Stem Cell Factor (SCF) is a putative biomarker of antidepressant response.
Growth factors involved in neurogenesis and neuroplasticity could play a role in biological processes that drive depression recovery. Combined total sleep deprivation and morning light therapy (TSD + LT) can acutely reverse depressive symptoms, thus allowing to investigate the neurobiological correlates of antidepressant response. We tested if changes on plasma levels of Brain Derived Neurotrophic Factor (BDNF), S100 calcium binding protein B (S100-B), Stem Cell Factor (SCF), Insulin-like Growth Factor-Binding Protein 2 (IGFBP-2), Epidermal Growth Factor (EGF), Platelet-Derived Growth Factor-BB (PDGF-BB), and Vascular Endothelial Growth Factor (VEGF) are associated with response to TSD + LT in 26 inpatients affected by a major depressive episode in the course of bipolar disorder. Regional grey matter (GM) volumes were assessed at baseline, and BOLD fMRI neural responses to a moral valence decision task were recorded before and after treatment. 61.5 % of patients responded to treatment. SCF plasma levels increased significantly more in responders, and correlated with GM volumes in frontal and parietal cortical areas. The pattern of change of SCF also associated with both GM volumes and changes of BOLD fMRI neural responses in the anterior cingulate and medial prefrontal cortex. SCF is both a hematopoietic growth factor and a neurotrophic factor, involved in neuron-neuron and neuron-(micro) glia interactions, fostering neuronal growth and an anti-inflammatory milieu. We correlated SCF levels with antidepressant response and with functional and structural MRI measures in cortical areas that are involved in the cognitive generation and control of affect. SCF may be a candidate growth factor that contributes to neurotrophic and immune effects that are involved in the process of remission/recovery from depression.


[Research progress of pyruvate kinase type M2 in hepatocellular carcinoma].
Primary hepatocellular carcinoma is one of the most common high-grade malignant tumors in the world. Its incidence ranks fifth among malignant tumors in China, and various therapeutic measures have poor curative effect. Pyruvate kinase type M2 is a key enzyme in the glycolytic pathway, and its abnormal expression in liver cancer is closely related to the proliferation, metastasis, diagnosis, treatment, prognosis, as well as drug and radiation resistance. Therefore, multi-pathway targeted regulation of pyruvate kinase type M2 use is expected to become a new direction for the treatment of primary liver cancer.


Generation of transgene-free lung disease-specific human induced pluripotent stem cells using a single excisable lentiviral stem cell cassette.
The development of methods to achieve efficient reprogramming of human cells while avoiding the permanent presence of reprogramming transgenes represents a critical step toward the use of induced pluripotent stem cells (iPSC) for clinical purposes, such as disease modeling or reconstituting therapies. Although several methods exist for generating iPSC free of reprogramming transgenes from mouse cells or neonatal normal human tissues, a sufficiently efficient reprogramming system is still needed to achieve the widespread derivation of disease-specific iPSC from humans with inherited or degenerative diseases. Here, we report the use of a humanized version of a single lentiviral "stem cell cassette" vector to accomplish efficient reprogramming of normal or diseased skin fibroblasts obtained from humans of virtually any age. Simultaneous transfer of either three or four reprogramming factors into human target cells using this single vector allows derivation of human iPSC containing a single excisable viral integration that on removal generates human iPSC free of integrated transgenes. As a proof of principle, here we apply this strategy to generate >100 lung disease-specific iPSC lines from individuals with a variety of diseases affecting the epithelial, endothelial, or interstitial compartments of the lung, including cystic fibrosis, α-1 antitrypsin deficiency-related emphysema, scleroderma, and sickle-cell disease. Moreover, we demonstrate that human iPSC generated with this approach have the ability to robustly differentiate into definitive endoderm in vitro, the developmental precursor tissue of lung epithelia.


Ankle-Foot-Orthosis "Hermes" Compensates Pathological Ankle Stiffness of Chronic Stroke-A Proof of Concept.
Individuals with an upper motor neuron syndrome, e.g., stroke survivors, may have a pathological increase of passive ankle stiffness due to spasticity, that impairs ankle function and activities such as walking. To improve mobility, walking aids such as ankle-foot orthoses and orthopaedic shoes are prescribed. However, these walking aids generally limit the range of motion (ROM) of the foot and may therewith negatively influence activities that require a larger ROM. Here we present a new ankle-foot orthosis "Hermes", and its first experimental results from four hemiparetic chronic stroke patients. Hermes was designed to facilitate active ankle dorsiflexion by mechanically compensating the passive ankle stiffness using a negative-stiffness mechanism. Four levels of the Hermes' stiffness compensation (0%, 35%, 70% and 100%) were applied to evaluate active ROM in a robotic ankle manipulator and to test walking feasibility on an instrumented treadmill, in a single session. The robotic tests showed that Hermes successfully compensated the ankle joint stiffness in all four patients and improved the active dorsiflexion ROM in three patients. Three patients were able to walk with Hermes at one or more Hermes' stiffness compensation levels and without reducing their preferred walking speeds compared to those with their own walking aids. Despite a small sample size, the results show that Hermes holds great promise to support voluntary ankle function and to benefit walking and daily activities.


Ovarian dermoid cyst-associated autoimmune hemolytic anemia: a case report with emphasis on pathogenic mechanisms.
Autoimmune hemolytic anemia (AIHA) as a manifestation of ovarian dermoid cyst (ODC) is a rare paraneoplastic syndrome of unknown pathogenesis. Among mechanisms postulated to explain this association, cross-reactivity between cyst and red blood cell (RBC) antigens, and local production of RBC autoantibodies by intracyst B lymphocytes are the most likely. Studies to test these hypothesis were done in a patient diagnosed of AIHA associated with a nonpalpable ODC, in whom the AIHA subsided after tumor excision. The RBC-bound autoantibody was an IgG directed against the Rh complex. The cyst's fluid content lacked detectable RBC autoantibodies or immunoglobulins, the latter being measured by a high-sensitivity assay. It also failed to inhibit the ability of the purified autoantibody to agglutinate RBCs. Ovarian dermoid cyst histology disclosed that (1) the biotin-labelled RBC autoantibody did not bind to ODC structures; (2) scanty amounts of small mature lymphocytes (50% CD45RO+; 50% CD20+) were present only in a few tissue sections; (3) plasma cells producing IgM or IgG were extremely scarce; and (4) deposits of immunoglobulins were not detected into the ODC. These data fail to support any of the aforementioned hypotheses on the pathogenesis of this paraneoplastic syndrome. Other possible mechanisms are discussed, and a wider use of imaging diagnosis to search for ODC in women with AIHA is emphasized.


Structural insight into the ligand specificity of a thermostable family 51 arabinofuranosidase, Araf51, from Clostridium thermocellum.
The digestion of the plant cell wall requires the concerted action of a diverse repertoire of enzyme activities. An important component of these hydrolase consortia are arabinofuranosidases, which release L-arabinofuranose moieties from a range of plant structural polysaccharides. The anaerobic bacterium Clostridium thermocellum, a highly efficient plant cell wall degrader, possesses a single alpha-L-arabinofuranosidase (EC 22.214.171.124), CtAraf51A, located in GH51 (glycoside hydrolase family 51). The crystal structure of the enzyme has been solved in native form and in 'Michaelis' complexes with both alpha-1,5-linked arabinotriose and alpha-1,3 arabinoxylobiose, both forming a hexamer in the asymmetric unit. Kinetic studies reveal that CtAraf51A, in contrast with well-characterized GH51 enzymes including the Cellvibrio japonicus enzyme [Beylot, McKie, Voragen, Doeswijk-Voragen and Gilbert (2001) Biochem. J. 358, 607-614], catalyses the hydrolysis of alpha-1,5-linked arabino-oligosaccharides and the alpha-1,3 arabinosyl side chain decorations of xylan with equal efficiency. The paucity of direct hydrogen bonds with the aglycone moiety and the flexible conformation adopted by Trp(178), which stacks against the sugar at the +1 subsite, provide a structural explanation for the plasticity in substrate specificity displayed by the clostridial arabinofuranosidase.


An audit of pressure sores caused by intermittent compression devices used to prevent venous thromboembolism.
When intermittent compression devices (ICDs) are used to prevent venous thromboembolism (VTE) they can cause pressure sores in a selected group of women, undergoing long operations. A prospective audit pre and post intervention showed a reduced risk with an alternative device, without increasing the risk of VTE.


Lung transplantation for patients with end-stage Sauropus androgynus-induced bronchiolitis obliterans (SABO) syndrome.
Sauropus androgymus (SA), a vegetable of the Euphorbiaceae family, is a common food source in Malaysia. In Taiwan, over 30 patients have developed progressive respiratory failure after consuming the extract from raw SA leaves as a means of losing weight. Symptoms consistent with a severe obstructive ventilatory defect progressed, despite cessation of SA intake and treatment with bronchodilators, corticosteroids, cytotoxic agents and plasmaphresis. Five patients with end-stage Sauropus androgynus-induced bronchiolitis obliterans (SABO) syndrome underwent lung transplantation. There was no early mortality. One patient died of post-transplant lymphoproliferative disorder and another patient died of bronchial stenosis with infection, 5 and 3.5 months, respectively, post-transplantation. The remaining 3 patients have been followed from 29 to 34 months, with improved general condition and pulmonary function. Perfusion/ventilation scans revealed that these improvements were exclusively attributed to the functional grafts. We believe that lung transplantation is the only effective modality of treatment for patients with end-stage SABO syndrome.


Photoinduced reduction of manganese(III) meso-tetrakis(1-methylpyridinium-4-yl)porphyrin at AT and GC base pairs.
The photoreduction of water-soluble cationic manganese(III) meso-tetrakis(1-methylpyridium-4-yl)porphyrin (Mn(III)(TMPyP)(4+)) bound to a synthetic polynucleotide, either poly[d(A-T)2] or poly[d(G-C)2], was examined by conventional absorption and circular dichroism (CD) spectroscopy, transient absorption, and transient Raman spectroscopy. Upon binding, Mn(III)(TMPyP)(4+) produced a positive CD signal for both polynucleotides, suggesting external binding. In the poly[d(A-T)2]-Mn(III)(TMPyP)(4+) adduct case, an interaction between the bound porphyrin was suggested. The transient absorption spectral features of Mn(III)(TMPyP)(4+) in the presence of poly[d(A-T)2] and poly[d(G-C)2] were similar to those of the photoreduced products, Mn(II)(TMPyP)(4+), whereas Mn(III)(TMPyP)(4+) in the absence of polynucleotides retained its oxidation state. This indicated that both poly[d(A-T)2] and poly[d(G-C)2] act as electron donors, resulting in photo-oxidized G and A bases. The transient Raman bands (ν2 and ν4) that were assigned to porphyrin macrocycles exhibited a large downshift of ~25 cm(-1), indicating the photoreduction of Mn(III) to Mn(II) porphyrins when bound to both polynucleotides. The transient Raman bands for pyridine were enhanced significantly, suggesting that the rotation of peripheral groups for binding with polynucleotides is the major change in the geometry expected in the photoreduction process. These photoinduced changes do not appear to be affected by the binding mode of porphyrin.


Urban and agricultural sources of pyrethroid insecticides to the Sacramento-San Joaquin Delta of California.
While studies have documented the presence of pyrethroid insecticides at acutely toxic concentrations in sediments, little quantitative data on sources exist. Urban runoff, municipal wastewater treatment plants and agricultural drains in California's Sacramento-San Joaquin River Delta were sampled to understand their importance as contributors of these pesticides to surface waters. Nearly all residential runoff samples were toxic to the amphipod, Hyalella azteca, and contained pyrethroids at concentrations exceeding acutely toxic thresholds, in many cases by 10-fold. Toxicity identification evaluation data were consistent with pyrethroids, particularly bifenthrin and cyfluthrin, as the cause of toxicity. Pyrethroids passed through secondary treatment systems at municipal wastewater treatment facilities and were commonly found in the final effluent, usually near H. azteca 96-h EC(50) thresholds. Agricultural discharges in the study area only occasionally contained pyrethroids and were also occasional sources of toxicity related to the organophosphate insecticide chlorpyrifos. Discharge of the pyrethroid bifenthrin via urban stormwater runoff was sufficient to cause water column toxicity in two urban creeks, over at least a 30 km reach of the American River, and at one site in the San Joaquin River, though not in the Sacramento River.


[Comparative study of lymphocyte non-histone proteins].
The non-histone chromosomal proteins of bovine lymphocytes were investigated by the two dimensional gel electrophoresis of O'Farrell. The 0.35 M NaCl extractable proteins from lymphocyte nuclei, the high mobility group proteins (HMG) and some proteins released from nuclei by DNase I were compared on the basis of their electrophoretic patterns.


Cellular mechanisms of protection and repair induced by radiation exposure and their consequences for cell system responses.
The complex biological systems that constitute living organisms operate at various levels of organization, from the atomic-molecular to the cellular to the organ-organism level. The response of an organism to disturbances that are detrimental to structure and function generally begin at the level of organization where the primary injury has occurred. Detriment that occurs from simultaneous or sequential, or single or multiple interactions at a relatively low level of organization tends to be transferred to higher levels. However, at each level of organization there is a given probability of such detriment being removed according to the tolerance to injury that is peculiar to that level. There is thus a direct relationship between the frequency of injurious events at a lower level of organization, and the degree of structural complexity of the system at the high level at which such detriment is eventually manifested. The extent of structural disruption at any given level determines the degree of functional failure at that level. In the exposure of tissue to ionization radiation, the primary injury begins with energy deposition events (tracks or hits) consisting of many ionizations and excitations in localized clusters of submicroscopic dimensions at the atomic-molecular level of organization within the cell, and the cell is affected as a whole. The cell is the elementary unit of life and the sum of the individual cell responses determines the response of the tissue and the organism. Individual cell responses are nevertheless found to differ in type and degree depending on the absorbed dose. With decreasing values of absorbed dose to the tissue, the probability of a cell being hit by an energy deposition event decreases linearly. At very low values of absorbed dose to tissue, only a fraction of the total cell population experiences single hits and these are of different sizes. The size distribution or spectrum of these hits is invariant, independent of their total number over a considerable range at low-dose levels and is determined only by the type and quality of the given radiation. The probability that a hit cell will suffer a given detriment such as a chromosomal aberration, gene mutation or death has been shown to increase in a sigmoid fashion with increasing hit size.(ABSTRACT TRUNCATED AT 400 WORDS)


A stochastically curtailed single-arm phase II trial design for binary outcomes.
Phase II clinical trials are a critical aspect of the drug development process. With drug development costs ever increasing, novel designs that can improve the efficiency of phase II trials are extremely valuable.Phase II clinical trials for cancer treatments often measure a binary outcome. The final trial decision is generally to continue or cease development. When this decision is based solely on the result of a hypothesis test, the result may be known with certainty before the planned end of the trial. Unfortunately, there is often no opportunity for early stopping when this occurs.Some existing designs do permit early stopping in this case, accordingly reducing the required sample size and potentially speeding up drug development. However, more improvements can be achieved by stopping early when the final trial decision is very likely, rather than certain, known as stochastic curtailment. While some authors have proposed approaches of this form, these approaches have various limitations.In this work we address these limitations by proposing new design approaches for single-arm phase II binary outcome trials that use stochastic curtailment. We use exact distributions, avoid simulation, consider a wider range of possible designs and permit early stopping for promising treatments. As a result, we are able to obtain trial designs that have considerably reduced sample sizes on average.


Exploring the Developmental Impact of Cystic Fibrosis on Lung Transplant Candidacy: Considerations for Adulthood.
The average life expectancy for cystic fibrosis (CF) has increased over the past four decades resulting in a higher rate of adult CF patients. Adults seeking lung transplant to address CF-related advanced lung disease (ALD) represent a small, yet growing, subset of lung transplant recipients. Psychosocial factors such as adherence to medical recommendations, self-management of medical care, and caregiver support have been identified as positive prognostic factors in lung transplant outcomes. These factors are also implicated in the pediatric chronic illness literature and are crucial as patients begin to transition to a more autonomous and independent role in their own health management. Adults with CF facing ALD must navigate through another transitional phase as lung transplant requires additional supports and new expectations. A case series is used to highlight specific psychosocial considerations in this population and to explore the seemingly dichotomous relationship between independent self-management and caregiver support.


Antinociceptive and anti-inflammatory activities of the essential oil of Nepeta crispa Willd. in experimental rat models.
This study was conducted to evaluate the antinociceptive and anti-inflammatory activities of the essential oil of Nepeta crispa. The study was done using the tail-flick and formalin test pain models and the paw oedema model of inflammation. Male Wistar rats were used as the animal model. The essential oil dose-dependently produced analgesia in the acute pain models, including the tail-flick (p < 0.001) and the first phase of the formalin test (p < 0.01). In the late phase of the formalin test, as a model of chronic pain, the essential oil significantly reduced the pain-induced behaviour (p < 0.01). Nepeta crispa essential oil caused potent anti-inflammatory effects in the formalin-induced paw inflammation model and significantly reduced the paw oedema in all applied doses (p < 0.01). Its effects on pain in both the acute and chronic pain models and its anti-inflammatory effect suggest both central and peripheral mechanisms of action for the essential oil obtained from N. crispa.


Effect of perindopril on coronary remodelling: insights from a multicentre, randomized study.
This study sought to evaluate the effect of perindopril in coronary remodelling. In this sub-study of a double-blind, multicentre trial, patients without clinical evidence of heart failure were randomized to perindopril 8 mg/day or placebo for at least 3 years and IVUS investigation was performed at both time-points. Positive and negative remodelling were defined as a relative increase (positive remodelling) or decrease (negative remodelling) of the mean vessel cross-sectional area (CSA)>2 SD of the mean intra-observer difference. A total of 118 matched evaluable IVUS (711 matched 5 mm segments) were available at follow-up. After a median follow-up of 3.0 (inter-quartile range 1.9, 4.1) years, there was no significant difference in the change of plaque CSA between perindopril (360 segments) and placebo (351 segments) groups, P=0.27. Conversely, the change in vessel CSA was significantly different between groups (perindopril -0.18+/-2.4 mm2 vs. placebo 0.19+/-2.4, P = 0.04). Negative remodelling occurred more frequently in the perindopril than in the placebo group (34 vs. 25%, P=0.01). In addition, the placebo group showed a larger, although not significant, mean remodelling index (RI) than the perindopril group (1.03+/-0.2 vs. 1.00+/-0.2, P=0.06). The temporal change in vessel dimensions assessed by the RI was significantly correlated with the change in plaque dimensions (r=0.48, P<0.0001). In this sub-analysis of a multicentre, controlled study, long-term administration of perindopril was associated with a constrictive remodelling pattern without affecting the lumen.


Large variabilities in host strain susceptibility and phage host range govern interactions between lytic marine phages and their Flavobacterium hosts.
Phages are a main mortality factor for marine bacterioplankton and are thought to regulate bacterial community composition through host-specific infection and lysis. In the present study we demonstrate for a marine phage-host assemblage that interactions are complex and that specificity and efficiency of infection and lysis are highly variable among phages infectious to strains of the same bacterial species. Twenty-three Bacteroidetes strains and 46 phages from Swedish and Danish coastal waters were analyzed. Based on genotypic and phenotypic analyses, 21 of the isolates could be considered strains of Cellulophaga baltica (Flavobacteriaceae). Nevertheless, all bacterial strains showed unique phage susceptibility patterns and differed by up to 6 orders of magnitude in sensitivity to the same titer of phage. The isolated phages showed pronounced variations in genome size (8 to >242 kb) and host range (infecting 1 to 20 bacterial strains). Our data indicate that marine bacterioplankton are susceptible to multiple co-occurring phages and that sensitivity towards phage infection is strain specific and exists as a continuum between highly sensitive and resistant, implying an extremely complex web of phage-host interactions. Hence, effects of phages on bacterioplankton community composition and dynamics may go undetected in studies where strain identity is not resolvable, i.e., in studies based on the phylogenetic resolution provided by 16S rRNA gene or internal transcribed spacer sequences.


Pain assessment.
Pain usually is the major complaint of patients with problems of the back, thus making pain evaluation a fundamental requisite in the outcome assessment in spinal surgery. Pain intensity, pain-related disability, pain duration and pain affect are the aspects that define pain and its effects. For each of these aspects, different assessment instruments exist and are discussed in terms of advantages and disadvantages. Risk factors for the development of chronic pain have been a major topic in pain research in the past two decades. Now, it has been realised that psychological and psychosocial factors may substantially influence pain perception in patients with chronic pain and thus may influence the surgical outcome. With this background, pain acceptance, pain tolerance and pain-related anxiety as factors influencing coping strategies are discussed. Finally, a recommendation for a minimum as well as for a more comprehensive pain assessment is given.


A blessing and a curse. Nursing student admissions complicated by oversubscription.
Oversubscription of students in a professional nursing program complicates the admission selection process. Recommended improvements include: adopting a point scoring tool for selected criteria, using the college computer database, identifying student special consideration needs, downsizing the admissions committee, and raising the required GPA.


In Situ Generation of Pseudorutile Oxide as the Cathode for Direct Electrolysis of CO2.
The conversion of CO2 into CO in high-temperature solid oxide electrolysis cells (SOECs) is an attractive route for the CO2 utilization using the intermittent renewables. The low-cost and highly catalytic cathode is important for the direct electrolysis of pure CO2. In this study, non-perovskite Fe0.5Mg0.25+0.5xTi0.25-0.5xNb1-xMoxO4 oxides (denoted as Mo-x when x is equal to 0, 0.1, and 0.2) are evaluated as the cathode of an SOEC for the direct electrolysis of CO2. Mo6+ doping converted the wolframite Mo-0 into an α-PbO2-type with cation disordering, while further doping to Mo-0.2 showed a wolframite with cation ordering again. The SOEC with Mo-0.2 as the cathode exhibits the best electrochemical performance for the direct electrolysis of CO2 as a large portion of the oxide converted into oxygen-deficient pseudorutile-type oxide with a nominal formula of M5O9 (M = cation). The pseudorutile, a crystallographic shear phase of rutile, can be obtained after 60 h of direct electrolysis in CO2 at a 1.3 V bias rather than a reduction under 5% H2. The SOEC with Mo-0.2 as the cathode imparted a stable current density of 0.45 A cm-2, which could be related to the production of pseudorutile decorated with nanoparticles of MoO2. These results show that molybdenum doping is an effective strategy for developing oxygen-deficient rutile (pseudorutile) for the electrolysis of CO2.


Global Perspective of Plant-Based Cosmetic Industry and Possible Contribution of Sri Lanka to the Development of Herbal Cosmetics.
The global consumption of plant-based cosmetics has shown spectacular growth in recent years because of rising consumer awareness regarding the long-term health benefits of natural ingredients. As the global demand for herbal cosmetics increases, there are ample opportunities for Sri Lanka as a tropical Asian country to expand its productions and global exports along with its unique biodiversity and inherited traditional knowledge. Therefore, the present review attempts to give an overview of the widely used medicinal plants in the global herbal cosmetic industry and strengths, challenges, and possible solutions for the development of the herbal cosmetic industry of Sri Lanka. Information was collected using electronic search (using Pub Med, Science Direct, Web of Science, Google Scholar, TEEAL, and Scopus) for articles published in peer-reviewed journals, industrial reports, market surveys, and library search for local books on ethnobotany. Important plant-derived ingredients used in the global herbal cosmetic industry are essential oils, colorants, oils, fats, and waxes. The traditional usage of 108 medicinal plant species (belonging to 58 families) in cosmetic treatments was identified from the local books of Sri Lanka. Of these, 49 plant species were reported as new ingredients for the herbal cosmetic industry. However, the lack of ethnobotanical and ethnopharmacological surveys to identify the cosmetic potential plants, insufficient or absence of continuous supply of raw materials for production in line with the existing demand, the lack of quality control of raw materials and finished cosmetic products, improper systematic cultivation systems for medicinal plants, poor postharvest practices, and the lack of innovations are major challenges encountered in Sri Lanka for the development of the herbal cosmetic industry. In conclusion, addressing these vital knowledge gaps is a timely requirement of the country for the sustainable development of the herbal cosmetic industry in Sri Lanka. Furthermore, assembling of the multidisciplinary cooperation of botanists, chemists, toxicologists, researchers, and biologists is crucial to analyze the interesting functional properties, efficacy, and effectiveness of documented medicinal plants with cosmetic potential.


An investigation report about the lack of VB1.
From August 1 to September 26, 2012, 30 workers who had the symptom of edema in both lower limbs were reported in Yancheng, Four severe edemas in both lower limbs workers were sent to the hospital, and one person of the workers died. The epidemiology investigation and laboratory testing (in the urine loading tests, the concentration of VB1 of the workers living in the factory for more than half of the year decreased far below the normal values) were conducted to explore the cause. Furthermore, after one-week intramuscular injection of thiamine treatment, the clinical symptoms of the workers had been improved greatly. Finally, the lake of the thiamine (VB1) was considered to be the reason of this incident.


A comparison of folic acid and 5-methyltetrahydrofolate for prevention of DNA damage and cell death in human lymphocytes in vitro.
Folic acid (FA), the most oxidized and stable form of folate, is commonly used as a dietary supplement and in culture media. FA must be reduced and methylated to become the metabolically active form found in blood and utilized by tissues, i.e. 5-methyltetrahydrofolate (5-MeTHF). 5-MeTHF is the methyl group donor required for the conversion of homocysteine to methionine catalyzed by vitamin B(12)-dependent methionine synthase. It is hypothesized that 5-MeTHF may be more effective than FA in reducing spontaneous DNA damage and improving cell proliferation because, unlike FA, it can donate a methyl group for methionine synthesis, which is required for cell division via polyamine production and for maintenance methylation of DNA after its conversion to S-adenosylmethionine. We aimed to determine whether FA and 5-MeTHF differed in their capacity to prevent genetic damage and cell proliferation of human lymphocytes in vitro. Lymphocytes from eight female volunteers (40-48 years) were cultured in RPMI 1640 medium containing 12-120 nM FA or 5-MeTHF for 9 days. Mitogenesis was stimulated with phytohemagglutinin and the medium changed on days 3 and 6. Cytokinesis was inhibited by adding cytochalasin B on day 8 and cells were harvested and transferred to microscope slides on day 9. Chromosome damage, cell death and cytostasis was measured using the cytokinesis-block micronucleus assay in its comprehensive mode. The results showed that the frequency of micronucleated binucleate cells was significantly lower at 120 nM FA compared with 120 nM 5-MeTHF (P < 0.05), however, at 12 nM concentration both forms of folate were associated with increased frequency of micronuclei and nuclear buds relative to 120 nM (P < 0.05). Apoptosis tended to be significantly higher in 5-MeTHF cultures compared with FA cultures, however, necrosis and nuclear division were similar between cultures. We conclude that 5-MeTHF is not more efficient than FA in preventing human lymphocyte genomic instability in this in vitro system. Further research is needed to clarify the role of choline and methionine concentration and the importance of the reduced folate carrier and the folate receptor in determining the relative bioavailability of 5-MeTHF and FA with regard to genome stability.


The pedicle screw-rod system is an acceptable method of reconstructive surgery after resection of sacroiliac joint tumours.
Hemipelvic resections for primary bone tumours require reconstruction to restore weight bearing along anatomic axes. However, reconstruction of the pelvic arch remains a major surgical challenge because of the high rate of associated complications. We used the pedicle screw-rod system to reconstruct the pelvis, and the purpose of this investigation was to assess the oncology, functional outcome and complication rate following this procedure. The purpose of this study was to investigate the operative indications and technique of the pedicle screw-rod system in reconstruction of the stability of the sacroiliac joint after resection of sacroiliac joint tumours. The average MSTS (Musculoskeletal Tumour Society) score was 26.5 at either three months after surgery or at the latest follow-up. Seven patients had surgery-related complications, including wound dehiscence in one, infection in two, local necrosis in four (including infection in two), sciatic nerve palsy in one and pubic symphysis subluxation in one. There was no screw loosening or deep vein thrombosis occurring in this series. Using a pedicle screw-rod after resection of a sacroiliac joint tumour is an acceptable method of pelvic reconstruction because of its reduced risk of complications and satisfactory functional outcome, as well as its feasibility of reconstruction for type IV pelvis tumour resection without elaborate preoperative customisation. Level IV, therapeutic study.


Recent advances in immunohematology.
Knowledge of the biochemistry and genetics of erythrocyte blood group antigens has been growing rapidly over the past several years. Last year, the molecular basis for the major Rh blood group antigens was delineated. In addition, the genetic and biochemical bases of several other blood group antigens were identified. One of the most interesting matches of blood group antigens to a functional membrane protein was that of the Diego antigens to the erythrocyte anion channel (band 3) protein. In addition, knowledge of the molecular basis of blood group antigens is now leading rapidly to the usefulness of molecular techniques in identifying blood group genotypes and even blood group antibody specificities. This knowledge has also broadened our understanding of the pathogenesis of erythrocyte disorders associated with null blood group phenotypes. The diagnosis and treatment of autoimmune hemolytic anemia has seen slow but steady progress. New techniques appear promising as methods for distinguishing clinically important from benign autoantibodies. The molecular targets for erythrocyte autoantibodies were also largely identified. Treatment of autoimmune hemolytic anemia is also slowly being improved with the use of agents such as intravenous gammaglobulin, danazol, and immunosuppressive agents, all of which have also been important in the treatment of autoimmune thrombocytopenic purpura.


Puppets as a strategy for communication with Brazilian children with cancer.
Children are considered competent social actors. Although they are able to express their opinions, they may have some difficulties in answering direct verbal questions, requiring researchers and health professionals to enter their world by using auxiliary resources for communication. This study presents the experience of using finger puppets as a playful strategy for improving interaction and communication with hospitalized children with cancer, aged seven to 12. It describes the strategy of making and using puppets as an auxiliary tool to communicate with children with cancer and presents the results and limitations of using puppets in clinical practice. The use of the puppets, creatively and in accordance with the children's motor, cognitive, and emotional development, showed benefits, such as allowing the children to freely express themselves; respecting their autonomy; and minimizing the hierarchical adult-child relationship. The use of puppets is an appropriate strategy to communicate with hospitalized children. This tool can also enrich clinical practice, as it encourages children with cancer to report their experience of being ill and also helps the health team during evaluation and intervention.


Time Trends in Stroke and Subtypes Mortality Attributable to Household Air Pollution in Chinese and Indian Adults: An Age-Period-Cohort Analysis Using the Global Burden of Disease Study 2019.
Household air pollution (HAP) exposure is recognized as a major health concern in areas relied on residential burning of solid fuels for cooking and heating. However, previous study has focused on mortality across time and reported changes in age-specific mortality globally but failed to distinguish cohort from period effects. Therefore, this study aimed to differentiate the relative contributions of period and cohort effects to overall time trends of HAP-attributable stroke mortality between the most presentative East and South Asia countries. Data were obtained from the Global Burden of Disease (GBD) database. The age, period, and cohort effects were estimated using the age-period-cohort (APC) model. The overall age-standardized mortality rates (ASMRs) of stroke in China decreased by 39.8% compared with 35.8% in India, while stroke subtypes in both the sexes and countries showed consecutive significant declines from 1990 to 2019. The age-specific and cohort-specific HAP-attributable stroke mortality declined over time in China and India. By APC analysis, substantially increasing age effects were presented for stroke and subtypes from 25 to 84 years. China had a rapid reduction in the independent period and cohort effects. Also, the risk of death for subarachnoid hemorrhage (SAH) had the most striking decline for both sexes in period and cohort effects. Reductions of India were less favorable than China, but the independent period and cohort effects progressively decreased during the entire period for both the sexes. Males experienced a slightly higher mortality risk than females in both countries. Although prominent reductions were observed in HAP-attributable stroke and subtypes mortality during the past 30 years, China and India still suffered uneven HAP-attributable stroke burden. Thus, it is of high significance to introduce advanced solid fuels replace technology and knowledge regarding clean fuel use.


Digital RNA Sequencing of Human Epidermal Keratinocytes Carrying Human Papillomavirus Type 16 E7.
High-risk human papillomavirus (HPV) infections are the predominant cause of cervical cancer and its early gene E7 plays an important role in cellular proliferation and cell-cycle progression. While tremendous progress has been made in exploring the molecular mechanisms in late tumorigenesis, many pathways showing how HPV deregulates host gene expression in early inapparent infections and early tumorigenesis still remain undefined. Digital RNA sequencing was performed and a total of 195 differentially expressed genes were identified between the HPV16 E7-transfected NHEKs and control cells (p < 0.05, fold-change > 2). GO enrichment showed that HPV16 E7 primarily affected processes involved in anti-viral and immune responses, while KEGG pathway analysis showed enrichment of gene clusters of associated with HPV infection and MAPK signaling. Of the differentially expressed genes, IFI6, SLC39A9 and ZNF185 showed a strong correlation with tumor progression and patient survival in the OncoLnc database while roles for AKAP12 and DUSP5 in carcinogenesis and poor prognosis have previously been established for other cancer types. Our study identified several novel HPV16 E7-regulated candidate genes with putative functions in tumorigenesis, thus providing new insights into HPV persistence in keratinocytes and early onset of tumorigenesis.


Cerebrospinal Fluid Levels of AFP and hCG: Validation of the Analytical Method and Application in the Diagnosis of Central Nervous System Germ Cell Tumors.
The determination of Human Chorionic Gonadotropin (hCG) and Alpha Fetoprotein (AFP) levels on serum and amniotic fluid plays a fundamental role in the diagnosis and follow-up of specific physiological or pathological conditions (e.g., pregnancy, threat of abortion or germ cell tumors). Recently, the quantification of hCG and AFP in other biological fluids has gained great attention to support the diagnosis, prognosis and follow-up of neoplastic diseases deriving from trophoblastic cells, such as germinomas. Most of the commercial kits for hCG and AFP assays are developed to be used on biological fluids such as serum/plasma and/or urine by manufacturing companies. The aim of this work was to evaluate the suitability of the analytical method certified for the use on serum, and/or amniotic fluid for the quantification of hCG and AFP in cerebrospinal fluid, carrying out an internal validation protocol. The data reported here show that the automated immunochemical method is fit for quantification of hCG and AFP in cerebrospinal fluid (CSF), allowing selective and specific diagnosis of secreting germ cell tumors. This is confirmed by the positive correlation between elevated levels of hCG or AFP and the diagnosis of brain tumors.


Obesity-induced Lymphedema Nonreversible following Massive Weight Loss.
Lymphedema is the progressive enlargement of tissue due to inadequate lymphatic function. Obesity-induced lymphedema of the lower extremities can occur once a patient's body mass index (BMI) exceeds 50. We report our first patient with obesity-induced lower extremity lymphedema who was followed prospectively before and after weight loss. A 46-year-old woman with a BMI of 80 presented to our Lymphedema Program complaining of bilateral lower extremity swelling. Lymphoscintigraphy showed impaired lymphatic drainage of both lower extremities consistent with lymphedema. She was referred to a bariatric surgical weight-loss center and underwent a sleeve gastrectomy. After reaching her new steady-state BMI of 36 eighteen months following her procedure, lymphoscintigraphy showed no improvement in lower extremity lymphatic function. Patients at risk for obesity-induced lymphedema should be counseled that they should seek weight-loss interventions before their BMI reaches 50, a threshold at which point lower extremity lymphedema may occur. Unlike other comorbidities that reverse following massive weight loss, obesity-induced lymphedema may not resolve.


Zoogloea dura sp. nov., a N2-fixing bacterium isolated from forest soil and emendation of the genus Zoogloea and the species Zoogloea oryzae and Zoogloea ramigera.
A motile, Gram-stain-negative, rod-shaped bacterium, designated G-4-1-14T, was obtained from forest soil sampled at Gwanggyo mountain, Gyeonggi-do, Republic of Korea. Cells were colourless, aerobic, grew optimally at 28-35 °C and hydrolysed DNA and casein. Phylogenetic analysis based on its 16S rRNA gene sequence revealed that strain G-4-1-14T formed a lineage within the genus Zoogloea. The closest members were Zoogloea resiniphila ATCC 70068T (98.6 % sequence similarity), Zoogloea caeni EMB43T (98.2 %), Zoogloea oryzae A-7T (97.7 %), Zoogloea ramigera IAM 12136T (96.9 %) and Zoogloea oleivorans BucT (96.2 %). The major respiratory quinone was ubiquinone-8 and the principal polar lipids were phosphatidylethanolamine, phosphatidyl-N-methylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. The predominant cellular fatty acids were summed feature 3 (iso-C15 :0 2-OH/C16 : 1 ω7c) and C16 : 0. The DNA G+C content was 65.9 mol%. The average nucleotide identity and digital DNA-DNA hybridization relatedness values between strain G-4-1-14T and other type strains were ≤81.6 and ≤24.9 %, respectively, which are below the species demarcation thresholds. Based on the results of phenotypic, phylogenetic and genomic analyses, strain G-4-1-14T represents a novel species in the genus Zoogloea, for which the name Zoogloea dura sp. nov. is proposed. The type strain is G-4-1-14T (=KACC 21618T=NBRC 114358T). In addition, we propose emendation of the genus Zoogloea and the species Zoogloea oryzae and Zoogloea ramigera.


Roles of microRNA-206 in osteosarcoma pathogenesis and progression.
MicroRNA-206 has proven to be down-regulated in many human malignancies in correlation with tumour progression. Our study aimed to characterize miR-206 contributions to initiation and malignant progression of human osteosarcoma. MiR-206 expression was detected in human osteosarcoma cell line MG63, human normal osteoblastic cell line hFOB 1.19, and paired osteosarcoma and normal adjacent tissues from 65 patients using quantitative RT-PCR. Relationships of miR-206 levels to clinicopathological characteristics were also investigated. Moreover, miR-206 mimics and negative control siRNA were transfected into MG63 cells to observe effects on cell viability, apoptosis, invasion and migration. We found that miR-206 was down-regulated in the osteosarcoma cell line MG63 and primary tumor samples, and decreased miR-206 expression was significantly associated with advanced clinical stage, T classification, metastasis and poor histological differentiation. Additionally, transfection of miR-206 mimics could reduce MG- 63 cell viability, promote cell apoptosis, and inhibit cell invasion and migration. These findings indicate that miR-206 may have a key role in osteosarcoma pathogenesis and development. It could serve as a useful biomarker for prediction of osteosarcoma progression, and provide a potential target for gene therapy.


Use of speech-to-text technology for documentation by healthcare providers.
Medical records are a critical component of a patient's treatment. However, documentation of patient-related information is considered a secondary activity in the provision of healthcare services, often leading to incomplete medical records and patient data of low quality. Advances in information technology (IT) in the health system and registration of information in electronic health records (EHR) using speechto- text conversion software have facilitated service delivery. This narrative review is a literature search with the help of libraries, books, conference proceedings, databases of Science Direct, PubMed, Proquest, Springer, SID (Scientific Information Database), and search engines such as Yahoo, and Google. I used the following keywords and their combinations: speech recognition, automatic report documentation, voice to text software, healthcare, information, and voice recognition. Due to lack of knowledge of other languages, I searched all texts in English or Persian with no time limits. Of a total of 70, only 42 articles were selected. Speech-to-text conversion technology offers opportunities to improve the documentation process of medical records, reduce cost and time of recording information, enhance the quality of documentation, improve the quality of services provided to patients, and support healthcare providers in legal matters. Healthcare providers should recognize the impact of this technology on service delivery.


Ganoderma atrum polysaccharide improves age-related oxidative stress and immune impairment in mice.
The aim of the present study was to investigate whether oxidative stress and immune dysfunction could be attenuated by Ganoderma atrum polysaccharide (PSG-1) in d-galactose (d-gal)-induced aging mice, and provide evidence for its effects. The results showed that PSG-1 significantly decreased lipid peroxidation in liver, brain, and spleen, but concomitantly increased the activities of superoxide dismutase, catalase, and glutathione peroxidase compared with the d-gal group. Elevation of glutathione contents and attenuation of glutathione disulfide contents were also found in PSG-1-treated animals. Furthermore, the results showed that PSG-1 treatment increased basal lymphocyte proliferation as well as T cell and B cell proliferation and enhanced interleukin-2 production. Taken together, the results suggested that PSG-1 had potential as a novel agent to promote health and improve aging-associated pathologies, at least in part, via modification of the redox system and improvement of immune function.


Exposure to the herbicide 2,4-D produces different toxic effects in two different phytoplankters: A green microalga (Ankistrodesmus falcatus) and a toxigenic cyanobacterium (Microcystis aeruginosa).
The extensive use of 2,4-dichlorophenoxiacetic acid (2,4-D) in agriculture is an important source of pollution to water and soil. Toxicity of commonly used herbicides to non-target, planktonic photosynthetic organisms has not been described completely yet. Therefore, we determined the effect of subinhibitory 2,4-D concentrations on the Chlorophycean alga Ankistrodesmus falcatus and on a toxigenic strain of the cyanobacterium Microcystis aeruginosa. Population growth, photosynthetic pigments, macromolecular biomarkers (carbohydrates, lipids, and protein), and antioxidant enzymes (catalase [CAT], glutathione peroxidase [GPx], and superoxide dismutase [SOD]) were quantified, and the integrated biomarker response (IBR) was calculated. Scanning electron microscope (SEM) and transmission electron microscope (TEM) observations were also performed. The 96-h median inhibitory concentration (IC50) for 2,4-D was 1353.80 and 71.20mgL-1 for the alga and the cyanobacterium, respectively. Under 2,4-D stress, both organisms increased pigments and macromolecules concentration, modified the activity of all the evaluated enzymes, and exhibited ultrastructural alterations. M. aeruginosa also increased microcystins production, and A. falcatus showed external morphological alterations. The green alga was tolerant to high concentrations of the herbicide, whereas the cyanobacterium exhibited sensitivity comparable to other phytoplankters. Both organisms were tolerant to comparatively high concentrations of the herbicide; however, negative effects on the assessed biomarkers and cell morphology were significant. Moreover, stimulation of the production of cyanotoxins under chemical stress could increase the risk for the biota in aquatic environments, related to herbicides pollution in eutrophic freshwater ecosystems.


Interstimulus interval and the selective-attention effect on auditory ERPs: "N1 enhancement" versus processing negativity.
The attention effect on the auditory event-related potential (ERP) in dichotic conditions was studied as a function of the interstimulus interval (ISI). Subjects attended to stimuli delivered to a designated ear and responded to infrequent pitch deviants in this input. The mean ISI was either 80, 160, 480, or 800 ms. Negative difference waves (Nds) were computed by subtracting ERPs to unattended standards from ERPs to the same stimuli when attended. The exogenous N1, as estimated from unattended standard ERPs, was larger contralaterally to the stimulus and inverted in polarity at mastoids. With decreasing ISIs, N1 diminished in amplitude much faster than did the Nd. In addition, N1 latency remained stable, whereas Nd peaked markedly earlier with shorter ISIs, almost perfectly coinciding with the exogenous N1. However, this temporal coincidence found in grand averages proved to be illusory in single subjects. The early Nd showed no contralateral asymmetry at its peak, but asymmetry was apparent during the ascending slope. These lateral asymmetries resembled those of the exogenous N1 but occurred later. The early Nd peak was, at least mainly, caused by an endogenous attention effect, the processing negativity (PN), even with very short ISIs, but an effect on the exogenous N1 could not be excluded.


Maximizing Photoluminescence Extraction in Silicon Photonic Crystal Slabs.
Photonic crystal modes can be tailored for increasing light matter interactions and light extraction efficiencies. These PhC properties have been explored for improving the device performance of LEDs, solar cells and precision biosensors. Tuning the extended band structure of 2D PhC provides a means for increasing light extraction throughout a planar device. This requires careful design and fabrication of PhC with a desirable mode structure overlapping with the spectral region of emission. We show a method for predicting and maximizing light extraction from 2D photonic crystal slabs, exemplified by maximizing silicon photoluminescence (PL). Systematically varying the lattice constant and filling factor, we predict the increases in PL intensity from band structure calculations and confirm predictions in micro-PL experiments. With the near optimal design parameters of PhC, we demonstrate more than 500-fold increase in PL intensity, measured near band edge of silicon at room temperature, an enhancement by an order of magnitude more than what has been reported.


Leveraging genetically simple traits to identify small-effect variants for complex phenotypes.
Polymorphisms underlying complex traits often explain a small part (less than 1 %) of the phenotypic variance (σ2P). This makes identification of mutations underling complex traits difficult and usually only a subset of large-effect loci are identified. One approach to identify more loci is to increase sample size of experiments but here we propose an alternative. The aim of this paper is to use secondary phenotypes for genetically simple traits during the QTL discovery phase for complex traits. We demonstrate this approach in a dairy cattle data set where the complex traits were milk production phenotypes (fat, milk and protein yield; fat and protein percentage in milk) measured on thousands of individuals while secondary (potentially genetically simpler) traits are detailed milk composition traits (measurements of individual protein abundance, mineral and sugar concentrations; and gene expression). Quantitative trait loci (QTL) were identified using 11,527 Holstein cattle with milk production records and up to 444 cows with milk composition traits. There were eight regions that contained QTL for both milk production and a composition trait, including four novel regions. One region on BTAU1 affected both milk yield and phosphorous concentration in milk. The QTL interval included the gene SLC37A1, a phosphorous antiporter. The most significant imputed sequence variants in this region explained 0.001 σ2P for milk yield, and 0.11 σ2P for phosphorus concentration. Since the polymorphisms were non-coding, association mapping for SLC37A1 gene expression was performed using high depth mammary RNAseq data from a separate group of 371 lactating cows. This confirmed a strong eQTL for SLC37A1, with peak association at the same imputed sequence variants that were most significant for phosphorus concentration. Fitting any of these variants as covariables in the association analysis removed the QTL signal for milk production traits. Plausible causative mutations in the casein complex region were also identified using a similar strategy. Milk production traits in dairy cows are typical complex traits where polymorphisms explain only a small portion of the phenotypic variance. However, here we show that these mutations can have larger effects on secondary traits, such as concentrations of minerals, proteins and sugars in the milk, and expression levels of genes in mammary tissue. These larger effects were used to successfully map variants for milk production traits. Genetically simple traits also provide a direct biological link between possible causal mutations and the effect of these mutations on milk production.


Molecular characterisation of the pifC gene encoding translation initiation factor 3, which is required for normal photosynthetic complex formation in Rhodobacter sphaeroides NCIB 8253.
In order to determine whether translation initiation events play a selective role in regulating the expression of photosynthetic complexes in the photosynthetic bacterium Rhodobacter sphaeroides, we have undertaken an initial study to investigate the potential role of translation initiation factor IF3, which also behaves as a pleiotropic regulatory factor in some bacteria. Following the isolation and purification of a 24-kDa IF3-like protein (PifC) from R. sphaeroides, we used nested PCR to clone and characterise the encoding gene, pifC (photosynthesis-affecting initiation factor). The 545-bp pifC encodes a protein exhibiting 60% identity (78.6% similarity) with the Escherichia coli IF3 (InfC) protein and, in common with all other IF3 genes identified to date, pifC possesses a rare initiation codon (AUA). Furthermore, in common with IF3, PifC was shown here to perform a discriminatory function towards CUG start codons, confirming its role and function as an IF3 in R. sphaeroides. Insertion of a kanamycin resistance cassette into the 5' end of pifC resulted in a viable phenotype which exhibits growth rates similar to wild type but which possesses reduced bacteriochlorophyll and photosynthetic complexes in semi-aerobic cultures. It is shown here that the mutant is still able to produce a PifC protein but that it possesses reduced IF3 activity. This may account for the viable nature of the mutant strain, and may indicate that the effect of the mutation on photosynthesis can be more severe than shown in the present study. The mechanisms by which PifC may exert its selective regulatory effect on photosynthesis expression are discussed.


Digital Wings: Innovations in Transition Readiness for Adolescent and Young Adult Transplant Recipients [corrected].
The Johns Hopkins University School of Medicine organized 2 multistakeholder symposia on February 2, 2018 and January 11, 2019 to address the problem of high graft failure in adolescent and young adult (AYA) solid organ transplant (SOT) recipients. Participants included international experts in transplantation, behavioral psychology, patient/parent advocacy, and technology. The objectives of the symposia were as follows: (1) to identify and discuss the barriers to and facilitators of effective transfer of care for AYA SOT recipients; (2) to actively explore strategies and digital solutions to promote their successful transfer of care; and (3) to develop meaningful partnerships for the successful development, evaluation, implementation, and dissemination of these digital solutions. Additionally, data were collected from 152 AYA SOT recipients demonstrating a substantial gap in how this population uses technologies for health-related activities, alongside an increased interest in an app to help them manage their transplant.


Proline cis-trans isomerization and protein folding.
Proline cis-trans isomerization plays a key role in the rate-determining steps of protein folding. The energetic origin of this isomerization process is summarized, and the folding and unfolding of disulfide-intact bovine pancreatic ribonuclease A is used as an example to illustrate the kinetics and structural features of conformational changes from the heterogeneous unfolded state (consisting of cis and trans isomers of X-Pro peptide groups) to the native structure in which only one set of proline isomers is present.


Conjugated bile acids and intestinal flora during the preruminant stage in goat. Influence of a lamb milk replacer.
A total of 45 preruminant goats were fed either goat milk or a milk substitute to compare the evolution of taurine and glycine conjugated bile acids and the evolution of the intestinal flora during the first month of life. Samples of hepatic bile were obtained from kids of 1, 7, 14, 21, and 28 days old and conjugated bile acids were measured by high performance liquid chromatography. Bacterial flora were determined in 14 and 28 day old animals. Ours results show that under our experimental conditions tauroconjugated bile acids clearly predominated over the conjugated with glycine. This pattern of preferential tauroconjugation persisted at all ages tested and in both groups studied. On the other hand, it seems that the quality of the protein and fat used in the elaboration of the milk replacer affects the intestinal flora and the postnatal evolution of conjugated bile acids.


Atomic filter based on stimulated Raman transition at the rubidium D1 line.
We report on a 795 nm atomic filter consisting of a stimulated Raman gain amplifier together with normal Faraday anomalous dispersion optical filtering (FADOF) at the rubidium D1 line. The filter is operated with a single transmission peak. The gain of the filter's transmission light signal is enhanced up to 85-fold compared to case operating without a stimulated Raman transition. Based on atomic coherence, the filter's minimum transmission bandwidth is less than 22 MHz. In each filtering channel, the signal light's frequency can be tuned by changing the detuning of the coupling light. Such a filter with stimulated Raman gain is more efficient in extracting weak signals in the presence of a strong light background compared with the normal FADOF. This expands the range of potential applications in optical communications and lidar technology. This filtering method can also be extended to the lines of other atoms.


Impaired small intestinal peristaltic reflexes and sensory thresholds are independent functional disturbances in patients with chronic unexplained dyspepsia.
To study disturbances of gastrointestinal motility and afferent (sensory) dysfunction in functional (unexplained) dyspepsia, and the interrelationships between motility and sensory dysfunction. Twelve patients with functional dyspepsia and 12 controls matched for age and gender were studied. Intestinal perception thresholds were tested by a standardized stepwise distension procedure in the third portion of the duodenum with a barostat device. Small intestinal motility was measured with a low compliance perfusion system proximal and distal to the distending balloon. First perception of duodenal balloon distension occurred at significantly (p <0.01) lower pressures in patients (23 +/- 3 mm Hg, mean +/- SEM) than in healthy controls (31 +/- 3 mm Hg). Patients had a lower maximal intestinal pain tolerance than controls (31 +/- 2 mm Hg vs. 39 +/- 1 mm Hg, p <0.05). Duodenal distension inhibited intestinal motility distal to the distending balloon (peristaltic reflex) more often in health controls (11/12) than in patients with functional dyspepsia (5/12, p <0.05). These alterations of small intestinal motility occurred at pressure values below the perception thresholds, and disturbed motility responses were not associated with perception thresholds. Disturbed peristaltic reflexes and decreased sensory thresholds for perception of intestinal sensations are prevalent but may be independent abnormalities in patients with unexplained dyspepsia.


A case of xanthogranulomatous appendicitis in the female pelvis.
Xanthogranulomatous inflammation is an uncommon form of chronic inflammatory process. Only a few isolated case reports of xanthogranulomatous appendicitis (XA) have been published. XA has nonspecific imaging findings and cannot be reliably differentiated on imaging from locally advanced malignancy. XA however follows a benign course and can potentially be treated with surgical resection.


Social capital and self-rated health in urban low income neighbourhoods in Chile.
To examine the potential association between social capital and self-rated health within a low income community of Santiago, Chile. Cross-sectional survey, based on in-home interviews in the municipality of Puente Alto in Santiago, Chile. The participants were 781 residents of four neighbourhoods within Puente Alto (mean age 45.5 years). Principal components analysis with varimax rotation identified five domains of social capital: perceived trust in neighbours, perceived trust in organisations, reciprocity within the neighbourhood, neighbourhood integration, and social participation (Cronbach alphas: 0.58 to 0.77). Trust and reciprocity were significantly associated with better self-rated health. For example, a one standard deviation increase in trust in neighbours was associated with an adjusted odds ratio of 1.10 (95% confidence interval, CI: 1.05 to 1.15) for reporting good self-rated health. By contrast, social participation was associated with a lower odds (0.89, 95% CI: 0.89 to 1.06) of reporting good health. Neighbourhood social cohesion, measured by trust and reciprocity, is associated with higher self-rated health. However, social participation did not appear to be associated with better health in this predominantly low income neighbourhood. These findings provide preliminary support to the relevance for social capital as a determinant of health in Chile.


[Scleroderma renal crisis].
Systemic sclerosis (SSc) is a multisystem disease whose clinical manifestations result from inflammation, vascular injury and obliteration, and cutaneous and visceral fibrosis. Scleroderma renal crisis (SRC) occurs in 5% of patients with particullary diffuse form of SSc. It is characterized by malignant hypertension and oligo/ anuric acute renal failure. SRC was once a uniformly fatal complication of SSc. The prognosis of SRC has significantly improved with the introduction of angiotensin-converting enzyme inhibitors (ACEi) as treatment. The treatment of SRC relies on tight control of blood pressure and aggressive treatment with ACEi, if needed in combination with other types of antihypertensive drugs.


Global assessment of polybrominated diphenyl ethers in farmed and wild salmon.
We have shown recently that levels of persistent, bioaccumulative contaminants (polychlorinated biphenyls, dioxins, and several chlorinated pesticides) are significantly higher in farmed than in wild salmon and that European farm-raised salmon have significantly greater toxic contaminant loads than those raised in North and South America. In this paper, we extend these results to polybrominated diphenyl ethers (PBDEs) and show that farm-raised salmon have higher levels of these compounds than wild salmon. We also show that farm-raised salmon from Europe have higher PBDE levels than those raised in North America and that both European and North American farm-raised salmon have higher PBDE levels than those farm-raised in Chile. Among the species of wild salmon, chinook had significantly elevated PBDE levels relative to the other wild species. These elevated PBDE levels may be related to chinook's feeding behavior and trophic level. Among all of the wild species we studied, chinook tend to feed higher in the food web throughout their adult life and grow to be larger individuals.


Incidence of ripening and chilling injury on the oxidative activities and Fatty Acid compositions of the mitochondria from mango fruits.
The succinate oxidation capacities of mitochondria isolated from mango fruits (Mangifera indica L.) stored at 4, 8, 12, and 20 C were investigated during storage. In normally ripening fruits (at 12 and 20 C) the oxidative capacities increased during the first 10 days and then decreased slowly. At lower temperatures (4 and 8 C), the fruits showed chilling injury symptoms, after about 10 days of storage and the succinate oxidation capacities of mitochondria decreased progressively. Plots of succinate oxidation capacities as against storage temperature showed a marked discontinuity between 12 and 8 C, only when chilling injury was observed on fruits stored at low temperature.The variations of mitochondrial fatty acid composition during the storage of fruits at different temperatures were also investigated. A marked decrease of the molar ratio palmitoleic acid/palmitic acid, the predominant fatty acids in mitochondrial lipids, was observed to accompany both the succinate oxidation decrease and the induction of chilling injury.


Phylogenomics and population genomics of SARS-CoV-2 in Mexico during the pre-vaccination stage reveals variants of interest B.126.96.36.199 and B.1.1.222 or B.1.1.519 and the nucleocapsid mutation S194L associated with symptoms.
Understanding the evolution of the SARS-CoV-2 virus in various regions of the world during the Covid-19 pandemic is essential to help mitigate the effects of this devastating disease. We describe the phylogenomic and population genetic patterns of the virus in Mexico during the pre-vaccination stage, including asymptomatic carriers. A real-time quantitative PCR screening and phylogenomic reconstructions directed at sequence/structure analysis of the spike glycoprotein revealed mutation of concern E484K in genomes from central Mexico, in addition to the nationwide prevalence of the imported variant 20C/S:452R (B.1.427/9). Overall, the detected variants in Mexico show spike protein mutations in the N-terminal domain (i.e. R190M), in the receptor-binding motif (i.e. T478K, E484K), within the S1-S2 subdomains (i.e. P681R/H, T732A), and at the basis of the protein, V1176F, raising concerns about the lack of phenotypic and clinical data available for the variants of interest we postulate: 20B/478K.V1 (B.1.1.222 or B.1.1.519) and 20B/P.4 (B.220.127.116.11). Moreover, the population patterns of single nucleotide variants from symptomatic and asymptomatic carriers obtained with a self-sampling scheme confirmed the presence of several fixed variants, and differences in allelic frequencies among localities. We identified the mutation N:S194L of the nucleocapsid protein associated with symptomatic patients. Phylogenetically, this mutation is frequent in Mexican sub-clades. Our results highlight the dual and complementary role of spike and nucleocapsid proteins in adaptive evolution of SARS-CoV-2 to their hosts and provide a baseline for specific follow-up of mutations of concern during the vaccination stage.


Dipeptidyl peptidase-4 inhibitors lower the risk of autoimmune disease in patients with type 2 diabetes mellitus: A nationwide population-based cohort study.
To evaluate the real-world effect of dipeptidyl peptidase-4 inhibitor (DPP4i) on the incidence of autoimmune diseases (AD), including rheumatoid arthritis (RA), inflammatory bowel diseases, multiple sclerosis and systemic lupus erythematosus. We identified new users of DPP4i (n = 497 619) or non-DPP4i (n = 643 165) oral combination therapy between 1 January 2011 and 30 June 2015 among patients with type 2 diabetes mellitus in the Korean national health insurance claims database. Patients were followed from the date of initiation of combination therapy until AD outcome, censoring for treatment discontinuation or switching, death or end of study (31 August 2016). Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for RA, inflammatory bowel diseases, other AD (multiple sclerosis and systemic lupus erythematosus), and the composite of all outcomes were estimated using propensity score (PS)-adjusted Cox model. In the PS-weighted and PS-matched analysis, the risk of incident RA was decreased for DPP4i initiators compared with non-DPP4i initiators (aHR 0.67 [95% CI 0.49-0.92] and aHR 0.72 [95% CI 0.51-1.01], respectively). In both analyses, the risk of incident composite AD was also decreased for DPP4i initiators compared with non-DPP4i initiators (aHR 0.82 [95% CI 0.68-0.99] and aHR 0.76 [95% CI 0.62-0.93], respectively). In this large population-based cohort study, upfront DPP4i combination therapy was associated with a lower risk of composite AD compared with initial non-DPP4i combination therapy.


Molecular characterization of ketolide-resistant erm(A)-carrying Staphylococcus aureus isolates selected in vitro by telithromycin, ABT-773, quinupristin and clindamycin.
The aim of this study was to investigate whether a Staphylococcus aureus strain that carried an inducibly expressed erm(A) gene might exhibit resistance to the non-inducers telithromycin, ABT-773, clindamycin, quinupristin, dalfopristin or the combination quinupristin-dalfopristin after incubation in the presence of inhibitory concentrations of any of these compounds. Whenever resistant mutants were obtained, these were investigated for the molecular basis of the altered resistance phenotype. Resistant mutants were not selected with dalfopristin or quinupristin-dalfopristin, but were obtained with the other four agents. Irrespective of which drug was used for selection, all mutants were cross-resistant to clindamycin, quinupristin, telithromycin and ABT-773, and exhibited structural alterations in the erm(A) translational attenuator. The structural alterations observed included deletions of 14, 83, 121, 131, 147 or 157 bp, three different tandem duplications of 23, 25 or 26 bp, two different types of point mutation, as well as the insertion of IS256. All these alterations either completely prevented the formation of mRNA secondary structures in the erm(A) regulatory region or favoured the formation of those mRNA secondary structures that allowed translation of the erm(A) transcripts. Deletions, which were observed in almost two-thirds of the mutants, might be explained by illegitimate recombination between different parts of the erm(A) regulatory region.


The key role of the intermolecular pi-pi interactions in the presence of spin crossover in neutral [Fe(abpt)2A2] complexes (A = terminal monoanion N ligand).
New iron(II) complexes of formulas [Fe(abpt) 2(tcm) 2] ( 1), [Fe(abpt) 2(tcnome) 2] ( 2), and [Fe(abpt) 2(tcnoet) 2] ( 3) (abpt = 4-amino-3,5-bis(pyridin-2-yl)-1,2,4-triazole, tcm (-) = [C(CN) 3] (-) = tricyanomethanide anion; tcnome (-) = [(NC) 2CC(OCH 3)C(CN) 2] (-) = 1,1,3,3-tetracyano-2-methoxypropenide anion; tcnoet (-) = [(NC) 2CC(OC 2H 5)C(CN) 2] (-) = 1,1,3,3-tetracyano-2-ethoxypropenide anion) have been synthesized and characterized by infrared spectroscopy, magnetic properties and by variable-temperature single-crystal X-ray diffraction. The crystal structure determinations of 1 and 2 reveal in both cases centrosymmetric discrete iron(II) monomeric structures in which two abpt chelating ligands stand in the equatorial plane and two terminal polynitrile ligands complete the distorted octahedral environment in trans positions. For 3, the crystallographic studies revealed two polymorphs, 3- A and 3- B, exhibiting similar discrete molecular structures to those found for 1 and 2 but with different molecular arrangements. In agreement with the variable-temperature single-crystal X-ray diffraction, the magnetic susceptibility measurements, performed in the temperature range 2-400 K, showed a spin-crossover phenomenon above room temperature for complexes 1, 3- A, and 3- B with a T 1/2 of 336, 377, and 383 K, respectively, while complex 2 remains in the high-spin ground state ( S = 2) in the whole temperature range. To understand further the magnetic behaviors of 1, 3-A, and 3-B, single-crystal X-ray diffraction measurements were performed at high temperatures. The crystal structures of both polymorphs could not be obtained above 400 K because the crystals decomposed. However, single-crystal X-ray data have been collected for compound 1, which reaches the full high-spin state at lower temperatures. Its crystal structure, solved at 400 K, showed a strong modification of the iron coordination sphere (average Fe-N = 2.157(3) A vs 1.986(3) A at 293 K). In agreement with the magnetic properties. Such structural behavior is a signature of the spin-state transition from low-spin (LS) to high-spin (HS). On the basis of the intermolecular pi stacking observed for the series described in this paper and for related complexes involving similar discrete structures, we have shown that complexes displaying frontal pi stacking present spin transition such as 1, 3-A, and 3-B and those involving sideways pi stacking such as complex 2 remain in the HS state.


Expression of C-type lectin, SIGNR3, on subsets of dendritic cells, macrophages, and monocytes.
The C-type lectin SIGNR3 is a mouse homologue of human DC-SIGN, which shares carbohydrate-binding specificity with human DC-SIGN. However, the expression profile of SIGNR3 is largely unknown. To examine the expression of SIGNR3 in immune cells, we generated SIGNR3-specific mAb and investigated SIGNR3 expression in vivo. SIGNR3 was expressed on a fraction of MHC II(+) DCs and Mϕs in the dermis and CD115(+)Ly6C(int-low) monocytes in the blood and BM. In the LNs, SIGNR3(+) cells localized adjacent to PNAd(+) HEV-like vessels. They were also found in interfollicular regions in sLNs but not mLNs. Those SIGNR3(+) cells expressed CD11b and variable levels of CD11c and MHC II. As in LNs, SIGNR3 was expressed on a large proportion of the CD11b(+)CD11c(int-high) cells in the spleen. In the lung, SIGNR3(+) cells belonged to the CD11b(+)CD11c(int) population, and Mϕs in the airway and lung faintly expressed SIGNR3. When PKH67-labeled CD115(+)Ly6C(high) BM monocytes were transferred into normal recipients, they up-regulated SIGNR3 expression along with the decrease in Ly6C expression during the circulation and upon arrival at the peripheral LNs through HEV. In addition, CD11b(high)Ly6C(high) monocytes that entered sLNs differentiated into CD11b(+) DCs in a couple of days, whereas those in the spleen, mLNs, and lung differentiated into CD11c(int) monocytic cells. These results suggest that SIGNR3 is a new differentiation marker for myeloid mononuclear cells and indicate that some DCs, especially in the sLNs, are possibly replenished by Ly6C(high) monocytes.


Interactive effects on CO2, drought, and ultraviolet-B radiation on maize growth and development.
Crop growth and development are highly responsive to global climate change components such as elevated carbon dioxide (CO2), drought, and ultraviolet-B (UV-B) radiation. Plant tolerance to these environmental stresses comprises its genetic potential, physiological changes, metabolism, and signaling pathways. An inclusive understanding of morphological, physiological, and biochemical responses to these abiotic stresses is imperative for the development of stress tolerant varieties for future environments. The objectives of this study were to characterize the changes in vegetative and physiological traits in maize hybrids in their response to multiple environmental factors of (CO2) [400 and 750μmolmol(-1) (+(CO2)], irrigation treatments based evapotranspiration (ET) [100 and 50% (-ET)], and UV-B radiation [0 and 10kJm(-2)d(-1) (+UV-B)] and to identify the multiple stress tolerant hybrids aid in mitigating projected climate change for shaping future agriculture. Six maize hybrids (P1498, DKC 65-81, N75H-GTA, P1319, DKC 66-97, and N77P-3111) with known drought tolerance variability were grown in eight sunlit, controlled environment chambers in which control treatment consisted of 400μmolmol(-1) [CO2], 100% ET-based irrigation, and 0kJ UV-B. Plants grown at +UV-B alone or combination with 50% ET produced shorter plants and smaller leaf area while elevated CO2 treatments ameliorated the damaging effects of drought and higher UV-B levels on maize hybrids. Plant height, leaf area, total dry matter chlorophyll, carotenoids, and net photosynthesis measured were increased in response to CO2 enrichment. Total stress response index (TSRI) for each hybrid, developed from the cumulative sum of response indices of vegetative and physiological parameters, varied among the maize hybrids. The hybrids were classified as tolerant (P1498), intermediate (DKC 65-81, N75H-GTA, N77P-3111) and sensitive (P1319 and DKC 66-97) to multiple environmental stresses. The positive correlation between TSRI and vegetative and physiological index developed in this study demonstrates that a combination of vegetative and physiological traits is an effective screening tool to identify germplasm best suited to cope with future changing climates. Furthermore, the tolerant hybrids identified in this study indicate that the possibility of cultivar selection for enhanced agronomic performance and stability in a water limited environment with higher UV-B, anticipated to occur in future climates.


Anxiety, locus of control, and coping strategies among end-stage renal disease patients undergoing maintenance hemodialysis.
End-stage kidney disease (ESKD) patients on maintenance hemodialysis (MHD) have a lot of anxiety. Anxiety and coping are associated with the locus of control; the present investigation aimed to study the state and trait anxiety, locus of control, and active and passive coping among patients on MHD. Thirty MHD patients and 30 controls were administered State-Trait Anxiety Inventory, Rotter's Locus of Control Scale, and Coping Responses Inventory. There were significantly higher scores on state and trait anxiety, respectively (67.53 ± 10.89 vs. 59.40 ± 6.97, P < 0.01, and 62.97 ± 8.45 vs. 58.07 ± 7.06, P < 0.05), and locus of control (11.27 ± 3.55 vs. 9.04 ± 1.86, P < 0.01) in patients as compared to controls. On coping responses, patients and controls differed on positive reappraisal (54.33 ± 4.67 vs. 51.17 ± 3.12, P < 0.01), seeking guidance and support (58.07 ± 5.51 vs. 53.27 ± 4.22, P < 0.01), problem solving (51.03 ± 4.70 vs. 47.57 ± 4.73, P < 0.01), cognitive avoidance (60.27 ± 6.76 vs. 56.80 ± 4.08, P < 0.05), acceptance or resignation (61.67 ± 6.30 vs. 58.83 ± 4.23, P < 0.01), emotional discharge (68.07 ± 6.78 vs. 64.30 ± 4.50, P < 0.05), approach coping (205.57 ± 10.55 vs. 189.70 ± 11.37, P < 0.01), and avoidance coping (255.30 ± 16.45 vs. 241.10 ± 10.50, P < 0.01). A higher prevalence of anxiety trait could be the cause of anxiety in MHD patients besides the medical problems. The locus of control among patients though a mixed one was significantly more toward externalism. Thus, there is a need to identify this group well in advance and prepared not only medically but also psychologically for MHD.


The effect of ginger powder and Chinese herbal medicine on production performance, serum metabolites and antioxidant status of laying hens under heat-stress condition.
This study was done to evaluate the effects of Chinese herbal medicine (CHM) and ginger powder on layers-production performance, serum metabolites and antioxidant status under heat stress condition. Two hundred and fifty Lohmann layers were randomly divided into 5 different, including two controls and three experimental groups (H1, H2, and H3). Control groups were fed the basic diet without supplementation, while, the feed of three experimental groups was supplemented with 3.32 g CHM, 10 g ginger powder, and 10 g ginger powder+ 3.32 g CHM per kg of diet, respectively. Results showed that feed consumption and production rate were decreased in the HC group, while, feed intake and production significantly improved when birds were given supplemented diet. The production rate and feed intake of the H3 group were even significantly higher than the NC group. The birds that received supplemented diet had higher glucose level compared to HC. Triglycerides and serum cholesterol had significantly decreased level in supplemented groups compared to HC. Fungal catalase (CAT) level was significantly improved in H2 and H3 groups. Nitric oxide (NO), glutathione peroxidase (GSH-PX) and Total Protein (T-AOC) level were significantly improved in supplemented groups. Findings showed that ginger powder and CHM could be a viable alternative to the synthetic antibiotic in poultry feed.


Involvement of p114-RhoGEF and Lfc in Wnt-3a- and dishevelled-induced RhoA activation and neurite retraction in N1E-115 mouse neuroblastoma cells.
The Wnt-induced planar cell polarity (PCP) signaling pathway is essential for polarized cell migration and morphogenesis. Dishevelled (Dvl) and its binding protein Daam1 mediate RhoA activation in this pathway. WGEF, a member of the Rho-guanine nucleotide exchange factor (Rho-GEF) family, was shown to play a role in Wnt-induced RhoA activation in Xenopus embryos. However, it has remained unknown which member(s) of a Rho-GEF family are involved in Wnt/Dvl-induced RhoA activation in mammalian cells. Here we identified p114-RhoGEF and Lfc (also called GEF-H1) as the Rho-GEFs responsible for Wnt-3a-induced RhoA activation in N1E-115 mouse neuroblastoma cells. We screened for Rho-GEF-silencing short-hairpin RNAs (shRNAs) that are capable of suppressing Dvl-induced neurite retraction in N1E-115 cells and found that p114-RhoGEF and Lfc shRNAs, but not WGEF shRNA, suppressed Dvl- and Wnt-3a-induced neurite retraction. p114-RhoGEF and Lfc shRNAs also inhibited Dvl- and Wnt-3a-induced RhoA activation, and p114-RhoGEF and Lfc proteins were capable of binding to Dvl and Daam1. Additionally, the Dvl-binding domains of p114-RhoGEF and Lfc inhibited Dvl-induced neurite retraction. Our results suggest that p114-RhoGEF and Lfc are critically involved in Wnt-3a- and Dvl-induced RhoA activation and neurite retraction in N1E-115 cells.


A case of direct intracranial extension of tuberculous otitis media.
We describe a very rare case of tuberculous otitis media (TOM) with direct intracranial extension. The patient was a 55-year-old man who presented to our ENT clinic for evaluation of severe headaches and right-sided otorrhea. A biopsy of granulation tissue obtained from the right external auditory canal demonstrated chronic inflammation that was suggestive of mycobacterial infection. Magnetic resonance imaging of the brain indicated intracranial extension of TOM through a destroyed tegmen mastoideum. After 2 months of antituberculous medication, the headaches and otorrhea were controlled, and the swelling in the external ear canal subsided greatly. Rarely does TOM spread intracranially. In most such cases, intracranial extension of tuberculosis occurs as the result of hematogenous or lymphogenous spread. In rare cases, direct spread through destroyed bone can occur, as it did in our patient.


Fine motor skill training enhances functional plasticity of the corticospinal tract after spinal cord injury.
Following central nervous system injury, axonal sprouts form distal to the injury site and extend into the denervated area, reconstructing neural circuits through neural plasticity. How to facilitate this plasticity has become the key to the success of central nervous system repair. It remains controversial whether fine motor skill training contributes to the recovery of neurological function after spinal cord injury. Therefore, we established a rat model of unilateral corticospinal tract injury using a pyramidal tract cutting method. Horizontal ladder crawling and food ball grasping training procedures were conducted 2 weeks before injury and 3 days after injury. The neurological function of rat forelimbs was assessed at 1, 2, 3, 4, and 6 weeks after injury. Axon growth was observed with biotinylated dextran amine anterograde tracing in the healthy corticospinal tract of the denervated area at different time periods. Our results demonstrate that compared with untrained rats, functional recovery was better in the forelimbs and forepaws of trained rats. The number of axons and the expression of growth associated protein 43 were increased at the injury site 3 weeks after corticospinal tract injury. These findings confirm that fine motor skill training promotes central nervous system plasticity in spinal cord injury rats.


[Psychophysiological and psychological aspects of mild hypertension].
The aetiopathogenesis of essential hypertension has been more intensively investigated in recent years mainly in genetic high-risk groups and patients with transitory and early forms of essential hypertension. A group of 29 patients with mild hypertension according to the WHO criteria were submitted to hypertensiological, psychological and psychophysiological specification in this study. Twenty-four hour blood measurements were performed for this purpose. The group could thus be divided into 18 patients with white-coat hypertension (WH) and 11 patients with real mild hypertension (H). Contrary to expectations, mild hypertensives had weaker systolic (p < 0.05) and diastolic (p < 0.01) blood pressure reactions to mental stress than white-coat hypertensives. Their cardiovascular recovery was not reduced after stress. Psychological differences between the groups were only found with respect to irritability (FP1: H 6.9 sd 2.1, WH 5.2 sd 2.1 stanine) and hypertensives compared to the reference random sample on the FPI scale emotional instability (6.5 stanine). Other psychosomatic studies should replicate the results obtained in this study in larger patient populations with white-coat and mild hypertension.


Neurotrophic protein S100 beta stimulates glial cell proliferation.
Nervous system development involves a coordinated series of events, including regulation of cell proliferation and differentiation by specific extracellular factors. S100 beta is a neurotrophic protein that has been implicated in regulation of cellular proliferation, but direct evidence was lacking. In this report, nanomolar concentrations of S100 beta are shown to stimulate proliferation of rat C6 glioma cells and primary astrocytes. An S100 mutant with a single amino acid change was inactive. S100 beta also stimulated increases in the steady-state levels of c-myc and c-fos protooncogene mRNAs and complemented the effects of platelet-derived growth factor. Two neuroblastoma cell lines did not proliferate in response to S100 beta, suggesting that the mitogenic activity of S100 beta is selective for astroglial cells. These results suggest that S100 beta may be involved in the coordinate development and maintenance of the central nervous system by synchronously stimulating the differentiation of neurons and the proliferation of astroglia.


Correlation of hemodynamic and functional variables with the angiographic extent of peripheral arterial occlusive disease.
The aim of the study was to determine whether hemodynamic and functional variables are related to the angiographic extent of lower limb atherosclerosis. In 150 patients with stable intermittent claudication, the Bollinger angiogram score was compared with the resting Doppler pressure values, and the initial claudication distance (ICD) and absolute claudication distance (ACD) with treadmill exercise. The extent of lower limb atherosclerosis correlated significantly with the age of the patients and the duration of the claudication. The angiogram scores of the patients were negatively correlated with the ankle systolic blood pressure (SBP) and the ankle/brachial index (ABI). In a multiple regression analysis, ABI was the most predictive variable for the angiographic severity of disease. ICD, ACD and work on the treadmill failed to correlate with the angiogram summation score. If patients were classified into groups for those with iliac or femoropopliteal disease, a weak correlation between ACD and femoropopliteal angiogram score was found. The comparison between Doppler measurements and treadmill exercise testing showed no significant correlation between SBP/ABI of the more diseased limb and ICD. However, both SBP and ABI did correlate significantly with ACD (r = 0.16, p < 0.05 and r = 0.20, p < 0.01, respectively). In conclusion, SBP and ABI are reliable parameters for indirect assessment of the angiographic extent of lower limb atherosclerosis. In contrast, the walking capacity of claudicant patients is independent of the angiographic severity of the disease.


Low forest productivity associated with increasing drought-tolerant species is compensated by an increase in drought-tolerance richness.
Many temperate forests are changing in composition due to a combination of changes in land-use, management and climate-related disturbances. Previous research has shown that in some regions these changes frequently favour drought-tolerant tree species. However, the effects of these changes in composition on forest functioning (e.g. productivity) are unclear. We studied 25 years of change in individual tree biomass growth, ingrowth and mortality, and community composition and total plot biomass across 2663 permanent forest plots in Catalonia (NE Spain) comprising 85,220 trees of 59 species. We focused on the relationship between community-level forest productivity and drought tolerance (DT), which was estimated using hydraulic traits as well as biogeographic indicators. We found that there was a small increase (1.6%-3.2% on average) in community-mean DT (DTcwm) during the study period, concurrent with a strong increase (12.4%-19.4% on average) in DT richness (DTric; i.e. trait range). Most importantly, we found that the mean DT was negatively related to forest productivity, which was explained because drought-tolerant tree species have lower tree-level growth. In contrast, DT richness was strongly and positively related to forest productivity, probably because it allowed for a more stable production along wet and dry periods. These results suggest a negative impact of ongoing climate change on forest productivity mediated by functional composition shifts (i.e. selection of drought-tolerant species), and a positive effect of increased DT richness as a consequence of land-use legacies. Such a trend towards functional diversification, although temporary, would increase forests' capacity to resist drought and place them in a better position to face the expected change in climate.


Trem2 deletion enhances tau dispersion and pathology through microglia exosomes.
Alzheimer's disease (AD) is a neurodegenerative disorder that manifests sequential Aβ and tau brain pathology with age-dependent onset. Variants in the microglial immune receptor TREM2 are associated with enhanced risk of onset in sporadic Alzheimer's disease (AD). While recent studies suggest TREM2 dysfunction can aggravate tau pathology, mechanisms underlying TREM2-dependent modulation of tau pathology remains elusive. Here, we characterized differences in progressive tau spreading from the medial entorhinal cortex (MEC) to the hippocampus in wildtype (WT) and Trem2 knockout (KO) mice by injection of AAV-P301L tau into the MEC, and correlated changes in hippocampal tau histopathology with spatial and fear memory. We also compared effects of intraneuronal dispersion between cultured microglia and neurons using a microfluidic dispersion assay, analyzed differences in microglial tau trafficking following uptake, and quantified exosomal tau secretion and pathogenicity from purified WT and Trem2 KO exosomes. Trem2 deletion in mice (Trem2 KO) can enhance tau spreading from the medial entorhinal cortex (MEC) to the hippocampus, which coincides with impaired synaptic function and memory behavior. Trem2 deletion in microglia enhances intraneuronal dispersion of tau in vitro between neuronal layers cultured in a microfluidic chamber, and the presence of exosome inhibitors can significantly reduce tau in exosomes and extracellular media from tau-loaded microglia. Although microglial Trem2 deletion has no effect on tau uptake, Trem2 deletion enhances distribution to endosomal and cellular pre-exosomal compartments following internalization. Trem2 deletion has little effect on exosome size, however, proteomic analysis indicates that Trem2 deletion can modulate changes in the microglial proteomic landscape with tau and LPS/ATP treatment conditions associated with exosome induction. Furthermore, exosomes from Trem2 KO microglia show elevated tau levels, and feature enhanced tau-seeding capacity in a tau FRET reporter line compared to exosomes from WT microglia. Together, our results reveal a role for Trem2 in suppressing exosomal tau pathogenicity, and demonstrates that Trem2 deletion can enhance tau trafficking, distribution and seeding through microglial exosomes.


Perturbations in Amino Acid Metabolism in Reserpine-Treated Zebrafish Brain Detected by 1H Nuclear Magnetic Resonance-Based Metabolomics.
Depression is a complex and disabling psychiatric disorder, which is expected to be a leading cause for disability by 2030. According to World Health Organization, about 350 million people are suffering with mental health disorders around the globe, especially depression. However, the mechanisms involved in stress-induced depression have not been fully elucidated. In this study, a stress-like state was pharmacologically induced in zebrafish using reserpine, a drug widely used to mediate depression in experimental animal models. Zebrafish received single intraperitoneal (i.p.) injections of 20, 40, and 80 mg/kg body weight reserpine doses and were subjected to open-field test at 2, 24, 48, 72, and 96 h after the treatment. Along with observed changes in behavior and measurement of cortisol levels, the fish were further examined for perturbations in their brain metabolites by 1H nuclear magnetic resonance (NMR)-based metabolomics. We found a significant increase in freezing duration, whereas total distance travelled was decreased 24 h after single intraperitoneal injection of reserpine. Cortisol level was also found to be higher after 48 h of reserpine treatment. The 1H NMR data showed that the levels of metabolites such as glutamate, glutamine, histamine, valine, leucine and histidine, lactate, l-fucose, betaine and γ-amino butyric acid (GABA), β-hydroxyisovalerate, and glutathione were significantly decreased in the reserpine-treated group. This study provided some insights into the molecular nature of stress that could contribute toward a better understanding of depression disorder.