Spatial variation in the community structure and response of benthic macroinvertebrates to multiple environmental factors in mountain rivers.
Exploring the response between benthic community changes and environmental variables has significance for restoring the health of river ecosystems. However, little is known of the impact on communities of interactions between multiple environmental factors, and frequent changes in the flow of mountain rivers are different from those in the flow of plain river networks, which also impact differently the benthic community. Thus, there is a need for research on the response of benthic communities to environmental changes in mountain rivers under flow regulation. In this study, we collected samples from the Jiangshan River in the dry season (November 2021) and the wet season (July 2022) to investigate the aquatic ecology and benthic macroinvertebrate communities in the watershed. Multi-dimension analyses were used to analyze the spatial variation in the community structure and response of benthic macroinvertebrates to multiple environmental factors. In addition, the explanatory power of the interaction between multiple factors on the spatial variation of communities, and the distribution characteristics of benthic community and their causes were investigated. The results showed that herbivores are the most abundant forms in the benthic community of mountain rivers. The structure of benthic community in Jiangshan River was significantly affected by water quality and substrate, whereas the overall community structure was affected by river flow conditions. Furthermore, nitrite nitrogen and ammonium nitrogen were the key environmental factors impacting the spatial heterogeneity of communities during the dry and wet season, respectively. Meanwhile, the interaction between these environmental factors showed a synergistic effect, enhancing the influence of these environmental factors on community structure. Thus, controlling urban and agricultural pollution and releasing ecological flow would be effective strategies to improve benthic biodiversity. Our study showed that using the interaction of environmental factors was a suitable way to evaluate the association between environmental variables and variation in benthic macroinvertebrate community structure in river ecosystems.


Potential Inhibitors of Galactofuranosyltransferase 2 (GlfT2): Molecular Docking, 3D-QSAR, and In Silico ADMETox Studies.
A strategy in the discovery of anti-tuberculosis (anti-TB) drug involves targeting the enzymes involved in the biosynthesis of Mycobacterium tuberculosis' (Mtb) cell wall. One of these enzymes is Galactofuranosyltransferase 2 (GlfT2) that catalyzes the elongation of the galactan chain of Mtb cell wall. Studies targeting GlfT2 have so far produced compounds showing minimal inhibitory activity. With the current challenge of designing potential GlfT2 inhibitors with high inhibition activity, computational methods such as molecular docking, receptor-ligand mapping, molecular dynamics, and Three-Dimensional-Quantitative Structure-Activity Relationship (3D-QSAR) were utilized to deduce the interactions of the reported compounds with the target enzyme and enabling the design of more potent GlfT2 inhibitors. Molecular docking studies showed that the synthesized compounds have binding energy values between -3.00 to -6.00 kcal mol-1. Two compounds, #27 and #31, have registered binding energy values of -8.32 ± 0.01, and -8.08 ± 0.01 kcal mol-1, respectively. These compounds were synthesized as UDP-Galactopyranose mutase (UGM) inhibitors and could possibly inhibit GlfT2. Interestingly, the analogs of the known disaccharide substrate, compounds #1-4, have binding energy range of -10.00 to -19.00 kcal mol-1. The synthesized and newly designed compounds were subjected to 3D-QSAR to further design compounds with effective interaction within the active site. Results showed improved binding energy from -6.00 to -8.00 kcal mol-1. A significant increase on the binding affinity was observed when modifying the aglycon part instead of the sugar moiety. Furthermore, these top hit compounds were subjected to in silico ADMETox evaluation. Compounds #31, #70, #71, #72, and #73 were found to pass the ADME evaluation and throughout the screening, only compound #31 passed the predicted toxicity evaluation. This work could pave the way in the design and synthesis of GlfT2 inhibitors through computer-aided drug design and can be used as an initial approach in identifying potential novel GlfT2 inhibitors with promising activity and low toxicity.


Evolution of the hyperimmunoglobulin E and recurrent infection (HIE, JOB's) syndrome in a young girl.
The hyperimmunoglobulin E and recurrent infection syndrome is difficult to diagnose in children with markedly elevated IgE and recurrent superficial Staphylococcus aureus infections who have not presented with a severe infection. The patient, the child of a woman with HIE, had elevated cord blood IgE. In early infancy, she had cutaneous colonization with S. aureus followed by frank impetiginous lesions. Anti-S. aureus IgE was easily detected with a highly specific ELISA assay at 2 years of age (2 years before her presentation with a S. aureus subcutaneous abscess). Thus, the measurement of anti-S. aureus IgE by this technique may be a useful laboratory test for the diagnosis of HIE before the appearance of a severe infection.


FDG-PET in radiotherapy treatment planning of advanced head and neck cancer--a prospective clinical analysis.
A prospective clinical analysis was carried out to assess the diagnostic and therapeutic impact of fluorodeoxyglucose positron emission tomography (FDG-PET) on planning radiotherapy in patients with advanced head and neck cancer in AJCC Stages III/IV. From July 1999 to May 2004 FDG-PET was performed in 49 patients prior to radiotherapy for exclusion of systemic disease, synchronous second or unknown primary tumors. 45/49 (91.9%) FDG-PET findings could be confirmed in comparison with conventional imaging and the clinical follow up of 9.5 months. 21/49 FDG-PET (42.8%) yielded new diagnostic information with therapeutic implications in 20/49 (40.8%) cases. The therapy strategy was changed in 14/49 patients, minor modifications in the portal design occurred in 6/49 patients. 9/49 (18.3%) FDG-PET supported a curative strategy, 11/49 (22.4%) a palliative one. FDG-PET is a useful and important diagnostic tool mainly for exclusion of systemic disease in advanced head and neck cancer, thus influencing radiotherapy in 20/49 (40.8%) of patients investigated in our study.


Highly multiplexed quantitation of gene expression on single cells.
Highly multiplexed, single-cell technologies reveal important heterogeneity within cell populations. Recently, technologies to simultaneously measure expression of 96 (or more) genes from a single cell have been developed for immunologic monitoring. Here, we report a rigorous, optimized, quantitative methodology for using this technology. Specifically: we describe a unique primer/probe qualification method necessary for quantitative results; we show that primers do not compete in highly multiplexed amplifications; we define the limit of detection for this assay as a single mRNA transcript; and, we show that the technical reproducibility of the system is very high. We illustrate two disparate applications of the platform: a "bulk" approach that measures expression patterns from 100 cells at a time in high throughput to define gene signatures, and a single-cell approach to define the coordinate expression patterns of multiple genes and reveal unique subsets of cells.


Tonsillar application of formalin-killed cells of Streptococcus sobrinus reduces experimental dental caries in rabbits.
Living Streptococcus sobrinus cells were orally inoculated into nonimmune rabbits and rabbits immunized with formalin-killed cells of S. sobrinus through tonsillar application to examine the anticaries potential of this method of immunization. The living S. sobrinus cell numbers and the caries areas in the rabbits immunized by tonsillar application decreased to a level one-fifth of that in nonimmune rabbits.


Generation of a human induced pluripotent stem cell line harboring the infant leukemia-associated fusion gene, KMT2A-AFF1 (IMSUTi002-A-2).
KMT2A-AFF1 (MLL-AF4), formed by chromosomal translocation t(4;11), is observed specifically in infant pro-B acute lymphoblastic leukemia, and the main driver of leukemogenesis. In this study, a human induced pluripotent stem cell (hiPSC) line harboring KMT2A-AFF1 (IMSUTi002-A-2), which has the ability to simultaneously induce the doxycycline-inducible expression of KMT2A-AFF1 and EGFP, was established. This hiPSC can be a powerful model for understanding infant leukemia and risk assessment of leukemogenesis.


Phenotypic presentation of Mendelian disease across the diagnostic trajectory in electronic health records.
To investigate the phenotypic presentation of Mendelian disease across the diagnostic trajectory in the electronic health record (EHR). We applied a conceptual model to delineate the diagnostic trajectory of Mendelian disease to the EHRs of patients affected by 1 of 9 Mendelian diseases. We assessed data availability and phenotype ascertainment across the diagnostic trajectory using phenotype risk scores and validated our findings via chart review of patients with hereditary connective tissue disorders. We identified 896 individuals with genetically confirmed diagnoses, 216 (24%) of whom had fully ascertained diagnostic trajectories. Phenotype risk scores increased following clinical suspicion and diagnosis (P < 1 × 10-4, Wilcoxon rank sum test). We found that of all International Classification of Disease-based phenotypes in the EHR, 66% were recorded after clinical suspicion, and manual chart review yielded consistent results. Using a novel conceptual model to study the diagnostic trajectory of genetic disease in the EHR, we demonstrated that phenotype ascertainment is, in large part, driven by the clinical examinations and studies prompted by clinical suspicion of a genetic disease, a process we term diagnostic convergence. Algorithms designed to detect undiagnosed genetic disease should consider censoring EHR data at the first date of clinical suspicion to avoid data leakage.


Relapsing acute non-lymphatic leukemia with changing phenotypes.
Morphological and cytochemical findings in a case of acute myeloid leukemia (AML) with 3 relapses are described. The disease began as a subtype M4 with atypical eosinophils according to the French-American-British (FAB)-classification. At the time of the first relapse, the phenotype had converted into an M2-subtype, while the second relapse presented the picture of an M1-type of acute myeloid leukemia with non-granulated peroxidase-positive blasts. When the third relapse occurred, the diagnosis was again an M4-type of acute myeloid leukemia. The observed changes of the phenotype can be interpreted as an expression of tumor cell heterogeneity, even though the observed emergence of new leukemic clones would be attributed entirely or in part to effects of the applied cytostatic drugs, because tumor cell heterogeneity concerns also the response to therapy, which may result in a growth advantage for certain leukemic subpopulations. In so far, AML behaves like all other human malignant neoplasias. In addition, morphological changes in leukemias such as are reported here, have been observed long before the introduction of cytostatic drugs. Also, the validity of the FAB-classification is discussed in the light of the presented observation. It is concluded that the FAB-classification is not a classification in a strict sense, but merely a crude and simplistic list of subtypes of acute myeloproliferative diseases that is difficult to reproduce and that disregards major aspects of this group of diseases, for instance tumor cell heterogeneity.


Expression of Concern: Fisetin rescues retinal functions by suppressing inflammatory response in a DBA/2J mouse model of glaucoma.
The Editor-in-Chief of Documenta Ophthalmologica is publishing an editorial expression of concern for the manuscript "Fisetin rescues retinal functions by suppressing inflammatory response in a DBA/2J mouse model of glaucoma" by Li et al. (2019) [1].


Evidence of deep percutaneous penetration associated with anti-inflammatory activity of topically applied Helicteres gardneriana extract: a photoacoustic spectroscopy study.
To apply the photoacoustic spectroscopy technique to investigate the penetration rate of topically applied Helicteres gardneriana extract used as anti-inflammatory agent. Experiments were performed ex vivo in a well-controlled group of mice. The crude extract was obtained from leaves of the plant Helicteres gardneriana. Croton oil was applied into the ventral surface of the mouse's right and left auricles in order to induce an inflammatory response. The left auricle was treated with crude extract, while the right one served as the control. After 6 h, the auricles were sectioned for measurements of edema intensity, myeloperoxidase activity and the formulation penetration rate. Croton oil induced inflammatory response in both auricles. The application of Helicteres gardneriana extract reduced significantly the edema of the auricle and inhibited the activity of the myeloperoxidase enzyme. The photoacoustic data showed that the propagation of the formulation was efficient to reach the deep region of the auricle, crossing the cartilage. The strong anti-inflammatory effect was associated with the observed deep penetration of the formulation. This pre-clinical study showed the anti-inflammatory effect of Helicteres gardneriana extract. The photoacoustic technique was useful to demonstrate that this anti-inflammatory activity was associated with deep percutaneous penetration.


Changes in the taste and textural attributes of apples in response to climate change.
The effects of climate change on the taste and textural attributes of foods remain largely unknown, despite much public interest. On the basis of 30-40 years of records, we provide evidence that the taste and textural attributes of apples have changed as a result of recent global warming. Decreases in both acid concentration, fruit firmness and watercore development were observed regardless of the maturity index used for harvest date (e.g., calendar date, number of days after full bloom, peel colour and starch concentration), whereas in some cases the soluble-solids concentration increased; all such changes may have resulted from earlier blooming and higher temperatures during the maturation period. These results suggest that the qualities of apples in the market are undergoing long-term changes.


Isolation and identification of strains of Bacteroides fragilis group from the digestive tract of Callithrix penicillata marmosets.
Thirty-five strains of the Bacteroides fragilis group were isolated from oral and intestinal samples from 5 wild caught, captive Callithrix penicillata. Nine oral strains of Bacteroides fragilis (7) and Bacteroides distasonis (2), and 26 intestinal strains of Bacteroides fragilis (14) and Bacteroides distasonis (12) were identified.


Assessment of the ability of the bioelectric effect to eliminate mixed-species biofilms.
Microbes have been able to persist in water distribution systems through the development of multicellular communities known as biofilms. This study evaluated the usefulness of the bioelectric effect for the elimination of water distribution system biofilms from annular reactors. The bioelectric effect did not have any bactericidal action either alone or when coupled with free chlorine.


Practice styles and preferences of ASCRS members--2002 survey.
A survey of the practice styles and preferences of members of the American Society of Cataract and Refractive Surgery (ASCRS) with a United States ZIP code was performed in August 2002. Approximately 18% (1056) of the 5816 questionnaires mailed were returned. Three profile questions were used to cross-tabulate: age of the respondent, geographic location, and volume of cataract surgery per month. The refractive surgical questions were cross-tabulated for the volume of laser in situ keratomileusis (LASIK). Data in this survey were compared with those in previous surveys of ASCRS members.


Inactivation of androgens by UDP-glucuronosyltransferases in the human prostate.
In the human prostate, dihydrotestosterone (DHT) -- the natural androgen having the highest affinity for the androgen receptor -- is not released directly into the systemic circulation from peripheral target tissues but it is rather converted in situ into two metabolites which have a low affinity for the androgen receptor: androsterone (ADT) and androstane-3alpha,17beta-diol (3alpha-DIOL). Several clinical observations indicate that these two androgen metabolites are further inactivated in the prostate by glucuronidation. In the human, the family of UDP-glucuronosyltransferase (UGT) enzymes comprises 18 members in three subfamilies: UGT1A, UGT2A and UGT2B. Identification of the substrates for each member has revealed that three UGT2B enzymes are mainly responsible for DHT, ADT and 3alpha-DIOL glucuronidation: UGT2B7, UGT2B15 and UGT2B17. Tissue distribution and cellular localization of UGT2B transcripts and proteins clearly indicate that only UGT2B15 and UGT2B17 are expressed in the prostate. Using the human prostate carcinoma LNCaP cell line, it was shown that UGT2B expression and activity are negatively regulated by several factors, including androgens. On the other hand, inhibition of UGT2B115/17 expression by small interfering RNA (siRNA) resulted in an induced response to DHT of androgen-receptor target genes such as PSA, KLK4, NKX3.1, TMPRSS2, SLC16A6 and VEGF. It is suggested that the conjugating activity of UGT enzymes in androgen target tissues is a mechanism for modulating the action of steroids and/or protecting the tissues from deleterious high concentrations of androgens.


Efficient transfer of chromosome-based DNA constructs into mammalian cells.
Artificial chromosomes, engineered minichromosomes and other chromosome-based DNA constructs are promising new vectors for use in gene therapy, protein production and transgenics. However, a major drawback in the application of chromosome-based DNA is the lack of a suitable and convenient procedure for large-scale cellular introduction, which is particularly frustrated by their size (1 by 2 microm). Here we present a method to transfer Artificial Chromosome Expression systems (ACEs) into mammalian cells, which relies on a combined approach of using cationic amphiphiles and high frequency ultrasound. Thus, when cells were preincubated with liposomes consisting of the cationic lipid SAINT-2 and the phospholipid dioleoylphosphatidylethanolamine (molar ratio 1:1), followed by ultrasound, ACEs could be introduced into mammalian cells, which resulted in the expression of ACEs-harbored reporter genes, such as Green Fluorescent Protein. Depending on cell type, transfection efficiencies ranged from 12% to 53%. Interestingly, no detectable delivery occurred when cells were treated alone with either ultrasound or liposomes. Evidence is provided, based on cellular entry of differently sized beads and trypan-blue permeation, which supports a mechanism in which integration of the lipids creates unstable membrane domains, which are particularly prone to ultrasound-induced pore formation. Time- and temperature-dependent experiments indicate that these pores display a transient stability. Hence, following ultrasound, the pores disappear as a function of time as suggested by a time-window for ACEs entry, and trypan blue exclusion, 80% of the cells becoming stained immediately following ultrasound, dropping to approximately 20% after 30 min. Co-expression of different genes in conjunction with fluorescence in situ hybridization (FISH) analysis indicates that the current procedure provides a means to introduce functionally active artificial chromosomes into eukaryotic cells.


Computerized model for accurate determination of ethylene oxide diffusion in sterilized medical supplies.
A computerized numerical model is described which is shown to be more generally applicable than analytical methods in the determination of ethylene oxide diffusion in polymeric material. Diffusion coefficients of ethylene oxide in poly(vinyl chloride) were determined from the rates of desorption both for conventional aeration with warm air and for microwave-assisted desorption and found to be concentration dependent. The model takes account of device geometry and concentration dependence of diffusion coefficient and its predictions are in agreement with experimental results for desorption. The model is also used to simulate the whole sterilization process with a view to a planned diminution of EO residuals after sterilization.


Parenteral nutrition support in major abdominal trauma patients.
32 out of 111 patients with major abdominal trauma were studied to evaluate the effects of total parenteral nutrition (TPN). There were 24 men and 8 women with average age of 31 years. 25 cases were recorded as blunt trauma. The others had penetrating wounds. An Abdominal Trauma Index (ATI) was used to score the injury severity. 68% (22 32 ) of the patients had a score of more than 15, and 25% (8 32 ) had a score over 25. TPN was carried out in 11 patients with complicated injuries of the pancreas and duodenum, in 15 cases with small bowel fistula secondary to extended intestinal trauma, and in 6 patients with severe intraabdominal abscesses after injury. The TPN mixture contained 32-42 kcal/kg/day of nonprotein energy and 0.21-0.30 g/kg/day of nitrogen. The average period of TPN support was 26 days. No TPN-related complication developed except 2 cases of catheter-related sepsis. The results demonstrated no significant change in body weight during TPN support. Weekly cumulative nitrogen balances were increased significantly after the use of TPN (from 15.5 g/week at the first week to 48.2 g/week at the fourth week, p < 0.01). There were increases in serum albumin, prealbumin, fibronectin and transferrin following TPN support (from 30.6 g/L, 142.8 mg/L, 103.3 mg/L and 1.2 g/L at day 0 to 35.7 g/L, p < 0.01, 256.3 mg/L, p < 0.01, 184.5 mg/L, p < 0.01, and 1.9 g/L, p < 0.05, at day 21 respectively). Blood sugar, cholesterol and triglyceride remained normal. In 4 patients with duodenal fistula and 6 cases with small bowel fistula (n = 15), the fistulae closed spontaneously. There were no deaths during TPN. We conclude that total parenteral nutrition is of value in the treatment of severe abdominal traumatic patients.


Hair as a retrospective calendar of cortisol production-Increased cortisol incorporation into hair in the third trimester of pregnancy.
Hair has long been used in toxicology, forensic science, doping control and other fields as a biological specimen for the detection of environmental agents, drugs, or toxins. Most recent evidence suggests that also hormones are incorporated and trapped inside the growing hair. This has led to the hypothesis that cortisol measurement of distinct hair segments could provide a retrospective calendar of cortisol production for the individual. In this first proof-of-concept study in humans, we analyzed cortisol in hair donated by mothers with a neonate child (n-Mothers; N=103), mothers with toddlers 3-9 months of age (t-Mothers; N=19), and control women (N=20). We cut hair strands from each women into at least three 3-cm segments, which, based on an average hair growth rate of 1cm per month, would represent hair grown over the past three, six, and nine months, respectively. Since in the third trimester of pregnancy there is a well-documented increased production of cortisol, we expected to see elevated levels of cortisol in the most proximal hair segment of women who had just given birth to a child (n-Mothers) compared with the control women. Likewise, we expected to see elevated levels in the second, third, or fourth segment of mothers of 3-month olds, 6-months olds, and 9-months olds, respectively. These hair segments, cut at 4-12 cm from the scalp, would represent hair grown throughout the third trimester of pregnancy. Results showed that there was a strong monotonic decline in cortisol concentration from the segment closest to the scalp to the most distal hair segment (p<0.0001). Cortisol levels decreased by 30-40% from one segment to the next for the most recent four hair segments. Segments from hair older than one year had similarly, low levels of cortisol. Comparisons of cortisol levels in hair between n-Mothers and control women yielded the expected results: cortisol levels in the first 3-cm hair segment (i.e., closest to the scalp) of n-Mothers were two-fold higher than in controls (p<0.0001), probably reflecting increased cortisol levels throughout the third trimester of pregnancy. No differences in cortisol content were apparent for the second or third 3-cm segments in n-Mothers (p>0.2). When hair from mothers with 6-9 months old toddlers was analyzed, the hair segment representing the third trimester period contained the same amount of cortisol as the hair grown more recently in mothers with 3-4 months old toddlers only. Age of the women, hair curvature, hair color, and frequency of hair washes per week were unrelated to cortisol levels. We conclude that cortisol measured in human hair can be a valid reflection of increased cortisol production for a period of up to six months. Due to a rapid decline of cortisol levels in human adult hair, a retrospective calendar of cortisol exposure may be limited to the past six months.


Selection of DNA Aptamer That Blocks the Fibrillogenesis of a Proteolytic Amyloidogenic Fragment of β2 m.
Dialysis-related amyloidosis (DRA) is a severe complication of hemodialysis that results in progressive destruction of bones and joints. Elevated concentrations of the β2 -microglobulin (β2 m) level in the serum of subjects on hemodialysis promote the formation of amyloid fibrils in osteoarticular tissues. β2 m lacking the N-terminal six residues of the mature protein (ΔN6β2 m) constitutes 25-30% of β2 m in ex vivo DRA amyloid. Unlike full-length wild-type β2 m, ΔN6β2 m forms amyloid fibrils at neutral pH in vitro. However, the role of ΔN6β2 m in DRA is, at present, poorly understood. In the present study, we screened novel phosphorothioate-modified aptamers directed against ΔN6β2 m using combinatorial chemistry in vitro. We identified 11 ΔN6β2 m aptamers; among the identified aptamers, clone #2, #8, and #10 aptamers had higher binding affinity to ΔN6β2 m than the others. Biolayer interferometry analysis revealed that KD values of clone #2, #8, and #10 aptamers were 56, 23, and 44 nM, respectively. Furthermore, the clone #8 aptamer inhibited fibril formation in a dose-dependent manner, as assessed by Thioflavin T fluorescence assay. Fibrils formed from ΔN6β2 m bind to Congo red, displaying changes in the absorbance spectrum of the dye characteristic of binding to amyloid fibrils, which was completely blocked by treatment with clone #8 aptamer. These results suggest the potential of ΔN6β2 m aptamers as tools for elucidating co-assembly mechanisms in amyloid formation.


[The effect of biostimulants and fungicides on the growth parameters of natural associations of soil microorganisms].
Biostimulants ivin and emistym take positive effect on the growth characteristics of natural association of soil microorganisms: they increase the specific growth rate, the number of generations, decrease the lag-phase and duration of redoubling the number of microorganisms. Presence of fungicides in the medium inhibits the growth of microorganisms. Under combined use of biostimulants and fungicides one cannot reveal the negative effect of fungicides on the natural associations of microorganisms, however the stimulating action of growth-regulating substances decreases.


Characteristics, mechanism, and management of pain in atopic dermatitis: A literature review.
Atopic dermatitis (AD) is a chronic, pruritic, immune-mediated inflammatory disease. Developments in basic science and clinical research have increased our understanding of AD. Although pain as a symptom of AD is underemphasized in previous studies, multiple researchers address pain as a frequent burden of AD. However, the exact role of pain in AD is not fully understood. Our review aimed to summarize the current evidence focusing on characteristics, mechanism, and management of pain in AD. We conducted a thorough literature review in the PubMed database to figure out different aspects discussing pain in AD, including pain symptoms, burden, the relationship between pain and itch, mechanism, and pain management in AD. AD patients affected by skin pain vary from 42.7%-92.2% with remarkable intensity and heavy burden. Skin pain and itch interacted both in symptoms and mechanisms. Atopic skin with the impaired barrier, neurogenic inflammation mediators, peripheral and central sensitization of pain may possibly explain pain mechanism in AD. Future research is needed to clarify the commonality and disparity of pain and itch in AD in order to seek efficacious medications and treatment.


Evaluation of Sensory Loss Obtained by Circum-Psoas Blocks in Patients Undergoing Total Hip Replacement: A Descriptive Pilot Study.
The transversalis fascia (TF) encases the quadratus lumborum and psoas major (PM) muscles, respectively, after they split caudalward approximately at the level of the iliac crest. The branches of the lumbar plexus variably exit medially and laterally from the TF-encased PM muscle. We hypothesized that the local anesthetic (LA) injections around the anterolateral edge of PM at the supra-iliac level and into the retro-psoas compartment at the L5/S1 level, which termed as the circum-psoas blocks, could block the lumbar plexus branches. Therefore, here we evaluated the sensory loss caused by the circum-psoas blocks. A total of 26 patients scheduled for total hip replacement were recruited for the study. After anesthesia induction, the ultrasound-guided circum-psoas blocks were performed in the lateral position with the affected side upward, in which the 0.3% ropivacaine was injected posterior to the TF and around the anterolateral edge of PM muscle at the supra-iliac level (25 mL), and into the retro-psoas compartment at the L5/S1 level (20 mL). The sensory block dermatomes and the muscle strength of quadriceps femoris were evaluated at 2 h or 6 h after surgery, respectively. The postoperative pain scores and opioid consumption were recorded. The median (interquartile range) highest and lowest dermatomes of sensory block were T10 (T9-T10) and S2 (S2-S2), respectively. The muscle strength of the quadriceps femoris evaluated at 6 h post-surgery was 4 (4-5) points. Total postoperative equivalent milligrams of oral morphine consumption in the first 24 h were 11.3 ± 3.6 mg. The circum-psoas blocks may be a promising approach for postoperative analgesia of hip surgery, since they provide a dermatomal coverage of sensory block from T8-11 to S1-3. Chinese Clinical Trial Registry, clinical trial number ChiCTR2100051247.


The yield of subsequent radiographs during nonoperative treatment of radial head and neck fractures.
After diagnosis of an isolated radial head or neck fracture and selection of nonoperative treatment, the value of subsequent radiographs is uncertain. This study tested the null hypothesis that there are no patient, surgeon, or injury factors associated with alteration in patient management based on subsequent radiographs. Secondarily, we tested the null hypothesis that the use of subsequent radiographs is not associated with patient, surgeon, and fracture characteristics. We identified 415 adult patients with nonoperative treatment for isolated Broberg and Morrey modified Mason type 1 or 2 fractures at a large urban hospital system during years 2013 and 2014. Patient demographics, fracture characteristics, provider characteristics, and treatment details were obtained from a hospital database. Bivariate analysis and multivariable logistic regression modeling were performed. One of 255 patients with 262 fractures that had subsequent radiographs (0.4%) was offered surgery but declined. In multivariable analysis, displaced fractures were more likely to have subsequent radiographs, but surgeon-to-surgeon variation was a far more influential factor. Radiographs subsequent to diagnosis do not alter treatment of radial head fractures with no associated ligament injuries or fractures. The substantial surgeon-to-surgeon variation in the use of subsequent radiographs suggests that this may be a good focus for quality improvement initiatives.


Investigation of the Role of Myocyte Orientations in Cardiac Arrhythmia Using Image-Based Models.
Cardiac electrical excitation-propagation is influenced by myocyte orientations (cellular organization). Quantitatively understanding this relationship presents a significant research challenge, especially during arrhythmias in which excitation patterns become complex. Tissue-scale simulations of cardiac electrophysiology, incorporating both dynamic action potential behavior and image-based myocardial architecture, provide an approach to investigate three-dimensional (3D) propagation of excitation waves in the heart. In this study, we aimed to assess the importance of natural variation in myocyte orientations on cardiac arrhythmogenesis using 3D tissue electrophysiology simulations. Three anatomical models (i.e., describing myocyte orientations) of healthy rat ventricles-obtained using diffusion tensor imaging at 100 μm resolution-were registered to a single biventricular geometry (i.e., a single cardiac shape), in which the myocyte orientations could be represented by each of the diffusion tensor imaging data sets or by an idealized rule-based description. The Fenton-Karma cellular excitation model was modified to reproduce rat ventricular action potential duration restitution to create reaction-diffusion cardiac electrophysiology models. Over 250 3D simulations were performed to investigate the effects of myocyte orientations on the following: 1) ventricular activation, 2) location-dependent arrhythmia induction via rapid pacing, and 3) dynamics of re-entry averaged over multiple episodes. It was shown that 1) myocyte orientation differences manifested themselves in local activation times, but the influence on total activation time was small; 2) differences in myocyte orientations could critically affect the inducibility and persistence of arrhythmias for specific stimulus-location/cycle-length combinations; and 3) myocyte orientations alone could be an important determinant of scroll wave break, although no significant differences were observed in averaged arrhythmia dynamics between the four myocyte orientation scenarios considered. Our results show that myocyte orientations are an important determinant of arrhythmia inducibility, persistence, and scroll wave break. These findings suggest that where specificity is desired (for example, when predicting location-dependent, patient-specific arrhythmia inducibility), subject-specific myocyte orientations may be important.


Long non-coding RNA Loc554202 induces apoptosis in colorectal cancer cells via the caspase cleavage cascades.
Aberrant expression of long noncoding RNAs (lncRNAs) has frequently been reported in cancer studies, including those of colorectal cancer (CRC). Increasing evidence suggests that lncRNAs are significantly correlated with the pathogenesis, development and metastasis of cancer. Loc554202 is a 2166-bp transcript on human chromosome 9p21.3, the expression of which is dysregulated in breast and lung cancer cells. However, its role in CRC remains under investigation. Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to assess the relative expression of Loc554202 in CRC cell lines and tissues. Gain and/or loss of function approaches were used to investigate the potential functional roles in cell proliferation and apoptosis in vitro and in vivo. qRT-PCR, western-blotting and immunohistochemistry were used to evaluate the mRNA and protein expression of apoptosis-related factors. Loc554202 was significantly downregulated in cancerous tissues and CRC cell lines compared with adjacent normal tissue and a normal human intestinal epithelial cell line. Low Loc554202 expression was closely associated with advanced pathologic stage and a larger tumor size. The overexpression of Loc554202 decreased the cell proliferation and induced apoptosis in vitro and hindered tumorigenesis in vivo. Loc554202 regulated cell apoptosis partly through the activation of specific caspase cleavage cascades. Our results suggest that Loc554202 may play an important role in the progression of CRC and could be a candidate prognostic biomarker or a target for new cancer therapies.


PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in in vivo fertilization.
PTX3 is a prototypic long pentraxin that plays a non-redundant role in innate immunity against selected pathogens and in female fertility. Here, we report that the infertility of Ptx3(-/-) mice is associated with severe abnormalities of the cumulus oophorus and failure of in vivo, but not in vitro, oocyte fertilization. PTX3 is produced by mouse cumulus cells during cumulus expansion and localizes in the matrix. PTX3 is expressed in the human cumulus oophorus as well. Cumuli from Ptx3(-/-) mice synthesize normal amounts of hyaluronan (HA), but are unable to organize it in a stable matrix. Exogenous PTX3 restores a normal cumulus phenotype. Incorporation in the matrix of inter-alpha-trypsin inhibitor is normal in Ptx3(-/-) cumuli. PTX3 does not interact directly with HA, but it binds the cumulus matrix hyaladherin tumor necrosis factor alpha-induced protein 6 (TNFAIP6, also known as TSG6) and thereby may form multimolecular complexes that can cross-link HA chains. Thus, PTX3 is a structural constituent of the cumulus oophorus extracellular matrix essential for female fertility.


Attachment orientations and loss adjustment among bereaved spouses.
Stressful life events such as losing a spouse can enhance inflammation. Responses to loss may depend, in part, on individual differences in attachment anxiety and avoidance. An individual's attachment orientation (i.e., an individual's levels of attachment anxiety and avoidance) reflects how an individual relates to others-- specifically, whether they feel their trusted others will reliably be there for them, and whether they feel comfortable opening up to and depending on their relationship partners. This study investigated the association between attachment orientations and poor loss adjustment in recently bereaved individuals (N = 100). Poor loss adjustment was operationalized as greater levels of inflammation and grief symptoms, as well as poorer self-reported mental and physical health. Attachment anxiety was associated with increased stimulated monocyte IL-6 and CCL4 production, but not TNFα. Likewise, attachment anxiety was associated with greater grief symptoms as well as poorer mental and physical health. In contrast, attachment avoidance was not associated with inflammation; it was, however, associated with less grief symptoms as well as better self-reported mental and physical health. Our findings provide evidence that attachment orientations may be associated with loss adjustment and adverse health outcomes following the recent loss of a spouse.


Adolescent Reproductive Health Outcomes Among Mexican-Origin Women on Both Sides of the U.S.-Mexico Border.
Much reproductive health research on the Latina population overlooks heterogeneity by national origin, nativity, and age and also ignores how U.S.-based populations differ from those in "sending" nations. The purpose of this study is to describe a history of adolescent birth, age at first sex, and contraceptive use at first sex in the Mexican-origin population in both the United States and Mexico. We developed a binational dataset merging two comparable nationally representative cross-sectional surveys in the United States and Mexico and used covariate balancing propensity scores to balance the age structure of our four samples: U.S.-born Latinas of Mexican origin, foreign-born Latinas of Mexican origin, U.S.-born non-Latina Whites, and Mexican women residing in Mexico. We used a negative binomial regression and calculated the predicted probability of experiencing at least one adolescent birth for each ethnicity/nativity group, stratified by 5-year age group. We also described age and contraceptive use at first sex. Foreign-born Latinas of Mexican origin and Mexicans in Mexico had similar adjusted probabilities of reporting an adolescent birth (30.1% and 29.9%, respectively), which were higher than those of Mexican-Americans (26.2%) and U.S.-born non-Latina Whites (11.6%). History of an adolescent birth is declining across all four groups among younger ages. Differences do not appear to be driven by the timing of first sex but by contraceptive use, which is increasing among younger age groups. Access to and use of effective contraception rather than timing of initiation of sexual activity is a key determinant of U.S. Latina and Mexican adolescent births.


Occurrence of specific secretory immunoglobulin A in bile after inoculation of Giardia lamblia trophozoites into rat duodenum.
We studied the appearance of specific secretory immunoglobulin A (IgA) antibody in bile after inoculation of live Giardia lamblia trophozoites into rat intestine. Serial bile specimens collected before and after inoculation of trophozoites were assayed for IgA antibodies by indirect immunofluorescence. Secretory IgA antibodies to Giardia lamblia were first detected in bile at 3 days after inoculation, remained elevated through 12 days, and then returned to control levels. Positive immunofluorescence of trophozoites for IgA was observed at bile titers of 1:80 to 1:160, whereas control biles were usually negative at dilutions of 1:10 or less. Scanning electron microscopic examination of Giardia in conjunction with immunocytochemistry revealed IgA antibodies bound to the flagella and surfaces of the trophozoites including the adhesive disk. These data demonstrate the occurrence of a secretory IgA immune response directed against surface antigens of Giardia lamblia trophozoites in the rat.


Genome Sequence of a Mycoplasma meleagridis Field Strain.
Mycoplasma meleagridis is a major cause of disease and economic loss in turkeys. Here, we report the genome sequence of an M. meleagridis field strain, which enlarges the knowledge about this bacterium and helps the identification of possible coding sequences for drug resistance genes and specific antigens.


Cost-Effectiveness of iGlarLixi in People with Type 2 Diabetes Mellitus Suboptimally Controlled on Basal Insulin Plus Metformin in the UK.
A cost-effectiveness analysis was conducted comparing a fixed-ratio combination (FRC) of insulin glargine 100 units/mL plus lixisenatide (iGlarLixi) versus the FRC of insulin degludec plus liraglutide (iDegLira) and the free-combination comparators insulin glargine plus dulaglutide (iGlar plus Dula) and basal insulin plus liraglutide (BI plus Lira). The IQVIA Core Diabetes Model was used to estimate lifetime costs and outcomes for a cohort of patients with type 2 diabetes mellitus (T2DM) from the UK healthcare perspective. Initial clinical data for iGlarLixi were based on the randomized, controlled LixiLan-L trial and the relative treatment effects for comparators were based on an indirect treatment comparison using data from the AWARD-9 (iGlar plus Dula), LIRA ADD2 BASAL (BI plus Lira), and DUAL V (iDegLira) trials. Costs were derived from publicly available sources. Lifetime costs (in British Pound Sterling [£]) and quality-adjusted life-years (QALYs) were predicted; net monetary benefit (NMB) for iGlarLixi versus comparators was derived using a willingness-to-pay threshold of £20,000. Extensive scenario and sensitivity analyses were conducted. Estimated costs were lowest with iGlarLixi (£31,295) compared with iGlar plus Dula (£38,790), iDegLira (£40,179), and BI plus Lira (£42,467). Total QALYs gained were identical with iGlarLixi and iDegLira (8.438), and comparable with iGlar plus Dula (8.439) and BI plus Lira (8.466). NMB for iGlarLixi was positive versus all comparators (£10,603.86 vs. BI plus Lira; £7,466.24 vs. iGlar plus Dula; £8.874.11 vs. iDegLira). In patients with T2DM with suboptimal glycemic control on basal insulin, iGlarLixi provides very similar outcomes and substantial cost savings, compared with other fixed and free combinations of insulins plus glucagon-like peptide-1 receptor agonists.


Can Transcatheter Aortic Valve Implantation (TAVI) Be Performed at Institutions Without On-Site Cardiac Surgery Departments?
Transcatheter aortic valve implantation [TAVI] represents a paradigm shift in therapeutic options for patients with severe aortic stenosis [AS]. In less than 20 years, TAVI has rapidly disseminated to include a significant proportion of AS patients. The number of AS patients needing TAVI is expected to further increase. Since there is a limited number of centers performing TAVI, wait times are expected to increase. This might have a critical impact of AS patient life as mortality rate of AS patients awaiting TAVI, is substantial, ranging from 2 to 10%. With time, as more patients were treated, improved experience, better imaging and devices, this technology became safer with more reliable results. Today most TAVI complications are related to vascular access [4-6%] and there is less need for emergency thoracic bail out [0.2-0.5%]. In this review, we summarize the prognosis while waiting, the outcomes of patients undergoing TAVI at institutions without on-site cardiac surgery departments and the data describing rates and outcomes of TAVI patients requiring treatment of intra-procedural life-threatening complications. Similar to coronary interventions in the past, TAVI should be considered also in centers without on-site cardiac surgery departments under certain conditions such as, experienced operators, heart team discussion, well established imaging modalities, skilled and qualified support personal, and adequate pre- and post-care facility.


Nurse consultants as higher level practitioners: factors perceived to influence role implementation and development in critical care.
This paper discusses the main factors perceived to influence higher level practice in critical care drawing upon personal experience as a critical care nurse consultant. Implementation and development of the role towards a higher level of practice has been influenced--both positively and negatively--by policy, legislative, organisational, cultural, professional and individual factors. Discussion focuses on professional, policy and organisational issues because--on reflection--these are the main factors that have facilitated and inhibited role implementation and development towards a higher level practice in the United Kingdom. Relevant research exploring advances in nursing practice in critical care, and how this has influenced the development of higher level practice in relation to the nurse consultant role, will also be discussed.


Catalytic dephosphorylation of adenosine monophosphate (AMP) to form supramolecular nanofibers/hydrogels.
The use of enzyme to instruct the self-assembly of the nucleoside of adenosine in water provides a new class of molecular nanofibers/hydrogels as functional soft materials.


Systemic to Pulmonary Artery Versus Right Ventricular to Pulmonary Artery Shunts for Patients With Pulmonary Atresia, Ventricular Septal Defect, and Hypoplastic Pulmonary Arteries.
The systemic-pulmonary shunts (SPS) and the right ventricle to pulmonary artery connection (RV-PA connection) are two palliative procedures for patients with pulmonary atresia, ventricular septal defect, and hypoplastic pulmonary arteries. Our aim is to compare early and midterm outcomes of these two procedures. Clinical data of 132 consecutive patients with PA/VSD who underwent the SPS or the RV-PA connection in Fuwai Hospital from January 2011 to June 2014 were retrospectively analyzed. Patients were divided into two groups according to the procedures. Early outcomes including duration of ventilation, length of intensive care unit (ICU) stay, complication incidence, and improvements in oxygen saturation (SpO2 ) were compared. Midterm outcomes including improvement on Nakata index and complete repair rate were evaluated. Death and complete repair were considered as the end-points. 80 patients underwent SPS, 52 patients underwent RV-PA connection. There were three early deaths and six late deaths in SPS group, while there was no early deaths and only one late death in the RV-PA connection group. For the early outcomes, the SO2 increase after RV-PA connection was significantly higher than that SO2 increase after SPS (20% vs. 15%, p < 0.001). There was no statistical difference in length of ICU stay, duration of ventilatory support, or rate of postoperative complications (all p > 0.05) between the SPS group and RV-PA connection group. The incidence of severe postoperative complications and redo-sternotomy rate of the SPS group was significantly higher than that of the RV-PA connection group (12.5% vs. 1.9% [p = 0.018], 11.3% vs. 1.9%, [p = 0.031]). For the median outcomes, the mean follow-up was 2.3 (0.6-4) years. No statistical difference on Nakata index increase (74.1 ± 23.4 mm(2) /m(2) vs. 84.2 ± 48.7 mm(2) /m(2) , p = 0.350) and the complete repair rate (37.2% vs. 42.5%, p = 0.581) was found between the two groups, but the interphase between the initial procedure and complete repair was shorter in RV-PA connection group than that in the SPS group (11.8 ± 3.5m vs. 16.8 ± 8.5 m, p = 0.038). There is a significant improvement in oxygen saturation and a more stable perioperative course for patients with RV-PA connection. There is also a shorter interval from the initial procedure to complete repair and a lower mortality after RV-PA connection.


Restoring circadian synchrony in vitro facilitates physiological responses to environmental chemicals.
The growing requirement of hazard and risk assessment of environmental chemicals and the efforts to minimize animal testing, increases the demand for innovative and predictive in vitro test systems in toxicology, reflecting the physiological conditions of human nature. Here, an elemental factor regulating a variety of physiological processes is the day-night rhythm. This circadian rhythm, describing a biological oscillation with a 24-h period is hardly acknowledged in toxicology and test method development. Whilst, in animals or humans the entire organism exhibits a rigorous cellular circadian synchrony, in conventional in vitro systems each cell follows its own rhythm, due to the absence of appropriate synchronizing signals. Here we investigated whether circadian synchronization of human cells in an in vitro system improves the cellular response and, thus, increases the sensitivity of the test system. Since the circadian regulation of metabolism is particularly well understood, and dioxin and dioxin-like compounds are of major concern for environmental health we focused on the ubiquitous drug metabolizing detoxification system mediated by the aryl hydrocarbon receptor (AHR). To this end, we applied various prototypical AHR activators onto different human cell lines under non-synchronized or circadian synchronized conditions and determined the dose response on representative endogenous target genes. Remarkably, the cellular response dynamic upon chemical treatment was substantially enhanced in circadian synchronized cells and followed a rhythmic expression pattern. This broader dynamic range was associated with a strikingly higher induction of AHR target genes and the corresponding enzymatic activity, thereby rather mimicking the in vivo situation. Our findings indicate that a synchronized circadian rhythm in a cell culture based test system can improve the physiological relevance of an appropriate in vitro method by reflecting the biological in vivo situation more closely. Accordingly, it is a promising tool to facilitate the wide acceptance of in vitro methods in the field of regulatory toxicology and to further optimize the toxicological assessment of environmental chemicals.


[Irradiation treatment of choroidal hemangiomas].
Therapeutic results obtained following the treatment of 24 cases of choroidal hemangiomas (21 solitary and 3 in a Sturge-Weber syndrome) treated with 60Co applicators or an accelerated proton beam were analyzed. The observation period was less than 2 years for 4 cases, 2 to 5 years for 10 cases, 5 to 10 years for 7 cases and more than 10 years for 3 cases. Reabsorption of retinal detachment without any recurrency was obtained for all the cases. The V.A. was increased in 16 cases, did not change in 4 cases and decreased in 4 other cases. Final V.A. was 6/7.5 or more in 9 cases (37.5%), 6/60 à 6/7.5 in 6 cases (25%), and 6/60 or less in 9 cases (37.5%). None of the cases we treated presented complications induced by radiotherapy (actinic papillitis, circulatory disturbances in the macular area, or neovascular glaucoma). The comparison of the results we obtained with cases treated by photocoagulation or external radiotherapy demonstrated a slight advantage in favour of the focalized radiotherapy, which is not statistically significant because of the small number of cases included in the studies. Meanwhile, contact radiotherapy and irradiation with an accelerated proton beam seems to be a substantial alternative for the treatment of large hemangiomas and tumors invading the macula.


Prenatal diagnosis of trisomy 20 mosaicism indicating an extra embryonic origin.
An additional case of amniotic fluid trisomy 20 mosaicism is presented. After careful counselling, the pregnancy continued and a phenotypically normal female was delivered. This case of amniocyte mosaicism establishes the source of aneuploid cell line as amnion. Since an extra-embryonic origin of the mosaicism has been confirmed, this should be carefully considered as a real possibility in counselling such families.


Molecular cloning and promoter analysis of squalene synthase and squalene epoxidase genes from Betula platyphylla.
Betula platyphylla is a rich repository of pharmacologically active secondary metabolites known as birch triterpenoids (TBP). Here, we cloned the squalene synthase (SS) and squalene epoxidase genetic (SE) sequences from B. platyphylla that encode the key enzymes that are involved in triterpenoid biosynthesis and analyzed the conserved domains and phylogenetics of their corresponding proteins. The full-length sequence of BpSS is 1588 bp with a poly-A tail, which contained an open reading frame (ORF) of 1241 bp that encoded a protein of 413 amino acids. Additionally, the BpSE full-length sequence of 2040 bp with a poly-A tail was also obtained, which contained an ORF of 1581 bp encoding a protein of 526 amino acids. Their organ-specific expression patterns in 4-week-old tissue culture seedlings of B. platyphylla were detected by real-time PCR and showed that they were all highly expressed in leaves, as compared to stem and root tissues. Additionaly, both BpSS and BpSE were enhanced following stimulation with ethephon and MeJA. The expression of BpSS was enhanced by ABA, whereas BpSE was not. The SA treatment did not affect the BpSS and BpSE transcripts notably. Using a genome walking approach, promoter sequences of 965 and 1193 bp, respectively, for BpSS and BpSE were isolated, and they revealed several key cis-regulatory elements known to be involved in the response to phytohormone and abiotic plant stress. We also found that the BpSS protein is localized in the cytoplasm. Opening reading frames of BpSS and BpSE were ligated into yeast expression plasmid pYES2 under control of GAL1 promoter and introduced into the yeast INVScl1 strain. The transformants were cultured for 12 h, the squalene content of galactose-induced BpSS expression yeast cells was 13.2 times of control (empty vector control yeast cells) by high-performance liquid chromatography (HPLC) test method. And, the squalene epoxidase activity of induced BpSE expression yeast cell was about 11.8 times of control. These indicated that we cloned birch BpSS and BpSE that were indeed involved in the synthesis of triteropenoids. This is the first report wherein SS and SE from B. platyphylla were cloned and may be of significant interest to understand the regulatory role of SS and SE in the triterpenoids biosynthesis of B. platyphylla. This is the first report wherein SS and SE from B. platyphylla were cloned and may be of significant interest to understand the regulatory role of SS and SE in the biosynthesis of birch triterpenoids.


Prediction of the GTPase activities by using the semiempirical molecular orbital theory.
Assuming that substrate-assisted catalysis is the mechanism of GTP hydrolysis for ras p21 and other GTP-binding proteins, we used the PM3 semiempirical molecular orbital method to predict from the calculated reaction profiles of GTP hydrolysis reactions the changes in GTPase activities caused by mutations. We succeeded in making qualitative predictions for mutants.


The impact of environmental pollution on labor supply: empirical evidence from China.
The current study focuses on determining mediating effect using the fixed and instrumental variable models to understand how PM2.5 affects labor supply. To approach study objectives, a 20-year dataset (from 2000 to 2019) of 287 Chinese prefecture-level cities were collected. To deal with potential endogeneity, the ventilation coefficient was used as an instrumental variable to identify the reverse causality between PM2.5 and labor supply. Results depicted that the PM2.5 pollution significantly and negatively impacts the labor supply. It was found that PM2.5 indirectly reduced labor forces because of pollution-induced health losses. Moreover, when the pollution level was above 30 μg/m3, the PM2.5 significantly reduced the labor supply. The result suggests that China's local and national governments should enact stringent policy measures to reduce air pollution.


Improved transcutaneous bilirubinometry: comparison of SpectR(X) BiliCheck and Minolta Jaundice Meter JM-102 for estimating total serum bilirubin in a normal newborn population.
To compare a new transcutaneous bilirubinometer, which uses multiple wavelength analysis of reflectance data (BiliCheck system), and the commonly used two-wavelength bilirubinometer (Jaundice Meter JM-102) to estimate serum bilirubin. Jaundiced newborn term infants (101 babies) had transcutaneous bilirubinometry (TCB) using each bilirubinometer, a determination of skin color using a skin color chart, and a total serum bilirubin determination. The variability of the BiliCheck system was less than the variability of the Jaundice Meter JM-102. The accuracy of the BiliCheck system was not affected by skin color, whereas the Jaundice Meter JM-102 was affected. Multiple wavelength analysis, as used in the BiliCheck system, is a significant improvement in TCB.


Correspondency between different affinity states and target size of the bovine striatal D2 dopamine receptor.
Target size analysis of the D2 dopamine receptor in the bovine striatum revealed the presence of two populations of this receptor, in terms of apparent molecular size. The size of large target was approximately 150 X 10(4) daltons, while that of small target was 11 X 10(4) daltons. The antagonist [3H]spiperone labeled both large and small sized D2 receptors, while agonist [3H]n-propylapomorphine (NPA) labeled only the former. In addition, the apparent molecular size of a functional unit for the GTP effect was calculated to be 150 X 10(4) daltons, such appearing to be identical to that of large target sized D2 dopamine receptors. Therefore, the large sized D2 receptor, probably an oligomeric complex consisting of D2 receptor recognition protein and guanine nucleotide regulatory protein, has a high affinity for both agonist and antagonist, while the small sized receptor, probably a monomeric or dimeric receptor recognition protein, has a high affinity for only the antagonist.


Cardio-hepatic syndrome in patients undergoing transcatheter aortic valve replacement.
Cardiohepatic syndrome (CHS) has been identified as an important but underrecognized survival predictor in multiple cardiovascular disease entities. The objectives of this study were to evaluate the prevalence and prognostic value of CHS in patients undergoing TAVR for severe aortic stenosis (AS). The study included patients with available laboratory parameters of hepatic function who underwent TAVR from July 2013 until December 2019 at our center. CHS was defined as an elevation of at least two of three laboratory cholestasis parameters above the upper limit of normal (bilirubin, alkaline phosphatase, and gamma glutamyl transferase). Study endpoints were three-year survival, technical and device failure (VARC 3), as well as New York Heart Association (NYHA) functional class at follow-up. Among a total of 953 analyzed patients (47.6% females, median age 80.0 [76.0-85.0] years) CHS was present in 212 patients (22.4%). In patients with vs. without CHS, rates of technical (6.1% vs. 8.4%, p = 0.29) and device failure (18.9% vs. 17.3%, p = 0.59) were comparable. NYHA functional class at baseline and follow-up was more severe in patients with CHS. Nevertheless, heart failure symptoms improved from baseline to follow-up irrespective of hepatic function. Three-year survival rates were significantly lower in patients with CHS (49.4 vs. 65.4%, p < 0.001). The predictive value of CHS persisted after adjustment in a multivariable analysis (hazard ratio 1.58, p < 0.01). In patients undergoing TAVR, CHS is prevalent in 22% of patients and is associated with increased postinterventional mortality. Thus, CHS should be included in the decision-making process within the TAVR heart team. Cardiohepatic syndrome (CHS) as defined by an elevation of at least two of three laboratory cholestasis parameters above the upper limit of normal was prevalent in 22% of patients undergoing TAVR for severe AS. The presence of CHS was associated with more severe heart failure symptoms and worse three-year survival.


[Childhood parvovirus B19 encephalitis].
Human parvovirus B19 (PVB19) causes erythema infectiosum or 5(th) disease in childhood, which mainly affects children between 3 and 15 years of age. PVB19 infections have also been described in association with a variety of neurologic manifestations including encephalitis. This 3-year 8-month-old boy developed febrile encephalitis (mental status change with seizures and left limb hypertonia) associated with a rash. The electroencephalographs revealed focal slowing with some spikes in front of the left centro-temporo-occipital areas ; bacteriological and biochemical cerebrospinal fluid (CSF) analysis were normal, brain radiologic studies (tomography and magnetic resonance imaging) were normal. The diagnosis of encephalitis associated with PVB19 primo infection was based on viral DNA detection in the serum and CSF using PCR and on the specific immunoglobulin M (without immunoglobulin G) detection in the serum. In France, encephalitis etiology is unknown in 48% of the cases. PVB19 accounts for 4.3% of undiagnosed meningoencephalitis in children. Although there is no specific sign, seizures and rash are reported in about one-half and one-quarter of cases, respectively. Even if PVB19 research is not cited in the French or American infectious disease society recommendations on the diagnosis and management of infectious encephalitis, this virus may be responsible, especially in cases of child febrile rash. Therefore, PVB19 research seems reasonable if the clinical presentation is concordant in children due to its diagnostic simplicity and efficacy.


Tetrahydroxy stilbene glycoside ameliorates neuroinflammation for Alzheimer's disease via cGAS-STING.
Alzheimer's disease (AD), also known as senile dementia, is the most common degenerative disease of the central nervous system. Neuroinflammation is currently believed to be a crucial factor in the progression of AD, while its exact mechanism remains unclear. In this study, we demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation. Treating with a natural active ingredient tetrahydroxy stilbene glucoside (TSG) from the Chinese herb Polygonum multiflorum that has been well known for its unique anti-aging effect, learning-memory ability of AD mice was distinctly improved. Meanwhile, it was observed that the expressions of serum inflammatory cytokines and the activation of microglia in cerebral cortex and hippocampus were suppressed after TSG treatment, which was probably attributable to the decrease of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) triggered immune response and NLRP3 inflammasome activation. Furthermore, cell culture experiments employing LPS combined with IFN-γ induced microglia activation showed that TSG reversed the polarization status of M1-type microglia to restore the quiescence, and cGAS-STING elevation was observed in the activated microglia and normalized by TSG incubation. In addition, TSG suppressed the production of inflammatory cytokines such as IL-1β, IL-6, TNF-α, IFN-α and IFN-β, as well as the expression of IFN regulatory proteins such as IFIT1 and IRF7 in the LPS/IFN-γ-stimulated inflammatory response in BV2 cell. Finally, it was also verified that TSG are, in part, through a cGAS-STING dependent pathway and triggered NLRP3 inflammasome activation to inhibit neuroinflammation through interfering with cGAS-STING inhibitors. Taken together, our findings highlight the health benefits of TSG and its potential application in preventing cognitive disorders by inhibiting neuroinflammation through cGAS-STING signaling pathway in AD.


The letter height superiority illusion.
Letters are identified better when they are embedded within words rather than within pseudowords, a phenomenon known as the word superiority effect (Reicher in Journal of Experimental Psychology, 81, 275-280, 1969). This effect is, inter alia, accounted for by the interactive-activation model (McClelland & Rumelhart in Psychological Review, 88, 375-407, 1981) through feedback from word to letter nodes. In this study, we investigated whether overactivation of features could lead to perceptual bias, wherein letters would be perceived as being taller than pseudoletters, or words would be perceived as being taller than pseudowords. In two experiments, we investigated the effects of letter and lexical status on the perception of size. Participants who had to compare the heights of letters and pseudoletters, or of words and pseudowords, indeed perceived the former stimuli as being taller than the latter. Possible alternative interpretations of this height superiority effect for letters and words are discussed.


The use of serum cholinesterase in succinylcholine apnoea.
Fifteen patients demonstrating unexpected prolonged apnoea lasting several hours after succinylcholine have been treated by a new preparation of human serum cholinesterase. Adequate spontaneous respiration was re-established in an average period of ten minutes after the injection. In 12 patients biochemical genetic examinations confirmed the presence of an atypical serum cholinesterase. In three patients none of the usual variants were found. It is therefore supposed that other unknown variants of serum cholinesterase exist which cannot hydrolyze succinylcholine. The use of serum cholinesterase in succinylcholine apnoea provided considerable relief to both patient and anaesthetist.


Genome-wide identification and expression analysis of VQ gene family under abiotic stress in Coix lacryma-jobi L.
Valine-glutamine (VQ) proteins are non-specific plant proteins that have a highly conserved motif: FxxhVQxhTG. These proteins are involved in the development of various plant organs such as seeds, hypocotyls, flowers, leaves and also play a role in response to salt, drought and cold stresses. Despite their importance, there is limited information available on the evolutionary and structural characteristics of VQ family genes in Coix lacryma-jobi. In this study, a total of 31 VQ genes were identified from the coix genome and classified into seven subgroups (I-VII) based on phylogenetic analysis. These genes were found to be unevenly distributed on 10 chromosomes. Gene structure analysis revealed that these genes had a similar type of structure within each subfamily. Moreover, 27 of ClVQ genes were found to have no introns. Conserved domain and multiple sequence alignment analysis revealed the presence of a highly conserved sequences in the ClVQ protein. This research utilized quantitative real-time PCR (qRT-PCR) and promoter analysis to investigate the expression of ClVQ genes under different stress conditions. Results showed that most ClVQ genes responded to polyethylene glycol, heat treatment, salt, abscisic acid and methyl jasmonate treatment with varying degrees of expression. Furthermore, some ClVQ genes exhibited significant correlation in expression changes under abiotic stress, indicating that these genes may act synergistically in response to adversarial stress. Additionally, yeast dihybrid verification revealed an interaction between ClVQ4, ClVQ12, and ClVQ26. This study conducted a genome-wide analysis of the VQ gene family in coix, including an examination of phylogenetic relationships, conserved domains, cis-elements and expression patterns. The goal of the study was to identify potential drought resistance candidate genes, providing a theoretical foundation for molecular resistance breeding.


Thermodynamics of co-translational folding and ribosome-nascent chain interactions.
Proteins can begin the conformational search for their native structure in parallel with biosynthesis on the ribosome, in a process termed co-translational folding. In contrast to the reversible folding of isolated domains, as a nascent chain emerges from the ribosome exit tunnel during translation the free energy landscape it explores also evolves as a function of chain length. While this presents a substantially more complex measurement problem, this review will outline the progress that has been made recently in understanding, quantitatively, the process by which a nascent chain attains its full native stability, as well as the mechanisms through which interactions with the nearby ribosome surface can perturb or modulate this process.


The Human Affectome Project: A dedication to Jaak Panksepp.
Mapping the neural basis of the Affectome was certainly the goal of Jaak Panksepp as he extended the work of a long line of thinkers from William James to Paul Maclean. Jaak's contribution was not just an incremental step, but a move to embrace feelings as a key component of affective science. His goal was to develop objective behavioral measures as he identified the neural substrates associated with affective states. He dedicated his career to studying the biological roots of emotional operating systems and his 1998 book "Affective Neuroscience" stands as a seminal accomplishment that provided a foundation for a field of research that has flourished since. His influences can be seen in many of the reviews created for this project and his early references to comfort zones are central to the human affectome. Indeed, Jaak was a tireless investigator who challenged our thinking, and he gave us many insights and gifts. We are immensely grateful for his contributions and this special issue is dedicated to his memory.


Neurocysticercosis.
Neurocysticercosis is the most common parasitosis of the central nervous system. Many forms, especially those inside the ventricles, carry a poor prognosis. Drug therapy is far from ideal. We propose and comment on the use of the endoscope to remove cysts, treat hydrocephalus, and to perform membrane fenestration as a way to simplify treatment. Many patients, especially those with obstructive forms, benefit from the adjunctive use of neuroendoscopy. Neurocysticercosis treatment remains challenging and multimodal. Endoscopes can be helpful in this setting.


Relationship between lower urinary tract symptoms frequency assessed by the IPSS and bothersomeness (SPI) among men older than 50 years old.
The International Prostatic Symptom Score (IPSS) evaluates urinary disorder symptoms frequently associated with benign prostatic obstruction, but does not take into account the bothersomeness they induce. The Symptom Problem Index (SPI) evaluates the degree of discomfort associated with each question on the IPSS. Our objective was to explore the relationships between these two rating scales. The IPSS and SPI self-administered scores were administrated to a cohort of 907 patients presenting with LUTS suggestive of BPO (Benign Prostatic Obstruction), for which 722 patients were evaluable. This diagnosis was made by GP (General Practitioner) in the 3-month period before their inclusion in the study. The correlation between SPI and IPSS was investigated and each symptom was classified according to its frequency and according to the bothersomeness it induced. The degree of bothersomeness associated with each IPSS symptom was evaluated and quantified based on quadratic function estimates. The mean IPSS score was 12.6+/-6.4, the mean SPI score was 12.2+/-6.5. The correlation coefficient between the IPSS and SPI scores was 0.70; the scores from the 2 rating scales showed a very high variability. On a 0-100% scale, where 100% represents a maximum bothersomeness, the induced bothersomeness ranged from 0 to 22.6% depending on the 7 symptoms. The two questionnaires do not collect the same information. The extent of variability between the two scales confirms that one scale cannot be replaced by the other. Considering the importance of bothersomeness associated with lower urinary tract symptoms for the therapy decision, the joint use of the IPSS and SPI seems appropriate.


[Counting and differentiation of blood corpuscles with a simple flow cytometer].
The performance of a simple flow cytometer for counting of blood cells was checked. The counting of erythrocytes, platelets as well as the differential counting of lymphocytes, monocytes and granulocytes was obtained by means of simple sample preparation.


Identification of EGFRvIII-derived CTL epitopes restricted by HLA A0201 for dendritic cell based immunotherapy of gliomas.
The type III variant of the epidermal growth factor receptor (EGFRvIII) mutation is present in 20-25% of patients with glioblastoma multiforme (GBM). EGFRvIII is not expressed in normal tissue and is therefore a suitable candidate antigen for dendritic cell (DC) based immunotherapy of GBM. To identify the antigenic epitope(s) that may serve as targets for EGFRvIII-specific cytotoxic T lymphocytes (CTLs), the peptide sequence of EGFRvIII was screened with two software programs to predict candidate epitopes restricted by the major histocompatibility complex class I subtype HLA-A0201, which is the predominant subtype in most ethnic groups. Three predicted peptides were constructed and loaded to mature human DCs generated from peripheral blood monocytes. Autologous CD8+ T cells were stimulated in vitro with the EGFRvIII peptide-pulsed DCs. One of the three peptides was found to induce EGFRvIII-specific CTLs as demonstrated by IFN-gamma production and cytotoxicity against HLA-A0201+ EGFRvIII transfected U87 glioma cells. These results suggest that vaccination with EGFRvIII peptide-pulsed DCs or adoptive transfer of in vitro elicited EGFRvIII-specific CTLs by EGFRvIII peptide-pulsed DCs are potential approaches to the treatment of glioma patients.


Isolation and characterization of autoantibodies against human cystatin C.
Hereditary cystatin C amyloid angiopathy (HCCAA) is a severe neurodegenerative disorder related to the point mutation in cystatin C gene resulting in human cystatin C (hCC) L68Q variant. One of the potential immunotherapeutic approaches to HCCAA treatment is based on naturally occurring antibodies against cystatin C. A recent growing interest in autoantibodies, especially in the context of neurodegenerative diseases, emerges from their potential use as valuable diagnostic markers and for controlling protein aggregation. In this work, we present characteristics of natural anti-hCC antibodies isolated from the IgG fraction of human serum by affinity chromatography. The electrophoresis (1-D and 2-D) results demonstrated that the isolated NAbs are a polyclonal mixture, but their electrophoretic properties did not allow to classify the new autoantibodies to any particular type of IgG. The Fc-glycan status of the studied autoantibodies was assessed using mass spectrometry analysis. For the isolated NAbs, the epitopic fragments in hCC sequence were identified by MS-assisted proteolytic excision of the immune complex and compared with the ones predicted theoretically. The knowledge of hCC fragments binding to NAbs and other ligands may contribute to the search for new diagnostic methods for amyloidosis of different types and the search for their treatment.


Three-photon imaging of mouse brain structure and function through the intact skull.
Optical imaging through the intact mouse skull is challenging because of skull-induced aberrations and scattering. We found that three-photon excitation provided improved optical sectioning compared with that obtained with two-photon excitation, even when we used the same excitation wavelength and imaging system. Here we demonstrate three-photon imaging of vasculature through the adult mouse skull at >500-μm depth, as well as GCaMP6s calcium imaging over weeks in cortical layers 2/3 and 4 in awake mice, with 8.5 frames per second and a field of view spanning hundreds of micrometers.


Determination of L-methionine-dl-sulphoxide in tissue extracts.
The amino acid fraction from rat liver, heart and skeletal muscle was prepared by the separation of sulphosalicylic acid extract on Dowex 50 H+ form. The presence of L-methionine-dl-sulphoxide in these extracts was identified and compared by three independent chromatographic methods: ion-exchange, Pico-Tag and reversed-phase high-performance liquid chromatography after precolumn derivatisation with diethylethoxymethylenemalonate. Quantitative data indicate that L-methionine-dl-sulphoxide is present in the intracellular pool at the levels of free methionine.


Lumbar Morel-Lavallée lesion: a case report and review of the literature.
Here we describe a rare post-traumatic lesion and discuss its management. Lumbar Morel-Lavallée is a rarely reported lesion. The cause is usually post-traumatic in a polytraumatic context, and care is often focused elsewhere. This leads to misdiagnosis with a risk of chronic pain and infection. In addition, there is no consensus for the management as few cases have been reported so far. A 35-year-old African woman was involved in a motor accident. Physical examination at the emergency department revealed moderate head trauma, a lumbar inflammatory mass, and a closed leg fracture. She underwent a whole-body computed tomography scan, which revealed a left frontal brain contusion and a large left paraspinal mass in favor of a lumbar Morel-Lavallée lesion. She benefited from osteosynthesis and conservative management of the cerebral and lumbar lesions. After 4 days, she complained of headaches and vomiting. Magnetic resonance imaging was requested. There was resorption of the cerebral contusion, and the lumbar mass was heterogeneous. She was discharged 10 days later without lower back pain and fully recovered from the headaches. Ultrasound of the lumbar soft tissue performed a month later showed no more collection. More frequent in young men, lumbar Morel-Lavallée lesion is underdiagnosed. Thus, there is no consensus on its treatment. However, conservative management followed by close monitoring is advisable in the acute phase. Other therapy includes surgery with or without the use of sclerosing agents. Early diagnosis prevents infections. Although the diagnosis is clinical, magnetic resonance imaging is the critical paraclinical examination for its assessment. Our case is interesting because it occurs in a woman following polytrauma, and to the best of our knowledge, it is an extremely rare lesion, especially in women.


Stability and immunogenicity of empty particles of foot-and-mouth disease virus.
Three strains of foot-and-mouth disease virus were shown to contain significant amounts of naturally occurring 75S, empty particles as well as the infectious, 140S full particles. One of these strains--A Pando (1970)--was studied in detail. The empty particles from this virus strain were shown to have an observed sedimentation coefficient of 67S in 0.04 M phosphate buffer; they were labile in SDS, non-infectious and probably RNA-free and, on heating, they broke down to 12S subunits as did the 140S particles. The empty particles differed from the full particles in their polypeptide composition since they contained VP0, but there was no evidence for a diminished content of VP4. The 75S particles were shown to be present in significant amounts and to be stable to AEI inactivation. At 4 degrees C they were stable for at least two years. In guinea pigs they were as immunogenic as the 140S particles. The antisera raised against the 75S particles had the same serological specificity in neutralization tests as sera prepared against the 140S particle. It was concluded that the 75S particles from the A Pando (1970) strain of FMD virus may provide as important a contribution as 140S particles to the immunogenicity of inactivated vaccines prepared from this virus strain.


An experimental technique to study the turnover of concentrated hyaluronan in the anterior chamber of the rabbit.
An experimental technique to study the turnover of hyaluronan in the anterior chamber in single animals has been developed. It is based on the fact that circulating hyaluronan labelled with tritium in the acetyl group is rapidly taken up by the liver and degraded to tritiated water. 3H-labelled hyaluronan was mixed with high concentration, high molecular weight hyaluronan (Healon) and injected into the anterior chamber of rabbits. The concentration of tritiated water in blood plasma was followed for up to 13 days. An initial rise of radioactivity in the blood was followed by an exponential decrease. From the exponential disappearance it was possible to calculate the rate of turnover of water in the body. This was used to correct the initial rise of tritium for water losses. After this correction the appearance of radioactive water in blood corresponded to the disappearance of hyaluronan from the eye plus a 45 min time-lag due to the catabolism in the liver. Using this technique it was found that trace amounts of radioactive hyaluronan and 0.055 ml and 0.2 ml of 1% hyaluronan exhibited half-lives in the anterior chamber of 1.5, 7 and 13 hr respectively. When the same technique was used for subcutaneously and intramuscularly injected hyaluronan half-lives of 50 and 30 hr, respectively, were recorded.


Design of nutrient gas-phase bioreactors: a critical comprehensive review.
To reach an efficient and economical gas-phase bioreactor is still one of the most critical challenges in biotechnology engineering. The numerous advantages of gas-phase bioreactors (GPBs) as well as disadvantages of these bioreactors should be exactly recognized, and efforts should be made to eliminate these defects. The first step in upgrading these bioreactors is to identify their types and the results of previous research. In the present work, a summary of the studies carried out in the field of cultivation in these bioreactors, their classification, their components, their principles and relations governing elements, modeling them, and some of their inherent engineering aspects are presented. Literature review showed that inoculation of shoots, roots, adventurous roots, callus, nodal explants, anther, nodal segment, somatic embryo, hairy roots, and fungus is reported in 15, 2, 2, 2, 3, 2, 1, 1, 37, and 5 cases, respectively.


Pelvic MRI and CT images are interchangeable for measuring peripouch fat.
A total of 27 pouch patients with inflammatory bowel diseases, who underwent pelvic MRI-DIXON and CT scan within one year, were included. Peripouch fat areas were measured at the middle height level of pouch (AreaM) and the highest level of pouch (AreaH). Our results demonstrated that measurements of perianal fat thickness, AreaM and AreaH based on MRI image were accurate and reproducible (correlation efficiency(r): intraobserver: 0.984-0.991; interobserver: 0.969-0.971; all P < 0.001). Bland-Altman analysis showed that more than 92.593% (25/27) of dots fell within the limits of agreement. We also identified strong agreements between CT and MRI image in measuring perianal fat thickness(r = 0.823, P < 0.001), AreaM (r = 0.773, P < 0.001) and AreaH (r = 0.862, P < 0.001). Interchangeable calculating formula to normalize measurements between CT and MRI images were created: Thickness_CT = 0.610 × Thickness_MRI + 0.853; AreaM_CT = 0.865 × AreaM_MRI + 1.392; AreaH_CT = 0.508 × AreaH_MRI + 15.001. In conclusion, pelvic MRI image is a feasible and reproducible method for quantifying peripouch fat. Pelvic MRI and CT images are interchangeable in retrospective measurements of peripouch fat, which will foster future investigation of the role of mesentery fat in colorectal diseases.


Molecular programs of fibrotic change in aging human lung.
Lung fibrosis is increasingly detected with aging and has been associated with poor outcomes in acute lung injury or infection. However, the molecular programs driving this pro-fibrotic evolution are unclear. Here we profile distal lung samples from healthy human donors across the lifespan. Gene expression profiling by bulk RNAseq reveals both increasing cellular senescence and pro-fibrotic pathway activation with age. Quantitation of telomere length shows progressive shortening with age, which is associated with DNA damage foci and cellular senescence. Cell type deconvolution analysis of the RNAseq data indicates a progressive loss of lung epithelial cells and an increasing proportion of fibroblasts with age. Consistent with this pro-fibrotic profile, second harmonic imaging of aged lungs demonstrates increased density of interstitial collagen as well as decreased alveolar expansion and surfactant secretion. In this work, we reveal the transcriptional and structural features of fibrosis and associated functional impairment in normal lung aging.


Measurement of in vitro microtubule polymerization by turbidity and fluorescence.
Tubulin polymerization may be conveniently monitored by the increase in turbidity (optical density, or OD) or by the increase in fluorescence intensity of diamidino-phenylindole. The resulting data can be a quantitative measure of microtubule (MT) assembly, but some care is needed in interpretation, especially of OD data. Buffer formulations used for the assembly reaction significantly influence the polymerization, both by altering the critical concentration for polymerization and by altering the exact polymer produced-for example, by increasing the production of sheet polymers in addition to MT. Both the turbidity and the fluorescence methods are useful for demonstrating the effect of MT-stabilizing or -destabilizing additives.


Inclusion of Acupuncture as an Adjunct Therapy in the Management of a Patient With Schizophrenia and Dissociative Identity Disorder: A Case Report.
The purpose of this case report is to describe the inclusion of acupuncture in the management of a patient with schizophrenia and dissociative identity disorder (DID). A 68-year-old man presented with schizophrenia and DID, which had been diagnosed at age 25. The patient was currently under psychiatric care and prescribed antipsychotic medications and psychiatric counseling. His predominant symptoms were anxiety, paranoia, and irritability. In addition, 2 to 5 personas manifested over the years that he referred to as the "Others." A Brief Psychiatric Rating Scale was 81 out of 126 on his first visit. Traditional Chinese medicine-style acupuncture was administered. Over the year, the severity of the patient's symptoms was reduced according to the Brief Psychiatric Rating Scale to 56 and was maintained between 55 and 61 for 6 months. Acupuncture included as an adjunct therapy to antipsychotic medication and psychiatric counseling may have reduced the severity of symptoms associated with schizophrenia and DID for this patient.


Magnolol alleviates hypoxia-induced pulmonary vascular remodeling through inhibition of phenotypic transformation in pulmonary arterial smooth muscle cells.
Phenotypic transformation and excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) play an important role in vascular remodeling during pulmonary hypertension (PH). Magnolol (5,5'-diallyl-2,2'-dihydroxybiphenyl) is the major bioactive constituent isolated from the bark of Magnolia Officinalis, which has anti-inflammatory, antioxidant, and cardiovascular protection effects. However, the effect of magnolol on the phenotypic transformation of PASMCs is still unknown. This study aims to evaluate the effects of magnolol on the phenotypic transformation of PASMCs induced by hypoxia. In vivo, Sprague Dawley rats were exposed to hypoxia (10% O2) for four weeks to establish a PH model. The results showed that hypoxia treatment led to an increase in right ventricle systolic pressure, Fulton index, collagen production, accompanied by upregulation in the expression of collagen Ⅰ, collagen Ⅲ, OPN, PCNA, CyclinD1, p-JAK2, and p-STAT3, as well as decreases in expression of SM-22α; these changes were attenuated by magnolol. In vitro, the primary cultured PASMCs were exposed to 3% O2 for 48 h to induce phenotypic transformation. Consistent with the findings in vivo, magnolol treatment could prevent the phenotypic transformation and hyperproliferation of PASMCs induced by hypoxia, accompanied by downregulation in the expression of p-JAK2 and p-STAT3. In summary, this study demonstrated that the protective effect of magnolol on PH vascular remodeling is related to the inhibition of phenotypic transformation and hyperproliferation of PASMCs by inhibiting the JAK2/STAT3 pathway.


Technical challenges and future directions in lead reconstruction for reduced-lead systems.
Reduced-lead electrocardiographic systems are currently a widely accepted medical technology used in a number of applications. They provide increased patient comfort and superior performance in arrhythmia and ST monitoring. These systems have unique and compelling advantages over the traditional multichannel monitoring lead systems. However, the design and development of reduced-lead systems create numerous technical challenges. This article summarizes the major technical challenges commonly encountered in lead reconstruction for reduced-lead systems. We discuss the effects of basis lead and target lead selections, the differences between interpolated vs extrapolated leads, the database dependency of the coefficients, and the approaches in quantitative performance evaluation, and provide a comparison of different lead systems. In conclusion, existing reduced-lead systems differ significantly in regard to trade-offs from the technical, practical, and clinical points of view. Understanding the technical limitations, the strengths, and the trade-offs of these reduced-lead systems will hopefully guide future research.


Investigation of a mechanism for accelerated breakdown of immune tolerance to the primary biliary cirrhosis-associated autoantigen, pyruvate dehydrogenase complex.
Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by autoreactive T- and B-cell responses to the highly conserved enzyme pyruvate dehydrogenase complex (PDC). In this study we have examined the breakdown of T-cell tolerance to self-PDC using a mouse model. Female SJL/J mice were sensitized intraperitoneally with foreign-PDC (bovine) and/or self-PDC (murine) in complete Freund's adjuvant, and serum, spleen, and liver tissue was taken 8 weeks later. Animals sensitized with foreign-PDC produced IgG antibodies that were reactive with both foreign and self-PDC, but splenic T cells from these animals only responded to stimulation with foreign PDC. Sensitization with self-PDC elicited neither antibodies nor reactive T cells. Significantly, cosensitization with mixed self-PDC and foreign-PDC resulted in a full breakdown of self-tolerance, with generation of both antibody and T-cell responses to self-PDC of the type seen exclusively in human PBC patients. Mild bile duct lesions deficient in CD8(+) T cells were seen 8 weeks after sensitization with either foreign or self-PDC. However, after sensitization with mixed self-PDC and foreign-PDC, these lesions were significantly larger and heavily infiltrated by CD8(+) T cells. Liver-infiltrating T cells derived from the self-PDC and foreign-PDC cosensitized but not from control animals showed reactivity with self-PDC, suggesting a possible role for autoreactive PDC-specific T-cell responses in the pathogenesis of the observed histologic changes. It is likely that B-cell cross-reactivity between foreign and self-PDC enhances the potential for breakdown of T-cell self-tolerance by allowing efficient presentation of self-antigens in the inoculum. This model may provide a useful system for investigating the etiology and treatment of PBC.


Analgesia induced by morphine injected into the pallidum.
Bilateral microinjections of morphine hydrochloride (10; 20; 30 micrograms/0.5 microliter/side) or saline were aimed at three different regions of the rat globus pallidus: dorsal, medial, ventral. Before and at various intervals after intrapallidal morphine (15; 30; 60; 90; 180 min), estimation of pain threshold was made by the hot plate procedure. Dose-dependent morphine analgesia was elicited from all three regions injected. Differences between the pallidal areas as to the intensity and duration of the drug's effect were noticed. Pretreatment with subcutaneous naloxone (1 mg/kg, s.c.) inhibited the morphine (20 micrograms) analgesia elicited from the medial and dorsal pallidum; it decreased and delayed the effect of morphine injected into the ventral pallidum. The results suggest that the three pallidal areas tested are involved to a different degree (medial/dorsal greater than ventral) in the morphine analgesia mediated by opiate receptors.


Nation related participation and performance trends in 'Norseman Xtreme Triathlon' from 2006 to 2014.
We investigated the nation related participation and performance trends in triathletes competing in 'Norseman Xtreme Triathlon' between 2006 and 2014 using mixed models, one-way analysis of variance and multi-variate regression analyses. A total of 1594 athletes (139 women and 1455 men) originating from 34 different countries finished the race. Most of the athletes originated from Norway, Germany, Great Britain, Sweden, USA and France. In the mixed model analysis considering all finishers (n = 1594), with calendar year, sex and country as independent and overall race time as dependent variable, calendar year (p < 0.0001), sex (p < 0.0001), country (p < 0.0001) and the interaction sex × calendar year (p = 0.012) were significant. In the model where overall race time was separated in the three disciplines, we found interactions such as country × discipline (p < 0.0001), year × discipline (p < 0.0001), sex × discipline (p < 0.0001), calendar year × sex (p = 0.044), calendar year × sex × discipline (p = 0.031). Overall race time decreased every year, above all in the year 2012. Women were slower than men, but women reduced this gender gap year after year and above all in the year 2007 (p = 0.001). Athletes from Norway and Germany were faster than those from Great Britain and other countries. Split times of the discipline decreased throughout the years. In particular, the discipline having more impact on overall race time was cycling. Most of the podiums were achieved by Norwegian women and men. For women, the fastest split and transition times were achieved by Norwegian women with exception of the run where German women were faster. Norwegian men were the fastest in split and transition times although French athletes were the fastest in swimming. Across years, the annual three fastest Norwegian women improved in cycling, running, overall race time and transition times but not Norwegian and German men. British men, however, improved running split times and transition times. To summarize, most of the finishers in 'Norseman Xtreme Triathlon' originated from Norway and the fastest race times were achieved by Norwegian women and men. Norwegian women improved race times across years but not Norwegian men.


Cloning, characterization and analysis of expression profiles of a cDNA encoding a hyoscyamine 6beta-hydroxylase (H6H) from Atropa baetica Willk.
A new cDNA encoding hyoscyamine 6beta-hydroxylase (H6H, EC 184.108.40.206), a bifunctional enzyme catalyzing the last two steps in the biosynthesis of scopolamine, was isolated from Atropa baetica roots (GenBank accession no. EF442802). The full cDNA sequence showed an ORF of 1035bp, coding for a protein with 344 amino acid residues. Sequence analyses at the nucleotide level showed that this ORF shares high identity with other H6H from different plant species, such as Anisodus tanguticus and Hyoscyamus niger with 90% identity, and an almost total identity with A. belladonna (98%). Tissue expression analyses showed that the gene transcript was tissue dependent, appearing exclusively in roots, thus being the only biosynthetic site for the production of scopolamine. Furthermore, Southern hybridization experiments revealed that this gene was not part of a multigene family as appears in low copy number. Phylogenetic tree analysis indicated that A. baetica H6H had a very close relationship with A. belladonna and to a lesser extent with H. niger.