Structure and function analysis of a type III preQ1-I riboswitch from Escherichia coli reveals direct metabolite sensing by the Shine-Dalgarno sequence.
Riboswitches are small noncoding RNAs found primarily in the 5' leader regions of bacterial messenger RNAs where they regulate expression of downstream genes in response to binding one or more cellular metabolites. Such noncoding RNAs are often regulated at the translation level, which is thought to be mediated by the accessibility of the Shine-Dalgarno sequence (SDS) ribosome-binding site. Three classes (I-III) of prequeuosine1 (preQ1)-sensing riboswitches are known that control translation. Class I is divided into three subtypes (types I-III) that have diverse mechanisms of sensing preQ1, which is involved in queuosine biosynthesis. To provide insight into translation control, we determined a 2.30 Å-resolution cocrystal structure of a class I type III preQ1-sensing riboswitch identified in Escherichia coli (Eco) by bioinformatic searches. The Eco riboswitch structure differs from previous preQ1 riboswitch structures because it has the smallest naturally occurring aptamer and the SDS directly contacts the preQ1 metabolite. We validated structural observations using surface plasmon resonance and in vivo gene-expression assays, which showed strong switching in live E. coli. Our results demonstrate that the Eco riboswitch is relatively sensitive to mutations that disrupt noncanonical interactions that form the pseudoknot. In contrast to type II preQ1 riboswitches, a kinetic analysis showed that the type III Eco riboswitch strongly prefers preQ1 over the chemically similar metabolic precursor preQ0. Our results reveal the importance of noncanonical interactions in riboswitch-driven gene regulation and the versatility of the class I preQ1 riboswitch pseudoknot as a metabolite-sensing platform that supports SDS sequestration.


Microstructure, mechanical, and in vitro properties of mica glass-ceramics with varying fluorine content.
The design and development of glass ceramic materials provide us the unique opportunity to study the microstructure development with changes in either base glass composition or heat treatment conditions as well as to understand processing-microstructure-property (mechanical/biological) relationship. In the present work, it is demonstrated how various crystal morphology can develop when F(-) content in base glass (K(2)O-B(2)O(3)-Al(2)O(3)-SiO(2)-MgO-F) is varied in the range of 1.08-3.85% and when all are heat treated at varying temperatures of 1000-1120 degrees C. For some selected heat treatment temperature, the heat treatment time is also varied over 4-24 h. It was established that with increase in fluoride content in the glass composition, the crystal volume fraction of the glass-ceramic decreases. Using 1.08% fluoride, more than 80% crystal volume fraction could be achieved in the K(2)O-B(2)O(3)-Al(2)O(3)-SiO(2)-MgO-F system. It was observed that with lower fluoride content glass-ceramic, if heated at 1040 degrees C for 12 h, an oriented microstructure with 'envelop like' crystals can develop. For glass ceramics with higher fluorine content (2.83% or 3.85%), hexagonal-shaped crystals are formed. Importantly, high hardness of around 8 GPa has been measured in glass ceramics with maximum amount of crystals. The three-point flexural strength and elastic modulus of the glass-ceramic (heat treated at 1040 degrees C for 24 h) was 80 MPa and 69 GPa of the sample containing 3.85% fluorine, whereas, similar properties obtained for the sample containing 1.08% F(-) was 94 MPa and 57 GPa, respectively. Further, in vitro dissolution study of the all three glass-ceramic composition in artificial saliva (AS) revealed that leached fluoride ion concentration was 0.44 ppm, when the samples were immersed in AS for 8 weeks. This was much lower than the WHO recommended safety limits of 1.5 ppm. Among all the investigated glass-ceramic samples, the glass ceramic with 3.85% F(-) content in base glass (heat treated at 1040 degrees C for 12 h), exhibits the adherence of Ca-P layer, which consists of spherical particles of 2-3 mum. Other ions, such as Mg(+2) and K(+1) ion concentrations in the solution were found to be 8 and 315 ppm after 8 weeks of leaching, respectively. The leaching of all metal ions is recorded to decrease with time, probably due to time-dependent kinetic modification of sample surface. Summarizing, the present study illustrates that it is possible to obtain a good combination of crystallization, mechanical and in vitro dissolution properties with the careful selection of base glass composition and heat treatment conditions.


Indolo[2,3-a]quinolizidines and Derivatives: Bioactivity and Asymmetric Synthesis.
Corynantheine alkaloids with a tetracyclic indole[2,3-a]-quinolizidine motif are an important issue in academia and in the life science industries due to their broad bioactivity profile. In particular, the main biological effects described for indoloquinolizidines include analgesic, anti-inflammatory, antihypertensive, and antiarrhythmic activities, as well as inhibition of multiple ion channels, affinity for opioid receptors, and activity against Leishmania. For that reason, in the last decades, numerous efforts have been invested in the development of novel synthetic strategies to obtain the indole[2,3-a]-quinolizidine system. This review focuses on the synthetic methodologies developed to target the most important alkaloids of this family, and highlights the potential use of these alkaloids or analogs to treat several diseases, ranging from cancer to neurodegenerative disorders.


Pattern perception and computational complexity: introduction to the special issue.
Research on pattern perception and rule learning, grounded in formal language theory (FLT) and using artificial grammar learning paradigms, has exploded in the last decade. This approach marries empirical research conducted by neuroscientists, psychologists and ethologists with the theory of computation and FLT, developed by mathematicians, linguists and computer scientists over the last century. Of particular current interest are comparative extensions of this work to non-human animals, and neuroscientific investigations using brain imaging techniques. We provide a short introduction to the history of these fields, and to some of the dominant hypotheses, to help contextualize these ongoing research programmes, and finally briefly introduce the papers in the current issue.


Distribution and pathophysiologic role of molybdenum-containing enzymes.
The importance of molybdenum-containing enzymes in the pathophysiology of a number of clinical disorders necessitates a comprehensive understanding of their histological localization and expression. The objectives of this review are to cover such enzymes so far reported and their enzyme- and immunohistochemical localization in various tissues and species, and to discuss their possible pathophysiological effects. The molybdenum cofactor is essential for the activity of the three molybdenum-containing enzymes, sulfite oxidase, xanthine oxidase and aldehyde oxidase. Sulfite oxidase serves as the terminal enzyme in the pathway of the oxidative degradation of sulfur amino acids, and is also involved in preventing the toxic effects of sulfur dioxide. Biochemical study has revealed a high activity of sulfite oxidase mainly in the liver, heart and kidney with lesser activity observed in other tissues. Subcellular observations have shown that this enzyme is present in the mitochondrial intermembraneous spaces. Xanthine oxidase is the final enzyme in the conversion of hypoxanthine to xanthine, and subsequently, to uric acid. Unlike sulfite and aldehyde oxidases, xanthine oxidase can be converted to xanthine dehydrogenase, and vice versa. Xanthine oxidase has been widely investigated for its role in post-ischemic reperfusion tissue injury. Enzyme- and immunohistochemical studies of its localization in various animal species and tissues have shown its ubiquitous distribution in the liver, small and large intestine, lung and kidney, and other tissues. Aldehyde oxidase shares a similar substrate specificity with xanthine oxidase. Although the tissue localization of this enzyme has not been studied as thoroughly as that of xanthine oxidase, aldehyde oxidase is reportedly found in the digestive gland of terrestrial gastropods, the antennae of certain moths as well as the mammalian liver. Recently, the ubiquitous distribution of aldehyde oxidase has been demonstrated in rat tissues. The aldehyde oxidase activity of herbivores exceeds that of carnivores, suggesting a possible role of this enzyme as a protection against the effects of toxic plants. The relationship between the tissue localization of these enzymes and their pathophysiological roles is reviewed.


Gynecologic injury in the nongravid female during blunt abdominal trauma.
Fifteen cases of uterine and adnexal findings in the nongravid female were identified among 220 exploratory laparotomies performed for blunt abdominal trauma. These include: 13 cases of ovarian cyst hemorrhage, one case of ovarian laceration, and one case of uterine and vaginal lacerations. All patients had positive peritoneal lavage. In 13 of the patients in this series, the bleeding was associated with and in proximity to an existing corpus luteum.


Cochlear pathology. Hazards of long-term implants.
There is increasingly diverse evidence that multichannel intrascalar or modiolar implants can cause long-term changes in cochlear structure. Experimental studies show that nerve-cell loss and osteogenesis are related to electrical stimulation. Low charge densities may limit such intracochlear changes. Middle-ear stimulation presents an alternative to the intracochlear implant, although its degree of effectiveness is not well characterized. Monitoring electrically produced auditory brain-stem responses may help detect progressive pathologic changes occurring in the implanted cochlea.


Lead pollution: records in Southern California coastal sediments.
The present anthropogenic lead fluxes into sediments from the Santa Monica, San Pedro, and Santa Barbara basins of Southern California are, respectively, 0.9, 1.7, and 2.1 micrograms of lead per square centimeter of sea bottom per year; the natural (prepollution) rates for these three basins were, respectively, 0.24, 0.26, and 1.0 microgram of lead per square centimeter per year. Studies of isotopic composition indicate that lead pollutants in coastal sediments are derived mainly from the combustion of lead additives in gasoline.


NADPH oxidase-derived reactive oxygen species mediate decidualization of human endometrial stromal cells in response to cyclic AMP signaling.
Differentiation of human endometrial stromal cells into specialized decidual cells is critical for embryo implantation and survival of the conceptus. Initiation of this differentiation process is strictly dependent on elevated cAMP levels, but the signal intermediates that control the expression of decidual marker genes, such as prolactin (PRL) and IGFBP1, remain poorly characterized. Here we show that cAMP-dependent decidualization can be attenuated or enhanced upon treatment of primary cultures with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (diphenylen iodonium) or activator (apocynin), respectively. Time-course analysis demonstrated that cAMP enhances endogenous reactive oxygen species production, apparent after 12 h of stimulation, which coincides with a dramatic increase in decidual PRL and IGFBP1 expression. Knockdown of the Rho GTPase RAC1, which disables activation of the NADPH oxidase homologs NADPH oxidase (NOX)-1, NOX-2, and NOX-3, had no effect on PRL or IGFBP1 expression. In contrast, silencing of NOX-4, or its cofactor p22(PHOX), inhibited the expression of both decidual markers. Finally, we show that the NOX-4/p22(PHOX) complex regulates the DNA-binding activity of CCAAT/enhancer binding protein-β, a key regulator of human endometrial stromal cell differentiation. Thus, NOX-4 activation and reactive oxygen species signaling play an integral role in initiating the endometrial decidual response in preparation of pregnancy.


Medication errors through a national pharmacovigilance database approach: a study for Malta.
To identify medication errors in the Maltese pharmacovigilance database and describe the frequency and characteristics of these events. A retrospective analysis of the Adverse Drug Events (ADEs) reported over 5 years in Malta was conducted. Medication errors were identified by comparing use against the product's Summary of Product Characteristics (SmPC) and then classified by type of medication error, seriousness and the stage of the medication use chain at which they occurred. 319 consolidated ADE reports met the inclusion criteria and were analysed. 56/319 consolidated ADEs were associated with serious patient harm. The 80-89 and the 50-59 age groups were associated with most medications used in error. 65% of errors originated in the community. Errors were identified in prescribing (52%), therapeutic monitoring (26%), patients' own (12%), dispensing (7%) and administration (3%) stages. The non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics were most commonly used in errors involving wrong doses, lack of therapeutic monitoring, interactions; contra-indications, prescribing for an unlicensed indication as well as an inappropriate duration of therapy. Pharmacovigilance databases are a useful source of information on medication errors and can be used to detect risks associated with the use of medicinal products.


Clues to vascular disorders at non-contrast CT of the chest, abdomen, and pelvis.
Non-contrast chest CT scans are commonly performed while CT scans of the abdomen and pelvis are performed in a select subset of patients; those with limited renal function, an allergy to iodinated contrast, in the setting of suspected renal calculus, retroperitoneal hematoma, common duct calculus, abdominal aortic aneurysm with or without rupture, and in patients undergoing a PET-CT scan. In the absence of intravenous contrast, vascular structures may prove challenging to evaluate, yet their assessment is an important component of every non-contrast CT examination. We describe the key imaging features of both arterial and venous pathology, and review clues and common associated non-vascular findings, which can help the radiologist identify vascular disorders at non-contrast CT. Briefly, alternative imaging options are discussed.


The Functions and Mechanisms of Long Non-coding RNA SNHGs in Gastric Cancer.
Gastric cancer is one of the most common malignancies worldwide. Despite significant advancements in surgical and adjuvant treatments, patient prognosis remains unsatisfactory. Long non-coding RNAs (lncRNAs) are a class of RNA molecules that lack protein-coding capacity but can participate in various mechanisms of tumor malignancy. Among them, small nucleolar host genes (SNHGs) represent a subgroup of lncRNAs. Studies have revealed their involvement not only in gastric cancer cell proliferation, invasion, migration, epithelialmesenchymal transition (EMT), and apoptosis but also in chemotherapy resistance and tumor stemness. This review comprehensively summarizes the biological functions, molecular mechanisms, and clinical significance of SNHGs in gastric cancer. It provides novel insights into potential biomarkers and therapeutic targets for the exploration of gastric cancer.


Design principles and statistical considerations in periodontal clinical trials.
Although clinical trials are a small subset of conducted biomedical research, they have become powerful investigational tools for the evaluation and approval of new treatments by clinician groups and regulatory agencies like the US Food and Drug Administration. To impact the delivery of care, trials in general must meet three criteria: clarity, comparability, and generalizability. Accordingly, trials can offer meaningful data if they have procedures which are well defined and subjects who represent a reasonably homogeneous population. The evaluation of periodontitis interventions presents several challenges due to the disease's heterogeneity and its irregular, episodic pattern; nevertheless, the intent of these novel interventions is to prevent, diagnose, inhibit, or reverse periodontal disease progression. Careful consideration of the trial's objectives should dictate clinical endpoints (primary and surrogate), comparison groups (placebo, standard therapy, test therapy), and equivalence versus superiority as the basis for conclusions. Several design elements such as control population specification, randomization, masking, sample size calculation, and standardization of procedures for patient care and assessment can decrease potential bias and variability. In both parallel and paired (split-mouth) design trials, multiplicities of endpoints, treatments, and subgroups require strategies which address the broader scope of chance findings without excessive loss of study power. Also, the longitudinal assessment of multiple periodontal sites within patients produces correlated data structures for which analytic methods need to account for the appropriate sampling unit. With these design and analytic elements, clinical trials can provide important evidence to investigators, patients, and governmental agencies for the introduction of novel interventions in periodontal practice.


The inhibition of endotoxin-induced local inflammation by LDH virus or LDH virus-infected tumors is mediated by interferon.
The footpad swelling reaction induced by local injection of S. marcescens lipopolysaccharide was found to be inhibited in mice given a transplantable tumor (TA3) or cell-free ascitic fluid from tumor-bearing mice. The tumor was shown to contain LDH virus, which is known to cause inapparent persistent infections in mice. Monoclonal antibodies directed against protein VP3 of the LDH virus could partially abrogate the anti-inflammatory effect of the TA3-ascitic fluid, and, conversely, the anti-inflammatory effect could be obtained by LDH virus isolated from the tumor and reproduced by serial passage of cell-free fluids. Inhibition of the footpad reaction was seen in the acute but not in the chronic phase of LDH virus infection, suggesting that the anti-inflammatory effect might be due to endogenous interferon (IFN) which, similarly, was only detectable in the acute phase. Newcastle disease virus, another potent interferon inducer, had a similar inhibitory effect on the footpad reactivity. Moreover, the inhibitory effect of LDH virus infection could partially be abrogated by administration of a polyclonal antibody directed against murine IFN-alpha,beta. Finally, passively administered natural murine IFN-alpha,beta or recombinant murine IFN-alpha 1 (but not recombinant murine IFN-beta) was found to cause inhibition of the footpad reaction. Since Gram-negative bacteria and their lipopolysaccharides have the ability to induce a systemic interferon response, our findings suggest that this interferon may play a modulatory role in local inflammation caused by these bacteria. Our findings also open a new perspective for interferon therapy of certain inflammatory reactions to bacterial infections.


ENVIRONMENTAL AND GENETIC DETERMINANTS OF PLANT SIZE IN VIOLA SORORIA.
Survivorship and fecundity in the forest herb, Viola sororia, are size-dependent. The basis of size variation among individuals of Viola sororia was investigated with a uniform environment experiment. Plants collected from natural populations were vegetatively reproduced and grown under two light regimes in a greenhouse. Analysis of quantitative variation showed: 1) significant differences between light treatments for characters related to plant shape and relative growth rate; 2) significant among-genet variation for plant size, plant shape and relative growth rate but none for physiological characters; and 3) a size threshold for cleistogamous seed production and rhizome production. Heritability estimates for the characters associated with plant size and shape ranged from 0.09 to 0.39, indicating significant genetic determination for these traits. In addition, among-genet differences in relative growth rate were substantial. The results of this study suggest that the size variation found in natural populations is not solely a function of environmental heterogeneity but is significantly influenced by the genotypes composing the population.


Stereotypes of individuals with learning disabilities: views of college students with and without learning disabilities.
To explore possible reasons for low self-identification rates among undergraduates with learning disabilities (LD), we asked students (38 with LD, 100 without LD) attending two large, public, research-intensive universities to respond to a questionnaire designed to assess stereotypes about individuals with LD and conceptions of ability. Responses were coded into six categories of stereotypes about LD (low intelligence, compensation possible, process deficit, nonspecific insurmountable condition, working the system, and other), and into three categories of conceptions of intelligence (entity, incremental, neither). Consistent with past findings, the most frequent metastereotype reported by individuals in both groups related to generally low ability. In addition, students with LD were more likely to espouse views of intelligence as a fixed trait. As a whole, the study's findings have implications for our understanding of factors that influence self-identification and self-advocacy at the postsecondary level.


LINC00174 Promotes Colon Cancer Progression by Regulating Inflammation and Glycolysis by Targeting the MicroRNA-2467-3p/Enolase 3 Axis.
To elucidate the mechanism by which LINC00174 promotes colon cancer progression by targeting the microRNA-2467-3p (miR-2467-3p)/enolase 3 (ENO3) axis to regulate inflammation and glycolysis. The expression of LINC00174 and ENO3 in colon cancer tissues, its relationship with survival rate, and correlation were analyzed using bioinformatic analysis. The effects of LINC00174 overexpression and silencing on the biological behavior of and inflammation in colon cancer cells were analyzed via transfection experiments. The target relationships between miR-2467-3p or LINC00174 and ENO3 were verified using sequence prediction and the dual-luciferase reporter assay, respectively. Furthermore, LINC00174- and/or miR-2467-3p-overexpressing cells were prepared to determine the effects on ENO3 protein levels and glycolysis. Finally, the effects of LINC00174 and/or miR-2467-3p overexpression on colon cancer, ENO3 protein levels, and inflammation were analyzed using a tumor-bearing mice model. LINC00174 and ENO3 were overexpressed and associated with a lower survival rate. LINC00174 was positively correlated with ENO3 in colon cancer tissues. Furthermore, the overexpression of LINC00174 in colon cancer cell lines promoted the proliferation, migration, and invasion of colon cancer cells and inflammation but inhibited apoptosis. The overexpression of miR-2467-3p inhibited ENO3 protein levels, which was attenuated via LINC00174 overexpression. Furthermore, it inhibited the biological behavior of and inflammation and glycolysis in colon cancer cells and blocked their LINC00174-induced promotion. Moreover, using animal experiments, the regulatory effects of LINC00174 on tumor growth, ENO3 protein levels, and inflammation via miR-2467-3p were confirmed. LINC00174 promotes the glycolysis, inflammation, proliferation, migration, and invasion of colon cancer cells and inhibits apoptosis. The cancer-promoting mechanism of LINC00174 is related to targeting miR-2467-3p to promote ENO3 protein levels.


Predictive Value of the Platelet-To-Lymphocyte Ratio in Diagnosis of Prostate Cancer.
To predict prostatic carcinoma using a logistic regression model on prebiopsy peripheral blood samples. Data of a total of 873 patients who consulted Urology Outpatient Clinics of Fatih Sultan Mehmet Training and Research Hospital between February 2008 and April 2014 scheduled for prostate biopsy were screened retrospectively. PSA levels, prostate volumes, prebiopsy whole blood cell counts, neutrophil and platelet counts, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), biopsy results and Gleason scores in patients who had established diagnosis of prostate cancer (PCa) were evaluated. This study was performed on a total of 873 cases, with an age range 48-76 years, divided into three groups as for biopsy results. with diagnoses of benign prostatic hyperplasia (BPH) (n=304, 34.8 %), PCa (n=265, 30.4%) and histological prostatitis (n=304; 34.8%). Intra- and intergroup comparative evaluations were performed. White blood cell and neutrophil counts in the histological prostatitis group were significantly higher than those of the BPH and PCa groups (p=0.001; p=0.004; p<0.01). A statistically significant intergroup difference was found for PLR (p=0.041; p<0.05) but not lymphocyte count (p>0.05). According to pairwise comparisons, PLR were significantly higher in the PCa group relative to BPH group (p=0.018, p<0.05, respectively). Though not statistically significant, higher PLR in cases with PCa in comparison with the prostatitis group was remarkable (p=0.067, and p>0.05, respectively). Meta-analyses showed that in patients with PSA levels over 4 ng/ml, positive predictive value of PSA is only 25 percent. Therefore, novel markers which can both detect clinically significant prostate cancer, and also prevent unnecessary biopsies are needed. Relevant to this issue in addition to PSA density, velocity, and PCA3, various markers have been analyzed. In the present study, PLR were found to be the additional predictor of prostatic carcinoma.


Medical Device Apps: An Introduction to Regulatory Affairs for Developers.
The Poly Implant Prothèse (PIP) scandal in France prompted a revision of the regulations regarding the marketing of medical devices. The new Medical Device Regulation (MDR [EU]) 2017/745 was developed and entered into force on May 25, 2017. After a transition period of 3 years, the regulations must be implemented in all EU and European Economic Area member states. The implementation of this regulation bears many changes for medical device development and marketing, including medical device software and mobile apps. Medical device development and marketing is a complex process by which manufacturers must keep many regulatory requirements and obligations in mind. The objective of this paper is to provide an introduction and overview of regulatory affairs for manufacturers that are new to the field of medical device software and apps with a specific focus on the new MDR, accompanying harmonized standards, and guidance documents from the European Commission. This work provides a concise overview of the qualification and classification of medical device software and apps, conformity assessment routes, technical documentation, clinical evaluation, the involvement of notified bodies, and the unique device identifier. Compared to the previous Medical Device Directive (MDD) 93/42/EEC, the MDR provides greater detail about the requirements for software qualification and classification. In particular, rule 11 sets specific rules for the classification of medical device software and will be described in this paper. In comparison to the previous MDD, the MDR is more stringent, especially regarding the classification of health apps and software. The implementation of the MDR in May 2020 and its interpretation by the authorities will demonstrate how app and software manufacturers as well as patients will be affected by the regulation.


Repetitive responses in squid giant axons and their premature annihilation by additional brief depolarizing currents.
The repetitive responses induced in squid giant axons by the application of sustained depolarizing currents under space clamp conditions are described. The relationships between membrane current, and a number of features of the repetitive response of the living axon are compared to computations made for the Hodgkin-Huxley equations. The comparison suggests that these equations adequately predict the form of the repetitive response, even so far as the ability of a brief additional depolarization to cause a premature end to the repetitive response.


Identification of oxidized methionine sites in erythrocyte membrane protein by liquid chromatography/electrospray ionization mass spectrometry peptide mapping.
In this study, we used peptide mapping combined with liquid chromatography/electrospray ionization mass spectrometry (LC/ESI MS) to examine the methionine oxidation of band 3 of erythrocyte membrane protein. Initially, we identified the methionine sites oxidized by chloramine T (N-chloro-p-toluenesulfoamide), a hydrophilic reagent. There were three oxidized methionines (Met 559, Met 741, and Met 909) in band 3, and these methionines were located in a hydrophilic region determined by previous topological studies of band 3. In addition, we found that C12E8, a polyoxyethylene detergent, leads to the oxidation of methionines in a transmembrane segment in band 3, and this oxidation occurs in a C12E8 preincubation time-dependent manner. In a previous study, it was found that peroxides accumulate in a polyoxyethylene detergent. Thus, our method enabled the direct and quantitative detection of protein damage due to detergent peroxides. Furthermore, we examined methionine oxidation in the presence of 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS) or diethyl pyrocarbonate (DEPC), which induced either an outward or an inward conformation in band 3, respectively. Our results indicated that the location of Met 741 was associated with the band 3 conformation induced by band 3-mediated anion transport. In conclusion, we found that methionine oxidation can be applied to examine membrane protein structures as follows: (1) for topological studies of membrane proteins, (2) for assessing the quality of proteins in detergent solubilization studies, and (3) for the detection of conformational changes in membrane proteins.


Analysis of the genome of a Korean isolate of the Pieris rapae granulovirus enabled by its separation from total host genomic DNA by pulse-field electrophoresis.
Most traditional genome sequencing projects involving viruses include the culture and purification of the virus particles. However, purification of virions may yield insufficient material for traditional sequencing. The electrophoretic method described here provides a strategy whereby the genomic DNA of the Korean isolate of Pieris rapae granulovirus (PiraGV-K) could be recovered in sufficient amounts for sequencing by purifying it directly from total host DNA by pulse-field gel electrophoresis (PFGE). The total genomic DNA of infected P. rapae was embedded in agarose plugs, treated with restriction nuclease and methylase, and then PFGE was used to separate PiraGV-K DNA from the DNA of P. rapae, followed by mapping of fosmid clones of the purified viral DNA. The double-stranded circular genome of PiraGV-K was found to encode 120 open reading frames (ORFs), which covered 92% of the sequence. BLAST and ORF arrangement showed the presence of 78 homologs to other genes in the database. The mean overall amino acid identity of PiraGV-K ORFs was highest with the Chinese isolate of PiraGV (~99%), followed up with Choristoneura occidentalis ORFs at 58%. PiraGV-K ORFs were grouped, according to function, into 10 genes involved in transcription, 11 involved in replication, 25 structural protein genes, and 15 auxiliary genes. Genes for Chitinase (ORF 10) and cathepsin (ORF 11), involved in the liquefaction of the host, were found in the genome. The recovery of PiraGV-K DNA genome by pulse-field electrophoretic separation from host genomic DNA had several advantages, compared with its isolation from particles harvested as virions or inclusions from the P. rapae host. We have sequenced and analyzed the 108,658 bp PiraGV-K genome purified by the electrophoretic method. The method appears to be generally applicable to the analysis of genomes of large viruses.


Bioimpedance and impedance vector patterns as predictors of league level in male soccer players.
Bioelectrical-impedance standards (resistance, reactance, and phase angle) are well established for the normal population or in the clinical setting and are considered indicators for cell mass, cell function, and hydration status. However, such standards do not exist for the male soccer population. Therefore, the goal of the current investigation was to provide a set of bioelectrical-impedance data of a large sample of soccer players with different performance levels. A sample of 893 players, registered in all Italian soccer divisions, was divided into 5 groups according to their performance level. Whole-body impedance measurements were performed during the first half of the competitive period. Besides estimation of body composition, bioelectrical-impedance vector analysis (BIVA) was performed. BIVA does not depend on equations and displays differences in hydration and body-cell mass (BCM). Individual vectors can be classified by using the 50%, 75%, and 95% tolerance ellipse. In comparison with the other divisions and the normal population, the mean vector of the elite level showed a shift to the left (P < .001). Compared with the elite level, players of a lower performance level had lower phase angles, BCM, and fat-free mass. In conclusion, soccer players belong to a specific population. Muscle mass and function, as indicated by BCM and phase angle, increase with increasing performance level. The soccer-specific tolerance ellipses might be used for classifying individual vectors and to define target regions for low-level players.


Synthesis and comprehensive characterizations of new cis-RuL(2)X(2) (X = Cl, CN, and NCS) sensitizers for nanocrystalline TiO(2) solar cell using Bis-phosphonated bipyridine ligands (L).
The preparation and the properties of several ruthenium complexes of the general formula cis-RuL(2)X(2) with L = 2,2'-bipyridine-4,4'-bisphosphonic acid, L' = 2,2'-bipyridine-5,5'-bisphosphonic acid, and X = Cl, CN, or NCS are reported. The synthesis of these complexes relies on the preparation of the key intermediates cis-Ru(bipyridinebis(diethyl ester phosphonate))Cl(2). The ground-state second pK(a) values of the thiocyanato complexes were determined and are 6.0 and 6.1 for cis-RuL(2)(NCS)(2) and for cis-RuL'(2)(NCS)(2), respectively. For these species, (13)C NMR and IR demonstrate that the thiocyanato ligands are bound to Ru via the N atom. The new complexes exhibit a blue-shifted electronic absorption spectrum with respect to the analogous complexes containing carboxylic acid groups. Density functional theory molecular orbital calculations show that the LUMO of the bipyridine phosphonated ligands is at higher energy than the corresponding dicarboxylate complexes and that the thiocyanato ligands are not simple spectator ligands, whose role is to enrich electron density on the ruthenium, but are also involved in transitions from PiRu-NCS to Pibpy that extend the absorbance of the dye in the low energy part of the absorption spectrum. The photoaction spectra recorded in a sandwich regenerative photovoltaic cell indicate that the cyano and thiocyanato complexes containing the bipyridine substituted in 4,4' positions exhibit a 90-95% photoconversion efficiency on the MLCT band, whereas those containing the bipyridine substituted in 5,5' positions display lower efficiency (60-65%). The most efficient complex in the series is cis-RuL(2)(NCS)(2); however, its overall efficiency is about 30% lower than the analogue cis-Ru(H(2)dcb)(2)(NCS)(2) (H(2)dcb = 2,2'-bipyridine-4,4'-dicarboxylic acid) due to a lower absorbance in the red part of the visible spectrum.


Mg2+-dependent conformational changes and product release during DNA-catalyzed RNA ligation monitored by Bimane fluorescence.
Among the deoxyribozymes catalyzing the ligation of two RNA substrates, 7S11 generates a branched RNA containing a 2',5'-linkage. We have attached the small fluorogenic probe Bimane to the triphosphate terminated RNA substrate and utilized emission intensity and anisotropy to follow structural rearrangements leading to a catalytically active complex upon addition of Mg(2+). Bimane coupled to synthetic oligonucleotides is quenched by nearby guanines via photoinduced electron transfer. The degree of quenching is sensitive to changes in the base pairing of the residues involved and in their distances to the probe. These phenomena permit the characterization of various sequential processes in the assembly and function of 7S11: binding of Mg(2+) to the triphosphate moiety, release of quenching of the probe by the 5'-terminal G residues of R-RNA as they engage in secondary base-pair interactions, local rearrangement into a distinct active conformation, and continuous release of the Bimane-labeled pyrophosphate during the course of reaction at 37°C. It was possible to assign equilibrium and rate constants and structural interpretations to the sequence of conformational transitions and catalysis, information useful for optimizing the design of next generation deoxyribozymes. The fluorescent signatures, thermodynamic equilibria and catalytic function of numerous mutated (base/substituted) molecules were examined.


[Tumors of the anterior mediastinum--surgical treatment and prognosis].
This paper reports on 96 mediastinal tumors situated exclusively or mainly in the anterior mediastinum. Early surgical intervention is always indicated to establish the diagnosis and to ensure as radical a tumor resection as possible. The surgical approach depends on the tumor size and localization and is made either by sternotomy or thoracotomy. The prognosis depends on the histological classification of the tumors: out of 30 patients with lymphomas, 19 survived as compared to 10 out of 21 patients with thymoma and 15 out of 18 patients with mesenchymal tumors. Of 16 patients with endothoracic and retrosternal goiters, none died of a cause connected with the goiter and nine out of 11 patients with mesodermal tumors survived. The indication for surgery should be established extensively, since one third of the tumors is malignant and the surgical lethality (1.8%) is very low.


Health demand in primary care context: what do people think about physicians?
This research aims to explore the link between health demand and representation of medical function in a sample of 86 individuals (aged between 18 and 74) from Italy. A questionnaire has been administered for the analysis of cultural models (Carli & Paniccia 1999) in terms of affective symbolisations characterising physician-patient relationship. The questionnaire has been constructed according to a socio-constructivist methodology and allows to explore two specific emotional areas: (1) The view about medical profession and health care setting in general, (2) the experience referred to one's own general practitioner. Five clusters of subjects have been identified, thanks to multivariate statistic techniques (multiple correspondence analysis (MCA) and cluster analysis (CA). They show respectively: A deep concern for health and a paternalistic dynamics with physician (20.9% of the sample); a general distrust of the health service and a fatalistic view about health leading to avoid the use of visits (16.3%); a passive and dependent position in relation to physician seen as a skilled and powerful technician (20.9%); a little compliance with physician considered as a bureaucrat that must satisfy any request (20.9%); an active role in health management and a greater confidence in medical function for a better quality of life (20.9%). Results point out some differences by age, education and occupation. In particular, participants with university schooling (p < 0. 01) and professionals (p < 0. 05) show less motivation to use primary care services, while participants aged from 45 to 74 years (p < 0.05) and with elementary-middle schooling (p < 0.05) are more confident in medical function for health promotion. Findings suggest some indications on health demand and provide development lines for improving communication in primary care context.


Inhibition of pentylenetetrazole-induced seizure in mice by using a 4 Hz magnetic field: a comparative study with a 60 Hz magnetic field.
We investigated the comparative effects of 4 and 60 Hz magnetic fields on pentylenetetrazole (PTZ)-induced seizure in mice. For this study, we measured the latent time to seizure, seizure duration, and lethality induced by PTZ in mice exposed to 4 and 60 Hz magnetic fields (MF) for 30 min. Compared to sham-exposed controls, the latent time to tail twitching and seizure in the 4 Hz MF group was significantly decreased while the latent time to seizure in the 60 Hz MF group was significantly increased. The seizure duration in the 4 Hz MF group was significantly decreased while that in the 60 Hz MF group was significantly increased. More importantly, while the mice exposed to a 60 Hz MF experienced significantly increased lethality after seizure convulsion, those exposed to a 4 Hz MF showed no lethality, with a shortening of the duration of seizure. This beneficial effect of a 4 Hz MF on seizure has the same implication as the anti-oxidative effects of a 4 Hz MF observed in our previous work. The results of our current and previous works indicate that a 4 Hz MF may be used as a therapeutic physical agent for the treatment of oxidative stress-induced diseases, including seizure, with or without chemical drugs.


Investigation of the role of Blankaartia acuscutellaris (Acari: Trombiculidae) as a vector of scrub typhus in central Thailand.
Monthly collections of rodents were conducted in Phitsanulok Province, central Thailand in 1993 to investigate the role of the mite Blankaartia acuscurellaris as a vector of scrub typhus. Overall, a total of 41 rodents were collected and examined for the presence of the red colored larvae of B. acuscutellaris and yellow larvae of Leptotrombidium deliense and Ascoshoengastia sp. A total of 787 B. acuscutellaris and 1390 yellow larvae were placed into pools, triturated and isolation of Orientia tsutsugamushi attempted in laboratory mice. The sera of 8 of the collected rodents had elevated antibodies to O. tsutsugamushi indicating active infections; however, O. tsutsugamushi was not isolated from rodent tissues or pools of larvae. The results of this survey suggest that B. acuscutellaris may not be an important vector of scrub typhus, but more studies are needed in endemic areas.


Semaglutide: First Global Approval.
Novo Nordisk has developed a subcutaneous formulation of semaglutide (Ozempic®), a modified human glucagon-like peptide-1 (GLP-1) analogue, for the treatment of type 2 diabetes mellitus. It has been developed using Novo Nordisk's proprietary protein-acylation technology, and is administered using an injection device. Semaglutide lowers blood glucose by stimulating the release of insulin and also lowers body weight. Once-weekly subcutaneous semaglutide has recently been approved in the US, Puerto Rico and Canada, and has received a positive opinion in the EU for the treatment of patients with type 2 diabetes. It will be launched as the Ozempic® Pen, a pre-filled device. Semaglutide is also under regulatory review in Japan and Switzerland for the treatment of type 2 diabetes. Clinical development for obesity, non-alcoholic steatohepatitis and non-alcoholic fatty liver disease is underway worldwide. This article summarizes the milestones in the development of semaglutide leading to this first approval for type 2 diabetes.


[Evaluation of antioxidant properties of enriched bakery products in experiment on laboratory animals].
The purpose was to study the effect of enriched bakery products in the diet of rats on indicators of prooxidant-antioxidant system of blood serum. Experiment was carried out on male Wistar rats with initial weight 140-180 g. After a quarantine during the preparatory period rats for 14 days were accustomed to the partial (50%) replacement of the standard diet by bakery products with standard compounding. Then, 7 groups of rats were formed: the 1st group of rats (control group, n=10) continued to receive bakery products of a standard composition; groups with the 2nd on 7th (experimental, n=8 in everyone) received enriched bakery products: the 2nd group - with blueberry powder; the 3rd group - with mountain ash powder; the 4th group - with sea-buckthorn powder; the 5th group - with flour of a pine nut; the 6th group - with rice bran oil; the 7th group - with pumpkin oil. The intensity of free radical oxidation and antioxidant activity (by chemiluminescence method), activity of superoxide dismutase and level of secondary oxidation products reacted with thiobarbituric acid (by spectrophotometry) were monitored in rat blood serum. It has been shown that the use of bakery products with different compounding in the animal diet had different effects on indicators of prooxidant-antioxidant system of blood serum. Bakery products containing sea buckthorn pomace powder, flour of pine nut and rice bran oil reduced intensity of free radical oxidation in rat blood serum by 36.0, 24.6 and 18.8%, respectively. It is suggested that bakery products containing flour of pine nut products brake a free radical oxidation in rat blood serum in case of simultaneous content of natural antioxidants and melanoidins. The anthocyanins of powder from blueberry berries can render antioxidant effect and slow down formation of by-products of oxidation. No statistically significant change on indicators of prooxidant-antioxidant system of blood serum of rats treated with bakery products with rowan powder or pumpkin oil was found, that may be due to animal refusal to eat such products.


Sociability of Indian free-ranging dogs (Canis lupus familiaris) varies with human movement in urban areas.
Cohabiting with humans in the same ecological space requires significant variation in the behavioral repertoire of animals. Behavioral variation can potentially improve the chances of survival of an individual. The influence of humans can be measured by quantifying specific behavioral parameters of the interacting individuals. Sociability or the tendency to be friendly toward others is one of many personality traits in animals that can provide us with insights regarding their relationship with humans. Free-ranging dogs are one of the successful urban-adapted species that interact with humans regularly, which, in turn, influences their behavioral properties. In this study, we tested 600 adult dogs from 60 sites across India, categorized as high, low, and intermediate human flux zones, to understand their degree of sociability toward an unfamiliar human. Initially, a "positive vocalization phase" was carried out. Unresponsive dogs were further tested in a "stimulus phase." The first phase was characterized by positive vocal sounds, while the second one included both food and positive vocalization. In addition, we surveyed a total of 1,200 people from the 60 sites to understand their perception of free-ranging dogs. Dogs in the IF zones were highly sociable compared to the other zones. High human flux zone dogs were reluctant to approach initially but showed an increased approach when food was provided. Low human flux zone dogs were the least sociable, and even the food reward had minimal impact on them. Our study provides the first evidence of behavioral variation in the degree of sociability of free-ranging dogs in urban environments. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


[Non-cardiac transcatheter intervention: operative possibilities in a hemodynamics laboratory].
New possibilities for transcatheter treatment of the cardiovascular system are guaranteed with the improvement of materials and the availability of new devices. Nevertheless, a rationalization of the potential activity in this sector seems to be necessary, and it could arise through the presence of Catheterization Laboratories "open" to diagnostic procedures and therapy that are not confined to the coronary system. This clinical study reports the experiences and results of our work in this field. During the period from May 1995 to May 1997, our laboratory performed 205 diagnostic procedures that did not involve the coronary system. Based on this diagnostic work, there emerged 91 cases with an indication for transcatheter intervention, which was subsequently performed at our laboratory. There were 68 peripheral angioplasty procedures on the iliofemoral axis, 2 angioplasties of the subclavian artery, 8 of the renal artery, 2 procedures involving the treatment of A-V fistulas, one case of femoral pseudoaneurysm treatment and 10 cases of transcutaneous pericardiotomy performed with a balloon catheter. All the procedures were performed by our laboratory staff using materials that are normally at our disposal. Successful results were obtained in 65 out of the 68 peripheral angioplasty procedures and in all of the 8 renal and 2 subclavian angioplasties. The positioning of the endoprosthesis for the closure of the A/V fistula was effective in one of the two cases. The transcatheter treatment of the femoral pseudoaneurysm was successful. In all cases where a pericardiotomy was performed with a balloon catheter, there was no reoccurrence of cardiac tamponade during the follow-up period. No complications were noted as a result of any of the procedures. Our experience documents how it is possible to increase the diagnostic and therapeutic options in a Catheterization Laboratory. However, willingness on the part of the staff to update their skills continually and collaborate with other specialists is necessary in order to maintain optimal operative standards.


'Glocalizing' land-use and forest governance in the tropics: examining research partnerships and international forest policies affecting Brazil, DRC and Indonesia.
Background: International and market forces are key drivers of deforestation and forest degradation, with transnational and market-based solutions in land-use and forest governance often missing economic, distributive, and environmental targets. Methods: This paper tackles both the framing and effectiveness of transnational initiatives affecting forest lands and peoples in the Global South, and the quality of relationships between institutions in the Global North and the Global South. Through more equitable research partnerships, this paper draws lessons from case studies in Indonesia (legality verification system in different forest property regimes), the Democratic Republic of the Congo (lifting of a moratorium on new logging concession), and Brazil (FSC in the Amazon region and the Amazon Fund). Results: International partnerships have privileged market-based instruments and commodity exchange between Global South and Global North countries, and the benefits of such mechanisms are unevenly distributed. Complementary and alternative policy instruments are discussed for each geography. Conclusions: Glocalizing land-use and forest governance implies in advancing equitable research partnerships between institutions in the Global South and Global North, and strengthening a community of practice for critical enquiry and engagement in partnerships for sustainable development. Land-use, climate and forest governance mechanisms must redress power dynamics, and partnership models, and commit to improving well-being and sustainable livelihood outcomes.


An intergranular strain concept for material models formulated as rate equations.
The intergranular strain concept was originally developed to capture the small-strain behaviour of the soil with hypoplastic models. A change of the deformation direction leads to an increase of the material stiffness. To obtain elastic behaviour for smallstrains, only the elastic part of the material stiffness matrix is used. Two different approaches for an application of this concept to nonhypoplastic models are presented in this article. These approaches differ in the determination of the elastic stress response, which is used for reversible deformations. The first approach determines an elastic response from the original material model, and the second one uses an additional elastic model. Both approaches are applied on barodesy. The simulations are compared with experimental results and with simulations using hypoplastic models with the original intergranular strain concept.


Influence of Reduction with NaBH4 and HCl in Obtaining Amino Derivatives of Cashew Gum and Cytotoxic Profile.
Tree-exuded gums are natural polymers that represent an abundant raw material in the food and pharmaceutical industries. The cashew gum can be obtained by exudation of trees of the genus Anacardium, a native species of the Brazilian northeast; its polymer consists of monosaccharide units propitious to the action of chemical reactions that tend to improve their intrinsic characteristics among them, as the degree of hydro-solubility. The objective of this work was to modify the exudate gum of Anacardium occidentale (cashew gum (CG)) through an amine reaction. The modification was confirmed by Nuclear Magnetic Resonance (1H NMR), infrared spectroscopy (FTIR), gel permeation chromatography (GPC), zeta potential, and thermogravimetric analysis (TG). In addition, the chemical modification altered the molar mass and surface charge of the CG, and the amino group binding to the CG polymers was confirmed by FTIR spectra. In addition, cytotoxicity tests were performed where cell viability was estimated by an MTT assay on RAW 264.7 macrophages. Through these tests, it was found that the amine caused an increase in the thermal stability of the amino compounds and did not present cytotoxic potential at concentrations below 50.0 mg/L.


Designing hydrogel adhesives for corneal wound repair.
Today, corneal wounds are repaired using nylon sutures. Yet there are a number of complications associated with suturing the cornea, and thus there is interest in an adhesive to replace or supplement sutures in the repair of corneal wounds. We are designing and evaluating corneal adhesives prepared from dendrimers--single molecular weight and highly branched polymers. We have explored two strategies to form these ocular adhesives. The first involves a photocrosslinking reaction and the second uses a peptide ligation reaction to couple the individual dendrimers together to form the adhesive. These adhesives were successfully used to repair corneal perforations, close the flap produced in a LASIK procedure, and secure a corneal transplant.


Plastid-Nucleus Distance Alters the Behavior of Stromules.
Plastids send "retrograde" signals to the nucleus to deliver information regarding their physiological status. One open question concerning this signal transfer is how the signal bridges the cytoplasm. Based on individual reports of plastid derived tubular membrane extensions connecting to nuclei, these so-called stromules have been suggested to function as communication routes between plastids and nuclei in response to biotic stress. However, based on the data currently available it is unclear whether interactions between stromules and nuclei are truly intentional or observed as a result of an inflated stromule frequency throughout the cell, and are thus a random event. The source of this uncertainty stems from missing information regarding the relative distribution of all plastids and stromules within a given cell. A comprehensive analysis of the upper epidermis of Arabidopsis thaliana rosette leaves was performed via a combination of still images and time-lapse movies of stromule formation in the context of the whole cell. This analysis could definitively confirm that stromule formation is not evenly distributed. Stromules are significantly more frequent within 8 μm of the nucleus, and approximately 90% of said stromules formed facing the nucleus. Time-lapse movies revealed that this enrichment of stromules is achieved via a 10-fold higher frequency of stromule initiation events within this 8 μm zone compared to the cell periphery. Following the movement of plastids and nuclei it became evident that movement and formation of stromules is correlated to nucleus movement. Observations suggest that stromules "connecting" to the nucleus are not necessarily the result of plastids sensing the nucleus and reaching out toward it, but are rather pulled out of the surface of nucleus associated plastids during opposing movement of these two organelles. This finding does not exclude the possibility that stromules could be transferring signals to the nucleus. However, this work provides support for an alternative hypothesis to explain stromule-nuclear interactions, suggesting that the main purpose of nucleus associated stromules may be to ensure a certain number of plastids maintain contact with the constantly moving nucleus.


Traumatic brain injury in the pediatric population.
Traumatic brain injury (TBI) is a common injury among children. Most TBIs are mild and do not require hospitalization. However, whether or not the patients require acute hospitalization, TBIs may have long-lasting consequences. There is little research on the nutrient needs of these patients, and recommendations are frequently based on data from adults with TBI. It is clear that calorie and protein needs are elevated with acute TBI. However, calorie needs are also decreased by therapies such as sedation, chemical paralysis, and barbiturate coma. Long-term calorie needs may be lower for "comatose" patients. Enteral feeding is preferred and possible for patients with TBI, though gastric feeding may be problematic in some patients. In the acute phase, patients with TBI can also have dysregulation of fluid and electrolyte balance, which may require alterations in nutrition care. Dysphagia is common after moderately severe TBI and requires a multidisciplinary approach for treatment. Future opportunities for research on pediatric TBI are numerous and may include ongoing clarification of macronutrient needs, as well as investigation into the roles of specific nutrients such as zinc, antioxidants, and anti-inflammatory compounds.


[Prevention of venous thromboembolic complications in firearm injury].
Prevention of venous thromboembolic complications in wounded is a complex problem which has not yet been fully resolved throughout the world. Current state of venous thrombosis prevention in wounded in different countries and certain ways of its improvement are analyzed in the article.


Phosphorylation and cytotoxicity of therapeutic nucleoside analogues: a comparison of alpha and gamma herpesvirus thymidine kinase suicide genes.
Thymidine kinase (TK) genes from three alpha-herpesviruses (i.e., human herpes simplex type 1, varicella-zoster virus, equid herpesvirus 4) and two y-herpesviruses (i.e., Epstein-Barr virus and Saimiri herpesvirus 2) were cloned in expression vectors based on zeocin resistance by complementation of a TK-defective Escherichia coli strain. In vivo complementation of an appropriate yeast strain and in vitro enzymatic measurements demonstrated that all viral TKs possess a second phosphorylating activity corresponding to the thymidylate kinase function in contrast to the E coli TK, which is deprived of this activity. When expressed in an engineered E coli strain rendered resistant to purine and pyrimidine nucleoside analogs, the viral TKs sensitize host bacteria to 3'-azido-3'-deoxythymidine (AZT), 3'-deoxy-2',3'-didehydrothymidine (D4T), dideoxyinosine, or fluorodeoxyuridine (5-FUdR). The extent of activation of all these analogs, in this bacterial assay, was found to be greatly superior for the two gamma-virus TKs, compared to the alpha-virus TKs, including the reference suicide gene, HSV1-TK. TK from the two gamma-Epstein-Barr and Saimiri 2 viruses were also found to be more efficient in sensitizing murine melanoma B16 tumor cells to pyrimide nucleoside analogs.


Transurethral microwave therapy in 200 patients with a minimum followup of 2 years: urodynamic and clinical results.
We investigated the long-term efficacy of the second generation Targis thermotherapy device (Urologix, Inc., Minneapolis, Minnesota) for decreasing outflow obstruction caused by benign prostatic hyperplasia. At a minimum followup of 24 months 200 patients with bladder outlet obstruction documented on urodynamics and cystoscopy document with preserved detrusor function underwent transurethral microwave therapy while under local anesthesia. In 45% of cases the general American Society of Anesthesiologists health score was 3 or greater. After a median observation time of 42 months (range 2 to 72) 43 patients (22%) who required additional treatment (repeat thermotherapy, transurethral prostate resection or permanent cystostomy) were excluded from further analysis, as were 15 (7.5%) who died of causes unrelated to treatment during followup and 13 (6.5%) who were lost to followup or refused followup investigations. In the 162 patients evaluated 6 months after treatment the median International Prostate Symptom Score decreased from 23 points (range 10 to 34) before treatment to 3 (range 0 to 21) and remained stable at 12 and 24 months. Median maximum flow increased from 6 ml. per second (range 1 to 15) before treatment to 14.5 (range 4 to 50) 6 months after treatment and remained stable at 12 and 24 months. Median post-void residual urine volume decreased from 170 ml. (range 35 to 720) before treatment to 17 (range 0 to 327) after 6 months and then remained unchanged. Urodynamic evaluation in the 162 patients after 6 months showed a decrease from pretreatment median detrusor opening pressure of 87.5 to 53 cm. water. Median detrusor pressure at maximum flow decreased from 86 to 58 cm. water 6 (p <0.0001). At the 24-month followup 59 of the 129 evaluable patients agreed to undergo repeat urodynamic evaluation. Pressure flow analysis in these 59 cases revealed a decrease in median minimal urethral opening pressure from 70 to 40 cm. water at 6 months and to 38 cm. water at 24 months (p <0.0001). Median detrusor pressure at maximum flow decreased significantly from the pretreatment value of 86 to 55 cm. water at 6 months and 58 cm. water at 24 months (p <0.0001). In patients with a good initial response to treatment, which is achieved in approximately 80%, transurethral microwave therapy provides excellent long-term subjective and objective results. Improved urinary flow, decreased post-void residual urine volume and urodynamic parameters remain stable at 2 years. Transurethral microwave therapy with second generation microwave equipment did not compromise any conventional treatment needed in the 22% of patients who were nonresponders at 6 months.


Evidence from the stop-EGFP mouse supports a niche-sharing model of epidermal proliferative units.
The classical model of epidermal proliferative units (EPUs) postulates that each EPU is composed of a single column of corneocytes plus epidermal cells directly below the column and is maintained by a single stem cell within the unit. Using the stop-enhanced green fluorescent protein (stop-EGFP) transgenic mouse system, we previously showed epidermal stem cell clonal lineages could produce multiple adjacent corneocytes (i.e. epidermal cells belonging to multiple adjacent EPUs), contradicting the classical EPU model. One possible problem with our earlier study was that N-ethyl-N-nitrosourea (ENU) was used to generate mutations for clonal analysis. This could alter the normal environment of the epidermal tissue and might lead to an artificial expansion of stem cell clonal lineages. In this study, we replicate our earlier findings using untreated stop-EGFP mice and relying on spontaneous mutations to generate clonal cell lineages. We propose an alternative to the classical EPU model to explain the dynamic nature of epidermal proliferation. Our niche-sharing model of EPUs allows epidermal cells to horizontally migrate among EPUs, so that multiple stem cells cooperatively maintain a larger proliferative compartment.


Squamous Cell Carcinoma Originating from Adult Laryngeal Papillomatosis: Case Report and Review of the Literature.
The malignant transformation of laryngeal papillomatosis (LP) into squamous cell carcinoma (SCC) can occur in up to 4% of LP cases. The low-risk HPV types 6 and 11 are those that are most commonly related to LP; however, high-risk HPV types may be present. The present study reviews the literature on cases of malignant transformation of LP in adults and reports a clinical case. A 47-year-old male patient exhibiting hoarseness for 4 months presented an exophytic lesion in the right palatine tonsil and a digitiform-like lesion in the right vocal fold. The biopsy revealed a well-differentiated SCC in the vocal cord, which showed a transition zone with a squamous papillomatous lesion. By using the chromogenic in situ hybridization (CISH) test, both lesions showed a positive result for high-risk HPV types 16 and 18 and negative for low-risk HPV types 6 and 11. The final diagnosis was SCC arising from LP. The patient underwent surgical treatment. After 36 months of follow-up, no signs of recurrence were observed. The literature review revealed 25 cases of malignant transformation into SCC of LP with adult onset. Of these, only 9 cases were assessed by CISH and/or PCR for HPV identification, of which 7 were positive. The current study focuses on the eighth case, suggesting the involvement of the high-risk HPV types in its pathogenesis. LP is considered a benign lesion with the potential for malignant transformation, which reinforces the need for its early diagnosis and the constant monitoring of patients with LP.


Multi-stimuli responsive supramolecular gels based on a D-π-A structural cyanostilbene derivative with aggregation induced emission properties.
Developing multi-stimuli responsive fluorescent gel materials in a single system remains challenging. Gelator molecules with classical fluorophores suffer from the aggregation-caused quenching (ACQ) effect, limiting their applications further. Herein, a novel V-shaped cyanostilbene-based molecule (BAPBIA) with aggregation induced emission (AIE) characteristics and great gelation ability was synthesized and was found to exhibit multi-stimuli responsive behaviors. Reversible gel-sol phase transitions together with emission quenching are realized in response to external stimuli including heat, light and fluoride ions. Especially, the introduction of a dimethylaniline group (donor) and a cyano group (acceptor) generates a D-π-A structure, further leading to an intramolecular charge transfer (ICT) effect, which enlarges the emission contrast with the variation of the distribution of charge. Thus, upon trifluoroacetic acid (TFA) triggered protonation of the dimethylaniline group, not only a gel-sol transition but also emission color switching (yellow-to-blue) is achieved due to the loss of the ICT effect. This work paves an easy way to construct fully reversible multi-stimuli responsive fluorescence modulation smart materials.


Cladocera from the Upper Xingu River Basin with the description of a new genus of the Chydoridae (Crustacea: Branchiopoda: Anomopoda).
In this study, we investigated cladocerans (Crustacea: Branchiopoda) collected in six water bodies from the Upper Xingu River Basin, Central Brazil. In total, we found eighteen species belonging to three families. Furthermore, we also describe a new and highly specialized genus of Chydoridae. Kisakiellus aweti gen. nov., sp. nov. which shares some morphological traits with members of Chydorinae, particularly the exopodite of the fourth limb armed with seven setae. The new genus bears several autapomorphies and does not exhibit any clear affinities with any other genus of the subfamily. Apparently, K. aweti gen. nov., sp. nov. has a positive rheotactic behavior and the morphological characters related to this habitat trait are discussed. Many regions of the Upper Xingu River Basin are still in need of faunal inventories, a fact that gains more relevance due to the high potential for cryptic biodiversity. So, it is possible that an increase on the sampling effort in this basin will have a positive impact on the known diversity of Cladocera.


Using protease inhibitors in antigen presentation assays.
The major histocompatibility complex (MHC) class I restricted pathway of antigen processing allows the presentation of intracellular antigens to cytotoxic T lymphocytes. The proteasome is the main protease in the cytoplasm and the nucleus, which is responsible for the generation of most peptide ligands of MHC-I molecules. Peptides produced by the proteasome can be further trimmed or destroyed by numerous cytosolic or endoplasmic reticulum (ER) lumenal proteases. Small molecule inhibitors are useful tools for probing the role of proteases in MHC class I antigen processing. Here, we describe different methods to test the impact of protease inhibitors in antigen presentation assays.


Cloning of genes specifically expressed in rice embryogenic cells.
We have examined differences in gene expression pattern between embryogenic callus (EC) and nonembryogenic callus (NEC) derived from mature seed embryo of rice (Oryza sativa L. cv Donggin). Three EC-specific transcripts were identified by differential display of amplified cDNAs. Specific expression of two partial cDNAs, designated as REC1 and REC2, respectively, was confirmed by a northern blot analysis. Partial nucleotide sequence of the clone REC1 showed no homology with any known genes, but partial amino acid sequence deduced from the clone REC2 exhibited 55-82% homology with nickel-cobalt-resistant proteins identified from a bacterium, Alcaligenes eutrophus CH34.


Comparison between optical coherence tomography angiography and immunolabeling for evaluation of laser-induced choroidal neovascularization.
This study aimed to investigate the differences between images obtained by optical coherence tomography angiography (OCTA) with those from immunohistochemical labeling of laser-induced choroidal neovascularization (CNV) in a mouse model. CNV was induced by laser photocoagulation (GYC-2000, NIDEK; wavelength 532 nm) in the left eyes of 10 female C57BL/6J mice aged 6 weeks. The laser parameters included a 100-μm spot, 100-ms pulse duration and 200-mW incident power to rupture Bruch's membrane. OCT and OCTA CNV images were obtained using the RS-3000 Advance (NIDEK) 5 days post-laser photocoagulation. After OCTA imaging, the isolated choroid/retinal pigment epithelium complexes were fluorescently labeled with CD31 (an endothelial cell marker), platelet-derived growth factor receptor β (PDGFRβ, a pericyte-like scaffold marker), α-smooth muscle actin (α-SMA) and collagen I. Area measurements of the lesions obtained by enface OCTA were compared with immunolabeled CD31+ CNV lesions in choroid flat-mounts. We also examined structural correlations between the PDGFRβ+ pericyte-like scaffold and OCTA images. Laser-induced CNV was clearly detected by enface OCTA, appearing as a hyperflow lesion surrounded by a dark halo. Area measurements of the CNV lesion by immunolabeling were significantly larger than those obtained by enface OCTA (p = 0.006). The CNV lesion beneath the periphery of the pericyte-like scaffold was not clearly visible by enface OCTA due to the dark halo; however, the lesion was detectable as blood flow by cross-sectional OCTA and was also highly labeled by CD31. The periphery of the pericyte-like scaffold appeared to develop into subretinal fibrosis and this region was rich in myofibroblasts. Enface OCTA was unable to detect the entire area of laser-induced CNV in mice, with an undetectable portion located beneath the fibrotic periphery of the pericyte-like scaffold. Due to this OCTA fibrosis artifact, OCTA imaging has limited potential for accurately estimating CNV lesions.


[The infrahyoid musculocutaneous flap: experience of 153 cases in the reconstruction of the oropharynx and oral cavity after tumoral excision].
The infrahyoid musculocutaneous flap was described by Wang in 1986. The authors utilize this type of flap since 1994 with an importance that increases in the field of head and neck reconstructive surgery. Their experience of 153 reconstructions in oropharynx and oral cavity showed 128 (84%) cases with good cicatrisation and 25 (16%) with complications. In the cases with complications, they noted 17 partials necrosis (50% of the skin area), 4 late cicatrisation and 4 total necrosis. Only the total necrosis necessitated the other new flap. These results show that the fiability and function of this flap creates an indispensable flap in reconstruction of the oropharynx and oral cavity.


HGF Modulates Actin Cytoskeleton Remodeling and Contraction in Testicular Myoid Cells.
The presence of the HGF/Met system in the testicular myoid cells was first discovered by our group. However, the physiological role of this pathway remains poorly understood. We previously reported that HGF increases uPA secretion and TGF-β activation in cultured tubular fragments and that HGF is maximally expressed at Stages VII-VIII of the seminiferous epithelium cycle, when myoid cell contraction occurs. It is well known that the HGF/Met pathway is involved in cytoskeletal remodeling; moreover, the interaction of uPA with its receptor, uPAR, as well as the activation of TGF-β have been reported to be related to the actin cytoskeleton contractility of smooth muscle cells. Herein, we report that HGF induces actin cytoskeleton remodeling in vitro in isolated myoid cells and myoid cell contraction in cultured seminiferous tubules. To better understand these phenomena, we evaluated: (1) the regulation of the uPA machinery in isolated myoid cells after HGF administration; and (2) the effect of uPA or Met inhibition on HGF-treated tubular fragments. Because uPA activates latent TGF-β, the secretion of this factor was also evaluated. We found that both uPA and TGF-β activation increase after HGF administration. In testicular tubular fragments, HGF-induced TGF-β activation and myoid cell contraction are abrogated by uPA or Met inhibitor administration.


Coronary artery bypass grafting for postinfarction angina pectoris.
The variables that predict increased operative risk and postoperative morbidity among patients who undergo coronary artery bypass grafting (CABG) early after myocardial infarction for persistent or recurrent ischemia are incompletely defined. In a recent 3-year interval (1985-1987), 240 patients underwent CABG within 30 days of a documented myocardial infarction. Thirty-day mortality was 3.3% (eight patients). Twenty variables were examined by univariate and multivariate analysis for their effects on early mortality. Left main coronary artery disease (p = 0.0003), female sex (p = 0.0059), and preoperative left ventricular dysfunction (increased left ventricular wall motion score) (p = 0.0135) were significant independent predictors of increased 30-day mortality. Postoperative inotropic support for low cardiac output was required for 55.6% of patients operated upon within 24 hours of infarction as compared with 11.6% of patients operated upon between 1 and 30 days (p less than 0.01). Significantly more patients undergoing emergent CABG required postoperative intra-aortic balloon pumping and inotropic support than those patients who underwent urgent or elective operation (23.8% vs. 4.6% and 52.4% vs. 10%, respectively) (p less than 0.01). Other studies confirm that preoperative left ventricular dysfunction, presence of cardiogenic shock, or intra-aortic balloon pumping are important predictors of operative risk. Other variables that may be important include advanced age, female sex, left main coronary artery disease, and anterior transmural infarction. The timing and urgency of operation have not been shown to be significant and independent determinants of increased operative risk.(ABSTRACT TRUNCATED AT 250 WORDS)


Impact of flushing with aseptic non-touch technique using pre-filled flush or manually prepared syringes on central venous catheter occlusion and bloodstream infections in pediatric hemato-oncology patients: A randomized controlled study.
To compare standardized flushing methods with aseptic non-touch technique; (1) Manually prepared syringes (2) Single-use prefilled flush syringes. Forty-eight PHO patients with Hickman or Port catheters were recruited to participate in a prospective, randomized study. Standardized flushing methods with aseptic non-touch technique (ANTT) using single-use pre-filled flush syringes (intervention group) or manually prepared syringes (control group) also included the pulsatile technique, use of 10-mL syringe size with 0.9% NaCl for flushing, flushing once a day, flushing training of the nurses. The effects of standardized flushing methods on occlusion and CLABSI evaluated. Of the patients in the intervention group, 8.7% (n: 2) had catheter occlusion, while this rate was 20.0% (n: 5) in the control group. Of the patients in the intervention group, 8.7% (n: 2) had CLABSI, while this rate was 36.0% (n: 9) in the control group. While there was no difference in occlusion, there was a difference between the groups in terms of CLABSI development. In the intervention group, CLABSI rate was 1.9/1000 per catheter-days, in the control group CLABSI rate was 10.1/1000 per catheter-days. In the intervention group, occlusion rate was 1.9/1000 per catheter-days, in the control group, occlusion rate was 5.6/1000 per catheter-days. Standardized flushing and single-use prefilled flush syringes are effective in reducing CLABSI rates in PHO patients.


Hypoxia-inducible factor-1alpha obstructs a Wnt signaling pathway by inhibiting the hARD1-mediated activation of beta-catenin.
Although a splice variant of mouse mARD1s was found to acetylate and destabilize hypoxia-inducible factor-1alpha (HIF-1alpha), human hARD1 has no such activities. Nonetheless, hARD1 has been reported to bind directly with HIF-1alpha. Here, we addressed the functional significance of the hARD1-HIF-1alpha interaction. Because hARD1 acetylates and activates beta-catenin, we examined whether HIF-1alpha regulates the hARD1-mediated activation of Wnt signaling. It was found that HIF-1alpha binds hARD1 through the oxygen-dependent degradation domain and, in so doing, dissociates hARD1 from beta-catenin, which prevents beta-catenin acetylation. In LiCl-stimulated HEK293 or cancer cell lines with active Wnt signaling, beta-catenin acetylation and activity were suppressed in hypoxia, and these suppressions were mediated by HIF-1alpha. Moreover, HIF-1alpha disruption of hARD1/beta-catenin repressed TCF4 activity, resulting in c-Myc suppression and p21(cip1) induction. In addition, we confirmed that the HIF-1alpha NH(2) terminal inactivates TCF4 by directly binding beta-catenin. In conclusion, HIF-1alpha was found to inactivate the Wnt signaling by binding to hARD1 or beta-catenin, which may contribute to the hypoxia-induced growth arrest of tumor cells.


Post-pubertal effects of the Alt-RAMEC/FM and RME/FM protocols for the early treatment of Class III malocclusion: a retrospective controlled study.
To assess the stability of the effects of the modified Alt-RAMEC and facial mask (FM) protocol at a post-pubertal observation. Twenty-one Class III patients (11 males and 10 females, 6.5 ± 0.7 years) treated consecutively with the Alt-RAMEC/FM approach and presenting with lateral cephalograms taken before treatment (T1), after treatment (T2), and at post-pubertal observations (T3) were compared with 22 Class III patients (9 males and 13 females, 6.9 ± 1.2 years) treated with the rapid maxillary expansion (RME) and FM protocol and with 15 Class III untreated subjects (7 males and 8 females, 6.2 ± 2.2 years). At T3, all patients showed a post-pubertal skeletal maturation stage (CS4-CS6). Descriptive statistics and statistical comparisons between the three groups at T1 and for the T3-T1, T2-T1, and T3-T2 changes were assessed by means of the ANOVA or Kruskal-Wallis test. During the overall observation period, Alt-RAMEC/FM and RME/FM protocols produced statistically significant favourable effects when compared with the Control group (ANB + 2.8° and +2.2°, respectively; Wits appraisal +4.4 mm and +2.7 mm, respectively). No statistically significant differences were found between the outcomes of the Alt-RAMEC/FM and RME/FM protocols neither at the post-pubertal or short-term observations. Retrospective study and the comparison with an historical control sample of subjects with untreated Class III malocclusion. The Alt-RAMEC/FM protocol cannot be recommended as the approach of choice for the therapy of Class III dentoskeletal disharmony in very young subjects compared to the conventional RME/FM protocol.


Enhancement characteristics of retroperitoneal lymphomatous lymph nodes.
Previous studies of CT enhancement of lymphomatous lymph nodes (LLN) of the neck and the mediastinum showed that the LLN had lower enhancement values than normal lymph nodes. To elucidate the contrast medium enhancement curves of LLN in the retroperitoneum by comparing the curves of LLN with those of normal lymph nodes, to test whether differences between these curves could be of diagnostic value, and to compare the present enhancement curves of LLN of the retroperitoneum with the curves of LLN of the neck and the mediastinum from previous similar investigations. Twenty-eight consecutive patients with LLN of the retroperitoneum (three with Hodgkin's lymphoma [HL]) and 21 control patients with sarcomas and thus presumably normal retroperitoneal nodes underwent dynamic CT examinations. The previous, similar investigation of lymph nodes of the neck comprised 28 patients with LLN and the investigation of mediastinal lymph nodes comprised 24 patients with LLN. The enhancement curves of the retroperitoneal LLN had significantly lower attenuation than those of the retroperitoneal control nodes. A combination of peak contrast value and time to peak adjusted to total body weight yielded a diagnostic accuracy which at the best showed a sensitivity of 90.5% with a specificity of 82.6%. The LLN of the retroperitoneum had higher attenuation values than corresponding nodes of the mediastinum but no significant difference was found between LLN of the retroperitoneum and LLN of the neck in previous similar investigations. The comparison of enhancement curves of retroperitoneal LLN with retroperitoneal control nodes showed a marked similarity with and substantiates our previous findings in lymph nodes of the neck and of the mediastinum. The best diagnostic accuracy was achieved by combining the parameters peak contrast value and time to peak and adjusting these values to the body weight. Peak enhancement of the retroperitoneal LLN was higher and arrived earlier than that of the mediastinal nodes from the previous investigation.


Overproduction and purification of the Aeromonas hydrophila CphA metallo-beta-lactamase expressed in Escherichia coli.
The Aeromonas hydrophila CphA metallo-beta-lactamase was overexpressed in a soluble secreted form in Escherichia coli using a T7 RNA polymerase-based expression system, and a simple protocol based on a single cation-exchange chromatographic step was developed, which is suitable for rapid purification of the overexpressed enzyme from E. coli lysates. A yield of up to 30 micrograms of purified enzyme per milliliter of culture was obtained. The purified enzyme preparation showed properties identical to those previously reported in the literature.


A widespread cyanobacterium supported by polyphasic approach: proposition of Koinonema pervagatum gen. & sp. nov. (Oscillatoriales)1.
Several new genera originally classified as the genus Phormidium, a polyphyletic and taxonomically complex genus within the Oscillatoriales, were recently described. The simple morphology of Phormidium does not reflect its genetic diversity and the delimitation of a natural group is not possible with traditional classification systems based on morphology alone. Therefore, this study used morphological, ecological, and molecular approaches to evaluate four populations morphologically similar to Ammassolinea, Kamptonema, and Ancylothrix (simple, curved, and gradually attenuated at the ends trichome), found in subtropical and tropical Brazilian regions. 16S rRNA gene sequences grouped all the strains in a highly supported clade with other two European strains isolated from thermal springs surrounding areas. The 16S-23S ITS secondary structure corroborated the phylogenetic analysis with all the strains having similar structures. Consequently, a genetically well-defined and cryptic new genus, Koinonema gen. nov., is proposed containing the aquatic, mesophilic, and morphologically homogeneous new species, Koinonema pervagatum sp. nov.


The Effects of Hydroalcoholic Extract of Nigella sativa Seeds on Serum Estradiol and Prolactin Levels and obstetric Criteria due to Hypothyroidism in Rat.
The aim of this study was investigation of the effects of Nigella sativa (NS) seeds on hypothyroid pregnant rats and their progenies. Hypothyroidism was induced by propylthiouracil (PTU) 0.03% in drinking water. Female rats were divided into seven groups: control, PTU, PTU-NS (100, 200, and 400 mg/kg), and NS (100 and 400 mg/kg). All treatments were done 20 days before mating and during pregnancy. The weight of rat dams and progenies, number of progenies and serum T4, estradiol and prolactin (PRL) levels in rat dams were measured for all groups. Serum T4 in all PTU-NS groups before mating was significantly increased versus PTU group. Body weight of rat dams before mating in all groups of PTU-NS was increased versus PTU group by P < 0.001, P < 0.05, and P < 0.001, respectively and in NS 100 and NS 400 was increased versus control group (P < 0.001). The number of offspring was significantly decreased in PTU and PTU-NS versus control group. The weight of progenies in NS 400 was higher than control group (P < 0.001) and was increased in PTU-NS 200 and PTU-NS 400 versus PTU group by P < 0.001 and P < 0.05, respectively. Serum PRL level in rat dams in control, PTU, and PTU-NS groups were not statistically different between groups but significantly increased in NS 400 group when compared to control group. Estradiol levels were not significantly different in rat dams at 5 days after delivery. These results demonstrated that feeding of rat dams with NS extract before mating has positive protective effects on progenies. These effects may be due to antioxidant properties of NS in reducing oxidative stress and thyroid damages induced by PTU.


Role of alkali ions in limiting the capacity of the 110 degrees C peak of quartz to remember the firing temperature.
Establishment of a reliable thermoluminescence (TL) technique to record the firing temperature has not been possible so far. Attempts made so far have resulted in incoherent results. Recent studies involving thermal effects on TL properties of the 110 degrees C glow peak of quartz by various workers have demonstrated the crucial role of monovalent ions in the TL process. In the light of these results, an attempt is made to understand the mechanism which disables quartz to remember and manifest its firing temperature using its 110 degrees C peak.


Cellular and molecular biology of membranous nephropathy.
There have been dramatic increases in the understanding of the molecular mechanisms involved in membranous nephropathy (MN) over the past 2 decades. Most of these have come directly from studies carried out in the Heymann nephritis models of MN in rats, which closely simulate the clinical and pathologic features of the human disease. Once considered a prototypical example of circulating immune complex trapping in glomeruli, we now recognize that MN develops, in both the rat and man, consequent to an autoimmune process involving antibodies directed to antigens on the foot processes of podocytes that form subepithelial immune deposits. Proteinuria is a consequence of sublytic complement C5b-9 attack on podocytes. The podocyte response to sublytic C5b-9 includes up-regulated expression of genes for production of oxidants, proteases, prostanoids, growth factors, CTGF, transforming growth factor (TGF) and TGF receptors leading to overproduction of extracellular matrix components that result in 'spike' formations. Other podocyte changes including detachment, apoptosis and alterations in cell cycle regulatory proteins favoring hypertrophy over proliferation also contribute to proteinuria and to development of glomerular sclerosis. Finally, progression of chronic proteinuric MN to chronic kidney disease (CKD) and renal failure likely results in part from additional effects of sublytic C5b-9 on proximal tubular epithelial cells, resulting in interstitial inflammation and fibrosis with a fall in glomerular filtration rate (GFR). Expanded understanding of the molecular pathophysiology of MN has important implications for monitoring disease activity, predicting disease course and designing new approaches to therapy for this common glomerular disease.


[Effect of probiotic supplementation during pregnancy and infancy in preventing atopic dermatitis in children: a Meta analysis].
To systematically review the effect of probiotic supplementation during pregnancy and infancy in preventing atopic dermatitis in children. RevMan5.3 was used to perform a Meta analysis of randomized controlled trials on the effect of probiotic supplementation during pregnancy and infancy in preventing atopic dermatitis in children published between January 2008 and May 2018 across the world. A subgroup analysis was conducted according to the type of probiotics for intervention, follow-up time, time of probiotic supplementation, and study areas. A total of 22 articles were selected, with 3 280 cases in the intervention group and 3 281 cases in the control group. The results of pooled effect size showed that probiotic supplementation during pregnancy and/or infancy significantly reduced the incidence rate of atopic dermatitis (RR=0.81, 95%CI: 0.70-0.93, P<0.05). According to the subgroup analysis, the intervention with Lactobacillus and Bifidobacterium had a significant effect (RR=0.68, 95%CI: 0.52-0.90, P<0.05); probiotic supplementation during both pregnancy and infancy also had a significant effect (RR=0.77, 95%CI: 0.66-0.90, P<0.05); probiotic supplementation during pregnancy and/or infancy had a better effect in preventing atopic dermatitis in children aged ≤2 years than in those aged >2 years (RR=0.74, 95%CI: 0.61-0.90, P<0.05); probiotic supplementation had a significant effect in Australia (RR=0.83, 95%CI: 0.73-0.96, P<0.05) and Europe/the United States (RR=0.74, 95%CI: 0.61-0.91, P<0.05). Heterogeneity was mainly due to follow-up time (I2=62.7%) and time of probiotic supplementation (I2=53.5%). Probiotic supplementation during pregnancy and infancy helps to prevent atopic dermatitis in children, and mixed Lactobacillus-Bifidobacterium intervention has a better effect.


Changes in the temperature-mortality relationship in France: Limited evidence of adaptation to a new climate.
Documenting trends in the health impacts of ambient temperature is key to supporting adaptation strategies to climate change. This paper explores changes in the temperature-related mortality in 18 French urban centers between 1970 and 2015. A multicentric time-series design with time-varying distributed lag nonlinear models was adopted to model the shape of the relationship and assess temporal changes in risks and impacts. The general shape of the temperature-mortality relationship did not change over time, except for an increasing risk at very low percentiles and a decreasing risk at very high percentiles. The relative risk at the 99.9th percentile compared to the 50th percentile of the 1970-2015 temperature distribution decreased from 2.33 [95% confidence interval (CI): 1.95:2.79] in 1975 to 1.33 [95% CI: 1.14:1.55] in 2015. Between 1970 and 2015, 302,456 [95% CI: 292,723:311,392] deaths were attributable to non-optimal temperatures, corresponding to 5.5% [95% CI: 5.3:5.6] of total mortality. This burden decreased progressively, representing 7.2% [95% CI: 6.7:7.7] of total mortality in the 1970s to 3.4% [95% CI: 3.2:3.6] in the 2000s. However, the contribution of hot temperatures to this burden (higher than the 90th percentile) increased. Despite the decreasing relative risk, the fraction of mortality attributable to extreme heat increased between 1970 and 2015, thus highlighting the need for proactive adaptation.


Accumulation of tri-n-butyltin chloride and triphenyltin chloride by oral and via gill intake of goldfish (Carassius auratus).
1. The bioconcentration factors (BCF) of both chemicals via gill intake of goldfish reached plateaux after 21 days of exposure. The average BCF values of Bu3SnCl and Ph3SnCl (N = 2) were 1976 and 1384, respectively, after 21-28 days of exposure. 2. The BCF values by oral intake of goldfish reached plateaux after 28 days for Bu3SnCl but did not for Ph3SnCl. The BCF values of Bu3SnCl and Ph3SnCl were 0.04 and 0.10, respectively, after 35 days. 3. The order of the BCF values via gill intake was reversed compared with that by oral intake. Further, the contamination of freshwater fish by these compounds was discussed using the results of these experiments.


Development and application of a rapid detection system for human papillomavirus and Herpes simplex virus-2 by loop-mediated isothermal amplification assay.
Human papillomavirus (HPV) infection is an important factor that causes cervical cancer and non-melanoma skin cancer (NMSC), while HSV-2 plays an important role when HR-HPV triggers the cancer. Thus, a quick and convenient assay in the detection of HPV and HSV-2in the screening of HPV and HSV-2 infection is required. Two respective HPV and HSV-2 detection methods were established based on loop-mediated isothermal amplification (LAMP) assay. Specific outer primers, inner primers, and loop primers were designed according to the conserved domains of HPV and HSV-2 genomes, respectively, while degenerate primers were used for HPV assay. After optimizing the reaction conditions, the results were observed by LAMP Tubidimeter real-time LA-320. Standard plasmids HPV-L-P and HSV-2-L-P were cloned and used in sensitivity tests of HPV LAMP and HSV-2 LAMP, respectively. Fifty samples of actinic keratosis (AK), 20 samples of squamous cell carcinoma (SCC), 50 samples of basal cell carcinoma (BCC) and 20 samples of seborrheic keratosis (SK) were detected by HPV assay. Seventy three clinical samples of vaginitis, chronic cervicitis, cervical intraepithelial neoplasias and cervical cancer level positive were detected with HPV and HSV-2 assays. The reaction conditions of two assays were the same with a reaction temperature of 63 °C and a reaction time of 45 min. The sensitivity of HPV LAMP assay was 10 copies/μL, while that of the HSV-2 LAMP assay was 100 copies/μL. No cross-reactivity was observed. The HPV positive rates of AK, SCC, BCC and SK samples were 80% (40/50), 75% (15/20), 44% (22/50) and 21% (15/72), respectively. As an economic and quick diagnostic tool, LAMP assay is conducive to the extensive screening of HPV and HSV-2 and has huge potential to be promoted in resource-limited hospitals.


Integration of XNAT/PACS, DICOM, and Research Software for Automated Multi-modal Image Analysis.
Traumatic brain injury (TBI) is an increasingly important public health concern. While there are several promising avenues of intervention, clinical assessments are relatively coarse and comparative quantitative analysis is an emerging field. Imaging data provide potentially useful information for evaluating TBI across functional, structural, and microstructural phenotypes. Integration and management of disparate data types are major obstacles. In a multi-institution collaboration, we are collecting electroencephalogy (EEG), structural MRI, diffusion tensor MRI (DTI), and single photon emission computed tomography (SPECT) from a large cohort of US Army service members exposed to mild or moderate TBI who are undergoing experimental treatment. We have constructed a robust informatics backbone for this project centered on the DICOM standard and eXtensible Neuroimaging Archive Toolkit (XNAT) server. Herein, we discuss (1) optimization of data transmission, validation and storage, (2) quality assurance and workflow management, and (3) integration of high performance computing with research software.


Case Report: Partial response to single-agent pembrolizumab in a chemotherapy-resistant metastatic pancreatic cancer patient with a high tumor mutation burden.
Single-agent immune checkpoint blockade has shown no clinical benefits in pancreatic cancer. Recently, the programmed cell death protein 1 (PD-1) antibody pembrolizumab has been recommended as a treatment option for high tumor mutational burden (TMB) solid tumors based on the data from a basket trial. However, no pancreatic cancer patients were enrolled in that trial. Whether pancreatic cancer patients with high TMB respond to PD-1 blockade as well remains unclear. Here, we report a case with a partial response to single-agent immunotherapy with pembrolizumab in pancreatic cancer with high TMB after the failure of several lines of chemotherapy. This result indicates that single-agent immunotherapy may be effective in pancreatic cancer patients with high TMB. In addition, in order to understand the basic immune state of our patients, we also analyzed the changes in immune cells in peripheral blood with cytometry by time-of-flight mass spectrometry (CyTOF) before and after pembrolizumab treatment.


[HIV-associated neurocognitive disorders].
HIV infection is an important medical and social problem. In Poland, similarly to other countries, patients with HIV infections are mostly young people. Apart from typical immunologic pathologies, the HIV infection leads to some neurocognitive, motoric and behavioral disorders. The aim of this paper is to present the up-to-date knowledge of HIV-associated neurocognitive disorders (HAND).