[Changes in the concentrations of catecholamines and cortisol in balanced anesthesia and total intravenous anesthesia].
To compare hormone response to stress caused by surgery performed under balanced general anesthesia and total intravenous anesthesia. Two randomly formed groups of 24 patients each were studied. All patients were scheduled for lumbar laminectomy to correct disc hernias, with one group receiving balanced anesthesia with isoflurane (expiratory fraction between 0.5% and 0.6%), and the second group receiving total intravenous anesthesia (TIVA) (propofol infusion changed every 10 min from 12 to 6 mg/kg/h). Analgesics and relaxants were given by continuous infusion at preestablished doses (fentanyl 2 micrograms/kg/h; vecuronium 0.05 mg/kg/h). Cortisol and catecholamine (adrenalin, noradrenaline and dopamine) levels were determined at the following times: the morning of surgery (baseline), 5 min after intubation, 5 min after incision, 30 and 60 min after intubation; 5 min after tube removal and upon admission to the recovery unit. Cortisol levels decreased from baseline (14 +/- 3 pg/ml) until 30 min after intubation (4 +/- 2 pg/ml; p < 0.05) in the balanced anesthesia group. Adrenaline levels followed the same pattern (baseline 77 +/- 7 versus 57 +/- 10 pg/ml 30 min after intubation). Dopamine levels were statistically different (p < 0.05) at baseline (42 +/- 3 pg/ml), after intubation (38 +/- 2 pg/ml) and after incision (35 +/- 3 pg/ml), but the difference disappeared 30 minutes after intubation (38 +/- 8 pg/ml). Noradrenaline levels after incision (425 +/- 116 pg/ml) were significantly different from those at baseline (671 +/- 124 pg/ml), and the difference was evident until 60 min after incision. In the TIVA group we found significantly higher cortisol levels after intubation (21 +/- 0 pg/ml) than after baseline (14 +/- 2 pg/ml); this level decreased after extubation (7 +/- 0 pg/ml; p < 0.05). Adrenaline levels were significantly higher than at baseline (64 +/- 11 pg/ml) at times corresponding to intubation (76 +/- 5 pg/ml) and extubation (48 +/- 5 pg/ml). Noradrenaline increased significantly over baseline (497 +/- 99 pg/ml) after incision (597 +/- 90 pg/ml) and decreased significantly after 30 min. The increases in cortisol were significantly greater in the TIVA group than in the control group after intubation (21 +/- 0 versus 8 +/- 3 pg/ml, respectively) after intubation, after incision (18 +/- 2 versus 6 +/- 3 pg/ml) and 30 minutes after intubation (15 +/- 2 versus 4 +/- 2 pg/ml). Similar differences were found for dopamine after intubation (49 +/- 2 versus 38 +/- 2 pg/ml) and after incision (45 +/- 5 versus 35 +/- 3 pg/ml). Hormone levels are significantly higher during intravenous anesthesia than during balanced anesthesia, and the difference is evident from the earliest measurement performed.


Perceptual learning improves contrast sensitivity and visual acuity in adults with anisometropic amblyopia.
To evaluate the effects of perceptual learning on contrast-sensitivity function and visual acuity in adult observers with amblyopia, 23 anisometropic amblyopes with a mean age of 19.3 years were recruited and divided into three groups. Subjects in Group I were trained in grating detection in the amblyopic eye near pre-training cut-off spatial frequency. Group II received a training regimen of repeated contrast-sensitivity function measurements in the amblyopic eye. Group III received no training. We found that training substantially improved visual acuity and contrast-sensitivity functions in the amblyopic eyes of all the observers in Groups I and II, although no significant performance improvement was observed in Group III. For observers in Group I, performance improvements in the amblyopic eyes were broadly tuned in spatial frequency and generalized to the fellow eyes. The latter result was not found in Group II. In a few cases tested, improvements in visual acuity following training showed about 90% retention for at least 1 year. We concluded that the visual system of adult amblyopes might still retain substantial plasticity. Perceptual learning shows potential as a clinical tool for treating child and adult amblyopia.


Superoxide production: a procalcifying cell signalling event in osteoblastic differentiation of vascular smooth muscle cells exposed to calcification media.
Recent studies showed that hydrogen peroxide (H(2)O(2)) enhanced bone markers expression in vascular smooth muscle cells (VSMCs) implicated in osteoblastic differentiation. This study aimed at investigating the role of NAD(P)H oxidase in vascular calcification processes. A7r5 rat VSMCs were incubated with beta-glycerophosphate (10 mm) or uremic serum to induce a diffuse mineralization. H(2)O(2) production by VSMCs was determinated by chemiluminescence. NAD(P)H oxidase sub-unit (p22(phox)), Cbfa-1, ERK phosphorylation and bone alkaline phosphatase (ALP) expressions were measured by Western blotting. VSMCs exhibited higher production of H(2)O(2) and early expression of p22(phox) with beta-glycerophosphate or uremic serum within 24 h of treatment. beta-glycerophosphate-induced oxidative stress was associated with Cbfa-1 expression followed by ALP expression and activity, meanwhile the VSMCs expressing ALP diffusely calcified their extracellular matrix. Interestingly, diphenyleneiodonium partly prevented the osteoblastic differentiation. Results from this model strongly suggest a major implication of vascular NAD(P)H oxidase in vascular calcification supported by VSMCs osteoblastic differentiation.


gamma-beta-Thalassaemia studies showing that deletion of the gamma- and delta-genes influences beta-globin gene expression in man.
In gamma-beta-thalassaemia, human gamma- and beta-globin gene expression is suppressed; this results in a severe anaemia in newborns which subsequently develops into a beta-thalassaemia syndrome in adult life. This hereditary disease is now shown to be the result of a deletion of at least 40,000 base pairs of the gammadeltabeta-globin gene locus. The gamma- and delta-globin genes are deleted in the affected chromosome but, surprisingly, the beta-globin gene is still present, together with a large segment of the DNA sequences flanking the gene on its 5'-side and the entire region on the 3'-side of the gene. Hence, a deletion of DNA far from the beta-globin gene results in the suppression of its activity.


Three years later: report on the state of well-being of patients with chronic tinnitus who underwent modified tinnitus retraining therapy.
Successful management of patients with chronic tinnitus is an important health issue. One of the tinnitus management strategies used at our Tinnitus Center is a combination of tinnitus retraining therapy (TRT) with physiotherapy and psychological management [called modified TRT (MTRT)]. We have used this type of management for over a decade and have described the protocol in detail elsewhere. In the present study, we wanted to determine the effect of MTRT on the well-being of tinnitus patients 3 years after treatment onset. One hundred and thirty patients with chronic tinnitus were assessed using psychometric instruments immediately before 7-day MTRT, immediately after the therapy and 3 years later. Patients with very severe tinnitus-related distress associated with major depression and a risk of suicide were excluded from this study. MTRT resulted in a sustained reduction of tinnitus-related distress. Moreover, the quality of life of patients had increased, as assessed by a separate questionnaire. The effect of MTRT was influenced by the degree of tinnitus-related distress and by the patients' age, the latter being gender dependent. Hearing loss and tinnitus duration had only a minor influence on the therapeutic effect. Taken together, we report a positive change in the state of well-being of patients with chronic tinnitus measurable with various psychometric instruments 3 years after the onset of MTRT.


Response properties of single neurons in the zebra finch auditory midbrain: response patterns, frequency coding, intensity coding, and spike latencies.
The avian mesencephalicus lateralis, dorsalis (MLd) is the auditory midbrain nucleus in which multiple parallel inputs from lower brain stem converge and through which most auditory information passes to reach the forebrain. Auditory processing in the MLd has not been investigated in songbirds. We studied the tuning properties of single MLd neurons in adult male zebra finches. Pure tones were used to examine tonotopy, temporal response patterns, frequency coding, intensity coding, spike latencies, and duration tuning. Most neurons had no spontaneous activity. The tonotopy of MLd is like that of other birds and mammals; characteristic frequencies (CFs) increase in a dorsal to ventral direction. Four major response patterns were found: 1) onset (49% of cells); 2) primary-like (20%); 3) sustained (19%); and 4) primary-like with notch (12%). CFs ranged between 0.9 and 6.1 kHz, matching the zebra finch hearing range and the power spectrum of song. Tuning curves were generally V-shaped, but complex curves, with multiple peaks or noncontiguous excitatory regions, were observed in 22% of cells. Rate-level functions indicated that 51% of nononset cells showed monotonic relationships between spike rate and sound level. Other cells showed low saturation or nonmonotonic responses. Spike latencies ranged from 4 to 40 ms, measured at CF. Spike latencies generally decreased with increasing sound pressure level (SPL), although paradoxical latency shifts were observed in 16% of units. For onset cells, changes in SPL produced smaller latency changes than for cells showing other response types. Results suggest that auditory midbrain neurons may be particularly suited for processing temporally complex signals with a high degree of precision.


Psychological status and weight-related distress in overweight or at-risk-for-overweight children.
To associate psychological status, weight-related distress, and weight status during childhood in overweight or at-risk-for-overweight children. We associated self-report of depression, trait anxiety, and weight-related distress (body size dissatisfaction and weight-related peer teasing after controlling for the effects of weight) in 164 children (black 35%; age 11.9 +/- 2.5 years; girls 51%) who were overweight or at-high-risk-for-overweight and were not seeking weight loss. Overall, heavier children reported more psychological and weight-related distress. Black children reported more anxiety and body size dissatisfaction than white children, despite equivalent weights. However, psychological distress was not significantly associated with weight in white children. Girls reported more weight-related distress than boys. Depression was associated with weight-related teasing in all predictive models, except in the model using only black subjects. Trait anxiety was associated with report of peer teasing when using all subjects. Depression was also significantly associated with children's report of body size dissatisfaction in models using all subjects, only girls, or white subjects, but not in analyses using only boys or black subjects. For boys peer teasing was associated with body size dissatisfaction. In models including only black children, depression and trait anxiety were not significantly associated with either report of peer teasing or body size dissatisfaction. Regardless of race or sex, increasing weight is associated with emotional and weight-related distress in children. However, associations of psychological status, weight, and weight-related distress differ for girls and boys, and for black and white children.


Generalized Fano lineshapes reveal exceptional points in photonic molecules.
The optical behavior of coupled systems, in which the breaking of parity and time-reversal symmetry occurs, is drawing increasing attention to address the physics of the exceptional point singularity, i.e., when the real and imaginary parts of the normal-mode eigenfrequencies coincide. At this stage, fascinating phenomena are predicted, including electromagnetic-induced transparency and phase transitions. To experimentally observe the exceptional points, the near-field coupling to waveguide proposed so far was proved to work only in peculiar cases. Here, we extend the interference detection scheme, which lies at the heart of the Fano lineshape, by introducing generalized Fano lineshapes as a signature of the exceptional point occurrence in resonant-scattering experiments. We investigate photonic molecules and necklace states in disordered media by means of a near-field hyperspectral mapping. Generalized Fano profiles in material science could extend the characterization of composite nanoresonators, semiconductor nanostructures, and plasmonic and metamaterial devices.


Analysis of time-to-event data using a flexible mixture model under a constraint of proportional hazards.
Cox proportional hazards (PH) model evaluates the effects of interested covariates under PH assumption without specified the baseline hazard. In clinical trial applications, however, the explicitly estimated hazard or cumulative survival function for each treatment group helps to assess and interpret the meaning of treatment difference. In this paper, we propose to use a flexible mixture model under the PH constraint to fit the underline survival functions. Simulations are conducted to evaluate its performance and show that the proposed mixture PH model is very similar to the Cox PH model in terms of estimating the hazard ratio, bias, confidence interval coverage, type-I error and testing power. Application to several real clinical trial examples demonstrates that the results from this approach are almost identical to the results from Cox PH model. The explicitly estimated hazard function for each treatment group provides additional useful information and helps the interpretation of hazard comparisons.


Comparison of radium-228 determination in water among Australian laboratories.
The National Health and Medical Research Council and Natural Resource Management Ministerial Council of Australia developed the current Australian Drinking Water Guidelines which recommend an annual radiation dose value of 1 mSv year-1. One of the potential major contributors to the radiation dose from drinking water is radium-228, a naturally occurring radionuclide arising from the thorium decay series. Various methods of analysing for radium-228 in water have been established and adapted by analytical radiochemistry laboratories. Seven laboratories in Australia participated in analysing radium-228 spiked water samples with activity concentrations ranging from 6 mBq L-1 to 20 Bq L-1. The aim of the exercise was to compare and evaluate radium-228 results reported by the participating laboratories, the methods used and the detection limits. This paper presents the outcome of the exercise.


A multifactorial obesity model developed from nationwide public health exposome data and modern computational analyses.
Obesity is both multifactorial and multimodal, making it difficult to identify, unravel and distinguish causative and contributing factors. The lack of a clear model of aetiology hampers the design and evaluation of interventions to prevent and reduce obesity. Using modern graph-theoretical algorithms, we are able to coalesce and analyse thousands of inter-dependent variables and interpret their putative relationships to obesity. Our modelling is different from traditional approaches; we make no a priori assumptions about the population, and model instead based on the actual characteristics of a population. Paracliques, noise-resistant collections of highly-correlated variables, are differentially distilled from data taken over counties associated with low versus high obesity rates. Factor analysis is then applied and a model is developed. Latent variables concentrated around social deprivation, community infrastructure and climate, and especially heat stress were connected to obesity. Infrastructure, environment and community organisation differed in counties with low versus high obesity rates. Clear connections of community infrastructure with obesity in our results lead us to conclude that community level interventions are critical. This effort suggests that it might be useful to study and plan interventions around community organisation and structure, rather than just the individual, to combat the nation's obesity epidemic.


Early Detection and Chemoprevention of Lung Cancer.
Despite advances in targeted treatments, lung cancer remains a common and deadly malignancy, in part owing to its typical late presentation. Recent developments in lung cancer screening and ongoing efforts aimed at early detection, treatment, and prevention are promising areas to impact the mortality from lung cancer. In the past several years, lung cancer screening with low-dose chest computed tomography (CT) was shown to have mortality benefit, and lung cancer screening programs have been implemented in some clinical settings. Biomarkers for screening, diagnosis, and monitoring of response to therapy are under development. Prevention efforts aimed at smoking cessation are as crucial as ever, and there have been encouraging findings in recent clinical trials of lung cancer chemoprevention. Here we review advancements in the field of lung cancer prevention and early malignancy and discuss future directions that we believe will result in a reduction in the mortality from lung cancer.


A historical perspective on the lateral diffusion model of GTPase activation and related coupling of membrane signaling proteins.
Aspects of our discovery of lateral diffusion of the G protein coupled receptor (GPCR) rhodopsin and that a single activated rhodopsin can non-covalently catalyze GTP binding to thousands of GTPases per second on rod disk membranes via this diffusion are summarized herein. Rapid GTPase coupling to membrane-bound phosphodiesterase (PDE) further amplifies the signal via cGMP hydrolysis, essential to visual transduction. Important generalizations from this work are that biomembranes can uniquely concentrate, orient for reaction and provide a solvent appropriate to rapid, powerful and appropriately controlled sequential interaction of signaling proteins. Of equal importance to function is timely control and termination of such powerful amplification via receptor phosphorylation (quenching) and arrestin binding. Downstream kinetic modulation by GTPase activating proteins (GAPs) and regulators of G protein signaling (RGS) and related mechanisms as well as limitations set by membrane domain fencing, structural protein binding etc. can be essential in relevant systems.


Targeted deletion of adenosine A(3) receptors augments adenosine-induced coronary flow in isolated mouse heart.
To determine whether adenosine A(3) receptors participate in adenosine-induced changes in coronary flow, isolated hearts from wild-type (WT) and A(3) receptor knockout (A(3)KO) mice were perfused under constant pressure and effects of nonselective and selective agonists were examined. Adenosine and the selective A(2A) agonist 2-[p-(2-carboxyethyl)]phenylethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680) produced augmented maximal coronary vasodilation in A(3)KO hearts compared with WT hearts. Selective activation of A(3) receptors with 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA) at nanomolar concentrations did not effect coronary flow, but at higher concentrations it produced coronary vasodilation both in WT and A(3)KO hearts. Cl-IB-MECA-induced increases in coronary flow were susceptible to both pharmacological blockade and genetic deletion of A(2A) receptors. Because deletion or blockade of adenosine A(3) receptors augmented coronary flow induced by nonselective adenosine and the selective A(2A) receptor agonist CGS-21680, we speculate that this is due to removal of an inhibitory influence associated with the A(3) receptor subtype. These data indicate that the presence of adenosine A(3) receptors may either inhibit or negatively modulate coronary flow mediated by other adenosine receptor subtypes.


Optimizing control of acromegaly: integrating a growth hormone receptor antagonist into the treatment algorithm.
Acromegaly is associated with significant morbidities and a 2- to 3-fold increase in mortality because of the excessive metabolic action of GH and IGF-I, a marker of GH output. Reductions in morbidity correspond with decreases in IGF-I, and mortality is lowered following normalization of IGF-I or GH levels. Therefore, this has become an important end point. Current guidelines for the treatment of acromegaly have not considered recent advances in medical therapy, in particular, the place of pegvisomant, a GH receptor antagonist. Treatment goals include normalizing biochemical markers, controlling tumor mass, preserving pituitary function, and relieving signs and symptoms. Surgery reduces tumor volume and is considered first-line therapy. Radiation reduces tumor volume and GH and IGF-I levels, but the onset of action is slow and hypopituitarism typically develops. Therefore, pharmacotherapy is often used following surgery or as first-line therapy for nonresectable tumors. Dopamine agonists can be considered in patients exhibiting minimal disease or those with GH-prolactin-cosecreting tumors but will not achieve hormone normalization in most patients. Somatostatin analogs effectively suppress GH and IGF-I in most patients, but intolerance (e.g. diarrhea, cramping, gallstones) can occur. Pegvisomant, the newest therapeutic option, blocks GH action at peripheral receptors, normalizes IGF-I levels, reduces signs and symptoms, and corrects metabolic defects. Pegvisomant does not appear to affect tumor size and has few adverse effects. Pegvisomant is the most effective drug treatment for acromegaly in normalizing IGF-I and producing a clinical response; it is the preferred agent in patients resistant to or intolerant of somatostatin analogs.


Late-onset blebitis/endophthalmitis: incidence and outcomes with mitomycin C.
To assess the outcomes of patients who had late infections after undergoing filtering surgery with mitomycin C with respect to treatment, resultant vision, and maintenance of intraocular pressure. A retrospective review of 233 eyes that underwent trabeculectomy with mitomycin C with or without coincident cataract extraction and intraocular lens insertion from August 1993 to June 1997 was undertaken. Records were examined for postoperative infection occurring at least 6 months after filtering surgery. Age, sex, date, and type of surgery were reviewed and entered into a computerized database. Bleb infections occurred in 6 of 233 (2.6%) eyes that underwent mitomycin C filtering surgery. Four of these developed endophthalmitis. The average postoperative time until infection was 24.7 months. Two patients had bleb leaks, one of which progressed to endophthalmitis. On resolution of infection, all blebs remained functional, and vision returned to preblebitis acuities in 67%. Aggressive topical antibiotic therapy with daily observation may be appropriate in selected cases of late-onset blebitis and endophthalmitis. Eyes may continue to have good visual outcomes and functioning filters without need for additional surgery or hospitalization. Early recognition and appropriate management of infections may play a role in these outcomes.


Understanding the Unusual Reduction Mechanism of Pd(II) to Pd(I): Uncovering Hidden Species and Implications in Catalytic Cross-Coupling Reactions.
The reduction of Pd(II) intermediates to Pd(0) is a key elementary step in a vast number of Pd-catalyzed processes, ranging from cross-coupling, C-H activation, to Wacker chemistry. For one of the most powerful new generation phosphine ligands, PtBu3, oxidation state Pd(I), and not Pd(0), is generated upon reduction from Pd(II). The mechanism of the reduction of Pd(II) to Pd(I) has been investigated by means of experimental and computational studies for the formation of the highly active precatalyst {Pd(μ-Br)(PtBu3)}2. The formation of dinuclear Pd(I), as opposed to the Pd(0) complex, (tBu3P)2Pd was shown to depend on the stoichiometry of Pd to phosphine ligand, the order of addition of the reagents, and, most importantly, the nature of the palladium precursor and the choice of the phosphine ligand utilized. In addition, through experiments on gram scale in palladium, mechanistically important additional Pd- and phosphine-containing species were detected. An ionic Pd(II)Br3 dimer side product was isolated, characterized, and identified as the crucial driving force in the mechanism of formation of the Pd(I) bromide dimer. The potential impact of the presence of these side species for in situ formed Pd complexes in catalysis was investigated in Buchwald-Hartwig, α-arylation, and Suzuki-Miyaura reactions. The use of preformed and isolated Pd(I) bromide dimer as a precatalyst provided superior results, in terms of catalytic activity, in comparison to catalysts generated in situ.


[Pharmacokinetic and clinical studies on the use of ceftizoxime in premature and newborn infants. The Chemotherapy Research Group for Mother and Child].
A pharmacokinetic and clinical study of ceftizoxime (CZX), a newly developed cephem antibiotic intended for parenteral use, was conducted in premature and newborn infants, and resulted in the following findings. 1. Pharmacokinetics (1) Average serum half-lives (T 1/2) following a one shot intravenous dose of 20 mg/kg of CZX to mature and premature newborn infants in age groups of 0-3, 4-7, 8-14, and 15-30 days were: 4.14, 3.01, 2.57, and 1.98 hours (for mature infants) and 5.26, 4.59, 3.71, and 2.64 hours (for premature infants), respectively, decreasing with ages in days of the infants. (2) Average T 1/2's after a one shot 10 mg/kg dose was similar to that after a 20 mg/kg dose. Serum concentrations of CZX were dose-dependent. (3) T 1/2 after 1-hour intravenous drip infusion revealed a same trend after one shot injection. (4) Urinary in the first approximately 6 hours recoveries following a 20 mg/kg one shot dose to mature and premature newborn infants were as follows: 35% (0-3 days old) and 45-55% (4 days old and older) in mature infants and 30% (0-3 days old) and 45% (4 days old and older) in premature infants. 2. Therapeutic effectiveness (1) The subjects examined were 112 newborn infants consisting of 83 with infections and 29 who received CZX for prophylaxis. The 83 infants had 86 cases of infections, which were classified as A, when the causative organisms were identified and as B, when the causative organisms were not identified. Rates of therapeutic effectiveness were 95.0% for group A and 95.7% for group B. Bacteriological effectiveness were studied on 41 strains isolated from group A, and were as high as 89.5% for Gram-positive organisms and 95.5% for Gram-negative organisms. The rate of successful prophylaxis for the 29 infants was 96.6%. (2) Side effects did not occur among the 120 newborn infants. Laboratory tests with abnormalities included leukopenia, neutropenia, eosinophilia, thrombocytosis and increased GOT or GPT. These pharmacodynamic and clinical findings have fully substantiated the satisfactory therapeutic usefulness of CZX in both the treatment and prevention of neonatal infections in the usual dose of 20 mg/kg, which is to be given b.i.d. for infants up to 3 days old; b.i.d. or t.i.d. for infants 4 to 7 days old, and t.i.d. or q.i.d. for infants 8 days old and older. The drug can be given in a daily dose as high as 120 mg/kg when infection is severe.


In vitro antibacterial activity of bovine dialyzable leukocyte extract.
The rapidly developing resistance of many infectious pathogenic organisms to modern drugs has spurred scientists to search for new sources of antibacterial compounds. One potential candidate, bDLE (dialysis at 10 to 12 kDa cut-off) and its fractions ("S" and "L" by 3.5 kDa cut-off and I, II, III, and IV by molecular exclusion chromatography), was evaluated for antibacterial activity against pathogenic bacterial strains (Staphylococcus aureus, Streptococcus pyogenes, Lysteria monocytogenes, Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhi) using standard antimicrobial assays. A minimum inhibitory concentration (MIC) of bDLE and its fractions was determined by agar and broth dilutions methods. Only bDLE and its "S" fraction had an effect upon all bacteria evaluated (MIC ranging from 0.29 to 0.62 U/ml), and the bactericidal and bacteriostatic effects (evaluated by MTT assay) were bacterial species-dependent. These results showed a remarkable in vitro antibacterial property of bDLE against several pathogenic bacteria.


Mesenchymal stem cells relieve fibrosis of Schistosoma japonicum-induced mouse liver injury.
Mesenchymal stem cells (MSCs) have gained popularity for their potential as seed cells to treat various human diseases, including pathogenic infections. Schistosoma japonicum (S. japonicum) infection is characterized by formation of parasite egg granulomas and host liver fibrosis. MSCs have been proposed as useful treatments of S. japonicum infection, but the efficacy and underlying mechanisms remain unknown. Herein, we report that MSCs were able to ameliorate S. japonicum-induced liver injury in vivo and this effect was enhanced by combining MSCs with conventional drug praziquantel (PZQ). Kunming strains of mice were infected with S. japonicum and treated with vehicle, MSCs, PZQ or PZQ + MSCs. MSC treatment not only prolonged the survival time of infected mice but reduced egg granuloma diameter and decreased the concentrations of serum transforming growth factor-β1 and hyaluronic acid. MSC treatment also inhibited collagen deposition and reduced the expression of collagen type 3, α-smooth muscle actin and vimentin in infected mouse liver tissues. Collectively, our findings suggest that MSC treatment represents a novel therapeutic approach for S. japonicum-induced liver injury and fibrosis.


POLLINATION IN FLORAL SCENT MORPHS OF POLEMONIUM VISCOSUM: A MECHANISM FOR DISRUPTIVE SELECTION ON FLOWER SIZE.
Plants of Polemonium viscosum have flowers that are either sweet or skunky in scent. The two morphs are preferentially pollinated by insects of strongly contrasting body size: bumblebee queens specialize on sweet flowers, flies on skunky ones. In this study 13 characters were examined in plant specimens from five populations to identify major components of intraspecific variation in flower and inflorescence morphology and test their correlation with floral scent. Factor analysis identified four major axes of morphological variation. The first explained 22% of the variance among specimens and correlated strongly with four flower size characters: sepal length, corolla tube length, corolla lobe width, and corolla lobe length. Floral scent morphs differed significantly in the multivariate representation of flower size defined by these characters. Sweet flowers had wider corolla lobes, longer corolla tubes, and longer sepals than skunky ones. Corolla lobe width accounted for the greatest amount of intermorph divergence. Divergence in flower size between morphs was maintained in mixed populations at four locations in alpine Colorado, with corollas of sweet flowers significantly broader or more flared than those of skunky flowers. Patterns of pollen receipt suggest that this difference is adaptive. In the sweet morph, pollination intensity and purity increased significantly with corolla flare. Conversely, in the skunky morph, corolla flare had little influence on pollination intensity and had a strong negative effect on purity. These findings suggest that selection for effective pollination should favor intraspecific divergence in flower size in Polemonium viscosum.


pLoc-mVirus: Predict subcellular localization of multi-location virus proteins via incorporating the optimal GO information into general PseAAC.
Knowledge of subcellular locations of proteins is crucially important for in-depth understanding their functions in a cell. With the explosive growth of protein sequences generated in the postgenomic age, it is highly demanded to develop computational tools for timely annotating their subcellular locations based on the sequence information alone. The current study is focused on virus proteins. Although considerable efforts have been made in this regard, the problem is far from being solved yet. Most existing methods can be used to deal with single-location proteins only. Actually, proteins with multi-locations may have some special biological functions. This kind of multiplex proteins is particularly important for both basic research and drug design. Using the multi-label theory, we present a new predictor called "pLoc-mVirus" by extracting the optimal GO (Gene Ontology) information into the general PseAAC (Pseudo Amino Acid Composition). Rigorous cross-validation on a same stringent benchmark dataset indicated that the proposed pLoc-mVirus predictor is remarkably superior to iLoc-Virus, the state-of-the-art method in predicting virus protein subcellular localization. To maximize the convenience of most experimental scientists, a user-friendly web-server for the new predictor has been established at http://www.jci-bioinfo.cn/pLoc-mVirus/, by which users can easily get their desired results without the need to go through the complicated mathematics involved.


The myth of innocence: sexual scripts and the recognition of child sexual abuse by female perpetrators.
Although child sexual abuse has been studied extensively, minimal attention has been paid to sexual abuse by females. This paper explores the prevalence of female sex offending and reveals the paradoxes that exist within the available data. Moreover, it highlights the role of traditional sexual scripts in impeding the official recognition of the problem. Traditional sexual scripts, particularly the perception of females as sexually passive, harmless, and innocent, appear not only to have influenced broader societal views concerning sexuality and sexual abuse but also to have permeated the criminal law, victim reporting practices, and professional responses to female sex offending. The implicit denial of women s potential for sexual aggression within these three domains may ultimately contribute to the underrecognition of the problem in official sources.


Deciphering the molecular mechanisms underlying the plasma membrane targeting of PRMT8.
Arginine methylation plays crucial roles in many cellular functions including signal transduction, RNA transcription, and regulation of gene expression. Protein arginine methyltransferase 8 (PRMT8), a unique brain-specific protein, is localized to the plasma membrane. However, the detailed molecular mechanisms underlying PRMT8 plasma membrane targeting remain unclear. Here, we demonstrate that the N-terminal 20 amino acids of PRMT8 are sufficient for plasma membrane localization and that oligomerization enhances membrane localization. The basic amino acids, combined with myristoylation within the N-terminal 20 amino acids of PRMT8, are critical for plasma membrane targeting. We also found that substituting Gly-2 with Ala [PRMT8(G2A)] or Cys-9 with Ser [PRMT8(C9S)] induces the formation of punctate structures in the cytosol or patch-like plasma membrane localization, respectively. Impairment of PRMT8 oligomerization/dimerization by Cterminal deletion induces PRMT8 mis-localization to the mitochondria, prevents the formation of punctate structures by PRMT8(G2A), and inhibits PRMT8(C9S) patch-like plasma membrane localization. Overall, these results suggest that oligomerization/dimerization plays several roles in inducing the efficient and specific plasma membrane localization of PRMT8. [BMB Reports 2019; 52(10): 601-606].


An Interobserver Agreement Study with a New Classification for Rib Fractures.
Background: No consensus exists about the indication for surgical rib fixation in patients with rib fractures. Comparison between studies is difficult since a classification system is lacking for rib fractures. We introduced the first classification system for rib fractures, analogue to the Muller AO classification system and tested the classification with an interobserver agreement study. Methods: The classification is build up by four characters: the first one describes the rib number, the second character describes the location of the fracture in cranial-caudal fashion, the third character describes the fracture type and the fourth character described the subtype of the fracture. An interobserver agreement study was performed with the new classification. Results: Twenty CT scans of patients with rib fractures were analyzed. A total of 197 unilateral and bilateral rib fractures were scored by four reviewers. The interobserver agreement was substantial [Fleiss of 0.62 (95% CI 0.59 0.65)]. Conclusion: This is the first classification for rib fractures worldwide. The interobserver agreement of the classification was substantial. This classification is the first step in identifying patients who would benefit from surgical rib fixation.


2,2'-Bi(9,9-dihexylfluorene).
The central part of the title molecule, C(50)H(66), is planar, all the rings being in the same plane; the lateral chains are also planar (excluding H atoms), almost perpendicular to the ring plane and grafted on the same side of the molecule. The molecule has nearly a mirror plane, perpendicular to the central C-C bond, instead of the centre of symmetry expected. The orientation of the plane of the rings is approximately 45 degrees from the unit-cell b axis, so that neighbouring molecules are essentially perpendicular.


Functional and conformational properties of phaseolin (Phaseolus vulgris L.) and kidney bean protein isolate: a comparative study.
Kidney bean (Phaseolus vulgris L.) seed is an underutilised plant protein source with good potential to be applied in the food industry. Phaseolin (also named G1 globulin) represents about 50 g kg(-1) of total storage protein in the seed. The aim of the present study was to characterise physicochemical, functional and conformational properties of phaseolin, and to compare these properties with those of kidney bean protein isolate (KPI). Compared with kidney bean protein isolate (KPI), the acid-extracted phaseolin-rich protein product (PRP) had much lower protein recovery of 320 g kg(-1) (dry weight basis) but higher phaseolin purity (over 950 g kg(-1)). PRP contained much lower sulfhydryl (SH) and disulfide bond contents than KPI. Differential scanning calorimetry analyses showed that the phaseolin in PRP was less denatured than in KPI. Thermal analyses in the presence or absence of dithiothreitol, in combination with SH and SS content analyses showed the contributions of SS to the thermal stability of KPI. The analyses of near-UV circular dichroism and intrinsic fluorescence spectra indicated more compacted tertiary conformation of the proteins in PRP than in KPI. PRP exhibited much better protein solubility, emulsifying activity index, and gel-forming ability than KPI. The relatively poor functional properties of KPI may be associated with protein denaturation/unfolding, with subsequent protein aggregation. The results presented here suggest the potential for acid-extracted PRP to be applied in food formulations, in view of its functional properties.


A Novel Microbubble Capable of Ultrasound-Triggered Release of Drug-Loaded Nanoparticles.
Drug-loaded microbubbles have shown attractive potential in disease treatment applications. The present work presents a unique ultrasound (US)-triggered system in which drug-loaded nanoparticles and perfluorocarbon gas are encapsulated within the internal space of microbubbles. The prepared curcumin-loaded albumin nanoparticle payload microbubbles (CcmANP-MB) exhibited a mean diameter of 4895.1 nm ± 421.2 nm and a drug-loading efficiency of 2.23% ± 0.08% (297% increase compared with the drug loading of common drug-loaded microbubbles). US allowed the release of the internal payload. In vitro US-triggered drug release experiments showed that the drug release of CcmANP-MB was delayed by lipid membranes and significantly increased after sonication. In vitro and in vivo US imaging experiments demonstrated that CcmANP-MB evidently enhances US imaging, which indicates that the microbubbles possess good acoustic properties even after encapsulation of nanoparticles. Tumor bearing mice were administered with CcmANP-MB through the tail vein and were then exposed to ultrasound, which resulted in an enhanced drug accumulation in tumor tissues and a significant increase in tumor growth inhibition rate (57.1%) compared with CcmANP-MB alone (28.8%) as well as curcumin-loaded albumin nanoparticle (26.2%). Therefore, the combination of lecithin microbubbles and albumin nanoparticles provides a platform for targeted drug delivery in clinical therapy and disease diagnosis.


Child mortality levels and trends by HIV status in Blantyre, Malawi: 1989-2009.
Continuous evaluation of child survival is needed in sub-Saharan Africa where HIV prevalence among women of reproductive age continues to be high. We examined mortality levels and trends over a period of ∼20 years among HIV-unexposed and -exposed children in Blantyre, Malawi. Data from 5 prospective cohort studies conducted at a single research site from 1989 to 2009 were analyzed. In these studies, children born to HIV-infected and -uninfected mothers were enrolled at birth and followed longitudinally for at least 2 years. Information on sociodemographic, HIV infection status, survival, and associated risk factors was collected in all studies. Mortality rates were estimated using birth-cohort analyses stratified by maternal and infant HIV status. Multivariate Cox regression models were used to determine risk factors associated with mortality. The analysis included 8286 children. From 1989 to 1995, overall mortality rates (per 100 person-years) in these clinic-based cohorts remained comparable among HIV-uninfected children born to HIV-uninfected mothers (range 3.3-6.9) or to HIV-infected mothers (range 2.5-7.5). From 1989 to 2009, overall mortality remained high among all children born to HIV-infected mothers (range 6.3-19.3) and among children who themselves became infected (range 15.6-57.4, 1994-2009). Only lower birth weight was consistently and significantly (P < 0.05) associated with higher child mortality. HIV infection among mothers and children contributed to high levels of child mortality in the African setting in the pretreatment era. In addition to services that prevent mother-to-child transmission of HIV, other programs are needed to improve child survival by lowering HIV-unrelated mortality through innovative interventions that strengthen health infrastructure.


Estimation of time-dependent area under the ROC curve for long-term risk prediction.
Sensitivity, specificity, and area under the ROC curve (AUC) are often used to measure the ability of survival models to predict future risk. Estimation of these parameters is complicated by the fact that these parameters are time-dependent and by the fact that censoring affects their estimation just as it affects estimation of survival curves or coefficients of survival regression models. The authors present several estimators that overcome these complications. One approach is a recursive calculation over the ordered times of events, analogous to the Kaplan-Meier approach to survival function estimation. Another is to first apply Bayes' theorem to write the parameters of interest in terms of conditional survival functions that are then estimated by survival analysis methods. Simulation studies demonstrate that the proposed estimators perform well in practical situations, when compared with an estimator (c-statistic, from logistic regression) that ignores time. An illustration with data from a cardiovascular follow-up study is provided.


Nivolumab in two cases of refractory mycosis fungoides erythroderma.
Mycosis fungoides (MF) is the most common subtype of primary cutaneous T cell lymphoma (CTCL). The erythrodermic form (T4) especially impairs health-related quality of life (HR-QoL), making patients often incapable of self-care. Mycosis fungoides and Sézary syndrome (SS) are immunogenic neoplasms and can be recognized by the patient's immune system. The disease is chronic and immunotherapy allows for long-term control of CTCL. The paper presents a description of 2 cases of nivolumab use in the salvage treatment of erythroderma in the course of refractory mycosis fungoides. Nivolumab was used as emergency treatment, and previously patients exhausted the available treatment options. The discussed cases confirm the effectiveness of immunotherapy in the treatment of primary cutaneous T cell lymphomas. The applied treatment achieved the effect of more than one year of response (15 months), as well as a significant benefit in terms of subjective and objective quality of life. The effect was mainly related to the condition of the skin. The use of the PD-1 checkpoint inhibitor allowed for over 12 months of control in advanced, refractory and heavily pretreated cutaneous lymphoma, and was very well tolerated. More research is needed on the use of such inhibitors in the treatment of cutaneous lymphomas.


Soil acidification amendments change the rhizosphere bacterial community of tobacco in a bacterial wilt affected field.
Application of soil amendments has been wildly used to increase soil pH and control bacterial wilt. However, little is known about causal shifts in the rhizosphere microbial community of crops, especially when the field naturally harbors the disease of bacterial wilt to tobacco for many years due to long-term continuous cropping and soil acidification. In this study, biochar (CP), lime (LM), oyster shell powder (OS) and no soil amendment additions (Control; CK) were assessed for their abilities to improve the soil acidification, change the composition of rhizosphere soil bacterial communities and thus control tobacco bacterial wilt. The results showed that oyster shell powder significantly increased soil pH by 0.77 and reduced the incidence of tobacco bacterial wilt by 36.67% compared to the control. The Illumina sequencing -based community analysis showed that soil amendment applications affected the composition of rhizosphere bacterial community and increased the richness and diversity. In contrast, the richness and diversity correlated negatively to disease incidence. Using LEfSe analyses, 11 taxa were found to be closely related with disease suppression, in which Saccharibacteria, Aeromicrobium, and Pseudoxanthomonas could be potential indicators of disease suppression. Our results suggested that the suppression of bacterial wilt after the application of soil amendments (especially oyster shell powder) was attributed to the improved soil pH and increased bacterial richness and diversity.


Optimization of the enzymatic hydrolysis of chicken meat using response surface methodology.
The hydrolysis of chicken breast meat by the commercial protease Alcalase 2.4L was studied to evaluate the influence of temperature (43 to 77 degrees C), enzyme:substrate ratio (0.8% to 4.2%), and pH (7.16 to 8.84) on the responses of degree of hydrolysis and protein recovery. The enzymatic hydrolysis was optimized for maximum degree of hydrolysis and protein recovery using response surface methodology. The optimum conditions determined were the following: 52.5 degrees C, 4.2% (w/w) enzyme:substrate ratio, and a pH value of 8.00. Under these conditions, a degree of hydrolysis of 31% and protein recovery of 91% were obtained. A characterization of the protein hydrolysate obtained using the optimized process conditions was carried out, evaluating the chemical composition, electrophoretic profile and amino acid composition.


The quantification of surgical changes in nasal tip support.
To quantify the changes in the strength of nasal tip support associated with various surgical modifications and to identify the procedures that best maintain or augment tip support. Case study in 2 phases. Phase 1 included 10 patients undergoing primary rhinoplasty, 5 undergoing secondary rhinoplasty, and 5 control patients. Fresh cadavers were used in phase 2. A purpose-built instrument (Beaty Tensegrometer; G. M. Tooling, Chamblee, Ga) was used to measure nasal tip support before and after surgical modifications. In the patients who underwent primary rhinoplasty, there was a 25% decrease in tip support when the ligamentous attachments between the lateral crura were divided. Reconstruction of these attachments increased tip support over baseline by 35%. With a columellar strut and ligament reconstruction, tip support was increased by 44%. In the secondary rhinoplasty group, reconstruction with the dynamic adjustable rotation tip-tensioning technique increased nasal tip support over baseline by 70%. In cadavers, intercartilaginous incisions and delivery of the lower lateral cartilages caused a loss of tip support, while raising the skin-soft tissue envelope with the open technique did not. Extensive resection of the lower lateral cartilages caused a loss of tip support. This study demonstrates that nasal tip support can be reliably quantified in a reproducible manner. Use of the open approach, reconstruction of the attachments between the lateral crura, conservative resection of the lower lateral cartilages, and the dynamic adjustable rotation tip-tensioning technique for secondary rhinoplasty best preserve nasal tip support.


Cell-free production of VDAC directly into liposomes for integration with biomimetic membrane systems.
The mitochondrial voltage-dependent anion channel (VDAC) is a pivotal protein since it provides the major transport pathway between the cytosol and the mitochondrial intermembrane space and it is implicated in cell apoptosis by functioning as a gatekeeper for the trafficking of mitochondrial death molecules. VDAC is a beta-barrel channel with a large conductance, and we use it as a model transport protein for the design of biomimetic systems. To overcome the limitations of classical overexpression methods for producing and purifying membrane proteins (MPs) we describe here the use of an optimized cell-free system. In a one-step reaction VDAC is obtained directly integrated into liposomes and purified by ultracentrifugation. We then combine proteoliposomes with different bilayers models in order to validate VDAC insertion and functionality. This VDAC biomimetic model is the first example validating the use of a cell-free expression system for production of MPs into liposomes and tethered bilayers as a toolbox to build a wide range of biomimetic devices.


Cervical spine loading characteristics in a cadaveric C5 corpectomy model using a static and dynamic plate.
Anterior plates are used to increase the initial stability of anterior cervical spine fusions; however, plating has been suggested to cause graft stress shielding, leading to reduced fusion rates. The objectives of this study were to quantify the effects of graft size and plating (static versus dynamic) and the role of the posterior elements on load transmission in anterior cervical fusion. A C5 corpectomy was performed on six human cervical spines (C3-C7). An instrumented height-adjustable graft and dynamic cervical plate were used to measure axial load transmission. Each specimen underwent axial compressive testing with dynamic and static plate configurations, optimal and undersized graft heights, and posterior elements intact and removed. Dynamic plating allowed significantly more load transmission by the graft, particularly in the undersized graft configuration. The posterior elements play a significant role in load transmission.


Oxysophocarpine reduces oxygen-glucose deprivation-induced microglial activation and injury.
Microglial over-activation and apoptosis are associated with ischemic brain diseases. These processes may be hindered by oxysophocarpine (OSC) that generates anti-inflammatory and anti-apoptotic activities. However, the precise roles of OSC in microglial inflammation and apoptosis induced by oxygen-glucose deprivation/reoxygenation (OGD/R) remain unclear. In this study, we found that OSC reduced OGD/R-induced inflammation in BV-2 microglia. OSC elevated cell viability and prevented the release of lactate dehydrogenase. OSC downregulated cyclooxygenase 2 and inducible nitric oxide synthase and reduced the levels of inflammatory mediators, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1, prostaglandin E2, and nitric oxide. OSC inhibited the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation protein 88 (MyD88) and blocked the activation of nuclear factor (NF)-κB. In addition, OSC suppressed OGD/R-elicited BV-2 cell apoptosis, as indicated as follows: The restored mitochondrial membrane potential and the reduced caspase-3 activity; the decrease of Bax and cleaved caspase-3 and the increase of Bcl-2; the enhanced phosphorylation of Akt and mTOR. These results implied that OSC impedes OGD/R-induced inflammation and apoptosis of microglial cells. Therefore, OSC may be potentially used for ischemic stroke therapy.


Effect of dexamethasone on oral glucose tolerance in healthy adults.
To determine the dose-response and time course of action of a single dose of dexamethasone on plasma glucose and insulin dynamics in healthy adults. Participants included healthy adults who met the following inclusion criteria: 18 to 65 years of age, body mass index of 18 to 25 kg/m2, no family history of diabetes mellitus, not taking any medication known to affect glucose tolerance, and nonpregnant state for female participants. Each participant underwent 3 sequential blocks of 75-g oral glucose tolerance tests (OGTTs) on days 1, 2, and 3; this sequence was repeated on 3 different occasions separated by more than 2 weeks. On the first day of each block, participants reported to the research center after a 10- to 12-hour overnight fast, and fasting baseline blood samples for glucose, insulin, and C-peptide were obtained. Baseline (0 mg) OGTT was then performed with a 75-g glucose load, and blood samples were collected at 30, 60, 90, and 120 minutes for measurements of glucose, insulin, and C-peptide. After the baseline OGTT on day 1, a single dose of either 2-, 4- or 8-mg of dexamethasone was administered orally. Twenty-four and 48 hours later, participants returned for additional OGTTs. Ten healthy volunteers (4 male and 6 female) were enrolled. The effect of dexamethasone was maximal 24 hours after 8-mg dexamethasone compared with the effect observed after no dexamethasone administration. At 60 minutes during the OGTT (following 8-mg dexamethasone), blood glucose increased from 127 ± 7.1 mg/dL (6.35 ± 0.36 mmol/L) to 176 ± 19 mg/dL (8.8 ± 0.95 mmol/L), insulin increased from 49.3 ± 3.2 μIU/mL (342 ± 22 pmol/L) to 119.7 ± 10.1 μIU/mL (831 ± 70 pmol/L), and C-peptide increased from 6376 ± 510 pg/L (1913 ± 153 pmol/L) to 10 143 ± 1016 pg/L (3043 ± 305 pmol/L); the 60-minute levels returned towards baseline at 48 hours. Smaller changes were observed with 2- and 4-mg dexamethasone. Twenty-four hours after 8-mg dexamethasone, there was a 2.2- and 1.5-fold increase in homeostasis model assessment of insulin resistance and homeostasis model assessment of β cells, respectively, and a 2.5-fold decrease in the Matsuda sensitivity index. A single oral dose of 8-mg dexamethasone increases blood glucose, insulin, and C-peptide levels maximally at 24 hours, 1 hour following 75-g OGTT. A dexamethasone stress test might identify persons at increased risk for type 2 diabetes.


[Treatment of lumbar and dorso-lumbar scoliosis using the Boston orthosis and the 3-valve orthosis. Comparative study of the results in the frontal and horizontal planes].
A study was made of 30 patients presenting with lumbar and thoracolumbar scoliosis; 15 patients had been treated with a 3-valve orthosis and 15 with a Boston brace. The mean age at the commencement of treatment was 14 years for the 3-valve orthosis and 14 years 4 months for the Boston brace. The total duration of treatment was 11.1 months for the 3-valve orthosis and 11.8 months for the Boston brace. The patients with the 3-valve orthoses presented with an initial mean curve of 30 degrees and with the Boston braces a curve of 24 degrees. The mean follow-up after removal of the brace was 17 months for the 3-valve orthosis and 12 months for the Boston braces. The efficacy of the two orthoses was studied in the frontal and horizontal planes, taking into account the overall rotation of the curve and the segmental rotation of each vertebra in the curve. The Boston brace and the 3-valve orthosis were identical in the correction of the curve. The overall derotation was better with the 3-valve orthosis. Segmentally, the 3-valve orthosis was more effective at the apex of the curve whilst the Boston brace was more effective at the extremities of the curve. The ilio-lumbar angle and the trunk instability were corrected better by the Boston brace. The specific indication for the 3-valve orthosis seems, therefore, to be scolioses in which there is a predominance of rotation at the apex of the curve. The Boston brace has its main indication in cases where rotation is considerably close to or at the ends of the curve.


Mycophenolate mofetil inhibits intimal hyperplasia and attenuates the expression of genes favouring smooth muscle cell proliferation and migration.
Intimal hyperplasia remains the leading cause of late graft failure following heart transplantation. The immunosuppressive drug mycophenolate mofetil has been shown to inhibit the development of intimal hyperplasia. This study aimed to assess the efficacy of a combination of mycophenolate mofetil, calcineurin inhibition, and sirolimus on the development of intimal hyperplasia. Male Sprague-Dawley rats received mycophenolate mofetil (30 mg/kg per day) and either tacrolimus (0.1 mg/kg per day), cyclosporine (5 mg/kg per day), or sirolimus (0.05 mg/kg per day) and were compared to an untreated control group. All animals underwent left common carotid artery balloon angioplasty. Morphometric analysis was performed on representative transverse sections, and intima medial ratios calculated at 2 weeks. Profibrotic gene expression was assessed with competitive RT-PCR at 2 weeks for metalloproteinase-2, metalloproteinase-9, TIMP-1, collagen III, and TGF-beta. Sections were stained with sirius red, and extracellular matrix deposition was quantified. Mycophenolate mofetil in combination with rapamycin was associated with the greatest reduction in intimal thickening (intima medial ratio 0.79; range 0.45-0.86), compared to its combination with either cyclosporine (1.41; range 1.06-1.68, P < .02) or tacrolimus (0.93; range 0.81-1.37, P < .05) and controls (1.47; range 1.02-2.04, P < .005). Mycophenolate mofetil and rapamycin significantly inhibited all profibrotic genes studied compared to controls (P < .01) but there were no differences between tacrolimus and cyclosporine. Mycophenolate mofetil and sirolimus significantly attenuated extracellular matrix deposition compared to tacrolimus and cyclosporin (P < .023). The benefits of mycophenolate mofetil in combination with sirolimus are preferential over those with cyclosporine or tacrolimus. Randomised trials are warranted to assess if mycophenolate mofetil should be an alternative agent to calcineurin-inhibitors when used in combination with sirolimus.


[Embolization of varicocele with ethanol].
Embolization with ethanol was performed in 40 varicocele patients to prevent recurrence due to collateral formation. A prescribed amount of ethanol (0.5-4 ml) was injected slowly into the testicular vein with the catheter tip as close as possible to the inguinal region. Embolization with stainless steel coils was also performed in 15 of the 40 patients. Immediately after embolization, three varicoceles were reduced in size, and 37 disappeared. Recurrence was recognized in only two patients. These patients were embolized at a proximal site above lumbar vertebra IV. Spermatic data have improved for 13 patients but not for one azoospermatic patient. Serious complications were recognized in only one patient, who received an injection of 15 ml ethanol in one dose. Therefore, we conclude that embolization with ethanol is an useful treatment for varicocele.


Admission base deficit and lactate levels in Canadian patients with blunt trauma: are they useful markers of mortality?
Elevated base deficit (BD) and lactate levels at admission in patients with injury have been shown to be associated with increased mortality. This relationship is undefined in the Canadian experience. The goal of this study was to define the association between arterial blood gas (ABG) values at admission and mortality for Canadians with severe blunt injury. A retrospective review of 3,000 consecutive adult major trauma admissions (Injury Severity Score, ≥ 12) to a Canadian academic tertiary care referral center was performed. ABG values at the time of arrival were analyzed with respect to associated mortality and length of stay. A total of 2,269 patients (76%) had complete data available for analysis. After exclusion of patients who sustained a penetrating injury or were admitted for minor falls (ground levels or low height), 445 had an ABG drawn within 2 hours of arrival. Patients who died displayed a higher median lactate (3.6 vs. 2.2, p < 0.0001), a worse median BD (-10 vs. -5, p < 0.0001), and a lower pH (7.23 vs. 7.31, p < 0.0001) at arrival compared with those of survivors. A statistically significant association was also observed between lactate and BD values at arrival and both mortality and length of stay (p < 0.0001). Despite population differences, ABGs at admission in Canadian patients with blunt trauma accurately reflect mortality in a similar manner to the previously published literature. Survival curves with lactate and BD values at arrival should be available to all clinicians within their individual trauma centers for both acute care and quality assurance. Prognostic study, level III.


Long-Term Outcome after Rehabilitation of Bilateral Total Hip Arthroplasty in Renal Transplant Recipient - A Case Report.
Total hip replacement is generally proposed for renal transplant patients with avascular osteonecrosis of the femoral head. The purpose of the study is to report the long-term outcome after rehabilitation of bilateral total hip arthroplasty in a patient with renal transplantation suffering from avascular osteonecrosis of the both femoral heads. The patient S.D, 49 years old at follow-up. Few months after renal transplantation, the patient had got avascular osteonecrosis of both femoral head. One year after transplantation the total hip arthroplasty for both hip joints were performed. Three years later repeat total hip arthroplasty surgery for left hip was performed. After any surgery intervention the patient was referred for inpatient rehabilitation. For clinical assessment the clinical findings and Harris Hip Score have been used. The rehabilitation program consisted of exercises, occupational therapy, and patient education. After any rehabilitation treatment the patient had improvement of clinical findings. At follow-up assessment outcome for both hip function was good - Harris Hip Score was 81 points. Rehabilitation is integral part of multidisciplinary treatment of renal transplant recipient after total hip arthroplasty. Regular exercise training of these patients is very important for improving of their long-term outcome.


C5a receptor-deficient mice are protected from thrombophilia and endothelial cell activation induced by some antiphospholipid antibodies.
Recent findings indicate that complement activation--involving specifically C3 and C5--contributes to antiphospholipid (aPL)-mediated thrombosis. Two complement effector pathways are initiated by the cleavage of C5, C5a and C5b, which leads to the formation of the C5b-9 membrane attack complex. To delineate and distinguish the role of C5a from the C5b-9 membrane attack complex seeded by C5b, we examined the in vivo effects (thrombosis) of aPL on C5a receptor-deficient (C5aR-/-) mice. C5aR-/- and C5aR+/+ mice were injected with IgM or with IgG from two different patients with APS (IgM-APS or IgG-APS) or with control IgM or IgG (IgM-NHS or IgG-NHS) twice. Complement fixing activity of the Ig fractions and anticardiolipin activity in the sera of the mice were determined by enzyme-linked immunosorbent assay. Surgical procedures to study thrombus dynamics were performed. IgM-APS but not IgG-APS fixed C1q to cardiolipin-coated plates. IgM-APS significantly enhanced thrombus size in C5aR+/+ mice compared to C5aR+/+ mice treated with IgM-NHS (3198 +/- 2361 microm2 versus 585 +/- 460 microm2). C5aR-/- mice treated with IgM-APS showed a significant reduction in thrombi size as compared with C5aR+/+ mice (676 +/- 690 microm2 versus 3198 +/- 2361 microm2; P = 0.001). IgG-APS enhanced thrombus formation significantly in C5aR+/+ when compared to IgG-NHS-treated mice (3507 +/- 965 microm2 versus 1321 +/- 798 microm2), and these effects were not altered in C5aR-/- mice (3400 +/- 1681 microm2). The data indicate that C5aR-/- mice are protected from the thrombogenic effects of some aPL antibodies.


Research Advances in Clinical and Imaging Characteristics of Intraductal Papillary Mucinous Neoplasm of the Bile Duct.
Understanding on the intraductal papillary mucinous neoplasm of the pancreas (IPMN-P) has dramatically improved in the past three decades. A new disease named intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) reported in recent years shares several similar clinical features with IPMN-P. The clinical manifestations and imaging characteristics of IPMN-B have been gradually recognized. This review summarizes some of the typical cases reported since 2000 and find that clinical manifestations of IPMN-B include epigastric discomfort,biliary colic,jaundice,intermittent fever,sometimes without any symptoms; imaging triads for IPMN-B are mucobilia,dilated bile duct,and bile duct mural nodule.


Ultra-High-Responsivity Vertical Nanowire-based Phototransistor under Standing-Wave Plasmon Mode Interaction Induced by Near-Field Circular OLED.
High-responsivity photodevices are strongly desired for various demanding applications, such as optical communications, logic circuits, and sensors. The use of quantum and photon confinement has enabled a true revolution in the development of high-performance devices. Unfortunately, many practical optoelectronic devices exhibit intermediate sizes where resonant enhancement effects seem to be insignificant. Here we design and fabricate an ultra-high-responsivity organic-light-emitting-diode-induced nanowire resonance phototransistor (ONRPT) based on standing-wave resonance in the nanoscale cavity, subjected to a near-field light. Observations of the ONRPT in standing-wave resonance mode indicate a >104 enhancement in the on/off ratio and a six times higher subthreshold slope when compared with the ONRPT in non-resonance mode. The ONRPT, which leads itself to outstanding electrical and favorably stable performance, opens up a plethora of opportunities for high-efficiency energy devices and allows for nanowire applications in the solar cell, piezo-photonic detectors, and optical modulators.


N-linked glycosylated beta-peptides are resistant to degradation by glycoamidase A.
Beta-peptides are resistant to degradation by a variety of proteolytic enzymes that rapidly degrade natural alpha-peptides. This is one of many characteristics that make beta-peptides an attractive class of compounds for drug discovery efforts. To further understand the molecular recognition properties of beta-peptides and the ability of enzymes to degrade them, we have synthesized a series of N-linked glycosylated beta- and alpha-peptides, and tested their stability towards a glycosidase. We found that glyco-beta-peptides that contain N-acetylglucosamine (1) or N,N-diacetylchitobiose (2) are completely stable to degradation by glycoamidase A. In comparison, the glyco-alpha-peptides 3 and 4 containing N-acetylglucosamine or N,N-diacetylchitobiose are degraded. Inhibition experiments using increasing concentrations of a glyco-beta-peptide fail to inhibit degradation of the corresponding glyco-alpha-peptide, even when the glyco-beta-peptide is at a 128-fold higher concentration than the glyco-alpha-peptide. Evidently, the glyco-beta-peptides have a much weaker affinity for the active site of the glycosidase than the corresponding glyco-alpha-peptide. These and the results with proteolytic enzymes suggest that the additional CH(2) group introduced into the alpha-amino acid residues causes beta-peptides not to be recognized by hydrolytic enzymes. The results described herein suggest the potential of beta-peptides that are functionalized with carbohydrates for biological and biomedical investigations, without having to be concerned about the carbohydrate being removed.


Assessing the Impact of Health Education Intervention on Asthma Knowledge, Attitudes, and Practices: A Cross-Sectional Study in Erbil, Iraq.
Asthma causes chronic coughing, wheezing, dyspnea, and chest pressure. This study assessed asthmatic patients' knowledge, attitudes, and practice (KAP) of bronchial asthma and proper education on its meaning, risk factors, symptoms, diagnosis, management, and prevention practices. We performed a cross-sectional interventional asthma KAP survey in Erbil, Iraq. We adapted a validated study questionnaire from KAP studies in other nations to the Erbil situation and culture. In Erbil, Kurdistan, Iraq, two major hospitals' asthma clinics were studied. We chose 250 asthmatic patients from October 2018 to July 2019. Health education was comprehensive. The health education program used a Kurdish PowerPoint with a printout. Twenty-five groups received two weeks of one-hour health education pre-intervention. Each group was questioned before, 2 weeks after, and 12 weeks after health education. All data were analyzed by SPSS v26. The mean age of the respondents was 37.52 ± 15.16, with 48.7% of the respondents having a positive family history of asthma. After 2 weeks of health education intervention, respondents had a higher knowledge score and positive attitudes compared to pre-education, and after 12 weeks of education, there was a significant difference (p < 0.001) with improvised prevention practice. Health education programs led to considerable improvements in asthmatic patients' knowledge, attitudes, and practices regarding their condition. After receiving health education for a period of two weeks, the majority of the participants answered correctly regarding asthma, its causes, and the elements that trigger asthma attacks.


Analysis of histone post translational modifications in primary monocyte derived macrophages using reverse phase×reverse phase chromatography in conjunction with porous graphitic carbon stationary phase.
A two dimensional-liquid chromatography (2D-LC) based approach was developed for the identification and quantification of histone post translational modifications in conjunction with mass spectrometry analysis. Using a bottom-up strategy, offline 2D-LC was developed using reverse phase chromatography. A porous graphitic carbon stationary phase in the first dimension and a C18 stationary phase in the second dimension interfaced with mass spectrometry was used to analyse global levels of histone post translational modifications in human primary monocyte-derived macrophages. The results demonstrated that 84 different histone peptide proteoforms, with modifications at 18 different sites including combinatorial marks were identified, representing an increase in the identification of histone peptides by 65% and 51% compared to two different 1D-LC approaches on the same mass spectrometer. The use of the porous graphitic stationary phase in the first dimension resulted in efficient separation of histone peptides across the gradient, with good resolution and is orthogonal to the online C18 reverse phase chromatography. Overall, more histone peptides were identified using the 2D-LC approach compared to conventional 1D-LC approaches. In addition, a bioinformatic pipeline was developed in-house to enable the high throughput efficient and accurate quantification of fractionated histone peptides. The automation of a section of the downstream analysis pipeline increased the throughput of the 2D-LC-MS/MS approach for the quantification of histone post translational modifications.


Patient acceptability of a wheel chair recliner developed to perform dental procedures at wheelchair itself: A cross-sectional study.
Transfer from a wheelchair and discomfort in dental chair are two important barriers for access to dental care among wheelchair-bound patients. The authors have devised an automated wheelchair recliner that helps to mimic the dental chair functioning at wheelchair itself. The aim of this study was to analyze the performance and acceptability of wheelchair recliner among wheelchair-bound patients. Tertiary care settings, cross-sectional design. A total of 100 wheelchair-bound adult patients (aged >21 years) were evaluated for acceptability of the recliner. The patients were assessed using eight-item covering patient comfort/acceptability related to positioning, reclining, repositioning, fear of falls, joy, discomfort, perception regarding dentist's discomfort, and use in future on a scale of 0-4 with 0 indicating least satisfying and four indicating most satisfying experience. Overall, patient experience was graded as poor, fair, good, very good, and excellent. The Chi-square test was used to compare the results. IBM Stats package 21.0 was used. Mean ± standard deviation, Numbers/percentages and Chi-square test were used to compare results. The confidence level of the study was 95%. The age of patients ranged from 22 to 83 years (mean age 52.26 ± 18.58 years). Majority were males (58%) and had temporary (60%) disability. On a 4-point scale, the mean scores of patients ranged from 2.47 ± 1.23 (positioning) to 3.40 ± 0.74 (intent to use in future). Overall experience was rated as good to very good by 77% of patients. No significant association of age, sex, or type of disability was seen with overall patient experience. The acceptability rates were good to very good among wheelchair-bound patients and were unaffected by their age, sex, and type of disability.


Computational modelling of the hybrid procedure in hypoplastic left heart syndrome: a comparison of zero-dimensional and three-dimensional approach.
Previous studies have employed generic 3D-multiscale models to predict haemodynamic effects of the hybrid procedure in hypoplastic left heart syndrome. Patient-specific models, derived from image data, may allow a more clinically relevant model. However, such models require long computation times and employ internal pulmonary artery band [dint] dimension, which limits clinical application. Simpler, zero-dimensional models utilize external PAB diameters [dext] and provide rapid analysis, which may better guide intervention. This study compared 0-D and 3-D modelling from a single patient dataset and investigated the relationship dint versus dext and hemodynamic outputs of the two models. Optimum oxygen delivery defined at dint=2mm corresponded to dext=3.1 mm and 3.4 mm when models were matched for cardiac output or systemic pressure, respectively. 0-D and 3-D models when matched for PAB dimension produced close equivalence of hemodynamics and ventricular energetics. From this study we conclude that 0-D model can provide a valid alternative to 3D-multiscale in the hybrid-HLHS circulation.


Time-Resolved Magneto-Optical Kerr Effect of Magnetic Thin Films for Ultrafast Thermal Characterization.
Thermomagnetic and magneto-optical effects are two fundamental but unique phenomena existing in magnetic materials. In this work, we demonstrate ultrafast time-resolved magneto-optical Kerr effect (TR-MOKE) as an advanced thermal characterization technique by studying the original factors of the MOKE signal from four magnetic transducers, including TbFe, GdFeCo, Co/Pd, and CoFe/Pt. A figure of merit is proposed to evaluate the performance of the transducer layers, corresponding to the degree of the signal-to-noise ratio in TR-MOKE measurements. We observe improved figure of merit for rare-earth transition-metal-based TbFe and GdFeCo transducers and attribute this improvement to their relatively larger temperature-dependent magnetization and the Kerr rotation angle at the saturated magnetization state. Furthermore, an optimal thickness of TbFe is found to be ∼18.5 nm to give the best performance. Our findings will facilitate the nanoscale thermal characterization and the device design where the thermo-magneto-optical coupling plays an important role.


FR II radio galaxies at low frequencies - I. Morphology, magnetic field strength and energetics.
Due to their steep spectra, low-frequency observations of Fanaroff-Riley type II (FR II) radio galaxies potentially provide key insights in to the morphology, energetics and spectrum of these powerful radio sources. However, limitations imposed by the previous generation of radio interferometers at metre wavelengths have meant that this region of parameter space remains largely unexplored. In this paper, the first in a series examining FR IIs at low frequencies, we use LOFAR (LOw Frequency ARray) observations between 50 and 160 MHz, along with complementary archival radio and X-ray data, to explore the properties of two FR II sources, 3C 452 and 3C 223. We find that the morphology of 3C 452 is that of a standard FR II rather than of a double-double radio galaxy as had previously been suggested, with no remnant emission being observed beyond the active lobes. We find that the low-frequency integrated spectra of both sources are much steeper than expected based on traditional assumptions and, using synchrotron/inverse-Compton model fitting, show that the total energy content of the lobes is greater than previous estimates by a factor of around 5 for 3C 452 and 2 for 3C 223. We go on to discuss possible causes of these steeper-than-expected spectra and provide revised estimates of the internal pressures and magnetic field strengths for the intrinsically steep case. We find that the ratio between the equipartition magnetic field strengths and those derived through synchrotron/inverse-Compton model fitting remains consistent with previous findings and show that the observed departure from equipartition may in some cases provide a solution to the spectral versus dynamical age disparity.


Alternating Wet-Dry Cycles Rather than Sulfate Fertilization Control Pathways of Methanogenesis and Methane Turnover in Rice Straw-Amended Paddy Soil.
Alternate wet-drying (AWD) and sulfate fertilization have been considered as effective methods for lowering CH4 emissions from paddy soils. However, there is a clear knowledge gap between field studies that focus on the quantification of emissions and laboratory studies that investigate mechanisms. To elucidate mechanisms of CH4 production and oxidation under field conditions, rice was planted in straw-amended mesocosms with or without sulfate fertilization under continuously flooded conditions (FL) or two wet-dry cycles. CO2 and CH4 concentrations in soil air and their natural C isotope compositions were measured at stem elongation, booting, and flowering stages. CH4 concentration reached 51 mg C L-1 at the flowering stage under FL, while it decreased to 0.04 mg C L-1 under AWD. Relative 13C enrichment in CH4 and depletion in CO2 under AWD indicated CH4 oxidation. Ample organic substrate supply may have reduced competition between sulfate-reducing bacteria and methanogenic archaea, and therefore, it explains the absence of a decrease in CH4 concentrations in sulfate treatments. 13C enrichment in CO2 over time (6 and 7‰ with and without sulfate fertilizers, respectively) under FL indicates continuous contribution of hydrogenotrophic methanogenesis to CH4 production with ongoing rice growth. Overall, AWD could more efficiently reduce CH4 production than sulfate fertilization in rice straw-amended paddy soils.


Infertility and cortisol: a systematic review.
Stress and infertility form a complex relationship. In line with this, various stress-related biological markers have been investigated in infertility. This systematic review was performed using PRISMA guidelines (i) to report whether cortisol is highly present in infertile patients compared to fertile control; (ii) to report whether there is any significant difference in the cortisol level in infertile subjects that conceive and those that didn't at the end of assisted reproduction treatments. Original articles involving human (male and female) as subjects were extracted from four electronic databases, including the list of references from the published papers. Sixteen original full-length articles involving male (4), female (11), and both genders (1) were included. Findings from studies that compared the cortisol level between infertile and fertile subjects indicate that (i) Male: three studies reported elevated cortisol level in infertile patients and one found no significant difference; (ii) Female: four studies reported increased cortisol level in infertile subjects and three studies found no significant difference. Findings from studies that measured the cortisol level from infertile patients that conceived and those that didn't indicate that (i) Male: one study reported no significant difference; (ii) Female: one study reported elevated cortisol in infertile patients that conceived, whereas two studies reported increased cortisol in infertile patients that was unable to conceive. Five studies found no significant difference between the groups. In the present review we only included the cortisol value that was measured prior to stimulation or IVF treatment or during natural or spontaneous cycles, despite this, there are still variations in the sampling period, assessment techniques and patients' characteristics. Hence, at present, we are still unable to conclude that cortisol is significantly elevated in infertile patients. We warrant future studies to standardize the time of biological sample collection and other limitations that were addressed in the review to negate the unwanted influencing factors.


Combined effects of quercetin and curcumin on anti-inflammatory and antimicrobial parameters in vitro.
In this in-vitro study, combinatory anti-inflammatory interactions between Quercetin (Q) and Curcumin (C) along with their combined antimicrobial activity against MRSA were studied. Anti-inflammatory markers of (i) COX-2 expression, (ii) NFκβ activation and (iii) NO levels were investigated. Antimicrobial synergy was tested by checkerboard assay. We found that, treatment with the "low-concentration combination group" (QC), where Q and C were combined, resulted in significant downregulation of COX-2 expression (P < 0.0001) and inhibition of NFκβ activation in cells (P < 0.0001), to a similar extent to that induced by higher concentrations of Q and C alone. QC treatment was also found to induce a significant reduction in NO production (P < 0.0001). QC was significantly more effective in the reduction of total NO levels when compared to Q alone (P < 0.001). Checkerboard assay indicated that the combination of Q and C provides better killing of MRSA in lower dilutions than standalone Minimum Inhibitory Concentrations. These results suggest that combining low concentrations of Q and C yield similar or better anti-inflammatory effectiveness when compared to treatment with each agent alone. Moreover, they co-operate synergistically in the context of antimicrobial activity, with an increased effectiveness when compared to Q or C alone at high concentrations.


The fate of the Warsaw Ghetto Medical Faculty.
The Warsaw Ghetto, in existence from 1940 to 1943, was the largest ghetto in Nazi-occupied Europe. The 400,000-500,000 Jews incarcerated within its walls were deprived not only of food and medicine but also of education. Nonetheless, Jewish physicians served the community as befits their profession, and against all odds obtained permission to conduct a course on sanitary measures to combat epidemics, which they transformed into a veritable, clandestine medical school. This review follows the fate of the school faculty, with an emphasis on the achievements of the survivors.


Symmetries shape the current in ratchets induced by a biharmonic driving force.
Equations describing the evolution of particles, solitons, or localized structures, driven by a zero-average, periodic, external force, and invariant under time reversal and a half-period time shift, exhibit a ratchet current when the driving force breaks these symmetries. The biharmonic force f(t)=1 cos(qomegat+phi1)+2 cospomegat+phi2) does it for almost any choice of vphi1 and phi2, provided p and q are two coprime integers such that p+q is odd. It has been widely observed, in experiments in semiconductors, in Josephson junctions, photonic crystals, etc., as well as in simulations, that the ratchet current induced by this force has the shape v proportional, variant1p2q cos(pphi1-qphi2+theta0) for small amplitudes, where theta0 depends on the damping ( theta0=pi/2 if there is no damping, and theta0=0 for overdamped systems). We rigorously prove that this precise shape can be obtained solely from the broken symmetries of the system and is independent of the details of the equation describing the system.


A Systematic Review and Bibliometric Analysis of the Scientific Literature on the Early Phase of COVID-19 in Italy.
Background: Studying the scientific literature about COVID-19 and Italy, one of the first countries to be hit by the pandemic, allows an investigation into how knowledge develops during a public health emergency. Methods: A systematic review of the literature was conducted to identify articles published on the topic between January and April 2020. Articles were classified according to type of study. Co-occurrence of terms, and geographic and temporal trends were analyzed. Results: Of the 238 articles included in the systematic review, the majority (37%) focused on hospital and clinical management of COVID-19, while 23.9% were commentaries. Epidemiological studies constituted 45.5% of the articles published by authors with non-Italian affiliations. Conclusion: The scientific articles on COVID-19 in Italy were varied in type of study, though with limited international impact. The lockdown and the pressure placed on hospitals during the first wave of the pandemic mainly resulted in publications on disease management and commentaries.


A mathematical model for the cell age-dependent decline of creatine in human cell cells.
A mathematical model is proposed to describe the decline of creatine concentration in red blood cells during the course of cell aging. It is based on experimental data concerning two processes of creatine transport across the red cell membrane: a) an active transport, and b) exchange diffusion. The model corresponds well with data obtained from density-fractionated human red cells in normal steady-state erythropoiesis as well as in acutely and chronically activated erythropoiesis. Degradation of the carrier system for active transport is postulated to be the cause of the time course of decline of the cellular creatine concentration.


Λ_{c}→Λl^{+}ν_{l} Form Factors and Decay Rates from Lattice QCD with Physical Quark Masses.
The first lattice QCD calculation of the form factors governing Λ_{c}→Λℓ^{+}ν_{ℓ} decays is reported. The calculation was performed with two different lattice spacings and includes one ensemble with a pion mass of 139(2) MeV. The resulting predictions for the Λ_{c}→Λe^{+}ν_{e} and Λ_{c}→Λμ^{+}ν_{μ} decay rates divided by |V_{cs}|^{2} are 0.2007(71)(74) and 0.1945(69)(72) ps^{-1}, respectively, where the two uncertainties are statistical and systematic. Taking the Cabibbo-Kobayashi-Maskawa (CKM) matrix element |V_{cs}| from a global fit and the Λ_{c} lifetime from experiments, this translates to branching fractions of B(Λ_{c}→Λe^{+}ν_{e})=0.0380(19)_{LQCD}(11)_{τ_{Λ_{c}}} and B(Λ_{c}→Λμ^{+}ν_{μ})=0.0369(19)_{LQCD}(11)_{τ_{Λ_{c}}}. These results are consistent with, and two times more precise than, the measurements performed recently by the BESIII Collaboration. Using instead the measured branching fractions together with the lattice calculation to determine the CKM matrix element gives |V_{cs}|=0.949(24)_{LQCD}(14)_{τ_{Λ_{c}}}(49)_{B}.


Parameter independent low-power heteronuclear decoupling for fast magic-angle spinning solid-state NMR.
Major advances have recently been made in the field of heteronuclear dipolar decoupling in solid-state nuclear magnetic resonance (NMR). These developments have improved the resolution and sensitivity of the NMR spectrum of spins coupled to protons. One such new scheme, denoted as rCWApA, has proven to be robust with practically no need for parameter optimization [A. Equbal et al. Chem. Phys. Lett., 635, 339 (2015)]. Most of the experiments with rCWApA have been carried out in the regimes of slow to moderate magic-angle spinning while simultaneously applying high decoupling radio-frequency amplitudes. Here, we explore the performance of the rCWApA sequence and its predecessor rCWA in the regime of low-power radio-frequency irradiation and fast magic-angle spinning. The robustness of the refocused continuous-wave (rCW) schemes to experimental parameters such as pulse lengths and offset irradiation is demonstrated. Numerical simulations and analytical theory have been used to understand the effects of various nuclear spin interactions on the decoupling performance of the low-power rCW decoupling scheme relative to other decoupling methods. This has lead to the design of an "optimum low-power decoupling sequence" that can be used without parameter optimization. This result is particularly important in the context of samples with low signal to noise.


Juvenile hyaline fibromatosis: a case report.
Juvenile hyalinefibromatosis (JHF) is a rare autosomal recessive (4q21) genodermatosis characterized by a triad of cephalic fibrous outgrowths, gingival hypertrophy and flexion contractures. This paper presents a case report of juvenile hyaline fibromatosis.


Polymorphic tumor necrosis factors microsatellite TNFa4 is associated with resistance of Hodgkin lymphoma to chemotherapy and with replapses after therapy.
The response of tumors to chemotherapy (CHT) exhibits wide individual variations. We examined the incidence of polymorphic TNF genes in 61 patients treated for Hodgkin lymphoma. During treatment, the patients were divided as responders or non-responders, depending upon the amount of CHT required for a clinical eradication of the tumor. The incidence of TNFa4, a microsatellite allele associated with low TNF production in leukocytes, was significantly higher in responders than in non-responders (25.7% vs 0 %, p=0.04). We also examined the incidence of tumor relapses 2-5 years after treatment. The incidence of TNFa4 was also significantly higher in patients with relapses, than in those without relapses (41.1% vs 9.3%, p=0.007). These results indicate that TNFa4 is a marker of resistance of Hodgkin lymphoma to chemotherapy and most probably is a marker of bad prognosis.


Production of glycerides from glycerol and fatty acid by immobilized lipases in non-aqueous media.
Immobilized Mucor miehei lipase catalyzes synthesis reactions between glycerol and oleic acid. No organic solvent is necessary to solubilize the substrates, which allows for the use of a reaction medium solely composed of the necessary substrates. Water produced in the reaction evaporates due to the high temperature used for the process. A conversion of 86% of oleic acid into triolein is obtained when using the substrates in stoichiometric amounts. Varying the ratio of glycerol over oleic acid allows for the preferential synthesis of one of the glycerides. Some batch reactors have been set up using different means of removing the water: spontaneous evaporation, molecular sieves, vacuum, and dry air bubbling.


Highly Regioselective Aromatic C-H Allylation of N-(Arylmethyl)sulfonimides with Allyl Grignard Reagents Involving Benzylic C-N Cleavage.
A new pair of reaction partners has been established for the aromatic C-H functionalization of benzyl electrophiles with nucleophiles via palladium-catalyzed benzylic C-N cleavage. A range of N-(1-naphthylmethyl)sulfonimides, N-(2-thienylmethyl)sulfonimides, and N-(2-furanylmethyl)sulfonimides smoothly underwent palladium-catalyzed aromatic C-H allylation with allyl Grignard reagents at room temperature, delivering structurally diverse substituted 1-allylnaphthalenes and 2-allylheteroarenes in moderate to excellent yields with extremely high regioselectivities. Replacing the N-(arylmethyl)sulfonimide with an (arylmethyl)ammonium salt, an arylmethyl chloride, or an arylmethyl phosphate as the benzyl electrophile leads to a dramatic erosion of the regioselectivity.


Allan-Herndon-Dudley syndrome.
Allan-Herndon-Dudley Syndrome (AHDS) is a rare X-linked disorder caused by mutation in the gene encoding the monocarboxylate transporter-8. Abnormal transport function is reflected by elevated free T3 and decreased free T4 levels along with clinical features characterized by neurological abnormalities including global developmental delay, central hypotonia, rotatory nystagmus, impaired hearing, spasticity and contractures of joints. We report a child with classical clinical features along with confirmatory deranged thyroid levels in blood.


Ecomorphology and sensory biology of bats.
This special issue of The Anatomical Record is inspired by and dedicated to Professor Kunwar P. Bhatnagar, whose lifelong interests in biology, and long career studying bats, inspired many and advanced our knowledge of the world's only flying mammals. The 15 articles included here represent a broad range of investigators, treading topics familiar to Prof. Bhatnagar, who was interested in seemingly every aspect of bat biology. Key topics include broad themes of bat development, sensory systems, and specializations related to flight and diet. These articles paint a complex picture of the fascinating adaptations of bats, such as rapid fore limb development, ear morphologies relating to echolocation, and other enhanced senses that allow bats to exploit niches in virtually every part of the world. In this introduction, we integrate and contextualize these articles within the broader story of bat ecomorphology, providing an overview of each of the key themes noted above. This special issue will serve as a springboard for future studies both in bat biology and in the broader world of mammalian comparative anatomy and ecomorphology.


Effects and Mechanisms of Fruit and Vegetable Juices on Cardiovascular Diseases.
Many studies have indicated that consumption of vegetables and fruits are positively related to lower incidence of several chronic noncommunicable diseases. Although composition of fruit and vegetable juices is different from that of the edible portion of fruits and vegetables, they contain polyphenols and vitamins from fruits and vegetables. Drinking vegetable and fruit juices is very popular in many countries, and also an efficient way to improve consumption of fruits and vegetables. The studies showed that fruit and vegetable juices affect cardiovascular risk factors, such as lowering blood pressure and improving blood lipid profiles. The main mechanisms of action included antioxidant effects, improvement of the aspects of the cardiovascular system, inhibition of platelet aggregation, anti-inflammatory effects, and prevention of hyperhomocysteinemia. Drinking juices might be a potential way to improve cardiovascular health, especially mixtures of juices because they contain a variety of polyphenols, vitamins, and minerals from different fruits and vegetables. This review summarizes recent studies on the effects of fruit and vegetable juices on indicators of cardiovascular disease, and special attention is paid to the mechanisms of action.


One-lung anesthesia update.
One-lung ventilation is used during a variety of cardiac, thoracic, and major vascular procedures. Endobronchial tubes, bronchial blockers, and occasionally, single-lumen tubes are used to isolate the lungs. Patients with difficult airways and pediatric patients provide special challenges for lung isolation. Finally, intraoperative hypoxia and hypercarbia in patients with intrinsic lung disease frequently complicate one-lung anesthesia. The concepts and controversies in lung isolation techniques are discussed.


Handed asymmetry in nematodes.
Like most animals, C. elegans and other nematodes exhibit several internal left-right asymmetries with an essentially invariant (dextral) handedness. Handedness is established in early cleavage, resulting in a markedly left-right-asymmetric embryo on which bilateral symmetry must be superimposed later in embryogenesis. Some of the asymmetric cell interactions that accomplish this have been identified, but the mechanism that initially establishes dextral rather than sinistral handedness is not understood, in C. elegans or any other embryo. Analysis of mutations that result in reversal of handedness, such as spn-1 in C. elegans, should help elucidate this process. A model involving centriolar segregation is proposed as a possible mechanism for handedness choice.


Pharmacologic profile of the selective mitochondrial-K(ATP) opener BMS-191095 for treatment of acute myocardial ischemia.
ATP-sensitive potassium channel (K(ATP)) openers as a class protect ischemic myocardium. The protective effects are independent of vasodilator activity and effects on action potential shortening, actions typically associated with sarcolemmal K(ATP) activation. BMS-191095 is a novel mitochondrial K(ATP) opener which protects ischemic myocardium while having no electrophysiologic or vasodilator effects (determined in vitro and in vivo). The cardioprotective effects were determined in isolated rat hearts subjected to ischemia and reperfusion. Protective effects were deduced from increased time to contracture formation during ischemia, improved reperfusion recovery of contractile function, and reduced reperfusion LDH release. The cardioprotective effects of BMS-191095 were observed at concentrations at which this compound selectively opened cardiac mitochondrial K(ATP) channels. This effect was consistent with the pharmacologic profile of this agent. The protective effects were abolished by mitochondrial K(ATP) inhibition. Unlike first-generation K(ATP) openers, BMS-191095 is expected to protect ischemic myocardium with little hemodynamic sequelae and without any proarrhythmic potential. BMS-191095 is potentially useful clinically as a cardioprotective agent. It is also a useful tool for basic research.