Total and specific IgG4 antibody levels in atopic eczema.
Total IgG4 and IgG4 antibody levels specific for 10 allergens (three inhaled and seven ingested) were measured by radioimmunoassay of sera taken from three groups of adult patients: (1) 32 cases of atopic eczema, (2) 28 cases of respiratory allergy and (3) 156 normal volunteers. In all three groups IgG4 antibody activity was mainly directed against common foods, and generally the group with atopic eczema had higher total and specific IgG4 levels than the cases of respiratory allergy, who in turn had higher titres than the normal group. There was within each group a tendency for men to have more total IgG4 than women and the difference was statistically significant among the normals. There was evidence of an IgG4 restricted response in atopic eczema because despite the group's elevated total IgG4 its total IgG4 remained within normal limits. Furthermore specific IgG4 was correlated with the corresponding specific IgE level in five of the 10 allergens examined. These results are generally consistent with the view that IgG4 levels are raised in cases of atopic eczema due to prolonged exposure to an allergen which initiated an IgE response.


Anxiety and the restitutional function of homosexual cruising.
Psychoanalytical exploration of latent homosexuality, of homosexual cruising and the related fantasies indicates that it is (among other things) an act of restitution, an effort to resurrect the father, to contradict the ambivalent wishes to rob and murder him, to make sure that he is alive and well and not the victim of the cruiser's competitiveness and destructiveness, to idealize him and render him into an object of love; thus to avoid anxiety and to preclude the father's wrath and retaliation. That such restitutional attempts fail and instead reflect the murderous (both the anal and the genital) intent is no surprise for the psychoanalyst who regularly witnesses contradictory aims in the manifestations of all the neuroses and psychoses including the obsessional. The observations (as well as a host of other clinical phenomena) indicate the intimate relation of anxiety to the aggressive strivings (despite the fact that anxiety instigates repression of the sexual wishes). Anxiety serves as a precipitant of repression and symptom formation while guilt, both conscious and unconscious manifestations, is a product of the oedipal sexual wishes.


A bipartite boundary element restricts UBE3A imprinting to mature neurons.
Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of function from the maternal allele of UBE3A, a gene encoding an E3 ubiquitin ligase. UBE3A is only expressed from the maternally inherited allele in mature human neurons due to tissue-specific genomic imprinting. Imprinted expression of UBE3A is restricted to neurons by expression of UBE3A antisense transcript (UBE3A-ATS) from the paternally inherited allele, which silences the paternal allele of UBE3A in cis However, the mechanism restricting UBE3A-ATS expression and UBE3A imprinting to neurons is not understood. We used CRISPR/Cas9-mediated genome editing to functionally define a bipartite boundary element critical for neuron-specific expression of UBE3A-ATS in humans. Removal of this element led to up-regulation of UBE3A-ATS without repressing paternal UBE3A However, increasing expression of UBE3A-ATS in the absence of the boundary element resulted in full repression of paternal UBE3A, demonstrating that UBE3A imprinting requires both the loss of function from the boundary element as well as the up-regulation of UBE3A-ATS These results suggest that manipulation of the competition between UBE3A-ATS and UBE3A may provide a potential therapeutic approach for AS.


The Association between Varicella Vaccination and Herpes Zoster in Children: A Semi-National Retrospective Study.
Varicella vaccination in children has been performed worldwide in recent years. Despite established effectiveness, many countries still do not routinely vaccinate children against varicella, probably due to concerns about complications, such as herpes zoster infection. We aimed to compare the herpes zoster incidence in children before and after implementing the mandatory varicella vaccine in Israel in 2008. As a secondary aim, we characterized several parameters, including age, sex, and ethnic sector among herpes zoster cases, and we evaluated the complication rate to identify data relevant to the immunization status of the pediatric population. A retrospective study was conducted between 2000 and 2021, including patients aged 0-18 years old in a large cohort in southern Israel. A time series analysis and complication rates evaluations were performed in the pre- and post-vaccination eras. A total of 109.24 herpes zoster cases per 100,000 population per year were diagnosed between 2000 and 2007 (pre-vaccination era), compared to 354.71 herpes zoster cases per 100,000 population per year diagnosed between 2008 and 2021 (post-vaccination era) (p < 0.001). No change in the complication rate was documented. Thus, we concluded that there is an association between the varicella vaccine implementation program and the increase in the rate of herpes-zoster occurrence without a concurrent negative contribution to herpes zoster-related morbidity.


[Influence of vitamin D on fertility and fetal development--review of literature].
Cholecalciferol was qualified by FDA (Food and Drug Administration) into the A category if administered in recommended doses and to the D category if the doses exceed RDA (Recommended Dietary Allowance). There are very divergent opinions among researchers concerning the optimal daily dose of vitamin D-according to some of them, the optimal dose of vitamin D should exceed 400 Ul/24h. On the other hand, there is no data to estimate the optimal dose and to formulate recommendations. It is necessary to conduct research on animal models to fully comprehend the symptoms and syndromes caused by excess or deficiency of cholecalciferol. However, the conclusions of the research done on animals should not be over-generalized. Moreover, some data concerning the influence of vitamin D administered during the pregnancy on fetal development are often ambiguous. All these facts are the reason why recommendations of vitamin D supplementation in pregnancy still remain uncertain and need thorough investigation.


How specific are venous symptoms for diagnosis of chronic venous disease?
The objective of this study is to evaluate whether and which 'venous' symptoms are characteristic for patients affected with chronic venous disease compared to patients with other diseases of the lower limbs (e.g. arthrosis, peripheral arterial disease, spinal disc herniation). A cross-sectional study was performed to compare the frequency of venous symptoms among 76 patients with chronic venous disease and reflux and 74 patients with other diseases of the legs without reflux. The VEINES-Sym of the VEINES-QOL/Sym questionnaire was used to evaluate the frequency of symptoms. Demographic, clinical classification and ultrasound findings were also noted. A total of 122 patients were included for analysis (response rate of 87%). Presence of venous symptoms was slightly more often reported in the chronic venous disease group than in the non-chronic venous disease group, but differences were small and statistically non-significant. Severity of chronic venous disease as classified by the CEAP classification was not associated with higher proportions of patients reporting symptoms than in non-chronic venous disease patients, except for swelling (p = .016) and itching (p = .007) in C3-C6 patients. The largest difference between the chronic venous disease and non-chronic venous disease group was observed for the time of the day at which symptoms were most intense; patients with chronic venous disease were more likely to experience symptoms at the end of the day (p < .001). The small differences in prevalence of reported 'venous' symptoms between chronic venous disease patients and patients with other diseases of the legs suggest that these symptoms may be less specific for patients with chronic venous disease and refluxing veins than is usually assumed.


Penicillin-resistant and multidrug-resistant Streptococcus pneumoniae in a pediatric hospital in Zagreb, Croatia.
Sixty-four penicillin-resistant Streptococcus pneumoniae isolates [benzylpenicillin minimal inhibitory concentrations (MICs) between 0.05 and 1.6 micrograms/ml] recovered at the Pediatric Hospital "Dr. Fran Mihaljevic" in Zagreb, Croatia between October 1990 and March 1993 were analyzed for serotype, antibiotic susceptibility patterns, and chromosomal relatedness using pulsed-field gel electrophoretic (PFGE) analysis of chromosomal DNA fragmented by digestion with the SmaI endonuclease. Hospital "Dr. Fran Mihaljevic" services the capital of Croatia and its vicinity. Most of the isolates were from nasopharyngeal carriage, but several isolates were from otitis media, sinusitis, and meningitis. Most isolates belonged to either serotype 23F (36/64) or 19F (12/64); the rest, including three 15C isolates, were in 11 additional distinct serotypes. The overwhelming majority (25/36) of the serotype 23F isolates had penicillin MIC values of 1-2 micrograms/ml and shared variants of a common PFGE pattern, closely related to the PFGE identified in multiresistant pneumococci of the same serotype with wide geographic spread to Spain, Portugal, France, and the United States. This group of bacteria was also resistant to tetracycline, chloramphenicol, and sulfamethoxazole/trimethoprim. In contrast to the relative genetic and phenotypic homogeneity of the more highly penicillin resistant isolates, pneumococci with penicillin MICs between 0.5 and 0.4 microgram/ml (29/64) were distributed in 13 different serotypes and as many as 20 distinct PFGE patterns.


Teaching Children with Autism in Small Groups with Students Who are At-Risk for Academic Problems: Effects on Academic and Social Behaviors.
Students with ASD are often taught in individual instructional arrangements, even when they receive educational services in inclusive settings. Providing intervention in small group arrangements may increase opportunities for social interactions, particularly when these opportunities are systematically planned. In this study, academic instruction was conducted in small groups consisting of one student with ASD and peers who were socially competent but at risk for academic failure. All students learned targeted academic behaviors and increased their use of targeted social behaviors during instructional sessions. Generalization of social behaviors to a less-structured context was variable. Results suggest that small group instruction may be a feasible and preferred alternative to individual instruction for students with ASD.


Observation of the shock-induced β-Sn to b.c.t.-Sn transition using time-resolved X-ray diffraction.
Time-resolved X-ray diffraction measurements have been carried out on dynamically compressed Sn up to a maximum pressure of ∼13 GPa at the European Synchrotron Radiation Facility. The phase transition from β-Sn to body-centered tetragonal (b.c.t.) Sn has been observed using synchrotron X-ray diffraction for the first time undergoing shock compression and release. Following maximum compression, the sample releases to lower pressures for several nanoseconds until the reverse transition occurs. The data are in good agreement with previous shock boundaries that indicate that the β-Sn phase is stable ∼2 GPa higher than the static boundary upon compression and the b.c.t.-Sn phase is stable ∼1 GPa lower upon release. The transition to the high-pressure phase reveals a loss of texture in the X-ray diffraction data from the `quasi' single-crystal β-Sn structure to a more powder-like Debye-Scherrer ring.


[Newer antimycotics. I. Derivatives of phenyl-hydrazine (author's transl)].
The author produced a number of derivatives of phenyl-hydrazine and its analogues, investigated their antimicrobial efficiency in vitro, and discussed the association of chemical structure with the fungistatic effect in the series of phenyl-hydrazine-derivatives. From the author's results it can be concluded that the halogen-substituted phenyl-hydrazines and their N-(acetyl)-derivatives exert a moderate fungistatic effect (Tab. 1). In the series of N-aryl-sulphonyl-N'-phenyl-hydrazines only the compounds derived from 3,4-dichloro-phenyl-hydrazine proved to be effective; the other representatives of this type were fully ineffective (Tab. 1). The majority of the halogen-substituted N-aroyl-N'-phenyl-hydrazines exerted a relatively strong fungistatic activity with a broad spectrum of efficiency (Tab. 2). On the contrary, their analogues having a -CO-NH- group in place of the -CO-NH-NH-group, were fully inactive (Tab. 3). From the investigated derivatives of phenyl-hydrazine, the N-benzoyl-, N-(2-chloro-benzoyl)-, N-(4-chloro-benzoyl)- and N-furoyl-derivatives of 3- and 4-chloro-phenyl-hydrazine, furthermore the N-benzoyl- and N-furoyl-derivatives of 3,4-dichloro-phenyl-hydrazine were most effective (Tab. 2). The acute toxicity in the mouse of these effective compounds was relatively small; they were found to be significantly less toxic than tetramethyl-thiuramdisulfide (Tab. 4). On the basis of an intensive fungistatic efficiency and small toxicity of the halogen-substituted N-aroyl-N'-phenyl-hydrazines, it seems that a number of representatives of these types of chemical compounds could be given a role in the chemotherapy of superficial human and animal dermatomycoses, and also in the chemoprophylaxis of certain phytomycoses.


Trust in the face of conflict: the role of managerial trustworthy behavior and organizational context.
The authors explored the role of attributions in shaping employees' trust in their managers in the context of negative events. The authors examined how 2 forms of managerial trustworthy behavior (open communication and demonstrating concern for employees) and organizational policies relate to attributions, trust in the manager, and organizational citizenship behavior. Participants were 115 credit union employees who responded to a critical incident regarding a disagreement with their managers. As hypothesized, trustworthy behavior was negatively related to attributions of personal responsibility for negative encounters, and this relationship was stronger when human resource policies were perceived as unfair. Managerial trustworthy behavior was also positively related to trust in the manager and organizational citizenship behavior. Personal attributions partially mediated the relationship between trustworthy behavior and trust.


Size effects of polystyrene nanoparticles on atopic dermatitislike skin lesions in NC/NGA mice.
Nano-sized particles are diffusing in the environment with the development of nanotechnology. Polystyrene (PS) nanoparticles are modified industrial products and pharmaceutical agents, however, adverse effects of PS nanoparticles remain to be elucidated. In the present study, we investigated the effects of PS nanoparticles with different sizes on the atopic dermatitis (AD)-like skin lesions in NC/Nga mice assumed to show the skin barrier defect/dysfunction in the presence or absence of mite allergen. Male NC/Nga mice were injected intradermally with three different-sized PS nanoparticles (25, 50, or 100 nm) and/or mite allergen into their right ears. We evaluated clinical scores, ear thickening, histological findings and the local protein expression of inflammatory molecules in the ear and Ig production in serum. PS nanoparticles aggravated AD-like skin lesions related to mite allergen, which was paralleled by the local protein levels of interleukin-4, CCL2/monocyte chemotactic protein-1, CCL3/macrophage inflammatory protein-1 alpha, and CCL4/macrophage inflammatory protein-1 beta. In contrast, PS nanoparticles decreased interferon-gamma expression. Furthermore, exposure to PS nanoparticles induced ear swelling and CC-chemokine expression in the absence of allergen. These effects were greater with the smaller PS nanoparticles than with the larger ones regarding overall trend. These results suggest that exposure to PS nanoparticles under skin barrier defect/dysfunction can exacerbate AD-like skin lesions related to mite allergen in a size-dependent manner. The enhancing effects may be accounted for by T helper 2-biased immune responses. Furthermore, PS nanoparticles can evoke skin inflammation via the overexpression of CC-chemokines even in the absence of allergen in atopic subjects.


The impact of pediatric asthma education on morbidity. Assessing the evidence.
We reviewed the literature evaluating pediatric asthma education interventions to assess their impact on morbidity (school absences and health care utilization). Thirteen studies were analyzed, most of which reported favorable outcomes. Of the ten studies reporting on school absences, only seven used tests of statistical significance when reporting on postintervention reductions, and of those, only two found a significant decrease in absenteeism. Similarly, among the studies reporting on utilization, not all used tests of statistical significance when reporting on postintervention decreases in physician visits, ER visits, and hospitalization. Only four of the ten studies used adequate sample sizes to detect a 20 percent reduction in school absences, and stratification of the sample by severity of asthma suggests that some programs do reduce health care utilization among those children with more severe disease. We conclude that the effectiveness of asthma educational programs on reducing school absences and health care utilization may be small. These programs are best directed toward children with moderate or severe disease. Finally, it is important for pediatricians, children with asthma, and their families to have realistic expectations about what these programs may accomplish.


Antagonists for the human oxytocin receptor: an in vitro study.
The oxytocin antagonist [Mpa1, D-Tyr(Et)2, Thr4, Orn8]-oxytocin has been successfully used for treating premature labour. The interactions of this antagonist with neurohypophysialhormone receptors in the human myometrium were investigated. Competition curves among [3H]oxytocin, [3H]arginine vasopressin, [3H][1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)2-(O-methyl)-tyrosine, 8-arginine] vasopressin, the corresponding unlabelled peptides and a series of oxytocin antagonists including [Mpa1,D-Tyr(Et)2,Thr4,Orn8]-oxytocin were constructed from results taken from the myometrium of pregnant women and rabbits, and were analysed simultaneously using the computer program LIGAND. The biological activity of [Mpa1,D-Tyr(Et)2,Thr4,Orn8]-oxytocin in the human uterus was investigated by studying its effect on oxytocin-induced intracellular Ca2+ mobilization in human myometrial cells in culture that were expressing high concentrations of oxytocin receptors. The results indicate that [Mpa1,D-Tyr(Et)2,Thr4,Orn8]-oxytocin and related antagonists are selective for the oxytocin receptor in the myometrium of pregnant rabbits but not of pregnant women. In women, they bind with high affinity to the V1 vasopressin receptor. In myometrial cells [Mpa1,D-Tyr(Et)2,Thr4,Orn8]- oxytocin inhibits the oxytocin-induced increase in intracellular Ca2+ concentration in a dose-dependent fashion, with an IC50 value of 5 nmol l-1. The uterine relaxant effect of this antagonist might result not only from the block of the oxytocin receptor, but also from interaction with the V1 vasopressin receptor.


The effect of month of birth on the attainments of primary and secondary school pupils.
Previous research has produced conflicting results regarding the effects of season of birth and age-position on cognitive attainments. In Northern Ireland the school year divides the summer season into two providing an opportunity to evaluate the relative contribution of season of birth and age-position effects. To investigate the relationship between attainment in literacy skills and month of birth for primary and secondary school pupils and to determine the relationship between motor skills and month of birth in primary school pupils. One thousand one hundred and twenty four primary school pupils participated, and results for key stage 3 (KS3) English and GCSE English Language, for 3,493 Year 10 and 3,697 Year 12 secondary school pupils, respectively, were obtained. Primary school pupils were individually assessed using standardised reading and spelling tests, as well as tests of motor skill. They were also assessed using a standardised group reading test in their class groups. For the secondary school pupils, the results for two year cohorts, in KS3 English and GCSE English language, respectively, were analysed. For the primary school pupils there was evidence of both a season of birth and an age-position effect on all of the cognitive measures, particularly in the early years of schooling. There was, also, evidence of a significant age-position effect at both KS3 and GCSE in favour of the older pupils. For the younger primary school pupils there was evidence of significant age-position effects on both motor measures. The findings from the present study suggest that month of birth may be related to both season of birth and age-position effects. These effects may be compounded, particularly in the early years of primary school, when summer born children are youngest in their year, as in England. In Northern Ireland, age-position effects are also evident in secondary school public examination results, which may have implications for long-term life choices.


Arsenic immobilisation in soil using electricity-induced spreading of iron in situ.
An in situ method for spreading iron amendments to arsenic (As)-contaminated soil has been investigated in the laboratory and field. This study tested the distribution of Fe from corroding electrodes through soil using a low-voltage direct current in a laboratory setting and validated the method in the field for As immobilisation in contaminated soil. Laboratory tests revealed that the corrosion of Fe electrodes in soil occurred in a way similar to that during the Fe electrocoagulation in water, which decreased the As concentrations in flow-through water from 150 μg L-1 to undetectable levels. Method validation over one year in the field using electric current pulses with reversing polarity revealed a decrease in As concentration in groundwater by 72-97% in five of the six groundwater wells within the experimental area. This method of introducing Fe amendments to soil can reduce the need for soil excavation upon chemical immobilisation of contaminants in soil.


Anthracene-Argon Clusters Generated in Superfluid Helium Nanodroplets: New Aspects on Cluster Formation and Microsolvation.
About two decades after extensive studies on anthracene-Arn clusters in the gas phase, we report corresponding studies in superfluid helium droplets. With AN as a small fluorophore and spectroscopic data from the gas phase and helium droplets, both the formation of clusters and the microsolvation in superfluid helium droplets can be studied. As expected for helium droplets, a significantly higher number of isomeric variants of the respective cluster sizes are obtained, because metastable variants are stabilized by the low temperature and the surrounding helium. Moreover, spectroscopic data recorded in helium droplets reveal cluster configurations with Ar atoms shielded by a helium solvation layer. Surprisingly, AN-Arn clusters with more than four Ar atoms do not appear to form rigid configurations. The helium droplet data in combination with the gas phase spectra may serve as a suitable reference for further theoretical investigations on solvation and cluster formation in superfluid helium droplets.


[Value of ultrasound shear wave elasticity imaging in diagnosis of Hashimoto's thyroiditis].
To investigate the correlation between Young's modulus of the thyroid tissue measured by in shear wave elastography (SWE) and the clinical manifestations of Hashimoto's thyroiditis in different stages. A total of 104 patients with the clinical diagnosis of Hashimoto's thyroiditis were enrolled in this study, including 26 with hyperthyroidism, 29 with normal thyroid function, 27 with subclinical hypothyroidism, 22 with clinical hypothyroidism, with 50 healthy volunteers serving as the healthy control group. All the subjects underwent SWE to obtain the Young's modulus value of the thyroid tissue. Univariate analysis of variance was used to compare the Young's modulus among the groups, and Pearson correlation analysis was used to analyze the correlation between the Young's modulus of the thyroid tissue and serum levels of thyroid microsomal antibody (TMAb) and thyroid globulin antibody (TGAb). In the 4 groups of patients, the Young's modulus increased significantly in the order of hyperthyroidism group, normal thyroid function group, subclinical hypothyroidism group and clinical hypothyroidism group (F=60.983, P<0.01). The Young's modulus was significantly lower in hyperthyroidism group than in the other 3 groups (P<0.05), and was significantly lower in normal thyroid function group than in subclinical hypothyroidism group and clinical hypothyroidism group (P<0.05). The Young's modulus of the thyroid tissue measured by shear wave elastography is related with the clinical manifestations of Hashimoto's thyroiditis in different stages, but the relevance needs to be further confirmed by multi-center, randomized, controlled studies involving a larger sample size.


Class III peroxidases are activated in proanthocyanidin-deficient Arabidopsis thaliana seeds.
It has previously been shown that proanthocyanidins (PAs) in the seed coat of Arabidopsis thaliana have the ability to scavenge superoxide radicals (O2(-)). However, the physiological processess in PA-deficit seeds are not clear. It is hypothesized that there exist alternative ways in PA-deficient seeds to cope with oxidative stress. The content of hydrogen peroxide (H2O2) and its relevance to the activities of superoxide dismutase (SOD), catalase (CAT) and peroxidases was investigated in both wild-type and PA-deficit mutant seeds. A biochemical staining approach was used to detect tissue localizations of peroxidase activities in PA-deficit mutant seeds. PA-deficient mutants possess significantly lower levels of H2O2 than the wild-type, despite their higher accumulation of superoxide radicals. Screening of the key antioxidant enzymes revealed that peroxidase activity was significantly over-activated in mutant seeds. This high peroxidase activity was mainly confined to the seed coat zone. Interestingly, neither ascorbate peroxidase nor glutathione peroxidase, just the guaiacol peroxidases (class III peroxidases), was specifically activated in the seed coat. However, no significant difference in peroxidase activity was observed in embryos of either mutants or the wild-type, although gene expressions of several candidate peroxidases were down-regulated in the embryos of PA-deficient seeds. The results suggest that enhanced class III peroxidase activity in the seed coat of PA-deficient mutants is an adaptive strategy for seed development and survival.


Ovarian Transcriptome Analysis of Portunus trituberculatus Provides Insights into Genes Expressed during Phase III and IV Development.
Enhancing the production of aquatic animals is crucial for fishery management and aquaculture applications. Ovaries are specialized tissues that play critical roles in producing oocytes and hormones. Significant biochemical changes take place during the sexual maturation of Portunus trituberculatus, but the genetics of this process has not been extensively studied. Transcriptome sequencing can be used to determine gene expression changes within specific periods. In the current study, we used transcriptome sequencing to produce a comprehensive transcript dataset for the ovarian development of P. trituberculatus. Approximately 100 million sequencing reads were generated, and 126,075 transcripts were assembled. Functional annotation of the obtained transcripts revealed important pathways in ovarian development, such as those involving the vitellogenin gene. Also, we performed deep sequencing of ovaries in phases III and IV of sexual maturation in P. trituberculatus. Differential analysis of gene expression identified 506 significantly differentially expressed genes, which belong to 20 pathway, transporters, development, transcription factors, metabolism of other amino acids, carbohydrate and lipid, solute carrier family members, and enzymes. Taken together, our study provides the first comprehensive transcriptomic resource for P. trituberculatus ovaries, which will strengthen understanding of the molecular mechanisms underlying the sexual maturation process and advance molecular nutritional studies of P. trituberculatus.


Predictive factors for new-onset atrial fibrillation in acute coronary syndrome patients undergoing percutaneous coronary intervention.
The aim of this study is to investigate the predictive factors for new-onset atrial fibrillation (AF) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). A total of 934 ACS patients admitted into the Department of Cardiology from February 2015 to February 2017 were collected. All patients were treated with PCI after admission and followed up for 1 year. Data of patients, such as age, gender, past medical history, dyslipidemia, cardiogenic shock, heart failure, medication, culprit vessel, echocardiographic characteristics and types of ACS were collected. Patients enrolled were divided into AF group and non-AF group according to whether there was new-onset AF or not. The clinical baseline data, coronary angiographic results and echocardiographic characteristics were compared between the two groups. The left atrial volume index (LAVI) and incidence rate of AF were compared using the histogram, and multivariate Logistic regression analyses were conducted for independent risk factors for new-onset AF in ACS patients undergoing PCI. In terms of clinical baseline data and coronary angiographic results, the average age and proportions of female, hypertension, heart failure, cardiogenic shock and application of β-receptor blockers and antiarrhythmic drugs in AF group were significantly increased compared with those in non-AF group (P<0.05). In terms of echocardiographic characteristics, the mitral E peak, LAVI, and proportions of E/Em>15 and proportions of left ventricular ejection fraction (LVEF) <40% were significantly increased (P<0.05), but LVEF was obviously decreased (P<0.05) in AF group compared with those in non-AF group. According to multivariate Logistic regression analyses, cardiogenic shock, LAVI and age were independent risk factors for new-onset AF in ACS patients undergoing PCI. The comparison among patients with different LAVI showed that with the increase of LAVI, the incidence rate of AF was gradually increased. Cardiogenic shock, LAVI and advanced age are independent predictive factors for new-onset AF in ACS patients undergoing PCI. The incidence rate of AF was gradually increased with the increase of LAVI.


Alpha-adrenoceptor blockade by phentolamine causes beta-adrenergic vasodilation by increased catecholamine release due to presynaptic alpha-blockade.
We tested whether the alpha 1- and alpha 2-blocking agent phentolamine can be used to assess the contribution of alpha-adrenergic constriction in circulatory control. In 15 conscious dogs at rest, phentolamine (2 mg/kg i.v.) caused hypotension (-17 mm Hg mean arterial pressure), vasodilation (-29% total peripheral resistance), tachycardia, and an increase in cardiac output, oxygen consumption, and plasma catecholamines. Following beta-adrenoceptor blockade (2 mg/kg i.v. nadolol), phentolamine still produced hypotension and increased plasma catecholamine levels, but neither vasodilation nor augmented oxygen consumption. During beta-blockade, phentolamine caused a 28-fold decrease in the vasoconstrictor response to norepinephrine infusions. An equihypotensive dosage of the alpha 1-adrenoceptor blocking agent prazosin (1.2 mg/kg i.v.) did not elevate heart rate, cardiac output, plasma catecholamines, or oxygen consumption. The prazosin-induced vasodilation was not attenuated by prior beta-blockade, in contrast to the phentolamine-induced vasodilation. It is concluded that phentolamine increased catecholamine release by presynaptic alpha 2-blockade, thereby suppressing the autoinhibition of transmitter release. This excess of catecholamines causes a rise of oxygen consumption and vasodilation by beta-adrenergic stimulation. Under beta-blockade, this excess competitively counteracts the postsynaptic vascular alpha-blockade. The combination of pre- and postsynaptic effects invalidates the use of phentolamine in the assessment of alpha-adrenoceptor-mediated vasoconstrictor tone.


Effect of dietary inclusion of small quantities of Mucuna pruriens seed meal on sexual behavior, semen characteristics, and biochemical parameters in rabbit bucks (Oryctolagus cuniculus).
The aim of this work was to investigate the effects of Mucuna pruriens seed meal (MSM) on sexual behavior, semen, and biochemical parameters in rabbit bucks. Twenty-four 12-week-old rabbit bucks weighing 1002 to 1156 g were randomly allocated to three experimental diets containing 0, 1.5, and 3% of MSM in a 3-month trial. Sexual behavior parameters such as mounting latency, mounting frequency, successful mounting frequency, intromission latency, and post ejaculatory interval were monitored at the end of the experiment by mating with receptive females. Thereafter, rabbits were weighed, stunned, and humanely sacrificed and testes, epididymis, and vas deferens were harvested for evaluation of organ weights and semen characteristics. Results indicate that supplementing rabbit diet with MSM induced a significant decrease (P < 0.05) in mounting latency (69.7%) and intromission latency (19.7%), while it significantly (P < 0.05) increased successful mounting frequency (60%) as well as relative weight of testis (33.3%) and vas deferens (54.5%). There was a dose-dependent increase (P < 0.05) in sperm motility (35.7%) and concentration (65.9%), serum albumin (19.1%) and protein concentration (9.9%), and a decrease in sperm morphological alterations (68.3%), serum cholesterol (13.4%), and urea (11.6%) in treatment groups where MSM was supplemented at 3% compared to controls. From the findings, it appears MSM is a potential enhancer of male reproductive performance that can be recommended to rabbit farmers for improving reproductive performance and quality of semen, hence a boon to reproduction and production in rabbit farming industry.


Summary of Oncologic and Functional Outcomes.
Large cohort and collaborative studies to date have shown that the short-term oncological outcomes appear to be at least as good as traditional laparoscopic surgery. These results need confirmation in randomized controlled trials, which are currently underway (GRECCAR 11 and COLOR III). The functional data on transanal total mesorectal excision is still very scarce and more mature data on quality of life and function outcomes are eagerly awaited.


The efficacy of lapatinib and nilotinib in combination with radiation therapy in a model of NF2 associated peripheral schwannoma.
Neurofibromatosis type 2 (NF2), a neurogenetic condition manifest by peripheral nerve sheath tumors (PNST) throughout the neuroaxis for which there are no approved therapies. In vitro and in vivo studies presented here examine agents targeting signaling pathways, angiogenesis, and DNA repair mechanisms. In vitro dose response assays demonstrated potent activity of lapatinib and nilotinib against the mouse schwannoma SC4 (Nf2 -/-) cell line. We then examined the efficacy of everolimus, nilotinib, lapatinib, bevacizumab and radiation (RT) as mono- and combination therapies in flank and sciatic nerve in vivo NF2-PNST models. Data were analyzed using generalized linear models, two sample T-tests and paired T-tests, and linear regression models. SC4(Nf2 -/-) cells implanted in the flank or sciatic nerve showed similar rates of growth (p = 0.9748). Lapatinib, nilotinib and RT significantly reduced tumor growth rate versus controls in the in vivo flank model (p = 0.0025, 0.0062, and 0.009, respectively) whereas bevacizumab and everolimus did not. The best performers were tested in the in vivo sciatic nerve model of NF2 associated PNST, where chemoradiation outperformed nilotinib or lapatinib as single agents (nilotinib vs. nilotinib + RT, p = 0.0001; lapatinib versus lapatinib + RT, p < 0.0001) with no observed toxicity. There was no re-growth of tumors even 14 days after treatment was stopped. The combination of either lapatinib or nilotinib with RT resulted in greater delays in tumor growth rate than any modality alone. This data suggest that concurrent low dose RT and targeted therapy may have a role in addressing progressive PNST in patients with NF2.


[Clinical application of the scapular free flap extended to the upper arm].
To apply the scapular free flap extended to the upper arm for resurfacing the face and neck, as well as the upper lip in one stage. The scapular free flap was designed with extended portion to the posterior and interior part of the upper arm. Then the free flap was transferred to resurface the face and neck with the routine portion and to resurface the upper lip with the extended portion. 6 cases with extensive upper lip, facial and cervical burn scar were treated with the extended scapular free flaps. The flap size ranged from 22 cm x 11 cm to 40 cm x 9.5 cm (36.57 cm x 10.20 cm in average) for the routine portion and from 7 cm x 4 cm to 12 cm x 4 cm (10.32 cm x 3.67 cm in average) for the extended portion. All flaps survived completely. There are direct communicating branches ("choke vessel") between the circumflex scapular artery (CSA) and the posterior humeral circumflex artery (PHCA). When the blood supply of PHCA is cut off, the CSA can provide blood supply through the communicating branches to the upper arm skin area previously nourished by PHCA. So the blood supply of the extended portion of the scapular free flap is not only from the branches of CSA, but also from the direct communicating branches between the CSA and PHCA. The extended scapular free flap has a reliable blood supply and can be applied to construct the facial and cervical scar contraction with the extended portion to resurface the upper lip. The satisfactory result can be expected.


Motor learning in animal models of Parkinson's disease: Aberrant synaptic plasticity in the motor cortex.
In Parkinson's disease (PD), dopamine depletion causes major changes in the brain, resulting in the typical cardinal motor features of the disease. PD neuropathology has been restricted to postmortem examinations, which are limited to only a single time of PD progression. Models of PD in which dopamine tone in the brain is chemically or physically disrupted are valuable tools in understanding the mechanisms of the disease. The basal ganglia have been well studied in the context of PD, and circuit changes in response to dopamine loss have been linked to the motor dysfunctions in PD. However, the etiology of the cognitive dysfunctions that are comorbid in PD patients has remained unclear until now. In this article, we review recent studies exploring how dopamine depletion affects the motor cortex at the synaptic level. In particular, we highlight our recent findings on abnormal spine dynamics in the motor cortex of PD mouse models through in vivo time-lapse imaging and motor skill behavior assays. In combination with previous studies, a role of the motor cortex in skill learning and the impairment of this ability with the loss of dopamine are becoming more apparent. Taken together, we conclude with a discussion on the potential role for the motor cortex in PD, with the possibility of targeting the motor cortex for future PD therapeutics. © 2017 International Parkinson and Movement Disorder Society.


Vegetation cover induces developmental plasticity of lateralization in tadpoles.
Lateralization of cognitive functions influences a large number of fitness-related behaviors and shows, in most species, substantial variation in strength and direction. Laboratory works and field data have suggested that this variation is often due to adaptive phenotypic plasticity. Strong lateralization should be favored in some ecological conditions, for example, under high risk of predation. For anuran tadpoles, the presence of cover affects predation risk, with tadpoles being more exposed to predators in environments with reduced cover. We tested the hypothesis that the amount of cover experienced early in life affects lateralization in the edible frog, Pelophylax esculentus, tadpoles. We exposed embryos and larvae to high or low vegetation cover environments. For half of the subjects, the treatment was constant whereas the remaining subjects were switched to the opposite treatment after hatching. In agreement with the theoretical expectation, tadpoles exposed to low vegetation cover for the entire development were more lateralized and showed a stronger alignment in directionality of lateralization compared with tadpoles exposed to high vegetation cover. This indicates a possible role of natural variation in vegetation abundance and developmental plasticity as determinants of between-population and between-individual differences in lateralization. We also found that shifting from high to low vegetation cover treatments and vice versa disrupted lateralization alignment, suggesting that developmental trajectories for this trait are determined at the embryonic stage and need environmental stability to be fully expressed.


Geographic association of Rickettsia felis-infected opossums with human murine typhus, Texas.
Application of molecular diagnostic technology in the past 10 years has resulted in the discovery of several new species of pathogenic rickettsiae, including Rickettsia felis. As more sequence information for rickettsial genes has become available, the data have been used to reclassify rickettsial species and to develop new diagnostic tools for analysis of mixed rickettsial pathogens. R. felis has been associated with opossums and their fleas in Texas and California. Because R. felis can cause human illness, we investigated the distribution dynamics in the murine typhus-endemic areas of these two states. The geographic distribution of R. felis-infected opossum populations in two well-established endemic foci overlaps with that of the reported human cases of murine typhus. Descriptive epidemiologic analysis of 1998 human cases in Corpus Christi, Texas, identified disease patterns consistent with studies done in the 1980s. A close geographic association of seropositive opossums (22% R. felis; 8% R. typhi) with human murine typhus cases was also observed.


Production of refolded Toxoplasma gondii recombinant SAG1-related sequence 3 (SRS3) and its use for serodiagnosis of human toxoplasmosis.
SAG1-related sequence 3 (SRS3) is one of the major Toxoplasma gondii tachyzoite surface antigens and has been shown to be potentially useful for the detection of toxoplasmosis. This protein is highly conformational due to the presence of six disulfide bonds. To achieve solubility and antigenicity, SRS3 depends on proper disulfide bond formation. The aim of this study was to over-express the SRS3 protein with correct folding for use in serodiagnosis of the disease. To achieve this, a truncated SRS3 fusion protein (rtSRS3) was produced, containing six histidyl residues at both terminals and purified by immobilized metal affinity chromatography. The refolding process was performed through three methods, namely dialysis in the presence of chemical additives along with reduced/oxidized glutathione and drop-wise dilution methods with reduced/oxidized glutathione or reduced DTT/oxidized glutathione. Ellman's assay and ELISA showed that the protein folding obtained by the dialysis method was the most favorable, probably due to the correct folding. Subsequently, serum samples from individuals with chronic infection (n = 76), probable acute infection (n = 14), and healthy controls (n = 81) were used to determine the usefulness of the refolded rtSRS3 for Toxoplasma serodiagnosis. The results of the developed IgG-ELISA showed a diagnostic specificity of 91% and a sensitivity of 82.89% and 100% for chronic and acute serum samples, respectively. In conclusion, correctly folded rtSRS3 has the potential to be used as a soluble antigen for the detection of human toxoplasmosis.


[Intravenous or oral N acetylcysteine therapy in paracetamol poisoned patients. Should treatment guidelines be reviewed?].
Danish paracetamol (PCM) poisoned patients are treated with N-acetylcysteine (NAC) intravenously for 36 hours. This probably leads to overtreatment. Today, patients with poor prognoses can be identified and, in addition, NAC may have serious side effects. We reviewed the literature (route of administration, duration and timing of treatment) and found that intravenous NAC often leads to side effects (some serious), primarily when serum paracetamol is low. These patients are often only mildly poisoned and they may therefore benefit from a shorter, orally administered regimen (equally efficient and with fewer side effects than intravenously administered NAC).


Congenital heart disease in patients with anomalous intrathoracic heart location.
The purpose of this paper is to analyze 107 patients with anomalous heart location, divided into 6 main group, depending on type of heart formation, location of cardiac apex and topography of abdominal viscera. In most of the patients the associated congenital cardiac defects that were diagnosed were extremely severe, multiple, and cyanotic. Biplane angiocardiography is the most valuable instrument in the diagnosis of anomalous heart location. Surgical treatment of congenital cardiac defects in the presence of anomalous heart location has specific features, but in most of the patients these anomalies did not interfer with the total correction of potentially correctable defects.


Upfront Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors or Targeted Therapy: An Observational Study from the International Metastatic Renal Cell Carcinoma Database Consortium.
The role of upfront cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the era of immune checkpoint inhibitors is unclear. To evaluate the relationship between upfront CN and clinical outcomes in the setting of mRCC treated with immune checkpoint inhibitors or targeted therapy. Using the International Metastatic RCC Database Consortium, we retrospectively identified patients diagnosed with de novo mRCC treated with immune checkpoint inhibitors or targeted therapy. Overall survival (OS) was compared between the two groups using the Kaplan-Meier method and multivariable Cox regressions adjusting for known prognostic factors. We identified a total of 4639 eligible patients with mRCC. Among the 4202 patients treated with targeted therapy and 437 patients treated with immune checkpoint inhibitors, 2326 (55%) and 234 (54%) patients received upfront CN prior to treatment start. In multivariable analyses, CN was associated with significantly better OS in both the immune checkpoint inhibitor-treated (hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.41-0.90, p = 0.013) and the targeted therapy treatment (HR: 0.72; 95% CI, 0.67-0.78, p < 0.001) group. There was no difference in OS benefit of CN between the immune checkpoint inhibitor and targeted therapy treatment groups (interaction p = 0.6). Limitations include selection of patients from large academic centers and the retrospective nature of the study. Upfront CN is associated with a significant OS benefit in selected patients treated by either immune checkpoint inhibitors or targeted therapy, and still has a role in selected patients in the era of immune checkpoint inhibitors. Before effective systemic therapies were available for metastatic kidney cancer, surgical removal of the primary (kidney) tumor was the mainstay of treatment. The role of removing the primary tumor has recently been called into question given that more effective systemic therapies have become available. In this study, we find that removal of the primary kidney tumor still has a benefit for selected patients treated with highly effective modern systemic therapies, including targeted therapies and immune checkpoint inhibitors.


Challenges in diagnosis and management of delirium in Lewy body disease.
Delirium is an acute onset and fluctuating impairment of cognition, attention and arousal, often precipitated by acute illness. Lewy body disease (LBD) is an umbrella term for a range of clinical conditions, including Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). People living with LBD seem to be more susceptible to delirium than those with other subtypes of dementia. To describe the challenges in clinical diagnosis and management of LBD. A systematic review of published literature on diagnosis and management of delirium in LBD. Delirium is particularly challenging to diagnose in LBD as many of the clinical characteristics which define delirium such as inattention, fluctuating arousal, complex visual hallucinations and delusions, are also common to LBD. Distinguishing delirium from LBD can be very difficult clinically especially in the prodromal stages. Both under and over diagnosis of delirium, and under and over treatment of the symptoms have the potential to compromise the care and safety of people with a diagnosed or undiagnosed LBD. Clinicians are currently working with an extremely limited set of evidence-based management options for those with delirium in the context of a LBD diagnosis. For patients with LBD and their families this is an area of clinical practice that needs focused research.


Cross-Selectivity Enhancement of Poly(vinylidene fluoride-hexafluoropropylene)-Based Sensor Arrays for Detecting Acetone and Ethanol.
Two methods for cross-selectivity enhancement of porous poly(vinylidene fluoride-hexafluoropropylene) (PVDF-HFP)/carbon black (CB) composite-based resistive sensors are provided. The sensors are tested with acetone and ethanol in the presence of humid air. Cross-selectivity is enhanced using two different methods to modify the basic response of the PVDF-HFP/CB sensing platform. In method I, the adsorption properties of PVDF-HFP/CB are altered by adding a polyethylene oxide (PEO) layer or by treating with infrared (IR). In method II, the effects of the interaction of acetone and ethanol are enhanced by adding diethylene carbonate (DEC) or PEO dispersed in DEC (PEO/DEC) to the film. The results suggest the approaches used in method I alter the composite ability to adsorb acetone and ethanol, while in method II, they alter the transduction characteristics of the composite. Using these approaches, sensor relative response to acetone was increased by 89% compared with the PVDF-HFP/CB untreated film, whereas sensor relative response to ethanol could be decreased by 57% or increased by 197%. Not only do these results demonstrate facile methods for increasing sensitivity of PVDF-HFP/CB film, used in parallel they demonstrate a roadmap for enhancing system cross-selectivity that can be applied to separate units on an array. Fabrication methods, experimental procedures and results are presented and discussed.


Pressure-time product and work of breathing during biphasic continuous positive airway pressure and assisted spontaneous breathing.
The pressure-time product (PTP) and work of breathing (W) were measured in 19 intubated patients during weaning from mechanical ventilation after aortocoronary bypass surgery. The patients were supported by two different ventilatory modes: biphasic continuous positive airway pressure (Biphasic CPAP; a ventilatory mode that permits spontaneous breathing at two different levels of airway pressure during inspiration and during expiration) and pressure-support ventilation (denominated as assisted spontaneous breathing, ASB). Our aim was to compare the energy cost of breathing imposed by both modes. The PTP was obtained by integrating the area enclosed by the esophageal and chest-wall static recoil pressure curves. The W performed by the patient (Wp) was calculated using Campbell's diagram method, based on the esophageal pressure curve and normalized per liter of ventilation. Two comparable support levels, corresponding to a high and a low degree of mechanical support, were studied for each ventilator mode. The levels of support were generally higher than that necessary to overcome inspiratory resistance. We found significantly higher PTP values during biphasic CPAP than during ASB (p < 0.01), whereas the Wp was the same with biphasic CPAP and ASB at both support levels. We conclude that because of the higher PTP values measured during biphasic CPAP, this mode of ventilation appears to have been more exhausting for our patients. The discrepancy between PTP and Wp is probably due to the different mechanisms of support given by the two ventilatory modes and the greater patient effort is related to those respiratory cycles that are not helped by the ventilator and which represent nearly half of the breaths during biphasic.


One too many: the surprising heterogeneity of Drosophila macrophages.
Macrophages are motile cells that roam the extracellular spaces within organs or the body cavity and carry out essential functions in organ development and immunity. New work published in The EMBO Journal adds surprising new insights into the heterogeneity of Drosophila macrophages revealing many similarities to their vertebrate counterparts.


Host-microbial Cross-talk in Inflammatory Bowel Disease.
A vast community of commensal microorganisms, commonly referred to as the gut microbiota, colonizes the gastrointestinal tract (GI). The involvement of the gut microbiota in the maintenance of the gut ecosystem is two-fold: it educates host immune cells and protects the host from pathogens. However, when healthy microbial composition and function are disrupted (dysbiosis), the dysbiotic gut microbiota can trigger the initiation and development of various GI diseases, including inflammatory bowel disease (IBD). IBD, primarily includes ulcerative colitis (UC) and Crohn's disease (CD), is a major global public health problem affecting over 1 million patients in the United States alone. Accumulating evidence suggests that various environmental and genetic factors contribute to the pathogenesis of IBD. In particular, the gut microbiota is a key factor associated with the triggering and presentation of disease. Gut dysbiosis in patients with IBD is defined as a reduction of beneficial commensal bacteria and an enrichment of potentially harmful commensal bacteria (pathobionts). However, as of now it is largely unknown whether gut dysbiosis is a cause or a consequence of IBD. Recent technological advances have made it possible to address this question and investigate the functional impact of dysbiotic microbiota on IBD. In this review, we will discuss the recent advances in the field, focusing on host-microbial cross-talk in IBD.


MIRD Pamphlet No. 14 revised: A dynamic urinary bladder model for radiation dose calculations. Task Group of the MIRD Committee, Society of Nuclear Medicine.
The constant-volume urinary bladder model in the standard MIRD Pamphlet No. 5 (Revised) phantom has recognized limitations. Various investigators have developed detailed models incorporating more physiologically realistic features, such as expanding bladder contents and residual volume, and variable urinary input rate, initial volume and first void time. We have reviewed these published models and have developed a new model for calculation of radiation absorbed dose to the urinary bladder wall incorporating these aspects. The model consists of a spherical source with variable volume to simulate the bladder contents and a wall represented by a spherical shell of constant volume. The wall thickness varies as the source expands or contracts. The model provides for variable urine entry rate (three different hydration states), initial bladder contents volume, residual volume and first void time. The voiding schedule includes an extended nighttime gap during which the urine entry rate is reduced to one-half the daytime rate. Radiation-absorbed dose estimates have been calculated for the bladder wall surface (including photon and electron components) and at several depths in the wall (electron component) for 2-18F-fluoro-2-deoxy-D-glucose, 99mTc-diethylenetriaminepentaacetic acid (DTPA), 99mTc-HEDP, 99mTc-pertechnetate, 99mTc-red blood cells (RBCs), 99mTc-glucoheptonate, 99mTc-mercaptoacetyltriglicine chelator (MAG3), 99mTc-methylene diphosphonate (MDP), 99mTc-hexamethylpropylene amine oxime (HMPAO), 99mTc-human serum albumin (HSA), 99mTc-MIBI (rest and stress), 123I-/124I-/131I-OIH, 123I/131I-NaI, 125I-iothalamate, 111In-DTPA and 89Sr-SrCl. The new model tends to give a higher radiation absorbed dose to the bladder wall surface than the previous models. Large initial bladder volumes and higher rates of urine flow into the bladder result in lower bladder wall dose. The optimal first voiding time is from 40 min to 3 hr postadministration, depending on radiopharmaceutical. The data as presented in tabular and graphic form for each compound provide guidance for establishing radiation absorbed dose reduction protocols.


Preparation of High-Viability Single-Cell Suspensions from African Turquoise Killifish Brain Tissue.
Studying the brain at the single-cell level has become increasingly popular in recent years. This, however, remains challenging, especially in emerging model organisms. To carry out single-cell sequencing, the preparation of a high-viability single-cell suspension is critical. In this protocol, we describe how to prepare a high-viability single-cell suspension starting from brain tissue of the African turquoise killifish (Nothobranchius furzeri). The protocol consists of dissection, enzymatic and mechanical dissociation of the brain tissue, and debris removal. The protocol described here has been successfully used for 10× Genomics single-cell sequencing of the telencephalon of adult killifish, which requires a cell viability of at least 70%. In addition to single-cell sequencing experiments, the single-cell suspension generated can be used for other applications, including cell culture and flow cytometry.


Correlation of aortic valve area obtained by the velocity-encoded phase contrast continuity method to direct planimetry using cardiovascular magnetic resonance.
Aortic stenosis (AS) is the most common valvular heart disease resulting in surgical intervention. Transthoracic echocardiography (TTE) utilizing the continuity equation is commonly used to determine aortic valve area (AVA). However, sometimes TTE can be limited by poor acoustic windows, heavy valvular calcification, or eccentric jet morphology. Cardiovascular magnetic resonance (CMR) provides an alternative non-invasive method for the evaluation of AVA using direct planimetry. Prior studies have shown good correlation between CMR and other modalities, such as TTE, TEE, and cardiac catheterization. CMR can also assess AVA by using the continuity equation employing velocity-encoded phase contrast (VEPC) imaging. We sought to assess whether velocity-encoded phase-contrast MRI can provide an alternate means of quantifying AVA by CMR. Twenty-two consecutive AS patients were imaged with CMR. AVA was determined by VEPC imaging and by direct planimetry. Mean AVA by planimetry was 1.05+/-0.41 cm2 and 1.00+/-0.4 cm2 by VEPC, with a strong correlation (R2=0.86, p<0.0001) between the two methods. The mean difference of AVA was 0.05+/-0.15 (95% CI=[0.02-0.08]), and the limits of agreement were -0.26 to 0.36 cm2. The mean difference between 2 observers for planimetry was 0.030+/-0.07 (95% CI=[0.02-0.04]) with limits of agreement of -0.11 to 0.16 cm2 and for VEPC was 0.008+/-0.085 (95% CI=[-0.01-0.026]) with limits of agreement of -0.16 to 0.18 cm2. VEPC CMR is an alternative method to direct planimetry for accurately determining AVA. Both techniques can be easily incorporated into a single CMR exam to increase the confidence of AVA determination utilizing cardiac magnetic resonance imaging.


Effectiveness of probiotics in type 2 diabetes: a meta-analysis.
An increasing number of studies suggest that the use of probiotics may have a beneficial effect in patients with type 2 diabetes. The aim of the study was to assess the ability of probiotics to modify selected cardiometabolic risk factors in subjects with type 2 diabetes. PubMed, Embase, Cochrane Library, and Scopus databases were thoroughly reviewed up to January 2015 to search for randomized controlled trials (RCTs) that examined the effect of probiotics on selected modifiable cardiometabolic parameters in patients with type 2 diabetes. The following endpoints were considered: fasting plasma glucose (FPG), insulin concentration, insulin resistance, hemoglobin A1c (HbA1c), as well as the levels of total cholesterol, triglycerides, low-density and high-density lipoprotein cholesterols, and C-reactive protein (CRP). A total of 571 RCTs were initially identified, of which 8 trials with 438 individuals were selected for meta-analysis. The effects of probiotics were calculated for each parameter. The meta-analysis showed a significant effect of probiotics on reducing HbA1c levels (standardized mean difference [SMD], -0.81; confidence interval [CI], -1.33 to -0.29, P = 0.0023; I2 = 68.44%; P = 0.0421 for heterogeneity) and HOMA-IR (SMD, -2.10; CI -3.00 to -1.20, P <0.001; I2 = 82.91%; P = 0.0029 for heterogeneity). Supplementation with probiotics did not have a significant effect on FPG, insulin, and CRP levels as well as the lipid profile. Our meta-analysis suggests that probiotic supplementation might improve, at least to some extent, metabolic control in subjects with type 2 diabetes. However, larger well-designed, longterm RCTs are needed to confirm any potentially beneficial relationship between the use of probiotics and modifiable cardiometabolic risk factors in patients with type 2 diabetes.


The role of TIPS for portal vein patency in liver transplant patients with portal vein thrombosis.
The purpose of this research was to study the efficacy and outcomes of transjugular intrahepatic shunt (TIPS) in end-stage liver disease (ESLD) patients with portal vein thrombosis (PVT) eligible for orthotopic liver transplant. Nine consecutive patients with PVT underwent TIPS as a nonemergent elective outpatient procedure. The primary indication for TIPS was to maintain portal vein patency for optimal surgical outcome. Eight patients underwent contrast enhanced computed tomography (CT) and 1 magnetic resonance imaging diagnosing PVT. Shunt creation was determined by available targets at the time of TIPS and by prior imaging. Patients were followed with portography, ultrasound, CT, or magnetic resonance imaging, and the luminal occlusion was estimated before and after TIPS. Primary endpoints were transplantation, removal from the transplant list, or death. Stabilization, improvement, or complete resolution of thrombosis was considered successful therapy. Failures included propagation of thrombosis or vessel occlusion, and poor surgical anatomy due to PVT. Of 9 patients with PVT, TIPS was successfully placed in all patients without complication or TIPS-related mortality. Eight of 9 patients (88.8%) had improvement at follow-up. One patient failed therapy and re-thrombosed. Two patients (22.2%) were transplanted without complication and had no PVT at the time of transplant. Eight of 9 patients were listed for transplant at the time of their TIPS. Eight of 9 PVTs were nonocclusive. Four of 9 patients (44%) had evidence of cavernous transformation. Two patients expired during follow-up 42 and 44 months after TIPS. Three patients remain on the transplant list. One patient has not been listed due to nonprogression of disease. One patient has been removed from the transplant list because of comorbid disease. In conclusion, TIPS is safe and effective in patients with PVT and ESLD requiring transplant. Patients can be successfully transplanted with optimal surgical anatomy.


Regulatory focus as a mediator of the influence of initiating structure and servant leadership on employee behavior.
In this research, the authors test a model in which the regulatory focus of employees at work mediates the influence of leadership on employee behavior. In a nationally representative sample of 250 workers who responded over 2 time periods, prevention focus mediated the relationship of initiating structure to in-role performance and deviant behavior, whereas promotion focus mediated the relationship of servant leadership to helping and creative behavior. The results indicate that even though initiating structure and servant leadership share some variance in explaining other variables, each leadership style incrementally predicts disparate outcomes after controlling for the other style and dispositional tendencies. A new regulatory focus scale, the Work Regulatory Focus (WRF) Scale, also was developed and initially validated for this study. Implications for the results and the WRF Scale are discussed.


MoS₂ nanoplatelet fillers for enhancement of the properties of waterborne pressure-sensitive adhesives.
Nanocomposite pressure-sensitive adhesives (PSAs) composed of polyurethane (PU)/(meth)acrylates reinforced with MoS2 nanoplatelets were prepared by blending aqueous dispersions. MoS2 crystals were exfoliated by sonication in water in the presence of poly(vinylpyrrolidone) (PVP, molecular weight of 10,000 g mol(-1)) to prepare an aqueous dispersion. Waterborne colloidal polymer particles (latex) were synthesized by miniemulsion photopolymerization in a continuous tubular reactor. The adhesive and mechanical properties from the resulting nanocomposite films were determined as the MoS2 fraction was increased. A superior balance of viscoelastic properties was achieved with 0.25 wt % loading of the MoS2 nanoplatelets, leading to a tack adhesion energy that was three times greater than that for the original PSA.


Impact of Cultivation and Subsequent Burial on Cydia pomonella (Lepidoptera: Tortricidae) and Conotrachelus nenuphar (Coleoptera: Curculionidae).
We assessed the efficacy of cultivation as a potential management strategy for codling moth, Cydia pomonella L. (Lepidoptera: Tortricidae), and plum curculio, Conotrachelus nenuphar Herbst (Coleoptera: Curculionidae) in apple orchards. Cocooned codling moth pupae and thinning apples infested with plum curculio larvae were cultivated over in the field. Emergence, percent burial, damage to buried fruit, and depth of burial was recorded. In the laboratory, both insects were buried at variable depths in sand and potting soil and emergence was measured. A greater proportion of plum curculio larvae buried in infested fruit under laboratory conditions survived to adulthood compared with unburied infested fruit, down to 15 cm. No codling moth adults emerged from under 1 cm or more of sand. Buried codling moth larvae experienced drastically reduced survival to adulthood compared with unburied larvae. These results indicate that strip cultivation may negatively impact codling moth diapausing larvae and pupae on the ground, but not likely to negatively impact plum curculio in infested dropped apples.


The Crohn's disease polymorphism, ATG16L1 T300A, alters the gut microbiota and enhances the local Th1/Th17 response.
Inflammatory bowel disease (IBD) is driven by dysfunction between host genetics, the microbiota, and immune system. Knowledge gaps remain regarding how IBD genetic risk loci drive gut microbiota changes. The Crohn's disease risk allele ATG16L1 T300A results in abnormal Paneth cells due to decreased selective autophagy, increased cytokine release, and decreased intracellular bacterial clearance. To unravel the effects of ATG16L1 T300A on the microbiota and immune system, we employed a gnotobiotic model using human fecal transfers into ATG16L1 T300A knock-in mice. We observed increases in Bacteroides ovatus and Th1 and Th17 cells in ATG16L1 T300A mice. Association of altered Schaedler flora mice with B. ovatus specifically increased Th17 cells selectively in ATG16L1 T300A knock-in mice. Changes occur before disease onset, suggesting that ATG16L1 T300A contributes to dysbiosis and immune infiltration prior to disease symptoms. Our work provides insight for future studies on IBD subtypes, IBD patient treatment and diagnostics.


Glial Calcium Waves are Triggered by Seizure Activity and Not Essential for Initiating Ictal Onset or Neurovascular Coupling.
It has been postulated that glia play a critical role in modifying neuronal activity, mediating neurovascular coupling, and in seizure initiation. We investigated the role of glia in ictogenesis and neurovascular coupling through wide-field multicell and 2-photon single cell imaging of calcium and intrinsic signal imaging of cerebral blood volume in an in vivo rat model of focal neocortical seizures. Ictal events triggered a slowly propagating glial calcium wave that was markedly delayed after both neuronal and hemodynamic onset. Glial calcium waves exhibited a stereotypical spread that terminated prior to seizure offset and propagated to an area ~60% greater than the propagation area of neural and vascular signals. Complete blockage of glial activity with fluoroacetate resulted in no change in either neuronal or hemodynamic activity. These ictal glial waves were blocked by carbenoxolone, a gap junction blocker. Our in vivo data reveal that ictal events trigger a slowly propagating, stereotypical glial calcium wave, mediated by gap junctions, that is spatially and temporally independent of neuronal and hemodynamic activities. We introduce a novel ictally triggered propagating glial calcium wave calling into question the criticality of glial calcium wave in both ictal onset and neurovascular coupling.


Violence against Nursing Students in the Workplace: An Iranian Experience.
Background Workplace violence has a great impact on the quality of patient care and satisfaction. This study aimed to determine the extent of violence experienced by nursing students, and its predisposing factors. Methods This was a cross-sectional study which was conducted on 150 nursing students in teaching hospitals of Ardabil University of Medical Sciences. A questionnaire form was used for data collection. Results Participants stated they were abused physically (12.7%), verbally (73.3%), racial (40.7%), and sexually (5.3%). The lack of awareness of the population about the tasks of the nursing students (40.0%) was the most important risk factor for violence against them. Conclusion The violence against nursing students is a common problem in the workplace. It is mainly caused by the lack of awareness of people from the duties of the nursing students. Therefore, it is necessary to educate the population about the responsibilities of nurses and nursing students.


A complex peripheral code for salt taste in Drosophila.
Each taste modality is generally encoded by a single, molecularly defined, population of sensory cells. However, salt stimulates multiple taste pathways in mammals and insects, suggesting a more complex code for salt taste. Here, we examine salt coding in Drosophila. After creating a comprehensive molecular map comprised of five discrete sensory neuron classes across the fly labellum, we find that four are activated by salt: two exhibiting characteristics of 'low salt' cells, and two 'high salt' classes. Behaviorally, low salt attraction depends primarily on 'sweet' neurons, with additional input from neurons expressing the ionotropic receptor IR94e. High salt avoidance is mediated by 'bitter' neurons and a population of glutamatergic neurons expressing Ppk23. Interestingly, the impact of these glutamatergic neurons depends on prior salt consumption. These results support a complex model for salt coding in flies that combinatorially integrates inputs from across cell types to afford robust and flexible salt behaviors.


Diagnostic performance and prognostic impact of FDG-PET in suspected recurrence of surgically treated non-small cell lung cancer.
The differentiation of recurrent lung cancer and post-therapeutic changes remains a problem for radiological imaging, but FDG-PET allows biological characterisation of tissues by visualising glucose metabolism. We evaluated the diagnostic performance and prognostic impact of FDG-PET in cases of suspected relapse of lung cancer. In 62 consecutive patients, 73 FDG-PET scans were performed for suspected recurrence after surgical therapy of lung cancer. FDG uptake by lesions was measured as the standardised uptake value (SUV). PET results were compared with the final diagnosis established by biopsy or imaging follow-up. SUV and clinical parameters were analysed as prognostic factors with respect to survival. FDG-PET correctly identified 51 of 55 relapses and gave true negative results in 16 of 18 remissions (sensitivity, specificity, accuracy: 93%, 89%, 92%). SUV in recurrent tumour was higher than in benign post-therapeutic changes (10.6+/-5.1 vs 2.1+/-0.6, p<0.001). Median survival was longer for patients with lower FDG uptake in recurrent tumour (SUV<11: 18 months, SUV > or = 11: 9 months, p<0.01). Long-term survival was observed mainly after surgical re-treatment (3-year survival rate 38%), even if no difference in median survival for surgical or non-surgical re-treatment was detected (11 vs 12 months, p=0.0627). For patients subsequently treated by surgery, lower FDG uptake predicted longer median survival (SUV<11: 46 months, SUV> or = 11: 3 months, p<0.001). SUV in recurrent tumour was identified as an independent prognostic factor (p<0.05). FDG-PET accurately detects recurrent lung cancer. SUV in recurrent tumour is an independent prognostic factor. FDG-PET helps in the selection of patients who will benefit from surgical re-treatment.


Therapeutic potential of interferon-gamma in tuberculosis.
Tuberculosis is one of the critical health problems worldwide. The search for ways to improve the results of tuberculosis treatment and overcome drug resistance lies in understanding the pathogenesis of the development of the infectious process. The interferon system, particularly the role of interferon-gamma, has been identified as the main link in the immune response in tuberculosis. The clinical efficacy of interferon-gamma has been studied and evaluated in clinical trials since the end of the last century. There was obtained evidence of the clinical efficacy of interferon-gamma as part of complex therapy. Recent experimental data make it possible to consider interferon-gamma as a promising therapeutic option for the treatment of multidrug-resistant tuberculosis as part of complex therapy worthy of further studies.


[Cationic liposomes in gene delivery].
Cationic liposomes have been extensively explored as gene delivery vector for several reasons. It is because disadvantages of viral vectors include risk of replication, possible immunogenicity, and the difficulty of obtaining a large quantity of viral vectors. Currently, a variety of cationic components for liposome formulations have been developed. The components are broadly divided into two classes based on the chemical structure of hydrophobic moieties: long aliphatic (saturated or unsaturated) hydrocarbons and cholesterol ring. A variety of hydrophilic moieties also include tertiary amines, ammonium salt and spermine. The role of liposomes is to condense DNA to form complexes with high affinity to cell surfaces where possible fusion or destabilization of the membrane and/or endocytosis are involved. However, at present, little structure-activity relationships are known. Some vectors are on clinical trials approved by NIH.


Animal science departments of the future.
Departments of animal science were established in agricultural colleges of public universities just over 100 yr ago, shortly before the founding of today's American Society of Animal Science. These departments and colleges have been remarkably resilient, changing little structurally. Yet, the future portends significant changes in these departments and colleges in response to shifts in how public higher education is financed and how society views the roles of animals in providing food and companionship. Funding for public higher education will continue to decline as a percentage of government appropriations. Public universities will garner more funding from gifts, endowments, grants, contracts, and tuition but will be held more accountable than today by public officials. Departments of animal science will retain strong constituencies and will be major units of most agricultural colleges; however, their students and faculty will be more diverse. Departments of animal science will focus on more species of animals and on a greater role of animals in society. Disciplines of faculty members in departments of animal science will become broader, and research projects will be more complex and have longer horizons, ultimately focused more on sustainability. Departments will share more resources across state and national boundaries, and there will be less duplication of effort regionally. Departments of animal science will continue to be important academic units of universities into the 22nd century.


Synthesis and evaluation of a (18) F-labeled 4-phenylpiperidine-4-carbonitrile radioligand for σ1 receptor imaging.
We report the design and synthesis of several 4-phenylpiperidine-4-carbonitrile derivatives as σ1 receptor ligands. In vitro radioligand competition binding assays showed that all the ligands exhibited low nanomolar affinity for σ1 receptors (Ki (σ1 ) = 1.22-2.14 nM) and extremely high subtype selectivity (Ki (σ2 ) = 830-1710 nM; Ki (σ2 )/Ki (σ1 ) = 680-887). [(18) F]9 was prepared in 42-46% isolated radiochemical yield, with a radiochemical purity of >99% by HPLC analysis after purification, via nucleophilic (18) F(-) substitution of the corresponding tosylate precursor. Biodistribution studies in mice demonstrated high initial brain uptakes and high brain-to-blood ratios. Administration of SA4503 or haloperidol 5 min prior to injection of [(18) F]9 significantly reduced the accumulation of radiotracers in organs known to contain σ1 receptors. Two radioactive metabolites were observed in the brain at 30 min after radiotracer injection. [(18) F]9 may serve as a lead compound to develop suitable radiotracers for σ1 receptor imaging with positron emission tomography.


The option value of innovative treatments in the context of chronic myeloid leukemia.
To quantify in the context of chronic myeloid leukemia (CML) the additional value patients receive when innovative treatments enable them to survive until the advent of even more effective future treatments (ie, the "option value"). Observational study using data from the Surveillance, Epidemiology and End Results (SEER) cancer registry comprising all US patients with CML diagnosed between 2000 and 2008 (N = 9,760). We quantified the option value of recent breakthroughs in CML treatment by first conducting retrospective survival analyses on SEER data to assess the effectiveness of TKI treatments, and then forecasting survival from CML and other causes to measure expected future medical progress. We then developed an analytical framework to calculate option value of innovative CML therapies, and used an economic model to value these gains. We calculated the option value created both by future innovations in CML treatment and by medical progress in reducing background mortality. For a recently diagnosed CML patient, the option value of innovative therapies from future medical innovation amounts to 0.76 life-years. This option value is worth $63,000, equivalent to 9% of the average survival gains from existing treatments. Future innovations in CML treatment jointly account for 96% of this benefit. The option value of innovative treatments has significance in the context of CML and, more broadly, in disease areas with rapid innovation. Incorporating option value into traditional valuations of medical innovations is both a feasible and a necessary practice in health technology assessment.


CO extrusion in homogeneous gold catalysis: reactivity of gold acyl species generated through water addition to gold vinylidenes.
Herein, we describe a new gold-catalyzed decarbonylative indene synthesis. Synergistic σ,π-activation of diyne substrates leads to gold vinylidene intermediates, which upon addition of water are transformed into gold acyl species, a type of organogold compound hitherto only scarcely reported. The latter are shown to undergo extrusion of CO, an elementary step completely unknown for homogeneous gold catalysis. By tuning the electronic and steric properties of the starting diyne systems, this new reactivity could be exploited for the synthesis of indene derivatives in high yields.


Awareness of surgical smoke hazards and enhancement of surgical smoke prevention among the gynecologists.
Surgical smoke is the gaseous by-product produced by heat generating devices in various surgical operations including laser conization and loop electrosurgical procedures that often are performed by gynecologists. Surgical smoke contains chemicals, blood and tissue particles, bacteria, and viruses, which has been shown to exhibit potential risks for surgeons, nurses, anesthesiologists, and technicians in the operation room due to long term exposure of smoke. In this review, we describe the detailed information of the components of surgical smoke. Moreover, we highlight the effects of surgical smoke on carcinogenesis, mutagenesis, and infection in gynecologists. Furthermore, we discussed how to prevent the surgical smoke via using high-filtration masks and smoke evacuation systems as well as legal guidelines for protection measures among the gynecologists.


Multidrug-resistant tuberculosis in rural China: lack of public awareness, unaffordable costs and poor clinical management.
China has the second highest global incidence and prevalence of multidrug-resistant tuberculosis (MDR-TB). We describe here the life experience of a rural Chinese farmer with complicated and aggressive TB. It is unclear if this patient contracted MDR-TB initially or developed MDR-TB during treatment because the initial laboratory results are dubious. The lack of public awareness of TB in rural China fuelled by a belief in toxicity of TB treatment, as mentioned by his brother, caused the patient to stop his TB treatment repeatedly long before completion. The cost of MDR-TB treatment in China is unaffordable for most Chinese, especially those in rural areas. He paid about ¥300 000 (almost US$50 000) for his TB treatment. He was discharged early twice for 'financial difficulties'. This case highlights excessive costs, lack of public awareness, poor patient education, inadequate follow-up, lack of coordination between clinical services and the importance of treatment adherence.


Phenomenological approach to eukaryotic chemotactic efficiency.
Eukaryotic cells are capable of detecting small chemical gradients for a wide range of background concentrations. Ultimately, fluctuations place a limit on gradient sensing and recent work has focused on the role of stochastic receptor occupancy as one possible limiting factor. Here, we use a phenomenological approach to add spontaneous motility fluctuations to receptor noise and predict the directional statistics of eukaryotic chemotaxis. Specifically, an Itô diffusion equation with direction-dependent multiplicative noise is developed and analytically studied. We show that our approach can naturally accommodate recent experimental data for the chemotaxis of the social amoeba Dictyostelium.


Chromosome bands and the subunit structure of Chinese hamster metaphase chromosomes.
Isolated Chinese hamster chromosomes dissociate into a series of specific chromatin subunits approximately the size of stainable chromosome bands upon reduction of the divalent ion concentration during or after isolation. At high pH the chromatin in some bands is differentially removable during chromosome isolation, leaving a banded chromosome with a pattern typical of most G-band procedures. This provides an alternate molecular mechanism to explain the production of banded chromosomes by a variety of staining procedures. These results also suggest an approach to chromatin fractionation, using metaphase chromosomes as a starting material.


Effect of the catechol-O-methyltransferase inhibitor entacapone on the steady-state pharmacokinetics and pharmacodynamics of warfarin.
To investigate the influence of a multiple-dose regimen with the catechol-O-methyltransferase inhibitor entacapone on the pharmacokinetics and pharmacodynamics of warfarin. In a randomized, double-blind, two-way cross-over study, 12 healthy subjects (gender ratio 1 : 1) received treatment for 1 week with either entacapone 200 mg four times daily or placebo during individually optimized treatment with warfarin (INR 1.4-1.8). The effect of entacapone on the steady-state pharmacokinetics of both R- and S-warfarin was determined and, in addition, INR values were measured. The key pharmacokinetic variables were AUCss, Cmax and tmax. Entacapone increased the exposure to R-warfarin by 18% (90% CI: 111, 126%), and caused a 13% (6, 19%) increase in INR values. No effect was seen on the pharmacokinetics of the pharmacologically more potent S-enantiomer. Safety and tolerability variables did not show any difference between the treatment phases. In healthy subjects, entacapone displays a slight pharmacokinetic interaction with R-warfarin but, based on the lack of a clinically relevant pharmacodynamic interaction, it appears that it can also be used safely in Parkinson's disease patients who are receiving warfarin.


Alterations in fascin-expressing germinal center dendritic cells in neoplastic follicles of B-cell lymphomas.
Germinal center dendritic cells (GCDCs) have essential functions in retention of immune complexes within secondary follicles, B-lymphocyte antigenic stimulation, B-cell activation, homing of B-cells via adhesion molecules such as ICAM-1 and VCAM-1, and B-cell survival via apoptosis. The neoplastic cells of follicular lymphomas (FLs) are thought to derive from follicular B lymphocytes, but their relationship to GCDCs remains unclear. This study used immunohistochemical staining for fascin, a 55-kDa actin-bundling protein strongly expressed in GCDCs and their processes, to evaluate their distribution in neoplastic follicles. Forty-two cases of B-cell FL were evaluated, and immunoreactive staining for fascin was compared with six cases of Castleman's disease (CD) and six cases of follicular hyperplasia. FLs generally revealed decreased or absent fascin-staining GCDCs, suggesting loss of fascin expression by dendritic cells in neoplastic follicles compared with hyperplastic follicular centers. In some follicles, there was partial retention of dendritic architecture with islands of residual syncytial network. Interdigitating reticulum cells in the parafollicular regions revealed normal fascin expression with intense staining of dendritic processes. In contrast with FLs, cases of follicular hyperplasia revealed normal or increased fascin-positive follicular dendritic cells, and in cases of hyaline vascular CD, follicular dendritic cells revealed tight syncytial networks. These results suggest that GCDCs are deficient in neoplastic follicles, compared with benign reactive or hyperplastic follicles. This alterations in the germinal center microenvironment might explain the inability of FL cells to present antigen to T lymphocytes and to mount an effective antitumor immune response.


Myeloid cell sirtuin-1 expression does not alter host immune responses to Gram-negative endotoxemia or Gram-positive bacterial infection.
The role of sirtuin-1 (SIRT1) in innate immunity, and in particular the influence of SIRT1 on antimicrobial defense against infection, has yet to be reported but is important to define since SIRT1 inhibitors are being investigated as therapeutic agents in the treatment of cancer, Huntington's disease, and autoimmune diseases. Given the therapeutic potential of SIRT1 suppression, we sought to characterize the role of SIRT1 in host defense. Utilizing both pharmacologic methods and a genetic knockout, we demonstrate that SIRT1 expression has little influence on macrophage and neutrophil antimicrobial functions. Myeloid SIRT1 expression does not change mortality in gram-negative toxin-induced shock or gram-positive bacteremia, suggesting that therapeutic suppression of SIRT1 may be done safely without suppression of myeloid cell-specific immune responses to severe bacterial infections.


SPONTANEOUS MUTATIONAL GENOTYPE-ENVIRONMENT INTERACTION FOR FITNESS-RELATED TRAITS IN DROSOPHILA MELANOGASTER.
Spontaneous mutations were allowed to accumulate for 104-161 generations in 113-176 inbred lines, independently maintained by a single brother-sister mating per generation, all of them derived from a completely homozygous population of Drosophila melanogaster. In each of two to three consecutive generations, all lines were scored for fecundity, egg-to-pupa and pupa-to-adult viabilities, both in the standard laboratory culture medium (ST) and in three harsh media differing from the former by a single factor: higher temperature (HT), higher NaCl concentration (HSC), or a much reduced concentration of nutrients (D). Relative to the standard medium, productivity (fecundity × viability) decreased by 25% (HT), 66% (HSC), and 80% (D). In each medium, mutational variances of those traits and mutational covariances between all possible pairs were calculated from the between-line divergence (codivergence). Mutational correlations between character states in different media were also obtained. Because we used inbred lines, those estimates were mainly due to the accumulation of mildly detrimental mutations, deleterious mutations of large effect being underrepresented. For all traits, mutational heritabilities ranged from 1.41 × 10-4 to 11.24 × 10-4 , and did not increase with intensified environmental harshness. Mutational correlations between character states in different media were usually not large (average absolute value 0.31), reflecting a high degree of environmental specificity of the mutations involved. In our results, mutations quasi-neutral in ST conditions and mildly detrimental in more stressful media were not, as a class, important. Mutational correlations between fecundity and egg-to-pupa viability were small and positive in all media. Those involving pupa-to-adult viability were positive in HT, nonsignificant in HSC, and negative in ST and D, showing how the genetic covariance structure of quantitative traits in populations may change in variable environments.


Effects of age and renal function on vitamin D status in men.
In general, no study has examined the relationship between vitamin D status and key parameters of bone mineral homeostasis in healthy men in Iran. The effects of age and renal function on vitamin D status were determined in a cross-sectional study on a healthy population of Iranian men. From January through February 2001, 520 men, aged 20 - 74 years were selected through a cluster randomized sampling from Shiraz. Serum 25-hydroxyvitamin D, intact parathyroid hormone, calcium, phosphorus, alkaline phosphatase, creatinine, and albumin were measured. Pearson and partial correlation coefficients were used to determine the association between variables. Five hundred twenty men with a mean+/-SD age of 45+/-15 years and a mean+/-SD 25-hydroxyvitamin D level of 35+/-17 nmol/L were enrolled into the study. Over 33.9% of men in Shiraz had a low level of 25-hydroxyvitamin D (<or=25 nmol/L). Serum 25-hydroxyvitamin D did not decline with age in men. Serum parathyroid hormone increased significantly by age in men, but it did not correlate with the decline in creatinine clearance. Men had a decline in serum phosphorus (r=0.23, P<0.0001) and calcium (r=0.14, P=0.001) concentrations by age. Creatinine clearance declined with age. In healthy men, the serum level of 25-hydroxyvitamin D did not decline with age. Nonetheless, the prevalence of vitamin D deficiency is high which warrants consideration of dietary vitamin D supplement in men.


Liver and kidney ultrastructural changes caused by acetylsalicylic acid treatment during pregnancy in rats.
The worldwide use of acetylsalicylic acid (ASA) as an analgesic-antipyretic drug, including during pregnancy, prompted us to investigate its potentially deleterious effects in that condition. Pregnant rats were treated with ASA (1, 10 or 100 mg/kg once a day) from the first day up to term pregnancy. No histological changes were noticed in maternal and fetal livers or kidneys when examined under light microscopy, but some definite dose-dependent effects of ASA were observed on electron microscopy examination. In livers and kidneys of pregnant rats treated with the highest doses of ASA we observed cytoplasmic derangement, mitochondrial cristolysis and abnormally shaped rough endoplasmic reticulum. Similarly, in foetal livers and kidneys from this group we observed degenerative cytoplasmic vacuoles and ballooned mitochondria with cristae derangement and myelin figures. Our data point out the fact that both maternal and foetal tissues can be importantly affected by ASA at the ultrastructural level, without overt signs of toxicity.


Biodiversity as a solution to mitigate climate change impacts on the functioning of forest ecosystems.
Forest ecosystems are critical to mitigating greenhouse gas emissions through carbon sequestration. However, climate change has affected forest ecosystem functioning in both negative and positive ways, and has led to shifts in species/functional diversity and losses in plant species diversity which may impair the positive effects of diversity on ecosystem functioning. Biodiversity may mitigate climate change impacts on (I) biodiversity itself, as more-diverse systems could be more resilient to climate change impacts, and (II) ecosystem functioning through the positive relationship between diversity and ecosystem functioning. By surveying the literature, we examined how climate change has affected forest ecosystem functioning and plant diversity. Based on the biodiversity effects on ecosystem functioning (B→EF), we specifically address the potential for biodiversity to mitigate climate change impacts on forest ecosystem functioning. For this purpose, we formulate a concept whereby biodiversity may reduce the negative impacts or enhance the positive impacts of climate change on ecosystem functioning. Further B→EF studies on climate change in natural forests are encouraged to elucidate how biodiversity might influence ecosystem functioning. This may be achieved through the detailed scrutiny of large spatial/long temporal scale data sets, such as long-term forest inventories. Forest management strategies based on B→EF have strong potential for augmenting the effectiveness of the roles of forests in the mitigation of climate change impacts on ecosystem functioning.


Spatial dependency in child malnutrition across 640 districts in India: need for context-specific planning and interventions.
Child malnutrition remains a matter of concern in India as the current levels are high and the decline is slow. National Family Health Survey (NFHS-4, 2015-16) data, for the first time, provides credible, good quality data at district level on social, household and health characteristics. Techniques of spatial analysis on data in respect of 640 districts were used to identify spatial characteristics of the nutrition levels for children in the 0-60-month age group. Further, the principal component analysis (PCA) was used to identify 7 important correlates of the malnutrition out of 21 relevant components provided in the NFHS-4. The paper further uses three techniques, ordinary least squares (OLS), spatial lag model (SLM) and spatial error model (SEM) to assess the strength of correlation between the malnutrition levels and the shortlisted correlates. The use of SLM and SEM shows improvement in the strength of the association (high R-square) compared to OLS. Women's height and Iodized salt in stunting, child anaemia in wasting, women's height and child anaemia in underweight were found to be significant factors (P < 0.01) along with spatial autoregressive constant. Such analysis, in combination with PCA, has shown to be more effective in prioritizing the programme interventions for tackling child malnutrition.


Effect of a forefoot off-loading postoperative shoe on muscle activity, posture, and static balance.
We investigated whether a forefoot off-loading postoperative shoe (FOPS) alters standing posture, ankle muscle activity, and static postural sway and whether any effects are altered by wearing a shoe raise on the contralateral side. Posture, ankle muscle activity, and postural sway were compared in 14 healthy participants wearing either a FOPS or a control shoe with or without a contralateral shoe raise. Participants were tested under different sensory and support surface conditions. Additionally, reductions in peak pressure under the forefoot while walking were assessed with and without a contralateral shoe raise to determine whether the FOPS continued to achieve its primary off-loading function. Compared with the control condition, wearing a FOPS moved the center of pressure posteriorly, increased tibialis anterior muscle activity, and reduced ankle plantarflexor activity. These changes decreased when a contralateral shoe raise was added. No difference in postural sway was found between footwear conditions. Forefoot peak pressure was always reduced when wearing the FOPS. The posterior shift in center of pressure toward and behind the ankle joint axis is believed to result in the increase in tibialis anterior muscle activity that now acts as the primary stabilizer around the ankle. Instability may, therefore, increase in patients with weak tibialis anterior muscles (eg, diabetic neuropathy) who need to wear offloading devices for ulcer management. We suggest that the addition of a contralateral shoe raise fitted with a FOPS may potentially be beneficial in maintaining stability while off-loading the forefoot in this patient group.