Approximate emergent synchrony in spatially coupled spiking neurons with discrete interaction.
Models for perceptual grouping and contour integration are presented. Connection weights depend on distances and angle differences, while neurons evolve following a spiking dynamics (Izhikevich's model in most of the considered cases). Although the studied synapses depend on discrete three-valued functions, simulations display the emergence of approximate synchrony, making these cognitive tasks possible. Noise effects are examined, and the possibility of achieving similar results with a different neuron model is discussed.


Chronic administration of genistein improves aortic reactivity of streptozotocin-diabetic rats: mode of action.
Diabetes mellitus is associated with major cardiovascular risk factors which are responsible for excess morbidity and mortality. Soy isoflavones like genistein are beneficial for correcting the hyperglycemia and preventing some diabetic complications. Thus, the effect of chronic administration of genistein was studied on aortic reactivity of streptozotocin (STZ)-diabetic rats. Male diabetic rats received genistein 1 mg/kg/day (i.p.) for 4 weeks 3 days after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation responses to acetylcholine (ACh) and isosorbide dinitrate (ISD) were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to KCL and PE was significantly lower in genistein-treated diabetic rats relative to untreated diabetic ones. Endothelium removal abolished the significant difference between genistein-treated and untreated diabetic groups regarding contractile response to KCl and PE. Meanwhile, endothelium-dependent relaxation to ACh was significantly higher in genistein-treated diabetic rats as compared to diabetic ones. Pretreatment of rings with N(omega)-L-arginine methyl ester (L-NAME) and indomethacin (INDO) significantly attenuated the observed responses. Meanwhile, one-month diabetes resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity in aortic tissue and genistein treatment attenuated the increased MDA content and reduced activity of SOD. Therefore, chronic treatment of diabetic rats with genistein could prevent the abnormal functional changes in vascular reactivity in diabetic rats through nitric oxide- and prostaglandin-dependent pathways and via attenuating oxidative stress in the wall of aortic tissue.


The ergodic theorems of demography: a simple proof.
Standard proofs of the ergodic theorems of demography rely on theorems borrowed from positive matrix theory, tauberian theory, and the theory of time-inhomogeneous Markov matrices. These proofs are efficient and expedient, but they give little direct insight into the mechanism that causes ergodicity. This paper proposes a simple and unified proof of the two ergodic theorems. It is shown that the birth dynamics can be decomposed into a smoothing process that progressively levels out past fluctuations in the birth sequence and a reshaping process that accounts for current period-to-period changes in vital rates. The smoothing process, which causes the birth sequence to lose information on its past shape, is shown to be the ergodic mechanism behind both theorems.


Visante™ OCT measurement of central corneal thickness following Descemet's stripping endothelial keratoplasty.
A 63-year-old man with Fuchs' dystrophy and cataract underwent successful phacoemulsification, insertion of a posterior chamber intraocular lens, and Descemet's stripping endothelial keratoplasty (DSEK) of the right eye. At 1-month follow-up, measurement of central corneal thickness (CCT) obtained by ultrasound pachymetry was 549 μm. The ultrasound pachymetry measurement was thought to be an artifact, so anterior segment optical coherence tomography analysis of the right eye was performed. Both host and graft tissue were imaged in cross-section; optical coherence tomography measurement of CCT was 769 μm. Reliable measurements of CCT are clinically important following DSEK. This case demonstrates that anterior segment optical coherence tomography imaging and analysis software may provide a more appropriate measurement of CCT in patients who have undergone DSEK.


Ethics, climate change and health - a landscape review.
Anthropogenic climate change is unequivocal, and many of its physical health impacts have been identified, although further research is required into the mental health and wellbeing effects of climate change. There is a lack of understanding of the importance of ethics in policy-responses to health and climate change which is also linked to the lack of specific action-guiding ethical resources for researchers and practitioners. There is a marked paucity of ethically-informed health input into economic policy-responses to climate change-an area of important future work. The interaction between health, climate change and ethics is technically and theoretically complex and work in this area is fragmentary, unfocussed, and underdeveloped. Research and reflection on climate and health is fragmented and plagued by disciplinary silos and exponentially increasing literature means that the field cannot be synthesised using conventional methods. Reviewing the literature in these fields is therefore methodologically challenging. Although many of the normative challenges in responding to climate change have been identified, available theoretical approaches are insufficiently robust, and this may be linked to the lack of action-guiding support for practitioners. There is a lack of ethical reflection on research into climate change responses. Low-HDI (Human Development Index) countries are under-represented in research and publication both in the health-impacts of climate change, and normative reflection on health and climate change policy. There is a noticeable lack of ethical commentary on a range of key topics in the environmental health literature including population, pollution, transport, energy, food, and water use. Serious work is required to synthesise the principles governing policy responses to health and climate change, particularly in relation to value conflicts between the human and non-human world and the challenges presented by questions of intergenerational justice.


Single-cell enabled comparative genomics of a deep ocean SAR11 bathytype.
Bacterioplankton of the SAR11 clade are the most abundant microorganisms in marine systems, usually representing 25% or more of the total bacterial cells in seawater worldwide. SAR11 is divided into subclades with distinct spatiotemporal distributions (ecotypes), some of which appear to be specific to deep water. Here we examine the genomic basis for deep ocean distribution of one SAR11 bathytype (depth-specific ecotype), subclade Ic. Four single-cell Ic genomes, with estimated completeness of 55%-86%, were isolated from 770 m at station ALOHA and compared with eight SAR11 surface genomes and metagenomic datasets. Subclade Ic genomes dominated metagenomic fragment recruitment below the euphotic zone. They had similar COG distributions, high local synteny and shared a large number (69%) of orthologous clusters with SAR11 surface genomes, yet were distinct at the 16S rRNA gene and amino-acid level, and formed a separate, monophyletic group in phylogenetic trees. Subclade Ic genomes were enriched in genes associated with membrane/cell wall/envelope biosynthesis and showed evidence of unique phage defenses. The majority of subclade Ic-specfic genes were hypothetical, and some were highly abundant in deep ocean metagenomic data, potentially masking mechanisms for niche differentiation. However, the evidence suggests these organisms have a similar metabolism to their surface counterparts, and that subclade Ic adaptations to the deep ocean do not involve large variations in gene content, but rather more subtle differences previously observed deep ocean genomic data, like preferential amino-acid substitutions, larger coding regions among SAR11 clade orthologs, larger intergenic regions and larger estimated average genome size.


[Effect of ethanol on the biosynthesis of major components of triacylglycerols and phospholipids in the rat liver].
Content of triacylglycerols was increased in rat liver tissue after administration of ethanol. Independent studies of biosynthesis of fatty acid and glycerol components of glycerolipids exhibited that 3H-leucine was mainly consumed in synthesis of glycerol moiety of phospholipids and triacylglycerols, whereas 14C-acetate was utilized in synthesis of fatty acids. Ethanol activated most distinctly the synthesis of glycerol moiety as compared with the synthesis of triacylglycerol fatty acids. In rat liver tissue ethanol caused an accumulation of unsaturated and monoenic fatty acids, while the ratio of arachidonic acid in phospholipids was decreased. Synthesis of triacylglycerol fatty acids was activated in presence of ethanol with simultaneous decrease in the rate of the label incorporation into linoleic and arachidonic acids; synthesis of fatty acids was stimulated de novo but the following elongation and desaturation of linoleic acid was inhibited. Ethanol activated more effectively esterification of fatty acids with formation of triacylglycerols as compared with phospholipids. Incorporation of the label into glycerol molecule occurred in response to activation of glycero-glyconeogenesis by ethanol. Acetyl-CoA, derived from 14C-acetate, was mainly used in synthesis of triacylglycerols, diacylglycerols, free cholesterol and its esters. Acetyl-CoA, produced from 3H-leucine, was mostly common involved in synthesis of monoacylglycerols and phospholipids.


Physiological predictors of maximum treadmill walking performance in patients with intermittent claudication.
The purpose of this investigation was to identify physiological predictors of maximum treadmill walking performance (MWD) in patients with intermittent claudication. Forty-five claudicants performed a graded treadmill test to determine MWD, peak oxygen uptake, and gas exchange threshold. Calf muscle oxygenation (StO (2)) at 1 min and time to minimum StO (2) were also measured using near-infrared spectroscopy. On other occasions, peak calf blood flow, resting ankle-brachial index, and pulmonary oxygen uptake kinetics during steady-state walking were assessed. A forward stepwise multiple regression analysis was performed to determine predictors of MWD. A regression model comprising time to minimum StO (2), peak oxygen uptake, and StO (2) at 1 min explained 64% of the variation in MWD. The results suggest that cardiopulmonary fitness and the ability to match oxygen delivery to metabolic demand are important determinants of walking performance in claudicants, and that certain near-infrared spectroscopy variables might be useful in studies that evaluate the mechanisms of clinical improvement with different treatment interventions.


Dynamic Functional Connectivity Analysis Using Network-Based Brain State Identification, Application on Temporal Lobe Epilepsy.
Epilepsy is a brain network disorder caused by discharges of interconnected groups of neurons and resulting brain dysfunction. The brain network can be characterized by intra- and inter-regional functional connectivity (FC). However, since the BOLD signal is inherently non-stationary, the FC is evidenced to be varying over time. Considering the dynamic characteristics of the functional network, we aimed to obtain dynamic brain states and their properties using network-based analyses for the comparison of healthy control and temporal lobe epilepsy (TLE) groups and also lateralization of TLE patients. We used dwelling time, transition time, and brain network connection in each state as the dynamic features for this purpose. Results showed a significant difference in dwelling time and transition time between the healthy control group and both left TLE and right TLE groups and also a significant difference in brain network connections between the left and right TLE groups.


A pulmonary giant cell carcinoma in a dog.
A case of a large cell anaplastic carcinoma of the giant cell type in the lungs of a 5 year-old crossbred male Labrador is discussed. The dog was weak, depressed, febrile and markedly dyspnoeic. An intermittent moist cough and auscultable crackling rales were evident. Radiographic examination was indicative of pneumonia and pulmonic neoplasia. The dog died 36 hours after admission despite antibiotic and supportive therapy. At autopsy, the neoplasm appeared as numerous firm greyish-white nodules of varying size throughout all the lung lobes whilst in the right intermediate and diaphragmatic lobes the neoplasm was completely confluent. The microscopic features included: intra-alveolar composites of cells exhibiting considerable nuclear and cytoplasmic pleomorphism; the presence of numerous giant cells scattered throughout the tumour; the occurrence of tumour emboli within both venous and lymphatic vessels; and, metastatic foci in the bronchial and mediastinal lymph nodes. These features were considered to reflect a high degree of malignancy. Comparative and aetiological aspects of bronchogenic carcinomas in man and the dog are discussed.


Effects of integration time on in-water radiometric profiles.
This work investigates the effects of integration time on in-water downward irradiance Ed, upward irradiance Eu and upwelling radiance Lu profile data acquired with free-fall hyperspectral systems. Analyzed quantities are the subsurface value and the diffuse attenuation coefficient derived by applying linear and non-linear regression schemes. Case studies include oligotrophic waters (Case-1), as well as waters dominated by Colored Dissolved Organic Matter (CDOM) and Non-Algal Particles (NAP). Assuming a 24-bit digitization, measurements resulting from the accumulation of photons over integration times varying between 8 and 2048ms are evaluated at depths corresponding to: 1) the beginning of each integration interval (Fst); 2) the end of each integration interval (Lst); 3) the averages of Fst and Lst values (Avg); and finally 4) the values weighted accounting for the diffuse attenuation coefficient of water (Wgt). Statistical figures show that the effects of integration time can bias results well above 5% as a function of the depth definition. Results indicate the validity of the Wgt depth definition and the fair applicability of the Avg one. Instead, both the Fst and Lst depths should not be adopted since they may introduce pronounced biases in Eu and Lu regression products for highly absorbing waters. Finally, the study reconfirms the relevance of combining multiple radiometric casts into a single profile to increase precision of regression products.


Food intake, growth and tissue amino acids in rats fed acid analogues.
The objective of this study was to examine the effects of dietary additions of analogues of large neutral amino acids (LNAA), previously shown to inhibit entry of natural LNAA into brain, on food intake, growth and tissue concentrations of specific amino acids in young rats. A mixture of norleucine, norvaline, alpha-aminophenylacetate and alpha-aminooctanote (atypical amino acids, AAA) markedly depressed food intake and growth of rats fed a 6% protein diet (LP) for 10 d but not of rats fed a 50% protein diet (HP). Except in rats fed HP, dietary AAA usually decreased concentrations of LNAA more than of small neutral amino acids (SNAA) or lysine, especially in brain. Concentrations of LNAA, especially in brain and muscle of rats adapted to LP or HP meals and fed one LP-AAA meal were lower than in similar rats fed one LP meal without AAA; feeding an HP-AAA meal to such rats generally prevented or lessened these changes. AAA-induced changes in SNAA and lysine were usually small in meal-fed rats. When AAA induced decreases in LNAA, the branched-chain amino acids were usually most affected; valine and isoleucine sometimes were undetected in brain and muscle. Serotonin and dopamine concentrations were not low in brain despite low levels of tryptophan and tyrosine. Changes in tissue LNAA concentrations would appear to reflect in part competition by large neutral AAA for transport of natural LNAA from the blood.


GABA-A antagonist causes dramatic expansion of tuning in primary auditory cortex.
Responses from 80 neurons in primary auditory cortex of anesthetized chinchillas were investigated before and during iontophoresis of bicuculline (BIC), a GABA-A antagonist. BIC caused a significant increase in the spontaneous discharge rate (SR) and driven firing rate in most neurons. Threshold decreased in many neurons and the excitatory response area expanded significantly above and below the neuron's characteristic frequency (CF). These results indicate that many neurons in primary auditory cortex receive excitatory inputs from a much broader frequency range than previously believed. GABA-A mediated inhibition can significantly alter the excitability and tuning of auditory cortex and could contribute significantly to cortical plasticity due to experience and cochlear pathology.


Operative results of the inferior capsular shift procedure for multidirectional instability of the shoulder.
Neer and Foster previously described the inferior capsular shift procedure for treating multidirectional instability of the shoulder and reported preliminary results that were quite satisfactory. The purpose of our study was to perform a longer-term follow-up evaluation of the efficacy of the inferior capsular shift procedure for treating multidirectional instability of the shoulder. An inferior capsular shift procedure was used to treat multidirectional instability of the shoulder in forty-nine patients (fifty-two shoulders). All patients had failed to respond to an exercise program. In this series, the operative approach (anterior or posterior) was based on the major direction of the instability, as determined by the preoperative history and physical examination and as verified by examination with the patient under anesthesia. In all of the patients, the inferior capsular shift was the primary attempt at operative stabilization. The repair consisted of a lateral-side (or humeral-side) shift of the capsule to reduce capsular redundancy and, when necessary, a reattachment of the avulsed labrum to the anteroinferior aspect of the glenoid. A redundant capsular pouch was seen in all of the shoulders in this series. In addition, detachment of the anteroinferior aspect of the labrum was found in ten shoulders and an anterior fracture of the glenoid rim was seen in two shoulders. At an average of sixty-one months (range, twenty-four to 132 months), results were available for forty-nine shoulders (forty-six patients). Thirty shoulders (61 percent) had an excellent overall result, sixteen (33 percent) had a good result, one (2 percent) had a fair result, and two (4 percent) had a poor result. Forty-seven (96 percent) of the forty-nine shoulders remained stable at the time of follow-up. Two of the thirty-four shoulders that had been repaired through an anterior approach began to subluxate anteroinferiorly again. None of the fifteen shoulders that had been repaired through a posterior approach had recurrent instability. Full function, including the ability to perform strenuous manual tasks, was restored to forty-five shoulders (92 percent). A return to sports was possible after thirty-one (86 percent) of the thirty-six procedures done in athletes; however, a return to the premorbid level of participation was possible after only twenty-five (69 percent) of the thirty-six procedures. The results in this series demonstrate the efficacy and the durability of the results of the inferior capsular shift procedure for the treatment of shoulders with multidirectional instability. The procedure directly addresses the major pathological feature - a redundant joint capsule. Similar results were seen with either an anterior or a posterior approach, and we continue to approach shoulders with multidirectional instability on the side of greatest instability. A postoperative brace was reserved for patients in whom a posterior approach had been used or in whom an anterior approach had involved extensive posterior capsular dissection (ten of the thirty-four shoulders treated with the anterior approach).


Fetal hemoglobin in sickle cell anemia.
Fetal hemoglobin (HbF) can blunt the pathophysiology, temper the clinical course, and offer prospects for curative therapy of sickle cell disease. This review focuses on (1) HbF quantitative trait loci and the geography of β-globin gene haplotypes, especially those found in the Middle East; (2) how HbF might differentially impact the pathophysiology and many subphenotypes of sickle cell disease; (3) clinical implications of person-to-person variation in the distribution of HbF among HbF-containing erythrocytes; and (4) reactivation of HbF gene expression using both pharmacologic and cell-based therapeutic approaches. A confluence of detailed understanding of the molecular basis of HbF gene expression, coupled with the ability to precisely target by genomic editing most areas of the genome, is producing important preliminary therapeutic results that could provide new options for cell-based therapeutics with curative intent.


Compounds that enhance the tailing activity of Moloney murine leukemia virus reverse transcriptase.
In a previous study, we showed that MMLV-RT has a strong terminal transferase activity, and that the C-, G-, and T-tailing activities are enhanced by dGMP, dCMP, and dAMP, respectively. In this study, to achieve faster reaction and higher tailing efficiency, we screened other compounds for the ability to enhance the tailing activities of MMLV-RT, and determined the corresponding optimal concentrations. The C-, G-, and T-tailing activities were enhanced by guanine, cytosine, and adenine, respectively, and by derivatives thereof, suggesting a transient Watson-Click base pairing between an enhancer molecule and the nucleotide to be incorporated. In the presence of some additives (GMP and GDP for C-tailing and CMP for G-tailing), the tail length increased continuously, resulting in tail lengths of 7 to 15 (GMP and GDP) or 13 to 22 (CMP) nucleotides. Among the compounds that do not induce continuous addition, adenosine, deoxycytidine, and deoxyguanosine mostly enhanced T-, G-, and C-tailings, respectively. The enhancing chemicals described here will improve the feasibility of N-tailing by MMLV-RT in various biotechnological applications.


Semantic knowledge and episodic memory for faces in semantic dementia.
Previous studies have documented poor recognition memory for faces in patients with semantic dementia. Preserved face recognition memory was found in this study, however, so long as atrophy was confined predominantly to the left temporal lobe. Patients with structural damage to the right temporal lobe were typically impaired, with the status of the hippocampus and parahippocampal gyrus (including the perirhinal cortex) on the right being critical. Two single-case studies of patients with predominantly left temporal lobe pathology confirmed good recognition memory for famous faces, even if semantic knowledge about the celebrities depicted was severely degraded. An effect of semantic knowledge on recognition memory became apparent only when perceptually different photographs of the famous people were used at study and test. These results support the view that new episodic learning typically draws on information from both perceptual and semantic systems.


Fullerene and endometallofullerene Kagome lattices with symmetry-forced spin frustration.
Salts of fullerene C60˙- and endometallofullerene Sc3N@Ih-C80˙- radical anions with Bu3MeP+ cations ((Bu3MeP+)3(C60˙-)3·C6H4Cl2 (1) and (Bu3MeP+)3(Sc3N@Ih-C80˙-)3·C6H4Cl2 (2)) have been obtained. The C3 symmetry of the Bu3MeP+ cation provides 2D Kagome lattices with an equilateral triangle arrangement of fullerenes in accordance with trigonal crystal symmetry P31m. The C60˙- and Sc3N@Ih-C80˙- radical anions preserve their monomeric forms in 1 and 2 with the S = 1/2 spin state down to 1.9 K. The close packing of the fullerene radical anions results in strong antiferromagnetic coupling of the spins with Weiss temperatures of -108 K for 1 and -43 K for 2. Compound 1 is a rare example of a magnetic system in which in spite of the strong magnetic coupling of spins no long-range ordering is observed down to 1.9 K. The 13C NMR spectra of the 13C enriched sample of 1 support the absence of the antiferromagnetic ordering of spins down to 1.5 K. Thus, the crystals of 1 preserve large spin frustration forced by the trigonal symmetry. Therefore, compound 1 is a promising candidate for the first observation of a quantum spin liquid (QSL) state in a fullerene-based system. Isostructural salt 2 is the first compound that contains monomeric paramagnetic Sc3N@Ih-C80˙- radical anions stable down to 1.9 K, which show strong spin frustration. These data indicate the ability of endometallofullerenes to give exotic magnetic systems such as QSLs.


Postnatal induction and localization of R7BP, a membrane-anchoring protein for regulator of G protein signaling 7 family-Gbeta5 complexes in brain.
Members of the regulator of G protein signaling 7 (RGS7) (R7) family and Gbeta5 form obligate heterodimers that are expressed predominantly in the nervous system. R7-Gbeta5 heterodimers are GTPase-activating proteins (GAPs) specific for Gi/o-class Galpha subunits, which mediate phototransduction in retina and the action of many modulatory G protein-coupled receptors (GPCRs) in brain. Here we have focused on the R7-family binding protein (R7BP), a recently identified palmitoylated protein that can bind R7-Gbeta5 complexes and is hypothesized to control the intracellular localization and function of the resultant heterotrimeric complexes. We show that: 1) R7-Gbeta5 complexes are obligate binding partners for R7BP in brain because they co-immunoprecipitate and exhibit similar expression patterns. Furthermore, R7BP and R7 protein accumulation in vivo requires Gbeta5. 2) Expression of R7BP in Neuro2A cells at levels approximating those in brain recruits endogenous RGS7-Gbeta5 complexes to the plasma membrane. 3) R7BP immunoreactivity in brain concentrates in neuronal soma, dendrites, spines or unmyelinated axons, and is absent or low in glia, myelinated axons, or axon terminals. 4) RGS7-Gbeta5-R7BP complexes in brain extracts associate inefficiently with detergent-resistant lipid raft fractions with or without G protein activation. 5) R7BP and Gbeta5 protein levels are upregulated strikingly during the first 2-3 weeks of postnatal brain development. Accordingly, we suggest that R7-Gbeta5-R7BP complexes in the mouse or rat could regulate signaling by modulatory Gi/o-coupled GPCRs in the developing and adult nervous systems.


DNA restriction and modification in Escherichia coli: functional analysis of the role of the dnaC(D) gene product.
Escherichia coli strain PC-7 carries two independent temperature-sensitive mutations, one affecting the restriction and modification (R-M) phenotype and the other the DnaC(D) phenotype. The results of complementation and P1 transduction analysis of the mutation affecting the R-M phenotype implicate a fourth gene, designated hsdX, located close to the hsd three-gene complex. The properties of merodiploids constructed between appropriate recipients and F' elements with different mutations in hsdS, hsdR and hsdM genes might indicate that in strain PC-7 the temperature-sensitive products, determined by hsdR and hsdSK cistrons, are synthesized. The role of the temperature-sensitive dnaC(D) gene product in the formation of the restriction endonuclease was studied and no direct relation was found between the DnaC(D) and R-M phenotypes.


Allocation of rehabilitation services: who gets a home evaluation.
The purpose of this study was to (a) identify and describe the subpopulation of rehabilitation inpatients who receive specialized occupational therapy home evaluation services, and (b) examine these data for evidence of inequalities in access to services based on patient gender, race, age, and health insurance status. An archival review was conducted of all inpatient admissions (7,871) to a large urban rehabilitation hospital between January 1, 1994, and December 31, 1998. We had complete data on 7,791 of these patients of whom 6,038 were eligible to receive a home evaluation. Patient demographic data and Functional Independence Measure (FIM) data were obtained in electronic form from the hospital information system. Analysis showed that 12.4% (749/6038) of eligible inpatients received an in-home evaluation, and those who did were significantly more dependent (as measured by the FIM) than those who did not (p < 0.0001). We found no evidence of inequalities in access to this specialized rehabilitation service on the basis of gender, race, age, and type of medical insurance after controlling for level of functional independence. This study found no evidence of inequalities in the allocation of home evaluation services. However, it raises the larger question of how we determine whether inequalities exist. A proper assessment of inequalities in service provision requires that we know the principles by which these services should be allocated and have appropriate measures of the application of these principles. For programmatic and policy reasons, more research is needed to develop well-defined principles of resource allocation, and adequate measures of their impact so we can know whether resources and services are distributed in the way we intend.


Bereavement and spiritual change.
The thesis of this article is that bereavement is a life crisis that challenges one's assumptions about human existence and provides the grounds for spiritual change. Construing a new understanding of the meaning of human existence and revising assumptions about one's place in the universe is a singular form that indicates spiritual change at work. Three aspects must be present for a life crisis to produce spiritual change: The situation must create a psychological imbalance or disequilibrium that resists readily being stabilized; there must be time for reflection; and the person's life must forever afterwards be colored by the crisis. The premise of this article links spiritual change to what J.W. Fowler (1981) termed transformed faith consciousness and argues that the dual process model of coping with loss (M.S. Stroebe & H. Schut, 1995; M.S. Stroebe, H. Schut, & W.A. Stroebe, 1995; M.S. Stroebe, H. Schut, & J. Van Den Bout, 1994) provides a means to understand how dealing with grief can evoke spiritual change. Some brief case examples are used to examine the thesis that bereavement triggers spiritual change.


Wogonin induces retinal neuron-like differentiation of bone marrow stem cells by inhibiting Notch-1 signaling.
Age-related macular degeneration and retinitis pigmentosa are major causes of irreversible vision loss in the elderly and, despite sustained efforts, current treatments are largely ineffective. Wogonin is a bioactive plant flavonoid possessing a range of beneficial properties, including neuroprotective effects. We investigated the ability of wogonin to promote retinal neuron-like differentiation of bone marrow stem cells (BMSCs) and assessed the involvement of Notch-1 signaling in this process. Cultured mouse BMSCs were left untreated or exposed to neurotrophic factors in the presence or absence of wogonin, and western blotting, RT-PCR and immunofluorescence were used to identify changes in molecular markers of stemness and neuroretinal differentiation. Proteins in the Notch-1 signaling pathway, a main negative regulator of neurogenesis, were also examined by western blotting. We found that expression of stem cell markers was reduced, while markers of mature retinal neurons, bipolar cells and photoreceptors were increased in wogonin-treated BMSCs. Wogonin also dose-dependently decreased expression of Notch-1 signaling proteins. Moreover, blockade of Notch-1 both mimicked and enhanced the effect of wogonin to facilitate BMSC differentiation into retinal neuron-like cells. Wogonin thus appears to promote retinal neuron-like differentiation of BMSCs by antagonizing the inhibitory actions of Notch-1 signaling on neurogenesis and may be useful in the treatment of retinal degenerative diseases.


Non-corticosteroid treatment for nephrotic syndrome in children.
Eighty to ninety per cent of children with steroid-sensitive nephrotic syndrome (SSNS) have relapses. About half relapse frequently and are at risk of the adverse effects of corticosteroids. Non-corticosteroid immunosuppressive agents are used to prolong periods of remission in children who relapse frequently. However these non-corticosteroid agents also have significant potential adverse effects. Currently there is no consensus as to the most appropriate second line agent in children who are steroid sensitive, but who continue to relapse. To evaluate the benefits and harms of non-corticosteroid immunosuppressive agents in relapsing SSNS in children. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, reference lists of articles, abstracts from proceedings and contact with known investigators. Search date: August 2004 RCTs or quasi-RCTs were included if they were undertaken in children with relapsing SSNS, if they compared non-corticosteroid agents with placebo, prednisone or no treatment, different doses and/or durations of the same non-corticosteroid agent, different non-corticosteroid agents and outcome data at six months. Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as relative risk (RR) with 95% confidence intervals (CI). Twenty trials involving 923 children were identified. Cyclophosphamide (three trials: RR 0.44, 95% CI 0.26 to 0.73) and chlorambucil (two trials: RR 0.13, 95% CI 0.03 to 0.57) significantly reduced the relapse risk at six to twelve months compared with prednisone alone. In the single chlorambucil versus cyclophosphamide trial, there was no observed difference in relapse risk at two years (RR 1.31, 95% CI 0.80 to 2.13). Cyclosporin was as effective as cyclophosphamide (one trial: RR 1.07, 95% CI 0.48 to 2.35) and chlorambucil (one trial: RR 0.82, 95% CI 0.44 to 1.53) but the effect was not sustained when cyclosporin was ceased. During treatment, levamisole (three trials: RR 0.60, 95% CI 0.45 to 0.79) was more effective than steroids alone but the effect was not sustained. Mizoribine (one trial) and azathioprine (two trials) were no more effective than placebo or prednisone alone in maintaining remission. Eight week courses of cyclophosphamide or chlorambucil and prolonged courses of cyclosporin and levamisole reduce the risk of relapse in children with relapsing SSNS compared with corticosteroids alone. Clinically important differences in efficacy among these agents are possible and further comparative trials are still needed.


Use of heme iron concentrate in the fortification of weaning foods.
The purpose of this study was to evaluate the technological feasibility of fortifying homogenized weaning food with a porcine heme concentrate. The stability of iron and the organoleptic qualities of two infant weaning foods (a commercial homogenized nonfortified weaning food, NFWF, and the same food fortified with 0.5% of porcine heme concentrate, FWF) were tested throughout 8 months of storage at room temperature and at 37 degrees C. Heme iron decreased with storage time; however, the proportion of this highly available iron was considerably higher in FWF than in NFWF. The addition of heme iron changed significantly the color of the weaning food measured instrumentally, although high temperatures and length of storage time, did not modify Lab, chroma, and hue angle values in both samples. Organoleptic attributes presented a marked stability even in NFWF stored at room temperature and 37 degrees C.


Drug-drug interaction studies of cardiovascular drugs involving P-glycoprotein, an efflux transporter, on the pharmacokinetics of edoxaban, an oral factor Xa inhibitor.
Edoxaban, an oral direct factor Xa inhibitor, is in development for thromboprophylaxis, including prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). P-glycoprotein (P-gp), an efflux transporter, modulates absorption and excretion of xenobiotics. Edoxaban is a P-gp substrate, and several cardiovascular (CV) drugs have the potential to inhibit P-gp and increase drug exposure. To assess the potential pharmacokinetic interactions of edoxaban and 6 cardiovascular drugs used in the management of AF and known P-gp substrates/inhibitors. Drug-drug interaction studies with edoxaban and CV drugs with known P-gp substrate/inhibitor potential were conducted in healthy subjects. In 4 crossover, 2-period, 2-treatment studies, subjects received edoxaban 60 mg alone and coadministered with quinidine 300 mg (n = 42), verapamil 240 mg (n = 34), atorvastatin 80 mg (n = 32), or dronedarone 400 mg (n = 34). Additionally, edoxaban 60 mg alone and coadministered with amiodarone 400 mg (n = 30) or digoxin 0.25 mg (n = 48) was evaluated in a single-sequence study and 2-cohort study, respectively. Edoxaban exposure measured as area under the curve increased for concomitant administration of edoxaban with quinidine (76.7 %), verapamil (52.7 %), amiodarone (39.8 %), and dronedarone (84.5 %), and exposure measured as 24-h concentrations for quinidine (11.8 %), verapamil (29.1 %), and dronedarone (157.6 %) also increased. Administration of edoxaban with amiodarone decreased the 24-h concentration for edoxaban by 25.7 %. Concomitant administration with digoxin or atorvastatin had minimal effects on edoxaban exposure. Coadministration of the P-gp inhibitors quinidine, verapamil, and dronedarone increased edoxaban exposure. Modest/minimal effects were observed for amiodarone, atorvastatin, and digoxin.


A comparison of machine learning classifiers for pediatric epilepsy using resting-state functional MRI latency data.
Epilepsy affects 1 in 150 children under the age of 10 and is the most common chronic pediatric neurological condition; poor seizure control can irreversibly disrupt normal brain development. The present study compared the ability of different machine learning algorithms trained with resting-state functional MRI (rfMRI) latency data to detect epilepsy. Preoperative rfMRI and anatomical MRI scans were obtained for 63 patients with epilepsy and 259 healthy controls. The normal distribution of latency z-scores from the epilepsy and healthy control cohorts were analyzed for overlap in 36 seed regions. In these seed regions, overlap between the study cohorts ranged from 0.44-0.58. Machine learning features were extracted from latency z-score maps using principal component analysis. Extreme Gradient Boosting (XGBoost), Support Vector Machines (SVM), and Random Forest algorithms were trained with these features. Area under the receiver operating characteristics curve (AUC), accuracy, sensitivity, specificity and F1-scores were used to evaluate model performance. The XGBoost model outperformed all other models with a test AUC of 0.79, accuracy of 74%, specificity of 73%, and a sensitivity of 77%. The Random Forest model performed comparably to XGBoost across multiple metrics, but it had a test sensitivity of 31%. The SVM model did not perform >70% in any of the test metrics. The XGBoost model had the highest sensitivity and accuracy for the detection of epilepsy. Development of machine learning algorithms trained with rfMRI latency data could provide an adjunctive method for the diagnosis and evaluation of epilepsy with the goal of enabling timely and appropriate care for patients.


The diagnostic value of skin prick testing in children with food allergy.
The diagnostic accuracy of the skin prick test (SPT) in food allergy is controversial. We have developed diagnostic cut-off levels for SPT in children with allergy to cow milk, egg and peanut. Based on 555 open food challenges in 467 children (median age 3.0 yr) we defined food-specific SPT weal diameters that were '100% diagnostic' for allergy to cow milk (>or=8 mm), egg (>or=7 mm) and peanut (>or=8 mm). In children < 2 yr of age, the corresponding weal diameters were >or=6 mm, >or=5 mm and >or=4 mm, respectively. These SPT cut-off levels were prospectively validated in 90 consecutive children <or=2 yr with challenge-proven food allergy. In young infants under 6 months of age who have not previously been exposed to a particular food item, the SPT were often negative or below the diagnostic cut-off but reached the diagnostic cut-off at the time of challenge in the second year of life. We assessed the diagnostic agreement between food-specific immunoglobulin E (IgE) antibody levels and SPT in a cohort of 820 infants and children under 2 yr of age (median age 13.1 months) with suspected allergy to cow milk, egg or peanut. When applying published 95%-positive predictive CAP values, the diagnostic accuracy of SPT and IgE antibody levels was similar for cow milk, but SPT was more sensitive in diagnosing allergy to egg (p < 0.0001) and peanut (p < 0.0001). Further studies are required to define age-specific diagnostic IgE antibody and SPT cut-off levels use in infants under 2 yr of age with suspected food allergies.


[Isolation and purification of NADP-dependent "L-malate"-enzyme from corn leaves].
Isolation and purification of "malic-enzyme" NADP was done using fractionation by ammonium sulfate, anion-exchange chromatography on DEAE cellulose, gel-filtration through Sephadex G-200 and purification on DEAE Sephadex A-50. The isoenzyme isolated had a specific activity of 40-50 mkM/mg protein per min (approximately 80-fold purification) and contained negligible admixtures.


Mental health care from the public perspective: the Texas Medication Algorithm Project.
Medication treatment algorithms have been suggested as a strategy to provide uniform care at predictable costs. The Texas Medication Algorithm Project is a 3-phase study designed to provide solid data on the usefulness of medication algorithms. In phase 1, medication algorithms for the treatment of schizophrenia, major depressive disorder, and bipolar disorder were developed. Phase 2 was a feasibility study of these algorithms, and phase 3, now underway, compares the costs and outcome in 3 groups, one using a combination of an algorithm and patient/family education, a second using treatment as usual in a clinic that uses an algorithm for a different disorder, and a third using treatment as usual in a nonalgorithm clinic.


Chemical and Electrochemical Alkali Cations Intercalation/Release in an Ionic Hydrogen Bonded Network.
The chemical oxidation of a hydrogen bonded network, formed upon combination of a hydrogen bond donor dication (12+, a dicationic bis-amidinium organic moiety bearing four propyl chains) with [FeIII/II(CN)6]3-/4- anions has been studied using vibrational spectroscopies. The postsynthetic oxidation of the microcrystalline powder of X213-[FeII(CN)6]2 (X = Na, K, and Cs) by S2O82- into 13-[FeIII(CN)6]2 appeared to be partial for X = K+ and Cs+ and total for Na213-[FeII(CN)6]2. It corresponds to a two-step process involving a second order reaction. The reaction time appears to be dependent on the nature of the alkali cation and is faster for X = Na+. The integrity of the hydrogen bonded network, after oxidation, was also confirmed by powder X-ray diffraction. The flexible nature of the hydrogen bonded network allows alkali cation motions within the network during the oxidation process. In addition, the investigation of the electrochemical behavior evidenced an amorphous deposition on a gold electrode immersed into a solution containing (12+ and [FeIII(CN)6]3-) after 100 cycles. This is the first evidence of an electrochemical ion intercalation for a molecular hydrogen bonded network.


[Acute pericarditis associated with Plasmodium ovale malaria].
The purpose of this report is to describe a rare case of benign acute pericarditis associated with recurrent Plasmodium ovale malaria. It was observed in a 33-year-old soldier who was stationed in Djibouti after serving several previous stints in West Africa. A favorable clinical outcome was achieved using chloroquin (30 mg/kg on 6 days) in association with NSAID followed by salicylates for one month. Re-examination at one year showed no recurrence. This case shows that Plasmodium ovale malaria must be considered as a potential etiology for acute benign pericarditis in patients with a history of travel to endemic countries.


The opioid-prescribing practices of Australian general practice registrars: an interview study.
Approximately half of the opioids prescribed by Australian GP and GP registrars are for chronic non-cancer pain-despite limited therapeutic benefit, and serious risks of harm. Understanding the factors driving non-evidence-based opioid prescribing may improve GP training and education. To explore attitudes, beliefs, knowledge and self-reported factors influencing the opioid-prescribing decisions of Australian GP registrars. Telephone interviews were undertaken with 20 GP registrars in 2018-19. Interviews were 30-60 minutes in duration, audio-recorded and de-identified. Braun and Clarke's 6-phase framework was adopted for reflexive thematic analysis of data and managed using QSR NVivo software. Twenty registrars were recruited; 8 men and 12 women. Three themes were identified. Difficult chronic pain consultations negatively affected the registrar well-being. Registrars role modelled their supervisors' opioid-prescribing practices, even if they perceived it to be unsafe. Registrars lacked confidence in initiating, prescribing and weaning opioids, recognizing drug-seeking behaviours and declining to prescribe-but felt confident in their knowledge of opioid pharmacology. Registrars were aware of evidence-based prescribing recommendations and risk reduction strategies but struggled to translate this into practice. Non-evidence-based opioid prescribing by Australian GP registrars is multifactorial. Emotionally difficult pain consultations, poor supervision and low prescriber confidence may contribute to unsafe prescribing. Improving registrar prescribing may require interventions to improve risk reduction, training in communication and role modelling by supervisors.


Hyperbaric oxygen reduces tissue hypoxia and hypoxia-inducible factor-1 alpha expression in focal cerebral ischemia.
The usefulness of hyperbaric oxygen (HBO) and normobaric hyperoxia in acute ischemic stroke is being reexplored because both improve outcome in experimental cerebral ischemia. However, even the basic mechanisms underlying oxygen therapy are poorly understood. We investigated the effect of both oxygen therapies on tissue hypoxia and on the transcription factor hypoxia-inducible factor-1 alpha. Mice were subjected to filament-induced middle cerebral artery occlusion for 2 hours. Twenty-five minutes after filament introduction, mice breathed normobaric air, normobaric 100% O(2) (normobaric hyperoxia), or 100% O(2) at 3 ata (HBO) for 95 minutes. Hypoxic regions were mapped on tissue sections after preischemic infusion of the in vivo hypoxia marker EF-5. Hypoxia-inducible factor-1 alpha protein was measured after 2-hour middle cerebral artery occlusion using immunofluorescence and immunoblotting. Vascular endothelial growth factor expression was analyzed using in situ mRNA hybridization. Severity of ischemia did not differ among groups. HBO (35.2+/-10.4 mm(2)) significantly reduced the area of EF-5-stained hypoxic regions in focal cerebral ischemia compared with normobaric hyperoxia (46.4+/-11.2 mm(2)) and air (49.1+/-8 mm(2), P<0.05, analysis of variance). Topographically, EF-5 fluorescence was decreased in medial striatum and in cortical ischemic border areas. Immunohistochemistry and immunoblotting revealed lower hypoxia-inducible factor-1 alpha protein in the ischemic hemisphere of HBO-treated mice. Moreover, mRNA in situ hybridization showed lower expression of vascular endothelial growth factor in HBO and normobaric hyperoxia groups. Measurement of extrinsic and intrinsic markers of hypoxia revealed that HBO improves penumbral oxygenation in focal ischemia. Modification of the transcription factor hypoxia-inducible factor-1 alpha and its downstream targets may be involved in effects of HBO.


The cellular and molecular etiology of the craniofacial defects in the avian ciliopathic mutant talpid2.
talpid(2) is an avian autosomal recessive mutant with a myriad of congenital malformations, including polydactyly and facial clefting. Although phenotypically similar to talpid(3), talpid(2) has a distinct facial phenotype and an unknown cellular, molecular and genetic basis. We set out to determine the etiology of the craniofacial phenotype of this mutant. We confirmed that primary cilia were disrupted in talpid(2) mutants. Molecularly, we found disruptions in Hedgehog signaling. Post-translational processing of GLI2 and GLI3 was aberrant in the developing facial prominences. Although both GLI2 and GLI3 processing were disrupted in talpid(2) mutants, only GLI3 activator levels were significantly altered in the nucleus. Through additional fine mapping and whole-genome sequencing, we determined that the talpid(2) phenotype was linked to a 1.4 Mb region on GGA1q that contained the gene encoding the ciliary protein C2CD3. We cloned the avian ortholog of C2CD3 and found its expression was ubiquitous, but most robust in the developing limbs and facial prominences. Furthermore, we found that C2CD3 is localized proximal to the ciliary axoneme and is important for docking the mother centriole to the ciliary vesicle and cell membrane. Finally, we identified a 19 bp deletion in talpid(2) C2CD3 that produces a premature stop codon, and thus a truncated protein, as the likely causal allele for the phenotype. Together, these data provide insight into the cellular, molecular and genetic etiology of the talpid(2) phenotype. Our data suggest that, although the talpid(2) and talpid(3) mutations affect a common ciliogenesis pathway, they are caused by mutations in different ciliary proteins that result in differences in craniofacial phenotype.


Greater saphenous venous access as an alternative in children.
In the pediatric population, obtaining venous access in high-risk neonates, severely ill children with cardiac anomalies or very young children (<10 kg) can be very challenging. In the literature to date, the greater saphenous vein has not been primarily used by interventional radiologists as an entry site for venous access in children. To demonstrate the utility and effectiveness of using the greater saphenous vein as a venous access site for the placement of peripherally inserted central catheters in children. This is a retrospective study from a large tertiary care children's hospital from November 2010 to August 2012. Peripheral insertion of central venous catheters (PICC) using the greater saphenous vein was attempted in 86 children ranging in age from 3 days to 17 years (mean: 1.8 years). Indications included congenital heart disease, urinary tract infection, intravenous access, pneumonia, meningitis, total parenteral nutrition, sepsis and other infections. All procedures were performed by interventional radiologists. No insertion-related complications were identified. There was no follow-up planning, but no mechanical or infectious complications were brought to our attention. Of the 86 patients in whom PICC placement was attempted, placement was successful in 67 (78%). Forty-two PICCs were placed in the greater saphenous vein at the thigh level using US guidance and 25 at the ankle level using anatomical landmarks. The mean weight of the 67 patients who underwent successful placement was 9.98 kg, with 51 (76%) weighing <10 kg. The mean vessel diameter in placement failures was 1.35 mm compared to 1.83 mm in successful placement. Inability to obtain venous access was the cause of failure in all thigh access sites while inability to advance the catheter centrally was the cause of failure for all ankle access sites. A total of 1,060 catheter days (with a maximum dwell time of 97 days in one patient) were reviewed without complication. In children, the greater saphenous vein provides a safe, suitable alternative for venous access, particularly in very young children (<10 kg) and in a select group of older children who are not mobile. In the lower extremities, greater saphenous venous puncture and access may be a preferred initial access site in small children to preserve future venous access.


Student drug testing in the context of positive and negative school climates: results from a national survey.
Positive school climates and student drug testing have been separately proposed as strategies to reduce student substance use in high schools. However, the effects of drug testing programs may depend on the favorability of school climates. This study examined the association between school drug testing programs and student substance use in schools with different climates. The analysis was based on a nationally representative sample of 943 high school students (48% female) ranging from 14 to 19 years of age (62% identifying as white, 18% Hispanic, 13% African American, and 7% in other categories). Results showed that both male and female students in schools with positive climates reported lower levels of personal substance use. Drug testing was associated with lower levels of personal substance use in positive school climates, but only for female students. There was no relationship between drug testing and male students' substance use. The results are discussed in terms of the importance of considering school climates before implementing drug-testing programs in high schools.


Work-family interface from a life and career stage perspective: the role of demands and resources.
Work-family conflict and enrichment are experiences that occur daily and have substantial consequences for employees, their families, and the organizations that employ them. The aim of the current review is to make a link between life and career stage, work and family conditions, and the work-family interface. The basic proposition is that life stages partly determine career development, and consequently the specific working conditions (job demands and job resources) and family conditions (family demands and family resources) that individuals are exposed to. As a result, the specific demands and resources in the work and family domains determine to what extent individuals experience that work and family are conflicting or enriching life domains. In this review we suggest that individuals in early adulthood will experience high inter-role conflict and low facilitation due to high demands and low resources in both life domains, while individuals in late adulthood will experience the opposite pattern; that is, low conflict and high facilitation due to low demands and high resources in both domains. Individuals in middle adulthood will experience high work-family conflict but also high family-work facilitation due to the presence of high job demands and resources in both life domains. Integrating life and career stage perspectives and the experience of work-family interface is of notable practical utility because it provides a mechanism to make more informed decisions about the relative need for and corresponding benefits of work-family programs.


Communication moderates effects of residential mobility on relationship quality among ethnically diverse couples.
Although interpersonal communication is a defining feature of committed relationships, the quality of couple communication has not proven to be a straightforward cause of relationship quality. At the same time, emerging models argue that external circumstances likely combine with communication to generate changes in relationship quality. We integrate these 2 ideas by proposing that communication does exert effects on changes in relationship quality, but primarily when couples encounter challenging situations that require an adaptive response. In the present study we examine residential moves to different neighborhoods as one such adaptive challenge. We conducted a longitudinal study of 414 newlywed couples to examine whether observed communication moderates the effect of moving to higher- or lower-income neighborhoods on changes in relationship quality. Results indicate that communication exerts no main effects on relationship quality. Consistent with the proposed model, however, wives who displayed less positive, less effective, and more negative behaviors experienced greater decreases in relationship quality, but only when couples moved to substantially higher-income neighborhoods. Because communication may not affect relationship quality until couples encounter qualitatively new demands, strengthening relationships may pivot less on improving communication skills and more on ensuring that couples' circumstances do not overwhelm the skills that they already possess. (PsycINFO Database Record


Partial fourier shells trajectory for non-cartesian MRI.
Non-Cartesian MRI acquisition has demonstrated various advantages in many clinical applications. The shells trajectory is a 3D non-Cartesian MRI acquisition technique that samples the k-space using a series of concentric shells to achieve efficient 3D isotropic acquisition. Partial Fourier acquisition is an acceleration technique that is widely used in Cartesian MRI. It exploits the conjugate symmetry of k-space measurement to reduce the number of k-space samples compared to full-k-space acquisition, without loss of spatial resolution. For a Cartesian MRI acquisition, the direction of partial Fourier acceleration is aligned either with the phase encoded or frequency encoded direction. In those cases, the underlying image matrix can be reconstructed from the undersampled k-space data using a non-iterative, homodyne reconstruction framework. However, designing a non-Cartesian acquisition trajectory that is compatible with non-iterative homodyne reconstruction is not nearly as straightforward as in the Cartesian case. One reason is the non-iterative homodyne reconstruction requires (slightly over) half of the k-space to be fully sampled. Since the direction of partial Fourier acceleration varies throughout the acquisition in the non-Cartesian trajectory, directly applying the same partial Fourier acquisition pattern (as in Cartesian acquisitions) to a non-Cartesian trajectory does not necessarily yield a continuous, physically-achievable trajectory. In this work, we develop an asymmetric shells trajectory with fully-automated trajectory and gradient waveform design to achieve partial Fourier acquisition for the shells trajectory. We then demonstrate a non-iterative image reconstruction framework for the proposed trajectory. Phantom and in vivo brain scans based on spoiled gradient echo (SPGR) shells and magnetization-prepared shells (MP-shells) were performed to test the proposed trajectory design and reconstruction method. Our phantom and in vivo results demonstrate that the proposed partial Fourier shells trajectory maintains the desirable image contrast and high sampling efficiency from the fully sampled shells, while further reducing data acquisition time.


[Immigration and HIV: pulmonary, cutaneous and genitourinary syndromes. Eosinophilia].
Infectious diseases are the leading cause of mortality in less developed countries, many of which are located in tropical areas. These diseases have particular features than can hamper diagnosis unless clinicians are familiar with their characteristics. The present article describes the clinical pattern of pulmonary, cutaneous and genitourinary tropical diseases and the main principles of their diagnosis. Emphasis is placed on their geographical distribution and the influence of HIV infection.


Expression and characterization of a class III alcohol dehydrogenase gene from Gluconobacter frateurii in the presence of methanol during glyceric acid production from glycerol.
Some acetic acid bacteria have been shown to produce large amounts of glyceric acid (GA) from glycerol, which is a by-product of biodiesel fuel (BDF) production. Previously, a Gluconobacter strain was found that produced decreased amounts of GA from glycerol in the presence of methanol, a major ingredient of raw glycerol derived from the BDF industry. Thus, a comparative transcriptome analysis of Gluconobacter frateurii NBRC103465 was performed to investigate changes in gene expression during GA production from glycerol in the presence of methanol. Cells grown with methanol showed upregulated expression of a class III alcohol dehydrogenase homolog (adhC(Gf)) and decreased GA production. adhC(Gf) was cloned and expressed heterologously in Escherichia coli, and the presence of an additional protein with an approximate molecular mass of 39 kDa in the cytosol of the recombinant E. coli cells was identified by SDS-PAGE. Activity measurements of the cytosol revealed that the translational product of adhC(Gf) exhibited formaldehyde dehydrogenase activity in the presence of nicotinamide adenine dinucleotide and glutathione. Gluconobacter frateurii cells grown in 1% methanol-containing glycerol were found to have fivefold higher formaldehyde dehydrogenase activity than cells grown without methanol, suggesting that adhC(Gf) in G. frateurii cells functions in the dissimilation of methanol-derived formaldehyde.


Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis.
No safe and convenient regimen has proved to be effective for the management of recurrent vulvovaginal candidiasis. After inducing clinical remission with open-label fluconazole given in three 150-mg doses at 72-hour intervals, we randomly assigned 387 women with recurrent vulvovaginal candidiasis to receive treatment with fluconazole (150 mg) or placebo weekly for six months, followed by six months of observation without therapy. The primary outcome measure was the proportion of women in clinical remission at the end of the first six-month period. Secondary efficacy measures were the clinical outcome at 12 months, vaginal mycologic status, and time to recurrence on the basis of Kaplan-Meier analysis. Weekly treatment with fluconazole was effective in preventing symptomatic vulvovaginal candidiasis. The proportions of women who remained disease-free at 6, 9, and 12 months in the fluconazole group were 90.8 percent, 73.2 percent, and 42.9 percent, as compared with 35.9 percent, 27.8 percent, and 21.9 percent, respectively, in the placebo group (P< 0.001). The median time to clinical recurrence in the fluconazole group was 10.2 months, as compared with 4.0 months in the placebo group (P<0.001). There was no evidence of fluconazole resistance in isolates of Candida albicans or of superinfection with C. glabrata. Fluconazole was discontinued in one patient because of headache. Long-term weekly treatment with fluconazole can reduce the rate of recurrence of symptomatic vulvovaginal candidiasis. However, a long-term cure remains difficult to achieve.


Efficacy and long-term outcome of gastritis therapy in cheetahs (Acinonyx jubatus).
A prospective clinical trial evaluating efficacy and long-term outcome of treatments for lymphoplasmacytic gastritis in cheetahs (Acinonyx jubatus) was conducted. The study evaluated efficacy of 11 different antibiotic and antiinflammatory treatment protocols in 32 cheetahs (19 male, 13 female) for reducing gastric inflammation and Helicobacter colonization and monitored the course of disease through histologic grading of gastric biopsies. All cheetahs were biopsied up to I wk before treatment and then rebiopsied within 1 mo after treatment. Most animals were reassigned to a second treatment regimen within 6 mo. Each animal received from one to three treatments during the study period. After the trial, gastric biopsies were obtained from each cheetah annually until death or transfer from the facility to assess disease progression. The trial and follow-up period spanned 10 yr. At onset of the trial, all 32 cheetahs had some degree of gastritis, and 26 cheetahs (81%) were colonized with Helicobacter. Inflammatory lesions worsened regardless of treatment or the presence of Helicobacter. No treatment had a significant effect on inflammatory changes except the lansoprazole/clarithromycin/amoxicillin treatment group, which produced a short-term decrease in inflammation when compared to controls. Prednisone had no effect on gastric inflammation. Overall, 65% of colonized cheetahs were initially cleared of histologic evidence of Helicobacter by treatment, with short-term eradication occurring in 100% of the animals treated with omeprazole/clarithromycin/amoxicillin or tetracycline/metronidazole/Pepto-Bismol for 28 days. Long-term follow-up of treated animals in this study clearly demonstrated that these treatments had little effect on life-long progression of gastritis or on Helicobacter burden in individual cheetahs, although some treatments provided short-term reduction in gastritis and Helicobacter. These results provide evidence that Helicobacter alone is not the cause of gastritis in cheetahs and do not support the use of antibacterial treatments in cheetahs unless significant clinical signs (e.g., frequent vomiting/regurgitation, weight loss) are apparent.


Safety and efficacy of azacitidine in the treatment of elderly patients with myelodysplastic syndrome.
The goals of treating older patients with myelodysplastic syndrome (MDS) are different than for younger patients. Few elderly patients are able to pursue an allogeneic stem cell transplant for potential cure of the disease. The focus for the treatment of older patients with MDS is therefore not curative, but rather alleviation of symptoms, improvement in quality of life, maintenance or improvement of functional status, and continued independent living. Prolongation of survival is only important if functional status and quality of life can be maintained, and there is greater risk of losing these outcomes in elderly patients. Azacitidine is an important drug for the treatment of older patients with MDS. Data from the AZA-001 trial has shown a survival benefit for patients with high-risk disease treated with azacitidine. Importantly, treatment has also been shown to improve quality of life for MDS patients. Subset analysis of the data has shown that the drug can be used safely in even the oldest patients with MDS and is superior to treatment with other established regimens, such as low-dose cytarabine. Given the delay between the initiation of treatment and the clinical response, patients may need aggressive supportive care with antiemetics, prophylactic antibiotics, and transfusions to maintain them through therapy. Azacitidine provides a better quality of response when it is used beyond the first response, so ongoing treatment is generally recommended in responding patients. A new oral preparation of the drug is in development that will make the treatment more feasible and comfortable for elderly patients.


A hit-and-miss investigation of asymmetries in wheelchair navigation.
In contrast to the leftward inattention caused by right parietal damage, normal brain function shows a subtle neglect of the right and left sides in peripersonal and extrapersonal space, respectively. This study explored how these attentional biases cause healthy individuals to collide with objects on the right. In Experiment 1, participants navigated manual and electric wheelchairs through a narrow doorway. More rightward collisions were observed for the electric, but not the manual, wheelchair. Experiment 2 demonstrated that the rightward deviation for electric wheelchairs increased for wider doorways. Experiment 3 established that the rightward deviation is not the result of task-related vestibular input, using a remote control device to operate the wheelchair. The rightward deviation persisted in Experiment 4 when the doorway was removed, suggesting that the bias is the result of a mis-bisection of space. In Experiment 5, the rightward bias was replicated using an electric scooter, which is steered using handlebars. Finally, Experiment 6 required participants to point to the middle of the doorway, using a laser, before moving the scooter. Rightward mis-bisection was observed in both conditions. Rightward mis-bisection of lines in extrapersonal space provides the most parsimonious explanation of the rightward collisions and deviations.


Reversal of Conditioned Food Aversion Using a Cognitive Intervention: A Sham-Controlled, Randomized, Parallel Study.
Aversive conditioning weakens the gratifying value of a comfort meal. The aim was to determine the effect of a cognitive intervention to reverse aversive conditioning and restore hedonic postprandial response. This was a randomized, sham-controlled, single-blind, parallel study that was conducted on 12 healthy women (n = 6 in each group). The reward value of a comfort meal was measured on different days: at initial exposure, after aversive conditioning (administration of the same meal with a masked fat overload on the previous day) and after a cognitive intervention (disclosing the aversive conditioning paradigm in the test group vs. no explanation in the control group). The primary outcome, digestive wellbeing, was determined using graded scales at regular intervals before and after ingestion. At initial exposure, the comfort meal produced a rewarding experience that was impaired using aversive conditioning; upon re-exposure to the original meal, the cognitive intervention increased meal wanting and liking; improved digestive wellbeing and mood; tended to reduce postprandial satiety, bloating/fullness; and abolished discomfort/pain, thereby restoring the hedonic value of the comfort meal. By contrast, sham intervention had no effects, and the postprandial sensations remained like the responses to the offending meal. In this proof-of-concept study, we demonstrate that in healthy women, a mild, short-term acquired aversion to a comfort meal can be reversed using a cognitive intervention. gov ID: NCT05897411.


Choice of gender in 5alpha-reductase deficiency: a moving target.
Steroid 5alpha-reductase deficiency is a rare, male-limited autosomal recessive disorder caused by mutation in the SRD5A2 gene resulting in a deficiency of dihydrotestosterone (DHT) during fetal development. Here we report an affected 46,XY adolescent who was born with incompletely virilized genitalia and was raised in the female gender. At 12 years of age, the patient requested feminizing genital surgery. Surgery was withheld and psychiatric counseling was instituted. At 14 years of age, the patient's gender identity and role appeared to be in transition from a female to an increasingly male gender. This case demonstrates that in patients with disorders such as 5alpha-reductase deficiency, in which significant prenatal androgen exposures are combined with postnatal virilization, adult gender identity and gender role may be a dynamic process that is not complete until well after adolescence.


Total-circumference intraoperative frozen section analysis reduces margin-positive rate in breast-conservation surgery.
One problem existing in breast-conservation surgery is ipsilateral breast tumour recurrence, and one of its major risk factors is surgical margin positivity. We therefore investigated whether total-circumference surgical margin examination can reduce surgical margin-positive rates. A total of 122 cases were examined after BCS was performed between March 2004 and March 2006. After partial mastectomy, specimens were taken from the remnant breast side along the total-circumference of the mammary gland (width, approximately 5 mm). Intraoperative frozen section analysis was performed for those specimens. Margin-positive cases were defined as those showing malignancy within <or=5 mm of the final margin as revealed by final diagnosis. If intraoperative frozen section analysis had not been performed, 33 cases (27%) would have been diagnosed as margin-positive. However, it reduced the number of margin-positive cases to 12 (9.8%), and final margin-positivity rates were thus significantly reduced (P < 0.001). As for the accuracy of intraoperative frozen section analysis, sensitivity was 78.6%, specificity was 100%, correct diagnosis rate was 95.1%, positive predictive value was 100% and negative predictive value was 94.0%. False-negatives were caused by the detection of malignancy as revealed in permanent specimens. Margin-positive sites were not limited to the nipple and distal (peripheral) sites, with equivalent margin-positive cases found laterally. Total-circumference surgical margin examination by IFSA for BCS significantly reduced margin-positive rates from 27% to 9.8%.


Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1990.
An incidence survey of the Life Span Study (LSS) population found 1093 breast cancers among 1059 breast cancer cases diagnosed during 1950-1990. As in earlier breast cancer surveys of this population, a linear and statistically highly significant radiation dose response was found. In the analysis, particular attention was paid to modification of radiation dose response by age at exposure (e) and attained age (a). Dose-specific excess relative risk (ERR(1Sv)) decreased with increasing values of e and a. A linear dose-response model analysis, with e and a as exponential age modifiers, did not conclusively discriminate between the two variables as modifiers of dose response. A modified isotonic regression approach, requiring only that ERR(1Sv) be monotonic in age, provides a fresh perspective indicating that both e and a are important modifiers of dose response. Exposure before age 20 was associated with higher ERR(1Sv) compared to exposure at older ages, with no evidence of consistent variation by exposure age for ages under 20. ERR(1Sv) was observed to decline with increasing attained age, with by far the largest drop around age 35. Possible explanations for these observations are discussed, along with research approaches that might provide more information.


Quantitative assessment of left ventricular diastolic function via longitudinal and transverse flow impedances.
Flow impedance has been used to characterize the physical properties of the vascular system by assessing its phasic flow response to pulsatile pressure input in terms of resistance as a function of frequency. Impedance has also been used to characterize global diastolic left ventricular (LV) chamber properties. In early diastole the LV is a mechanical suction pump and accommodates filling by simultaneously expanding in two principal spatial directions: longitudinal (base-to-apex, long-axis) and transverse (radial, short-axis). Total (characteristic) impedance Z(C) is the product of longitudinal (Z(L)) and transverse (Z(T)) impedance as Z(C)(2)=Z(L)Z(T) where the two impedances reflect the relative spatial propensity for volume accommodation. In this work we compute Z(L) and Z(T) for the LV in early diastole. We analyze simultaneously recorded dual pressure-transducer and transthoracic echocardiographic flow data obtained during cardiac catheterization in 11 subjects. We found that Z(L) was 2 orders of magnitude smaller than Z(T) in all subjects, providing the first hemodynamic evidence, in concordance with cine-MRI imaging data that longitudinal volume accommodation is indeed, nature's preferred spatial filling mechanism. We also investigated the effect of impaired diastolic function on directional impedances and found that Z(L) increased (becomes worse) while Z(T) decreased (becomes better) indicating that as diastolic function becomes impaired radial filling compensates for decreased longitudinal volume accommodation to preserve stroke volume. These results provide mechanistic insight and show that normal diastolic function defines a properly impedance matched state and that diastolic dysfunction is equivalent to a state of impedance mismatch.


Ate1-mediated posttranslational arginylation affects substrate adhesion and cell migration in Dictyostelium discoideum.
The highly conserved enzyme arginyl-tRNA-protein transferase (Ate1) mediates arginylation, a posttranslational modification that is only incompletely understood at its molecular level. To investigate whether arginylation affects actin-dependent processes in a simple model organism, Dictyostelium discoideum, we knocked out the gene encoding Ate1 and characterized the phenotype of ate1-null cells. Visualization of actin cytoskeleton dynamics by live-cell microscopy indicated significant changes in comparison to wild-type cells. Ate1-null cells were almost completely lacking focal actin adhesion sites at the substrate-attached surface and were only weakly adhesive. In two-dimensional chemotaxis assays toward folate or cAMP, the motility of ate1-null cells was increased. However, in three-dimensional chemotaxis involving more confined conditions, the motility of ate1-null cells was significantly reduced. Live-cell imaging showed that GFP-tagged Ate1 rapidly relocates to sites of newly formed actin-rich protrusions. By mass spectrometric analysis, we identified four arginylation sites in the most abundant actin isoform of Dictyostelium, in addition to arginylation sites in other actin isoforms and several actin-binding proteins. In vitro polymerization assays with actin purified from ate1-null cells revealed a diminished polymerization capacity in comparison to wild-type actin. Our data indicate that arginylation plays a crucial role in the regulation of cytoskeletal activities.


Apocarotenoids Involved in Plant Development and Stress Response.
Carotenoids are isoprenoid pigments synthesized by all photosynthetic organisms and many heterotrophic microorganisms. They are equipped with a conjugated double-bond system that builds the basis for their role in harvesting light energy and in protecting the cell from photo-oxidation. In addition, the carotenoids polyene makes them susceptible to oxidative cleavage, yielding carbonyl products called apocarotenoids. This oxidation can be catalyzed by carotenoid cleavage dioxygenases or triggered nonenzymatically by reactive oxygen species. The group of plant apocarotenoids includes important phytohormones, such as abscisic acid and strigolactones, and signaling molecules, such as β-cyclocitral. Abscisic acid is a key regulator of plant's response to abiotic stress and is involved in different developmental processes, such as seed dormancy. Strigolactone is a main regulator of plant architecture and an important signaling molecule in the plant-rhizosphere communication. β-Cyclocitral, a volatile derived from β-carotene oxidation, mediates the response of cells to singlet oxygen stress. Besides these well-known examples, recent research unraveled novel apocarotenoid growth regulators and suggests the presence of yet unidentified ones. In this review, we describe the biosynthesis and biological functions of established regulatory apocarotenoids and touch on the recently identified anchorene and zaxinone, with emphasis on their role in plant growth, development, and stress response.


High Cure Rates With Grazoprevir-Elbasvir With or Without Ribavirin Guided by Genotypic Resistance Testing Among Human Immunodeficiency Virus/Hepatitis C Virus-coinfected Men Who Have Sex With Men.
This study was performed to investigate the efficacy and safety of grazoprevir-elbasvir guided by baseline resistance-associated substitutions (RASs) in the Swiss HCVree Trial. We performed hepatitis C virus (HCV) RNA screening among all men who have sex with men (MSM) enrolled in the Swiss HIV Cohort Study. Individuals with replicating HCV genotype 1 or 4 infection were eligible for grazoprevir-elbasvir treatment. Genotype 1a-infected individuals with baseline RASs and genotype 4-infected individuals with prior failure of HCV treatment received 16 weeks of grazoprevir-elbasvir combined with ribavirin. All other individuals received 12 weeks of grazoprevir-elbasvir alone. Patients reporting unprotected sex with occasional partners were offered a HCV risk reduction-oriented behavioral intervention. We screened 3722 MSM and identified 177 (4.8%) with replicating infection. A total of 122 individuals (3.3%) were eligible for study treatment. Six of 76 patients infected with genotype 1a (7.3%) harbored baseline RASs. Sustained virological response after 12 weeks of follow-up was achieved in 121 patients (99%), including all with genotype 1a infection. Overall, 8 serious adverse events occurred, none of which was related to the study drug. Seventy-five percent of eligible MSM participated in the risk counseling program. Grazoprevir-elbasvir for 12 or 16 weeks, with or without ribavirin, achieved high cure rates and had an excellent safety profile. Unique to other studies, the treatment duration was guided by the presence of baseline RASs among genotype 1a-infected individuals, and the treatment phase was accompanied by an HCV risk reduction-oriented behavioral intervention. This successful population-wide treatment approach lays the groundwork to achieve HCV elimination in coinfected MSM. NCT02785666.


Newts: sun-compass orientation.
Rough-skinned newts, captured from breeding ponds, oriented on courses that would have intersected the familiar shorelines at right angles, when released in a circular arena on land under the sun or moon. Pondward migrants oriented similarly. Reorientation failed under complete cloud cover and after 7 days of darkness in an environmental chamber, but persisted in newts whose eyes were excised and in those displaced more than 27 kilometers in darkness. Both normal and blind animals compensated for displacement in sunshine. Preliminary evidence suggests that alternative light receptors in blinded animals may be associated with the optic tectum. No evidence of olfactory guidance was observed.


Phenotypic profiling of solute carriers characterizes serine transport in cancer.
Serine is a vital amino acid in tumorigenesis. While cells can perform de novo serine synthesis, most transformed cells rely on serine uptake to meet their increased biosynthetic requirements. Solute carriers (SLCs), a family of transmembrane nutrient transport proteins, are the gatekeepers of amino acid acquisition and exchange in mammalian cells and are emerging as anticancer therapeutic targets; however, the SLCs that mediate serine transport in cancer cells remain unknown. Here we perform an arrayed RNAi screen of SLC-encoding genes while monitoring amino acid consumption and cell proliferation in colorectal cancer cells using metabolomics and high-throughput imaging. We identify SLC6A14 and SLC25A15 as major cytoplasmic and mitochondrial serine transporters, respectively. We also observe that SLC12A4 facilitates serine uptake. Dual targeting of SLC6A14 and either SLC25A15 or SLC12A4 diminishes serine uptake and growth of colorectal cancer cells in vitro and in vivo, particularly in cells with compromised de novo serine biosynthesis. Our results provide insight into the mechanisms that contribute to serine uptake and intracellular handling.


Membrane permeability of coelenterazine analogues measured with fish eggs.
To determine the suitability of various coelenterazine analogues for the regeneration of aequorin in living cells, the membrane permeabilities of 11 analogues were measured using the eggs of the killifish Fundulus grandis by soaking the eggs in solutions containing the analogues. The results indicated that e-coelenterazine, which has an exceptionally high rate of in vitro regeneration of aequorin, not only permeated poorly into the eggs but also was highly unstable. All other analogues tested permeated sufficiently into the eggs. The highest permeability was found with f-coelenterazine; the concentration of f-coelenterazine in the eggs was about five times that in the surrounding medium, assuming that the distribution of the compound in the egg is uniform.


Are CD44 spliced variants involved in human breast cancer metastasis?
Expression of CD44 isoforms has been investigated on normal breasts, fibroadenomas, cysts and breast cancers. Carcinomas express additional variants in comparison with normal breasts while fibroadenomas and cysts do not. Invasive cancers also express more variants than in situ carcinomas. Recent studies tend to demonstrate that overexpression of CD44 is not a survival prognostic factor whereas expression of exon 2v and/or 3v could be. Results for exons 4v to 10v are presently conflicting. Further studies will then be necessary to clarify the role of CD44 isoforms in mammary carcinogenesis and metastasis. Metastatic capacity could be linked with expression of additional variants but also with no transcription of variants associating exon 6v with either exon 10v or both exons 9 and 10v.


Localization and functional effects of adenosine A1 receptors on cardiac vagal afferents in adult rats.
There is evidence to suggest that during ischemia adenosine acts on cardiac vagal afferent neurons to activate systemic reflexes and to modulate cardiac nociception. The purpose of this study was to determine whether adenosine receptors are present and have direct cellular electrophysiological actions on cardiac vagal afferent neurons. In radioreceptor assays of nodose ganglion tissue from rats, binding was detectable for A1 (39.6 +/- 1.2 fmol/mg protein) but not A2a adenosine receptors. These findings were confirmed using the complementary approach of receptor-labeling autoradiography. Using in situ hybridization, we saw specific labeling over approximately 50% of neurons in the nodose ganglia, but not over nonneuronal cells. In colabeling studies, cardiac vagal afferent neurons were identified by retroneuronal labeling with fluororuby. Of cardiac vagal afferents approximately one-half were strongly positive for A1 adenosine receptors (immunocytochemistry). In patch-clamping experiments, adenosine inhibited peak inward calcium current in 7 of 11 cells by 48 +/- 13%. In conclusion, adenosine A1 receptors reside on a subset of vagal afferent neurons, including cardiac vagal afferents, and have electrophysiological effects that modulate neuroexcitability in cultured nodose ganglion neurons.


Implementation of a combined Cardiopulmonary Resuscitation and Treatment Escalation Plan document in a District General Hospital.
Documentation of appropriate escalation of treatment was identified as a problem for junior doctors and Critical Care Outreach Nurses at Musgrove Park Hospital. An audit of resuscitation and escalation documentation of all wards found that of the patients who were not for Cardiopulmonary resuscitation (and therefore not for full escalation of care), 78.4% had no documentation of the appropriate level of escalation of treatment should they deteriorate. The majority of junior doctors had experienced cases where they felt that inappropriate treatment had been given, where no escalation plan was documented. Using several Plan, Do, Study, Act (PDSA) cycles, drawing tools used in other trusts and departments, and the views of clinicians, we developed a treatment escalation plan (TEP) tool, to be included in the resuscitation form. This included consideration of referral to critical care, ward based non-invasive ventilation, and appropriate use of intravenous or oral antibiotics. This then prompted the responsible clinician to consider and document appropriate escalation of treatment. The CPR-TEP form was trialed using a quasi-experiment design allowing the aim to be tested using two groups - intervention and control. All patients in the intervention group were not for CPR and therefore had their TEP-CPR form filled in fully (n=68). The control group consisted of patients who were not for CPR but who did not have a TEP form filled in (n=36). The appropriateness of OOH (out of hours) treatment in those patients who experienced clinical deterioration was judged by questionnaire-based feedback from the in-hours team the following morning. Levels of inappropriate treatment between the two groups were compared to test the aim. At the end of the study period, questionnaire feedback indicated that 11.1% of patients in the group with the new CPR-TEP document had received inappropriate OOH care compared to 44.4% of patients in the group without the document. Using the TEP alongside resuscitation documentation prompts the responsible clinician to consistently consider and document the appropriate escalation of care for their patient, improving communication with the out of hours team and appropriate escalation of care in the event of patient deterioration.


Water striders (family Gerridae): mercury sentinels in small freshwater ecosystems.
To circumvent some of the previous limitations associated with contaminant-monitoring programs, we tested the suitability of the water strider (Hemiptera: Gerridae) as a mercury sentinel by comparing total mercury concentrations in water striders and brook trout (Salvelinus fontinalis) from a variety of stream sites in New Brunswick, Canada. There was a strong association between the two variables across sites (r(2)=0.81, P<0.001) in systems where both atmospheric deposition and a point source (an abandoned gold mine) were likely contributing to ambient mercury levels. In a small stream draining the gold mine tailings pile, water striders had mercury concentrations an order of magnitude higher than those from reference locations. Temporal variation at three southern New Brunswick stream sites was non-significant. These results suggest that water strider mercury levels accurately quantify food chain entry of the element. The use of sentinel species holds great potential for expanding contaminant-monitoring programs.


Hepatic artery infusion chemotherapy with the Infusaid pump: a Canadian experience.
Hepatic artery infusion of 5-fluoro-2'-deoxyuridine (FUDR), utilizing the implantable "Infusaid pump", was used to treat 16 patients with diffuse hepatic metastases from colorectal carcinoma. Pump implantation was associated with minimal morbidity and no deaths. The pumps have now been in use for 190 treatment-months without serious complication. Six patients died of cancer between 3 and 26 months (mean 13 months) after insertion of the pump. Five died with recurrent disease outside the liver. Ten patients were alive 6 to 17 months (mean 12 months) after pump implantation. Follow-up ultrasonography in 13 patients documented regression of hepatic lesions in 7, no change in 4 and progression in 2. Regional perfusion chemotherapy can be instituted safely and treatment carries acceptable morbidity. Survival is prolonged relative to historic controls. Death ultimately occurs because of distant metastases. True assessment of the efficacy of this therapy demands prospective randomized trials of regional perfusion versus conventional therapy, with care to incorporate objective means of assessing quality of life during treatment.


Rhamnolipid Micelles Assist Azithromycin in Efficiently Disrupting Staphylococcus aureus Biofilms and Impeding Their Re-Formation.
Biofilm is highly resistant to antibiotics due to its heterogeneity and is implicated in over 80% of chronic infections; these refractory and relapse-prone infections pose a huge medical burden. In this study, rhamnolipid (RHL), a biosurfactant with antibiofilm activity, was loaded with the antibiotic azithromycin (AZI) to construct a stable nanomicelle (AZI@RHL) that promotes Staphylococcus aureus (S. aureus) biofilm disruption. AZI@RHL micelles made a destruction in biofilms. The biofilm biomasses were reduced significantly by 48.2% (P<0.05), and the main components polysaccharides and proteins were reduced by 47.5% and 36.8%, respectively. These decreases were about 3.1 (15.9%), 7.3 (6.5%), and 1.9 (19.5%) times higher compared with those reported for free AZI. The disruption of biofilm structure was observed under a confocal microscope with fluorescent labeling, and 48.2% of the cells in the biofilm were killed. By contrast, the clearance rates of cells were only 20% and 17% when treated alone with blank micelles or free AZI. Biofilm formation was inhibited up to 92% in the AZI@RHL group due to effects on cell auto-aggregation and eDNA release. The rates for the other groups were significantly lower, with only 27.7% for the RHL group and 12% for the AZI group (P<0.05). The low cell survival and great formation inhibition could reduce biofilm recolonization and re-formation. The antibiofilm efficacy of rhamnolipid was improved through micellar nanoparticle effects when loading azithromycin. AZI@RHL provides a one-step solution that covers biofilm disruption, bacteria inactivation, recolonization avoidance, and biofilm re-formation inhibition.


The impact of polymer additive for N95 masks on gamma-ray attenuation properties.
This article explores the effectiveness of gamma rays attenuation of various N95 respirator samples by analysing several theoretical parameters such as the Effective Atomic Numbers (Zeff), Half Value Layer (HVL), Mean Free Path (MFP), Mass Attenuation Coefficients (MAC), Tenth Value Layer (TVL), Exposure Build Up Factors (EBF) and Energy Absorption Build Up Factors (EABF). For the selected N95 mask samples, the MAC values corresponding to the energy levels between 0.015 and 20 MeV are measured using the WinXCOM software and the MATLAB code. The parameters including Zeff, TVL, HVL, and MFP are computed using the MAC values derived from the WinXCOM program. EBF and EABF are computed in relation to the penetration depth and incident photon energy by using the (G-P) fitting approximation in estimating the photon build-up factor. The findings showed that having the lowest TVL, HVL, and MFP, the N2 sample has the best output in terms of radiation attenuation purposes. In conclusion, the N2 sample which outperforms other samples is the most promising mask sample when it comes to gamma-ray attenuation features.


Should intravenous immunoglobulin be used in infants with isoimmune haemolytic disease due to ABO incompatibility?
The use of intravenous immunoglobulin in isoimmune haemolytic disease due to ABO incompatibility is recommended by the American Academy of Pediatrics and the National Blood Authority, Australia. However, the evidence these recommendations are based on appears limited and, in some instances, outdated. In our article, we review the current available literature to help answer the question, 'In infants with isoimmune haemolytic disease due to ABO incompatibility [P], does use of intravenous immunoglobulin and intensive phototherapy [I] compared with intensive phototherapy alone [C] provide any clinically important benefits [O]?'


Effects of histamine on the metabolism of isolated rat hepatocytes: roles of H1- and H2-histamine receptors.
In isolated rat hepatocytes histamine stimulates in a dose-dependent fashion three of the major metabolic pathways: glycogenolysis (70-80% increase over basal), gluconeogenesis from lactate (50-60%), and ureagenesis (50-60%). It was observed that both H1 and H2 receptors mediate the action of histamine and that, in control hepatocytes, the H1-mediated action predominates over the H2. The H1-mediated effect diminished in the absence of extracellular calcium, whereas the H2-mediated action did not. Interestingly, in hepatocytes from hypothyroid rats, the H2 action increased and the H1-mediated effect decreased as compared to those in the controls, with an inversion in efficacy (i.e., H1 greater than H2 in the controls and H2 greater than H1 in cells from hypothyroid rats). Furthermore, it was observed that pertussis toxin treatment and forskolin both enhance the H2-mediated effects without altering the H1-mediated actions of histamine (i.e., H1 approximately equal to H2). The active phorbol ester, phorbol 12-myristate 13-acetate, did not alter the effect of the autacoid. In summary, the data show that histamine modulates liver metabolism through H1 and H2 receptors. The relative importance of the two receptor types in mediating the actions of histamine varies depending on the specific conditions used.


Deprescribing fall-risk increasing drugs (FRIDs) for the prevention of falls and fall-related complications: a systematic review and meta-analysis.
Prevention of falls and fall-related injuries is a priority due to the substantial health and financial burden of falls on patients and healthcare systems. Deprescribing medications known as 'fall-risk increasing drugs' (FRIDs) is a common strategy to prevent falls. We conducted a systematic review to determine its efficacy for the prevention of falls and fall-related complications. Systematic review and meta-analysis. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL and grey literature from inception to 1 August 2020. Randomised controlled trials of FRID withdrawal compared with usual care evaluating the rate of falls, incidence of falls, fall-related injuries, fall-related fractures, fall-related hospitalisations or adverse effects related to the intervention in adults aged ≥65 years. Two reviewers independently performed citation screening, data abstraction, risk of bias assessment and certainty of evidence grading. Random-effects models were used for meta-analyses. Five trials involving 1305 participants met eligibility criteria. Deprescribing FRIDs did not change the rate of falls (rate ratio (RaR) 0.98, 95% CI 0.63 to 1.51), the incidence of falls (risk difference 0.01, 95% CI -0.06 to 0.09; relative risk 1.04, 95% CI 0.86 to 1.26) or rate of fall-related injuries (RaR 0.89, 95% CI 0.57 to 1.39) over a follow-up period of 6-12 months. No trials evaluated the impact of deprescribing FRIDs on fall-related fractures or hospitalisations. There is a paucity of robust high-quality evidence to support or refute that a FRID deprescribing strategy alone is effective at preventing falls or fall-related injury in older adults. Although there may be other reasons to deprescribe FRIDs, our systematic review found that it may result in little to no difference in the rate or risk of falls as a sole falls reduction strategy. CRD42016040203.