[Preparation and bio-evaluation of tissue engineered scaffold based on decellularized whole heart extracellular matrix].
To investigate a method for preparing decellularized rat heart scaffold, and to detect and evaluate the decellularized scaffold. The decellularized rat heart scaffold was prepared by retrograde perfusion with a combination of enzymatic and Triton X-100 detergent methods to remove the populations of resident cells, and then the decellularized scaffold was observed by gross, toluidine blue staining, HE staining, scanning electron microcope (SEM), Alcian blue staining, and immunohistochemisty staining to evaluate the structure and essential component of extracellular maxtix (ECM) in the scaffold. Tissue engineered scaffold based on decellularized whole heart ECM was successfully prepared, which maintained not only the gross morphology of the heart, but also the intact vascular structure and ultrastructural conformation that certified by toluidine blue staining, HE staining, and SEM analyses. Alcian blue staining and immunohistochemisty staining showed that the essential components of ECM, such as collagen type I, glycosaminoglycan, fibronectin, and Laminin were remained in decellularized whole heart matrix. The decellularized whole heart ECM prepared by method mentioned can maintain the intact structure of rat heart and basic compositions of extracellular matrices, so it could be suitable for further studies of tissue engineered scaffolds for whole heart reconstruction.


Decree No. 229/987, 5 May 1987.
This Decree creates a Women's Institute under the Ministry of Education and Culture. The Institute is to be composed of representatives of various governmental agencies and nongovernmental organizations and is to have as its objectives the following: a) to make a diagnosis of the situation of women in Uruguay; b) to propose legislative reforms and other policies necessary to achieve the effective participation of women in society as well as in the making of political decisions; and c) to propose the means necessary to execute decisions adopted by the Conference "Women, Population, Development."


Are placental lakes of any clinical significance?
The aim of this study was to determine prospectively whether an association exists between the finding of placental lakes at the 20 week scan and an increased risk of uteroplacental complications or a poor pregnancy outcome. We studied the placental appearances in 1,198 consecutive second trimester ultrasound scans performed for routine foetal abnormality screening at our institution. The placental thickness was measured at its widest diameter in the sagittal plane and the presence or absence of placental lakes was recorded. The birth weight in each case was plotted against the centile charts in use at the hospital and recorded. Specific outcome measures included foetal growth restriction (IUGR) with a birth weight below the 5th centile, pre-eclampsia, placental abruption, and perinatal deaths. Placental lakes were seen in 17.8 per cent of the scans. There was no significant association with either maternal socio-demographic factors or perinatal mortality (OR 0.94, 95 per cent CI 0.35-2.51). No association was seen with maternal cigarette smoking (OR 1.07, 95 per cent CI 0.75-1.52), a birth weight below the 5th centile (OR 0.68, 95 per cent CI 0.39-1.18), the development of pregnancy induced hypertension (OR 0.68, 95 per cent CI 0.35-1.32), severe pre-eclampsia (OR 0.72, 95 per cent CI 0.21-2.50), or placental abruption (OR 1.79, 95 per cent CI 0.46-6.99). A finding of placental lakes was six times more likely with a thick placenta >3 cm at 20 weeks gestation (OR 6.30, 95 per cent CI 4.39 to 9.05). A finding of placental lakes during the second trimester ultrasound scan does not appear to be associated with uteroplacental complications or an adverse pregnancy outcome. The lesions are more prevalent with increasing placental thickness.


Tertiary-spectrum manipulation in apochromats.
By combining achromatic and superachromatic lens groups we may achieve improved tertiary-spectrum residuals in apochromatic systems. The application of this technique is reported. The significance of a secondary spectrum and a tertiary spectrum in lens design is also reviewed.


Nonparallel transcriptional divergence during parallel adaptation.
How underlying mechanisms bias evolution toward predictable outcomes remains an area of active debate. In this study, we leveraged phenotypic plasticity and parallel adaptation across independent lineages of Trinidadian guppies (Poecilia reticulata) to assess the predictability of gene expression evolution during parallel adaptation. Trinidadian guppies have repeatedly and independently adapted to high- and low-predation environments in the wild. We combined this natural experiment with a laboratory breeding design to attribute transcriptional variation to the genetic influences of population of origin and developmental plasticity in response to rearing with or without predators. We observed substantial gene expression plasticity, as well as the evolution of expression plasticity itself, across populations. Genes exhibiting expression plasticity within populations were more likely to also differ in expression between populations, with the direction of population differences more likely to be opposite those of plasticity. While we found more overlap than expected by chance in genes differentially expressed between high- and low-predation populations from distinct evolutionary lineages, the majority of differentially expressed genes were not shared between lineages. Our data suggest alternative transcriptional configurations associated with shared phenotypes, highlighting a role for transcriptional flexibility in the parallel phenotypic evolution of a species known for rapid adaptation.


Photochemical approach toward deposition of gold nanoparticles on functionalized carbon nanotubes.
The development of new methods for the facile synthesis of hybrid nanomaterials is of great importance due to their importance in nanotechnology. In this work, we report a new method to deposit Au nanoparticles on the surface of single-walled carbon nanotubes (SWCNTs). Our approach consists of a one pot synthesis in which Au nanoparticles are generated in the presence of a photoreducing agent (Irgacure-2959) and carboxyl or polymer-functionalized SWCNTs (f-SWCNTs). We have observed that when carbon nanotubes are functionalized with polymers containing pendant amino groups, the latter can act as specific nucleation sites for well-dispersed deposition of Au nanoparticles. The surface coverage of the Au nanoparticles can be observed by transmission electron spectroscopy. These observations are compared to that of carboxyl functionalized SWCNTs, in which less surface coverage was observed. The f-SWCNT/Au nanocomposites were also characterized by UV-vis, infrared, and Raman spectroscopy and thermogravimetric analysis (TGA). This facile and effective route can be implemented to deposit gold nanoparticles on other surface-functionalized carbon nanotubes.


Alpha2A-adrenoceptor mediated tachypnea in awake goats.
To further elucidate the role of alpha2-adrenoceptors (alpha2-ARs) in the control of respiratory rhythm we examined the ventilatory effects of guanfacine (a preferentially selective alpha2A-AR agonist) and clonidine (a non-selective alpha2-AR agonist) in awake adult goats. Systemic administration of guanfacine in cumulative doses (20 microg/kg; 140-180 microg/kg total cumulative dose) increased breathing in all animals in a dose-dependent manner. The excitatory effect was entirely mediated by increases in respiratory frequency. The magnitude of the guanfacine-induced tachypnea was similar to that produced by systemic administration of cumulative doses of clonidine (1-2 microg/kg; 4-10 microg/kg total cumulative dose) in the same animals studied on a separate day. Both guanfacine- and clonidine-induced tachypnea was reversed by the preferentially selective alpha2A-AR antagonist RX821002 (2-6 microg/kg IV). Unlike clonidine however, guanfacine administration did not produce slow arrhythmic breathing episodes (irregular TE intervals and central apneas) that are characteristic of alpha2-AR stimulation with alpha2-AR agonists in the awake goat. The results suggest that alpha2-AR agonist-induced ventilatory excitation (tachypnea) requires the activation of alpha2A-ARs whereas clonidine-induced ventilatory depression (arrhythmic breathing) requires the activation of an alternate alpha2-AR subtype (presumably alpha2C-ARs). The results further demonstrate that alpha2-AR pathways exert an important influence on respiratory rhythm in the awake goat.


Open reduction internal fixation of the unstable mallet fracture.
Unstable mallet fractures of the digit pose a challenge when treated surgically. We present the results of a technique, not earlier described, for the fixation of these uncommon injuries. The technique involves anatomical reduction and stable fixation of the distal articular fragment combined with stabilization of the distal interphalangeal joint with buried Kirschner wires allowing early mobilization of the digit. Twenty patients with an average follow-up of 12.7 months (10 mo to 21 mo) are presented. Results were good/excellent (Crawford's criteria) in 16 patients, fair in 3, and poor in 1 with those operated upon within 2 weeks postinjury achieving the best results. There were no incidences of fixation failure, loss of reduction, or posttraumatic osteoarthritis. One patient had a minor infection, but there were no cases of nail deformity or wound breakdown. There was high patient satisfaction and all patients returned to work after treatment. We conclude that this is a reliable technique with minimal complications and is comparable with other published operative and nonoperative treatment modalities.


Heavy Atom Detergent/Lipid Combined X-ray Crystallography for Elucidating the Structure-Function Relationships of Membrane Proteins.
Membrane proteins reside in the lipid bilayer of biomembranes and the structure and function of these proteins are closely related to their interactions with lipid molecules. Structural analyses of interactions between membrane proteins and lipids or detergents that constitute biological or artificial model membranes are important for understanding the functions and physicochemical properties of membrane proteins and biomembranes. Determination of membrane protein structures is much more difficult when compared with that of soluble proteins, but the development of various new technologies has accelerated the elucidation of the structure-function relationship of membrane proteins. This review summarizes the development of heavy atom derivative detergents and lipids that can be used for structural analysis of membrane proteins and their interactions with detergents/lipids, including their application with X-ray free-electron laser crystallography.


Comparing safety and adequacy between surgical biopsy versus core needle biopsy in diagnosing neuroblastoma.
Adequate tissue biopsy is essential for diagnosis and risk stratification of neuroblastoma (NB). Historically, NB diagnosis has relied on tissue obtained via surgical biopsy. However, core needle biopsy may provide a safe and adequate method of obtaining tissue in pediatric patients. The aim of this study is to compare the adequacy and safety between core needle biopsy and surgical biopsy for the diagnosis of NB in children at our institution. Institutional approval was obtained. Medical records of patients diagnosed with NB from 2004 - 2019 were retrospectively reviewed. Patients had either core needle biopsy (CNB) or surgical biopsy (SB) including open/minimally invasive biopsy. Data included patient demographics, tumor location and size, sample adequacy for diagnosis and risk stratification, post-biopsy complications, length of hospital stay, and need for repeat biopsy. Statistical analysis was conducted using the Mann-Whitney U test or Student's t-test. Thirty-eight patients were included; 53 biopsies were performed including 41 SB and 12 CNB. Patient and tumor characteristics were similar in both groups, as well as the biopsy adequacy for diagnosis and risk stratification. In all cases, there was no need for repeat biopsy. The CNB group demonstrated reduced length of stay (2 ± 0.4 days vs 5 ± 0.5 days; P < 0.0001) and fewer complications (8%) than the SB group (44%) (P = 0.038). Core needle biopsy is an acceptable modality for diagnosis and risk stratification in the pediatric population. Advantages include decreased length of stay and fewer post-procedure complications.


First Report of Pseudonectria buxi causing Volutella blight on Boxwood (Buxus microphylla) in the Republic of Korea.
Boxwood (Buxus spp.) are evergreen landscaping plants commonly used as hedges and fresh greenery. In July and August 2020, boxwood (Buxus microphylla Sieb. et Zucc) samples with blight symptoms were collected from the parterres of Seoul National University (Seoul, Republic of Korea). Diseased leaves and stem tissues were soaked in 1% sodium hypochlorite for 1 min, rinsed with sterile water, cultured on potato dextrose agar (PDA; Difco, Sparks, MD, USA) and incubated at 25 ℃ for 5 days. Four isolates (B2S72-1, B2S7-3, B3B2, and B4L3-3) were pure-cultured using the single-spore isolation method. Light pink-colored sporodochia containing one-celled, fusoid conidia were observed on PDA. Mean conidial size was 9.11 × 3.79 µm and ranged from 7.68 to 10.71 × 3.18 to 4.92 μm. Morphological features suggested that these isolates possessed the same characteristics as previously described for P. buxi (Bezerra, 1963, Yang et al., 2021). Genomic DNA was extracted from each isolate and the internal transcribed spacer (ITS) region of the ribosomal DNA (rDNA), β-tubulin coding sequence, and D1/D2 region of the large subunit of the rDNA gene cluster (LSU) were amplified using the primer pairs ITS4/ITS5 (White et al., 1990), Btub4Rd/Btub2Fd (Woudenberg et al., 2009), and LR0R/LR5 (Rehner & Samuels, 1994, Vilgalys & Hester, 1990), respectively. The sequences were deposited in GenBank (GenBank accessions No. OM169273-OM169276, OM176571-OM176574, OM176566-OM176569). BLAST search showed high similarity to GenBank sequences of the ex-type strain of P. buxi for ITS (≥99.50%, MH892589.1 and MH892583.1). In addition, neighbor-joining (NJ) phylogeneticnalysis was performed using MEGA-X based on the combined sequences. The four isolates were clustered on the same clade with Pseudonectria buxi reference strains with a high bootstrap value (100 %). For the pathogenicity test, leaves of 1-year-old boxwood were given a single cut with a razor blade and a 5-mm PDA mycelial plug was placed on the wound site. Plants were kept in a transparent box at 25°C with a 12-h photoperiod. After 21 days, inoculated leaves had turned yellow and orange to pink sporodochia were observed. P. buxi was successfully reisolated from the symptomatic tissues but not from the control leaves, therefore Koch's postulates were completed. To our knowledge, this is the first report of Volutella blight caused by P. buxi in the Republic of Korea.


Performance of seedlings of Mediterranean woody species under experimental gradients of irradiance and water availability: trade-offs and evidence for niche differentiation.
The aim of the study was to assess the potential importance for Mediterranean plants of trade-offs in the response to irradiance and water availability at the regeneration stage. Survival and growth patterns across an experimentally imposed irradiance gradient (1, 6, 20 and 100% sunlight) were studied in seedlings of eight Mediterranean woody species, together with the impact of a simulated summer drought. We found evidence of some of the trade-offs previously reported for non-Mediterranean plant communities, such as between survival in the shade and relative growth rate (RGR) at high light, but no evidence for others, such as between shade and drought tolerances. The impact of drought on survival and RGR was stronger in high light than in deep shade. The observed species-specific differences in performance provide a mechanistic basis for niche differentiation at the regeneration stage, contributing to possible explanations of species coexistence in Mediterranean ecosystems.


Digital breast tomosynthesis plus mammography, magnetic resonance imaging plus mammography and mammography alone: A comparison of diagnostic performance in symptomatic women.
To compare the diagnostic efficiency of digital breast tomosynthesis (DBT) plus digital mammography (DM) and magnetic resonance imaging (MRI) plus DM in symptomatic women. The protocol used in our study was accepted by the ethics committee at our hospital, and informed consent was obtained from all patients. Between June and December 2014, 197 patients with 238 histologically proven lesions all underwent DM, DBT and MRI. Two radiologists were responsible for interpreting all images according to the Breast Imaging Reporting and Data System (BI-RADS). The diagnostic performance of each method was assessed by receiver-operating characteristic (ROC) curve. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were compared using McNemar's test and Fisher's exact test. A Kappa test was used to assess the interobserver agreement. The area under the ROC curve (AUC) was lower in the group that underwent DM alone (Radiologist1 [R1], 0.849; Radiologist2 [R2], 0.850) than in the group that underwent DBT plus DM (R1, 0.907, P = 0.0204; R2, 0.900, P = 0.0239) and MRI plus DM (R1, 0.939, P = 0.0006; R2, 0.935, P = 0.0009). However, the difference between the group that received DBT plus DM and the group that received MRI plus DM was not significant (R1, P = 0.1262; R2, P = 0.0843). The accuracy (R1, 71.8%; R2, 71.4%) and sensitivity (R1, 71.9%; R2, 71.2%) of DM were lower than those of DBT ((accuracy: R1, 85.3%, P = 0.001; R2, 83.6%, P < 0.001; sensitivity: R1,92.1%, P < 0.001; R2, 90.8%, P < 0.001) and MRI combined with DM (accuracy: R1, 90.3%, P = 0.001; R2, 90.7%, P < 0.001; sensitivity: R1, 94.7%, P < 0.001; R2, 95.4%, P < 0.001). In contrast, no significant difference was observed between DBT and MRI combined with DM (accuracy: R1, P = 0.644; R2, P = 0.360; sensitivity: R1, P = 0.502; R2, P = 0.359). The interobserver agreement of each method was excellent (k = 0.894 0.919 and 0.882 for DM, DBT and MRI combined with DM, respectively). The diagnostic performance of DBT and MRI combined with DM is superior to that of DM alone in symptomatic women; MRI plus DM is slightly better than that of DBT plus DM, but this difference was not statistically significant.


Chemokine Receptors: Cloning Strategies
Chemokines activate leukocytes by binding to G protein-coupled receptors on the cell surface. Cloning DNA that codes for chemokine receptors is important because it can lead rapidly to detailed information about their structure, function, expression, regulation, and evolution, information that often cannot be obtained as readily or as precisely by studying the native protein directly. Many cloning strategies can be used; however, three common elements are required: (i) a library of cloned DNA molecules from an appropriate source; (ii) a gene transfer method for producing the receptor in a naive cell type; and (iii) functional assays to identify relevant clones or to qualify clones identified by other means. A particularly productive cloning strategy has been to isolate from a relevant library those DNA molecules that have sequence similarity to closely related G protein-coupled receptors and then to screen their encoded products with chemokine functional assays. This strategy has been used for five of the six known human leukocyte chemokine receptors, and two herpesvirus-encoded chemokine receptors. The cloning strategy that will lead most rapidly to success cannot be known a priori, since idiosyncratic properties of each receptor can foil even the most rational approach.


Biomarkers in DILI: One More Step Forward.
Despite being relatively rare, drug-induced liver injury (DILI) is a serious condition, both for the individual patient due to the risk of acute liver failure, and for the drug development industry and regulatory agencies due to associations with drug development attritions, black box warnings, and postmarketing withdrawals. A major limitation in DILI diagnosis and prediction is the current lack of specific biomarkers. Despite refined usage of traditional liver biomarkers in DILI, reliable disease outcome predictions are still difficult to make. These limitations have driven the growing interest in developing new more sensitive and specific DILI biomarkers, which can improve early DILI prediction, diagnosis, and course of action. Several promising DILI biomarker candidates have been discovered to date, including mechanistic-based biomarker candidates such as glutamate dehydrogenase, high-mobility group box 1 protein and keratin-18, which can also provide information on the injury mechanism of different causative agents. Furthermore, microRNAs have received much attention lately as potential non-invasive DILI biomarker candidates, in particular miR-122. Advances in "omics" technologies offer a new approach for biomarker exploration studies. The ability to screen a large number of molecules (e.g., metabolites, proteins, or DNA) simultaneously enables the identification of 'toxicity signatures,' which may be used to enhance preclinical safety assessments and disease diagnostics. Omics-based studies can also provide information on the underlying mechanisms of distinct forms of DILI that may further facilitate the identification of early diagnostic biomarkers and safer implementation of personalized medicine. In this review, we summarize recent advances in the area of DILI biomarker studies.


HIV seroprevalence among homeless patients admitted to a psychiatric inpatient unit.
This study was conducted to determine the seroprevalence of HIV-1 antibodies among hospitalized homeless mentally ill patients. From December 1989 through May 1991 the authors collected discard blood samples from patients consecutively admitted to a psychiatric unit designated for the care of severely mentally ill persons removed from the streets of New York City. The blood samples were tested for HIV-1 antibodies, and the results were analyzed for associations with age, gender, ethnicity, male homosexual activity, and use of injected drugs. The HIV seroprevalence was 6.4% (13 of 203 samples). Patients between ages 18 and 39 accounted for 51.2% of the admissions and 84.6% of the 13 positive results, a seroprevalence of 10.6% for this subsample. Patients under age 40 were more than six times as likely to test positive for HIV antibodies as those 40 or over. Ethnicity did not predict seropositivity. Women were as likely as men to be infected. Although clinicians had noted high-risk behavior on the charts for only three (23.1%) of the 13 positive cases, a recorded history of use of injected drugs was associated with a 6.5-fold greater risk of HIV seropositivity. One in every 16 patients admitted to the special unit was HIV positive. Age under 40 and use of injected drugs were strongly associated with seropositivity. Because information on high-risk behavior was infrequent, the reasons for younger patients' greater risk are unclear. The homeless mentally ill require outreach efforts to reduce the risk of acquiring or transmitting HIV.


Heat shock protein 70, heat shock protein 32, and vascular endothelial growth factor production and their effects on lipopolysaccharide-induced apoptosis in porcine aortic endothelial cells.
Lipopolysaccharide (LPS) is a highly proactive molecule that causes in vivo a systemic inflammatory response syndrome and activates in vitro the inflammatory pathway in different cellular types, including endothelial cells (EC). Because the proinflammatory status could lead to EC injury and apoptosis, the expression of proinflammatory genes must be finely regulated through the induction of protective genes. This study aimed at determining whether an LPS exposure is effective in inducing apoptosis in primary cultures of porcine aortic endothelial cells and in stimulating heat shock protein (Hsp)70 and Hsp32 production as well as vascular endothelial growth factor (VEGF) secretion. Cells between third and eighth passage were exposed to 10 microg/mL LPS for 1, 7, 15, and 24 hours (time-course experiments) or to 1, 10, and 100 microg/mL LPS for 7 and 15 hours (dose-response experiments). Apoptosis was not affected by 1 microg/mL LPS but significantly increased in a dose-dependent manner with the highest LPS doses. Furthermore, apoptosis rate increased only till 15 hours of LPS exposure. LPS stimulated VEGF secretion in a dose-dependent manner; its effect became significant after 7 hours and reached a plateau after 15 hours. Both Hsp70 and Hsp32 expressions were induced by LPS in a dose-dependent manner after 7 hours. Subsequent studies were addressed to evaluate the protective role of Hsp32, Hsp70, and VEGF. Hemin, an Hsp32 inducer (5, 20, 50 microM), and recombinant VEGF (100 and 200 ng/mL), were added to the culture 2 hours before LPS (10 microg/mL for 24 hours); to induce Hsp70 expression, cells were heat shocked (42 degrees C for 1 hour) 15 hours before LPS (10 microg/mL for 24 hours). Hemin exposure upregulated Hsp32 expression in a dose-dependent manner and protected cells against LPS-induced apoptosis. Heat shock (HS) stimulated Hsp70 expression but failed to reduce LPS-induced apoptosis; VEGF addition did not protect cells against LPS-induced apoptosis at any dose tested. Nevertheless, when treatments were associated, a reduction of LPS-induced apoptosis was always observed; the reduction was maximal when all the treatments (HS + Hemin + VEGF) were associated. In conclusion, this study demonstrates that LPS is effective in evoking "the heat shock response" with an increase of nonspecific protective molecules (namely Hsp70 and Hsp32) and of VEGF, a specific EC growth factor. The protective role of Hsp32 was also demonstrated. Further investigations are required to clarify the synergic effect of Hsp32, Hsp70, and VEGF, thus elucidating the possible interaction between these molecules.


Estimation of skin impedance models with experimental data and a proposed model for human skin impedance.
The skin is a complex biological tissue whose impedance varies with frequency. The properties and structure of skin changes with the location on the body, age, geographical location and other factors. Considering these factors, skin impedance analysis is a sophisticated data analysis. However, despite all these variations, various researchers have always worked to develop an equivalent electrical model of the skin. The two most important categories of electrical models are RC-based model and CPE-based model which focus on the physiological stratification and biological properties of skin, respectively. In this work, experimental skin impedance data is acquired from ten sites on the body to find the fitting model. It is observed that a hybrid of fractional-order CPE-based model and higher-order RC layered-based model can provide the best fitting electrical model of skin. A new model is developed with this hybrid orders. Genetic algorithm is used for the extraction of parameter components. Least error of fitting has been observed for the proposed model as compared with the other models. This model can be used in correlating many skin problems and in the development of diagnostic tools. It will offer an additional supportive tool in-vitro to the medical specialist.


Hypothesis: a selective advantage for cystic fibrosis heterozygotes.
European populations have both a particularly long history of pulmonary tuberculosis and extremely high frequencies of cystic fibrosis (CF). While carriers of the recessive gene are asymptomatic for CF disease, their fibroblasts produce excessive amounts of hyaluronic acid, whose role in successful isolation of virulent pathogens appears to be especially adaptive in host resistance to the human strain of Mycobacterium tuberculosis. CF heterozygosity may have been an adaptation to a disease environment once dominated by this infection.


Robustness considerations in selecting efficient two-color microarray designs.
The main goal of microarray experiments is to select a small subset of genes that are differentially expressed among competing mRNA samples. For a given set of such mRNA samples, it is possible to consider a number of two-color cDNA microarray designs with a fixed number of arrays. Appropriate criteria can be used to select an efficient design from such a set of alternative experimental designs. In practice, however, microarray expression data often contain missing observations and the most efficient design (with complete observations) for a specific setup may not be efficient in the presence of missing observations. In this article, we propose two criteria to address the robustness of microarray designs against missing observations. We demonstrate the simultaneous use of efficiency and robustness criteria to select good microarray designs for both one-factor and multi-factor experiments.


[Metabolic syndrome and mild hypertension].
The clinical definition of Metabolic Syndrome in Japan was issued in April, 2005 by a committee which is consisted of related 8 Japanese societies. The Japanese definition indicates that both abdominal obesity(AO male > or = 85 cm, female > or = 90cm) as a required component, and two out of three following factors, high blood pressure(BP > or = 130/ > or = 85mmHg), dyslipidemia(high triglyceride: TG > or = 150 mg/dL and/or low HDL-cholesterol : HDL-C < 40 mg/dL), and high fasting plasma glucose (FPG > or = 110 mg/dL) are necessary for the diagnosis. This concept is mostly the same with IDF. The blood pressure criteria of Japanese definition is over 130/85 mmHg. Frequency of high normal blood pressure and mild hypertension were 21.5% and 30.0% in male and 18.4% and 24.2% in female over 40 years old, respectively. High blood pressure was most frequent risk factor among metabolic syndrome components. The control of high normal or mild hypertension is very important to prevent the cardiovascular risk in metabolic syndrome.


Chlorophenol stress affects aromatic amino acid biosynthesis-a genome-wide study.
Chlorophenols are a class of chemicals commonly used in preservatives, disinfectants, algaecides, herbicides and pesticides. However, there is a growing evidence that these compounds are a threat to human health. This is alarming as many chlorophenols are common pollutants found in the global environment at potentially biohazardous levels. Despite chlorophenols being abundant, widely used and poisonous, we know relatively little about their mechanism of toxicity in eukaryotes. Thus, we performed genome-wide growth screens using Saccharomyces cerevisiae to understand the molecular basis of chlorophenol toxicity. Of ∼4850 single gene knockout strains tested, 393 mutants showed growth sensitivity to treatment with 4-chlorophenol (4-CP), 2,4-dichlorophenol (2,4-DCP) or pentachlorophenol (PCP). Only eight mutants showed growth hypersensitivity to all the three treatments and harboured deletions in genes important for aromatic amino acid biosynthesis (ARO1, ARO7) or mitochondrial protein synthesis and respiration (ATP5, ISA1, RML2, GET2, SLS1, MRPL38).


School Nurse Advocacy for Student Health, Safety, and School Attendance: Impact of an Educational Activity.
School nurses are expected to advocate for policies and procedures that support student health, safety, and school attendance. An educational activity to improve school nurse advocacy was developed and implemented based on advocacy literature, self-efficacy theory, and continuing education guidelines. A quantitative, repeated measure descriptive project design was used to compare school nurses' advocacy measures before and following an educational activity and 6 weeks after the activity. Immediately after the education, there were significant increases in advocacy knowledge (p < .001), confidence (p < .001), and recalled behaviors (p < .01) for a convenient sample of 51 Massachusetts school nurses. There were no significant differences across pre-, post-, and 6-week survey responses (n = 6); however, advocacy outcomes from immediately after the education were maintained at 6 weeks. More effective school nurse advocacy may improve youth population health, increase safety for students at school, and improve school attendance.


Evaluating Stress Physiology and Parasite Infection Parameters in the Translocation of Critically Endangered Woylies (Bettongia penicillata).
Translocation can be stressful for wildlife. Stress may be important in fauna translocation because it has been suggested that it can exacerbate the impact of infectious disease on translocated wildlife. However, few studies explore this hypothesis by measuring stress physiology and infection indices in parallel during wildlife translocations. We analysed faecal cortisol metabolite (FCM) concentration and endoparasite parameters (nematodes, coccidians and haemoparasites) in a critically endangered marsupial, the woylie (Bettongia penicillata), 1-3 months prior to translocation, at translocation, and 6 months later. FCM for both translocated and resident woylies was significantly higher after translocation compared to before or at translocation. In addition, body condition decreased with increasing FCM after translocation. These patterns in host condition and physiology may be indicative of translocation stress or stress associated with factors independent of the translocation. Parasite factors also influenced FCM in translocated woylies. When haemoparasites were detected, there was a significant negative relationship between strongyle egg count and FCM. This may reflect the influence of glucocorticoids on the immune response to micro- and macro-parasites. Our results indicate that host physiology and infection patterns can change significantly during translocation, but further investigation is required to determine how these patterns influence translocation success.


Characterization of Aniline Tetramer by MALDI TOF Mass Spectrometry upon Oxidative and Reductive Cycling.
By combining electrochemical experiments with mass spectrometric analysis, it is found that using short chain oligomers to improve the cycling stability of conducting polymers in supercapacitors is still problematic. Cycling tests via cyclic voltammetry over a potential window of 0 to 1.0 V or 0 to 1.2 V in a two-electrode device configuration resulted in solid-state electropolymerization and chain scission. Electropolymerization of the aniline tetramer to generate long chain oligomers is shown to be possible despite the suggested decrease in reactivity and increase in intermediate stability with longer oligomers. Because aniline oligomers are more stable towards reductive cycling when compared to oxidative cycling, future conducting polymer/oligomer-based pseudocapacitors should consider using an asymmetric electrode configuration.


Guidelines for the naming of genes, gene products, and mutants in the opportunistic protists.
The opportunistic protists encompass a wide diversity of organisms including Pneumocystis, Toxoplasma, cryptosporidia, microsporidia, and related genera. Recent advances in the molecular biology and cellular biochemistry of these organisms have led to the identification of an ever growing numbers of key genes and their cognate proteins. Until now, these molecules have not been designated using any consistent nomenclature system, leading to considerable confusion. The participants of the 11th International Workshop on Opportunistic Protists met on August 3, 2010 to reach consensus of a nomenclature system for genes, gene products, and mutants in the opportunistic protists. The following summary reports the consensus agreement to move toward a unified nomenclature system for these organisms. The system is adapted from that used for Saccharomyces cerevisiae.


Sarpogrelate and rosuvastatin synergistically ameliorate aortic damage induced by hyperlipidemia in apolipoprotein E-deficient mice.
The current study aimed to investigate whether sarpogrelate and rosuvastatin possess anti-arterial injury, and attempted to elucidate the mechanism of action underlying this activity. Sarpogrelate, a 5-hydroxytryptamine type 2A antagonist, is extensively used to prevent arterial thrombosis; however, its effects on atherosclerosis remain unknown. In the present study, sarpogrelate combined with rosuvastatin or rosuvastatin alone were administered to male ApoE-/- mice fed a high-fat diet (HFD) for 8 weeks. Metabolic parameters in the blood samples were analyzed using an automatic analyzer. Aortic tissues were stained with hematoxylin and eosin for morphological analysis. The expression levels of oxidized-low density lipoprotein (LDL) specific scavenging receptors, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and cluster of differentiation 68 were detected via immunostaining. mRNA expression levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α were determined via reverse transcription-quantitative PCR analysis, while protein expression levels of LOX-1 and phosphor(p)-ERK were determined via western blot analysis. The results demonstrated that sarpogrelate combined with rosuvastatin treatment significantly decreased total cholesterol and LDL cholesterol levels in the serum, and alleviated intimal hyperplasia and lipid deposition, accompanied by decreased inflammatory cell infiltration and lower expression levels of inflammatory cytokines, compared with rosuvastatin monotherapy or HFD treatment. Furthermore, sarpogrelate combined with rosuvastatin treatment significantly decreased the expression levels of LOX-1 and p-ERK. Taken together, these results suggest that the positive effects of sarpogrelate combined with rosuvastatin treatment on aortic injury may be associated with the regulation of the LOX-1/p-ERK signaling pathway. Sarpogrelate and rosuvastatin synergistically decreased aortic damage in ApoE-/- HFD mice, and thus provide a basis for the treatment of aortic injury caused by hyperlipidemia with sarpogrelate.


[Clinical efficiency of tanshinone IIA-sulfonate in treatment of liver fibrosis of advanced schistosomiasis].
To evaluate the clinical efficiency of tanshinone IIA-sulfonate (STS) in the treatment of liver fibrosis of advanced schistosomiasis. A total of 73 advanced schistosomiasis patients were selected into a treatment group and 55 cases of advanced schistosomiasis were selected into a control group, and dipstick dye immunoassay assay (DDIA) for schistosomiasis and HBsAg of all the patients were negative. The patients in the treatment group received STS for 14 days, and all the patients in both groups received the conventional liver-protecting treatment for 14 days. All the patients in both groups received the measurements of portal vein, 4 indicators of liver fibrosis (P III P, C IV, HA, LN), and 3 indicators of serum enzyme activities (ALT, AST, gamma-GT). After the treatments, the inside diameters of the portal vein and the degrees of the positive results of indicators of serum enzyme activities of all the patients of both groups decreased, but there were no statistically significant differences compared with those before the treatment. In the treatment group, the degrees of the positive results of indicators of liver fibrosis decreased somewhat, but there were no statistically significant differences compared with those before the treatment except C IV. In the control group, the degrees of the positive results of indicators of liver fibrosis fluctuated. In the treatment group, the indicator of liver fibrosis, CIV improved and the 2 indicators of liver fibrosis, PIIIP and HA improved significantly, but the indicators of serum enzyme activities did not improve. STS is effective in the treatment of liver fibrosis of advanced schistosomiasis.


Use of enteric-coated mycophenolate sodium in liver transplant patients with intestinal intolerance caused by mycophenolate mofetil.
Post-transplant gastrointestinal (GI) side effects can impair a patient's quality of life (QoL). This study investigates the improvement in GI side effects and related QoL changes in recipients of liver transplantation (OLT) after converting patients from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS). Thirty-four patients who underwent OLT and suffered from GI intolerability were included in this study. Infectious causes of GI intolerability were excluded. QoL assessed by the Gastrointestinal Quality of Life Index was evaluated before conversion and at months 3, 6 and 12 post-conversion. All patients received baseline immunosuppression of one calcineurin inhibitor, MMF, with or without steroids. Patients were converted from MMF to EC-MPS on an equimolar basis. Paired t-test was used to assess differences in mean score changes over time. Conversion from MMF to EC-MPS for GI intolerability post-OLT shows statistically significant improvement in GI-related QoL at 3, 6, and 12 months when compared to baseline assessments (p < 0.05 for total mean score); nonetheless, one-third of patients discontinued EC-MPS. No rejection episodes, deaths or graft loss were seen during the study period. OLT recipients who develop GI side effects caused by MMF can be safely converted to EC-MPS with improvement to their QoL.


[Conditioning in resuscitated rats with originally different behavioral patterns].
Male white rats divided in three groups on the basis of their behavior in the elevated plus-maze were subjected to 10-min cardiac arrest. Analysis of the results of their subsequent food and active avoidance conditioning revealed the effects of the following factors: (1) a factor of initial typological features of the higher nervous activity, (2) a factor of general brain mechanisms of postresuscitation, and (3) a factor of postresuscitation features in rats with different behaviors, which represented changes in different mechanisms of conditioned reflex performance in these animals.


Pulmonary Langerhans cell histiocytosis "de novo" after lung transplantation.
A pulmonary Langerhans cell histiocytosis is presented in a 40 year-old woman two years after bilateral lung transplantation for emphysema without any signs of Langerhans cells proliferation in the explanted lungs. A microsatellite molecular analysis showed the proliferating cells were generated in a recipient cellular clone. The patient did not quit smoking after transplantation. No signs of disease were detected in the implanted lungs before surgery. Strict control of immunosupressive drug levels stabilized the disease. A "de novo" monoclonal origin of stem cells, probably from the bone marrow is suggested. The reason she did not develop disease in the native lungs is unknown, although we suggest an interaction between tobacco or some other antigens and local cellular receptors.


Valorization of Fig (Ficus carica L.) Waste Leaves: HPLC-QTOF-MS/MS-DPPH System for Online Screening and Identification of Antioxidant Compounds.
Fig (Ficus carica L.) leaves are produced each year and often disposed, resulting in a waste of resources. Fig waste leaves are rich in flavonoids, which have strong antioxidant activity; however, the variety and chemical structure of antioxidants in fig leaves have not been reported in detail. To take full advantage of fig waste leaves, antioxidant capacity of different extracts (petroleum ether, ethyl acetate, and water) was evaluated by 1, 1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS), and ferric-ion-reducing antioxidant power (FRAP) methods. The results showed that flavonoids in ethyl acetate extraction had the highest content (83.92 ± 0.01 mg/g), maximum DPPH scavenging activity (IC50 0.54 mg/mL), highest ABTS scavenging rate (80.28%), and FRAP (3.46 mmol/g). Furthermore, an HPLC-QTOF-MS/MS-DPPH method was developed to identify 11 flavonoids in fig waste leaves. This rapid and efficient method can not only be used for screening the antioxidant components in fig waste leaves, but also can be combined with mass spectrometry to identify the compounds with antioxidant capacity. There are three flavonoids with significant antioxidant capacity, which are 3-O-(rhamnopyranosyl-glucopyranosyl)-7-O-(glucopyranosyl)-quercetin, isoschaftoside, and rutin. The results confirmed that fig waste leaves contain a variety of antioxidant components, which contributed to increase the value of fig waste leaves as antioxidants.


An economic analysis of family size decision making with reference to the developing areas of South Africa.
A neoclassical utility framework is used to analyze links between decisions about family size and socioeconomic variables using data for 175 women in KwaZulu, South Africa. The demand curve for children is specified within a simultaneous model of family decision-making. "Child education, women's opportunity cost of time and formal market participation were negatively related to fertility, reflecting substitution from numbers of children (time intensive) to fewer, more educated children (less time intensive) as opportunity costs rise. Child labour was positively related to fertility. Strategies to reduce population growth rates should therefore include improvements in women's education and employment opportunities to raise their time costs, and time-saving devices to reduce demand for child labour."


On the microbiological profile of traditional Portuguese sourdough.
Traditional manufacture of bread from maize has been noted to play important roles from both economic and social standpoints; however, enforcement of increasingly strict hygiene standards requires thorough knowledge of the adventitious microbiota of the departing dough. To this goal, sourdough as well as maize and rye flours from several geographic locations and in two different periods within the agricultural year were assayed for their microbiota in sequential steps of quantification and identification. More than 400 strains were isolated and taxonomic differentiation between them was via Biomerieux API galleries (375 of which were successfully identified) following preliminary biochemical and morphological screening. The dominant groups were yeasts and lactic acid bacteria (LAB). The most frequently isolated yeasts were Saccharomyces cerevisiae and Candida pelliculosa. The most frequently isolated LAB were (heterofermentative) Leuconostoc spp. and (homofermentative) Lactobacillus spp.; L. brevis, L. curvatus, and L. lactis ssp. lactis were the dominant species for the Lactobacillus genera; Lactococcus lactis ssp. lactis for lactococci; Enterococcus casseliflavus, E. durans, and E. faecium for enterococci; and Streptococcus constellantus and S. equinus for streptococci.


The association between chronic diseases and the age at natural menopause: a systematic review.
Despite several existing studies on the age at natural menopause (ANM) and its related factors, epidemiologic data on the associations between chronic diseases and ANM are scarce with conflicting and inconclusive results. The aim of this systematic review was to summarize the results of the studies investigating the association between chronic disease and ANM. PubMed, Scopus, and Web of Science were searched for retrieving and summarizing studies published up to October 2020 investigating the association between chronic medical conditions and ANM. All types of observational studies published in the English language were eligible to be included in the systematic review. Studies needed to report the effect of at least one chronic disease on ANM. Studies with other designs, studies with unreliable and incomplete results, and those that assessed none of the chronic diseases as outcomes of interest were excluded. Of the 6294 records retrieved by searching the databases, a total of 28 observational studies were included for this review. According to the Newcastle-Ottawa scale, nine studies were classified as high-quality, fifteen studies as moderate, and four as low-quality. Among the five studies investigating the association between polycystic ovary syndrome (PCOS) and ANM, three studies reported that PCOS was associated with a later ANM, whereas others found no such association. Eight studies showed that diabetes was associated with an earlier ANM, whereas eight other studies found no such association. While only one study showed a younger age at the onset of menopause in patients with a history of hypertension, five studies did not report such an effect. Only one study assessed the effect of dyslipidemia on ANM and showed no association between these variables. While three studies documented the effects of cardiovascular diseases (CVD) and heart disease on earlier ANM, one study found no association between these diseases and ANM. Most included studies showed the association of mood disorders with earlier ANM. There were no sufficient data for assessing the effects of thyroid, skin, and autoimmune diseases on ANM. Chronic diseases particularly cardio-metabolic disturbances, cardiovascular events, and psycho-emotional disorders are associated with earlier menopause, whereas other diseases such as PCOS may lead to later menopause. Accordingly, early diagnosis and managing chronic medical conditions in women can potentially prevent early or late menopause.


Integrated analysis of transcriptomic and proteomic data of Desulfovibrio vulgaris: zero-inflated Poisson regression models to predict abundance of undetected proteins.
Integrated analysis of global scale transcriptomic and proteomic data can provide important insights into the metabolic mechanisms underlying complex biological systems. However, because the relationship between protein abundance and mRNA expression level is complicated by many cellular and physical processes, sophisticated statistical models need to be developed to capture their relationship. In this study, we describe a novel data-driven statistical model to integrate whole-genome microarray and proteomic data collected from Desulfovibrio vulgaris grown under three different conditions. Based on the Poisson distribution pattern of proteomic data and the fact that a large number of proteins were undetected (excess zeros), zero-inflated Poisson (ZIP)-based models were proposed to define the correlation pattern between mRNA and protein abundance. In addition, by assuming that there is a probability mass at zero representing unexpressed genes and expressed proteins that were undetected owing to technical limitations, a Potential ZIP model was established. Two significant improvements introduced by this approach are (1) the predicted protein abundance level values for experimentally detected proteins are corrected by considering their mRNA levels and (2) protein abundance values can be predicted for undetected proteins (in the case of this study, approximately 83% of the proteins in the D.vulgaris genome) for better biological interpretation. We demonstrated the use of these statistical models by comparatively analyzing proteomic and microarray results from D.vulgaris grown on lactate-based versus formate-based media. These models correctly predicted increased expression of Ech hydrogenase and decreased expression of Coo hydrogenase for D.vulgaris grown on formate.


Hypopigmented mycosis fungoides: treatment and a 6(1/2)-year follow-up of 9 patients.
The clinical course of hypopigmented mycosis fungoides has not been well described. We sought to review the management and follow-up of patients with hypopigmented mycosis fungoides evaluated between January 1990 and August 1998. There were 7 African American and 2 Asian patients (5 male and 4 female patients); 8 had stage Ia and 1 had stage Ib disease. The mean age at diagnosis was 34.4 years, the mean latent period was 9.2 years, and the mean follow-up period after diagnosis was 6.5 years. Treatment modalities used included psoralen UVA, UVB, and topical mechlorethamine. Eight had complete clinical responses, and another had a partial response. The remission period ranged from 2 months to 3 years. In all but one patient, lesions recurred; all responded rapidly to another course of therapy. Hypopigmented mycosis fungoides is characterized by early onset, occurrence in dark-skinned individuals, and good response to therapy. Recurrences are common. In most, it has a biologically benign course.


Multiresidue method for detection of pesticides in beef meat using liquid chromatography coupled to mass spectrometry detection (LC-MS) after QuEChERS extraction.
Beef meat is an important food that can be contaminated by pesticides. This study aimed to optimize a multiresidue method for identification and quantification of pesticides in beef meat by liquid chromatography coupled to mass spectrometry detection (LC-MS). The extraction and clean-up procedures were adapted from the QuECHERS method. From the 188 analytes tested, the method was validated as qualitative method for 19 compounds and as quantitative method for 152 compounds. The results were satisfactory, yielding coefficients of variation of less than 20% and recoveries ranging from 70% to 120% and expanded uncertainty of less than 50%. The quantification limit was typically 10 µg kg-1 (but 25 µg kg-1 for 12 of the compounds) and the detection limit was 5.0 µg kg-1. Thirty-two real samples of commercialized beef meat were analyzed without any residual pesticide being found. Thus, the results showed that the multiresidue method for detecting 171 pesticides, using adapted QuECHERS for extraction and LC-MS for detection, is suitable for analyzing beef meat.


Colour vision in thrips (Thysanoptera).
Insects are an astonishingly successful and diverse group, occupying the gamut of habitats and lifestyle niches. They represent the vast majority of described species and total terrestrial animal biomass on the planet. Their success is in part owed to their sophisticated visual systems, including colour vision, which drive a variety of complex behaviours. However, the majority of research on insect vision has focused on only a few model organisms including flies, honeybees and butterflies. Especially understudied are phytophagous insects, such as diminutive thrips (Thysanoptera), in spite of their damage to agriculture. Thrips display robust yet variable colour-specific responses despite their miniaturized eyes, but little is known about the physiological and ecological basis of their visual systems. Here, we review the known visual behavioural information about thrips and the few physiological studies regarding their eyes. Eye structure, spectral sensitivity, opsin genes and the presence of putative colour filters in certain ommatidia strongly imply dynamic visual capabilities. Finally, we discuss the major gaps in knowledge that remain for a better understanding of the visual system of thrips and why bridging these gaps is important for expanding new possibilities for applied pest management strategies for these tiny insects. This article is part of the theme issue 'Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods'.


Persistent Sweet's syndrome occurring in a child with a primary immunodeficiency.
Sweet's syndrome (SS) occurs most commonly in association with inflammatory or neoplastic disorders. Only rarely has it been associated with immunodeficiency disorders. We describe a child with a T-cell immunodeficiency who had a persistent neutrophilic dermatosis that was histologically and clinically consistent with SS. SS associated with immunodeficiencies may occur as a reaction to an underlying infection or a defect in immunoregulation. Such patients, however, may not be able to produce the classic fever and neutrophilia associated with SS. They may fail to respond to standard treatment for SS and may suffer a prolonged and persistent course.


Combining bioengineered human dermal replacement and multilayered compression dressings to manage ulcers in a person with diabetes mellitus: a case study.
Multiple modalities exist for the care of lower extremity ulcers associated with venous insufficiency and complications of diabetes mellitus, (eg, neuropathy). Although reports about the use of topical adjunctive treatment modalities in the treatment of foot ulcers in persons with diabetes mellitus exist, little is known about the safety of topical treatment when used in combination with compression therapy to manage venous insufficiency. A patient with diabetes mellitus, neuropathy, a 3.3 cm x 3.0 cm x 1 mm heel ulcer and a 8.1 cm x 4.9 cm x 3 mm lower leg ulcer secondary to venous insufficiency presented at the authors' clinic. After 8 weeks of therapy using a combination of bioengineered human dermal replacement and multilayered compression dressings, lower leg edema was reduced, the heel ulcer healed, and the leg ulcer continued to improve. No complications were observed. The results observed suggest that studies examining the effects of treatment regimens that address the multifactorial etiology of some lower extremity ulcers are warranted.


Dynamics of populations in a changing environment.
We present an individual-based model of a population that lives in a changing environment. The individuals forming the population are subject to mutations and selection pressure. Using Monte Carlo simulations we have shown that, depending on the values of the mutation rate and selection, the population may reach either an active phase (it will survive) or an absorbing phase (it will become extinct). We have determined that the transition between the two states (phases) is continuous. We have shown that when the selection is weaker the population lives in all available space, while if the selection is stronger, it will move to the regions where the living conditions are better, avoiding those with more difficult conditions. The dependence of the mean time to extinction on the rate of mutations has been determined and discussed.


The Arabidopsis thaliana SNF2 homolog AtBRM controls shoot development and flowering.
Chromatin remodeling is essential for the reprogramming of transcription associated with development and cell differentiation. The SWI/SNF complex was the first chromatin remodeling complex characterized in yeast and Drosophila. In this work we have characterized an Arabidopsis thaliana homolog of Brahma, the ATPase of the Drosophila SWI/SNF complex. As its Drosophila counterpart, Arabidopsis thaliana BRAHMA (AtBRM) is a nuclear protein present in a high molecular mass complex. Furthermore, the N terminus of AtBRM interacts, in the two-hybrid system, with CHB4 (AtSWI3C), an Arabidopsis homolog of the yeast SWI/SNF complex subunit SWI3. The AtBRM gene is primarily expressed in meristems, organ primordia and tissues with active cell division. Silencing of the expression of the AtBRM gene by RNA interference demonstrated that AtBRM is required for vegetative and reproductive development. The AtBRM silenced plants exhibited a reduction in overall plant size with small and curled leafs, as well as a reduction in the size of the inflorescence meristem. In the absence of AtBRM, Arabidopsis flowers have small petals and stamens, immature anthers, homeotic transformations and reduced fertility. The AtBRM silenced plants flower earlier than wild-type plants both under inductive and non-inductive photoperiods. Furthermore, levels of CO, FT and SOC1 transcripts were up-regulated under non-inductive conditions suggesting that AtBRM is a repressor of the photoperiod-dependent flowering pathway.


Intrathecal antibody synthesis in Lyme neuroborreliosis: use of recombinant p41 and a 14-kDa flagellin fragment in ELISA.
The intrathecal synthesis of IgM and IgG antibodies to Borrelia burgdorferi sonicate, to recombinant flagellin (41 kDa) and to a tryptic peptide of the flagellin (14-kDa fragment) was determined by ELISA in paired cerebrospinal fluid (CSF) and serum samples from 35 patients with Lyme neuroborreliosis (LNB) and in 10 patients with neurosyphilis. The antibody index (AI = QBb/QIg) was calculated from the ratio between CSF/serum quotients for specific antibodies (QBb) and total immunoglobulins (QIg). For the examination of IgG antibodies, the sonicate ELISA was performed with and without pre-absorption with Treponema phagedenis. Of 35 patients with LNB, 31 had intrathecal IgG response to B. burgdorferi demonstrated by sonicate ELISA (24 after absorption of cross-reactive antibodies), 29 had a response demonstrated by flagellin ELISA and 21 of 35 by 14-kDa ELISA. In patients with neurosyphilis the AI (IgG) was elevated in the sonicate ELISA in 7 of 10 samples (none of 10 after absorption of cross-reactive antibodies), in the flagellin ELISA in 5 of 10 samples and in the 14-kDa ELISA in none of 10 samples. Intrathecal synthesis of IgM antibodies to B. burgdorferi was demonstrated in patients with neuroborreliosis by sonicate ELISA in 20 of 35 samples, by flagellin ELISA in 16 of 35 samples and by 14-kDa ELISA in 9 of 35 samples. No intrathecal synthesis of B. burgdorferi-specific IgM could be detected by any assay in patients with neurosyphilis.(ABSTRACT TRUNCATED AT 250 WORDS)


Sudden death in a child with epilepsy: potential cerebellar mechanisms?
Epilepsy is the most common neurological disorder in humans. People with epilepsy are more likely to die prematurely than those without epilepsy, with the most common epilepsy-related category of death being sudden unexpected death in epilepsy (SUDEP). The central mechanisms underlying the fatal process remain unclear, but cardiac and respiratory mechanisms appear to be involved. Recently, cerebellar, thalamic, basal ganglia and limbic brain structures have been shown to be implicated in respiratory and cardiac rate regulation. We discuss here the potential mechanisms underlying the fatal process, with a description of cerebellar actions likely failing in that SUDEP process.


Environmentally sensitive paramagnetic and diamagnetic contrast agents for nuclear magnetic resonance imaging and spectroscopy.
Even though alterations in the microenvironmental properties of tissues underlie the development of the most prevalent and morbid pathologies, they are not directly observable in vivo by Magnetic Resonance Imaging (MRI) or Spectroscopy (MRS) methods. This circumstance has lead to the development of a wide variety of exogenous paramagnetic and diamagnetic MRI and MRS probes able to inform non invasively on microenvironmental variables such as pH, pO(2), ion concentration o even temperature. This review covers the fundamentals of environmental contrast and the current arsenal of endogenous and exogenous MRI and MRS contrast enhancing agents available to visualize it. We begin describing the physicochemical background necessary to understand paramagnetic and diamagnetic contrast enhancement with a special reference to novel magnetization transfer and (13)C hyperpolarization strategies. We describe then the main macrocyclic structures used to support the environmentally sensitive paramagnetic sensors, including CEST and PARACEST pH sensitive probes, temperature probes and enzyme activity or gene expression activatable probes. Finally we address the most commonly used diamagnetic contrast agents including imidazolic derivatives to reveal extracellular pH and tissue pO(2) values by MRS. The potential applications of these agents in multimodal and molecular imaging approaches are discussed.


Effects of inorganic mercury on the olfactory pits of zebrafish larvae.
Mercury compounds are highly toxic; due to the rising levels of mercury pollution, both human and environmental exposure to mercury are increasing. Occupational exposure to inhaled mercury can be high, causing adverse effects not only in the lungs, but in the olfactory system as well. Olfaction plays a critical role in the survival of fish and other vertebrates, and impaired olfaction can substantially impact human quality of life. We present a study of the effects of mercury exposure in the olfactory pits of zebrafish larvae using a combination of X-ray fluorescence imaging and immunohistochemistry. We show that mercury accumulates in the sensory cells of the olfactory pits and also that it may also damage primary neurons, such as those that innervate olfactory pits.


Nanocrystalline LaOCl:Tb(3+)/Sm(3+) as promising phosphors for full-color field-emission displays.
Nanocrystalline LaOCl:Tb(3+)/Sm(3+) phosphors were synthesized by a Pechini-type sol-gel process. Under UV and electron-beam excitation, LaOCl:Tb(3+)/Sm(3+) show the characteristic emission of Tb(3+) ((5)D(3,4)-->(7)F(6),...2) and Sm(3+) ((4)G(5/2)-->(6)H(5/2,7/2,9/2)), respectively. In particular, the cathodoluminescence (CL) color of LaOCl:Tb(3+) can be tuned from blue to green by changing Tb(3+)-doped concentration, and their CL intensities (brightness) are higher than those of commercial products Y(2)SiO(5):Ce(3+) and ZnO:Zn, respectively. White CL can be realized by codoping with Tb(3+) and Sm(3+) in a single-phase LaOCl host. The obtained white light is very close to the standard white light. These phosphors are promising for application in field-emission displays.


Cancer of the uterine cervix is susceptible to anti-EGF-R antibody EMD 55,900 therapy.
Among a variety of cancer therapeutics targeting the epidermal growth factor receptor (EGF-R), monoclonal antibodies have shown some therapeutic potential in the treatment of various tumours of different entities. Nevertheless, several high EGF-R-expression carcinomas show no response to this treatment. Tumours of the uterine cervix represent a group, in which the response to anti-EGF-R treatment is hardly predictable, despite a relatively high expression of the receptor. To assess the antitumour activity of anti-EGF-R monoclonal antibody EMD 55,900 in vivo, a series of experiments were performed in the nude mouse model using xenotransplanted primary carcinomas of the uterine cervix. EMD 55,900 was found to be capable of inhibiting the growth of primary carcinomas of the uterine cervix at different stages of tumour development. The therapeutic response was not dependent on EGF-R expression solely, but also on the pre-treatment microvessel density.


Case Report: An "Immune-Cold" EGFR Mutant NSCLC With Strong PD-L1 Expression Shows Resistance to Chemo-Immunotherapy.
Long-term survival benefit has been noticed in non-small-cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), such as PD-1 inhibitors. However, it is still controversial whether patients with EGFR-activating mutations may benefit from ICIs. Recently, in stage IIIA NSCLC, chemo-immunotherapy has led to significant pathological response, yet patients with the presence of known EGFR mutations were excluded from some randomized trials of neoadjuvant therapy. Herein, we report a case of a 50-year-old female patient, who was initially diagnosed as stage IIIA lung squamous cell carcinoma. Immunohistochemistry analysis showed that the patient presented with high PD-L1 expression. Then, chemo-immunotherapy was given to the patient but the disease progressed quickly with distant metastasis. A re-biopsy revealed a poorly differentiated lung adenocarcinoma together with EGFR p.L858R mutation. Then the patient received gefitinib, which resulted in significant regression of primary lung lesion. A detailed examination of pre-treatment tumor sections demonstrated rare infiltration of CD8+ T cells, indicating that the current patient presented with an "immune-cold" microenvironment, which might explain the primary resistance to chemo-immunotherapy. Taken together, our case indicated that comprehensive detection of PD-L1 expression, driver gene status, together with tumor immune microenvironment, may offer a better prediction of treatment efficacy.


Unusual cause for miliary lung mottling in a child.
A 12-year-old boy presented to us with a diagnosis of disseminated tuberculosis which was made based on a history of prolonged fever, multiple neck swellings and radiological findings of bilateral multiple micronodular opacities. Examination showed a diffuse thyroid gland swelling. He was diagnosed to have papillary thyroid carcinoma with distant metastases to cervical lymphnode on histopathology and to lungs.


The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice.
The complement system is an important component of the innate immune response to bacterial pathogens, including Streptococcus pneumoniae. The classical complement pathway is activated by antibody-antigen complexes on the bacterial surface and has been considered predominately to be an effector of the adaptive immune response, whereas the alternative and mannose-binding lectin pathways are activated directly by bacterial cell surface components and are considered effectors of the innate immune response. Recently, a role has been suggested for the classical pathway during innate immunity that is activated by natural IgM or components of the acute-phase response bound to bacterial pathogens. However, the functional importance of the classical pathway for innate immunity to S. pneumoniae and other bacterial pathogens, and its relative contribution compared with the alternative and mannose-binding lectin pathways has not been defined. By using strains of mice with genetic deficiencies of complement components and secretory IgM we have investigated the role of each complement pathway and natural IgM for innate immunity to S. pneumoniae. Our results show that the proportion of a population of S. pneumoniae bound by C3 depends mainly on the classical pathway, whereas the intensity of C3 binding depends on the alternative pathway. Furthermore, the classical pathway, partially targeted by the binding of natural IgM to bacteria, is the dominant pathway for activation of the complement system during innate immunity to S. pneumoniae, loss of which results in rapidly progressing septicemia and impaired macrophage activation. These data demonstrate the vital role of the classical pathway for innate immunity to a bacterial pathogen.


The effect of fumaric acid esters and dithranol on acanthosis and hyperproliferation in psoriasis vulgaris.
In this study we investigated the histological changes, regression of acanthosis and rate of proliferation, that accompany the healing of psoriatic lesions after fumaric acid esters and dithranol treatment. Biopsies were taken before and during therapy as well as from neighbouring untreated, clinically uninvolved skin and healthy, non-psoriatic volunteers. Specimens were assessed using computer-supported image analysis and immunohistology. The parameters primarily examined were the height of the rete pegs and of the epithelium above the papillary body, the rate of proliferation, the actual number of cells in the two epidermal compartments and the cellular density in the epidermis. Both fumaric acid esters and dithranol reduce the degree of acanthosis; however, the mechanism and the rate of the reduction differ. While under fumaric acid esters the reduction is more rapid at first but subsequently slows down, dithranol leads to a slow but steady decrease of epidermal thickness, so that at the end of our study the degree of acanthosis was less under dithranol. As an underlying mechanism of action, we found that fumaric acid esters reduce the rate of proliferation and thereby decrease the number of cells per rete peg as well as the size of the individual keratinocytes. Dithranol in contrast does not reduce cell renewal. The decrease of the number of cells in the rete pegs might be caused by an increased differentiation time.


Hemorheological parameters as determinants of myocardial tissue hematocrit values.
It is well known that the hematocrit in microvessels with diameters smaller than 1000 microm is lower than either venous or arterial hematocrit, thereby resulting in significantly lower mean hematocrit values for vessels perfusing a given tissue (i.e., lower tissue hematocrit). The mechanisms that underlie this reduction of microvascular hematocrit include axial migration, plasma skimming and the Fahraeus Effect. It has been previously demonstrated in rats that a linear hematocrit gradient normally exists through the thickness of the left ventricular myocardium, and that this gradient is sensitive to alterations of the rheological properties of the circulating blood. The gradient is abolished if the RBC in the perfusate are rigid; fibrinogen infusions, and thus increases of both plasma viscosity and RBC aggregation, also affect this gradient. In a new series of studies, it has been observed that enhanced RBC aggregation affects the myocardial hematocrit gradient regardless of alterations of plasma viscosity. Although the exact mechanisms responsible for the myocardial hematocrit gradient, as well as its physiological significance, are not yet clearly known, it is possible to speculate that alterations in local hematocrit could adversely affect myocardial perfusion and function.


Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in Patients With Multiple Comorbidities: Long-Term Safety and Efficacy Results From a Tertiary Care Community Hospital.
Cure rates of Clostridium difficile infection (CDI) with fecal microbiota transplant (FMT) have been promising. However, there is debate regarding success of FMT in patients with comorbidities. Electronic chart review was done to collect data on patients who underwent FMT from January 2015 to August 2017. Charts were analyzed in November 2018 with a median follow-up of 25.4 months (interquartile range 20 - 31 months). Twenty patients underwent FMT. The primary success rate at our institution was 90% and overall success rate was 100%. Six patients (43%) had FMT failure (two early and four late). This case series is a description of our center's initial experience with FMT for treatment of recurrent CDI. Our high success rate reiterates the efficacy and safety of FMT in this population including patients with comorbidities.


Beyond the diathesis-stress paradigm: Effect of the environmental sensitivity × pubertal tempo interaction on depressive symptoms.
Based on the Differential Susceptibility Theory, we examined whether the relationship between pubertal maturation and depressive symptoms can be moderated by individual differences in environmental sensitivity. The current article used the three-wave data collected from Japanese adolescents aged from 12 to 15 years (girls = 111, boys = 98). Consequently, a significant Sensitivity × Pubertal Development interaction was observed in 12- to 13-year-old boys, but not girls. Sensitive boys who experienced accelerated physical maturation reported decreased depressive symptoms, while those who experienced less maturation had increased depressive symptoms. The shape of the interaction supported both the Differential Susceptibility Theory and the Diathesis-Stress Model. Our findings suggest that sensitivity during early puberty among boys could be reconsidered as susceptibility rather than vulnerability.


The impact of different proportions of a treated effluent on the biotransformation of selected micro-contaminants in river water microcosms.
Attenuation of micro-contaminants is a very complex field in environmental science and evidence suggests that biodegradation rates of micro-contaminants in the aqueous environment depend on the water matrix. The focus of the study presented here is the systematic comparison of biotransformation rates of caffeine, carbamazepine, metoprolol, paracetamol and valsartan in river water microcosms spiked with different proportions of treated effluent (0%, 0.1%, 1%, and 10%). Biotransformation was identified as the dominating attenuation process by the evolution of biotransformation products such as atenolol acid and valsartan acid. Significantly decreasing biotransformation rates of metoprolol were observed at treated effluent proportions ≥ 0.1% whereas significantly increasing biotransformation rates of caffeine and valsartan were observed in the presence of 10% treated effluent. Potential reasons for the observations are discussed and the addition of adapted microorganisms via the treated effluent was suggested as the most probable reason. The impact of additional phosphorus on the biodegradation rates was tested and the experiments revealed that phosphorus-limitation was not responsible.


Associations between objectively assessed and questionnaire-based sedentary behaviour with body mass index and systolic blood pressure in Kuwaiti adolescents.
Kuwait has one of the highest obesity rates in the world. This study examined the associations between sedentary behaviour (objectively measured and self-reported), adiposity and systolic blood pressure in a sample of adolescents residing in Kuwait. Data was obtained from the Study of Health and Activity among adolescents in Kuwait (2012-2013). The sample included a total of 435 adolescents (201 boys). Outcomes were age- and sex specific body mass index Z-scores and systolic blood pressure. Exposures were total sedentary behaviour measured by accelerometry and time spent in some sedentary behaviours (television viewing, video games, computer use and total screen-time). We used multiple linear regression analyses, adjusted for age, governorate, maternal education and physical activity, to examine associations between sedentary behaviour and adiposity and systolic blood pressure. Only 2 statistically significant associations were found between sedentary behaviour and the study outcomes: body mass in boys was directly associated with higher sedentary time [β (95% CIs) 0.003 (0.00 to 0.06)]; body mass index was inversely associated with videogames in both sexes [girls: β (95% CIs) - 0.17 (- 0.48 to - 0.04); boys: - 0.24 (- 0.57 to - 0.12)]. In this sample of Kuwaiti adolescents, sedentary behaviour showed limited deleterious associations with adiposity and systolic blood pressure.


Novel coronavirus infection and acute kidney injury in two renal transplant recipients: a case report.
The causative virus of coronavirus disease 2019 (COVID-19) may cause severe fatal pneumonia. The clinical presentation includes asymptomatic infection, severe pneumonia, and acute respiratory failure. Data pertaining to acute renal injury due to COVID-19 in patients who have undergone renal transplantation are scarce. We herein report two cases of COVID-19 along with acute kidney injury following kidney transplantation.Case presentation: Two patients with COVID-19 underwent renal transplantation and were subsequently diagnosed with acute kidney injury. The first patient presented with progressive respiratory symptoms and acute renal injury. He was treated with diuretics and suspension of immunosuppressive therapy; however, the patient died. The second patient presented with respiratory tract symptoms, hypoxemia, and progressive deterioration of renal function followed by improvement. Her mycophenolate mofetil was stopped after admission, and tacrolimus was discontinued 10 days later. Moxifloxacin and methylprednisolone were continued in combination with albumin and gamma globulin infusion. A diuretic was administered, and prednisone was gradually reduced along with tacrolimus. The patient exhibited a satisfactory clinical recovery. Patients who develop COVID-19 after kidney transplantation are at risk of acute kidney injury, and their prednisone, immunosuppressant, and gamma globulin treatment must be adjusted according to their condition.