Quality of life is not only for people served--it is also for staff: the Multi-Focal Approach.
To date, little attention has been given to the concept of quality of life around human resources employment programmes for staff working with persons with a dual diagnosis. This article describes the implementation of quality of life principles to service provision for people with dual diagnosis and its application to staff training. This type of experiential training facilitated change in staff's attitude to, and treatment of, the people served. Human resources development programmes should be based on the same core quality of life principles and domains that guide service delivery on the individual level.


IFATS collection: Identification of hemangioblasts in the adult human adipose tissue.
The stromal-vascular fraction (SVF) of human adipose tissue contains, among other cell types, mesenchymal stem cells and precursors of adipocyte and endothelial cells. Here we show that, in addition, the nonhematopoietic fraction of the SVF has hematopoietic activity, since all types of hematopoietic colony-forming units (CFUs) developed when cultured in methylcellulose-based medium. This hematopoietic activity was restricted to the CD45(-)CD105(+) cell subset, well correlated with KDR(+) cell content, and increased after culture with a combination of early-acting hematopoietic cytokines. Most of the CD45(-)KDR(+)CD105(+) cells were nonadherent and did not express CD31, and this subset included both CD34(-) and CD34(+) cells. Moreover, these nonadherent cells migrated in response to KDR gradient, and when they were cultured in the presence of both hematopoietic and endothelial growth factors, a wave of CFUs was followed by a wave of mixed colonies comprising adherent elongated and nonadherent round hematopoietic cells. These mixed hematopoietic-endothelial (Hem-End) colonies were able to generate secondary Hem-End colonies and exhibited both hematopoietic and endothelial activity, as demonstrated by in vitro functional assays. These findings demonstrate for the first time the existence of primitive mesodermal progenitors within the SVF of human adipose tissue that exhibit in vitro hematopoietic and hemangioblastic activities, susceptible to being used in cell therapy and basic cell research. Disclosure of potential conflicts of interest is found at the end of this article.


Selection of fixation devices in proximal femur rotational osteotomy: clinical complications and finite element analysis.
To compare the postoperative stability between large cancellous screws fixation and dynamic hip screws fixation in transtrochanteric rotational osteotomy. Finite element analysis was designed to validate the clinical outcomes of fixation failure in transtrochanteric rotational osteotomy. From 1997 to 2000, transtrochanteric rotational osteotomy had been done in 20 osteonecrotic hips. Fixation with large cancellous screws as suggested by Sugioka had been used in the first five hips. Unfortunately, fixation failures were encountered in all of the five cases. The fixation mode was then shifted to a combination of plate and screws, no fixation failure had been observed postoperatively. A finite element analysis was designed to investigate the causes of fixation failure. Finite element models for four dynamic hip screw instrumented femora and four large screws instrumented femora simulating four different levels of bone cut were created. The von Mises stress distributions of each model were analyzed and compared for a loading condition simulating single-legged stance. Analysis results confirmed our clinical observation that fixation with screws had higher stress concentration on the proximal femur. Improper bone cut, especially those that are too distal from the intertrochanteric line, had higher risks of fixation failure. Transtrochanteric rotational osteotomy is a technically demanding procedure such that surgical principles should be abided carefully to avoid catastrophic complications. Finite element analysis results demonstrated that dynamic hip screw fixation provides better stability and prevents fixation failure that corresponds with the clinical observation.


Genetic and biochemical studies of protein sorting to the yeast vacuole.
Studies of vacuolar protein sorting in yeast are revealing important new insights into the mechanisms of intracellular membrane trafficking. Recent work has raised questions about the prevailing view concerning membrane protein transport to the vacuole, and has indicated roles in vacuolar protein sorting for GTP-binding proteins, clathrin, a serine/threonine protein kinase and a phosphatidylinositol 3-kinase.


Neuronal cholecystokinin-like immunoreactivity is postprandially released from primate hypothalamus.
By use of the push-pull perfusion technique, release of neuronal cholecystokinin-like immunoreactivity (CCK-LI) from hypothalamus of owl monkeys was investigated in relation to an intragastric meal. In overnight fasted, halothane-anesthetized owl monkeys, levels of CCK-LI in the hypothalamic push-pull perfusate were below assay sensitivity (less than 4 pg/30 min). After intragastric administration of a carbohydrate/amino acid meal, however, a 10-fold increase in CCK-LI release (51 +/- 7 pg/30 min) was observed in 5 out of 15 perfusion sites during the first postprandial 30 min. During the subsequent two 30-min intervals, release of CCK-LI was still increased with 32 +/- 5 pg/30 min and 15 +/- 6 pg/30 min, respectively. Thereafter, CCK-LI release was below assay sensitivity again. Addition of 40 mM potassium chloride (KCl) to the perfusion solution, which causes neuronal depolarization, resulted in a second increase in CCK-LI release of 56 +/- 7 pg/30 min which was comparable to the meal-induced release. All sites that exhibited an increase in CCK-LI were located in the anterolateral aspect of the hypothalamus. In experiments without meal-induced release, KCl did not have any effect on CCK-LI in perfusate, suggesting that these particular sites did not contain CCK-releasing terminals. High performance liquid chromatography (HPLC) identified the C-terminal octapeptide of CCK (CCK-8) as the predominant molecular form of CCK within the owl monkey hypothalamus. No gastrin-17 was present.(ABSTRACT TRUNCATED AT 250 WORDS)


Tilt-table testing of patients with pacemaker and recurrent syncope.
The diagnosis of recurrent syncope in patients with pacemakers (PM) is quite challenging and the etiology of syncope is often multifactorial. To portray the mechanism of syncope in PM patients, we report the results of head-up tilt table testing (HUT) in a series of patients with PM, originally implanted for reasons other than neurally mediated syncope, referred due to syncope or pre-syncope (aborted syncope, vertigo, suspected orthostatic hypotension). Forty-one patients with PM undergoing a HUT in our syncope unit between January 1st, 2007 and December 31st 2011 were included. A standard HUT protocol with nitroglycerine provocation was used and the test results were classified according to current guidelines. Baseline data were retrieved from the medical records. Overall, 54% of patients had a positive response to HUT. Vasodepressor or orthostatic hypotensive response were the most prevalent responses accounting for 72% of patients with a positive test. There were no differences between groups with positive or negative test result regarding age, gender, resting blood pressure and heart rate, daily fluid intake, pacing mode, pacing indication or pacing rhythm at rest. HUT in patients with pacemakers has a high diagnostic yield. Although, the majority of patients had a vasodepressor or orthostatic hypotensive response, cardioinhibitory response leading to syncope was also seen.


Change in parathyroid hormone levels from baseline predicts hypocalcemia following total or completion thyroidectomy.
This study aims to identify the strongest predictor of postoperative hypocalcemia following thyroid surgery. Study of patients who underwent total/completion thyroidectomy. No patients received postoperative calcium supplementation. Demographic and perioperative data were collected including preoperative baseline parathyroid hormone (PTH) levels, PTH levels at 30 min and 6 h post-excision, and 18 h post-excision calcium levels. Of 124 patients studied, 20.2% developed temporary hypocalcemia (Ca <8.5 mg/dL at 18 h post-excision). In multivariate analyses, absolute PTH levels at 30 min and 6 h post-excision as well as change in PTH from baseline at 30 min and 6 h post-excision were statistically significantly associated with postoperative hypocalcemia. Per 10 units decrease in PTH from baseline at 30 min post-excision, the risk of developing temporary hypocalcemia increases by 17%. Absolute PTH levels and change in PTH from baseline at 30 min and 6 h post-excision predict hypocalcemia after total or completion thyroidectomy.


Preconception exposure to dietary levels of genistein affects female reproductive outcomes.
Genistein is a phytoestrogen found in soy and soy-based products. Previously, we found that genistein adversely affected estradiol levels and follicle growth in vitro. Proper hormone production and follicle growth are key regulators of normal fertility. Therefore, we hypothesized that genistein adversely affects female fertility and pregnancy outcomes. To test this hypothesis, we dosed sexually mature female CD-1 mice (35days) with 0, 300, 500, or 1000ppm genistein for 30, 60, 150, and 240days. At the end of the dosing periods, we measured mating rate, pregnancy rate, fertility rate, gestation time, parturition time, pup mortality, litter size, average pup weight, and estradiol and progesterone levels. We found that chronic, preconception exposure to genistein affects gestation time, parturition time, litter size, pup weight, and pup mortality. Additionally, genistein exposure for 240days appears to have a protective effect on fertility rate, but does not affect hormone levels in vivo.


Eicosanoids: role in experimental renal disease.
Because of their vasodilator and vasoconstrictor properties, vasoactive prostaglandins and thromboxane A2 have been proposed as modulators of the hemodynamic changes that occur in experimental models of renal disease. Increased synthesis of vasodilatory prostaglandins (PGE2) and perhaps prostaglandin I2 (PGI2) play a role in the maintenance of renal blood flow and GFR during states of impaired perfusion. In contrast, thromboxane A2 has been implicated as the vasoconstrictor responsible for the reduction of renal blood flow and GFR in certain animal models of experimental renal disease. These products and other metabolites of arachidonic acid may also participate in the immunological events underlying the onset and/or progression of experimental renal disease. It is evident that the pathophysiologic role of eicosanoids in experimental renal disease is not fully understood. Additional studies and further understanding of the many other potential roles of eicosanoids on immunological events, hemodynamic states, mesangial cell physiology, etc. are needed to comprehend more fully the extent of the participation of eicosanoids in the pathogenesis and pathophysiology of renal disease.


In vivo measurement and mapping of skin redox stress induced by ultraviolet light exposure.
Exposure of skin to UV light presents a potent oxidative stress and this could alter the skin redox state. In this context, we evaluated the ability of electron paramagnetic resonance (EPR) imaging to provide noninvasive in vivo mapping of the redox status of the skin of living rats. The redox status was measured using a topically applied nitroxyl spin probe, (15)N-PDT. The nitroxyl intensity profile obtained across the skin layers showed that the concentration of the probe was higher in the epidermis and lower in the dermis and hypodermis. Skin permeability and reduction metabolism were evaluated in the skin exposed to UVB (312 nm) radiation. Exposure of skin to UVB decreased the overall reduction rate constant of the nitroxyl probe to 25 +/- 6% of the value obtained in the untreated skin. EPR imaging data showed that after the UVB treatment, the reduction rate constant decreased to 41 +/- 1% in epidermis, 28 +/- 1% in dermis, and 21 +/- 8% in hypodermis layers. The data suggested that UVB decreased the overall reducing capability of the skin with a larger decrease in the dermis and hypodermis. In summary, in vivo EPR imaging measurements showed significant alterations in the redox state of the skin exposed to UV light.


Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis.
COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome. To quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome. Systematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists. Primary research articles which evaluated individuals at least 12 weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected. Two reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Tukey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model. The co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks following COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences associated with post-COVID-19 syndrome. The literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32 (95% CI, 0.27, 0.37; p < 0.001; n = 25,268; I2 = 99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001; n = 13,232; I2 = 98.0). Moreover, narrative synthesis revealed elevations in proinflammatory markers and considerable functional impairment in a subset of individuals. A significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena. PROSPERO (CRD42021256965).


HER-2/neu-derived peptide epitopes are also recognized by cytotoxic CD3(+)CD56(+) (natural killer T) lymphocytes.
The human HER-2/neu gene encodes a 185 kDa transmembrane glycoprotein recognized by MHC class I-restricted CTLs. Here, we report that HER-2/neu peptide CTL epitopes can also be recognized by cytotoxic NK-T lymphocytes. Unfractionated peptides derived from HLA-A2(+), HER-2/neu(+) tumor cells acid cell extract (ACE), collected from patients with metastatic ovarian cancer, were used as antigen to generate in vitro cytotoxic effectors. ACE was able to elicit from cancer patients' PBMCs both alphabetaTCR(+)CD3(+)CD56(-) and alphaTCR(+)CD3(+)CD56(+) (NK-T) CTLs that lysed ACE-sensitized T2 cells in an HLA-A2-restricted manner. The same CTL lines also recognized T2 cells pulsed with HER-2/neu-derived CTL peptide epitopes, a HER-2/neu-transfected HLA-A2(+) cell line and autologous tumor cells. alphaTCR(+)CD3(+)CD56(+) CTL lines also exhibited NK-like cytotoxicity against autologous tumor cells. CTL clones were isolated from alphaTCR(+)CD3(+)CD56(+) bulk cultures displaying both MHC- and non-MHC-restricted cytotoxicity, thus confirming the dual cytolytic function of such cells. Our data demonstrate that ACE from metastatic ovarian tumors can be used as multiepitope vaccines for generating in vitro, besides classical CTLs, NK-T cells exerting efficient MHC- and non-MHC-restricted cytotoxicity against autologous tumor targets. Such NK-T cells expressing dual cytotoxic activity may prove advantageous in cancer immunotherapy.


Free radical chemistry. Relationship to exercise.
Free radicals are molecules or molecular fragments containing an unpaired electron in the valence shell. Radicals interested only a few chemists until 18 years ago when an enzyme was discovered which functioned to remove a specific oxygen-centered radical. That discovery renewed interest in radicals and has already begun to alter thinking on many clinical problems. Free radicals have been shown to be common phenomena that play a role in normal biochemistry but require an elaborate control system to be held in check. Since oxygen-centered radicals are produced in intermediate metabolism, exercise should increase their production and that has been shown to be so. There is also evidence that the consumption of large quantities of ambient oxygen during exercise induces harmful chemistry known as lipid peroxidation. Presently, there are insufficient data available to ascertain how the human body tolerates such increased production of free radicals and lipid peroxidation and how the consequences of that chemistry might relate to the overall well being of exercising humans.


Amelioration of collagen-induced arthritis by human recombinant soluble FcgammaRIIb.
Immune complex (IC) binding to Fc gamma receptors (FcgammaRs) is central for inflammatory reactions seen in autoimmune diseases. Consequently, a therapeutic agent with a possibility to interfere with binding of pathogenic IC to FcgammaRs would be valuable in autoimmune disorders such as rheumatoid arthritis (RA). Here we have explored the therapeutic effect of a recombinant soluble human FcgammaRIIb (sFcgammaRIIb) protein in collagen-induced arthritis (CIA). In vitro studies of the sFcgammaRIIb demonstrated binding to mouse IgG, suggesting that sFcgammaRIIb can absorb pathogenic IgG anti-collagen type II (CII) IC in vivo. Hence, administration of sFcgammaRIIb significantly reduced CIA severity compared to control treated mice. The sFcgammaRIIb treated mice had significantly less IgG anti-CII antibodies in serum and lower mRNA levels of inflammatory cytokines compared to control mice. In conclusion, sFcgammaRIIb treatment ameliorates CIA by reducing IC-stimulated inflammation and joint swelling. This suggests that recombinant sFcgammaRIIb may be useful as therapeutic agent in RA.


Human blood PIG-A mutation and micronucleated reticulocyte flow cytometric assays: Method optimization and evaluation of intra- and inter-subject variation.
We previously described flow cytometry-based methods for scoring the incidence of micronucleated reticulocytes (MN-RET) and PIG-A mutant phenotype reticulocytes (MUT RET) in rodent and human blood samples. The current report describes important methodological improvements for human blood analyses, including immunomagnetic enrichment of CD71-positive reticulocytes prior to MN-RET scoring, and procedures for storing frozen blood for later PIG-A analysis. Technical replicate variability in MN-RET and MUT RET frequencies based on blood specimens from 14 subjects, intra-subject variability based on serial blood draws from 6 subjects, and inter-subject variation based on up to 344 subjects age 0 to 73 years were quantified. Inter-subject variation explained most of the variability observed for both endpoints (≥77%), with much lower intra-subject and technical replicate variability. The relatively large degree of inter-subject variation is apparent from mean and standard deviation values for MN-RET (0.15 ± 0.10%) and MUT RET (4.7 ± 5.0 per million, after omission of two extreme outliers). The influences of age and sex on inter-subject variation were investigated, and neither factor affected MN-RET whereas both influenced MUT RET frequency. The lowest MUT RET values were observed for subjects <11 years old, and males had moderately higher frequencies than females. These results indicate that MN-RET and MUT RET are automation-compatible biomarkers of genotoxicity that bridge species of toxicological interest to include human populations. These data will be useful for appropriately designing future human studies that include these biomarkers of genotoxicity, and highlight the need for additional work aimed at identifying the sources of inter-individual variability reported herein.


Selected autoimmune diseases in the dog.
In summary, previous attempts to explain the role of inheritance in autoimmune disorders through family studies have been hampered by the variable degree of phenotypic expression. Our evidence utilizing dogs in family studies is consistent with the concept that genetic factors play some role in determining disease susceptibility. Recognizing the complexity of the genetic components involved in these studies, we have proposed a hypothesis of two classes of genes, one that relates to immunoregulation and another that specifies pathologic lesions (and thus the clinical signs). This dual system of interacting genes provides a rational explanation for many of the observations previously encountered in both human and canine studies.


Use of the Femurett adjustable prosthesis in the assessment and walking training of new above-knee amputees.
The Lic Femurett adjustable training prosthesis was evaluated on 51 above-knee amputees attending the Oxford Disablement Services Centre. In the elderly it proved superior to the Pneumatic Post-Amputation Mobility Aid (P.P.A.M.-Aid) in the assessment of their ability to use a prosthesis, and is useful for walking training once the stump is fully healed; it does not replace the P.P.A.M-Aid at the early post-operative stage.


Resistance development to bioinsecticides in Aedes aegypti (Culicidae: Diptera), the vector of dengue fever in Saudi Arabia.
A laboratory strain of Aedes aegypti (L) was subjected repeatedly to larval selection pressure with two bacterial insecticides, spinosad (Saccharopolyspora spinosa) and bacilod (Bacillus thuringiensis israelensis). The results indicated that the mosquito Ae. aegypti acquired low resistance to spinosad and bacilod by about 3.1 and 2.4-fold, respectively, due to selection pressure for fifteen successive generations. The slope values of the selected strains were increased gradually from one generation to the next, indicating moderate homogeneity between individuals in their response to the test bio-insecticide. Moreover, larval selection with current bacterial bioinsecticides prolonged the time required to digest a blood meal. It showed an evident decrease in the reproductive potential of adult mosquitoes surviving selected larvae.


Basis to Aid Crisis: Favipiravir Oral Solution for Hospital Compounding During COVID-19 Drug Shortage.
The COVID-19 pandemic outbreak has been overwhelming the healthcare system worldwide. A rapidly growing number of younger pediatric patients in Thailand necessitated the formulation of favipiravir, the most locally accessible antiviral agent against COVID-19, into a child-friendly dosage form as a safer alternative to a dispersion of crushed tablets in simple syrup. While striving to quickly develop a liquid formulation that is feasible for any local hospital production units, an oral solution was chosen due to its simplicity. Despite the large dose and poor aqueous solubility of favipiravir, a combination of pH control and use of poloxamer as a solubilizing agent has enabled us to streamline the manufacturing process of a 200 mg/15 mL oral solution for hospital compounding. To ensure its efficacy and safety, a specification for quality control was also established in accordance with the ICH quality guidelines and USP. The finished product stability was subsequently demonstrated under the conditions of 5°C ± 3°C, 25°C ± 2°C/75% RH ± 5% RH, 30°C ± 2°C/75% RH ± 5% RH, and 40°C ± 2°C/75% RH ± 5% RH. The results indicated that our formulation can be stored at 30°C ± 2°C/75% RH for 30 days, which will very well serve the need to allow drug distribution and patient use during the crisis, while the shelf-life can be extended to 60 days when stored at 5°C ± 3°C. Thus, accessibility to an essential medical treatment has been successfully enhanced for pediatric patients in Thailand and neighboring countries during the COVID-19 outbreak.


Long-term exercise stimulates adenosine monophosphate-activated protein kinase activity and subunit expression in rat visceral adipose tissue and liver.
Adenosine monophosphate-activated protein kinase (AMPK) is activated in response to adenosine triphosphate depletion caused by the metabolic and nutritional state. Mammalian AMPK is a heterotrimeric enzyme composed of a catalytic alpha subunit and 2 regulatory subunits (beta and gamma). Although much attention has been focused on exercise-induced AMPK activation in skeletal muscle, little information is available on the role of AMPK in adipose tissue and liver. Acetyl-coenzyme A carboxylase (ACC) is a well-known downstream target of AMPK. The ACC contains serine residues that are phosphorylated by AMPK. The present study was undertaken to determine whether long-term exercise of medium intensity (60% of Vo2max for 12 weeks) may influence AMPK enzyme activity, gene/protein expression, and subsequent ACC phosphorylation in rat adipose tissue (visceral and subcutaneous) and liver. We initially demonstrated that long-term exercise induced a significant increase in phosphorylation of Thr172 in the AMPK alpha1 subunit and of Ser79 in ACC in visceral adipose tissue rather than subcutaneous tissue. We also demonstrated that the AMPK alpha1-,alpha2-subunit messenger RNA (mRNA) level as well as the corresponding protein levels were increased in response to long-term exercise, whereas the other subunits were not altered significantly. In contrast to that of visceral adipose tissue, long-term exercise did not induce any significant effect on any of the AMPK subunit mRNA levels or alpha1-,alpha2-subunit protein levels in subcutaneous adipose tissue. In addition to adipose tissue, we demonstrated that long-term exercise induced an increase in both AMPK/ACC phosphorylation and alpha1-,alpha2-subunit mRNA/protein expression in the liver. Although the precise physiologic relevance of AMPK activation in these tissues remains unknown, it is possible that it might play an important role in long-term exercise-induced adaptation mechanisms and may lead to an improvement in certain metabolic abnormalities in metabolic diseases.


Cellular uptake of quercetin and luteolin and their effects on monoamine oxidase-A in human neuroblastoma SH-SY5Y cells.
Monoamine oxidase-A (MAO-A) is the main enzyme in the metabolism of the neurotransmitter serotonin (5-hydroxytryptamine). Elevated activity of MAO-A in the brain may contribute to the pathogenesis of depressive disorders. Plant flavonoids, such as flavonol quercetin and flavone luteolin, have been suggested to be potential antidepressant compounds because they exert a suppressive effect on the MAO-A reaction. We evaluated the effects of these flavonoids on MAO-A activity and protein level using SH-SY5Y as model serotoninergic nerve cells. Quercetin and luteolin were incorporated into SH-SY5Y cells rapidly and converted to O-methylated derivatives. Luteolin accumulated in cells after 24-h incubation, whereas quercetin disappeared completely from cell fractions and culture medium. Addition of ascorbic acid prevented the disappearance of quercetin and allowed it to exert its cytotoxicity (similar to luteolin) at >10 μM. Luteolin and quercetin were incorporated into mitochondria fractions within 1-h incubation and attenuated MAO-A activity slightly but significantly. After 24-h incubation, luteolin attenuated MAO-A activity, but quercetin needed ascorbic acid for its attenuation. Neither luteolin nor quercetin significantly affected MAO-A protein level. These data suggest that luteolin and quercetin can be direct inhibitors of MAO-A in nerve cells by targeting mitochondria.


Enhanced metronidazole removal by binary-species photoelectrogenic biofilm of microaglae and anoxygenic phototrophic bacteria.
High efficient removal of antibiotics during nutriments recovery for biomass production poses a major technical challenge for photosynthetic microbial biofilm-based wastewater treatment since antibiotics are always co-exist with nutriments in wastewater and resist biodegradation due to their strong biotoxicity and recalcitrance. In this study, we make a first attempt to enhance metronidazole (MNZ) removal from wastewater using electrochemistry-activated binary-species photosynthetic biofilm of Rhodopseudomonas Palustris (R. Palustris) and Chlorella vulgaris (C. vulgaris) by cultivating them under different applied potentials. The results showed that application of external potentials of -0.3, 0 and 0.2 V led to 11, 33 and 26-fold acceleration in MNZ removal, respectively, as compared to that of potential free. The extent of enhancement in MNZ removal was positively correlated to the intensities of photosynthetic current produced under different externally applied potentials. The binary-species photoelectrogenic biofilm exhibited 18 and 6-fold higher MNZ removal rate than that of single-species of C. vulgaris and R. Palustris, respectively, due to the enhanced metabolic interaction between them. Application of an external potential of 0V significantly promoted the accumulation of tryptophan and tyrosine-like compounds as well as humic acid in extracellular polymeric substance, whose concentrations were 7.4, 7.1 and 2.0-fold higher than those produced at potential free, contributing to accelerated adsorption and reductive and photosensitive degradation of MNZ.


Extirpation and fulguration of multiple superficial bladder tumour recurrences under intravesical lignocaine anaesthesia.
To register the results, complications and patient acceptance of bladder tumour operations under local anaesthesia. Intravesical lignocaine was the anaesthesia used in 30 patients with multiple bladder tumour recurrences. The largest tumour was extirpated with large flexible biopsy forceps and the others were fulgurated. All visible tumours were extirpated or fulgurated except in one patient, where the operation had to be terminated due to unsatisfactory anaesthesia. All left the hospital within 2 h of surgery. Complications were minor and patient acceptance was very high. These operations have previously been performed under spinal anaesthesia in this department and the present modification reduced costs by approximately 70%. Patients who had only minor discomfort associated with routine cystoscopy under urethral anaesthesia were well suited for extirpation and fulguration of multiple small tumours under intravesical lignocaine.


IL-6 accelerates renal fibrosis after acute kidney injury via DNMT1-dependent FOXO3a methylation and activation of Wnt/β-catenin pathway.
Maladaptive repair following acute kidney injury (AKI) can trigger inflammation and fibrosis, while progressive renal interstitial fibrosis is critical for the transition of AKI to chronic kidney disease. The aim of this study was to investigate the effect of pro-inflammatory IL-6 on the renal fibrosis after AKI as well as the underlying mechanism. Bioinformatics analysis was performed to identify potential genes related to renal fibrosis. An in vitro model of AKI was established by hypoxia-reoxygenation (H/R) in mouse renal tubular epithelial cells (mRTECs). Gain- and loss-of-function approaches were employed to identify the effects of IL-6/FOXO3a on the renal fibrosis following AKI. The methylation level of FOXO3a promoter was assessed by methylation specific PCR. An AKI mouse model was established by ischemia-reperfusion. Adenovirus-packaged shRNA targeting IL-6 or FOXO3a was utilized for further exploration of their roles in vivo. IL-6 was highly expressed in H/R-exposed mRTECs and kidney tissues of AKI mice rendered with renal fibrosis. Knockdown of IL-6 slowed the renal fibrosis after AKI. IL-6 induced DNMT1 to promote FOXO3a promoter methylation and thus inhibited FOXO3a expression. This inhibition led to promotion of renal fibrosis through activating the Wnt/β-catenin pathway. Further in vivo results verified that loss of IL-6 disrupted the Wnt/β-catenin pathway through reversing DNMT1-mediated inhibition of FOXO3a and consequently attenuated renal fibrosis. All in all, these results suggest that targeting IL-6 contributes to protection against renal fibrosis after AKI through mediating the DNMT1/FOXO3a/Wnt/β-catenin axis, which may serve as promising target for the treatment of AKI and prevention against chronic kidney disease.


High Thermoelectric Power Factor of a Diketopyrrolopyrrole-Based Low Bandgap Polymer via Finely Tuned Doping Engineering.
We studied the thermoelectric properties of a diketopyrrolopyrrole-based semiconductor (PDPP3T) via a precisely tuned doping process using Iron (III) chloride. In particular, the doping states of PDPP3T film were linearly controlled depending on the dopant concentration. The outstanding Seebeck coefficient of PDPP3T assisted the excellent power factors (PFs) over 200 μW m-1K-2 at the broad range of doping concentration (3-8 mM) and the maximum PF reached up to 276 μW m-1K-2, which is much higher than that of poly(3-hexylthiophene), 56 μW m-1K-2. The high-mobility of PDPP3T was beneficial to enhance the electrical conductivity and the low level of total dopant volume was important to maintain high Seebeck coefficients. In addition, the low bandgap PDPP3T polymer effiectively shifted its absorption into near infra-red area and became more colorless after doping, which is great advantage to realize transparent electronic devices. Our results give importance guidance to develop thermoelectric semiconducting polymers and we suggest that the use of low bandgap and high-mobility polymers, and the accurate control of the doping levels are key factors for obtaining the high thermoelectric PF.


Draft Genome Sequence of Pedococcus sp. Strain 5OH_020, Isolated from California Grassland Soil.
The draft genome sequence of the soil bacterium Pedococcus sp. strain 5OH_020, isolated on a natural cobalamin analog, comprises 4.4 Mbp, with 4,108 protein-coding genes. Its genome encodes cobalamin-dependent enzymes, including methionine synthase and class II ribonucleotide reductase. Taxonomic analysis suggests that it is a novel species within the genus Pedococcus.


Characterization and source apportionment of particle number concentration at a semi-urban tropical environment.
Principal component analysis (PCA) and correlation have been used to study the variability of particle mass and particle number concentrations (PNC) in a tropical semi-urban environment. PNC and mass concentration (diameter in the range of 0.25->32.0 μm) have been measured from 1 February to 26 February 2013 using an in situ Grimm aerosol sampler. We found that the 24-h average total suspended particulates (TSP), particulate matter ≤10 μm (PM10), particulate matter ≤2.5 μm (PM2.5) and particulate matter ≤1 μm (PM1) were 14.37 ± 4.43, 14.11 ± 4.39, 12.53 ± 4.13 and 10.53 ± 3.98 μg m(-3), respectively. PNC in the accumulation mode (<500 nm) was the most abundant (at about 99 %). Five principal components (PCs) resulted from the PCA analysis where PC1 (43.8 % variance) predominates with PNC in the fine and sub-microme tre range. PC2, PC3, PC4 and PC5 explain 16.5, 12.4, 6.0 and 5.6 % of the variance to address the coarse, coarser, accumulation and giant fraction of PNC, respectively. Our particle distribution results show good agreement with the moderate resolution imaging spectroradiometer (MODIS) distribution.


Sporadic Creutzfeldt-Jakob disease: A case report and review of literature.
Creutzfeldt-Jakob Disease is a rare neurodegenerative disease and earlier diagnosis is usually difficult. Combining clinical features with electroencephalogram, laboratory parameters, and neuroimaging findings will facilitate the diagnosis.


Antibiofilm activity of a lytic Salmonella phage on different Salmonella enterica serovars isolated from broiler farms.
Bacteriophages have been mainly used in treating infections caused by planktonic bacterial cells in the veterinary sector. However, their applications as antibiofilm agents have received little attention. Accordingly, a previously isolated Salmonella infecting Siphoviridae phage was investigated for host range against 15 Salmonella enterica isolates (S. Cape, S. Gallinarum, 4 S. Enteritidis, 3 S. Montevideo, S. Uno, S. Oritamerin, S. Belgdam, S. Agona, S. Daula, and S. Aba) recovered from the litters of commercial broiler farms. All S. enterica isolates were examined for their biofilm activity using a microtiter plate assay and for adrA, csgD, and gcpA genes using conventional PCR. The phage efficacy against established biofilms produced by the selected seven S. enterica isolates (S. Gallinarum, S. Enteritidis, S. Montevideo, S. Uno, S. Oritamerin, S. Belgdam, and S. Agona) was assessed using microtiter plate assay and reverse transcriptase real-time PCR over different incubation times of 5 and 24 h. All S. enterica isolates were strong biofilm formers. Moreover, the phage effectively reduced the biofilm activity of the established S. enterica biofilms in the microtiter plate assay using the independent sample t-test (P < 0.050). Furthermore, the relative expression levels of csgD, gcpA, and adrA genes in the biofilm cells of S. enterica isolate after phage treatment were significantly up-regulated to variable degrees using the independent sample t-test (P < 0.050). In conclusion, the present study revealed the potential use of Salmonella phage in reducing established biofilms produced by S. enterica serovars isolated from broiler farms.


Investigating the environmental, behavioural, and sociodemographic determinants of attendance at a city-wide public health physical activity intervention: Longitudinal evidence over one year from 185,245 visits.
Understanding the determinants of attendance at public health interventions is critical for effective policy development. Most research focuses on individual-level determinants of attendance, while less is known about environmental-level determinants. Data were obtained from the Leeds Let's Get Active public health intervention in Leeds, England. Longitudinal data (April 2015-March 2016) on attendance were obtained for n = 25,745 individuals (n = 185,245 total visits) with baseline data on sociodemographic determinants and lifestyle practices obtained for n = 3621 individuals. This resulted in a total of n = 744,468 days of attendance and non-attendance. Random forests were used to explore the relative importance of the determinants on attendance, while generalised linear models were applied to examine specific associations (n = 3621). The probability that a person will attend more than once, the number of return visits, and the probability that a person will attend on a particular day were investigated. When considering if a person returned to the same leisure centre after one visit, the most influential determinant was the distance from their home. When considering number of return visits overall however, age group was the most influential. While distance to a leisure centre was less important for predicting the number of return visits, the difference between estimates for 300 m and 15,000 m was 7-10 visits per year. Finally, calendar month was the most important determinant of daily attendance. This longitudinal study highlights the importance of both individual and environmental determinants in predicting various aspects of attendance. It has implications for strategies aiming to increase attendance at public health interventions.


Detection of anti-domain I antibodies by chemiluminescence enables the identification of high-risk antiphospholipid syndrome patients: A multicenter multiplatform study.
Classification of the antiphospholipid syndrome (APS) relies predominantly on detecting antiphospholipid antibodies (aPLs). Antibodies against a domain I (DI) epitope of anti-β2glycoprotein I (β2GPI) proved to be pathogenic, but are not included in the current classification criteria. Investigate the clinical value of detecting anti-DI IgG in APS. From eight European centers 1005 patients were enrolled. Anti-cardiolipin (CL) and anti-β2GPI were detected by four commercially available solid phase assays; anti-DI IgG by the QUANTA Flash® β2GPI domain I assay. Odds ratios (ORs) of anti-DI IgG for thrombosis and pregnancy morbidity proved to be higher than those of the conventional assays. Upon restriction to patients positive for anti-β2GPI IgG, anti-DI IgG positivity still resulted in significant ORs. When anti-DI IgG was added to the criteria aPLs or used as a substitute for anti-β2GPI IgG/anti-CL IgG, ORs for clinical symptoms hardly improved. Upon removing anti-DI positive patients, lupus anticoagulant remained significantly correlated with clinical complications. Anti-DI IgG are mainly present in high-risk triple positive patients, showing higher levels. Combined anti-DI and triple positivity confers a higher risk for clinical symptoms compared to only triple positivity. Detection of anti-DI IgG resulted in higher ORs for clinical manifestations than the current APS classification criteria. Regardless of the platform used to detect anti-β2GPI/anti-CL, addition of anti-DI IgG measured by QUANTA Flash® did not improve the clinical associations, possibly due to reduced exposure of the pathogenic epitope of DI. Our results demonstrate that anti-DI IgG potentially helps in identifying high-risk patients.


Unconstrained muscle-tendon workloops indicate resonance tuning as a mechanism for elastic limb behavior during terrestrial locomotion.
In terrestrial locomotion, there is a missing link between observed spring-like limb mechanics and the physiological systems driving their emergence. Previous modeling and experimental studies of bouncing gait (e.g., walking, running, hopping) identified muscle-tendon interactions that cycle large amounts of energy in series tendon as a source of elastic limb behavior. The neural, biomechanical, and environmental origins of these tuned mechanics, however, have remained elusive. To examine the dynamic interplay between these factors, we developed an experimental platform comprised of a feedback-controlled servo-motor coupled to a biological muscle-tendon. Our novel motor controller mimicked in vivo inertial/gravitational loading experienced by muscles during terrestrial locomotion, and rhythmic patterns of muscle activation were applied via stimulation of intact nerve. This approach was based on classical workloop studies, but avoided predetermined patterns of muscle strain and activation-constraints not imposed during real-world locomotion. Our unconstrained approach to position control allowed observation of emergent muscle-tendon mechanics resulting from dynamic interaction of neural control, active muscle, and system material/inertial properties. This study demonstrated that, despite the complex nonlinear nature of musculotendon systems, cyclic muscle contractions at the passive natural frequency of the underlying biomechanical system yielded maximal forces and fractions of mechanical work recovered from previously stored elastic energy in series-compliant tissues. By matching movement frequency to the natural frequency of the passive biomechanical system (i.e., resonance tuning), muscle-tendon interactions resulting in spring-like behavior emerged naturally, without closed-loop neural control. This conceptual framework may explain the basis for elastic limb behavior during terrestrial locomotion.


Correction to: Bone defect reconstruction with a novel biomaterial containing calcium phosphate and aluminum oxide reinforcement.
An amendment to this paper has been published and can be accessed via the original article.


Feedforward growth rate control mitigates gene activation burden.
Heterologous gene activation causes non-physiological burden on cellular resources that cells are unable to adjust to. Here, we introduce a feedforward controller that actuates growth rate upon activation of a gene of interest (GOI) to compensate for such a burden. The controller achieves this by activating a modified SpoT enzyme (SpoTH) with sole hydrolysis activity, which lowers ppGpp level and thus increases growth rate. An inducible RelA+ expression cassette further allows to precisely set the basal level of ppGpp, and thus nominal growth rate, in any bacterial strain. Without the controller, activation of the GOI decreased growth rate by more than 50%. With the controller, we could activate the GOI to the same level without growth rate defect. A cell strain armed with the controller in co-culture enabled persistent population-level activation of a GOI, which could not be achieved by a strain devoid of the controller. The feedforward controller is a tunable, modular, and portable tool that allows dynamic gene activation without growth rate defects for bacterial synthetic biology applications.


Names and their meanings: A dual-process account of proper-name encoding and retrieval.
The ability to pick out a unique entity with a proper name is an important component of human language. It has been a primary focus of research in the philosophy of language since the nineteenth century. Brain-based evidence has shed new light on this capacity, and an extensive literature indicates the involvement of distinct fronto-temporal and temporo-occipito-parietal association cortices in proper-name retrieval. However, comparatively few efforts have sought to explain how memory encoding processes lead to the later recruitment of these distinct regions at retrieval. Here, we provide a unified account of proper-name encoding and retrieval, reviewing evidence that socio-emotional and unitized encoding subserve the retrieval of proper names via anterior-temporal-prefrontal activations. Meanwhile, non-unitized item-item and item-context encoding support subsequent retrieval, largely dependent on the temporo-occipito-parietal cortex. We contend that this well-established divergence in encoding systems can explain how proper names are later retrieved from distinct neural structures. Furthermore, we explore how evidence reviewed here can inform a century-and-a-half-old debate about proper names and the meanings they pick out.


Quality of life. Issues for persons with neuromuscular diseases.
Improving quality of life has always been a goal of rehabilitation medicine. However, health care providers often do not know much about the quality of life of individuals with neuromuscular diseases, nor what factors are critical to achieving a good quality of life. Lack of knowledge about subjective quality of life factors can negatively influence expectations and selection of treatments. In the most glaring cases, a physician's subjective but incorrect assessment of a disabled individuals' quality of life may prevent life-sustaining interventions. As a group, the quality of life of individuals with NMD is not much different than nondisabled controls and is substantially better than presumed by the general public and, often times, by health care workers. Nevertheless, their quality of life is reduced in certain areas. Surprisingly, level of disability is not a critical factor that significantly alters life satisfaction. Presumably, this is because physical functioning has been adequately managed. The greatest problems that individuals with neuromuscular disease identified were: lack of information about the disease and services; poor coordination of services; negative attitudes; and a diminished expectation of their potential. In addition, people with severe disabilities had significant problems obtaining, financing, and managing personal care attendants. Factors related to a good quality of life were related to perceived control, perceived health status, but not disability. The more that people could do for themselves, either on their own or with personal care assistants, assistive devices, and use of technology, the better their quality of life.


Symbiotic bacterial communities in rainforest fungus-farming ants: evidence for species and colony specificity.
Animals may host diverse bacterial communities that can markedly affect their behavioral physiology, ecology, and vulnerability to disease. Fungus-farming ants represent a classical example of mutualism that depends on symbiotic microorganisms. Unraveling the bacterial communities associated with fungus-farming ants is essential to understand the role of these microorganisms in the ant-fungus symbiosis. The bacterial community structure of five species of fungus-farmers (non-leaf-cutters; genera Mycocepurus, Mycetarotes, Mycetophylax, and Sericomyrmex) from three different environments in the Brazilian Atlantic rainforest (lowland forest, restinga forest, and sand dunes) was characterized with amplicon-based Illumina sequencing of 16 S ribosomal RNA gene. Possible differences in bacterial communities between ants internal to the nest (on the fungus garden) and external foragers were also investigated. Our results on the richness and diversity of associated bacteria provide novel evidence that these communities are host- and colony-specific in fungus-farming ants. Indeed, the bacterial communities associated with external foragers differ among the five species, and among colonies of the same species. Furthermore, bacterial communities from internal ants vs. foragers do not differ or differ only slightly within each ant species. This study highlights the importance of describing ant-associated bacterial communities to better understand this host-bacterial interaction in the social environment of insect colonies and provides the foundation for future studies on the ecological and evolutionary processes that drive the success of fungus-farming ants.


Penetrating thermal vascular injury in a child: a case report.
Penetrating vascular trauma in children is most commonly seen in wartime settings or more recently as a result of attempts at invasive imaging. Treatment of these patients can be more complicated than treatment of trauma in adults and must include maintenance of symmetric limb growth, compensatory growth of the vascular graft and its anastomoses, and the need for very long-term graft patency. This report describes the care of a 5-year-old child who was impaled by a hot metal pipe and sustained a penetrating thermal injury to the distal external iliac artery and vein. Issues such as conduit choice, extraanatomic reconstruction, anastomotic suture technique, and soft tissue coverage are reviewed in the report.


Where to measure water quality ? Application to nitrogen pollution in a catchment in France.
Information on the water quality of rivers can be used to judge the effectiveness of past policies or to guide future environmental policies. Consequently, the location of water quality monitoring stations (WQMSs) plays an important role in river pollution control. In the 2000s, a literature developed on the optimization of WQMS location to identify pollution hot spots, average quality, or to minimize the detection time of a potential source of accidental pollution. This article is part of a new literature aimed at locating WQMSs in order to optimize the economic value of information (EVOI) generated by water quality monitoring networks (WQMNs). The field of study is a catchment in northeastern France where the purpose of quality measurement is to define a policy of reduction of agricultural nitrogen fertilizers in order to reach the standard of 50 mg/l of nitrate at the WQMS. Agro-hydrological and economic models estimate the net benefit of input reduction depending on the location of the WQMS on the basis of different assumptions concerning the ecological damage generated by nitrate. We show that the magnitude of the ecological damage and, consequently, the perception of the contamination generated by nitrate in water, play a decisive role on the optimal location of the WQMS, as well as on the benefit of the economic optimization of locations, compared to traditional optimization. Locating WQMSs in a way that maximizes EVOI will be more attractive for very high or very low levels of damage. However, in this context, linking damage to nitrate concentration or to concentration coupled with riparian population density alone will have little impact.


Use of agricultural bio-wastes to remove arsenic from contaminated water.
Arsenic (As) is a highly toxic metalloid. High As levels have been recorded in groundwater aquifers at a global scale. This study investigated As level in groundwater of District Vehari and assessed the potential of different agricultural by-products (sugarcane bagasse, cottonseed hulls, soybean hulls, corncobs and rice husk) to remove As from water. The study was carried out in two steps. In the first step, a total of 38 groundwater samples were obtained from Vehari. Groundwater samples were analyzed for total As contents and physicochemical parameters. Results indicated that As content ranged from below detection limit to 49 µg/L in the groundwater samples. The values of hazard quotient and cancer risk were up to 1.5 and 0.0004, respectively, which delineated severe risk of As poisoning. During the second step, six As-contaminated groundwater samples (total As contents: 49, 40, 29, 24, 18, 16 µg/L) were selected to remove As using agricultural by-products. Furthermore, four As solutions (200, 100, 50 and 25 µg/L) were prepared in the laboratory. Results revealed that corncobs and soybean hulls removed, respectively, 98% and 71% As from aqueous mediums after 120 min. Moreover, agricultural by-products were less effective in removing As from groundwater samples than synthetic solutions. The adsorption/removal capacity of by-products was lower at low initial As concentration compared to high initial levels, which needs further studies to explore the underlying mechanisms. Overall, the As removal efficiency of agriculture by-products differed significantly with respect to initial As level, contamination category, type of agricultural by-products and interaction duration. Therefore, these aspects need to be optimized before the possible use of an agricultural by-product as a potential biosorbent.


A collaborative approach to outpatient care of patients with HIV infection.
Patients with human immunodeficiency virus (HIV)-related disease have a host of related medical and other problems that respond to a collaborative model of health care. At the Infectious Disease Clinic at the Department of Veterans Affairs Medical Center, San Francisco, physicians and nurses provide collaborative outpatient health care for more than 500 HIV-infected patients in several specialty clinics.


Multiplexed detection of waterborne pathogens in circular microfluidics.
Microfluidic lab-on-a-chip presents an ideal solution for bacterial sensing and identification due to its advantages like large surface-to-volume ratio, requirement of low sample volume and multiplexing possibility. The present work deals with the development of an immunosensor chip using circular microchannels fabricated directly with microdimensional copper wire and permanent magnet for capture of Fe(3)O(4) magnetic nanoparticle (MNP) conjugate. The MNP facilitate capture of the antigen in a confined space and hence, enhanced fluorescence signal for detection. The multiplexed microfluidic chip permits visual detection and quantification of waterborne pathogens viz. Escherichia coli and Salmonella typhimurium simultaneously. CdTe quantum dots (QDs) with different emission wavelengths were conjugated with anti-E. coli and anti-S. typhimurium antibodies for concurrent fluorescence detection. The present technique provides an inexpensive yet powerful tool to image and quantify pathogens at low numbers with passage of large sample volumes.


Heat Shock Protein Genes Undergo Dynamic Alteration in Their Three-Dimensional Structure and Genome Organization in Response to Thermal Stress.
Three-dimensional (3D) chromatin organization is important for proper gene regulation, yet how the genome is remodeled in response to stress is largely unknown. Here, we use a highly sensitive version of chromosome conformation capture in combination with fluorescence microscopy to investigate Heat Shock Protein (HSP) gene conformation and 3D nuclear organization in budding yeast. In response to acute thermal stress, HSP genes undergo intense intragenic folding interactions that go well beyond 5'-3' gene looping previously described for RNA polymerase II genes. These interactions include looping between upstream activation sequence (UAS) and promoter elements, promoter and terminator regions, and regulatory and coding regions (gene "crumpling"). They are also dynamic, being prominent within 60 s, peaking within 2.5 min, and attenuating within 30 min, and correlate with HSP gene transcriptional activity. With similarly striking kinetics, activated HSP genes, both chromosomally linked and unlinked, coalesce into discrete intranuclear foci. Constitutively transcribed genes also loop and crumple yet fail to coalesce. Notably, a missense mutation in transcription factor TFIIB suppresses gene looping, yet neither crumpling nor HSP gene coalescence is affected. An inactivating promoter mutation, in contrast, obviates all three. Our results provide evidence for widespread, transcription-associated gene crumpling and demonstrate the de novo assembly and disassembly of HSP gene foci.


Cytotoxicity of bovine leucocytes for parainfluenza type-3 virus-infected cells.
The cytotoxic effect of bovine neutrophils, alveolar macrophages, monocytes and lymphocytes for parainfluenza type-3 (PI-3) virus-infected cells in 51chromium-release assays is described. Specific lysis of virus-infected target cells with PI-3 virus antibody and complement was first observed 8 h after infection coincident with the appearance of haemadsorption-positive cells. Specific lysis increased rapidly reaching a peak 18-24 h after infection. This increase was paralleled by the increase in the percentage of cells with surface haemagglutinin. Target cells were subsequently used in 51chromium-release assays between 18 and 20 h after virus infection. Antibody-independent killing of PI-3 virus-infected cells was observed with neutrophils, alveolar macrophages and lymphocytes. Levels of specific lysis up to 30% for neutrophils and 68% for alveolar macrophages were observed, although there was considerable variation in activity from animal to animal. Lymphocyte preparations showed levels of cytotoxicity up to 20% in some cases while monocytes had low killing ability. Addition of PI-3 virus-specific antibodies enhanced killing by neutrophils, monocytes and lymphocytes but inhibited killing by alveolar macrophages. Complement, particularly guinea pig complement, was cytotoxic for virus-infected but not for uninfected cells, and also considerably enhanced the cytotoxic effect of neutrophils and lymphocytes.


Effect of triadimefon and its metabolite on adult amphibians Xenopus laevis.
The decrease in the population of amphibians all over the world has raised concerns. Adult X. laevis frogs were exposed to 0, 1 and 10 mg/L triadimefon and triadimenol. After 14 or 28 days exposure, we collected male and female specimens to study swimming activity, lactic dehydrogenase (LDH) and antioxidant enzyme activity in blood samples, histopathology of liver and thyroid tissue, thyroid hormone levels and thyroid hormone-related gene expression levels in brains. Our results showed that triadimefon and triadimenol could affect the swimming activity of frogs and that this was distinct at different levels of triadimenol. Moreover, triadimefon and triadimenol exposure produced a greater effect on superoxide dismutase (SOD) in females than in males, which was reverse to the finding for glutathione S-transferase (GST) and catalase (CAT). After 28 days exposure, triadimefon produced more toxic effects on the liver than observed for triadimenol. Besides this, triadimefon and triadimenol exposure exerted a greater effect on liver histology and thyroid hormone levels in male frogs than in the females. Our results also found that the expression of genes related to thyroid hormone in brains depended on the exposure level and time, as well as the sex of the treated individual. This study shed light on the relationships between the toxicity of metabolite products and their parent compounds and provided further understanding of the risk of pesticide use on amphibians.


Neighbourhood environment as a predictor of television watching among girls.
Television watching, a sedentary activity, has been associated with overweight in children. While the family environment is known to influence television watching, little is known about the influence of the neighbourhood environment. This study is an exploratory examination of the association of socioeconomic characteristics of the neighbourhood environment with television watching among 9-10 year old girls. Data collected by the Berkeley site of the National Heart, Lung and Blood Institute Growth and Health Study (NGHS) in 1987-8 from 787 girls who had a complete set of measurements relevant to the analysis were used. These measures included parental education, household income, race and weekly hours spent watching television. Addresses of the girls were geocoded and the median household income for the census tracts in which they lived was used to indicate neighbourhood socioeconomic characteristics. Multilevel modelling procedures were used to estimate fixed effect coefficients for individual and neighbourhood level variables. Living in high income areas was associated with less television watching, a finding that held even when controlling for parental education, household income and race. Race and parental education were also associated with television watching. Television watching among girls was associated not only with the socioeconomic characteristics of their households, but also of their neighbourhoods. Future studies should explore the mechanisms that mediate this relation and determine if these results are generalisable to other populations.


Application of transesophageal echocardiography for localization in totally implantable venous access port implantation through subclavian approach in children.
A totally implantable venous access port (TIVAP) is important in children who need intravenous infusion for a long time. A number of studies have shown methods for locating the tip of the TIVAP catheter. To explore whether transesophageal echocardiography (TEE) can be used to accurately locate the TIVAP catheter tip through a subclavian approach and to improve the rate of correct TIVAP catheter placement and reduce complications of TIVAP placement. In 36 children who needed TIVAP implantation surgery, we used real-time TEE guidance to place the catheter tip around the crista terminalis. In all children, chest X-rays were used to figure out whether the catheter tip as localized by TEE was within the T5-T7 segment. Then, we compared the length of the catheter calculated by the height formula and the actual catheter length applied under TEE guidance. The medical records, surgical details, nursing records, and recorded complications were collected during the follow-up. The success rate of TIVAP implantation was 100% in all enrolled patients and no hemopneumothorax or pinch-off syndrome occurred. Compared with TEE, chest X-ray showed a coincidence rate of 80.56% in correctly detecting the TIVAP catheter tip locate. The height-derived catheter length (11.0 [9.6, 11.8]) cm and the TEE-derived catheter length (10.0 [9.3, 10.8]) cm were significantly different (p < .001). TEE can be used to guide TIVAP catheter positioning through a left subclavian approach in children accurately and successfully and more accurate than chest X-ray and height calculation formula.


[Intra-arterial chemotherapy. Presentation of a method to insure patency of the catheter].
Following some brief remarks on the main techniques of antineoplastic chemotherapy, a simple technique for guaranteeing patency of the endarterial catheter is presented. Using a special microchannel infusor, it was possible to prevent catheter obstruction in 100% of the cases treated.


De novo designed self-assembling helicomimetic lipooligoureas with antibacterial activity.
The overuse of antibiotics has led to a rise in infections caused by multidrug-resistant bacteria, resulting in a need for new antibacterial compounds with different modes of action. In this paper, we describe a new class of compounds called lipooligoureas, which are foldamer-based mimetics of antimicrobial lipopeptides. The lipooligoureas consist of an acyl chain connected to the N-terminus of an oligourea head group that exhibits a well-defined 2.5-helix secondary structure, which is further stabilized by the attachment of the lipophilic chain to the oligourea moiety. These compounds meet the established criteria for membranolytic compounds by possessing an amphiphilic structure that promotes the internalization and partitioning of the molecules into the lipid membrane. The presence of positively charged urea residues promotes electrostatic interactions with the negatively charged bacterial membrane. The subtle structural differences in oligourea head group influence the compounds' aggregation behavior, with the number and position of positively charged urea residues correlating with their aggregation ability. The biological activity of these compounds in inhibiting bacterial growth is correlated with their ability to aggregate, with stronger antibacterial properties exhibited by those that aggregate more easily. However, the concentration inhibiting bacterial growth is significantly lower than the critical aggregation concentration values, suggesting that the mechanism of action involves the monomeric forms of lipooligoureas. Nonetheless, a mechanism based on membrane-induced aggregation cannot be ruled out. The lipooligoureas exhibit higher activity towards Gram-positive bacteria than against Gram-negative bacteria, which is indicative of certain selectivity of these compounds. It is also demonstrated that lipooligoureas exhibit increased stability against proteolytic degradation in human blood serum.


Hypothermic versus normothermic cardiopulmonary bypass in patients with valvular heart disease.
The aim of this study was to test the hypothesis that normothermic cardiopulmonary bypass (CPB) is as effective as hypothermic CPB in terms of cardiac protection (cTnI level) and outcome in patients with valvular heart disease. Prospective randomized study. A tertiary cardiothoracic referral center. 140 patients who had valvular heart disease, with/without coronary artery disease, surgically treated under CPB. The patients were allocated randomly to undergo either hypothermic (temperature [T], 31 °C-32 °C) or normothermic CPB (T>36 °C). The primary endpoint was the dynamics of troponin I. The secondary endpoints were ventilation time, the need for inotropic support, intensive care unit (ICU) and hospital stay durations, complications, and mortality. There were no significant intergroup differences in dynamics of troponin I. Ventilation time was significantly lower in the hypothermic group (6 (5-9) and 8 (5-12); p = 0.01). Normothermic CPB in patients with valvular heart disease was as effective as hypothermic perfusion in terms of myocardial protection after the surgery assessed by cTnI release. The short ventilation duration in patients who underwent hypothermic CPB needs to be confirmed in a future investigation.


Homologous recombination deficiency in triple negative breast cancer.
Triple negative breast cancer (TNBC) represents a heterogeneous subtype of breast cancer characterized by an unfavorable prognosis due to its aggressive biology. The median overall survival (OS) for patients with metastatic TNBC is around 9-12 months with conventional cytotoxic agents. Considering this suboptimal outcome, which is induced despite of medical treatment, new therapeutic strategies would be urgently needed. The ultimate goal of precision medicine is to identify specific molecular alterations that permit considering effective targeted drug(s). Germline BRCA mutations occur in 10-20% of TNBC patients while somatic mutations occur in 3-5% of them. Alterations in the homologous recombination (HR) system are typical of BRCA mutant tumors, but can also be identified in tumors that do not carry this mutation, defining a subgroup of patients referred to as BRCAness. In this review, we focus on the role of homologous recombination deficiency (HRD) as both predictive and prognostic factor in different settings of TNBC patients treated with DNA damaging drugs and poly ADP ribose polymerase (PARP) inhibitors.


Preclinical toxicity and pharmacology of liposome-entrapped cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum(II).
Liposome-entrapped cis-bis-neodecanoate-trans-R,R-1,2-diaminocylohexane platinum(II) (L-NDDP) is a new lipophilic cisplatin derivative formulated in a liposomal carrier currently in phase I clinical trials. The preclinical toxicity and pharmacology of L-NDDP were studied in mice and dogs. At the LD50 dose (i.v. bolus) in mice (60.5 mg/kg or 181.5 mg/m2), a tenfold decrease in the granulocyte and platelet counts was observed in the absence of renal toxic effects. In dogs, the maximum tolerated dose (MTD) of L-NDDP given i.v. over a period of 45-60 min was 150 mg/m2. This dose produced significant vomiting (6-18 episodes), minimal renal dysfunction, a maximal decrease in granulocyte and platelet counts of from 30% to 70%, and acute and transient elevation of liver enzymes. Higher doses (225 and 300 mg/m2) resulted in severe gastrointestinal (GI) toxicity in one animal and the death of two others within 48 h. Autopsy results showed multifocal hemorrhages in the lungs, GI tract, kidney, and liver. Three dogs were treated monthly with the MTD up to a cumulative dose of 637.5-712.5 mg/m2 with excellent tolerance. No cumulative myelosuppression or liver dysfunction was observed, whereas a slight increase in the creatinine baseline level was detected in all three animals. Autopsy results at the end of the study showed mild changes limited to the liver, kidney, and GI tract. Pharmacologic studies showed that the drug was cleared, fitting a two-compartment model with a mean t1/2 alpha of 7.1 min and a t1/2 beta of 87.8 h. These studies show that L-NDDP can safely be given at therapeutic doses to animals and that the dose-limiting toxic effects consists of myelosuppression in mice and a multiorgan hemorrhagic syndrome related to vascular injury in dogs.


Schwann cell growth factors.
Purified rat Schwann cells were found to proliferate very slowly in normal growth medium containing 10% fetal calf serum (FCS). Crude extracts of bovine pituitary or brain markedly enhanced Schwann cell growth, while similar extracts of nerve roots, liver and kidney did not. Pituitary extracts were more potent than brain extracts, and extracts from both anterior and posterior pituitary were active. The mitogenic activity of pituitary extracts was reduced by treatment with trypsin, and abolished by pronase and by boiling. A variety of known anterior and posterior pituitary hormones, as well as fibroblast, epidermal and nerve growth factors, were not mitogenic. FCS (greater than 1%) was required for Schwann cell proliferation, but even high concentrations of FCS did not substitute for pituitary or brain extracts, and serum from various other species did not support Schwann cell growth. Although various agents that increase cyclic AMP levels (such as cholera toxin) had been shown to be Schwann cell mitogens, extracts of pituitary or brain did not increase cyclic AMP levels. Extracts of various bovine tissues, including pituitary, brain, liver and kidney, acted synergistically with cholera toxin in stimulating Schwann cell proliferation, although the increase in cyclic AMP induced by the mixture was not greater than that seen with cholera toxin alone. We conclude that there are at least two separate pathways for stimulating Schwann cell division, only one of which involves an increase in intracellular cyclic AMP.


Risk factors and tumor response associated with hydrocephalus after gamma knife radiosurgery for vestibular schwannoma.
This study was designed to investigate the clinical characteristics and risk factors of hydrocephalus after gamma knife radiosurgery (GKRS) for vestibular schwannoma. The authors retrospectively reviewed clinical and neuroimaging findings of 221 patients who underwent GKRS for newly diagnosed vestibular schwannoma. Mean patient age was 54.1 years (range 7-83 years), mean tumor volume was 3,010.4 mm(3) (range 34.7 to 14,300 mm(3)), mean marginal dose was 12.5 Gy (range 11 to 15 Gy), and mean follow-up duration was 31.9 months (range 1 to 107.6 months). Surgical intervention for cerebrospinal fluid (CSF) diversion after GKRS was necessary in 11 (5 %) of the patients. Median time between GKRS and ventriculoperitoneal (VP) shunt placement was 15.5 months (range 1.8-37.8 months). These 11 patients showed female predominance (11 females) and mean tumor volume was significantly larger than in the other without hydrocephalus (6,509 vs. 2,726 mm(3); p < 0.01). Decreases in tumor enhancement and swelling were observed in all 221 patients, and CSF protein was found to be elevated in five of nine patients with available data at the time of the shunt procedure. Hydrocephalic symptoms improved after VP shunt and tumor sizes further decreased at last follow-up in all patients. Hydrocephalus after radiosurgery may co-occur with a temporary change of tumor volume after radiation treatment. Therefore, hydrocephalus should be kept in mind during the time of tumor volume transition. Furthermore, the authors suggest that frequent patient monitoring for hydrocephalus be maintained for up to 3-4 years after GKRS.


How do lifestyle choices affect the link between living alone and psychological distress in older age? Results from the AgeHeaPsyWel-HeaSeeB study.
Social isolation is widespread and strongly associated with worsening health-related outcomes across the life-course. Despite this broad base of knowledge, there is a paucity of research on the interactive effect of lifestyle choices and living arrangements on later life psychological state particularly in low- and middle-income settings. The aim of this study is to examine the influence of living alone on psychological distress in older people and to explore the protective roles of social participation and physical activity participation. We used cross-sectional data from the 2016-17 Aging, Health, Psychological Well-being and Health-seeking Behavior Study (AgeHeaPsyWel-HeaSeeB) involving a representative sample of 1200 adults aged 50+ years in Ghana. The study focused on a latent measure of Kessler Psychological Distress Scale (K10) and on the General Practice Physical Activity Questionnaire (GPPAQ). Ordinary Least Squares (OLS) regression models evaluated the interactive effects of living arrangements and lifestyle choices on the K10 score. Living alone was independent predictor of psychological distress in the overall sample, among females, urban dwellers and all age groups. However, lifestyle choices of physical activity and social participation significantly moderated these associations. Moreover, in the stratified analysis, physical activity moderated the association for males, rural-dwellers and those 65+ years whilst social participation moderated the association for females, urban-dwellers and those 50-64 years. Lifestyle choices i.e. social participation and physical activity, and demographic factors i.e. age, gender, and residential status strongly attenuate the positive association of living alone with the risk of psychological distress in older age. These findings may inform intervention initiatives targeted at improving mental health of chronically detached and isolated older people.


Somatic mutations in disorders with disrupted brain connectivity.
Mutations occur during cell division in all somatic lineages. Because neurogenesis persists throughout human life, somatic mutations in the brain arise during development and accumulate with the aging process. The human brain consists of 100 billion neurons that form an extraordinarily intricate network of connections to achieve higher level cognitive functions. Due to this network architecture, perturbed neuronal functions are rarely restricted to a focal area; instead, they are often spread via the neuronal network to affect other connected areas. Although somatic diversity is an evident feature of the brain, the extent to which somatic mutations affect the neuronal structure and function and their contribution to neurological disorders associated with disrupted brain connectivity remain largely unexplored. Notably, recent reports indicate that brain somatic mutations can indeed play a critical role that leads to the structural and functional abnormalities of the brain observed in several neurodevelopmental disorders. Here, I review the extent and significance of brain somatic mutations and provide my perspective regarding these mutations as potential molecular lesions underlying relatively common conditions with disrupted brain connectivity. Moreover, I discuss emerging technical platforms that will facilitate the detection of low-frequency somatic mutations and validate the biological functions of the identified mutations in the context of brain connectivity.


Mitral valve repair after excision of a fibrolipoma.
A 2-year-old patient with severe mitral regurgitation associated with a mass originating from the anterior leaflet of the mitral valve is reported. Excision of the tumor and mitral valve repair was performed. Four years later the child remains asymptomatic with no recurrence of the tumor or regurgitation.


Visual outcomes after blunt ocular trauma.
To describe the prognosis and retinal location in patients presenting with acute traumatic maculopathy and extramacular retinal injuries. Retrospective, noninterventional case series. All patients presenting with commotio retinae or sclopetaria retinae to the Birmingham Midland Eye Centre Eye Casualty from October 1, 2007, to February 23, 2011. The notes of all patients presenting with ocular trauma in the specified time period were examined to identify suitable patients and demographic and injury data were extracted. Outcome was assessed by visual acuity (VA). For macular commotio retinae, 53 patients were identified, of whom 34 had adequate follow-up to determine final VA. The median presenting VA was 20/40; 25 patients (74%) recovered to ≥ 20/30. The median extent of visual recovery was 0.18 logarithm of the minimum angle of resolution (logMAR). For extramacular commotio retinae, 117 patients were identified, of whom 58 had adequate follow-up to determine final VA. The median presenting VA retinae was 20/30; 55 patients (95%) recovered to ≥ 20/30. The median extent of visual recovery was logMAR 0.076. There was 1 case of extramacular sclopetaria retinae. The 3 most common retinal locations of extramacular commotio retinae, in order of frequency, were inferotemporal (37%), temporal (17%), and superotemporal (17%); <5% of cases were in a nasal location. This is the first report on the prognosis of acute traumatic maculopathy and extramacular commotio retinae. After macular injury, 26% of patients were left with a VA of ≤ 20/30, although the proportion with visual impairment is higher than this because (1) a deterioration from 20/15 to 20/30 is significant to many patients; and (2) additional patients are visually impaired by symptomatic paracentral visual field defects despite a normal VA. Reduced VA after extramacular commotio retinae may represent occult macular injury or previously undiagnosed visual impairment in the affected eye. Extramacular commotio occurs mostly in an inferotemporal to temporal location, consistent with direct trauma to the sclera overlying the injured retina. The authors have no proprietary or commercial interest in any of the materials discussed in this article.


Correlation of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with metabolic parameters in patients undergoing sleeve gastrectomy.
Obesity and its related diseases, type 2 diabetes (T2D) and overall metabolic syndrome, often show a low-grade of chronic inflammation due to loss of balance between pro- and anti-inflammatory signals. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are considered cost-effective markers for the detection of this subclinical inflammation. To evaluate the potential prognostic factor of NLR and PLR as inflammatory biomarkers on weight loss and T2D remission after sleeve gastrectomy (SG). University Medical Institutions. Patients who underwent SG as primary treatment for severe obesity were included. Anthropometric and blood parameters were measured at baseline and postoperatively (1, 2, and 5 yr after surgery). The prognostic ability of NLR and PLR was evaluated by a receiver operator characteristic curve and a cutoff point was calculated. A value of P < .05 was considered significant. A total of 182 patients were analyzed. Preoperative NLR showed an inverse correlation with excess weight loss (Spearman -.525; P = .033) and units of body mass index lost (Spearman -.502; P = .039) 5 years after surgery. Preoperative NLR also showed a direct correlation with fasting glucose (Spearman .685; P = .002) and Homeostasis Model Assessment of Insulin Resistance (Spearman .764; P < .001). Lower preoperative NLR is also associated with a complete remission of T2D at 5 years. Preoperative PLR did not show any correlation with the variables studied. The preoperative NLR is a potential prognostic factor of long-term weight loss and T2D remission in patients undergoing SG. PLR does not correlate with metabolic parameters in these patients.


Anti-sense DNA d(GGCCCC)n expansions in C9ORF72 form i-motifs and protonated hairpins.
The G4C2 hexanucleotide repeat expansion mutation (HREM) in C9ORF72, represents the most common mutation associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Three main disease mechanisms have been proposed to date: C9ORF72 haploinsufficiency, RNA toxicity, and accumulation of dipeptide repeat proteins. Pure GC content of the HREM potentially enables the formation of various non-B DNA structures such as G-quadruplexes and i-motifs. These structures are proposed to act as promoters and regulatory elements affecting replication, transcription and translation of the surrounding region. G-quadruplexes have already been shown on the G-rich sense DNA and RNA strands (G4C2)n, the structure of the anti-sense (G2C4)n strand remains unresolved. Similar C-rich sequences may, under acidic conditions, form i-motifs consisting of two parallel duplexes in a head to tail orientation held together by hemi-protonated C(+)-C pairs. We show that d(G2C4)n repeats do form i-motif and protonated hairpins even under near-physiological conditions. Rather than forming a DNA duplex, i-motifs persist even in the presence of the sense strand. This preferential formation of G-quadruplex and i-motif/hairpin structures over duplex DNA, may explain HREM replicational and transcriptional instability. Furthermore, i-motifs/hairpins can represent a novel pharmacological target for C9ORF72 associated ALS and FTLD.


TC21 mediates transformation and cell survival via activation of phosphatidylinositol 3-kinase/Akt and NF-kappaB signaling pathway.
The signaling pathways of TC21-mediated transformation and cell survival are not well-established. In this study, we have investigated the role of PI3-K/Akt signaling pathway in oncogenic-TC21-mediated transformation and cell survival. We found that oncogenic-TC21 stimulated the PI3-K activity. This was associated with the activation of Akt, a key component of PI3-K signaling pathway. We also found that TC21 interacted and formed complex with PI3-K. Mutations in the GTP-binding region of TC21, which enhanced GTP-binding potential of this protein, also stimulated its association with PI3-K, suggesting that PI3-K may preferentially interact with the GTP-bound form. Suppression of PI3-K and Akt by specific inhibitors LY294002 and Wortmannin reversed TC21-induced transformation. Likewise, inhibition of PI3-K activity by the PI3-K phosphotase PTEN reduced TC21-mediated focus formation in NIH3T3 cells. Investigation of TC21's effect on cell survival revealed that mutant-TC21 expressing cells were more resistant to etoposide- and cisplatin-induced cell death, and this was associated with the activation of anti-apoptotic protein NF-kappaB, a downstream target of Akt. Treatment of PI3-K inhibitor LY294002 significantly suppressed TC21-mediated NF-kappaB activation. In conclusion, we have identified PI3-K as an effector of TC21 and demonstrated that the PI3-K/Akt signaling pathway plays important roles in TC21-mediated transformation and cell survival.


Probiotic-mediated p38 MAPK immune signaling prolongs the survival of Caenorhabditis elegans exposed to pathogenic bacteria.
The host-microbiota cross-talk represents an important factor contributing to innate immune response and host resistance during infection. It has been shown that probiotic lactobacilli exhibit the ability to modulate innate immunity and enhance pathogen elimination. Here we showed that heat-inactivated probiotic strain Lactobacillus curvatus BGMK2-41 stimulates immune response and resistance of the Caenorhabditis elegans against Staphylococcus aureus and Pseudomonas aeruginosa. By employing qRT-PCR and western blot analysis we showed that heat-inactivated BGMK2-41 activated PMK-1/p38 MAPK immunity pathway which prolongs the survival of C. elegans exposed to pathogenic bacteria in nematode killing assays. The C. elegans pmk-1 mutant was used to demonstrate a mechanistic basis for the antimicrobial potential of BGMK2-41, showing that BGMK2-41 upregulated PMK-1/p38 MAPK dependent transcription of C-type lectins, lysozymes and tight junction protein CLC-1. Overall, this study suggests that PMK-1/p38 MAPK-dependent immune regulation by BGMK2-41 is essential for probiotic-mediated C. elegans protection against gram-positive and gram-negative bacteria and could be further explored for development of probiotics with the potential to increase resistance of the host towards pathogens.


[Mutagenic activity of organic esters are likely to form from bromo-2 ethanol generated during fumigation using ethylene oxide].
The mutagenic potencies of 13 bromoethyl esters of natural organic acids, have been studied, by Ames's test (strains TA 98 and TA 100, with and without system of metabolisation, S9 mix). None of the 8 bromoethyl esters of linoleic, oleic, palmitic, stearic, lauric, myristic, cinnamic and fumaric acids is genotoxic. On the other hand the 5 others derived from gallic, oxalic, tartric acids (strain TA 100 with and without S9 mix), malic and citric acids (strain TA 100 with S9 mix) are mutagenic, the ester of gallic acid giving still a doubtful mutagenic response; their mutagenic potencies are 2 to 3 times smaller than that of bromo-2 ethanol. This observation, complemently with the mutagenicity of some organic esters of the chloro-2 ethanol, proves the potential danger of ethylene oxide used for the fumigation of foods or vegetables and medicinal plants containing much chloride and/or bromide.


Remote monitoring in implantable defibrillator therapy.
The major device manufacturers have introduced systems for remote patient monitoring. These remote monitoring systems promise more efficient patient management, especially in today's clinical setting with the growing number of defibrillator implantations. The aim of this article is to present the role of remote patient monitoring in implantable cardioverter-defibrillator follow-up, its potential benefits and its barriers to widespread diffusion. (Neth Heart J 2008;16:53-6.).


Use of homologous vein grafts for chronic hemodialysis.
The Authors propose using of homologous saphenous vein grafts, coming from a normal saphenectomy by stripping in patients affected by primary varicose veins. The graft is preserved in a particular solution at 4 degrees C in a normal refrigerator and transplanted in uremic patients, which have no more vessels suitable for creating a conventional arteriovenous fistula.


Latent inhibition and schizophrenia: Pavlovian conditioning of autonomic responses.
Latent inhibition (LI) is an important model for understanding cognitive deficits in schizophrenia. Disruption of LI is thought to result from an inability to ignore irrelevant stimuli. The study investigated LI in schizophrenic patients by using Pavlovian conditioning of electrodermal responses in a complete within-subject design. Thirty-two schizophrenic patients (16 acute, unmedicated and 16 medicated patients) and 16 healthy control subjects (matched with respect to age and gender) participated in the study. The experiment consisted of two stages: preexposure and conditioning. During preexposure two visual stimuli were presented. one of which served as the to-be-conditioned stimulus (CSp + ) and the other one was the not-to-be-conditioned stimulus (CSp - ) during the following conditioning ( = acquisition). During acquisition, two novel visual stimuli(CSn + and CSn - ) were introduced. A reaction time task was used as the unconditioned stimulus (US). LI was defined as the difference in response differentiation observed between preexposed and non-preexposed sets of CS + and CS - . During preexposure, the schizophrenic patients did not differ in electrodermal responding from the control subjects, neither concerning the extent of orienting nor the course of habituation. The exposure to novel stimuli at the beginning of the acquisition elicited reduced orienting responses in unmedicated patients compared to medicated patients and control subjects. LI was observed in medicated schizophrenic patients and healthy controls, but not in acute unmedicated patients. Furthermore LI was found to be correlated with the duration of illness: it was attenuated in patients who had suffered their first psychotic episode.


Cache site selection by chipmunks (Tamias spp.) and its influence on the effectiveness of seed dispersal in Jeffrey pine (Pinus jeffreyi).
The effectiveness of Jeffrey pine (Pinus jeffreyi) seed dispersal performed by seed-caching yellow pine chipmunks (Tamias amoenus) and lodgepole chipmunks (Tamias speciosus) was compared to that of wind dispersal in the Sierra Nevada of western Nevada. Wind-dispersed seeds typically fall under or near the parent tree. Chipmunks removed 90 and 97% of 1064 radioactive seeds from each of two simulated wind-dispersed seed shadows in less than 24 h. "Wind-dispersed" seeds were deployed within 12 m of the two "source" trees, but chipmunk caches were found from 2-69 m from the trees. Chipmunks carried nearly all seeds away from source trees, greatly reducing the density of seeds under and near source trees. Caches contained from 1-35 seeds and most were buried 7-21 mm deep. Chipmunks cached in open bitterbrush shrubland with mineral soils much more than expected and cached in closed-canopy Jeffrey pine and lodgepole pine forests with thick needle litter much less than expected. Many Jeffrey pine seedlings and saplings grow in the bitterbrush habitat and few grow in the pine forests. Ten and 20% of the original caches survived until April, the time of seed germination, at the two sites. The movement of wind-dispersed seeds is random relative to environmental variables important in seedling survival, and the wind in coniferous forests cannot quickly bury seeds. The quality of seed dispersal rendered by chipmunks was superior to that provided by the wind because the chipmunks quickly harvested seeds on the ground, moved them away from source trees, and buried them in the ground in habitats and microhabitats where they were more likely to establish new seedlings. The increased quality of seed dispersal provided by animals relative to the wind may help explain why over twenty species of pines have evolved seeds and cones that are adapted for dispersal by seed-caching animals.


Cyclosporin-binding proteins of Plasmodium falciparum.
A number of cyclosporins, including certain non-immunosuppressive ones, are potent inhibitors of the intraerythrocytic growth of the human malarial parasite Plasmodium falciparum. The major cyclosporin-binding proteins of P. falciparum were investigated by affinity chromatography on cyclosporin-Affigel followed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, Western blotting, and peptide mass fingerprinting. The two bands obtained on gels were shown to correspond to cyclophilins, PfCyP-19A (formerly PfCyP-19) and PfCyP-19B, whose genes had been characterised previously. PfCyP-19B was an abundant protein of intraerythrocytic P. falciparum (up to 0.5% of parasite protein) that was present in the highest amounts in schizont-stage parasites. Unexpectedly, given its apparent signal sequence, it was located primarily in the cytosol of the parasite. The peptidyl-prolyl cis-trans isomerase activity of recombinant PfCyP-19B had the same profile of susceptibility to cyclosporin derivatives as the bulk isomerase activity of crude P. falciparum extracts. The binding of cyclosporins to cyclophilins may be relevant to the mechanism of action of the drug in the parasite.


The covered wagon journey: student chronicles in advanced holistic nursing.
This article recounts the experiences of a first cohort of graduate students in a newly implemented advanced holistic nursing (AHN) track, one of only a handful in the nation, and the first in Florida. The increasing popularity of complementary and alternative healing processes represents the insufficiency of a health system of fragmented care and a desire for holistic healing that is beyond mainstream allopathic care. Graduate holistic nurse education equips nurses to explore the commitment needed to advance the evolution of health care. The covered wagon journey is a metaphor for this meaningful participation. Students journaled their experiences as cotravelers in a lone wagon: embarking on a courageous journey, forging a path of discovery, and reaching their destination as pioneers. This cohort experience embodied the central tenets of holistic nursing, thus creating conscious change and unity within a learning community. The future of AHN is addressed in the context of the contemporary health care environment.


Correlation of postoperative recurrence in hepatocellular carcinoma with demethylation of repetitive sequences.
Restriction landmark genomic scanning (RLGS) was utilized to identify novel genomic alterations in hepatocellular carcinoma (HCC). Thirty-one HCC samples were examined by RLGS. Two high intensity spots were common to several RLGS profiles of different HCCs. Nucleotide sequencing and homology search analysis showed that these spots represented repetitive sequences, Human tandem repeat sequence (Genbank, L09552) and centromeric NotI cluster (Genbank, Y10752). These intensified signals were attributable to the occurrence of demethylated areas in the recognition sequence of the NotI site of the corresponding fragments. The intensity of these spots in the RLGS profile reflects their degree of demethylation, which was significantly correlated with postoperative recurrence, even in patients regarded as belonging to the good prognosis group by conventional prognostic factors. Multivariate analysis showed that the intensities of the two spots retained independent prognostic value. This is a new type of predictive factor for HCC based on epigenetic changes in hepatocarcinogenesis, and in the future it is expected to be of great value in making preoperative diagnosis and selecting postoperative therapy.