Hypogonadal men with type 2 diabetes mellitus have smaller bone size and lower bone turnover.
Both hypogonadism and type 2 diabetes mellitus (T2D) are associated with increased fracture risk. Emerging data support the negative effect of low testosterone on glucose metabolism, however, there is little information on the bone health of hypogonadal men with diabetes. We evaluated the bone mineral density (BMD), bone geometry and bone turnover of hypogonadal men with T2D compared to hypogonadal men without diabetes. Cross-sectional study, men 40-74years old, with average morning testosterone (done twice) of<300ng/dl. Areal BMD (aBMD) was measured by DXA; volumetric BMD (vBMD) and bone geometry by peripheral-quantitative-computed-tomography; serum C-telopeptide (CTX), osteocalcin, sclerostin and sex hormone-binding globulin (SHBG) by ELISA, testosterone and 25-hydroxyvitamin D (25OHD) by automated immunoassay and estradiol by liquid-chromatography/mass-spectrometry. Groups were compared by ANOVA adjusted for covariates. One-hundred five men, 49 with and 56 without diabetes were enrolled. Adjusted vBMD at 38% tibia was higher in diabetic than non-diabetic men (857.3±69.0mg/cm3 vs. 828.7±96.7mg/cm3, p=0.02). Endosteal (43.9±5.8mm vs. 47.1±7.8mm, p=0.04) and periosteal (78.4±5.0mm vs. 81.3±6.5mm, p=0.02) circumferences and total area (491.0±61.0mm2 vs. 527.7±87.2mm2, p=0.02) at 38% tibia, were lower in diabetic men even after adjustments for covariates. CTX (0.25±0.14ng/ml vs. 0.40±0.19ng/ml, p<0.001) and osteocalcin (4.8±2.8ng/ml vs. 6.8±3.5ng/ml, p=0.006) were lower in diabetic men; there were no differences in sclerostin and 25OHD. Circulating gonadal hormones were comparable between the groups. Among hypogonadal men, those with T2D have higher BMD, poorer bone geometry and relatively suppressed bone turnover. Studies with larger sample size are needed to verify our findings and possible even greater risk for fractures among hypogonadal diabetic men.


EMG artifact minimization during clinical EEG recordings by special analog filtering.
A multichannel analog filter for minimizing EMG artifact in routine EEG recordings is described. A 20-channel readily portable version has been implemented which can be easily interfaced with standard electroencephalographs at the auxiliary input/output connectors, in such a way that the filter can be inserted or removed for all channels simultaneously, or, selected channels can be filtered individually. That such an on-line filter be explored was suggested by the remarkable results for minimizing EMG artifact from EEG recordings at seizure onset by off-line computer-based digital filtering recently reported by Gotman, Ives and Gloor. A 4-pole Butterworth filter, i.e., having a maximally flat amplitude response in the passband and having a cut-off frequency, i.e., 30% attenuation point, of 12.5 Hz was selected, the same cut-off frequency as that of the digital filter used by Gotman et al. With this cut-off frequency, which represents a compromise, residual EMG artifact is relatively small. With higher cut-off frequencies, EMG artifact can appear as pseudo-beta activity. Minimization of pseudo-beta activity is obtained, however, at the expense of the elimination of true beta activity. On the other hand, activity of alpha frequencies or lower can be readily identified in the filter output, even with severe EMG artifact in the unfiltered EEG. Other problems in EMG filtering are discussed. Since the analog filter has a non-linear phase characteristic, in contrast to the linear phase characteristic of the finite-impulse-response digital filter used by Gotman et al., the possibility existed that distortion of the wave form of EEG spikes could result, as well as attenuation of their amplitudes. However, the wave forms of filtered spikes in the write-out of the analog filter were found to be essentially identical with those from a one-channel on-line finite-impulse-response computer-based filter having a linear phase characteristic. This finding indicates that phase shift in the analog filter is not a problem, at least for clinical EEG.


Cognitive behavioural therapy in multiple sclerosis: a randomized controlled pilot study of acceptance and commitment therapy.
The aim of this study was to design a trial that could evaluate the effect of acceptance and commitment therapy as a group-intervention for multiple sclerosis patients with psychological distress. Randomized controlled trial with assessment at pretreatment, end of treatment, and at 3-month follow-up. Multiple sclerosis outpatients with elevated symptoms of anxiety and/or depression (n = 21). Patients were randomly assigned to acceptance and commitment therapy or relaxation training. Both treatments consisted of 5 sessions over 15 weeks containing didactic sessions, group discussions, and exercises. Outcome was assessed by self-rated symptoms of anxiety, depression, and a measure of acceptance. At 3-month follow-up, the relaxation training group had a significant decline in anxiety symptoms whereas the acceptance and commitment therapy group showed a maintained improvement in rated acceptance at follow-up. The results reflect the different emphases of the therapies. Acceptance and commitment therapy is aimed at living an active, valued life and increasing acceptance, while relaxation training focuses directly on coping strategies to handle emotional symptoms. The results are preliminary, but supportive of further study of brief group interventions for reducing psychological distress in patients with multiple sclerosis.


Training the public health emergency response workforce: a mixed-methods approach to evaluating the virtual reality modality.
To produce and evaluate a novel virtual reality (VR) training for public health emergency responders. Following a VR training designed to test key public health emergency responder competencies, a prospective cohort of participants completed surveys rating self-assessed skill levels and perceptions of training methods. The VR training sessions were administered in a quiet room at the US Centers for Disease Control and Prevention (CDC), Atlanta, Georgia. All participants volunteered from a list of CDC emergency international surge responders. Perceived impact of the training on responder skills was self-reported via a Likert 5-point scale questionnaire. Assessments were modelled according to the Expanded Technology Acceptance Model measuring participant perceived usefulness of and intention to use the new technology. Inductive coding of qualitative feedback resulted in the identification of central themes. From November 2019 to January 2020, 61 participants were enrolled. Most (98%) participants self-rated above neutral for all skills (mean 4.3; range 1.21-5.00). Regression modelling showed that the perceived ease of use of the VR and ability to produce demonstrable results as likely drivers of further use. Participants agreed that others would benefit from the training (97%), it was representative of actual response scenarios (72%) and they would use lessons learnt in the field (71%). Open-response feedback highlighted feeling being immersed in the training and its utility for public health responders. At a time when a trained emergency public health workforce is a critical need, VR may be an option for addressing this gap. Participants' impressions and feedback, in the setting of their high skill level and experience, highlighted the utility and benefit of using VR to deliver training. Further research is needed to determine skill acquisition through VR training among a pool of future responders with limited to no response experience.


WWP1-dependent ubiquitination and degradation of the lung Krüppel-like factor, KLF2.
The zinc-finger transcription factor Krüppel-like factor-2 plays an important role in pulmonary development, inhibition of adipocyte differentiation, and maintaining quiescence in single-positive T cells. KLF2 levels rapidly decrease during adipogenesis and activation of T cells, but the pathways involved remain unclear. Previously, we identified WWP1, a HECT-domain E3-ubiquitin ligase, as an interacting partner of KLF2. This led us to speculate that KLF2 may be targeted for ubiquitination. Here, we demonstrate that WWP1 interacts with KLF2 in vivo and mediates both poly-ubiquitination and proteasomal degradation of KLF2. Deleting the inhibitory domain of KLF2 abrogated KLF2-WWP1 interactions and abolished WWP1-mediated poly-ubiquitination and down-regulation of KLF2. Furthermore, lysine-121 in the inhibitory domain of KLF2 is critical for ubiquitin-conjugation. Finally, the catalytic cysteine of WWP1 is not required for KLF2-ubiquitination. Our experiments demonstrate for the first time that WWP1 promotes ubiquitination and degradation of KLF2 and is not involved in the ubiquitin-transfer reaction.


Increased myocardial expression of osteopontin in patients with advanced heart failure.
The expression of the adhesion protein osteopontin (OP) is associated with cardiac hypertrophy and is significantly increased after transition to heart failure in experimental animal models. We, therefore, hypothesized that OP could be upregulated in heart failure in humans. In the present study, we investigated the expression of OP in myocardial biopsies obtained from patients with heart failure due to dilated cardiomyopathy (mean LVEF=30.3+/-4.4%, mean+/-S.D., n=10, group A) compared to patients with a normal left-ventricular ejection fraction (mean LVEF=61+/-11.2%, n=9; group B). Myocardial immunoreactivity for OP was examined using two different antibodies against OP. The expression of cardiac myocyte OP was significantly upregulated in group A in comparison to group B (P<0.0001). Both groups also displayed OP immunoreactivity in non-myocytes, including vascular smooth muscle cells and cardiac fibroblasts (P=not significant). Statistical analysis revealed a significant correlation of increased OP immunoreactivity in cardiac myocytes of patients with impaired left ventricular function, assessed by hemodynamic data (LVEF, RVEF, LVESVI, LVEDVI and LVEDP, R=-0.828, -0.671, 0.751, 0.685 and 0.461, respectively; all P<0.05). Furthermore, OP expression correlated with cardiac myocyte hypertrophy (mean diameter 21.0+/-1.8 microm in group A and 16.6+/-2.1 microm in group B; P<0.0001). In conclusion, the present study indicates, that factors and/or mechanisms involved in heart failure in patients with dilated cardiomyopathy, lead to induction of OP expression in humans.


Identification of ozone sensitivity for NO2 and secondary HCHO based on MAX-DOAS measurements in northeast China.
In this study, tropospheric formaldehyde (HCHO) vertical column densities (VCDs) were measured using multi-axis differential optical absorption spectroscopy (MAX-DOAS) from January to November 2019 in Shenyang, Northeast China. The maximum HCHO VCD value appeared in the summer (1.74 × 1016 molec/cm2), due to increased photo-oxidation of volatile organic compounds (VOCs). HCHO concentrations increased from 08:00 and peaked near 13:00, which was mainly attributed to the increased release of isoprene from plants and enhanced photolysis at noon. The HCHO VCDs observed by MAX-DOAS and OMI have a good correlation coefficient (R) of 0.78, and the contributions from primary and secondary HCHO sources were distinguished by the multi-linear regression model. The anthropogenic emissions showed unobvious seasonal variations, and the primary HCHO was relatively stable in Shenyang. Secondary HCHO contributed 82.62%, 83.90%, 78.90%, and 41.53% to the total measured ambient HCHO during the winter, spring, summer, and autumn, respectively. We also found a good correlation (R = 0.78) between enhanced vegetation index (EVI) and HCHO VCDs, indicating that the oxidation of biogenic volatile organic compounds (BVOCs) was the main source of HCHO. The ratio of secondary HCHO to nitrogen dioxide (NO2) was used as the tracer to analyze O3-NOx-VOC sensitivities. We found that the VOC-limited, VOC-NOx-limited, and NOx-limited regimes made up 93.67%, 6.23%, 0.11% of the overall measurements, respectively. In addition, summertime ozone (O3) sensitivity changed from VOC-limited in the morning to VOC-NOx-limited in the afternoon. Therefore, this study offers information on HCHO sources and corresponding O3 production sensitivities to support strategic management decisions.


Interactions between aging and cortical cholinergic deafferentation on attention.
Pre-existing trauma to basal forebrain corticopetal cholinergic neurons has been hypothesized to render this system vulnerable to age-related processes. The present longitudinal study assessed the interactions between the effects of partial cortical cholinergic deafferentation and aging on sustained attention performance. After pre-surgical training, animals were given sham-surgery or bilateral infusions of the immunotoxin 192 IgG-saporin into the basal forebrain. The lesion was intended to yield a limited loss of cortical cholinergic inputs and thus to produce minor immediate effects on sustained attention performance. All animals were tested continuously until age 36 months. The attentional performance of lesioned and sham-lesioned animals did not dissociate until age 31 months, when the lesioned animals exhibited an impairment in overall sustained attention performance. Importantly, this impairment interacted with the effects of time-on-task, and thus reflected a specific impairment in attentional processes. These results support the notion that pre-existing damage to the basal forebrain corticopetal cholinergic neurons yields age-related impairments in the attentional capabilities that depend on the integrity of this neuronal system.


Imitation among infants in a day-care center and the development of locomotion.
To examine the relationship between imitation and locomotor development among peers during infancy, we observed free play in a class of infants in a day-care center over a one-year period. The analysis included 16 infants (mean age was 8.3 months (SD=2.3) at the beginning of the observation) and 5 caregivers. The longitudinal data were divided into the crawling, cruising, and walking periods, and the imitation of object manipulation that took place among the infants during each period was analyzed. With the development of locomotion, peer-to-peer imitation became frequent. Infants who had acquired the ability to walk demonstrated imitation more frequently in triadic interactions than in dyadic interactions. Imitation took place between infants, but it was often mediated by caregivers rather than directly between infants. The results suggest that the acquisition of locomotor skills is a link in a developmental cascade from motor development to infant peer interaction. However, it is reasonable to interpret the results as indicating that the development of locomotion does not directly affect infant interactions in isolation, but rather that walking increases both the sharing and manipulation of objects with caregivers and proximity to peers, and their combined effects form a cascade.


Kinetics of ethanol oxidation catalyzed by yeast alcohol dehydrogenase in aqueous solutions of sodium dodecylsulfate.
A study has been made of the effect of sodium dodecylsufate (SDS) addition on the oxidation of ethanol catalyzed by yeast alcohol dehydrogenase. Experiments were performed at pH = 8.1 and SDS concentrations employed were below and above the surfactant critical micelle concentration (CMC). The double reciprocal plots obtained in the absence and in the presence of the surfactant were compatible with a sequential bi-bi ordered mechanism. In the presence of the surfactant the initial reaction rates were consistently lower than in pure buffer at all the surfactant concentrations considered (0.5-50 mM). This effect is mainly due to an increase in the dissociation constant of beta-NAD(+) which reaches its maximum value (7,100 +/- 1,700 microM) at the CMC. Above the CMC the effect of the surfactant is mainly due to an increase in the Michaels constants of the alcohol, with values of 41 +/- 1 mM for 15 mM SDS and 50 +/- 1 mM for 50 mM SDS. The catalytic rate constant was found to be practically independent of the presence of the surfactant in the range of concentrations considered (up to 50 mM).


Water recycle system in an artificial closed ecosystem - Lunar Palace 1: Treatment performance and microbial evolution.
Water recycle systems have important implications to realize material circulation in biological regeneration life support systems, which is of significance for long-term space missions and future planetary base. Based on membrane biological activated carbon reactor (MBAR) technologies, the 'Lunar Palace 365' experiment established various treatment processes for condensate wastewater, domestic wastewater, urine, and used nutrient solutions. The 370-day operation data showed the CODMn index of purified condensate wastewater decreased to 0.74 ± 0.15 mg/L, which met the standards for drinking water quality. The average removal rate of organic contaminants in domestic wastewater by the MBAR was 85.7% ± 10.2%, and this MBAR also had a stable nitrification performance with effluent NO3--N concentrations fluctuating from 145.57 mg/L to 328.59 mg/L. Moreover, the purification of urine achieved the conversion of urea-N to NH4+-N and thus the partial recovery of nitrogen. 16S rDNA sequencing results revealed the evolution of microbial diversity and composition during the long-term operation. Meiothermus, Rhodanobacter, and Ochrobactrum were the dominant microorganisms in various MBARs.


Bilateral posterior cerebral artery territory infarction in a SARS-Cov-2 infected patient: discussion about an unusual case.
In time of SARS-Cov2 pandemic, neurologists need to be vigilant for cerebrovascular complications of Covid-19. We present a case of bilateral occipito-temporal infarction revealed by a sudden cortical blindness with haemorrhagic transformation after intravenous thrombolysis in a diabetic patient infected by Covid-19. Differential diagnoses are discussed in front of this unusual presentation and evolution.


Gene therapy using human FMRP isoforms driven by the human FMR1 promoter rescues fragile X syndrome mouse deficits.
Fragile X syndrome (FXS) is caused by the loss of the fragile X messenger ribonucleoprotein 1 (FMRP) encoded by the FMR1 gene. Gene therapy using adeno-associated virus (AAV) to restore FMRP expression is a promising therapeutic strategy. However, so far AAV gene therapy tests for FXS only utilized rodent FMRPs driven by promoters other than the human FMR1 promoter. Restoration of human FMRP in appropriate cell types and at physiological levels, preferably driven by the human FMR1 promoter, would be more suitable for its clinical use. Herein, we generated two human FMR1 promoter subdomains that effectively drive gene expression. When AAVs expressing two different human FMRP isoforms under the control of a human FMR1 promoter subdomain were administered into bilateral ventricles of neonatal Fmr1 -/y and wild-type (WT) mice, both human FMRP isoforms were expressed throughout the brain in a pattern reminiscent to that of mouse FMRP. Importantly, human FMRP expression attenuated social behavior deficits and stereotyped and repetitive behavior, and reversed dysmorphological dendritic spines in Fmr1 -/y mice, without affecting WT mouse behaviors. Our results demonstrate that human FMR1 promoter can effectively drive human FMRP expression in the brain to attenuate Fmr1 -/y mouse deficits, strengthening the notion of using AAV gene therapy for FXS treatment.


Role of endogenous cannabinoids in ischemia/reperfusion injury following testicular torsion in rats.
The role of endogenous cannabinoids in ischemia/reperfusion induced germ cell apoptosis in rats was investigated. Baseline group was for basal normal values. The Sham operated group served as a control group. The torsion/detorsion (T/D) group underwent torsion (1 h) and detorsion; AN1, AN2, and AN3 groups received anandamide (10 mg/kg) 30 min before torsion, 30 min after torsion, and just after detorsion, respectively. In the AM251 group, AM251 (0.5 mg/kg) was injected 45 min before torsion and in the AN/AM group, AM251 and anandamide were injected 45 and 30 min before torsion, respectively. Lipid peroxidation, antioxidant enzymes, and germ cell apoptosis was determined. Malondialdehyde (MDA) levels in the T/D group were significantly higher than the control group. Moreover, MDA values in the AN1, AN2, and AN3 groups were significantly lower than T/D. There were significant decreases in catalase and superoxide dismutase activities in the T/D group versus the control group. These values in the AN1, AN2, and AN3 groups were significantly higher than T/D. It was also shown that MDA levels in the AN/AM group were significantly higher than the AN1 group. In the AN/AM group, catalase and superoxide dismutase activities were significantly lower versus the AN1 group. The mean germ cell apoptosis scores in all animals with testicular T/D were significantly higher than the control group. There was no difference between the apoptotic indices in the AN1, AN2, AN3, and T/D groups. Apoptosis scores in AM251 and AN/AM were significantly higher compared with the T/D and AN1 groups. Although anandamide increased antioxidant markers, it failed to reduce germ cell apoptosis. AM251 worsened the antioxidant defense system, which is reflected as higher germ cell apoptosis.


Ultrasonography for fetal weight estimation: the Birnholz equation.
In the population of 563 normal live births, subject to the selection criteria of this study, the mean ultrasonographically-estimated fetal weight calculated using the Birnholz equation accurately predicts the mean true birth weight with less than 1 percent error. However, on a pairwise basis, the error was found to be systematic (rather than random) with a large standard error of the estimate (+/- 300 g). The equation consistently underestimated the mean birth weight between 1500-3750 g and consistently overestimated it thereafter.


End-to-end automatic pathology localization for Alzheimer's disease diagnosis using structural MRI.
Structural magnetic resonance imaging (sMRI) is an essential part of the clinical assessment of patients at risk of Alzheimer dementia. One key challenge in sMRI-based computer-aided dementia diagnosis is to localize local pathological regions for discriminative feature learning. Existing solutions predominantly depend on generating saliency maps for pathology localization and handle the localization task independently of the dementia diagnosis task, leading to a complex multi-stage training pipeline that is hard to optimize with weakly-supervised sMRI-level annotations. In this work, we aim to simplify the pathology localization task and construct an end-to-end automatic localization framework (AutoLoc) for Alzheimer's disease diagnosis. To this end, we first present an efficient pathology localization paradigm that directly predicts the coordinate of the most disease-related region in each sMRI slice. Then, we approximate the non-differentiable patch-cropping operation with the bilinear interpolation technique, which eliminates the barrier to gradient backpropagation and thus enables the joint optimization of localization and diagnosis tasks. Extensive experiments on commonly used ADNI and AIBL datasets demonstrate the superiority of our method. Especially, we achieve 93.38% and 81.12% accuracy on Alzheimer's disease classification and mild cognitive impairment conversion prediction tasks, respectively. Several important brain regions, such as rostral hippocampus and globus pallidus, are identified to be highly associated with Alzheimer's disease.


A 13C-NMR study of the biosynthesis of 3-methylpentacosane in the American cockroach.
13C-NMR spectrometry was used to examine the in vivo incorporation of 13C-labeled precursors into 3-methylpentacosane in the cockroach Periplaneta americana. Natural abundance 13C-NMR of 3-methylpentacosane showed that carbons 1 through 6, 23 through 25 and the branching methyl carbon (C26) each gave distinct signals, with carbons 7 through 22 indistinguishable from each other. The label from dipotassium 2-[methyl-13C]methylmalonate was incorporated primarily into the methyl branch of 3-methylpentacosane, demonstrating the 2-methylmalonate is the precursor to the methyl branch unit. The carboxyl carbon from sodium [1-13C]propionate was incorporated exclusively into the 4-position. This indicates that propionate, as a 2-methylmalonyl derivative, is incorporated as the second unit during chain synthesis rather than toward the end of the elongation process. The labeled carbon from sodium [1-13C]acetate was incorporated into carbons 2, 6 and 24 and the labeled carbon from [2-13C]acetate was incorporated into carbons 1, 5, 23 and 25 of 3-methylpentacosane, respectively. These data are consistent with an elongation-decarboxylation pathway for 3-methylpentacosane biosynthesis.


Peripubertal proliferation of progenitor cells in the preoptic area of Japanese quail (Coturnix japonica).
Brain structures related to reproduction are thought to depend on the action of gonadal steroids acting either during early life (organizing irreversible effects) or adulthood (activating transient effects). More recently puberty has become a focus of attention and it was demonstrated that action of sex steroid hormones at this time plays a critical role in the final organization of brain and behavior. We studied by BrdU immunohistochemistry the ontogeny from hatching to sexual maturity of a previously identified cell population in the preoptic area labeled by a BrdU injection at the end of embryonic period (E12) of sexual differentiation in male and female Japanese quail. After an initial increase between E12 and hatching, the density of BrdU-immunoreactive cells decreased until the beginning of puberty but then increased again during sexual maturation in the caudal preoptic area specifically. Divisions of these cells took place in the brain parenchyma as indicated by the large numbers of pairs of labeled cells. No sex difference affecting these processes could be detected at any stage of development. Large numbers of new cells thus arise around puberty in the caudal preoptic area and presumably contribute to the reorganization of this structure that precedes the emergence of adult reproductive behaviors.


The innate immune receptor RP105 promotes metabolic syndrome by altering gut microbiota composition and intestinal barrier function.
Radioprotective 105 (RP105) plays a key role in the development of high-fat diet (HFD)-induced metabolic disorders; however, the underlying mechanisms remain to be understood. Here, we aimed to uncover whether RP105 affects metabolic syndrome through the modification of gut microbiota. We confirmed that body weight gain and fat accumulation by HFD feeding were suppressed in Rp105-/- mice. Fecal microbiome transplantation from HFD-fed donor Rp105-/- mice into HFD-fed recipient wild-type mice significantly improved various abnormalities associated with metabolic syndrome, including body weight gain, insulin resistance, hepatic steatosis, macrophage infiltration and inflammation in the adipose tissue. In addition, HFD-induced intestinal barrier dysfunction was attenuated by fecal microbiome transplantation from HFD-fed donor Rp105-/- mice. A 16S rRNA sequence analysis indicated that RP105 modified gut microbiota composition and was involved in the maintenance of its diversity. Thus, RP105 promotes metabolic syndrome by altering gut microbiota composition and intestinal barrier function.


Effect of YM796, a novel muscarinic agonist, on the impairment of passive avoidance response in senescence-accelerated mice.
We compared the effects of YM796 [(-)-S-2,8-dimethyl-3-methylene-1-oxa-8- azaspiro[4,5]-decane L-tartrate monohydrate], a novel muscarinic agonist, on passive avoidance response with those of the cholinomimetics AF102B [(+/-)-cis-2-methylspiro-(1,3-oxathiolane-5,3')-quinuclidine hydrochloride] and NIK247 [9-amino-2,3,5,6,7,8-hexahydro1H-cyclopenta(b)- quinoline monohydrate hydrochloride] in senescence-accelerated mice. SAMP8@YAN (SAM-P/8, senescence-accelerated-prone substrain) showed an age-dependent shortening in the latency of step-through when compared with SAMR1/YAN (SAM-R/1, senescence-accelerated-resistant substrain). The shortened latency of step-through in SAMP8@YAN was prolonged by administration of YM796 (0.3 and 1 mg/kg, PO), AF102B (3 and 10 mg/kg PO), and NIK247 (30 mg/kg, PO) in a bell-shaped manner. In contrast, amitriptyline (10, 30, and 50 mg/kg, PO), with cholinolytic properties, had no effect on this shortened latency of step-through. These results suggest that YM796, AF102B, and NIK247 ameliorated the disturbance of learning behavior, presumably due to facilitation of the central cholinergic system in SAMP8@YAN mice and that SAMP8@YAN may be an appropriate age-dependent model of amnesia for evaluating pharmacological actions of drugs.


Assessment of novel ICT-EMS systems to improve emergency patient transportation during the COVID-19 pandemic.
This study aimed to examine the usability, feasibility, acceptability, and appropriateness of the information and communication technology for emergency medical services (ICT-EMS) systems to improve the transportation of emergency patients during the COVID-19 pandemic. Emergency medical technicians (EMTs) (n = 229) employed at 7 fire stations operated by the North Chungcheong Fire Service Headquarters, South Korea were trained to use ICT-EMS devices prior to a 1-month implementation period. System Usability Scale (SUS), Feasibility of Intervention Measure (FIM), Acceptability of Intervention Measure (AIM), and Intervention Appropriateness Measure (IAM) questionnaires were conducted in the 4th week of the 1-month implementation period to assess the perceived usability, feasibility, acceptability, and appropriateness of the ICT-EMS systems. Among a total of 229 EMTs, 187 EMTs (81.7%) completed the survey. The overall SUS score was significantly low (score of 35.6) indicating an overall negative perception of the ICT-EMS systems. With regard to the feasibility, acceptability, and intervention appropriateness of ICT-EMS, roughly 50 (26.7%) participants agreed that ICT-EMS implementation was possible, appealing, and suitable. Many potential areas of improvement were identified within the ICT-EMS systems. System alterations regarding usability, feasibility, acceptability, and appropriateness may be necessary to successfully implement the ICT-EMS systems.


Neamine dimers targeting the HIV-1 TAR RNA.
Natural aminoglycoside antibiotics, such as neomycin, target bacterial ribosomal RNA. Neomycin also binds strongly to HIV TAR and RRE RNA through the predominant interactions of its neamine core. In the search for antiviral agents targeting multiple binding sites for aminoglycosides in RNA, we report here the synthesis of new neamine dimers and a trimer in which the neamine cores are connected by different linking chains attached at the 4'- and/or 5-positions. Inhibition of TAR-Tat complexation by these oligomers was studied via fluorimetric binding assays performed under two ionic strengths. All dimers strongly inhibit TAR-Tat association, with IC50 values 17-85 times better than the value obtained with neomycin. These results demonstrate that modifying neamine at the 4'- or the 5-position is a promising strategy in the search for antiviral agents.


Cationic proteins from human neutrophil granulocytes. Evidence for their chymotrypsin-like properties.
Three cationic proteins from the granules of human neutrophil granulocytes were obtained in a high degree of purity be means of affinity chromatography on 4-phenylbutylamine-Sepharose. Together with lysozyme, the three cationic proteins exhibit the highest electrophoretic mobility toward the cathode in acrylamide gels at moderately acid pH, among the granule constituents that are solubilized in 0.1 M phosphate buffer, pH 7.0, containing 1 M NaCl. The three cationic proteins represent a group of "neutral proteases" distinct from elastase and collagenase. They hydrolyze casein, azocasein and the chymotrypsin substrate N-acetyl-L-tyrosine ethyl ester. Optimal activity is found at pH 7.4-7;5. The enzymes are inhibited by the specific chymotrypsin inhibitor N-tosyl-L-phenylalanylchloromethane and by the naturally occurring inhibitors alpha-antichymotrypsin, alpha-1-antitrypsin, as well as by the trypsin inhibitors from soy beans and limabeans.


Degradation of toluene in surface dielectric barrier discharge (SDBD) reactor with mesh electrode: Synergistic effect of UV and TiO2 deposited on electrode.
Combing with photo-catalysis and photo-catalyst, a surface dielectric barrier discharge (SDBD) reactor with a mesh electrode was applied for toluene degradation and a high mineralization was achieved. The degradation performance comparison between SDBD reactors with a mesh and a spring electrode was carried out as well. A significant improvement in carbon balance and CO2 selectivity were obtained in mesh SBDB reactor compared with that of spring's one. For instance, when only plasma was applied, the carbon balance and CO2 selectivity of mesh SDBD reactor were 84% and 42.6%, while only 64.5% and 31.8% in spring one, the carbon balance and CO2 selectivity were improved by 30.3% and 34% at SIE of 300 J L-1, respectively. Synergistic effects of photo-catalysis and photo-catalyst were conducted with a 254 nm UV lamp and TiO2 deposited on the mesh electrode by atmospheric pressure (AP) plasma technology. The results showed that TiO2 and UV irradiation both presented promoting effect on toluene degradation in SDBD reactor with mesh electrode. According to the experimental results, the carbon balance rose to 89.5% and 93.9% at SIE of 300 J L-1, when UV or TiO2 was applied. With the application of TiO2 and UV together, a highest carbon balance of 95.9% was obtained at the same SIE. At the same SIE, the CO2 selectivity was promoted by 42.8% or 55.3% with the application of UV or TiO2, and the promotion finally reached at 59.1% when TiO2 and UV were applied together. Additionally, the degradation efficiency of toluene was also enhanced with the introduction of TiO2 and UV irradiation. Increases in toluene degradation efficiency of 19. 7% and 26.8% were obtained at SIE of 300 J L-1, respectively. When both TiO2 and UV were applied, the enhancement could rise to 41.6%.


Fractalkine and minocycline alter neuronal activity in the spinal cord dorsal horn.
Fractalkine (FKN) evokes nociceptive behavior in nai ve rats, whereas minocycline attenuates pain acutely after neuronal injury. We show that, in nai ve rats, FKN causes hyperresponsiveness of lumbar wide dynamic range neurons to brush, pressure and pinch applied to the hindpaw. One day after spinal nerve ligation (SNL), minocycline attenuates after-discharge and responses to brush and pressure. In contrast, minocycline does not alter evoked neuronal responses 10 days after SNL or sciatic constriction, but increases spontaneous discharge. We speculate that microglia rapidly alter sensory neuronal activity in nai ve and neuropathic rats acutely, but not chronically, after injury.


The dynamics and mechanisms of interleukin-1alpha and beta nuclear import.
Pro-inflammatory members of the interleukin-1 (IL-1) family of cytokines (IL-1alpha and beta) are important mediators of host defense responses to infection but can also exacerbate the damaging inflammation that contributes to major human diseases. IL-1alpha and beta are produced by cells of the innate immune system, such as macrophages, and act largely after their secretion by binding to the type I IL-1 receptor on responsive cells. There is evidence that IL-1alpha is also a nuclear protein that can act intracellularly. In this study, we report that both IL-1alpha and IL-1beta produced by microglia (central nervous system macrophages) in response to an inflammatory challenge are distributed between the cytosol and the nucleus. Using IL-1-beta-galactosidase and IL-1-green fluorescent protein chimeras (analyzed by fluorescence recovery after photobleaching), we demonstrate that nuclear import of IL-1alpha is exclusively active, requiring a nuclear localization sequence and Ran, while IL-1beta nuclear import is entirely passive. These data provide valuable insights into the dynamic regulation of intracellular cytokine trafficking.


Expression of titin-linked putative mechanosensing proteins in skeletal muscle after power resistance exercise in resistance-trained men.
Little is known about the molecular responses to power resistance exercise that lead to skeletal muscle remodeling and enhanced athletic performance. We assessed the expression of titin-linked putative mechanosensing proteins implicated in muscle remodeling: muscle ankyrin repeat proteins (Ankrd 1, Ankrd 2, and Ankrd 23), muscle-LIM proteins (MLPs), muscle RING-finger protein-1 (MuRF-1), and associated myogenic proteins (MyoD1, myogenin, and myostatin) in skeletal muscle in response to power resistance exercise with or without a postexercise meal, in fed, resistance-trained men. A muscle sample was obtained from the vastus lateralis of seven healthy men on separate days, 3 h after 90 min of rest (Rest) or power resistance exercise with (Ex + Meal) or without (Ex) a postexercise meal to quantify mRNA and protein levels. The levels of phosphorylated HSP27 (pHSP27-Ser15) and cytoskeletal proteins in muscle and creatine kinase activity in serum were also assessed. The exercise increased (P ≤ 0.05) pHSP27-Ser15 (∼6-fold) and creatine kinase (∼50%), whereas cytoskeletal protein levels were unchanged (P > 0.05). Ankrd 1 (∼15-fold) and MLP (∼2-fold) mRNA increased, whereas Ankrd 2, Ankrd 23, MuRF-1, MyoD1, and myostatin mRNA were unchanged. Ankrd 1 (∼3-fold, Ex) and MLPb (∼20-fold, Ex + Meal) protein increased, but MLPa, Ankrd 2, Ankrd 23, and the myogenic proteins were unchanged. The postexercise meal did not affect the responses observed. Power resistance exercise, as performed in practice, induced subtle early responses in the expression of MLP and Ankrd 1 yet had little effect on the other proteins investigated. These findings suggest possible roles for MLP and Ankrd 1 in the remodeling of skeletal muscle in individuals who regularly perform this type of exercise.NEW & NOTEWORTHY This is the first study to assess the early changes in the expression of titin-linked putative mechanosensing proteins and associated myogenic regulatory factors in skeletal muscle after power resistance exercise in fed, resistance-trained men. We report that power resistance exercise induces subtle early responses in the expression of Ankrd 1 and MLP, suggesting these proteins play a role in the remodeling of skeletal muscle in individuals who regularly perform this type of exercise.


Effects of serum versus plasma on agglutination of antibody-coated indicator cells by human rheumatoid factors.
Plasma and serum contain an inhibitor (I) of the agglutination of rabbit IgG-coated sheep erythrocytes by human rheumatoid factor (RF). Plasma but not serum contains an inhibitor of the inhibitor (I/I) which allows RF to interact with its target. In normal blood, there is more I than I/I, and I can be removed by solid-phase chromatography through concanavalin A (Con A). Plasma I/I is heat labile being eliminated by heating at 56 degrees C for 30 min. Addition of exogenous calcium clots EDTA plasma, causing an irreversible loss of I/I, and suggesting its involvement in the clotting cascade. The absence of I/I from Factor V-deficient plasma and destruction of I/I by Russell's viper venom indicate I/I either is associated with or is a part of Factor V. These findings suggest a balanced interplay between I and I/I, and indicate results of immunological tests done in vitro may not accurately reflect immune function in vivo. This seems to represent an unexplored link between hemostasis and immunity.


[The effect of external factors on ATP synthesis during sudden pH increase in mitochondria].
Fast alkaline jump in aging uncoupled mitochondria results in the ATP synthesis. This process is completely inhibited with oligomycin and by 60-70% with FCCP. The NADH experiments have shown that mitochondrial membranes do not change their orientation during aging.


Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors Have No Significant Relationship With Postoperative Arthrofibrosis After Shoulder Arthroscopy.
To determine the effect of perioperative angiotensin II receptor blocker (ARB) or angiotensin-converting enzyme inhibitors (ACEi) on postoperative arthrofibrosis, as defined by requiring manipulation under anesthesia (MUA) or new diagnosis of adhesive capsulitis (AC) following arthroscopic shoulder procedures. Patients were retrospectively identified using Current Procedural Terminology surgical billing codes to identify patients who underwent any shoulder arthroscopic procedure at a single urban academic institution from 2012 to 2020 with a minimum 2-year follow-up. Patients were excluded if <30 years old at time of surgery, as these patients rarely use ARB and ACEi medications, or if they had pre-existing AC. Demographics, active medication prescriptions at the time of surgery, and medical comorbidities were recorded. Multivariable logistic regression was performed to determine the effect of ARB/ACEi on subsequent MUA or AC by 90 days, 1 year, and 2 years. In total, 5,559 patients were included in the final analysis. A majority of the cohort (53.4%) underwent arthroscopic surgery between the ages of 50 to 69 years. Most patients were male (61.8%) and without obesity (67.3%). In total, 18.9% and 15.0% were taking an ARB or ACEi medication perioperatively, respectively. Within 2 years' postoperatively, 51 patients (0.9%) underwent subsequent ipsilateral MUA, and 174 patients (3.1%) developed AC. Patients taking ARBs had a 17.5% rate of postoperative arthrofibrosis within 2-years compared with 19.1% in those not on ARBs, although this difference was not significant (P = .58). Likewise, no significant difference was found between those taking ACEi versus not (15.0% vs 15.0%, P = .99). Individual generic ARB/ACEi subgroup analysis did not demonstrate any significant associations with rate of postoperative arthrofibrosis (P > .05). ARBs or ACEi did not significantly affect the rate of postoperative arthrofibrosis following shoulder arthroscopy, however female sex, diabetes mellitus, and Black/African American race were associated with an increased rate of necessitating MUA or developing AC within 2 years postoperatively. Level III, retrospective cohort study.


Analysis of ciliary membrane protein dynamics using SNAP technology.
The sensory functions of the primary cilium rely on receptors and other membrane proteins that are specifically sorted to the ciliary compartment, which is a subdomain of the plasma membrane. Defects in this process underlie a large number of human diseases, yet it is poorly understood. Thus, it is of great interest to understand the mechanisms by which the cell sorts and traffics proteins to the ciliary membrane. Here, we provide an overview of our method to study the sorting and trafficking of ciliary membrane proteins using SNAP technology. This technology enables pulse-chase analysis of the movement of proteins through the endomembrane system and onto the cilium.


Complete Genome Sequence of the Nonmotile Myxococcus xanthus Strain NM.
Myxobacteria exhibit multicellular swarming behavior, which depends on the coordination of cell motility. Unlike other myxobacteria, Myxococcus xanthus NM is not capable of forming swarms due to a defective motility system. Here, we present the 9.35-Mbp genome sequence of this nonmotile myxobacterium.


Evaluating the psychometric properties of the German adaptation of the client attachment to therapist scale.
The present study examines the psychometric properties of the German adaptation of the Client Attachment to Therapist Scale (CATS). The validity of the scale as originally proposed has recently been brought into question, as patients were identified as "pseudosecure". We examined the measure's factorial structure, as well as reliability and validity towards related measures using a clinical sample of N = 354 participants. We found the original model, consisting of 36 items to be lacking in terms of model fit and construct validity. A shortened 12-item version exhibited markedly improved model fit and reliability. Correlations to related constructs demonstrated that none of the scale's validity was lost by shortening it. Furthermore, we showed scalar invariance across groups of age and sex. The shortened CATS-S can be recommended for future use in clinical research in German-speaking populations as a valid, reliable, and economical alternative to the longer version.


Red cell microparticle enumeration: validation of a flow cytometric approach.
There is growing interest in the clinical application of red blood cell (RBC) microparticle (MP) enumeration as they have been postulated to be effectors of coagulation and inflammation following transfusion and in sickle cell disease. No uniform approach in MP enumeration exists and a key limitation is the lack of an internal validation process. We present and validate a flow cytometric approach where an internal standard is utilized. Glycophorin A(+) Annexin V(+) events were enumerated using MPs isolated from RBC units or plasma samples obtained from volunteers. A mixture of absolute counting (7·6 μm) and calibration beads (0·5, 0·9 and 3 μm) at a fixed ratio was added to each sample. RBC MPs were initially selected based upon a fluorescence threshold, and the 0·5- and 0·9-μm beads defined the upper and lower light scatter distribution of MPs. The ratio of 7·6:3-μm bead events was used as an internal standard to validate the precision of MP enumeration across samples (coefficient of variation = 2·5-7·2%) and remained constant in both platelet-rich plasma (PRP) and platelet-free plasma (PFP). RBC MP counts increased in both PRP and PFP obtained from whole blood stimulated with ionophore and increasing calcium concentrations, with PRP showing higher MP counts than PFP at every concentration studied. This method is a useful strategy to detect RBC MP counts across bio-samples provided that the flow cytometer can reliably discriminate the size of the calibration beads.


ZD1839 ('Iressa'), a specific oral epidermal growth factor receptor-tyrosine kinase inhibitor, potentiates radiotherapy in a human colorectal cancer xenograft model.
The effect of ZD1839 ('Iressa'), a specific inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor, on the radiation response of human tumour cells (LoVo colorectal carcinoma) was evaluated in vitro and in vivo. ZD1839 (0.5 microM, incubated days 1-5) significantly increased the anti-proliferative effect of fractionated radiation treatment (2 Gy day(-1), days 1-3) on LoVo cells grown in vitro (P=0.002). ZD1839 combined with either single or fractionated radiotherapy in mice bearing LoVo tumour xenografts, also produced a highly significant increase in tumour growth inhibition (P< or = 0.001) when compared to treatment with either modality alone. The radio-potentiating effect of ZD1839 was more apparent when radiation was administered in a fractionated protocol. This phenomenon may be attributed to an anti proliferative effect of ZD1839 on tumour cell re-population between radiotherapy fractions. These data suggest radiotherapy with adjuvant ZD1839 could enhance treatment response. Clinical investigation of ZD1839 in combination with radiotherapy is therefore warranted.


Microstructural Integrity of Peripheral Nerves in Charcot-Marie-Tooth Disease: An MRI Evaluation Study.
Charcot-Marie-Tooth (CMT) disease is diagnosed through clinical findings and genetic testing. While there are neurophysiological tools and clinical functional scales in CMT, objective disease biomarkers that can facilitate in monitoring disease progression are limited. To investigate the utility of diffusion tensor imaging (DTI) in determining the microstructural integrity of sciatic and peroneal nerves and its correlation with the MRI grading of muscle atrophy severity and clinical function in CMT as determined by the CMT neuropathy score (CMTNS). Prospective case-control. Nine CMT patients and nine age-matched controls. 3 T T1 -weighted in-/out-of phase spoiled gradient recalled echo (SPGR) and DTI sequences. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) values for sciatic and peroneal nerves were obtained from DTI. Muscle atrophy was graded according to the Goutallier classification using in-/out-of phase SPGRs. DTI parameters and muscle atrophy grades were compared between CMT and controls, and the relationship between DTI parameters, muscle atrophy grades, and CMTNS were assessed. The Wilcoxon Signed Ranks test was used to compare DTI parameters between CMT and controls. The relationship between DTI parameters, muscle atrophy grades, and CMTNS were analyzed using the Spearman correlation. Receiver operating characteristic (ROC) analyses of DTI parameters that can differentiate CMT from healthy controls were done. There was a significant reduction in FA and increase in RD of both nerves (P < 0.05) in CMT, with significant correlations between FA (negative; P < 0.05) and RD (positive; P < 0.05) with muscle atrophy grade. In the sciatic nerve, there was significant correlation between FA and CMTNS (r = -0.795; P < 0.05). FA and RD could discriminate CMT from controls with high sensitivity (77.8-100%) and specificity (88.9-100%). There were significant differences of DTI parameters between CMT and controls, with significant correlations between DTI parameters, muscle atrophy grade, and CMTNS. Level of Evidence 2 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53:437-444.


Methoxyindole synthesis in the retina of the frog (Rana esculenta) during a diurnal period.
In the present study, the synthesis of methoxyindoles in the neural part and in the pigment epithelial layer of the retina of the frog eye was investigated on the basis of naturally occurring substrate at regular intervals during a 24 hour period. Melatonin, 5-methoxytryptophol and 5-methoxyindole acetic acid were synthesized by the neural part of the retina only, while 5-methoxytryptamine and 5-methoxytryptophan were produced by both, the neural part of the retina and the pigment epithelium. The synthesis of melatonin and of 5-methoxytryptamine showed a diurnal rhythmicity. The results obtained clearly indicate that another cell type, i.e. pigment cells, is involved in indole metabolism besides photoreceptor elements. A possible functional relationship between different methoxyindoles and different retino-motor processes in the amphibian eye is discussed.


Sensitive method for determination of DON in cocoa by means of HPLC-techniques.
The mycotoxin deoxynivalenol (DON) is one of a group of mycotoxins known as type B trichothecenes and is particularly formed by the mould speciesFusarium graminearum andFusarium culmorum. The frequency of the occurrence of DON in certain raw materials and the concentrations found make it one of the world's most significant mycotoxin contaminants. Positive findings of the toxin especially have been established in cereal-based foods, as well as in oilseeds.The main objective of this study was to set up a current situation assessment of the possible occurrence of deoxynivalenol in cocoa and cocoa products. As there was no analytical method for determining DON in cocoa and cocoa products, a special method was developed. The applicability and consistency of the method was confirmed by performing recovery assays on various cocoa products. A special post-column derivatisation procedure was developed to increase selectivity and raise sensitivity by a factor of 80.The method was used to test 230 samples for possible DON content, ranging from cocoa beans to cocoa bean shells, nibs, cocoa liquor and cocoa powders through to finished cocoa-based products. The results suggest that DON may occasionally occur in cocoa beans in very low concentrations.


[A 67-year-old patient with recurrent hypoglycemia].
A 67 year old female patient was admitted to our clinic with recurrent hypoglycemia in December 2006. Laboratory findings revealed an elevated insulin, and C-peptide. Imaging techniques revealed a tumor of the pancreas involving the spleen with metastases of the liver, expressing somatostatin receptors. Ultrasound-guided biopsy was performed and confirmed the suspected insulinoma. Since the hypoglycemias could not sufficiently be controlled by subcutaneous administration of octreotide and by oral glucose intake, surgical debulking was performed in a palliative intention. After resection the patient was free of hypoglycemia. In case of diagnosed insulinoma, underlying MEN (multiple endocrine neoplasia) should be considered. Excision of the tumor is recommended in patients with benign solitary insulinomas. If complete excision is impossible, there are several therapeutic options that aim at preventing hypoglycemia. Thus, in contrast to other extended tumors, surgery is reasonable in malignant insulinoma even in case of metastatic disease.


Responses of syntrophic microbial communities and their interactions with polystyrene nanoplastics in a microbial electrolysis cell.
Microbial electrochemical technologies are promising for simultaneous energy recovery and wastewater treatment. Although the inhibitory effects of emerging pollutants, particularly micro/nanoplastics (MPs/NPs), on conventional wastewater systems have been extensively studied, the current understanding of their impact on microbial electrochemical systems is still quite limited. Microplastics are plastic particles ranging from 1 μm to 5 mm. However, nanoplastics are smaller plastic particles ranging from 1 to 100 nm. Due to their smaller size and greater surface area, they can penetrate deeper into biofilm structures and cell membranes, potentially disrupting their integrity and leading to changes in biofilm composition and function. This study first reports the impact of polystyrene nanoplastics (PsNPs) on syntrophic anode microbial communities in a microbial electrolysis cell. Low concentrations of PsNPs (50 and 250 μg/L) had a minimal impact on current density and hydrogen production. However, 500 μg/L of PsNPs decreased the maximum current density and specific hydrogen production rate by ∼43 % and ∼48 %, respectively. Exposure to PsNPs increased extracellular polymeric substance (EPS) levels, with a higher ratio of carbohydrates to proteins, suggesting a potential defense mechanism through EPS secretion. The downregulation of genes associated with extracellular electron transfer was observed at 500 μg/L of PsNPs. Furthermore, the detrimental impact of 500 μg/L PsNPs on the microbiome was evident from the decrease in 16S rRNA gene copies, microbial diversity, richness, and relative abundances of key electroactive and fermentative bacteria. For the first time, this study presents the inhibitory threshold of any NPs on syntrophic electroactive biofilms within a microbial electrochemical system.


Dispositions of junctional feet in muscles of invertebrates.
The structure and disposition of the feet occupying the junctions between sarcoplasmic reticulum (SR) and surface membrane/transverse tubules were studied in muscles from a variety of invertebrates. Feet were imaged by rotary shadowing of isolated junctional SR vesicles and by filtering of micrographs from grazing views of the junction in thin sections. The overall size and shape of invertebrate feet is the same as that of feet in skeletal and cardiac muscle of vertebrates. However, the arrangement of feet in invertebrate muscles differs from that in vertebrates. These findings are discussed in terms of known variations in properties of excitation-contraction coupling of the two phyla.


Radionuclides in the ground-level atmosphere in Vilnius, Lithuania, in March 2011, detected by gamma-ray spectrometry.
This study presents the ground-level air monitoring results obtained in Vilnius, the capital of Lithuania, on 14 March-14 April 2011 after the recent earthquake and subsequent Tsunami having a crucial impact on Japanese nuclear reactors at the Fukushima Daiichi Nuclear Power Plant (NPP) on 11 March 2011. To collect representative diurnal aerosol samples a powerful sampling system ensuring the air filtration rate of 5500 m(3) h(-1) was used. The following artificial gamma-ray emitting radionuclides have been determined: (129m)Te, (132)Te (in equilibrium with its daughter (132)I), (131)I, (134)Cs, (136)Cs and (137)Cs. Activity concentration of the globally distributed fission product (137)Cs has increased from a background value of 1.6 μBq m(-3) to the value of 0.9 mBq m(-3) at the beginning of April. The activity ratio (134)Cs/(137)Cs was found to be close to 1, with a slightly higher activity of (134)Cs. The maximum aerosol-associated (131)I activity concentration of 3.45 mBq m(-3) was by four orders of magnitude lower than that measured at the same location in April-May 1986 as a consequence of the Chernobyl NPP accident. The estimated gaseous fraction of iodine-131 constituted about 70% of the total (131)I activity.


Biological and serological variability, evolution and molecular epidemiology of Zucchini yellow mosaic virus (ZYMV, Potyvirus) with special reference to Caribbean islands.
Zucchini yellow mosaic virus (ZYMV, Potyvirus) emerged as an important pathogen of cucurbits within the last 20 years. Its origins and mechanisms for evolution and worldwide spread represent important questions to understand plant virus emergence. Sequence analysis on a 250 nucleotide fragment including the N-terminal part of the coat protein coding region, revealed one major group of strains, and some highly divergent isolates from distinct origins. Within the major group, three subsets of strains were defined without correlation with geographic origin, year of collection or biological properties. ZYMV was first observed in Martinique and Guadeloupe in 1992 and 1994, respectively. We studied the evolution of ZYMV variability on both islands in the few years following the putative virus introduction. In Martinique, molecular divergence remained low even after 6 years, suggesting a lack of new introductions. Interactions between strains resulted in a stability of the high biological variability, while the serological diversity decreased and molecular divergence remained low. In Guadeloupe, as in Martinique in 1993, serological variability was high shortly after virus introduction. While the first introduction in Guadeloupe was independent from Martinique, the 'Martinique' type was detected in 1998, suggesting further introductions, maybe through viruliferous aphids or imported plant material.


A new dual immunoassay for tumor markers based on chemiluminescence signal amplification by magnetic mesoporous silica and enzyme modified gold nanoparticles.
A sensitive dual immunoassay was proposed for the determination of carcinoembryonic antigen (CEA) and α-fetoprotein (AFP) based on signal amplification. Monoclonal antibodies immobilized on magnetic mesoporous silica particles (Fe(3)O(4)/SiO(2)) were prepared as the primary probe. Horseradish peroxidase (HRP) labeled antibodies co-coated with HRP on gold nanoparticles (AuNPs) were used as the secondary probe to achieve signal amplification. HRP tags were retained in the flow cells after a sandwich immunoassay. By controlling two switches on the two channels, chemiluminescent substrates were injected orderly man way, and then signals for CEA and AFP were sequentially detected by HRP-luminol-H(2)O(2). Due to the increased amount of HRP on AuNPs and the increased amount of monoclonal antibodies on Fe(3)O(4)/SiO(2), the signals were largely amplified. Under the optimal conditions, CEA and AFP could be detected in the linear ranges of 1.0 - 80 and 1.0 - 75 ng mL(-1) with detection limits of 0.25 and 0.5 ng mL(-1), respectively.


Adverse drug reactions during treatment of urinary tract infections.
Adverse reactions reported to the Swedish Adverse Drug Reaction Committée concerning Sulfapral (a sulphonamide combination for urinary tract infections) and nitrofurantoin were remarkably similar. The commonest hypersensitivity reactions were in skin and lung. During the 10-year period 1966-75 reactions to the sulphonamide were fewer (n=327) than those reported for nitrofurantoin (n=781), but the former appeared to carry a higher mortality rate - 4.6% of reported sulphonamide reactions were fatal as compared to only 1.0% for nitrofurantoin (P less than 0.001). The number of reactions to the sulphonamide tended to remain constant, whereas those to nitrofurantoin increased rapidly, both absolutely as well as relative to sales of the drug.


Performance and its determinants in the Portuguese municipal solid waste utilities.
The unprecedented population increase brings several consequences to the environment, including the rise of urbanization levels and municipal solid waste (MSW) production - one expects that it may reach 3.4 billion tons per year by 2050. This paper contributes to the debate of efficiency measurement of MSW utilities management using the Portuguese case study. Our objectives are twofold. First, we assess the efficiency levels of municipalities in MSW collection through the Data Envelopment Analysis model, choosing total costs, staff, and vehicles as inputs, and the quantity of MSW collected (selective and refuse waste) as outputs. The efficiency results point to an average inefficiency level of about 35% and potential cost savings of over €96 million yearly. Second, by using a set of fifteen performance indicators monitored by the regulatory agency, we evaluate their relationship with the efficiency of MSW utilities, through the order-m model. Our results suggest that, in opposition to the management model, the rural/urban nature of councils helps explain part of the inefficiency. In general, the conditional-to-unconditional efficiency ratios reached values statistically different from 1, meaning that those indicators help explaining their efficiency distribution and the benchmarks profile, and need to be considered in future performance analyses. Remarkable and influential indicators include the accessibility to the service (average ratio = 0.95), the recycling rate (0.94), the monetization of the vehicle fleet (0.92), the pollution resulting from greenhouse gas emissions of waste collection vehicles (0.81), and council size measured by the population or the number of households (0.47).


The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee.
This WHO/ISUP system is an attempt to develop as broad a consensus as possible in the classification of urothelial neoplasms, building upon earlier works and classification systems. It is meant to serve as a springboard for future studies that will help refine this classification, thus enabling us to provide better correlation of these lesions with their biologic behavior using uniform terminology.


Bacterial expression of immunoglobulin VH proteins.
A bacterial expression system in Escherichia coli has been developed that produces as much as 10 mg/l of culture of the VH protein associated with monoclonal antibodies specific for the 5-dimethylaminonaphthalene-2-sulfonyl (Dns) group. This system has been applied to the expression of the VH genes derived from a low-affinity, IgM-producing hybridoma and from a high-affinity, IgG-producing cell line. The plasmid vectors (contributed by Dr William F. Studier) utilize a T7 expression cassette whose activity is initiated by infection with a lambda phage derivative carrying the T7 RNA polymerase gene. The VH proteins were extracted from the bacterial pellet in 8 M urea and purified by chromatography in 8 M urea. Recombinants with the homologous light (L) chains were prepared to yield VHL molecules. These were used to measure intrinsic affinity for Dns-lysine by resonance energy transfer. The association constants were 7 x 10(6) M-1 and 7 x 10(9) M-1 for the low- and high-affinity systems, respectively. These values are not significantly different from those observed with monoclonal antibodies secreted from the corresponding cell lines. This system lends itself to the quantitative evaluation of the binding properties of the VH protein itself as well as the modulation of affinity by site-directed mutagenesis.


Perioperative changes in TGF-β1 levels predict the oncological outcome of cryoablation-receiving patients with localized prostate cancer.
To evaluate the cytokine transforming growth factor beta 1 (TGF-β1) as a predictor of oncological outcomes in patients after cryoablation. Perioperative blood samples from prostate cancer (PC) patients who underwent total gland cryoablation between October 2011 and March 2013 were collected prospectively. Plasma TGF-β1 levels were quantified using magnetic bead immunoassay. The perioperative change in TGF-β1 was defined as the change in TGF-β1 from before surgery to 1-2 months after surgery. Biochemical recurrence (BCR) was defined according to the Phoenix criteria. The Mann-Whitney U, Kruskal-Wallis rank sum, and Chi-square test were used to compare the clinical characteristics of the subsets. The Cox proportional hazard model was applied for the comparison of recurrence risk among the groups. A total of 75 PC patients were included. During a median follow-up period of 12 months (range: 2.5-47 months), 11 patients had BCR, and 64 patients did not. Significantly greater changes in the perioperative TGF-β1 levels (median: 470.3 vs. 78.9 pg/ml) were observed in patients with than without BCR (p < 0.05). According to the changes in TGF-β1 levels, the patients were further divided into 4 groups, which were determined in the quartile categories of perioperative TGF-β1 levels. Group 4 (≥430) predicted the worst BCR outcome. Perioperative plasma TGF-β1 levels were associated with BCR after prostate cryoablation for localized PC. Increase in postoperative plasma TGF-β1 may be a novel predictor for poor oncological outcomes and prompt a more aggressive follow-up or earlier salvage treatment.


MRI Evaluation of Mullerian Duct Anomalies: Practical Classification by the New ASRM System.
To describe variable mullerian duct anomalies using magnetic resonance imaging (MRI) and to classify these anomalies according to the available classification systems, namely the American Fertility Society (AFS) system, the European Society of Human Reproduction and Embryology (ESHRE) system, and the new American Society for Reproductive Medicine (ASRM) system. Retrospective chart review. The pelvic MRI studies and the clinical records of 64 females with mullerian congenital anomalies were retrospectively reviewed between January 2010 and December 2021. The mean age was 22 years (age range 2-63 years). Detailed imaging findings were recorded, and the resulting mullerian anomalies were then classified according to the three classification systems of interest. Variable mullerian anomalies were found among patients with multiple frequencies. Mullerian agenesis and hypoplasia were found in 12 patients (19%) and 16 patients (25%), respectively. Uterus didelphys was found in 5 patients (8%). Twelve (19%) patients had septate uterus, while 8 (12.5%) had a bicornuate anomaly. Unicornuate uterus was present in 7 patients (11%). Isolated vaginal anomaly was diagnosed in 4 patients (6%). Renal/urinary tract imaging was available for 27 (42%) patients, and accompanying urinary tract anomalies were noted in 10 of them (37%). Few ovarian and other extra-renal anomalies were observed. MRI could efficiently delineate the mullerian anomalies regardless of their complexity. Most of these anomalies were more efficaciously categorized by the ESHRE and the new ASRM systems, compared to the originally widely used AFS system. The new ASRM classification was found to be more practical as it is a modification of the original AFS system, using drawings with clear descriptions instead of symbols. This is particularly helpful in the radiological era, saving time and effort.


Hunchback prevents notch-induced apoptosis in the serotonergic lineage of Drosophila Melanogaster.
The serotonergic lineage (NB7-3) in the Drosophila ventral nerve cord produces six cells during neurogenesis. Four of the cells differentiate into neurons: EW1, EW2, EW3 and GW. The other two cells undergo apoptosis. This simple lineage provides an opportunity to examine genes that are required to induce or repress apoptosis during cell specification. Previous studies have shown that Notch signaling induces apoptosis within the NB7-3 lineage. The three EW neurons are protected from Notch-induced apoptosis by asymmetric distribution of Numb protein, an inhibitor of Notch signaling. In a numb1 mutant EW2 and EW3 undergo apoptosis. The EW1 and GW neurons survive even in a numb1 mutant background suggesting that these cells are protected from Notch-induced apoptosis by some factor other than Numb. The EW1 and GW neurons are mitotic sister cells, and uniquely express the transcription factor Hunchback. We present evidence that Hunchback prevents apoptosis in the NB7-3 lineage during normal CNS development and can rescue the two apoptotic cells in the lineage when it is ectopically expressed. We show that hunchback overexpression produces ectopic cells that express markers similar to the EW2 neuron and changes the expression pattern of the EW3 neuron to a EW2 neuron. In addition we show that hunchback overexpression can override apoptosis that is genetically induced by the pro-apoptotic genes grim and hid.


Rapidly progressive bone destruction of the finger as first presentation of systemic metastases from lung cancer.
We report a case of a man with locally advanced lung adenocarcinoma and no evidence of metastatic disease presenting with rapid onset pain and swelling of his right second finger. Radiographically and clinically this was felt to be osteomyelitis and he was treated with intravenous antibiotics. He clinically worsened, and upon biopsy was found to have metastatic adenocarcinoma of the digit. He was treated with radiotherapy with some symptom improvement. He shortly thereafter developed diffuse skeletal metastases.


Femoroacetabular impingement: question-driven review of hip joint pathophysiology from asymptomatic skeletal deformity to end-stage osteoarthritis.
Femoroacetabular impingement (FAI), together with its two main pathomechanisms, cam and pincer, has become a trending topic since the end of the 1990s. Despite massive academic research, this hip disorder still conceals obscure aspects and unanswered questions that only a question-driven approach may settle. The pathway that leads a FAI asymptomatic morphology through a FAI syndrome to a FAI-related osteoarthritis is little known. Contact mechanics provides a shareable and persuasive perspective: cam FAI is based on shear contact stress at joint level with consequent cartilage wear; pincer FAI, contrariwise, determines normal contact stress between acetabular rim and femoral neck and squeezes the labrum in between, with no cartilage wear for many years from the onset. Pincer prognosis is then far better than cam. As a matter of fact, cartilage wear releases fragments of extracellular matrix which in turn trigger joint inflammation, with consequently worsening lubrication and further enhanced wear. Inflammation pathobiology feeds pathotribology through a vicious loop, finally leading to hip osteoarthritis. The association of cam and pincer, possibly overdiagnosed, is a synergic combination that may damage the joint rapidly and severely. The expectations after FAI surgical correction depend strictly on chondral layer imaging, on time elapsed from the onset of symptoms and on clinic-functional preoperative level. However, preemptive surgical correction is not recommended yet in asymptomatic FAI morphology. LEVEL OF EVIDENCE: V.


Prolonged recovery of retinal structure/function after gene therapy in an Rs1h-deficient mouse model of x-linked juvenile retinoschisis.
X-linked juvenile retinoschisis (RS) is a common cause of juvenile macular degeneration in males. RS is characterized by cystic spoke-wheel-like maculopathy, peripheral schisis, and a negative (b-wave more reduced than a-wave) electroretinogram (ERG). These symptoms are due to mutations in the RS1 gene in Xp22.2 leading to loss of functional protein. No medical treatment is currently available. We show here that in an Rs1h-deficient mouse model of human RS, delivery of the human RS1 cDNA with an AAV vector restored expression of retinoschisin to both photoreceptors and the inner retina essentially identical to that seen in wild-type mice. More importantly, unlike an earlier study with a different AAV vector and promoter, this work shows for the first time that therapeutic gene delivery using a highly specific AAV5-opsin promoter vector leads to progressive and significant improvement in both retinal function (ERG) and morphology, with preservation of photoreceptor cells that, without treatment, progressively degenerate.


Long-term effects of brain trypsinization before cell seeding on cell morphology and surface composition.
The relation between the pattern of proteins localized in the surface of astroglial cells and cell differentiation was investigated in primary cultures derived from neonatal rat brains, dissociated either mechanically (MDC) or by 3 (TDC3) and 30 minutes (TDC30) trypsinization. Morphological and ultrastructural studies revealed a bed layer composed of flat, polygonal young and differentiated astrocytes in all types of cultures and a surface layer composed of small, ovoide undifferentiated cells which were more numerous in TDC30 than in TDC3 and MDC. The enrichment in undifferentiated cells, induced by prolonged brain trypsinization prior cell seeding, was observed during two weeks in culture; latter, by day 20, the cell population in all cultures was that of differentiated astrocytes. The presence of structural and enzymatic cell markers indicated that the cell population in MDC and TDC3 as well as in TDC3, including the small cells, was of astroglial origin. Concomitant with the morphological changes, cells in TDC30 were less accessible to surface labeling than those composing MDC. Subsequent electrophoresis of the labeled surface proteins demonstrated that a 140-130 K complex was the most "sensible" to brain trypsinization and that their accessibility to the surface probing was maximal during the differentiation of astrocytes in MDC or of small cells in TDC30. By day 20, these components were not significantly labeled in both, MDC, and TDC30, cultures. The use of two types of astrocytes primary culture which were different in the ratio of differentiated to undifferentiated cells and their surface labeling at different growth stages showed a variation in the composition of surface proteins during the cell maturation. The increased accessibility of some surface proteins to external probing when the cells developed to differentiated astrocytes might suggest their involvement in cell differentiation.


Role of zinc and alpha2 macroglobulin on thymic endocrine activity and on peripheral immune efficiency (natural killer activity and interleukin 2) in cervical carcinoma.
Decreased natural killer (NK) activity as well as interleukin 2 (IL-2) are risk factors for the progression of cervical carcinoma. NK activity and IL-2 may be thymus controlled. Plasma levels of active thymulin, a zinc-dependent thymic hormone (ZnFTS), are reduced in cancer because of the low peripheral zinc bioavailability. Zinc and thymulin are relevant for normal immune functions. Alpha2-macroglobulin is an inhibitor of matrix metalloproteases (MMPs) against invasive tumour proliferation. Because alpha2-macroglobulin has a binding affinity (Kd) for zinc that is higher than does thymulin, it may play a key role in immune efficiency in cancer. Plasma samples of 22 patients (age range 35-60 years) with locally advanced squamous cervical carcinoma and with FIGO stage Ib2-IIb were examined. They showed reduced active thymulin, decreased NK activity and IL-2 production, increased soluble IL-2 receptor (sIL-2R) and augmented alpha2-macroglobulin in the circulation, whereas plasma zinc levels were within the normal range for age. Significant positive correlations were found between zinc or active thymulin and alpha2-macroglobulin (r = 0.75, P < 0.01, r = 0.78, P < 0.01, respectively) in cancer patients. In vitro zinc increases IL-2 production from peripheral blood mononuclear cells (PBMCs) of cancer patients. These data suggest that an increase in alpha2-macroglobulin, which competes with thymulin for zinc binding, may be involved in causing a thymulin deficit with a consequent decrease of IL-2 and NK cytotoxicity. Thus, physiological zinc treatment in cervical carcinoma maybe restores impaired central and peripheral immune efficiency.


Non-steroidal anti-inflammatory drug use and the risk of Parkinson disease: a retrospective cohort study.
Using the British Columbia Linked Health Databases, we explored the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of developing Parkinson's disease (PD). We followed a cohort of older adults in the Province of British Columbia from 1997 to 2003. A time-dependent Cox model was used to estimate adjusted rate ratios for users and non-users of NSAIDs. The results of our study did not show a protective effect of NSAIDs for PD (rate ratio 0.84, 95% CI 0.81-1.09).


Evaluating perinatal and neonatal outcomes among children with vascular Ehlers-Danlos syndrome.
Birth outcomes data for patients with vascular Ehlers-Danlos syndrome (VEDS) are limited. Patients with a pathogenic or likely pathogenic COL3A1 variant were included. Outcomes included gestational age (GA), birthweight (BW), and maternal complications. Birth outcomes were first compared with that of US population data, then compared by sex, maternal affected status, and COL3A1 genotype. A total of 41 children were included (70.7% male), including 32 with high-risk (missense and splice site) variants. Preterm birth (<37 weeks) was more common in patients with VEDS than in the US population (48.8% vs 12.2%, P < .0001). Low BW (<2.5 kg) was also more common in patients with VEDS than in the US population (P < .0001), although, it was appropriate after GA adjustment (median GA-adjusted z-score 0.01 vs z-score 0.0, P = .26). No differences in GA or BW were observed by sex or maternal affected status. Those with high-risk variants were more likely to be born preterm than those with haploinsufficient variants, although this did not meet significance criteria (53% vs 33%, P = .35). Of the 6 affected mothers, 5 had perinatal complications. Preterm birth is more common in children with VEDS than in the general population. Maternal affected status is not associated with preterm birth, suggesting that risk is conferred by the fetal VEDS diagnosis alone.


Fabrication of uniform Ru-doped NiFe2O4 nanosheets as an efficient hydrogen evolution electrocatalyst.
Here we demonstrate the synthesis of uniform Ru-doped NiFe2O4 nanosheets with robust hydrogen evolution reaction (HER) activity in alkaline solution, with an extremely low overpotential of 18 mV versus a reversible hydrogen electrode (RHE) at a current density of 10 mA cm-2 and a Tafel slope of 27 mV dec-1.


Posterior chamber intraocular lens implantation by ophthalmology residents. A prospective study of cataract surgery.
The UCLA Cataract Surgery Study Group evaluated extracapsular cataract extraction with posterior chamber intraocular lens implantation (ECCE-posterior chamber IOL) performed by eight senior ophthalmology residents with faculty supervision and five faculty ophthalmologists experienced in intraocular lens surgery. The first 18 consecutive ECCE-posterior chamber IOL operations performed by each resident and faculty surgeon after July 1, 1981, were analyzed. All 234 operations and follow-up conformed to a predetermined protocol. Resident surgery achieved 20/40 or better final visual acuity in 88% of eyes; faculty surgery achieved 20/40 or better in 89%. Excluding cases with macular degeneration or other pre-existing eye disease, resident surgery achieved 20/40 or better final visual acuity in 95% of eyes; faculty surgery achieved 20/40 or better in 96%. There was no statistically significant difference between the results of resident surgery and faculty surgery. With supervision, ophthalmology residents achieved results generally equivalent to results obtained by experienced ophthalmic surgeons.


Biliary cholesterol absorption in normal and L-thyroxin-fed rats.
Infusion of bile containing labeled cholesterol into bile fistula rats has permitted an in vivo study of the movements and of the absorption of biliary cholesterol in the digestive tract. The specific activities of cholesterol were similar in the micelles and the sediment of the luminal content after a 6 hr infusion, indicating rapid exchange of cholesterol between these fractions. In animals fed a basal diet, the biliary cholesterol absorption was higher (83%) than that of dietary cholesterol (70%). Bile cholesterol is essentially absorbed in the jejunum while the absorption of cholesterol from the diet takes place all along the small intestine but preferentially in its second and third quarters. Both alimentary cholesterol and bile cholesterol enter the top cells of the villi in preference to those of the crypts. In L-thyroxin-fed rats, a parallel decrease in biliary and dietary cholesterol absorption was observed. The increase in the intestinal transit of cholesterol and epithelium cell renewal of the jejunum accounted for this observation.


Serum lipoprotein(a) positively correlates with coronary artery calcification in low-risk chinese han patients: a study from a single center.
Elevated plasma levels of lipoprotein(a) (Lp(a)) and a higher degree of coronary artery calcification (CAC) are both considered to be risk factors for atherosclerosis. However, previous studies have demonstrated that the relationship between Lp(a) levels and the degree of CAC indicates significant heterogeneity that may be due to varying ethnicities. The purpose of this study was to examine the predictive power of Lp(a) for CAC as measured by multidetector computed tomography (MDCT) in the Han ethnic group of China. A total of 1082 subjects were recruited in this study. The patients were divided into four groups: patients without hypertension or diabetes were group 1, patients with hypertension were group 2, patients with diabetes were group 3 and patients with both hypertension and diabetes were group 4. CAC score (CACs), lipid profiles (Lp(a), LDL, HDL, TG, TC), HbA1C, glucose, personal health history and body morphology were measured in all participants. The predictive power of Lp(a) for calcified atherosclerotic plaque was determined by correlations and ordinal logistic regression. There was no significant difference in the CACs between group 2 and group 3 (z = 1.790, p = 0.736), and there were significant differences among the other groups. However, there was no significant difference in the total Lp(a) among the 4 groups (χ(2) = 0.649, p = 0.885). Only In group 1, Lp(a) was a statistically significant predictor of the presence of calcified coronary plaque using ordinal logistic regression. Levels of Lp(a) positively correlate with CACs among Chinese Han people who are without diabetes and hypertension, suggesting that Lp(a) may be an important risk factor for the presence of calcified atheromas.


Human kallikrein 6 inhibitors with a para-amidobenzylanmine P1 group identified through virtual screening.
A series of hK6 inhibitors with a para-amidobenzylamine P1 group and a 2-hydroxybenzamide scaffold linker was discovered through virtual screening. The X-ray structure of hK6 complexed with compound 9b was determined to a resolution of 1.68Å. The tertiary folding of the hK6 complexed with the inhibitor is conserved relative to the structure of the apo-protein, whereas the interaction between hK6 and the inhibitor is consistent with both the SAR and the in silico model used in the virtual screening.


Osteogenic differentiation and calcification of human aortic smooth muscle cells is induced by the RCN2/STAT3/miR-155-5p feedback loop.
Vascular calcification (VC) is associated with the high morbidity and mortality of cardiovascular diseases in dialysis patients and is a process in which vascular smooth muscle cells (VSMCs) actively differentiate into osteoblast-like cells. Reticulocalbin-2 (RCN2) is involved in the process of osteogenic differentiation under diabetic conditions, but its regulatory role under hyperphosphatemic conditions and the related mechanisms remain unclear. In this study, the importance of the interactions among RCN2, STAT3 and miR-155-5p during the osteogenic differentiation and calcification of human aortic VSMCs (HASMCs) were investigated. RCN2 was measured in femoropopliteal artery plaque specimens from 6 peripheral arterial disease (PAD) patients with chronic kidney disease (CKD) and 6 PAD patients without CKD. RCN2 protein and mRNA expression were assessed in the high phosphate-induced aortic rings culture ex vivo model. In vitro calcification assays and molecular mechanism studies were performed in HASMCs. Immunohistochemical staining results revealed increased RCN2 expression in the calcified plaques of femoral arteries of patients with CKD and in a high phosphate-induced aortic culture ex vivo model. RCN2 promoted HASMCs osteogenic differentiation and calcification by inducing STAT3 phosphorylation. Furthermore, inhibition of STAT3 activation by cryptotanshinone (CT) promoted miR-155-5p expression in HASMCs. In turn, miR-155-5p inhibited RCN2 mRNA expression, while RCN2 overexpression partially offset the miR-155-5p-mediated inhibition of HASMC calcification, acting as a positive feedback loop. These results demonstrate that RCN2 is a crucial regulator of VC under hyperphosphatemic conditions. RCN2/STAT3/miR-155-5p feedback loop is important in VC and targeting each member of this feedback loop could potentially reverse high phosphate-induced VC.


Identification of a human immunodeficiency virus-1 protease cleavage site within the 66,000 Dalton subunit of reverse transcriptase.
The human immunodeficiency virus-1 reverse transcriptase is a heterodimer of related 51 and 66 kDa subunits. The smaller subunit arises by viral protease-catalyzed cleavage of the carboxy-terminal domain of the 66 kDa species. Comparison of the amino acid composition analyses of the isolated 51 kDa and 66 kDa subunits indicates that the carboxyl terminus of 51 kDa is Phe440. This site was confirmed in vitro using purified recombinant protease and a peptide spanning the postulated cleavage area. The sequence surrounding this site does not show significant homology to other protease cleavage sites in the viral gag and pol precursors; thus, this new information may contribute to our understanding of the sequence specificity of the viral protease.


Insight into the comparison of key aroma-active compounds between camellia oils from different processing technology.
Currently, the difference between key odorants of camellia oils from different processing technology (i.e., extra virgin camellia oil (EVCO), virgin camellia oil (VCO), fragrant camellia oil (FCO)) is unclear. In this study, a total of 91 odorants were identified by comprehensive two-dimensional gas chromatography and quadrupole mass spectrometry (GC × GC-qMS). The headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) provided fingerprint information for 57 odorants distinguished between EVCO, VCO, and FCO. Moreover, 76 odorants were shown flavor dilution (FD) factors range from 1 to 729, and fruity esters (ethyl 2-hydroxypropanoate, ethyl decanoate, and ethyl phenylacetate) with FD factors ≥ 27 and odor activity values ≥ 1 are the unique odorants in EVCO. (E, E)-2,4-Heptadienal, (E, E)-2,4-nonadienal, and d-limonene are the aroma-active compounds in VCO. While furfural and 3-ethyl-2,5-dimethylpyrazine with FD factors ≥ 243 are the major contributors to roasted and nutty odor in FCO. This work provides aroma markers for quality assessment of camellia oils.


Growth inhibition of human fibroblasts by epidermal growth factor in the presence of arachidonic acid.
The effect of epidermal growth factor on growth of human fibroblasts was investigated in serum-free medium supplemented with various fatty acids. When linoleic acid, arachidonic acid, or eicosapentaenoic acid was added, each inhibited epidermal growth factor-induced cell growth and showed cytotoxicity at high concentrations (greater than 10 microM). This cytotoxic effect was not observed in the presence of indomethacin, suggesting that prostaglandin production is important in mediation of the growth inhibition. Prostaglandin E2 was increased more than ten thousand times by epidermal growth factor in combination with arachidonic acid.


Cortical regulation of two-stage rapid eye movement sleep.
Rapid eye movement (REM) sleep is a sleep state characterized by skeletal muscle paralysis and cerebral cortical activation. Yet, global cortical dynamics and their role in regulating REM sleep remain unclear. Here we show that in mice, REM sleep is accompanied by highly patterned cortical activity waves, with the retrosplenial cortex (RSC) as a major initiation site. Two-photon imaging of layer 2/3 pyramidal neurons of the RSC revealed two distinct patterns of population activities during REM sleep. These activities encoded two sequential REM sleep substages, characterized by contrasting facial movement and autonomic activity and by distinguishable electroencephalogram theta oscillations. Closed-loop optogenetic inactivation of RSC during REM sleep altered cortical activity dynamics and shortened REM sleep duration via inhibition of the REM substage transition. These results highlight an important role for the RSC in dictating cortical dynamics and regulating REM sleep progression.


Efficacy of prophylactic inferior vena caval filters in prevention of pulmonary embolism in the absence of deep venous thrombosis.
There is an increasing use of inferior vena caval filters (IVCFs) as prophylactic activity in the absence of a deep venous thrombosis (DVT) to prevent pulmonary embolism (PE) in high-risk patients. These devices are effective in preventing PE in the presence of lower extremity DVT, when anticoagulation is contraindicated or has failed. An electronic databases search of MEDLINE, PubMed, The Cochrane Library, and Google Scholar for relevant articles listed between January 2000 and December 2014 was performed. The review was confined to patients without a history of previous venous thromboembolism and no evidence of changes on venous duplex imaging suggestive of previous DVT. At present, the use of prophylactic IVCF is predominantly in the trauma, orthopedic, and bariatric surgical populations. Currently, no class I studies exist to support insertion of an IVCF in a patient without an established DVT or PE. However, there is a body of class II and class III evidence that would support the use of IVCFs in certain "high-risk" patients who do not have a documented DVT or the occurrence of a PE. Widespread use of prophylactic IVCFs is not supported by evidence and should be discouraged.


Polymorphisms in ATP-binding cassette transporters associated with maternal methylmercury disposition and infant neurodevelopment in mother-infant pairs in the Seychelles Child Development Study.
ATP-binding cassette (ABC) transporters have been associated with methylmercury (MeHg) toxicity in experimental animal models. To evaluate the association of single nucleotide polymorphisms (SNPs) in maternal ABC transporter genes with 1) maternal hair MeHg concentrations during pregnancy and 2) child neurodevelopmental outcomes. Nutrition Cohort 2 (NC2) is an observational mother-child cohort recruited in the Republic of Seychelles from 2008-2011. Total mercury (Hg) was measured in maternal hair growing during pregnancy as a biomarker for prenatal MeHg exposure (N=1313) (mean 3.9ppm). Infants completed developmental assessments by Bayley Scales of Infant Development II (BSID-II) at 20months of age (N=1331). Genotyping for fifteen SNPs in ABCC1, ABCC2 and ABCB1 was performed for the mothers. Seven of fifteen ABC SNPs (ABCC1 rs11075290, rs212093, and rs215088; ABCC2 rs717620; ABCB1 rs10276499, rs1202169, and rs2032582) were associated with concentrations of maternal hair Hg (p<0.001 to 0.013). One SNP (ABCC1 rs11075290) was also significantly associated with neurodevelopment; children born to mothers with rs11075290 CC genotype (mean hair Hg 3.6ppm) scored on average 2 points lower on the Mental Development Index (MDI) and 3 points lower on the Psychomotor Development Index (PDI) than children born to mothers with TT genotype (mean hair Hg 4.7ppm) while children with the CT genotype (mean hair Hg 4.0ppm) had intermediate BSID scores. Genetic variation in ABC transporter genes was associated with maternal hair Hg concentrations. The implications for MeHg dose in the developing child and neurodevelopmental outcomes need to be further investigated.


Bacterial NadQ (COG4111) is a Nudix-like, ATP-responsive regulator of NAD biosynthesis.
Nicotinamide-adenine dinucleotide (NAD) is centrally important to metabolic reactions that involve redox chemistry. In bacteria, NAD biosynthesis is controlled by different transcription factors, depending on the species. Among the four regulators identified so far, the protein NadQ is reported to act as a repressor of the de novo NAD biosynthetic pathway in proteobacteria. Using comparative genomics, a systematic reconstruction of NadQ regulons in thousands of fully sequenced bacterial genomes has been performed, confirming that NadQ is present in α-proteobacteria and some β- and γ-proteobacteria, including pathogens like Bordetella pertussis and Neisseria meningitidis, where it likely controls de novo NAD biosynthesis. Through mobility shift assay and mutagenesis, the DNA binding activity of NadQ from Agrobacterium tumefaciens was experimentally validated and determined to be suppressed by ATP. The crystal structures of NadQ in native form and in complex with ATP were determined, indicating that NadQ is a dimer, with each monomer composed of an N-terminal Nudix domain hosting the effector binding site and a C-terminal winged helix-turn-helix domain that binds DNA. Within the dimer, we found one ATP molecule bound, at saturating concentration of the ligand, in keeping with an intrinsic asymmetry of the quaternary structure. Overall, this study provided the basis for depicting a working model of NadQ regulation mechanism.


Cloacal exstrophy and cloacal exstrophy variants: a proposed system of classification.
A coding system that documents the abnormalities within the cloacal exstrophy complex is presented. Analysis allows the classification of these abnormalities into classical and variant series in a logical manner. The application of the coding system to selected reported material is described and it demonstrates the similarities between apparently divergent cases.


One-Shot Dilatation vs Metal Dilator During Percutaneous Nephrolithotomy in Flank-Free Supine Position: A Randomized Controlled Study.
Background: The creation and dilatation of the nephrostomy tract is a fundamental step in percutaneous nephrolithotomy (PCNL). In one-shot dilatation (OSD), we used a single Amplatz dilator over a central Alken rod. PCNL in the supine position is as effective and safe as in the prone position. The Barts flank-free modified supine position sums several advantages of the different supine positions. We evaluated the efficacy and safety of OSD compared with metal telescopic dilator (MTD) during PCNL while the patient was in Barts flank-free modified supine position. Materials and Methods: Within 2.5 years, 150 patients with kidney stone candidates for PCNL were randomized into two equal groups according to the dilatation technique. In the OSD group, dilatation was performed using a single Amplatz dilator (30F) and in the MTD group dilatation was performed by sequential MTD (9-30F). All PCNL procedures were done with patients in Barts flank-free modified supine position. Patient characteristics, operative data, and results were collected for statistical analysis. Results: There are no statistically significant differences between both groups regarding patients' characters. The tracts were effectively dilated in all patients. Statistical analyses show a significant difference (p ˂ 0.05) between both groups regarding the time of dilatation (seconds; 68 ± 15 vs 147 ± 18), time of X-ray exposure (seconds; during dilatation; 36 ± 10 vs 61 ± 15 and the total; 157 ± 16 vs 181 ± 20), hemoglobin loss (mg/dL; 0.7 ± 0.2 vs 1.2 ± 0.3), and hospital stay (days; 3 ± 0.6 vs 3.7 ± 0.7) with favorable results to OSD. Complication rates were comparable between the two groups. Conclusions: OSD is efficient as MTD during PCNL while patients are in Barts flank-free modified supine position, with less dilatation time, X-ray exposure, blood loss, and hospital stay than MTD.


Comparison of surgical intervention with functional treatment for acute ruptures of lateral ankle ligmant: a meta-analysis.
To compare the effect of surgical intervention on functional treatment. By searching the MEDLINE (1966 to October 2011), EMBASE (1980 to October 2011), the Chinese Biomedical Database Databases (1980 to October 2011), a total of 9 related RCT studies comparing surgical intervention with functional treatment were included in our study. RevMan software was taken to analyze the data. These 9 studies involved a total of 1 268 mostly young adults, including 580 patients with surgical treatment and 688 patients with functional treatment. The results showed the stability of ankle activity in surgical treatment group was better than that in functional treatment group, with the OR and 95% CI of 0.72 (0.52-0.99). No significant difference was found in the recurrence of the surgical and functional group. However, the movement disorder in the surgical treatment suggested increased risk than that in functional group, with the OR and 95% CI of 2.39 (0.98-5.85). Surgical group found more complication than the function group, such as deep vein thrombosis, deep venous thrombosis, tenderness of scar and sensory loss. In conclusion, our finding showed that surgical treatment could gain better efficacy than functional treatment, but may bring more complication. Therefore, further large sample size RCT is warranted.