Possible Effects of Copper and Ceruloplasmin Levels on Auditory Event Potentials in Boys with Attention Deficit Hyperactivity Disorder.
The aims of the present study were to investigate the relationship between levels of plasma copper (Cu) and ceruloplasmin (Cp) and amplitudes and latencies of P1, N2, and P3 in the parietal and frontal areas of children with attention deficit hyperactivity disorder (ADHD) as well as to compare these Cu levels and event-related potentials (ERPs) indices in controls. Boys (n=41) with ADHD were divided into two subgroups according to a median split of plasma Cu and Cp levels, separately. ERP indices from the parietal and frontal regions were recorded in children with ADHD and 24 normal boys (control group) using an auditory oddball paradigm. Parietal P3 latency was significantly longer, and parietal P3 amplitude, frontal P3 amplitude, and frontal N2 amplitudes were smaller in children with ADHD than in controls (all p values <0.017). Parietal P1 and frontal P1 latencies were significantly shorter in the higher Cu group than in the lower Cu group (both p values <0.017). Decreased latency of parietal P1 was dependent on plasma levels of Cu (p<0.05). Frontal N2 and parietal N2 amplitudes were significantly lower in the ADHD group with lower Cp levels than in the ADHD group with higher Cp levels (both p values <0.017). Decreased frontal N2 and parietal N2 amplitudes were dependent on plasma levels of Cp (both p values <0.05). Plasma Cu and Cp levels may have an effect on ERPs in ADHD, thus indicating the existence of effects on information processing. Cu levels may have a negative effect on the neuronal encoding of sound, whereas Cp levels may have a positive effect on the processes of cognitive control, conflict monitoring, and stimulus discrimination in children with ADHD.


Prenatal alcohol exposure results in hyperactivity of the hypothalamic-pituitary-adrenal axis of the offspring: modulation by fostering at birth and postnatal handling.
Exposure of fetal rats to alcohol results in permanent hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. In contrast, postnatal handling or fostering have been reported to restrain HPA activity. Because of the deleterious consequences of a hyperresponsive HPA axis, we thought that the possibility that postnatal manipulations might be able to reverse the influence of prenatal alcohol treatment deserved investigation. To test this hypothesis, we exposed rat dams to alcohol by inhalation during the second week of gestation. At birth, pups were either fostered or remained with their dam. For the first 3 weeks, litters were handled daily for 15 min or left undisturbed. At 22 days of age, male and female pups were decapitated under basal conditions, after 10 min of mild electro-footshock, or 10 min after footshock had been terminated. As expected, prenatal exposure to alcohol induced increased adrenocorticotropin (ACTH) secretion in response to footshock, and postnatal handling of control pups resulted in a suppression of corticosterone and ACTH release, although changes in this latter hormone did not reach statistical significance. Surprisingly, however, pups exposed to alcohol that were also fostered and handled after birth, showed an ACTH response to footshock stress that was significantly larger than all other groups. This unexpected response may be due to alterations in maternal-pup behaviors and may indicate that these manipulations act on different neuronal substrates within the central HPA of young rats. Further studies are needed to determine whether adrenal regulation is also altered in animals exposed to alcohol prenatally and reared in a similar manner.


Tumor-related Microbiome in the Breast Microenvironment and Breast Cancer.
Despite the significant progress in diagnosis and treatment over the past years in the understanding of breast cancer pathophysiology, it remains one of the leading causes of mortality worldwide among females. Novel technologies are needed to improve better diagnostic and therapeutic approaches, and to better understand the role of tumor-environment microbiome players involved in the progression of this disease. The gut environment is enriched with over 100 trillion microorganisms, which participate in metabolic diseases, obesity, and inflammation, and influence the response to therapy. In addition to the direct metabolic effects of the gut microbiome, accumulating evidence has revealed that a microbiome also exists in the breast and in breast cancer tissue. This microbiome enriched in the breast environment and the tumor microenvironment may modulate effects potentially associated with carcinogenesis and therapeutic interventions in breast tissue, which to date have not been properly acknowledged. Herein, we review the most recent works associated with the population dynamics of breast microbes and explore the significance of the microbiome on diagnosis, tumor development, response to chemotherapy, endocrine therapy, and immunotherapy. To overcome the low reproducibility of evaluations of tumor-related microbiome, sequencing technical escalation and machine deep learning algorithms may be valid for standardization of assessment for breast-related microbiome and their applications as powerful biomarkers for prognosis and predictive response in the future.


Motion-Compensated Compression of Dynamic Voxelized Point Clouds.
Dynamic point clouds are a potential new frontier in visual communication systems. A few articles have addressed the compression of point clouds, but very few references exist on exploring temporal redundancies. This paper presents a novel motion-compensated approach to encoding dynamic voxelized point clouds at low bit rates. A simple coder breaks the voxelized point cloud at each frame into blocks of voxels. Each block is either encoded in intra-frame mode or is replaced by a motion-compensated version of a block in the previous frame. The decision is optimized in a rate-distortion sense. In this way, both the geometry and the color are encoded with distortion, allowing for reduced bit-rates. In-loop filtering is employed to minimize compression artifacts caused by distortion in the geometry information. Simulations reveal that this simple motion-compensated coder can efficiently extend the compression range of dynamic voxelized point clouds to rates below what intra-frame coding alone can accommodate, trading rate for geometry accuracy.


Neonatal and maternal hair zinc levels in a nonhuman primate model of the fetal alcohol syndrome.
The role of zinc deficiency in the etiology of ethanol-associated fetotoxicity was assessed by measurement of maternal and newborn hair zinc content in a nonhuman primate model of the fetal alcohol syndrome. The model best approximates the human situation for length of gestation and type of placentation, coupled with the ability to control for nutritional factors. All mothers received 110% of their minimum daily caloric requirements as a balanced, nutritionally complete diet, including a minimum of 3.5 mg zinc per day. Over a 2-year period, maternal hair samples from 17 pregnancies (using 12 females) were obtained at term. There were 16 live, full-term neonates (nine ethanol exposed and seven control) from whom samples were taken within 1 hr of birth. The ethanol-exposed infant monkeys had a significantly higher incidence of craniofacial dysmorphology and developmental delay compared to the controls. There was no difference in hair zinc levels between ethanol-exposed and control animals for either the mothers or the newborns. Neonatal levels were, however, consistently higher than corresponding maternal. Although the findings cannot exclude transient or early gestational zinc deficiency as a factor, they provide further evidence that ethanol (and/or its metabolites) is the proximate toxin in the type of fetal injury seen in the fetal alcohol syndrome.


Effects of intramuscular injections of selenium and vitamin E on selenium-vitamin E deficiency in young pigs.
Effects of intramuscular injections of selenium and vitamin E on lesions in pigs with selenium-vitamin E deficiency syndrome were determined in 2 factorial experiments, using a total 69 pigs. The pigs were fed a selenium-vitamin E deficient, 22.3% protein ration, supplemented with methionine, minerals, and vitamins. Weekly intramuscular injections of isotonic saline solution, vitamin E, selenium, or vitamin E and selenium were given to the respective treatment groups. Selenium-vitamin E deficiency lesions occurred only in pigs that were given saline injections. Weekly intramuscular injections of either selenium (as selenous acid buffered to pH (7.3) at the rate of 0.05 mg/kg of body weight or vitamin E at the rate of 20 IU/kg of body weight or the combination of selenium and vitamin E prevented cardiac and skeletal myodegeneration, hepatic necrosis, and death. Significant increases of serum aspartate aminotransferase activity values were noted in pigs with liver, heart, or skeletal muscle lesions, but these increases were not correlated with the extent of the lesions. Vascular lesions, epicardial and endocardial hemorrhages, and yellow discoloration of body fat were not features of this experimentally induced disease. These lesions may be related to factors other than the deficiency of selenium, vitamin E, or selenium and vitamin E in rations previously used in reported studies.


[Intra-individual reproducibility of tilt table studies in diagnosis of vasovagal syncope].
Neurally-induced syncope appears to be the underlying pathophysiologic mechanism in many patients with unexplained syncope. Diagnosis of vasovagal syncope, however, remains difficult and constitutes in many cases an exclusion diagnosis. The present study thus aimed to determine the yield of tilt-table testing in the work-up of patients with unexplained syncope and most importantly to examine the reproducibility of the results of this method. Twenty-four patients with a history of syncope and 11 healthy volunteers were examined on 2 days. In 10 patients, symptoms could be provoked during tilting, in 8 during both tests, in 2 only on one occasion. Only 1 of 11 volunteers developed presyncope during tilting which was not reproducible during the second test. These findings resulted in a sensitivity of 42% and a specificity of 91% for the protocol employed in this study. Overall reproducibility was 91% which suggests that this tilt-table protocol is suitable for evaluation of therapeutic interventions in patients with neurally-mediated syncope.


Switch of noninvasive ventilation (NIV) to continuous positive airway pressure (CPAP) in patients with obesity hypoventilation syndrome: a pilot study.
Obesity is a major worldwide public health issue. The main respiratory complication stemming from obesity is obesity hypoventilation syndrome (OHS). Most of the OHS patients diagnosed during an exacerbation are treated with non invasive ventilation (NIV). Up to date, no prospective study has demonstrated in real life conditions the feasibility of a systematic protocoled switch of NIV to continuous positive airway pressure (CPAP), once stability is achieved. In this prospective study, we included stable patients with OHS, with moderate to severe concomitant obstructive sleep apnea (OSA) and without obstructive pulmonary disease, who had been undergoing NIV for more than 2 months. The following measurements were performed, first with NIV and then after the switch to CPAP: diurnal arterial blood gas measurements; nocturnal oximetry and capnometry; mean compliance and AHI; measures of quality of life and quality of sleep. 22/30 patients accepted to participate in the study and 15/22 patients completed the study. There were no significant differences for pooled data in diurnal alveolar blood gases, nocturnal capnometry (p = 0.534), nocturnal oximetry (p = 0.218), mean compliance (p = 0.766), mean AHI (p = 0.334), quality of life or quality of sleep. Eighty percent of the patients treated in this study favored CPAP over NIV. This pilot study showed in real life conditions the possibility of a systematic switch of NIV to CPAP, in most stable patients with OHS, with similar efficacy on diurnal and nocturnal alveolar gas exchange, quality of life and quality of sleep. ISRCTN13981084 . Registered: 27 February 2017 (retrospectively registered).


ADAMTS13 Gene Mutations Influence ADAMTS13 Conformation and Disease Age-Onset in the French Cohort of Upshaw-Schulman Syndrome.
Congenital thrombotic thrombocytopaenic purpura (TTP) or Upshaw-Schulman syndrome (USS) is a rare, life-threatening, inherited thrombotic microangiopathy (TMA). USS is mostly due to bi-allelic recessive sequence variations of the a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13) gene inducing a severe ADAMTS13 deficiency (activity < 10 IU/dL). In healthy individuals, ADAMTS13 circulates in a folded conformation where CUB domains interact with the spacer domain. The spacer-CUB interaction is abrogated when ADAMTS13 is conformationally activated. This article evaluates the influence of ADAMTS13 sequence variations on both clinical/biological phenotype and ADAMTS13 conformation in USS. All USS patients from the French registry for TMAs (1 January 2000 to 1 June 2017) were investigated for ADAMTS13 genotype, phenotype (activity, antigen and autoantibodies) and conformation. Clinical records were analysed (inaugural acute TTP and follow-up). Child-onset USS was compared with adult-onset USS. Fifty-six USS patients from 51 families (34 child-onset and 22 adult-onset cases) were enrolled. Child-onset USS was characterized by a large panel of ADAMTS13 sequence variations (n = 43), spread all over ADAMTS13 gene and not correlated with either clinical features or plasmatic ADAMTS13 parameters. In contrast, adult-onset USS, consisting exclusively in pregnancy-induced TTP, included a smaller and distinct panel of ADAMTS13 sequence variations (n = 20) because of one mutation (p.Arg1060Trp) present in 82% of patients. ADAMTS13 conformation was studied in 16 USS patients (5 child-onset and 11 adult-onset USS, encompassing 16 distinct ADAMTS13 sequence variations) whose ADAMTS13 antigen levels were detectable: 14 of 16 patients (87.5%) exhibited abnormalities of ADAMTS13 conformation. In USS, age-onset defines two entities and ADAMTS13 sequence variations modify ADAMTS13 conformation.


Supplemental arachidonic acid-enriched oil improves the taste of thigh meat of Hinai-jidori chickens.
The Hinai-dori is a breed of chicken native to the Akita prefecture in Japan. A cross between the Hinai-dori and Rhode Island Red breeds has been commercialized as the Hinai-jidori chicken, one of the most popular brands in Japan. High arachidonic acid (AA) content is a characteristic feature of Hinai-jidori chicken meat. To elucidate the relationship between AA content and the palatability of the Hinai-jidori chicken, we examined the effects of palm oil (PO), corn oil (CO), and arachidonic acid-enriched oil (AAO) diet supplementation on the fatty acid content and sensory perceptions in thigh meat. Each oil and silicate was mixed at a ratio of 7:3, 5% of fresh matter was added to the finisher diet, and Hinai-jidori chickens were fed these diets for 2 wk before slaughter. In thigh meat, the AA content of the AAO group was significantly more than 2-fold higher than that of the PO and CO groups. Other fatty acid contents were not significantly different among the groups. Sensory evaluation showed that the total taste intensity, umami (l-glutamate taste), kokumi (continuity, mouthfulness, and thickness), and aftertaste of the AAO group were significantly higher than those of PO and CO groups in both chicken soup and steamed minced meat. These data suggest that the palatability of chicken meat can be improved by dietary AA supplementation.


Diffractive Imaging of Conical Intersections Amplified by Resonant Infrared Fields.
The fate of virtually all photochemical reactions is determined by conical intersections. These are energetically degenerate regions of molecular potential energy surfaces that strongly couple electronic states, thereby enabling fast relaxation channels. Their direct spectroscopic detection relies on weak features that are often buried beneath stronger, less interesting contributions. For azobenzene photoisomerization, a textbook photochemical reaction, we demonstrate how a resonant infrared field can be employed during the conical intersection passage to significantly enhance its coherence signatures in time-resolved X-ray diffraction while leaving the product yield intact. This transition-state amplification holds promise to bring signals of conical intersections above the detection threshold.


Intracellular mechanism responsible for reduced enzyme secretion from camostate-induced hypertrophied pancreas.
Chornic exogenous administration of cholecystokinin octapeptide (CCK8) to rats led to a reduced sensitivity of pancreatic acinar cells to both CCK8 and carbachol stimulation without changes in affinity or number of CCK or muscarinic receptors. In addition, repeated feeding of camostate, a synthetic protease inhibitor which stimulates endogenous CCK release, desensitized the response of the acini to caerulein. This study investigates whether an altered postreceptor signal transduction mechanism is responsible for the reduced amylase secretion. Four days of camostate treatment significantly increased pancreatic weight, protein and amylase, but not DNA content, indicating organ hypertrophy, CCK8 and carbachol stimulated amylase release from acini, isolated from camostate-treated rats, was significantly reduced without shifting the dose response curve compared to controls. There was no difference in total phosphoinositide turnover between the groups. In addition, CCK8 and carbachol stimulated 45Ca efflux and calcium ionophore stimulated amylase release were similar in both groups. These results indicate that the release of calcium from intracellular stores and the utilization of intracellular calcium to drive amylase secretion is not affected in the hypertrophied pancreas. In contrast, incubation of acini from camostate-treated rats with TPA (a phorbol ester which directly stimulates protein kinase C) showed a 48% reduction in amylase secretion. This suggests that a regulatory mechanism is present at the level of protein kinase C or beyond, which is responsible for the decrease in amylase release in the hypertrophied pancreas.


Gut Microbiota Enterotypes Mediate the Effects of Dietary Patterns on Colorectal Neoplasm Risk in a Chinese Population.
Colorectal cancer (CRC) risk is influenced by dietary patterns and gut microbiota enterotypes. However, the interaction between these factors remains unclear. This study examines this relationship, hypothesizing that different diets may affect colorectal tumor risk in individuals with varied gut microbiota enterotypes. We conducted a case-control study involving 410 Han Chinese individuals, using exploratory structural equation modeling to identify two dietary patterns, and a Dirichlet multinomial mixture model to classify 250 colorectal neoplasm cases into three gut microbiota enterotypes. We assessed the association between dietary patterns and the risk of each tumor subtype using logistic regression analysis. We found that a healthy diet, rich in vegetables, fruits, milk, and yogurt, lowers CRC risk, particularly in individuals with type I (dominated by Bacteroides and Lachnoclostridium) and type II (dominated by Bacteroides and Faecalibacterium) gut microbiota enterotypes, with adjusted odds ratios (ORs) of 0.66 (95% confidence interval [CI] = 0.48-0.89) and 0.42 (95% CI = 0.29-0.62), respectively. Fruit consumption was the main contributor to this protective effect. No association was found between a healthy dietary pattern and colorectal adenoma risk or between a high-fat diet and colorectal neoplasm risk. Different CRC subtypes associated with gut microbiota enterotypes displayed unique microbial compositions and functions. Our study suggests that specific gut microbiota enterotypes can modulate the effects of diet on CRC risk, offering new perspectives on the relationship between diet, gut microbiota, and colorectal neoplasm risk.


Long-term outcomes of less drug-eluting stents by the use of drug-coated balloons in de novo coronary chronic total occlusion intervention: A multicenter observational study.
Data on drug-coated balloons (DCB) for de novo coronary chronic total occlusion (CTO) are limited. We aimed to investigate the long-term outcomes of substitution of drug-eluting stents (DES) by DCB. We compared the outcomes of less DES strategy (DCB alone or combined with DES) and DES-only strategy in treating de novo coronary CTO in this prospective, observational, multicenter study. The primary endpoints were major adverse cardiovascular events (MACE), target vessel revascularization, myocardial infarction, and death during 3-year follow-up. The secondary endpoints were late lumen loss (LLL) and restenosis until 1-year after operation. Of the 591 eligible patients consecutively enrolled between January 2015 and December 2019, 281 (290 lesions) were treated with DCB (DCB-only or combined with DES) and 310 (319 lesions) with DES only. In the DCB group, 147 (50.7%) lesions were treated using DCB-only, and the bailout stenting rate was relatively low (3.1%). The average stent length per lesion in the DCB group was significantly shorter compared with the DES-only group (21.5 ± 25.5 mm vs. 54.5 ± 26.0 mm, p < 0.001). A total of 112 patients in the DCB group and 71 patients in the DES-only group (38.6% vs. 22.3%, p < 0.001) completed angiographic follow-up until 1-year, and LLL was much less in the DCB group (-0.08 ± 0.65 mm vs. 0.35 ± 0.62 mm, p < 0.001). There were no significant differences in restenosis occurrence between the two groups (20.5% vs. 19.7%, p > 0.999). The Kaplan-Meier estimates of MACE at 3-year (11.8% vs. 12.0%, log-rank p = 0.688) was similar between the groups. Percutaneous coronary intervention with DCB is a potential "stent-less" therapy for de novo CTO lesions with satisfactory long-term clinical results compared to the DES-only approach.


When theories of speech meet the real world.
Two theories of speech--one quite conventional, the other much less so--account very differently for the biological advantage of speech over writing/reading. The guiding assumption of the more conventional theory is that the elements of speech are sounds, and that these are served by processes of motor control and auditory perception that are in no way specialized for language. Accordingly, there must be a cognitive stage, beyond action and perception, where the motor and auditory representations are somehow invested with linguistic significance. On the conventional view, then, the sounds of speech are just like the letters of the alphabet. Neither has more than an arbitrary relation to language, hence the difference between them is trivially a matter of which of the equally large gaps between signal and message needs to be bridged. On the less conventional theory, the ultimate constituents of speech are not sounds, but articulatory gestures. Having evolved exclusively in the service of language, they form a natural class, a phonetic modality. Being phonetic to begin with, they do not require to be made so by cognitive translation. And that, very simply, is the advantage of speech over writing/reading. Speech has the corollary advantage that it is managed by a module biologically adapted to circumvent limitations of tongue and ear by automatically coarticulating the constituent gestures and coping with the complex acoustic consequences. But a result is that awareness of phonetic structure is not normally a product of having learned to speak: The module "spells"--that is, sequences phonetic segments--for the speaker and recovers the segments for the listener, leaving both in the dark about the way that is done; the gestural representations are immediately phonetic in nature, precluding the cognitive translation that would bring them to notice; and coarticulation destroys all correspondence in segmentation between acoustic and phonetic structures, making it that much harder to demonstrate the alphabetic nature of speech at the acoustic surface. Accordingly, special difficulty in becoming literate might be caused by a weakness of the phonetic module, for that would produce primary representations of a fragile sort, with the consequence that they would be that much harder to bring to awareness--as is required if they are to serve writers and readers as the units of an alphabetic script--and also that much less able to bear the weight of working memory.


Chemical modification of bagasse-based mesoporous carbons for chromium(III) ion adsorption.
Modified bagasse-based mesoporous carbons were prepared for the efficient chromium(III) ion adsorption and removal from aqueous solutions. Mesoporous carbons were prepared from bagasse with H3PO4 activation and subsequently oxidized with nitric acid and modified with ethylenediamine. The results showed that the modified carbon was rich in mesopores, oxygen and nitrogen-containing groups, and the Cr(III) adsorption capacity was greatly improved after modification, which was found to be higher than both pristine and oxidized carbons. The Cr(III) adsorption capacity on modified carbon was significantly influenced by the solution pH, and the optimum pH was 6 with the maximum Cr(III) adsorption capacity up to 24.61mg/g, which was almost 3 times higher than that for pristine carbon. Thermodynamic results manifested the adsorption was spontaneous and endothermic. Kinetic rates fitted the pseudo-second-order model very well. XPS study indicated the amino group was a key factor of the high efficient adsorption.


Pharmacogenetics and the serotonin transporter in late-life depression.
The etiologies of variable antidepressant response remain elusive. Aging and age-related illness add to the complexity and heterogeneity of late-life depression. The serotonin transporter (5-HTT) is the principal site of initial action for several antidepressants, including serotonin re-uptake inhibitors (SSRIs). The serotonin transporter-linked polymorphic region (5-HTTLPR) is the most widely studied polymorphism of the 5-HTT gene, SLC6A4, and is suspected of conferring vulnerability to elderly depression and resistance to treatment. To present an up-to-date account of the influence of 5-HTT polymorphisms on elderly depression, antidepressant response and susceptibility to medication side effects. A Medline search (1993 - 2008) of 5-HTT gene variation studies and analyses that included elderly depressed subjects was performed using the terms: 'serotonin transporter'; '5-HTT'; 'SERT'; '5-HTTLPR'; 'late-life depression'; 'elderly depression'; 'geriatric depression'; 'antidepressants' and 'SSRIs'. Reference sections were gleaned for relevant articles that may have been overlooked by the search strategy. 5-HTTLPR may influence treatment response variability in late-life depression in a number of ways. Indirectly, 5-HTTLPR seems to influence the likelihood of adverse effects and non-adherence. Directly, the promoter region may contribute to response variability during the initial stages of treatment, which is explained, in part, by a gene-concentration interaction for paroxetine. Subjects with the S allele may be at an increased risk of adverse drug reactions and may require higher initial SSRI plasma concentrations to maximize response. Conversely, patients with the L/L genotype may respond even at lower concentrations.


PHARMACOKINETICS OF A SINGLE DOSE OF ORAL AND SUBCUTANEOUS ENROFLOXACIN IN CARIBBEAN FLAMINGOS (PHOENICOPTERUS RUBER RUBER).
Enrofloxacin is a fluoroquinolone antimicrobial that is widely used in veterinary medicine because of its bactericidal activity and safety in a broad range of species. Caribbean flamingos, a member of the order Phoenicopteriformes, are popular in zoological collections and suffer from a variety of conditions that can result from or lead to bacterial infection. In this study, two groups of 7 adult captive Caribbean flamingos received a single dose of 15 mg/kg enrofloxacin, administered either orally or subcutaneously. Plasma concentrations of enrofloxacin and its metabolite, ciprofloxacin, were measured using liquid chromatography and mass spectrometry. Pharmacokinetic analysis was performed using noncompartmental methods. The pharmacokinetic parameters for both routes of administration were similar, with a mean peak plasma concentration (Cmax) of 5.25 and 5.77 μg/ml, a mean time to peak plasma concentration (Tmax) of 1.49 and 1.1 hr, a mean area under the curve (AUC) of 49.9 and 47.3 hr·μg/ml, and a mean terminal half-life (t1/2) of 5.83 and 6.46 hr for oral and subcutaneous dosing, respectively. Conversion to ciprofloxacin was minimal, with the AUC of ciprofloxacin representing <3% of the enrofloxacin AUC for both routes of administration. Based on the results of the present study, a dose of 15 mg/kg enrofloxacin delivered either orally or subcutaneously in the Caribbean flamingo every 24 hr is recommended for susceptible bacterial pathogens with a minimal inhibitory concentration ≤ 0.25 μg/ml.


A novel far-red fluorescent xenograft model of ovarian carcinoma for preclinical evaluation of HER2-targeted immunotoxins.
We have created a novel fluorescent model of a human ovarian carcinoma xenograft overexpressing receptor HER2, a promising molecular target of solid tumors. The model is based on a newly generated SKOV-kat cell line stably expressing far-red fluorescent protein Katushka. Katushka is most suitable for the in vivo imaging due to an optimal combination of high brightness and emission in the "window of tissue transparency". The relevance of the fluorescent model for the in vivo monitoring of tumor growth and response to treatment was demonstrated using a newly created HER2-targeted recombinant immunotoxin based on the 4D5scFv antibody and a fragment of the Pseudomonas exotoxin A.


Assessment of periodontal treatment needs among adults with diabetes in Finland.
People with diabetes have a high risk for periodontal disease, which can be considered one of the complications of diabetes. We evaluated periodontal treatment needs using the Community Periodontal Index of Treatment Needs (CPITN) in relation to diabetes-related factors and oral hygiene. The sample consisted of 120 dentate diabetics, all of whom were regular patients at the Salo Regional Hospital Diabetes Clinic. The nurses, who interviewed the patients, collected data on duration and type of diabetes, complications, and HbA1c level. Clinical periodontal examination included identification of visible plaque, the presence of calculus and use of the CPITN. The CPITN score 3 was the most prevalent. According to the logistic regression model, poor metabolic control was significantly related to pathologic pockets. No significant association was found between diabetes-related factors and the highest individual CPITN score of 4, which was, in turn, significantly associated with extensive calculus. Excessive periodontal treatment needs found, indicate that current dental care may be insufficient in adults with diabetes. Oral health among high-risk groups, especially those with poor metabolic control, should be promoted by collaboration between dental and health care professionals involved in diabetes care.


A central role for a region in the middle.
A domain called the 'Conserved region in the middle' is responsible for target recognition in the TORC2 complex in fission yeast and the mTORC2 complex in mammals.


Optimized high-resolution contrast-enhanced hepatobiliary imaging at 3 tesla: a cross-over comparison of gadobenate dimeglumine and gadoxetic acid.
To evaluate the signal to noise ratio (SNR) and contrast to noise ratio (CNR) performance of 0.05 mmol/kg gadoxetic acid and 0.1 mmol/kg gadobenate dimeglumine for dynamic and hepatobiliary phase imaging. In addition, flip angles (FA) that maximize relative contrast-to-noise performance for hepatobiliary phase imaging were determined. A cross-over study in 10 volunteers was performed using each agent. Imaging was performed at 3 Tesla (T) with a 32-channel phased-array coil using breathheld 3D spoiled gradient echo sequences for SNR and CNR analysis, and for FA optimization of hepatobiliary phase imaging. Gadobenate dimeglumine (0.1 mmol/kg) had superior SNR performance during the dynamic phase, statistically significant for portal vein and hepatic vein in the portal venous and venous phase (for all, P < 0.05) despite twice the approved dose of gadoxetic acid (0.05 mmol/kg), while gadoxetic acid had superior SNR performance during the hepatobiliary phase. Optimal FAs for hepatobiliary phase imaging using gadoxetic acid and gadobenate dimeglumine were 25-30° and 20-30° for relative contrast liver versus muscle (surrogate for nonhepatocellular tissues), and 45° and 20° (relative contrast liver versus biliary structures), respectively. Gadobenate dimeglumine may be preferable for applications that require dynamic phase imaging only, while gadoxetic acid may be preferable when the hepatobiliary phase is clinically important. Hepatobiliary phase imaging with both agents benefits from flip angle optimization.


PET/CT in lung cancer: Influence of contrast medium on quantitative and clinical assessment.
To evaluate the influence of intravenous contrast medium and different contrast medium phases on attenuation correction, PET image quality and clinical staging in combined PET/CT in patients with a suspicion of lung cancer. Sixty patients with a suspicion of lung cancer were prospectively enrolled for combined (18)F-FDG-PET/CT examination. PET images were reconstructed with non-enhanced and arterial and venous phase contrast CT. Maximum and mean standardised uptake values (SUVmax and SUVmean) and contrast enhancement (HU) were determined in the subclavian vein, ascending aorta, abdominal aorta, inferior vena cava, portal vein, liver and kidney and lung tumour. PET data were evaluated visually for clinical staging and image quality. SUVmax was significantly increased between contrast and non-contrast PET/CT at all anatomic sites (all P < 0.001). SUVmax was significantly increased for arterial PET/CT compared to venous PET/CT in the arteries (all P < 0.001). Venous PET/CT resulted in significantly higher SUVmax values compared to arterial PET/CT in the parenchymatous organs (all P < 0.05). Visual clinical evaluation of malignant lesions showed no differences between contrast and non-contrast PET/CT (P = 1.0). Contrast enhanced CT is suitable for attenuation correction in combined PET/CT in lung cancer; it affects neither the clinical assessment nor image quality of the PET images. • Positron emission tomography combined with computed tomography is now a mainstream investigation • There has been debate about whether CT contrast agents affect PET results • Contrast-enhanced CT is satisfactory for attenuation correction in lung cancer PET/CT • Multiphase CT does not affect PET; additional unenhanced CT is unnecessary • For quantitative follow-up PET analysis, an identical PET/CT protocol is required.


Formation of protective deposits by anti-erosive toothpastes-A microscopic study on enamel with artificial defects.
This study investigated formation of protective deposits on the enamel surface after application of several anti-erosive toothpastes with different active ingredients. NaF-containing Sensodyne Pronamel, SnCl2 /F-based Elmex Erosion Protection and calcium phosphate-based BioRepair Plus Sensitivity Control, SensiShield and Enamel Care toothpastes with claimed anti-erosive properties were tested. Artificial saliva and Elmex Erosion Protection mouth rinse served as control groups. The toothpastes were applied 30 times by a toothbrush for 2 min per day, mouth rinse for 30 s on polished enamel of thirty five human molars (n = 5) with series of five rhomboid-shaped indents of various length prepared by a Knoop indentor. After 15 and 30 applications, the shape of the indents and surface morphology was characterised using light and scanning electron microscopy. At the end of treatment, the samples were exposed to 0.2 wt. % citric acid (pH 3.30) to test resistance of the treated enamel to erosion. Pronounced differences were observed between protective properties of the toothpastes. While Sensodyne Pronamel and BioRepair Plus Sensitivity Control did not produce any protective deposits, Enamel Care formed a compact layer of deposits which protected the enamel surface against erosion. With Elmex Erosion Protection and SensiShield fractured indent edges and scratches on the treated enamel suggested that their abrasive properties prevailed over ability of active ingredients to form deposits. These results revealed that toothpastes with strong potential to form acid-resistant deposits on the enamel surface and of low abrasivity should be used for effective prevention of enamel erosion. SCANNING 38:380-388, 2016. © 2015 Wiley Periodicals, Inc.


Tick-Borne Zoonoses in the United States: Persistent and Emerging Threats to Human Health.
In the United States, ticks transmit the greatest diversity of arthropod-borne pathogens and are responsible for the most cases of all vector-borne diseases. In recent decades, the number of reported cases of notifiable tick-borne diseases has steadily increased, geographic distributions of many ticks and tick-borne diseases have expanded, and new tick-borne disease agents have been recognized. In this review, we (1) describe the known disease agents associated with the most commonly human-biting ixodid ticks, (2) review the natural histories of these ticks and their associated pathogens, (3) highlight spatial and temporal changes in vector tick distributions and tick-borne disease occurrence in recent decades, and (4) identify knowledge gaps and barriers to more effective prevention of tick-borne diseases. We describe 12 major tick-borne diseases caused by 15 distinct disease agents that are transmitted by the 8 most commonly human-biting ixodid ticks in the United States. Notably, 40% of these pathogens were described within the last two decades. Our assessment highlights the importance of animal studies to elucidate how tick-borne pathogens are maintained in nature, as well as advances in molecular detection of pathogens which has led to the discovery of several new tick-borne disease agents.


The alienness of the unconscious: on Laplanche's theory of seduction.
In this paper the author uses a clinical example as a focus for an exploration of his thesis that the parent is the 'other' who implants his or her unconscious message into the child by means of seduction. As the other is alien, the unconscious of the child cannot any longer be considered the centre of the person but is decentred by the implanted alienness. The author draws on Laplanche's seduction theory to argue that the unconscious message of seduction by the other is exclusively sexual and that it cannot be translated nor symbolized because an interpretative system shared by subject and object is lacking. The decentred alterity of the unconscious allows for comparison with a third object and hence a structural triangulation of the mind which is a prerequisite for symbolization. The role of the analyst in permitting a transference enactment and so facilitating the beginning of sexual symbolization is discussed in relation to the clinical example given at the start of the paper.


Internal urethrotomy for recurrence after perineal anastomotic urethroplasty for posttraumatic pediatric posterior urethral stricture: could it be sufficient?
To evaluate the long-term outcome of visual internal urethrotomy (VIU) after perineal anastomotic urethroplasty for posttraumatic pediatric posterior urethral strictures. Data of 22 boys who had undergone internal urethrotomy for recurrent stricture after perineal anastomotic urethroplasty for posttraumatic posterior urethral strictures between 1998 and 2008 were analyzed retrospectively regarding patient age, interval between anastomotic urethroplasty and internal urethrotomy, stricture length, surgical technique, and postoperative complications. VIU was performed in patients in whom a guidewire could be passed beyond the stricture segment. The eventual surgical success was defined as asymptomatic voiding without clinical evidence of residual stricture (good flow rate and absence of residual urine). The mean (range) age of patients was 12.2 (3-17) years. All patients had a road traffic accident with associated pelvic fracture. The perineal approach for anastomotic urethroplasty was adopted in all. The estimated stricture length was 0.5 cm or less in 15 patients and was 0.5 to 1 cm in 7 patients. The interval between anastomotic urethroplasty and internal urethrotomy was early-after 12 weeks or less-in 13 children or late-beyond 12 weeks-in the remaining 9. The overall mean interval was 18 (5-63) weeks. In all patients, a guidewire could be passed through the strictured area. One VIU was performed in 17 patients, 2 VIU in 3 patients, while 3 VIU were performed in 2 patients. There was no extravasation reported. The mean follow-up duration was 98 (38-210) months. VIU was successful in 20 of 22 (90%) patients. All patients voided with no symptoms and were continent. VIU offers high success rate and can be sufficient in recurrent strictures of less than 1 cm length after anastomotic urethroplasty in children whenever a guidewire can be passed through the stricture area.


Induction of NGFI-B gene expression during T cell activation. Role of protein phosphatases.
mRNA expression of the immediate-early gene NGFI-B was investigated in T cells during the G0/G1 transition as well as throughout the G1 phase. After stimulation of T lymphocytes with Con A or phorbol 12,13 dibutyrate (PDBu), NGFI-B gene expression showed an induction of at least sevenfold within 3 h of stimulation. Twenty-four h later, however, the level of NGFI-B transcripts had fallen to almost basal levels. Activation of the Ca2+ signaling pathway also produced an induction of this gene, although to a lesser extent than the one obtained after protein kinase C activation. Similar transient kinetics of NGFI-B mRNA were also observed after PDBu stimulation of G1 lymphoblasts. However, the induction of NGFI-B by IL-2 is dependent on the presence of cycloheximide. Con A-induced activation of NGFI-B gene expression was not overcome by cyclosporin A or by 8Br-cAMP, but was partially prevented by dexamethasone. In lymphoblasts, okadaic acid caused the induction of NGFI-B gene expression, indicating a role for the serine/threonine protein phosphatases PP1 and PP2A in the regulation of this gene in resting cells. Okadaic acid-induced NGFI-B transcripts were significantly more stable than PDBu-induced NGFI-B mRNA. Thus, the level of NGFI-B transcripts in T cells might be determined by the balance between the activities of several serine/threonine protein kinases and phosphatases. Together, these findings indicate that the transient induction of NGFI-B transcripts is associated with normal lymphocyte activation. Because the mRNA for NGFI-B codes for a zinc-finger DNA-binding protein, these results suggest that NGFI-B participates in transcriptional regulation during T cell activation.


Influence of the addition of rosemary essential oil on the volatiles pattern of porcine frankfurters.
The effect of the addition of increasing levels of rosemary essential oil (150, 300, and 600 mg/kg) on the generation of volatile compounds in frankfurters from Iberian and white pigs was analyzed using solid-phase microextraction coupled to gas chromatography and mass spectrometry (SPME-GC-MS). Lipid-derived volatiles such as aldehydes (hexanal, octanal, nonanal) and alcohols (pentan-1-ol, hexan-1-ol, oct-1-en-3-ol) were the most abundant compounds in the headspace (HS) of porcine frankfurters. Frankfurters from different pig breeds presented different volatile profiles due to their different oxidation susceptibilities as a likely result of their fatty acid composition and vitamin E content. Rosemary essential oil showed a different effect on the generation of volatiles depending on the type of frankfurter in which they were added. In frankfurters from Iberian pigs, the antioxidant effect of the essential oil improved with increasing levels, showing the highest activity at 600 mg/kg. In contrast, 150 mg/kg of the essential oil improved the oxidative stability of frankfurters from white pigs, whereas higher levels led to no effect or a prooxidant effect. The activity of the essential oil could have been affected by the different fatty acid compositions and vitamin E contents between types of frankfurters. SPME successfully allowed the isolation and analysis of volatile terpenes from frankfurters with added rosemary essential oil including alpha-pinene, beta-myrcene, l-limonene, (E)-caryophyllene, linalool, camphor, and 1,8-cineole, which might contribute to the aroma characteristics of frankfurters.


Decoherence-Induced Exceptional Points in a Dissipative Superconducting Qubit.
Open quantum systems interacting with an environment exhibit dynamics described by the combination of dissipation and coherent Hamiltonian evolution. Taken together, these effects are captured by a Liouvillian superoperator. The degeneracies of the (generically non-Hermitian) Liouvillian are exceptional points, which are associated with critical dynamics as the system approaches steady state. We use a superconducting transmon circuit coupled to an engineered environment to observe two different types of Liouvillian exceptional points that arise either from the interplay of energy loss and decoherence or purely due to decoherence. By dynamically tuning the Liouvillian superoperators in real time we observe a non-Hermiticity-induced chiral state transfer. Our study motivates a new look at open quantum system dynamics from the vantage of Liouvillian exceptional points, enabling applications of non-Hermitian dynamics in the understanding and control of open quantum systems.


Polariton crystallization in driven arrays of lossy nonlinear resonators.
We investigate the steady states of a lossy array of nonlinear optical resonators that are driven by lasers and interact via mutual photon tunneling. For weak nonlinearities, we find two-mode squeezing of polaritons in modes whose quasimomenta match the relative phases of the laser drives. For strong nonlinearities the spatial polariton density-density correlations indicate that the polaritons crystallize and are predominantly found at a specific distance from each other despite being injected by a coherent light source and damped by the environment.


Androgen receptor and its splice variants in prostate cancer.
Androgen receptor (AR) is a transcription factor that becomes active upon binding to androgens via its ligand-binding domain (LBD) or in response to signaling cascades initiated by growth factors and cytokines. The activity of AR requires regions within the N-terminal domain (NTD) in a manner that is distinct from the activation of related steroid hormone receptors. Unequivocal evidence has been amassed to consider that the AR axis is the most critical pathway for the progression of prostate cancer. Qualitatively distinct insights into AR pathobiology have been garnered including that AR-regulated gene expression is stage-specifically modulated during disease progression and that the ligand requirement for AR activity could be rendered dispensable because of the expression of constitutively active AR splice variants that are devoid of LBD. The recent appreciation of the clinical challenge that stems from non-gonadal androgens that are not inhibited by traditional hormonal therapies has been tangibly translated into the development of more potent drugs that can potentially lead towards achieving an androgen-free environment. The pre-clinical evidence that proves that AR NTD is a druggable target also forecasts a further paradigm shift in the management of advanced prostate cancer. These advancements together with the identification of more robust AR antagonists and their promising clinical outcome have renewed the hope that targeting the AR pathway remains a sound strategy in the clinical management of prostate cancer. Here, we address these developments with a greater emphasis on the rapidly growing literature on AR splice variants.


CYP2C9 structure-metabolism relationships: substrates, inhibitors, and metabolites.
The cytochrome P450 (CYP) family is composed of monooxygenases, which mediate the metabolism of xenobiotics and endogenous compounds. The characterization of the interactions between these enzymes and candidate drugs is an important part of the drug discovery process. CYP2C9, one isoform of the CYPs, mediates the oxidation of several important drugs. The aim of this work is to investigate the possibility to study inhibition and substrate interactions with CYP2C9, using docking and the site of metabolism predictions. The model compounds used for the study were the COX-2 inhibitor celecoxib and a series of 13 analogues known to be metabolized by CYP2C9. The results obtained using the two methods gave valuable information about important interactions of inhibitors and substrates with CYP2C9. The two methods could be used to predict the site of metabolism and to determine the productive docking pose for each compound. These predictions were verified by metabolite identification using LC/MS/MS after incubation with recombinant CYP2C9.


Chaperoning ribosome assembly.
Chaperones help proteins fold in all cellular compartments, and many associate directly with ribosomes, capturing nascent chains to assist their folding and prevent aggregation. In this issue, new data from Koplin et al. (2010. J. Cell Biol. doi: 10.1083/jcb.200910074) and Albanèse et al. (2010. J. Cell Biol. doi: 10.1083/jcb.201001054) suggest that in addition to promoting protein folding, the chaperones ribosome-associated complex (RAC), nascent chain-associated complex (NAC), and Jjj1 also help in the assembly of ribosomes.


[Echography of the hip in children].
Ultrasonography has emerged in recent literature as a reliable technique to visualise the infant hip. Its advantages are that non-osseous structures can be seen as well as bone, that a dynamic investigation can be performed, and that it lacks ionising radiation. This article describes the results of a screening study in 307 newborns. 13.4% of all clinically normal (stable) hips showed ultrasound abnormalities. 96.3% of these normalised spontaneously, however. Apparently the natural history of ultrasound abnormalities at birth is relatively mild. Furthermore, in a group of older children, Graf's alpha angle was related to the acetabular index on the radiograph. There was no linear relationship, but a tendency was noted to find higher (better) alpha angles together with lower (better) acetabular indices. Possibly ultrasound is superior to standard radiography in depicting subtle disturbances in ossification of the lateral edge of the acetabulum.


Surgical Management of Chronic Encapsulated Abdominal Wall Seroma 8 Years after Abdominoplasty.
Seroma is a common complication of body-contouring surgery. Current literature focuses on prevention or initial management of seroma formation; however, no definitive evidence exists to guide management of chronic or recurrent seromas. We describe a case of a recurrent abdominal wall seroma following abdominoplasty. The seroma was present for 8 years despite employing multiple treatment modalities. After presentation to our clinic, the patient was taken to the operating room, where the seroma pseudocapsule was excised, progressive tension sutures were utilized, and drains were placed. To date, there has been no recurrence of the seroma. We propose that chronicity, recurrence, and persistence of seroma are indications for surgical intervention.


A peptide with three hyaluronan binding motifs inhibits tumor growth and induces apoptosis.
A number of hyaluronan (HA) binding proteins such as soluble CD44, receptor for hyaluronan-mediated motility (RHAMM), and metastatin inhibit tumor growth and metastasis. To determine whether the HA binding motif is the element responsible for the antitumor effect of this family of proteins, we examined the biological activity of a 42-amino acid peptide (designated as BH-P) that contains three HA binding motifs [B(X(7))B] from human brain HA binding protein. In initial experiments with cultured cells, we found that synthetic BH-P inhibited the proliferation and colony formation of tumor cells. It also blocked the growth of tumors on the chorioallantoic membranes of 10-day chicken embryos. In addition, MDA-435 melanoma cells that had been transfected with an expression vector for BH-P grew at a slower rate in nude mice than the vector-alone transfectants. Final studies revealed that the BH-P could activate caspase-8, caspase-3, and poly(ADP-ribose) polymerase and trigger the apoptosis of tumor cells. Taken together, these results suggest that the HA binding motif that is present in HA binding proteins may be responsible for the antitumor effect exerted by the members of this family.


Ethanol inhibits γ-secretase proteolytic activity in vascular smooth muscle cells.
Ethanol (EtOH) inhibits Notch-mediated vascular smooth muscle cell (SMC) proliferation, an event that is key in vessel remodeling and atherogenesis. The object of this study was to determine whether EtOH inhibits Notch signaling in SMC at the level of γ-secretase, a protease that in concert with α-secretase catalyzes the release of the intracellular domain of the Notch receptor necessary for signaling. Human coronary artery SMCs (HCASMCs) were treated with a recombinant soluble Notch ligand, Delta-like ligand 4 (DLL4) (2 μg/ml), or transfected with a constitutively active Notch 1 intracellular domain (N1ICD), in the absence or presence of EtOH. EtOH (25 mM) treatment inhibited DLL4-stimulated CBF-1/RBP-Jk-dependent promoter activity (determined by luciferase assay) and downstream target gene HRT-3 mRNA levels. In contrast, EtOH had no effect on N1ICD-driven CBF-1/RBP-Jk-dependent promoter activity or HRT-3 expression. These data suggest that EtOH inhibits Notch signaling at, or prior to, Notch intracellular domain (NICD) generation. γ-Secretase activity was determined in solubilized membrane preparations from HCASMC treated with/without EtOH (25 mM) or the γ-secretase inhibitor DAPT (20 μM) using (i) a fluorometric assay and (ii) Western blot detection of cleavage products using a Flag-tagged Notch-based substrate, N100Flag. EtOH inhibited basal and DLL4-stimulated γ-secretase activity, and SMC growth to a similar extent as DAPT, whereas it had no effect on α-secretase (TACE/ADAM17) activity also determined by fluorometric assay. Moreover, EtOH treatment inhibited the expression of caveolin-1, a lipid raft protein implicated in regulating γ-secretase activity, and altered its cellular distribution in HCASMC. EtOH inhibits Notch signaling in vascular SMCs at the level of γ-secretase activity, possibly by affecting lipid raft function. Such a response might be expected to result in attenuation of pathologic vessel remodeling and thus may contribute to moderate alcohols' cardioprotective effects.


The functions of F-box proteins in regulating the epithelial to mesenchymal transition.
Epithelial to mesenchymal transition (EMT) has been unraveled to regulate the tumor invasion and metastasis processes. In this review, in order to better understand the regulatory mechanisms of EMT, we describe that F-box proteins could be critically involved in regulating the EMT process in human cancers. Specifically, we discuss how these F-box proteins directly control the stability of EMT regulators such as E-cadherin, β-catenin, Twist, Slug, Snail and ZEB. Moreover, we summary mechanistically how the F-box proteins govern EMT progression through regulation of EMT inducers including Notch, NF-κB, Akt, Hedgehog, mTOR, and HIF-1α. Therefore, targeting these F-box proteins could be useful for treating human cancers.


[Locally Dynamically Moving Average Algorithm for the Fully Automated Baseline Correction of Raman Spectrum].
The baseline correction is an, extremely important spectral preprocessing step and can significantly improve the accuracy of the subsequent spectral analysis algorithm. At present most of the baseline correction algorithms are manual and semi-automated. The manual baseline correction depends on the user experience and its accuracy is greatly affected by the subjective factor. The semi-automated baseline correction needs to set different optimizing parameters for different Raman spectra, which will be inconvenient to users. In this paper, a locally.dynamically moving average algorithm (LDMA) for the fully automated baseline correction is presented and its basic ideas.and steps are demonstrated in detail. In the LDMA algorithm the modified moving averaging algorithm (MMA) is used to strip the Raman peaks. By automatically finding the baseline subintervals of the raw Raman spectrum to divide the total spectrum range into multi Raman peak subintervals, the LDMA algorithm succeed in dynamically changing the window half width of the MA algorithm and controlling the numbers of the smoothing iterations in each Raman peak subinterval. Hence, the phenomena of overcorrection and under-correction are avoided to the most degree. The LDMA algorithm has achieved great effect not only to the synthetic Raman spectra with the convex, exponential, or sigmoidal baseline but also to the real Raman spectra.


Kinetics and regulation of pantothenate kinase from Escherichia coli.
Pantothenate kinase catalyzes the rate-controlling step in coenzyme A (CoA) biosynthesis and is regulated by feedback inhibition by CoA. Pantothenate kinase was purified to homogeneity from Escherichia coli and was shown to exist as a homodimer. Kinetic analysis indicated the presence of two ATP binding sites that exhibited positive cooperativity with a Hill coefficient of 1.46. Site-directed mutagenesis of lysine 101 to methionine (K101M) resulted in the inactivation of the enzyme, although dimer formation was not altered. The K101M mutant was unable to bind either adenosine 5'-O-(3-thiotriphosphate) or CoA, supporting the conclusion from kinetic analysis that both the substrate and inhibitor bind to the same site on the enzyme. CoA binding was not cooperative. Coexpression of the K101M mutant gene on a high copy number plasmid in the presence of a chromosomal copy of the wild-type gene resulted in the production of heterodimers between active and inactive subunits. Kinetic analysis of the chimeric heterodimers showed the absence of cooperative ATP interactions and indicated a sequential kinetic mechanism for pantothenate kinase with ATP binding first and pantothenate second. Thus, pantothenate kinase regulation involves the competitive binding of CoA to the ATP site, which blocks ATP binding at one site and prevents positive cooperative ATP binding to the second site on the dimer.


Resonant control of elastic collisions in an optically trapped fermi gas of atoms.
We have loaded an ultracold gas of fermionic atoms into a far-off resonance optical dipole trap and precisely controlled the spin composition of the trapped gas. We have measured a magnetic-field Feshbach resonance between atoms in the two lowest energy spin states, /9/2,-9/2> and /9/2,-7/2>. The resonance peaks at a magnetic field of 201.5+/-1.4 G and has a width of 8.0+/-1.1 G. Using this resonance, we have changed the elastic collision cross section in the gas by nearly 3 orders of magnitude.


Reading Fluency As a Predictor of School Outcomes across Grades 4-9.
This study analyzed the predictive relationship between reading fluency and school outcomes across school levels (primary, secondary, and high school), after controlling on the effect of reading comprehension. The sample included 489 children attending Italian primary (grades 4 and 5), secondary (grades 6 and 8), and high schools (grade 9). Students' reading fluency and comprehension were examined with a standardized reading achievement test. At the end of the school year, we requested the school reports of each participant. According to our data, reading fluency predicted all school marks in all literacy-based subjects, with reading rapidity being the most important predictor. School level did not moderate the relationship between reading fluency and school outcomes, confirming the importance of effortless and automatized reading even in higher school levels. Overall this study emphasizes the importance of identifying evidence-based tasks that can be administered in a short time and to many different individuals, which are easy to create, and are linked to school outcomes.


Coupling of a headspace autosampler with a programmed temperature vaporizer for stable carbon and hydrogen isotope analysis of volatile organic compounds at microgram per liter concentrations.
One major challenge for the environmental application of compound-specific stable isotope analysis (CSIA) is the necessity of efficient sample treatment methods, allowing isolation of a sufficient mass of organic contaminants needed for accurate measurement of the isotope ratios. Here, we present a novel preconcentration technique--the coupling of a headspace (HS) autosampler with a programmed temperature vaporizer (PTV)--for carbon (δ(13)C) and hydrogen (δ(2)H) isotope analysis of volatile organic compounds in water at concentrations of tens of micrograms per liter. The technique permits large-volume injection of headspace samples, maintaining the principle of simple static HS extraction. We developed the method for multielement isotope analysis (δ(13)C and δ(2)H) of methyl tert-butyl ether (MTBE), benzene, toluene, ethylbenzene, and o-xylene (BTEX), and analysis of δ(13)C for chlorinated benzenes and ethenes. Extraction and injection conditions were optimized for maximum sensitivity and minimum isotope effects. Injection of up to 5 mL of headspace sample from a 20 mL vial containing 13 mL of aqueous solution and 5 g of NaCl (10 min of incubation at 90 °C) resulted in accurate δ(13)C and δ(2)H values. The method detection limits (MDLs) for δ(13)C were from 2 to 60 μg/L (MTBE, BTEX, chlorinated ethenes, and benzenes) and 60-97 μg/L for δ(2)H (MTBE and BTEX). Overall, the HS-PTV technique is faster, simpler, isotope effect-free, and requires fewer treatment steps and less sample volume than other extraction techniques used for CSIA. The environmental applicability was proved by the analysis of groundwater samples containing BTEX and chlorinated contaminants at microgram per liter concentrations.


Impaired spatial selectivity and intact phase precession in two-dimensional virtual reality.
During real-world (RW) exploration, rodent hippocampal activity shows robust spatial selectivity, which is hypothesized to be governed largely by distal visual cues, although other sensory-motor cues also contribute. Indeed, hippocampal spatial selectivity is weak in primate and human studies that use only visual cues. To determine the contribution of distal visual cues only, we measured hippocampal activity from body-fixed rodents exploring a two-dimensional virtual reality (VR). Compared to that in RW, spatial selectivity was markedly reduced during random foraging and goal-directed tasks in VR. Instead we found small but significant selectivity to distance traveled. Despite impaired spatial selectivity in VR, most spikes occurred within ∼2-s-long hippocampal motifs in both RW and VR that had similar structure, including phase precession within motif fields. Selectivity to space and distance traveled were greatly enhanced in VR tasks with stereotypical trajectories. Thus, distal visual cues alone are insufficient to generate a robust hippocampal rate code for space but are sufficient for a temporal code.


Deconvoluting the Effect of the Hydrophobic and Hydrophilic Domains of an Amphiphilic Integral Membrane Protein in Lipid Bicontinuous Cubic Mesophases.
Lipidic bicontinuous cubic mesophases with encapsulated amphiphilic proteins are widely used in a range of biological and biomedical applications, including in meso crystallization, as drug delivery vehicles for therapeutic proteins, and as biosensors and biofuel cells. However, the effect of amphiphilic protein encapsulation on the cubic phase nanostructure is not well-understood. In this study, we illustrate the effect of incorporating the bacterial amphiphilic membrane protein Ag43, and its individual hydrophobic β(43) and hydrophilic α(43) domains, in bicontinuous cubic mesophases. For the monoolein, monoalmitolein, and phytantriol cubic phases with and without 8% w/w cholesterol, the effect of the full length amphiphilic protein Ag43 on the cubic phase nanostructure was more significant than the sum of the individual hydrophobic β(43) and hydrophilic α(43) domains. Several factors were found to potentially influence the impact of the hydrophobic β(43) domain on the cubic phase internal nanostructure. These include the size of the hydrophobic β(43) domain relative to the thickness of the lipid bilayer, as well as its charge and diameter. The size of the hydrophilic α(43) domain relative to the water channel radius of the cubic mesophase was also found to be important. The secondary structure of the Ag43 proteins was affected by the hydrophobic thickness and physicochemical properties of the lipid bilayer and the water channel diameter of the cubic phase. Such structural changes may be small but could potentially affect membrane protein function.


Is the reduction of spasticity by botulinum toxin a beneficial for the recovery of motor function of arm and hand in stroke patients?
To determine the functional benefit of botulinum toxin A (BtxA) in spasticity of arm flexors, we conducted an open-label study with 10 stroke patients. 480 mouse units BtxA (Dysport((R))) were injected into flexor muscles. Outcome measures were done by the Modified Ashworth Scale, Rivermead Motor Assessment (arm section), active and passive ranges of motion (ROM), grip strength and a 3-dimensional motion analysis. The functional capacity of the entire arm, even of the shoulder, and the ROM of fingers and wrist increased. Despite a diminution of muscle tone, grip strength remained unchanged or increased. An improvement of forearm extension was only observed in cases of preserved voluntary extensor motricity. Injection of BtxA into spastic distal flexor muscles may lead to a functional improvement of the entire arm. Grip strength is not necessarily reduced.


Illusory Feelings, Elusive Habits: People Overlook Habits in Explanations of Behavior.
Habits underlie much of human behavior. However, people may prefer agentic accounts that overlook habits in favor of inner states, such as mood. We tested this misattribution hypothesis in an online experiment of helping behavior (N = 809 adults) as well as in an ecological momentary assessment (EMA) study of U.S. college students' everyday coffee drinking (N = 112). Both studies revealed a substantial gap between perceived and actual drivers of behavior: Habit strength outperformed or matched inner states in predicting behavior, but participants' explanations of their behavior emphasized inner states. Participants continued to misattribute habits to inner states when incentivized for accuracy and when explaining other people's behavior. We discuss how this misperception could adversely influence self-regulation.


Encapsulation of porcine islets permits extended culture time and insulin independence in spontaneously diabetic BB rats.
The ability to culture porcine islets for extended times allows for both their functional assessment and the assurance of their microbiological safety prior to transplantation. We have previously shown that agarose-encapsulated porcine islets can be cultured for at least 24 weeks. In the current study, porcine islet agarose macrobeads cultured for up to 67 weeks were assessed for their ability to restore normoglycemia, respond to an intraperitoneal glucose challenge, maintain spontaneously diabetic BB rats free of insulin therapy for more than 6 months, and for their biocompatibility. Porcine islets were encapsulated in agarose macrobeads and subjected to weekly static perifusion assays for the assessment of insulin production. After in vitro culture for either 9, 40, or 67 weeks, 56-60 macrobeads were transplanted to each spontaneously diabetic BB rat. Transplanted rats were monitored daily for blood glucose levels. Glucose tolerance tests and assessments for porcine C-peptide were conducted at various intervals throughout the study. Normoglycemia (100-200 mg/dl) was initially restored in all islet transplanted rats. Moderate hyperglycemia (200-400 mg/dl) developed at around 30 days posttransplantation and continued throughout the study period of 201-202 days. Importantly, all rats that received encapsulated porcine islets continued to gain weight and were free of exogenous insulin therapy for the entire study. Porcine C-peptide (0.2-0.9 ng/ml) was detected in the serum of islet recipients throughout the study period. No differences were detected between recipient animals receiving islet macrobeads of various ages. These results demonstrate that the encapsulation of porcine islets in agarose macrobeads allows for extended culture periods and is an appropriate strategy for functional and microbiological assessment prior to clinical use.


Unoperated craniosynostosis patients: correction in adulthood.
The purpose of this project was to determine whether adult patients with frontal deformities caused by untreated craniosynostosis can undergo successful surgical correction. Thirteen unoperated adult craniosynostosis patients are reported: seven women and six men, with a mean age of 24 years. There were four plagiocephalies, four scaphocephalies, three oxycephalies, and two brachycephalies. Computed tomographic scans with cerebral contrast were obtained, and the projected computerized correction was discussed with the patients. Frontocranial remodeling with an intracranial approach was used in 11 cases, and a frontal implant plus nasal en bloc realignment was used in two. No significant perioperative complications occurred in this series. There were two late revisions for bony irregularities, through a limited approach. The morphologic correction was very satisfactory, emphasizing how important correct anatomy of the forehead and upper cranial vault is for the equilibrium of the face. Unoperated craniosynostosis creates a significant to severe disfigurement because of the frontal deformation. Therefore, only in mild cases can one propose a limited operation or an implant, avoiding an intracranial approach. In most cases, a radical intracranial approach is the only effective operation. Risks must be discussed with the patient, but the psychological impact of the disfigurement is so great that these young adults are usually willing to undergo a radical approach. Early operation in infancy is of course preferable, but if this was not performed for various reasons, it is still possible to correct the deformity, despite it being a much more complicated operation.


Male services during between-group conflict: the 'hired gun' hypothesis revisited.
In many group-living mammals, philopatric females form the stable core of the group and defend food or shelter against other groups of females. Where males are larger, their participation could give their female group the edge. How can females secure the contribution of males that are neither the father of current infants, nor the dominant male expecting to sire the next generation of infants? It has been proposed that females recruit these males as 'hired guns', receiving social support and copulations in exchange for fighting, against the interests of the dominant male. We first develop the logic of this hypothesis in unprecedented detail by considering the potential pay-off consequences for females and males. We then provide empirical evidence for the existence of hired guns in this context in several primate species. The game-theoretical aspects of the phenomenon remain to be studied, as is the distribution across contexts (e.g. predation avoidance) and species of the hired gun phenomenon. This article is part of the theme issue 'Intergroup conflict across taxa'.


Acute appendicitis with associated trichobezoar of feline hair.
A trichobezoar is an accumulation of ingested hair that forms a mass within the gastro-intestinal tract. Thrichobezoars usually consist of human hair and are known to cause obstruction and even perforation of gastrointestinal organs. There have been approximately seven reported cases of acute appendicitis with association trichobezoars found at the time of appendicectomy. We report a unique case of acute appendicitis with an associated trichobezoar of feline hair. A 15-year-old male presented with a 24-hour history of abdominal pain. A computed tomography scan demonstrated features of appendicitis with several hyperdensities within the base of the appendix. At the time of appendicectomy, the appendix was found to be perforated at the base. Faecoliths were identified containing numerous short, light-coloured hairs. Following the procedure, the family confirmed that they have a pet cat with short, light-coloured hair. The patient had an uneventful recovery.


[Results of treatment of displaced long bones fractures in children--comparison of different methods].
Authors compared functional results of treatment of 48 patients; 25 children with displaced supracondylar humeral fractures, 16 treated with skeletal traction (group I, mean age 7.9 year), 9 treated with closed reduction and percutaneous K-wire fixation (group II mean age 7.7 year), and 23 patients with displaced femoral shaft fractures, 10 treated with traction (group III, mean age 7.5 year), 13 treated with closed reduction and elastic intramedullary nailing. Good results after supracondylar humeral fractures were obtained in 37.5% of patients treated with traction and in 66.7% treated with percutaneous K-wire fixation, and after femoral fractures in 70% treated with traction and 84.6% treated with intramedullary nailing. The use of instrumental methods of treatment allowed to reduce significantly the duration of hospitalization (respectively: 19.8 vs. 6.4, and 28.5 vs. 9.5 days). In authors' opinion, a closed reduction secured by percutaneous K-wire fixation as well as a closed reduction with elastic intramedullary nailing are the methods of choice in treatment of discussed fractures in children.


Sex differences in baseline neuropsychological function and concussion symptoms of collegiate athletes.
To investigate sex differences in baseline neuropsychological function and concussion symptoms between male and female collegiate athletes. A post-test only design was used to examine baseline neuropsychological test scores and concussion symptoms. A total of 1209 NCAA Division I collegiate athletes from five northeastern universities in the USA completed a baseline ImPACT test. ImPACT, a computerised neuropsychological test battery, was administered during an athlete's pre-season. Female athletes performed significantly better than male athletes on baseline verbal memory scores (p = 0.001), while male athletes performed significantly better than female athletes on baseline visual memory scores (p = 0.001). Female athletes endorsed a significant number of mild baseline symptoms as compared to male athletes. Male and female athletes exhibit differences on baseline neuropsychological test performance and concussion symptoms.


Giardia lamblia EB1 is a functional homolog of yeast Bim1p that binds to microtubules.
Giardia lamblia, with two nuclei and a distinct polarized morphology, is an interesting organism for investigating how distribution of its microtubule (MT) is controlled during its cell cycle. In this study, we identified the end-binding protein 1 (EB1) of G. lamblia, a well-known microtubule-associated protein that organizes MTs in eukaryotes. Immunofluorescence assays using recombinant EB1 (rEB1)-specific antibodies demonstrated EB1 localization in nuclear membrane as well as in some cytoskeletal structures such as axomenes and median bodies of trophozoites of G. lamblia. Complementation experiments using the BIM1 knock-out mutant of yeast, the yeast homolog of mammalian EB1, showed that giardial EB1 was able to carry out a homologous function in controlling MT dynamics. In addition, rEB1 of G. lamblia co-precipitated with MTs by an in vitro binding assay, thereby demonstrating that G. lamblia EB1 is a MT-associated protein. These results, taken together, suggest that G. lamblia EB1 is a functional homolog of eukaryotic EB1 and is likely to be a determinant for MT distribution.


Clinical outcome prediction after thrombectomy of proximal middle cerebral artery occlusions by the appearance of lenticulostriate arteries on magnetic resonance angiography: A retrospective analysis.
Post-ischemic vasodynamic changes in infarcted brain parenchyma are common and range from hypo- to hyperperfusion. In the present study, appearance of the lenticulostriate arteries (LSAs) on postinterventional 3T time-of-flight (TOF)-MRA suggestive for altered post-stroke vasodynamics following thrombectomy was investigated. Patients who underwent thrombectomy for a proximal MCA occlusion and for whom postinterventional 3T TOF-MRA (median at day 3) was available, were included in this retrospective analysis (n=98). LSA appearance was categorized into presence (LSA-sign+) or absence (LSA-sign-) of vasodilatation in the ischemic hemisphere. Functional outcome was determined using the modified Rankin scale (mRS). LSA-sign+ was observed in 64/98 patients. Hypertension (adjusted OR: 0.171, 95% CI: 0.046-0.645) and preinterventional IV rtPA (adjusted OR: 0.265, 95% CI: 0.088-0.798) were associated with absence of the LSA-sign+. In multivariate logistic regression, LSA-sign+ was associated with substantial neurologic improvement (adjusted OR: 10.18, 95% CI: 2.69-38.57) and good functional outcome (discharge-mRS ≤ 2, adjusted OR: 7.127, 95% CI: 1.913-26.551 and day 90 mRS ≤ 2, adjusted OR: 3.786, 95% CI: 1.026-13.973) after correcting for relevant confounders. For all clinical endpoints, model fit improved when including the LSA-sign term (p<0.05). Asymmetrical dilatation of LSAs following successful thrombectomy indicates favorable neurologic and mid-term functional outcomes. This may indicate preserved cerebral blood flow regulatory mechanisms.


The use of GIS and multi-criteria evaluation (MCE) to identify agricultural land management practices which cause surface water pollution in drinking water supply catchments.
Diffuse pollution poses a threat to water quality and results in the need for treatment for potable water supplies which can prove costly. Within the Yorkshire region, UK, nitrates, pesticides and water colour present particular treatment problems. Catchment management techniques offer an alternative to 'end of pipe' solutions and allow resources to be targeted to the most polluting areas. This project has attempted to identify such areas using GIS based modelling approaches in catchments where water quality data were available. As no model exists to predict water colour a model was created using an MCE method which is capable of predicting colour concentrations at the catchment scale. CatchIS was used to predict pesticide and nitrate N concentrations and was found to be generally capable of reliably predicting nitrate N loads at the catchment scale. The pesticides results did not match the historic data possibly due to problems with the historic pesticide data and temporal and spatially variability in pesticide usage. The use of these models can be extended to predict water quality problems in catchments where water quality data are unavailable and highlight areas of concern.


Can adjuvant chemotherapy improve the prognosis of adult ovarian granulosa cell tumors?: A narrative review.
Adult granulosa cell tumors (aGCTs) are rare ovarian neoplasms with a relatively favorable prognosis. They follow an indolent course, characterized by a prolonged natural history and a tendency to late recurrences, Around a quarter of patients develop recurrence and More than 70% of women with recurrence die from their disease, The percentage of patients received chemotherapy increases over time, whether adjuvant chemotherapy improve the prognosis of aGCTs is equivocal? The purpose of this review is to summarize the previously published evidence to evaluate whether adjuvant chemotherapy improve the prognosis of aGCTs to provide guidance for clinical practice. EMBASE, PubMed, Web of Science, WanFang Data and Chinese National Knowledge Infrastructure are searched up to December 2020, used the search strategy of ovar* and granulosa cell* and (tumor* or tumour* or malignan* or cancer* or carcinom* or neoplasm*) and chemotherapy. The screening process was conducted strictly based on inclusion and exclusion criteria. Clinical studies based on human including randomized controlled trial, quasi-randomised controlled trials, nonrandomised trials cohort study and case control study were included without restriction of time. The percentage of patients received chemotherapy increases over time, but the benefit of adjuvant chemotherapy is lack of high-grade evidence of prospective study, based on the current retrospective studies, we still do not have the evidence to confirm the survival benefit of adjuvant chemotherapy in early stage, advanced stage or recurrent aGCT with no residual tumor, but for inoperable disseminated disease or disease with suboptimal cytoreduction, adjuvant chemotherapy maybe an Optable options. Multinational prospective randomised controlled trials are urgently needed to validate the role of adjuvant chemotherapy. Further research on molecular mechanisms and developing novel targeted medicines may improve the survival of aGCTs.


[Epidemiology of childhood cancer].
The knowledge of the epidemiology of cancer in childhood is relevant of a strict methodology allowed by the activation of population-based specific registries, case-control and cohort studies. Descriptive epidemiology is a mean of survey and of public health, while analytic epidemiology contributes to define the role of genetic and environmental factors, along with their interaction. The collected data help indirectly to improve the care of the child with cancer and to a better understanding of the carcinogenesis.


Comparison of the clinical efficacy and toxicity of nebulized polymyxin monotherapy and combined intravenous and nebulized polymyxin for the treatment of ventilator-associated pneumonia caused by carbapenem-resistant gram-negative bacteria: a retrospective cohort study.
Objective: To investigate the clinical efficacy and toxicity of nebulized polymyxin monotherapy and combined intravenous and nebulized polymyxin for the treatment of VAP caused by CR-GNB. Additionally, among patients treated with nebulized polymyxin monotherapy, we compared the clinical efficacy and toxicity of polymyxin B and polymyxin E. Methods: This study was a single-center, retrospective study. Included patients received aerosolized polymyxin for at least 72 h with or without intravenous polymyxin for the management of CR-GNB VAP. The primary endpoint was clinical cure at the end of polymyxin therapy. Secondary endpoints included AKI incidence, time of bacteria-negative conversion, duration of MV after inclusion, length of stay in ICU, and all-cause ICU mortality. Results: 39 patients treated with nebulized polymyxin monotherapy were assigned to the NL-polymyxin group. 39 patients treated with nebulized polymyxin combined with intravenous use of polymyxin were assigned to the IV-NL-polymyxin group. Among the NL-polymyxin group, 19 patients were treated with polymyxin B and 20 with polymyxin E. The clinical baseline characteristics before admission to the ICU and before nebulization of polymyxin were similar between the two groups. No differences were found between the two study groups in terms of microorganism distribution, VAP cure rate, time of bacteria-negative conversion, duration of MV after inclusion, length of stay in ICU and all-cause ICU mortality. Similarly, survival analysis did not differ between the two groups (χ2 = 3.539, p = 0.06). AKI incidence was higher in the IV-NL-polymyxin group. When comparing the clinical efficacy and toxicity to polymyxin B and polymyxin E, there was no difference between the two groups in terms of VAP cure rate, time of bacteria-negative conversion, duration of MV after inclusion, length of stay in ICU, SOFA score, CPIS, AKI incidence and all-cause ICU mortality. Conclusion: Our study found that nebulized polymyxin monotherapy was non-inferior to combination therapy with intravenous polymyxin in treating CR-GNB-VAP. Furthermore, we observed no differences in clinical efficacy or related toxic side effects between polymyxin B and polymyxin E during nebulized polymyxin therapy as monotherapy. However, future prospective studies with larger sample sizes are required to confirm these findings.


Capnocytophaga cynodegmi peritonitis in a peritoneal dialysis patient.
The first reported case of peritonitis caused by Capnocytophaga cynodegmi is presented. The patient was treated with peritoneal dialysis and had contact with a cat. C. cynodegmi is part of the normal oral flora of dogs and cats but is very rarely isolated in clinical specimens from humans.


Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Exploratory Study to Evaluate the Efficacy and Safety of HAD-B1 for Dose-Finding in EGFR Mutation Positive and Locally Advanced or Metastatic NSCLC Subjects Who Need Afatinib Therapy.
Afatinib is a target anticancer drug of the second-generation EGFR TKI type, showing an advantage in treatment effect compared to conventional chemotherapy. However, patients on EGFR-TKI drugs also usually progress after 9 to 13 months according to secondary resistance. HAD-B1 is composed of drugs that are effective against lung cancer. This study is an exploratory study to evaluate the efficacy and safety between dosage groups by conducting a clinical trial in subjects requiring afatinib drug treatment in non-small cell lung cancer with EGFR mutation positive to determine the optimal dosage for HAD-B1 administration. At the final visit compared to before administration, each change in the disease control rate was measured according to the HAD-B1 doses of the test group 1 (972 mg), the test group 2 (1944 mg), and the control group. The efficacy and safety of HAD-B1 were compared and evaluated through sub-evaluation variables. As a result of the study, there was no statistically significant difference in the disease control rate at 12 weeks after dosing, but complete and partial remission were evaluated as 1 patient each in the test group 1, and none in the other groups. There was no statistically significant difference between groups in the sub-evaluation variable. In addition, there was no problem of safety from taking the test drug. However, the initially planned number of subjects was 66, but the number of enrolled subjects was only 14, which may limit the results of this study.


Bulk spin polarization of Co(1-x)Fe(x)S2.
We report on a new method to determine the degree of bulk spin polarization in single crystal Co(1-x)Fe(x)S2 by modeling magnetic Compton scattering with ab initio calculations. Spin-dependent Compton profiles were measured for CoS2 and Co0.9Fe0.1S2. The ab initio calculations were then refined by rigidly shifting the bands to provide the best fit between the calculated and experimental directional profiles for each sample. The bulk spin polarizations, P, corresponding to the spin-polarized density of states at the Fermi level, were then extracted from the refined calculations. The values were found to be P=-72+/-6% and P=18+/-7% for CoS2 and Co0.9Fe0.1S2, respectively. Furthermore, determinations of P weighted by the Fermi velocity (v(F) or v(F)2) were obtained, permitting a rigorous comparison with other experimental data and highlighting the experimental dependence of P on v(F).


Continuous ultrasound B-scanning of palpable breast masses.
Of 210 pathologically confirmed palpable breast masses examined by continuous ultrasound B-scanning using a 2.5- or 7-MHz transducer and mammography, fluid filled cysts more than 1 cm in diameter were diagnosed accurately in 75 cases. Of the 103 solid masses studied by echography, 31 were circumscribed (29 benign fibroadenomas and 2 circumscribed medullary carcinomas) and 72 were not. Infiltrating carcinoma represented the majority of the latter type, although 2 cases of chronic inflammation had the same echographic appearance. Thirty palpable breast masses less than 2 cm in diameter were not delineated with the 2.5-MHz transducer, and biopsy showed benign disease. The combiantion of mammography and continuous ultrasound B-scanning of palpable breast masses improved the diagnostic accuracy obtained with mammography alone and aided in the differentiation of nondiagnostic mammograms.


Why So Variable: Can Genetic Variance in Flowering Thresholds Be Maintained by Fluctuating Selection?
We use integral projection models (IPMs) and individual-based simulations to study the evolution of genetic variance in two monocarpic plant systems. Previous approaches combining IPMs with an adaptive dynamics-style invasion analysis predicted that genetic variability in the size threshold for flowering will not be maintained, which conflicts with empirical evidence. We ask whether this discrepancy can be resolved by making more realistic assumptions about the underlying genetic architecture, assuming a multilocus quantitative trait in an outcrossing diploid species. To do this, we embed the infinitesimal model of quantitative genetics into an IPM for a size-structured cosexual plant species. The resulting IPM describes the joint dynamics of individual size and breeding value of the evolving trait. We apply this general framework to the monocarpic perennials Oenothera glazioviana and Carlina vulgaris. The evolution of heritable variation in threshold size is explored in both individual-based models (IBMs) and IPMs, using a mutation rate modifier approach. In the Oenothera model, where the environment is constant, there is selection against producing genetically variable offspring. In the Carlina model, where the environment varies between years, genetically variable offspring provide a selective advantage, allowing the maintenance of genetic variability. The contrasting predictions of adaptive dynamics and quantitative genetics models for the same system suggest that fluctuating selection may be more effective at maintaining genetic variation than previously thought.


A dissociation between anterograde and retrograde amnesia after treatment with electroconvulsive therapy: a naturalistic investigation.
The aim of the present study is to investigate the cumulative effects of a clinically determined course of electroconvulsive therapy (ECT) on anterograde and retrograde amnesia. In this study, mood and memory were examined in the context of a protocol driven by therapeutic response, rather than by preordained research criteria. Twenty-two patients with major depressive disorder and 18 nondepressed controls were taught a series of faces and names before the initiation of ECT, and their retention of this information was examined after the end of treatment. Anterograde (ie, new learning) and retrograde memory (ie, recall of information learned before ECT) were assessed. Eleven ECT patients underwent unilateral (UL) stimulation, and 11 had a combination of UL and bilateral stimulation. Major depressive disorder patients and nondepressed controls participants were matched according to baseline memory abilities. Unilateral and unilateral/bilateral (UB) ECT patients were matched according to baseline depression and memory abilities. Treatment with ECT resulted in a dissociation between anterograde and retrograde memory; after treatment, major depressive disorder patients demonstrated significant retrograde amnesia, whereas there was no change in their anterograde memory. Unilateral and UB ECT patients performed equally well on tasks of anterograde memory. Contrary to our expectation, UB ECT was not associated with greater retrograde memory loss than was UL ECT treatment. However, a trend toward a group difference was present on 1 memory measure. Results of the study suggest that a clinical course of ECT is associated with isolated impairment for information learned before treatment (ie, retrograde memory), whereas there was no effect of ECT on posttreatment learning abilities (ie, anterograde memory).


Speciated ambient carbonyls in Rio de Janeiro, Brazil.
Carbonyls in urban air continue to receive scientific and regulatory attention as toxic air contaminants and for their important role in photochemical smog. However, few data are available for speciated carbonyls in urban air. Ambient concentrations of up to 61 carbonyls have been measured in Rio de Janeiro, Brazil. The most abundant carbonyls were formaldehyde and acetaldehyde (study-averaged concentrations of 10.8 +/- 4.1 and 10.4 +/- 4.6 microg m(-3), respectively, in samples of 3-h duration collected from May to November 2000 at a downtown location during the morning vehicle commute) followed by acetone, 2-butanone, and benzaldehyde. Ambient concentrations of other carbonyls (except acetophenone) correlated well with those of acetaldehyde and of formaldehyde. This study examines the ambient acetaldehyde/ambient formaldehyde concentration ratio in Brazilian cities since the mid-1980s in the context of changes in Brazil's reliance on ethanol as a vehicle fuel. This ratio has begun to decrease in recent years due to fleet turnover and is likely to decrease further as older cars fueled with ethanol are replaced by lower-emitting models that run on a gasoline-ethanol blend. The carbonyls measured are ranked with respect to ozone formation potential (using MIR coefficients) and reaction with OH (using carbonyl-OH reaction rate constants). Ozone formation is dominated by formaldehyde (43% of total) followed by acetaldehyde (32%) and methylglyoxal (8%); other carbonyls each contributed < or = 4% of total. For reaction with OH, acetaldehyde ranks first closely followed by formaldehyde.


Posttransplantation imatinib as a strategy to postpone the requirement for immunotherapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia.
Disease relapse is a major cause of treatment failure after reduced-intensity allografts and while donor lymphocyte infusions (DLIs) can be effective salvage therapy they are associated with severe graft-versus-host disease (GVHD) when administered early after transplantation. We have therefore examined whether imatinib mesylate can delay relapse and postpone the requirement for DLI in 22 patients with chronic myeloid leukemia (CML) allografted using a reduced-intensity regimen. Imatinib was commenced on day + 35 and continued until 1 year after transplantation. Posttransplantation imatinib was well tolerated and abolished the risk of relapse during this period. Twenty-one patients completed 11 months of imatinib therapy, 15 of whom subsequently relapsed and received DLI. Ten patients to date have achieved molecular remission after DLI. Adjunctive targeted therapy allows the kinetics of disease relapse after a reduced-intensity allograft to be manipulated and represents a novel strategy by which outcome may be improved in patients who undergo transplantation for CML and other leukemias.


PPARα Activation Protects against Anti-Thy1 Nephritis by Suppressing Glomerular NF-κB Signaling.
The vast increase of chronic kidney disease (CKD) has attracted considerable attention worldwide, and the development of a novel therapeutic option against a representative kidney disease that leads to CKD, mesangial proliferative glomerulonephritis (MsPGN) would be significant. Peroxisome proliferator-activated receptor α (PPARα), a member of the steroid/nuclear receptor superfamily, is known to perform various physiological functions. Recently, we reported that PPARα in activated mesangial cells exerted anti-inflammatory effects and that the deficiency of PPARα resulted in high susceptibility to glomerulonephritis. To investigate whether PPARα activation improves the disease activity of MsPGN, we examined the protective effects of a PPARα agonist, clofibrate, in a well-established model of human MsPGN, anti-Thy1 nephritis, for the first time. This study demonstrated that pretreatment with clofibrate (via a 0.02% or 0.1% clofibrate-containing diet) continuously activated the glomerular PPARα, which outweighed the PPARα deterioration associated with the nephritic process. The PPARα activation appeared to suppress the NF-κB signaling pathway in glomeruli by the induction of IκBα, resulting in the reduction of proteinuria and the amelioration of the active inflammatory pathologic glomerular changes. These findings suggest the antinephritic potential of PPARα-related medicines against MsPGN. PPARα-related medicines might be useful as a treatment option for CKD.


Intraductal papillary mucinous neoplasm and the pancreatic incidentaloma.
Asymptomatic pancreatic lesions (APL) are a commonly encountered problem in today's pancreatic surgical practices. Current literature regarding etiologies and incidence of APLs, particularly intraductal papillary mucinous neoplasm (IPMN), is presented. APLs constitute a wide spectrum of pathology (solid/cystic, benign/premalignant/malignant) but, overall, IPMN is now the most common diagnosis. The Sendai Guidelines and their function as a basis for risk stratification in branch duct IPMN are presented. The importance of traditionally analyzed cyst characteristics including size, presence of mucin or nodules and cyst fluid aspirate as indicators of malignancy is emphasized, noting also the potential correlation of main duct dilatation, thickened septae and elevated cyst fluid CEA with increased risk of malignancy. Current complication rates after resection of APLs are reviewed and found to be generally equivalent to those for symptomatic resections. A potential multidisciplinary treatment strategy is offered considering the costs of surgery versus repeated imaging or follow up endoscopy for these lesions. The decision for intervention is ultimately based on the Sendai Guidelines in the context of the individual patient.