Healthy urban environments for children and young people: A systematic review of intervention studies.
This systematic review collates, and presents as a narrative synthesis, evidence from interventions which included changes to the urban environment and reported at least one health behaviour or outcome for children and young people. Following a comprehensive search of six databases, 33 primary studies relating to 27 urban environment interventions were included. The majority of interventions related to active travel. Others included park and playground renovations, road traffic safety, and multi-component community-based initiatives. Public health evidence for effectiveness of such interventions is often weak because study designs tend to be opportunistic, non-randomised, use subjective outcome measures, and do not incorporate follow-up of study participants. However, there is some evidence of potential health benefits to children and young people from urban environment interventions relating to road safety and active travel, with evidence of promise for a multi-component obesity prevention initiative. Future research requires more robust study designs incorporating objective outcome measures.


Uncertainty analysis of parameters for modeling the transfer and fate of benzo(a)pyrene in Tianjin wastewater irrigated areas.
A Monte Carlo simulation for uncertainty analysis of three key parameters (local coal consumption rate Q(1L), dry deposition velocity of aerosol particulate Kp and biodegradation rate of benzo(a)pyrene in soil and sediment K(R3)) was conducted in this study. Results of the simulation indicate that the three parameters were influenced by uncertainty and that all equilibrium concentrations in the four bulk compartments and various sub-compartments were log-normally distributed. However, the results also indicated that among the six primary transfer fluxes, erosion associated with solids in soil and deposition associated with solids in water, along with output from sewers were also log-normally distributed, while deposition from air to soil and biodegradation in soil and sediment followed normal distributions. The effect of uncertainty on the model results of the three key parameters was derived using a comparison of upper and lower of confidence interval boundaries at the 95% level of confidence. The results reveal that uncertainty in the key parameters had a more significant influence on equilibrium concentrations of the chemical in the bulk compartments of soil and sediment than on concentrations in the other two bulk compartments, various sub-compartments and the six predominant transfer fluxes.


Effects of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine and related compounds on the uptake of [3H]3,4-dihydroxyphenylethylamine and [3H]5-hydroxytryptamine in neostriatal synaptosomal preparations.
1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) is known to cause a destruction of the dopaminergic nigrostriatal pathway in certain animal species including mice. MPTP and some structurally related analogs were tested in vitro for their capacity to inhibit the uptake of [3H]3,4-dihydroxyphenylethylamine-([3H]DA), [3H]5-hydroxytryptamine ([3H]5-HT), and [3H]gamma-aminobutyric acid [( 3H]GABA) in mouse neostriatal synaptosomal preparations. MPTP was a very potent inhibitor of [3H]5-HT uptake (IC50 value 0.14 microM), a moderate inhibitor of [3H]DA uptake (IC50 value 2.6 microM), and a very weak inhibitor of [3H]GABA uptake (no significant inhibition observed at 10 microM MPTP). In other experiments, MPTP caused some release of previously accumulated [3H]DA and [3H]5-HT, but in each case MPTP was considerably better as an uptake inhibitor than as a releasing agent. The 4-electron oxidation product of MPTP, i.e., 1-methyl-4-phenyl-pyridinium iodide (MPP+), was a very potent inhibitor of [3H]DA uptake (IC50 value 0.45 microM) and of [3H]5-HT uptake (IC50 value 0.78 microM) but MPP+ was a very weak inhibitor of [3H]GABA uptake. These data may have relevance to the neurotoxic actions of MPTP.


Does the association between smoking status and selected healthy foods depend on gender? A population-based study of 54 417 middle-aged Danes.
Smoking serves different functions for men and women. Thus, we wanted to investigate the association between smoking behaviour and intakes of selected healthy foods in men and women with special focus on differences and similarities between the two genders. In 1993-1997, a random sample of 80 996 men and 79 729 women aged 50-64 y was invited to participate in the study 'Diet, Cancer and Health'. In all, 27 179 men and 29 876 women attended a health examination and completed a 192-item food-frequency questionnaire (FFQ). The association between smoking status and low, median and high intakes of selected foods was examined among 25 821 men and 28 596 women. The greater Copenhagen and Aarhus area, Denmark. For both men and women, smoking status group was associated with diet, such that increasing level of smoking status ranging from never smokers over ex-smokers to currently heavy smokers was associated with a lower intake of the healthy foods: fresh fruit, cooked vegetables, raw vegetables/salad, and olive oil. For wine, increasing level of smoking status category was associated with a higher fraction of abstainers and heavy drinkers. The difference between the extreme smoking status categories was larger than the difference between men and women within smoking status categories such that never smoking men in general had a higher intake of healthy foods than heavy smoking women. Correction for age, educational level, and body mass index (BMI) did not affect the results. In this middle-aged population, intake of healthy foods were associated with smoking behaviour with a dose-response type of relationship. The overall pattern was similar for men and women.


Neuropeptide Y is a physiological substrate of fibroblast activation protein: Enzyme kinetics in blood plasma and expression of Y2R and Y5R in human liver cirrhosis and hepatocellular carcinoma.
Fibroblast activation protein (FAP) is a dipeptidyl peptidase (DPP) and endopeptidase that is weakly expressed in normal adult human tissues but is greatly up-regulated in activated mesenchymal cells of tumors and chronically injured tissue. The identities and locations of target substrates of FAP are poorly defined, in contrast to the related protease DPP4. This study is the first to characterize the physiological substrate repertoire of the DPP activity of endogenous FAP present in plasma. Four substrates, neuropeptide Y (NPY), peptide YY, B-type natriuretic peptide and substance P, were analyzed by mass spectrometry following proteolysis in human or mouse plasma, and by in vivo localization in human liver tissues with cirrhosis and hepatocellular carcinoma (HCC). NPY was the most efficiently cleaved substrate of both human and mouse FAP, whereas all four peptides were efficiently cleaved by endogenous DPP4, indicating that the in vivo degradomes of FAP and DPP4 differ. All detectable DPP-specific proteolysis and C-terminal processing of these neuropeptides was attributable to FAP and DPP4, and plasma kallikrein, respectively, highlighting their combined physiological significance in the regulation of these neuropeptides. In cirrhotic liver and HCC, NPY and its receptor Y2R, but not Y5R, were increased in hepatocytes near the parenchymal-stromal interface where there is an opportunity to interact with FAP expressed on nearby activated mesenchymal cells in the stroma. These novel findings provide insights into the substrate specificity of FAP, which differs greatly from DPP4, and reveal a potential function for FAP in neuropeptide regulation within liver and cancer biology.


From Ruthenium to Copper: A la carte Tools for the Synthesis of Molecules of Interest.
Well-defined ruthenium complexes and simple copper-ligand systems proved to be powerful catalysts for the construction of complex molecules from simple and abundant organic sources. In this account, chosen examples of reactions involving C-C bond formation catalyzed by [Ru(η(5)-C(5)H(5))-(CH(3)CN)(3)][PF(6)] will be presented. A practical synthesis of the versatile catalyst [Ru(η(5)-C(5)H(5))-(CH(3)CN)(3)][PF(6)] is also described via a simple and easy-handled procedure discovered in Geneva ten years ago. The second part of this review is focused on methodologies catalyzed by an association of a copper salt and a simple ligand for the formation of C-N, C-O and C-C bonds developed in our group in Montpellier. A brief overview of applications in life sciences and materials will conclude this article.


Fish oil supplementation of lactating mothers affects cytokine production in 2 1/2-year-old children.
n-3 PUFA influence immune functioning and may affect the cytokine phenotype during development. To examine whether maternal fish oil supplementation during lactation could modify later immune responses in children, 122 lactating Danish mothers with a fish intake below the population median were randomized to groups supplemented for the first 4 mon of lactation with 4.5 g/d of fish oil (equivalent to 1.5 g/d of n-3 long-chain PUFA) or olive oil. Fifty-three mothers with a fish intake in the highest quartile of the population were also included. The FA composition of erythrocyte membranes was measured at 4 mon and at 2 1/2 yr. Plasma immunoglobulin E (IgE) levels and cytokine production in lipopolysaccharide-stimulated whole-blood cultures were determined at 2 1/2 yr. Erythrocyte n-3 PUFA at 4 mon were higher in infants from the fish oil group compared with the olive oil group (P < 0.001) but were no longer different at 2 1/2 yr. The median production of lipopolysaccharide-induced interferon gamma (IFN-gamma) in the fish oil group was fourfold higher than that in the olive oil group (P = 0.034), whereas interleukin-10 (IL-10) production was similar. The IFN-gamma/IL-10 ratio was twofold higher in the fish oil group (P = 0.019) and was positively correlated with 20:5n-3/20:4n-6 in erythrocytes at 4 mon (P = 0.050). The percentages of atopic children and plasma IgE were not different in the two groups, but the study was not designed to look at atopy. Cytokine responses and erythrocyte FA composition in children of mothers with a high fish intake were intermediate in comparison with those in the randomized groups. Fish oil supplementation during lactation resulted in increased in vitro IFN-gamma production in the children 2 yr after the supplementation was given, which may reflect a faster maturation of the immune system.


Facilitation properties in electrically evoked compound action potentials depending on spatial location and on threshold.
Spiral ganglion neurons (SGNs) facilitation properties can be recorded utilizing electrically evoked compound action potential (ECAP). While intracochlear variation of the ECAP threshold in relation to its electrode channel is reported, no study investigated its impact on facilitation. In this study, we quantified intracochlear variation of the facilitation properties in cochlear implants (CI) using ECAPs. We hypothesized that the facilitation effect is dependent on the electrode channel and its ECAP threshold. Therefore, ECAPs were recorded in 23 CI subjects. For each subject, five default (channel-derived) and up to two additional (threshold-derived) stimulation sites were defined. Facilitation was quantified by the paradigm introduced by (Hey et al., 2017) with optimized parameter settings. For each channel the maximum facilitated amplitude was determined by a series of ECAP measurements. A linear mixed-effects model was used to investigate the impact of the electrode channel and ECAP threshold on the maximum facilitated amplitude. The maximum facilitated amplitude was found to be dependent on the ECAP threshold and independent on the electrode channel. We conclude that the facilitation paradigm is a useful and feasible tool to gain local information on the SGNs temporal processing patterns.


[A contact-free exposure meter for x-ray diagnostic equipment].
The paper describes a digital apparatus capable of measuring the duration of X-radiation within the range of 0.001-10.0 s with an error of 2%. The apparatus is used for exposure control in X-ray units having four- and six-pulse circuits.


Results of surgical treatment of pulmonary metastases.
Surgical removal of one or several metastases with a potentially curative aim is possible in the case of isolated pulmonary metastases. Surgery is part of a combined oncological concept. Between 1972 and 1986, surgical resection was indicated in 368 patients and 419 thoracotomies were carried out. Of the patients, 38% had more uni- or bilateral metastases than expected even after the most careful preoperative diagnostic examinations. The 5-year survival probability of all patients operated on was 33%. Corresponding to a differentiation between potentially curative and non-curative resections, the operation was classified as potentially curative in 73%. In this group, the 5-year survival was 39%. Differentiation into tumour groups (carcinomas of caval type, carcinomas of portal type and sarcomas) revealed no statistically significant differences in prognosis. Due to the excellent chemotherapeutical regimens, testicular teratomas achieved the best results in the early postoperative years. Long-term survival is decisively influenced by the removal of all visible and palpable metastases. If complete removal of all tumour tissue is possible, the number of metastases does not influence survival significantly. Besides radicality, the duration of the disease-free interval showed prognostic differences which were statistically significant (P less than 0.001). Considering the metastatic route and the type of primary tumour, there were slight prognostic differences which were not statistically significant. Recently, the median sternotomy has become the preferred method of access. Predominating resection procedures are wedge and segmental resections which yield the best survival rates.


[Revision TKA due to instability: diagnostics, treatment options and outcomes].
Instability after primary TKA is a frequent reason for revision surgery. Other mechanisms of failure must be ruled out before an in-depth analysis of instability. Diagnostic tools for instability consist of medical history, clinical examination, and imaging. The clinical examination must focus primarily on the extent of the instability, the location of the instability and the levels of instability. Varus and valgus stress radiographs in the mediolateral plane in extension and flexion, as well as anteroposterior stress images (drawer) are mandatory. In addition, the underlying cause (or a combination of causes) must be defined. Possible causes include malalignment, component malposition (rotation), bony and ligamentous insufficiencies and implant-associated instabilities. Once the mechanism of failure is understood in detail, various therapeutic options are available. Conservative therapy is only considered in patients where there is borderline instability, and the patient has adequate compensatory options in daily life. Some authors postulate the need for 3 months of conservative therapy in every case before possible surgery. Isolated inlay exchange is usually only a compromise and shows failure rates of up to 60%. Partial component exchange requires some preconditions and is technically demanding. If the indication is correct, the results are consistently comparable with those after full component revision. In the case of full component revision, attention must be paid to the degree of constraint to achieve stability but also to avoiding over-treatment (too highly constrained TKA with an probability of loosening). In general, the results after revision surgery are worse in cases of instability than in cases of exchange surgery due to aseptic loosening or patellar abnormalities but better than in cases of infection or arthrofibrosis.


Lack of consistent hormonal responses to capture during the breeding season of the bearded dragon, Pogona barbata.
The bearded dragon (Pogona barbata: Agamidae) is a diurnal, oviparous, multi-clutching lizard from Australia. We examined plasma hormonal responses to capture in males and females during the spring breeding season. Corticosterone concentrations at capture (0 h; < or =3 min after capture) were low (males: 1.81+/-0.63 ng/ml; females 2. 23+/-0.47 ng/ml) and within sexes were unrelated to the time of the day, snout-vent length or, in females, reproductive condition (vitellogenic, gravid, assumed spent). Corticosterone concentrations at capture were significantly and inversely correlated with body condition in males, but not in females. Unexpectedly, neither sex showed significant changes in mean concentrations of corticosterone at 3.5 or 24 h after capture compared with 0 h values. Corticosterone concentrations at 3.5 h after capture did not differ between dragons bled at capture or not. Concentrations of progesterone in both the sexes did not change between 0 h and 3.5 or 24 h after capture. Testosterone concentrations in males at capture were moderate (10.1+/-2.2 ng/ml), and unchanged at 3.5 h after capture. The adrenocortical axis of adult bearded dragons in the breeding season seems remarkably unresponsive to capture compared with many other reptiles. Low adrenocortical responses to capture may be a feature of reptiles known to adjust well to captivity.


Whole body hyperthermia selectively induces heat shock protein 72 in neurons of the rat spinal cord.
The aims of this study were to examine whether the heat shock response is operative in the spinal cord, and to identify the type of responsible cell. Immunoblot analysis using an antibody specific for a highly stress-inducible heat shock protein with a molecular mass of 72 kDa (HSP72) showed that exposing rats to whole body hyperthermia remarkably induced HSP72 protein in the spinal cord within 2 h. Northern blot analysis with a cDNA probe for human HSP72 demonstrated that whole body hyperthermia induced the expression of HSP72 mRNA within 30 min in the spinal cord. Immunohistochemical analysis showed that neurons in the gray matter appear to be a preferential target of the heat shock response, suggesting that the heat shock response might have a therapeutic implication for protection against spinal cord injury.


12-Month Cost Outcomes of Community Engagement Versus Technical Assistance for Depression Quality Improvement: A Partnered, Cluster Randomized, Comparative-Effectiveness Trial.
To compare community engagement and planning (CEP) for coalition support to implement depression quality improvement (QI) to resources for services (RS) effects on service-use costs over a 12-month period. Matched health and community programs (N=93) were cluster-randomized within communities to CEP or RS. Two Los Angeles communities. Adults (N=1,013) with depressive symptoms (Patient Health Questionnaire (PHQ-8) ≥10); 85% African American and Latino. CEP and RS to support programs in depression QI. Intervention training and service-use costs over 12 months. CEP planning and training costs were almost 3 times higher than RS, largely due to greater CEP provider training participation vs RS, with no significant differences in 12-month service-use costs. Compared with RS, CEP had higher planning and training costs with similar service-use costs.


Lognormal distribution of HBsAg strengths in an English population.
The frequency distribution of reverse passive haemagglutination titres for HBsAg in the sera of 78 positive blood donors found furing 2.5-year period closely follows a lognormal distribution curve. This lognormal distribution suggests that the total population of HBsAg-positive donors during this period was approximately 84. The modified Hepatest now in use will be expected to detect 82 of these, and to miss only 1 HBsAg-positive donor in 50,000 screening tests of Manchester blood donors.


A new fluorescent probe based on metallic deep eutectic solvent for visual detection of nitrite and pH in food and water environment.
Nitrite is a widely used food additive that has been shown to be carcinogenic and can cause health damage when consumed in excess. Therefore, developing a detection method is in demand. Here, we prepared a novel Fe-doped carbon dots (Fe-CDs) using metallic deep eutectic solvent (MDES) which showed high sensitivity and selectivity. Besides, it also showed excellent pH-dependent luminescence characteristics, which proved the feasibility as a pH sensor. Under the optimal conditions, the detection linear of nitrite ranged from 0.2 to 80 µM, and the detection limit was 50 nM. The recovery rate was between 98.8 % and 104.1 % in food and water samples. For pH monitoring, its fluorescence intensity was linearly correlated in the pH range from 2 to 7, accompanying a unique differential solution color change of colorless-yellow-green. Therefore, it can be used as an excellent fluorescent probe for detection of nitrite and pH in food and water environment.


Ice recrystallization in a model system and in frozen muscle tissue.
Recrystallization produces modifications on ice crystal sizes during storage and transport of frozen foods, reducing the advantages obtained by quick freezing and inducing physicochemical changes which alter their quality and shorten their shelf life. This process involves the growth of the larger crystals at the expense of the smaller ones, being the interfacial energy, the driving force of the phenomenon. In the present work recrystallization was analyzed using direct microscopic observation of ice crystals in a model solution (0.28 N NaCl) and indirect observation of frozen muscle tissue. The model solution allowed visualization of the interface behavior; from the analysis of the ice crystal frequency distributions, relationships between shape and size of the grains were established. A kinetic model based on the average system curvature was proposed obtaining a satisfactory fitness of the experimental data. Values of the kinetic constants determined at different temperatures allowed the estimation of the process activation energy. In muscle tissues isothermal freeze-substitution was used to observe the holes left by the ice in frozen semitendinous beef muscle stored at -5, -10, -15, and -20 degrees C during long periods of time. A different evolution of the mean ice crystal diameter was observed with respect to the model system. In meat samples, at long storage times, a limit diameter value was reached; this situation has been proved to be independent of temperature and initial size (freezing rate); a theoretical expression based on tissue characteristic parameters was proposed for its evaluation. Activation energy for recrystallization in muscle tissue was also determined, being comparable to values for protein denaturation and quality losses.


Development of snake antivenom antibodies in chickens and their purification from yolk.
Adult white leghorn hens hyperimmunised with Brazilian snake venoms of the genus Bothrops and/or Crotalus produced antibodies capable of recognising, combining with and neutralising the toxic and lethal components of the venoms. The antibodies were first detected by an enzyme-linked immunosorbent assay two weeks after starting the immunisation schedule, reached the highest titres by the third week and remained high for at least 24 weeks. These antibodies are transferred to the egg yolk from which they were isolated as enriched IgY preparations by a combination of methods using positive and negative precipitation with sodium sulphate and/or caprylic acid. The yolk-derived IgY preparations contained antibodies which blocked the phospholipase A2-dependent haemolytic activity of both venoms and the haemorrhagic activity of Bothrops venom, and neutralised the toxic lethal activities of the venoms with good efficacy. The median effective dose (ED50) of the IgY anti-Bothrops venom was 592.5 microliters/2LD50 and, 1.0 ml neutralised 0.0675 mg of venom. The ED50 of the IgY anti-Crotalus venom was 457.5 microliters/3LD50 and 1.0 ml neutralised 0.075 mg of venom.


Facile, large scale synthesis of water soluble AgInSe2/ZnSe quantum dots and its cell viability assessment on different cell lines.
I-III-VI chalcopyrite ternary quantum dots have emerged as a good alternative over the conventional II-VI and IV-VI chalcogenide binary QDs that usually consist of heavy metals such as Cd and Pb which has limited their bioapplications. Among the chalcopyrite QDs, AgInSe2 QDs has been the least developed due to the imbalanced cation reactivity, unwanted impurities, broad size distribution and resultant large particle sizes. In addition, the cell viability of these QDs still needs to be investigated on different cell lines both normal and cancerous ones. Herein, large-scale synthesis of water-soluble thioglycolic acid (TGA) capped and gelatin-stabilized AgInSe2 (AISe) core and AgInSe2/ZnSe (AISe/ZnSe) core/shell QDs in the absence of an inert atmosphere and their cell viability against different cell lines are reported. The optical and structural characteristics of the as-synthesized QDs were investigated by UV-visible (vis) absorption, photoluminescence (PL) and Fourier-transmission infrared (FTIR) spectroscopies, dynamic light scattering (DLS), X-ray diffraction (XRD), and high-resolution transmission electron microscope (HRTEM) techniques. Growth of ZnSe shell on the core AISe resulted in the blue shifting of the emission maximum position with the increased PL intensity. The QDs are small and spherical in shape with an average particle diameter of 2.8 nm and 3.2 nm for AISe and AISe/ZnSe QDs respectively. The in vitro cell viability assay revealed that the as-synthesized AISe/ZnSe QDs are not toxic towards cancerous (HeLa -cervical cancer and A549-lung cancer) and normal (BHK21 -Kidney) cell lines.


Chaotic dynamics of the fractional Lorenz system.
In this Letter we introduce a generalization of the Lorenz dynamical system using fractional derivatives. Thus, the system can have an effective noninteger dimension Sigma defined as a sum of the orders of all involved derivatives. We found that the system with Sigma<3 can exhibit chaotic behavior. A striking finding is that there is a critical value of the effective dimension Sigma(cr), under which the system undergoes a transition from chaotic dynamics to regular one.


Use of Malyugin pupil expansion device for intraoperative floppy-iris syndrome: results in 30 consecutive cases.
To evaluate a new disposable, small-pupil expansion device in tamsulosin patients with intraoperative floppy-iris syndrome (IFIS) having cataract surgery. Private practice, Los Altos, California, USA. The 5-0 polypropylene Malyugin pupil expansion device (MicroSurgical Technology) was used in 30 eyes from 21 tamsulosin patients having routine cataract surgery. The pupil diameter was measured at the beginning and end of surgery, and the severity of IFIS was graded. Intraoperative and postoperative complications were recorded. The device maintained a constant 6.0 mm pupil diameter throughout surgery. Although iris prolapse was still possible, there were no significant intraoperative or postoperative complications despite the fact that 93% of the eyes had moderate to severe IFIS. All eyes achieved a best corrected visual acuity of at least 20/25. There was a tendency for ring deformation if flash sterilization was used without sufficient cooling time. The disposable Malyugin pupil expansion device was highly effective at maintaining an adequate pupil opening in eyes with IFIS. It is easier and faster to use than iris retractors and other pupil expansion rings and represents an excellent small-pupil strategy.


First kinetic evidence for the CH/π and π/π solute-solvent interaction of C60 in the Diels-Alder reaction with cyclohexadiene.
The first CH/π solute-solvent interaction of C(60) was evidenced by the kinetic solvent effects in the Diels-Alder reaction with 1,3-cyclohexadiene based on the evaluation of linear free energy relationship of log k(2) with empirical solvent polarity and basicity parameters, E(T)(30) and D(π), respectively.


Chronic whiplash associated disorders and neck movement measurements: an instantaneous helical axis approach.
This paper presents an assessment tool for objective neck movement analysis of subjects suffering from chronic whiplash-associated disorders (WAD). Three-dimensional (3-D) motion data is collected by a commercially available motion analysis system. Head rotation, defined in this paper as the rotation angle around the instantaneous helical axis (IHA), is used for extracting a number of variables (e.g., angular velocity and range, symmetry of motion). Statistically significant differences were found between controls and subjects with chronic WAD in a number of variables.


Frog's tongue receptive areas: neural organization and gustatory function.
Lateral and medial branch of the frog's IXth nerve innervates rostral third and caudal two-thirds of the tongue surface, respectively. The amounts of gustatory signals in these branches differ in proportion to the area they supply.


Huntington's disease: animal models and transplantation repair.
Recent identification of the gene for Huntington's disease is currently attracting widespread attention. While having importance for predictive testing and the potential of elucidating the underlying disease process, this discovery does not yet provide any advances for therapeutic intervention. Here we review recent advances in the development of improved animal models of Huntington's disease and strategies for its repair. Novel toxins may better mimic the neuropathology, and provide important clues about the underlying metabolic disorder, of the human disease. In addition, recent experiments into the cellular morphology, development and function of striatal cell transplants in both rats and monkeys are now indicating the prospect of viable strategies for structural repair in this disorder.


Extra storage capacity in transition metal oxide lithium-ion batteries revealed by in situ magnetometry.
In lithium-ion batteries (LIBs), many promising electrodes that are based on transition metal oxides exhibit anomalously high storage capacities beyond their theoretical values. Although this phenomenon has been widely reported, the underlying physicochemical mechanism in such materials remains elusive and is still a matter of debate. In this work, we use in situ magnetometry to demonstrate the existence of strong surface capacitance on metal nanoparticles, and to show that a large number of spin-polarized electrons can be stored in the already-reduced metallic nanoparticles (that are formed during discharge at low potentials in transition metal oxide LIBs), which is consistent with a space charge mechanism. Through quantification of the surface capacitance by the variation in magnetism, we further show that this charge capacity of the surface is the dominant source of the extra capacity in the Fe3O4/Li model system, and that it also exists in CoO, NiO, FeF2 and Fe2N systems. The space charge mechanism revealed by in situ magnetometry can therefore be generalized to a broad range of transition metal compounds for which a large electron density of states is accessible, and provides pivotal guidance for creating advanced energy storage systems.


Psychometric properties of the German version of the Youth Psychopathic traits Inventory - short version.
The aim of the current study is to examine the psychometric properties of the German Version of the Youth Psychopathic traits Inventory-Short Version (YPI-S). A sample of 856 adolescents (age: 15-19) from the German-speaking part of Switzerland was included. All participants completed the 50-item YPI, of which we derived the 18 items of the YPI-S. Furthermore, participants completed the Massachusetts Youth Screening Instrument-Version-2 (MAYSI-2), as well a self-report delinquency questionnaire. We were able to replicate a three-factor structure and found moderate to good internal consistency for the total score as well as for the three dimensions of the YPI-S. Measurement invariance across gender was established. Furthermore, we found positive small to medium correlations with both internalizing and externalizing mental health problems, substance abuse problems, and offending behavior. Our results suggest that the German version of the YPI-S is a reliable and valid screening instrument for psychopathic traits in both boys and girls from the general population in the German-speaking part of Switzerland.


The Effect of Text Message-based Support Program (TextRehab) on Treatment Outcomes of Patients with Hand Flexor Tendon Injuries after Repair: A Randomized Controlled Trial Study Protocol.
Post-operative rehabilitation for patients with flexor tendon injuries is necessary for a full recovery. This randomized controlled trial study investigates the effectiveness of a text message-based rehabilitation program (i.e., TextRehab) on the improvement rate of hand rehabilitation in patients with flexor tendon injuries after repair. This study is designed as a randomized, three-month, single-center, two-arm, parallel controlled trial. A total of 40 patients will be randomly classified as either the control or intervention group. Both groups receive usual care; however, the intervention group is also asked to perform the designed rehabilitation activities through the TextRehab program. The activity instructions are sent to patients step by step at least once a day. Self-reported outcomes will be assessed at 6 and 12 weeks after discharge and include self-reported Patient Rated Wrist Evaluation, self-reported Quick-Disability of Arm, Shoulder, and Hand, and Visual Analogue Scale. Moreover, the reports of the physician regarding the grip strength and Total Active Motion will be assessed at week 12. The development of the message scheduling system and its contents is completed. This trial has the code of ethics in research (removed due to blinding issues). Study results are expected to be available in mid-2021. The TextRehab program is developed to provide advice, motivation, information, and care for patients with hand flexor tendon injuries after repair. This trial provides evidence of the effectiveness of sending text messages on persuading patients to perform home-based rehabilitation activities.


Impact of the Covid-19 pandemic context on the microbiological epidemiology and management of flexor sheath phlegmons.
The COVID-19 pandemic in France has recently modified the patients' lifestyles, as well as methods of medical and surgical management. This could explain subsequent changes to the microbiological spectrum, the severity, as well as the scalability of phlegmons of the flexor tendon sheath. The objective of this study was to construct an epidemiological and bacteriological inventory of these hand infections, and to compare the clinical and microbiological data, before and after the COVID-19 pandemic. The hypothesis of this work was that the phlegmons of the flexor tendon sheath presented specific microbiological characteristics in the tropical environment of our University Hospital Center, and that these characteristics could have changed with the recent introduction of hydro-alcoholic solution (HAS) associated to the COVID-19 pandemic. The preoperative epidemiological data of our patients were collected between January 2016 and December 2020. The stage of severity, according to the classification of Michon, the use of hydro-alcoholic solution, as well as the early clinical evolution were collected. The cohort was then divided into two groups in order to compare the microbiological profiles, the management and the clinical evolution of patients in the pre-COVID period with those in the post-COVID period. A total of 199 patients were included, 154 patients in the pre-COVID period and 26 in the post-COVID period. We found a majority of MSSA (58.3%, N=105) and negative samples comprised 18.9% (N=34). No statistically significant difference was found between the two groups regarding the bacteriological results. The clinical course was judged to be favorable in 93.5% of cases in the pre-COVID group compared to 80.8% in the post-COVID group (p=0.046). The use of HAS (p<0.0001), as well as the initial stage of severity according to Michon, were significantly higher in group 2 (p=0.04). The COVID-19 pandemic has not shown any change in the microbiological spectrum, despite the now daily use of HAS in everyday life. The postoperative clinical evolution was significantly less favorable after the onset of COVID and could be explained by an increase in cases with a more advanced initial stage of severity. IV, Observational epidemiological study.


[Systemic inflammatory rheumatic diseases competence network].
The foundation of the competence network for rheumatology, which is funded by the "Bundesministerium für Bildung und Forschung" (BMBF) since 1999, succeeded to create a unique research structure in Germany: medical doctors and scientists from six university rheumatology centres (Berlin, Düsseldorf, Erlangen, Freiburg, Hannover und Lübeck/Bad Bramstedt) work closely together with scientists doing basic research at the Deutsches Rheuma-Forschungszentrum (DRFZ), with rheumatological hospitals, reha-clinics, and rheumatologists. Jointly they are searching for causes of systemic inflammatory rheumatic diseases and try to improve therapies-nationwide and with an interdisciplinary approach. The primary objective of this collaboration is to transfer new scientific insights more rapidly in order to improve methods for diagnosis and patients treatment.


Functional consequences of acute tryptophan depletion on raphe nuclei connectivity and network organization in healthy women.
Previous research on central nervous serotonin (5-HT) function provided evidence for a substantial involvement of 5-HT in the regulation of brain circuitries associated with cognitive and affective processing. The underlying neural networks comprise core subcortical/cortical regions such as amygdala and medial prefrontal cortex, which are assumed to be modulated amongst others by 5-HT. Beside the use of antidepressants, acute tryptophan depletion (ATD) is a widely accepted technique to manipulate of 5-HT synthesis and its respective metabolites in humans by means of a dietary and non-pharmacological tool. We used a double-blind, randomized, cross-over design with two experimental challenge conditions, i.e. ATD and tryptophan (TRP) supplementation (TRYP+) serving as a control. The aim was to perturb 5-HT synthesis and to detect its impact on brain functional connectivity (FC) of the upper serotonergic raphe nuclei, the amygdala and the ventromedial prefrontal cortex as well as on network organization using resting state fMRI. 30 healthy adult female participants (age: M = 24.5 ± 4.4 yrs) were included in the final analysis. ATD resulted in a 90% decrease of TRP in the serum relative to baseline. Compared to TRYP + for the ATD condition a significantly lower FC of the raphe nucleus to the frontopolar cortex was detected, as well as greater functional coupling between the right amygdala and the ventromedial prefrontal cortex. FC of the raphe nucleus correlated significantly with the magnitude of TRP changes for both challenge conditions (ATD & TRYP+). Network-based statistical analysis using time series from 260 independent anatomical ROIs revealed significantly greater FC after ATD compared to TRYP+ in several brain regions being part of the default-mode (DMN) and the executive-control networks (ECN), but also of salience or visual networks. Finally, we observed an impact of ATD on the rich-club organization in terms of decreased rich-club coefficients compared to TRYP+. In summary we could confirm previous findings that the putative decrease in brain 5-HT synthesis via ATD significantly alters FC of the raphe nuclei as well as of specific subcortical/cortical regions involved in affective, but also in cognitive processes. Moreover, an ATD-effect on the so-called rich-club organization of some nodes with the high degree was demonstrated. This may indicate effects of brain 5-HT on the integration of information flow from several brain networks.


Association Between Voice Handicap Index and Praat Voice Analysis in Patients with Benign Vocal Cord Lesion Before and After Microscopic Laryngeal Surgery.
Benign vocal cord lesion is a benign mass formed in vocal cord in form of vocul nodule, vocal cord polyp, vocal cord cyst and vocal cord granuloma. Voice handicap index (VHI) is one of subjective voice analyses. This study aimed to analyse correlation between VHI score and praat voice analysis in benign vocal cord lesion before and after microscopic laryngeal surgery. This study was carried out from November 2009 to December 2010 at Outpatient Unit of Otorhinolaryngology, Head and Neck Surgery and Integrated Oncology Center of Dr. Soetomo General Hospital, Surabaya, Indonesia. Pearson's correlation test found a negative correlation between total VHI score with base frequency and harmonic-to-noise ratio (HNR) (r = - 0.186, p = 0.689; r = - 0.650, p = 0.114). On the other hand, there was a positive correlation between total VHI score with jitter and shimmer (r = 0.812, p = 0.027; r = 0.638, p = 0.123). It could be inferred that base frequency, shimmer and HNR after surgery had no significant correlation (p > 0.05), while VHI total score significantly correlated with jitter after surgery (p < 0.05). We found no correlation between VHI score and Praat voice analysis in patients with benign vocal cord lesion before and after surgery, except correlation between VHI functional subscale with HNR and VHI total score with jitter.


The use of CO2 laser in the treatment of oral white patches: outcomes and factors affecting recurrence.
Laser therapy has been a favoured treatment regime for oral leukoplakia since the mid 1980s. There is no information in the literature regarding factors affecting outcomes in patients with oral leukoplakia. Forty-three patients (mean age 60.3+/-13.6 years) with 73 primary oral leukoplakia were assessed for outcome and factors affecting survival. Dysplastic lesions were found in the majority of patients. The male to female ratio was 1.7:1 with 74% ex- or current smokers, 27% consuming alcohol and 31% continuing to smoke after treatment. The mean observation time was 47.2+/-28.2 months (range 2-102 months). Disease-free survival was 55.4% at 3 years that dropped to 33.9% after 5 years. The malignant transformation rate was 7.3%. No significant prognostic factors were found on univariate analysis but alcohol consumption (P=0.034) and previous malignancy (P=0.018) were found to be significant prognostic indicators using multivariate analysis. Continuation to smoke approached significance (P=0.061). Similar disease-free survival and malignant transformation rates with minimal complications were found as compared to the literature. Recommendations for minimizing recurrence are presented. Long-term follow up and removal of aetiological factors, such as smoking and alcohol, are advised.


Natural orifice specimen extraction for colorectal surgery: Early adoption in a Western population.
Natural orifice specimen extraction (NOSE) challenges the limits of minimally invasive colorectal surgery by exploiting a natural opening for specimen delivery. Technically challenging, it is less painful, requires smaller wounds and abolishes the possibility of incisional hernia. These advantages of NOSE are seen in the obese (body mass index [BMI] >30 kg/m2 ). This audit aims to demonstrate the feasibility of NOSE colectomy in an Australian population. Prospective data collected from 2007 to the present were retrospectively analysed. Only patients with mucosally benign colorectal conditions were included: complex diverticulosis, post-malignant polypectomy and volvulus. Left sided mucosal malignancies were excluded. Study end-points included postoperative length of stay, anastomotic leak rate and wound complications. In total, 159 patients underwent NOSE, mean age 59 years (19-88), mean BMI 28.2 kg/m2 (17-45). Ten (6.2%) patients developed retroperitoneal small bowel herniation; seven required further surgery. There were five (3.1%) anastomotic leaks, seven (4.4%) postoperative ileus and three (1.9%) anastomotic bleeds. One (0.6%) patient had a superficial wound infection. There were no port site hernias. Patients with BMI <30 kg/m2 (98 patients) and BMI >30 kg/m2 (59 patients) were compared; there was no difference in anastomotic leak rate (P = 0.60), complication rate (P = 0.71) and length of stay (P = 0.63). However, duration of operation increased with BMI (P = 0.000). This large series of NOSE colectomy from Australia suggests that NOSE is comparable to conventional laparoscopic colectomy in terms of postoperative outcome. Given that obesity has not featured in the NOSE literature, our study suggests that NOSE, for benign disease, is safe in obese patients, without added morbidity.


Evidence for mutual inhibition of opposite Ia interneurones in the human upper limb.
The H-reflex technique was used to collect indirect evidence for changes in excitability of the interneurones mediating reciprocal Ia inhibition between wrist extensors and flexors. Stimulating the radial nerve results in an inhibition of the flexor carpi radialis (FCR) H-reflex and evidence has previously been presented that the early phase of inhibition is mediated by extensor-coupled Ia interneurones (Ext Ia INs), i.e. by inhibitory interneurones fed by muscle spindle Ia afferents from wrist extensors. Variations in the level of this inhibition were used to assess changes in excitability of Ext Ia INs. Stimulation of group I fibres from flexors was shown to depress the "reference" Ia inhibition, i.e. to inhibit the Ext Ia INs. The central latency of this interneuronal inhibition was compatible with a disynaptic linkage between flexor Ia afferents and Ext Ia INs. Its threshold and time course profile could almost exactly be superimposed on those of reciprocal Ia inhibition from flexors to extensor carpi radialis (ECR) motoneurones (MNs). This suggests that the Ia inhibitions to extensor MNs and extensor Ia INs are collateral effects mediated by the same flexor-coupled Ia interneurones. In two subjects, in whom it was possible to elicit an H-reflex in the ECR, inhibition of flexor-coupled Ia interneurones by activation of extensor Ia interneurones could similarly be demonstrated.


The best use of adjuvant chemotherapy: new drugs and new use of "old" drugs.
Modern chemotherapy has diminished the risks of distant relapse and death in many subgroups of patients with early stage breast cancer. Although the initial trials relied on empirically designed regimens, studies are increasingly based on preclinical science and reflect the growing understanding of the molecular basis of cancer. Empiric clinical trials proved the worth of combination chemotherapy, the limited value of very long courses of treatment, and the benefits of adding first anthracyclines and then later taxanes. More recent trials have demonstrated the limits on empiric dose escalation and the benefits of optimized scheduling. Many trials are currently focused on novel targeted agents. Based on several decades of studies in thousands of women it is reasonable to consider a combination of chemotherapy agents for patients with hormone unresponsive or otherwise high-risk tumors. Anthracyclines and taxanes should be incorporated into the treatment plans of patients in the higher risk subsets and the specific regimens should be taken from the several randomized studies. When available, eligible patients should be enrolled on prospective clinical trials.


Constraint-induced movement therapy after stroke: efficacy for patients with minimal upper-extremity motor ability.
To examine the effects of constraint-induced movement therapy (CIMT) on chronic moderate-to-severe upper-extremity motor impairment after stroke. Within-subjects design; pre- and posttesting as well as 1-month follow-up. Outpatient clinic within a rehabilitation hospital. Twenty participants, each greater than 12 months poststroke. Three weeks of CIMT including restraint of the nonparetic upper extremity and 6 hours of training a day. Fugl-Meyer Assessment (FMA), Graded Wolf Motor Function Test (GWMFT), and Motor Activity Log (MAL). There was a statistically significant effect of treatment on upper-extremity motor impairment as assessed by the FMA, the MAL, and the functional ability scale of the GWMFT. There was a trend toward an effect of CIMT on mean speed of performance on the GWMFT. Post hoc analysis showed significant differences between motor impairment scores between pretreatment and posttreatment assessments, and improvements in motor impairment scores remained stable 1 month after completion of formal treatment. Improvements appeared to be mostly in the use of the involved upper extremity for bimanual activities. CIMT conferred significant changes in objective measures in subjects with chronic moderate-to-severe impairments after stroke. Additional studies of long-term benefits of this treatment on poststroke motor impairments and related functional disabilities are warranted.


Role of ISG15 post-translational modification in immunity against Mycobacterium tuberculosis infection.
ISG15 encoded by a type I interferon (IFN) inducible gene mediates an important cellular process called ISGylation. ISGylation emerges as a powerful host tactic against intracellular pathogens like Mycobacterium tuberculosis (Mtb). However, the exact role of ISGylation in immunity remains elusive. To shed light on how ISGylation, which is both interesting and complex, participates in immunity against Mtb, this manuscript summarized the current knowledge about the structural characteristics and targets of ISG15 and how ISGylation cross-talks with other host post-translational modifications to exert its effect.


Development-dependent expression of low molecular weight GTP-binding proteins in embryonic chicken brain.
Expression of low molecular weight GTP-binding proteins in particulate and soluble fractions of embryonic chicken brain was analysed by SDS-PAGE and incubation of blotted proteins with [alpha-32P]GTP. At least seven GTP-binding proteins with apparent molecular weights between 21 and 29 kDa were demonstrated by this technique in membranes and microsomal fractions, whereas only four species were present in the cytosol. Levels of several small GTP-binding proteins were developmentally regulated in membrane and microsomal fractions, but not in the cytosol of embryonic chicken brain. Major GTP-binding proteins G28 and G26 were strongly increased in microsomal but not in membrane fractions between E6 and hatched chicken brain, whereas the minor protein G24 decreased in both membrane and microsomal fractions over this time. The differential expression of low molecular weight GTP-binding proteins in embryonic chicken brain suggests important roles for these proteins in brain development.


Sex steroid binding proteins in non-mammalian vertebrates.
High affinity cytosolic and nuclear steroid binding macromolecules have been identified in steroid target tissues of representative amphibians, reptiles and birds. In addition to these traditional "receptors" evidence exists which indicates the presence of other steroid binding proteins, varying in affinity and specificity, in the cytosol of steroid targets (liver, oviduct) of these same species. The possible relationships between cytosolic binding proteins of differing affinity and specificity and their relevance to hormone action in non-mammalian species is discussed.


The Effectiveness of Noninvasive Interventions for Temporomandibular Disorders: A Systematic Review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.
To determine the effectiveness and cost-effectiveness of noninvasive interventions for temporomandibular disorders (TMD). We systematically searched MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Central register from 1990 to 2014 for effectiveness studies and the Cochrane Health Technology Assessment Database, EconLit, NHS Economic Evaluation Database, and Tufts Medical Center Cost-Effectiveness Analysis Register from 1990 to 2014 for cost-effectiveness studies. Random pairs of independent reviewers critically appraised eligible studies using the Scottish Intercollegiate Guidelines Network criteria. Evidence from eligible studies was synthesized using best-evidence synthesis methodology. Our search for effectiveness studies yielded 16,995 citations; 31 were relevant and 7 randomized controlled trials (published in 8 articles) had a low risk of bias. We found no relevant cost-effectiveness studies. The evidence suggests that for persistent TMD: (1) cognitive-behavioral therapy and self-care management lead to similar improvements in pain and disability but cognitive-behavioral therapy is more effective for activity interference and depressive symptoms; (2) cognitive-behavioral therapy combined with usual treatment provides short-term benefits in pain and ability to control pain compared with usual treatment alone; (3) intraoral myofascial therapy may reduce pain and improve jaw opening; and (4) structured self-care management may be more effective than usual treatment. The evidence suggests that occlusal devices may not be effective in reducing pain and improving motion for TMD of variable duration. Evidence on the effectiveness of biofeedback is inconclusive. The available evidence suggests that cognitive-behavioral therapy, intraoral myofascial therapy, and self-care management are therapeutic options for persistent TMD.


Maturation of the mismatch response in pre-school children: Systematic literature review and meta-analysis.
Event-related potentials (ERPs), specifically the Mismatch Response (MMR), holds promise for investigating auditory maturation in children. It has the potential to predict language development and distinguish between language-impaired and typically developing groups. However, summarizing the MMR's developmental trajectory in typically developing children remains challenging despite numerous studies. This pioneering meta-analysis outlines changes in MMR amplitude among typically developing children, while offering methodological best-practices. Our search identified 51 articles for methodology analysis and 21 for meta-analysis, involving 0-8-year-old participants from 2000 to 2022. Risk of Bias assessment and methodology analysis revealed shortcomings in control condition usage and reporting of study confounders. The meta-analysis results were inconsistent, indicating large effect sizes in some conditions and no effect sizes in others. Subgroup analysis revealed the main effects of age and brain region, as well as an interaction of age and time-window of the MMR. Future research requires a specific protocol, larger samples, and replication studies to deepen the understanding of the auditory discrimination maturation process in children.


Interfacial properties and foam stability effect of novel gemini-type surfactants in aqueous solutions.
Static and dynamic surface tension and interfacial rheological behavior of a novel anionic gemini-type surfactant without a spacer group, sodium 2,3-didodecyl-1,2,3,4-butane tetracarboxylate (GS), were investigated. Very low values for critical micelle concentration (8.9x10(-5) M) as well as equilibrium surface tension (22.7 mN m(-1)) were observed for the aqueous solutions. Dynamic surface tension (DST) is very slow and less sensitive to the surfactant concentration than the conventional monomeric surfactant, suggesting the presence of a significant adsorption barrier for GS owing to a complicated molecular structure. Presence of a small concentration of GS in sodium dodecyl sulfate (SDS) solution shows a synergistic effect to form mixed micelles and lowers the cmc considerably. This synergism between GS and SDS and slow exchange of GS between bulk and interface create a rigid air-liquid interface of the SDS-GS solution, which is reflected in a higher elasticity value for the interface of the SDS-GS solution than for the SDS solution. It has been found that the presence of a small concentration of GS in SDS solution increases the foam stability noticeably. Although the stability of the wet foam is correlated with the film elasticity, the stability of dry foam cannot be explained in terms of film elasticity alone.


Application of a multiphase microreactor chemostat for the determination of reaction kinetics of Staphylococcus carnosus.
Bioreactors at the microliter scale offer a promising approach to accelerate bioprocess development. Advantages of such microbioreactors include a reduction in the use of expensive reagents. In this study, a chemostat operation mode of a cuvette-based microbubble column bioreactor made of polystyrene (working volume of 550 µL) was demonstrated. Aeration occurs through a nozzle (Ø ≤ 100 µm) and supports submerged whole-cell cultivation of Staphylococcus carnosus. Stationary concentrations of biomass and glucose were determined in the dilution rate regime ranging from 0.12 to 0.80 1/h with a glucose feed concentration of 1 g/L. For the first time, reaction kinetics of S. carnosus were estimated from data obtained from continuous cultivation. The maximal specific growth rate (µmax = 0.824 1/h), Monod constant (KS = 34 × 10- 3gS/L), substrate-related biomass yield coefficient (YX/S = 0.315 gCDW/gS), and maintenance coefficient (mS = 0.0035 gS/(gCDW·h)) were determined. These parameters are now available for further studies in the field of synthetic biology.


Association of virome dynamics with mosquito species and environmental factors.
The pathogenic viruses transmitted by mosquitoes cause a variety of animal and human diseases and public health concerns. Virome surveillance is important for the discovery, and control of mosquito-borne pathogenic viruses, as well as early warning systems. Virome composition in mosquitoes is affected by mosquito species, food source, and geographic region. However, the complex associations of virome composition remain largely unknown. Here, we profiled the high-depth RNA viromes of 15 species of field-caught adult mosquitoes, especially from Culex, Aedes, Anopheles, and Armigeres in Hainan Island from 2018 to 2020. We detected 57 known and 39 novel viruses belonging to 15 families. We established the associations of the RNA viruses with mosquito species and their foods, indicating the importance of feeding acquisition of RNA viruses in determining virome composition. A large fraction of RNA viruses were persistent in the same mosquito species across the 3 years and different locations, showing the species-specific stability of viromes in Hainan Island. In contrast, the virome compositions of single mosquito species in different geographic regions worldwide are visibly distinct. This is consistent with the differences in food sources of mosquitoes distributed broadly across continents. Thus, species-specific viromes in a relatively small area are limited by viral interspecific competition and food sources, whereas the viromes of mosquito species in large geographic regions may be governed by ecological interactions between mosquitoes and local environmental factors. Video Abstract.


The role of radiation therapy in the treatment of glomus jugulare tumors.
The records of 14 patients who received irradiation for incompletely excised, inoperable or recurrent glomus jugulare tumors were retrospectively reviewed. Ages ranged from 12 to 66 years, and the male to female ratio was 1:3. With a follow-up time of 1.3 to 17.2 years (mean of 7.7 years), 11/14 remain clinically disease-free. Doses of at least 4000 rad are shown to be effective in controlling glomus jugular tumors.


Sensitisation and allergic reactions to alpha-1,3-galactose in Podlasie, Poland, an area endemic for tick-borne infections.
Ticks transmit several pathogens and seem implicated in the production of specific IgE antibodies to alpha-1,3-galactose (α-gal sIgE). They cause delayed and immediate allergy to mammalian meat and medication including antivenoms, vaccines and monoclonal antibodies. We assessed the prevalence of α-gal sIgE in forest workers and healthy controls in the Podlasie voivodeship, north-eastern Poland; the relationship between α-gal sIgE and allergy to α-gal-containing products; the correlation between α-gal sIgE and anti-Borrelia burgdorferi and anti-tick-borne encephalitis virus (TBEV) antibodies; the relationship between α-gal sIgE and markers of infection with lesser-known pathogens transmitted by ticks such as Anaplasma phagocytophilum. Production of α-gal sIgE was closely related to tick bites. The odds ratio for detectable α-gal sIgE was 9.31 times higher among people with a history of tick bites (OR 9.3; p < .05). There was no correlation with the history of TBE, Lyme disease or human granulocytic anaplasmosis. However, serum α-gal sIgE correlated with anti-TBEV IgM antibodies in CSF. There was a strong correlation between α-gal sIgE and total IgE and sIgE to pork and beef. Our data support the link between I.ricinus ticks and the production of α-gal sIgE and confirm that the pathogens carried by ticks we examined for do not seem implicated in this immune response.


Mixed lymphocytic and collagenous inflammation of the entire gastrointestinal tract under therapy with serotonin and norepinephrine reuptake inhibitors.
Drug-induced injury to the gastrointestinal tract has gained growing significance in recent years, and the list of causative medications keeps expanding. Herein, we present the case of a 45-year-old female with major depressive disorder treated with two serotonin and norepinephrine reuptake inhibitors (venlafaxine and duloxetine). She developed nausea and weight loss. Endoscopic evaluation of the upper and lower gastrointestinal tract rendered grossly normal mucosa in all segments. Histological examination, however, revealed lymphocytic esophagitis, collagenous gastritis, celiac disease-like intraepithelial lymphocytosis of the duodenum, and incomplete collagenous colitis. Gastrointestinal side effects of psychoactive drugs are largely underrecognized. This is the first report of a mixed lymphocytic and collagenous pattern of injury affecting esophagus, stomach, duodenum, and colon triggered by combined treatment with venlafaxine and duloxetine. In patients with unclear symptoms, obtaining biopsies from mucosa that is normal upon endoscopic inspection may render decisive clues for clinical management.


Diabetes risk during pregnancy among second-generation immigrants: A national cohort study in Sweden.
Gestational diabetes is more common in many first-generation immigrant women in Europe and other Western countries. Less is known about second-generation immigrant women; such knowledge is needed to understand generational influences on diabetes risk. We aimed to study second-generation immigrant women regarding the presence of all types of diabetes during pregnancy. A cohort study was conducted using the Swedish National Birth Register, the National Patient Register, and the Total Population Register. We used Cox regression analysis to compute hazard ratios (HRs) and 99% confidence intervals (99% CI) for any diabetes during pregnancy and specific subtypes (gestational diabetes, pre-existing diabetes type 1, pre-existing diabetes type 2) in second-generation immigrant women compared with Swedish-born women with two Swedish-born parents while adjusting for sociodemographic factors, family history of diabetes, body mass index, smoking habits, and comorbidities. The study population included a total of 989,986 deliveries and 17,938 diabetes cases. The fully adjusted HR (with 99% CI) for any type of diabetes during pregnancy among second-generation immigrant women was 1.11 (1.05-1.18). Higher risks were found in women with parents from Africa, Asia, or Eastern Europe, as well as Denmark. A lower risk for pre-existing type 1 diabetes was found overall and for women with parents from most geographic regions. In this national cohort study, the risk of all types of diabetes during pregnancy was increased in second-generation immigrant women. Diabetes prevention and treatment is especially important in these women both before and during pregnancy.


Correcting dysbiosis in the lungs of COPD, one pathogen at a time.
In this issue of Cell Host & Microbe, Liang et al. demonstrate through genomic analysis of the sputum microbiome from COPD patients and preclinical models that Staphylococcus aureus promotes lung function decline via regulation of homocysteine levels. Homocysteine can promote lung injury by promoting neutrophil apoptosis-to-NETosis shift via AKT1-S100A8/A9 axis.


Circulating endothelial progenitor cells decreased in patients with sclerodermatous chronic graft-versus-host disease.
Chronic graft-versus-host disease (cGVHD) is a common late complication of allogeneic stem cell transplantation (allo-SCT). Some cGVHD patients develop skin lesions, and the skin lesions in sclerodermatous cGVHD (s-cGVHD) patients resemble those in progressive systemic sclerosis (PSS), which is characterized by impaired production of circulating endothelial progenitor cells (EPCs). We investigated, retrospectively, whether low EPC production may promote the development of sclerodermatous lesions in cGVHD. Peripheral blood (PB) was obtained from 14 healthy volunteers and 27 allo-SCT patients. Five patients developed s-cGVHD. CD34(+) cells were purified by using the magnetic cell-sorting separation system, and the CD34(+)/CD133(+)/vascular endothelial growth factor (VEGF) receptor-2(+) EPCs were quantified. The endothelial cell colony-formation potential was evaluated. Serum VEGF and basic fibroblast growth factor (b-FGF) concentrations were measured by ELISA. The s-cGVHD patients had significantly lower median circulating EPCs frequencies than non-s-cGVHD patients or control (145 of 20 mL [interquartial range-IQR 107-193] versus 1083.5 [IQR 669.3-2151]; P = .0023, and versus 1530.5 [IQR 961.3-2158]; P = .0012, respectively). They also had impaired median endothelial-forming ability compared to non-s-cGVHD patients or controls (3.8 [IQR 1.0-4.3] versus 12.8 [IQR 8.8-28.8], and versus 26.4 [IQR 23.6-30.6], respectively; P = .0012). Their VEGF and b-FGF serum levels were also higher than in controls. In conclusion, s-cGVHD patients show findings consistent with those seen in PSS with impaired vasculogenesis that may limit blood perfusion and may contribute to the development of sclerodermatous lesions.


[Extramedullary plasmocytoma of the left tonsil. A rare cause of tonsillar asymmetry].
The plasmocytoma is a tumor, which can only rarely be found in the oropharynx. In this respective case an asymmetria of the tonsils was caused by an extramedullary plasmocytoma. Even if the asymmetria of the tonsils has a harmless nature, a tumor growth always has to be considered when thinking of the differential diagnosis. First of all, squamous-cell carcinoma has to be taken into account, more rarely with malignant lymphoma. Tonsillektomie added by immunhistological examination of the preparation brings diagnostic certainty.


Permanent brain damage possibly caused by theophylline in two elderly patients with airway obstruction.
Two aged patients with bronchial asthma and chronic obstructive pulmonary disease who suffered convulsions that resulted in permanent brain damage during treatment with the recommended therapeutic dose of theophylline are presented here. A dose or concentration of theophylline lower than the recommended one should be considered in the treatment of some aged patients with pulmonary obstructive disease.


Characteristics of oral squamous cell carcinoma focusing on cases unaffected by smoking and drinking: A multicenter retrospective study.
Some oral squamous cell carcinoma (OSCC) cases are unaffected by smoking or drinking. This study aimed to clarify distinctive groups among OSCC patients and examine the characteristics of multiple primary carcinomas (MPCs). We analyzed data from 970 patients. The patients were divided into three groups: all individuals <45 years (<45 y), smokers/drinkers ≥45 years (SD ≥45 y), and non-smokers/non-drinkers ≥45 years (NSND ≥45 y). Tongue cancers were more common in the <45 y group than in the other groups (p < 0.001). The NSND ≥45 y group was significantly older and more likely to be female than the SD ≥45 y group (p < 0.001). MPCs in the upper aerodigestive tract were more common in men and smokers/drinkers, whereas women were at risk for multiple primary OSCCs (p = 0.022). The "young tongue" and "elderly female" subgroups and characteristics of MPCs suggest carcinogenic factors of OSCC other than smoking and drinking.


Examination of the "null" model of connor and simberloff for species co-occurrences on Islands.
Among birds of the Bismarck Archipelago, only certain combinations of the species in a guild coexist on islands, and some species that are very similar ecologically have mutually exclusive distributions. Diamond (1975) interpreted these patterns as biologically significant, involving effects such as competition. Connor and Simberloff (1979) claimed such patterns to be not recognizably different from random, because they were scarcely distinguishable from those generated by a "null" distribution supposedly not incorporating competition.On examining the analysis by Connor and Simberloff, we find that it actually yields the opposite conclusion: three faunas tested have grossly non-random structures, while their test is unworkable for the fourth fauna. The method of Connor and Simberloff for generating a null distribution has many fatal weaknesses: dilution of relevant data from guilds with irrelevant data from the whole species pool; hidden incorporation of effects of competition into the constraints; inability to recognize a checkerboard, the extreme example of a distribution produced by competition; reliance on inefficient Monte Carlo simulations; severe constraints that sometimes make generation of a null distribution impossible; failure to weight species combinations; and failure to identify the direction of non-randomness or the species combinations most responsible.Finally, we use other recent studies by Simberloff and coleagues to examine the value of constructing null hypotheses in community ecology.


Evidence for the presence of a new plasma factor which acts synergistically to ADP induced platelet aggregation.
The existence of a new factor (AF) in mice acting synergistically with known proaggregatory stimuli has been suggested by the present study in the plasma of mice challenged with intravenous collagen and adrenaline. Indomethacin, nordihydroguaretic acid (NDGA), BW 755C, phentolamine, cimetidine and ketanserin could not block the response of AF. Activity of the factor remained unaltered after treatment with pancreatic phospholipase A2, collagenase, CP/CPK, trypsin and heparin. Fractionation of the plasma indicated the presence of AF in acetone precipitate. Activity was destroyed by pronase and it was lost after dialysis and charcoal treatment. Existence of such a factor which is heat resistant, is of low molecular weight and is proaggregatory in nature in the thrombotic mice plasma and which requires calcium ions for the expression of its activity, has not been reported earlier.


Protective effect of fenugreek (Trigonella foenum graecum) seeds in experimental ethanol toxicity.
The study investigates the effect of aqueous extract of fenugreek seeds (Trigonella foenum graecum) on lipid peroxidation and antioxidant status in experimental ethanol toxicity in rats. The ability of the seed extract to prevent iron-induced lipid peroxidation in vitro was also investigated. Ethanol feeding for 60 days resulted in significant increases in the activities of serum aspartate transaminase, alanine transaminase and alkaline phosphatase. The levels of serum lipid hydroperoxides and thiobarbituric acid reactive substances in liver and brain were also significantly elevated. Significantly lower activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and glutathione reductase were observed in liver and brain accompanied by depletion in glutathione, ascorbic acid and alpha-tocopherol concentrations. Activity of Ca(2+) ATPase in brain was significantly lowered. Simultaneous administration of aqueous extract of fenugreek seeds with ethanol prevented the enzymatic leakage and the rise in lipid peroxidation and enhanced the antioxidant potential. The seeds exhibited appreciable antioxidant property in vitro which was comparable with that of reduced glutathione and alpha-tocopherol. Further, histopathological examination of liver and brain revealed that, aqueous extract of fenugreek seeds could offer a significant protection against ethanol toxicity.


A perfusion system developed for 31P NMR study of melanoma cells at tissue-like density.
A perfusion culture system has been developed for 31P NMR study of human uveal melanoma metabolism by adapting the Vitafiber I cartridge system (Amicon). 31P NMR spectra collected weekly during periods of up to 10 weeks demonstrated increasing levels of phosphorus metabolites as the anchorage-dependent cells grew to tissue-like density.


Implantation of model AMS 700 penile prosthesis: long-term results.
The American Medical Systems inflatable penile prosthesis has undergone periodic design changes to improve device reliability and longevity while maintaining a high degree of patient and partner satisfaction. Previous data reported from this institution did not consider these frequent design changes and the assessment of device reliability incorporated consecutive cases involving several different designs. This study was designed to evaluate followup data on 120 patients who received the model 700 inflatable penile prosthesis, permitting assessment of device reliability of a single design. Two groups were evaluated: a pre-fix group of 57 patients and a post-fix group of 63 patients. Over-all, 11.7 per cent of the total group required revision (21 per cent of the pre-fix and 3.2 per cent of the post-fix groups). Careful life-table analysis of the results with the current model 700 device (post-fix) reveals that this model has a 97 per cent chance of maintaining normal mechanical function for 3 years. Further assessment of these patients in the future will provide additional data on long-term reliability of this design.


[Selection of patients with rectal tumors for local excision based on preoperative diagnosis. Results of a consecutive evaluation study of 552 patients].
The aim of our study was to evaluate the accuracy of clinical staging (CS), biopsies, and endoluminal ultrasonic examination (EUS) in preoperative staging of rectal tumors treated with transanal local excision. This local excision is an adequate procedure for benign rectal polyps and low-risk T1 carcinoma. The study included 552 patients with rectal adenocarcinoma, villous adenoma, or tumors with other histologic characteristics who underwent a transanal excision (transanal endoscopic microsurgery n=513 or transanal excision n=39). We compared the results of CS, biopsies, and EUS with postoperative pathology findings. Preoperative histological diagnosis of the rectal carcinoma depended on tumor size (52% in cancers <3 cm, 25% in cancers >3 cm; p=0.001) and was correct in 56% of cases. Transanal ultrasonography (uT0/1) had superior sensitivity (95% vs 78%) and a higher positive predictive value (93% vs 85%) than clinical staging (CS I) in detecting adenoma or T1 rectal carcinoma, whereas specificity was similar in both (62% vs 58%). In patients in whom preoperative histological analysis revealed adenomas, transanal ultrasonography was accurate (uT0/1) for the postoperatively assessed adenoma pT1 in 97%, whereas diagnosis (uT0/1) was correct in only 71% of cases in which preoperative histological analyses showed rectal carcinomas. In patients with rectal tumors, preoperative staging with transanal ultrasonography and biopsy is essential for the indication and allows selection of patients for transanal local excision.


Classification of human immunodeficiency virus-infected patients with chronic kidney disease using a combination of proteinuria and estimated glomerular filtration rate.
In 2012, the Kidney Disease: Improving Global Outcomes (KDIGO) updated the 2002 Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guideline for chronic kidney disease (CKD). The 2012 KDIGO guideline elaborated the identification and prognosis of CKD by combining albuminuria with estimated glomerular filtration rate (eGFR). Identification of CKD with a high risk for a poor prognosis was investigated in human immunodeficiency virus (HIV)-infected individuals by applying the new guideline. A total of 1,447 HIV-infected patients (1,351 male, 96 female; mean age 44.4 ± 11.5 years) were classified using a combination of eGFR and dipstick proteinuria, as a convenient alternative to albuminuria. Proteinuria was classified into 3 grades-(A1) - and +/- , (A2) 1+ and 2+ , and (A3) 3+ and 4+. eGFR was classified into 6 grades-(G1) ≤90, (G2) 60-89, (G3a) 45-59, (G3b) 30-44, (G4) 15-29, and (G5) <15 mL/min/1.73 m(2). Mean CD4 cell count was 487 ± 214 /μL, with 80.7 % of patients having an undetectable HIV-RNA level. The prevalence of CKD stage ≤2 and stage ≥3 classified according to KDOQI staging was 93.4 and 6.6 %, respectively. Using the new KDIGO classification, the prevalence of CKD with either a low (green) or moderately increased (yellow) risk was 96.9 %, while the prevalence for a high (orange) and very high (red) risk was 3.1 %. The use of the new KDIGO classification may reduce the prevalence of HIV-infected CKD individuals who are at high risk for a poor prognosis by nearly a half.


Prolonged replication of BA.1 and BA.2 Omicron lineages compared to Delta variant in nasopharyngeal samples from COVID-19 patients.
We aimed to characterize and compare the viral loads (VL) of the Omicron BA.1 and BA.2 lineages and the Delta variant in nasopharyngeal samples from newly diagnosed COVID-19 patients and their kinetics over time. The kinetics of the VL were measured on the CT data from 215 SARS-CoV-2 positive patients who presented at least two positive PCRs a day apart and were screened for SARS-CoV-2 viral lineages. We observed no significant difference in median CT value during the first diagnostic test between the Delta variant and the two Omicron lineages. However, the kinetics of CT decreases for the BA.1 and BA.2 lineage were significantly lengthier in time than the kinetics for the Delta variant. The BA.2 lineage presented lower median CT value (-2 CT) (inversely proportional to the VL) than the BA.1 lineage. BA.2 Omicron lineage presented higher VL than BA.1 Omicron lineage at diagnostic. Omicron BA.1 and BA.2 lineages have more prolonged replication than the Delta variant.


[Detection of DNA strand breakage in human spermatozoa by use of single-cell gel electropheresis].
To establish the single-cell gel electropherosis (SCGE) protocol for detection of DNA strand breakage in human spermatozoa. The slides on which sperm cells and agarose were layered were immersed in a cold lysing solution of pH10 to lyse the sperm cells. Sperm nuclei were then pretreated with 10 mmol/L of DTT for 1 h, 10 microg/ml of RNase A for 4 h and 200 microg/ml of proteinase K for 15 h. Lastly, electrophoresis was performed in electrophoresis running buffer(pH10) at 12V (0.46V/cm) and 100 mA for 1 h. Sperm nuclei were stained with 15 microg/ml of EtBr for 5 min. The percentage of comet cells was counted. The in vitro hydrogen peroxide-induced DNA damage in human spermatozoa was measured with SCGE established by this laboratory. The comet sperm cells in human spermatozoa ranged from 2% to 38%. There was a significant variance on the percentage of comet cells between different subjects. Hydrogen peroxide increased the percentage of comet sperm in a dose- and time-dependent manner. SCGE may be used to detect DNA strand breakage in human spermatozoa. Hydrogen peroxide-induced DNA damage in human sperm cells was detected successfully using SCGE protocol established by this laboratory.


Glycosidases in cancer and invasion.
Glycosidases have been demonstrated to be elevated in the interstitial fluid of tumors, sera of animals and patients with tumors, and in some tumor tissue as compared to normal adjacent tissue. Elevations of serum beta-N-acetylglucosaminidase and beta-glucuronidase most commonly have been found to occur and these enzymes have been shown to be secreted into the extracellular medium by many different tumor cell types in vitro. The mechanism of cellular release of these hydrolytic enzymes probably involves tumor lysosomal exocytosis. Increased tumor glycosidase levels may promote increased tumor cell shedding from primary tumors, local invasion and perhaps be responsible directly, or indirectly for structural changes in tumor cell surface glycoconjugates. These cell surface changes could facilitate tumor cell thrombus formation, secondary site implantation and attachment in the microcirculation to endothelial cells and/or subendothelial basement membrane components. Other studies have demonstrated a correlation between metastatic cell potential and increased endoglycosidase and polysaccharide lyase activity. Generally, metastatic tumor cell variants have been found to be more invasive and capable of degrading proteoglycan basement membrane components, in part due to these increased levels of degradative enzymes. Hence, it is of considerable interest to develop inhibitors against these enzymes. Initial studies with glucuronidase inhibitors in the therapy of bladder tumors have been promising and with the advent of better agents and the use of appropriate in vitro metastatic models it may be possible to design and develop agents which interfere in various metastatic events and limit tumor progression.


In vivo imaging of brain nicotinic acetylcholine receptors with 5-[123I]iodo-A-85380 using single photon emission computed tomography.
The distribution and kinetics of 5-[123I]iodo-A-85380, a novel ligand for brain nicotinic acetylcholine receptors (nAChRs), were evaluated in the Rhesus monkey using single photon emission computed tomography (SPECT). Peak levels of radioactivity were measured in brain at 90 min after injection of the tracer. Accumulation of radioactivity was highest in the thalamus, intermediate in the frontal cortex and basal ganglia, and lowest in the cerebellum. The ratio of specific to nonspecific binding (V3") in the thalamus, estimated from the (thalamic-cerebellar)/cerebellar radioactivity ratio, reached a value of 6 at 4 h post-injection. Specific binding was reduced by subcutaneous injection of 1 mg/kg cytisine at 2.25 h after injection of radiotracer. At 2.5 h after cytisine administration, radioactivity in the thalamus was reduced by 84%, in the frontal cortex, by 76%, and in the basal ganglia, by 57% of the level measured at the time of cytisine administration, demonstrating that the binding was reversible. On the basis of these findings, together with other data indicating high affinity, receptor subtype selectivity, low nonspecific binding and lack of toxicity in animals, 5-[123I]iodo-A-85380 appears to be a promising ligand for SPECT imaging of nAChRs in the human brain.


Toxic Environment of war: Maternal prenatal heavy metal load predicts infant emotional development.
People in war zones are exposed to heavy metal contamination deriving from new-generation weapons, in addition to exposure to psychologically traumatizing war events. Pregnant women and their children-to-be are particularly vulnerable to both biological and psychological war effects. The aim of the current study was to analyse the impact of maternal prenatal heavy metal contamination on infant emotional development and to examine the potential moderating role of maternal symptoms of post-traumatic stress disorder (PTSD) in the association between heavy metal load and infant emotional development. The participants were 502 Palestinian mothers, pregnant in their first trimester during the 2014 War on Gaza. The mothers were recruited at their delivery (T1) and followed at the infants' age of 6-7 months (T2; N = 392). The load of five weapon-related heavy metals (chromium, mercury, vanadium, strontium, and uranium) was analysed by Inductively Coupled Plasma Mass Spectrometry (ICP/MS) from mothers' hair samples at childbirth (T1). Assessment of maternal PTSD symptoms was based on the Harvard Trauma Questionnaire (HTQ) and infant emotional development on the Infant Behavior Questionnaire (IBQ), both reported by mothers (T2). Two of the analysed metals, chromium and uranium, adversely predicted children's early emotional development, indicated by decreased positive affectivity, increased negative emotionality, and problems in early orientation and regulation. Mother's PTSD did not moderate the impact of heavy metal contamination on children's emotional development. Adverse impact of war is not limited to those who experience it directly, but is passed on to future generations through multiple mechanisms. International organizations are obliged to protect parents and infants from the modern weaponry in wars.


Electron microscopic examination of the mucosa of the small intestine in infection due to giardia lamblia.
A rare form of Giardia lamblia infection presenting the clinical picture of nutritive allergy is described. Diagnosis was made by electron microscopic examination of biopsy material from the small intestine. The ultrastructural characteristics of Giardia lamblia as well as the relation of the parasite to the epithelial cells are discussed. It is concluded that the clinical signs are related to the mechanical destruction of the microvilli of the epithelial cells and the superficial mucoid layer (fuzzy coat).


Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by Ibrutinib induces apoptosis.
Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy that characteristically shows overexpression of cyclin-D1 due to an alteration in the t(11;14)(q13;q32) chromosomal region. Although there are some promising treatment modalities, great majority of patients with this disease remain incurable. The B-cell antigen receptor (BCR) signaling plays a crucial role in B-cell biology and lymphomagenesis. Bruton tyrosine kinase (BTK) has been identified as a key component of the BCR signaling pathway. Evidence suggests that the blockade of BTK activity by potent pharmacologic inhibitors attenuates BCR signaling and induces cell death. Notably, the expression levels and the role of BTK in MCL survival are still elusive. Here, we demonstrated a moderate to strong BTK expression in all MCL cases (n=19) compared to benign lymphoid tissues. Treatment of MCL cell lines (Mino or Jeko-1) with a potent BTK pharmacologic inhibitor, Ibrutinib, decreased phospho-BTK-Tyr(223) expression. Consistent with this observation, Ibrutinib inhibited the viability of both Mino and JeKo-1 cells in concentration- and time-dependent manners. Ibrutinib also induced a concentration-dependent apoptosis in both cell lines. Consistently, Ibrutinib treatment decreased the levels of anti-apoptotic Bcl-2, Bcl-xL, and Mcl-1 protein. These findings suggest that BTK signaling plays a critical role in MCL cell survival, and the targeting of BTK could represent a promising therapeutic modality for aggressive lymphoma.


Tandem Living Insertion and Controlled Radical Polymerization for Polyolefin-Polyvinyl Block Copolymers.
Practical synthesis of polyolefin-polyvinyl block copolymers remains a challenge for transition-metal catalyzed polymerizations. Common approaches functionalize polyolefins for post-radical polymerization via insertion methods, yet sacrifice the livingness of the olefin polymerization. This work identifies an orthogonal radical/spin coupling technique which affords tandem living insertion and controlled radical polymerization. The broad tolerance of this coupling technique has been demonstrated for diverse radical/spin traps such as 2,2,5-trimethyl-4-phenyl-3-azahexane-3-nitroxide (TIPNO), 1-oxyl-(2,2,6,6-tetramethylpiperidine) -4-yl-α-bromoisobutyrate (TEMPO-Br), and N-tert-butyl-α-phenylnitrone (PBN). Subsequent controlled radical polymerization is demonstrated with nitroxide-mediated polymerization (NMP) and atom transfer radical polymerization (ATRP), yielding polyolefin-polyvinyl di- and triblock copolymers (Đ<1.3) with acrylic, vinylic and styrenic segments. These findings highlight radical trapping as an approach to expand the scope of polyolefin-functionalization techniques to access polyolefin macroinitiators.


The politics of non-communicable diseases in the global South.
In this paper, we explore the emergence of non-communicable diseases (NCDs) as an object of political concern in and for countries of the global South. While epidemiologists and public health practitioners and scholars have long expressed concern with the changing global distribution of the burden of NCDs, it is only in more recent years that the aetiology, politics and consequences of these shifts have become an object of critical social scientific enquiry. These shifts mark the starting point for this special issue on 'The Politics of NCDs in the Global South' and act as the basis for new, critical interventions in how we understand NCDs. In this paper, we aim not only to introduce and contextualise the six contributions that form this special issue, but also to identify and explore three themes - problematisation, care and culture - that index the main areas of analytical and empirical concern that have motivated analyses of NCDs in the global South and are central to critical engagement with their political contours.


The fate of flaxseed-lignans after oral administration: A comprehensive review on its bioavailability, pharmacokinetics, and food design strategies for optimal application.
Lignans are one of the most important and abundant phytochemicals found in flaxseed-diets. These have shown to possess several health-benefits, including anticancer, antioxidant, neuroprotective, cardioprotective, and estrogenic-properties etc. The potential of lignans health-promoting effects are circumscribed due to their poor-bioavailability resulting from their bound structure. Recent studies have demonstrated that various food design strategies can enhance the release of bound-lignans from agro-industrial residues, resulting in a higher bioaccessibility and bioavailability. This review focuses primarily on the bioavailability of flaxseed lignans, key factors affecting it and their pharmacokinetics, different strategies to improve the contents of lignans, their release and delivery. Present study will help to deepen our understanding of the applications of lignans and their dietary-supplements in the prevention and treatment of diseases. Several absorption issues of lignans have been observed such as impaired-bioavailability and variability in pharmacokinetics and pharmacodynamics. Therefore, the development of novel strategies for optimizing lignan bioavailability is critical to ensure its successful application, such as the delivery of lignans to biological targets via "targeted designs." In addition, some detailed examination is required to identify and understand the basis of variation in lignans bioavailability caused by interactions with the gastrointestinal system.


A case of achondroplasia with downward displacement of the brain stem.
We report a case of achondroplasia with downward displacement of the brain stem. Although upward displacement and anterior angulation deformity of the brain stem are common findings in achondroplasia, they were not observed in this case, because of a coexistent Chiari malformation.


Solving combinatorial problems: the 15-puzzle.
We present a series of experiments in which human subjects were tested with a well-known combinatorial problem called the 15-puzzle and in different-sized variants of this puzzle. Subjects can solve these puzzles reliably by systematically building a solution path, without performing much search and without using distances among the states of the problem. The computational complexity of the underlying mental mechanisms is very low. We formulated a computational model of the underlying cognitive processes on the basis of our results. This model applied a pyramid algorithm to individual stages of each problem. The model's performance proved to be quite similar to the subjects' performance.


S100A9 induces reactive oxygen species-dependent formation of neutrophil extracellular traps in abdominal sepsis.
Recent evidence suggests that targeting S100A9 reduces pathological inflammation in abdominal sepsis. Herein, we investigated the role of S100A9 in neutrophil extracellular trap (NET) formation in septic lung damage. NETs were detected by electron microscopy in the lung and by confocal microscopy in vitro. Stimulation of isolated mouse bone marrow-derived neutrophils with S100A9 triggered formation of NETs. Blocking TLR4 and RAGE reduced S100A9-induced generation of NETs and DNA-histone complexes. Moreover, S100A9 challenge increased generation of reactive oxygen species (ROS) in bone marrow neutrophils. Co-incubation with the NADPH oxidase inhibitor not only decreased ROS formation but also attenuated induction of DNA-histone complexes in S100A9-stimulated neutrophils. Abdominal sepsis was induced by cecal ligation and puncture (CLP) in male C57BL/6 mice. Administration of the S100A9 inhibitor ABR-238901 decreased CLP-induced formation of NETs in lungs and DNA-histone complexes in plasma. In addition, transmission electron microscopy revealed that S100A9 was abundantly expressed on NETs in the lungs in CLP mice. By use of intravital microscopy, we found that local injection of NETs increased leukocyte adhesion and migration in the mouse cremaster muscle microvasculature. Notably, treatment with ABR-238901 attenuated NET-induced leukocyte adhesion and extravasation in the cremaster muscle, suggesting that NET-associated S100A9 promotes leukocyte recruitment in vivo. Taken together, these novel findings suggest that S100A9 triggers ROS-dependent formation of NETs via TLR4 and RAGE signaling in neutrophils. Moreover, S100A9 regulates both formation of NETs and NET-induced leukocyte recruitment in vivo. Thus, targeting S100A9 might be useful to ameliorate lung damage in abdominal sepsis.


Anandamide modulates growth and lipid metabolism in the zebrafish Danio rerio.
Endocannabinoids are known to be lipidic mediators with several biological functions as the stimulation of food intake and lipid metabolism via cannabinoid receptor CB1. Many evidences, such as the presence of CB1 mRNA in fat tissue, suggest a peripheral role for endocannabinoids in regulating lipogenesis and body weight in mammals. As animal models constitute good tools to study endocannabinoid system dynamics, we analyzed the role of the endocannabinoid anandamide (AEA) in modulating lipid metabolism and growth in zebrafish larvae and adults. The data obtained indicated that AEA administered via water modulates the transcription of its own receptor CB1, besides to up-regulate gene expression of sterol regulatory element binding protein (SREBP) and of the insulin-like growth factors (IGF-1 and IGF-2). The results here obtained represent the first evidence in fish of the endocannabinoid system involvement in lipid metabolism and growth.


Molecular signaling underlying bulleyaconitine A (BAA)-induced microglial expression of prodynorphin.
Bulleyaconitine (BAA) has been shown to possess antinociceptive activities by stimulation of dynorphin A release from spinal microglia. This study investigated its underlying signal transduction mechanisms. The data showed that (1) BAA treatment induced phosphorylation of CREB (rather than NF-κB) and prodynorphin expression in cultured primary microglia, and antiallodynia in neuropathy, which were totally inhibited by the CREB inhibitor KG-501; (2) BAA upregulated phosphorylation of p38 (but not ERK or JNK), and the p38 inhibitor SB203580 (but not ERK or JNK inhibitor) and p38β gene silencer siRNA/p38β (but not siRNA/p38α) completely blocked BAA-induced p38 phosphorylation and/or prodynorphin expression, and antiallodynia; (3) BAA stimulated cAMP production and PKA phosphorylation, and the adenylate cyclase inhibitor DDA and PKA inhibitor H-89 entirely antagonized BAA-induced prodynorphin expression and antiallodynia; (4) The Gs-protein inhibitor NF449 completely inhibited BAA-increased cAMP level, prodynorphin expression and antiallodynia, whereas the antagonists of noradrenergic, corticotrophin-releasing factor, A1 adenosine, formyl peptide, D1/D2 dopamine, and glucagon like-peptide-1 receptors failed to block BAA-induced antiallodynia. The data indicate that BAA-induced microglial expression of prodynorphin is mediated by activation of the cAMP-PKA-p38β-CREB signaling pathway, suggesting that its possible target is a Gs-protein-coupled receptor - "aconitine receptor", although the chemical identity is not illustrated.


ASK1 and MAP2K6 as modifiers of age at onset in Huntington's disease.
Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disease associated with abnormal expansions of a stretch of perfect CAG repeats in the HD gene. The number of repeat units is predictive for the age at onset (AO) of neurological symptoms. Part of the remaining variation in AO is attributed to modifier genes. In this study, genes involved in apoptosis were investigated as candidates for modulating AO in HD. A panel of 304 candidate genes was screened for allelic associations with motor AO via linked micro-satellite markers by pooling the DNAs of HD individuals from opposite ends of the AO distribution. After genotyping promising markers from the pooling experiment individually, markers revealed consolidated evidence for association in a candidate region comprising the genes MAP3K5 (ASK1)/PEX7 at 6q23.3 and in the gene MAP2K6 at 17q24.3. Fine-mapping of these candidate regions in a cohort of 250 Caucasian HD patients using single nucleotide polymorphism (SNP) markers delimitated the precise locations of association. Certain variations in an ASK1-PEX7 haplotype block explain 2.6% of additional variance in AO in our HD cohort. In males, 4.9% additional variance could be attributed to MAP2K6 genotype variations. Altogether, ASK1-PEX7 haplotypes and MAP2K2 genotype variations explain 6.3% additional variance in AO for HD. We hypothesise that sequence variations of ASK1 and MAP2K6 lead to partially sex-specific changes in the levels and/or phosphorylation states of p38 and p38-regulated proteins that might contribute to the observed delaying effects in the AO of HD.