Carbon nanotubes and glucose oxidase bionanocomposite bridged by ionic liquid-like unit: preparation and electrochemical properties.
For their biocompatibility and potential bionanoelectronic applications, integration of carbon nanotubes (CNTs) with biomolecules such as redox enzyme is highly anticipated. Therein, CNTs are expected to act not only as an electron transfer promoter, but also as immobilizing substrate for biomolecules. In this report, a novel method for immobilization of biomolecules on CNTs was proposed based on ionic interaction, which is of universality and widespread use in biological system. As illustrated, glucose oxidase (GOD) and single-walled carbon nanotubes (SWNTs) were integrated into a unitary bionanocomposite by means of ionic liquid-like unit on functionalized SWNTs. The resulted bionanocomposite illustrated better redox response of immobilized GOD in comparison of that prepared by weak physical absorption without ionic interaction. As a potential application of concept, the electrochemical detection of glucose was exemplified based on this novel bionanocomposite.


Dissipation of hydrological tracers and the herbicide S-metolachlor in batch and continuous-flow wetlands.
Pesticide dissipation in wetland systems with regard to hydrological conditions and operational modes is poorly known. Here, we investigated in artificial wetlands the impact of batch versus continuous-flow modes on the dissipation of the chiral herbicide S-metolachlor (S-MET) and hydrological tracers (bromide, uranine and sulforhodamine B). The wetlands received water contaminated with the commercial formulation Mercantor Gold(®) (960 g L(-1) of S-MET, 87% of the S-enantiomer). The tracer mass budget revealed that plant uptake, sorption, photo- and presumably biodegradation were prominent under batch mode (i.e. characterized by alternating oxic-anoxic conditions), in agreement with large dissipation of S-MET (90%) under batch mode. Degradation was the main dissipation pathway of S-MET in the wetlands. The degradate metolachlor oxanilic acid (MOXA) mainly formed under batch mode, whereas metolachlor ethanesulfonic acid (MESA) prevailed under continuous-flow mode, suggesting distinct degradation pathways in each wetland. R-enantiomer was preferentially degraded under batch mode, which indicated enantioselective biodegradation. The release of MESA and MOXA by the wetlands as well as the potential persistence of S-MET compared to R-MET under both oxic and anoxic conditions may be relevant for groundwater and ecotoxicological risk assessment. This study shows the effect of batch versus continuous modes on pollutant dissipation in wetlands, and that alternate biogeochemical conditions under batch mode enhance S-MET biodegradation.


Optical Coherence Tomography Angiography Findings in X-Linked Retinoschisis.
The aim of the study was to determine optical coherence tomography angiography (OCTA) findings and to identify mutations in the RS1 gene in a three-generation family with X-linked juvenile retinoschisis (XLRS). Clinical and genetic assessments were performed in 12 family members. OCTA was performed at baseline (12 members including cases and carriers) and after acetazolamide administration (three cases). Twenty healthy subjects (20 eyes, controls) were chosen for comparison. Molecular genetic analysis of the RS1 gene was performed in all family members. Deep capillary plexus density was reduced in cases compared with controls (P < .01) and was negatively related with retinal thickness (P < .05). After treatment, retinal thickness decreased (P < .05) and deep capillary plexus density increased (P < .05) in cases. In three cases and in four carriers, p.Arg197 His mutation was found. OCTA shows reduced macular deep vessel density in patients with XLRS probably related to vessel displacement and disruption due to schitic cysts. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e20-e31.].


Thyroid computed tomography imaging: pictorial review of variable pathologies.
Focal and diffuse thyroid abnormalities are commonly encountered during the interpretation of computed tomography (CT) exams performed for various clinical purposes. These findings can often lead to a diagnostic dilemma, as the CT reflects the nonspecific appearances. Ultrasound (US) examination has a superior spatial resolution and is considered the modality of choice for thyroid evaluation. Nevertheless, CT detects incidental thyroid nodules (ITNs) and plays an important role in the evaluation of thyroid cancer. In this pictorial review, we cover a wide spectrum of common and uncommon, incidental and non-incidental thyroid findings from CT scans. We also discuss the most common incidental thyroid findings, best practices for their evaluation, and recommendations for their management. In addition, we explore the role of imaging in the assessment of thyroid carcinoma (before and after treatment) and preoperative thyroid goiter, as well as localization of ectopic and congenital thyroid tissue. • Thyroid disorders tend to have non-specific CT appearances. • ITNs are common on neck CT. • ITN management depends on nodule size, age, health status, lymphadenopathy, and invasion. • CT is used in assessment of cancer extension, mass effect, invasion, and recurrence. • CT plays a role in preoperative planning in patients with symptomatic goiter.


Application of the singular value and pivoted QR decompositions to reduce experimental efforts in compressor characterization.
Compressor characterization, either by running experiments in a turbocharger test rig or by detailed CFD modelling, can be expensive and time-consuming. In this work, a novel method is proposed which can be used to build a complete compressor map from a reduced number of measured operating points combined with a previously collected database. The methodology is based on the application of the Singular Value Decomposition (SVD) method to acquire the orthonormal bases of a matrix which contains the information of previous compressor observations. These bases are used along with pivoted QR decomposition to obtain the minimum number of measurement points which are required to implement this technique as well as its optimal placement within the map. The reconstruction of two different compressor maps was made to validate the method. The results show a substantially better trade-off between number of testing points and accuracy compared to standard equidistributed sampling.


Exploring how bedside nurses care for patients with chronic pain: a grounded theory study.
In the United States it is estimated that over 30% of the population suffers from some form of chronic pain (Institute of Medicine of the National Academies Report, 2011). Therefore, it is likely that 30% of patients who are admitted to the hospital for acute care needs also have an underlying chronic pain issue. When patients are admitted for concerns that are not related to their chronic pain, the chronic pain may be overlooked in deference to acute medical issues. Nurses dealing with pain in the acute care setting may limit their assessment and management of pain to acute pain. Although there is a significant body of research related to the management of acute pain (Bell & Duffy, 2009; Brennen, Obs, Carr, & Cousins, 2007; Dihle, Bjolseth, & Helseth, 2006; McDonnell, Nicholl, & Read, 2003; Wang & Tsai, 2010) and the management of chronic pain (Bruckenthal, 2010; Clarke & Iphofen, 2005; Kaasalainen et al., 2011; Matthews & Malcom, 2007; Papaleontiou et al., 2010, Reid et al., 2008), few studies were found that explained how nurses care for patients with pre-existing chronic pain in the acute care setting. The purpose of this study was to develop a theoretical understanding of nurses' assessment and decision-making behaviors related to the care of patients with chronic pain in the acute care setting.


[Traffic accidentability and risky driving behavior in young people in New Caledonia. Results of study Situation Sociale et Comportements de Santé des Jeunes en Nouvelle-Calédonie].
New Caledonia has one of the highest global rates of death from road accidents: 240 deaths per million inhabitants in 2011 with a majority of young people. However, research on driving behaviors has remained rare. A cross-sectional survey based on face-to-face questionnaire with 1400 male and female youth aged 16 to 25 was conducted in 2007. It was used to measure the frequency of accidents and to compute a score of driving behaviors and their associations with socio-demographic characteristics, lifestyles as well as other health behaviors. RESULTS - A total of 10.6% of boys and 6.5% of girls reported a car accident in the previous twelve months period. Among male participants risky driving behavior was associated with having a degree (ORa=2, 95% CI [1.1-3.8]), sport practices (ORa=3.7, 95% CI [1.9-7.05]), involvement in a fight in the last twelve months (ORa=2.2, 95% CI [1.4-3.4]) and precocity of cannabis use (ORa=1.8, 95% CI [1.2-2.8]). Youth living in couple and those with children presented with higher risk-taking scores. Among female participants, young age at cannabis initiation (ORa=3.1, 95% CI [1.5-6.4]) and at sexual debut (ORa=2.4, 95% CI [1.1-5.1]) were associated with driving risk-taking. Finally, younger age at first alcohol intoxication was associated with risky behavior on the road in both sexes. These results highlighted the multidimensional nature of risk-taking behaviors on the road and showed that they are part of, for boys and girls, a larger pattern of risky behaviors. Such results suggest to include behaviors on the road in a comprehensive approach of prevention.


The impact of frozen embryos on emotional reactions during in vitro fertilization.
Emotional reactions of couples were investigated during in vitro fertilization (IVF) at a private clinic in Sweden. The purpose was to compare such reactions between couples who obtained supernumerary embryos that could be cryopreserved and couples without such embryos. Forty women and men undergoing IVF treatment monitored individually their emotional reactions daily for one complete treatment cycle from the first day of down-regulation until the outcome of treatment was known. Ratings were extracted and analyzed from two separate days; the very first day of treatment and the day of embryo transfer. The group of women (n=16; 40%) with supernumerary embryos suitable for cryopreservation reported a greater increase in optimism than the group (n=24; 60%) without such embryos (p=0.024). Correspondingly, women with supernumerary embryos reported less pessimism than women without such embryos (p=0.014). Among men there was no difference in optimism or pessimism between the groups. The women and men with supernumerary embryos did not differ in distress reactions compared to those women and men without such embryos. There was no correlation between optimism and distress on the day of embryo transfer in women; r=-0.167 and men; r=-0.135 respectively. The presence of frozen embryos increased optimistic and reduced pessimistic feelings about pregnancy among women undergoing IVF treatment. However, the couples' increased optimism on the day of embryo transfer did not seem to reduce their experience of distress.


Renal BOLD-MRI does not reflect renal function in chronic kidney disease.
Renal blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) is a noninvasive fast technique to characterize renal function. Here we evaluated the impact of renal function on the relaxation rate (R2(*)) in the cortex and medulla to provide baseline data for further use of renal BOLD-MRI. This parameter was evaluated in 400 patients scheduled for abdominal imaging who underwent transversal blood oxygen level-dependent measurements with a multi-echo gradient-echo sequence with 12 echo times. The loss of phase coherence (T2(*)) maps were generated in which kidney regions of interest were selected to differentiate the medulla and cortex, and R2(*) was equated to 1/T2(*). Individual R2(*) values were, in turn, correlated to the eGFR (MDRD formula of 280 patients with available serum creatinine measurements), age, and gender each for 1.5 and 3.0 T field-strength scans of 342 patients. At both the field strengths, no significant differences in R2(*) of the cortex and medulla were found between patient gender, age, eGFR, or between different stages of chronic kidney disease determined using the KDOQI system. Thus, BOLD-MRI of a non-specific patient population failed to discriminate between the patients with various stages of chronic kidney disease.


Analysis of autapomorphic point mutations provides a key for the tangled taxonomic distinction of the closely related species, Euplotes crassus, E. minuta and E. vannus (Ciliophora, Euplotida).
A well-defined clade of the Euplotes phylogenetic tree is represented by marine species characterized by a single-type dargyrome and ten fronto-ventral cirri. Three of them, namely Euplotes crassus, E. minuta and E. vannus, form a complex of closely related species of large use in experimental ciliatology. Despite morphometric and genetic analyses having substantiated their taxonomic separation, ambiguities still persist in strain assignments to one or another species. In addition to objective reasons intrinsic to significant overlapping of most morphological parameters, ambiguities also result from divergences (inherited from past literature) in deciding which of the two morphotypes, E. crassus or E. vannus, is characterized by a larger or a medium cell body size (E. minuta being clearly distinct by a smaller morphotype). By analysing nuclear SSU-rRNA gene and ITS region sequences from 37 strains, previously assigned to E. crassus, E. minuta and E. vannus based on conventional taxonomic parameters, we identified and used ITS autapomorphic point mutations to design three species-specific primers. In combination with an Euplotes-generic primer, they proved to be very effective in running polymerase chain reactions that produce amplicons of species-specific size that reliably resolve ambiguities in assigning strains to E. crassus, E. minuta or E. vannus.


Update on vitamin D status in sunshine-abundant Thailand, 2019-2020.
The prevalence of vitamin D deficiency worldwide remains unknown. In the Thai 4th National Health Examination Survey (2008-2009) cohort, ∼45% and 7% of the adult population had serum 25-hydroxyvitamin-D [25(OH)D] levels below the threshold of 75 and 50 nmol/L, respectively. Vitamin D has been a hot topic in the scientific community. The aim of this study was to uncover the current situation regarding vitamin D status in Thailand. Participants were 4098 adults ages 10 to 96 y, randomly selected from the Thai 6th National Health Examination Survey (2019-2020) cohort. Serum 25(OH)D levels were measured by liquid chromatography/tandem mass spectrometry. Data were expressed as mean ± SE and adjusted odds ratio (95% CI). Mean vitamin D status based on serum 25(OH)D was 88.2 nmol/L and differed by age, sex, residency, and religion. The prevalence of serum 25(OH)D <75 and <50 nmol/L were 31% and 4%, respectively. The prevalence of vitamin D deficiency was lower in individuals who lived in the northeastern part of Thailand or were male. The risk for vitamin D deficiency was lower than that in 2009. In multiple linear regression analysis, female sex, younger age, urbanization, a higher body mass index, Muslim religion, and living in Bangkok or the central region of Thailand were independently associated with lower serum 25(OH)D levels. The vitamin D status in the Thai population has improved over the past 10 y. This improvement may reflect an increased awareness related to adequate vitamin D status.


Novel biologic approaches to hematologic malignancies.
Biologic agents have made a major impact on the treatment of hematologic malignancies and will continue to play a major role as we better understand their function in normal and malignant cell regulation. The examples provided in this chapter are a brief introduction to the potential of these agents. Many have yet to be used in conjunction with current cytotoxic therapy in these diseases, and perhaps combinations will prove even more successful. This possibility provides substantial ground for further investigation and therapy.


Multi-omics profiling of CSF from spinal muscular atrophy type 3 patients after nusinersen treatment: a 2-year follow-up multicenter retrospective study.
Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in the SMN1 gene resulting in reduced levels of the SMN protein. Nusinersen, the first antisense oligonucleotide (ASO) approved for SMA treatment, binds to the SMN2 gene, paralogue to SMN1, and mediates the translation of a functional SMN protein. Here, we used longitudinal high-resolution mass spectrometry (MS) to assess both global proteome and metabolome in cerebrospinal fluid (CSF) from ten SMA type 3 patients, with the aim of identifying novel readouts of pharmacodynamic/response to treatment and predictive markers of treatment response. Patients had a median age of 33.5 [29.5; 38.25] years, and 80% of them were ambulant at time of the enrolment, with a median HFMSE score of 37.5 [25.75; 50.75]. Untargeted CSF proteome and metabolome were measured using high-resolution MS (nLC-HRMS) on CSF samples obtained before treatment (T0) and after 2 years of follow-up (T22). A total of 26 proteins were found to be differentially expressed between T0 and T22 upon VSN normalization and LIMMA differential analysis, accounting for paired replica. Notably, key markers of the insulin-growth factor signaling pathway were upregulated after treatment together with selective modulation of key transcription regulators. Using CombiROC multimarker signature analysis, we suggest that detecting a reduction of SEMA6A and an increase of COL1A2 and GRIA4 might reflect therapeutic efficacy of nusinersen. Longitudinal metabolome profiling, analyzed with paired t-Test, showed a significant shift for some aminoacid utilization induced by treatment, whereas other metabolites were largely unchanged. Together, these data suggest perturbation upon nusinersen treatment still sustained after 22 months of follow-up and confirm the utility of CSF multi-omic profiling as pharmacodynamic biomarker for SMA type 3. Nonetheless, validation studies are needed to confirm this evidence in a larger sample size and to further dissect combined markers of response to treatment.


Studies on the effects of estrogen on antibody responses in asymptomatic HB virus carriers and non-responders to HB vaccine inoculation.
Antibody-forming cells against trinitrophenylated sheep red blood cells (TNP-SRBC) were induced to similar extents, when peripheral blood mononuclear cells from normal individuals, non-responders to HB vaccine inoculation and asymptomatic HBV carriers were stimulated in vitro with pokeweed mitogen (PWM). Although these antibody responses were significantly augmented by adding estrogen simultaneously with PWM to mononuclear cell cultures prepared from normal individuals, no such augmentation was demonstrable in cultures from asymptomatic HBV carriers and non-responders to HB vaccine inoculation. Interleukin-1 production and DNA synthesis in PWM- and PHA-stimulated mononuclear cell were also increased by estrogen in normal individuals, but not in the other two groups. These observations suggest that asymptomatic HBV carriers and non-responders to HB vaccine inoculation share a similar deficiency, not found in normal subjects, with regard to the modulatory effects of estrogen.


Analysis of conformational and sequential IgE epitopes on the major allergen Cry j 2 of Japanese cedar (Cryptomeria japonica) pollen in humans by using monoclonal antibodies for Cry j 2.
Japanese cedar (Cryptomeria japonica; CJ) pollinosis is a type I allergy induced by CJ pollen, and Cry j 2 is one of the major allergens in this pollen. In a previous study, we analyzed IgE epitopes on Cry j 2 in humans by using synthetic peptides. The main purpose of this study was to identify B-cell epitopes on Cry j 2 in patients with CJ pollinosis by using monoclonal antibodies (mAbs) for Cry j 2. We used ELISA with mAbs for the epitope analysis. Sera samples were collected from 80 patients with CJ pollinosis, and allergenic epitopes for mAbs and human IgE were identified using ELISA with synthetic peptides. The importance of the epitopes for human IgE was analyzed using an inhibition ELISA. Four independent epitopes (epitope #1, #2, #3, and #4) were identified on Cry j 2 with the use of mAbs. Epitope #3 and #4, corresponding to peptides No. 25 and No. 33, respectively, were newly determined as epitopes for mAbs and human IgE. Inhibition ELISA showed that not only epitope #2 (sequential) but epitope #1 (conformational) may play an important role in the CJ pollinosis. Our results revealed 4 epitopes, including two new ones, on Cry j 2. We also found that inhibition ELISA with appropriate mAbs could be a viable method of evaluating the importance of the conformational and sequential epitopes for human IgE. These results are beneficial for the development of safer and more efficient therapeutic strategies for treating CJ pollinosis.


Phonon engineering in Yb:La2CaB10O19 crystal for extended lasing beyond the fluorescence spectrum.
Since the first invention of the laser in 1960, direct lasing outside the fluorescence spectrum is deemed impossible owing to the "zero-gain" cross-section. However, when electron-phonon coupling meets laser oscillation, an energy modulation by the quantized phonon can tailor the electronic transitions, thus directly creating some unprecedented lasers with extended wavelengths by phonon engineering. Here, we demonstrate a broadband lasing (1000-1280 nm) in a Yb-doped La2CaB10O19 (Yb:LCB) crystal, far beyond its spontaneous fluorescence spectrum. Numerical calculations and in situ Raman verify that such a substantial laser emission is devoted to the multiphonon coupling to lattice vibrations of a dangling "quasi-free-oxygen" site, with the increasing phonon numbers step-by-step (n = 1-6). This new structural motif provides more alternative candidates with strong-coupling laser materials. Moreover, the quantitative relations between phonon density distribution and laser wavelength extension are discussed. These results give rise to the search for on-demand lasers in the darkness and pave a reliable guideline to study those intriguing electron-phonon-photon coupled systems for integrated photonic applications.


Limited recovery from post-acute sequelae of SARS-CoV-2 at 8 months in a prospective cohort.
In a longitudinal cohort, a significant proportion of patients had persistent symptoms 8 months after initial #COVID19 infection. There was no significant improvement in symptoms or health-related quality of life between 4- and 8-month assessments. https://bit.ly/2Wtb7IX.


Augmented anandamide signalling in the substantia nigra pars reticulata mediates panicolytic-like effects in mice confronted by Crotalus durissus terrificus pit vipers.
The endocannabinoid modulation of fear and anxiety due to the on-demand synthesis and degradation is supported by a large body of research. Although it has been proposed that anandamide (AEA) in the substantia nigra pars reticulata (SNpr) seems to be important for the organisation of innate fear-related behaviours, a role for endogenous AEA has yet to be clarified. Mice were treated with the fatty acid amide hydrolase (FAAH) selective inhibitor URB597 at different concentrations (0.01, 0.1, 1 nmol/0.1 µL) in the SNpr and confronted by rattlesnakes (Crotalus durissus terrificus). The most effective dose of URB597 (1 nmol) was also preceded by microinjections of the CB1 receptor antagonist AM251 (0.1 nmol) into the SNpr, and mice were then confronted by the venomous snake. URB597 (0.1 and 1 nmol) in the SNpr decreased the expression of defensive behaviours such as defensive attention, escape, and time spent inside the burrow of mice confronted by rattlesnakes. Moreover, pretreatment of SNpr with AM251 suppressed these antiaversive effects of URB597 in this midbrain structure. Overall, these data clearly indicate that the panicolytic consequences of endogenous AEA enhancement in the SNpr are mediated by CB1 receptor signalling.


Deporting "Bad Hombres"? The Profile of Deportees under Widespread versus Prioritized Enforcement.
U.S. President Trump's administration has vowed to boost immigration enforcement to get rid of "bad hombres," or undocumented immigrants with criminal records. Using past data on the alleged detention motives for a representative sample of Mexican deportees, we evaluate how prior widespread and prioritized enforcement has fared in that regard. We find that while the early sweeping approach to enforcement raised deportees' propensity of being detained for minor offenses, the trend reversed with prioritized enforcement. These findings inform policy tactics that, aside from proving effective in prioritizing serious criminal offenses, can also lead to significant savings to taxpayers.


Rare occurrence of metastasis from lung cancer to the anus: case report and review of the literature.
Anal metastases from lung cancer are infrequent, and there are only 10 published cases. Life expectancy is no longer than 1 year after diagnosis because of the typically advanced stage of disease. Treatment, which is typically inefficient, is administered with the intent to cure or avoid local complications. We report a case of a patient with non-small cell lung cancer presenting with perianal metastasis mimicking an abscess. Because perianal masses may be misdiagnosed, patients with lung and other cancers should be evaluated for metastatic disease.


Efficacy and Tolerance of Single-dose Azithromycin for Treatment of Chlamydial Cervicitis During Pregnancy.
The intent of this study was to determine the efficacy and tolerance of single-dose oral azithromycin in the treatment of pregnant women with endocervical chlamydial carriage. A retrospective review of clinic records over a two-year period identified pregnant patients treated with a single 1-g dose of azithromycin for chlamydial carriage. The side effects and subsequent chlamydial carriage (test of cure) were noted. A total of 146 pregnant women treated with azithromycin was reviewed. A cure rate of 96% was found. Side effects were reported in 5%. A single 1-g oral dose of azithromycin is effective for the treatment of chlamydia and is well tolerated in pregnant women.


Comparative effects of almitrine and raubasine, singly and in combination, on electroencephalographic activity in young and old rats.
A new method for quantification of electroencephalographic (EEG) signals was used to study the effects of almitrine and raubasine, alone and in combination, in two groups of six unanesthetized rats, aged 8 months (young) and 22 months (old). Coadministration of almitrine (7.5 mg/kg-1 i.p.) and raubasine (2.5 mg/kg-1 i.p.) induced an increased EEG power from 7 to 30 Hz; the frequencies concerned were identical in young and old rats, but the degree of their power variations was more marked in old rats. Almitrine induced a 20 to 50% increase in EEG power in young rats on nearly all spectral components. The effects of almitrine were only seen in the low-frequency range in old rats. Raubasine increased the EEG power in the 10 to 20 Hz frequency range; these effects were significantly greater in old rats. In both age groups, the effects on EEG power observed with coadministration of almitrine and raubasine were significantly different from those expected if raubasine and almitrine add their individual effects. These results show that a) almitrine and raubasine modify cortical electrical activity in a different manner as a function of age; b) the modification of the EEG activity induced by the coadministration is suggestive of an interaction between the cortical effects of each drug; and c) the modification of EEG power induced by the coadministration is qualitatively identical in young and old rats but quantitatively more marked in old rats.


Pseudo-continuous arterial spin labeling MRI study of patients with obsessive-compulsive disorder.
Arterial spin labeling (ASL) magnetic resonance imaging is a novel technique that can measure regional cerebral blood flow (rCBF). Here we used pseudo-continuous ASL (pCASL) to examine the structural and functional imaging data in patients with obsessive-compulsive disorder (OCD). We estimated the gray matter volume imaging and pCASL imaging data by means of a voxel-by-voxel statistical analysis. We evaluated the differences of rCBF and gray matter volume between the OCD patients and healthy subjects. We detected a significant rCBF reduction in OCD patients in the right posterior cingulate extending to the lingual gyrus, thalamus, and hippocampus, and a significant increase in the left temporal gyrus and left frontal white matter region, compared with healthy subjects. We also observed a significant reduction in gray matter volume of OCD patients in the right hippocampus. We also estimated the correlation between the clinical severity of OCD and the rCBF and gray matter volumes, and found significant negative correlations between the severity of illness and the regional gray matter volume in the bilateral anterior cingulate corti. Our study demonstrated significant changes of rCBF in the cortico-striato-thalamo-cortical pathway around the hippocampus in OCD patients. These findings may help to elucidate the pathogenesis of OCD.


Engineering a calcium-dependent conformational change in Calbindin D9k by secondary elements replacement.
EF-hand is a common motif in Ca2+-binding proteins, some of which present a conformational change upon Ca2+-binding, a relevant property for signal transduction. In the present work, we investigated the behavior of Calbindin D9k, a modulator protein with a high affinity for Ca2+ but structurally insensitive to its presence. Its non-canoncal N-terminal EF-hand was replaced by chimeric motifs, containing increasing structural elements from the sensor troponin C SCIII motif. We demonstrated that the loop and helix II were the necessary elements for a conformational change promoted by calcium in chimeric Calbindin D9k. Fusion of the isolated chimeric motifs to an activity reporter gene showed the loop as the minimal element to promote a conformational change. The discrepancy between these results is discussed in the light of inter-motif interactions and helix I participation in modulating the Ca2+ affinity and restricting motif conformation.


Event-related potentials and item recognition in depressed, schizophrenic and alcoholic patients.
Auditory event-related potentials (ERPs) to pure tones and performance on a measure of item recognition were compared in 20 controls, 14 alcoholics, 20 depressed and 21 schizophrenic patients. Compared with normal controls, P2 and N2 were delayed and of diminished amplitude in the psychopathological groups. Increased amplitude of P1 in alcoholics, diminished N1 in depressed patients, increased latencies of N1 in schizophrenics and N2 in alcoholics were pathology-specific. Unusual patterns of response in the item recognition test (elevated intercept and flattened slope) and its relationship with ERPs distinguished the diagnostic groups from the controls. Support for the preferential involvement of the left hemisphere in schizophrenia and of the right hemisphere in depression was found. Disinhibition of CNS activity in the response of alcoholics (increased P1 and delayed P3) was indicated. The findings suggested that discriminant analysis of auditory ERPs to simple, pure tones, in conjunction with psychometric data significantly differentiated pathologic groups from each other and from controls.


Comprehensive review of the current literature on impact of ambient air pollution and sleep quality.
Air pollution is associated with increasing morbidity, mortality and decreasing health and life span. Accumulating epidemiological and experimental evidence has shown that exposure to ambient air pollutants such as particulate matters (PM) and gaseous components [eg, nitrogen dioxide (NO2), ozone (O3)] has detrimental effects on sleep quality. We conducted this comprehensive review to explore the association between ambient air pollution and sleep quality. A systematic search was conducted with the databases of PubMed and Web of Science from inception to November 2019. Overall, 15 studies with 133,695 subjects that evaluated the association between ambient air pollution and sleep quality were conducted in 10 different countries (ie, USA, Brazil, Canada, Chile, China, Egypt, Germany, Iran, Mexico, and Turkey). Most included studies in the current review have shown that one or more air pollutants have negative influences on sleep quality. Air pollutants might be one of the triggers for poor sleep quality via disparate mechanisms including but not limited to the central ventilator control centers, central nervous system, allergic and non-allergic mechanisms. The possible association between air pollution and select chronic diseases (eg, mental illnesses, cardiovascular diseases) and behaviors (eg, impulsivity) may also play important roles in explaining the association between ambient air pollution and sleep quality. The associations and underlying mechanisms between ambient air pollutants and sleep quality need to be clarified with long-term, multi-centered cohort studies.


Undernutrition during suckling and latent learning ability of rehabilitated adult male rats.
The present report investigates the effects of early undernutrition on the latent learning ability of rehabilitated adult male rats in a simple maze task. Rats were undernourished during suckling by feeding their dams an 8% casein diet. Well-nourished dams received a 25% casein diet during the same period. Rats were weaned at 21 days of age and nutritionally rehabilitated until they became adults, when behavioral task was conducted. Under a nonappetitive condition, rats were exposed either to an open field or to a maze apparatus. They were thereafter deprived of water and tested in the maze apparatus. Both well-nourished and undernourished rats that had been previously exposed to the maze performed better than those exposed to the open field. Nutritional treatment had no effect on performance of either the latent learning or of the open-field groups. These results suggest that rehabilitated adult rats are able to learn about the environment when no immediate reinforcement is involved. The discrepancy between our findings and results reported by others may be due to differences in task complexity and/or perhaps to the fact that nutritional rehabilitation also plays a role in reversing some of the deleterious effects of early undernutrition on learning ability of rats.


Viral replication centers and the DNA damage response in JC virus-infected cells.
JCV is a human polyomavirus (PyV) that establishes a persistent infection in its host. Current immunomodulatory therapies, such as Natalizumab for multiple sclerosis, can result in JCV reactivation, leading to the debilitating brain disease progressive multifocal leukoencephalopathy (PML). JCV is among the viruses that recruit and modulate the host DNA damage response (DDR) to replicate its genome. We have identified host proteins recruited to the nuclear sites of JC viral DNA (vDNA) replication using three cell types susceptible to infection in vitro. Using confocal microscopy, we found that JCV recruited a similar repertoire of host DDR proteins to these replication sites previously observed for other PyVs. Electron tomography of JCV "virus factories" showed structural features like those described for murine PyV. These results confirm and extend previous observations for PyVs to JCV emphasizing a similar replication strategy among members of this virus family.


Comparative Analysis of Gene Expression Patterns for Oral Epithelium-Related Functions with Aging.
Epithelial cells and functions of the epithelium are critical to the health of the oral cavity. We used a nonhuman primate model to profile the transcriptome of gingival tissues in health across the lifespan and hypothesized that in older animals, epithelial-related transcriptome patterns would reflect epithelial cells that are aggressively responsive to the surrounding environment and less able to modulate and resolve the noxious challenge from the bacteria. Rhesus monkeys (n = 34) with a healthy periodontium were distributed into four groups: ≤3 years (young), 3-7 years (adolescent), 12-16 years (adult), and 18-23 years (aged), and a buccal gingival sample from the premolar/molar region of each animal was obtained. RNA was subjected to a microarray analysis (GeneChip® Rhesus Macaque Genome Array, Affymetrix), and 336 genes examined that are linked to epithelium and epithelial cell functions categorized into 9 broad functional groups: extracellular matrix and cell structure; extracellular matrix remodeling enzymes; cell adhesion molecules, cytoskeleton regulation; inflammatory response; growth factors; kinases/cell signaling; cell surface receptors; junction associated molecules; autophagy/apoptosis; antimicrobial peptides; and transcription factors. Total of 255 genes displayed a normalized signal >100, and differences across the age groups were observed primarily in extracellular matrix and cell structure, cell adhesion molecules, and cell surface receptor gene categories with elevations in the aged tissues. Keratins 2, 5, 6B, 13, 16, 17 were all significantly increased in healthy-aged tissues versus adults, and keratins 1 and 2 were significantly decreased in young animals. Approximately 15 integrins are highly expressed in the gingival tissues across the age groups with only ITGA8, ITGAM (CD11b), and ITGB2 significantly increased in the aged tissues. Little impact of aging on desmosomal/hemidesmosomal genes was noted. These results suggest that healthy gingival aging has a relatively limited impact on the broader functions of the epithelium and epithelial cells, with some effects on genes for extracellular matrix and cell adhesion molecules (e.g., integrins). Thus, while there is a substantial impact of aging on immune system targets even in healthy gingiva, it appears that the epithelial barrier remains reasonably molecularly intact in this model system.


Interleukin-6 and insulin incrase and nitric oxide and adiponectin decrease in blind dogs with pituitary-dependent hyperadrenocorticism.
In this study, two populations of dogs with pituitary dependent hypercortisolism (PDH) were compared over a 2-year period. One group had normal vision (Group A, n=27) and one group was blind (Group B, n=20). Group B was characterised by the rapid appearance of the clinical signs of PDH that precede blindness. We found increases in pre-adrenocorticotropic hormone cortisol (P=0.002), IL-6 (P=0.0001), insulin, and insulin sensitivity (detected with the Homeostatic Model Assessment, P<0.0001) in Group B but not in Group A. The nitric oxide (NO) and the total adiponectin concentrations decreased (P=0.0001 and P=0.02, respectively) in Group B versus Group A. The IL-6 and insulin concentrations and the HOMA-A index were positively correlated with the cortisol concentration and were negatively correlated with the NO concentration. With the exception of adiponectin, the other variables were associated with blindness. We concluded that blindness in PDH is a haemodynamic event associated with metabolic changes, with the increase in the IL-6 concentration and the decrease in the NO concentration affecting the retinal vasculature and producing a high risk of vision loss.


RT distribution analysis of category congruence effects with masked primes.
In the number magnitude decision task ("Is the number bigger/smaller than 5?"), response to a target (e.g., 3) is faster following a masked prime congruent with the target (e.g., 1) than it is following an incongruent prime (e.g., 9). This category congruence effect has been reported to be "interference-dominant" relative to a neutral prime (e.g., the # sign, the number 5) on the basis of the analysis of mean response time (RT). Using RT distribution analysis as well as mean RTs, we identified two bases for this pattern. One relates to the choice of neutral baseline: The # prime, unlike the digit prime, does not factor in the cost of perceptual transition between the prime and target, and therefore underestimates facilitation and overestimates the interference effect. The second basis of the interference-dominant pattern is a disproportionate slowdown of congruent trials in the slow RT bins. Furthermore, this slowdown is greater for primes that had been used as targets than it is with "novel" primes that have not been responded to as targets. We interpret the results as suggesting that the category congruence effect has two components with different time courses-one based on stimulus-response mapping, and the other on semantic categorization.


Office-based transurethral devascularisation of low grade non-invasive urothelial cancer using diode laser. A feasibility study.
Frequent recurrence of non-muscle invasive bladder tumours (NMIBC) requiring transurethral resection of bladder tumour (TUR-BT) and lifelong monitoring makes the lifetime cost per patient the highest of all cancers. A new method is proposed for the removal of low grade NMIBCs in an office-based setting, without the need for sedation and pain control and where the patient can leave immediately after treatment. An in vitro model was developed to examine the dose/response relationship between laser power, treatment time, and distance between laser fibre and target, using a 980 nm diode laser and chicken meat. The relationship between depth and extent of tissue destruction and the laser settings was measured using microscopy and non-parametric statistical analysis. A patient with low grade stage Ta tumour and multiple comorbidity, and therefore not fit for general anaesthesia, had a tumour devascularised using the laser at the tumour base, in the outpatient department. The tumour was left in the bladder. In the in vitro model, depth of tissue destruction increased with laser illumination up to 30 seconds, where median depth was 4.1 mm. With longer illumination the tissue destruction levelled off. The width of tissue destruction was 2-3 mm independent of laser illumination time. The in vivo laser treatments devascularised the tumour, which was later shed from the mucosa and passed out with the urine in the days following treatment. Pain score was 0 on a visual log scale (0-10). The tumour had completely disappeared two weeks after treatment. This diode laser technique may provide almost pain-free office-based treatment of low grade urothelial cancer using flexible cystoscopes in conscious patients. A prospective randomised study will be scheduled to compare the technique with standard TUR-BT in the operating theatre.


An evaluation of the Child Perceptions Questionnaire in the UK.
To assess the reliability and validity of the Child Perceptions Questionnaire (CPQ11-14), an oral health related quality of life measure for 11-14 year old children, for use in the UK. Cross-sectional questionnaire and clinical analytical study. Orthodontic and paediatric dentistry clinics at a dental hospital and one general dental practice. Eighty-nine children between 11 and 14 years of age attending for an examination. The children were invited to complete the CPQ11-14, global oral health and impact on life overall ratings. Clinical data on caries status, malocclusion and presence of dental opacities and gingivitis were collected. CPQ11-14 was summarised as the total score (sum of the item codes) and the number of impacts reported often or every day. The Cronbach's alpha for the total scale was 0.87 and ranged from 0.59 to 0.83 for the subscales indicating acceptable internal consistency. The intraclass correlation coefficient on repeated application of the measure was 0.83 (95% CI = 0.76-0.90) suggesting almost perfect agreement. Summary measures of CPQ11-14 correlated with the global oral health rating indicating acceptable criterion validity. Impact on life overall was related to all summary measures of CPQ11-14. Number of impacts correlated with the total number of missing teeth and missing teeth due to caries. No other relationships between clinical and CPQ11-14 data were apparent. The CPQ11-14 shows acceptable reliability, criterion and construct validity in relation to life overall. Relationships with clinical data were more tenuous. If this measure is to be used to compare the impacts of oral diseases in similar settings in the UK a large sample will be required.


Management of a failed endodontic treatment for a maxillary second molar with two separate palatal roots.
Complexity of root canal system and variations in internal anatomy of teeth require careful analysis of preoperative cone beam computed tomography or multiangle radiographs to locate and identify possible extra roots or canals. A fourth canal in upper molars is expected, and much effort should be made when planning the endodontic treatment to avoid missing a canal.


[Extensive cellulitis during chicken-pox. Six causes (author's transl)].
The authors report 6 cases of extensive cellulitis, in 6 children with chicken-pox. This is a rare complication during this disease. If streptococcal etiology is not always proved, clinical aspect and the dramatic reponse to treatment by penicillin G, characterize this kind of complication.


PPARα activation improves endothelial dysfunction and reduces fibrosis and portal pressure in cirrhotic rats.
Peroxisome proliferator-activated receptor α (PPARα) is a transcription factor activated by ligands that regulates genes related to vascular tone, oxidative stress, and fibrogenesis, pathways implicated in the development of cirrhosis and portal hypertension. This study aims at evaluating the effects of PPARα activation with fenofibrate on hepatic and systemic hemodynamics, hepatic endothelial dysfunction, and hepatic fibrosis in CCl(4)-cirrhotic rats. Mean arterial pressure (MAP), portal pressure (PP), and portal blood flow (PBF) were measured in cirrhotic rats treated with oral fenofibrate (25mg/kg/day, n=10) or its vehicle (n=12) for 7 days. The liver was then perfused and dose-relaxation curves to acetylcholine (Ach) were performed. We also evaluated Sirius Red staining of liver sections, collagen-I mRNA expression, and smooth muscle actin (α-SMA) protein expression, cyclo-oxygenase-1 (COX-1) protein expression, and cGMP levels in liver homogenates, and TXB(2) production in perfusates. Nitric oxide (NO) bioavailability and eNOS activation were measured in hepatic endothelial cells (HEC) isolated from cirrhotic rat livers. CCl(4) cirrhotic rats treated with fenofibrate had a significantly lower PP (-29%) and higher MAP than those treated with vehicle. These effects were associated with a significant reduction in hepatic fibrosis and improved vasodilatory response to acetylcholine. Moreover, a reduction in COX-1 expression and TXB(2) production in rats receiving fenofibrate and a significant increase in NO bioavailability in HEC with fenofibrate were observed. PPARα activation markedly reduced PP and liver fibrosis and improved hepatic endothelial dysfunction in cirrhotic rats, suggesting it may represent a new therapeutic strategy for portal hypertension in cirrhosis.


Investigation of the species-specific degradation behaviour of methylmercury and ethylmercury under microwave irradiation.
The degradation behaviour of methylmercury (MeHg) under microwave irradiation is investigated, as is the (different) degradation behaviour of ethylmercury (EtHg) under similar irradiation. A simple and highly sensitive SPME-GC-pyrolysis-AFS system was used to analyse the aqueous MeHg and EtHg standard solutions after derivatization with sodium tetraphenylborate (NaBPh(4)). Samples were irradiated in a microwave digester at microwave powers ranging from 20 to 160 W for durations of 2 to 10 min. The different tolerances towards microwave treatment of the two organomercury species were evident. Practically no degradation was experienced for MeHg for up to 8 minutes of irradiation at 120 W or for up to 4 minutes at 160 W. Significant analyte loss was observed for EtHg after 2 minutes at 40 W of microwave power.


Functional Mapping for Glioma Surgery, Part 1: Preoperative Mapping Tools.
Although intraoperative mapping of brain areas was shown to promote greater extent of resection and reduce functional deficits, this was shown only recently for some noninvasive techniques. Yet, proper surgical planning, indication, and patient consultation require reliable noninvasive techniques. Because functional magnetic resonance imaging, tractography, and neurophysiologic methods like navigated transcranial magnetic stimulation and magnetoencephalography allow identifying eloquent areas prior to resective surgery and tailor the surgical approach, this article provides an overview on the individual strengths and limitations of each modality.


Strong phylogenetic effects on floral scent variation of oil-secreting orchids in South Africa.
Evolution involves the interplay between natural selection and phylogenetic constraint. This is particularly evident among the flowering plants where form and diversity of flowers attest to the importance of both pollinator-mediated selection and phylogenetic constraint. Although this has been studied mostly using visible floral characters, invisible volatile chemicals emitted by the flowers should be subject to these same evolutionary forces. Unfortunately, most analyses of floral volatiles have over-emphasized the importance of natural selection and underplayed phylogenetic constraint without quantifying their respective roles in the evolution and composition of floral scents. We used multivariate analyses to test the relative importance of pollinators vs. phylogeny in determining the composition of floral scents among oil-secreting orchids in southern Africa. Floral scents of 42 oil-secreting taxa/ecotypes distributed among 12 subclades in the tribe Diseae were sampled using headspace adsorption and gas chromatography-mass spectroscopy. We identified 257 scent compounds distributed over nine different compound classes, with the majority of scents dominated by aliphatic or benzenoid compounds. The only significant predictor of floral scent among these orchids above the species level was phylogeny. Nevertheless, in two of the clades there were differences in scent profiles at the species and ecotype level that corresponded to different pollinators and were thus suggestive of pollinator-mediated selection. Scent variation was greater than expected and phylogeny was more important than pollinator-mediated selection in predicting the composition of floral scents of oil-secreting orchids, despite the specialized nature of the pollinator reward system.


Understanding experiences of mental health help-seeking in Arab populations around the world: a systematic review and narrative synthesis.
Racial and ethnic disparities in mental health service utilisation and access is well established. Mental illness is common among Arab populations globally, but most individuals display negative attitudes towards mental health and do not seek professional help. The aim of this systematic review was to determine 1) help-seeking behaviours 2) help-seeking attitudes and 3) help-seeking barriers and facilitators, related to mental health services among Arab adults. A pre-defined search strategy and eligibility criteria allowed for database searching using terms related to: mental health, Arabs, help-seeking, as well as experiences and behaviours. Seventy-four articles were included and analysed through narrative synthesis. Results were reported using the PRISMA guidelines. The review protocol was registered prospectively on PROSPERO (CRD42022319889). Arabs across the world have negative attitudes towards formal help-seeking and are reluctant to seek help, despite the presence of psychological distress. There is little information on factors that influence help-seeking behaviours and rates of service use. Preference for informal help sources such as family and friends were expressed and considered more acceptable. Low mental health literacy, stigma, gender, age, education, religion, acculturation, and immigrant status were the most common factors influencing help-seeking attitudes. Barriers to help-seeking included stigma, privacy and confidentiality, trust, mental health literacy, language, logistics, and culture related barriers. Increasing societal and family awareness, external support and encouragement, shared culture between the client and therapist, quality of doctor patient relationship, and feelings of connectedness with the host country among refugees were mentioned facilitators. Mixed findings for the role of religion, and family and community, in relation to facilitating or hindering help-seeking were reported. There is an increased likelihood and preference to seek informal sources of psychological support among Arabs. Contextual and cultural factors impeding help-seeking for Arabs are common across the world. Future research should address actual utilisation rates of services to better understand factors that influence help-seeking behaviours and facilitators to help-seeking. Increasing mental health literacy and developing anti stigma campaigns is necessary. Developing culturally informed interventions should inform future efforts to promote help-seeking among this population.


Association of the use of diabetes technology with HbA1c and BMI-SDS in an international cohort of children and adolescents with type 1 diabetes: The SWEET project experience.
To examine the association between the use of diabetes technology (insulin pump [CSII], glucose sensor [CGM] or both) and metabolic control (HbA1c) as well as body adiposity (BMI-SDS) over-time in a cohort of children and adolescents with type 1 diabetes (T1D), that have never used these technologies before. Four thousand six hundred forty three T1D patients (2-18 years, T1D ≥1 year, without celiac disease, no CSII and/or CGM before 2016) participating in the SWEET prospective multicenter diabetes registry, were enrolled. Data were collected at two points (2016; 2019). Metabolic control was assessed by glycated hemoglobin (HbA1c) and body adiposity by BMI-SDS (WHO). Patients were categorized by treatment modality (multiple daily injections [MDI] or CSII) and the use or not of CGM. Linear regression models, adjusted for age, gender, duration of diabetes and region, were applied to assess differences in HbA1c and BMI-SDS among patient groups. The proportion of patients using MDI with CGM and CSII with CGM significantly increased from 2016 to 2019 (7.2%-25.7%, 7.8%-27.8% respectively; p < 0.001). Linear regression models showed a significantly lower HbA1c in groups that switched from MDI to CSII with or without CGM (p < 0.001), but a higher BMI-SDS (from MDI without CGM to CSII with CGM p < 0.05; from MDI without CGM to CSII without CGM p < 0.01). Switching from MDI to CSII is significantly associated with improvement in glycemic control but increased BMI-SDS over-time. Diabetes technology may improve glucose control in youths with T1D although further strategies to prevent excess fat accumulation are needed.


Optical sensing nanostructures for porous silicon rugate filters.
Porous silicon rugate filters [PSRFs] and combination PSRFs [C-PSRFs] are emerging as interesting sensing materials due to their specific nanostructures and superior optical properties. In this work, we present a systematic study of the PSRF fabrication and its nanostructure/optical characterization. Various PSRF chips were produced with resonance peaks that are adjustable from visible region to near-infrared region by simply increasing the periods of sine currents in a programmed electrochemical etching method. A regression analysis revealed a perfect linear correlation between the resonant peak wavelength and the period of etching current. By coupling the sine currents with several different periods, C-PSRFs were produced with defined multiple resonance peaks located at desired positions. A scanning electron microscope and a microfiber spectrophotometer were employed to analyze their physical structure and feature spectra, respectively. The sensing properties of C-PSRFs were investigated in an ethanol vapor, where the red shifts of the C-PSRF peaks had a good linear relationship with a certain concentration of ethanol vapor. As the concentration increased, the slope of the regression line also increased. The C-PSRF sensors indicated the high sensitivity, quick response, perfect durability, reproducibility, and versatility in other organic gas sensing.


Prenatal ethanol and stress in mice: 2. Development and behavior of fostered offspring.
On days 12 to 17 of gestation, B6D2F2 mice were pair-fed liquid diets containing either 25% ethanol-derived calories or an isocaloric amount of maltose-dextrin. During this time, half the mice in each dietary condition also underwent two daily one-hour periods of restraint stress. All pups were fostered at birth to untreated mothers whose pups, in turn, were fostered to the treated mothers. Two additional groups of untreated dams were included, the pups in one group being fostered to other untreated dams while the rest remained with their biological mothers. Prenatal ethanol retarded neurobehavioral development on day 32 postconception and also decreased pup body weight at birth and at weaning, and brain weight on day 32 and at weaning. Prenatal stress decreased body weight at birth in the pair-fed controls only, increased open field activity at weaning and affected retention of a learned passive avoidance task. Undernutrition due to the pair feeding procedure decreased pup birth weight. There were a few effects on untreated pups fostered to treated dams, but these were marginal. These results do not support a role of stress-induced physiological changes in ethanol teratogenicity.


Structural and functional characterization of osmotically inducible protein C (OsmC) from Thermococcus kodakaraensis KOD1.
Osmotically inducible protein C (OsmC) is involved in the cellular defense mechanism against oxidative stress caused by exposure to hyperoxides or elevated osmolarity. OsmC was identified by two-dimensional electrophoresis (2DE) analysis as a protein that is overexpressed in response to osmotic stress, but not under heat and oxidative stress. Here, an OsmC gene from T. kodakaraensis KOD1 was cloned and expressed in Escherichia coli. TkOsmC showed a homotetrameric structure based on gel filtration and electron microscopic analyses. TkOsmC has a significant peroxidase activity toward both organic and inorganic peroxides in high, but not in low temperature.


Preoperative pulmonary blood flow and one-lung anaesthesia.
The distribution of pulmonary blood flow was measured in supine patients before surgery by means of lung perfusion scanning with 99mTc-macroaggregated albumin in an attempt to predict values of PaO2 during subsequent one-lung anaesthesia. The PaO2 values during one-lung anaesthesia were well correlated with the preoperative lung perfusion partition ratios (r = 0.84, p less than 0.05). In 9 of 40 patients, PaO2 was less than 80 mmHg during one-lung ventilation (FIO2 0.99). In these patients the lung perfusion ratios of the dependent lung were as low as 41.0-48.2 per cent. These results indicate that preoperative measurement of pulmonary blood flow can predict values of PaO2 during one-lung anaesthesia.


Child maltreatment and teenage first births: a relationship mediated by chronic sociodemographic stress?
Data were obtained from low-income, single-parent mothers for a test of the "life course" hypothesis that chronic stress mediates the relationship between teenage motherhood and both physical abuse and neglect of children. Large numbers of live births, a life history of unemployment, and low educational achievement were the measured stressors. Findings support the hypothesis, showing the number of live births as the most important mediator for both types of maltreatment.


Association between human leukocyte antigen class I and II alleles and hepatitis C virus infection in high-risk hemodialysis patients awaiting kidney transplantation.
Recent evidences have shown that several host genetic factors influence susceptibility or protection to hepatitis C virus (HCV) infection. There are controversial data regarding the associations of human leukocyte antigens (HLA) and the clearance or progression of HCV. The aim of this study was to investigate whether particular HLA molecules were associated with HCV infection in recipients awaiting kidney transplantation considered at high-risk to infection due to protracted hemodialysis treatment. To this purpose, 301 kidney recipients with HCV infection and 1103 uninfected recipients were examined for HLA class I and II molecules. In our case-control study, HLA-A(*)26 is positively associated with HCV infection while HLA-A(*)29, -B(*)40 and -DRB1(*)01 are negatively associated with HCV infection. Multiple logistic regression analysis demonstrated that age (OR = 1.02; 95% CI = 1.01-1.04; p < 0.00), HLA-A(*)26, -A(*)29, -B(*)40 and -DRB1(*)01 [(OR = 1.54; 95% CI = 1.03-2.30; p = 0.03); (OR = 0.50; 95% CI = 0.26-0.99; p = 0.05); (OR = 0.42; 95% CI = 0.23-0, 7; p = 0.01); (OR = 0.62; 95% CI = 0.41-0, 94; p = 0.03); respectively] are independent predictors of HCV infection. Our results suggest that particular HLA molecules, as host genetic factors, may have a relationship with susceptibility or protection to HCV infection also in recipients awaiting kidney transplantation.


Morphological changes along an altitude gradient and their consequences for an andean giant rosette plant.
Selected morphological features were measured in five populations of the giant rosette plant Espeletia schultzii occurring along an elevation gradient from 2600 to 4200 m in the Venezuelan Andes. Pith volume per amount of leaf area increases with elevation resulting in significantly larger water storage capacity at higher elevations. Thickness of leaf pubescence and, therefore, leaf boundary layer resistance, also increases with elevation resulting in both potentially higher leaf temperatures relative to air temperature and higher leaf to air vapor pressure gradients. The net effect on transpiration rate would depend on ratios of stomatal to boundary layer resistance and leaf energy balance. At higher elevations the central rosette leaves are more vertically oriented and the leaf bases show a pronounced curvature as the intersection with the main axis is approached. This gives these rosettes a distinctly paraboloid appearance and probably enhances capture and retention of incident long and shortwave radiation by the apical bud and expanding leaves. Features which result in enhanced water storage capacity and higher plant temperatures relative to air temperature without greatly increasing water loss are adaptive in high altitude paramo habitats where water availability and growth are limited by year round low temperatures (mean 2-3° C).


Functional characterization of two alternatively spliced transcripts of tomato ABSCISIC ACID INSENSITIVE3 (ABI3) gene.
Alternative splicing can produce transcripts that encode proteins with altered functions. The transcripts of the ABSCISIC ACID INSENSITIVE3 (ABI3)/VIVIPAROUS1 (VP1) gene, which is an important component in abscisic acid (ABA) signaling, are subjected to alternative splicing in both monocotyledons and dicotyledons. We identified two alternatively spliced tomato (Solanum lycopersicum) SlABI3 transcripts, SlABI3-F and SlABI3-T, which encode the nucleus-localized full-length and truncated proteins, respectively. The tissue-specific accumulation of SlABI3-F and SlABI3-T was determined, particularly in seeds at different developmental stages and in response to phytohormonal and abiotic stress. Ectopic over-expression of SlABI3-F and SlABI3-T resulted in the induction of seed-specific genes SlSOM, SlEM1 and SlEM6 in vegetative tissues. However, over-expression of SlABI3-F, but not SlABI3-T, activated expression of the downstream gene SlABI5 and conferred hypersensitivity to exogenous ABA during seed germination and primary root growth. In addition, the SlABI3-F protein interacted with SlABI5 much stronger than SlABI3-T did in the yeast two-hybrid assay. These results suggest that SlABI3-F and SlABI3-T have similar and distinct functionality in the ABA signaling, dependent on which tissue/organ they accumulate in.


LC-MS/MS method for determination of hederacolchiside E, a neuroactive saponin from Pulsatilla koreana extract in rat plasma for pharmacokinetic study.
A simple, rapid, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was applied to pharmacokinetic study of a neuroactive oleanolic-glycoside saponin, hederacolchiside E from SK-PC-B70M, a standardized extract of Pulsatilla koreana in rat. Rat plasma samples were pretreated by protein precipitation with acetonitrile, eluted from C(18) column, and analyzed using electrospray ionization (ESI)-MS/MS in negative ion mode. Digoxin was used as an internal standard. The standard curves were linear (r>0.997) over the concentration ranges of 2-500 ng/mL. The intra- and inter-day precisions were measured to be below 9% and accuracy between 90 and 111% for all quality control samples at 2, 20, 100, and 500 ng/mL (n=5). The lower limits of quantification (LLOQ) for hederacolchiside E was 2 ng/mL and the limit of detection (LOD) 0.5 ng/mL using 20 microL of plasma sample. Subsequently, hederacolchiside E was determined in rat plasma samples after oral administration of SK-PC-B70M. The mean maximum plasma concentrations of hederacolchiside E were 0.07, 0.13, and 0.36 microg/mL and the mean areas under the plasma concentration versus time curve 0.56, 1.27, and 6.46 microg h/mL at doses of 100, 200, and 400 mg/kg, respectively, which indicated non-linear pharmacokinetic pattern. In conclusion, this method was successfully applied to the pharmacokinetic study of hederacolchiside E after an oral administration of SK-PC-B70M to rats.


Detection of m6A-associated SNPs as potential functional variants for coronary artery disease.
To investigate the effects of m6A-single nucleotide polymorphisms (SNPs) on coronary artery disease (CAD). We examined the association of m6A-SNPs with CAD in about 185,000 cases and controls and further performed eQTL and differential expression analyses to support the identified m6A-SNPs. Among the 4390 m6A-SNPs detected, 304 seemed to be associated with CAD (p < 0.05). SNP rs12286 was significantly associated with CAD at genome-wide level (p = 4.5 × 10-9). rs12286 was predicted to influence m6A methylation and have the potential to alter regulatory motifs binding, which may in turn regulate the expression of ADAMTS7 (p = 1.26 × 10-8). The present study found plenty of CAD-associated m6A-SNPs and demonstrated the potential functionality of the identified SNPs.


Locked in grief: a qualitative study of grief among family members of missing persons in southern Sri Lanka.
The psychological and social issues experienced by family members of missing persons are different from normal grief following the death of a loved one. The term "Ambiguous loss" describes this psychological phenomenon. Ambiguous loss acts as a barrier to adjusting to grief, leading to symptoms of depression and intra and interpersonal relational conflicts. An in-depth phenomenological understanding of this subjective experience is important. A qualitative study was conducted among close family members of persons who had gone missing during the civil conflict and the 2004 tsunami in southern Sri Lanka following formal ethical approval from an university ethics review committee. Purposive and snowballing sampling methods were used to recruit the participants. Theoretical sample saturation was achieved with 24 family members of missing persons. Responders were mothers, fathers, wives, husbands, and siblings of missing individuals. In-depth interviews were recorded with the help of a semi-structured guide, after informed consent. The recordings were transcribed and coded by three independent investigators. The investigators through consensus arrived at the phenomenological themes and grounded them through reflexivity. The triangulation process involved cross-checking observational notes made by the interviewers and consulting the interviewees. We interviewed 24 first degree relatives of missing individuals. Twenty-one of the interviewees were unsure about the fate of the missing individual, while three of them believed the missing individual to be dead. Of the 24 missing individuals, 20 were males and 18 had gone missing in civil conflicts and 6 in the Indian Ocean Tsunami. Six predominant phenomenological themes were identified. Those were lack of closure, hope, guilt, helplessness, perpetual suffering, and an emotional vacuum. These phenomenological experiences are highlighted by the interviewees through a range of utterances that hold profound cultural, social and emotional significance of unresolved and vacillating grief. The highlighted phenomenology of grief in surviving family members of those who go missing following traumatic events demands a response from health and social services in every country that experiences disaster. The surviving loved one is 'locked in grief' indefinitely and future research on evidence-based interventions to overcome this predicament is warranted.


Design, synthesis, in vitro anticancer, molecular docking and SAR studies of new series of pyrrolo[2,3-d]pyrimidine derivatives.
The current study involves the design and synthesis of a newly synthesized pyrrolo[2,3-d]pyrimidine derivatives to contain chlorine atoms in positions 4 and 6 and trichloromethyl group in position 2 using microwave technique as a new and robust approach for preparation of this type of pyrrolo[2,3-d]pyrimidine derivatives. The chemical structure of the synthesized pyrrolo[2,3-d]pyrimidine derivatives 3-19 was well-characterized using spectral and elemental analyses as well as single-crystal X-ray diffraction. All compounds were tested in vitro against seven selected human cancer cell lines, namely, MCF7, A549, HCT116, PC3, HePG2, PACA2 and BJ1 using MTT assay. It was found that compounds 14a, 16b and 18b were the most active toward MCF7 with IC50 (1.7, 5.7, and 3.4 μg/ml, respectively) relative to doxorubicin (Dox.) (26.1 μg/ml). Additionally, compound 17 exerted promising cytotoxic effects against HePG2 and PACA2 with IC50 (8.7 and 6.4 μg/ml, respectively) relative to Dox. (21.6 and 28.3 μg/ml, respectively). The molecular docking study confirmed our ELISA result which showed the promising binding affinities of compounds 14a and 17 against Bcl2 anti-apoptotic protein. At the gene expression level, P53, BAX, DR4 and DR5 were up-regulated, while Bcl2, Il-8, and CDK4 were down-regulated in 14a, 14b and 18b treated MCF7 cells. At the protein level, compound 14b increased the activity of Caspase 8 and BAX (18.263 and 14.25 pg/ml) relative to Dox. (3.99 and 4.92 pg/ml, respectively), while the activity of Bcl2 was greatly decreased in 14a treated MCF7 (2.4 pg/ml) compared with Dox. (14.37 pg/ml). Compounds 14a and 14b caused cell cycle arrest at the G1/S phase in MCF7. Compounds 16b and 18b induced the apoptotic death of MCF7 cells. In addition, the percentage of fragmented DNA was increased significantly in 14a treated MCF7 cells.


Clinical features and immunotherapy outcomes of anti-glutamic acid decarboxylase 65 antibody-associated neurological disorders.
We described the clinical and neuroimaging characteristics of seven Chinese patients with anti-GAD65 antibody-associated neurological disorders of whom epileptic seizures were the initial and main symptoms. All patients were given immunotherapy and followed up monthly. The outcome demonstrates that immunotherapy is helpful for non-seizure manifestations of anti-GAD65-associated neurological autoimmunity and is less effective in the treatment of seizures, yet partial responses can still occur in the early stage. Taken together we suggest a trial with immunotherapy in all patients in the early stage of the disease, and in patients with non-epilepsy symptoms in the later stage.


A Molecular Hybridization Approach for the Design of Potent, Highly Selective, and Brain-Penetrant N-Myristoyltransferase Inhibitors.
Crystallography has guided the hybridization of two series of Trypanosoma brucei N-myristoyltransferase (NMT) inhibitors, leading to a novel highly selective series. The effect of combining the selectivity enhancing elements from two pharmacophores is shown to be additive and has led to compounds that have greater than 1000-fold selectivity for TbNMT vs HsNMT. Further optimization of the hybrid series has identified compounds with significant trypanocidal activity capable of crossing the blood-brain barrier. By using CF-1 mdr1a deficient mice, we were able to demonstrate full cures in vivo in a mouse model of stage 2 African sleeping sickness. This and previous work provides very strong validation for NMT as a drug target for human African trypanosomiasis in both the peripheral and central nervous system stages of disease.


Endoscopic components separation for abdominal compartment syndrome.
Sustained intraabdominal pressures of 14 to 20 mm Hg have significant pathophysiological consequences, but there is currently no satisfactory low-morbidity procedure appropriate for intervention early in the disease process of abdominal compartment syndrome (ACS). The anatomical principles of abdominal wall components separation were used to develop a percutaneous procedure that increased abdominal capacity and decreased abdominal pressure. Using a porcine model, we determined abdominal capacity changes by helium insufflation. Corn oil was then used to create an episode of sustained intraabdominal hypertension and changes in intraabdominal pressure and intestinal mucosal oxygenation were determined. Endoscopic abdominal wall components separation (EACS) increased abdominal capacity by 1 L (from 0.89 +/- 0.39 L to 1.95 +/- 0.48 L; P <0.001). During intraabdominal hypertension, EACS decreased abdominal pressure by 31.6% (from 15.9 +/- 2.1 to 11.0 +/- 1.5 mm Hg; P <0.001). Intestinal PO(2) was increased by 61% (18.8 +/- 11.4 to 30.3 +/- 11.7; P = 0.012) A minimally invasive procedure (EACS) is feasible and has demonstrated effectiveness in a porcine model of ACS.


Reducing preoperative fasting in elective adult surgical patients: a case-control study.
The practice of fasting from midnight prior to surgery is an outdated one. The aim of this study was to assess the impact of an evidence-based protocol for reduced preoperative fasting on fasting times, patient safety, and comfort. A non-randomised case-control study of preoperative fasting times among adult surgical patients undergoing elective procedures was conducted. Consecutive patients were allocated to a reduced preoperative fasting protocol allowing fluids and solids up to 2 and 6 h prior to anaesthesia, respectively (n = 21). These were compared to control patients identified from an historic study of preoperative fasting times who followed the traditional fast from midnight (n = 29). Fasting times and details of patients' subjective comfort were collected using an interview-assisted questionnaire. Incidence of intraoperative aspirations was obtained from anaesthetic records. Significant reductions in fasting times for fluids (p = 0.000) and solids (p = 0.000) were achieved following implementation of the fasting protocol. Less preoperative thirst (0.000), headache (0.012) and nausea (0.015) were reported by those who had a shorter fast. Intraoperative aspiration did not occur in either group. Implementation of this protocol for reduced preoperative fasting achieved an appreciable reduction in fasting times and enhanced patient comfort. Patient safety was not compromised. Further modifications of our protocols are necessary to meet the international best practice. We recommend its implementation across all surgical groups in our institution.


Predictive coding of action intentions in dorsal and ventral visual stream is based on visual anticipations, memory-based information and motor preparation.
Predictions of upcoming movements are based on several types of neural signals that span the visual, somatosensory, motor and cognitive system. Thus far, pre-movement signals have been investigated while participants viewed the object to be acted upon. Here, we studied the contribution of information other than vision to the classification of preparatory signals for action, even in the absence of online visual information. We used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis (MVPA) to test whether the neural signals evoked by visual, memory-based and somato-motor information can be reliably used to predict upcoming actions in areas of the dorsal and ventral visual stream during the preparatory phase preceding the action, while participants were lying still. Nineteen human participants (nine women) performed one of two actions towards an object with their eyes open or closed. Despite the well-known role of ventral stream areas in visual recognition tasks and the specialization of dorsal stream areas in somato-motor processes, we decoded action intention in areas of both streams based on visual, memory-based and somato-motor signals. Interestingly, we could reliably decode action intention in absence of visual information based on neural activity evoked when visual information was available and vice versa. Our results show a similar visual, memory and somato-motor representation of action planning in dorsal and ventral visual stream areas that allows predicting action intention across domains, regardless of the availability of visual information.


Highly Selective Electrocatalytic Olefin Hydrogenation in Aqueous Solution.
Selective hydrogenation of olefins with water as the hydrogen source at ambient conditions is still a big challenge in the field of catalysis. Herein, the electrocatalytic hydrogenation of purely aliphatic and functionalized olefins was achieved by using graphdiyne based copper oxide quantum dots (Cux O/GDY) as cathodic electrodes and water as the hydrogen source, with high activity and selectivity in aqueous solution at high current density under ambient temperature and pressure. In particular, the sp-/sp2 -hybridized graphdiyne catalyst allows the selective hydrogenation of cis-trans isomeric olefins. The chemical and electronic structure of the GDY results in the incomplete charge transfer between GDY and Cu atoms to optimize the adsorption/desorption of the reaction intermediates and results in high reaction selectivity and activity for hydrogenation reactions.


Non-invasive monitoring of cytotoxicity based on kinetic changes of cellular autofluorescence.
A quantitative, non-destructive cellular autofluorescence based in vitro imaging assay has been developed and applied to study the cytotoxicity of Sodium Lauryl Sulfate (SLS) and HgCl2 on Balb/c 3T3 cells. A phenomenological double logistic model was proposed to quantify and relate the observed kinetic changes of fluorescence to the toxic potency of chemical compounds. This work forms the basis for cellular autofluorescence measurements in in vitro toxicity screening assays.


Biochemical and mutational analyses of a multidomain cellulase/mannanase from Caldicellulosiruptor bescii.
Thermophilic cellulases and hemicellulases are of significant interest to the biofuel industry due to their perceived advantages over their mesophilic counterparts. We describe here biochemical and mutational analyses of Caldicellulosiruptor bescii Cel9B/Man5A (CbCel9B/Man5A), a highly thermophilic enzyme. As one of the highly secreted proteins of C. bescii, the enzyme is likely to be critical to nutrient acquisition by the bacterium. CbCel9B/Man5A is a modular protein composed of three carbohydrate-binding modules flanked at the N terminus and the C terminus by a glycoside hydrolase family 9 (GH9) module and a GH5 module, respectively. Based on truncational analysis of the polypeptide, the cellulase and mannanase activities within CbCel9B/Man5A were assigned to the N- and C-terminal modules, respectively. CbCel9B/Man5A and its truncational mutants, in general, exhibited a pH optimum of ∼5.5 and a temperature optimum of 85°C. However, at this temperature, thermostability was very low. After 24 h of incubation at 75°C, the wild-type protein maintained 43% activity, whereas a truncated mutant, TM1, maintained 75% activity. The catalytic efficiency with phosphoric acid swollen cellulose as a substrate for the wild-type protein was 7.2 s(-1) ml/mg, and deleting the GH5 module led to a mutant (TM1) with a 2-fold increase in this kinetic parameter. Deletion of the GH9 module also increased the apparent k(cat) of the truncated mutant TM5 on several mannan-based substrates; however, a concomitant increase in the K(m) led to a decrease in the catalytic efficiencies on all substrates. These observations lead us to postulate that the two catalytic activities are coupled in the polypeptide.


Discrete poly(A)- RNA species from rat liver mitochondria are fragments of 16S mitochondrial rRNA carrying its 5'-termini.
During electrophoresis in polyacrylamide gels containing 7M urea the major discrete components of preparations of rat liver mitochondrial poly(A)+ and poly(A)- RNA species have similar mobilities. Poly(A)- RNA components hybridize to the 16S rRNA gene of mtDNA. Analysis of 5'-terminal sequences of these components revealed their identity to the 5'-terminal sequence of 16S rRNA. These results show that poly(A)- RNA components are fragmentation products of 16S rRNA. Fragmentation occurs nonrandomly from the 3'-end of the original rRNA molecules and lead to formation of products with electrophoretic mobilities similar to those of poly(A)+ RNA components.


The effect of nitrous oxide on cortical cerebral blood flow during anesthesia with halothane and isoflurane, with and without morphine, in the rabbit.
The effect of nitrous oxide on cortical cerebral blood flow (CBF) was examined during a varying background anesthetic state in the New Zealand White rabbit. Seventy percent nitrous oxide resulted in significant and similar increases in CBF during anesthesia with both 0.5 MAC of halothane (44 +/- 14 to 63 +/- 17 ml.100 g-1.min-1) (mean +/- SD) and anesthesia with isoflurane (34 +/- 9 to 41 +/- 11 ml.100 g-1.min-1). During anesthesia with 1.0 MAC halothane or isoflurane, N2O also increased CBF, but the increments (halothane, 73 +/- 34 to 111 +/- 54 ml.100 g-1 min-1; isoflurane 34 +/- 13 to 69 +/- 34 ml.100 g-1.min-1) were significantly greater than those observed at 0.5 MAC. When 0.5 MAC halothane or isoflurane was supplemented with morphine (10 mg/kg followed by an infusion of 2 mg.kg-1.min-1), the CBF effect of N2O was not significantly different from that observed with 0.5 MAC alone. It was concluded that, in the rabbit, the effects of N2O on cortical CBF vary with the background anesthetic state and that the increase in CBF caused by N2O becomes greater as the end-tidal concentration of halothane or isoflurane increases from 0.5 to 1.0 MAC. Morphine, when added to 0.5 MAC of halothane or isoflurane, does not alter the effect of 70% N2O on cortical CBF.


Early diastolic function during exertion influences exercise intolerance in patients with hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) patients with preserved left ventricular ejection fraction (LVEF) often develop dyspnea and exercise intolerance. Diastolic dysfunction may contribute to exercise intolerance in these patients. This study aimed to clarify our hypothesis as to whether diastolic function rather than systolic function would be associated with exercise intolerance in HCM using two-dimensional (2D) speckle tracking echocardiography during exercise. Thirty-three HCM patients (mean age 59.3 ± 15.7 years) underwent 2D speckle tracking echocardiography at rest and during submaximal semi-supine bicycle exercise. Global longitudinal strain (LS), LS rate during systole (LSRs), early diastole (LSRe), and late diastole (LSRa) were measured. The symptom-limited cardiopulmonary exercise testing was performed using a cycle ergometer for measuring the peak oxygen consumption (peak [Formula: see text]). In the multivariate linear regression analysis, peak [Formula: see text] did not associate with strain or strain rate at rest. However, peak [Formula: see text] correlated with LS (β = -0.403, p = 0.007), LSRe (β = 6.041, p = 0.001), and LSRa (β = 5.117, p = 0.021) during exercise after adjustment for age, gender, and heart rate. The first quartile peak [Formula: see text] (14.2 mL/min/kg) was assessed to predict exercise intolerance. The C-statistic of delta LSRe was 0.74, which was relatively greater than that of delta LS (0.70) and delta LSRa (0.58), indicating that early diastolic function rather than systolic and late diastolic function affects exercise intolerance. LSRe during exercise is closely associated with the peak [Formula: see text]. Early diastolic function during exercise is an important determinant of exercise capacity in patients with HCM.


Comparative analysis of vocal fold vibration using high-speed videoendoscopy and digital kymography.
To compare high-speed videoendoscopy (HSV) and digital kymography (DKG) in the vocal fold vibration analysis of normophonic women with no vocal fold abnormalities. Prospective study comparing quantitative parameters extracted by HSV and DKG. Eighteen normophonic women whose age ranged from 18 to 45 years participated in the study. The procedures comprised HSV and DKG of the medial line of the vocal folds. The parameters evaluated were fundamental frequency (F0), open quotient (OQ), and duration of vibration cycle phases (open phase, closed phase, opening phase, and closing phase). The F0 results of HSV and DKG were similar. However, significant differences were found in both duration of vibration cycle phases and OQ, indicating a longer open phase in the vocal fold vibration when this phase was measured by HSV. The results emphasize the need to set up different normative threshold values for both HSV and DKG.


Total synthesis of zyzzyanones A-D.
Zyzzyanones A-D is a group of biologically active marine alkaloids isolated from Australian marine sponge Zyzzya fuliginosa. They contain a unique bispyrroloquinone ring system as the core structure. The first total synthesis of all four zyzzyanones is described here. The synthesis of these alkaloids started from a previously known 6-benzylamino indole-4,7-quinone derivative and involves 6-7 steps. The key step in the synthesis involves the construction of a pyrrole ring in one step using a Mn(OAc)3 mediated oxidative free radical cyclization reaction of a 6-benzylamino indole-4,7-quinone derivative with 4-benzyloxyphenyl acetaldehyde diethyl acetal in CH3CN.


Possible involvement of the circadian pathway in alcohol use disorder in a South African adolescent cohort.
Alcoholism has an estimated heritability of between 40 and 60% and it is thought that several genes of small effect may contribute to the risk of developing this disorder. Studies of the genetics of alcohol use disorder (AUD) may, however, be confounded by issues of comorbidity. The aim of this investigation was to assess associations between variants in a range of candidate genes and AUD in a unique sample of adolescents without comorbidity. Our cohort consisted of 80 adolescents with an AUD diagnosis and 80 matched controls of mixed ancestry ethnicity. An Illumina Infinium iSelect custom 6000 bead chip was used to genotype 5348 SNPs in 378 candidate genes. Association analysis, gene-based analysis and polygenic scoring were performed. There was no statistical association between any of the investigated SNPs and AUD after correction for multiple testing. However, from the gene-based analysis it was found that the circadian rhythm genes NR1D1 and BHLHE41 are associated with AUD. While preliminary, these data provide some evidence that the circadian pathway may be relevant to the pathophysiology of AUD. Study of early onset non-comorbid populations with AUD may be useful in identifying target genes for study in larger more representative samples.


Evaluation of circulating endothelial and platelet microparticles in men with ankylosing spondylitis.
To evaluate the profiles of endothelial microparticles (EMP) and platelet microparticles (PMP) in men with ankylosing spondylitis (AS) and healthy subjects. We also aimed to determine whether microparticles (MP) correlate with disease activity, function, and spinal mobility indices. There were 82 men with AS and 53 healthy controls. Subjects with a history of chronic diseases including coronary artery disease, hypertension, diabetes mellitus, and dyslipidemia were excluded. MP were stained with monoclonal antibodies against platelets and endothelial cells and quantified using flow cytometry. MP that were positive for both CD42a+/CD31+ and total CD42a+ were identified as PMP; and MP consisting of CD42a-/CD31+ and total CD144+ were considered EMP. EMP and PMP were similar between the patient and control groups (p > 0.05). Comparison of patients with AS in the active disease state (BASDAI ≥ 4) and in the inactive state showed that EMP and PMP were not different between the groups (p > 0.05). Correlation analysis revealed no correlation with Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, or Bath Ankylosing Spondylitis Metrology Index. C-reactive protein was significantly correlated with PMP and CD42a-/CD31+ EMP (p < 0.05). Comparison of patients with AS treated with anti-tumor necrosis factor (anti-TNF) drugs, subjects treated conventionally, and healthy controls revealed that PMP and CD42a-/CD31+ EMP were significantly downregulated in patients receiving biological agents. Circulating EMP and PMP, known to be indicators and mediators of vascular injury, were not significantly altered in men with AS who did not have classical cardiovascular risk factors. Significantly downregulated MP in patients receiving biological agents suggested that anti-TNF treatment may have a beneficial effect on vascular function in AS.


Lack of favorable effect of immunomodulators on outbred syngeneic rodent islet transplantation.
We studied the effect of two immunomodulators, lobenzarit disodium and OK-432, on outbred syngeneic islet transplantation. Six hundred fresh islets taken from two male Wistar rats were transplanted intraportally into other male Wistar rats that had been made diabetic with streptozotocin. Lobenzarit was given to 12 recipients and OK-432 to seven recipients intraperitoneally for 1 month, while nine controls received only intraperitoneal saline. Both drug-treated groups could not maintain lower fasting plasma glucose levels or higher fasting body weights at each time as compared with controls. The islet survival time in lobenzarit-treated (23.5 +/- 8.0 days) and OK-432-treated (25.3 +/- 13.4 days) groups was not longer than that (21.6 +/- 9.4 days) of the control group. All the pancreatic insulin contents of the seven surviving controls, ten surviving lobenzarit and five surviving OK-432 recipients were less than 0.8% of the mean insulin content obtained from 12 normal male rats. The hepatic insulin content of both drug-treated groups was not higher than that of the control group. These results suggest that lobenzarit disodium and OK-432 cannot protect outbred syngeneic islet grafts.


Prefrontal cortex activity in self-initiated movements is condition-specific, but not movement-related.
Activity of the prefrontal cortex (PFC) has been observed in previous block-design brain imaging studies of self-initiated movements. However, the meaning of these activations remained unclear. A functional MRI experiment was carried out, which utilized an epoch and an event-related analysis approach to the data. We hypothesized that event-related activity of the PFC would argue for a contribution to movement preparation. In contrast, epoch-, but not event-related activity pointed to tonic activations, probably reflecting enhanced attentional states or working memory processing. Twenty-one subjects were examined with 845 T2*-weighted images. During active phases, subjects were instructed to perform self-initiated movements of the right index finger with intertrial intervals of about 8 s. On single subject level, epoch- and event-related regressors were entered into a combined model, estimating the exclusive contribution of either regressor. For statistical inference on multisubject level, random effects analyses were performed. For the epoch regressor, activity within the right dorso- and ventrolateral prefrontal cortex, the bilateral insula, and the right inferior parietal lobe was observed. The event-related regressor detected activity within the right inferior parietal lobe, ventral from the activity found with the epoch regressor. The present results indicate a condition-, but not a movement-related function of the PFC in self-initiated movements. Furthermore, anatomically distinct regions within the inferior parietal cortex seem to be involved in condition-specific and movement-related processes. The observed condition-specific activations are suggested to reflect attentional or working memory processes, supervising task performance, rather than movement preparation or initiation.


Emerging targets and new small molecule therapies in Parkinson's disease treatment.
Parkinson's disease (PD) is a common chronic degenerative disease of the central nervous system. Due to a rapidly aging society worldwide, PD morbidity is on the rise; however, the treatment of PD with conventional drugs carries serious adverse reactions and cannot fix the root cause of PD, the degeneration of dopaminergic neurons, which limits conventional drug usage in clinical practice. In recent years, research on the pathogenesis of PD and its clinical manifestations has led to the discovery of an increasing number of novel targets in PD, including several small molecule targeted compounds. In this paper, we analyze and summarize the most recently published PD literature and review several recently discovered novel targets in PD and their small molecule targeted pharmacologically active agents based on their mechanisms of action and pharmacodynamic profiles.


Large African herbivores, bruchid beetles and their interactions with Acacia seeds.
This study investigated the interactions of large African herbivores and bruchid seed beetles with Acacia seeds. The germination of bruchid-infested and uninfested seeds was compaed. The effects of pod consumption by large herbivores on bruchid infestation and seed germination was also assessed. Bruchid-infested seeds did germinate, and the germination of bruchid-infested and uninfested A. tortilis, A. nilotica and A. hebeclade seeds did not differ. Pod ingestion by large herbivores lowered the bruchid infestation of consumed and defaecated seeds compared to uningested seeds. Uninfested, ingested and voided A. tortilis seeds germinated seeds. Furthermore, infested A. tortilis seeds egested by giraffe, kudu and ostrich germinated better than infested, uningested seeds. Pod ingestion by large herbivores may reduce bruchid infestation, increase Acacia seed germination and therefore increase potential Acacia seedling recruitment.


Neural markers of proactive and reactive cognitive control are altered during walking: A Mobile Brain-Body Imaging (MoBI) study.
The processing of sensory information and the generation of motor commands needed to produce coordinated actions can interfere with ongoing cognitive tasks. Even simple motor behaviors like walking can alter cognitive task performance. This cognitive-motor interference (CMI) could arise from disruption of planning in anticipation of carrying out the task (proactive control) and/or from disruption of the execution of the task (reactive control). In young healthy adults, walking-induced interference with behavioral performance may not be readily observable because flexibility in neural circuits can compensate for the added demands of simultaneous loads. In this study, cognitive-motor loads were systematically increased during cued task-switching while underlying neurophysiologic changes in proactive and reactive mechanisms were measured. Brain activity was recorded from 22 healthy young adults using 64-channel electroencephalography (EEG) based Mobile Brain/Body Imaging (MoBI) as they alternately sat or walked during performance of cued task-switching. Walking altered neurophysiological indices of both proactive and reactive control. Walking amplified cue-evoked late fontal slow waves, and reduced the amplitude of target-evoked fronto-central N2 and parietal P3. The effects of walking on evoked neural responses systematically increased as the task became increasingly difficult. This may provide an objective brain marker of increasing cognitive load, and may prove to be useful in identifying seemingly healthy individuals who are currently able to disguise ongoing degenerative processes through active compensation. If, however, degeneration continues unabated these people may reach a compensatory limit at which point both cognitive performance and control of coordinated actions may decline rapidly.