Generation of microRNA-30e-producing recombinant viral hemorrhagic septicemia virus (VHSV) and its effect on in vitro immune responses.
MicroRNAs (miRNAs) are non-coding small RNAs involved in the regulation of gene expression. In the present study, we firstly reported the use of a fish RNA virus, viral hemorrhagic septicemia virus (VHSV), as a delivery vehicle of a miRNA-30e, and the effect of miR-30e produced by the recombinant VHSV on the immune responses of Epithelioma papulosum cyprini (EPC) cells was investigated. The expression of functional miR-30e using a CMV promoter-driven vector was verified by the significantly lower eGFP expression in cells transfected with a vector containing miR-30e sponge sequence than that in cells transfected with a control vector that had mutated miR-30e sponge sequence. Furthermore, the down-regulation of reporter gene containing 3'-UTR of NF-κb inhibitor α-like protein B (NFκbiαb) by miR-30e was demonstrated, suggesting that miR-30e overexpression can increase immune responses related to NF-κB activation through inhibition of IκB. A miR-30e-expressing recombinant VHSV (rVHSV-A-miR30e) that had primary microRNA-30e sequence between N and P genes was rescued using the reverse genetic method, and the successful expression of miR-30e in the cells infected with rVHSV-A-miR30e was demonstrated using Northern blot and qRT-PCR. Cells infected with rVHSV-A-miR30e showed the increase of NF-κB activation and type I interferon induced genes expression, suggesting that rVHSV-A-miR30e can produce functional miR-30e in fish cells, and VHSV can be used as a vehicle to deliver functional microRNAs in fish.


The Influence of Listening to Music on Adults with Left-behind Experience Revealed by EEG-based Connectivity.
The human brain has a close relationship with music. Music-induced structural and functional brain changes have been demonstrated in the healthy adult. In the present study, adults with left-behind experience (ALB) were divided into two groups. The experimental group (ALB-E) took part in the music therapy experiment with three stages, including before listening to music (pre-stage), initially listening to music (mid-stage) and after listening to music (post-stage). The control group (ALB-C) did not participate in music therapy. Scalp resting-state EEGs of ALB were recorded during the three stages. We found no significant frequency change in the ALB-C group. In the ALB-E group, only the theta power spectrum was significantly different at all stages. The topographical distributions of the theta power spectrum represented change in trends from the frontal regions to the occipital regions. The result of Granger causal analysis (GCA), based on theta frequency, showed a stronger information flow from the middle frontal gyrus to the middle temporal gyrus (MFG → MTG) in the left hemisphere at the pre-stage compared to the post-stage. Additionally, the experimental group showed a weaker information flow from inferior gyrus to superior temporal gyrus (IFG → STG) in the right hemisphere at post-test stage compared to the ALB-C group. Our results demonstrate that listening to music can play a positive role on improving negative feelings for individuals with left behind experience.


Etiology of facial fractures in elderly Finns during 2006-2007.
The purpose of the present study was to clarify the trauma mechanisms and resulting facial fractures in geriatric patients and to compare them with those of younger adults. A cohort of 117 geriatric patients was compared with 136 patients aged 20 to 50 years. The statistical significance of differences between the age groups was evaluated with χ(2) tests. Falls on the ground were significantly more frequent among geriatric patients (P < .001), whereas assault was more frequent in controls (P < .001). Accident rates in geriatric patients were significantly higher during the winter months (P = .04). Fractures of the midface in general (P = .001) and of the nasal bone (P = .004) and orbit (P = .015) in particular were more frequent in geriatric patients. Age-related factors and preexisting medical problems predispose the elderly to falls and subsequent fractures. Footwear traction devices are recommended during the cold season. Orbital fractures should be strongly suspected in the elderly.


[Clinical evaluation of amoxicillin sustained-release preparation in urinary tract infection].
C-AMOX, a new prolonged acting preparation of amoxicillin was administered to 122 cases by oral administration of daily dosage 500 mg twice. Clinical effectiveness of C-AMOX was evaluated in 115 out of 122 cases (acute simple cystitis 87 cases, acute pyelonephritis 6 cases, complicated urinary tract infection 19 cases and others 3 cases), and the following results were obtained. 1. The clinical effect for 87 cases of acute simple cystitis was excellent in 54 cases (62%), moderate in 24 cases (27.6%) and poor 9 cases (10.3%), overall effective rate being 89.7%. 2. The clinical effect for 19 cases of complicated urinary tract infection was excellent in 6 cases (31.6%), good 8 cases (42.1%) and poor 5 cases (26.3%), overall effective rate being 73.7%. 3. Adverse reaction occurred in 2 patients, one gastric discomfort and the other one slight diarrhoea. No laboratory abnormalities attributable to C-AMOX were observed in the present study.


Devising and delivering objectives for disease state management.
Comprehensive, objective plans of clinical care that reflect the optimal diagnosis and treatment must be developed. Standardized plans of patient care that are centered around a specific disease entity meet outcomes management and maximize health delivery quality. This integration is embodied in the philosophy of disease state management.


Early knee status affects self-reported knee function 1 year after non-surgically treated anterior cruciate ligament injury.
The primary aim was to assess impact of early knee status on self-reported knee function at 3 and 12 months and on quadriceps strength at 12 months after non-surgically treated ACL injury. The secondary aim was to describe the recovery of muscle strength during the first year after the injury. Prospective cohort study. 70 patients (42 males; mean age 27 ± 7 years) with acute ACL injury. Knee symptoms, knee function and sporting activities were assessed with the International Knee Documentation Committee Subjective Knee Form (IKDC-SKF). Muscle strength was assessed with an isokinetic dynamometer. Clinical assessment performed at baseline was used to evaluate early knee status. Global knee function, knee joint stability during ADL, gait pattern and one-legged squat assessed in mean 2 weeks after injury hadimpact on self-reported knee function at 3 and 12 months (r2 0.105-0.267). Mean limb symmetry index (LSI) of muscle strength and jump performance were 91-98% at 12 months. Early knee symptoms affect self-reported knee function at 3 and 12 months, while other factors are important for gaining muscle strength. Muscle strength recovered during the first year after ACL injury and reached mean LSI above 90%. Prospective cohort study, level II.


Polymorphisms in the FKBP5 gene are associated with attention deficit and hyperactivity disorder in Korean children.
Attention deficit hyperactivity disorder (ADHD) is a common and heritable childhood psychiatric disorder. Recently, many studies reported a down-regulated hypothalamus-pituitary-adrenal axis (HPA-axis) with low cortisol levels in children with ADHD. The FK506 binding protein 5 or FKBP5 gene regulates the negative feedback of the HPA-axis, and genetic variants in this gene showed an association with ADHD. We investigated the genetic association between FKBP5 gene polymorphisms and susceptibility to ADHD in Korean children. We conducted a case-control study with 150 ADHD children and 322 controls. Genotyping of FKBP5 rs9394309 and rs7748266 was performed by using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). Our results showed that rs7748266 polymorphism has significant genotype (p = 0.021) and allele (p = 0.009) frequency differences between children with ADHD and the control group. CT genotype [odds ratio (OR) 1.70, 95 % confidence interval (CI) 1.134-2.540, p = 0.010] and T allele (OR 1.54, 95 % CI 1.114-2.117, p = 0.009) were associated with increased risk of ADHD. In addition, dominant (p = 0.006) and over-dominant genetic (p = 0.016) models showed significant associations with ADHD. In the stratified analysis, a significant result was obtained from the girl samples (p = 0.048). The OR of the girls with ADHD with CT genotype was 2.29 (95 % CI 1.170-4.469, p = 0.014). In contrast to rs7748266 polymorphism, rs9394309 polymorphism did not show any significant result (p > 0.05). Haplotype analysis also revealed a significant difference of the TG haplotype for rs7748266 - rs9394309 (p = 0.028, global haplotype association p-value of 0.0091). Conclusively, we confirmed that FKBP5 gene polymorphisms were associated with ADHD in Korean children. These results suggested that FKBP5 may factor in the development of ADHD.


Genome-wide prediction and transcriptome analysis of sugar transporters in four ascomycete fungi.
The import of plant-derived small sugars by sugar transporters (STs) has received increasing interest due to its important biological role and great industrial potential. STs are important targets of genetic engineering to improve fungal plant biomass conversion. Comparatively analysis of the genome-wide prevalence and transcriptomics of STs was performed in four filamentous fungi: Aspergillus niger, Aspergillus nidulans, Penicillium subrubescens and Trichoderma reesei. Using phylogenetic analysis and literature mining, their predicted STs were divided into ten subfamilies with putative sugar specificities assigned. In addition, transcriptome analysis revealed complex expression profiles among different STs subfamilies and fungal species, indicating a sophisticated transcriptome regulation and functional diversity of fungal STs. Several STs showed strong co-expression with other genes involved in sugar utilization, encoding CAZymes and sugar catabolic enzymes. This study provides new insights into the diversity of STs at the genomic/transcriptomic level, facilitating their biochemical characterization and metabolic engineering.


A new smoking cessation 'cascade' among women with or at risk for HIV infection.
The aim of this study was to define a smoking cessation 'cascade' among USA women with and without HIV and examine differences by sociodemographic characteristics. An observational cohort study using data from smokers participating in the Women's Interagency HIV Study between 2014 and 2019. We followed 1165 women smokers with and without HIV from their first study visit in 2014 or 2015 until an attempt to quit smoking within approximately 3 years of follow-up, initial cessation (i.e. no restarting smoking within approximately 6 months of a quit attempt), and sustained cessation (i.e. no restarting smoking within approximately 12 months of a quit attempt). Using the Aalen-Johansen estimator, we estimated the cumulative probability of achieving each step, accounting for the competing risk of death. Forty-five percent of smokers attempted to quit, 27% achieved initial cessation, and 14% achieved sustained cessation with no differences by HIV status. Women with some post-high school education were more likely to achieve each step than those with less education. Outcomes did not differ by race. Thirty-six percent [95% confidence interval (95% CI): 31-42] of uninsured women attempted to quit compared with 47% (95% CI: 44-50) with Medicaid and 49% (95% CI: 41-59) with private insurance. To decrease smoking among USA women with and without HIV, targeted, multistage interventions, and increased insurance coverage are needed to address shortfalls along this cascade.


Rapid ventricular parasystole with possible multilevel exit block.
A case of ventricular parasystole firing at the extremely rapid rate of 214 beats per minute in a 73 year old woman is described. Manifest cycle lengths of parasystolic complexes varied widely due to variable degrees of exit block, which could be best interpreted by the concept of multilevel block or alternating Wenckebach periodicity in the ventriculo-ectopic junction. Discontinuation of digoxin reduced the degree of exit block and unmasked parasystolic tachycardia.


Pathological findings in poststrabismus surgery endophthalmitis.
Bacterial entry into the vitreous cavity via inadvertent scleral perforation is one postulated mechanism for poststrabismus surgery endophthalmitis. In a review of 746 cases, we identified 2 pediatric enucleation specimens related to complications of strabismus surgery. In both cases, the patients developed postoperative endophthalmitis and no light perception vision, and the eyes were enucleated when they became phthisical or painful. In both submitted cases, pathology showed a thick band of scar tissue emanating focally from the sclera into the vitreous. Although no needle tracts were visualized, pathological findings were consistent with scleral perforation.


The genealogy, site frequency spectrum and ages of two nested mutant alleles.
In this paper we consider the genealogy of two nested mutant alleles, assuming the constant-size neutral coalescent model with infinite sites mutation. We study the conditional genealogy and derive explicit formulas for the joint and marginal site frequency spectra for the double, single and zero mutant allele. In addition, we find the mean ages of the two mutations. We show that the age of the youngest mutation does not depend on the frequency of the single mutant allele and that the frequency spectra for the single mutant allele and the zero mutant allele are the same.


Anthropometric measurements of term singletons at 6 years of age born from fresh and frozen embryo transfer: A multicenter prospective study in Japan.
The purpose of this study is to compare anthropometric measurements between term singletons conceived via fresh embryo transfer (FreET) and frozen embryo transfer (FET) and those born via natural conception (NC) or fertility treatments milder than assisted reproductive technology (non-ART) at 6 years of age. A total of 8149 children were enrolled, and questionnaires about anthropometric measures (weight, height, BMI) were addressed to parents, when the children were 1.5, 3, and 6 years of age. A total of 3299 term singletons were enrolled at birth: 533, 476, 916, and 1374 in the NC, non-ART, FreET, and FET groups, respectively. A total of 1635 term singletons (290, 176, 467, and 702 in the NC, non-ART, FreET, and FET groups respectively) were enrolled until 6 years of age (follow-up rate, approximately 50%). When non-ART group was used as control, the FreET children were 1.0 cm taller than the non-ART children at 6 years of age, after adjusting for confounding factors. However, no differences were observed in the anthropometric data among the non-ART, ART, and NC children at 6 years of age. At 6 years of age, term singletons were taller in the FreET group than in the non-ART group, after adjusting for confounders.


Preparation and characterization of a novel polylactic acid/hydroxyapatite composite scaffold with biomimetic micro-nanofibrous porous structure.
Combining synthetic polymer scaffolds with inorganic bioactive factors is widely used to promote the bioactivity and bone conductivity of bone tissue. However, except for the chemical composition of scaffold, the biomimetic structure also plays an important role in its application. In this study, we report the fabrication of polylactic acid/hydroxyapatite (PLA/HA) composite nanofibrous scaffolds via phase separation method to mimic the native extracellular matrix (ECM). The SEM analysis showed that the addition of HA dramatically impacted the morphology of the PLA matrix, which changed from 3D nanofibrous network structure to a disorderly micro-nanofibrous porous structure. At the same time, HA particles could be evenly dispersed at the end of the fiber. The FTIR and XRD demonstrated that there was not any chemical interaction between PLA and HA. Thermal analyses showed that HA could decrease the crystallization of PLA, but improve the thermal decomposition temperature of the composite scaffold. Moreover, water contact angle analysis of the PLA/HA composite scaffold demonstrated that the hydrophilicity increased with the addition of HA. Furthermore, apatite-formation ability tests confirmed that HA could not only more and faster induced the deposition of weak hydroxyapatite but also induced specific morphology of HA.


[Value of indirect immunofluorescence test in the diagnosis and prognosis of intestinal and extra-intestinal amoebiasis in endemic areas (author's transl)].
A comparative study of 108 patients with patient amoebiasis and a reference group of 85 free of the disease but living in endemic area. The positivity of the test has been more frequent and has given higher titers in the extra-intestinal forms than in the intestinal ones. The positivity rate in the reference group has been 15 per 100.


Lysophosphatidylcholine stimulates EGF receptor activation and mesangial cell proliferation: regulatory role of Src and PKC.
Lysophosphatidylcholine (LPC), a major component of oxidized-low density lipoproteins (ox-LDL), modulates various pathobiological processes involved in vascular and glomerular diseases. Although several studies have shown increased plasma concentrations of ox-LDL as well as LPC in patients with renal disease, the role of LPC in mesangial cell proliferation and associated signaling mechanisms are not clearly understood. In this study, we have shown that LPC induced the phosphorylation of epidermal growth factor receptor (EGFR), as well as the p42/44 MAP kinases. LPC activated Src-kinase and protein kinase C (PKC), and both Src kinase inhibitor PP-2 and PKC inhibitor inhibited the activation of EGFR by LPC. LPC (5-25 microM) stimulated human mesangial cell proliferation by 4-5 fold. Preincubation of mesangial cells with the Src inhibitor (PP-2), or PKC inhibitor (bisindolylmaleimide GF109203-X), or EGF receptor kinase inhibitor (AG1478), or MEK inhibitor (PD98059) significantly inhibited LPC-mediated mesangial cell proliferation. The data suggest that LPC, by activating Src and PKC signaling pathways, stimulates EGF receptor transactivation and down-stream MAP kinase signaling resulting in mesangial hypercellularity, which is a characteristic feature of diverse renal diseases.


Direct enantiomeric resolution of cyclic alcohol derivatives of polycyclic aromatic hydrocarbons by chiral stationary phase high-performance liquid chromatography.
The enantiomers of some cyclic alcohol derivatives of phenanthrene, benz[a]anthracene, benzo[a]pyrene, cholanthrene, and 3-methylcholanthrene were resolved by high-performance liquid chromatography using a commercially available preparative column packed with an (R)-N-(3,5-dinitrobenzoyl)phenylglycine ionically bonded to gamma-aminopropylsilanized silica. Resolution of enantiomers was confirmed by ultraviolet-visible absorption, mass and circular dichroism spectral analyses. This method has been applied to the determination of optical purity of 1-hydroxycholanthrene and 1-hydroxy-3-methylcholanthrene formed in the metabolism of cholanthrene and 3-methylcholanthrene, respectively, by rat liver microsomes.


Surrogate endpoint evaluation using data from one large global randomized controlled trial.
Robust identification of surrogate endpoints can help accelerate the development of pharmacotherapies for diseases traditionally evaluated using true endpoints associated with prolonged follow-up. The meta-analysis-based surrogate endpoint evaluation (SEE) integrates data from multiple, usually smaller, trials to statistically confirm a surrogate endpoint as a robust proxy for the true endpoint. To test the applicability of SEE when only a single, larger trial is available, we analysed the cardiovascular (CV) survival endpoint from the large multinational trial LEADER (9340 subjects) that confirmed the CV safety of a diabetes drug (liraglutide). We evaluated if using country as a trial unit adequately facilitated the meta-analysis and calculation of R2 by country group. Data were grouped by country, ensuring at least 30 CV deaths (497 in total) in each of the nine resulting by-country groups. In a two-step SEE on the grouped dataset, we first fitted the group-specific Cox proportional hazard models; next, on the trial-level, we regressed the estimated hazard ratio (HR; liraglutide vs placebo) of the true endpoints (CV death: 497 events, or all-cause death: 828 events) on the HR of the surrogate endpoint (major CV adverse event [MACE]: 1302 events) and derived the group-specific R2 and its 95% confidence interval (CI). Group-level surrogacy of MACE was supported for CV death but not for all-cause death, with [Formula: see text] values of 0.85 [0.63;1.00]95% CI and 0.23 [0.00;0.67]95% CI, respectively. Sensitivity analyses using different grouping approaches (e.g. grouping by region) corroborated the robustness of the conclusions as well as the appropriateness of the data-grouping approaches. We derived a specific grouping approach to successfully apply SEE on data from a single trial. This may allow for the statistically robust identification and validation of surrogate endpoints based on the abundance of large monolithic outcome trials conducted as part of drug development programmes in, for example, diabetes.


A new approach towards tetrahedral imidazolate frameworks for high and selective CO2 uptake.
Successful development of a new synthetic approach towards tetrahedral imidazolate frameworks (TIFs) via combining an auxiliary uninegative linker into the zinc-imidazolate tetrahedral assembly leads to new TIF materials (TIF-A1 to TIF-A3) with distinct structural topologies and high CO(2) uptake capacity.


Morphology and cross-linkage of stereocilia in the guinea-pig labyrinth examined without the use of osmium as a fixative.
Hair cells of the guinea-pig cochlea and vestibular system were prepared for electron-microscopic examination by fixing in glutaraldehyde without the use of osmium. An extensive array of cross-links was seen between the apical ends of the stereocilia, by both scanning and transmission electron microscopy. Some cross-links ran laterally between stereocilia of the same row. Others ran laterally between the stereocilia of the different rows, holding the tips of the shorter stereocilia in towards the longer stereocilia of the next row. In addition, each tip on the shorter stereocilia gave rise to a single, upwards pointing link, which ran upwards to join the adjacent taller stereocilium of the next row. We suggest that distortion of this link might be involved in the mechanics or even the membrane biophysics of sensory transduction. With this method of preservation, all the apical surface membranes of the hair cells appeared rough, and contained dense granules. The roughness was greatest in the parts of the stereocilia to which the cross-links were attached. The mitochondrial and synaptic membranes of the hair cells appeared normal.


Dietary α-tocopherol content modulates responses to moderate ethanol consumption.
Rats were fed with diets containing differing amounts of α-tocopherol for 21 days. For the latter 14 days of this period, one half of the rats also received ethanol (7% v/v) in the drinking water. Treatments did not alter the rate of weight gain between groups. Hepatic glutathione levels were depressed by ethanol treatment in rats receiving diets deficient in α-tocopherol or containing normal levels of the vitamin (50 ppm). However, this depression was not found in rats maintained on a high α-tocopherol diet (1000 ppm). The high α-tocopherol diet also prevented the ethanol-induced inhibition of proteolytic activity within the liver. A dose-dependent reduction of rates of hepatic generation of reactive oxygen species was effected by this vitamin. Within the central nervous system, the only region showing an ethanol-induced lowering of glutathione levels, was the midbrain of rats receiving the α-tocopherol deficient diet.


Pharmacokinetics and depressor effect of delapril in patients with essential hypertension.
The pharmacokinetics and depressor effect of a nonsulfhydryl angiotensin-converting enzyme inhibitor, delapril, was assessed by administering a single dose of 30 mg to nine patients with mild to moderate essential hypertension. Orally administered delapril is a prodrug and must be deesterified to its active metabolites, delapril diacid and 5-hydroxy delapril diacid. The pharmacokinetic parameters for delapril, delapril diacid, and 5-hydroxy delapril diacid were, respectively: t 1/2 0.30, 1.21, and 1.40 hours; Cmax 489, 635, and 229 ng/ml; AUC 572, 1859, and 948 ng X hr/ml. Delapril produced significant decreases in systolic blood pressure and angiotensin-converting enzyme activity 24 hours after dosing. There were no significant changes in the endogeneous creatinine clearance after the drug. Thus delapril may represent a useful antihypertensive agent for control of blood pressure in patients with essential hypertension.


Downregulation of phosphodiesterase 4B (PDE4B) activates protein kinase A and contributes to the progression of prostate cancer.
Prostate cancer is the most commonly diagnosed non-cutaneous cancer in American men. Unfortunately, few successful therapies for castration-resistant prostate cancer (CRPC) exist. The protein kinase A (PKA) pathway is a critical mediator of cellular proliferation and differentiation in various normal and cancerous cells. However, the PKA activity and the mechanism of regulation in CRPC remain unclear. Then, in this study, we intended to reveal the PKA activity and the mechanism of regulation in CRPC. Western blotting, quantitative real-time polymerase chain reaction, cytotoxicity analysis, and cell proliferation assay were used to resolve the regulatory role of PKA in prostate cancer cell line, LNCaP and their derivatives. cAMP-specific phosphodiesterase 4B (PDE4B) was downregulated and the PKA pathway was activated in castration-resistant LNCaP derivatives (CxR cells). Rolipram activated the PKA pathway via inhibition of PDE4B, resulting in AR transactivation while the PKA inhibitor, H89 reduced AR transactivation. In response to hydrogen peroxide and in hydrogen peroxide-resistant LNCaP derivatives (HPR50 cells) PDE4B was decreased and as a result PKA activity was increased. Moreover, PDE4B expression was reduced in advanced prostate cancer and PDE4B knockdown promoted castration-resistant growth of LNCaP cells. Oxidative stress may suppress PDE4B expression and activate the PKA pathway. The PDE4B/PKA pathway contributed to progression of androgen-dependent prostate cancer to CRPC. This pathway may represent an attractive therapeutic molecular target.


Purified recombinant phage lysin LySMP: an extensive spectrum of lytic activity for swine streptococci.
Bacteriophage lysin has attracted considerable attentions as possible antimicrobial agents for solution of antibiotic resistance. SMP was a Streptococcus suis serotype 2 bacteriophage isolated from nasal swabs of healthy Bama minipigs. The putative SMP bacteriophage lysin, designated LySMP, was recombinantly expressed in Escherichia coli BL21, and chromatographically purified. Treated with 0.8% of beta-mercaptoethanol, LySMP exhibited an extensive lysin spectrum than those of whole phage against bacteria investigated. S. suis serotype 2, S. suis serotype 7 and S. suis serotype 9 strains were recovered from diseased pigs between 1998 and 2005 in China. Fifteen of seventeen strains of S. suis serotype 2 could be lysed, as well as S. suis serotype 7 and 9, Streptococcus equi ssp. zooepidemicus and Staphylococcus aureus. But E. coli and Salmonella enterica were not affected. Purified LySMP showed high degrading efficiency against PMSF or lysozyme treated cells comparing to PBS washed cells. Optimum pH and temperature conditions for the lysin were investigated by turbidity reduction assay. The lysin exerted efficient lysis activity at 37 degrees C, pH 5.2. The turbidity of bacterium investigated was observed to decrease by 1.2-68% in 30 min. Result indicated that putative LySMP could be a candidate antimicrobial agent in controlling S. suis infection.


[Burgdorf's reaction (painful acral erythema) in patients with acute lymphoblastic leukemia following medium-dose methotrexate therapy].
Erythematous changes of the palms with associated oedema, blistering and desquamation were observed in two children during chemotherapy for acute lymphoblastic leukaemia, after methotrexate in doses of 1,000 mg/m2. These changes correspondent to those described in the literature as Burgdorf's reaction. In Poland it was never reported as yet.


Infant attention to auditory discrepancy.
Groups of 7 1/2-month-old infants heard 1 of 8 episodes consisting of no, slight, moderate, or a large discrepancy between a habituated standard and a transformed auditory stimulus. The patterns of cardiac deceleration, regarded as an index of attention supported the hypothesis that attentiveness is an inverted-U function of the degree of discrepancy between stimulus event and schema.


Liver resection for colorectal cancer metastases involving the caudate lobe.
Up to 5 per cent of liver resections for colorectal cancer metastases involve the caudate lobe, with cancer-involved resection margins of over 50 per cent being reported following caudate lobe resection. Outcomes of consecutive liver resections for colorectal metastases involving the caudate lobe between 1996 and 2009 were reviewed retrospectively, and compared with those after liver surgery without caudate resection. Twenty-five patients underwent caudate and 432 non-caudate liver resection. Caudate resection was commonly performed as part of extended resection. There were no differences in operative complications (24 versus 21·1 per cent; P = 0·727) or blood loss (median 300 versus 250 ml; P = 0·234). The operating time was longer for caudate resection (median 283 versus 227 min; P = 0·024). Tumour size was larger in the caudate group (median 40 versus 27 mm; P = 0·018). Resection margins were smaller when the caudate lobe was involved by tumour, than in resections including tumour-free caudate or non-caudate resection; however, there was no difference in the proportion of completely excised tumours between caudate and non-caudate resections (96 versus 96·1 per cent; P = 0·990). One-year overall survival rates were 90 and 89·3 per cent respectively (P = 0·960), with 1-year recurrence-free survival rates of 62 and 71·2 per cent (P = 0·340). Caudate lobe surgery for colorectal cancer liver metastases does not increase the incidence of resection margin involvement, although when the caudate lobe contains metastases the margins are significantly closer than in other resections.


Cerebral white matter lesions in patients with Crohn's disease.
To investigate the incidence, characteristics, and predisposing factors for cerebral white matter lesions in patients with Crohn's disease. We retrospectively evaluated the incidence and characteristics of cerebral T2 white matter abnormalities in 54 patients with Crohn's disease and compared to 100 age-matched controls. We also investigated potential co-morbidities known to be associated with white matter abnormalities in Crohn's patients with normal and abnormal Magnetic Resonance Imaging (MRI). Seventy-two percent of patients with Crohn's disease had T2 white matter abnormalities, as compared with 34% of the age-matched controls (P < .001). Lesion severity and size were not significantly different between the two groups; however, periventricular distribution and fulfillment of the Barkhof MRI criteria were overrepresented in Crohn's population. History of hypertension, diabetes, and migraine; gender, duration of disease and prior exposure to anti-tumor necrosis factor were not significantly different between Crohn's patients with and without white matter abnormalities; however, patients with lesions were significantly older than those without. Patients with Crohn's disease have a higher incidence of white matter T2 hyperintensities as compared with controls. Age was the only significant factor for the abnormalities within Crohn's group. White matter T2 hyperintensities are likely another extra-intestinal manifestation of Crohn's disease.


Natural glass alteration under a hyperalkaline condition for about 4000 years.
Silicate glasses are durable materials in our daily life, but corrosion rate accelerates under alkaline aqueous environment. Such situation has raised concerns, for example, in nuclear waste disposal where vitrified wastes encounter to alkaline leachate from surrounding concrete materials. Here we report volcanic glass example surviving with a hyperalkaline groundwater (pH > 11) and high flow rate for about 4000 years. The tiny glass fragments were extracted from the volcanic ash layer sandwiched between ultramafic sediments using microanalytical techniques. Sharp elemental distributions at the glass surface, where amorphous-like smectite precursors and crystalline smectites coexist, suggest the corrosion by an interface-coupled dissolution-precipitation mechanism rather than inter-diffusion. The corrosion rate was maintained at, the minimum, 2.5 orders of magnitude less than the rate observed for fresh glass, even in the presence of Fe and Mg that might have consumed Si through the silicate precipitation.


Criminal and Civil Responsibility of the Donor in a Case of Transmission of Malaria by a Blood Transfusion in a Nonendemic Country.
The blood donation process is strictly regulated by law. The process includes the necessity of a medical history taken to determine if a donor is suitable to donate, which shall guarantee both donor and recipient safety. Supplementary screening for a limited number of infections is performed by antibody (HIV, HCV, syphilis) or antigen (HBV) tests or NAT (HIV, HCV, HBV). With regard to a possible infection due to (sexual) risk behavior or foreign travel, blood donation facilities are predominantly dependent on information provided by the donor. This is especially true for malaria in nonendemic areas such as Europe. Transmission of malaria by a blood transfusion in a nonendemic country that led to fulminant septic shock and death of the patient happened. From a legal perspective, the donor thus assumes a high level of responsibility with regard to the accuracy and completeness of the information provided on the donor questionnaire. Incorrect information may, as in this Austrian case reported, result in civil or criminal responsibility of the donor.


Analysis of the correlation between the longitudinal trajectory of SOFA scores and prognosis in patients with sepsis at 72 hour after admission based on group trajectory modeling.
To identify the distinct trajectories of the Sequential Organ Failure Assessment (SOFA) scores at 72 h for patients with sepsis in the Medical Information Mart for Intensive Care (MIMIC)-IV database and determine their effects on mortality and adverse clinical outcomes. A retrospective cohort study was carried out involving patients with sepsis from the MIMIC-IV database. Group-based trajectory modeling (GBTM) was used to identify the distinct trajectory groups for the SOFA scores in patients with sepsis in the intensive care unit (ICU). The Cox proportional hazards regression model was used to investigate the relationship between the longitudinal change trajectory of the SOFA score and mortality and adverse clinical outcomes. A total of 16,743 patients with sepsis were included in the cohort. The median survival age was 66 years (interquartile range: 54-76 years). The 7-day and 28-day in-hospital mortality were 6.0% and 17.6%, respectively. Five different trajectories of SOFA scores according to the model fitting standard were determined: group 1 (32.8%), group 2 (30.0%), group 3 (17.6%), group 4 (14.0%) and group 5 (5.7%). Univariate and multivariate Cox regression analyses showed that, for different clinical outcomes, trajectory group 1 was used as the reference, while trajectory groups 2-5 were all risk factors associated with the outcome (P < 0.001). Subgroup analysis revealed an interaction between the two covariates of age and mechanical ventilation and the different trajectory groups of patients' SOFA scores (P < 0.05). This approach may help identify various groups of patients with sepsis, who may be at different levels of risk for adverse health outcomes, and provide subgroups with clinical importance.


Interleukin 21 blockade modulates activated T- and B-cell homeostasis via B-cell activating factor pathway-mediated inhibition in a murine model of acute graft-versus-host disease.
Interleukin (IL) 21 plays a key role in the development of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. Therapeutic manipulation of IL-21 activity may improve acute GVHD during the early-posttransplant period. We investigated the mechanisms regulating T- and B-cells during IL-21 blockade in acute GVHD. Interleukin 21 blockade enhanced regulatory T and T helper (Th) 2 cell differentiation and inhibited Th1- and Th17-derived transcription factors and cytokines as a modulator of activated T-cells. Interleukin 21(-/-) cell recipients showed increased mature B- and marginal-zone B-cells, but decreased memory B-cells, germinal center formation, and plasma cells that did not lead to immunoglobulin production. B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are involved in the induction and maintenance of T- and B-cell responses. We observed decreased levels of only BAFF during acute GVHD and confirmed that mammalian target of rapamycin complex 1 was reduced by the BAFF/BAFF-receptor pathway. Therefore, this study suggests that IL-21 blockade modulates activated T- and B-cell homeostasis via BAFF-pathway-mediated inhibition in acute GVHD following murine allogeneic bone marrow transplantation.


c-di-GMP-binding protein, a new factor regulating cellulose synthesis in Acetobacter xylinum.
A protein which specifically binds cyclic diguanylic acid (c-di-GMP), the reversible allosteric activator of the membrane-bound cellulose synthase system of Acetobacter xylinum, has been identified in membrane preparations of this organism. c-di-GMP binding is of high affinity (KD 20 nM), saturable and reversible. The equilibrium of the reaction is markedly and specifically shifted towards the binding direction by K+. The c-di-GMP binding protein, structurally associated with the cellulose synthase, appears to play a major role in modulating the intracellular concentration of free c-di-GMP and thus may constitute an essential factor in regulating cellulose synthesis in vivo.


Correction: Characterizing surface wetting and interfacial properties using enhanced sampling (SWIPES).
Correction for 'Characterizing surface wetting and interfacial properties using enhanced sampling (SWIPES)' by Hao Jiang et al., Soft Matter, 2019, 15, 860-869, DOI: .


Clinical characteristics of 1544 Brazilians aged 60 years and over with laboratory evidence for SARS-CoV-2.
Infection with the new coronavirus responsible for Severe Acute Respiratory Syndrome (SARS-CoV-2) continues to spread worldwide. In Brazil, there are already more than 230 thousand dead, many of these older adults. To present the clinical characteristics of older Brazilian adults infected by COVID-19, in the epidemiological weeks (EW) 34-52, and to verify factors responsible for the increased risk of death. Retrospective and observational study conducted with secondary publicly available data, provided by the Brazilian Ministry of Health. 1,544 confirmed cases of registered COVID-19 infection were included between August 16 and December 26, 2020, aged 60 or older. Demographic data, comorbidity, symptoms for disease, clinical information: days of hospitalization, chest X-ray, type of RT-PCR. 48% of patients admitted to the ICU with evidence for SARS-CoV-2 died. Symptoms and comorbidities related to increased chance of death (OR) were immunodeficiency (188%), kidney disease (166%), neurological disease (103%), dyspnea (86%), pneumopathy (55%), O2 saturation <95% (53%), respiratory discomfort (49%), age (36%), sore throat (31%), and sex (0.5%). There was a 5% increase in the chance of death for each year of life. Heart disease and Diabetes mellitus were the most frequent comorbidities, but did not indicate an increased risk of death from SARS-CoV-2 infection. Age, sex, sore throat, dyspnea, respiratory discomfort, O2 saturation <95%, neurological disease, pneumopathy, immunodeficiency, and kidney disease were significantly associated with risk of death from COVID-19.


5-HT inhibits lateral entorhinal cortical neurons of the rat in vitro by activation of potassium channel-coupled 5-HT1A receptors.
Serotonin (1-40 microM) reduced input resistance by 20.6 +/- 6% and hyperpolarized stellate and pyramidal neurons of layers two and three of the lateral entorhinal cortex. 5-Carboxamidotryptamine, a 5-HT1 agonist, and the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin mimicked the action of serotonin. The reversal potential of 5-HT-mediated hyperpolarizations was sensitive to the extracellular K+ concentration, indicating a potassium conductance change. Serotonin treatment suppressed excitatory amino acid-mediated synaptic potentials (by 48%, Kd = 6.9 microM) and responses to exogenously applied glutamate (70.1 +/- 17% of control, n = 7), but did not alter paired-pulse facilitation, indicating a postsynaptic site of action. Intracellular application of QX-314, a blocker of potassium conductance, significantly reduced depression of synaptic potentials by 5-HT agonists. In cells filled with QX-314, responses to exogenously applied glutamate were not reduced by serotonin or 5-carboxamidotryptamine application. These results indicate that the observed conductance increase associated with 5-HT application accounts for most if not all of the observed depressant effects of 5-HT1A agonists on excitatory amino acid-mediated neurotransmission.


Estimating eye care workforce supply and requirements.
To estimate the workforce supply and requirements for eye care in the United States. Three models were constructed for analysis: supply of providers, public health need for eye care, and demand (utilization) for eye care. Ophthalmologists, other physicians, and optometrists were included in the models. Public health need was determined by applying condition-specific prevalence and incidence rates from population-based and other epidemiologic studies. Demand was determined by use of national databases, such as the National Ambulatory Care Survey, National Hospital Discharge Survey, and Medicare Part B. Time requirements for care were obtained through a stratified sample survey of the membership of the American Academy of Ophthalmology. Under modeling assumptions that use a work-time ratio of one between optometrists and ophthalmologists and between specialist and generalist ophthalmologists, a significant excess of eye care providers exists relative to both public health need and demand. Changes in the work-time ratio, work-hours per year per provider, care patterns for the same condition, or other factors could significantly reduce or eliminate the surplus relative to need. If optometrists are the preferred primary eye care provider, ophthalmologists would be in excess under all demand scenarios and all need scenarios where the optometrist to ophthalmologist work-time ratio is greater than 0.6. No excess of ophthalmologists would exist if ophthalmologists are the preferred primary eye care provider. Data on the appropriate work time ratio will help refine estimates of the imbalance between supply and requirements.


Accurate Assessment via Process Data.
Accurate assessment of a student's ability is the key task of a test. Assessments based on final responses are the standard. As the infrastructure advances, substantially more information is observed. One of such instances is the process data that is collected by computer-based interactive items and contain a student's detailed interactive processes. In this paper, we show both theoretically and with simulated and empirical data that appropriately including such information in the assessment will substantially improve relevant assessment precision.


Trigeminal and cervical radiculitis after tozinameran vaccination against COVID-19.
In this report, we describe a patient who developed an acute trigeminal neuritis and cervical radiculitis after receiving a Pfizer-BioNtech vaccination (tozinameran) against SARS-CoV-2.


Tape: an alternative to stirrups or wedges in positioning for infant cystoscopy.
Performing a cystourethroscopy in children can range from reviewing a 100 kg teenage male with posterior urethritis, to assessing a 3 kg neonate with posterior urethral valves. Across this range the patient needs to be positioned in a way that allows passage of the rigid cystoscope and visualisation of the urethra and bladder. We describe a technique for positioning the legs of infants for cystoscopy using skin friendly tape, rather than wedges, stirrups or boots. The advantage of this being that it is cheap, adaptable and holds the infant in the perfect position, without needing complex equipment.


"What Matters to Me": What pediatric stem cell transplant patients want their providers to know.
Engagement of pediatric patients in conversations about their healthcare can lead to better psychological and physical outcomes. We used a communication tool called "What Matters to Me" (WMTM) to provide insight into what seriously ill children want to tell their healthcare providers about what is important to them. Content analysis of completed tools. 21 pediatric patients hospitalized on a stem cell transplant unit. Direct content analysis. Three themes were identified: importance of personal identity, preferences for communication, and preferences for care delivery. Children and adolescents with serious medical illnesses are willing to share what matters to them with members of their care team. WMTM provides an opportunity for pediatric units to systematically offer this opportunity to pediatric patients. Children and adolescents are able to identify and share what matters to them with their healthcare providers, providing an opportunity for engagement in medical care.


A radioimmunoassay for human antibody specific for microbial antigens.
A simple and sensitive method for detecting and quantitating antibody specific for microbial antigens is described. Bacterial, fungal, parasitic or viral antigens attached to bromoacetyl cellulose or the intact cells themselves were added to a series of two-fold dilutions of human serum. After a short incubation period, which allowed human antibody to attach to the antigens, the complex was thoroughly washed and carbon-14 labeled anti-human light chain antibody was added to each dilution. The resulting complex was washed, collected on a filter pad, placed in a scintillation vial and radioassayed. The relationship between radioactivity bound and --log2 of the serum dilution was linear. The endpoint for each assay and a confidence interval was calculated by doing inverse prediction from simple linear regression. Results obtained using this assay indicated the presence of antibody in a pool of normal human sera specific for herpes virus and for both cell surface and intracellular antigens of Streptococcus mutans, Naegleria fowleri, and Cryptococcus neoformans. In general the dominant response was against the intracellular antigens rather than cell surface antigens.


Biotin derivatives of endothelin: utilization for affinity purification of endothelin receptor.
Three different types of biotinylated endothelin 1 (ET-1) derivatives, [Cys1]-biotinylated ET-1, [Lys9]-biotinylated ET-1, and [Cys1][Lys9]-dibiotinylated ET-1, were obtained when the biotinylation reaction was carried out with sulfosuccinimidyl-6-(biotinamido)hexanoate in an aqueous solvent. The binding of [Lys9]-biotinylated ET-1 to the ET receptor was as efficient as that of natural ET-1, whereas the binding of either [Cys1]-biotinylated ET-1 or [Cys1][Lys9]-dibiotinylated ET-1 was significantly reduced. When ET-1 was reacted with succinimidyl-6-(biotinamido)hexanoate in an organic solvent, ET-1 was exclusively modified at lysine 9. The ET receptor was then isolated from human placenta by affinity chromatography with [Lys9]-biotinylated ET-1 and avidin-agarose. The purified ET receptor was active in ET binding and was resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis into two polypeptides with apparent molecular masses of 45 and 35 kDa. The NH2-terminal amino acid sequence indicated that the two polypeptides were from an identical subtype of the ET receptor (ETB, the ligand-nonselective type). A signal peptide from Met1 to Gly26 was missing from the 45-kDa ETB, whereas 64 amino acids at the NH2 terminus were missing from the 35-kDa ETB due to proteolytic cleavage which occurred between Arg64 and Ser65. Indeed, incubation of purified ETB with endopeptidase Arg-C resulted in degradation of the 45-kDa ETB, giving rise to the 35-kDa species by a specific cleavage at Arg64. The 35-kDa ETB was active in binding to ET-1, indicating that the NH2-terminal 64-amino-acid residues are not essential for ligand binding.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of Zr substitution on soot combustion over cubic fluorite-structured nanoceria: Soot-ceria contact and interfacial oxygen evolution.
Ceria is widely used as a catalyst for soot combustion, but effects of Zr substitution on the reaction mechanism is ambiguous. The present work elucidates effects of Zr substitution on soot combustion over cubic fluorite-structured nanoceria. The nanostructured CeO2, Ce0.92Zr0.08O2, and Ce0.84Zr0.16O2 composed of 5-6 nm crystallites display Tm-CO2 (the temperature at maximum CO2 yield) at 383, 355, and 375°C under 10 vol.% O2/N2, respectively. The size of agglomerate decreases from 165.5 to 51.9-57.3 nm, which is beneficial for the soot-ceria contact. Moreover, Zr increases the amount of surface oxygen vacancies, generating more active oxygen (O2- and O-) for soot oxidation. Thus, the activities of Ce0.92Zr0.08O2 and Ce0.84Zr0.16O2 in soot combustion are better than that of CeO2. Although oxygen vacancies promote the migration of lattice O2-, the enriched surface Zr also inhibits the mobility of lattice O2-. Therefore, the Tm-CO2 of Ce0.84Zr0.16O2 is higher than that of Ce0.92Zr0.08O2. Based on reaction kinetic study, soot in direct contact with ceria preferentially decomposes with low activation energy, while the oxidation of isolated soot occurs through diffusion with high activation energy. The obtained findings provide new understanding on the soot combustion over nanoceria.


Designing in vitro assay systems for hazard characterization. basic strategies and related technical issues.
Adverse effects of chemicals on humans are typically assessed following four steps: hazard identification, hazard characterization, exposure assessment and risk characterization. Hazard characterization is defined as the qualitative and/or quantitative evaluation of the nature of the adverse effects associated with biological, chemical and physical agents of interest. For chemical agents, hazard characterization is based on a series of in vitro and/or in vivo data obtained from mechanistic, kinetic and dose-response studies on the agent of concern, which are analyzed and integrated for extrapolation to eventually match human conditions. Thus, an accurate experimental design and the development of test methods capable of generating data relevant to hazard characterization are essential for the useful risk assessment of chemicals, including inhaled materials. It should, however, be stressed that hazard characterization has widely been limited to single chemicals. The hazard characterization of airborne mixtures therefore poses a new problem in toxicology, which calls for a novel approach to its scientific assessment. During the last three decades, a number of epidemiological and experimental studies have been conducted focusing on two kinds of inhaled complex mixtures, namely cigarette smoke and diesel exhausts. A new approach to the assessment of airborne complex mixtures may be elaborated through the appropriate, combined use of the findings of such studies. In this context, the present review article is intended to illustrate some basic strategies for and technical issues related to the hazard characterization of inhaled complex mixtures, thereby taking up representative epidemiological and experimental data from published papers on tobacco smoke.


Climate change and elevational range shifts in insects.
On mountains, unique in their steep and rapid climatic gradients, many insects are shifting their elevational range limits to track recent temperature change. In a review of the range shift literature to date, most of the 1478 montane insect populations tested so far are shifting to higher elevations, but there is conspicuous variation in the responses. We discuss the impact of study methodology as well as potential abiotic and biotic factors that may underlie this variation in climate change response. We encourage more empirical studies spanning greater insect biodiversity and directly testing how variation in species' traits, biogeography, and abiotic-biotic context shapes variation in range shift responses.


Recycling waste classification using emperor penguin optimizer with deep learning model for bioenergy production.
The growth and implementation of biofuels and bioenergy conversion technologies play an important part in the production of sustainable and renewable energy resources in the upcoming years. Recycling sources from waste could efficiently ease the risk of world source strain. The waste classification was a good resolution for separating the waste from the recycled objects. It is inefficient and expensive to rely solely on manual classification of garbage and recycling sources. Convolutional neural networks (CNNs) have lately been used to classify recyclable waste, and this is the primary way for recycling the waste. This study presents a recycling waste classification using emperor penguin optimizer with deep learning (RWC-EPODL) model for bioenergy production. RWC-EPODL model focuses on recycling waste materials recognition and classification. When it comes to detecting and classifying trash, the RWC-EPODL model uses two stages. At the initial stage, the RWC-EPODL model uses AX-RetinaNet model for the recognition of waste objects. In addition, Bayesian optimization (BO) algorithm is applied as hyperparameter optimizer of the AX-RetinaNet model. Following the EPO algorithm with a stacked auto-encoder (SAE) model, the EPO algorithm is used to fine-tune the parameters of the SAE technique for trash classification. The RWC-EPODL model's experimental validation is examined through a number of studies. The RWC-EPODL approach has a 98.96 percent success rate. The comparative result analysis reported the better performance of the RWC-EPODL model over recent approaches.


What do parents want for their children who are overweight when visiting the paediatrician?
The objective of this study was to determine whether parental preferences regarding primary care weight-management strategies differ by child age, gender, overweight severity, race/ethnicity or parental agreement that their child is overweight. A survey was administered to parents of 2- to 18-year-old children who are overweight at an academic primary-care clinic regarding perception of child overweight, helpful/harmfulness of having the child present during weight discussions, and dietary-advice preferences. Multivariable analyses examined factors associated with preferred weight-management strategies, after adjustment for parent/child characteristics. Eighty-three per cent of parents agreed that a child's presence during weight discussions is helpful/very helpful, 74% that paediatricians should prescribe specific diets, and 55% preferred specific vs. general dietary advice only (N = 219). In multivariable analyses, characteristics associated with helpfulness of child presence included older child age (vs. 2-5 year olds, 6-11 year olds: odds ratio [OR], 4.6; 95% CI, 1.3-16; 12- to 18-year-olds: OR, 23; 95% CI, 4-136), male gender (OR, 5.0; 95% CI, 1.7-10) and obesity (vs. overweight: OR, 2.8; 95% CI, 1.7-12). Characteristics associated with preferring specific diets included Latino race/ethnicity (OR, 5.3; 95% CI, 3-12), older age (vs. 2-5 year olds, 6-11 year olds: OR, 2.8; 95% CI, 1.1-7; 12-18 year olds: OR, 3.7; 95% CI, 1.5-10) and agreement that the child is overweight (OR, 2.3; 95% CI, 1.1-5) and, for specific dietary advice, older age (vs. 2-5 year olds: OR, 2.3; 95% CI, 1.1-5) and agreement that the child is overweight (OR, 2.1; 95% CI, 1.2-4). Findings suggest that weight-management strategies tailored to child age, gender, over-weight severity, race/ethnicity and parental agreement that their child is overweight may prove useful in improving child weight status.


Calcium mediated functional interplay between myocardial cells upon laser-induced single-cell injury: an in vitro study of cardiac cell death signaling mechanisms.
The electromechanical function of myocardial tissue depends on the intercellular communication between cardiomyocytes (CMs) as well as their crosstalk with other cell types. Cell injury, and subsequent death trigger inflammation as in myocardial infarction (MI) resulting in myocardial remodeling. Although mechanisms underlying myocardial cell death have been studied so far, the signaling events following single cell death and spontaneous response of connected cells in the myocardial tissue is still barely understood. Here, we investigated the effect of laser-induced single cell death on Calcium (Ca2+) concentrations and transport in myocardial cell clusters in vitro. Spatial and temporal changes in intracellular Ca2+ concentrations [Ca2+]i were studied using a fluorescent calcium indicator, Fluo-4AM. Spontaneous signaling events following cell death were studied in rat embryonic cardiomyocytes and non-myocytes using separate cell culture systems. Cell death triggered spontaneous increase in intracellular Ca2+ levels ([Ca2+]i) of surrounding cells. The spread of the observed propagating Ca2+ signal was slow and sustained in myocytes while it was rapid and transient in fibroblasts (Fbs). Further, sustained high Ca2+ levels temporarily impaired the contractility in CMs. The cell-type specific effect of ablation was confirmed using separate cultures of CMs and Fbs. Comparing Ca2+ propagation speed in myocytes and fibroblasts, we argue for a diffusion-driven Ca2+ propagation in myocytes, but not in fibroblasts. Radial and sequential Ca2+ diffusion across the CMs through cell-cell contacts and presence of Cx43-based intercellular junctions indicated a gap junction flow of Ca2+. These findings illustrate the spontaneous Ca2+-mediated functional interplay in myocardial cell clusters upon mechanical injury and, further, the difference in Ca2+ signaling in cardiomyocytes and fibroblasts. Video Abstract.


Duchenne muscular dystrophy.
Advances in the understanding of the genetic basis for Duchenne muscular dystrophy over the past 4 years has led to the quick application of molecular diagnostics. More recently, attention has turned towards acquiring a better understanding of dystrophin biochemistry and the pathophysiologic consequences of dystrophin deficiency.


A study of excitatory neuromuscular transmission in the bovine trachea.
1. The excitatory innervation of bovine tracheal smooth muscle has been studied with the sucrose-gap apparatus.2. Single 2 ms electrical stimuli applied to the whole tissue excited intrinsic nerves, and produced a small transient depolarization of the smooth muscle, the excitatory junction potential (e.j.p.). The e.j.p. caused a twitch-type contraction; twitches and e.j.p.s summated during repetitive stimulation but facilitation was not observed, and action potentials were never elicited.3. The effects of electrical stimulation could be abolished by atropine (5 x 10(-7) mol/l) and augmented by neostigmine (4 x 10(-6) mol/l), and were mimicked by exogenous acetylcholine (1.0 mug/ml).4. With the electron microscope, the density of innervation was found to be low (one axon per ninety smooth muscle cells). Axons were found in small groups in the clefts between bundles of cells, but no axons penetrated within the muscle bundles. Naked axon varicosities containing agranular vesicles were seen, but no axon approached within 200 nm of a smooth muscle cell.5. It is difficult to reconcile the sparsity of innervation with the dependence of the tissue on nerve excitation to initiate activity.


Physical and mental health complications post-COVID-19: Scoping review.
Several long-lasting health complications have been reported in previous coronavirus infections. Therefore, the aim of this study was to review studies that evaluated physical and mental health problems post-COVID-19. Articles for inclusion in this scoping review were identified by searching the PubMed, Scopus, Web of Science and Google Scholar databases for items dated from 1 January to 7 November 2020. Observational studies evaluating physical health (musculoskeletal symptoms, functional status) or mental health status with a follow-up period longer than 1 month after discharge or after the onset of symptoms were included. This scoping review included 34 studies with follow-up periods of up to 3 months post-COVID-19. The most commonly reported physical health problems were fatigue (range 28% to 87%), pain (myalgia 4.5% to 36%), arthralgia (6.0% to 27%), reduced physical capacity (six-minute walking test range 180 to 561 m), and declines in physical role functioning, usual care and daily activities (reduced in 15% to 54% of patients). Common mental health problems were anxiety (range 6.5% to 63%), depression (4% to 31%) and post-traumatic stress disorder (12.1% to 46.9%). Greater fatigue, pain, anxiety and depression were reported in female patients and individuals admitted to intensive care. An overall lower quality of life was seen up to 3 months post-COVID-19. This review highlights the presence of several physical and mental health problems up to 3 months post-COVID-19. The findings point to the need for comprehensive evaluation and rehabilitation post-COVID-19 to promote quality of life.


Efficacy of ethanol ablation as a treatment of benign head and neck cystic lesions.
To evaluate the efficacy and safety of ethanol ablation in the treatment of benign head and neck cystic lesions. A total of 25 patients who received ethanol ablation (EA) of head and neck cystic lesions by an otolaryngologist at a single institution between October 2017 and October 2020 were identified. Patient demographics, clinical characteristics, treatment details, and treatment outcomes at follow up visits were obtained by retrospective review of electronic medical records. 25 patients who underwent ethanol ablation of head and neck cystic lesions were included, with a mean age of 49.1 years old (Interquartile range (IQR),32.5-65.5 years) and 12 males (47.0%). The most common cysts treated with EA were thyroglossal duct cysts (n = 8, 32.0%) and lymphoepithelial parotid cysts (n = 7, 28.0%). The mean volume prior to treatment was 10.57 mL (IQR, 1.58-8.81 mL). Mean volume following EA was 1.30 mL (range, 0.10-0.97 mL) with 74.40% cyst reduction by volume (IQR, 48.56-96.29%) (p = 0.002). The mean time to the last follow-up was 5 months (range, 3-6 months). One patient received surgery despite treatment success to obtain a definitive diagnosis of the mass. No other patients received further surgical management. The treatment success of EA, as defined by >70% volume reduction or the resolution of symptoms, was 92.0%. All patients were satisfied with the outcome and had no reported complications. EA is an effective and safe alternative to surgery for the treatment of head and neck cystic lesions that can be performed in an outpatient setting by an otolaryngologist.


Forensic evaluation of two nucleic acid extraction systems and validation of a RT-qPCR protocol for identification of SARS-CoV-2 in post-mortem nasopharyngeal swabs.
The COVID-19 outbreak has represented a challenge for the international scientific community and particularly for forensic sciences. The lack of Coronavirus post-mortem testing led the National Institute of Toxicology and Forensic Sciences (INTCF) from Spain to verify the performance and utility of a quantitative reverse transcription PCR (RT-qPCR) clinical diagnosis protocol for SARS-CoV-2 detection (TaqPath™ COVID-19 CE-IVD RT-PCR Kit), to shed light on the cause of death (COD) in potentially COVID-19 cases in judicial autopsies. Two different RNA extraction methods were also tested (EZ1® DSP Virus Kit on the EZ1® Advanced XL robot versus MagMAX™ Viral/Pathogen Nucleic Acid Isolation Kit) regarding extraction efficiency, precision and contamination. RT-qPCR was evaluated for precision, specificity, limit of detection and concordance. Both the automated and the manual RNA extraction procedures showed good efficiency, but the automated virus extraction by bio-robot produced more reproducible results than the manual extraction. The SARS-CoV-2 RT-qPCR assay showed high sensitivity with a detection limit up to 10 copies/reaction and high specificity, as no cross-reactivity was detected between any of the 12 different RNA viruses tested, including three types of coronaviruses (SARS-CoV, NL63 and 229E). Reproducibility and repeatability of the studied method as well as concordance with other SARS-CoV-2 molecular detection protocols were also demonstrated.


Prevalence and progression of chronic kidney disease among patients with type 2 diabetes: Insights from the DISCOVER study.
We report the prevalence and change in severity of chronic kidney disease (CKD) in DISCOVER, a global, 3-year, prospective, observational study of patients with type 2 diabetes (T2D) initiating second-line glucose-lowering therapy. CKD stages were defined according to estimated glomerular filtration rate (eGFR). Overall, 7843 patients from 35 countries had a baseline serum creatinine measurement. Of these (56.7% male; mean age: 58.1 years; mean eGFR: 87.5 mL/min/1.73 m2 ), baseline prevalence estimates for stage 0-1, 2, 3 and 4-5 CKD were 51.4%, 37.7%, 9.4% and 1.4%, respectively. A total of 5819 patients (74.2%) also had at least one follow-up serum creatinine measurement (median time between measurements: 2.9 years, interquartile range: 1.9-3.0 years). Mean eGFR decreased slightly to 85.7 mL/min/1.73 m2 over follow-up. CKD progression (increase of ≥1 stage) occurred in 15.7% of patients, and regression (decrease of ≥1 stage) in 12.0%. In summary, a substantial proportion of patients with T2D developed CKD or had CKD progression after the initiation of second-line therapy. Renal function should be regularly monitored in these patients, to ensure early CKD diagnosis and treatment.


Ethanol utilization regulatory protein: profile alignments give no evidence of origin through aldehyde and alcohol dehydrogenase gene fusion.
The suggestion that the ethanol regulatory protein from Aspergillus has its evolutionary origin in a gene fusion between aldehyde and alcohol dehydrogenase genes (Hawkins AR, Lamb HK, Radford A, Moore JD, 1994, Gene 146:145-158) has been tested by profile analysis with aldehyde and alcohol dehydrogenase family profiles. We show that the degree and kind of similarity observed between these profiles and the ethanol regulatory protein sequence is that expected from random sequences of the same composition. This level of similarity fails to support the suggested gene fusion.


Endoscopic Ultrasound-Guided Fine Needle Aspiration versus Percutaneous Ultrasound-Guided Fine Needle Aspiration in Diagnosis of Focal Pancreatic Masses.
Pancreatic carcinoma is one of the leading cancer morbidity and mortality world-wide. Controversy has arisen about whether the percutaneous approach with computed tomography/ultrasonography-guidance fine needle aspiration (US-FNA) or endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the preferred method to obtain diagnostic tissue. Our purpose of this study is to compare between the diagnostic accuracy of EUS-FNA and percutaneous US-FNA in diagnosis of pancreatic cancer. A total of 197 patients with pancreatic masses were included in the study, 125 patients underwent US-FNA (Group 1) and 72 patients underwent EUS-FNA (Group 2). EUS-FNA has nearly the same accuracy (88.9%) as US-FNA (87.2%) in diagnosis of pancreatic cancer. The sensitivity, specificity, positive predictive value and negative predictive value for EUS-FNA was 84%, 100%, 100%, 73.3% respectively. It was 85.5%, 90.4%, 94.7%, 76% respectively for US-FNA. EUS-FNA had a lower complication rate (1.38%) than US-FNA (5.6%). EUS-FNA has nearly the same accuracy as US-FNA of pancreatic masses with a lower complication rate.


Altered directional connectivity in Parkinson's disease during performance of a visually guided task.
Recent animal studies have suggested that cortical areas may play a greater role in the modulation of abnormal oscillatory activity in Parkinson's disease (PD) than previously recognized. We investigated task and medication-dependent, EEG-based directional cortical connectivity in the θ (4-7Hz), α (8-12Hz), β (13-30Hz) and low γ (31-50Hz) frequency bands in 10 PD subjects and 10 age-matched controls. All subjects performed a visually guided task previously shown to modulate abnormal oscillatory activity in PD subjects. We examined the connectivity in the simultaneously-recorded EEG between 5 electrode regions of interest (fronto-central, left and right sensorimotor, central and occipital) using a sparse, multivariate, autoregressive-based partial directed coherence method. For comparison, we utilized traditional Fourier analysis to evaluate task-dependent frequency spectra modulation in these same regions. While the spectral analysis revealed some overall differences between PD and control subjects, it demonstrated relatively modest changes between regions. In contrast, the partial directed coherence-based analysis revealed multifaceted, regionally and directionally-dependent alterations of connectivity in PD subjects during both movement preparation and execution. Connectivity was particularly altered posteriorly, suggesting abnormalities in visual and visuo-motor processing in PD. Moreover, connectivity measures in the α, β and low γ frequency ranges correlated with motor Unified Parkinson's Disease Rating Scores in PD subjects withdrawn from medication. Levodopa administration only partially restored connectivity, and in some cases resulted in further exacerbation of abnormalities. Our results support the notion that PD is associated with significant alterations in connectivity between brain regions, and that these changes can be non-invasively detected in the EEG using partial directed coherence methods. Thus, the role of EEG to monitor PD may need to be further expanded.


Heterotrophic capacities of Plectonema boryanum.
Acquisition of the dark heterotrophic growth capacity on glucose in Plectonema boryanum involves both adaptation and enrichment of a fast-growing genotype. The adaptation includes induction of functions involved in glucose incorporation and increase in glucose-6-phosphate dehydrogenase activity. Photosynthetic products are implicated in the control of both systems. Efficient energy conversion in the dark, as measured by cyanophage multiplication, correlates in time with the increase in potential for glucose incorporation while heterotrophic growth capacity correlates with the increase in glucose-6-phosphate dehydrogenase activity. The lower efficiency of heterotrophic growth compared to photoautotrophic growth is discussed in light of the conservation of the photosynthetic potency in the heterotrophic cells.


IL-36 promotes anti-viral immunity by boosting sensitivity to IFN-α/β in IRF1 dependent and independent manners.
The functions of the IL-36 cytokines remain poorly understood. We report a previously unrecognized mechanism whereby IL-36 promotes innate antiviral immunity in mouse and human models of herpes simplex virus-1 (HSV-1) infections. HSV-1 actively suppresses production of type I interferon (IFN); our data reveal that IL-36 overcomes this immune evasion strategy by increasing cellular sensitivity to IFN. IL-36β deficient mice display impaired IFN responses and poorly restrict viral replication in skin keratinocytes. In mouse and human keratinocytes IL-36 elicits an antiviral state driven by STAT1 and STAT2 via enhanced expression of IFNAR1 and IFNAR2 subunits of the type I IFN receptor. The degree of IFN regulatory factor 1 (IRF1) involvement is species dependent, with IRF1 playing a more prominent role in human cells. Similar mechanisms are activated by IL-1. Overall, IL-36 acts as an antiviral cytokine by potentiating type I IFN signaling and thereby upholds immune responses to viruses that limit the production of IFNs.


Emission characteristics, environmental impact assessment and priority control strategies derived from VOCs speciation sourcely through measurement for wooden furniture-manufacturing industry in China.
Volatile organic compounds (VOCs) from wooden furniture-manufacturing industry is an important emission source. The VOC content levels, source profiles, emission factors and inventories, O3 and SOA formation, and priority control strategies were investigated from the source. One hundred sixty-eight representative woodenware coatings were sampled, and VOC species and contents were determined. The VOC, O3 and SOA emission factors per gram of coatings for three types of woodenware coatings were quantified. The total VOC, O3 and SOA emissions from wooden furniture-manufacturing industry in 2019 were 976,976 t/a, 2,840,282 t/a, 24,970 t/a, and solvent-based coatings accounted for 98.53 %, 99.17 % and 99.6 % of the total VOC, O3 and SOA emissions, respectively. Aromatics and esters were major organic groups, contributing 49.80 % and 36.03 % to total VOC emissions, respectively. Aromatics contributed 86.14 % and 100 % to total O3 and SOA emissions, respectively. The top 10 species contributing to VOC, O3 and SOA had been identified. Four benzene series, including o-Xylene, m-Xylene, toluene and ethylbenzene, were ranked as the first-class priority control species, accounting for 85.90 % and 99.89 % of the total O3 and SOA, respectively. Priority should be given to solvent-based coatings, aromatics and four benzene series for future O3 and SOA reduction for wooden furniture-manufacturing industry.


Detection of systemic pesticide residues in tea products at trace level based on SERS and verified by GC-MS.
Surface-enhanced Raman spectroscopy (SERS) has the potential to detect pesticide residues in agricultural products. However, some systemic pesticides, such as chlorpyrifos, can enter the plant tissue, and not just stay on the surface. Consequently, many SERS studies halted at practical application because of its complexity. In this work, SERS technology was used to detect chlorpyrifos residues in tea products at the semiquantitative level. A simple pretreatment method effectively avoided interference of other fluorescent substances, and all major peaks could be distinguished on the basis of a novel substrate. A principal component analysis algorithm was applied to form a regression model, and a nanogram detection limit was obtained. Furthermore, chlorpyrifos residues in the same tea products were also measured by gas chromatography-mass spectrometry, and the results show a small range of errors. From the comparative study of the two detection methods, the results suggest the great promise of SERS technology for rapid inspection of agricultural products.


[Primary extragonadal choriocarcinoma of the bladder. A case report with a compilation of the 19 cases published so far].
We report on a 73-year-old man with a primary extragonadal choriocarcinoma of the urinary bladder associated with transitional cell carcinoma. So far only 19 cases of choriocarcinoma of the bladder have been published in the literature. With reference to the cases reported in the English literature, the relationships between serum beta-HCG level, mode of therapy and clinical course are pointed out. Finally, the possible explanations for pathogenesis are discussed and the signs and symptoms that are mandatory for diagnosis of this entity are defined.


The structure of O-polysaccharide isolated from Cronobacter universalis NCTC 9529T.
The O-polysaccharide (OPS) was isolated from Cronobacter universalis NCTC 9529(T), a new species in the genus Cronobacter, which was created by the reclassification of the species Enterobacter sakazakii. Purified polysaccharide was analyzed by NMR spectroscopy ((1)H, COSY, TOCSY, ROESY, HSQC, and HSQC-TOCSY) and chemical methods. The monosaccharide derivatives were analyzed by gas chromatography and gas chromatography-mass spectrometry. These experiments enabled the type and number of monosaccharides in the repeating unit of OPS, their positions of linkages, and absolute configuration to be determined. Together the chemical analysis established a structure of the OPS of C. universalis NCTC 9529(T). [structure: see text]. OPS isolated from C. universalis was structurally characterized for the first time.


Tandem autologous hematopoietic cell transplantation with sequential use of total marrow irradiation and high-dose melphalan in multiple myeloma.
The goal of this phase II trial was to evaluate safety and efficacy of a tandem autologous hematopoietic cell transplantation (auto-HCT) using sequentially total marrow irradiation (TMI) at the dose of 12 Gy (4 Gy on days -3, -2, and -1) and melphalan 200 mg/m2 for patients with multiple myeloma (MM). TMI was performed using helical tomotherapy. Additional "boosts" (total 24 Gy) were applied for patients with active lesions as revealed by PET-FDG. Fifty patients with median age 58 years (41-64 years) were included and received tandem auto-HCT. TMI resulted in absolute neutropenia in all patients. Grade 3 infections were reported in 30% patients. Other toxicities were rare. Proportion of patients who achieved at least very good partial response increased from 46% before the first auto-HCT to 82% after tandem transplantation. Complete remission rates changed from 10% to 42%, respectively. The probabilities of overall and progression-free survival at 5 years were 74% and 55%, respectively. No patient died without progression. We conclude that conditioning with TMI ± PET-guided "boosts" represents personalized treatment approach in MM and is characterized by very good toxicity profile. Tandem auto-HCT using TMI in sequence with high-dose melphalan appears safe with encouraging early efficacy.


The Role of Anterior Ankle Arthroscopy in the Management of Ankle Arthritis: Literature Review, Patient Evaluation, Goals of Treatment and Technique.
The current body of literature regarding anterior ankle arthroscopic debridement for anterior ankle impingement (AAI) cases with ankle osteoarthritis (OA) has significant limitations. The reported poor outcomes lack the necessary rigor in patient selection, preoperative evaluations and in most reports, the use of a systematic operative approach. Furthermore, the lack of postoperative evaluation by authors using physical examination and radiologic studies to determine the etiology of ongoing pain leaves open the possibility that treatment of impingement was incomplete. For these reasons, it would be inappropriate to conclude that anterior arthroscopic debridement has no role in the treatment of ankle OA. Critical analysis of some studies provides encouragement that this can be a useful intermediate treatment of appropriately selected patients with AAI and ankle OA. The level of required detail in the physical examination and radiologic evaluation is much greater than for more straight-forward cases of soft tissue impingement or simple osteophyte impingement in otherwise healthy joints. The success of the treatment requires a systematic approach to the evaluation and performance of the procedure, which is perhaps why results in the literature have been suboptimal in most series. Future studies should apply this rigorous approach to patient selection, procedure performance, and postoperative analysis to best clarify which patients can be best served with this procedure as part of the various intermediate treatment options for ankle OA.


[Nucleic acid and ribonucleoprotein status during early development of fish embryos (Salmo irideus and Salmo trutta fario)].
1. The total amount of nucleic acids as well as DNA and RNA were analysed biochemically in embryos of the troutsS. irideus andS. trutta fario from cleavage to early differentiation stages. In the same developmental stages ribonucleoprotein (RNA and basic protein) was investigated cytochemically at different embryonic regions. The phase of gastrulation was of main interest. 2. The results of both methods show that the quantity of RNA and ribonucleoprotein increases beginning with themorula stage. The maximum is reached in theblastula. 3. When during the blastoderm stage RNA and basic protein are stained histochemically a characteristic gradient of intensity can be determined. From the increase of RNA and basic protein in periblast and blastoderm and from the gradual staining effect itself one can conclude that RNA and basic protein is transported from the yolk through the periblast into the embryo. There should exist atransfer of substances possibly as ribonucleoprotein particles. The limited time of this transfer during early embryogenesis shows that this phenomenon is not the result of energetic yolk utilization but it is connected with the following differentiation processes. 4. After injection of actinomycin D into the blastocoel development is stopped at the beginning ofgastrulation. Therefore a new synthesis of messenger RNA should be necessary for further development. 5. The ribosomal RNA is constant duringgastrulation but the amount of basic protein decreases in this time. During neurulation and the beginning differentiation phase a new increase of RNA takes place but now the quantity of basic protein does not change. 6. In contrast to investigations of the Urodele development in the trout embryo no change of RNA and basic protein is found during gastrulation in the invaginating material and the covering neuroectoderm. Therefore no transfer of substances takes place between the two blastemas. There are many differences in the embryonic development of Urodela and Teleosts. Nevertheless in both classesa relation between the yolk system and the embryonic blastema results in the beginning of thedifferentiation processes. This results point to the possible morphogenetic importance of the yolk system.


Protein Nutritional Status and Frailty: A Mendelian Randomization Study.
Observational studies have suggested that better protein nutritional status may contribute to prevention of frailty. We sought to examine this hypothesis using a Mendelian randomization (MR) analysis. We conducted a two-sample MR study using GWAS summary statistics data of the UK Biobank. We applied genetically predicted serum albumin as a primary exposure measure and serum total protein as a secondary exposure measure. The outcome measure was the Rockwood frailty index (FI) based on 49 deficits from 356,432 individuals (53.3% of them were women, with a mean ± SD age of 56.7 ± 8.0 y. The association between serum protein measures and FI was mainly analyzed by use of the inverse variance weighted method. A genetically predicted serum albumin concentration was not statistically significantly associated with FI in the full sample. However, in women, we observed a preventive association between genetically predicted serum albumin and FI (β = -0.172 per g/L; 95% CI: -0.336, -0.007; P = 0.041). In the full sample, genetically predicted serum total protein was inversely associated with FI (β: -0.153 per g/L; 95% CI: -0.251, -0.056; P = 0.002). In both women and men, higher serum total protein was significantly inversely associated with FI; regression coefficients were -0.148 per g/L (95% CI: -0.287, -0.009; P = 0.037) for women, -0.154 per g/L (95% CI: -0.290, -0.018; P = 0.027) for men. The present MR study implies that better protein nutritional status modestly contributes to reducing the risk of frailty.


Loss of tafazzin results in decreased myoblast differentiation in C2C12 cells: A myoblast model of Barth syndrome and cardiolipin deficiency.
Barth syndrome (BTHS) is an X-linked genetic disorder resulting from mutations in the tafazzin gene (TAZ), which encodes the transacylase that remodels the mitochondrial phospholipid cardiolipin (CL). While most BTHS patients exhibit pronounced skeletal myopathy, the mechanisms linking defective CL remodeling and skeletal myopathy have not been determined. In this study, we constructed a CRISPR-generated stable tafazzin knockout (TAZ-KO) C2C12 myoblast cell line. TAZ-KO cells exhibit mitochondrial deficits consistent with other models of BTHS, including accumulation of monolyso-CL (MLCL), decreased mitochondrial respiration, and increased mitochondrial ROS production. Additionally, tafazzin deficiency was associated with impairment of myocyte differentiation. Future studies should determine whether alterations in myogenic determination contribute to the skeletal myopathy observed in BTHS patients. The BTHS myoblast model will enable studies to elucidate mechanisms by which defective CL remodeling interferes with normal myocyte differentiation and skeletal muscle ontogenesis.


18F-labelled N,N-dimethylamphetamine analogues for brain imaging studies.
The radiochemical yields of nine N,N-dimethyl-2-(substituted phenyl)-isopropylamines (amphetamine analogues) were determined following reaction with [18F]acetyl hypofluorite in a 0.1 M HCl solution at room temperature. The meta-dimethoxy substituted amphetamines gave the highest radiofluorination yields (24-32% at EOB). Purification of the 18F-labelled amphetamines was achieved in 10-20 min. 5-18F-2,4-Dimethoxy-N,N-dimethylamphetamine (5-18F-2,4-DNNA) was utilized to determine brain and lung uptake in rates. Positron emission tomography studies were conducted in a dog to determine the dynamic brain uptake and retention of this agent. The 5-18F-2,4-DNNA exhibited decreased initial uptake and more rapid loss of radioactivity in cerebral tissue compared to the iodinated homologue.


Spatiotemporal variation of nitrogen and phosphorus and its main influencing factors in Huangshui River basin.
The foundation of managing excess nutrients in river is the identification of key physical processes and the control of decisive influencing factors. The existing studies seldom consider the influence of rainfall-runoff relationship and only focus on a few anthropogenic activities and natural attributes factors. To address this issue, a comprehensive set of influencing factors including rainfall-runoff relationship (represented by runoff coefficient), basic physical and chemical parameters of water quality, land use types, landscape patterns, topography, and socioeconomic development was constructed in this study. M-K test and cluster analysis were conducted to identify the temporal mutation and spatial clustering characteristics of NH3-N and TP in Huangshui River basin, respectively. Partial least squares regression was used to elucidate the linkages between water contaminants and the factors. As shown in the results, the temporal mutations of NH3-N and TP were obvious in the middle reaches, with 4 out of 7 catchments in the middle reaches have a larger number of mutations of NH3-N than other catchments. The cluster analysis results of NH3-N and TP among catchments were similar. This study also indicated that although the Huangshui River basin was located in the upper reaches of the Yellow River, the influences of rainfall-runoff relationship on spatiotemporal changes of NH3-N and TP in its sub-basins were limited. Only the temporal change of NH3-N in Jintan catchment in the upstream area was significantly affected by runoff coefficient. The indexes of proportion of water area (PWA), proportion of impervious area (PIA), and proportion of primary industry (PPI) were the top three influencing factors of temporal variation of NH3-N and TP for most catchments in the middle reaches. The temporal change of NH3-N in Jintan catchment in the upstream area was obviously affected by runoff coefficient. The spatial variation of NH3-N and TP were all affected by PWA and proportion of secondary industry significantly. The results of this study can provide theoretical basis and technical support for the control and management of nitrogen and phosphorus pollution in upper reaches of rivers.


Sensitivity of histopathological and histochemical parameters in the digestive gland of the apple snail Pomacea canaliculata exposed to cypermethrin.
The aim of this study was to evaluate the toxic effects of the pesticide cypermethrin (CYP) in the digestive gland of the apple snail, Pomacea canaliculata, analysing histological and histochemical alterations. Adult snails were exposed to sublethal CYP concentrations (10, 25, and 100 µg/L) under acute (1 day) and sub-chronic (14 days) conditions. Histological analyses of the morphology of the digestive gland were performed and a histopathological condition index (HI) was calculated. Also, both intracellular accumulation of lipofuscins (LF) and neutral lipids (NL) were evaluated. CYP exposure induced tissue damage to this organ, such as disorganisation of the connective tissue, fibrosis, haemocytic infiltration, atrophy, and necrosis under acute and sub-chronic conditions. These alterations, integrated into a single HI value, revealed notable CYP effects during both acute and sub-chronic exposures. Cell type replacement, measured as VvBAS, was only observed in the sub-chronic treatment. Under acute conditions, the pyrethroid affected NL accumulation at the highest concentration, while in sub-chronic conditions NL accumulation was only observed at the lowest concentrations. P. canaliculata also showed a dose-dependent response of LF under acute CYP exposure conditions. However, under sub-chronic conditions, this parameter was not sensitive to pesticide exposure. All these relevant structural lesions may affect the normal function of the digestive gland, even though the species presented additional mechanisms, as infiltration of hemocyte and basophilic cell hyperplasia, that help it to tolerate the exposure to pollutants. This study showed that some histological and histochemical parameters are sensitive in P. canaliculata at CYP concentrations to which the snail could be exposed in the environments it inhabits.


Ultrasound imaging of the thoracic epidural space.
In thoracic epidural anesthesia, the "loss of resistance" technique is the standard technique for the identification of the epidural space (EDS), the feedback to the operator is often solely tactile. Our aim was to establish ultrasonography for the prepuncture demonstration of the anatomic structures surrounding the thoracic EDS and to evaluate its precision and imaging quality. We examined 20 volunteers. In each participant, the extradural space and the neighboring anatomic landmarks in the intervertebral space Th 5-6 were identified using 2 imaging techniques: magnetic resonance imaging (MRI) and ultrasonography. We compared corresponding images regarding distance measurements and the visibility of anatomic landmarks. The capacity of ultrasound imaging (US) to depict the thoracic EDS was limited. Due to the better overview, MR images were easier to interpret. However, US proved to be of better value than MRI in the depiction of the dura mater. All important landmarks for the puncture of the thoracic EDS could be identified with both techniques. The overall correlation was satisfactory. US depicted the different structures of the thoracic EDS with an acceptable precision (confidence interval, 4.6 to 8.7 mm). US showed good correlation with MRI, which is a standard imaging technique for the depiction of the spine. We anticipate that prepuncture ultrasonography may facilitate thoracic epidural anesthesia by needle placement.


Acute cervical radiculopathy after anterior scalene muscle massage: A case report.
Deep tissue massage (DTM) is a form of therapeutic massage therapy for muscles and is often used to treat musculoskeletal pain. This was an uncommon case of acute cervical radiculopathy that occurred after DTM. A 47-year-old Asian woman with low weight visited our clinic due to complaints of sudden unilateral paralysis, radiating pain in the left shoulder, and wrist weakness after undergoing a 3-minute DTM of the anterior scalene muscle. Electrodiagnostic examination indicated acute injuries in the left cervical 5 and 6 (cervical 5 and cervical 6) nerve roots. Acute cervical radiculopathy associated with anterior scalene DTM. The patient underwent ultrasound-guided cervical 5 and cervical 6 selective nerve root block twice through the injection of 0.25% lidocaine and 20 mg dexamethasone and regularly participated in a biweekly rehabilitation program and a home exercise program. After a 6-month follow-up, the patient's shoulder and wrist strength had recovered, and the electrodiagnostic findings had improved. DTM of the anterior scalene muscle should be carefully performed to avoid cervical nerve root injury, particularly in underweight patients.


Variations in bioconcentration of human pharmaceuticals from sewage effluents into fish blood plasma.
The "Fish Plasma Model" has been proposed for prioritizing pharmaceuticals for in-depth environmental risk assessment efforts. The model compares estimated drug concentrations in fish plasma with human therapeutic plasma concentrations in order to assess the risk for a pharmacological interaction in the fish. In this study the equation used to estimate bioconcentration from water to fish blood plasma was field-tested by exposing rainbow trout in situ to sewage effluents from three treatment plants. Measured plasma levels of diclofenac, naproxen, ketoprofen and gemfibrozil were similar or lower than those modelled, which is acceptable for an early tier. However, measured levels of ibuprofen were >200 times higher than modelled for the largest plant (Gryaab Göteborg). Comparing measured fish plasma concentrations to the human therapeutic concentrations ranked the relative risks from the pharmaceuticals. Diclofenac and gemfibrozil, followed by ibuprofen, presented the highest risk for target interactions, whereas naproxen and ketoprofen presented little risk. Remarkably, measured bioconcentration factors varied considerably between sites. This variation could not be attributed to differences in water concentrations, temperatures, pH or exposure times, thereby suggesting that chemical characteristics of effluents and/or recipient waters strongly affected the uptake/bioconcentration of the pharmaceuticals.


Autoradiographic study of the distribution of LH(HCG) receptors in the ovary of untreated and gonadotrophin-primed immature rats.
The LH(HCG) receptors in the ovaries of immature rats which were either untreated, or primed with PMSG and HCG, have been studied with a histochemical method which has proved to be as effective as when earlier used in the rat testis. This method, which consists of the topical application of 125I-HCG to picric acid-formaldehyde (PAF) fixed frozen sections followed by autoradiography, is also suitable for quantitative studies on the distribution of receptors. In the ovary of the immature 26 days old rat, the LH(HCG) receptors are localized exclusively in the interstitial and thecal tissues. After PMSG treatment many receptors appear in the granulosa of the large antral follicles. These receptors are most numerous in the outer layers of cells and least numerous in the inner. At the same time there are fewer receptors in the thecal and interstitial cells which have undergone the process of luteinization. After PMSG and HCG treatment the newly formed corpora lutea have few receptors, but these become progressively more numerous on subsequent days. It is suggested that, in the rat, the luteinization of the ovarian LH-target cells is associated with an initial decrease in the number of their LH(HCG) receptors.


Macular Atrophy in Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial Comparing Ranibizumab and Aflibercept (RIVAL Study).
To investigate differences in the development of macular atrophy (MA) over 24 months between treat-and-extend (T&E) ranibizumab and aflibercept in patients with neovascular age-related macular degeneration (nAMD). A phase 4 randomized, partially masked, multicenter study. Individuals 50 years of age or older diagnosed with active, treatment-naïve subfoveal choroidal neovascularization secondary to nAMD with baseline best-corrected visual acuity (BCVA) of 23 logarithm of minimum angle of resolution letters or more. Patients were randomized 1:1 to receive either intravitreal injections of ranibizumab 0.5 mg or aflibercept 2.0 mg and were treated according to the same reading center-guided T&E regimen after 3 initial monthly injections. The primary outcome was mean change in square root area of MA from baseline to month 24. Key secondary outcomes included number of injections and mean change in BCVA from baseline to months 12 and 24. Two hundred seventy-eight patients were included in the analysis (ranibizumab 0.5 mg, n = 141; aflibercept 2.0 mg, n = 137). Mean change in square root area of MA from baseline to month 24 was +0.36 mm (95% confidence interval [CI], 0.27-0.45 mm) for ranibizumab and +0.28 mm (95% CI, 0.19-0.37 mm) for aflibercept (treatment difference, +0.08 mm [95% CI, -0.05 to 0.21 mm]; P = 0.24). The proportion of patients with MA increased from 7% (10/141) to 37% (43/117) for ranibizumab and from 6% (8/137) to 32% (35/108) for aflibercept from baseline to month 24. The average number of injections received per year was similar between both groups: 9.6 (95% CI, 9.2-10.0) for ranibizumab and 9.5 (95% CI, 9.1-9.9) for aflibercept. The mean change in BCVA from baseline to month 24 was +6.6 letters (95% CI,4.7-8.5 letters) for the ranibizumab group and +4.6 letters (95% CI, 2.7-6.6 letters) for the aflibercept group ( P = 0.15). Rates of adverse events (AEs) were similar between both groups. No significant differences in the rate of development or growth of MA over 24 months were observed between ranibizumab and aflibercept in nAMD patients treated using an identical T&E regimen.