Long-term consequences of neonatal fluoxetine exposure in adult rats.
Serotonin (5-HT) plays important roles during neural development. Administration of selective serotonin reuptake inhibitor (SSRI)-type medication during gestation may influence the maturation of the fetal brain and subsequent brain functions. To mimic the condition of late-gestation SSRI exposure, we administered fluoxetine (FLX) in neonatal rats during the first postnatal week, which roughly corresponds to the third trimester period of human gestation. FLX-exposed adult male rats exhibited reduced locomotor activity and depression-like behaviors. Furthermore, sensorimotor gating capacity was also impaired. Interestingly, increased social interaction was noticed in FLX-exposed rats. When the levels of 5-HT and tryptophan hydroxylase were examined, no significant changes were found in FLX rats compared to control (CON) rats. The behavioral phenotypes of FLX rats suggested malfunction of the limbic system. Dendritic architectures of neurons in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) were examined. Layer II/III mPFC pyramidal neurons in FLX rats had exuberant dendritic branches with elongated terminal segments compared to those in CON rats. In BLA pyramidal neurons, the dendritic profiles were comparable between the two groups. However, in FLX rats, the density of dendritic spines was reduced in both mPFC and BLA. Together, our results demonstrated the long-lasting effects of early FLX treatment on emotional and social behaviors in adult rats in which impaired neuronal structure in the limbic system was also noticed. The risk of taking SSRI-type antidepressants during pregnancy should be considered.


Likelihood-based hypothesis tests for brain activation detection from MRI data disturbed by colored noise: a simulation study.
Functional magnetic resonance imaging (fMRI) data that are corrupted by temporally colored noise are generally preprocessed (i.e., prewhitened or precolored) prior to functional activation detection. In this paper, we propose likelihood-based hypothesis tests that account for colored noise directly within the framework of functional activation detection. Three likelihood-based tests are proposed: the generalized likelihood ratio (GLR) test, the Wald test, and the Rao test. The fMRI time series is modeled as a linear regression model, where one regressor describes the task-related hemodynamic response, one regressor accounts for a constant baseline and one regressor describes potential drift. The temporal correlation structure of the noise is modeled as an autoregressive (AR) model. The order of the AR model is determined from practical null data sets using Akaike's information criterion (with penalty factor 3) as order selection criterion. The tests proposed are based on exact expressions for the likelihood function of the data. Using Monte Carlo simulation experiments, the performance of the proposed tests is evaluated in terms of detection rate and false alarm rate properties and compared to the current general linear model (GLM) test, which estimates the coloring of the noise in a separate step. Results show that theoretical asymptotic distributions of the GLM, GLR, and Wald test statistics cannot be reliably used for computing thresholds for activation detection from finite length time series. Furthermore, it is shown that, for a fixed false alarm rate, the detection rate of the proposed GLR test statistic is slightly, but (statistically) significantly improved compared to that of the common GLM-based tests. Finally, simulations results reveal that all tests considered show seriously inferior performance if the order of the AR model is not chosen sufficiently high to give an adequate description of the correlation structure of the noise, whereas the effects of (slightly) overmodeling are observed to be less harmful.


The genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy due to mutations in ALDH7A1.
Pyridoxine-dependent epilepsy is a disorder associated with severe seizures that may be caused by deficient activity of α-aminoadipic semialdehyde dehydrogenase, encoded by the ALDH7A1 gene, with accumulation of α-aminoadipic semialdehyde and piperideine-6-carboxylic acid. The latter reacts with pyridoxal-phosphate, explaining the effective treatment with pyridoxine. We report the clinical phenotype of three patients, their mutations and those of 12 additional patients identified in our clinical molecular laboratory. There were six missense, one nonsense, and five splice-site mutations, and two small deletions. Mutations c.1217_1218delAT, I431F, IVS-1(+2)T > G, IVS-2(+1)G > A, and IVS-12(+1)G > A are novel. Some disease alleles were recurring: E399Q (eight times), G477R (six times), R82X (two times), and c.1217_1218delAT (two times). A systematic review of mutations from the literature indicates that missense mutations cluster around exons 14, 15, and 16. Nine mutations represent 61% of alleles. Molecular modeling of missense mutations allows classification into three groups: those that affect NAD+ binding or catalysis, those that affect the substrate binding site, and those that affect multimerization. There are three clinical phenotypes: patients with complete seizure control with pyridoxine and normal developmental outcome (group 1) including our first patient; patients with complete seizure control with pyridoxine but with developmental delay (group 2), including our other two patients; and patients with persistent seizures despite pyridoxine treatment and with developmental delay (group 3). There is preliminary evidence for a genotype-phenotype correlation with patients from group 1 having mutations with residual activity. There is evidence from patients with similar genotypes for nongenetic factors contributing to the phenotypic spectrum.


Construction and characterization of Cy3- or Cy5-conjugated hairpin pyrrole-imidazole polyamides binding to DNA in the nucleosome.
Sequence-specific DNA-binding modules, N-methylpyrrole (Py)-N-methylimidazole-(Im) polyamides have been recently conjugated with fluorophores, and some of these conjugates could be used for the detection of specific DNA sequences. In this study, we synthesized two Py-Im polyamides 1 and 2, which interact with the 145-bp nucleosome positioning sequence 601. We conjugated the cyanine dye Cy3 or Cy5 with 1 or 2. In the absence of target DNA, the fluorescent conjugate of a Py-Im polyamide had lower fluorescence intensity compared with Cy3 or Cy5 alone. In the presence of either the target DNA or the nucleosome, the fluorescence intensity of the conjugates increased. Furthermore, we observed a Förster resonance energy transfer between the Cy3-Py-Im polyamide and the Cy5-Py-Im polyamide on the nucleosome. These results open up the possibilities that fluorescent conjugates of Py-Im polyamides can be used for characterization of the dynamic interactions within protein-DNA complexes.


Non-polymeric asymmetric binary glass-formers. II. Secondary relaxation studied by dielectric, 2H NMR, and 31P NMR spectroscopy.
We investigate the secondary (β-) relaxations of an asymmetric binary glass former consisting of a spirobichroman derivative (SBC; Tg = 356 K) as the high-Tg component and the low-Tg component tripropyl phosphate (TPP; Tg = 134 K). The main relaxations are studied in Paper I [B. Pötzschner et al., J. Chem. Phys. 146, 164503 (2017)]. A high Tg contrast of ΔTg = 222 K is put into effect in a non-polymeric system. Component-selective studies are carried out by combining results from dielectric spectroscopy (DS) for mass concentrations cTPP ≥ 60% and those from different methods of 2H and 31P NMR spectroscopy. In the case of NMR, the full concentration range (10% ≤ cTPP ≤ 100%) is covered. The neat components exhibit a β-relaxation (β1 (SBC) and β2 (TPP)). The latter is rediscovered by DS in the mixtures for all concentrations with unchanged time constants. NMR spectroscopy identifies the β-relaxations as being alike to those in neat glasses. A spatially highly restricted motion with angular displacement below ±10° encompassing all molecules is involved. In the low temperature range, where TPP shows the typical 31P NMR echo spectra of the β2-process, very similar spectral features are observed for the (deuterated) SBC component by 2H NMR, in addition to its "own" β1-process observed at high temperatures. Apparently, the small TPP molecules enslave the large SBC molecules to perform a common hindered reorientation. The temperature dependence of the spin-lattice relaxation time of both components is the same and reveals an angular displacement of the SBC molecules somewhat smaller than that of TPP, though the time constants τβ2 are the same. Furthermore, T1(T) of TPP in the temperature region of the β2-process is absolutely the same as in the mixture TPP/polystyrene investigated previously. It appears that the manifestations of the β-process introduced by one component are essentially independent of the second component. Finally, at cTPP ≤ 20% one finds indications that the β2-process starts to disintegrate. More and more TPP molecules get immobilized upon decreasing cTPP. We conclude that the β-process is a cooperative process.


Phytochemical composition of nuts.
Observational studies suggest nut consumption is inversely associated with the incidence of cardiovascular disease and cancer. In addition to being rich in several vitamins and minerals, unsaturated fatty acids, and fiber, tree nuts and peanuts contain numerous phytochemicals that may contribute to promoting health and reducing the risk of chronic disease. While many of these bioactive constituents remain to be fully identified and characterized, broad classes include carotenoids, phenols, and phytosterols. Phytosterols in nuts range from 95-280 mg/100 g. alpha- and beta-Carotene, beta-cryptoxanthin, lutein, and zeaxanthin are found in microg/100 g amounts in some nuts but at 1-3 mg/100 g in pistachios and none at all in Brazils, macadamias, and peanuts. Phenols, including phenolic acids, flavonoids, and stilbenes, are present in nuts. Walnuts are particularly rich in total phenols with 1625 mg gallic acid equivalents/100 g. The stilbene resveratrol is found in peanuts and pistachios at 84 and 115 microg/100 g, respectively. The flavonoid content of nuts as provided in USDA Database for the Flavonoid Content of Selected Foods, lists totals in pecans at 34, almonds at 15, and pistachios and hazelnuts at 12 mg/100 g. Proanthocyanidins are found in almonds, cashews, hazelnuts, pecans, pistachios, peanuts, and walnuts, with concentrations varying from 9-494 mg/100 g. Nut phytochemicals have been associated with numerous bioactivities known to affect the initiation and progression of several pathogenic processes. However, as complete phytochemical profiles are lacking for most nuts, information is limited regarding their bioavailability and metabolism, so further research on this topic is warranted.


A perinatal continuing education program: its effects on the knowledge and practices of health professionals.
To determine whether there was an increase in knowledge when an interdisciplinary group of health care providers participated in the same comprehensive perinatal continuing education program and to determine whether care practices followed before the program differed from those followed 1 year after its completion. Administration of a 100-item comprehensive pretest and a similar posttest measuring knowledge before the continuing education program and 1 year after taking it, as well as an ex post facto audit of medical records of newborns who were sick and at risk. Hospitals throughout the state of Oklahoma that provide perinatal care. Test data were derived from health care providers in 24 hospitals; data on care practices were obtained from 12 hospitals. A comprehensive program of perinatal continuing education. Physicians, nurses, and other providers of perinatal health care. Scores on a 100-item test measuring knowledge of perinatal care and newborn care practices taught in the educational program. Pretest and posttest scores demonstrated an increase in scores at the p < 0.001 level for each group of providers studied. There was a statistically significant increase in use of two care practices and a definite trend toward an increase in the use of three others. A continuing education program delivered to a multidisciplinary group of health care providers can increase knowledge and improve perinatal care to newborns who are sick and at risk.


Universal influenza immunization. Were Ontario family physicians prepared?
To explore family physicians' experiences during the first year of Ontario's universal influenza immunization program. Qualitative study using in-depth interviews. Thames Valley region of southwestern Ontario. A maximum variation sample of nine family physicians selected by snowball sampling after initial consultation with a local family physician advisory committee. Interviews were audiotaped and transcribed verbatim. Analysis was sequential, using a combination of editing, immersion, and crystallization. Interview transcripts were read by individual members of the team who met to compare findings at several stages during data collection. The program affected family physicians because immunization strategies designed for immunizing high-risk patients needed to be modified to deal with greater numbers of patients. While generally supportive of the program, physicians found it difficult to implement. Responses reflected ongoing conflict between individual and public health priorities, particularly regarding children and pregnant women. The program could have been more effective if the culture and climate of Ontario family practice had been considered during its development and implementation.


'The Virtual Check-In': A tool to facilitate virtual patient interaction for early clinical learners in a longitudinal integrated clerkship.
This article was migrated. The article was marked as recommended. In response to restrictions on learner placements in clinical environments during the COVID-19 pandemic the authors developed a tool, 'The Virtual Check-In', for clinical clerks in the University of Calgary Longitudinal Integrated Clerkship. These learners, who had been pulled from their rural and remote communities because of the pandemic, used the tool to continue to develop their clinical skills while working with their preceptors and patients online. This paper describes the rapid development of the tool using Kern's principles for curriculum development and implementation, the format and uses of the final tool, and its potential use in other contexts.


[Halo instrumentation for the correction and immobilization of the cervical spine].
An instrument set for application in patients requiring a correction treatment and/or a temporary fixation of the cervical spine is described. The halo is combined with a cast or a brace employing the 8 mm Hoffmann External Fixator system supplemented by three additional, newly designed parts. Applications of the instrument set in the treatment of traumatic fracture, fibrous dysplasia and ankylosing spondylitis are described.


Effect of a platelet-activating factor (PAF) antagonist, SR 27417A, on PAF-induced gas exchange abnormalities in mild asthma.
Inhaled platelet-activating factor (PAF), both in normals and in asthmatic patients, provokes transient systemic effects, neutropenia, bronchoconstriction and arterial oxygenation abnormalities similar to those shown in spontaneous exacerbations of asthma. To investigate the efficacy of a new PAF-receptor antagonist, SR 27417A, on all these changes after PAF challenge, 12 nonsmoking patients (four females and eight males) (mean+/-SEM) age 24+/-1 yrs with mild asthma (forced expiratory volume in one second (FEV1) 93+/-3% predicted) were studied in a double-blind, placebo-controlled, cross-over fashion 2 weeks apart. PAF aerosol challenge (18 microg) was carried out 3 h after oral administration of either SR 27417A (20 mg) or placebo. Respiratory system resistance (Rrs) and arterial blood gases and neutrophil cell counts were measured at baseline, before compound/placebo administration, and at 5, 15 and 45 min after PAF. Compared to vehicle, SR 27417A brought about moderate attenuation of PAF-induced neutropenia at 5 min (by 140%; p<0.025), and rebound neutrophilia at 15 and 45 min (p<0.025), increases of Rrs (by 90-65%) (p<0.01) and of alveolar-arterial pressure difference for oxygen (PA-a,O2) at 5 min (by 68%) and 15 min (by 63%), and decreases of arterial oxygen tension (Pa,O2) at 5 min (by 57%; p<0.025, each). Furthermore, systemic effects and platelet aggregation tests (p<0.001) were abolished after the administration of the compound. We conclude that SR 27417A is effective in inhibiting systemic, cellular and pulmonary effects after platelet-activating factor challenge in patients with mild bronchial asthma.


Overnight recordings of intracranial pressure and electroencephalography in neurosurgical patients. Part I: Intracranial pressure waves and their clinical correlations.
Simultaneous overnight recordings of intracranial pressure (ICP) and electroencephalography (EEG) were conducted on 85 neurosurgical patients with intracranial hypertension and/or ventriculomegaly. Intracranial pressure waves were classified into five types according to the pattern of appearance, and their correlation with sleep cycles and clinical conditions of patients were investigated. A-waves appeared exclusively in patients with long-standing intracranial hypertension, and episodic B-waves appeared in patients with chronic hydrocephalus or a postoperative tumor-free condition. When these episodic pressure waves appeared, the patients were conscious and sleep cycles including REM stage were observed. Persistent, high pressure B-waves were seen mostly in patients with an acute phase of intracranial hemorrhages. The consciousness of these patients ranged from drowsy to stupor. EEG showed alternate appearances of light sleep and waking rhythms in accordance with cyclic oscillations of B-waves which coincided with periodic, apneic respiratory rhythms. When markedly regular B-waves of moderately high pressure appeared continuously, the patients were severely impaired in consciousness and were mainly in a subacute phase of intracranial hemorrhages. EEG showed continuous slow activities and sleep stages were not scored in these patients. No characteristic clinical features were found in patients whose ICP remained within normal range without pressure waves throughout the recording.


Yolk hormones and sexual conflict over parental investment in the pied flycatcher.
Female birds might be able to manipulate the parental effort of their male partner through elevated transfer of hormones to the eggs, since these hormones affect many chick traits that males might use as cues for adjusting the level of their investment. We experimentally studied whether female pied flycatchers Ficedula hypoleuca could manipulate male investment via yolk androgens. There is much more variation in yolk androgen levels between females than within clutches, and in order to change the androgen levels of the eggs, we swapped whole clutches between nests. To estimate the androgen levels of the clutch, we measured the androgen content of a single egg per clutch. Females did not succeed in manipulating male effort using yolk androgens, since there was no relationship between the division of parental care within a pair and either original or foster egg androgen levels. One of these relationships should have occurred if females were manipulating males. The proportion of feeding visits by the male was higher when the male was old (55%) than when he was young (45%) and females laid eggs with higher androgen levels when mated with a young male. Young males did not exhibit any responses to yolk androgen levels either, which indicates that females cannot exploit their effort more than that of old males. We suggest that females may allocate yolk androgens to adjust the growth trajectories of the chicks to poor growing conditions when mated with young males that are poor providers or occupying a poor territory.


Functional analysis of chicken vimentin distal promoter regions in cultured lens cells.
Synthesis of the cytoskeletal intermediate filament protein vimentin (Vim) in the lens is unexpected due to the mesenchymal preference of Vim-encoding gene (Vim) expression and the epithelial origin of the lens. Previous studies indicated that chicken Vim gene expression in cultured lens cells is regulated by both positive- and negative-acting sequence elements within the first -767 nucleotides (nt) of its promoter. Here, we demonstrate the existence of additional upstream chicken Vim promoter elements which function in transfected lens cells. Sequences within the nt -1360/-1156 region repressed promoter activity in transfected lens cells to levels lower than that observed for the previously defined more proximal repressor elements. The -1612/-1360 region activated promoter activity to levels similar to those observed for the strongest previously defined proximal promoter. The nt sequence analysis of the upstream promoter region revealed the presence of multiple consensus repressor and activator transcription-factor-binding sites. Several of these sites have been implicated for lens expression of enzyme-crystallin-encoding genes (cry), suggesting that Vim expression may share features with the cry genes for recruitment and high-level expression in the lens.


The radial forearm flap in head and neck reconstruction.
The radial forearm flap has proven to be a very reliable and versatile technique for reconstructing head and neck defects. It is of particular value where segmental defects in the mandible and intraoral mucosa exist, and in reconstructing defects within radiated tissue. The skin of the flap drapes well over the radial bone to allow denture fitting. The radial bone provides an adequate bony strut to allow essentially normal mandibular function. In a previously radiated bed, the flap (from a non-irradiated area) has the virtue of being highly vascular, thus benefiting wound healing. The lack of bulk in the flap prevents separation at the site of inset as wound healing occurs. It is a one-stage reconstruction, and since the donor site is on the upper extremity, early patient mobilization is possible. The donor defect is cosmetically acceptable, and since it lies against the body in the position of rest, it is not frequently exposed. The osseous portion of the flap in a postmenopausal woman should be approached with caution and patients should be warned of the risk of radius fracture. This flap is capable of providing tissue for reconstruction of the head and neck and should be considered for closure of all major defects, particularly those with bone defects or in defects created postirradiation.


Emerging Two-Dimensional Crystallization of Cucurbit[8]uril Complexes: From Supramolecular Polymers to Nanofibers.
The binding of imidazolium salts to cucurbit[8]uril, CB[8], triggers a stepwise self-assembly process with semiflexible polymer chains and crystalline nanostructures as early- and late-stage species, respectively. In such a process, which involves the crystallization of the host-guest complexes, the guest plays a critical role in directing self-assembly toward desirable morphologies. These include platelet-like aggregates and two-dimensional (2D) fibers, which, moreover, exhibit viscoelastic and lyotropic properties. Our observations provide a deeper understanding of the self-assembly of CB[8] complexes, with fundamental implications in the design of functional 2D systems and crystalline materials.


Moderate physical activity is associated with lower ApoB/ApoA-I ratios independently of other risk factors in healthy, middle-aged men.
Low-density lipoprotein is recognized as a primary vascular risk factor. However, recent data favor apolipoprotein (apo)B and apoA-I as risk factors with higher predictive values than conventional lipids. We investigated how leisure-time physical activity relates to the serum apoB/apoA-I ratio in middle-aged men. The results showed that compared with a sedentary lifestyle, moderate physical activity was associated with a decreased apoB/apoA-I ratio (1.01 ± 0.28 vs 0.87 ± 0.24, P < .05) and increased apoA-I levels (1.30 ± 0.20 g/L vs 1.43 ± 0.22 g/L, P < .05), whereas vigorous activity was required to observe a reduction in apoB levels (1.27 ± 0.28 g/L vs 1.14 ± 0.24 g/L, P < .05). A covariate analysis showed that leisure time physical activity was also associated with reduced apoB/apoA-I ratios after adjustment for smoking, systolic blood pressure and waist circumference. Importantly, this association was seen at moderate levels of physical activity, supporting the notion that some activity is better than none.


The CT appearances of sclerosing mesenteritis and associated diseases.
Sclerosing mesenteritis is characterized by non-specific inflammation of the mesenteric fat associated with variable amount of fibrosis. The aetiology is unclear; the pathogenesis is obscure, and even its nomenclature remains variable. It is a rare condition with imaging features that can be mistaken either for a mesenteric neoplasm or for a wide variety of non-neoplastic inflammatory conditions. Knowledge of the imaging features of this condition may prevent unwarranted aggressive therapy. This review discusses the pathogenesis, clinical manifestations of this condition, as well as illustrating the characteristic computed tomography (CT) features of sclerosing mesenteritis. A rational approach to the differential diagnosis is discussed.


Proposal of bioinstrumentation using shape deformation of amputated upper limb.
Some upper limb amputees have been annually supplied with myoelectric prostheses by social rehabilitation promotion services. However, the persons supplied with the prostheses have been limited because a supply system has not been established yet. Accordingly, we propose a new bioinstrumentation using the shape deformation of the amputated upper limbs without using the myoelectricity generated on the skin of the upper limbs. The repeatability is superior to the myoelectricity because the shape deformation is directly measured by strain gages and also the cost is much superior to the myoelectricity.


[Influence of conditions of artificial hibernation on energy metabolism indices in rats].
Influence of the conditions of artificial hibernation on the content of ATP, ADP, AMP, cAMF in the blood and liver of rats is studied. It is established, that the entering and stay of animals in the conditions of artificial hibernation is accompanied by a decrease of the content of ADP and P(l). The animal coming out of the condition of artificial hibernation is accompanied by an increase of the content of ATP and cAMP and achievement in twenty-four hours of the level of monitoring values.


Adjunct laboratory tests in the diagnosis of early-onset neonatal sepsis.
Early-onset sepsis remains a major diagnostic problem in neonatal medicine. Definitive diagnosis depends on cultures of blood or other normally sterile body fluids. Abnormal hematological counts, acute-phase reactants, and inflammatory cytokines are neither sensitive nor specific, especially at the onset of illness. Combinations of measurements improve diagnostic test performance, but the optimal selection of analytes has not been determined. The best-established use of these laboratory tests is for retrospective determination that an infant was not infected, based on failure to mount an acute-phase response over the following 24 to 48 hours.


[Aneurysmal bone cyst of the temporal and zygomatic region].
Aneurysmal bone cyst are commonly seen in long bone and vertebrae. There are rare in skull bones especially in the temporal bone and zygomatic arch. We report one case in a young male of 15 years old. The main symptom was swelling of the temporo mandibular region. Clinical, radiological and therapeutic aspects of the disease are discussed with regards to the literature. The diagnosis is based on good imaging and histopathological analysis. Surgical removal is the main treatment.


Toxicity and transcriptomic analysis in Hyalella azteca suggests increased exposure and susceptibility of epibenthic organisms to zinc oxide nanoparticles.
Nanoparticles (NPs) are expected to make their way into the aquatic environment where sedimentation of particles will likely occur, putting benthic organisms at particular risk. Therefore, organisms such as Hyalella azteca, an epibenthic crustacean which forages at the sediment surface, is likely to have a high potential exposure. Here we show that zinc oxide (ZnO) NPs are more toxic to H. azteca compared with the corresponding metal ion, Zn(2+). Dissolution of ZnO NPs contributes about 50% of the Zn measured in the ZnO NP suspensions, and cannot account for the toxicity of these particles to H. azteca. However, gene expression analysis is unable to distinguish between the ZnO NP exposures and zinc sulfate (ZnSO4) exposures at equitoxic concentrations. These results lead us to hypothesize that ZnO NPs provide an enhanced exposure route for Zn(2+) uptake into H. azteca, and possibly other sediment dwelling organisms. Our study supports the prediction that sediment dwelling organisms are highly susceptible to the effects of ZnO NPs and should be considered in the risk assessment of these nanomaterials.


Evaluation of the adjunctive benefits of platelet-rich plasma in subantral sinus augmentation.
Subantral sinus augmentation is often necessary to permit placement of endosseous implants. Recent efforts to improve wound healing have focused on autogenous sources of bioactive mediators, such as platelet-rich plasma (PRP), which offer the potential to enhance the biological activity of bone replacement grafts. The purpose of this randomized, single-blinded, controlled study was to compare bone formation after subantral maxillary sinus augmentation with freeze-dried bone allograft (FDBA) plus PRP versus FDBA plus resorbable membrane. Ten patients underwent bilateral maxillary subantral sinus augmentation, with sites within subjects randomized to receive FDBA plus PRP or FDBA plus membrane. Core biopsy specimens were obtained 4.5 to 6 months after the grafting procedure at time of implant placement. Histomorphometric analysis revealed a significantly higher percentage of vital tissue in sinuses after treatment with FDBA and PRP (78.8 +/- 8.3) than with FDBA and membrane (63.0 +/- 15.7). Moreover, the percentage of bone formation in sinuses augmented with the combination of FDBA plus PRP (33.3 +/- 11.3) was nonsignificantly (P </= 0.10) higher than in sinuses grafted with FDBA plus membrane (26.5 +/- 6.8). Residual graft particles constituted a significantly higher percentage of the regenerate in sinuses treated with FDBA plus membrane than in sinuses augmented with FDBA plus PRP (37.0 +/- 15.7) versus (21.2 +/- 8.3, respectively). When comparing the relative proportion of vital bone to residual graft particles, a significant difference also was observed between sinuses treated with FDBA and membrane compared with sinuses augmented with FDBA and PRP (0.98 +/- 0.77 versus 1.82 +/- 0.88, respectively). The results of this study suggest that the combination of FDBA and PRP enhances the rate of formation of bone compared with FDBA and membrane, when used in subantral sinus augmentation. Future research is needed to determine the clinical significance and the cost- and risk-benefit considerations of the approach.


The pitfalls of lung cancer screening.
Lung cancer screening has received extensive attention for a number of years. As yet the goal of such a screening programme, a reduction in lung cancer mortality proven by a large randomised controlled trial, has not been achieved. Instead we are left with a number of unanswered questions and practical problems. In addition to the basic requirements for an effective screening programme, this review will identify the main pitfalls in lung cancer screening, with particular reference to multislice computed tomography. The specific difficulties relating to the identification of unimportant disease, the failure to identify important disease successfully, the consequences of investigating and treating identified disease and the financial costs will all be discussed.


Antidepressant treatment and risk of suicide attempt by adolescents with major depressive disorder: a propensity-adjusted retrospective cohort study.
The US FDA has issued an advisory warning of a possible link between antidepressant treatment for paediatric patients with major depressive disorder (MDD) and an increased risk of suicidal behaviour. A large database of paid health insurance claims for adolescents with MDD provided the opportunity to examine this possible relationship. To examine the potential empirical link between antidepressant treatment and suicide attempts among adolescents aged 12-18 years using a community sample of managed care enrollees across the US. A retrospective longitudinal cohort using paid insurance claims for all healthcare and prescription fills for adolescents who were newly diagnosed with MDD and had at least 6 months of follow-up data. A multivariate Cox proportional hazards regression analysis was used to test the hypothesis that antidepressant use increased the risk of suicide attempt, adjusting for propensity for allocation to each treatment group and for demographic and clinical characteristics. Managed care plans including both commercial and Medicaid plans in the east, midwest, south and western regions of the US from January 1997 to March 2003. All adolescent insurance members aged 12-18 years at first diagnosis of MDD. Suicide attempts as indicated by medical utilisation with International Classification of Diseases (9th edition) [ICD-9] or 10th edition (ICD-10) codes in any healthcare setting or by any covered provider. 24 119 adolescents met inclusion criteria (63% female). Crude suicide attempt rates ranged from 0.0-2.3% by index treatment group. Treatment with SSRIs (hazard ratio) [HR] = 1.59; CI 0.89, 2.82), other antidepressants (HR = 1.03; CI 0.43, 2.44), or multiple antidepressants (HR = 1.43; CI 0.70, 2.89) after index MDD diagnosis resulted in no statistically increased risk of suicide attempt. Treatment with antidepressant medication for at least 180 days (6 months) reduced the likelihood of suicide attempt compared with antidepressant treatment for <55 days (8 weeks) [HR = 0.34; CI 0.21, 0.55]. Other variables that were independently associated with greater risk of suicide attempts included female gender, severity of illness indicators, younger age at time of MDD diagnosis, and living in the midwest or west. Antidepressant medication use had no statistically significant effect on the likelihood of suicide attempt in a large cohort of adolescents across the US after propensity adjustment for treatment allocation and controlling for other factors. The relationship between suicidal behaviour and antidepressant medication use is complex and requires further investigation.


NMR-metabolomics profiling of mammary gland secretory tissue and milk serum in two goat breeds with different levels of tolerance to seasonal weight loss.
Goats are of special importance in the Mediterranean and tropical regions for producing a variety of dairy products. The scarcity of pastures during the dry season leads to seasonal weight loss (SWL), which affects milk production. In this work, we studied the effect of feed-restriction on two dairy goat breeds, with different tolerance levels to SWL: the Majorera breed (tolerant) and the Palmera breed (susceptible). Nuclear magnetic resonance (NMR) was used to compare the metabolome of an aqueous fraction of the mammary gland and milk serum from both breeds. Goats in mid-lactation were divided by breed, and each in two feed-regime groups: the control group and the restricted-fed group (to achieve 15-20% reduction of body weight at the end of the experiment). Milk and mammary gland samples were collected at the end of the experimental period (23rd day). (1)H NMR spectra were collected from the aqueous extract of the mammary gland biopsies and the milk serum. Profiling analysis has led to the identification of 46 metabolites in the aqueous extract of the mammary gland. Lactose, glutamate, glycine and lactate were found to be the most abundant. Analysis of milk serum allowed the identification of 50 metabolites, the most abundant being lactose, citrate and creatine. Significant differences were observed, in mammary gland biopsies and milk serum, between control and restricted-fed groups in both breeds, albeit with no differences between the breeds. Variations seem to be related to metabolism adaptation to the low-energy diet and are indicative of breed-specific microflora. Milk serum showed more metabolites varying between control and restricted groups, than the mammary gland. The Majorera breed also showed more variations than the Palmera breed in milk samples, which could be an indication of a prompt adaptation to SWL by the Majorera breed.


Dispersive multiplexing in multimode optical fiber
Recently developed ideas in the field of wireless communications suggest that the presence of scattering can be used to enhance, rather than degrade, the total information capacity of a transmission system. This concept is applied to data transmission over multimode optical fiber, and the result is an optical multiplexing that can increase the capacity of such fiber. Experimental results demonstrate the feasibility of this approach. The technique may play an important role in future high-bandwidth local area networking applications.


Bacterial endotoxin is an active component of cigarette smoke.
Chronic bronchitis in cigarette smokers shares many clinical and histologic features with environmental lung diseases attributed to bacterial endotoxin (lipopolysaccharide [LPS]) inhalation. Experimental LPS inhalation mimics many of the acute effects of cigarette smoke in the lower airway. Therefore, we reasoned that LPS may be a biologically active component of cigarette smoke. The Limulus amebocyte lysate (LAL) assay was used to measure LPS in the tobacco and filter tip components of unsmoked 1R4F experimental cigarettes and commercially available "light" cigarettes, as well as in mainstream (MS) and sidestream (SS) smoke particles generated with an automated smoking machine and collected on ventilator mainflow filters. Blood LPS activity and plasma cytokine concentrations were measured in groups of healthy smokers and nonsmokers who reported to the walk-in clinic at the Baltimore VA Medical Center for unrelated complaints. Blood LPS levels were measured by LAL assay and plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), soluble TNF receptors I and II (sTNFR I and sTNFR II) were measured by enzyme-linked immunosorbent assay. Bioactive LPS was detected in both the tobacco portion (1R4F, 17.8+/-1.0 microg/cigarette; light, 26.8+/-7.3 microg/cigarette [mean+/-SE]) and filter tips (1R4F, 0.67+/-0.55 microg/cigarette; light, 0.70+/-0.39 microg/cigarette) of cigarettes. Bioactive LPS was also detected in both MS (1R4F, 120+/-64 ng/cigarette; light: 45.3+/-16 ng/cigarette) and SS smoke (1R4F, 18+/-1.5 ng/cigarette; light: 75+/-49 ng/cigarette). Although systemic absorption of inhaled LPS may occur, we failed to detect any differences between nonsmokers and smokers in median blood LPS levels (median values, 66.75 and 72.1 pg/mL, respectively; p = 0.55) or plasma concentrations of TNF-alpha (0 vs 0 pg/mL, respectively; p = 0.71), sTNFR I(1,469 vs 1,576 pg/mL, respectively), sTNFR II (2,011 vs 3,110 pg/mL, respectively), or IL-6 (8.8 vs 0 pg/mL, respectively; p = 0.20). Smoking one pack of cigarettes per day delivers a dose of respirable LPS that is comparable to the levels of LPS associated with adverse health effects in cotton textile workers. Thus, we suggest that the bioactive LPS in cigarette smoke may contribute to the pathogenesis of chronic bronchitis that develops in susceptible cigarette smokers.


Early activation of sperm by HCO(3) (-) is regulated hormonally in the murine uterus.
Sperm deposited in the female genital tract receive signals for capacitation. Past work indicates that HCO(3) (-) is the initiating signal that the female reproductive tract contains the HCO(3) (-) -permeant anion channel cystic fibrosis transmembrane conductance regulator (CFTR) and that mutations in CFTR cause subfertility in both sexes. In this study, we examined whether CFTR controls uterine HCO(3) (-) content and sperm responses to it. Both CFTR protein and mRNA were absent in prepubertal murine uterus, but appeared in pubertal and adult tissues. Thus, CFTR is upregulated during development. Uterine CFTR mRNA additionally increased upon induced oestrus, most abundantly in uterus body and distal horns. Uterine fluid of oestrous females contained two-, and nearly fourfold more HCO(3) (-) than that of dioestrous and prepubertal animals, correlating with increased CFTR expression. For sperm incubated in and recovered from prepubertal uteri, flagellar beat frequency was no different from that before incubation. However, for sperm recovered from dioestrous and oestrous uteri, beat frequency was two- and fourfold higher, respectively. Thus, uterine HCO(3) (-) content may have physiological consequences for sperm motility. The male reproductive tract showed no regional distributions or developmental dependence of CFTR expression. Although the sperm flagellum showed CFTR immunoreactivity, CFTR blockers GlyH-101 or CFTR(inh) -172 did neither diminish HCO(3) (-) -evoked increases in sperm motility nor protein tyrosine phosphorylation. Our results indicate that in the uterus, both CFTR expression and the supply of HCO(3) (-) are upregulated hormonally. We propose that these changes coordinate ovulation with increases in sperm motility and promote other components of capacitation by pathways that do not require CFTR in sperm.


Antibody affinity. VIII. Measurement of affinity of anti-lactose antibody by fluorescence quenching with a DNP-containing ligand.
The method of fluorescence quenching by bound ligand for the measurement of antibody affinity has been extended to anti-lactose antibodies. The basis for this extension is the use of a lactosyl ligand covalently linked to the 2,4-dinitrophenyl (DNP) group. This group serves as a sensor of the bound state by causing fluorescence quenching similar to that observed with anti-DNP antibody. The synthesis and characterization of this new ligand, N-(Nalpha-acetyl,Nepsilon-DNP-L-lysyl)-rho-aminophenyl-beta-lactoside, are described. The affinity of its interaction with three rabbit IgG and one equine IgM antilactose antibody preparations has been measured. The Qmax values range from 24 to 47% and the calculated association constants from 2.5 times 10-5 M-1 to 7.2 times 10-5 M-1. For one IgG preparation, measurement of the association constant by equilibrium dialysis with the tritiated ligand gave a value of 6.75 times 10-5 M-1 compared to the value of 7.2 times 10-5 M-1 obtained by fluorescence quenching. It is evident that with monoclonal anti-lactose antibody the accurate determination of Qmax, which is possible in this system, provides another structurally dependent clonal characterization of the variable region of the antibody. This optical probe along with others can be used for the identification of individual clones of antibody-producing cells through time and inheritance.


Time of day shapes Arabidopsis drought transcriptomes.
Under natural conditions, it is common for plants to experience water deprivation (drought) for periods of days or longer. Plants respond to drought stress by reconfiguring their transcriptome activity. Transcriptome changes in response to drought are dynamic, and are shaped by mitigating factors like time during the diurnal cycle. To date, analyses of drought-induced transcriptome remodelling have concentrated on dynamic changes induced by rapid desiccation, or changes at a single time point following gradual water stress. To gain insights into the dynamics of transcriptome reconfiguration in response to gradual drying of the soil, the drought-induced transcriptomes of Arabidopsis thaliana were examined at four time points over a single diel period - midday, late day, midnight, and pre-dawn. Transcriptome reconfigurations were induced by drought in advance of changes to relative water content, leaf water loss, and chlorophyll content. Comparative analyses support the hypothesis that the drought-responsive transcriptomes were shaped by invocation of distinct hormonal and stress response pathways at different times of the day. While a core set of genes were drought responsive at multiple time points throughout the day, the magnitude of the response varied in a manner dependent on the time of day. Moreover, analysis of a single time point would fail to identify suites of drought-responsive genes that can only be detected through assessment of the dynamics of diurnal changes, emphasising the value of characterising multiple time-of-day-specific drought transcriptomes.


The effect of cationic albumin-conjugated PEGylated tanshinone IIA nanoparticles on neuronal signal pathways and neuroprotection in cerebral ischemia.
Targeted treatment of ischemic stroke remains problem due to the complex pathogenesis of this disease and the difficulty in drug delivery across the blood-brain barrier (BBB). In the present study, the delivery efficiency of cationic bovine serum albumin-conjugated tanshinone IIA PEGylated nanoparticles (CBSA-PEG-TIIA-NPs) in rat brain was investigated. We further explored whether the protective mechanism of CBSA-PEG-TIIA-NPs in cerebral ischemia was associated with modulating neuronal signaling pathways. The experimental cerebral ischemia model was established to evaluate the treatment efficacy of CBSA-PEG-TIIA-NPs. The pharmacokinetics demonstrated that CBSA-PEG-TIIA-NPs could obviously prolong circulation time and increase plasma concentration compared with intravenously administrated TIIA solution. The biodistribution and brain uptake study confirmed that CBSA-PEG-TIIA-NPs possessed better brain delivery efficacy with a high drug accumulation and fluorescence quantitative level in brain. CBSA-PEG-TIIA-NPs effectively reduced infarction volume, neurological dysfunctions, neutrophils infiltration and neuronal apoptosis. Moreover, CBSA-PEG-TIIA-NPs significantly suppressed the expression of pro-inflammatory cytokines TNF-α and IL-8; upregulated the expression of anti-inflammatory cytokines IL-10 and increase TGF-β1 level in the ischemic brain. In addition, treatment with CBSA-PEG-TIIA-NPs markedly inhibited the mRNA expressions of GFAP, MMP-9, COX-2, p38MAPK, ERK1/2 and JNK, downregulated the protein levels of GFAP, MMP-9 and COX-2, as well as decreased the phosphorylation of ERK1/2, p38MAPK and JNK. These results demonstrated that CBSA-PEG-TIIA-NPs displayed remarkable neuroprotective effects on ischemic stroke through modulation of MAPK signal pathways involved in the cascades of neuroinflammation.


Imaging diagnosis--temporomandibular joint dysplasia in a Basset Hound.
A 5-month-old intact male Basset Hound presented for evaluation of pain and crepitation during manipulation of the temporomandibular joint, worse on the right side. A computed tomography (CT) scan of the head was performed. The CT images demonstrated the osseous features of temporomandibular joint dysplasia and facilitated a 3D reconstruction, which allowed better visualization of the dysplastic features. The patient responded to conservative management with a tape muzzle with no recurrence reported by the owner 6 months after presentation.


Kluyvera cryocrescens sepsis in a preterm infant.
Kluyvera cryocrescens, formerly accepted as a benign saprophytic microorganism, is an opportunistic pathogen and its infection is very rare in humans. This report describes a preterm infant born at 30 weeks of gestational age and successfully treated for K. cryocrescens sepsis in the 3rd week of life. To our knowledge, this is the first case of K. cryocrescens sepsis in a newborn. The potential of K. cryocrescens as a serious pathogen should be recognized especially in patients such as preterm infants in whom the prognosis may be compromised without appropriate treatment.


Sex and Genotype Modulate the Dendritic Effects of Developmental Exposure to a Human-Relevant Polychlorinated Biphenyls Mixture in the Juvenile Mouse.
While many neurodevelopmental disorders (NDDs) are thought to result from interactions between environmental and genetic risk factors, the identification of specific gene-environment interactions that influence NDD risk remains a critical data gap. We tested the hypothesis that polychlorinated biphenyls (PCBs) interact with human mutations that alter the fidelity of neuronal Ca2+ signaling to confer NDD risk. To test this, we used three transgenic mouse lines that expressed human mutations known to alter Ca2+ signals in neurons: (1) gain-of-function mutation in ryanodine receptor-1 (T4826I-RYR1); (2) CGG-repeat expansion in the 5' non-coding portion of the fragile X mental retardation gene 1 (FMR1); and (3) a double mutant (DM) that expressed both mutations. Transgenic and wildtype (WT) mice were exposed throughout gestation and lactation to the MARBLES PCB mix at 0.1, 1, or 6 mg/kg in the maternal diet. The MARBLES mix simulates the relative proportions of the twelve most abundant PCB congeners found in serum from pregnant women at increased risk for having a child with an NDD. Using Golgi staining, the effect of developmental PCB exposure on dendritic arborization of pyramidal neurons in the CA1 hippocampus and somatosensory cortex of male and female WT mice was compared to pyramidal neurons from transgenic mice. A multilevel linear mixed-effects model identified a main effect of dose driven by increased dendritic arborization of cortical neurons in the 1 mg/kg PCB dose group. Subsequent analyses with genotypes indicated that the MARBLES PCB mixture had no effect on the dendritic arborization of hippocampal neurons in WT mice of either sex, but significantly increased dendritic arborization of cortical neurons of WT males in the 6 mg/kg PCB dose group. Transgene expression increased sensitivity to the impact of developmental PCB exposure on dendritic arborization in a sex-, and brain region-dependent manner. In conclusion, developmental exposure to PCBs present in the gestational environment of at-risk humans interfered with normal dendritic morphogenesis in the developing mouse brain in a sex-, genotype- and brain region-dependent manner. Overall, these observations provide proof-of-principle evidence that PCBs interact with heritable mutations to modulate a neurodevelopmental outcome of relevance to NDDs.


A nanoenzyme linked immunochromatographic sensor for rapid and quantitative detection of SARS-CoV-2 nucleocapsid protein in human blood.
The establishment of a simple, low-cost, high-sensitive and rapid immunoassay for detecting SARS-CoV-2 antigen in human blood is an effective mean of discovering early SARS-CoV-2 infection and controlling the pandemic of COVID-19. Herein, a smartphone based nanozyme linked immunochromatographic sensor (NLICS) for the detection of SARS-CoV-2 nucleocapsid protein (NP) has been developed on demand. The system is integrated by disposable immunochromatography assay (ICA) and optical sensor devices. Immunoreaction and enzyme-catalyzed substrate color reaction were carried out on the chromatographic strip in a device, of which the light signal was read by a photometer through a biosensor channel, and the data was synchronously transmitted via the Bluetooth to the app in-stored smartphone for reporting the result. With a limit of detection (LOD) of 0.026 ng/mL NP, NLICS had the linear detection range (LDR) between 0.05 and 1.6 ng/mL NP, which was more sensitive than conventional ICA. NLICS took 25 min for reporting results. For detection of NP antigen in clinical serum samples from 21 COVID-19 patients and 80 healthy blood donor controls, NLICS and commercial enzyme linked immunosorbent assay (ELISA) had 76.2% or 47.6% positivity, and 100% specificity, respectively (P = 0.057), while a good correlation coefficient (r = 0.99) for quantification of NP between two assays was obtained. In conclusion, the NLICS was a rapid, simple, cheap, sensitive and specific immunochromatographic sensing assay for early diagnosis of SARS-CoV-2 infection.


The peptide hemopressin acts through CB1 cannabinoid receptors to reduce food intake in rats and mice.
Hemopressin is a short, nine amino acid peptide (H-Pro-Val-Asn-Phe-Lys-Leu-Leu-Ser-His-OH) isolated from rat brain that behaves as an inverse agonist at the cannabinoid receptor CB(1), and is shown here to inhibit agonist-induced receptor internalization in a heterologous cell model. Since this peptide occurs naturally in the rodent brain, we determined its effect on appetite, an established central target of cannabinoid signaling. Hemopressin dose-dependently decreases night-time food intake in normal male rats and mice, as well as in obese ob/ob male mice, when administered centrally or systemically, without causing any obvious adverse side effects. The normal, behavioral satiety sequence is maintained in male mice fasted overnight, though refeeding is attenuated. The anorectic effect is absent in CB(1) receptor null mutant male mice, and hemopressin can block CB(1) agonist-induced hyperphagia in male rats, providing strong evidence for antagonism of the CB(1) receptor in vivo. We speculate that hemopressin may act as an endogenous functional antagonist at CB(1) receptors and modulate the activity of appetite pathways in the brain.


Traffic injury deaths in West Azarbaijan province of Iran: a cross-sectional interview-based study on victims' characteristics and pre-hospital care.
This study highlights the socio-demographics and death circumstances of victims of fatal road traffic injuries (RTIs) in one Iranian province. A representative sample of cases was selected from a national register and interviews were conducted with the victims' family members. The study shows that there is a strong association between victim attributes (e.g. sex, age, occupation, education or marital status) and category of road-user. Although men are over-represented in all categories, women die above all as car passengers or pedestrians. Deaths of vulnerable road-users are more frequent among the younger and older age groups. Two-thirds of all deaths occurred before arrival at the hospital and 11% of the victims received ambulance transport. The patterns of fatal RTIs observed in the province differ somewhat from the rest of Iran and other low- and middle-income countries. Not only pre- but also post-crash counter-measures could help save lives in the region.


The Influence of Chloride for the Interpretation of Plasma Bicarbonate During the Treatment of Diabetic Ketoacidosis.
Hyperchloremic metabolic acidosis can occur in diabetic ketoacidosis (DKA) and may affect the acid-base interpretation during treatment. This study aims to describe the prevalence of hyperchloremia during the treatment of DKA and its effect on the interpretation of bicarbonate value. A cross-sectional study, including all cases of DKA in patients aged 1 to 18 years old admitted from 2010 to 2015, was performed. Laboratory tests were performed on admission (baseline), 2 and 6 hours after admission, and when resolution of DKA was achieved. Adjusted bicarbonate value was calculated using regression equations. Seventy-nine DKA episodes were included. The average age was 13.3 ± 3.8 years. Baseline levels were as follows: plasma glucose, 479 ± 133 mg/dL; pH 7.1 ± 0.083; bicarbonate, 9.65 ± 2.9; and anion gap, 23.9 ± 7.5. The time to achieve resolution of DKA was 12.2 ± 4.4 hours, and the decrease in capillary glucose was 25.5 (19.7-38.2) mg/dL per hour. After 6 hours of treatment, the proportion of patients presenting hyperchloremia increased from 23% to 77%. By using adjusted bicarbonate, the percentage of patients achieving resolution of DKA after 6 hours of treatment would have been 35.4% (confidence interval 95%, 28-49), in comparison with 24.1% (confidence interval 95%, 18-37) using observed bicarbonate (P = 0.004). The hyperchloremia developed during the treatment of DKA could modify the value of measured plasma bicarbonate concentration and unnecessarily prolong the initial phase of treatment.


Flow-induced vibration analysis of constricted artery models with surrounding soft tissue.
Arterial stenosis is a vascular pathology which leads to serious cardiovascular diseases. Blood flow through a constriction generates sound and vibration due to fluctuating turbulent pressures. Generated vibro-acoustic waves propagate through surrounding soft tissues and reach the skin surface and may provide valuable insight for noninvasive diagnostic purposes. Motivated by the aforementioned phenomena, vibration of constricted arteries is investigated employing computational models. The flow-induced pressure field in an artery is modeled as broadband harmonic pressure loading based on previous studies in the literature and applied on the inner artery wall. Harmonic analysis is performed for determining radial velocity responses on the outer surface of the models. Results indicate that stenosis severities higher than 70% lead to significant increase in response amplitudes, especially at high frequencies between 250 and 600 Hz. The findings agree well with experimental and theoretical results in the literature considering bending mode frequencies, amplitude scales, and mainly excited frequency ranges. It is seen that artery vibration is sensitive to the phase behavior of pressure loading but its effect becomes less significant with the presence of surrounding tissue. As the surrounding tissue thickness increases, radial velocity response amplitudes decrease but the effect of changes in tissue elastic modulus is more pronounced.


Contribution of 155Gd Mössbauer data to the study of the magnetic interaction in heterodinuclear 3d-Gd (3d = Cu, Ni) coordination complexes.
The valence shell of the gadolinium element corresponds to 4f7 5d1 6s2, so that the trivalent GdIII ion possesses free 5d and 6s orbitals. It has been previously shown by CASSCF methods that the 5d orbitals, along with the 6s Gd orbitals, which are expected to be unoccupied, present a slight spin density and that the magnetic behaviour of CuII-GdIII complexes can only be reproduced if the 5d Gd orbitals are taken into account in the active space. 155Gd Mössbauer isomer shifts of 3d-Gd complexes, L1CuGd(NO3)3, L1NiGd(NO3)3·acetone, L2Cu(acetone)Gd(NO3)3, L2Ni(H2O)2Gd(NO3)3 where L1 and L2 are hexadentate Schiff base ligand, are almost unchanged (0.62-0.64 mm s-1 relative to 155Eu/SmPd3 source) though the values are slightly smaller than a typical ionic compound GdF3 (0.67 mm s-1). The very similar isomer shift values of the 3d-Gd complexes indicate that there is no change in the small electron density of the 6s orbital and that the spin delocalization or spin polarization concerns the 5d Gd orbitals, in agreement with the crystal structure and Mössbauer spectrum of the Gd complex of nitrogen-coordinating tridentate ligand PrnTBP, [Gd(PrnTBP)3](OTf)3. Thus the observed 155Gd Mössbauer isomer shifts of 3d-Gd complexes give an experimental proof for the participation of 5d Gd orbitals to the magnetic interaction in these 3d-Gd complexes.


Genetically depauperate but widespread: the case of an emblematic Mediterranean pine.
Genetic variation is generally considered a prerequisite for adaptation to new environmental conditions. Thus the discovery of genetically depauperate but geographically widespread species is unexpected. We used 12 paternally inherited chloroplast microsatellites to estimate population genetic variation across the full range of an emblematic circum-Mediterranean conifer, stone pine (Pinus pinea L.). The same chloroplast DNA haplotype is fixed in nearly all of the 34 investigated populations. Such a low level of variation is consistent with a previous report of very low levels of diversity at nuclear loci in this species. Stone pine appears to have passed through a severe and prolonged demographic bottleneck, followed by subsequent natural- and human-mediated dispersal across the Mediterranean Basin. No other abundant and widespread plant species has as little genetic diversity as P. pinea at both chloroplast and nuclear markers. However, the species harbors a nonnegligible amount of variation at adaptive traits. Thus a causal relationship between genetic diversity, as measured by marker loci, and the evolutionary precariousness of a species, cannot be taken for granted.


Analysis of monoamine oxidase A (MAOA) promoter polymorphism in Finnish male alcoholics.
Alterations in monoamine oxidase A (MAOA) expression and enzyme activity may be associated with alcoholism and impulsive behavior. Therefore, functional polymorphisms in the MAOA gene would be good candidates to consider in the interindividual differences that exist in the susceptibility to alcoholism. One variant that has been considered as a candidate in alcoholism is a repeat polymorphism in the MAOA gene promoter. We analyzed a cohort of Finnish males with either type 1 or type 2 alcoholism, as well as controls, for differences in the distribution of MAOA promoter alleles. Based on other studies, we postulated that type 2 alcoholism, which is associated with antisocial behavior, but not type 1 alcoholism, would be correlated with the inheritance of the low promoter activity allele. However, we failed to find a difference in allele distribution in type 1 and type 2 alcoholics. In addition, there was no difference in the allele distribution when each group of alcoholics was compared with controls. However, when both groups of alcoholics were pooled and compared with controls, the difference in allele distribution reached a trend towards significance. Our results suggest a minimal association between the MAOA low activity promoter alleles and alcoholism, regardless of the presence or absence of antisocial behavior. Interestingly, approximately 3% of type 2 alcoholics were found to be heterozygous for the MAOA promoter polymorphism. Since MAOA is X-linked, the heterozygotes are probable cases of Klinefelter's syndrome (47,XXY) suggesting that X-chromosome aneuploidy may increase the risk for developing type 2 alcoholism.


Interspecific variation of calls in clownfishes: degree of similarity in closely related species.
Clownfishes are colorful coral reef fishes living in groups in association with sea anemones throughout the Indo-Pacific Ocean. Within their small societies, size hierarchy determines which fish have access to reproduction. These fishes are also prolific callers whose aggressive sounds seem to play an important role in the social hierarchy. Agonistic interactions being involved in daily behaviour suggest how acoustic communication might play an important role in clownfish group. Sounds were recorded and compared in fourteen clownfish species (some of which have never been recorded before) to evaluate the potential role of acoustic communication as an evolutionary driving force. Surprisingly, the relationship between fish size and both dominant frequency and pulse duration is not only species-specific; all the specimens of the 14 species are situated on exactly the same slope, which means the size of any Amphiprion can be predicted by both acoustic features. The number of pulses broadly overlaps among species, whereas the pulse period displays the most variation even if it shows overlap among sympatric species. Sound comparisons between three species (A. akallopisos, A. ocellaris and A. frenatus) having different types of teeth and body shape do not show differences neither in the acoustic waveform nor in the power spectrum. Significant overlap in acoustic features demonstrates that the sound-producing mechanism is highly conservative among species. Differences in the calls of some species are due to size dimorphism and the sound variation might be in this case a by-product. This morphological constraint does not permit a consideration of acoustic communication as the main driving force in the diversification of clownfishes. Moreover, calls are not produced to find mate and consequently are less subject to variations due to partner preference, which restricts the constraints of diversification. Calls are produced to reach and defend the competition to mate access. However, differences in the pulse period between cohabiting species show that, in some case, sounds can help to differentiate the species, to prevent competition between cohabiting species and to promote the diversification of taxa.


Comparative efficacy and safety study of two chondroitin sulfate preparations from different origin (avian and bovine) in symptomatic osteoarthritis of the knee.
Some argued that clinical efficacy of Chondroitin Sulfate (CS) could vary upon the product origin. The objective of this trial is to compare the effect of 2 CS medicinal products from different origin: Structum(®) (avian, 1000mg/day) and Chondrosulf(®) (bovine, 1200mg/day). This was a randomized, double-blind, double placebo, active-controlled, parallel-group study using a non-inferiority design. Symptomatic osteoarthritis of the knee patients, according to American College of Rheumatology criteria, aged 50-80 years received either Structum(®) (500mg BID) or Chondrosulf(®) (400mg TID) during 24 weeks. Inclusion criteria were: global pain in the target knee ≥ 40mm on a Visual Analog Scale (VAS 0-100), a Lequesne's Algofunctional Index (LFI) score ≥ 7 (range: 0-24) and a radiological Kellgren-Lawrence grade 2 or 3. Primary outcome was the mean change over 24 weeks of pain VAS and LFI score. Secondary outcomes were patient's and physician's global assessments, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International responders rate, analgesics intake and Medical Outcomes Survey Short-Form 12 (SF-12). Safety was assessed by recording adverse events. A non-inferiority test was performed on the Structum(®)-Chondrosulf(®) difference for VAS and LFI score changes. Predefined non inferiority limit was settled as the lower limit of the 95% CI above -5mm and -1pt for pain VAS and LFI score respectively. 837 patients were randomized: 817 available for the full analysis dataset (FAS), 692 for the per protocol (PP) analysis. No statistical and clinical differences were observed for demographics and disease characteristics between the 2 groups. PP analysis showed no difference between groups on mean variations of pain VAS or LFI scores over 24 weeks. Mean Pain VAS decreased by 23.9mm (17.5) in Structum(®) group and 23.8mm (17.2) in Chondrosulf(®) group (difference: 0.012 [CI95%: -2.6 ; 2.6]). Mean LFI score decreased by 3.2 (2.4) and 3.1 (2.4) respectively (difference: 0.139 [CI95%: -0.2 ; 0.5]). The lower limits of the 2 CI were above predefined non inferiority margin, which demonstrated the non inferiority of Structum(®) in comparison with Chondrosulf(®). FAS analysis gave similar results. Secondary efficacy outcomes analysis showed the same trends. Responders rate were 76.3% and 73.8% respectively (PP, W24). Treatments were well tolerated: 2.4% in Structum(®) group and 4.5% in Chondrosulf(®) group withdrew from the study for safety reasons. Structum(®) and Chondrosulf(®) were equally effective in reducing functional impairment and relieving pain over 6 months in knee osteoarthritis patients, without any safety concerns. http://www.controlled-trials.com Number: ISRCTN04305346.


Improved isolation of anaerobic bacteria from the gingival crevice area of man.
A roll tube technique (Hungate method) was employed in an attempt to cultivate a maximal portion of the organisms in the gingival crevice area of man. This technique achieves an anaerobic state by flushing the local environment with oxygen-free gas. Once collected, the crevicular debris was immediately placed into sterile oxygen-free test tubes which were flushed out by the oxygen-free gas. In this manner, the samples were weighed, dispersed, diluted, and cultured in roll tubes and plates. The medium for control (Brewer Jar technique) and Hungate techniques was Heart Infusion Agar fortified with 10% defibrinated horse blood. When the Hungate technique was used, the recovery of viable bacteria, as a percentage of the direct microscopic count, was significantly greater than plates incubated aerobically or utilizing the Brewer Anaerobic technique. Cultural counts by using the Hungate method averaged 41.3% for six samples when 90% nitrogen and 10% hydrogen were used, 70.4% for eight samples when 85% nitrogen, 10% hydrogen, and 5% carbon dioxide were used, and 63.4% for eight samples when 100% carbon dioxide was the gaseous atmosphere. At no time were cultural counts, by using anaerobic plates (Brewer Jar), more than 24% of the direct microscopic count. This suggests that exclusion of oxygen and the presence of carbon dioxide maximized recovery of gingival crevice bacteria.


Cortical responses to social stimuli in infants at elevated likelihood of ASD and/or ADHD: A prospective cross-condition fNIRS study.
Autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) are highly prevalent neurodevelopmental conditions that often co-occur and present both common and distinct neurodevelopmental profiles. Studying the developmental pathways leading to the emergence of ASD and/or ADHD symptomatology is crucial in understanding neurodiversity and discovering the mechanisms that underpin it. This study used functional near-infrared spectroscopy (fNIRS) to investigate differences in cortical specialization to social stimuli between 4- to 6-month-old infants at typical and elevated likelihood of ASD and/or ADHD. Results showed that infants at both elevated likelihood of ASD and ADHD had reduced selectivity to vocal sounds in left middle and superior temporal gyrus. Furthermore, infants at elevated likelihood of ASD showed attenuated responses to visual social stimuli in several cortical regions compared to infants at typical likelihood. Individual brain responses to visual social stimuli were associated with later autism traits, but not ADHD traits. These outcomes support our previous observations showing atypical social brain responses in infants at elevated likelihood of ASD and align with later atypical brain responses to social stimuli observed in children and adults with ASD. These findings highlight the importance of characterizing antecedent biomarkers of atypicalities in processing socially relevant information that might contribute to both phenotypic overlap and divergence across ASD and ADHD conditions and their association with the later emergence of behavioural symptoms.


Effect of denture soft liner on mandibular ridge resorption in complete denture wearers after 6 and 12 months of denture insertion: A prospective randomized clinical study.
Soft liners act as a cushion between the denture base and the residual ridge. Hence, it is important to study their effect on resorption of mandibular denture bearing area. Therefore, the purpose of this study was to evaluate the influence of soft denture liner on mandibular ridge resorption after 1 year in completely denture wearers. Twenty-eight completely edentulous patients having age between 45 and 60 years with well-formed ridges in class I jaw relations were selected as per the inclusion and exclusion criterion. Randomization chart was used to enroll participants in experimental and control groups who were given mandibular dentures with and without soft denture liner, respectively. Vertical measurements were made on orthopantomograph and analyzed using Adobe Photoshop 7.0 software at five points, i.e., one at central incisor and two points at right and left first premolars and two in each first molar region. On application of repeated measures analysis of variance, both groups showed a significant change in bone height after denture delivery (P < 0.05). Intergroup comparison (Wilcoxon rank sum test) of bone height in different regions at various time intervals showed statistically significant difference in bone levels (P < 0.05) from baseline to 6 months and baseline to 12months (P < 0.01), while the difference was statistically not significant during 6 and 12 months' period. The use of soft denture liner significantly reduces the residual ridge resorption in complete denture wearers as compared to conventional denture wearers (without denture liner) over a period of 1 year.


Efficacy of methotrexate and misoprostol for early abortion.
Medical termination of pregnancy (medical abortion) as an alternative to surgical abortion has many advantages since it does not require anesthetics and there is no risk of cervical laceration or uterine perforation. In the present study, we evaluated the efficacy of methotrexate and intravaginally administered misoprostol for early abortion. The study population consisted of 32 women seeking abortion of a normal intrauterine pregnancy of 8 weeks or less documented by ultrasound. The dose of methotrexate was 50 mg/m2 intramuscularly and the dose of misoprostol was 800 micrograms intravaginally. The final outcome of treatment was evaluated on day 14 or 16, and an abortion was considered successful if pregnancy was terminated without a surgical procedure. Abortion occurred in only 23 (71.8%) of 32 women. There were 9 failures (28.1%); 3 were ongoing pregnancies (9.3%) and 6 were incomplete abortions (18.7%) requiring suction curettage. After the exclusion of treatment failures, the mean duration of vaginal bleeding was 16.3 +/- 2 days. No serious side effects occurred as a result of methotrexate and misoprostol treatment. The use of methotrexate and intravaginal misoprostol for the termination of pregnancy requires larger studies to determine the safety and efficacy of this medical abortion, a comparison with RU 486 in prospective controlled randomized trials is necessary.


A "One-Stop" Screening Protocol for Haemoglobinopathy Traits and Iron Deficiency in Sri Lanka.
Introduction: The high frequencies of carriers of severe haemoglobinopathies and of iron deficiency in Southeast Asia require reliable and affordable tests to improve on current screening procedures. Objectives: We evaluate a "one stop" approach using the THALCON dichlorophenolindophenol (DCIP) and one-tube osmotic fragility (OF) tests and measurement of Zinc Protoporphyrin (ZPP) to detect and distinguish HbE and β-thalassaemia traits from iron deficiency. We compare findings with current screening practice in Sri Lanka that relies on the identification of low mean red cell volume and/or mean red cell hemoglobin for this purpose. Methods: Between November 2017 and May 2018, we undertook a cross-sectional survey of secondary school students in Gampaha district, Sri Lanka. The THALCON-DCIP and OF tests were compared to capillary electrophoresis (CE), used as a gold standard to detect haemoglobinopathies. ZPP was measured in whole blood. Plasma ferritin and C-reactive protein (CRP) were measured in students with a raised ZPP concentration. Results: We collected venous blood samples from 1,324/1,332 (99.4%) students. The median age of the students was 17 (IQR 16-18) years, all were Sinhalese and 814/1,324 (61.5%) were female. CE identified 3 students with HbE trait and 26 students with β-thalassaemia trait. The THALCON-DCIP test was positive only in the 3 students with HbE (sensitivity 100%, 95% CI 29.2-100.0; specificity 100%, 95% CI 99.7-100.0). The THALCON-OF test identified all 26 students with β-thalassaemia trait (sensitivity = 100%, 95% CI 86.8-100.0) and 287 students with a normal CE result (specificity = 77.9%; 95% CI 75.5-80.1). It was also positive in 2/3 (66.7%) students with HbE trait. Iron deficiency (ZPP > 70 μmol/mol heme) was present in 118/1,240 (9.5%) students with a normal hemoglobin genotype, all of whom had plasma ferritin <15 ng/ml and CRP <5 mg/L. Conclusion: This one-stop approach offers reliable and affordable population screening for both haemoglobinopathy traits and iron deficiency in resource-limited settings where these conditions are common and ensures that iron supplements are targeted only to those who require them. Further work is warranted to refine the OF test to reduce the number of false positive results.


Imaging for Target Delineation in Head and Neck Cancer Radiotherapy.
The definition of tumor involved volumes in patients with head and neck cancer poses great challenges with the increasing use of highly conformal radiotherapy techniques eg, volumetric modulated arc therapy and intensity modulated proton therapy. The risk of underdosing the tumor might increase unless great care is taken in the process. The information gained from imaging is increasing with both PET and MRI becoming readily available for the definition of targets. The information gained from these techniques is indeed multidimensional as one often acquire data on eg, metabolism, diffusion, and hypoxia together with anatomical and structural information. Nevertheless, much work remains to fully exploit the available information on a patient-specific level. Multimodality target definition in radiotherapy is a chain of processes that must be individually scrutinized, optimized and quality assured. Any uncertainties or errors in image acquisition, reconstruction, interpretation, and delineation are systematic errors and hence will potentially have a detrimental effect on the entire radiotherapy treatment and hence; the chance of cure or the risk of unnecessary side effects. Common guidelines and procedures create a common minimum standard and ground for evaluation and development. In Denmark, the treatment of head and neck cancer is organized within the multidisciplinary Danish Head and Neck Cancer Group (DAHANCA). The radiotherapy quality assurance group of DAHANCA organized a workshop in January 2020 with participants from oncology, radiology, and nuclear medicine from all centers in Denmark, treating patients with head and neck cancer. The participants agreed on a national guideline on imaging for target delineation in head and neck cancer radiotherapy, which has been approved by the DAHANCA group. The guidelines are available in the Supplementary. The use of multimodality imaging is being recommended for the planning of all radical treatments with a macroscopic tumor. 2-[18F]FDG-PET/CT should be available, preferable in the treatment position. The recommended MRI sequences are T1, T2 with and without fat suppression, and T1 with contrast enhancement, preferable in the treatment position. The interpretation of clinical information, including thorough physical examination as well as imaging, should be done in a multidisciplinary setting with an oncologist, radiologist, and nuclear medicine specialist.


Noradrenaline treatment of rats stimulates H2O2 generation in liver mitochondria.
Treatment of rats with noradrenaline stimulated H2O2 generation in liver mitochondria using succinate, choline or glycerol 1-phosphate as substrate. The dehydrogenase activity with either succinate or choline as substrate showed no change, whereas that with glycerol 1-phosphate increased. The effect was obtained with noradrenaline, but not with dihydroxyphenylserine. Phenoxybenzamine and yohimbine, but not propranolol, prevented the response to noradrenaline treatment. Phenylephrine could stimulate H2O2 generation, whereas isoprenaline had only a marginal effect. Theophylline treatment slightly decreased the generation of H2O2 in liver mitochondria, but treatment with pargyline, Ro4-1284 and dibutyryl cyclic AMP had little effect. These studies showed that noradrenaline might possibly be acting through the alpha 2-adrenergic system.


To trust or not to trust: social decision-making in post-institutionalized, internationally adopted youth.
Chronic parental maltreatment has been associated with lower levels of interpersonal trust, and depriving environments have been shown to predict short-sighted, risk-averse decision-making. The present study examined whether a circumscribed period of adverse care occurring only early in life was associated with biases in trust behavior. Fifty-three post-institutionalized (PI) youth, adopted internationally on average by 1 year of age, and 33 never-institutionalized, non-adopted youth (Mage = 12.9 years) played a trust game. Participants decided whether or not to share coins with a different anonymous peer in each trial with the potential to receive a larger number of coins in return. Trials were presented in blocks that varied in the degree to which the peers behaved in a trustworthy (reciprocal) or untrustworthy (non-reciprocal) manner. A comparison condition consisted of a computerized lottery with the same choices and probabilistic risk as the peer trials. Non-adopted comparison youth showed a tendency to share more with peers than to invest in the lottery and tended to maintain their level of sharing across trials despite experiencing trials in which peers failed to reciprocate. In contrast, PI children, particularly those who were adopted over 1 year of age, shared less with peers than they invested in the lottery and quickly adapted their sharing behavior to peers' responses. These results suggest that PI youth were more mistrusting, more sensitive to both defection and reciprocation, and potentially more accurate in their trusting decisions than comparison youth. Results support the presence of a sensitive period for the development of trust in others, whereby conditions early in life may set long-term biases in decision-making.


Blood cadmium is associated with increased fracture risk in never-smokers - results from a case-control study using data from the Malmö Diet and Cancer cohort.
Several studies have shown associations between cadmium (Cd) exposure and an increased risk of fractures. However, the size of the risk is still unclear and proper adjustment for smoking is a challenge. The aim of this study was to quantify the association between dietary cadmium measured in blood and fracture risk in the general Swedish population through a large population-based case-control study in never-smokers. The study included 2113 incident cases with osteoporosis-related fractures and the same number of age- and sex-matched controls in never-smokers from the Swedish population-based Malmö Diet and Cancer study cohort. Cd in blood (B-Cd) was analyzed at baseline (1991-1996). Incident osteoporosis-related fractures (of the hip, distal radius, and proximal humerus) up to the year 2014 were identified using the National Patient Register. Associations between B-Cd and fractures were analyzed using logistic regression. Median B-Cd was 0.22 μg/L (P25 = 0.16, P75 = 0.31) among 2103 cases and 0.21 (P25 = 0.15, P75 = 0.30) among 2105 controls. The risk of fracture was significantly increased (OR 1.58; 95 % confidence interval 1.08-2.31, per μg/L of B-Cd), after adjustment for age, sex, BMI, physical activity, and fiber consumption. In analyses by cadmium quartiles, the OR increased monotonically and was significant in the highest quartile of B-Cd (for B-Cd > 0.31 versus B-Cd < 0.15 μg/L; OR 1.21; 95 % confidence interval 1.01-1.45). Even modestly increased blood cadmium in never-smokers is associated with increased risk of incident osteoporosis-related fractures.


Nuclear hormone receptor signaling in amphioxus.
The nuclear hormone receptors (NRs) form a superfamily of transcription factors unified by conserved protein structure and mode of function. While most members of this superfamily are activated by ligands, such as thyroid hormones, steroids, vitamin D or retinoic acid, other NRs are called orphan receptors because they have no known ligand. NR-dependent signaling is crucial for vertebrate development with the majority of receptors being expressed in the developing embryo. Due to massive gene duplications during vertebrate diversification, there are usually more NRs in vertebrates than in invertebrates. In this study, we examine the evolutionary diversification of the NR superfamily and of NR-dependent signaling in chordates (vertebrates, tunicates, and amphioxus). We take advantage of the unique features of the genome of the invertebrate amphioxus, which is characterized by a vertebrate-like gene content without having undergone massive duplications, to assess the NR signaling complement (NRs and NR coregulators) of the ancestral chordate. We find 33 NRs in amphioxus, which are more NRs than originally anticipated. This increase is mainly due to an amphioxus-specific duplication of genes encoding receptors of the NR1H group. In addition, there are three heterologous NRs in amphioxus that could not be placed within the framework of the NR superfamily. Apart from these exceptions, there is usually one amphioxus NR or NR signaling coregulator for each paralogous group of two, three, or four human receptors suggesting that the ancestral chordate had a set of 22 different NRs plus one copy of each NR coregulator.


Laser pressure catapulting (LPC): optimization LPC-system and genotyping of colorectal carcinomas.
Genotype analysis is becoming more and more useful in clinical practice, since specific mutations in tumors often correlate with prognosis and/or therapeutic response. Unfortunately, current molecular analytical techniques often require time-consuming and costly steps of analysis, thus making their routine clinical use difficult. Moreover, one of the most difficult problems arising during tumor research is that of their cell heterogeneity, which depends on their clear molecular heterogeneity. SSCP analysis discriminates by means of aberrant electrophoresis migration bands, mutated alleles which may represent as little as 15-20% of their total number. Nevertheless, in order to identify by sequencing the type of alteration revealed by this technique, only the mutated allele must be isolated. The advent of laser microdissection is a procedure which easily solves these problems of accuracy, costs, and time. The aims of this study were to perfect the system of laser pressure catapulting (LPC) laser microdissection for the assessment of the mutational status of p53 and k-ras genes in a consecutive series of 67 patients with colorectal carcinomas (CRC), in order to compare this technique with that involving hand-dissection and to demonstrate that since the LPC system guarantees more accurate biomolecular analyses, it should become part of clinical routine in this field. The LPC-system was perfected with the use of mineral oil and the LPC-membrane. To compare the techniques of hand- and LPC-microdissection, alcohol-fixed, paraffin-embedded tissue from 67 cases of CRC were both hand- and laser-microdissected. In either case, dissected samples were analyzed by SSCP/sequencing and direct sequencing for k-ras and p53 gene mutations. LPC-microdissection made it possible to pick up mutations by direct sequencing or SSCP/sequencing, whereas hand-microdissection mutations were identified only by means of SSCP followed by sequencing; direct sequencing did not reveal any mutation. In the 67 patients examined by either method, 36% (24/67) showed p53 mutations, 32 of which identified. Seventy-eight percent (25/32) were found in the conserved areas of the gene, while 12% (4/32) were in the L2 loop, 50% (16/32) were in the L3 loop, and 12% (4/32) in the LSH motif of the protein. Moreover, of the 67 cases examined, 40% (27/67) showed mutations in k-ras, with a total of 29 mutations identified. Of these, 14 (48%) were found in codon 12 and 15 (52%) in codon 13. The modifications which we brought to the LPC system led to a vast improvement of the technique, making it an ideal substitution for hand-microdissection and guaranteeing a considerable number of advantages regarding facility, accuracy, time, and cost. Furthermore, the data obtained from the mutational analyses performed confirm that the LPC system is more efficient and rapid than hand-microdissection for acquiring useful information regarding molecular profile and can therefore be used with success in clinical routine.


[Antipsychotic efficacy of neuroleptic neuropeptides in schizophrenia. Review of clinical data].
Recently much interest has been shown in the antipsychotic efficacy of neuroleptic-like neuropeptides in schizophrenia. In this article the clinical effects of the non-opioid fragments of gamma-endorphin, the so-called gamma-type endorphins DT gamma E and DE gamma E are reviewed. In addition, preliminary clinical studies of peptides related to cholecystokinin are considered. It is concluded that gamma-type endorphins possess antipsychotic properties in a subgroup of patients who may belong to Type I schizophrenia. With cholecystokinin-related peptides, in particular ceruletide, antipsychotic effects have been reported, which seem to be more or less comparable to those observed with gamma-type endorphins.


The epidemiology of inflammatory bowel disease.
The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are chronic relapsing disorders of unknown aetiology. The aim of this review is to present the latest epidemiology data on occurrence, disease course, risk for surgery, as well as mortality and cancer risks. Gold standard epidemiology data on the disease course and prognosis of patients with inflammatory bowel disease (IBD) are based on unselected population-based cohort studies. The incidence of ulcerative colitis (UC) and Crohn's disease (CD) has increased overall in Europe from 6.0 per 100,000 person-years in UC and 1.0 per 100,000 person-years in CD in 1962 to 9.8 per 100,000 person-years and 6.3 per 100,000 person-years in 2010, respectively. The highest incidence of IBD is found on the Faroe Islands. Overall, surgery rates have been declining over the last decades, partly due to aggressive medical therapy. Among IBD patients, mortality risk is increased by up to 50% in CD when compared to the background population, but this is not the case for UC. In CD, 25 - 50% deaths are disease-specific deaths, e.g. malnutrition, postoperative complications and intestinal cancer. In UC, disease-specific causes of deaths include colorectal cancer (CRC), and surgical and postoperative complications. The risk of CRC and small bowel cancer is increased two- to eightfold among IBD patients. Various subgroups carry increased risk of malignancy, e.g. those with persistent inflammation, long-standing disease, extensive disease, young age at diagnosis, family history of CRC and co-existing primary sclerosing cholangitis. The risk of extra-intestinal cancers, including lymphoproliferative disorders (LD) and intra- and extrahepatic cholangio carcinoma, is significantly higher among IBD patients. In recent years, self-management and patient empowerment, combined with evolving eHealth solutions, has utilized epidemiological knowledge on disease patterns and has been improving compliance and the timing of adjusting therapies, thus optimizing efficacy by individualizing medication in the community setting.


Analysis of factors that influence survival with post-transplant lymphoproliferative disorder in renal transplant recipients: the Israel Penn International Transplant Tumor Registry experience.
Significant mortality is associated with post-transplant lymphoproliferative disorder (PTLD) in kidney transplant recipients (KTX). Univariate/multivariate risk factor survival analysis of US PTLD KTX reported to Israel Penn International Transplant Tumor Registry from November 1968 to January 2000 was performed. PTLD presented 18 (median) (range 1-310) months in 402 KTX. Death rates were greater for those diagnosed within 6 months (64%) versus beyond 6 months (54%, p = 0.04). No differences in death risk for gender, race, immunosuppression, EBV, B or T cell positivity were identified. Death risk increased for multiple versus single sites (73% vs. 53%, hazards ratio (HR) 1.4). A 1-year increase in age increased HR for death by 2%. Surgery was associated with increased survival (55% vs. 0% without surgery) (p < 0.0001). Patients with allograft involvement, treated with transplant nephrectomy alone (n = 20), had 80% survival versus 53% without allograft removal (n = 15) (p < 0.001). Overall survival was 69% for allograft involvement alone versus 36% for other organ involvement plus allograft (n = 19 alive) (p < 0.0001). Death risk was greater for multiple site PTLD and increasing age, and risks were additive. Univariate analysis identified increased death risk for those not receiving surgery, particularly allograft involvement alone.


Penicillamine in rheumatoid disease: a long-term study.
Eighty-five patients with rheumatoid disease were treated with penicillamine, and 69 completed more than one year's treatment. The main reason for discontinuing penicillamine in the 16 patients who withdrew was adverse reaction. The number of adverse reactions, however, declined when patients were given lower maintenance doses of penicillamine. In those who tolerated the drug the results of treatment were good. To prevent side effects the drug should be introduced gradually and maintenance doses should be the lowest which produce a satisfactory response. Urine should be monitored for protein and blood for changes in platelet and white cell counts at frequent intervals throughout treatment.


Mapping the refractive index of optically transparent samples by means of optical nanoantenna attached to fiber microaxicon.
We demonstrate analytically and numerically that the detection of the spectral response of a single spherical Au nanoantenna allows one to map very small (down to 5·10(-4) RIU) variations of the refractive index of an optically transparent sample. Spectral shift of the dipole local plasmon resonance wavelength of the nanoantenna and the spectral sensitivity of the method developed was estimated by using simple analytical quasi-static model. A pointed scanning probe based on fiber microaxicon with the Au spherical nanoantenna attached to its tip was proposed to realize the RI mapping method. Finite-difference time-domain numerical simulations of the spectral properties of the proposed probe are in good agreement with the theoretical quasi-electrostatic estimations for a radius of the nanoantenna not exceeding the skin depth of Au.


Comparative Pathology of Domestic Pigs and Wild Boar Infected with the Moderately Virulent African Swine Fever Virus Strain "Estonia 2014".
Endemically infected European wild boar are considered a major reservoir of African swine fever virus in Europe. While high lethality was observed in the majority of field cases, strains of moderate virulence occurred in the Baltic States. One of these, "Estonia 2014", led to a higher number of clinically healthy, antibody-positive animals in the hunting bag of North-Eastern Estonia. Experimental characterization showed high virulence in wild boar but moderate virulence in domestic pigs. Putative pathogenic differences between wild boar and domestic pigs are unresolved and comparative pathological studies are limited. We here report on a kinetic experiment in both subspecies. Three animals each were euthanized at 4, 7, and 10 days post infection (dpi). Clinical data confirmed higher virulence in wild boar although macroscopy and viral genome load in blood and tissues were comparable in both subspecies. The percentage of viral antigen positive myeloid cells tested by flow cytometry did not differ significantly in most tissues. Only immunohistochemistry revealed consistently higher viral antigen loads in wild boar tissues in particular 7 dpi, whereas domestic pigs already eliminated the virus. The moderate virulence in domestic pigs could be explained by a more effective viral clearance.


Pulmonary cryptococcosis in patients without HIV infection: factors associated with disseminated disease.
Cryptococcus neoformans is an uncommonly recognized cause of pneumonia in HIV-negative patients. Because of its propensity to disseminate to the meninges and other sites, a lumbar puncture is recommended for patients with pulmonary cryptococcosis, regardless of other risk factors. This study explored clinical and laboratory features to help predict which patients had pulmonary disease alone versus those who had pulmonary plus extrapulmonary disease. A retrospective chart review at 15 medical centers was performed from 1990 to 2000 of all HIV-negative patients who had pulmonary cryptococcosis. Demographic, clinical, radiographic, and laboratory features were evaluated to determine factors that differentiated those patients who had extrapulmonary disease. Among 166 patients who had pulmonary cryptococcosis, 122 had pulmonary infection only and 44 had pulmonary plus extrapulmonary (disseminated) disease. A negative serum cryptococcal antigen titer was more common in patients with pulmonary disease alone (p < 0.01). Multivariate analysis demonstrated that patients who had disseminated disease were more likely than those who only had pulmonary disease to have cirrhosis (p = 0.049), headache (p < 0.001), weight loss (p = 0.003), fever (p = 0.035), altered mental status (p < 0.001), and to be receiving high-dose corticosteroids (p = 0.008). In this large cohort of HIV-negative patients with pulmonary cryptococcosis, there were easily distinguished clinical and laboratory features among patients with pulmonary disease alone versus those with pulmonary plus extrapulmonary disease. These findings may be helpful in the evaluation of HIV-negative patients with pulmonary cryptococcosis with regard to the need for lumbar puncture or to search for disseminated disease.