NONSPORULATING, RESPIRATION-DEFICIENT VARIANTS OF SACCHAROMYCES PASTORIANUS INDUCED BY CYCLOHEXIMIDE.
Lomander, L. (Gothenburg University, Gothenburg, Sweden), and K. Gundersen. Nonsporulating, respiration-deficient variants of Saccharomyces pastorianus induced by cycloheximide. J. Bacteriol. 86:956-965. 1963.-When grown on cycloheximide-containing solid medium, Saccharomyces pastorianus gave rise to rough colonies, consisting of two morphologically and physiologically different kinds of organisms, named primary colony organisms and secondary colony organisms. The primary colony organisms were slow-growing and cycloheximide-resistant as compared with the secondary ones which, like the parent organisms, were fast-growing in the absence of cycloheximide, but were inhibited when cycloheximide was incorporated in the medium. Cell aggregates, large swollen cells, and dwarf cells were found among the secondary colony organisms. The primary colony organisms were smaller than normal cells but were larger than the dwarf cells. The primary colony organisms also proved to have lost the faculty to sporulate, whereas the secondary colony organisms sporulated like the untreated parents. In contrast to the normal organisms and the secondary colony organisms, the primary colony organisms did not consume oxygen in manometric experiments with glucose as a substrate. On solid medium without cycloheximide, the latter organisms grew considerably better in a nitrogen atmosphere than in air.


Implementation of a screening, brief intervention, and referral to treatment program using the electronic medical record in a pediatric trauma center.
The purpose of this project was to develop and implement a consistent process for (1) screening adolescents by history for alcohol and substance abuse and (2) providing a motivational interview for change and appropriate referrals as needed. In the 18 months since we implemented the program, 534 patients were eligible for screening. Of these, 442 actually underwent screening and of these, 32 screened positive, thus receiving a brief intervention by social work and referral for further treatment. Use of the electronic medical record was key to the implementation and sustainability of this project.


Ultrathin SU-8 membrane for highly efficient tunable cell patterning and massively parallel large biomolecular delivery.
Cell patterning is a powerful technique for the precise control and arrangement of cells, enabling detailed single-cell analysis with broad applications in therapeutics, diagnostics, and regenerative medicine. This study presents a novel and efficient technique that enables massively parallel high throughput cell patterning and precise delivery of small to large biomolecules into patterned cells. The innovative cell patterning device proposed in this study is a standalone, ultrathin 3D SU-8 micro-stencil membrane, with a thickness of 10 μm. It features an array of micro-holes ranging from 40 μm to 80 μm, spaced apart by 50 μm to 150 μm. By culturing cells on top of this SU-8 membrane, the technique achieves highly efficient cell patterns varying from single-cell to cell clusters on a Petri dish. Utilizing this technique, we have achieved a remarkable reproducible patterning efficiency for mouse fibroblast L929 (80.5%), human cervical SiHa (81%), and human neuroblastoma IMR32 (89.6%) with less than 1% defects in undesired areas. Single-cell patterning efficiency was observed to be highest at 75.8% for L929 cells. Additionally, we have demonstrated massively parallel high throughput uniform transfection of large biomolecules into live patterned cells by employing an array of titanium micro-rings (10 μm outer diameter, 3 μm inner diameter) activated through infrared light pulses. Successful delivery of a wide range of small to very large biomolecules, including propidium iodide (PI) dye (668.4 Da), dextran (3 kDa), siRNA (13.3 kDa), and β-galactosidase enzyme (465 kDa), was accomplished in cell patterns for various cancer cells. Notably, our platform achieved exceptional delivery efficiencies of 97% for small molecules like PI dye and 84% for the enzyme, with corresponding high cell viability of 100% and 90%, respectively. Furthermore, the compact and reusable SU-8-based membrane device facilitates highly efficient cell patterning, transfection, and cell viability, making it a promising tool for diagnostics and therapeutic applications.


Reduced fertility and neuroendocrine dysfunction in women with epilepsy.
A reduction of fertility in women with epilepsy has been reported since 1950 and is confirmed in recent epidemiological studies. This phenomenon has usually been attributed to the increase of medical and socioeconomic problems in these patients or to hyposexuality, which has been consistently observed in epileptic subjects. Recently, a higher occurrence of reproductive endocrine diseases has been reported in epileptic women and proposed as an important cause of reduced fertility. In particular, polycystic ovary syndrome and hypothalamic ovarian failure have been reported in epileptic women with increased frequency compared to the general population. Moreover, an abnormal pattern of luteinizing hormone (LH) pulsatility has been observed in normally cycling, drug-free epileptic women. We suggest that epilepsy may interfere with the functional activity of the gonadotropin releasing hormone (GnRH) pulse generator. It is possible that paroxysmal discharges spreading within the hypothalamus might affect the regularity of the GnRH pulse generator; alternatively, a neurotransmitter dysfunction might at the same time be responsible both for the lowering of the seizure threshold and for the dysfunction of GnRH secretion. The consequent alteration of LH pulsatility might in the long run, under the effect of additional factors, give rise to a clinical reproductive endocrine disorder.


Vitamin D polymorphisms and calcium homeostasis: a new concept of normal gene variants and physiologic variation.
The initial findings on the vitamin D receptor have opened the field of the genetics of osteoporosis to targeted genetic studies and may open the way to genome scan approaches. Interaction between genetics, the environment, and lifestyle factors will also be an important target for future research. Understanding the physiology of such gene effects will likely open the way to more specific treatments and the selection of more appropriate and effective treatment options.


Regulation of phospholipase C delta1 by sphingosine.
Sphingosine, which is on the pathway of sphingomyelin degradation, activates phospholipase C (PLC) delta1 moderately. In the liposome assay effect of sphingosine on PLC delta1 activity depends on KCl concentration. Stimulation of PLC delta1 by sphingosine increased as the KCl concentration is increased from 0 to 100 mM, and then diminished with the increasing KCl. In the liposome assay sphingosine diminishes inhibition of PLC delta1 by sphingomyelin. To determine the domain of PLC delta1 which interacts with sphingosine active proteolytic fragments of PLC delta1 were generated by trypsin digestion of the native enzyme. Sphingosine affects the activity of PLC delta1 fragment which lacked the amino-terminal domain (first 60 amino acids) but not the active fragment that has cleaved the domain spanning the X and Y region of PLC delta1. These observations indicate that for interaction of sphingosine with PLC delta1 intact domain that span regions of conservation, designated as X and Y is necessary. When the activity of PLC delta1 was assayed with PIP2 in the erythrocyte membrane as substrate, sphingosine strongly inhibited PLC delta1. The other homolog of sphingosine 4-hydroxysphinganine (phytosphingosine) inhibited PLC delta1 to much lesser extent. The activity of PLC delta1 was inhibited by 68% and 22% in the presence of 20 microM sphingosine and phytosphingosine, respectively. This inhibition was completely abolished by deoxycholate at a concentration of 1.5 mM. These observations suggest that sphingosine may regulate activity of PLC delta1 in the cell.


Poly(N-isopropylacrylamide)-based semi-interpenetrating polymer networks for tissue engineering applications. 1. Effects of linear poly(acrylic acid) chains on phase behavior.
Poly(N-isopropylacrylamide)-based [P(NIPAAm)-based] semi-interpenetrating polymer networks (semi-IPNs), consisting of P(NIPAAm)-based hydrogels and linear poly(acrylic acid) [P(AAc)] chains, were synthesized, and the effects of the P(AAc) chains on semi-IPN injectability and phase behavior were analyzed. In P(NIPAAm)- and P(NIPAAm-co-AAc)-based semi-IPN studies, numerous reaction conditions were varied, and the effects of these factors on semi-IPN injectability, transparency, phase transition, lower critical solution temperature (LCST), and volume change were examined. The P(AAc) chains did not significantly affect the LCST or volume change of the semi-IPNs, compared to control hydrogels. However, the P(AAc) chains affected the injectability, transparency, and phase transition of the matrices, and these effects were dependent on chain amount and molecular weight (MW) and on interactions between the P(AAc) chains and the solvent and/or copolymer chains in P(NIPAAm-co-AAc) hydrogels. These results can be used to design "tailored" P(NIPAAm)-based semi-IPNs that have the potential to serve as functional scaffolds in tissue engineering applications.


Novel null mutations in the EYS gene are a frequent cause of autosomal recessive retinitis pigmentosa in the Israeli population.
To characterize the role of EYS, a recently identified retinal disease gene, in families with inherited retinal degenerations in the Israeli and Palestinian populations. Clinical and molecular analyses included family history, ocular examination, full-field electroretinography (ERG), perimetry, autozygosity mapping, mutation detection, and estimation of mutation age. Autozygosity mapping was performed in 171 consanguineous Israeli and Palestinian families with inherited retinal degenerations. Large homozygous regions, harboring the EYS gene, were identified in 15 of the families. EYS mutation analysis in the 15 index cases, followed by genotyping of specific mutations in an additional 121 cases of inherited retinal degenerations, revealed five novel null mutations, two of which are founder mutations, in 10 Israeli and Palestinian families with autosomal recessive retinitis pigmentosa (arRP). The most common mutation identified was a founder mutation in the Moroccan Jewish subpopulation. The ESTIAGE program produced an estimate that the age of the most recent common ancestor was 26 generations. The retinal phenotype in most patients was typical yet relatively severe RP, with an early age of onset and nonrecordable ERGs on presentation. The results demonstrate that EYS is currently the most commonly mutated arRP gene in the Israeli population, mainly due to founder mutations. EYS mutations were associated with an RP phenotype in all patients. The authors concluded that the gene plays only a minor role in causing other retinal phenotypes.


Exploring the Impact of Sociodemographic Characteristics and Health Literacy on Adherence to Dietary Recommendations and Food Literacy.
This study investigates food literacy-related abilities and adherence to dietary recommendations in relation to sociodemographic characteristics and health-related features (health literacy, self-rated health and morbidity) in the North-Western region of Romania. This is a secondary analysis of cross-sectional data collected in 2019 from a representative and randomised sample of 1572 individuals. A questionnaire was employed to record participants' sociodemographic characteristics, food-related and health-related features. Most participants were non-adherent to dietary recommendations for fruit and vegetables (83.5%), fish and seafood (61.3%), and water intake (67.9%). However, most participants reported an adequate ability to understand the connection between nutrition and health (89.1%), to distinguish between healthy and less healthy options (84.4%), and to acquire nutrition information (75.6%). Non-adherence to dietary recommendations and low food literacy abilities were more prevalent in disadvantaged groups (older age, rural settings, retirement or social welfare, low educational attainment, formerly married). Health literacy was negatively associated with not adhering to dietary recommendations and poor self-rated food literacy abilities. The study suggests that low socioeconomic status negatively impacts food literacy and adherence to dietary recommendations among Romanian adults. Identifying target populations to improve food-related abilities and health literacy can aid public health services in improving health outcomes.


Mast cell degranulating peptide: a multi-functional neurotoxin.
This review discusses our present knowledge of the structure and activities of the mast cell degranulating peptide (MCDP). This peptide is a basic, 22 amino acid residue component of honey bee venom with striking immunological and pharmacological activities. MCDP is a potent anti-inflammatory agent, but at low concentrations it is a strong mediator of mast cell degranulation and histamine release. MCDP is also an epileptogenic neurotoxin, an avid blocker of the potassium channels and can cause a significant lowering of the blood pressure in rats. Some of the biological activities of MCDP appear to have distinct mechanisms and may represent a good illustration of the structure-function relationship.


[Quorum sensing in Gram-negative bacteria: signal molecules, inhibitors and their potential therapeutic application].
Quorum Sensing (QS) is a phenomenon of chemical cell-to-cell communication consisting in the synthesis and secretion of signal molecules called autoinducers into the environment, which contribute in regulation of various physiological processes. QS was identified in different bacterial species, including symbiotic and pathogenic bacteria. QS systems play a crucial role in regulation of expression of genes which control motility, biofilm formation, and synthesis of virulence factors by pathogenic bacteria. These systems recognize signal molecules of different specificity which belong to a few groups and enable intra- and interspecific communication of bacterial cells as well as communication with cells of eukaryotic organisms (hosts). Inhibition of QS called Quorum Quenching (QQ) is now regarded to be a promising strategy to combat bacterial infections. So far, a large group of substances of natural and synthetic origin with a function of QS inhibitors, which can have potential therapeutic applications, has been identified.


A protocol for shoot multiplication from foliar meristem of Vanda spathulata (L.) Spreng.
Leaf explants collected from flowering plants of Vanda spathulata were cultured in Mitra medium with combinations of 6-benzyladenine (BA; 13.2-88.8 microM) and indole-3-acetic acid (IAA; 0.0 -85.6 microM). Combination of BA (66.6 microM) and IAA (28.5 microM) induced maximum shoots (17.33) from foliar meristems (leaf base). BA individually did not induce caulogenesis in leaf explants. For optimized multiplication, BA:IAA (2:1 microM) was essential at 22.2- 88.8 microM of BA. Re-cultured leaf explants produced lesser number of shoots compared to original explants and were nearly equal at combinations of 22.2-44.4 microM of BA and 5.7-28.5 microM of IAA. Rooting of shoots (> 95%) occurred in medium containing banana pulp (75 gl(-1)) and IAA (5.7 microM) within 3-9 weeks. Plantlets with 2-5 roots of 2-5 cm length established easily in community pots at 80-90% rates without hardening.


Effect of hyperthyroidism and propylthiouracil treatment on liver biochemical tests.
Liver biochemical test (LBT) changes can be commonly observed in hyperthyroid patients. Those kinds of changes could also be observed because of propylthiouracil (PTU) therapy. We prospectively evaluated LBT changes because of PTU use for 1 year in patients who had been diagnosed with hyperthyroidism first. We studied 64 patients who had been diagnosed with hyperthyroidism. These patients took at least 1-year PTU treatment. We analysed LBT at diagnosis and after 2 and 12 months of treatment with PTU. Prior to PTU treatment, 30 (46.8%) of the 64 patients had at least one LBT abnormality. We observed at least one LBT abnormality in 11 (32%) patients after 2 months and nine (26%) patients after 12 months of treatment with PTU in 34 patients whose CBT were normal before treatment. We did not observe any deterioration in clinical picture and bilirubin levels. Elevated serum LBT during the pretreatment and PTU treatment period is common and usually transient and asymptomatic. PTU could be used for long times by lowering the dose and close follow-up in patients who have elevated LBT during the pretreatment and after PTU treatment period.


Assessing the Relationship between Anxiety and Revision Surgery following Autologous Breast Reconstruction.
Revision procedures address contour irregularities and aesthetic concerns following autologous breast reconstruction. Mental health diagnoses are known to influence patient satisfaction with reconstruction. The authors aimed to identify oncologic, reconstructive, and demographic factors, including mental health diagnoses, associated with the number of revisions after autologous breast reconstruction. The medical records of all adult women undergoing abdominal free flap-based breast reconstruction at a major academic institution between 2011 and 2016 were reviewed. Multivariate logistic regression was used to identify factors associated with receipt of revisions. Negative binomial regression was used to identify characteristics associated with number of revisions received. Of 272 patients identified, 55.2 percent received one revision, 23.2 percent received two revisions, and 10.3 percent received three or more revisions after autologous breast reconstruction (median, one; range, zero to five). After adjustment on multivariate analysis, anxiety (OR, 4.34; p = 0.016) and bilateral reconstruction (OR, 3.10; p = 0.017) were associated with receipt of any revisions; other oncologic and reconstructive factors including breast cancer stage, receipt of radiation therapy, and type or timing of free flap reconstruction were not associated with revisions. Using univariate negative binomial regression, anxiety (incidence rate ratio, 1.34; p = 0.006), Caucasian race (incidence rate ratio, 1.24; p = 0.02), and bilateral reconstruction (incidence rate ratio, 1.39; p = 0.04) were predictive of increased numbers of revisions received. After stepwise selection on multivariate analysis, anxiety remained the only significant predictor of increased numbers of revisions. Preoperative anxiety significantly influences the number of revisions after autologous breast reconstruction. Further research is necessary to better understand the interplay among mental health, patient preference, and outcomes in breast reconstruction. Risk, III.


The Carboxy-Terminal Region of Flavobacterium johnsoniae SprB Facilitates Its Secretion by the Type IX Secretion System and Propulsion by the Gliding Motility Machinery.
Flavobacterium johnsoniae SprB moves rapidly along the cell surface, resulting in gliding motility. SprB secretion requires the type IX secretion system (T9SS). Proteins secreted by the T9SS typically have conserved C-terminal domains (CTDs) belonging to the type A CTD or type B CTD family. Attachment of 70- to 100-amino-acid type A CTDs to a foreign protein allows its secretion. Type B CTDs are common but have received little attention. Secretion of the foreign protein superfolder green fluorescent protein (sfGFP) fused to regions spanning the SprB type B CTD (sfGFP-CTDSprB) was analyzed. CTDs of 218 amino acids or longer resulted in secretion of sfGFP, whereas a 149-amino-acid region did not. Some sfGFP was secreted in soluble form, whereas the rest was attached on the cell surface. Surface-attached sfGFP was rapidly propelled along the cell, suggesting productive interaction with the motility machinery. This did not result in rapid cell movement, which apparently requires additional regions of SprB. Secretion of sfGFP-CTDSprB required coexpression with sprF, which lies downstream of sprB SprF is similar in sequence to Porphyromonas gingivalis PorP. Most F. johnsoniae genes encoding proteins with type B CTDs lie immediately upstream of porP/sprF-like genes. sfGFP was fused to the type B CTD from one such protein (Fjoh_3952). This resulted in secretion of sfGFP only when it was coexpressed with its cognate PorP/SprF-like protein. These results highlight the need for extended regions of type B CTDs and for coexpression with the appropriate PorP/SprF-like protein for efficient secretion and cell surface localization of cargo proteins.IMPORTANCE The F. johnsoniae gliding motility adhesin SprB is delivered to the cell surface by the type IX secretion system (T9SS) and is rapidly propelled along the cell by the motility machinery. How this 6,497-amino-acid protein interacts with the secretion and motility machines is not known. Fusion of the C-terminal 218 amino acids of SprB to a foreign cargo protein resulted in its secretion, attachment to the cell surface, and rapid movement by the motility machinery. Efficient secretion of SprB required coexpression with the outer membrane protein SprF. Secreted proteins that have sequence similarity to SprB in their C-terminal regions are common in the phylum Bacteroidetes and may have roles in adhesion, motility, and virulence.


Prostaglandin E2 promotes BeWo spheroids implantation in RL95-2 cell monolayers.
Integrin αvβ3 (ITG αvβ3) participates in the process of implantation between the embryo and the endometrium. This study investigated the effects of prostaglandin E2 (PGE2) on endometrial receptivity and implantation efficiency of the embryo, and their possible mechanisms. Quantitative real-time reverse transcription PCR (qRT-PCR) and western blotting were used to detect the changes in mRNA and protein levels of ITG αvβ3 in RL95-2 cells after administering PGE2. BeWo trophoblast cells and RL95-2 endometrial epithelial cells were used to establish an in vitro model, which was used to observe the adhesion rate and spreading efficiency between BeWo spheroids and RL95-2 cell monolayers after pretreatment with different concentrations of PGE2. PGE2 at 200 nM increased the mRNA and protein levels of ITG αv significantly (p < 0.05); 100 nM PGE2 increased the mRNA and protein levels of ITG β3 significantly (p < 0.05). PGE2 at 200 nM increased significantly the adhesion and spreading efficiency of BeWo spheres to RL95-2 cell monolayers. An appropriate concentration of PGE2 might increase the expression of ITG αvβ3, which would, promote embryo adhesion and spreading efficiency. This study provides further evidence that increased expression of ITG αvβ3 might promote implantation by improving endometrial receptivity.


Tissue engineering; strategies, tissues, and biomaterials.
Current tissue regenerative strategies rely mainly on tissue repair by transplantation of the synthetic/natural implants. However, limitations of the existing strategies have increased the demand for tissue engineering approaches. Appropriate cell source, effective cell modification, and proper supportive matrices are three bases of tissue engineering. Selection of appropriate methods for cell stimulation, scaffold synthesis, and tissue transplantation play a definitive role in successful tissue engineering. Although the variety of the players are available, but proper combination and functional synergism determine the practical efficacy. Hence, in this review, a comprehensive view of tissue engineering and its different aspects are investigated.


Proliferating cell nuclear antigen immunolocalization in gastro-intestinal epithelia.
Proliferating cell nuclear antigen (PCNA), also called DNA polymerase delta-associated protein, is found in the cells of the proliferative compartment of normal tissues and is essential for DNA replication. It can be recognized by many monoclonal antibodies to various epitopes on the molecule. In this investigation one of these, PC10, has been used on formalin-fixed, paraffin-embedded, human and rodent gastro-intestinal epithelial tissues to assess numerically the labelling index of PC10 and to compare it, in the rat liver and gastrointestinal tract, with the S-phase fraction as determined by bromodeoxyuridine (BrdUrd) labelling. The distribution of PC10-labelled cells was recorded with respect to cell position in the intestinal crypts of man. In tissues where both modes of assessment were used, PC10 staining in the well-established proliferative compartments was found to be more extensive than that of BrdUrd. The higher labelling index with PC10 can be explained by its identification of PCNA outside the S phase of the cell cycle and also by the long half-life of PCNA protein in post-proliferative intestinal epithelial cells as they migrate towards the villus. Nevertheless the data suggest PC10 immunostaining in gastro-intestinal epithelia is an operational marker of cell proliferation which is reproducible, quantifiable and can be performed on routinely processed tissues.


Cognitive and affective trait and state factors influencing the long-term symptom course in remitted depressed patients.
Major depressive disorder (MDD) is characterized by a high risk for relapses and chronic developments. Clinical characteristics such as residual symptoms have been shown to negatively affect the long-term course of MDD. However, it is unclear so far how trait repetitive negative thinking (RNT) as well as cognitive and affective momentary states, the latter experienced during daily-life, affect the long-term course of MDD. We followed up 57 remitted depressed (rMDD) individuals six (T2) and 36 (T3) months after baseline. Clinical outcomes were time to relapse, time spent with significant symptoms as a marker of chronicity, and levels of depressive symptoms at T2 and T3. Predictors assessed at baseline included residual symptoms and trait RNT. Furthermore, momentary daily life affect and momentary rumination, and their variation over the day were assessed at baseline using ambulatory assessment (AA). In multiple models, residual symptoms and instability of daily-life affect at baseline independently predicted a faster time to relapse, while chronicity was significantly predicted by trait RNT. Multilevel models revealed that depressive symptom levels during follow-up were predicted by baseline residual symptom levels and by instability of daily-life rumination. Both instability features were linked to a higher number of anamnestic MDD episodes. Our findings indicate that trait RNT, but also affective and cognitive processes during daily life impact the longer-term course of MDD. Future longitudinal research on the role of respective AA-phenotypes as potential transdiagnostic course-modifiers is warranted.


Heart rate variability assessment of overreaching in active and sedentary females.
Resting heart rate variability (HRV) profile was compared between sedentary and active females before, during, and after a 2-week overreaching protocol. Twenty currently active and 20 sedentary females were subdivided within their groups to either an experimental or control group. The active and sedentary experimental groups completed an overreaching protocol; endurance exercise, 40 minutes per session at an intensity of 70-90 % heart rate reserve, 7 d.wk(-1). The active experimental group showed an increase in low frequency power and a decrease in high frequency power over the intervention weeks (LF : HF ratio; Baseline = 2.0 [1.1], End week 1 = 2.4 [1.9], End week 2 = 3.2 [1.9], Recovery = 1.9 [1.0] mean [SD]) although this was not statistically significant (p > or = 0.05) for within group effects. The sedentary experimental group however, showed a significant (p < or = 0.05) increase in low frequency power and a decrease in high frequency power during the overreaching phase suggesting a move towards a predominance of resting sympathetic cardiac modulation (LF:HF ratio; Baseline = 1.6[1.1], End week 1 = 3.4 [1.6], End week 2 = 4.4 [3.0], Recovery = 1.8 [0.9]). These findings arose in the absence of any significant change in resting heart rate. Time domain analysis however failed to provide similar findings in either experimental group. Neither control group showed any significant changes. These data suggest a more marked change in sympathovagal balance in sedentary people when exposed to an overreaching protocol than in active individuals.


Control of the Singular Points Location for Miniature Switches with Magnetically Driven Contacts.
This paper presents and discusses usefulness and possibility of control of the singular points location of a driving magnetic field under as structure considerations as well as selection of energizing magnet systems for miniature electromagnetic switches. The sample results of theoretical analysis and experimental testing concern selected reed switches with normally open contacts as well as a developed miniature switch with a metallic ball contact. It must be noted that the switch with the contact performed by means of the metallic tiny ball can be effectively used both as a change-over switch as well as a detector of the energizing magnetic field distribution under designing and assembling of any electromagnetic contact device preferably with an increased degree of integration and miniaturization.


[The protective effects of SB203580 against mortality and radiation induced intestinal injury of mice].
This study is to investigate the protective effects of the SB203580 against radiation induced mortality and intestinal injury of mice. A total of 67 male C57BL/6 mice (20.0-22.0 g) were matched according to body weight and randomly assigned to one of three groups: control, total body irradiation exposure (IR, 7.2 Gy) only, and IR (7.2 Gy) + SB203580 (15 mg x kg(-1)). 30 days survival rate was observed in the experiment. In intestinal injury experiment, the expression levels of caspase-3, Ki67, p53 and p-p38 were assayed in the mice intestine crypts. The results showed that the 30 days survival rate was 100% (control), 0 (IR) and 40% (IR+ SB203580), separately. Compared to the IR groups, the positive cells of caspase-3, p53 and p-p38 in crypt cells decreased 33.00%, 21.78% and 34.63%, respectively. The rate of positive cells of Ki67 increased 37.96%. Significant difference was found between all of them (P < 0.01). SB203580 potently protected against radiation-induced lethal and intestinal injury in mice, and it may be a potential radio protector.


N-demethylation of p-chloro-N-methylaniline catalyzed by subcellular fractions from the avocado pear (Persea americana).
Subcellular fractions from the avocado pear ( Persea americana) catalyzed formation of p-chloroaniline from p-chloro-N-methylaniline. Fractions prepared by centrifugation of avocado homogenates at 20, 000g for 20 min formed p-chloroaniline (2900 +/- 500 pmol min-1 mg protein-1) with an NADPH-generating system. p-Chloroaniline formation required reduced pyridine nucleotide (NADPH was 6-7 times more effective than NADH) and O2. N-Demethylation was inhibited by CO (55% inhibition at CO:O2 = 1) and was not inhibited by CN. Cytochrome P-450 was detected in the 20, 000g pellet at levels of 300-380 pmol/mg protein. This particulate preparation was also active in catalyzing the NADPH-dependent epoxidation of the chlorinated cyclodiene aldrin. Improvements to a colorimetric procedure for measuring p-chloroaniline increased the sensitivity of the procedure fourfold, and allowed use of samples containing high amounts of lipid. Avocado pear is suitable tissue for further studies on the oxidation of foreign compounds by higher plants.


Choristoma of the optic nerve: neuroimaging characteristics and association with spinal cord lipoma.
A 54-year-old patient presented with amaurosis of the right eye that resulted from a dysontogenetic tumor of the right optic nerve. The tumor involved the intraorbital, intracanalicular and intracerebral portion of the right optic nerve, without involvement of the chiasm. Although the patient had refused further diagnostic surgical exploration, we show that it is possible to establish the diagnosis of choristoma of the optic nerve by means of modern neuroimaging techniques based on computed tomography and magnetic resonance imaging. It appears from neuroimaging that choristomata of the optic nerve and spinal cord lipomas represent different manifestations of the same type of tumor. The neuroimaging characteristics of both kinds of tumors are discussed.


Differential induction of hepatic estrogen receptor and vitellogenin gene transcription in Xenopus laevis.
Low levels of estrogen receptor (200-500 per cell) are present in the liver of hormonally naive male Xenopus. However, administration of estradiol results in a rapid 2- to 5-fold increase in cellular estrogen receptor content concurrent with the de novo transcriptional activation of the genes for the yolk protein precursor vitellogenin. Studies on Xenopus embryogenesis suggest that estrogen receptor induction is required for the activation of vitellogenin transcription. The purpose of the present study was to examine the mechanism of estrogen receptor induction in male Xenopus liver. The experimental protocol used 4-hydroxytamoxifen, an antiestrogen with a high affinity for the estrogen receptor, to inhibit the effects of estradiol. Changes in estrogen receptor content were then determined through the use of an exchange assay. 4-Hydroxytamoxifen alone suppressed the level of estrogen receptor from 800 sites per cell in hormonally naive animals to 250 sites per cell. Administration of estradiol 24 h after the antiestrogen resulted in the induction of estrogen receptor to a level equivalent to that found in control animals (800 sites per cell). However, under the same conditions, estradiol was unable to overcome the antiestrogen inhibition of vitellogenin gene transcription. Although 4-hydroxytamoxifen displayed a high affinity for the hepatic estrogen receptor, it did not inhibit the binding of estradiol to a middle affinity cytoplasmic estrogen-binding protein. These results suggest that different mechanisms are involved in the induction of estrogen receptor and vitellogenin gene transcription.


Implantation of an arteriovenous graft through the peripheral vascular access in the presence of superior vena cava stenosis but a patent azygos vein: A case report.
Long-term indwelling central venous catheters (CVCs) may cause complications, such as central venous disease (CVD). CVD eliminates the possibility of establishing new arteriovenous access. We herein describe a case in which an arteriovenous graft (AVG) is implanted through the peripheral veins and blood flows back to the patent azygos vein, secondary to superior vena cava stenosis. This shows that if the CVD is correctable or the collateral circulation is an alternative vascular pathway that allows blood to return back to the right atrium, the internal fistula flow is well-balanced with the collateral circulation and there are no clinical symptoms of CVD, an arteriovenous access can be established for the operation. This provides a viable, long-term vascular access option for hemodialysis patients with central venous resource depletion.


Initial approach to blood access for the chronic hemodialysis patient--the bovine heterograft.
Experience with the modified bovine heterograft arteriovenous fistula for hemodialysis in 79 grafts in 73 patients over an 18 mo period is analyzed. An immediate (30 day) patency rate of 97.5%, and a 12 mo cumulative patency rate of 73.9% was observed. Early and late complication rates were acceptably low, despite early usage in 80% of cases. It is concluded that the bovine fistula provides an acceptable blood access route for the initial approach to the patient in urgent need of hemodialysis.


FOXP1 molecular cytogenetics and protein expression analyses in primary cutaneous large B cell lymphoma, leg-type.
FOXP1 protein is expressed in normal activated B cells and overexpressed in a subset of diffuse large B-cell lymphomas, including primary cutaneous large B-cell lymphomas (PCLBCL), leg type. High expression of FOXP1 has been associated to an unfavourable prognosis with independent survival significance. However, little is known regarding the mechanisms underlying the overexpression of FOXP1 in PCLBCL, leg type. Our aims were to analyze FOXP1 cytogenetic status and protein expression in a series of PCLBCL, leg type. Finally, we compared the observed results with those obtained in a group of patients with primary cutaneous follicle centre lymphoma (PCFCL). Fifteen patients with PCLBCL, leg type and nine patients with primary cutaneous follicle centre lymphoma (PCFCL) were included in the study. For each biopsy specimen, FOXP1 translocation and copy number changes were evaluated by fluorescence in situ hybridization (FISH) and protein expression by immunohistochemistry (IHC). Immunohistochemistry showed FOXP1 staining in 13 PCLBCL, leg type, whereas all PCFCL were negative. FISH analysis disclosed no translocations involving FOXP1 gene in any of the cases. However, FOXP1 gene gains (3 to 4 copies) were observed in 82% of samples of PCLBCL, leg type and in 37% of PCFCL. FOXP1 expression was independent from FOXP1 translocation. Our results confirm that overexpression of FOXP1 is present in a considerable proportion of PCLBCL, leg type and might indicate an unfavourable prognosis. Mechanisms not related to translocation seem to be responsible for this overexpression.


Efficient transformation of the beetle Tribolium castaneum using the Minos transposable element: quantitative and qualitative analysis of genomic integration events.
Genetic transformation in insects holds great promise as a tool for genetic manipulation in species of particular scientific, economic, or medical interest. A number of transposable elements have been tested recently as potential vectors for transformation in a range of insects. Minos is one of the most promising elements because it appears to be active in diverse species and has the capacity to carry large inserts. We report here the use of the Minos element as a transformation vector in the red flour beetle Tribolium castaneum (Coleoptera), an important species for comparative developmental and pest management studies. Transgenic G(1) beetles were recovered from 32.4% of fertile G(0)'s injected with a plasmid carrying a 3xP3-EGFP-marked transposon and in vitro synthesized mRNA encoding the Minos transposase. This transformation efficiency is 2.8-fold higher than that observed when using a plasmid helper. Molecular and genetic analyses show that several independent insertions can be recovered from a single injected parent, but that the majority of transformed individuals carry single Minos insertions. These results establish Minos as one of the most efficient vectors for genetic transformation in insects. In combination with piggyBac-based transgenesis, our work allows the introduction of sophisticated multicomponent genetic tools in Tribolium.


In vitro activity of ticarcillin plus clavulanic acid against 632 clinical isolates.
A total of 632 clinical bacterial isolates were tested for susceptibility to twofold dilutions of ticarcillin alone and in combination with 1, 2, and 4 micrograms of clavulanic acid (CA) (Timentin) per ml by a reference microdilution method. With the addition of CA, ticarcillin MICs were reduced eightfold or greater with 54 of 59 (92%) strains of the family Enterobacteriaceae with ticarcillin MICs of greater than or equal to 64 micrograms/ml. The inhibitory effect of CA on pseudomonads was minimal. Ticarcillin MICs for beta-lactamase-producing Haemophilus influenzae, Neisseria gonorrhoeae, and most Staphylococcus aureus were reduced to less than or equal to 0.5 micrograms/ml when CA was added. For dilution susceptibility testing of ticarcillin-clavulanic acid, dilutions of ticarcillin combined with 2 micrograms of CA per ml is suggested.


Emergency in leprosy: involvement of the larynx.
We present eight patients with larynx involvement in leprosy. Seven were classified as lepromatous and one was borderline leprosy in reversal reaction. One patient required an emergency tracheostomy and one had an almost complete uppe airway obstruction.


Intraretinal and intra-optic nerve head silicone oil vacuoles using adaptive optics.
The authors report the in vivo visualization through multimodal imaging of silicone oil in the vitreous cavity, optic nerve, and retina of a patient 11 years after surgical removal of the main tamponade. Contact B-scan ultrasonography revealed countless small echogenic particles in the vitreous cavity and a hyperreflective structure within the optic nerve head. Swept-source optical coherence tomography showed multiple round hyporeflective spaces within the substance of the prelaminar optic nerve head. Adaptive optics imaging revealed numerous particles in the optic nerve head and within the retina in the same plane as the photoreceptors, with similar size and shape to the silicone oil droplets in the vitreous cavity. The authors hypothesize that in this case, the silicone oil droplets in the retina and optic nerve head may be associated with the patient's otherwise unexplained progressive visual loss.


Mapping the Interactions of Selective Biochemical Probes of Antibody Conformation by Hydrogen-Deuterium Exchange Mass Spectrometry.
Protein-based pharmaceuticals represent the fastest growing group of drugs in development in the pharmaceutical industry. One of the major challenges in the discovery, development, and distribution of biopharmaceuticals is the assessment of changes in their higher-order structure due to chemical modification. Here, we investigated the interactions of three different biochemical probes (Fab s) generated to detect conformational changes in a therapeutic IgG1 antibody (mAbX) by local hydrogen-deuterium exchange mass spectrometry (HDX-MS). We show that two of the probes target the Fc part of the antibody, whereas the third probe binds to the hinge region. Through HDX-ETD, we could distinguish specific binding patterns of the Fc -binding probes on mAbX at the amino-acid level. Preliminary surface plasmon resonance (SPR) experiments showed that these domain-selective Fab probes are sensitive to conformational changes in distinct regions of a full-length therapeutic antibody upon oxidation.


Oncogenic Metabolism Acts as a Prerequisite Step for Induction of Cancer Metastasis and Cancer Stem Cell Phenotype.
Metastasis is a major obstacle to the efficient and successful treatment of cancer. Initiation of metastasis requires epithelial-mesenchymal transition (EMT) that is regulated by several transcription factors, including Snail and ZEB1/2. EMT is closely linked to the acquisition of cancer stem cell (CSC) properties and chemoresistance, which contribute to tumor malignancy. Tumor suppressor p53 inhibits EMT and metastasis by negatively regulating several EMT-inducing transcription factors and regulatory molecules; thus, its inhibition is crucial in EMT, invasion, metastasis, and stemness. Metabolic alterations are another hallmark of cancer. Most cancer cells are more dependent on glycolysis than on mitochondrial oxidative phosphorylation for their energy production, even in the presence of oxygen. Cancer cells enhance other oncogenic metabolic pathways, such as glutamine metabolism, pentose phosphate pathway, and the synthesis of fatty acids and cholesterol. Metabolic reprogramming in cancer is regulated by the activation of oncogenes or loss of tumor suppressors that contribute to tumor progression. Oncogenic metabolism has been recently linked closely with the induction of EMT or CSC phenotypes by the induction of several metabolic enzyme genes. In addition, several transcription factors and molecules involved in EMT or CSCs, including Snail, Dlx-2, HIF-1α, STAT3, TGF-β, Wnt, and Akt, regulate oncogenic metabolism. Moreover, p53 induces metabolic change by directly regulating several metabolic enzymes. The collective data indicate the importance of oncogenic metabolism in the regulation of EMT, cell invasion and metastasis, and adoption of the CSC phenotype, which all contribute to malignant transformation and tumor development. In this review, we highlight the oncogenic metabolism as a key regulator of EMT and CSC, which is related with tumor progression involving metastasis and chemoresistance. Targeting oncometabolism might be a promising strategy for the development of effective anticancer therapy.


Paracrias pluteus (Hymenoptera, Eulophidae) in Brazil: new distribution and host records, and with a new host group for Paracrias.
Bruchines damage agricultural crops and trees, reducing the quantity and quality of the seeds. The aim of this study is to record, for the first time, Paracrias pluteus as a parasitoid on the immature stages of Sennius spodiogaster and Sennius cupreatus on seeds of Melanoxylon brauna in Teixeiras, Minas Gerais State, Brazil. Paracrias pluteus is a parasitoid without previous host records and known only from Costa Rica. Specimens obtained in this study add to knowledge of the biology of Paracrias species with a new host group (Chrysomelidae: Bruchinae), and the first host record and a new distribution for Paracrias pluteus.


13C NMR spectroscopy of alternating poly(gamma-benzyl D-L-glutamate) in alpha- and double-helical conformations.
Carbon-13 NMR spectra of alpha single-helical and pipiDL double-helical conformations of alternating poly (gamma-benzyl D-L-glutamate) are presented. In both cases, the existence of doublet for the backbone carbon atoms is consistent with D and L residues being in different conformational states when engaged in the same helix. The resonances of the Calpha atoms in both helices, which are found at identical chemical shifts, and comparison with the 1H NMR observation, favor the hypotheses that solvent molecules are located inside the helical core of the double helices.


Cancer immunosuppression and autoimmune disease: beyond immunosuppressive networks for tumour immunity.
Cancer immunosuppression evolves by constitution of an immunosuppressive network extending from a primary tumour site to secondary lymphoid organs and peripheral vessels and is mediated by several tumour-derived soluble factors (TDSFs) such as interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF). TDSFs induce immature myeloid cells and regulatory T cells in accordance with tumour progression, resulting in the inhibition of dendritic cell maturation and T-cell activation in a tumour-specific immune response. Tumour cells grow by exploiting a pro-inflammatory situation in the tumour microenvironment, whereas immune cells are regulated by TDSFs during anti-inflammatory situations--mediated by impaired clearance of apoptotic cells--that cause the release of IL-10, TGF-beta, and prostaglandin E2 (PGE2) by macrophages. Accumulation of impaired apoptotic cells induces anti-DNA antibodies directed against self antigens, which resembles a pseudo-autoimmune status. Systemic lupus erythematosus is a prototype of autoimmune disease that is characterized by defective tolerance of self antigens, the presence of anti-DNA antibodies and a pro-inflammatory response. The anti-DNA antibodies can be produced by impaired clearance of apoptotic cells, which is the result of a hereditary deficiency of complements C1q, C3 and C4, which are involved in the recognition of phagocytosis by macrophages. Thus, it is likely that impaired clearance of apoptotic cells is able to provoke different types of immune dysfunction in cancer and autoimmune disease in which some are similar and others are critically different. This review discusses a comparison of immunological dysfunctions in cancer and autoimmune disease with the aim of exploring new insights beyond cancer immunosuppression in tumour immunity.


Endocrine causes of recurrent pregnancy loss.
To review the available data on endocrine disorders and recurrent pregnancy loss. Our group found that most endocrine disorders do not seem to be correlated with a diagnosis of recurrent pregnancy loss (RPL). The exception to this is testing for thyroid stimulating hormone and thyroid antibodies, which is recommended due to a strong correlation with recurrent pregnancy loss and positive anti-thyroid peroxidase antibodies. The available literature supports testing thyroid function and antibodies in women with RPL. Testing for other endocrine disorders is only warranted if otherwise clinically indicated, independent from a history of recurrent pregnancy loss.


Lack of effect of acute repaglinide administration on postprandial lipaemia in patients with type 2 diabetes mellitus.
The effect of acute repaglinide administration (2 mg) on postprandial glycaemia and lipaemia has been examined in 20 subjects with type 2 diabetes mellitus. Each subject received in the morning, after a 12 to 14 h fast, a standard mixed meal (total energy 783 kcal), preceded by one tablet of 2 mg repaglinide or placebo. Chylomicrons and chylomicron-deficient plasma were prepared by ultracentrifugation. Triglyceride levels in CM fraction (CM-triglycerides) in total plasma as well as in CM-deficient plasma (non-CM-triglycerides) were determined. A significant reduction in postprandial glycaemia was observed after repaglinide administration compared to placebo ( p < 0.001). Plasma concentrations of total triglycerides, CM-triglycerides, non-CM-triglycerides, free fatty acids and the other plasma lipids measured, were not significantly different between the two phases of the study. It is concluded that, in contrast to sulphonylureas, acute repaglinide administration does not improve postprandial lipaemia in patients with type 2 diabetes.


The role of spinal nuclear factor-kappa B in spinal hyperexcitability.
In behavioral experiments, inhibition of nuclear factor-kappaB activation by systemic administration of the IkappaB kinase inhibitor S1627 has been shown to attenuate inflammatory and neuropathic pain. Here, we specifically investigated with electrophysiological recordings in anesthetized rats whether spinal application of S1627 influences hyperexcitability of dorsal horn neurons during an acute knee joint inflammation. Spinal application of S1627 before and early during development of inflammation totally prevented spinal hyperexcitability suggesting an important role of spinal nuclear factor-kappaB in this process. During established inflammation, however, S1627 did not reduce the responses of neurons to mechanical stimulation of the inflamed knee within 2.5 h after spinal administration, thus suggesting that spinal hyperexcitability is not maintained by continuous nuclear factor-kappaB activation.


Diastereoselectivity in the self-assembly of As2L2Cl2 macrocycles is directed by the As-pi interaction.
The As-pi interaction, in conjunction with reversible As-thiolate bond formation, is used to direct the self-assembly of dinuclear As2L2Cl2 (L = a dithiolate) macrocycles that exist as equilibrium mixtures of both syn and anti diastereomers. The diastereomeric excess of these self-assembly reactions is controlled in a predictable manner by prudent choice of different achiral, isomeric ligands. A general method for the preparation of As2L2Cl2 macrocycles is established, and strategies to control the diastereoselective self-assembly of regioisomeric macrocycles in solution and the crystalline state are described. A mechanism for the interconversion between diastereomers (a slow process on the NMR time scale) is suggested, and variable-temperature NMR spectroscopic data show that the diastereomeric excess (de) decreases with increasing temperature. anti-As2(L2,6)2Cl2 crystallizes in monoclinic space group P2(1)/n with a = 6.3949(13), b = 19.675(4), c = 10.967(2) A, beta = 106.817(3) degrees , and Z = 2. anti-As2(L1,5)2Cl2 crystallizes in monoclinic space group P2(1)/c with a = 6.813(4), b = 19.085(12), c = 10.277(6) A, beta = 107.788(10) degrees , and Z = 4. syn-As2(L1,4)2Cl2.CHCl3 crystallizes in triclinic space group P(-) with a = 19.313(4), b = 19.923(4), c = 24.508(5) A, alpha = 78.110(4) degrees , beta = 78.860(5) degrees , gamma = 89.183(5) degrees , and Z = 12. As2(L1,4)2Cl2.C6H6 crystallizes in monoclinic space group P2(1)/n with a = 10.3332(7), b = 34.375(2), c = 17.8593(12) A, beta = 98.9650(10) degrees , and Z = 8.


Mechanism of expiratory muscle activation during lower thoracic spinal cord stimulation.
Lower thoracic spinal cord stimulation (SCS) may be a useful method to restore an effective cough mechanism. In dogs, two groups of studies were performed to evaluate the mechanism of the expiratory muscle activation during stimulation at the T(9)-T(10) level, which results in the greatest changes in airway pressure. In one group, expiratory muscle activation was monitored by evoked muscle compound action potentials (CAPs) from the internal intercostal muscles in the 10th, 11th, and 12th interspaces and from portions of the external oblique innervated by the L(1) and L(2) motor roots. SCS, applied with single shocks, resulted in short-latency CAPs at T(10) but not at more caudal levels. SCS resulted in long-latency CAPs at each of the more caudal caudal recording sites. Bilateral dorsal column sectioning, just below the T(11) spinal cord level, did not affect the short-latency CAPs but abolished the long-latency CAPs and also resulted in a fall in airway pressure generation. In the second group, sequential spinal root sectioning was performed to assess their individual mechanical contribution to pressure generation. Section of the ventral roots from T(8) through T(10) resulted in negligible changes, whereas section of more caudal roots resulted in a progressive reduction in pressure generation. We conclude that 1) SCS at the T(9)-T(10) level results in direct activation of spinal cord roots within two to three segments of the stimulating electrode and activation of more distal roots via spinal cord pathways, and 2) pathway activation of motor roots makes a substantial contribution to pressure generation.


Air pollution control through biotrickling filters: a review considering operational aspects and expected performance.
The biological removal of pollutants, especially through biotrickling filters (BTFs), has recently become attractive for the low investment and operational costs and the low secondary pollution. This paper is intended to investigate the state of the art on BTF applications. After an overview on the biodegradation process and the typical parameters involved, this paper presents the analysis of a group of 16 literature studies chosen as the references for this sector. The reference studies differ from one another by the pollutants treated (volatile organic compounds [VOC], hydrogen sulphide, nitrogen oxides and trimethylamine), the geometry and size of the BTFs, and the procedures of the tests. The reference studies are analyzed and discussed in terms of the operational conditions and the results obtained, especially with respect to the removal efficiencies (REs) and the elimination capacities (ECs) of the pollutants considered. Empty bed residence time (EBRT), pollutant loading rate, temperature, pH, oxygen availability, trickling liquid flow rate, inoculum selection and biomass control strategies revealed to be the most important operational factors influencing the removal performance of a BTF.


The effect of temperature on water desalination through two-dimensional nanopores.
Two-dimensional (2D) materials such as graphene, molybdenum sulfide, and hexagonal boron nitride are widely studied for separation applications such as water desalination. Desalination across such 2D nanoporous membranes is largely influenced by the bulk transport properties of water, which are, in turn, sensitive to the operating temperature. However, there have been no studies on the effect of temperature on desalination through 2D nanopores. We investigated water desalination through hydrogen functionalized graphene nanopores of varying pore areas at temperatures 275.0 K, 300.0 K, 325.0 K, and 350.0 K. The water flux showed a direct relation with the diffusion coefficient and an inverse relation with the hydrogen-bond lifetime. As a direct consequence, the water flux was found to be related to the temperature as per the Arrhenius equation, similar to an activated process. The results from the present study improve the understanding on water and ion permeation across nanoporous 2D materials at different temperatures. Furthermore, the present investigation suggests a kinetic model, which can predict the water and ion permeation based on the characteristics of the nanopore.


Identification of hepatic mitogenic and cytochrome P-450-inducing fractions of unleaded gasoline in B6C3F1 mice.
Unleaded gasoline (UG), a complex mixture of over 300 hydrocarbons, induced liver tumors selectively in female mice and exhibited liver tumor promoting activity. UG also induced cell proliferation and cytochrome P-450-related enzyme activities in mouse liver, properties commonly associated with liver tumor promoters. To determine if the mitogenic and/or cytochrome P-450-inducing properties of UG reside in individual fractions of UG, UG was separated into four fractions on the basis of boiling point (BP): fraction 1, BP < 66 degrees C; fraction 2, 66 degrees C < BP < 100 degrees C; fraction 3, 100 degrees C < BP < 132 degrees C; fraction 4, BP > 132 degrees C. Fractions 1 and 2 were combined to form "light UG" (BP < 100 degrees C), and fractions 3 and 4 were combined to form "heavy UG" (BP > 100 degrees C). Female B6C3F1 mice were implanted with osmotic pumps containing 5-bromo-2'-deoxyuridine (BrdU) on d 1, treated by intragastric intubation with corn oil or 3000 mg/kg/d of light, heavy, or whole UG on d 2-4, and euthanized on d 5. Pentoxyresorufin O-dealkylase (PROD) and ethoxyresorufin O-deethylase (EROD) activities were assayed in hepatic microsomes, and hepatocyte BrdU labeling index (LI) was determined in liver sections. Whole UG and heavy UG caused comparable increases in hepatic PROD and EROD activities and the hepatocyte LI. Light UG caused relatively small increases in hepatic PROD and EROD activities and did not increase the hepatocyte LI. When fractions 3 and 4 were tested separately in the above treatment protocol, both fractions strongly induced hepatic PROD and weakly induced hepatic EROD activities. However, only fraction 3 increased the hepatocyte LI. To isolate mitogenic components in fraction 3, equimolar doses of individual chemicals in fraction 3 were tested in the above treatment protocol. Toluene did not increase the hepatocyte LI, whereas 2,2,3-trimethylpentane (TMP), 2,2,4-TMP, and 2,3,4-TMP all dramatically increased the hepatocyte LI. Thus, while the hepatic cytochrome P-450-inducing activity of UG was concentrated in components of UG with BPs > 100 degrees C, this activity apparently resides in UG components with a wide range of BPs. The mitogenic activity of UG, in contrast, was highly concentrated in components of UG with BPs ranging from approximately 100 to 132 degrees C, and quite possibly in specific TMPs.


Single use of tetracycline with and without diclofenac sodium as local drug delivery in pocket therapy: a clinico-microbiological study.
Local drug delivery is a non-surgical method in the treatment of periodontitis. Different chemotherapeutic agents are used for local drug delivery; one such agent is tetracycline, a broad-spectrum antibiotic. Recent studies have also shown that the use of non-steroidal anti-inflammatory drugs reduces pro-inflammatory cytokines and acts as host modulator. Thus, an attempt was made to compare and evaluate the efficacy of tetracycline alone and in combination with diclofenac sodium as a local drug delivery. A total of 36 sites with chronic periodontitis were divided into three groups with 12 sites each (i.e. group A, antibiotics alone; group B, antibiotics in combination with non-steroidal anti-inflammatory drugs; and group C, control group). For all the groups, the following parameters (plaque index, papillary bleeding index, probing pocket depth, and microbial analysis) were assessed and statistically analyzed. The antibiotic and non-steroidal anti-inflammatory drug combination group showed a statistically-significant improvement in clinical parameters and a shift in microbial flora when compared to the group with antibiotics alone. However, the control group failed to show any statistically-significant improvement. Antibiotics in combination with non-steroidal anti-inflammatory drugs are more efficient than using antibiotics alone as local drug delivery for the treatment of periodontal pockets.


A Mixed Methods Study Exploring Older Womens' Attitudes Toward Osteoporosis Medications: Adapting a Health Communication Framework.
Background: Bisphosphonates (BPs) can reduce fracture risk for adults with osteoporosis (OP), but they have rare risks, complicating decision making. Guided by an established health decision and communication framework, we explored older women's feelings and positions toward taking BPs. Materials and Methods: Using a mixed-methods design, we interviewed women >65 years of age who had never taken BPs. After learning about BPs, participants responded to items about their feelings toward medication benefits/risks. They then identified their overall position toward taking BPs (corresponding to Unquestioning Acceptors, Cautious Acceptors, Hesitants, Probable Refusers, and Definite Refusers). We analyzed data using qualitative content analysis and summarized quantitative data with descriptive statistics. Results: Thirty women participated. Acceptors (N = 17, 56.6%) worried about OP-related fractures. Hesitant participants (N = 12, 40%) worried about BP risks, yet expressed openness toward medications if given opportunities to gather information and talk to clinicians. One Refuser expressed distrust in clinicians and pharmaceuticals. Conclusions: Understanding women's positions toward BPs might improve decision-making processes for OP treatment. Clinicians could tailor communication based on patients' identified BP position. Acceptors might be comfortable with succinct conversations describing medications. Hesitant patients might need more information from resources such as decision aids. Building trust with patients questioning BPs can support future conversations.


Management of the depressive component of bipolar disorder.
Acute bipolar depression (ABD) and breakthrough depression occurring during maintenance therapy of bipolar disorder are associated with significant morbidity and an increased risk of suicide. Lithium is an effective mood stabilizer for ABD, but its onset of antidepressant action is slow and additional antidepressant therapy is often prescribed. The extent to which other mood stabilizers (e.g., carbamazepine and valproate) have antidepressant activity is unclear. Preliminary initial research suggests three potential advantages that selective serotonin reuptake inhibitors have over tricyclic antidepressant for ABD: possibly greater efficacy, fewer adverse effects, and a lower frequency of antidepressant-induced mania. Bupropion may also have significant advantages. However, further research is needed to confirm these findings. Monoamine oxidase inhibitors are the antidepressant of choice for atypical bipolar depression. Electroconvulsive therapy (ECT) has the highest response rate of all treatments for ABD. Further research is needed to explore combination treatments with mood stabilizers and antidepressants for the effective treatment of ABD.


Chaos, strange attractors, and fractal basin boundaries in nonlinear dynamics.
Recently research has shown that many simple nonlinear deterministic systems can behave in an apparently unpredictable and chaotic manner. This realization has broad implications for many fields of science. Basic developments in the field of chaotic dynamics of dissipative systems are reviewed in this article. Topics covered include strange attractors, how chaos comes about with variation of a system parameter, universality, fractal basin boundaries and their effect on predictability, and applications to physical systems.


Deep Learning Performance of Ultra-Widefield Fundus Imaging for Screening Retinal Lesions in Rural Locales.
Retinal diseases are the leading cause of irreversible blindness worldwide, and timely detection contributes to prevention of permanent vision loss, especially for patients in rural areas with limited medical resources. Deep learning systems (DLSs) based on fundus images with a 45° field of view have been extensively applied in population screening, while the feasibility of using ultra-widefield (UWF) fundus image-based DLSs to detect retinal lesions in patients in rural areas warrants exploration. To explore the performance of a DLS for multiple retinal lesion screening using UWF fundus images from patients in rural areas. In this diagnostic study, a previously developed DLS based on UWF fundus images was used to screen for 5 retinal lesions (retinal exudates or drusen, glaucomatous optic neuropathy, retinal hemorrhage, lattice degeneration or retinal breaks, and retinal detachment) in 24 villages of Yangxi County, China, between November 17, 2020, and March 30, 2021. The captured images were analyzed by the DLS and ophthalmologists. The performance of the DLS in rural screening was compared with that of the internal validation in the previous model development stage. The image quality, lesion proportion, and complexity of lesion composition were compared between the model development stage and the rural screening stage. A total of 6222 eyes in 3149 participants (1685 women [53.5%]; mean [SD] age, 70.9 [9.1] years) were screened. The DLS achieved a mean (SD) area under the receiver operating characteristic curve (AUC) of 0.918 (0.021) (95% CI, 0.892-0.944) for detecting 5 retinal lesions in the entire data set when applied for patients in rural areas, which was lower than that reported at the model development stage (AUC, 0.998 [0.002] [95% CI, 0.995-1.000]; P < .001). Compared with the fundus images in the model development stage, the fundus images in this rural screening study had an increased frequency of poor quality (13.8% [860 of 6222] vs 0%), increased variation in lesion proportions (0.1% [6 of 6222]-36.5% [2271 of 6222] vs 14.0% [2793 of 19 891]-21.3% [3433 of 16 138]), and an increased complexity of lesion composition. This diagnostic study suggests that the DLS exhibited excellent performance using UWF fundus images as a screening tool for 5 retinal lesions in patients in a rural setting. However, poor image quality, diverse lesion proportions, and a complex set of lesions may have reduced the performance of the DLS; these factors in targeted screening scenarios should be taken into consideration in the model development stage to ensure good performance.


Simulation-based trauma education for medical students: A review of literature.
Medical students often do not feel prepared to manage emergency situations after graduation. They experience a lack of practical skills and show significant deficits in cognitive performance to assess and stabilize trauma patients. Most reports in the literature about simulation-based education pertain to postgraduate training. Simulation-based trauma education (SBTE) in undergraduate medical education could improve confidence and performance of recently graduated doctors in trauma resuscitation. We reviewed the literature in search of SBTE effectiveness for medical students. A PubMed, Embase and CINAHL literature search was performed to identify all studies that reported on the effectiveness of SBTE for medical students, on student perception on SBTE or on the effectiveness of different simulation modalities. Eight studies were included. Three out of four studies reporting on the effectiveness of SBTE demonstrated an increase in performance of students after SBTE. SBTE is generally highly appreciated by medical students. Only one study directly compared two modalities of SBTE and reported favorable results for the mechanical model rather than the standardized live patient model. SBTE appears to be an effective method to prepare medical students for trauma resuscitation. Furthermore, students enjoy SBTE and they perceive SBTE as a very useful learning method.


Identification and Expression of the CorA/MRS2/ALR Type Magnesium Transporters in Tomato.
Magnesium (Mg2+) is the most abundant divalent ion in plants, participating in numerous metabolic processes in growth and development. CorA/MRS2/ALR type Mg2+ transporters are essential for maintaining Mg2+ homeostasis in plants. However, the candidate protein and its potential functions in the tomato plant have not been fully understood. In this study, we identified seven MGT genes (SlMRS2) in tomato based on sequence similarity, domain analysis, conserved motif identification, and structure prediction. Two SlMRS2 genes were analyzed in the bacterial strain MM281, and a functional complementary assay demonstrated their high-affinity transport of Mg2+. Quantitative real-time PCR analysis revealed that the expressions of these Mg2+ transporters were down-regulated in leaves under Mg2+ limitation, with a greater impact on lower and middle leaves compared to young leaves. Conversely, under Mg2+ toxicity, several genes were up-regulated in leaves with a circadian rhythm. Our findings indicate that members of the SlMRS2 family function as Mg2+ transporters and lay the groundwork for further analysis of their distinct functions in tomato.


The attitude of kidney transplant recipients towards elective arteriovenous fistula ligation.
Arteriovenous fistulas (AVF) are a source of various complications. Among previously hemodialyzed kidney transplant recipients (KTxR), the AVF may persist over time. The patients' decisions whether to ligate the functioning AVF may be prompted by many factors. Our knowledge of benefits concerning the procedure as well as patients' attitude towards it is scarce. Evaluation of the patients' opinion on the persistent AVF ligation after a successful kidney transplantation. An anonymous survey was carried out among 301 previously hemodialyzed KTxR. The patients were recruited during scheduled visits in the Transplantation Outpatient Unit. All subjects completed an anonymous questionnaire including questions about their attitude towards the matter in question. 69 patients (22.9%) have considered AVF closure. The most common causes for such attitude were esthetic reasons (n = 29) and concerns about heart health (n = 13). Among those 69 subjects, 18 have presented with symptomatic AVF due to multiple symptoms. Symptomatic AVFs were localized on the forearm in 14 out of 18 cases. As many as 116 (38.5%) cases have never wanted to ligate the AVF and 116 (38.5%) subjects did not have a clear opinion. In our study we report 158 (52.5%) cases of non-functioning AVFs. The main reason for the above was spontaneous AVF thrombosis (121 cases). Only 24 subjects reported to rely on the physician-provided information about the AVF management. One fourth of KTRs have ever considered AVF ligation. There is a distinct need for educating patients on the possibilities of post-transplantation AVF management.


Structural comparison of phospholipase-A2-binding regions in phospholipase-A2 receptors from various mammals.
We determined the nucleotide sequence of a mouse cDNA encoding the receptor for pancreatic group I phospholipase A2 (PLA2-I). Interspecies structural comparison of the mouse receptor with bovine PLA2-I receptor, whose structure had been clarified, revealed that the fourth carbohydrate-recognition domain (CRD)-like domain (CRD-like 4) was the most conserved among the domains in the PLA2-I receptor, suggesting the functional importance of CRD-like 4. A transient expression experiment with a truncated form of the receptor consisting of three CRD-like domains, from the third to the fifth, demonstrated that the PLA2-I-binding site of the receptor is constituted from these three CRD-like domains, supporting the functional indispensability of CRD-like 4 in the receptor. Since the PLA2-I-binding region was thus assigned to be CRD-like domains 3-5, we further analyzed the structures of the PLA2-I-binding regions in the PLA2-I receptors from the rat, rabbit and human. Furthermore, the obtained PLA2-I receptor cDNA fragments from these animals made it possible to examine the tissue expression patterns of this receptor in various mammals. The results, together with the results of the genomic structural analysis of this gene, indicated that a PLA2 receptor recently characterized by Lambeau et al. [Lambeau, G., Ancian, P., Barhanin, J. & Lazdunski, M. (1994) J. Biol. Chem. 269, 1575-1578] is a rabbit counterpart of the PLA2-I receptor although these two PLA2 receptors have distinctive PLA2-binding specificities.


Efficacy and tolerability of rizatriptan 10 mg compared with sumatriptan 100 mg: an evidence-based analysis.
Acute migraine attacks have a strong impact on quality of life and require immediate therapeutic intervention to achieve rapid pain relief. The introduction of triptans into the market in 1993 has increased the therapeutic options in migraine patients considerably. The seven currently available triptans show many similar characteristics but there are also some clinically relevant pharmacological differences. Rizatriptan 10 mg has demonstrated, in a head-to-head study, higher response rates and a more rapid onset of action than sumatriptan 100 mg, together with a favorable tolerability profile. Meta-analyses of double-blind placebo-controlled studies confirmed the superior efficacy of rizatriptan. Owing to the limited efficacy of sumatriptan, a more effective triptan treatment is needed in the majority of patients with acute migraine attacks.


Mathematic models and material removal characteristics of multigesture jetting using magnetorheological fluid.
This paper investigates the removal characteristics of the multigesture jetting of magnetorheological jet polishing (MJP). It discusses four main jetting models that satisfy precise polishing, which are complemented by an integrated polishing tool. Based on fluid impact dynamics theory, the paper analyzes the characteristics of abrasives in flowing slurry, such as velocities and stresses, during impinging. Together with the material removal mechanism, the paper establishes mathematical models for material removal for different jetting gestures. Experiments conducted on K9 optical glasses indicate that the actual polishing spots are consistent with the theoretical models. The removal capabilities of each jetting model have been investigated, including removal shape, power spectral density, removal track, and surface roughness. Using the tilted and rotating jetting models, a unimodal footprint could be obtained. The experiments also concluded that the tilted jetting model has a high removal capability and oblique jetting allowed us to easily obtain low-surface roughness, 1.46 nm for a 45° incident angle.


Formation and Self-assembly of Gold Nanoplates through an Interfacial Reaction for Surface-Enhanced Raman Scattering.
3D hierarchical architectures assembled from individual particles have attracted great interest because they displayed novel properties from the individual building blocks as well as their complex structures. Here we present a new strategy to form 3D hierarchical gold (Au) nanostructures via an interfacial reduction reaction. An aniline (ANI) derivative, N-(3-amidino)-aniline (NAAN), and HAuCl4 were separately dissolved in toluene and water to form an organic/water interface. Au nanoplates formed at the interface and subsequently moved to the aqueous phase. As a capping agent for the nanoplate formation, the oxidized NAAN, i.e., poly(N-(3-amidino)-aniline) (PNAAN), also facilitated the self-assembly of Au nanoplates into 3D hierarchical Au nanoflowers (AuNFs) through π-π stacking. The individual AuNF exhibited good surface-enhanced Raman scattering (SERS) response both in enhancement factor and reproducibility because it integrates the SERS enhancement effects of individual Au nanoplates and their hierarchical structures. This is the first report depicting the one-pot formation and self-assembly of Au nanoplates into 3D organized hierarchical nanostructures through the molecular interaction of conducting polymer.


[TREATMENT OF PATIENTS WITH CHRONIC RECURRENT HERPES VIRUS INFECTION OF GENITAL LOCALIZATION: A CLINICAL STUDY OF FORTEPREN PREPARATION].
Selection of optimal dosage regimen, length of treatment course (frequency of administration), safety, tolerance and clinical effectiveness evaluation of the medical preparation fortepren in patients with chronical recurrent herpes virus infection of genital localization. The medical product of antiviral and immune modulating effect--fortepren (sodium polyprenyl phosphate) as a 4 mg/ml solution for injections combined with the base course of acyclic nucleoside acyclovir, 400 mg tablets, held studies. 40 male and female patients participated in the study. After a 10-day acyclovir course (400 mg x 3 times a day) for removing the acute phase, 4 groups of 10 individuals were formed: 1--5 ml (20 mg) of fortepren i/m once at day 13 ± 2 after the start of the study after the completion of the treatment of the acute phase of the disease; 2--5 ml (20 mg) fortepren i/m 3 times at an interval of 21 days; 3--2 ml (8 mg) fortepren i/m 3 times at an interval of 21 days; 4 (control)--5 ml of placebo i/m at remission stage 3 times at an interval of 21 days. Increase of the duration of inter-recurrence period, decrease of the severity of the recurrences, state of skin and mucous damage elements, improvements of immunologic parameters were considered during effectiveness evaluation. Significant differences in the frequency of recurrences of genital herpes were shown for 3 months of observation in experimental and control groups. A significant reduction of genital herpes recurrence frequency from 3.52 ± 0.09 (before treatment) to 2.89 ± 0.08 (after treatment) was noted in patients of group 3 (p < 0.001). The frequency of recurrences in the control group was 3.84 ± 0.10, that was higher than the parameters in all the experimental groups. A significant reduction of the rash area was noted in group 3, moreover, a redution of frequency of detection of clinical manifestations of genital herpes in the form of vesicle elements after treatment in groups 2 (p = 0.02) and 3 (p = 0.005) was found. Evaluation of local symptoms has established that burning have caused minimal discomfort for patients of groups 3 and 4 and itch and soreness--of groups 1 and 3. The least pronounced exacerbations were noted in patients of group 3. Intramuscular administration of fortepren preparation was established to result in the increase of titers of leukocyte virus-induced interferon for the whole duration of treatment. An intramuscular dose of 2 ml (8 mg) at recurrence stage 3 times at an interval of 21 days after the completion of the 10-day base course of treatment of the acute phase of chronical recurrent herpes virus infection of genital localization using acyclovir was accepted as an optimal dosage regimen. Analysis of the obtained results has shown an acceptable safety profile and a good level of tolerance for fortepren preparation.


Shear thickening in a model colloidal suspension.
We study the rheology of model colloidal suspensions using molecular-dynamics simulations. We relate the onset of shear thickening to the transition from a low-viscosity regime, in which the solvent facilitates the flow of colloids, to a high-viscosity regime associated with jamming of the colloids and the formation of chains of colloids. In the low-viscosity regime, the colloidal particles are, on average, surrounded by two layers of solvent particles. On the contrary, in the high-viscosity regime, the solvent is expelled from the interstice between the jammed colloids. The thickening in suspensions is shown to obey the same criterion as in simple fluids. This demonstrates that jamming, even without the divergence of lubrication interactions, is sufficient to observe shear thickening.


Central Blood Pressure Responses to Dietary Sodium and Potassium Interventions.
To explore how central hemodynamics respond to dietary sodium and potassium interventions, and whether the responses are associated with metabolic traits. We conducted a dietary intervention study including a 7-day low-sodium (51.3 mmol sodium/day) intervention, a 7-day high-sodium (307.8 mmol sodium/day) intervention, and a 7-day high-sodium with potassium supplementation (60.0 mmol potassium/day) intervention among 99 northern Chinese subjects aged 18-60 years. Five metabolic traits included abdominal obesity, high triglycerides, low HDL cholesterol, raised blood pressure (BP), and high glucose. Central hemodynamics were measured at baseline and during each intervention. Central systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), and augmentation index (AIx@75) significantly decreased during low-sodium intervention, increased during high-sodium intervention, and then decreased during potassium supplementation. We observed potential linear trends toward significance of central SBP and PP responses to low-sodium intervention, and significant linear trends of responses to high-sodium intervention as the number of metabolic traits grows. For example, among participants with 0 or 1, 2 or 3, and 4 or 5 metabolic traits, central SBP responses to high-sodium intervention were 8.8 [95% confidence interval (5.8, 11.8)], 9.3 (7.1, 11.6), and 14.0 (11.6, 16.3) mmHg, respectively (P for trend = 0.009). Significant linear trends of central SBP and DBP responses to potassium supplementation were also observed. Central BP and AIx@75 were lowered by sodium reduction and potassium supplementation, and elevated by sodium-loading. The responses of central BP were pronounced among individuals with metabolic traits clustering. Trial Number NCT00721721 (The current study is registered on ClinicalTrials.gov; https://clinicaltrials.gov).


[The clinical significance of tissue polypeptide antigen (TPA) in the patients with gynecologic tumor].
In order to estimate the clinical significance of tissue polypeptide antigen (TPA), TPA was measured by radioimmunoassay in sera from patients with various gynecological tumors. They were 40 uterine myomas, 94 cervical cancers, 21 endometrial cancers, 3 vulval cancers, 51 benign ovarian tumors and 78 malignant ovarian tumors including 18 low potential malignant tumors (LPM). The mean TPA values in patients with benign as well as malignant tumors were significantly higher than that of 97 healthy volunteers (68 +/- 17 U/l; Upper limit; 107 U/l). Among the cervical cancer patients, serum TPA level and positive ratio became higher as the disease progressed. In the advanced cases, the mean serum TPA value and positive ratio were 149 +/- 64 U/l and 75%, respectively. The mean TPA value in the endometrial cancer patients was significantly higher than that of myoma patients. Among the patients with ovarian tumor, serum TPA was elevated in 14% of benign cases, 28% of LPM cases, 47% of stage I cases and 82% of the advanced cases. Serum TPA values varied directly with the stage and malignancy of disease. The present study revealed that TPA is a useful markers in the diagnosis of gynecological tumors, especially for ovarian cancers.


The Novel Toll-Like Receptor 2 Agonist SUP3 Enhances Antigen Presentation and T Cell Activation by Dendritic Cells.
Dendritic cells (DCs) are highly specialized antigen-presenting cells that play crucial roles in innate and adaptive immunity. Previous studies suggested that Toll-like receptor (TLR) agonists could be used as potential adjuvants, as activation of TLRs can boost DC-induced immune responses. TLR2 agonists have been shown to enhance DC-mediated immune responses. However, classical TLR2 agonists such as Pam3CSK4 are not stable enough in vivo, which limits their clinical applications. In this study, a novel structurally stable TLR2 agonist named SUP3 was designed. Functional analysis showed that SUP3 induced much stronger antitumor response than Pam3CSK4 by promoting cytotoxic T lymphocytes activation in vivo. This effect was achieved through the following mechanisms: SUP3 strongly enhanced the ability of antigen cross-presentation by DCs and subsequent T cell activation. SUP3 upregulated the expression of costimulatory molecules on DCs and increased antigen deposition in draining lymph nodes. More interestingly, SUP3 induced less amount of pro-inflammatory cytokine production in vivo compared to other TLR agonists such as lipopolysaccharide. Taken together, SUP3 could serve as a novel promising immune adjuvant in vaccine development and immune modulations.


The Arabidopsis KINβγ Subunit of the SnRK1 Complex Regulates Pollen Hydration on the Stigma by Mediating the Level of Reactive Oxygen Species in Pollen.
Pollen-stigma interactions are essential for pollen germination. The highly regulated process of pollen germination includes pollen adhesion, hydration, and germination on the stigma. However, the internal signaling of pollen that regulates pollen-stigma interactions is poorly understood. KINβγ is a plant-specific subunit of the SNF1-related protein kinase 1 complex which plays important roles in the regulation of plant development. Here, we showed that KINβγ was a cytoplasm- and nucleus-localized protein in the vegetative cells of pollen grains in Arabidopsis. The pollen of the Arabidopsis kinβγ mutant could not germinate on stigma, although it germinated normally in vitro. Further analysis revealed the hydration of kinβγ mutant pollen on the stigma was compromised. However, adding water to the stigma promoted the germination of the mutant pollen in vivo, suggesting that the compromised hydration of the mutant pollen led to its defective germination. In kinβγ mutant pollen, the structure of the mitochondria and peroxisomes was destroyed, and their numbers were significantly reduced compared with those in the wild type. Furthermore, we found that the kinβγ mutant exhibited reduced levels of reactive oxygen species (ROS) in pollen. The addition of H2O2 in vitro partially compensated for the reduced water absorption of the mutant pollen, and reducing ROS levels in pollen by overexpressing Arabidopsis CATALASE 3 resulted in compromised hydration of pollen on the stigma. These results indicate that Arabidopsis KINβγ is critical for the regulation of ROS levels by mediating the biogenesis of mitochondria and peroxisomes in pollen, which is required for pollen-stigma interactions during pollination.


Protection of mammalian cells from severe acute respiratory syndrome coronavirus infection by equine neutralizing antibody.
The aetiological agent for severe acute respiratory syndrome (SARS) has been determined to be a new type of coronavirus (SARS-CoV) that infects a wide range of mammalian hosts. Up to now, there have been no specific drugs to protect against SARS-CoV infection, thus developing effective strategies against this newly emerged viral infection warrants urgent efforts. Adoptive immune therapy with pathogen-specific heterologous immunoglobulin has been successfully used to control the dissemination of many viral infections. To investigate whether a neutralizing antibody against SARS-CoV raised in an artiodactylous host can have a protective role on primate cells, we prepared serum IgGs and their pepsin-digested F(ab')2 fragments from horses inoculated with purified SARS-CoV (BJ-01 strain). The protective effect of the F(ab')2 fragments against SARS-CoV infection was determined in cultured Vero E6 cells by cytopathic effect (CPE), MTT and plaque-forming assays and in a Balb/c mouse model by CPE and quantitative RT-PCR. The results showed the neutralization titres of F(ab')2 from three horses all reached at least 1:1600, and 50 microg of the F(ab')2 fragments could completely neutralize 1x10(4) TCID50- SARS-CoV in vivo. Additionally, we observed that F(ab')2, against BJ-01 strain could also protect cells from infection by the variant GZ-01 strain in vitro and in vivo. Our work has provided experimental support for testing the protective equine immunoglobulin in future large primate or human trials.


Early Attachment Disruption, Inflammation, and Vulnerability for Depression in Rodent and Primate Models.
Early experiments in nonhuman primates established the relation between disruption of filial attachment and depressive-like outcomes. Subsequent studies in rats and mice have been instrumental in linking depressive-like outcomes to disturbances in maternal behavior. Another aspect of attachment disruption, absence of the attachment object per se, may be studied more effectively in a different laboratory rodent-the guinea pig. Here, we discuss the rationale for using guinea pigs for this work. We then review guinea pig studies providing evidence for inflammatory mechanisms mediating both depressive-like behavior during separation as well as sensitization of stress responsiveness such as is thought to lead to increased vulnerability to depression at later ages. Finally, we discuss recent complementary work in adult monkeys that suggests cross-species generalizability of broad principles derived from the guinea pig experiments. Overall, the findings provide experimental support for human research implicating inflammatory mechanisms in the development of increased stress responsiveness and vulnerability to depression following attachment disruption and other forms of early-life stress. Specifically, the findings suggest inflammatory mechanisms may set in motion a cascade of underlying processes that mediate later increased stress responsiveness and, therefore, depression susceptibility.


Generation of Hydrogen by Visible Light-Induced Water Splitting with the Use of Semiconductors and Dyes.
Photosynthesis that occurs in plants involves both the oxidation of water and the reduction of carbon dioxide. Plants carry out these reactions with ease, by involving electron-transport chains. In this article, hydrogen generation by the reduction of water in the laboratory by using semiconductor nanostructures through artificial photosynthesis is examined. Dye-sensitized photochemical generation of hydrogen from water is also discussed. Hydrogen generation by these means has great technological relevance, since it is an environmentally friendly fuel. The way in which oxygen can be generated by the oxidation of water using metal oxide catalysts is also shown.


Nodular melanosis due to epithelial neoplasms: a finding not restricted to regressed melanomas.
Nodular or tumoral melanosis consists of nodular or sheetlike deposits of melanophages in the dermis. When nodular melanosis is present, a completely regressed malignant melanoma is a major diagnostic consideration. We present a case of nodular melanosis due to regression of a pigmented basal cell carcinoma with pilar differentiation. In addition to this case, we present five additional cases of epithelial neoplasms with melanin deposition in the stroma. In each case, the source of the melanin was non-neoplastic dendritic melanocytes intermingled among the tumor cells. Therefore, if nodular melanosis is found, pigmented epithelial neoplasms should also be considered in the differential diagnosis.


The Oldest Co-opted gag Gene of a Human Endogenous Retrovirus Shows Placenta-Specific Expression and Is Upregulated in Diffuse Large B-Cell Lymphomas.
Vertebrate genomes contain endogenous retroviruses (ERVs) that represent remnants of past germline infections by ancient retroviruses. Despite comprising 8% of the human genome, the human ERVs (HERVs) do not encode a replication competent retrovirus. However, some HERV genes have been co-opted to serve host functions, most notably the viral envelope-derived syncytins involved in placentation. Here, we identify the oldest HERV intact gag gene with an open reading frame, gagV1. Its provirus contains an intact env, envV1, and the first open reading frame found in an HERV gag leader, pre-gagV1, which encodes a novel protein. This HERV is linked to a related gag gene, gagV3, and these three genes all show patterns of evolutionary conservation in primates. gagV1 and pre-gagV1 orthologs are present in all simian primate lineages indicating that this HERV entered the germline of the common simian primate ancestor at least 43 Ma, whereas gagV3 is found in Old and New World monkeys. gagV1 and gagV3 have undergone recurrent gene conversion events and positive selection. Expression of gagV1, gagV3, and pre-gagV1 is restricted to the placenta in humans and macaques suggesting co-option for placenta-specific host functions. Transcriptomic analysis of human tumors also found upregulated levels of gagV1 transcripts in diffuse large B-cell lymphomas. These findings suggest that these HERV-V genes may be useful markers for the most common type of non-Hodgkin's lymphoma and that they may have contributed to the successive domestications of env and gag genes in eutherians involved in the ongoing ERV-driven evolution of the placenta.


Bacteria on the Soles of Patient-Issued Nonskid Slipper Socks: An Overlooked Pathogen Spread Threat?
This is the first study to determine whether nonskid slipper socks in contact with the hospital floor and worn into bed contaminate bed linen. The main purpose of the study was to determine whether contamination of hospital linen occurred with bacteria transferred from the soles of nonskid slipper socks that have touched the floor. This study mimicked real patients walking on a hospital floor wearing slipper socks and getting back into bed with the slipper socks on. Swab samples were collected from the surfaces of the hospital floor, nonskid slipper sock bottoms, and bed linen in 2 Midwestern hospitals. From the samples, bacterial isolates were identified and tested for antibiotic resistance. Isolates obtained from the samples were identified on all 3 surfaces at both hospitals, indicating spread of the bacteria from floor to the bed linen via the nonskid slipper socks. Antibiotic sensitivity test revealed that a significant number of isolates collected were resistant to at least 2 antibiotics tested. This study demonstrates cross-contamination of bed linen with potentially pathogenic bacteria present on the hospital floor via contact with patient-worn nonskid slipper socks. A simple practice change regarding the wearing of slipper socks could play an important role in preventing pathogen transfer to the bed linen. Awareness of the likelihood of hand contamination after touching the sock bottoms that have come in contact with the hospital floor should also be considered.


Recurrent miscarriage and autoimmunity.
Both organ-specific and systemic autoimmunity are associated with an increased prevalence of recurrent miscarriage (RM). The precise mechanism for this is unclear, as cross-reactivity between trophoblastic and maternal host autoantigens has not been demonstrated. In the antiphospholipid antibody syndrome, prothrombotic mechanisms are evident, along with direct inhibitory actions against trophoblastic activity. In many types of both systemic and organ-specific immunity, however, a disturbed T-helper cell profile is seen. This is also evident in women with RM. In both cases, reduced numbers of T regulatory cells have been reported. These are required to regulate excessive activity of the Th1 and the proinflammatory Th17 subsets that, when operating through excessive natural killer cell activity, may have antipregnancy effects. Checking for underlying autoimmunity is therefore a critical analysis in women with RM and future therapies will probably be aimed at correcting the deficiency of regulatory T cells or correcting excessive Th1 and Th17 function.


Management of internal genital warts: do we all agree? A postal survey.
A postal survey was undertaken to determine whether there was any consensus of opinion regarding the management of internal genital warts in genitourinary medicine clinics in the UK. Overall, 110 forms were returned (57% response). The majority of clinics would refer patients with cervical warts for colposcopy especially if the patient was over the age of 25 or HIV-positive. Proctoscopy or anoscopy was performed in 60% of clinics for patients with perianal warts to determine the presence of warts within the anal canal or rectum. Only 24% of patients with intra-anal warts are referred directly to surgery for biopsy, increasing to 61% if the patient has HIV infection. Cryotherapy is the main treatment for all types of internal warts. Our findings suggest there is no consensus and we recommend that all HIV-positive patients with anal or cervical condyloma should be investigated for evidence of intraepithelial neoplasia.