportion of dogs presenting that were microchipped and surgically sterilised in participating communities. The intervention also resulted in significant reductions in dog attack incidents and euthanasia of dogs in council pounds in communities that participated for three or more years. Ongoing monitoring and evaluation of DPM interventions is critical to determine if impacts are being achieved. This study demonstrates the potential benefits of a DPM intervention for community safety and dog welfare and highlights the utility of routinely collected data. We also suggest benchmarks for indicators of community engagement to guide planning and monitoring of similar interventions.


The dendrites of single brain-stem motoneurons intracellularly labelled with horseradish peroxidase in the cat. An ultrastructural analysis of the synaptic covering and the microenvironment.
Two laryngeal motoneurons intracellularly stained with horseradish peroxidase were studied ultrastructurally. The precise position of the ultrastructural observations made along the dendrites was obtained from the computer-reconstruction of the motoneurons in three dimensions. The shape and the size of the synaptic boutons, the percentage of membrane covered by bouton appositions and active zones, the number of boutons per 100 microns2 (packing density) were analysed on the soma and on the labelled dendrites at different distances from the soma up to 1000 microns. The results revealed no important regional differences in the mean length of synaptic apposition. The packing density was in the range of 9.3-14.9 boutons per 100 microns2 and was not correlated with the distance from the soma. The percentage apposition covering was higher on the soma and the proximal part of the dendrites than on the remaining part of the dendritic arborization. Close appositions between labelled dendrite and unlabelled somata and/or dendrites together with dendro-dendritic synapses suggested the possibility that the dendrites may be involved in local cell-to-cell communication. Microdendrites emerging from the soma or the proximal dendrites were contacted by synaptic boutons which may be more efficient as revealed by computation.


Comprehensive clinical evaluation of TomoEQA for patient-specific pre-treatment quality assurance in helical tomotherapy.
Based on a previous study on the feasibility of TomoEQA, an exit detector-based patient-specific pre-treatment quality assurance (QA) method for helical tomotherapy, an in-depth clinical evaluation was conducted. Data of one hundred patients were analyzed to evaluate the clinical usefulness of TomoEQA for patient-specific pre-treatment QA in comparison with the conventional phantom-based method. Additional investigations were also performed under unusual measurement conditions to validate the off-axis region. In addition to the clinical evaluation of TomoEQA, a statistical analysis was conducted to determine the plan parameters that affect the pass/failure results of pre-treatment QA. The average and standard deviations of the gamma passing rate and point dose error for TomoEQA were comparable to those of the conventional QA method. For TomoEQA, the average values of the gamma passing rate and point dose error were 96.32% (standard deviation (1 sigma) = 3.94; 95% confidence interval (CI), 95.55 to 97.09) and - 1.12% (standard deviation (1 sigma) = 1.04; CI, - 1.32 to - 0.92), respectively. For the conventional QA method, the average values of the gamma passing rate and point dose error were 95.95% (standard deviation (1 sigma) = 4.35; 95% confidence interval (CI), 95.10 to 96.80) and - 1.20% (standard deviation (1 sigma) = 1.61; CI, - 1.52 to - 0.88), respectively. Further experiments on the off-axis region demonstrated that TomoEQA can provide accurate results for 3D dose analysis, which is inherently difficult in the conventional QA method. Through a statistical analysis based on the results of TomoEQA, it was validated that the total fraction (Total Fx), monitor units, beam-on-time, leaf-of-time below 100 ms, and planning target volume diameter were statistically significant for the pass/failure of the pre-treatment QA results. TomoEQA is a clinically beneficial alternative to the conventional phantom-based QA method.


Advanced chronic kidney disease is associated with higher serum concentration of monocyte microparticles.
Advanced chronic kidney disease is associated with high rates of cardiovascular disease. Considering the crucial role of capillaries in renal function, our study aimed to evaluate microparticles related to vascular physiology examining the link between stages of chronic kidney disease with circulating endothelial (EMP), platelet (PMP) and monocytic (MMP) microparticles. Cross-sectional study with blinded endpoints included subjects of both sexes, aged 40-75 years (n = 247), with established cardiovascular disease (coronary heart disease, ischemic stroke, or peripheral artery disease). They were stratified 1:1 by the presence or absence of decreased glomerular filtration rate (GFR < 60 mL/min/1.73 m2) estimated by the CKD-EPI criteria, and according to the stages of CKD. Microparticles were quantified by flow-cytometry using specific antibodies to identify endothelial, platelet, and monocytic derived microparticles. Higher percentages of circulating MMP (p = 0.036), but not for EMP or PMP, were observed in subjects with reduced GFR. Circulating MMP were also related to the stages of chronic kidney disease (trend analysis across renal stages, p = 0.038). Higher percentages of circulating MMP were found in subjects with reduced GFR, and their percentages were progressively higher according to the stage of chronic renal function.


Transcriptome sequencing of maraena whitefish (Coregonus maraena).
Maraena whitefish (Coregonus maraena, Bloch, 1779) is a high-quality food fish belonging to the family Salmonidae with considerable economic relevance in the Baltic area. Aquaculture of this species is fundamental for its successful conservation and thus sustainable fisheries. Robust fishes obtained from breeding lines build the basis for effective aquaculture. Doubtless, the utilization of transcriptome sequencing and identification of genetic markers contribute to this aim. 454 FLX Titanium Sequencing provided 1.31 million sequence reads representing a first insight into the C. maraena transcriptome. The 454 Newbler Assembly arranged 29,094 contigs with an average length of 798bp. We found a whole series of transcripts highly probably resulting from ancient genome duplication and annotated 2887 different transcripts with an average length of 812bp. Functional annotation obtained a transcript composition predominantly comprising enzyme-coding genes.


Factors influencing the sequelae of high tension electrical injuries.
The purpose of this study was to conduct a retrospective analysis of the clinical spectrum, treatment and morbidity of the patients who have suffered high tension electrical injuries with current passage through their body (59 patients). Voltage, localization and surgical treatment seem to be the main factors influencing the lesion and the morbidity. The following points were considered: (1) Is there any relation between known factors such as voltage and the localization of the points of contact with the incidence and the type of complications and sequelae? (2) Do the observations show that wound management and the excision of dead tissues is the most adequate? From factors studied in our patients (voltage, point of entry and pathway of current, associated multiple trauma or flame burns, surgical treatment) we have found that the voltage does not have any influence on the severity of the wound nor on the percentage of sequelae (cataracts, limb amputation, neurologic complications). The current pathway, as well as its points of entry, does not show any relation with the presence of renal failure, cardiac arrhythmia and cataracts. A clear relationship between the point of entry of the current and the appearance of neurologic injury with presence of paralysis and permanent regional anaesthesia at the same level was observed. The presence of associated burns was not related to any other complications or sequelae. For those patients whose length of contact has been shorter we find a lower rate of amputations despite having associated limb fractures. Fasciotomy incisions appear to confer benefit as this series shows that this procedure decreases the rate of limb amputations.


Optimum design of a grazing-incidence flat-field spectrograph with a spherical varied-line-space grating.
A grazing-incidence spectrograph is designed by use of the flat-field image-focusing property of a spherical varied-line-space grating. Optimum grating parameters for mechanical ruling are selected by application of genetic algorithms. Two gratings, one for 2-5-nm and the other for 5-20-nm spectral regions, are designed, and their fabrication tolerances are analyzed.


Identifying Transcripts with Tandem Duplications from RNA-Sequencing Data to Predict BRCA1-Type Primary Breast Cancer.
Patients with cancers that are deficient for homologous recombination repair (HRD) may benefit from PARP inhibitor treatment. Therefore, methods that identify such cancers are crucial. Using whole genome sequencing data, specific genomic scars derived from somatic mutations and genomic rearrangements can identify HRD tumors, with only BRCA1-like HRD cancers profoundly displaying small (<10 kb) tandem duplications (TDs). In this manuscript we describe a method of detecting BRCA1-type HRD in breast cancer (BC) solely from RNA sequencing data by identifying TDs surfacing in transcribed genes. We find that the number of identified TDs (TD-score) is significantly higher in BRCA1-type vs. BRCA2-type BCs, or vs. HR-proficient BCs (p = 2.4 × 10-6 and p = 2.7 × 10-12, respectively). A TD-score ≥2 shows an 88.2% sensitivity (30 out of 34) to detect a BRCA1-type BC, with a specificity of 64.7% (143 out of 221). Pathway enrichment analyses showed genes implicated in cancer to be affected by TDs of which PTEN was found significantly more frequently affected by a TD in BRCA1-type BC. In conclusion, we here describe a novel method to identify TDs in transcripts and classify BRCA1-type BCs with high sensitivity.


Suppression of kindled seizures by paracrine adenosine release from stem cell-derived brain implants.
Stem cells and their derivatives have emerged as a promising tool for cell-based drug delivery because of (a) their unique ability to differentiate into various somatic cell types, (b) the virtually unlimited donor source for transplantation, and (c) the advantage of being amenable to a wide spectrum of genetic manipulations. Previously, adenosine-releasing embryonic stem (ES) cells have been generated by disruption of both alleles of adenosine kinase (Adk-/-). Lack of ADK did not compromise the cells' differentiation potential into embryoid bodies or glial precursor cells. The aim of the present study was to investigate the potential of differentiated Adk-/- ES cell progeny for seizure suppression by paracrine adenosine release. To isolate paracrine effects of stem cell-derived implants from effects caused by network integration, ES cell-derived embryoid bodies and glial precursor cells were encapsulated into semipermeable polymer membranes and grafted into the lateral brain ventricles of kindled rats. While seizure activity in kindled rats with wild-type Adk+/+ implants remained unaltered, rats with adenosine-releasing Adk-/- ES cell-derived implants displayed transient protection from convulsive seizures and a profound reduction of afterdischarge activity in EEG recordings. Long-term seizure suppression was precluded by limited viability of the encapsulated cells. We thereby provide a proof-of-principle that Adk-/- ES cell-derived brain implants can suppress seizure activity by a paracrine mode of action. Adk-deficient stem cells therefore represent a potential tool for the treatment of epileptic disorders.


Preoperative duplex vein mapping (DVM) reduces costs in patients undergoing infrainguinal bypass surgery: results of a prospective randomised study.
Surgical site infections (SSIs) after bypass procedures provoke major costs. The aim of this prospective randomised trial was to assess if preoperative duplex vein mapping (DVM) reduces costs generated by SSI. Patients undergoing primary infrainguinal bypass were randomised to DVM of the ipsilateral greater saphenous vein (group A) or none (group B). Costs were calculated by the hospital's accounting department. From December 2009 to April 2011, 130 patients (65 each group) were enrolled. Both cohorts were equal regarding demographics, risk factors and costs for primary bypass surgery, respectively. SSIs were classified minor (A: n = 13 vs. B: n = 13, P = n.s.) and major (A: n = 1 vs. B: n = 12, P = .0154). Preoperative DVM was the only significant factor to prevent major SSI (P = .011). Theatre costs for SSI: A: 537 € versus B 6553 € (P = .16). Recovery room/intensive care unit (ICU) costs for SSI: A: 0 € versus B: 8016 € (P = .22). Surgical ward costs for SSI: A: 2823 € versus B: 22 386 € (P = .011). Costs for outpatient visits due to SSI: A: 6265 € versus B: 12 831 € (P = .67). Total costs of patients without SSI: 8177 € versus major SSI: 10 963 € (P < .001). DVM significantly reduces costs generated by re-admission in patients suffering from major SSI.


Survival disparities among non-elderly American adults with locally advanced gastric cancer undergoing gastrectomy by health insurance status.
The impact of health insurance status on the survival outcomes of patients with locally advanced gastric cancer (LAGC) receiving gastrectomy have not been addressed in depth. We aim to identify definite associations of health insurance status with cancer-specific survival (CSS) and overall survival (OS) in this population. We identified LAGC patients aged 18 to 64 years undergoing gastrectomy with complete insurance records, between January 1, 2007, and December 31, 2016, from 18 Surveillance, Epidemiology, and End Results database registries. Relationships between health insurance status and OS/CSS were explored by Kaplan-Meier time-to-event analysis and uni-/multi-variate Cox regression. Probable baseline confounder was adjusted by multiple propensity score (mPS)-adjusted analysis. In total, 5,860 patients met the inclusion criteria. In the multivariate Cox regression, Medicaid coverage was related to poorer OS than private insurance. Non-insurance or Medicaid coverage versus private insurance tended to present poorer OS in the mPS-adjusted model, but this result was insignificant for CSS. Our observational study of exposure-outcome associations suggests that limited or no insurance is moderately linked with OS among LAGC patients undergoing gastrectomy and aged 18-64 years. Healthcare accessibility and broad insurance coverage probably strengthen some disparity outcomes.


Consumptive Hypothyroidism due to Hepatic Hemangiomas: A Case Series and Review of the Literature.
Consumptive hypothyroidism (CH) is a rare and potentially overlooked complication of hepatic hemangiomas (HH) overexpressing the enzyme deiodinase, which converts thyroxine (T4) to reverse triiodothyronine (rT3). Here, we report a case series of 3 patients and a systematic review of the literature. Hypothyroidism (mean serum TSH 52.03 mIU/L) was detected at a mean age of 4.6 months (range 3-6) in 3 infants with infantile hepatic hemangiomas, treated with thyroxine (mean dose 12 µg/kg/day). All received treatment with propranolol (1-3 mg/kg/day) from the mean age of 4 months. Hormonal treatment was stopped at a mean age of 20 months (range 12-30). Hypothyroidism reoccurred in a patient concurrently with the increase of liver lesions, requiring liver transplantation (LT) at age 39 months.Literature review retrieved 42 studies (48 patients): HH (n = 43) were isolated in 24 infants and associated with cutaneous hemangiomas in 19. Hemangiomas were only cutaneous in 5.In the first 43 patients, hypothyroidism was detected at a mean age of 1 month; 21 of 43 patients were prescribed propranolol alone (n = 8) or associated with other medicaments (n = 13); 2 of 43 patients underwent LT. Hormonal treatment consisted of T4 in 35 of 43 patients and T3 in 10.CH associated with only cutaneous and extrahepatic visceral hemangiomas (n = 5), detected at a mean age of 7 months (TSH mean levels at diagnosis of 150.3 mIU/L). Three of 5 patients received treatment with propranolol ± other medicaments. All 5 patients were treated with T4. Periodical thyroid function assessment is necessary in patients with hepatic hemangiomas, particularly when lesions' size and number increase rapidly.


Microdevice for plasma separation from whole human blood using bio-physical and geometrical effects.
In this research work, we present a simple and efficient passive microfluidic device for plasma separation from pure blood. The microdevice has been fabricated using conventional photolithography technique on a single layer of polydimethylsiloxane, and has been extensively tested on whole blood and enhanced (upto 62%) hematocrit levels of human blood. The microdevice employs elevated dimensions of about 100 μm; such elevated dimensions ensure clog-free operation of the microdevice and is relatively easy to fabricate. We show that our microdevice achieves almost 100% separation efficiency on undiluted blood in the flow rate range of 0.3 to 0.5 ml/min. Detailed biological characterization of the plasma obtained from the microdevice is carried out by testing: proteins by ultra-violet spectrophotometric method, hCG (human chorionic gonadotropin) hormone, and conducting random blood glucose test. Additionally, flow cytometry study has also been carried on the separated plasma. These tests attest to the high quality of plasma recovered. The microdevice developed in this work is an outcome of extensive experimental research on understanding the flow behavior and separation phenomenon of blood in microchannels. The microdevice is compact, economical and effective, and is particularly suited in continuous flow operations.


Nuclear factor-kappaB inhibition improves myocardial contractility in rats with cirrhotic cardiomyopathy.
Cytokines such as tumour necrosis factor (TNF-alpha) contribute to the pathogenesis of cirrhotic cardiomyopathy. Nuclear factor-kappaB (NF-kappaB) is crucial for cytokine regulation, and induces cardiac dysfunction in several heart disease models. We aimed to elucidate possible NF-kappaB involvement in cirrhotic cardiomyopathy. Rats were bile duct ligated (BDL) to produce cirrhosis; controls received sham operation. Animals were studied 4 weeks later. Two NF-kappaB inhibitors were used: pyrrolidine dithiocarbamate (PDTC) and Bay 11-7082. Four groups were studied in most protocols: sham control, sham+PDTC, BDL and BDL+PDTC. Additional contractility studies were performed with Bay 11-7082. Myocardial NF-kappaB and TNF-alpha expression was measured by Western blot and ELISA. The contractility of isolated cardiomyocytes was observed under direct microscopy. Nuclear factor-kappaB and TNF-alpha levels were increased in cirrhotic hearts compared with controls. PDTC significantly reduced NF-kappaB activity and TNF-alpha expression in cirrhotic hearts; controls were unaffected. Cirrhotic cardiomyocytes showed decreased systolic and diatolic velocity compared with sham controls. Both PDTC and Bay 11-7082 restored contractile function in cirrhotic cardiomyocytes, but did not affect controls. Inhibition of the increased NF-kappaB activity in cirrhotic hearts was associated with improvement of attenuated cardiomyocyte contractility. NF-kappaB, via effects on cytokine expression, may contribute to the pathogenesis of cirrhotic cardiomyopathy.


Risk and outcome of pyelonephritis among renal transplant recipients.
Urinary tract infection is the most common infectious disease requiring hospitalisation following renal transplantation. However, the risk and outcome of post-transplant pyelonephritis remains unclear. This population-based cohort study was conducted from 1 January 1990 to 31 December 2009. Each member of a Danish population-based, nationwide cohort of first-time renal transplant recipients was matched by age and gender with up to 19 population controls. Information on hospital discharge diagnosis, emigration, and mortality was obtained from nationwide administrative databases. Individuals were observed from the date of first renal transplantation and until graft loss, emigration, or death. Risk factors were assessed by Poisson regression. The incidence rate (IR) of first-time hospitalisation for pyelonephritis was 18.5 (95 % confidence interval [CI]: 16.4-20.9) per 1,000 person-years of follow-up (PYFU) among renal transplant recipients (N = 2,656) and 0.26 (CI: 0.21-0.31) per 1,000 PYFU among population controls (N = 49,226) yielding an incidence rate-ratio (IRR) of 72.0 (95 % CI: 57.8-89.7). Among renal transplant recipients, the risk of pyelonephritis decreased during the entire study period and was lowest in 2005-09 (IRR = 0.46, CI: 0.31-0.68). The highest risk of pyelonephritis was observed within the first six months post-transplantation (IR = 69.9 per 1,000 PYFU; CI: 56.4-86.7). Other risk factors for post-transplant pyelonephritis included female gender, high Charlson comorbidity index score, HLA-DR mismatch, cause of renal failure, and calendar period. Interestingly, we found that the combined risk of graft loss and death was 45 %, (CI: 19-77 %) higher in renal transplant recipients following post-transplant pyelonephritis compared to those who had no admission due to pyelonephritis. The risk of first-time hospitalisation for pyelonephritis among renal transplant recipients is high. Further, post-transplant pyelonephritis was associated with excess risk of graft loss and death; this indicates that strategies aimed at reducing upper urinary tract infections are likely to enhance renal graft survival.


Diagnostic performance of screening tools for the detection of obstructive sleep apnea in people living with HIV.
Many people living with human immunodeficiency virus (PLWH) have undiagnosed obstructive sleep apnea (OSA), which may contribute to commonly reported fatigue and the high cardiovascular disease burden in this population. Our objective was to assess the utility of traditional OSA screening tools (STOP-BANG, Berlin Questionnaire, and Epworth Sleepiness Scale) for detecting OSA in PLWH. Adult PLWH were recruited from sleep/ human immunodeficiency virus clinics and the community into a larger clinical trial that included completion of these questionnaires before in-laboratory polysomnography. Discriminatory performance of these screening tools was assessed using area under receiver operating characteristic curves (AUC). The reference standard for the primary analysis was OSA based on an apnea-hypopnea index ≥ 5 events/h using recommended "1A"-criteria (hypopnea with 3% desaturation and/or arousal). Secondary analyses explored acceptable "1B"-criteria (hypopnea with 4% desaturation) and/or higher apnea-hypopnea index cut-offs (≥ 15 events/h). 120 PLWH were included (mean age: 50 ± 11 years; body mass index: 27 ± 4 kg/m2, 84% male) and OSA was diagnosed in 75% using 1A-criteria. In the primary analysis, the discriminatory performance of the 3 screening tools was low (AUCs 0.58 to 0.70) and similar across the tools (P ≥ .14). In secondary analyses, STOP-BANG showed moderate-high discriminatory ability (AUCs 0.77-0.80) and performed significantly better (P ≤ .008) than the Berlin Questionnaire or Epworth Sleepiness Scale (AUCs 0.53-0.62). OSA was highly prevalent in our cohort of PLWH. Although STOP-BANG could reasonably identify moderate-severe OSA, the tools were not reliable for mild disease. Specifically, the questionnaires perform poorly for PLWH with mild OSA manifesting with arousals, yet such people may be at risk of fatigue/sleepiness and impaired memory consolidation. Registry: ClinicalTrials.gov; Title: Obstructive Sleep Apnea Endotypes and Impact on Phenotypes of People Living with HIV (PLWH/OSA); Identifier: NCT03575143; URL: https://clinicaltrials.gov/ct2/show/NCT03575143. Schmickl CN, Bosompra N-O, DeYoung PN, et al. Diagnostic performance of screening tools for the detection of obstructive sleep apnea in people living with HIV. J Clin Sleep Med. 2022;18(7):1797-1804.


Comparison of Two Apnea Test Methods, Oxygen Insufflation and Continuous Positive Airway Pressure During Diagnosis of Brain Death: Final Report.
Deterioration of the pulmonary function after the apnea test (AT) conducted with the classic oxygen insufflation AT (I-AT) is often observed during the brain death (BD) diagnosis procedure. In the present study, two AT methods were compared before a method is recommended for the currently revised Polish BD criteria. Classic I-AT and continuous positive airway pressure AT (CPAP-AT) were performed in 60 intensive care unit patients. I-AT was performed at the end of two series of clinical tests, and approximately 1-1.5 h later, after BD was confirmed, a different method, CPAP-AT with 100% FiO2 and CPAP value of 10 cm H2O provided by a ventilator in CPAP mode was performed. The patients in I-AT and CPAP-AT groups were further divided into two subgroups: non-hypoxemic (NH) with good lung function before AT (PaO2/FiO2 index ≥ 200 mmHg) and hypoxemic (H) with poor lung function (PaO2/FiO2 index < 200 mmHg). PaO2 and PaCO2 were recorded prior to I-AT and CPAP-AT at time-point one (T1), 5 min after each test at time-point two (T2), and after 10 min prior to the end of tests at time-point three (T3). The I-AT NH subgroup consisted of 50 patients, and CPAP-AT NH subgroup 43 patients. The I-AT H subgroup consisted of 10 patients, and the CPAP-AT H subgroup 17 patients. In the I-AT NH subgroup, a gradual decrease in PaO2/FiO2 was observed throughout the AT but not in the CPAP-AT NH subgroup. The PaO2/FiO2 ratio during the AT in the CPAP-AT H group was stable with a slight tendency to increase but not in the I-AT H group. During the first 5 min of the AT, the mean increase in CO2 was approximately 5 mmHg/min. Most patients in all groups met the AT criteria after 5 min of the test. The results from the study show that I-AT may compromise pulmonary function in some cases and is one of the reasons for the recommendation of a safer option, CPAP-AT, in the currently revised Polish BD criteria. During AT, the mean CO2 increase rate was 5 mmHg/min, which, in most patients, would allow the test to be completed after just 5 min.


[Modern medical support for smoking cessation].
In view of the high morbidity and mortality associated with tobacco, smoking cessation is one of the most urgent medical challenges. It is effective when psychosocial support is combined with accompanying medication. In view of the associated rate of occurrence of cardiovascular diseases, COPD/emphysema as well as lung cancer, it is highly cost-effective. The nicotine replacement substances Bupropion and Varenicline used in smoking cessation therapies demonstrate a well-documented increase in effectiveness. Their use is not complicated. An increase in the overall cessation success rate by a factor of 2-3 is obtained when using an accompanying course of medication.


Working memory and processing speed abilities are related to habituation and change detection in school-aged children: An ERP study.
High cognitive performance is related to efficient brain processing while accomplishing complex cognitive tasks. This efficiency is observed through a rapid engagement of the brain regions and the cognitive processes required for task accomplishment. However, it is unclear if this efficiency is also present in basic sensory processes such as habituation and change detection. We recorded EEG with 85 healthy children (51 males) aged between 4 and 13 years old, while they listened to an auditory oddball paradigm. Cognitive functioning was evaluated using the Weschler Intelligence Scales for Children Fifth Edition and the Weschler Preschool & Primary School for Intelligence Fourth Edition. Auditory evoked potentials (AEPs) analyses and repeated measure analysis of covariance as well as regression models were performed. The analysis revealed that P1 and N1 repetition effects were observed across levels of cognitive functioning. Further, working memory abilities were related to repetition suppression on the auditory P2 component amplitude, while faster processing speed was related to repetition enhancement on the N2 component amplitude. Also, Late Discriminative Negativity (LDN) amplitude, a neural correlate of change detection, increased with working memory abilities. Our results confirm that efficient repetition suppression (i.e. greater reduction in amplitudes with greater levels of cognitive functioning) and more sensitive change detection (greater amplitude changes of the LDN) are related to the level of cognitive functioning in healthy children. More specifically, working memory and processing speed abilities are the cognitive domains related to efficient sensory habituation and change detection.


Non-linear osmotic brush regime: simulations and mean-field theory.
We investigate polyelectrolyte brushes in the osmotic regime using both theoretical analysis and molecular dynamics simulation techniques. In the simulations at moderate Bjerrum length, we observe that the brush height varies weakly with grafting density, in contrast to the accepted scaling law, which predicts a brush thickness independent of the grafting density. We show that such behavior can be explained by considering lateral electrostatic effects (within the non-linear Poisson-Boltzmann theory) combined with the coupling between lateral and longitudinal degrees of freedom due to the conserved polymer volume (which are neglected in scaling arguments). We also take the non-linear elasticity of polyelectrolyte chains into consideration, which makes significant effects as chains are almost fully stretched in the osmotic regime. It is shown that all these factors lead to a non-monotonic behavior for the brush height as a function of the grafting density. At large grafting densities, the brush height increases with increasing the grafting density due to the volume constraint. At small grafting densities, we obtain a re-stretching of the chains for decreasing grafting density, which is caused by lateral electrostatic contributions and is controlled by the counterion-condensation process around polyelectrolyte chains. These results are obtained assuming all counterions to be trapped within the brush, which is valid for sufficiently long chains of large charge fraction.


Propranolol for Off-label Treatment of Patients With Melanoma: Results From a Cohort Study.
Preclinical and retrospective studies showed that β-blockers inhibit angiogenesis and disrupt migration of melanoma cells via inhibition of noradrenaline-dependent responses. To study the clinical effectiveness of β-blocker therapy in patients with melanoma and to determine whether propranolol improves progression-free survival in patients with melanoma. We conducted a prospective study in patients treated for melanoma in our center with propranolol for off-label use. Patients with histologically confirmed stage IB to IIIA cutaneous melanoma and no evidence of metastasis were eligible for the study. At the time of diagnosis, they were asked to take propranolol (80 mg daily) as an off-label adjuvant treatment. If they accepted the treatment, they were considered part of the propranolol cohort (PROP). If they refused treatment but agreed to participate in the study control group, they were considered part of the nonpropranolol cohort (No-PROP). The primary outcome was progression-free survival. Disease progression was assessed by evaluating the presence of lymphatic, in-transit, or visceral metastases, and the cause of death was recorded. Among the 53 patients (median [interquartile range] age 63 [48-75] years; 33 men) included in the study, 19 were eligible for the PROP cohort. Thirty-four patients otherwise eligible but unwilling to take propranolol were enrolled in the No-PROP cohort. The 2 cohorts were comparable in terms of demographic characteristics and primary prognostic factors at baseline. After adjusting for known prognostic factors, Cox models confirmed that use of propranolol at the time of diagnosis was significantly inversely associated with recurrence of melanoma with approximately an 80% risk reduction for propranolol users (hazard ratio, 0.18; 95% CI, 0.04-0.89; P = .03). In the absence of randomized, double-blind, placebo-controlled clinical trials, this study is the first off-label study of which we are aware of propranolol for melanoma treatment. These results confirm recent observation that β-blockers protect patients with thick cutaneous melanoma from disease recurrence. This study is in accordance with the present policy of "drug repurposing" in oncology. Repurposing the vast arsenal of approved drugs with a nononcology primary purpose may prove an attractive and inexpensive strategy for offering more effective treatment options to patients with cancer.


Endocurietherapy of penis cancer.
Forty-five carcinomas of the penis have been treated with curietherapy using 192Ir to a dose of 6500 rad. With a minimum follow-up of 4 years, it appears that small lesions (less than 30 mm) have excellent local results (2 recurrences in 14 cases). With only a slight potential for lympatic extension, these patients are alive without evidence of disease after 4 years. The lesions of moderate size (30-40 mm) have a poorer prognosis because of more frequent lymphatic extention and disseminated metastases; in contrast, the local results are still quite satisfactory (4 recurrences in 24 cases). The large lesions (more than 40 mm) recur or necrotize (5 recurrences and 2 necroses in 7 cases). In conclusion, curietherapy of epidermoid carcinomas of the penis is an excellent primary treatment for small or moderate lesions (T1, T2, and T3a) if one wishes to avoid surgical mutilation.


Smile photograph analysis and its connection with focal length as one of identification methods in forensic anthropology and odontology.
To positively identify a highly decomposed body forensic experts often use information obtained from the dentition. In this study authors try to employ a method of comparing incisal borders of the anterior teeth from antemortem (AM) and postmortem (PM) photographs within an experimental scenario with living individuals. The second purpose was to determine how focal length of the lens affects compared smile lines. The research was divided into two stages. In procedure 1, the participants (28 individuals) were asked to provide a photo (for the purpose of the research considered as "antemortem") in which the anterior teeth were visible. A series of experimental photographs (considered as "postmortem") were then taken trying to reproduce the position of the person's head in relation to "AM" picture as faithfully as possible. The procedure 2 (10 individuals) consisted of taking "AM" photos under controlled conditions using an accidental focal length, then taking "PM" photos using a priori established focal lengths: 18 mm, 55 mm and 80 mm. In both procedures, the final stage involved marking and comparing the incisal borders from "AM" and "PM" photographs. Procedure 1 showed that in 82% of cases the compared smile lines are fully compatible. 11% was marked as "tolerable", and only 2% as "insufficient". Procedure 2 proved that the choice of focal length when taking a PM photograph is significant and that the medium focal lengths (range of 55-85 mm) are suggested in case of unknown focal length in AM photo. The results indicate that this method can be reliably applied in forensic cases when AM photographs of deceased are available.


Development and validation of a new treatment outcome score for men with LUTS.
To develop, validate, and test elements of a new outcome score for men with lower urinary tract symptoms (LUTS). Elements of well-established questions from the International Prostate Symptom Score (IPSS) assessment were combined with both established noninvasive objective determinants of voiding function including maximum uroflow (Qmax), postvoid residual urine volume (PVR), total number voids, maximum voided volume (MVV) as well as a subjective patient assessment parameter, to create a new LUTS treatment outcome instrument which we have termed the "LUTS outcome score" (LOS). The LOS is comprised of eight items; each assigned a score of 0, 1, or 2. Thus, the score ranges from 0 (best) to 16 (worst). Patients were divided into surgical/non- surgical (pharmacologic or behavior modification) treatment groups. Content validity and cutoff values for cure/improve/fail were established by an expert panel. Criterion validity was established by comparison to the IPSS. Internal reliability analysis was performed to obtain information about the relationships between individual items in the scale. Individual LOS items were correlated with the subjective outcome score. We also calculated the correlations between the LOS, IPSS, subjective post-treatment response, and age. Internal consistency, based on the average inter-item correlation was calculated using Cronbach's alpha statistic. Associations between continuous variables were examined by calculating the Pearson correlation coefficient, and between ordinal variables, using Spearman's rho. Test-retest analysis was recorded to determine reproducibility of the patient subjective outcome score. Seventy-seven men who underwent treatment for LUTS for at least 6 months participated in the study. All completed a detailed pretreatment and post-treatment clinical evaluation consisting of history/physical, questionnaire, voiding diary, urinalysis, Q, PVR, and videourodynamic study. Subjective responses of cured/improved/failed status following treatment were assessed by independent investigators. A high level of internal consistency was observed among the LOS symptom questions, Cronbach's alpha = 0.81 for the total cohort. The LOS correlated directly and significantly with the patient's subjective post-treatment response (r = 0.75, P < 0.001), age (r = 0.27, P = 0.02), and with the total IPSS (r = 0.62, P < 0.001). The IPSS also correlated directly and significantly with the patient's subjective post-treatment response (r = 0.48, P < 0.001) but did not correlate with the patient's age (r = 0.10, P = 0.41). When the subjective parameter for post-treatment response was subtracted from the LOS, the resulting correlation (r = 0.52, P < 0.001) approximated that obtained using the IPSS. The LOS is valid and internally consistent. Unlike the IPSS, it combines subjective, semisubjective, and objective parameters. Because of the objective components, it diminishes the possibility of overestimating cure and underestimating improvement relying only on patient's symptoms. Further, we believe it will prove to be useful for post hoc analysis in patients who have not had pre-treatment assessment.


Dysplastic nevi. Their significance and management.
Dysplastic nevi are found in a significant percentage of the population and are a sign that an individual with these nevi has a greater risk for developing a melanoma than do individuals without them. For patients with dysplastic nevi who also have two or more members of their primary family afflicted by melanomas, the risk of developing a melanoma is especially high. Guidelines for the care of patients with all forms of dysplastic nevi are outlined.


Comparison of Lipid Profile Parameters and Oxidized Low-Density Lipoprotein Between Normal and Preeclamptic Pregnancies in a Tertiary Care Hospital in Nepal [Retraction].
[This retracts the article DOI: 10.2147/IJWH.S117850.].


Surgical techniques for benign parotid tumors: segmental resection vs extracapsular lumpectomy.
In 80 patients surgical techniques for benign parotid gland tumor have been reviewed and evaluated. Segmental resection was introduced during partial superficial parotidectomy. The superficial lobe of the parotid gland was divided into four sections according to the distribution of the tumors. Total parotidectomy was applied to remove deep lobe and recurrent tumors, together with the superficial lobe, followed by retrograde dissection of the facial nerve. This technique was termed the hamburger technique. Furthermore, with a margin of normal tissue, extracapsular lumpectomy was used. Segmental resection is at method of extirpation by dissecting the facial nerve, whereas extracapsular lumpectomy is a method of extirpation by dissecting the tumor itself with a safety margin.


Reaction of human granulopoiesis to high-dose cyclophosphamide therapy.
The reaction pattern of an unperturbed human granulopoiesis to pulses of high-dose chemotherapy (cyclophosphamide 2000 mg/m2 plus vincristine 1.4 mg/m2 or adriamycin 20 mg/m2) was serially studied in 6 patients. The stem cells committed to granulopoiesis (CFU-C) of the bone marrow and the cells of the proliferative granulocytic marrow pool were considerably reduced during the first 8 days. Granulopoietic regeneration was first recognizable by increased proliferative activity of bone marrow CFU-C (3H-thymidine technique). The cytotoxic drug-induced injury to the early compartments of granulopoiesis, and granulocytic regeneration proceed sequentially through the ensuing, increasingly differentiated granulocytic compartments. In the peripheral blood, depletion and repletion of the CFU-C pool precede the corresponding changes of segmented neutrophils by 7 to 9 days; during granulocytic regeneration, peripheral blood CFU-C show a transient greatly overshooting decrease.


Antibody Responses to a Reverse Genetics-Derived Bivalent Inactivated Equine Influenza Vaccine in Thoroughbred Horses.
Updating vaccine strains is important to control equine influenza (EI). Previously, we reported that a monovalent inactivated EI vaccine derived from a virus generated by reverse genetics (RG) elicited immunogenicity in horses. In the present study, we compared antibody responses to a bivalent inactivated EI vaccine generated by RG and a commercially available bivalent inactivated EI (CO) vaccine derived from wild-type equine influenza viruses in Thoroughbred horses. The CO vaccine contained A/equine/Ibaraki/1/2007 (Florida sub-lineage clade 1) and A/equine/Yokohama/aq13/2010 (Florida sub-lineage clade 2) as vaccine strains. We generated two RG viruses possessing the hemagglutinin and neuraminidase genes from A/equine/Ibaraki/1/2007 or A/equine/Yokohama/aq13/2010. These viruses were inactivated by formalin, and the hemagglutinin titer of the RG vaccine was adjusted to be the same as that of the CO vaccine. Sixteen unvaccinated yearlings (7 for the RG vaccine group and 9 for the CO vaccine group) received two doses of a primary vaccination course four weeks apart. Thirty-two vaccinated adult horses (18 in the RG-vaccinated group and 14 in the CO vaccine group) received a single dose of a booster vaccination. The patterns of hemagglutination inhibition antibody response to the primary and booster vaccinations were similar for the RG and CO groups in unvaccinated yearlings and vaccinated adult horses. These results suggest that a bivalent vaccine derived from RG viruses elicits equivalent immunogenicity to that elicited by a CO vaccine derived from wild-type viruses. RG viruses can, therefore, be used in multivalent as well as monovalent vaccines for horses.


Neuropsychiatric consequences of childhood group A streptococcal infection: A systematic review of preclinical models.
In recent years, clinical studies have shown strong epidemiological evidence of an increased risk of developing neuropsychiatric disorders after childhood exposure to streptococcal infection, including the Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS). New preclinical studies on group A streptococcus (GAS) exposure investigate how to disentangle the influences of immune activation to induce long-term neurobehavioral effects associated with neuropsychiatric disorders such as obsessive-compulsive disorder, schizophrenia or autism. The present systematic review collects neurobehavioral evidence regarding the use of GAS exposure in animal models to study the vulnerability to different neuropsychiatric disorders, improving our understanding of its possible causes and consequences, and compares its contribution with other preclinical models of immune activation in a variety of paradigms. Specifically, we reviewed the effects of postnatal GAS exposure, in comparison with post- and prenatal exposure to Lipopolysaccharide (LPS) and Polyinosinic:polycytidylic acid (Poly I:C), on the long-term effects concerning psychomotor, cognition and socioemotional outcomes in rodents. GAS exposure in animal models has revealed different behavioral alterations such as reduced locomotion and motor coordination, a deficit in sensorimotor gating, learning, working memory, altered social behavior, and increased anxiety and stereotyped behavior. Most of the results found are in accordance with other immune activation models -LPS and Poly I:C-, with some discrepancies. The systematic review of the literature supports the preclinical model of GAS exposure as a valid model for studying the neurobehavioral consequences of streptococcal infections. Future studies on streptococcal infection could contribute increasing our knowledge on preventive actions or treatments for neuropsychiatric disorders.


[Long-term follow-up of a French cohort of retroperitoneal fibrosis].
Retroperitoneal fibrosis (RPF) is a rare disease with an expanding etiologic spectrum. We aimed to analyze non-invasive diagnosis strategy, associated disorders, monitoring, treatment and prognosis. Retrospective cohort study in a single tertiary center. Eighteen RPF cases (11 males) followed between 1996 and 2009 were reviewed. Blood CRP level was high in all cases before treatment. CT scan, associated or not with MRI or 18-FDG PET-scan, confirmed the diagnosis in 15 patients. Histological analysis of a surgical biopsy specimen was performed in only three cases. Ten patients suffered retroperitoneal fibrosis secondary to systemic vasculitis (granulomatosis with polyangeitis, n=1, Takayasu aortitis, n=2), systemic fibrosis with Riedel thyroiditis (n=1) and atheromatous periaortitis (n=6). Fifteen patients were treated with corticosteroids with a mean treatment duration of 60 months (12-228). Dependency to corticosteroids was recorded in ten patients. Patients with fibrosis related to vasculitis were younger, had a higher CRP level, more frequent corticosteroid dependency and a higher relapse rate. Relapses were successfully treated with steroids. Immunosuppressive treatment was only prescribed in the setting of systemic vasculitis. No patient died, after a 6±2 years follow-up. Late relapses could occur, sometimes years after steroid therapy cessation. In our study, RPF occurred as a secondary disorder in 60% of the cases. Disease extension, relapse rate and treatment response varied according to the underlying cause of RPF, pleading for an extensive and systematic initial assessment. Since no death or end-stage renal insufficiency was observed, RPF might be considered as a steroid-sensitive and benign disorder.


Structure of Rapid Response Car Operations in an Urban Trauma Service.
Emergency medical vehicle collisions are an inherent risk for health care providers, patients, and other road users. Air ambulance services often use rapid response cars (RRCs) to maintain operational resilience. We aim to describe the operational concept of London's Air Ambulance (LAA) RRCs and activity over a 1-year period. This was a retrospective dispatch database study. The RRC operational concept, car configuration, and training are also described. LAA implemented principles from motorsports and aviation including car configuration, training, navigation, and communication. RRCs were activated a total of 2,241 times during the study period (average of 6.1 activations per day). RRCs traveled a total of 22,973 km and a median of 8.7 km (interquartile range = 5-15.1) with blue lights; there were missing data for 123 (5%) activations. Furthermore, the RRCs spent a total of 28,536 minutes with blue lights and a median of 12 minutes (interquartile range = 7-18); there were missing data for 89 (4%) activations. The safety management system included 5 reports, none of which were related to serious RRC incidents. Translating lessons from aviation and motorsports, LAA has developed an RRC operation concept to improve safety and operational capacity. One-year operational data indicate high activity without any serious incidents.


Therapeutic implication of Sonic Hedgehog as a potential modulator in ischemic injury.
Sonic Hedgehog (SHh) is a homology protein that is involved in the modeling and development of embryonic tissues. As SHh plays both protective and harmful roles in ischemia, any disruption in the transduction and regulation of the SHh signaling pathway causes ischemia to worsen. The SHh signal activation occurs when SHh binds to the receptor complex of Ptc-mediated Smoothened (Smo) (Ptc-smo), which initiates the downstream signaling cascade. This article will shed light on how pharmacological modifications to the SHh signaling pathway transduction mechanism alter ischemic conditions via canonical and non-canonical pathways by activating certain downstream signaling cascades with respect to protein kinase pathways, angiogenic cytokines, inflammatory mediators, oxidative parameters, and apoptotic pathways. The canonical pathway includes direct activation of interleukins (ILs), angiogenic cytokines like hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and hypoxia-inducible factor alpha (HIF-), which modulate ischemia. The non-canonical pathway includes indirect activation of certain pathways like mTOR, PI3K/Akt, MAPK, RhoA/ROCK, Wnt/-catenin, NOTCH, Forkhead box protein (FOXF), Toll-like receptors (TLR), oxidative parameters such as GSH, SOD, and CAT, and some apoptotic parameters such as Bcl2. This review provides comprehensive insights that contribute to our knowledge of how SHh impacts the progression and outcomes of ischemic injuries.


Elevation of calcitonin immunoreactivity in the pituitary and thyroid glands of genetically obese rats (fa/fa).
This paper contains the first demonstration of quantitative changes in the levels of calcitonin-like immunoreactivity in the pituitary. The concentration of calcitonin-like material in lean Zucker rats (?/+) was 0.42 +/- 0.09 ng/mg wet weight of pituitary. The pituitaries of obese rats (fa/fa) contained significantly greater levels (1.56 +/- 0.56 ng/mg wet weight). This 271% increase represents the first indication that pituitary calcitonin-like material may have a physiological role in genetically obese rats. Thyroidal calcitonin also elevated in the obese (111%). These large elevations in the calcitonin content of the glands of obese rats were not accompanied by significant elevations of calcitonin in the blood. This suggests that obese rats have problems with mechanisms for the release of calcitonin into the blood and might not be able to combat hypercalcemia as effectively as leans. However, this hypothesis remains to be tested.


Embryonic neural stem cells in a 3D bioassay for trophic stimulation studies.
Progenitors were discovered in the corpus striatum several years ago, but little is known about their proliferation and differentiation. The aim of this study was to analyze embryonic progenitor cells from the corpus striatum using a bioassay with trophic stimulation. Primary cells obtained from brains of rat embryos at E13-14 were dissected from striatum niches and cultured in stem cell media. These floating dispersed cells clumped together to forming floating bodies like irregular spheres (spheroids), which were placed in type I collagen gel and cultured under basal conditions or with the addition of NGF, NT-3, or NTN. Optimum growth of neurites was obtained, and after 24 and 48 h, they were measured for number and length. The expression of proliferation markers such as PCNA and Ki67, and of neural progenitor markers such as GFAP, nestin, vimentin, O4, A2B5, Pax6, S100, TubIII, and NeuN, was then analyzed. The initial behavior in cell cultures showed distinguishable spheroids that, when placed in 3D gels and with trophic support, generated neurites. A similar effect was observed in glial cell outgrowth from the spheroids. Our assay showed high reproducibility, short culture time, and high resolution for tracing neuron-neurite outgrowth or visualizing glial outgrowth in a few hours.