A new family of satellite DNA sequences as a major component of centromeric heterochromatin in owls (Strigiformes).
We isolated a new family of satellite DNA sequences from HaeIII- and EcoRI-digested genomic DNA of the Blakiston's fish owl ( Ketupa blakistoni). The repetitive sequences were organized in tandem arrays of the 174 bp element, and localized to the centromeric regions of all macrochromosomes, including the Z and W chromosomes, and microchromosomes. This hybridization pattern was consistent with the distribution of C-band-positive centromeric heterochromatin, and the satellite DNA sequences occupied 10% of the total genome as a major component of centromeric heterochromatin. The sequences were homogenized between macro- and microchromosomes in this species, and therefore intraspecific divergence of the nucleotide sequences was low. The 174 bp element cross-hybridized to the genomic DNA of six other Strigidae species, but not to that of the Tytonidae, suggesting that the satellite DNA sequences are conserved in the same family but fairly divergent between the different families in the Strigiformes. Secondly, the centromeric satellite DNAs were cloned from eight Strigidae species, and the nucleotide sequences of 41 monomer fragments were compared within and between species. Molecular phylogenetic relationships of the nucleotide sequences were highly correlated with both the taxonomy based on morphological traits and the phylogenetic tree constructed by DNA-DNA hybridization. These results suggest that the satellite DNA sequence has evolved by concerted evolution in the Strigidae and that it is a good taxonomic and phylogenetic marker to examine genetic diversity between Strigiformes species.


Chest imaging representing a COVID-19 positive rural U.S. population.
As the COVID-19 pandemic unfolds, radiology imaging is playing an increasingly vital role in determining therapeutic options, patient management, and research directions. Publicly available data are essential to drive new research into disease etiology, early detection, and response to therapy. In response to the COVID-19 crisis, the National Cancer Institute (NCI) has extended the Cancer Imaging Archive (TCIA) to include COVID-19 related images. Rural populations are one population at risk for underrepresentation in such public repositories. We have published in TCIA a collection of radiographic and CT imaging studies for patients who tested positive for COVID-19 in the state of Arkansas. A set of clinical data describes each patient including demographics, comorbidities, selected lab data and key radiology findings. These data are cross-linked to SARS-COV-2 cDNA sequence data extracted from clinical isolates from the same population, uploaded to the GenBank repository. We believe this collection will help to address population imbalance in COVID-19 data by providing samples from this normally underrepresented population.


Protein kinase A activators produce a short-term, but not long-term, increase in respiratory-drive transmission at the hypoglossal motor nucleus in vivo.
Synaptic plasticity is an intrinsic and conserved feature of neuronal activity that has been most extensively studied in the context of learning and memory in Aplysia and the mammalian hippocampus. However, the intracellular mechanisms underlying plasticity at motor nuclei, influencing motor behaviour, are less well studied. In vitro experiments in neonatal rodents indicate that protein kinase A (PKA) modulates respiratory-drive transmission at the hypoglossal motor nucleus (HMN), which innervates the genioglossus muscle of the tongue. We hypothesised that PKA activators at the HMN would increase genioglossus activity in vivo, whereas a PKA inhibitor would suppress activity indicative of constitutive PKA activation. Since PKA activators are importantly involved in models of long-term augmentation of neuronal activity following massed stimulation [16], we also hypothesised that application of PKA activators to the HMN would produce long-term facilitation of genioglossus activity. Experiments were performed in 25 isoflurane-anaesthetised, tracheotomised, spontaneously breathing adult rats. Microdialysis perfusion of 8-Br-cAMP (direct PKA activator) into the HMN increased genioglossus activity compared to baseline levels with artificial cerebrospinal fluid (P<0.001). Application of forskolin (indirect PKA activator) had a similar effect (P<0.002). Genioglossus activity progressively decreased back to baseline during a 90-min washout with artificial cerebrospinal fluid, demonstrating a lack of long-term facilitation of genioglossus activity. Similar to massed application of 8-Br-cAMP to the HMN, intermittent application produced a short-term (P<0.001), but not long-term, increase in genioglossus activity in vivo. Application of Rp-8-Cl-cAMPS (PKA inhibitor) did not decrease genioglossus activity, indicating a lack of constitutive PKA activation.


Disseminated tuberculosis in rare association with hemophagocytic lymphocytosis - A case report from central India.
Hemophagocytic Lymphohistiocytosis (HLH) is an uncommon, diverse and rare genetic hyper-inflammatory syndrome. HLH associated with tuberculosis (TB-HLH) has been described as a clinical and diagnostic quandary. The co-existence leads to significantly higher morbidity and mortality. Our case highlights the presence of disseminated tuberculosis and worsening of the case due to underlying hemophagocytic syndrome leading to rapid deterioration of patient prognosis. Prompt diagnosis and treatment remains help to improve patient management.


Possibilities and limits of the midline interhemispheric approach.
Based on experience in 17 children operated upon between 1978 and 1984, the possibilities and limitations of the interhemispheric parafalx approach to lesions of the anterior and posterior lateral ventricles and the third ventricle are described. The interhemispheric approach seems more advantageous than transcortical approaches since additional cortical and white matter lesions can be avoided. The limitations of visibility are the same as in transcortical approaches.


Jeotgalibacillus aurantiacus sp. nov., a novel orange-pigmented species with a carotenoid biosynthetic gene cluster, isolated from wetland soil.
A Gram-stain-positive, orange-pigmented, rod-shaped and flagellated bacterial strain T12T was isolated from wetland soil in Kunyu Mountain Wetland in Yantai, China. The strain was able to grow at 15-40 °C (optimum 37 °C), at 0.0-9.0% NaCl (optimum 2%, w/v) and at pH 5.5-9.0 (optimum 8.5). A phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain T12T is a member of the family Planococcaceae, sharing 97.6% and 97.1% sequence similarity with the type strains of Jeotgalibacillus salarius and Jeotgalibacillus marinus, respectively. Genome-based analyses revealed a genome size of 3,506,682 bp and a DNA G + C content of 43.7%. Besides, the genome sequence led to 55.0-74.6% average amino acid identity values and 67.8-74.7% average nucleotide identity values between strain T12T and the current closest relatives. Digital DNA-DNA hybridization of strain T12T with the type strains of Jeotgalibacillus proteolyticus and J. marinus demonstrated 19.0% and 20.3% relatedness, respectively. The chemotaxonomic analysis showed that the sole quinone was MK-7. The predominant cellular fatty acids were iso-C15:0, anteiso-C15:0, C16:1ω7c alcohol and iso-C14:0. The polar lipids consisted of an unidentified aminolipid, phosphatidylglycerol, diphosphatidylglycerol and two unidentified phospholipids. Based on the polyphasic characterization, strain T12T is considered to represent a novel species, for which the name Jeotgalibacillus aurantiacus sp. nov. is proposed. The type strain is T12T (= KCTC 43296 T = MCCC 1K07171T).


Isolated lateropulsion of the trunk in cerebellar infarct.
MRI in a 63-year-old male with isolated lateropulsion of the trunk disclosed an infarct in the inferior portion of the right cerebellar hemisphere, suggesting an end-zone type infarct in the lateral branch of the right posterior inferior cerebellar artery (1PICA) or a borderzone infarct between 1PICA and superior cerebellar artery. A close clinico-topographical relationship between isolated lateropulsion of the trunk and lesion in the territory of 1PICA was demonstrated.


[Detection and antigenic distribution of hepatitis B virus in liver tissue and its relation to other serological markers of viral replication].
The aim of this work has been the production of specific monoclonal antibodies against HBV-antigens and their utilisation in order to study their distribution on liver tissue. The monoclonal antibodies anti-HBc and anti-HBs were obtained by the modified hybridoma technique. This study was performed on 50 patients affected by several chronic hepatopathies. For the detection of the antigens, avidin-biotin-peroxidase complex immunostaining was used. Both cytoplasmic and membranous HBsAg were detected in 15 out of 16 HBsAg+ patients; 8 of 12 HBsAg-/anti-HBc+ patients and 1 HBsAg-/antiHBc- patient. Cytoplasmic and nuclear HBcAg was observed in 12 of 16 HBsAg+ patients and 4 of 20 HBsAg- patients. Although the presence of serum HBsAg is an index of liver infection, in some HBsAg-/antiHB+ patients (20%) with undetectable levels of HBsAg, hepatic injury may be disclosed by the detection of other markers of active viral replication.


Identification of epigenetic mechanisms in paddy crop associated with lowering environmentally related cadmium risks to food safety.
Cadmium (Cd) is a toxic metal that contributes to human diseases such as pediatric cancer and cardiovascular dysfunction. Epigenetic modification caused by Cd exposure is the major factor in etiology of environmentally-relevant diseases. However, the underlying epigenetic mechanism for Cd uptake and accumulation in food crops, particularly those growing in Cd-contaminated environments, is largely unknown. This study investigated uncharacterized regulatory mechanisms and biological functions of global DNA hypomethylation at CG sites that are associated with gene expression for Cd detoxification and accumulation in the food crop rice. Mutation of the CG maintenance enzyme OsMET1 confers rice tolerance to Cd exposure. Genome-wide analysis of OsMET1 loss of function mutant Osmet1 and its wild type shows numerous loci differentially methylated and upregulated genes for Cd detoxification, transport and accumulation. We functionally identified a new locus for a putative cadmium tolerance factor (here termed as OsCTF) and demonstrated that Cd-induced DNA demethylation is the drive of OsCTF expression. The 3'-UTR of OsCTF is the primary site of DNA and histone (H3K9me2) demethylation, which is associated with higher levels of OsCTF transcripts detected in the Osmet1 and Ossdg714 mutant lines. Mutation of OsCTF in rice led to hypersensitivity to Cd and the Osctf line accumulated more Cd, whereas transfer of OsCTF back to the Osctf mutant completely restored the normal phenotype. Our work unveiled an important epigenetic mechanism and will help develop breeding crops that contribute to food security and better human health.


Validity of congenital malformation diagnostic codes recorded in Québec's administrative databases.
To assess the validity of the diagnostic codes of congenital malformations (CMs) recorded in two of Québec's administrative databases. A cohort of pregnancies and infants born to asthmatic and non-asthmatic women in 1990-2002 was reconstructed using Québec's administrative databases. From this cohort, we selected 269 infants with a CM and 144 without CM born to asthmatic women, together with 284 and 138 infants, respectively, born to non-asthmatic women. The diagnoses of CMs recorded in the databases were compared with the diagnoses written by the physicians in the infants' medical charts. The positive predictive values (PPV) and negative predictive values (NPV) for all, major, and several specific CMs were estimated. The PPVs for all CMs and major CMs were 82.2% (95% confidence interval (CI): 78.5%-85.9%) and 78.1% (74.1%-82.1%), respectively, in the asthmatic group and were 79.2% (75.4%-83.1%) and 69.0% (64.6%-73.4%), respectively, in the non-asthmatic group. PPVs >80% were found for several specific CMs, including cardiac, cleft, and limb CMs in both groups. The NPV for any CM was 88.2% (95% CI: 85.1%-91.3%) in the asthmatic group and 94.2% (92.2%-96.2%) in the non-asthmatic group. Québec's administrative databases are valid tools for epidemiological research of CMs. The results were similar between infants born to women with and without asthma.


Distribution of somatostatin receptor 5 in mouse and bullfrog retinas.
Somatostatin (SRIF), as a neuroactive peptide in the CNS, may act as a neuromodulator through activation of five specific receptor subtypes (sst(1)-sst(5)). In this work we conducted a comparative study of the expression of sst(5) in mouse and bullfrog retinas by immunofluorescence double labeling. Basically, the expression profiles of sst(5) in the retinas of the two species were similar. That is, in the inner retina sst(5) was localized to dopaminergic and cholinergic amacrine cells, stained by tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) respectively, and cells in the ganglion cell layer, whereas in the outer retina immunostaining for sst(5) was observed in horizontal cells. However, a more widespread, abundant distribution of labeling for sst(5), as compared to mouse retina, was seen in bullfrog retina: strong labeling for sst(5) was diffusely distributed in both outer and inner plexiform layers (OPL and IPL) in the bullfrog retina, but the labeling was only observed in the IPL of the mouse retina. In addition, bullfrog photoreceptors, both rods and cones, but not mouse ones, were labeled by sst(5). In combination with the experiments showing that SRIF-immunoreactivity was mainly found in the inner retina, our results suggest that SRIF, released from SRIF-containing cells in the inner retina, may play a neuromodulatory role in both outer and inner retina mediated by volume transmission via sst(5) in bullfrog retina, while the SRIF action may be largely restricted to the mouse inner retina.


Influence of biological, environmental and technical factors on phenolic content and antioxidant activities of Tunisian halophytes.
Halophyte ability to withstand salt-triggered oxidative stress is governed by multiple biochemical mechanisms that facilitate retention and/or acquisition of water, protect chloroplast functioning, and maintain ion homeostasis. Most essential traits include the synthesis of osmolytes, specific proteins, and antioxidant molecules. This might explain the utilization of some halophytes as traditional medicinal and dietary plants. The present study aimed at assessing the phenolic content and antioxidant activities of some Tunisian halophytes (Cakile maritima, Limoniastrum monopetalum, Mesembryanthemum crystallinum, M. edule, Salsola kali, and Tamarix gallica), depending on biological (species, organ and developmental stage), environmental, and technical (extraction solvent) factors. The total polyphenol contents and antioxidant activities (DPPH and superoxide radicals scavenging activities, and iron chelating and reducing powers) were strongly affected by the above-cited factors. Such variability might be of great importance in terms of valorising these halophytes as a source of naturally secondary metabolites, and the methods for phenolic and antioxidant production.


Human T-cell leukemia virus type 2 post-transcriptional control protein p28 is required for viral infectivity and persistence in vivo.
Human T-cell leukemia virus (HTLV) type 1 and type 2 are related but distinct pathogenic complex retroviruses. HTLV-1 is associated with adult T-cell leukemia and a variety of immune-mediated disorders including the chronic neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis. In contrast, HTLV-2 displays distinct biological differences and is much less pathogenic, with only a few reported cases of leukemia and neurological disease associated with infection. In addition to the structural and enzymatic proteins, HTLV encodes regulatory (Tax and Rex) and accessory proteins. Tax and Rex positively regulate virus production and are critical for efficient viral replication and pathogenesis. Using an over-expression system approach, we recently reported that the accessory gene product of the HTLV-1 and HTLV-2 open reading frame (ORF) II (p30 and p28, respectively) acts as a negative regulator of both Tax and Rex by binding to and retaining their mRNA in the nucleus, leading to reduced protein expression and virion production. Further characterization revealed that p28 was distinct from p30 in that it was devoid of major transcriptional modulating activity, suggesting potentially divergent functions that may be responsible for the distinct pathobiologies of HTLV-1 and HTLV-2. In this study, we investigated the functional significance of p28 in HTLV-2 infection, proliferation, and immortaliztion of primary T-cells in culture, and viral survival in an infectious rabbit animal model. An HTLV-2 p28 knockout virus (HTLV-2Deltap28) was generated and evaluated. Infectivity and immortalization capacity of HTLV-2Deltap28 in vitro was indistinguishable from wild type HTLV-2. In contrast, we showed that viral replication was severely attenuated in rabbits inoculated with HTLV-2Deltap28 and the mutant virus failed to establish persistent infection. We provide direct evidence that p28 is dispensable for viral replication and cellular immortalization of primary T-lymphocytes in cell culture. However, our data indicate that p28 function is critical for viral survival in vivo. Our results are consistent with the hypothesis that p28 repression of Tax and Rex-mediated viral gene expression may facilitate survival of these cells by down-modulating overall viral gene expression.


Chromosomal instability and progressive loss of chromosomes in HeLa cells during adaptation to hyperoxic growth conditions.
By sequential selection for resistance to stepwise increased levels of atmospheric O2, a genetic variant of HeLa cells was obtained capable of stable proliferation under an atmosphere containing 80% O2 (HeLa-80). This cell strain has previously been characterized in terms of growth characteristics, morphology and antioxidant status (Joenje et al., 1985). In an attempt to find cytogenetic clues possibly related to the O2-tolerant character, metaphases of HeLa-80 cells were analyzed and compared to the parental (HeLa-20) strain. Numerical analysis revealed a progressive decrease in the number of chromosomes per cell during selection for O2 resistance, from a modal number of 112 in HeLa-20 cells to 84 in HeLa-80 cells. Cytogenetic endpoints for genetic damage revealed increased frequencies in HeLa-80 cells of both chromosomal aberrations (29.7 versus 6.9% aberrant cells) and sister-chromatid exchanges (0.46 +/- 0.13 versus 0.31 +/- 0.10 SCE/chromosome). G-banded metaphases failed to reveal cytogenetic evidence of gene amplification (homogeneously staining regions, double minutes) in the karyotype of HeLa-80 cells.


Restriction fragment length polymorphism based phylogenetic analysis of Avena L.
We report a molecular approach to the study of the phylogenetic relationships of Avena diploid and polyploid species based on RFLP detected with three cDNA probes of nuclear genes belonging to multigenic families (low pI α-amylase, avenin, and globulin). All the probes were highly informative in the detection of polymorphism between oat species. Associations between species were determined from cluster (UPGMA) analysis based on distance values calculated from RFLP data separately for each of the two levels of ploidy. Results were in general agreement with morphology based phylogenetic analyses, confirming the large differentiation among A and C genomes in the evolution of diploid species and the genetic homogeneity among A. brevis, A. strigosa, and A. nuda and the recently discovered A. atlantica. A certain divergence was observed between two endemic species (A. canariensis and A. damascena) and the other diploid species with the A genome. The analysis of tetraploid species relationships confirms the differentiation of the barbata complex (A. wiestii, A. barbata, A. abyssinica, and A. vaviloviana) from the maroccana-murphyi-agadiriana group, which, despite some similarities in morphological and biochemical traits, seems to have accumulated deep genetic differences along its evolutionary pathway.


Antibody Printing Technologies.
Antibody microarrays are routinely employed in the lab and in the clinic for studying protein expression, protein-protein, and protein-drug interactions. The microarray format reduces the size scale at which biological and biochemical interactions occur, leading to large reductions in reagent consumption and handling times while increasing overall experimental throughput. Specifically, antibody microarrays, as a platform, offer a number of different advantages over traditional techniques in the areas of drug discovery and diagnostics. While a number of different techniques and approaches have been developed for creating micro and nanoscale antibody arrays, issues relating to sensitivity, cost, and reproducibility persist. The aim of this review is to highlight current state-of the-art techniques and approaches for creating antibody arrays by providing latest accounts of the field while discussing potential future directions.


Beneficial changes in biomass and lipid of microalgae Anabaena variabilis facing the ultrasonic stress environment.
This study investigated the beneficial effects of ultrasonic treatment on the biomass, lipid and protein of the microalgae Anabaena variabilis. The microalgae after 11days cultivation (initial algae) were treated at the powers of 200, 350 and 500W for 10min and then cultured continuously for 3days (day 12-14). The power of 200W induced the highest lipid content 37.8% on day 12. The subsequent experiments tested the ultrasonic treatment times of 5, 10, 20 and 40min at 200W in the initial algae. The significantly improved lipid content 46.9% and productivity 54.2mg/L/d were obtained almost 1.46 and 1.86times more than that of the control algae respectively after 1day of continuous cultivation at 5min. The proper ultrasonic treatment showed the feasibility and high efficiency in promoting lipid accumulation without negatively influencing the biomass, fatty acid profiles and protein content.


Targeting Nrf2 signaling pathway and oxidative stress by resveratrol for Parkinson's disease: an overview and update on new developments.
Parkinson's disease (PD) as a prevalent neurodegenerative condition impairs motor function and is caused by the progressive deterioration of nigrostriatal dopaminergic (DAergic) neurons. The current therapy solutions for PD are ineffective because they could not inhibit the disease's progression and they even have adverse effects. Natural polyphenols, a group of phytochemicals, have been found to offer various health benefits, including neuroprotection against PD. Among these, resveratrol (RES) has neuroprotective properties owing to its capacity to protect mitochondria and act as an antioxidant. An increase in the formation of reactive oxygen species (ROS) leads to oxidative stress (OS), which is responsible for cellular damage resulting in lipid peroxidation, oxidative protein alteration, and DNA damage. In PD models, it's been discovered that RES pretreatment can diminish oxidative stress by boosting endogenous antioxidant status and directly scavenging ROS. Several studies have examined the involvement of RES in the modulation of the transcriptional factor Nrf2 in PD models because this protein recognizes oxidants and controls the antioxidant defense. In this review, we have examined the molecular mechanisms underlying the RES activity and reviewed its effects in both in vitro and in vivo models of PD. The gathered evidence herein showed that RES treatment provides neuroprotection against PD by reducing OS and upregulation of Nrf2. Moreover, in the present study, scientific proof of the neuroprotective properties of RES against PD and the mechanism supporting clinical development consideration has been described.


Is nocturia of young adulthood a remnant of childhood nocturnal enuresis?
Nocturia and nocturnal enuresis (NE) share similar aetiopathological factors, and may represent two different situations involving the same underlying issue. In this study, we tried to evaluate the relation between NE of childhood and nocturia of young adulthood. A total of 577 female university students aged 17-24 years were included in the survey. A face-to-face questionnaire was administered concerning present nocturia and past NE history. A non-validated questionnaire, created by the authors, was used to evaluate the presence and the frequency of childhood NE and present nocturia. All participant data were checked by telephone contact with their parents. The overall prevalence rates of nocturia and history of nocturnal enuresis in the study population were 8.6 % and 15 % respectively. Sixteen per cent of nocturics and 15 % of non-nocturics had a history of childhood NE (p = 0.837). The childhood NE was graded as severe or infrequent. The presence of nocturia was compared between participants with severe NE and infrequent NE, and no significant difference was observed (11.1 % vs 7.8 %, p = 0.713). Nocturia frequency was compared with the history of childhood NE and we found that as the nocturia frequency increased, the rate of childhood NE also increased. There was no relation between young adulthood nocturia and childhood NE in our study population, but as the severity of nocturia increased, the relation between nocturia and NE became more relevant.


Automatic severity grade classification of diabetic retinopathy using deformable ladder Bi attention U-net and deep adaptive CNN.
Long-term exposure to diabetes mellitus leads to the formation of diabetic retinopathy (DR), which can cause vision loss in working-age adults. Early stage diagnosis of DR is highly essential for preventing vision loss and preserving vision in people with diabetes. The motivation behind the severity grade classification of DR is to develop an automated system that can assist ophthalmologists and healthcare professionals in the diagnosis and management of DR. However, existing methods suffer from variability in image quality, similar structures of the normal and lesion regions, high dimensional features, variability in disease manifestations, small datasets, high training loss, model complexity, and overfitting, which leads to high misclassification errors in the severity grading system. Hence, there is a need to develop an automated system using improved deep learning techniques to provide a reliable and consistent grading of DR severity with high classification accuracy using fundus images. To solve these issues, we proposes a Deformable Ladder Bi attention U-shaped encoder-decoder network and Deep Adaptive Convolutional Neural Network (DLBUnet-DACNN) for accurate severity classification of DR. The DLBUnet performs lesion segmentation that can be divided into three parts: the encoder, the central processing module and the decoder. In the encoder part, deformable convolution is used instead of convolution to learn different shapes of the lesion by understanding the offset location. Afterwards, Ladder Atrous Spatial Pyramidal Pooling (LASPP) using variable dilation rates is introduced in the central processing module. LASPP enhance the tiny lesion features and variable dilation rates avoid gridding effects and can learn better global context information. Then the decoder part uses a bi-attention layer contains spatial and channel attention, which can learn contour and edges of the lesion accurately. Finally, the severity of DR is classified using a DACNN by extracting the discriminative features from the segmentation results. Experiments are conducted on the Messidor-2, Kaggle, and Messidor datasets. Our proposed method DLBUnet-DACNN achieves better results in terms of accuracy of 98.2, recall of 0.987, kappa coefficient of 0.993, precision of 0.98, F1-score of 0.981, Matthews Correlation Coefficient (MCC) of 0.93 and Classification Success Index (CSI) of 0.96 when compared to existing methods.


Detection of intracellular Ca2+ transients in sympathetic neurones using arsenazo III.
Changes in cytosolic calcium ion concentration ([Ca2+]i) have been implicated in a wide variety of cellular stimulus--transduction roles. In nerve cells, it is believed that electrical activity raises [Ca2+]i by allowing influx of Ca2+ through voltage-dependent channels in the surface membrane. Elevation of neuronal [Ca2+]i may also occur due to release of Ca2+ from intracellular storage sites. Transient increases in [Ca2+]i are thought to trigger neurotransmitter release, and to modulate axonal transport, energy metabolism and growth cone movement. Intracellular Ca2+ also appears to regulate membrane potassium channels and thereby to regulate electrical excitability. Although [Ca2+]i transients have been measured in a few giant invertebrate neurones, detection of such transients in a vertebrate neurone has not been previously reported. We have measured [Ca2+]i in bullfrog sympathetic neurones by photometry of a microinjected calcium indicator dye, arsenazo III (refs 14-16), and report here that action potentials and voltage-clamped depolarizations cause long-lasting increases in [Ca2+]i. Aslo, exposure to the drug theophylline can cause spontaneous periodic increases in [Ca2+]i. Comparisons of [Ca2+]i signals with simultaneous intracellular recordings of membrane potential suggest that the kinetics of the post-tetanic hyperpolarization (PTH) following a series of action potentials or the spontaneous hyperpolarizations induced by theophylline directly reflect the kinetics of the [Ca2+]i transient.


Arthroscopic ankle fusion to manage sequel of loss of lateral malleoli in compound crushed ankle injury.
Defect in the lateral malleolus along with lateral ligamentous injury of ankle is rare. It occurs mainly due to resection of distal fibula tumors and severe trauma leading to loss of lateral malleolus. Lateral malleoli has the major contribution in weight transmission to foot and ankle stability. To avoid persistent pain and gait abnormality due to ankle instability, reconstruction of bony defect is inevitable. Methods to address these defects are iliac crest bone grafting, vascular and nonvascular proximal fibula transfer, patella tendon bone graft and allograft. Donor site morbidity, allograft related problems are not rare. Arthrodesis of ankle gives painless stable joint. Arthrodesis can be performed by open and arthroscopic methods. Open method has more soft tissue dissection and too difficult in scenario with previous skin grafting with adherent skin to bone. We managed a case of compound ankle injury with loss of lateral malleolus with loss of lateral ligament in stages, first management of compound crushed ankle followed by arthroscopic ankle arthrodesis. Even after 6 year of follow patient has stable pain less ankle with satisfactory gait.


2,5-disubstituted bicyclo[2.1.1]hexanes as rigidified cyclopentane variants.
Identification of rigid counterparts for common flexible scaffolds is crucial to the advancement of medicinal chemistry. Here we showcase a new class of building blocks, 2,5-disubstituted bicyclo[2.1.1]hexanes that can act as rigidified cis-, or trans-1,3-disubstituted cyclopentanes, common motifs in drugs. The scalable synthesis of these structures was enabled through the use of C-H functionalization logic and cycloaddition reactions.


Electrostatics Plays a Crucial Role in HIV-1 Protease Substrate Binding, Drugs Fail to Take Advantage.
HIV-1 protease (HIVPR) is an important drug target for combating AIDS. This enzyme is an aspartyl protease that is functionally active in its dimeric form. Nuclear magnetic resonance reports have convincingly shown that a pseudosymmetry exists at the HIVPR active site, where only one of the two aspartates remains protonated over the pH range of 2.5-7.0. To date, all HIVPR-targeted drug design strategies focused on maximizing the size-shape complementarity and van der Waals interactions of the small molecule drugs with the deprotonated, symmetric active site envelope of crystallized HIVPR. However, these strategies were ineffective with the emergence of drug resistant protease variants, primarily due to the steric clashes at the active site. In this study, we traced a specificity in the substrate binding motif that emerges primarily from the asymmetrical electrostatic potential present in the protease active site due to the uneven protonation. Our detailed results from atomistic molecular dynamics simulations show that while such a specific mode of substrate binding involves significant electrostatic interactions, none of the existing drugs or inhibitors could utilize this electrostatic hot spot. As the electrostatic is long-range interaction, it can provide sufficient binding strength without the necessity of increasing the bulkiness of the inhibitors. We propose that introducing the electrostatic component along with optimal fitting at the binding pocket could pave the way for promising designs that might be more effective against both wild type and HIVPR resistant variants.


Herbal Medicine for Patients with Cognitive Impairment: An Observational Study.
The potential effects of herbal medicine for patients with cognitive disorders have been reported in various human and animal studies. This study aimed to explore the effect of herbal medicine treatment according to the Korean Medicine (KM) pattern identification for patients with mild cognitive impairment and early dementia. Twenty patients with mild cognitive impairment or mild dementia who planned to receive herbal medicine treatment were enrolled. Herbal formulae were prescribed based on the KM pattern for 12-24 weeks. Seoul Neuropsychological Screening Battery II (SNSB-II) and Montreal Cognitive Assessment (MoCA) were assessed at the baseline, after 12 weeks, and after 24 weeks (Trial registration: cris.nih.go.kr, KCT0004799). Herbal medicine products, including Yukmijihwang-tang, Samhwangsasim-tang, Palmul-tang, Banhasasim-tang, and Yukgunja-tang, were prescribed to the patients. Among the SNSB-II five cognitive function domains, the T scores for language, visuospatial function, memory, and frontal/executive function increased over time. The MoCA score also improved following the treatment (mean difference 4.23 [95% CI: 2.60, 5.86], p < 0.0001 at 12-week follow-up compared to the baseline). Considering the KM pattern scores, phlegm-dampness and fire-heat scores tended to improve after the treatment. No serious adverse events related to the intervention were reported. The potential effect of herbal medicine formulae products on improving cognitive functions in patients with cognitive impairment was observed. Further research is needed to objectify the KM pattern identification process and evaluate the KM pattern-related signs and symptoms.


Mechanics of the syrinx in Gallus gallus. II. Electromyographic studies of ad libitum vocalizations.
Records of electrical activity in the tracheal muscles of domestic chickens were obtained for a variety of ad libitum vocalizations. Primary attention was given to an analysis of events during the most complex call, crowing. Three pairs of muscles, Mm, tracheohyoideus, tracheolateralis, and sternotrachealis, can affect the configuration of a chicken's syrinx. The firing patterns of the three muscle pairs are related to their different abilities to affect the tension of the syringeal membranes. The influence of M. tracheohyoideus is most indirect and imprecise, and its role the least clearly defined. It appears to adjust the position of the trachea so that the syrinx is isolated from unpredictable and/or undesireable consequences of nuchal position and tracheal elasticity, and also helps draw the glottis caudad, thereby deepening the pharyngeal chamber. The other two muscles interact to control the tension of the vocal membranes. M. sternotrachealis relaxes the membranes by drawing the drum of the trachea caudad, or, via the syringeal ligament, by rotating the pessulus cranioventrad, or both. M. tracheolateralis tenses the membranes and/or prevents caudal movement of the orgin of M. sternotrachedalis, a necessity if the syringeal ligament is to rotate the pessulus. Vocalization depends on both syringeal configuration and appropriated air flow. Hence, tracheal muscles, syrinx, air sacs, and ventilatory muscles cooperate to form a vocal system. Cooperation elicits a surprising degree of redundancy. At least one call, a high pitched wail, may be produced by two very different techniques.


Downregulation of cell surface receptors by the K3 family of viral and cellular ubiquitin E3 ligases.
The mK3, K3, and K5 gene products from the gamma2 group of gamma-herpesviruses are the founding members of a family of membrane-associated ubiquitin E3 ligases. As part of the viral immunoevasion strategy, expression of these proteins results in a decrease in cell-surface major histocompatibility complex class I molecules and other immunoreceptors including intercellular adhesion molecule-1, CD86, and CD1d. These viral gene products all possess a characteristic cytosolic N-terminal RING-CH domain, responsible for ubiquitination of the target protein, and two membrane-spanning segments required for substrate specificity. For the majority of substrates, ubiquitination at the cell surface leads to rapid internalization and endolysosomal degradation, while mK3 ubiquitinates class I molecules associated with the peptide-loading complex resulting in proteasome-mediated degradation. Related viral genes with similar functions have been found in poxviruses, suggesting appropriation of these genes from the eukaryotic host. Ten membrane-associated RING-CH (MARCH) human genes with a similar organization have now been identified, and their overexpression leads to ubiquitination and downregulation of a variety of cell-surface immunoreceptors. While all the MARCH proteins are predicted to act as ubiquitin E3 ligases, their physiological role and substrates remain to be defined.


Methyl jasmonate enhances memory performance through inhibition of oxidative stress and acetylcholinesterase activity in mice.
Current research effort focuses on the development of safer natural compounds with multipronged mechanisms of action that could be used to ameliorate memory deficits in patients with Alzheimer's disease, as cure for the disease still remains elusive. In this study, we evaluated the effect of methyl jasmonate (MJ), a naturally occurring bioactive compound on memory, acetylcholinesterase activity and biomarkers of oxidative stress in mice. Male Swiss mice were treated with intraperitoneal injection of MJ (10-40 mg/kg) alone or in combination with scopolamine (3mg/kg) once daily for 7 days. Thirty minutes after the last treatment, memory functions were assessed using Y-maze and object recognition tests. Thereafter, acetylcholinesterase activity and levels of biomarkers of oxidative stress were assessed in mice brains using standard biochemical procedures. MJ significantly enhanced memory performance and reversed scopolamine-induced cognitive impairment in mice. MJ demonstrated significant inhibition of acetylcholinesterase activity suggesting increased cholinergic neurotransmission. It further decreased malondialdehyde concentrations in mouse brain indicating antioxidant activity. Moreover, MJ significantly increased glutathione levels and activity of antioxidant enzymes (catalase and superoxide dismutase) in mice brains. The increased oxidative stress; evidenced by elevated levels of malondialdehyde and decreased antioxidant defense systems in scopolamine-treated mice was attenuated by MJ. The results of this study suggest that MJ may be useful in conditions associated with memory dysfunctions or age-related cognitive decline. The positive effect of MJ on memory may be related to inhibition of oxidative stress and enhancement of cholinergic neurotransmission through inhibition of acetylcholinesterase activity.


Multidrug and extensively drug-resistant tuberculosis in Canada 1997-2008: demographic and disease characteristics.
Nationwide Canadian public health surveillance. Description of demographic features and disease characteristics of drug-resistant tuberculosis (TB) in Canada over a 12 year period. Continuous surveillance of all cases of culture-confirmed TB in Canada. Demographic and microbiologic features were analyzed and comparisons between drug-susceptible, multidrug-resistant (MDR), and drug-resistant not-MDR were made. Cases of extensively drug resistant TB are described. 15,993 cases of culture-confirmed TB were reported during the study period. There were 5 cases of XDR-TB, 177 cases of MDR-TB, and 1,234 cases of first-line drug resistance not-MDR. The majority of drug-resistant cases were reported in foreign-born individuals, with drug-resistant cases diagnosed earlier post-arrival in Canada compared to drug-susceptible cases. In MDR-TB isolates, there was a high rate of drug-resistance to other first- and second-line drugs, making reliable empiric therapeutic recommendations for MDR-TB difficult. There was a statistically significant association between both MDR and drug-resistance not-MDR, and the risk of a negative treatment outcome (defined as treatment failure, absconded, or treatment ongoing >3 yrs). Drug-resistance complicates TB management even in developed nations with well-established TB control programs. The predominantly international origin of drug-resistant cases highlights the need for global strategies to combat TB.


Symptomatic relief: left ventricular assist devices versus resynchronization therapy.
In patients who have end-stage heart failure, medical therapy is of limited use, and heart transplantation is frequently not an option because of the shortage of donor hearts. Two new treatment options, left ventricular assist devices (LVADs) and implantable cardiac resynchronization therapy (CRT) devices, can improve survival and quality of life in patients who have heart failure. Both types of devices are easy to implant. However, LVADs carry the risk of infection and mechanical failure, and CRT is ineffective in a substantial proportion of patients who have heart failure. Therefore, methods must be devised to identify patients who have heart failure who are likely to benefit from these devices. Data suggest that early LVAD implantation, before end-stage heart failure develops, is critical to slowing or reversing disease progression. Similarly, in indicated patients who have less advanced disease, CRT may be particularly beneficial.


A Comparative Study of Iranian Female Primary School Teachers' Quality of Life With and Without Voice Complaints.
As the largest group of professional voice users, teachers are more likely to face voice disorders because of their specific job conditions. This study aimed to compare the quality of life in female teachers with and without voice complaints. This is a cross-sectional descriptive-analytical study. This was a cross-sectional study of samples of primary school female teachers with (n = 60) and without (n = 60) voice disorders. All teachers were serving in Tehran, Iran. Professional background information was obtained through interviews, and quality of life was measured using the 36-item Short Form Health Survey questionnaire. A comparison was made between the study groups to analyze the data. The mean age of teachers was 44 (standard deviation = 3.95) years. There were no significant differences between the two groups regarding their professional background. However, significant differences were observed between the two groups in all subscales of the 36-item Short Form Health Survey, including physical and social functioning, role limitations because of either physical or emotional problems, bodily pain, general health, vitality, and mental health (P < 0.05). Findings of this study point to the effect of voice complaint on quality of life and showed that teachers with voice complaints suffer from poor health-related quality of life. Therefore, both voice-specific and unspecific assessment methods are required for clinical diagnostics.


An insight into sex-specific neurotoxicity and molecular mechanisms of DEHP: A critical review.
Di-2-Ethylhexyl Phthalate (DEHP) is often used as an additive in polyvinyl chloride (PVC) to give plastics flexibility, which makes DEHP widely used in food packaging, daily necessities, medical equipment, and other products. However, due to the unstable combination of DEHP and polymer, it will migrate to the environment in the materials and eventually contact the human body. It has been recorded that low-dose DEHP will increase neurotoxicity in the nervous system, and the human health effects of DEHP have been paid attention to because of the extensive exposure to DEHP and its high absorption during brain development. In this study, we review the evidence that DEHP exposure is associated with neurodevelopmental abnormalities and neurological diseases based on human epidemiological and animal behavioral studies. Besides, we also summarized the oxidative damage, apoptosis, and signal transduction disorder related to neurobehavioral abnormalities and nerve injury, and described the potential mechanisms of neurotoxicity caused by DEHP. Overall, we found exposure to DEHP during the critical developmental period will increase the risk of neurobehavioral abnormalities, depression, and autism spectrum disorders. This effect is sex-specific and will continue to adulthood and even have an intergenerational effect. However, the research results on the sex-dependence of DEHP neurotoxicity are inconsistent, and there is a lack of systematic mechanisms research as theoretical support. Future investigations need to be carried out in a large-scale population and model organisms to produce more consistent and convincing results. And we emphasize the importance of mechanism research, which can enhance the understanding of the environmental and human health risks of DEHP exposure.


Occurrence and accumulation of microplastics in commercial fish in the coastal waters of the Lvsi fishing ground in China.
In recent years, there has been an exponential increase in the research popularity of microplastics (MPs) in offshore marine environments. However, there is still a gap in the research on the accumulation of MPs in different tissues of aquatic organisms and the trophic transfer of MPs between aquatic organisms. The common occurrence of MPs in the gills and guts of 11 species of commercial fishes was examined in the coastal waters of the Lvsi fishing ground (LSFG). The obtained results showed that >85 % of MPs existed in the gills and guts of these fish, and the abundance was 2.39 ± 1.38 pieces/fish and 2.56 ± 1.42 pieces/fish, respectively. Fibrous and blue are the most common colors and shapes of MPs, and PET is the main polymer type. At the species level, the abundance of MPs in the gills and guts of a few fishes (e.g., Larimichthys polyactis, Setipinna tenuifilis, Collichthys lucidus) decreased with increasing body length and body weight (P < 0.05). At the community level, this situation was not significant (P > 0.05). With increasing trophic level (TL), MPs tended to decrease in the gills (trophic magnification factor, TMF = 0.86) but did not significantly vary in the gut. We believe that MPs are multidimensional pollutants, and their accumulation in tissues/organs of organisms has not been accurately and qualitatively determined. To establish the relationship of MP transport and trophic transfer among water, sediments and organisms, we suggest that more efforts should be made to investigate MPs in aquatic organisms in the coastal waters of LSFG and to increase the examination of MPs in the water column and sediments. This study will help us improve our understanding of MPs pollution, and provide a good reference and basis for the management, monitoring and implementation of pollutants in marine organism of coastal water.


Mastoid: a vestigial function in humans?
At the present time, the function of the mastoid remains unknown. One of the main hypotheses accredited in the literature interprets the mastoid as a pressure buffer. Other theories underline the role of the mastoid mucosa in pressure regulation by transmucosal gas exchanges. The question is what advantage does air reabsorption and the creation of a certain degree of negative pressure that mastoid seems to produce, bring to the middle ear and hearing? In the authors' opinion, it is possible that the mastoid, or, in general, every kind of mucosa contained in the middle ear of mammals, would act to create a quite constant, although slight, negative pressure to obtain favorable compliance and impedance conditions in the middle ear to hear and transmit high frequency sounds and ultrasounds. The Eustachian tube, in this perspective, would compensate excessive values of negative pressure. Clearly, that function of mastoid pneumatization in humans would have lost its role, due to the absence of a sensorineural system to analyse ultrasounds.


AMD3100 and G-CSF disrupt the cross-talk between leukemia cells and the endosteal niche and enhance their sensitivity to chemotherapeutic drugs in biomimetic polystyrene scaffolds.
The multidrug resistance of leukemia cells is closely related to the microenvironment. The present leukemia microenvironment models focus on two-dimensional co-culture system in vitro which does not mimic the in vivo cell growth, while the 3D polystyrene (PS) scaffolds have the advantage. Stromal cell derived factor-1 may be involved in the shielding of endosteal niche from leukemia cells by binding to its receptor CXCR4, but the relationship between SDF-1/CXCR4 axis and leukemia cells is unclear. The experiments were built on the 3D PS scaffolds coated with osteoblasts. Stromal cells and MV4-11 cells were plated on the scaffolds. Then G-CSF, AMD3100 and cytarabine were added. Adhesive rate, SDF-1 level, migration state, apoptosis rate, and cell cycle of leukemia cells were observed after incubation at 24h and 48h. G-CSF decreased the level of SDF-1 and inhibited the expression of CXCR4 and promoted stationary phase leukemia cells to enter the mitotic phase and enhanced the killing effect of chemotherapeutic drugs. AMD3100 disrupted the interaction between tumors and matrix, mobilized the leukemia cells to keep away from the protective microenvironment and strengthened the cytotoxic effect of Ara-C. The combination of G-CSF and AMD3100 had stronger effects on killing the leukemia cells induced by Ara-C. It demonstrates that AMD3100 and G-CSF may inhibit adhesion and migration abilities of leukemia cells with the bone marrow niche. Both of them inhibit the role of SDF-1/CXCR4 directly or indirectly. Thus inhibiting SDF-1/CXCR4 axis may be helpful to the treatment of refractory AML.


High precision transponder localization using a novel electromagnetic positioning system in patients with localized prostate cancer.
The Micropos 4DRT system is being developed to provide accurate, precise, objective, and continuous target localization during radiotherapy. This study involves the first in vivo use of the system, aiming to evaluate the localization accuracy of this electromagnetic positioning technique compared with radiographic localization and to assess its real-time tracking ability. An active positioning marker was inserted in the prostatic urethra of 10 patients scheduled to receive radiotherapy for localized prostate cancer. A receiving sensor plate (antennae system) was placed at a known position in the treatment tabletop. Initial in vivo system calibrations were performed in three subjects. Ten additional patients were then enrolled in a study arm that compared radiographic transponder location to radiotransponder location simultaneously acquired by the Micropos 4DRT system. Frontal and side radiographs were taken with the radiopaque transponder located at three different positions within the prostatic urethra. The transponder insertions were all successful and without complications. Comparison of the transponder location as per the Micropos 4DRT system with the radiographic transponder localization showed an average (+/-SD) absolute and relative 3D difference of 2.7+/-1.2 and 1.7+/-1.0mm, respectively. Continuous transponder tracking capability was also demonstrated. Electromagnetic positioning using the Micropos transponder system is feasible in vivo. Evaluation of this novel non-ionizing localization system, in this study using a transponder positioned in the prostatic urethra, indicates transponder localization accuracy to isocenter comparable with X-ray localization of a radiopaque marker.


Influence of dietary NaCl intake on renin gene expression in the kidneys and adrenal glands of rats.
The aim of this study was to examine the influence of dietary NaCl intake on renin gene expression in the kidneys and adrenal glands of adult rats. Rats were kept on low (0.02%, w/w), normal (0.6%) or high (4%) NaCl diets and plasma renin activity (PRA) and the relative abundance of renin messenger ribonucleic acid (mRNA) in renal and adrenal tissue were followed for 20 days. In animals on a normal-salt diet PRA and renal renin mRNA levels did not change with time. PRA values in animals on the low-salt diet increased transiently (about threefold) and then declined again during the third week of treatment. Renal renin mRNA levels in these animals paralleled the changes of PRA. Conversely, in the animals kept on a high-salt diet PRA values decreased transiently and renal renin mRNA decreased continuously to about 50% of control values. Arterial blood pressure measured in conscious animals was not significantly influenced by the different salt diets. To establish whether the changes in renin mRNA levels are mediated by renal nerve input, animals on the different diets were also studied after unilateral renal denervation. Renal nerve section led to a 50% decrease of renin mRNA levels in the denervated kidneys in animals kept on the normal-salt diet. In the animals on the low-salt diet renin mRNA rose to similar levels in the denervated to those in the innervated kidney, while in animals receiving a high-salt diet renin mRNA was further decreased in the denervated kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)


Human breast milk T lymphocytes display the phenotype and functional characteristics of memory T cells.
Naive (unsensitized) and memory (antigen-primed) T cells can be phenotypically distinguished on the basis of the high or low intensity with which they express a number of immunologically relevant lymphocyte membrane antigens, including CD45R, CDw29, UCHL1, LFA-1, LFA-3, CD2 and Pgp-1. Here we report that in contrast to the two major T cell subsets found in the blood, milk T lymphocytes are almost exclusively composed of the one which exhibits the CD45Rlow, CDw29, UCHL1, LFA-1high memory T cell phenotype. In addition, while milk and autologous blood cells expressed similar levels of CD3 surface antigens, CD2 and ICAM-1 expression was approximately twofold greater on the milk T lymphocytes. This agrees with the finding that whereas colostrum T cells respond poorly to PHA, they proliferate and produce interferon-gamma normally when stimulated with either the anti-CD3 or anti-CD2 monoclonal antibodies. The selective colonization of the mammary gland during lactation by a population of T lymphocytes which displays the phenotype and functional characteristics of memory T cells may be one of the mechanisms whereby the suckling infant benefits form its mother's immunological experience.


Polyunsaturated fatty acids and child neurodevelopment among a population exposed to DDT: a cohort study.
Child neurodevelopment has been positively linked to maternal intake of polyunsaturated fatty acids (PUFAs) during pregnancy; however, it is unknown if that relationship persists among populations exposed to environmental neurotoxicants. The aim of this work was to assess whether maternal dietary intake of PUFAs during pregnancy is positively associated with child neurodevelopment, whose mothers were environmentally exposed to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT). A prospective cohort study with 276 mother-child pairs was performed in Mexico. Neurodevelopment was assessed by Bayley Scales II from children age 1 to 30 months. Dietary PUFAs intake was estimated by Food Frequency Questionnaire at 1st and 3rd trimester of pregnancy. DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene, the main metabolite of DDT) maternal serum levels were determined by electron capture gas chromatography. Longitudinal multivariate linear mixed-effects analysis, which combines mental (MDI) and motor (PDI) Bayley scales in a single model, were performed. Our results show that in a sample environmentally exposed to DDT, maternal ingestion of DPA during the first trimester of pregnancy was positively associated with MDI (β = 0.10, 95% CI 0.02, 0.18) in children from 1 to 30 months. Likewise, our results suggest that dietary ALA may be also related to MDI. DPA may benefit neurodevelopment even in populations exposed to DDT. Our results strengthen the importance of PUFAs intake during the prenatal period.


Heterogeneity of biotransformation of fluoranthene in perifused liver cells.
Pathways of biotransformation of the carcinogenic polycyclic hydrocarbon fluoranthene in individual isolated perifused liver cells were delineated using noninvasive microfluorescence spectroscopic techniques. An example of heterogeneity of coupling between phase I and phase II enzymes detected in a population of beta-naphthoflavone-induced rat liver cells demonstrates the usefulness of the experimental model of perifused liver cells.


Weakly supervised inference of personalized heart meshes based on echocardiography videos.
Echocardiography provides recordings of the heart chamber size and function and is a central tool for non-invasive diagnosis of heart diseases. It produces high-dimensional video data with substantial stochasticity in the measurements, which frequently prove difficult to interpret. To address this challenge, we propose an automated framework to enable the inference of a high resolution personalized 4D (3D plus time) surface mesh of the cardiac structures from 2D echocardiography video data. Inferring such shape models arises as a key step towards accurate personalized simulation that enables an automated assessment of the cardiac chamber morphology and function. The proposed method is trained using only unpaired echocardiography and heart mesh videos to find a mapping between these distinct visual domains in a self-supervised manner. The resulting model produces personalized 4D heart meshes, which exhibit a high correspondence with the input echocardiography videos. Furthermore, the 4D heart meshes enable the automatic extraction of echocardiographic variables, such as ejection fraction, myocardial muscle mass, and volumetric changes of chamber volumes over time with high temporal resolution.


Time-domain reflectrometry studies of water binding and structural flexibility in chymotrypsin.
Time-domain dielectric spectroscopy has been employed to probe the hydration properties and structural flexibility of chymotrypsin (EC 220.127.116.11). The dielectric properties of the hydrated protein above 100 MHz have been used to identify two categories of protein-bound water, the first being irrotationally bound to the protein with a second, relatively weakly bound, having a rotational freedom comparable with that of normal bulk water. A dielectric dispersion observed, centred at 12 MHz, has been attributed to the relaxation of the polar components of the protein structure. This dielectric loss became increasingly significant above a transition in the hydration dependence, where water is relatively weakly bound to the chymotrypsin. This is discussed in terms of the formation of water clusters on the protein surface which screen electrostatic interactions between protein-charged groups.


Patient-friendly hospital environments: exploring the patients' perspective.
To investigate the perceptions and attitudes of patients to the built environments of NHS Trust hospitals, in order to inform design excellence so as to make future hospitals places and spaces responsive to patient needs. An exploratory study of patients perceptions based on qualitative semi-structured personal interviews. Fifty one-to-one interviews held with hospital in-patients across the four directorates of surgery, medicine, care of the elderly and maternity at Salford Royal Hospitals NHS Trust, Salford, UK. The research found that there was much similarity in the priorities, issues and concerns raised by patients in each of the four directorates. Patients perceived the built environment of the hospital as a supportive environment. Their accounts in each area pointed to the significance of the factors that immediately impacted on them and their families. Patients identified having a need for personal space, a homely welcoming atmosphere, a supportive environment, good physical design, access to external areas and provision of facilities for recreation and leisure. Responses suggest that patient attitudes and perceptions to the built environment of hospital facilities relates to whether the hospital provides a welcoming homely space for themselves and their visitors that promotes health and wellbeing. The findings have important implications for capital development teams, clinical staff, managers and NHS Estates personnel. Although the study has immediate relevance for Salford Royal Hospitals Trust, findings and recommendations reported provide NHS Estates and other relevant stakeholders with evidence-based knowledge and understanding of patients' perceptions and expectations of and preferences for particular facilities and estates provision in NHS hospitals.


Rapid affinity purification and properties of rat liver sorbitol dehydrogenase.
A 23-h affinity chromatography purification procedure for sorbitol dehydrogenase (L-iditol:NADl-oxidoreductase, EC 22.214.171.124) prepared from freshly excised rat liver has been developed that resulted in an 18% yield of an apparently homogeneous preparation (purification = 439-fold). The molecular weight of the enzyme was approx. 96 000. The enzyme was specific for NAD+ (NADH), but had no requirement for NADP+ (NADPH). The purified preparation shows significant activity with structurally related polyols and ketoses. Km values for sorbitol and fructose are 0.35 and 110 mM (at pH 7.1), respectively.


The integration of transcriptome-wide association study and mRNA expression profiling data to identify candidate genes and gene sets associated with dental caries.
The aim of this study was to identify candidate genes and gene sets associated with dental caries by an integrative analysis of transcriptome-wide association study (TWAS) and messenger RNA (mRNA) expression profiling of dental caries. A genome-wide association study (GWAS) dataset of dental caries was obtained from the UK Biobank. A TWAS of dental caries was conducted with the FUSION tool using the gene expression reference weights of musculoskeletal, whole blood, and peripheral blood genes. The dental caries-associated genes identified by the TWAS were further subjected to gene ontology (GO) and pathway enrichment analyses to explore dental caries-related gene sets. Finally, the TWAS results of dental caries were compared with genome-wide mRNA expression profiling of dental caries to detect common genes and gene sets. The TWAS identified 165 musculoskeletal genes, 110 whole blood genes, and 228 peripheral blood genes. GO analysis of the genes identified by the TWAS detected 57 GO terms. For pathway enrichment analysis, we detected 12 candidate pathways. After comparing the TWAS-identified genes with the mRNA expression profiling data, we detected 6 common genes. Further comparing the GO results of the TWAS and mRNA expression profiling identified 5 common GO terms. We identified a group of dental caries-associated genes and GO terms, providing novel clues for understanding the genetic mechanisms of dental caries.


[Postoperative Sleep Disturbance in Patients Undergoing Arthroplasty: Risk Prediction Modeling Based on Logistic Regression].
To construct a risk predictive model for postoperative sleep disturbance (PSD) in patients undergoing arthroplasty by using logistic regression. We retrospectively collected the data of 4286 patients who underwent joint replacement surgeries at a tertiary-care hospital in Chengdu, China between January 1, 2017 and September 30, 2021. With 3001 cases in the training set and 1285 cases in the test set, we constructed the model by using a logistic regression algorithm to screen for predictors in Matlab, displaying the predicted risks of postoperative sleep disturbance with nomographs. The performance of the model was assessed by the area under the curve ( AUC) of the receiver operating characteristic curve, accuracy, precision, recall, F1 value, and calibration curve. A total of 9 predictors, including post-admission preoperative sleep disturbance, ward type, body mass index, smoking status, range of diseases, joint mobility (flexion), joint mobility (extension), preoperative last hemoglobin, and type of surgery, were eventually included in the study for predictive modeling . The performance assessment findings of the predictive model were as follows, AUC value, 0.708 (95% confidence interval: 0.677-0.740), accuracy, 75.20%, precision, 65.80%, recall, 43.70%, and F1 value, 0.525. The calibration curve showed good agreement between the predicted probabilities and the actual data. The model constructed in the study has good predictive efficacy and the nomographs are simple and easy to use. With this model, health workers can make preoperative prediction of the risk of PSD in arthroplasty patients based on the predictors, which facilitates early prevention and reduces the risk of postoperative sleep disturbance in patients.


The bovine immunodeficiency-like virus (BIV) is transcriptionally active in experimentally infected calves.
We have studied the infection by the bovine immunodeficiency-like virus (BIV) in three experimentally infected calves, by polymerase chain reaction (PCR) and reverse transcription-polymerase chain reaction (RT-PCR), from the peripheral blood mononuclear cells (PBMC). Two primer pairs located in the gag and pol regions of the viral genome allowed to detect the viral genomic DNA by PCR, as well as the unspliced genomic viral RNA transcript, by RT-PCR. We also present the evidence of the presence in peripheral blood mononuclear cells (PBMCs) of a mRNA transcript of the regulatory trans-activator tat gene, according to the splicing pattern of the viral genome, by use of reverse transcription followed by nested PCR. The active expression of the virus in these animals was further assessed by the sequential rescue of the virus from unstimulated PBMCs in cell culture, from 4 weeks until 15 months following the infection.


Up-regulation of FOXN3-AS1 in invasive ductal carcinoma of breast cancer patients.
Oncogenic and tumor-suppressive roles of long non-coding RNA make them an appropriate target for expression analysis in cancer studies. In this study, we selected two lncRNAs (EMX2OS and FOXN3-AS1) that are resided near the GWAS-identified SNPs for breast cancer (rs2901157 and rs141061110). These transcripts have been identified in different cancer types as either oncogenes or tumor suppressors. In the present investigation, we aimed to quantify the expression level of EMX2OS and FOXN3-AS1 in 44 breast cancer samples and normal adjacent tissues (ANCTs). The FOXN3-AS1 expression level was significantly increased in breast cancer samples compared with ANCTs (P value = 0.02), Also its amounts could distinguish two sets of samples with an accuracy of 70% (P value = 0.009). We have found an association between FOXN3-AS1 expression and tumor size (P value = 0.02). On the other hand, no significant differences were found in the EMX2OS expression level between two sets of samples (P value = 0.44); however, EMX2OS expression level has a significant association with the age of the patients (P value = 0.03). According to our result, FOXN3-AS1 can be demonstrated as a probable diagnostic marker in breast cancer so we suggest further functional studies to find the precise role of these lncRNAs in breast cancer progression.


Molecular Biomarkers for the Detection of Clinically Significant Prostate Cancer: A Systematic Review and Meta-analysis.
Prostate cancer (PCa) is the second most common type of cancer in men. Individualized risk stratification is crucial to adjust decision-making. A variety of molecular biomarkers have been developed in order to identify patients at risk of clinically significant PCa (csPCa) defined by the most common PCa risk stratification systems. The present study aims to examine the effectiveness (diagnostic accuracy) of blood or urine-based PCa biomarkers to identify patients at high risk of csPCa. A systematic review of the literature was conducted. Medline and EMBASE were searched from inception to March 2021. Randomized or nonrandomized clinical trials, and cohort and case-control studies were eligible for inclusion. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Pooled estimates of sensitivity, specificity, and area under the curve were obtained. Sixty-five studies (N = 34 287) were included. Not all studies included prostate-specific antigen-selected patients. The pooled data showed that the Prostate Health Index (PHI), with any cutoff point between 15 and 30, had sensitivity of 0.95-1.00 and specificity of 0.14-0.33 for csPCa detection. The pooled estimates for SelectMDx test sensitivity and specificity were 0.84 and 0.49, respectively. The PHI test has a high diagnostic accuracy rate for csPCa detection, and its incorporation in the diagnostic process could reduce unnecessary biopsies. However, there is a lack of evidence on patient-important outcomes and thus more research is needed. It has been possible to verify that the application of biomarkers could help detect prostate cancer (PCa) patients with a higher risk of poorer evolution. The Prostate Health Index shows an ability to identify 95-100 for every 100 patients suffering from clinically significant PCa who take the test, preventing unnecessary biopsies in 14-33% of men without PCa or insignificant PCa.


Characterization of the nanoscale structure of milk fat.
The nanoscale structure of milk fat (MF) crystal networks is extensively described for the first time through the characterization of milk fat-crystalline nanoplatelets (MF-CNPs). Removing oil by washing with cold isobutanol and breaking-down crystal aggregates by controlled homogenization allowed for the extraction and visualization of individual MF-CNPs that are mainly composed of high melting triacylglycerols (TAGs). By image analysis, the length and width of MF-CNPs were measured (600 nm × 200 nm-900 nm × 300 nm). Using small-angle X-ray scattering (SAXS), crystalline domain size, (i.e., thickness of MF-CNPs), was determined (27 nm (d001)). Through interpretation of ultra-small-angle X-ray scattering (USAXS) patterns of MF using Unified Fit and Guinier-Porod models, structural properties of MF-CNPs (smooth surfaces) and MF-CNP aggregations were characterized (RLCA aggregation of MF-CNPs to form larger structures that present diffused surfaces). Elucidation of MF-CNPs provides a new dimension of analysis for describing MF crystal networks and opens-up opportunities for modifying MF properties through nanoengineering.


Comparison of Survival Outcomes between Minimally Invasive Surgery and Open Radical Hysterectomy in Early-Stage Cervical Cancer.
To compare the survival outcomes between minimally invasive surgery (MIS) and laparotomy radical hysterectomy in patients with early-stage cervical cancer. We conducted a retrospective study involving women who received a radical hysterectomy for cervical cancer, stage IA1 with lymphovascular invasion, IA2, IB1, IB2, or IIA from 2008 to 2016. Clinicopathologic and perioperative outcomes were compared using appropriate statistical methodologies. Oncologic survival outcomes were analyzed using the Kaplan-Meier method. Among the 105 cases identified, 58 (55.2%) and 47 (44.8%) women underwent MIS and open radical hysterectomy, respectively. Over a median follow-up period of 62 months, women who underwent MIS and open radical hysterectomy had a 5-year overall survival rate of 87.9% and 89.4% (p = 0.845) and a 5-year disease-free survival rate of 82.5% and 86.7% (p = 0.624), respectively. For early-stage cervical cancer, patients who underwent MIS radical hysterectomy had survival outcomes that were comparable to those who underwent open surgery at our institute.


Disruption of protein synthesis as antifungal mode of action by chitosan.
The antimicrobial activity of chitosan has been acknowledged for more than 30 years and yet its mode-of-action remains ambiguous. We analyzed chemical-genetic interactions of low-molecular weight chitosan using a collection of ≈ 4600 S. cerevisiae deletion mutants and found that 31% of the 107 mutants most sensitive to chitosan had deletions of genes related primarily to functions involving protein synthesis. Disruption of protein synthesis by chitosan was substantiated by an in vivo β-galactosidase expression assay suggesting that this is a primary mode of antifungal action. Analysis of the yeast gene deletion array and secondary assays also indicate that chitosan has a minor membrane disruption effect - a leading model of chitosan antimicrobial activity.


Modeling Inflammation on Neurodevelopmental Disorders Using Pluripotent Stem Cells.
Neurodevelopmental disorders (ND) are characterized by an impairment of the nervous system during its development, with a wide variety of phenotypes based on genetic or environmental cues. There are currently several disorders grouped under ND including intellectual disabilities (ID), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorders (ASD). Although NDs can have multiple culprits with varied diagnostics, several NDs present an inflammatory component. Taking advantage of induced pluripotent stem cells (iPSC), several disorders were modeled in a dish complementing in vivo data from rodent models or clinical data. Monogenic syndromes displaying ND are more feasible to be modeled using iPSCs also due to the ability to recruit patients and clinical data available. Some of these genetic disorders are Fragile X Syndrome (FXS), Rett Syndrome (RTT), and Down Syndrome (DS). Environmental NDs can be caused by maternal immune activation (MIA), such as the infection with Zika virus during pregnancy known to cause neural damage to the fetus. Our goal in this chapter is to review the advances of using stem cell research in NDs, focusing on the role of neuroinflammation on ASD and environmental NDs studies.


Studies of neutralizing properties of antacid preparations. Part 5: Dissolution kinetics of dihydroxyaluminum aminoacetate.
The acid dissolution process of dihydroxyaluminum aminoacetate (1) has been studied by pH-stat method. The neutralization reaction was examined by monitoring the appearance of aluminum ion and aminoacetic acid in the reaction medium. The Weibull distribution function was applied to the quantitative interpretation of neutralization rate data. The mechanism of acid neutralization of 1 is discussed.


Effect of tamoxifen and kallikrein on sperm parameters including hypoosmotic swelling test in subfertile males. A retrospective analysis.
151 subfertile men presenting OAT-syndrome were investigated in respect of an improvement of sperm parameters under therapy with tamoxifen, kallikrein and combined treatment of both drugs. After therapy with 30 mg tamoxifen per day (75 patients), a significant elevation of density and swelling test was seen. Medication with 600 IE kallikrein per day (36 patients) revealed only a slight improvement of motility. Also combined treatment of 30 mg tamoxifen with 600 IE kallikrein per day produced only an elevation of motility without any significant change of other sperm parameters.


Practice Variation Research in Degenerative Lumbar Disc Surgery: A Literature Review on Design Characteristics and Outcomes.
Literature review. To describe whether practice variation studies on surgery in patients with lumbar degenerative disc disease used adequate study methodology to identify unwarranted variation, and to inform quality improvement in clinical practice. Secondary aim was to describe whether variation changed over time. Literature databases were searched up to May 4th, 2021. To define whether study design was appropriate to identify unwarranted variation, we extracted data on level of aggregation, study population, and case-mix correction. To define whether studies were appropriate to achieve quality improvement, data were extracted on outcomes, explanatory variables, description of scientific basis, and given recommendations. Spearman's rho was used to determine the association between the Extreme Quotient (EQ) and year of publication. We identified 34 articles published between 1990 and 2020. Twenty-six articles (76%) defined the diagnosis. Prior surgery cases were excluded or adjusted for in 5 articles (15%). Twenty-three articles (68%) adjusted for case-mix. Variation in outcomes was analyzed in 7 articles (21%). Fourteen articles (41%) identified explanatory variables. Twenty-six articles (76%) described the evidence on effectiveness. Recommendations for clinical practice were given in 9 articles (26%). Extreme Quotients ranged between 1-fold and 15-fold variation and did not show a significant change over time (rho= -.33, P= .09). Practice variation research on surgery in patients with degenerative disc disease showed important limitations to identify unwarranted variation and to achieve quality improvement by public reporting. Despite the availability of new evidence, we could not observe a significant decrease in variation over time.


Achieving a Representative Sample of Asian Americans in Biomedical Research Through Community-Based Approaches: Comparing Demographic Data in the All of Us Research Program With the American Community Survey.
Underrepresented persons are often not included in biomedical research. It is unknown if the general Asian American population is being represented in All of Us. The purpose of this study was to compare the Asian demographic data in the All of Us cohort with the Asian nationally representative data from the American Community Survey. Demographic characteristics and health literacy of Asians in All of Us were examined. Findings were qualitatively compared with the Asian data in the 2019 American Community Survey 1-year estimate. Compared with the national composition of Asians, less All of Us participants were born outside the United States (64% vs 79%), were younger, and had higher levels of education (76% vs 52%). Over 60% of All of Us participants reported high levels of health literacy. This study had implications for the development of strategies that ensure diverse populations are represented in biomedical research.


Mechanisms of phosphatidylserine influence on viral production: A computational model of Ebola virus matrix protein assembly.
Ebola virus (EBOV) infections continue to pose a global public health threat, with high mortality rates and sporadic outbreaks in Central and Western Africa. A quantitative understanding of the key processes driving EBOV assembly and budding could provide valuable insights to inform drug development. Here, we use a computational model to evaluate EBOV matrix assembly. Our model focuses on the assembly kinetics of VP40, the matrix protein in EBOV, and its interaction with phosphatidylserine (PS) in the host cell membrane. It has been shown that mammalian cells transfected with VP40-expressing plasmids are capable of producing virus-like particles (VLPs) that closely resemble EBOV virions. Previous studies have also shown that PS levels in the host cell membrane affects VP40 association with the plasma membrane inner leaflet and that lower membrane PS levels result in lower VLP production. Our computational findings indicate that PS may also have a direct influence on VP40 VLP assembly and budding, where a higher PS level will result in a higher VLP budding rate and filament dissociation rate. Our results further suggest that the assembly of VP40 filaments follow the nucleation-elongation theory, where initialization and oligomerization of VP40 are two distinct steps in the assembly process. Our findings advance the current understanding of VP40 VLP formation by identifying new possible mechanisms of PS influence on VP40 assembly. We propose that these mechanisms could inform treatment strategies targeting PS alone or in combination with other VP40 assembly steps.


Now you see me, now you don't: evidence that chimpanzees understand the role of the eyes in attention.
Chimpanzees appear to understand something about the attentional states of others; in the present experiment, we investigated whether they understand that the attentional state of a human is based on eye gaze. In all, 116 adult chimpanzees were offered food by an experimenter who engaged in one of the four experimental manipulations: eyes closed, eyes open, hand over eyes, and hand over mouth. The communicative behavior of the chimpanzees was observed. More visible behaviors were produced when the experimenter's eyes were visible than when the experimenter's eyes were not visible. More vocalizations were produced when the experimenter's eyes were closed than when they were open, but there were no differences in other attention getting behaviors. There was no effect of age or rearing history. The results suggest that chimpanzees use the presence of the eyes as a cue that their visual gestures will be effective.


Potential role of TrkB agonist in neuronal survival by promoting CREB/BDNF and PI3K/Akt signaling in vitro and in vivo model of 3-nitropropionic acid (3-NP)-induced neuronal death.
Striatal neurons depends on an afferent supply of brain-derived neurotrophic factor-(BDNF) that explicitly interacts with tropomyosin receptor kinase B (TrkB) receptor and performs sundry functions including synaptic plasticity, neuronal differentiation and growth. Therefore, we aimed to scrutinize an active molecule that functions identical to BDNF in activating TrkB receptor and it's downstream targets for restoring neuronal survival in Huntington disease (HD). Data from in vitro Neuro-2a cell line showed that treatment with 7,8-dihydroxyflavone (7,8-DHF), improved 3-nitropropionic acid (3-NP) induced neuronal death by stabilizing the loss of mitochondrial membrane potential and transiently increased the activity of cAMP-response element-binding protein (CREB) and BDNF via TrkB receptor activation. Consistent with in vitro findings, our in vivo results stated that treatment with 7,8-DHF at a dose of 10 mg/kg body weight ameliorated various behavior alterations caused by 3-NP intoxication. Further histopathological and electron microscopy evidences from striatal region of 3-NP mice brain treated with 7,8-DHF showed more improved neurons with intact mitochondria and less autophagic vacuoles. Protein expression analysis of both in vitro and in vivo study showed that 7,8-DHF promotes neuronal survival through upregulation and phosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt at serine-473/threonine-308). Akt phosphorylation additionally phosphorylates Bad at serine-136 and inhibits its translocation to mitochondria thereby promoting mitochondrial biogenesis, enhanced ATP production and inhibit apoptosis mediated neuronal death. These aforementioned findings help in strengthening our hypothesis and has come up with a novel neuroprotective mechanism of 7,8-DHF against 3-NP induced neuronal death.


Virulence factors of clinical isolates of Aeromonas caviae.
The mechanism of pathogenicity of 13 Aeromonas caviae strains isolated from fecal specimens of children with diarrhea was examined. Isolates possessed several virulence agents. Six of 13 isolates produced cholera-like toxin, all strains exhibited adhesive ability and secreted catecholate siderophores. Six isolates were able to grow in heat-inactivated serum. Production of hemolysins was not detected. The isolates had relatively high values of LD50 in a mouse model, which suggests that there is no linkage between pathogenicity to mice and the diarrheagenic ability of the isolates.


[Diagnosis and interventional therapy for ductal gallstones].
Different imaging modalities recently underwent considerable improvements for the visualization of ductal gallstones. The declining significance of endoscopic retrograde cholangiopancreatography (ERCP) has been accepted unanimously. This paradigm shift is mostly due to improvements in transabdominal ultrasound, the increased availability of endoscopic ultrasound, and the use of magnetic resonance cholangiopancreatography (MRCP). In particular, MRCP is limited only in visualizing very small intraductal gallstones due to spatial resolution restrictions, whereas the detection rate of larger concretions is comparable to that with ERCP and endoscopic ultrasound. Patients with biliary pancreatitis benefit greatly from noninvasive MRCP visualization, establishing it as the preferred imaging modality. Particularly if ductal gallstones requiring further intervention are highly suspected, ERCP is preferable to other imaging modalities. If that suspicion is moderate, MRCP would be the imaging modality of choice, and transabdominal ultrasound would be performed if ductal gallstones are considered improbable. In up to 90% of cases, removal can be achieved endoscopically. Using a percutaneous approach smaller concretions can be extracted directly. However, larger gallstones need to be broken down into smaller fragments. For lithotripsy, either cholangioscopically-guided laser or electrohydraulic procedures are easy and effective. In case of strictures due to biliodigestive anastomoses, additional papillary balloon dilatation may be required.


CdTe QDs@ZIF-8 composite-based recyclable ratiometric fluorescent sensor for rapid and sensitive detection of chlortetracycline.
The residue problem in animal food products caused by the abuse of chlortetracycline (CTC) is one of the food safety issues that have attracted much attention. Herein, a composite was generated by embedding CdTe quantum dots (QDs) into ZIF-8 for ratiometric fluorescent analysis of CTC. With adding CTC, the green luminescence of CTC appeared under the sensitization effect of Zn2+ in ZIF-8, but the red luminescence of CdTe QDs was reduced by the inner filtration effect of CTC. On this basis, CTC was detected by the composite with a short response time of 1 min, and the limit of detection was calculated to be 37 nM that was 17 times lower than the maximum residue limit of CTC in animal food products (626 nM). Excellent recyclability of the composite was also observed, and CTC was consecutively measured at least six times. The composite was used to determine CTC in basa fish and pure milk with satisfactory recoveries (91.0-110.0%). Portable test strips were further manufactured and the visual determination of CTC was obtained. These results convictively demonstrate that CdTe QDs@ZIF-8 composite as a recyclable ratiometric fluorescent sensor achieves the rapid and sensitive measurement of CTC residue in animal food products.


COVID-19 risk perception framework of the public: an infodemic tool for future pandemics and epidemics.
Understanding the risk perceptions of the public is central for risk communications and infodemic management during emergency and preparedness planning as people's behavior depends on how they perceive the related risks. This qualitative study aimed to identify and describe factors related to COVID-19 risk perceptions of the public in Finland and to make this information readily available to those who communicate with the public during crises. The study is part of a larger project exploring crisis narratives through a mixed-methods approach. The study was based on a dataset of over 10,000 comments on the Facebook and Twitter posts of the Finnish Institute of Health and Welfare (THL) between March-May 2021. The data were analyzed qualitatively using thematic analysis. The study identified concepts linked with the pandemic risk perception that included knowledge, perceptions, personal experiences, trust, attitudes, and cultural values. The findings resulted in a framework of risk perceptions that can be used as taxonomy and a set of key concepts and keywords in social listening to monitor risk perception during future epidemics and pandemics.


Assessing outcomes through congruence of course objectives and reflective work.
Course outcomes have been assessed by examining the congruence between statements of commitment to change (CTCs) and course objectives. Other forms of postcourse reflective exercises (for example, impact and unmet-needs statements) have not been examined for congruence with course objectives or their utility in assessing course outcomes. This study assessed the congruence of course objectives and statements of commitment to change, effects on practice, unmet-needs, and the utility of supplementing CTCs with other forms of reflective work in course evaluations. A 3-module course on Alzheimer's disease and other dementias provided end-of-course CTC statements, follow-up data, and statements of effects on practice and unmet needs. Statements were aligned to module objectives and analyzed descriptively. Of the 932 physicians who registered for 1 of the 3 modules, 404 provided CTCs, 302 provided impact statements, and 265 provided unmet-needs statements. Sixty percent of the CTCs could be assigned to an objective for their module, and between 14% and 25% of CTCs were assigned to objectives for another module. Three-quarters of CTCs were fully or partially implemented. Physicians did not have an opportunity to implement the new content in 70% of nonimplemented CTCs. Fewer impact and unmet-needs statements were congruent with course objectives than CTCs. Commitment-to-change statements had more congruence with objectives than did impact or unmet-needs statements. These latter statements, particularly those that could not be assigned to an objective, may reinforce and supplement the information provided by CTC analyses.


A meta-analysis of cleft maxillary osteotomy and distraction osteogenesis.
This meta-analysis aims to provide evidence-based data to assist surgeons to make an informed choice between distraction osteogenesis or conventional osteotomy for cleft lip and palate patients. A PUBMED search of the National Library of Medicine from 1966 to December 2003 was conducted. Keywords used in the search were 'cleft', 'distraction', 'maxilla', 'maxillary', 'advancement', 'osteotomy', and 'orthognathic surgery'. This study concluded that distraction osteogenesis tends to be preferred to conventional osteotomy for younger CLP patients with more severe deformities. In such cases it was feasible to use distraction to correct moderate to large movement of the maxilla by either complete or incomplete Le Fort I osteotomy, and a concurrent mandibular osteotomy was less frequently required. Intra-operative and post-operative complications were uncommon with either technique, and some of the traditional ischemic complications related to conventional osteotomy were replaced by infection of the oral mucosa due to the prolonged retention of the distractors. There is still no conclusive data on any differences in surgical relapse, velopharyngeal function and speech between the two techniques. Both distraction osteogenesis and conventional osteotomy can deliver a marked improvement in facial aesthetics.


Induction of cytochrome P450-1A by the equine estrogen equilenin, a new endogenous aryl hydrocarbon receptor ligand.
Equilenin is one of 10 kinds of estrogens that are found in pregnant mares' urine. It has been used extensively for estrogen replacement therapy in postmenopausal women. Typical inducers of the cytochrome P4501A1 (CYP1A1), such as TCDD, benzo(a)pyrene (B(a)P) and 3-methylcholanthrene, have a planar molecular structure in common and bind to the aryl hydrocarbon receptor (AhR). The structure of equilenin differs from classic estrogens by the presence of two additional double bonds in ring B of the steroid nucleus, and it is planar. This structural similarity of equilenin to the typical AhR agonist prompted us to investigate the capability of equilenin to induce CYP1A1 expression. Administration of equilenin to two mouse strains (C57BL and DBA) that exhibit different degrees of responsiveness to an Ah-receptor agonist and showed that equilenin was capable of dose-dependently increasing both the ethoxyresorufin O-deethylase activity and CYP1a proteins in both strains of mice. Equilenin also induced CYP1A1 mRNA in treated HepG2 cell lines and transcriptional activity in an XRE-directed luciferase reporter gene. Competitive binding studies using C57BL AhR indicated equilenin weakly displaced (3)H-B(a)P from AhR. Together, these data show that equilenin, an equine steroid hormone, served as an AhR ligand in the present study.


Consequences of CO2 acidosis for transmembrane Na+ transport and membrane current in rabbit cardiac Purkinje fibres.
1. The influence of sarcolemmal Na(+)-H+ exchange on intracellular Na+ activity (aiNa), intracellular pH (pHi) and membrane holding current (Ih) was investigated in rabbit cardiac Purkinje fibres. pHi and aiNa were measured with liquid sensor ion-selective microelectrodes. A two-microelectrode voltage clamp was used while recording pHi or aiNa.pHi was varied by alternating a nominally CO2-free HEPES buffer and a CO2-HCO3-buffer. 2. The intrinsic buffer capacity was calculated from the decrease in pHi after addition of CO2. The most accurate estimate was obtained when transmembrane pHi regulation was blocked and equalled 18.4 +/- 1.0 mequiv H+/pH unit (mean +/- S.E.M.). 3. aiNa started to rise when pHi fell below 7.0. A hyperpolarization paralleled the increase in aiNa. The magnitude of the rise in aiNa and the hyperpolarization were steeply dependent on pHi. 4. Inhibition of the Na(+)-K+ pump by K(+)-free superfusion increased aiNa. The rate of rise in aiNa was highly dependent on pHi. The rates of rise in 5% (pHi = 7.00 +/- 0.03), 7% (pHi = 6.89 +/- 0.04) and 15% CO2 (pHi = 6.74 +/- 0.02) at constant external pH (pHo) relative to the rate in HEPES solution (pHi = 7.24 +/- 0.02) were: 1.5 +/- 0.2, 2.4 +/- 0.1 and 3.1 +/- 0.2. The acid-induced rise in aiNa was abolished by 2 mM-amiloride. 5. Extracellular acidosis slowed down the recovery of pHi and depressed the rate of rise in aiNa upon intracellular acidification. When both pHi and pHo were decreased to 6.7 the acid-dependent rate increase fell to about 10% of the value found at pHo 7.4. 6. The tetrodotoxin (TTX)-sensitive Na+ current was not influenced by the change in pHi in the range 6.7-7.2. 7. Intracellular acidosis was associated with an early aiNa-independent depolarization and an inward shift in Ih. Current-voltage plots revealed that the initial inward current shift reversed at -81.5 mV on average, showed inward rectification and was largely depressed in the presence of 1 mM-Ba2+. These observations indicate a decrease in K+ conductance when pHi falls. 8. The increase in aiNa elicited a Na(+)-K+ pump-dependent outward current which could override the initial aiNa-independent current shift. At a pHo of 6.7 the initial fall in Ih remained, while the secondary outward current was largely depressed. 9. The rate of active Na+ extrusion and Na(+)-K+ pump current were suppressed by about 30% at pHi 6.7 compared to pHi 7.2.(ABSTRACT TRUNCATED AT 400 WORDS)


Neurophysiological investigation of diabetic impotence. Are sacral response studies of value?
The role of electrophysiologically elicited sacral responses in the detection of the neurological component of diabetic impotence has been evaluated in a detailed study using properly defined diagnostic criteria. The results prove that these tests are not reliable indicators of neuropathy and their relevance in the routine investigation of diabetic impotence is of questionable value.


Effects of selenium status and supplementary seleno-chemical sources on mouse T-cell mitogenesis.
Although selenium is thought to be essential for various immune responses, the excess supplementation may have an adverse effect on certain immunological functions. The present study was designed to determine the effective chemical forms of selenium and their optimal levels on T-cell mitogenesis with splenic cells from mice given a selenium-deficient diet for 8 weeks to avoid effects of cellular selenium sources. Although selenium in tissues, except for spleen and thymus, was almost depleted by feeding selenium-deficient diet, the lymphoid organs still contained low levels of selenium. Both activities of cellular glutathione peroxidase (cGPx) and thioredoxin reductase (TR) in liver and splenic cells showed a tendency to decrease by selenium deficiency. However, splenic cells were tolerant against decrease of the selenoenzyme activities, and TR was also more tolerant than cGPx. T-cell proliferation of the selenium-insufficient splenic cells induced by concanavalin A was increased by addition of Na2SeO3, Na2SeO4, Na2Se, seleno-DL-cystine, seleno-L-methionine and selenocystamine. Their promoting action was observed at levels lower than 0.1 micromol/L and was completely suppressed at the highest concentration (1 micromol/L), except for selenocystamine. Na2SeO3 was one of the efficient selenocompounds for the mitogenesis, which was concomitant with the significant induction of cGPx and TR. However, recovery of cGPx activity in the selenium-insufficient cells by supplementary Na2SeO3 was only partial,while TR activity was readily recovered from selenium deficiency. These results therefore indicate that only low levels of selenium is essential for T-cell mitogenesis even in selenium-insufficient splenic cells, and TR, which is readily recovered by Na2SeO3, may be the critical enzyme.