Cyclopentenone causes cell cycle arrest and represses cyclin D1 promoter activity in MCF-7 breast cancer cells.
Evidence indicates that overexpression of cyclin D1 is an important event in malignant transformation of breast cancer cells. Therefore, cyclin D1 is a potential target for mechanistically-based chemoprevention/treatment of breast cancer. Treatment of serum-stimulated quiescent MCF-7 breast cancer cells with cyclopentenone (2-cyclopenten-1-one) blocked progression through G1 and into S phase. Growth arrest of the cyclopentenone-treated cells in G1 was associated with changes in the levels of several proteins that control the cell cycle, including a dramatic decrease in cyclin D1 protein expression. Cyclopentenone also decreased the abundance of cyclin D1 mRNA and nuclear transcripts, indicating that it regulated cyclin D1 expression at the transcriptional level. Cyclopentenone selectively inhibited the activity of the cyclin D1 and cyclin A promoters but not the activity of several other control promoters. Deletion analysis indicated that the cyclopentenone response element was located in the cyclin D1 core promoter. Additional functional studies showed that a sequence within the core promoter (CycY, located downstream from the initiator element) played an important role in activation of the cyclin D1 promoter in MCF-7 cells. Electrophoretic mobility shift assays demonstrated specific binding of the transcription factor BTEB to the CycY site. The cyclopentenone response element did not correspond to the CycY site but rather mapped to the initiator element itself. The overall results suggest that cyclopentenone interferes with the transcription initiation complex that assembles over the cyclin D1 initiator element, leading to selective inhibition of cyclin D1 gene transcription.


Plasticity of thalamocortical axons is regulated by serotonin levels modulated by preterm birth.
Sensory inputs are conveyed to distinct primary areas of the neocortex through specific thalamocortical axons (TCA). While TCA have the ability to reorient postnatally to rescue embryonic mistargeting and target proper modality-specific areas, how this remarkable adaptive process is regulated remains largely unknown. Here, using a mutant mouse model with a shifted TCA trajectory during embryogenesis, we demonstrated that TCA rewiring occurs during a short postnatal time window, preceded by a prenatal apoptosis of thalamic neurons-two processes that together lead to the formation of properly innervated albeit reduced primary sensory areas. We furthermore showed that preterm birth, through serotonin modulation, impairs early postnatal TCA plasticity, as well as the subsequent delineation of cortical area boundary. Our study defines a birth and serotonin-sensitive period that enables concerted adaptations of TCA to primary cortical areas with major implications for our understanding of brain wiring in physiological and preterm conditions.


Histone lysine methacrylation is a dynamic post-translational modification regulated by HAT1 and SIRT2.
Histone lysine crotonylation is a posttranslational modification with demonstrated functions in transcriptional regulation. Here we report the discovery of a new type of histone posttranslational modification, lysine methacrylation (Kmea), corresponding to a structural isomer of crotonyllysine. We validate the identity of this modification using diverse chemical approaches and further confirm the occurrence of this type of histone mark by pan specific and site-specific anti-methacryllysine antibodies. In total, we identify 27 Kmea modified histone sites in HeLa cells using affinity enrichment with a pan Kmea antibody and mass spectrometry. Subsequent biochemical studies show that histone Kmea is a dynamic mark, which is controlled by HAT1 as a methacryltransferase and SIRT2 as a de-methacrylase. Altogether, these investigations uncover a new type of enzyme-catalyzed histone modification and suggest that methacrylyl-CoA generating metabolism is part of a growing number of epigenome-associated metabolic pathways.


Disrupting interaction between miR-132 and Mmp9 3'UTR improves synaptic plasticity and memory in mice.
As microRNAs have emerged to be important regulators of molecular events occurring at the synapses, the new questions about their regulatory effect on the behavior have araised. In the present study, we show for the first time that the dysregulated specific targeting of miR132 to Mmp9 mRNA in the mouse brain results in the increased level of Mmp9 protein, which affects synaptic plasticity and has an effect on memory formation. Our data points at the importance of complex and precise regulation of the Mmp9 level by miR132 in the brain.


Fault-tolerant nonlinear adaptive flight control using sliding mode online learning.
An expanded nonlinear model inversion flight control strategy using sliding mode online learning for neural networks is presented. The proposed control strategy is implemented for a small unmanned aircraft system (UAS). This class of aircraft is very susceptible towards nonlinearities like atmospheric turbulence, model uncertainties and of course system failures. Therefore, these systems mark a sensible testbed to evaluate fault-tolerant, adaptive flight control strategies. Within this work the concept of feedback linearization is combined with feed forward neural networks to compensate for inversion errors and other nonlinear effects. Backpropagation-based adaption laws of the network weights are used for online training. Within these adaption laws the standard gradient descent backpropagation algorithm is augmented with the concept of sliding mode control (SMC). Implemented as a learning algorithm, this nonlinear control strategy treats the neural network as a controlled system and allows a stable, dynamic calculation of the learning rates. While considering the system's stability, this robust online learning method therefore offers a higher speed of convergence, especially in the presence of external disturbances. The SMC-based flight controller is tested and compared with the standard gradient descent backpropagation algorithm in the presence of system failures.


Correction: Gold(I) complexes based on six-membered phosphorus heterocycles as bio-active molecules against brain cancer.
Correction for 'Gold(i) complexes based on six-membered phosphorus heterocycles as bio-active molecules against brain cancer' by Saskia Roesch et al., Chem. Commun., 2020, DOI: 10.1039/d0cc05761d.


A comparative validation of a child food frequency questionnaire using red blood cell membrane fatty acids.
There are limited validated tools available for the assessment of dietary intake in pediatric populations. This report describes a comparative validation study of selected fatty acid intakes in children assessed by food frequency questionnaire (FFQ), compared with erythrocyte membrane fatty acids. Overall, 46 overweight and 47 healthy-weight children aged 5-12 years (mean±SD, 9.1±1.3years, body mass index 20.5±4.0) were recruited; dietary fatty acid intakes assessed by parent report using a 135-item semi-quantitative FFQ, were compared with selected child erythrocyte membrane fatty acids assessed from fasting samples using gas chromatography. Spearman's rank correlation coefficients were calculated between fatty acid intake estimates (% of energy) and erythrocyte membrane concentrations (%mol/mol). Significant correlations were found between dietary and erythrocyte eicosapentanoic acid (EPA) concentration (r=0.24, P<0.05) with a statistical trend for total omega three (∑n-3) fatty acids (r=0.22, P=0.06) and linoleic acid (r=0.32, P=0.07) in the healthy-weight children only. Parental report of selected child fatty acid intakes using an FFQ can be used to provide an estimate of child intake of EPA, but further work is required to quantify this relationship for other fatty acids and in other populations.


On semidiscrete constant mean curvature surfaces and their associated families.
The present paper studies semidiscrete surfaces in three-dimensional Euclidean space within the framework of integrable systems. In particular, we investigate semidiscrete surfaces with constant mean curvature along with their associated families. The notion of mean curvature introduced in this paper is motivated by a recently developed curvature theory for quadrilateral meshes equipped with unit normal vectors at the vertices, and extends previous work on semidiscrete surfaces. In the situation of vanishing mean curvature, the associated families are defined via a Weierstrass representation. For the general cmc case, we introduce a Lax pair representation that directly defines associated families of cmc surfaces, and is connected to a semidiscrete [Formula: see text]-Gordon equation. Utilizing this theory we investigate semidiscrete Delaunay surfaces and their connection to elliptic billiards.


Theory and experimental method for determining individual kinetic constants of fast-acting, irreversible proteinase inhibitors.
A theory and experimental method are presented to characterize the kinetics of fast-acting, irreversible proteinase inhibitors. The theory is based upon formal analysis of the case of an irreversible inhibitor competing with a substrate for the active-site of a proteinase. From this theory, an experimental method is described by which the individual microscopic kinetic constants for the interaction of the inhibitor with the proteinase can be determined. These are, for a two-step inhibition reaction sequence, the equilibrium dissociation constant and the first-order rate constant for inhibition, and, for a one-step inhibition reaction sequence, the second-order rate constant for inhibition. The theory and experimental method were validated by an analysis of the inhibition of trypsin by the two-step synthetic inhibitor p-nitrophenyl p-guanidinobenzoate and the one-step protein inhibitor bovine pancreatic trypsin inhibitor. The substrate used in these experiments is a new, fluorogenic substrate for trypsin-like serine proteinases (Cbz-Ile-Pro-Arg-NH)2-Rhodamine, the synthesis and properties of which are described.


Physical literacy and the participant perspective: Exploring the value of physical literacy according to individuals experiencing disability through composite narratives.
Physical literacy (PL) is essential to the holistic human experience, emphasizing embodied capability and affording opportunities for inclusive engagement. Despite its recent use as a core programming element, PL from the experiential point of view of individuals experiencing disability has yet to be explored. Excluding these perspectives promotes a culture of ableism, one that devalues the embodied capabilities of those experiencing the world differently. The purpose of this study was to highlight the participant perspective related to PL and explore the value individuals experiencing disability attribute to PL and its development. Using the communities of practice theoretical model of knowledge as a conceptual framework, 13 participants experiencing disability participated in two focus groups. Participants' experiences were thematized via the use of thematic analysis, and voices were portrayed through composite narratives, highlighting the shared participant experience and value associated with PL. Three themes emerged: (1) imagine the possibilities, (2) dance like nobody's watching, and (3) no wrong way to move. Composite narratives reflect PL as a valued means of exploration and learning, personal growth, and opportunity related to physical activity and social interaction. Participant value was considered to be enhanced via a learning climate affording opportunities for developing autonomy and a sense of belonging. This research provides an authentic understanding of PL within the context of disability, and what might be used to facilitate its development in such an environment. Individuals experiencing disability contributed to this knowledge and must be continually involved to ensure PL development is inclusive to all.


Modified "tubeless" percutaneous nephrolithotomy using a tail-stent.
"Tubeless" percutaneous renal surgery has previously been described at our institution. Avoiding external nephrostomy tube drainage significantly decreases the pain and morbidity of percutaneous renal surgery. However, internal drainage with a double-J ureteral stent still results in bothersome bladder symptoms, especially in younger male patients. In addition, removal of the stent requires uncomfortable office cystoscopy. We report a technical enhancement of our "tubeless" technique that uses a novel tail-stent for internal drainage. A tubeless approach to any renal surgery should only be attempted in select uncomplicated cases. The exclusion criteria should include operative times longer than 2 hours, three or more percutaneous accesses, significant perforations or disruptions of the collecting system, significant residual stone burden, and significant bleeding. In these instances, and when second-look nephroscopy is desired, traditional external nephrostomy tube drainage should be used. In our select cases, in lieu of the standard double-J stent, we place a 7F/3F tail-stent with the string attached exiting the urethral meatus. Care is taken in correct placement to avoid having the tail of the stent exiting the meatus. In our initial 4 patients, tail-stents were successfully placed. The pain scores were low and stent symptoms appeared minimal. All stents were easily removed without the use of cystoscopy. Fluoroscopic visualization of the 3F tail is poor, and positioning of the tail can be difficult. Nevertheless, this modification appears feasible and safe with excellent patient satisfaction.


A truncated intracellular Dicer-like molecule involves in antiviral immune recognition of oyster Crassostrea gigas.
The enzyme Dicer is best known for its role as an endoribonuclease in the small RNA pathway, playing a crucial role in recognizing viral double-stranded RNA (dsRNA) and inducing down-stream cascades to mediate anti-virus immunity. In the present study, a truncated Dicer-like gene was identified from oyster Crassostrea gigas, and its open reading frame (ORF) encoded a polypeptide (designed as CgDCL) of 530 amino acids. The CgDCL contained one N-terminal DEAD domain and a C-terminal helicase domain, but lack the conserved PAZ domain, ribonuclease domain (RIBOc) and dsRNA binding domain. The mRNA transcripts of CgDCL were detected in all the examined tissues with high expression levels in lip, gills and haemocytes, which were 62.06-fold, 48.91-fold and 47.13-fold (p < 0.05) of that in mantle, respectively. In the primarily cultured oyster haemocytes, the mRNA transcripts of CgDCL were significantly induced at 12 h after poly(I:C) stimulation, which were 4.04-fold (p < 0.05) of that in control group. The expression level of CgDCL mRNA in haemocytes was up-regulated significantly after dsRNA and recombinant interferon-like protein (rCgIFNLP) injection, which was 12.87-fold (p < 0.01) and 3.22-fold (p < 0.05) of that in control group, respectively. CgDCL proteins were mainly distributed in the cytoplasm of haemocytes. The recombinant CgDCL protein displayed binding activity to dsRNA and poly(I:C), but no obvious dsRNA cleavage activity. These results collectively suggest that truncated CgDCL from C. gigas was able to be activated by poly(I:C), dsRNA and CgIFNLP, and functioned as an intracellular recognition molecule to bind nucleic acid of virus, indicating a potential mutual cooperation between RNAi and IFN-like system in anti-virus immunity of oysters.


Monoclonal anti-epidermal growth factor receptor (ior EGF/r3) antibody pharmacokinetic studies on nude mice I: a radio-receptor analysis applied to drug serum quantification.
Due to its antagonistic properties upon ligand-epidermal growth factor receptor (EGFr) interaction, the monoclonal antibody anti-EGFr ior EGF/r3 is considered a potential therapeutic agent against several epithelium-derived tumours. This paper affords further analysis of the relevant corporal interaction of this monoclonal antibody in terms of its pharmacodynamic properties, using nude mice, following a single bolus intravenous dose administration. The radio-receptor assay allows quantification of the serum ior EGF/r3 level. The dose selection procedure, according to the Kolmogorov-Smirnov test, suggested using doses of 12.5-16 mg kg(-1) for pharmacokinetic assessments. The experimental data were best fitted to a bi-exponential function (r2 = 0.985), through the classical two-compartment open modelling approach. The model selection was corroborated by the AKAIKE information criteria, and also the SCHWARTZ and ESTRIP test were used. The estimated pharmacokinetic parameters (e.g. t 1/2 beta = 34.65 h, Vc = 2.84 mL, Vss = 4.21 mL and CL = 0.09 mL h(-1)) bear out the strategies for the evaluation of the therapeutic application of this drug. Finally, the radio-receptor analysis has provided a rationale for the proposed serum monoclonal antibody ior EGF/r3 quantification to characterize its concentration-time course.


Hierarchical Modulation of Optical Anisotropy Driven by Metal Cation Polyhedra in Fluorooxoborates MII B4 O6 F2 (MII =Be, Mg, Pb, Zn, Cd).
The enhancement mechanism of birefringence is very important to modulate optical anisotropy and materials design. Herein, the different cations extending from alkaline-earth to alkaline-earth, d10 electron configuration, and 6s2 lone pair cations are highlighted to explore the influence on the birefringence. A flexible fluorooxoborate framework from AEB4 O6 F2 (AE=Ca, Sr) is adopted for UV/deep-UV birefringent structures, namely, MII B4 O6 F2 (MII =Be, Mg, Pb, Zn, Cd). The maximal enhancement on birefringence can reach 46.6 % with the cation substitution from Ca, Sr to Be, Mg (route-I), Pb (route-II), and Zn, Cd (route-III). The influence of the cation size, the stereochemically active lone pair, and the binding capability of metal cation polyhedra is investigated for the hierarchical improvement on birefringence. Significantly, the BeB4 O6 F2 structure features the shortest UV cutoff edge 146 nm among the available anhydrous beryllium borates with birefringence over 0.1 at 1064 nm, and the PbB4 O6 F2 structure has the shortest UV cutoff edge 194 nm within the reported anhydrous lead borates that hold birefringence larger than 0.1 at 1064 nm. This work sheds light on how metal cation polyhedra modulate birefringence, which suggests a credible design strategy to obtain desirable birefringent structures by cation control.


Bactericidal activity of rat leucocytic extracts. II. Characterization of the bactericidal substance in leucocyte mitochondrial extracts.
The bactericidal substance present in mitochondrial extracts from rat leucocytes was found to be non-dialyzable, fractionated at 30 per cent (NH(4)SO(4) saturation and was able to withstand temperatures up to 100 degrees C. The tentative identification of a lipoprotein as the responsible bactericidal substance is based on various observations; an ultraviolet absorption at a peak associated with alpha, beta unsaturated fatty acids, 205 to 208 mmicro, inactivation of the bactericidal substance by ether treatment at -70 degrees C. but not at 0 degrees C. and inhibition of the bactericidal activity with lipase treatment as well as with trypsin.


Separating lymph node stations by the surgeon from the gastric cancer specimen improves the quality of nodal status evaluation.
In gastric cancer (GC), the pN-stage is an important prognostic factor influencing treatment. Along with the depth of invasion of the tumor, the presence of nodal metastases is one of the most important prognostic factors guiding treatment strategies in gastric cancer. Examining a small number of lymph nodes may lead to understaging of the disease; hence, it is essential for the nodal status to be precisely assessed. In this study, we explored whether dissecting lymph node stations into separate samples by the surgeon from the gastric cancer surgical specimen affects the quality of nodal status evaluation and patient outcome. The clinical data of 130 GC patients treated at the Helsinki University Hospital between 2016 and 2019 was reviewed. The performed operations included 59 total and 71 subtotal gastrectomies. The processing of the surgical specimen before the pathological examination was assessed from the operation records and pathology reports. The association of the number of examined lymph nodes with other variables was assessed, and multivariate survival analysis was performed to explore the independent prognostic factors in disease-specific survival. Dissecting lymph node stations into separate specimens before pathological evaluation yielded a significantly greater number of examined lymph nodes compared with a specimen without intervention (median 34.5 vs 21.0, p < 0.001). The pT-stage, the pN-stage, and the extent of lymphadenectomy were identified as independent prognostic factors, whereas dissecting the specimen's lymph node stations did not associate with survival. Dissecting lymph node stations into separate specimens results in a greater number of examined lymph nodes, which has the potential to lead to a more reliable pN-stage assessment.


Total urinary and free serum hydroxyproline in metastatic bone disease.
The present study examines the possibility of correlation between free serum and urinary total hydroxyproline and whether this correlation can be applied to clinical conditions. The correlation between the two indices was 0.80 (P less than 0.001) in 18 patients, mostly suffering from malignant disease. On comparing the same measurements in 37 patients, all with known metastatic bone disease, we found 29/37 normal results for free serum hydroxyproline, whereas only 2/37 values of urinary total hydroxyproline were normal. The authors therefore conclude that urinary total hydroxyproline, measured as the ratio hydroxyproline/creatinine in a fresh specimen of early-morning urine, is the best index of collagen breakdown in metastatic bone disease and preferable to measurement of free serum hydroxyproline.


The presence or absence of certain behaviors associated with infantile autism in severely retarded autistic and nonautistic retarded children and very young normal children.
The modified Behavior Observation Scale adapted from Freeman et al. was used to compare normal, retarded, and autistic children with very low developmental ages and to determine the types of behavior that could differentiate these three diagnostic categories of children. Examination of the data revealed that there was much more overlap between autistic and retarded children than between autistic and normal children. However, a behavioral pattern of autism could be delineated and very retarded autistic children could be distinguished from the nonautistic retarded children. The autistic behavioral pattern included subclusters of symptoms that might be interpreted as disturbances of sensory modulation and motility.


Object permanence in lemurs.
Object permanence, the ability to mentally represent objects that have disappeared from view, should be advantageous to animals in their interaction with the natural world. The objective of this study was to examine whether lemurs possess object permanence. Thirteen adult subjects representing four species of diurnal lemur (Eulemur fulvus rufus, Eulemur mongoz, Lemur catta and Hapalemur griseus) were presented with seven standard Piagetian visible and invisible object displacement tests, plus one single visible test where the subject had to wait predetermined times before allowed to search, and two invisible tests where each hiding place was made visually unique. In all visible tests lemurs were able to find an object that had been in clear view before being hidden. However, when lemurs were not allowed to search for up to 25-s, performance declined with increasing time-delay. Subjects did not outperform chance on any invisible displacements regardless of whether hiding places were visually uniform or unique, therefore the upper limit of object permanence observed was Stage 5b. Lemur species in this study eat stationary foods and are not subject to stalking predators, thus Stage 5 object permanence is probably sufficient to solve most problems encountered in the wild.


In silico modeling of non-linear drug absorption for the P-gp substrate talinolol and of consequences for the resulting pharmacodynamic effect.
The aim of the present work was to demonstrate P-glycoprotein's involvement in the non-linear talinolol pharmacokinetics using an advanced compartment and transit model (ACAT) and to compare the results predicted from the model to the finding of a phase I dose escalation study with oral talinolol doses increasing from 25 to 400 mg. Besides minimum input parameters for the compound (pKa(s), solubility at one or more pH's, Peff, doses, formulation, diffusivity), physiological and pharmacokinetic properties, transporter data are included in these predictions. The simulations assumed higher expression levels in lower gastrointestinal regions, in particular in the colon, which is in accordance with the results of intestinal rat perfusion studies and intestinal distribution data from rats, catfishes, micropigs and humans reported in the literature. Optimized values for P-glycoprotein (P-gp) Km and Vmax were used for the final simulation results and for a stochastic virtual trial with 12 patients. Talinolol, a P-gp substrate, exhibits non-linear dose AUC relationship after administration of 25, 50, 100 and 400 mg immediate-release tablets. This dose dependency is due to a decrease of efflux transport caused by saturation of P-gp by talinolol. It was found that oral bioavailability increases after administration of higher doses of talinolol. The predicted bioavailability of the p.o. 25, 50, 100 and 400 mg doses of talinolol was 64, 76, 85, 94%, respectively. Pharmacokinetic parameters (AUC, Cmax) from in silico simulations are within acceptable range comparing with data, observed in vivo. However, the in vitro value of Km for talinolol's interactions with P-gp could not be used in the simulation and still reproduce the observed non-linear dose dependence. For each of the four doses, GastroPlus was used to model pharmacodynamic (PD) response and to optimize the values of CLe, Emax, and EC5o with the effect compartment linked indirectly to the central compartment. For all simulations, EC50 was 114 nM and E0 was 83 bpm. Comparison between the results of the in vivo study and the in silico simulations determined the quality and reliability of the in silico predictions and demonstrate the simulation of dose dependent absorption. In contrast to previous simulation work for the non-linear dose dependence of interaction with intestinal transporters or enterocyte metabolism, optimized Km and Vmax values were required to reproduce the clinically observed non-linear dose dependence. The model developed may be useful in the prediction of absorption of other P-gp substrates including pharmacodynamic consequences.


Solitary common iliac artery inflammatory aneurysm in a healthy woman: case report and review of the literature.
Inflammatory aneurysms represent only 3-10% of all aortoiliac aneurysms and tend to be more common in men. We report a case of a solitary inflammatory aneurysm of the right common iliac artery in a healthy young woman. The patient presented with persistent abdominal and right flank pain. She had no risk factors for vascular disease, except mild hypertension and a strong family history of aneurysm disease. Her work-up demonstrated a 3.0 cm right common iliac artery aneurysm with intramural thrombus, focal calcification, and perianeurysmal inflammation without evidence of systemic atherosclerosis. There was right hydroureteronephrosis secondary to ureteral compression by the inflammatory aneurysm. She underwent open right common iliac artery aneurysmorraphy with polytetrafluoroethylene interposition graft and concomitant ureterolysis without complication. She remains asymptomatic more than 1 year postoperatively with no evidence of additional aneurysm disease, resolution of her hydroureteronephrosis, and normal kidney function. We report a rare case of a solitary inflammatory aneurysm of the right common iliac artery in a healthy young woman, with a review of the current literature on inflammatory aneurysms.


Targeting the microglial NLRP3 inflammasome and its role in Parkinson's disease.
Excessive activation of microglia and subsequent release of proinflammatory cytokines play a crucial role in neuroinflammation and neurodegeneration in Parkinson's disease (PD). Components of the nucleotide-binding oligomerization domain and leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome complex, leucine-rich-repeat- and pyrin-domain-containing 3, caspase-1, and apoptosis-associated speck-like protein containing a CARD, are highly expressed in activated microglia in PD patient brains. Findings suggest that neurotoxins, aggregation of α-synuclein, mitochondrial reactive oxygen species, and disrupted mitophagy are the key regulators of microglial leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome activation and release of interleukin-1β and interleukin-18 caspase-1-mediated pyroptotic cell death in the substantia nigra of the brain. Although this evidence suggests the leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome may be a potential drug target for treatment of PD, the exact mechanism of how the microglia sense these stimuli and initiate leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome signaling is unknown. Here, the molecular mechanism and regulation of microglial leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome activation and its role in the pathogenesis of PD are discussed. Moreover, the potential of both endogenous and synthetic leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome modulators, long noncoding RNA, microRNA to develop novel therapeutics to treat PD is presented. Overall, we recommend that the microglial leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome can be a potential target for PD treatment. © 2019 International Parkinson and Movement Disorder Society.


Cardiac MRI evaluation of hypertrophic cardiomyopathy: left ventricular outflow tract/aortic valve diameter ratio predicts severity of LVOT obstruction.
To evaluate if left ventricular outflow tract/aortic valve (LVOT/AO) diameter ratio measured by cardiac magnetic resonance (CMR) imaging is an accurate marker for LVOT obstruction in patients with hypertrophic cardiomyopathy (HCM) compared to Doppler echocardiography. In all, 92 patients with HCM were divided into three groups based on their resting echocardiographic LVOT pressure gradient (PG): <30 mmHg at rest (nonobstructive, n = 31), <30 mmHg at rest, >30 mmHg after provocation (latent, n = 29), and >30 mmHg at rest (obstructive, n = 32). The end-systolic dimension of the LVOT on 3-chamber steady-state free precession (SSFP) CMR was divided by the end diastolic aortic valve diameter to calculate the LVOT/AO diameter ratio. There were significant differences in the LVOT/AO diameter ratio among the three subgroups (nonobstructive 0.60 ± 0.13, latent 0.41 ± 0.16, obstructive 0.24 ± 0.09, P < 0.001). There was a strong linear inverse correlation between the LVOT/AO diameter ratio and the log of the LVOT pressure gradient (r = -0.84, P < 0.001). For detection of a resting gradient >30 mmHg, the LVOT/AO diameter ratio the area under the receiver operating characteristic (ROC) curve was 0.91 (95% confidence interval [CI] 0.85-0.97). For detection of a resting and/or provoked gradient >30 mmHg, the LVOT/AO diameter ratio area under the ROC curve was 0.90 (95% CI 0.84-0.96). The LVOT/AO diameter ratio is an accurate, reproducible, noninvasive, and easy to use CMR marker to assess LVOT pressure gradients in patients with HCM.


Induction of the proto-oncogene c-jun by angiotensin II.
Angiotensin (Ang) II causes hypertrophy of rat aortic smooth muscle cells in culture and results in the rapid activation of c-fos. This study demonstrated that Ang II also activated c-jun and, in addition, could activate the AP-1 enhancer element. These data add support for a role of Ang II as an important mediator of vascular smooth muscle cell growth.


Congenital Malformations in a Holstein-Fresian Calf with a Unique Mosaic Karyotype: A Case Report.
A Holstein-Fresian calf with multiple congenital malformations was subjected postmortem to anatomical and genetic investigation. The calf was small (20 kg), had shortened limbs and was unable to stand up. It lived only 44 days. Detailed anatomical investigation revealed the following features: head asymmetry, the relocation of the frontal sinus and eye orbits, hypoplastic thymus without neck part, ductus Botalli, unfinished obliteration in umbilical arteries, and a bilateral series of tooth germs in the temporal region. Cytogenetic examination, performed on in vitro cultured fibroblasts, showed a unique mosaic karyotype with a marker chromosome-60,XX[9 2%]/60,XX,+mar[8%], which was for the first time described in cattle. No other chromosome abnormalities indicating chromosome instabilities, like chromatid breaks or gaps were identified, thus teratogenic agent exposure during pregnancy was excluded. The marker chromosome (mar) was small and it was not possible to identify its origin, however, sequential DAPI/C (4',6-diamidino-2-phenylindole) band staining revealed a large block of constitutive heterochromatin, which is characteristic for centromeric regions of bovine autosomes. We suppose that the identified marker chromosome was a result of somatic deletion in an autosome and its presence could be responsible for the observed developmental malformations. In spite of the topographic distance among the affected organs, we expected a relationship between anatomical abnormalities. To the of our best knowledge, this is the first case of a mosaic karyotype with a cell line carrying a small marker chromosome described in a malformed calf.


Temporal variations in the nutrient content of Norwegian farmed Atlantic salmon (Salmo salar), 2005-2020.
The changes in the feed of farmed Atlantic salmon (Salmo salar) towards a more plant-based diet affect the nutritional value of the fillets. By compiling the contents of a range of nutrients in 1108 samples of Norwegian farmed Atlantic salmon collected between 2005 and 2020, we found that the median contents of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) have decreased by > 60%. However, farmed Atlantic salmon remains a considerable source of EPA and DHA, with one and two portions being sufficient to meet the weekly adequate intake of EPA and DHA for adults (175 g) and two-year-olds (80 g), respectively. Farmed Atlantic salmon also remains a considerable source of protein, selenium, vitamin B12, and vitamin D3. Together, we demonstrate that farmed Atlantic salmon can contribute substantially to the nutrient intake of the consumers. These data are important for the Norwegian food composition table and future risk-benefit assessments on fatty fish consumption.


A facile label-free electrochemiluminescence biosensor for target protein specific recognition based on the controlled-release delivery system.
This paper described a novel label-free electrochemiluminescence assay for target protein based on a controlled delivery system. Iron oxide magnetic mesoporous silica nanocontainers were prepared by using a general procedure. The prepared magnetic mesoporous silica nanocontainers were applied to load the guest molecules [Ru(bpy)3](2+). Aptamers were used as gatekeepers on the pore outlets of the nanocontainers. In the presence of target proteins, the specific aptamer-protein interactions were employed as triggers for uncapping the pores and releasing the guest molecules from the nanocontainers. The amount of the guest molecule [Ru(bpy)3](2+) released from the magnetic mesoporous silica nanocontainers was monitored by the electrochemiluminescence assay. The results show that the releasing amount of [Ru(bpy)3](2+) is proportional to the thrombin concentration in the range of 0.6 pM-0.8 nM with a detection limit of 0.5 pM (S/N=3). The present work demonstrates that the fabricated nanocontainer using aptamer as the cap is a highly sensitive and selective key-in lock gating system for the label-free ECL biosensor.


Investigation of cerium and yttrium ions effects on microbial nitrogen fixation and determination of inhibition.
Critical investigation of the effect of yttrium and cerium ions in culture media for nitrogen-fixing bacteria showed strong inhibition. There was a decrease in the amount of nitrogen fixed; simultaneously, in the samples containing cerium ions, carbon consumption values increased as the molarity of metal ion was enhanced. Inhibition rate was invariably maximum at the highest concentration of metal ions.


The structure of INI1/hSNF5 RPT1 and its interactions with the c-MYC:MAX heterodimer provide insights into the interplay between MYC and the SWI/SNF chromatin remodeling complex.
c-MYC and the SWI/SNF chromatin remodeling complex act as master regulators of transcription, and play a key role in human cancer. Although they are known to interact, the molecular details of their interaction are lacking. We have determined the structure of the RPT1 region of the INI1/hSNF5/BAF47/SMARCB1 subunit of the SWI/SNF complex that acts as a c-MYC-binding domain, and have localized the interaction regions on both INI1 and on the c-MYC:MAX heterodimer. c-MYC interacts with a highly conserved groove on INI1, while INI1 binds to the c-MYC helix-loop-helix region. The binding site overlaps with the c-MYC DNA-binding region, and we show that binding of INI1 and E-box DNA to c-MYC:MAX are mutually exclusive.


Antinociceptive and motor effects of delta/mu and kappa/mu combinations of intrathecal opioid agonists.
Interactions between selective opioid agonists acting at spinal mu-, delta-, and kappa-opioid receptors were evaluated by co-administering a low-antinociceptive dose of the selective delta-agonist, DPDPE, or the selective kappa-agonist, U50,488H, with sequentially increasing doses of the selective mu-agonist, DAMGO, intrathecally. Antinociceptive synergy (i.e., a more than additive antinociceptive effect) was observed with both combinations of opioid agonists tested. The demonstration of antinociceptive synergy suggests that the subtypes of spinal opioid receptors can act, at least in part, through a common neural circuit. Since our measure of antinociception, the Randall-Selitto paw-withdrawal test, is dependent on a normally functioning motor system, we also evaluated the effects of these same combinations of opioid peptides on motor coordination using a rotarod treadmill. A low-antinociceptive dose of DPDPE or U50,488H co-administered intrathecally, with sequentially increasing doses of DAMGO, did not worsen the decrement in rotarod performance observed with the same doses of DAMGO administered as a single agent. In fact, the low-antinociceptive dose of DPDPE significantly attenuated the decrease in rotarod performance produced when the same dose of DAMGO was administered as a single agent. The results of this study suggest that intrathecal combinations of selective mu- with both delta- or kappa-selective opioid agonists can produce antinociceptive synergy without producing an increase in motor side effects.(ABSTRACT TRUNCATED AT 250 WORDS)


Trial of new vascular clips for aortic anastomosis in a canine model.
We created a new vascular clip designed for aortic surgery. The purposes of this investigation were to examine surgical applicability in a clinically relevant aortic replacement model and to assess biomechanical strength of the clipped anastomosis and serial histologic changes in the clipped anastomotic site. Twenty-one beagles underwent descending thoracic aortic replacement. Distal anastomosis was performed with the new clips, mimicking the cuffed anastomosis technique, and proximal anastomosis was carried out by conventional suture anastomosis. Tissue specimens of the anastomotic sites were harvested at 1, 3, 6, and 12 months postoperatively for examination. There was no significant difference in the time required to carry out clip anastomosis (12.2 +/- 1.3 minutes) and suture anastomosis (13.7 +/- 0.9 minutes; P = .38). Neither type of anastomotic site was disrupted by raising the intraluminal pressure to 280 mm Hg. Microscopically, the areas of aortic wall compressed by vascular clips appeared as hyalinized areas adjacent to surrounding collagen fibers, with no significant infiltration of inflammatory cells. Identical histologic changes were observed at the site of the sutured anastomosis. The media at the clipped anastomosis site was significantly thinner than that at the sutured anastomosis site at 1 month after the operation. However, there was no significant difference in the thickness of the media at 3 months. The new vascular clips were effective in this clinically relevant model, with appropriate biomechanical strength, and the anastomotic sites underwent similar histologic changes to those observed after suture anastomosis.


Effects of indomethacin, prostaglandin E2 and prostaglandin F2 alpha on mouse blastocyst attachment and trophoblastic outgrowth in vitro.
A study was performed in order to investigate the participation of prostaglandins (PGs) during implantation. The effects of indomethacin on mouse blastocyst attachment and trophoblastic outgrowth were examined in vitro. Studies were also carried out on cultures supplemented with PGE2 and/or PGF2 alpha along with indomethacin. (1) Blastocyst attachment and trophoblastic outgrowth were inhibited by indomethacin dose-dependency. (2) In the cultures supplemented with indomethacin and PGE2 or PGF2 alpha, respectively, the inhibitory effects of indomethacin were reduced. (3) In the cultures supplemented with all three substances with treatment (1) and (2), inhibition of indomethacin was partially reversed, but still lower than control group without indomethacin. The above results indicate that both PGE2 and PGF2 alpha have a promoting effect on implantation, and PGF2 alpha was more effective than PGE2.


Synthesis and biological activity of lactones en route to Altohyrtin A.
Lactones 2 and 7 were synthesised and tested against six human tumour cell lines (Pancreas-a, BXPC-3), (Thyroid ca, KAT-4), (Thyroid ca, SW1736), (Lung-NSC, NCI-H460), (Pharynx-sq, FADU) and (Prostate, DU-145). Lactone 7 proved inactive, but lactone 2 displayed some activity against four of the six cell lines examined. Both lactones were converted into an intermediate 5 en route to Altohyrtin A.


CT scanning in acute abdominal injuries.
Computed tomography has become an important adjunct in the evaluation of the patient with blunt abdominal trauma. It provides quantitative information about hemoperitoneum as well as qualitative information about the source of hemoperitoneum. CT scanning also evaluates the retroperitoneal organs and retroperitoneal hematoma more accurately than any other available imaging technique. Like any other diagnostic tool, the CT scan must not be overused or abused. This technique should be applied only to stable patients and only in institutions with up-to-date equipment, a committed radiology and surgery staff, and appropriate monitoring equipment in the CT suite. If proper technique is used, then high-quality scans can be obtained which, if interpreted by experienced personnel in the light of the clinical findings, can improve our management of selected trauma patients.


Molecular imaging-guided extracellular vesicle-based drug delivery for precise cancer management: Current status and future perspectives.
Extracellular vesicles (EVs), the mediators of intercellular communication, have attracted the attention of researchers for the important roles they play in cancer treatment. Compared with other inorganic nano-materials, EVs possess the advantages of higher biocompatibility, better physiochemical stability, easier surface modification, and excellent biosafety. They can be used as an advanced drug delivery system with an improved therapeutic index for various therapeutic agents. Engineered EV-based imaging and therapeutic agents (engineered EVs) have emerged as useful tools in targeted cancer diagnosis and therapy. Non-invasive tracing of engineered EVs contributes to a better evaluation of their functions in cancer progression, in vivo dynamic biodistribution, therapeutic response, and drug-loading efficiency. Recent advances in real-time molecular imaging (MI), and innovative EV labeling strategies have led to the development of novel tools that can evaluate the pharmacokinetics of engineered EVs in cancer management, which may accelerate further clinical translation of novel EV-based drug delivery platforms. Herein, we review the latest advances in EVs, their characteristics, and current examples of EV-based targeted drug delivery for cancer. Then, we discuss the prominent applications of MI for tracing both natural and engineered EVs. Finally, we discuss the current challenges and considerations of EVs in targeted cancer treatment and the limitations of different MI modalities. In the coming decades, EV-based therapeutic applications for cancer with improved drug loading and targeting abilities will be developed, and better anti-cancer effects of drug delivery nanoplatform will be achieved.


Effect of Ginkgo biloba extract on plasma steroid concentrations in healthy volunteers: a pilot study.
To determine if a standardized ginkgo supplement significantly alters concentrations of circulating androgenic steroids in humans. Open-label, fixed-treatment order, crossover study. University general clinical research center. Eleven healthy volunteers (six men, five women). Volunteers received ginkgo biloba 240 mg/day for 14 days. Plasma concentrations of cortisol, 11-deoxycortisol, 17alpha-hydroxyprogesterone, testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, androstenedione, and free testosterone, as well as free androgen index and combined concentrations of androsterone sulfate and epiandrosterone sulfate, were analyzed in all subjects before and after their 14-day course of ginkgo biloba. Ginkgo biloba did not significantly alter endogenous steroid levels compared with baseline values (p < 0.05). A 14-day oral administration of a widely used, standardized ginkgo extract at a generally advocated dosage of 240 mg/day did not significantly alter concentrations of major circulating steroids in men and women.


A Study of Diabetes Teaching in Canadian Medical Schools.
To assess the current status of diabetes teaching in Canadian medical schools. Faculty primarily responsible for teaching undergraduate diabetes education were identified at all 17 Canadian medical schools and were asked to provide their undergraduate diabetes curricula. The curricula were analyzed by method of teaching. Reponses were obtained from14 of 17 (82%) medical schools. The average number of teaching hours in the entire undergraduate program was 15.4 and ranged from 7 to 22.5 hours. Formats included lectures, small groups, workshops, assigned readings, problem-based learning and laboratory studies. Lectures made up 48% of the curriculum, followed by small groups at 26%. There has been an increased use of small group sessions in undergraduate diabetes education, in keeping with generalized changes in medical school curricula. Future study is warranted in assessing the impact of differing undergraduate teaching methods on eventual competency.


The value of phenformin and ethyloestrenol in the prevention of deep venous thrombosis in patients undergoing surgery.
The effect of phenformin and ethyloestrenol on the incidence of post-operative deep venous thrombosis was studied in 314 surgical patients in a double-blind randomised trial. Although the laboratory tests suggested that the regime produced an increase in activators of the fibrinolytic system, the drugs used did not lower the incidence of post-operative deep venous thrombosis. Possible explanations of this paradox are advanced.


Approaches for chemically synthesized siRNA and vector-mediated RNAi.
Successful applications of RNAi in mammalian cells depend upon effective knockdown of targeted transcripts and efficient intracellular delivery of either preformed si/shRNAs or vector expressed si/shRNAs. We have previously demonstrated that 27 base pair double stranded RNAs which are substrates for Dicer can be up to 100 times more potent than 21mer siRNAs. In this mini-review we elaborate upon the rationale and design strategies for creating Dicer substrate RNAs that provide enhanced knockdown of targeted RNAs and minimize the utilization of the sense strand as RNAi effectors. Expression of shRNAs or siRNAs in mammalian cells can be achieved via transcription from either Pol II or Pol III promoters. There are certain constrictions in designing such vectors, and these are described here. Additionally, we review strategies for inducible shRNA expression and the various viral vectors that can be used to transduce shRNA genes into a variety of cells and tissues. The overall goal of this mini-review is to provide an overview of available approaches for optimizing RNAi mediated down regulation of gene expression in mammalian cells via RNA interference. Although the primary focus is the use of RNAi mediated cleavage of targeted transcripts, it is highly probable that some of the approaches described herein will be applicable to RNAi mediated inhibition of translation and transcriptional gene silencing.


Violence-prevention climate in the turnover intention of nurses experiencing workplace violence and work frustration.
To determine the moderating effect of a violence-prevention climate and the mediating effect of work frustration on the relationship between workplace violence (WPV) and the turnover intention of nurses. To maintain the stability and work quality of nurses, WPV should be studied to provide effective prevention measures. A cross-sectional study with a convenience sample was adopted. Participants were nurses from three hospitals in Taiwan. Of 1,531 questionnaires, 973 were valid for analysis (63.6%). A total mediating effect of work frustration on nurses' own experiences of WPV increased turnover intention. Witnessing WPV toward coworkers caused a significant partial mediating effect on work frustration that further increased turnover intention. A violence-prevention climate had a significant moderating effect on the work frustration and turnover intention of nurses after they had witnessed violence against others. Effective policies and an incentivized reporting system can foster a safe and friendly work environment not only for nurses who experience violence but also for those who witness violence. Nursing managers and leaders must create a positive consultative pipeline to ensure a safe climate and environment for both the victims of WPV and the nurses who witness violence against others.


Metabolic signature of cervical mucus in ewe breeds with divergent cervical sperm transport: a focus on metabolites involved in amino acid metabolism.
Cervical artificial insemination (AI) with frozen-thawed semen in sheep has yielded unacceptably low pregnancy rates. The exception is in Norway where vaginal AI yields non-return rates in excess of 60%, which has been attributed to the ewe breed used. This study aimed to characterise, for the first time, the ovine follicular phase cervical mucus metabolome, with a focus on the amino acid profile. Cervical mucus was collected from four European ewe breeds with known differences in pregnancy rates following cervical AI with frozen-thawed semen. These were Suffolk (low fertility), Belclare (medium fertility), Norwegian White Sheep (NWS) and Fur (both high fertility). A total of 689 metabolites were identified in the cervical mucus of all the four ewe breeds. Of these, 458 metabolites were altered by ewe breed, which had the greatest effect in the dataset (P < 0.05). We detected 194 metabolites involved in the amino acid pathway, of which 133, 56 and 63 were affected by ewe breed, type of cycle and their interaction, respectively (P < 0.05). N-methylhydantoin and N-carbamoylsarcosine (degradation products of creatinine pathway) exhibited the greatest fold change decrease in the Suffolk breed compared to Fur and NWS (P < 0.001). Oxidized metabolites were also decreased in Suffolk compared to high fertility breeds (P < 0.05). In contrast, other metabolites such as 3-indoxyl-sulfate, putrescine, cadaverine were significantly increased in Suffolk at the synchronised cycle. The suboptimal amino acid profile in the cervical mucus of the low fertility Suffolk breed may have negative consequences for sperm transport.


Ki-67 (MIB 5) immunostaining of mouse lung tumors induced by 4-nitroquinoline 1-oxide.
We immunostained mouse lung tumors using a mouse monoclonal antibody against recombinant Ki-67 antigen (clone; MIB 5) to establish an MIB 5 immunostaining method and to determine the extent of MIB 5 labeling to monitor cell proliferation activity in mouse lung tumors. A/J mice, treated with 4-nitroquinoline 1-oxide, were killed after 18 months. One hour before killing, bromodeoxyuridine (BrdU) was injected intraperitoneally. Lung tissues including tumors were fixed with phosphate-buffered 4% paraformaldehyde and embedded in paraffin. For MIB 5 immunostaining, two antigen-retrieval buffers, citrate buffer pH 6 and TRIS-HCl buffer pH 9.5 containing 5% urea, were tested, and constant and reproducible staining was obtained only with the TRIS-HCI buffer. The mean values of the MIB 5-positive cell index (PCI), the BrdU labeling index (LI), and the mitotic cell count for adenocarcinomas were 4.6%, 2.3%, and 7/mm2, and those for adenomas were 1.2%, 0.7%, and 1.3/mm2, respectively. Each of these values was significantly higher for adenocarcinomas than for adenomas. A close correlation was seen between the MIB 5 PCI and the BrdU LI for adenocarcinomas and adenomas and between the MIB 5 PCI and the mitotic cell count in adenocarcinomas. Thus, MIB 5 immunostaining is a useful method for assessing the proliferative activity of mouse tumor tissues.


Polybrominated diphenyl ethers in soils of the modern Yellow River Delta, China: occurrence, distribution and inventory.
The Yellow River is the second largest river in China. In this study, the levels of polybrominated diphenyl ethers (PBDEs) in the modern Yellow River Delta (mYRD) were firstly reported. Twenty PBDE congeners in soil/sediment samples from mYRD were measured. The total PBDE concentrations ranged from non-detectable to 18257ngkg(-1) with a mean value of 836ngkg(-1). BDE-209 was the dominant congener, accounting for ∼86.1-99.5% of the total PBDEs. The congener profiles of PBDEs with higher abundances of BDE-153 and BDE-183 were similar to those in sediment of the Bohai Sea, indicating that they shared similar sources. The concentrations and congener patterns varied among different regions. Higher levels of PBDEs were found in the middle area (MA), and more complicated congener compositions were also observed in the MA, whereas lower levels of PBDEs were found in the modern course (MC) and the old course (OC). Much more PBDEs were detected in the top layer (TL) soil where more congeners were also held compared to lower soil layers, implying that more PBDEs were emitted into this area in recent years/decades. Organic matter controlled the PBDE distribution in the soil. Soil in this area might be a source of BDE209 for the Bohai Sea.


Pentoxifylline inhibits lipopolysaccharide-induced inflammatory mediators in human second trimester placenta explants.
Intrauterine infection and inflammation during pregnancy, which leads to up-regulation of inflammatory cytokines and prostaglandin synthesis, has been implicated in the pathogenesis of preterm delivery and other pregnancy complications. Effective preventive and therapeutic strategies to reduce these outcomes are lacking to date. Pentoxifylline (PTX) is a non-specific phosphodiesterase inhibitor which raises intracellular cyclic adenosine monophosphate and decreases production of pro-inflammatory mediators while enhancing anti-inflammatory cytokines. We hypothesized that pentoxifylline will decrease lipopolysaccharide (LPS)-induced pro-inflammatory cytokines production in human placental explants. Placental explants derived from normal second trimester human placentas were treated with PTX, stimulated with LPS and cultured at 37 °C in 5% CO2. Conditioned media were assayed for pro- and anti-inflammatory mediators with multiplex immunoassays or ELISA, and explant tissues for mRNA with real time PCR. Means of PTX-treated and untreated samples were compared using paired t tests and Wilcoxon-signed rank tests. PTX preferentially inhibited placental expression and production of LPS-induced pro-inflammatory cytokines including TNF-α (25461 vs. 1908 pg/ml, p < 0.001), IL-1β (2921 vs. 1067 pg/ml, p < 0.001) and IFN-γ (2190 vs 427 pg/ml, p < 0.001) with relative preservation of anti-inflammatory mediators. The suppressive effects on LPS-induced placental inflammation were independent of the timing of PTX administration in relation to LPS-induced stimulation. Our study suggests that PTX attenuates the LPS-induced pro-inflammatory milieu in human placental explants. We speculate that PTX may have utility as a candidate anti-inflammatory agent for prophylaxis and/or treatment of human placental inflammation.


Spinal cord injuries in Enugu, Nigeria--preventable accidents.
This is a review of 72 patients who were treated for Spinal Cord Injuries in the University of Nigeria Teaching Hospital, Enugu, Nigeria, during the period January 1980 to January 1985. There were 20 patients who had tetraplegia as a result of their injuries and 52 with paraplegia. All the patients were treated conservatively. The catchment area of the hospital is in the rain forest belt of West Africa where tall palm trees grow. Palm tree climbers use jigs which are woven from palm fronds. The climbing jigs are prone to snapping during periods of low humidity between the months of November and March. During this period of the year the tensile strength of the jigs is greatly reduced. Our experience is that the commonest cause of spinal cord injury is a fall from palm trees. Climbers should be educated about the time related jig failure, falls and subsequent spinal cord injury. Alternative sources for stronger materials for weaving jigs, and increased growing of shorter species of palm trees from which harvesting of palm nuts take place at ground level are advocated. Other causes of spinal cord injuries and preventive measures are discussed.


Nitrogen and phosphorus retention budgets of a semiarid plain basin under different human activity intensity.
Excessive nitrogen (N) and phosphorus (P) runoff from human activities results in degraded water quality. It is, therefore, crucial to quantitatively assess nutrient inputs over time and their impact on riverine nutrient exports. In this study, we estimated the long-term (1995-2015) nutrient inputs at the county scale by integrating Net Anthropogenic Nitrogen Input (NANI) and Net Anthropogenic Phosphorus Input (NAPI) methods, and nutrient exports into rivers by the Export Coefficient Model (ECM) for a semiarid plain basin, the Baiyangdian (BYD) Basin, China. The results showed that N and P input intensities in the year 2015 reached 18852 kg N km2 yr-1 and 2073 kg P km-2 yr-1, showing a 35% and 11% increase in comparison with 1995, respectively. About 60% of these nutrients were derived from fertilizer application. The multi-year averaged N and P exported to rivers was 548 kg N km-2 yr-1 and 79 kg P km-2 yr-1, respectively. Hotspots for nutrient budgets were found in the southeastern counties. Hotspots covered about 12% of the total land, but contributed by 38-52% of total nutrient budgets. The nutrient export ratios showed no significantly temporal variations, and only about 2.15-2.89% of NANI and NAPI were exported into rivers. The low nutrient export ratio was due to the low water discharge that limited the nutrient transportation in the semi-arid plain basin. As most of anthropogenic nutrient inputs were retained in the basin, their impacts on the pollution of soils and aquifers need to be considered and adequately addressed in the future. This study constructs the spatial quantitative nutrient budgets, which can provide effective information for region policy formulation.


Serum erythropoietin levels in kidney donors after renal transplantation.
Renal transplantation is the treatment of choice for many patients with end-stage renal disease. In the donor, renal excretory function is not affected after nephrectomy; however, little is known about other functions such as erythropoietin production. We studied the erythropoietin production in renal donors after nephrectomy. We included healthy individuals fulfilling the criteria for kidney donation. Blood samples were collected before and monthly from 1 to 6 months after nephrectomy. Complete blood cell counts and erythropoietin were assayed. Eight kidney donors were studied. A significant increase in erythropoietin levels was observed during the first 3 months, but no difference was observed by the 4th month as compared with basal values. Erythropoietin production rose during the first 3 months after nephrectomy. However, erythropoietin was normal by the 4th month. Unchanged hemoglobin levels may suggest that the compensatory production of erythropoietin could participate in the preservation of an adequate physiological status of the donor after nephrectomy.


Reliability of studies of iodine intake and recommendations for number of samples in groups and in individuals.
The iodine intake level in a population is determined in cross-sectional studies. Urinary iodine varies considerably and the reliability of studies of iodine nutrition and the number of samples needed is unsettled. We performed a longitudinal study of sixteen healthy men living in an area of mild to moderate iodine deficiency. Iodine and creatinine concentrations were measured in spot urine samples collected monthly for 13 months. From these data we calculated the number of urine samples needed to determine the iodine excretion level for crude urinary iodine and for 24 h iodine excretion estimated from age- and gender-specific creatinine excretions. We found that mean urinary iodine excretion varied from 30 to 87 microg/l (31 to 91 microg/24 h). Sample iodine varied from 10 to 260 microg/l (20 to 161 microg/24 h). Crude urinary iodine varied more than estimated 24 h iodine excretion (population standard deviation 32 v. 26; individual standard deviation 29 v. 21; Bartlett's test, P < 0.01 for both). The number of spot urine samples needed to estimate the iodine level in a population with 95 % confidence within a precision range of +/- 10 % was about 125 (100 when using estimated 24 h iodine excretions), and within a precision range of +/- 5 % was about 500 (400). A precision range of +/- 20 % in an individual required twelve urine samples or more (seven when using estimated 24 h iodine excretions). In conclusion, estimating population iodine excretion requires 100-500 spot urine samples for each group or subgroup. Less than ten urine samples in an individual may be misleading.


Communication and the healthy work environment: nurse managers' perceptions.
A qualitative design was used to decipher the viewpoints of nurse managers about communication trends associated with their leadership roles and unit subcultures. Disruptive behaviors such as poor communication and inadequate teamwork have been associated with patient harm and deficient workplace cultures. However, few studies have focused on nurse managers' perceptions of communication and a healthy workplace. A descriptive qualitative study was conducted using 12 in-depth interviews of 6 nurse managers to better understand communication patterns of managers. Analysis identified 5 themes and 13 subthemes. Workplace processes were identified that either promoted or hindered managers' abilities to set a positive tone and to stay connected to their staff, ensuring effective communication while meeting multiple unit and institutional challenges. Findings can be used to strengthen communication practices, obviate communication disconnects, and ensure a healthy workplace.


Fatal acute portal vein thrombosis associated with hepatic cysts in a patient with autosomal dominant polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) often involves polycystic liver disease (PLD). In severe cases, PLD can develop various complications. However, fatal acute portal vein thrombosis (APVT) associated with PLD has not been reported. A 64-year-old male reported mild consciousness disorder. He had been under maintenance hemodialysis for end-stage renal disease due to ADPKD with PLD. Because of recurring hepatic cyst infections, he had sustained high levels of C-reactive protein. Regarding the mild consciousness disorder, a diagnosis of hepatic encephalopathy was made based on an elevation of serum ammonia without any other abnormal liver function tests. Several days after his admission, hepatobiliary enzymes elevated, and acute liver failure progressed. Enhanced abdominal computed tomography suggested the possibility of complete occlusion of the portal vein by a thrombus. Based on an absence of obvious portosystemic collaterals, a diagnosis of APVT was made. The patient died 19 days after admission. Patients with PLD with repeated cystic infections have been seen to develop liver failure, and APVT formation may be one cause of the rapid progression of fatal liver failure. In conclusion, this is the first paper to report on the involvement of APVT in patients with PLD.


The role of semantic knowledge on the cognitive estimation task--evidence from Alzheimer's disease and healthy adult aging.
The current study investigated the role of semantic knowledge on the Cognitive Estimation Task (CET). In an initial experiment, the CET performance of 21 patients with frontal lobe lesions was compared with 21 healthy controls. The CET was found to be sensitive to the effects of frontal lobe lesions. In Experiment 2, 175 participants aged between 18 and 87 years performed the CET to examine the effects of healthy adult aging on the task. No significant age effects were evident. In Experiment 3, 27 patients with Alzheimer's disease (AD) were compared with 27 healthy controls on the CET. AD patients produced significantly more extreme cognitive estimates than the controls. A significant correlation was found between CET performance and performance on the General Knowledge of the World Task, a task intended to assess semantic knowledge. The hypothesis is put forward that healthy older adults are able to use their intact semantic knowledge to compensate for problem-solving deficits when generating cognitive estimates. In contrast, owing to degradation in semantic abilities, AD patients are unable to benefit from semantic knowledge and instead tend to produce bizarre cognitive estimates.


Topical diquafosol versus hyaluronic acid for the treatment of dry eye disease: a meta-analysis of randomized controlled trials.
Diquafosol enhances fluid transfer and mucin secretion on ocular surface, which has been suggested as an effective treatment for dry eye disease (DED). The aim of the systematic review and meta-analysis was to compare the efficacy and safety of topical diquafosol versus hyaluronic acid (HA) for DED. Relevant randomized controlled trials were obtained via search of electronic including PubMed, Embase, Cochrane Library, and Web of Science. A random-effects model was used to pool the results after incorporating the influence of potential heterogeneity. A total of nine RCTs involving 1295 patients with DED were included in the meta-analysis. Compared to treatment with 0.1% HA, topical treatment with 3% diquafosol significantly improved the Ocular Surface Disease Index (mean difference (MD): - 3.59, 95% confidence interval (CI): - 4.68 to - 2.50, p < 0.001; I2 = 6%), results of Schirmer's test (MD: 1.08 mm, 95% CI: 0.41 to 1.76, p = 0.002; I2 = 0%), tear breakup time (MD: 0.60 s, 95% CI: 0.20 to 0.99, p = 0.003; I2 = 63%), corneal fluorescein staining score (MD: - 0.20, 95% CI: - 0.37 to - 0.03, p = 0.02; I2 = 58%), and ocular rose bengal staining score (MD: - 0.62, 95% CI: - 0.88 to - 0.35, p < 0.001; I2 = 15%). No severe adverse events were reported. Topical use of diquafosol was associated with a higher risk of overall adverse events as compared to HA (odds ratio: 1.71, 95% CI: 1.08 to 2.71, p = 0.02; I2 = 18%). Topical treatment with 3% diquafosol may be more effective than 0.1% HA for patients with DED. However, the long-term efficacy and tolerability of diquafosol still need to be determined.


Obsessive compulsive disorder and response inhibition: Meta-analysis of the stop-signal task.
This systematic review and meta-analysis updates evidence pertaining to response inhibition in obsessive-compulsive disorder (OCD) as measured by the stop-signal task (SST). We conducted a meta-analysis of the literature to compare response inhibition in patients with OCD and healthy controls, metaregressions to determine relative influences of age and sex on response inhibition performance, and a risk of bias assessment for included studies using the Newcastle-Ottawa Scale (NOS). Stop-signal reaction time (SSRT), which estimates the latency of the stopping process deficit, was significantly longer in OCD samples than in controls, reflecting inferior inhibitory control (Raw mean difference = 23.43 ms; p = <.001; 95% CI [17.42, 29.45]). We did not observe differences in mean reaction time (MRT) in OCD compared with controls (Raw mean difference = 2.51 ms; p = .755; 95% CI [-13.27, 18.30]). Reaction time variability (RTSD) was reported in one study only. Age impacted effect size of SSRT, indicating inferior performance in older OCD patients than younger ones. We did not observe a significant effect of sex on SSRT or MRT scores. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Front-Line Therapy for Metastatic Renal Cell Carcinoma: A Perspective on the Current Algorithm and Future Directions.
Over the last decade, the treatment paradigm of metastatic renal cell carcinoma has rapidly evolved, with notable changes in the front-line setting. Combination therapies involving the use of either doublet therapy with immune checkpoint inhibitors or combination VEGFR-directed therapies with immune checkpoint inhibitors have significantly improved clinical outcomes, including prolonged overall survival and durable response to treatment. We aim to highlight the Food and Drug Administration-approved front-line therapy options, the navigation of treatment selection, and the future directions of metastatic renal cell carcinoma therapies.


Clinical outcomes and prognostic factors in bloodstream infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae among patients with malignancy: a meta-analysis.
The colonization of Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) in bloodstream infections (BSIs) has been increased dramatically worldwide, and it was associated with worse clinical outcomes in patients with malignancy. We performed the meta-analysis to investigate the prognosis and risk factors in BSIs caused by ESBL-PE in oncological patients. PubMed, EMBASE, and Cochrane Library were searched for related studies. All-cause mortality was considered as the primary outcome. Subgroup analyses, meta-regression analyses, and sensitivity analysis were used to investigate heterogeneity and reliability in results. 6,729 patients from 25 studies were eligible. Six studies enrolled oncological patients with BSIs caused by ESBL-PE only, while 19 studies both enrolled ESBL-PE and non-ESBL-PE infections. The results showed that BSIs caused by ESBL-PE in patients with malignancy was associated with higher mortality than non-ESBL-PE infections (RR = 2.21, 95% CI: 1.60-3.06, P < 0.001), with a significant between-study heterogeneity (I2 =78.3%, P < 0.001). Subgroup analyses showed that children (RR = 2.80, 95% CI: 2.29-3.43, P < 0.001) and hematological malignancy (RR = 3.20, 95% CI: 2.54-4.03, P < 0.001) were associated with a higher mortality. Severe sepsis/ septic shock, pneumonia, and ICU admission were the most common predictors of mortality. Our study identified that BSIs caused by ESBL-PE in patients with malignancy were associated with worse clinical outcomes compared with non-ESBL-PE infections. Furthermore, children and hematological malignancy were associated with higher mortality. Severe sepsis/ septic shock, pneumonia, and ICU admission were the most common predictors of mortality.


pH-susceptibility of HLA-DO tunes DO/DM ratios to regulate HLA-DM catalytic activity.
The peptide-exchange catalyst, HLA-DM, and its inhibitor, HLA-DO control endosomal generation of peptide/class II major histocompatibility protein (MHC-II) complexes; these complexes traffic to the cell surface for inspection by CD4+ T cells. Some evidence suggests that pH influences DO regulation of DM function, but pH also affects the stability of polymorphic MHC-II proteins, spontaneous peptide loading, DM/MHC-II interactions and DM catalytic activity, imposing challenges on approaches to determine pH effects on DM-DO function and their mechanistic basis. Using optimized biochemical methods, we dissected pH-dependence of spontaneous and DM-DO-mediated class II peptide exchange and identified an MHC-II allele-independent relationship between pH, DO/DM ratio and efficient peptide exchange. We demonstrate that active, free DM is generated from DM-DO complexes at late endosomal/lysosomal pH due to irreversible, acid-promoted DO destruction rather than DO/DM molecular dissociation. Any soluble DM that remains in complex with DO stays inert. pH-exposure of DM-DO in cell lysates corroborates such a pH-regulated mechanism, suggesting acid-activated generation of functional DM in DO-expressing cells.


Lack of effect on the sodium efflux of the microinjection of D-Ins(1,4,5)P3 into ouabain-poisoned barnacle muscle-fibers.
A study has been carried out using relatively intact mature muscle fibers from the barnacle Balanus nubilus to see whether D-Ins(1,4,5)P3 stimulates the ouabain-insensitive Na efflux following its microinjection and whether this is accompanied by a contraction of the fiber. Part of the impetus for a study of this type came from the on-going debate between Vergara, Rojas and co-workers and Lea and co-workers, the former group holding the view that skinned barnacle fibers and skeletal fibers in general are responsive to this isomer. The evidence brought forward indicates that the injection of D-Ins(1,4,5)P3 in concentrations in the range of 10(-2) M to 10(-6) M into cannulated unskinned fibers pretreated with ouabain fails to increase the residual efflux, and additionally fails to elicit a contraction. A similar picture emerges with the use of non-hydrolyzable DL-Ins(1,4,5)P3[S]3, analog following its injection in a concentration of 0.5 microM. Higher concentrations of the analog were unavailable for use. This work also involved verification of the idea that an effect might be obtainable in depolarized fibers. However, doubling or tripling K0+ and injection of the isomer or the analog simultaneously failed to support this idea. Since nothing is known as to whether D-Ins(1,4,5)P3 influences the behavior of the Na(+)-Ca2+ exchanger when operating in the reverse mode, experiments were done to check this possibility. ATPNa2 which is though to activate Na(+)-Ca2+ exchange was injected prior to the isomer or the analog but no significant results were obtained. A similar line of reasoning was followed, that of activating the L-type Ca2+ channel by injecting GTPNa2 which in addition is known to activate adenylate cyclase. Again, neither the isomer nor the analog were effective. Thus, the only conclusion possible is that in relatively intact, mature barnacle fibers there is no coupling between the phosphoinositide signalling pathway and two other key systems, viz. the Na(+)-Ca2+ exchanger when operating in the reverse mode and the L-type Ca2+ channel. Equally clear is that for some unknown reason the ouabain-insensitive Na efflux and the contractile apparatus are insensitive to D-Ins(1,4,5)P3[S]3.


Perioperative documentation. Integrating nursing diagnoses on the patient record.
The perioperative record maintains accurate communication between the OR and the postoperative care nurse. For example, the nurse can easily verify the type and placement of a drain by checking the area labeled "Potential for infection." The check-off format also makes the information consistent and easy-to-read, and the nurse does not have to decipher any handwriting. Another advantage of this format is that it is easy to retrieve data for nursing research. It is also suitable for computerization.


The effects of BIS-GMA and TEG-DMA on female mouse fertility.
The current study evaluated the effect of bisphenol A glycerolate dimethacrylate (BIS-GMA) and triethyleneglycol dimethacrylate (TEG-DMA) on female mouse fertility. Adult female mice were exposed to BIS-GMA or TEG-DMA (0, 25 and 100 microg/kg) intragastrically daily for 28 d and then mated with sexually mature untreated male mice and after mating their fertility was assessed. In females exposed to BIS-GMA at both doses significant increases in the total number of resorptions out of the total number of implantations were observed, with a significant increase in the number of animals with resorptions at the higher dose. Significant reductions in body weights and significant increases in ovary weights were also observed. Exposure to TEG-DMA at a dose of 100 microg/kg resulted in significant reductions in pregnancy rates and a significant increase in the total number of embryonal resorptions. Significant reductions in body and uterine weights were also observed in females exposed to TEG-DMA. The results suggest that both BIS-GMA and TEG-DMA have reproductive toxic effects in female mice.


Detecting nonculturable bacteria in the active mycorrhizal zone of the pine mushroom Tricholoma matsutake.
The fungus Tricholoma matsutake forms an ectomycorrhizal relationship with pine trees. Its sporocarps often develop in a circle, which is commonly known as a fairy ring. The fungus produces a solid, compact, white aggregate of mycelia and mycorrhizae beneath the fairy ring, which in Japanese is called a 'shiro'. In the present study, we used soil dilution plating and molecular techniques to analyze the bacterial communities within, beneath, and outside the T. matsutake fairy ring. Soil dilution plating confirmed previous reports that bacteria and actinomycetes are seldom present in the soil of the active mycorrhizal zone of the T. matsutake shiro. In addition, the results showed that the absence of bacteria was strongly correlated with the presence of T. matsutake mycorrhizae. The results demonstrate that bacteria, especially aerobic and heterotrophic forms, and actinomycetes, are strongly inhibited by T. matsutake. Indeed, neither bacteria nor actinomycetes were detected in 11.3% of 213 soil samples from the entire shiro area by culture-dependent methods. However, molecular techniques demonstrated that some bacteria, such as individual genera of Sphingomonas and Acidobacterium, were present in the active mycorrhizal zone, even though they were not detected in soil assays using the dilution plating technique.


Immunoreactivity of receptor and transporters for lactate located in astrocytes and epithelial cells of choroid plexus of human brain.
Glucose metabolism produces lactate and hydrogen ions in an anaerobic environment. Cerebral ischemia or hypoxia is believed to become progressively lactacidemic. Monocarboxylate transporters (MCTs) in endothelial cells are essential for the transport of lactate from the blood into the brain. In addition, it is considered that MCTs located in astrocytic and neuronal cells play a key role in the shuttling of energy metabolites between neurons and astrocytes. However, roles of lactate in the brain remain to be clarified. In this study, the localization of lactate transporters and a receptor for cellular uptake of lactate was immunohistochemically examined in autopsied human brains. Immunoreactivity for MCT1 was observed in the apical cytoplasmic membrane of some epithelial cells in the choroid plexus as well as astrocytes and the capillary wall, whereas that for MCT4 was found in the basolateral cytoplasmic membrane of small number of epithelial cells as well as astrocytes and the capillary wall. In addition, immunoreactivity for the hydroxy-carboxylic acid 1 receptor (HCA1 receptor), a receptor for cellular uptake of lactate, was also found on the basolateral cytoplasmic membrane of epithelial cells as well as astrocytic and neuronal cells. Immunoreactivity for lactate dehydrogenase (LDH)-B was observed in the cytoplasm of epithelial cells in the choroid plexus as well as astrocytes and the capillary wall. These immunohistochemical findings indicate the localization of MCT1, MCT4, the HCA1 receptor, and LDH-B in epithelial cells of the choroid plexus as well as astrocytes, and suggest the transport of intravascular lactate into the brain through epithelial cells of the choroid plexus as well as cerebral vessels and the possibility of lactate being utilized in epithelial cells.


The reversed-flow medio-distal fasciocutaneous island thigh flap: anatomic basis and clinical applications.
A new fasciocutaneous reversed-flow island flap of the thigh is presented which is independent of the presence of perfused blood vessels below the level of the knee joint-line. The pedicle, which is supplied by the proximal genicular anastomotic network, consists of the osteoarticular branch (OAB) and concomitant veins of the descending genicular artery. Based on cadaver dissections the OAB arose in 23/30 specimens (77%) together with the saphenous artery (SA). In 2/30 specimens (7%) the OAB originated directly from the superficial femoral artery and in 1/30 specimens (3%) the OAB was absent. The OAB gave off one to three cutaneous branches to the overlying skin in 26/30 specimens (87%). We were able to elevate a flap on the osteoarticular branch alone in 57%. Additional length could be added to the pedicle in 33% by including the most proximal part of the saphenous artery together with its first cutaneous branch. Thus, in 90% of the dissections a reversed-flow island flap could be raised which reached the proximal half of the leg, the knee and the most distal part of the thigh. We report our early clinical experience.


Chemical speciation of Co, Ni, Cu, and Zn in mine effluents and effects of dilution of the effluent on release of the above metals from their metal-dissolved organic carbon (DOC) complexes.
The paper explores the lability of DOC complexes of Co, Ni, Cu, and Zn in the mining effluent, and investigates the effects of dilution of the effluent on the release of metals from the metal-DOC complexes. This study was done using competing ligand exchange method in conjunction with adsorptive cathodic stripping voltammetry on effluent samples from Copper Cliff Mine, Sudbury, Canada, using two samples of the effluent: one, undiluted (100%) effluent, and the other, diluted (45%) effluent. The dilution was done with tap water in order to determine the effects of dilution on the metal complexes in the effluents when they were discharged into receiving streams of freshwaters. The dilution of the effluent had a small effect on release of Cu from the Cu-DOC complexes, but had a much greater effect on the release of Zn from the Zn-DOC complexes. The release of Ni and Co from their DOC complexes decreased drastically on dilution of the effluent. The much greater release of Cu from the Cu-DOC complexes compared to the release of Ni, Co, and Zn from their DOC complexes in both the undiluted and the diluted effluent was probably due to the higher absolute concentration of Cu and the higher [Cu]/[DOC] ratio. The drastic decrease in the release of Ni and Co from the Ni- and Co-DOC complexes in the diluted (45%) effluent compared with the undiluted (100%) effluent probably resulted from strengthening of the metal-DOC bond due to the reduced screening of charges by a smaller concentration of Ca2+ in the diluted (45%) effluent. This work also shows that change in the ionic strength produces conformational changes in and in aggregation and precipitation of the DOC and also changes in electrostatic interactions between the metal cations and the humate polyanions.


Spontaneous alternation and spatial learning in Dab1scm (scrambler) mutant mice.
Homozygous Dab1scm mutants with cell ectopias in cerebellar cortex, hippocampus, and neocortex were compared with non-ataxic heterozygous and wild-type controls in spontaneous alternation and Morris water maze tests. Although there were no group differences in alternation rates, wild-type and heterozygote groups alternated above chance levels, whereas homozygous Dab1scm mutants did not. In the Morris water maze, Dab1scm mutants were impaired in both hidden and visible platform subtests. The deficits in spontaneous alternation and water maze measures reproduce the phenotype previously described in Reln(rl-Orl) mutants, attributed to disturbance of the same molecular pathway involving reelin.


Long-distance dispersal of the beach strawberry, Fragaria chiloensis, from North America to Chile and Hawaii.
The beach strawberry, Fragaria chiloensis, is found in a narrow coastal band from the Aleutian Islands to central California and then jumps thousands of kilometres all the way to Hawaii and Chile. As it probably had a North American origin, it must have been introduced to the other locations by long-distance dispersal. The aim of this study was to determine which agent carried the beach strawberry to its Pacific and South American locations. A deductive framework was constructed to separate between the possible modes of long-distance dispersal involving animals, wind and ocean currents. Bird migration was subsequently identified as the most likely scenario, and then the routes, habitats, feeding preferences and flight distances of all the shorebird species were evaluated to determine the most likely carrier. Six species migrate between North America and Chile and feed on the beaches and rocky shores where F. chiloensis grows naturally: Black-bellied Plovers, Greater Yellowlegs, Ruddy Turnstones, Sanderlings, Whimbrels and Willets. Of these, only two eat fruit and migrate in long continuous flight: Ruddy Turnstones and Whimbrels. Two species travel between North America and Hawaii, eat fruit and forage on the beaches and rocky shores where F. chiloensis grows naturally: Pacific Golden-plovers and Ruddy Turnstones. Ruddy Turnstones eat far less fruit than Pacific Golden-plovers and Whimbrels, making them less likely to have introduced the beach strawberry to either location. We provide evidence that F. chiloesis seeds were probably dispersed to Hawaii by Pacific Golden-plovers and to Chile by Whimbrels.


Neuropathological Alzheimer's Disease Lesions in Nasu-Hakola Disease with TREM2 Mutation: Atypical Distribution of Neurofibrillary Changes.
Nasu-Hakola disease is a rare autosomal recessive disorder associated to mutations in TREM2 and DAP12 genes, neuropathologically characterized by leukoencephalopathy with axonal spheroids. We report the neuropathologic findings of a 51-year-old female with a homozygous mutation (Q33X) of TREM2 gene. Beside severe cerebral atrophy and hallmarks of Nasu-Hakola disease, significant Alzheimer's disease lesions were present. Neurofibrillary changes showed an atypical topographic distribution being severe at spots in the neocortex while sparing the mesial temporal structures. Our finding suggests that TREM2 genetic defects may favor Alzheimer's disease pathology with neurofibrillary changes not following the hierarchical staging of cortical involvement identified by Braak.


Resistance by the blue tick (Boophilus decoloratus) to the synthetic pyrethroid, fenvalerate.
The Shaw larval test, in conjunction with adult tick immersion and stall tests, was utilized to confirm that a field strain of B. decoloratus, from Natal, is highly resistant to the ixodicide fenvalerate (Factor of resistance 4,744). This resistance developed over a reported 18 months of usage for cattle dipping.


Strategic insight into enhanced photocatalytic remediation of pharmaceutical contaminants using spherical CdO nanoparticles in visible light region.
The sustainable control of pharmaceutical micropollutants in water and wastewater environments is a great challenge in the 21st century. To address these issues, unique CdO nanoparticles (NPs) were synthesized using a facile hydrothermal approach and investigated for photocatalytic control of the antibiotic tetracycline, multidrug-resistant bacteria (MDRB), and total coliform in the wastewater effluent. The NPs were characterized using a range of techniques and it exhibited a spherical-like crystal structure with a mean size of 40 nm. The vibrational stretching mode of 1419 cm-1 confirmed the formation of Cd-O (M - O). The synthesis protocol formed smoother surfaces and 1.88 eV band gap energy of CdO NPs, inducing excellent photocatalytic activity under visible LED light (blue and white) irradiation. The optimal catalyst dose and pH were 100 mg/L and 8-9, respectively. Blue light proved more effective than white light, resulting in 28% higher efficiency (93 ± 0.47%) in tetracycline degradation than white light under an identical intensity (20 mW/cm2). White light required a four-fold higher light intensity (80 mW/cm2) than blue light to induce comparable photocatalytic MDRB inactivation. Bacterial cell lysis by the photocatalytic treatment was confirmed by transmission electron microscopy (TEM). The used catalyst was easily recovered by 5 min of centrifugation and re-used without any noticeable change in the photocatalytic decomposition. The trapping experiment revealed that the CdO-based NPs contributed primarily to the generation of •O2- and •OH radicals (Type I), but the •O2- radicals were the dominant reactive oxygen species (ROS) in the photocatalytic process.


Minimally Effective Dose of Bone Morphogenetic Protein in Minimally Invasive Lumbar Interbody Fusions: Six Hundred Ninety Patients in a Dose-Finding Longitudinal Cohort Study.
Retrospective longitudinal cohort. We sought to demonstrate the minimally effective bone morphogenetic protein (BMP) dose to achieve fusion in minimally invasive transforaminal lumbar interbody fusions. Multiple studies have been conducted, which used a wide range of BMP doses for lumbar fusions highlighting associated risks and benefits. There is, however, a paucity in the literature in determining the minimally effective dose. Consecutive patients who underwent transforaminal lumbar interbody fusion from 2009 to 2014 were reviewed. Fusion was determined by a combination of computed tomography and dynamic x-ray by independent radiologists. We used backward stepwise multiple logistic regression with fusion as the dependent variable to determine whether BMP dose/level was a significant predictor for fusion. To determine the minimally effective dose of BMP/level, separate logistic regressions for different BMP dose ranges and sensitivity analyses were used. A P value ≤0.025 was considered significant. There were 1102 interspaces among 690 patients. Average BMP dose was 1.28 mg/level. Overall fusion was 95.2% with a mean follow-up of 19 months. BMP dose/level was a significant predictor for fusion. Odds of fusion increased by 2.02 when BMP dose range was increased from (0.16-1 mg/level) to (1.0-2 mg/level), but fusion odds did not increase when BMP dose increased to more than 2 mg/level. BMP dose/level was a significant predictor for fusion. There was a significant increase in odds of fusion when BMP dose increased from 0.16 to 1 mg/level to 1.0 to 2 mg/level. No benefit from increasing the dose more than 2 mg/level was found, suggesting 1.0 mg/level to be the minimally effective BMP dose. 3.


Regulation of CD47 expression in cancer cells.
CD47 is overexpressed in various types of cancers and it can directly bind with SIRPα, which is mainly located on macrophages. The binding of CD47-SIRPα transmits a "don't eat me" signal, which can prevent cancer cells from immune clearance. Targeting the phagocytosis checkpoint of CD47-SIRPα axis has shown remarkable anticancer effect in preclinical and clinical research, which indicates the potential application of CD47-SIRPα blockade for cancer treatment. In this case, the comprehensive description of the regulation of CD47 in different types of cancer cells has significant implications for furthering our understanding of the role of CD47 in cancer. Based on the current reports, we summarized the regulatory factors, i.e., cytokines, oncogenes, microRNAs as well as enzymes, of CD47 expression in cancer cells. Accordingly, we also proposed several points needing further research, hoping to provide useful insights for the future investigation on the regulation of CD47 in cancers.


Effectiveness of digital health using the transtheoretical model to prevent or delay type 2 diabetes in impaired glucose tolerance patients: protocol for a randomized control trial.
There is high prevalence of prediabetes and type 2 diabetes mellitus (T2DM) in Saudi Arabia that is still increasing. Early diagnosis of prediabetes, and immediate, effective intervention is yet unestablished. Conventional health promotion approaches are used to educate prediabetic patients. Behavior modification is very effective in prediabetics to delay T2DM. Thus, the main objective of this study is to examine the effect of the new behavioral model, the Transtheoretical Model short messages (text 4 change) to modify lifestyle to prevent or delay the onset of T2DM, through promotion of a healthy diet and increased physical activity, in impaired glucose tolerance patients. Another objective is to estimate the impact of this model on markers of cardiovascular and metabolic risks as T2DM is one of the modifiable risk factors to prevent cardiovascular diseases. This is a randomized controlled trial. One thousand and sixteen, eligible Saudi adults will be recruited from the Heart Health Promotion study (HHP), which was conducted at the King Saud University from July 2013 to April 2014. These adults were at a higher risk of developing T2DM within 2-3 years. The research team's database has a contact list and they will recruit individuals over 6-8 weeks. All participants will be randomized at a 1:1 ratio into two groups, receive group education about lifestyle modifications and written information about diet and physical activity. Text 4 change SMS texts will be sent only to the intervention group. All participants will be assessed at baseline, 6, 12, 18, 24, 30, and 36 months for behavioral change using a World Health Organization (WHO) STEPS questionnaire and for glycated hemoglobin, biochemical and anthropometric measurements using standard methods. This new approach for promoting the importance of behavior modification in prediabetics is expected to delay and/or prevent the development of T2DM in Saudi Arabia, subsequently reducing the risk of cardiovascular morbidity and mortality too. Results from this study will promote an innovative and high-tech way to decrease the burden of cardiovascular diseases in Saudi Arabia. International Standard Randomized Control Trial, registration number ISRCTN10857643. Registered 4 June, 2018.


Selective growth of natural cytotoxic but not natural killer effector cells in interleukin-3.
Interleukin-3 (IL-3) can promote the proliferation of certain classes of lymphocytes distinct from those that are dependent on interleukin-2 (IL-2) for growth. Culture conditions for its production are identical to those required for IL-2 and in both cases the producer cell appears to be Thy 1.2+, Lyt1+, Lyt2- However, unlike the IL-2 responder cells, the cells that proliferate in IL-3 are generally Lyt2-. Here we have measured the natural cytotoxic (NC) activity as well as natural killer (NK) cell activity of the IL-3-dependent cells. Both of these activities are part of a repertoire of spontaneous cytotoxic functions found in mice that might serve in early defence against infectious agents or immunosurveillance against tumours in vivo. We report a new finding that IL-3 selectively maintains NC cells but not NK cells in culture. This is in contrast to the known requirement for IL-2 in NK cell growth. This provides a means of isolating NC cells from NK cells in the mouse as an initial step in the study of the relative contribution of these two cell types in tumour immunity.


Influence of aryl hydrocarbon receptor and sulfotransferase 1A1 on bisphenol AF-induced clastogenesis in human hepatoma cells.
Bisphenol compounds (BPs) are ubiquitously existing pollutants. Recent evidence shows that they may be activated by human CYP1A1 for clastogenic effects; however, factors that influence/mediate CYP1A1-activated 4,4'-(hexafluoroisopropylidene)diphenol (BPAF) toxicity, particularly the aryl hydrocarbon receptor (AhR), sulfotransferase (SULT) 1A1 [known to conjugate 2,2-bis(4-hydroxyphenol)-propane (BPA)] and reactive oxygen species (ROS), remain unclear. In this study, a human hepatoma (HepG2) cell line was genetically engineered for the expression of human CYP1A1 and SULT1A1, producing HepG2-hCYP1A1 and HepG2-hSULT1A1, respectively. They were used in the micronucleus test and γ-H2AX analysis (Western blot) (indicating double-strand DNA breaks) with BPAF; the role of AhR in mediating BPAF toxicity was investigated by coexposure of AhR modulators in HepG2 and its derivative C3A (with no genetic modifications but enhanced CYP expression). The results indicated induction of micronuclei by BPAF (≥ 2.5 µM, for 2-cell cycle) in HepG2-hCYP1A1 and C3A, while inactive in HepG2 and HepG2-hSULT1A1; however, BPAF induced micronuclei in HepG2 pretreated with 3,3',4,4',5-pentachlorobiphenyl (PCB126, AhR activator), and BAY-218 (AhR inhibitor) blocked the effect of BPAF in C3A. In HepG2-hCYP1A1 BPAF selectively induced centromere-free micronuclei (immunofluorescent assay) and double-strand DNA breaks. In HepG2 cells receiving conditional medium from BPAF-HepG2-hCYP1A1 incubation micronuclei were formed, while negative in HepG2-hSULT1A1. Finally, the intracellular levels of ROS, superoxide dismutase and reduced glutathione in C3A and HepG2-hCYP1A1 exposed to BPAF were all moderately increased, while unchanged in HepG2 cells. In conclusion, like other BPs BPAF is activated by human CYP1A1 for potent clastogenicity, and this effect is enhanced by AhR while alleviated by SULT1A1.