Concentrating molasses distillery wastewater using biomimetic forward osmosis (FO) membranes.
Treatment of sugarcane molasses distillery wastewater is challenging due to the presence of complex phenolic compounds (melanoidins and polyphenols) having antioxidant properties. Due to zero liquid discharge regulations, Indian distilleries continue to explore effective treatment options. This work examines the concentration of distillery wastewater by forward osmosis (FO) using aquaporin biomimetic membranes and magnesium chloride hexahydrate (MgCl2.6H2O) as draw solution. The operational parameters viz. feed solution and draw solution flow rate and draw solution concentration were optimized using 10% v/v melanoidins model feed solution. This was followed by trials with distillery wastewater. Under the conditions of this work, feed and draw flow rates of 1 L/min and draw solution concentration of 2M MgCl2.6H2O for melanoidins model solution and 3M MgCl2.6H2O for distillery wastewater were optimal for maximum rejection. Rejection of 90% melanoidins, 96% antioxidant activity and 84% COD was obtained with melanoidins model feed, with a corresponding water flux of 6.3 L/m2h. With as-received distillery wastewater, the rejection was similar (85-90%) to the melanoidins solution, but the water flux was lower (2.8 L/m2h). Water recovery from distillery wastewater over 24 h study period was higher with FO (70%) than reported for RO (35-45%). Repeated use of the FO membrane over five consecutive 24 h cycles with fresh feed and draw solutions and periodic cleaning showed consistent average water flux and rejection of the feed constituents.


[Ecological risk assessment of Taihu Lake basin based on landscape pattern].
Taihu Lake basin was selected as the study site. Based on the landscape data of 2000, 2005, 2010 and 2015, the Markov and CLUE-S models were used to simulate the landscape types with different scenarios in 2030, and landscape ecological risk index was constructed. The shift of gravity center and spatial statistics were used to reveal landscape ecological risk of Taihu Lake basin with temporal and spatial characteristics. The results showed that the ecological risk mainly was at medium and low levels in Taihu Lake basin, and the higher ecological risk areas were mainly distributed at the Taihu Lake area during 2000 to 2015, and the low ecological risk was transferred from the southwest and south of Taihu Lake to the developed areas in the northern part of Taihu Lake area. Spatial analysis showed that landscape ecological risk had negative correlation with natural factors, which was weakened gradually, while the correlation with socioeconomic factors trended to become stronger, with human disturbance affecting the landscape ecological risk significantly. The impact of socioeconomic factors on landscape ecological risks differed in different urbanization stages. In the developing area, with the economic development, the landscape was increasingly fragmented and the ecological risk was correspondingly increased. While in the developed area, with the further development of the economy, the aggregation index was increased, and fragmentation and separation indexes were decreased, ecological construction was restored, and the landscape ecological risk began to decline. CLUE-S model simulation showed that the ecological risk of Taihu Lake basin would be reduced in future, mainly on the low and relatively low levels. Taihu Lake area, both in history and the future, is a high ecological risk zone, and its management and protection should be strengthened.


Relative permittivity in the electrical double layer from nonlinear optics.
Second harmonic generation (SHG) spectroscopy has been applied to probe the fused silica/water interface at pH 7 and the uncharged 11¯02 sapphire/water interface at pH 5.2 in contact with aqueous solutions of NaCl, NaBr, NaI, KCl, RbCl, and CsCl as low as several 10 μM. For ionic strengths up to about 0.1 mM, the SHG responses were observed to increase, reversibly for all salts surveyed, when compared to the condition of zero salt added. Further increases in the salt concentration led to monotonic decreases in the SHG response. The SHG increases followed by decreases are found to be consistent with recent reports of phase interference and phase matching in nonlinear optics. By varying the relative permittivity employed in common mean field theories used to describe electrical double layers and by comparing our results to available literature data, we find that models recapitulating the experimental observations are the ones in which (1) the relative permittivity of the diffuse layer is that of bulk water, with other possible values as low as 30, (2) the surface charge density varies with salt concentration, and (3) the charge in the Stern layer or its thickness varies with salt concentration. We also note that the experimental data exhibit sensitivity depending on whether the salt concentration is increased from low to high values or decreased from high to low values, which, however, is not borne out in the fits, at least within the current uncertainties associated with the model point estimates.


Comparison of Polypropylene Sling with Combined Transconjunctival Retractor Plication and Lateral Tarsal Strip for Correction of Involutional Lower Eye Lid Ectropion.
The study aims to compare the effectiveness and complications of transconjunctival retractor plication (TRP) with lateral tarsal strip (LTS) and the polypropylene sling (PS) surgery for treatment of involutional lower lid ectropion. A prospective randomised pilot study was conducted on 30 eyes of 30 patients suffering from epiphora having horizontal eyelid laxity >6mm and age >50 years at a tertiary care centre from December 2014 to March 2015. They were randomly divided into two equal groups for TRP with LTS (group A) and PS (group B). Success was defined as relief in epiphora and lid laxity ≤4mm at 12 months post operatively. There were 19 male and 11 female patients with age ranging from 55-80 years. The mean grade of ectropion was 2.80±1.32 in group A and 2.87±1.60 in group B. The preoperative horizontal laxity increased with the grade of ectropion (p <0.001) while medial canthal laxity was variable. The average surgical time per procedure in group A was 66 minutes and in group B was 24 minutes. Group A had a success rate of 93.33%, while group B had a success rate of 87%. Post-operative complications occurred in 2 eyes in group B only. Both LTS with TRP and PS are effective in the management of involutional ectropion. LTS with TRP though more invasive has higher success rates and a lower incidence of complications as compared to PS. However, PS is an easy to perform out- patient procedure that is faster and better tolerated in old patients.


Meta-analysis of glucose tolerance, insulin, and insulin resistance in antipsychotic-naïve patients with nonaffective psychosis.
Some studies have suggested that antipsychotic-naïve patients with nonaffective psychosis (NAP) have glucose intolerance. To conduct a systematic review and meta-analysis of fasting glucose (FG), two hour values in the oral glucose tolerance test (2HG), fasting insulin concentration (INS), and insulin resistance (IR). We identified possibly relevant studies, then selected studies, following usual guidelines, with two authors reviewing the manuscripts. We required studies to include subjects with nonaffective psychosis and control subjects. There were 911 patients and 870 control subjects in the analysis of FG; their average ages were respectively 28.7 and 29.5years. Significant differences were found for all four variables, with effect size estimates ranging from 0.21 to 0.58. As a group, at the time of first clinical contact for psychosis, people with NAP have a slight increase in FG, which most of them maintain in the normal range despite a small increase in IR by secreting additional INS. When faced with a physiological challenge such as a glucose tolerance test or antipsychotics, they are no longer able to maintain a normal glucose concentration.


Adenosine deaminase complexing protein in cancer studies.
ADCP is a dimeric glycoprotein of about 200KD, for which the physiological role is still obscure. This protein occurs mainly in a membrane bound form in various human tissues. In this paper we review the current literature on ADCP in cancer studies. Soluble ADCP was described to be consistently decreased or absent in cancers of lung, liver, kidney and colon. These findings could not be confirmed by immunohistochemical and quantitative biochemical studies in a series of colorectal-, prostatic-, and renal carcinomas. Only in a third of these tumors a decrease could be demonstrated, whereas in the other cases unaltered or even increased amounts were observed. However, in virally transformed human fibroblasts a consistent decrease or complete absence of ADCP was seen, while primary fibroblasts were found to contain high amounts of this protein. Recently, the use of ADCP as a differentiation marker in colonic cancer has been advocated. Furthermore the presence of ADCP in the serum of renal adenocarcinoma patients was found to be indicative of a better chance of five year survival. These studies suggest that ADCP may be a differentiation marker useful for immunohistochemical characterization of colonic and renal carcinomas as well as a serum marker useful for follow-up studies of these types of cancer, analogous to CEA. Finally, ADCP has been found to be selectively expressed by certain T-cell subsets and henceforth may be useful in the studies on leukemias.


Determining the Cause of Recurrent Miscarriages in a Couple: Importance of NOR in the Era of NGS.
Chromosomal abnormalities are a significant cause of human disorders. The characterization of such abnormalities helps in the identification of known/ new genes. The purpose of the present study was to identify the cause of miscarriages in a couple by using combined molecular and cytogenetic techniques. In this study, the clinical, cytogenetic and molecular cytogenetic evaluations were performed on a couple with recurrent miscarriages. Several methods like GTG banding, silver nitrate (NOR) staining, fluorescence in-situ hybridization (FISH) using whole chromosome paint probes (WCP) and bacterial artificial chromosome (BAC) clones were used. The chromosomal analysis on the metaphases revealed a karyotype of 46,XX in the wife and 46,XY,13p+ in her husband. To check the satellites on 13p region, NOR was performed which showed absence of satellites and presence of euchromatic material. On careful analysis, the satellites were observed on 11q terminal region. Thus, a balanced reciprocal translocation was detected which was confirmed by WCP and Acro-P-arm FISH. Fine mapping with BAC clones narrowed down the breakpoint regions. The application of the combined cytogenetic methods especially NOR helped in identification of the balanced reciprocal translocation with subsequent systematic characterization and the breakpoint regions were identified. The characterization of the breakpoint regions helped in identification of the carrier status which further paved the way for understanding the cause of recurrent miscarriages and proper genetic counseling.


Adding a dimension to cell fate.
Cell fate specification, gene expression and spatial restriction are process finely tuned by epigenetic regulatory mechanisms. At the same time, mechanical forces have been shown to be crucial to drive cell plasticity and boost differentiation. Indeed, several studies have demonstrated that transitions along different specification states are strongly influenced by 3D rearrangement and mechanical properties of the surrounding microenvironment, that can modulate both cell potency and differentiation, through the activation of specific mechanosensing-related pathways. An overview of small molecule ability to modulate cell plasticity and define cell fate is here presented and results, showing the possibility to erase the epigenetic signature of adult dermal fibroblasts and convert them into insulin-producing cells (EpiCC) are described. The beneficial effects exerted on such processes, when cells are homed on an adequate substrate, that shows "in vivo" tissue-like stiffness are also discussed and the contribution of the Hippo signalling mechano-transduction pathway as one of the mechanisms involved is examined. In addition, results obtained using a genetically modified fibroblast cell line, expressing the enhanced green fluorescent protein (eGFP) under the control of the porcine insulin gene (INS) promoter (INS-eGFP transgenic pigs), are reported. This model offers the advantage to monitor the progression of cell conversion in real time mode. All these observations have a main role in order to allow a swift scale-up culture procedure, essential for cell therapy and tissue engineering applied to human regenerative medicine, and fundamental to ensure an efficient translation process from the results obtained at the laboratory bench to the patient bedside. Moreover, the creation of reliable in vitro model represents a key point to ensure the development of more physiological models that, in turn, may reduce the number of animals used, implementing non-invasive investigations and animal welfare and protection.


Daily self-monitoring of body weight, step count, fruit/vegetable intake, and water consumption: a feasible and effective long-term weight loss maintenance approach.
Maintenance of weight loss remains a challenge for most individuals. Thus, practical and effective weight-loss maintenance (WTLM) strategies are needed. A two-group 12-month WTLM intervention trial was conducted from June 2007 to February 2010 to determine the feasibility and effectiveness of a WTLM intervention for older adults using daily self-monitoring of body weight, step count, fruit/vegetable (F/V) intake, and water consumption. Forty weight-reduced individuals (mean weight lost=6.7±0.6 kg; body mass index [calculated as kg/m²] 29.2±1.1), age 63±1 years, who had previously participated in a 12-week randomized controlled weight-loss intervention trial, were instructed to record daily body weight, step count, and F/V intake (WEV [defined as weight, exercise, and F/V]). Experimental group (WEV+) participants were also instructed to consume 16 fl oz of water before each main meal (ie, three times daily), and to record daily water intake. Outcome measures included weight change, diet/physical activity behaviors, theoretical constructs related to health behaviors, and other clinical measures. Statistical analyses included growth curve analyses and repeated measures analysis of variance. Over 12 months, there was a linear decrease in weight (β=-0.32, P<0.001) and a quadratic trend (β=0.02, P<0.01) over time, but no group difference (β=-0.23, P=0.08). Analysis of the 365 days of self-reported body weight for each participant determined that weight loss was greater over the study period in the WEV+ group than in the WEV group, corresponding to weight changes of -0.67 kg and 1.00 kg, respectively, and an 87% greater weight loss (β=-0.01, P<0.01). Overall compliance to daily tracking was 76%±5%. Daily self-monitoring of weight, physical activity, and F/V consumption is a feasible and effective approach for maintaining weight loss for 12 months, and daily self-monitoring of increased water consumption may provide additional WTLM benefits.


Medical literature as a potential source of new knowledge.
Specialized biomedical literatures have been found that are implicitly linked by arguments that they respectively contain, but which nonetheless do not cite or refer to each other. The combined arguments lead to new inferences and conclusions that cannot be drawn from the separate literatures. One such analysis identified one set of articles showing that dietary fish oils lead to certain blood and vascular changes, and a second set containing evidence that similar changes might benefit patients with Raynaud's syndrome. Yet these two literatures had no articles in common and had never before been cited together; neither literature mentioned the other or suggested that dietary fish oil might benefit Raynaud patients. Two years after publication of that analysis, the first clinical trial demonstrating such a beneficial effect was reported independently by others. A second example of literature synthesis, based on eleven indirect connections, led to an inference that magnesium deficiency might be a causal factor in migraine headache. A third example calls attention to implicit connections between arginine intake and blood levels of somatomedins, a potentially fruitful but neglected area of research with implications for the decline with age of thymic function and protein synthesis. A model and an online search strategy to aid in identifying other logically related noninteractive literatures is described. Such structures are probably not rare and may provide the foundation for a literature-based approach to scientific discovery.


National patterns of vulnerable decision points in school discipline.
In this study, we identified the specific discipline decision situations (i.e., vulnerable decision points [VDPs]) that contribute most to racial discipline disparities from a sample of 2020 schools across the United States. We also examined how much VDPs contributed to overall discipline disparities and the extent to which there was similarity among the strongest VDPs within each school. Last, we directly compared the VDP that contributed most to disparities in each school to situations with the highest rates of office discipline referrals (ODRs) to identify the extent of agreement with overall school discipline patterns. We found the most common VDPs within schools to be subjective behaviors (e.g., defiance, disruption) in classrooms throughout the day, with ODRs for physical aggression contributing notably to disparities among the top 10 VDPs. The strongest single VDP accounted for an average of 17% of racial disparities across the school and the top three VDPs accounted for 37% of disparities. The strongest three VDPs within schools also were remarkably consistent across behavior and location. Finally, there was moderate agreement between situations with the most ODRs and those with the strongest racial disparities, with 63% of schools in the sample having VDPs identical to their situations with most ODRs. In the absence of prescriptive analysis of their own school data, the results of this study provide school leaders and intervention researchers with more precise, promising targets for intervention to increase educational equity.


Spatially resolved analysis of short-range structure perturbations in a plastically bent molecular crystal.
The exceptional mechanical flexibility observed with certain organic crystals defies the common perception of single crystals as brittle objects. Here, we describe the morphostructural consequences of plastic deformation in crystals of hexachlorobenzene that can be bent mechanically at multiple locations to 360° with retention of macroscopic integrity. This extraordinary plasticity proceeds by segregation of the bent section into flexible layers that slide on top of each other, thereby generating domains with slightly different lattice orientations. Microscopic, spectroscopic and diffraction analyses of the bent crystal showed that the preservation of crystal integrity when stress is applied on the (001) face requires sliding of layers by breaking and re-formation of halogen-halogen interactions. Application of stress on the (100) face, in the direction where π···π interactions dominate the packing, leads to immediate crystal disintegration. Within a broader perspective, this study highlights the yet unrecognized extraordinary malleability of molecular crystals with strongly anisotropic supramolecular interactions.


Economic evaluation of vaccines in Canada: A systematic review.
Economic evaluations should form part of the basis for public health decision making on new vaccine programs. While Canada's national immunization advisory committee does not systematically include economic evaluations in immunization decision making, there is increasing interest in adopting them. We therefore sought to examine the extent and quality of economic evaluations of vaccines in Canada. We conducted a systematic review of economic evaluations of vaccines in Canada to determine and summarize: comprehensiveness across jurisdictions, studied vaccines, funding sources, study designs, research quality, and changes over time. Searches in multiple databases were conducted using the terms "vaccine," "economics" and "Canada." Descriptive data from eligible manuscripts was abstracted and three authors independently evaluated manuscript quality using a 7-point Likert-type scale scoring tool based on criteria from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). 42/175 articles met the search criteria. Of these, Canada-wide studies were most common (25/42), while provincial studies largely focused on the three populous provinces of Ontario, Quebec and British Columbia. The most common funding source was industry (17/42), followed by government (7/42). 38 studies used mathematical models estimating expected economic benefit while 4 studies examined post-hoc data on established programs. Studies covered 10 diseases, with 28/42 addressing pediatric vaccines. Many studies considered cost-utility (22/42) and the majority of these studies reported favorable economic results (16/22). The mean quality score was 5.9/7 and was consistent over publication date, funding sources, and disease areas. We observed diverse approaches to evaluate vaccine economics in Canada. Given the increased complexity of economic studies evaluating vaccines and the impact of results on public health practice, Canada needs improved, transparent and consistent processes to review and assess the findings of the economic evaluations of vaccines.


Epigenomic Views of Innate Lymphoid Cells.
The discovery of innate lymphoid cells (ILCs) with selective production of cytokines typically attributed to subsets of T helper cells forces immunologists to reassess the mechanisms by which selective effector functions arise. The parallelism between ILCs and T cells extends beyond these two cell types and comprises other innate-like T lymphocytes. Beyond the recognition of specialized effector functionalities in diverse lymphocytes, features typical of T cells, such as plasticity and memory, are also relevant for innate lymphocytes. Herein, we review what we have learned in terms of the molecular mechanisms underlying these shared functions, focusing on insights provided by next generation sequencing technologies. We review data on the role of lineage-defining- and signal-dependent transcription factors (TFs). ILC regulomes emerge developmentally whereas the much of the open chromatin regions of T cells are generated acutely, in an activation-dependent manner. And yet, these regions of open chromatin in T cells and ILCs have remarkable overlaps, suggesting that though accessibility is acquired by distinct modes, the end result is that convergent signaling pathways may be involved. Although much is left to be learned, substantial progress has been made in understanding how TFs and epigenomic status contribute to ILC biology in terms of differentiation, specification, and plasticity.


The use of the edinburgh postpartum depression scale in a population of teenager pregnant women in Mexico: a validation study.
:Depression may occur in teenager pregnant women. The use of a validated tool for screening depression is highly recommended. The Edinburgh postnatal depression scale (EPDS) is a screening tool for depression used in women during the postnatal period and pregnancy. However, the EPDS has not been validated in teenager pregnant women. Therefore, we sought to validate a Spanish translated Mexican version of the EPDS in a population of teenager pregnant women. One hundred and twenty teenager pregnant women attending routine prenatal consultations in a public hospital in Durango City, Mexico participated in the study. All participants submitted a revised Spanish translated Mexican version of the EPDS and were examined by a psychiatrist to evaluate the presence of depression by using DSM-IV criteria. Of the 120 teenager pregnant women studied, 2 had major depression and 25 had minor depression according to the DSM-IV criteria. The optimal EPDS cut-off for screening combined major and minor depression in teenager pregnant women was 8/9. At this threshold, we found a sensitivity of 70.4%, a specificity of 84.9%, a positive predictive value of 47.6%, a negative predictive value of 91.0%, and an area under the curve of 0.81 (95% confidence interval: 0.56-1.07). The EPDS can be used for screening depression in Mexican teenager pregnant women whenever a cut-off score of 8/9 is used.


The relevance of sexual responsiveness to sexual function in male stroke patients.
Stroke may have negative consequences for the patients' quality of life, including sexual function. Whereas physical impairment will influence sexual positions and movement during sex, depression and medication may reduce sexual desire. So far, data on sexual dysfunction after stroke are scant. Although some support for physical as well as psychological explanations has been shown, further research to find the remedies for those patients with sexual problems after stroke is needed. The focus of the present study is on the identification of relevant psychological factors. The aim of this study was to study the impact of anxiety, depression, and sexual responsiveness on sexual function in male stroke patients. Nineteen male stroke patients completed a number of self-report measures to assess psychological and sexual factors. Sexual function based on the International Index of Erectile Function, anxiety and depression based on the Symptom Checklist-90, and sexual responsiveness based on the Sexual Inhibition/Sexual Excitation Scale, including propensities for sexual excitation and sexual inhibition as a result of both performance failure and performance consequences, were assessed. Sexual excitation was positively related to sexual desire, whereas inhibition because of the threat of performance failure was negatively related to orgasmic function and sexual desire (P < 0.01). Patients with high levels of inhibition because of threat of performance failure were more likely to report low scores on overall sexual function than those with low levels. Although the statistical power is rather low, the results show the relevance of sexual responsiveness to sexual function in male stroke patients. The present study can be considered as a first step toward building a theoretical framework of relevant psychological and physical factors, which is needed to develop adequate interventions for those patients with sexual problems after stroke.


[Logopedic and psychological-pedagogic maintenance of infants with cerebral palsy].
The problem of perinatal pathology of the nervous system in infants is getting more and more urgent due to the progressive growth of the frequency of cerebral disorders in newborns. This pathology leads to the development of severe motor and speech disorders which inhibit the development of communication skills and social adaptation of children in future. Perinatal factors cause not only neurologic and mental disorders but impede and distort the formation of pre-speech functions, basic for speech development, in infants thus worsening their disability. Patients with cerebral palsy make up 57% of children acknowledged as disabled. Therefore, logopedic diagnostic methods are needed to allow identification of the structure of pre-speech defects in infant period of life, prediction of the level of nervous-mental development, planning and realization of a correction-educational route from the first months of life.


Improving medication adherence with adjuvant aromatase inhibitor in women with breast cancer: study protocol of a randomised controlled trial to evaluate the effect of short message service (SMS) reminder.
Medication adherence refers to whether a patient takes medication according to the frequency prescribed, or continues to take a prescribed medication. Inadequate adherence to medication may cause alterations in risk-benefit ratios, resulting in reduced benefits, increased risks or both, and is significantly associated with adverse clinical outcomes and higher healthcare costs. We aim to examine the effect of a computer generated short message service (SMS) reminder in improving medication adherence, and inhibiting the aromatisation process amongst breast cancer women receiving oral aromatase inhibitor therapy. In this randomised controlled trial, eligible patients will be equally allocated to receive either SMS reminder or standard care. The former receives weekly SMS reminder to take medication while the latter does not receive any. The primary endpoint of medication adherence at 1-year is assessed using the Simplified Medication Adherence Questionnaire, and compared using the χ2 test. Adjustment for baseline covariate and potential confounders will be made using the logistic regression. Secondary outcomes involving estrone and androstenedione levels will be compared using the analysis of covariance, whereas the estradiol levels (< 18.4 pmol/L versus ≥18.4 pmol/L) will be compared using the χ2 test, and the logistic regression. Further, the assessment of knowledge, attitude, behaviour, and barriers and facilitating factors of medication adherence will be made via logistic regression. This will be the first study to evaluate short-term clinical outcomes from SMS reminder for breast cancer patients on aromatase inhibitor therapy. Random allocation to SMS reminder or control arm ensures that patients in both arms will be comparable with respect to demographic and clinical characteristics, and any difference in outcomes can be attributed to the intervention. Participants are not blinded to the assignment of intervention, thus there may be potential for bias in outcome assessments. NCT02524548 . Retrospectively registered on 17 August 2015.


P2Y receptor signaling regulates phenotype and IFN-alpha secretion of human plasmacytoid dendritic cells.
Plasmacytoid dendritic cells (PDCs) play powerful regulatory roles in innate and adaptive immune responses and are a major source of type I interferon (IFN) following viral infection. During inflammation and mechanical stress, cells release nucleotides into the extracellular space where they act as signaling molecules via G protein-coupled P2Y receptors. We have previously reported on the regulation of myeloid dendritic cell (DC) function by nucleotides. Here, we report that human PDCs express several subtypes of P2Y receptors and mobilize intracellular calcium in response to nucleotide exposure. As a functional consequence, PDCs acquire a mature phenotype that is further enhanced in the context of CD40 ligation. Strikingly, nucleotides strongly inhibit IFN-alpha secretion induced by influenza virus or CpG-A. This effect is most pronounced for the uridine nucleotides UDP and UTP and the sugar nucleotide UDP-glucose, ligands of P2Y(6), P2Y(4), and P2Y(14), respectively. Nucleotide-induced inhibition of IFN-alpha production is blocked by suramin, a P2Y receptor antagonist. Pharmacological data point toward a role of protein kinase C in the negative regulation of type I IFN. Manipulating PDC function with P2Y receptor agonists may offer novel therapeutic strategies for autoimmune diseases or cancer.


Membrane perforations inhibit lysosome fusion by altering pH and calcium in Listeria monocytogenes vacuoles.
Listeria monocytogenes (Lm) evade microbicidal defences inside macrophages by secreting a pore-forming cytolysin listeriolysin O (LLO), which allows Lm to escape vacuoles. LLO also inhibits Lm vacuole fusion with lysosomes, which indicates LLO alters vacuole chemistry prior to release of Lm into cytoplasm. Using fluorescent probes to measure membrane permeability, calcium and pH, we identified small membrane perforations in vacuoles containing wild-type but not LLO-deficient (hly-) Lm. The small membrane perforations released small fluorescent molecules and persisted for several minutes before expanding to allow exchange of larger fluorescent molecules. Macropinosomes and hly- Lm vacuoles acidified and increased their calcium content ([Ca2+]vac) within minutes of formation; however, the small perforations made by LLO-expressing bacteria increased vacuolar pH and decreased [Ca2+]vac shortly after infection. Experimental increases in vacuolar pH inhibited Lm vacuole fusion with lysosomes. The timing of perforation indicated that LLO-dependent delays of Lm vacuole maturation result from disruption of ion gradients across vacuolar membranes.


[Relationship between finger length and ridge count in patients with Marfan syndrome].
Palmar dermatoglyphs were studied in 38 patients with lens dislocation. The patients were distributed into three groups: Marfan syndrome, mild Marfan syndrome, isolated lens dislocation. Marked arachnodacytyly was observed in the first group. In these patients increase in finger length was positively correlated with the ridge count. Moderate increase in finger length and ridge count was observed in the second group. The relative finger length was lower in patients with isolated lens dislocation than in unaffected persons, though the ridge count did not differ from the control. The relations noted between the finger length and ridge count in Marfan syndrome are in agreement with the suggestion that these two parameters are determined by common cause, namely, the morphogenetic gradient in digital primordia.


Vibrational spectra, theoretical calculations, and two-dimensional potential energy surface for the ring-puckering vibrations of 2,4,7-trioxa[3.3.0]octane.
2,4,7-Trioxa[3.3.0]octane (247TOO) is an unusual bicyclic molecule which can exist in four different conformational forms which are determined by the directions of the two ring- puckering motions. The vibrational assignments of 247TOO have been made based on its infrared and Raman spectra and theoretical density functional theory (DFT) calculations. The two ring-puckering motions (in-phase and out-of-phase) were observed in the Raman spectra of the liquid at 249 and 205 cm(-1) and these values correspond well to the DFT values of 247 and 198 cm(-1). Ab initio calculations were utilized to calculate the structures and conformational energies for the four energy minima and the barriers to interconversion and the data was utilized to generate a two-dimensional potential energy surface (PES) for the two ring-puckering motions. The resulting quantum state energies for this PES were then calculated in order to better understand the patterns that are produced when the PES has four energy minima at different energy values. The wave functions corresponding to the different quantum states were also calculated. The NMR spectrum of 247TOO showed the presence of the two lowest energy conformations, consistent with the results of the ab initio calculations.


Metabolic transit and toxicity of Maillard reaction products.
The feeding of Maillard reaction products (MRP) has been reported to lead to a variety of effects on metabolism which may be classed as "anti-nutritional" or "anti-physiological", depending on whether they are due to the loss of essential nutrients or to the presence of the MRP per se. This paper describes the sensitivity of essential nutrients in the "early" and "advanced" stages of the Maillard reaction, the metabolic transit of Amadori compounds, premelanoidins, melanoidins, hydroxymethyl-furfural, carboxymethyl-lysine, as well as the effects of MRP on pancreatic amylase and on urinary zinc excretion.


Low detection rate of HPV in oral and laryngeal carcinomas.
The presence of human papillomaviruses (HPVs) in 38 oral and 16 laryngeal lesions (verrucous hyperplasia, carcinoma in situ and carcinomas) was investigated using the polymerase chain reaction (PCR) technique. All biopsies were fresh frozen and a set of consensus and type-specific primers was used for PCR detection and HPV typing. In oral biopsies a low proportion of HPV-positive cases was found, despite the sensitive techniques. Only one case out of 38, a carcinoma in situ was positive (2.6%). It is thought that this finding reflects a minimal presence of HPV in the oral lesions, but a transient role of virus in the induction of carcinomas cannot be ruled out. Differences in relation to other studies may be geographical and/or methodological. In laryngeal carcinomas (and dysplasias), 3 out of 16 cases were HPV positive. This frequency (19%) concurs with most other studies.


Autonomous Cell Migration to CSF1 Sources via a Synthetic Protein-Based System.
Inflammatory lesions, often seen in diseases such as rheumatoid arthritis, atherosclerosis and cancer, feature an acidic (i.e., low pH) microenvironment rampant with cytokines, such as CSF1. For potential therapeutic intervention targeted at these CSF1 sources, we have assembled a system of four proteins inside a cell (i.e., HEK293) that initially had no natural CSF1-seeking ability. This system included a newly engineered CSF1 chimera receptor (named CSF1Rchi), the previously engineered Ca2+ activated RhoA (i.e., CaRQ), vesicular stomatitis virus glycoprotein G (VSVG) and thymidine kinase (TK). The binding of CSF1 to the CSF1Rchi generated a Ca2+ signal that activated CaRQ-mediated cellular blebbing, allowing autonomous cell migration toward the CSF1 source. Next, the VSVG protein allowed these engineered cells to fuse with the CSF1 source cells, upon low pH induction. Finally, these cells underwent death postganciclovir treatment, via the TK suicide mechanism. Hence, this protein system could potentially serve as the basis of engineering a cell to target inflammatory lesions in diseases featuring a microenvironment with high levels of CSF1 and low pH.


A case of congenital lipoid adrenal hyperplasia.
Lipoid congenital adrenal hyperplasia (lipoid CAH), a rare disorder of steroid biosynthesis, is the most severe form of CAH. In this disorder the synthesis of glucocorticoids, mineralocorticoids and sex steroids is impaired which result in adrenal failure, severe salt wasting crisis and hyperpigmentation in phenotypical female infants irrespective of genetic sex. In this report, we presented a 28-day-old phenotypic female infant, which referred with lethargy, failure to thrive and electrolyte abnormalities. Considering the clinical and biochemical findings, lipoid CAH was diagnosed and replacement therapy with standard doses of glucocorticoid and mineralocorticoid and sodium chloride was initiated. During follow-up, she had good clinical condition, but at 6 years of age, she refers with hypertension and adrenal insufficiency because of arbitrary drug discontinuation by mother. In ultrasonography an abdominal mass (the testicles) was reported. Chromosome study showed 46XY pattern. Orchiectomy was performed. We recommended that in cases with clinical presentation of adrenal insufficiency if there is not the facility to determine the karyotype, repeated ultrasonography perform during follow-up. In addition, investigating the genetic bases of the disorder would help us to determine the pathogenesis of lipoid CAH in our community. It would be helpful in prenatal diagnosis and treatment of the disorder to prevent its related comorbidities.


The effects of progesterone on matrix metalloproteinases in cultured human gingival fibroblasts.
Although pregnancy gingivitis is widely believed to result from elevated hormone concentrations, the mechanism(s) involved in the etiology of this condition remain unknown. Paradoxically, despite the apparent inflammation for a prolonged period, pregnancy gingivitis rarely progresses to periodontitis and usually resolves postpartum. We used several methods to test in vitro the hypothesis that the elevated progesterone levels of pregnancy might inhibit the production of some of the matrix metalloproteinases (MMPs) that are responsible for periodontal destruction. Cultured human gingival fibroblasts (GF) were tested in phenol red-free, serum-free medium with or without the progestogen, medroxyprogesterone acetate (MPA; 10(-6) M), using interleukin-1beta (IL-1beta) to initiate immune responses and MMP production. These MMP responses were examined by macroarrays, reverse transcription-polymerase chain reaction (RT-PCR), zymograms, and enzyme-linked immunosorbent assay (ELISA). Array analysis showed that pretreatment of GF with MPA reduced mRNA induction for MMPs-1, -3, and -10 in response to 6 to 8 hours incubation with IL-1beta. RT-PCR confirmed, that after 24 hours with IL-1beta , GF pretreated with MPA had undetectable levels of mRNA for MMPs-1, -2, -3, -7, -10, and -13. Zymograms of culture media from this 24-hour period showed reduction in several proteolytic activities. Examination of such 24-hour media using ELISA for MMP-3 and pro-MMP-13 confirmed that secretion of these enzymes was upregulated by IL-1beta and modulated downward by pretreatment with MPA. Production by GF of numerous MMPs in response to IL-1beta was significantly reduced by progesterone. This steroidal modulation of proteolytic enzymes could help to explain why pregnancy gingivitis typically is not characterized by progression to periodontitis.


Geographic distribution of insufficient sleep across the United States: a county-level hotspot analysis.
Insufficient sleep is associated with cardiometabolic risk and neurocognitive impairment. Determinants of insufficient sleep include many social and environmental factors. Assessment of geographic hot/coldspots may uncover novel risk groups and/or targets for public health intervention. The aim of this study was to discern geographic patterns in the first data set to include county-level sleep data. The 2009 Behavioral Risk Factor Surveillance System was used. Insufficient sleep was assessed with a survey item and dichotomized. Data from n = 2231 counties were available. Tests for significant spatial concentrations of high/low levels of insufficient sleep (hotspots/coldspots) used the Getis-Ord G* statistic of local spatial concentration, chosen due to the nature of missing data. Eighty-four counties were hotspots, with high levels of insufficient sleep (P < .01), and 45 were coldspots, with low insufficient sleep (P < .01). Hotspots were found in Alabama (1 county), Arkansas (1), Georgia (1), Illinois (1), Kentucky (25), Louisiana (1), Missouri (4), Ohio (7), Tennessee (12), Texas (9), Virginia (6), and West Virginia (16). Coldspots were found in Alabama (1 county), Georgia (2), Illinois (6), Iowa (6), Michigan (2), Minnesota (1), North Carolina (1), Texas (7), Virginia (12), and Wisconsin (6). Several contiguous hotspots and coldspots were evident. Notably, the 17 counties with the highest levels of insufficient sleep were found in a contiguous set at the intersection of Kentucky, Tennessee, Virginia, and West Virginia (all P < .0002). Geographic distribution of insufficient sleep in the United States is uneven. Some areas (most notably parts of Appalachia) experience disproportionately high amounts of insufficient sleep and may be targets of intervention. Further investigation of determinants of geographic variability needs to be explored, which would enhance the utility of these data for development of public health campaigns.


First Report of Fusarium Maize Ear Rot Caused by Fusarium kyushuense in China.
From September 2009 to October 2012, surveys to determine population structure of Fusarium species on maize were conducted in 22 provinces in China, where the disease incidence ranged from 5 to 20% in individual fields. Maize ears with clear symptoms of Fusarium ear rot (with a white to pink- or salmon-colored mold at the ear tip) were collected from fields. Symptomatic kernels were surface-sterilized (1 min in 0.1% HgCl2, and 30 s in 70% ethanol, followed by three rinses with sterile distilled water), dried, and placed on PDA. After incubation for 3 to 5 days at 28°C in the dark, fungal colonies displaying morphological characteristics of Fusarium spp. (2) were purified by transferring single spores and identified to species level by morphological characteristics (2), and DNA sequence analysis of translation elongation factor-1α (TEF) and β-tubulin genes. A large number of Fusarium species (mainly F. graminearum species complex, F. verticillioides, and F. proliferatum) were identified. These Fusarium species are the main causal agents of maize ear rot (2). Morphological characteristics of six strains from Anhui, Hubei, and Yunnan provinces were found to be identical to those of F. kyushuense (1), which was mixed with other Fusarium species in the natural infection in the field. Colonies grew fast on PDA with reddish-white and floccose mycelia. The average growth rate was 7 to 9 mm per day at 25°C in the dark. Reverse pigmentation was deep red. Microconidia were obovate, ellipsoidal to clavate, and 5.4 to 13.6 (average 8.8) μm in length. Macroconidia were straight or slightly curved, 3- to 5-septate, with a curved and acute apical cell, and 26.0 to 50.3 (average 38.7) μm in length. No chlamydospores were observed. Identity of the fungus was further investigated by sequence comparison of the partial TEF gene (primers EF1/2) and β-tubulin gene (primers T1/22) of one isolate (3). BLASTn analysis of the TEF amplicon (KC964133) and β-tubulin gene (KC964152) obtained with cognate sequences available in GenBank database revealed 99.3 and 99.8% sequence identity, respectively, to F. kyushuense. Pathogenicity tests were conducted twice by injecting 2 ml of a prepared spore suspension (5 × 105 spores/ml) into maize ears (10 per isolate of cv. Zhengdan958) through silk channel 4 days post-silk emergence under field conditions in Wuhan, China. Control plants were inoculated with sterile distilled water. The ears were harvested and evaluated 30 days post-inoculation. Reddish-white mold was observed on inoculated ears and the infected kernels were brown. No symptoms were observed on water controls. Koch's postulates were fulfilled by re-isolating the pathogen from infected kernels. F. kyushuense, first described on wheat in Japan (1), has also been isolated from rice seeds in China (4). It was reported to produce both Type A and Type B trichothecene mycotoxins (1), which cause toxicosis in animals. To our knowledge, this is the first report of F. kyushuense causing maize ear rot in China and this disease could represent a serious risk of yield losses and mycotoxin contamination in maize and other crops. The disease must be considered in existing disease management practices. References: (1) T. Aoki and K. O'Donnell. Mycoscience 39:1, 1998. (2) J. F. Leslie and B. A. Summerell. The Fusarium Laboratory Manual. Blackwell Publishing, Ames, IA, 2006. (3) F. Van Hove et al. Mycologia 103:570, 2011. (4) Z. H. Zhao and G. Z. Lu. Mycotaxon 102:119, 2007.


Adenocarcinoma of the Sinonasal Tract: A Review of the National Cancer Database.
Background Sinonasal adenocarcinoma (SNAC) is a rare malignancy arising from mucus-secreting glandular tissue. Limited large-scale studies are available due to its rarity. We evaluated SNAC in the National Cancer Database (NCDB), a source that affords multi-institutional, population studies of rare cancers and their outcomes. Methods The NCDB was queried for adenocarcinoma in the sinonasal tract. Multivariate analyses were performed to evaluate for factors contributing to overall survival (OS). Results A total of 553 patients were identified. The cohort was composed of 59.3% males. The nasal cavity was the most common primary site, representing 44.1% of cases. About 5.7% of patients presented with nodal disease, while 3.3% had distant metastases. About 40.6% of cases presented with stage IV disease. About 73.5% of patients underwent surgery, 54.2% received radiation therapy, and 27.7% had chemotherapy. Median OS was 71.7 months, while OS at 1, 2, and 5 years was 82, 73.0, and 52%, respectively. On multivariate analysis, advanced age (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02-1.05), Charlson-Deyo score of 1 (HR: 1.99; 95% CI: 1.20-3.30), advanced tumor grade (HR: 2.73; 95% CI: 1.39-5.34), and advanced tumor stage (HR: 2.71; 95% CI: 1.33-5.50) were associated with worse OS, whereas surgery (HR: 0.34; 95% CI: 0.20-0.60) and radiation therapy (HR: 0.55; 95% CI: 0.33-0.91), but not chemotherapy (HR: 1.16; 95% CI: 0.66-2.05), predicted improved OS. Conclusions SNAC is a rare malignancy with 5-year survival approximating 50%. Surgery and radiation therapy, but not chemotherapy, are associated with improved survival, and likely play a critical role in the interdisciplinary management of SNAC.


Multimodal semantic battery to monitor progressive loss of concepts in the semantic variant of primary progressive aphasia (svPPA): an innovative proposal.
Semantic variant primary progressive aphasia (svPPA) is a rare neurodegenerative disease characterized by a progressive loss of semantic knowledge. Patients with svPPA show anomia, impaired word comprehension, poor object recognition, and difficulties in retrieving semantic information. svPPA is also a unique "natural" model that allows clinicians and cognitive neuroscientists to study the organization of semantic memory because only semantic knowledge is affected in the initial period of the disease, with relative sparing of other cognitive domains. In the clinical practice, semantic memory is commonly tested only with verbal tests. The aim of the present study was to preliminary test a new Multimodal Semantic Battery developed in our laboratory, which comprised 11 subtests designed to assess the semantic knowledge of multiple items via all input modalities. The battery was administered twice, over four years, to a patient diagnosed with svPPA. We found that when extensively tested with multiple tests, in some cases, he was still able to recall semantic features of the items that otherwise would not have emerged with standard semantic tests. These results are discussed for the clinical practice: monitoring semantic memory through all modalities in a practical and reliable way could be useful for both clinicians and experimental researchers to better investigate the breakdown of semantic knowledge.


Hepatic Venous Outflow Stenosis After Auxiliary Left Hemiliver Transplantation Diagnosed by Ultrasonic Shear Wave Elastography Combined With Doppler Ultrasonography.
Hepatic vein stenosis after liver transplantation is a relatively rare complication that could even result in graft loss. However, it is difficult to arrive at a definite diagnosis at the early stage of postoperation, and there are few researches on ultrasonic shear wave elastography in the diagnosis of hepatic vein stenosis. We report the case of an 11-year-old male patient with cirrhosis due to hepatolenticular degeneration who received an auxiliary left hemiliver graft from his uncle. Massive ascites developed in 4 days after the operation. Stenosis was suspected at the site of anastomosis by Doppler ultrasonography when elevating the velocity of the left hepatic vein. Meanwhile, increased stiffness of the graft was revealed by ultrasonic shear wave elastography. The stenosis was confirmed by subsequent digital subtraction angiography. Ascites decreased gradually after the stent implantation. Our case indicates that ultrasonic shear wave elastography combined with Doppler ultrasonography is a promising method for noninvasive diagnosis of hepatic venous outflow stenosis following liver transplantation.


Electrosigmoidogram, electrorectogram and their relation.
The electric activity of the sigmoid colon (electrosigmoidogram=ESG) and rectum (electrorectogram=ERG) and their relationship was studied in nine patients. Slow waves or pacesetter potentials (PPs) of the sigmoid colon and rectum were recorded. The PP frequency and amplitude of the electrorectograms were higher (p less than 0.05) than electrosigmoidograms. Balloon distention of the sigmoid colon or rectum increased the frequency, amplitude and velocity of PPs and APs proximal to the balloon and led to their decrease distally. These effects were enhanced with increased balloon distention until the balloon was expelled. Balloon distention of the sigmoid colon did not affect the rectal electromechanical activity and vice versa. This study suggests that the movement of the sigmoid colon or rectum is of the "mass type".


The sickle cell trait in relation to the training and assignment of duties in the Armed Forces: I. Policies, observations, and studies.
Opinions differ widely concerning the risks assumed by individuals with sickle cell trait (SCT) while engaged in military activities that involve exposure to hypoxic environments and other stress situations. Some claim that there is no scientific evidence of greater risk to those with SCT than to those without it, and that any and all restrictions are unfounded and unjust. Others believe that the success of military missions with the least possible risk to the health and safety of individuals are major concerns and that restrictions on the selection, training, and assignment to duties are necessary. Clinical observations indicate that in vivo sickling of erythrocytes in individuals with the SCT may occur in association with cardiac, pulmonary, and other primary diseases. Past scientific investigations have been inadequate and the conclusions drawn have been conflicting. Future policies will be based on information from new investigations combined with facts revealed in the literature and from retrospective studies of the experiences of those with and without the SCT while on duty in the Armed Forces.


The roles of calcium/calmodulin-dependent and Ras/mitogen-activated protein kinases in the development of psychostimulant-induced behavioral sensitization.
Although the development of behavioral sensitization to psychostimulants such as cocaine and amphetamine is confined mainly to one nucleus in the brain, the ventral tegmental area (VTA), this process is nonetheless complex, involving a complicated interplay between neurotransmitters, neuropeptides and trophic factors. In the present review we present the hypothesis that calcium-stimulated second messengers, including the calcium/calmodulin-dependent protein kinases and the Ras/mitogen-activated protein kinases, represent the major biochemical pathways whereby converging extracellular signals are integrated and amplified, resulting in the biochemical and molecular changes in dopaminergic neurons in the VTA that represent the critical neuronal correlates of the development of behavioral sensitization to psychostimulants. Moreover, given the important role of calcium-stimulated second messengers in the expression of behavioral sensitization, these signal transduction systems may represent the biochemical substrate through which the transient neurochemical changes associated with the development of behavioral sensitization are translated into the persistent neurochemical, biochemical and molecular alterations in neuronal function that underlie the long-term expression of psychostimulant-induced behavioral sensitization.


PLANNING FOR DIVERSITY: EVALUATION OF A VOLUNTEER DISASTER RESPONSE PROGRAM.
The United States 'population is growing and diversifying rapidly. The nation is also experiencing an increase in the frequency and magnitude of disasters. Yet, most organizations that respond to these disaster events operate with a homogenous volunteer base - largely, white, middle class, and older. To improve program reach and effectiveness, diversifying volunteer pools is increasingly important. This article presents an evaluation of one response organization attempting to diversify its volunteer base geographically, ethnically, and linguistically, to better serve disaster survivors. Drawing on interviews with program leadership, the results, highlight two needs: 1) clear communication about the definition and rationale of diversity throughout the organization and 2) implementation of volunteer recruitment methods to address these goals.


Pedicle and antler regeneration following antlerogenic tissue removal in red deer (Cervus elaphus).
The physiological control mechanisms underlying the histogenesis of the pedicle, which precedes antler growth, from the frontal bones of male deer are poorly understood. The aim of this study was to investigate the extent of pedicle/antler regeneration after removal (for histological evaluation) of the antlerogenic region or pedicle tissue during pedicle development to determine whether the subsequent pattern of regeneration could contribute to the understanding of pedicle histogenesis and the mechanism of the transition between permanent pedicles and deciduous antlers. The contralateral pedicles of six stags were not removed and these data serve as controls. All deer were observed frequently and measurements of regeneration were made in March after all antler growth had ceased for that season. The development stage of the pedicle was determined by a combination of pedicle height measurements and histological studies. The results showed that pedicle formation histologically covers three stages: a period of intramembranous ossification (when the pedicle is less than 5 mm in height), a period when the ossification pattern changes (when the pedicle is between 5 and 28 mm in height) and a period of modified endochondral ossification (when the pedicle is over 30 mm in height). In all ossification stages some deer regenerated neither antlers nor pedicles. The pedicles which regenerated following the loss of antlerogenic tissue at the intramembranous ossification stage were shorter than the controls (P < 0.01), but longer than the pedicles regenerated after pedicle removal at the transitional stage in the pattern of ossification (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


MAGI2 Mutations Cause Congenital Nephrotic Syndrome.
Steroid-resistant nephrotic syndrome (SRNS), a heterogeneous disorder of the renal glomerular filtration barrier, results in impairment of glomerular permselectivity. Inheritance of genetic SRNS may be autosomal dominant or recessive, with a subset of autosomal recessive SRNS presenting as congenital nephrotic syndrome (CNS). Mutations in 53 genes are associated with human SRNS, but these mutations explain ≤30% of patients with hereditary cases and only 20% of patients with sporadic cases. The proteins encoded by these genes are expressed in podocytes, and malfunction of these proteins leads to a universal end point of podocyte injury, glomerular filtration barrier disruption, and SRNS. Here, we identified novel disease-causing mutations in membrane-associated guanylate kinase, WW, and PDZ domain-containing 2 (MAGI2) through whole-exome sequencing of a deeply phenotyped cohort of patients with congenital, childhood-onset SRNS. Although MAGI2 has been shown to interact with nephrin and regulate podocyte cytoskeleton and slit diaphragm dynamics, MAGI2 mutations have not been described in human SRNS. We detected two unique frameshift mutations and one duplication in three patients (two families); two siblings shared the same homozygous frameshift mutation, whereas one individual with sporadic SRNS exhibited compound heterozygosity. Two mutations were predicted to introduce premature stop codons, and one was predicted to result in read through of the normal translational termination codon. Immunohistochemistry in kidney sections from these patients revealed that mutations resulted in lack of or diminished podocyte MAGI2 expression. Our data support the finding that mutations in the MAGI2 gene are causal for congenital SRNS.


The volunteer anesthetist: a personal view.
The most common opportunities for nurse anesthetists to be involved in volunteer anesthesia overseas are usually on a surgical team to provide direct care for selected types of patients or to be involved in teaching local anesthesia providers. The challenges are numerous and unique in each setting. Sharing of knowledge, directly as an instructor or indirectly as a provider, provides for a great impact on health care delivery in many emerging nations. The anesthesia provider who is working to deliver care in another country must consider many variables before taking on such a venture. The type of surgical team or teaching assignment one accepts will determine the type of preparation that must be done before departing. In addition to the many organizational items, one should consider some personal issues as well. Lost wages, transportation costs, and lodging expenses are often paid for by the volunteer. Time away from one's family may also be a consideration. Health care, such as updated immunizations, must be attended to before to departure. Volunteers must be able to provide good care in less than ideal situations, and often with much less equipment and medications than are available in the United States. A review of some of the issues that one should consider before deciding to be a volunteer are outlined in this article. The nurse anesthetist who successfully anticipates and deals with the challenges of volunteer anesthesia will be rewarded with an intense degree of personal satisfaction. The ability to give back to the profession and those who would otherwise not have access to one's skills or knowledge produces a sense of accomplishment that is unique.


Extracorporeal Hyperoxygenation Therapy (EHT) for Carbon Monoxide Poisoning: In-Vitro Proof of Principle.
Carbon monoxide (CO) poisoning is the leading cause of poisoning-related deaths globally. The currently available therapy options are normobaric oxygen (NBO) and hyperbaric oxygen (HBO). While NBO lacks in efficacy, HBO is not available in all areas and countries. We present a novel method, extracorporeal hyperoxygenation therapy (EHT), for the treatment of CO poisoning that eliminates the CO by treating blood extracorporeally at elevated oxygen partial pressure. In this study, we proof the principle of the method in vitro using procine blood: Firstly, we investigated the difference in the CO elimination of a hollow fibre membrane oxygenator and a specifically designed batch oxygenator based on the bubble oxygenator principle at elevated pressures (1, 3 bar). Secondly, the batch oxygenator was redesigned and tested for a broader range of pressures (1, 3, 5, 7 bar) and temperatures (23, 30, 37 °C). So far, the shortest measured carboxyhemoglobin half-life in the blood was 21.32 min. In conclusion, EHT has the potential to provide an easily available and effective method for the treatment of CO poisoning.


Management of Poisoned Patients: Implementing a Blended Toxicology Curriculum for Emergency Medicine Residents.
This curriculum is appropriate for emergency medicine residents PGY 1-3 as a toxicology curriculum. The intent is to run this curriculum over one week. Toxicology is an important part of the emergency medicine (EM) curriculum and defined in the Council of Residency Directors (CORD) 2019 Model of Clinical Practice of Emergency Medicine as a key area of core content expected to be mastered by graduating EM seniors.1 Unfortunately, programs may not have time in their schedules for a dedicated toxicology curriculum, and residents may not have time to learn this important subject outside of conference didactics. Many emergency medicine programs have mandatory toxicology rotations, as many as 66% according to a 2018 study, with an additional 22% of EM programs offering an elective.2 At our institution, we have limited toxicology faculty available for instruction, and until now have only been able to incorporate occasional lectures into regular conference didactics, prompting our development of a new approach. Developing an asynchronous curriculum allows more dedicated time to study toxicology for our learners and allows greater flexibility for our limited toxicology faculty to teach during a synchronous component. Several asynchronous toxicology curricula have been developed previously.3,4 There have also been several novel synchronous toxicology curricular innovations for introduction during regular conference didactics.5,6 While some learners can benefit from asynchronous learning alone, it has been shown that having synchronous components in distance learning can be very important for improving learning experience and improving deep understanding rather than surface learning.7 Here we propose a one-week, blended asynchronous and synchronous rotation in toxicology that aims to give learners a foundation in important core toxicological concepts that they can implement on shift in the Emergency Department. The goal of this curriculum is to introduce EM residents to core toxicology concepts and to reinforce toxicology principles through a multimodal approach that leads to increased confidence in the management of poisoned patients on shift. The educational strategies used in this curriculum include: 1) Online asynchronous modules for each day of the week consisting of free open access medical education (FOAMed) articles, instruction on core topics, and daily quizzes. The content was created, organized, and published utilizing Articulate Rise 360 8 as a learning management system (LMS) but could easily be adapted to other LMS platforms, such as Google Classroom. The majority of educational content used to build the modules was based on Rosen's Emergency Medicine Concepts and Clinical Practice. (5th editions). 2) A virtual simulation session reviewing toxicology cases with a faculty member. Cases were initially oral boards style cases but were later adapted to independent learning sessions utilizing pre-made Full-Code 9 scenarios. This could likely be adapted to other platforms such as in-person simulation for institutions without Full Code subscriptions. 3) A virtual discussion and question & answer board review session with a staff toxicologist. Following completion of the course, residents were encouraged to fill out a survey developed by the writer of the course designed to assess their thoughts about the course, their confidence in recognizing toxidromes as well as their comfort in the medical management of the poisoned patient. This survey was developed in-house and utilized a Likert scale and was administered on Google Forms. In an effort to promote honest feedback, residents were made aware that submissions were anonymous and email information was not collected. Of the 22 participating residents (PGY1-3), 15 responded to our survey for a response rate of 68%. Overall, resident responses to the course were favorable. All participants except for one answered that they were "satisfied" or "very satisfied" with the course; the respondent who did not mark "satisfied" or "very satisfied" marked the option labeled "neutral." Similarly, 93% (14/15) of respondents "agreed" or "strongly agreed" that they would recommend this course to a colleague, and 86% (13/15) "agreed" or "strongly agreed" that the course was a valuable use of their time.Resident responses also indicated an increased confidence in both the recognition of toxidromes and the management of poisoned patients. The majority of respondents (9/15) indicated that their perceived confidence in recognizing toxidromes improved after completion of the course; the remainder, except for one, remarked the same level of confidence before and after completing the course. The resident who had a decline in their confidence said they were "confident" in recognizing toxidromes prior to the course and "somewhat confident" after the course. Unsurprisingly, perceived confidence in the medical management of toxicology patients improved for 87% (13/15) of respondents after having taken the course, with 2 respondents noting the same level of confidence before and after taking the course.Lastly, multiple residents wrote in the free-response section that the toxicology rotation had been directly helpful to them when managing various toxidromes with real cases in the emergency department. For example, one response noted that they had since managed both a tricyclic antidepressant and a calcium channel blocker overdose, which they felt more comfortable with after completing the course. Another resident wrote about the experience of having a pediatric patient suffering from an ingestion of both acetaminophen and aspirin who was placed on a bicarbonate drip. This blended synchronous and asynchronous approach to a toxicology course was a success with the residents. Based on our survey responses, the majority of the residents felt this was a valuable educational experience. Many of the residents commented on times after the course where they were directly able to apply the knowledge learned from the modules, which was also encouraging. While COVID limitations kept our synchronous aspects virtual, these were also successful with the residents. While we had initially used oral boards style cases for the simulation session, we had found that engagement with learners during these sessions was not as high as we had hoped. We subsequently switched to using the virtual simulation platform Full Code.8 The learners seemed to enjoy these cases much more with having more visual stimulus during the cases. It was also less work on the part of the faculty to have pre-written toxicology cases to use and lab values/imaging results a click away. However, for institutions without a Full Code subscription, oral boards style cases or in person simulation would be a worthwhile alternative. Additionally, video conference sessions with our toxicology faculty members were helpful for the residents to go over the information they had learned in a question-and-answer format.Regarding the synchronous aspect of the course, having written the modules ahead of time, it was very easy to upload into an LMS. We particularly found Articulate Rise7 to be helpful as an LMS, especially with integrating some interactive elements into each module. However, this could easily be adapted into any LMS your institution prefers, or even into slideshow software. General approach to poisoned patient, gastric decontamination, dialysis in toxicology, acetaminophen overdose (od), salicylate od, carbon monoxide poisoning, pediatric toxicology considerations, alcohol withdrawal, toxic alcohols, beta blocker od, calcium channel blocker od, tca od, serotonin syndrome, opiate od, body packers vs stuffers, marijuana, synthetic cannabinoids, gamma hydroxybutyric acid (ghb) od; cocaine toxicity, inhalant abuse, spider envenomations, snake envenomations, marine envenomations, mushroom toxicities, organophosphate poisoning.


Synergistic Effect of Endogenous and Exogenous Aldehydes on Doxorubicin Toxicity in Yeast.
Anthracyclines are frequently used to treat many cancers including triple negative breast cancer, which is commonly observed in African-American women (AA), and tend to be more aggressive, carry worse prognoses, and are harder to manage because they lack molecular targets. Although effective, anthracyclines use can be limited by serious side effects and eventually the development of drug resistance. In S. cerevisiae, mutants of HOM6 display hypersensitivity to doxorubicin. HOM6 is required for synthesis of threonine and interruption of the pathway leads to accumulation of the threonine intermediate L-aspartate-semialdehyde. This intermediate may synergize with doxorubicin to kill the cell. In fact, deleting HOM3 in the first step, preventing the pathway to reach the HOM6 step, rescues the sensitivity of the hom6 strain to doxorubicin. Using several S. cerevisiae strains (wild type, hom6, hom3, hom3hom6, ydj1, siz1, and msh2), we determined their sensitivity to aldehydes and to their combination with doxorubicin, cisplatin, and etoposide. Combination of formaldehyde and doxorubicin was most effective at reducing cell survival by 31-fold-39-fold (in wild type cells) relative to doxorubicin and formaldehyde alone. This effect was dose dependent on doxorubicin. Cotreatment with formaldehyde and doxorubicin also showed increased toxicity in anthracycline-resistant strains siz1 and msh2. The hom6 mutant also showed sensitivity to menadione with a 2.5-fold reduction in cell survival. The potential use of a combination of aldehydes and cytotoxic drugs could potentially lead to applications intended to enhance anthracycline-based therapy.


Efficacy and safety associated with the use of the Surfacer® Inside-Out® Access Catheter System: Results from a prospective, multicenter Food and Drug Administration-approved Investigational Device Exemption study.
Thoracic central venous obstruction is commonly associated with the use of central venous catheters. The Surfacer System to Facilitate Access in Venous Occlusions Study was an Food and Drug Administration-approved US Investigational Device Exemption study designed to evaluate the performance and safety of the Surfacer System when used to facilitate central venous access in patients with thoracic central venous obstruction. Thirty patients were enrolled in this prospective, multicenter, single-arm study between December 2017 and May 2019. Device performance and adverse events were collected peri-procedurally and at discharge. Enrollment included 15 female and 15 male subjects with a mean age of 55.5 ± 12.9 (range: 30-79) years. Twenty-eight patients (93.3%) required central venous access for hemodialysis access. Locations of thoracic central venous obstruction were graded from 1 to 4 based on severity and extension of venous occlusions. Seven patients (23.3%) had type 1, 6 (20.0%) type 2, 16 (53.3%) type 3, and 1 (3.3%) type 4 obstruction. Successful central venous catheter placement was achieved in 27 of 30 patients (90.0%). The procedure was discontinued in three (10.0%) due to tortuous anatomy discovered intraprocedurally. All 27 patients with successful CVC placement achieved adequate catheter patency and tip positioning with a mean overall procedural time and time to achieve central venous access with the Surfacer System being 44.1 ± 30.6 and 19.1 ± 25.1 min, respectively. There were no device-related adverse events or catheter malposition. The results of the SAVEUS Study confirm the safety and efficacy of the Surfacer System and the Inside-Out procedure when used for the placement of right-sided central venous access in patients with thoracic central venous obstruction.


Telomeres in ecology and evolution: A review and classification of hypotheses.
Research on telomeres in the fields of ecology and evolution has been rapidly expanding over the last two decades. This has resulted in the formulation of a multitude of, often name-given, hypotheses related to the associations between telomeres and life-history traits or fitness-facilitating processes (and the mechanisms underlying them). However, the differences (or similarities) between the various hypotheses, which can originate from different research fields, are often not obvious. Our aim here is therefore to give an overview of the hypotheses that are of interest in ecology and evolution and to provide two frameworks that help discriminate among them. We group the hypotheses (i) based on their association with different research questions, and (ii) using a hierarchical approach that builds on the assumptions they make, such as about causality of telomere length/shortening and/or the proposed functional consequences of telomere shortening on organism performance. Both our frameworks show that there exist parallel lines of thoughts in different research fields. Moreover, they also clearly illustrate that there are in many cases competing hypotheses within clusters, and that some of these even have contradictory assumptions and/or predictions. We also touch upon two topics in telomere research that would benefit from further conceptualization. This review should help researchers, both those familiar with and those new to the subject, to identify future avenues of research.


IDPpi: Protein-Protein Interaction Analyses of Human Intrinsically Disordered Proteins.
Intrinsically disordered proteins (IDPs) are characterized by the lack of a fixed tertiary structure and are involved in the regulation of key biological processes via binding to multiple protein partners. IDPs are malleable, adapting to structurally different partners, and this flexibility stems from features encoded in the primary structure. The assumption that universal sequence information will facilitate coverage of the sparse zones of the human interactome motivated us to explore the possibility of predicting protein-protein interactions (PPIs) that involve IDPs based on sequence characteristics. We developed a method that relies on features of the interacting and non-interacting protein pairs and utilizes machine learning to classify and predict IDP PPIs. Consideration of both sequence determinants specific for conformational organizations and the multiplicity of IDP interactions in the training phase ensured a reliable approach that is superior to current state-of-the-art methods. By applying a strict evaluation procedure, we confirm that our method predicts interactions of the IDP of interest even on the proteome-scale. This service is provided as a web tool to expedite the discovery of new interactions and IDP functions with enhanced efficiency.


Temporary Abdominal Closure Is Associated with Increased Risk for Fungal Intra-Abdominal Infections in Trauma Patients.
Background: Fungal infections are associated with increased morbidity and death. Few studies have examined risk factors associated with post-operative fungal intra-abdominal infections (FIAIs) in trauma patients after exploratory laparotomy. In this study, we evaluated potential risk factors for acquiring post-operative FIAIs and their impact on clinical outcomes. Methods: This was a retrospective analysis of trauma patients admitted from 2005 to 2018 who underwent exploratory laparotomy and subsequently had development of intra-abdominal infection (IAI). Demographics, comorbidities, culture data, antimicrobial usage, Injury Severity Scores (ISS), and clinical outcomes were abstracted. All post-operative IAIs were evaluated and stratified as either bacterial, fungal, combined, and with or without colonization. All groups were compared. Risk factors for the development of post-operative IAI and clinical outcomes were analyzed by Student t test and chi-square test. Multi-variable logistic regression was used to determine independent predictors of post-operative FIAIs. Results: There were 1675 patients identified as having undergone exploratory laparotomy in the setting of traumatic injury, 161 of whom were suspected of having IAI. A total of 105 (6.2%) patients had a diagnosis of IAI. Of these patients, 40 (38%) received a diagnosis of FIAI. The most common fungal pathogens were unspeciated yeast (48.3%), followed by Candida albicans (42.7%), C. glabrata (4.5%), C. dubliniensis (2.25%), and C. tropicalis (2.25%). There were no significant differences in demographics, comorbidities, and percentage of gastric perforations between FIAI and bacterial IAI (BIAI) groups. Patients with FIAIs, however, had a 75% temporary abdominal closure (TAC) rate compared with 51% in BIAIs (p = 0.01). The FIAI group had higher ISS (27 vs. 22, p = 0.03), longer hospital days (34 vs. 25, p = 0.02), and longer intensive care unit (ICU) days (17 vs. 9, p = 0.006) when compared with BIAI. The FIAI group also had a five-fold greater mortality rate. Logistic regression identified TAC as an independent risk factor for the development of post-operative FIAIs (odds ratio [OR] 6.16, confidence interval [CI] 1.14-28.0, p = 0.02). Conclusions: An FIAI after exploratory laparotomy was associated with greater morbidity and death. A TAC was associated independently with increased risk of FIAI after exploratory laparotomy in the setting of traumatic injury. Clinicians should suspect fungal infections in trauma patients in whom post-operative IAI develops after undergoing exploratory laparotomy using TAC techniques.


Drastic reorganization of the bioconvection pattern of Chlamydomonas: quantitative analysis of the pattern transition response.
Motile aquatic microorganisms are known to self-organize into bioconvection patterns. The swimming activity of a population of microorganisms leads to the emergence of macroscopic patterns of density under the influence of gravity. Although long-term development of the bioconvection pattern is important in order to elucidate the possible integration of physiological functions of individuals through bioconvection pattern formation, little quantitative investigation has been carried out. In the present paper, we present the first quantitative description of long-term behavior of bioconvection of Chlamydomonas reinhardtii, particularly focusing on the 'pattern transition response'. The pattern transition response is a sudden breakdown of the steady bioconvection pattern followed by re-formation of the pattern with a decreased wavelength. We found three phases in the pattern formation of the bioconvection of C. reinhardtii: onset, steady-state 1 (before the transition) and steady-state 2 (after the transition). In onset, the wavelength of the bioconvection pattern increases with increasing depth, but not in steady-states 1 or 2. By means of the newly developed two-axis view method, we revealed that the population of C. reinhardtii moves toward the bottom of the experimental chamber just before the pattern transition. This indicates that the pattern transition response could be caused by enhancement of the gyrotaxis of C. reinhardtii as a result of the changes in the balance between the gravitactic and gyrotactic torques. We also found that the bioconvection pattern changes in response to the intensity of red-light illumination, to which C. reinhardtii is phototactically insensitive. These facts suggest that the bioconvection pattern has a potential to drastically reorganize its convection structure in response to the physiological processes under the influence of environmental cues.


Barriers to use of oral rehydration therapy.
To identify potential barriers to the use of oral rehydration therapy (ORT) by pediatric practitioners. Cross-sectional, anonymous, self-administered survey of physicians' ORT knowledge, attitudes, and practice. A national continuing medical education conference. One hundred four general pediatricians primarily in private practice (66%) who completed training after 1980 (76%). Most respondents (83%) reported that ORT plays an important role in their management of dehydration. However, compliance with guidelines from the American Academy of Pediatrics for use of oral therapy is limited: 30% withhold ORT in children with vomiting or moderate dehydration, 50% fail to advise prompt refeeding, and only 3% advise use of a spoon or syringe. The degree of importance of ORT in physicians' practice was negatively associated with reported lack of convenience of ORT administration in the practice setting (P < .001), support staff preference for intravenous versus ORT (P < .001), need for additional training of support staff to implement ORT (P < .01), and likelihood of reimbursement for intravenous versus ORT (P = .07). Notably, degree of importance of ORT was not associated with physician ORT knowledge. Efforts to improve use of ORT should be expanded beyond physician education and focus on such barriers as support staff limitations and financial constraints.


[Screening for biliary atresia and stool color: method of colorimetric scale].
Biliary atresia is a rare disease, but it is the major cause of neonatal cholestasis and the major indication for liver transplantation in children. Kasaï procedure can restore bile flow and prevent or slow progression of disease in a proportion of patients. Data show that the earlier the Kasaï procedure is performed, the better is the outcome. Therefore, rapid referral to an experienced center, for prompt diagnosis and surgery, is strongly recommended. Unfortunately, the disease is often detected late and Kasaï procedure is performed after 60 days of age. In an attempt to achieve earlier diagnosis and better outcome of Kasaï procedure, we propose to institute routine screening for biliary atresia using a stool colorometric scale. This should help to identify earlier children who have acholic stools and may have biliary atresia. We postulate that this screening method will allow to improve the results of the Kasaï procedure and provide children with the best chance of survival with their native liver.


The protective effects of prostaglandin E1 on lung injury following renal ischemia-reperfusion in rats.
For the purposes of the present study, the protective effect of prostaglandin E1 (PGE1) on lung injury following renal ischemia-reperfusion (RIR) was investigated. Adult male rats were divided into four groups, namely, (I) control rats given physiological saline; (II) rats given PGE1 (20 μg/kg, intravenously); (III) rats subjected to RIR; and (IV) rats subjected to RIR given PGE1 30 min prior to ischemia and just before reperfusion. The right nephrectomy was performed in the RIR model. The left renal pedicle was occluded for 60 min to induce ischemia and then the left kidney was subjected to reperfusion for 60 min. The lungs of rats were used for microscopic and biochemical analyses. Although rats subjected to RIR did not exhibit heavy degenerative alterations in the lung structure, they possessed pulmonary interstitial edema. Lung glutathione levels and catalase, superoxide dismutase, glutathione peroxidase, and tissue factor (TF) activities were decreased in rats subjected to RIR, while lung lipid peroxidation, myeloperoxidase (MPO), xanthine oxidase and serum lactate dehydrogenase (LDH) activities, and blood urea and serum creatinine levels were increased in these rats when compared with the control group. PGE1 treatments resulted in the regression of oxidative stress via induction of antioxidant system, the decreased MPO and LDH activities, the reduced urea and creatinine levels, and the induced TF activity in rats subjected to RIR, while edema still remained permanent. We conclude that PGE1 may be useful in preventing lung injury with the exception of edema that occurred as a result of RIR in rats.


[Free fatty acid receptors and their physiological role in metabolic regulation].
Free fatty acids (FFAs) are not only essential nutrient components, but they also function as signaling molecules in various physiological processes. In the progression of genomic analysis, many orphan G-protein coupled receptors (GPCRs) are found. Recently, GPCRs deorphanizing strategy successfully identified multiple receptors for FFAs. In these FFA receptors (FFARs), GPR40 (FFAR1) and GPR120 are activated by medium- to long- chain FFAs. GPR40 is expressed mainly in pancreatic β-cell and mediates insulin secretion, whereas GPR120 is expressed abundantly in the intestine and regulates the secretion of cholecystokinin (CCK) and glucagons-like peptide-1 (GLP-1), it promotes insulin secretion. Due to these biological activity, GPR40 and GPR120 are potential drug target for type 2 diabetes and selective ligands have been developed. In this review, we provide recent development in the field and discuss their physiological roles and their potential as drug targets.


Carbonaceous Nanomaterials Have Higher Effects on Soybean Rhizosphere Prokaryotic Communities During the Reproductive Growth Phase than During Vegetative Growth.
Carbonaceous nanomaterials (CNMs) can affect agricultural soil prokaryotic communities, but how the effects vary with the crop growth stage is unknown. To investigate this, soybean plants were cultivated in soils amended with 0, 0.1, 100, or 1000 mg kg-1 of carbon black, multiwalled carbon nanotubes (MWCNTs), or graphene. Soil prokaryotic communities were analyzed by Illumina sequencing at day 0 and at the soybean vegetative and reproductive stages. The sequencing data were functionally annotated using the functional annotation of prokaryotic taxa (FAPROTAX) database. The prokaryotic communities were unaffected at day 0 and were altered at the plant vegetative stage only by 0.1 mg kg-1 MWCNTs. However, at the reproductive stage, when pods were filling, most treatments (except 1000 mg kg-1 MWCNTs) altered the prokaryotic community composition, including functional groups associated with C, N, and S cycling. The lower doses of CNMs, which were previously shown to be less agglomerated and thus more bioavailable in soil relative to the higher doses, were more effective toward both overall communities and individual functional groups. Taken together, prokaryotic communities in the soybean rhizosphere can be significantly phylogenetically and functionally altered in response to bioavailable CNMs, especially when soybean plants are actively directing resources to seed production.


Health follow-up of children in poverty situation: between the routine and eventuality of daily care.
This study aimed to identify how child care is delivered to children under two in their daily routine. Based on a qualitative approach, the study addresses the care site in the child care, through non-structured interviews with mothers and professionals from two health units in peripheral areas of Ribeirão Preto, SP, Brazil. Results point aspects of how professionals view the mothers and their families, how the child's health, the routine and eventuality of care are followed. Adherence is important in the child's follow up, the longitudinality of care and, mainly, the concern with the mothers' and families' values. Child care in primary health care has a contingency character; it must deal with eventuality, uncertainty and events linked to experiences, integrating practical and technical knowledge.


[Doppler echocardiographic investigation of left ventricular diastolic function in preterm infants with and without a patent ductus arteriosus].
We studied the influence of preload augmentation on Doppler-derived left ventricular diastolic function parameters in infants with a birth weight <1500 g. In 44 neonates with a closed duct and 29 neonates with an open ductus arteriosus a complete echocardiographic study including Doppler investigations of the mitral inflow signals and analysis of diastolic time intervals was performed. Neonates with an open duct had a lower median gestational age (27.1 vs. 29, P<0.01), a higher cardiac index (425 vs. 260 ml/min/kg, P<0.001), and a different M-mode left atrial to aortic diameter ratio (1.36 vs. 0.79, P<0.001), but birth weight, age at examination (6.6 vs. 7.9 days), and heart rate were similar compared to the neonates with a closed duct. Main differences in diastolic indexes existed in early and atrial filling integrals and peak velocities, early filling acceleration time, and isovolumic relaxation time. Most informative in neonates with an open ductus peak early filling velocity (41.2 vs. 30.4 cm, P<0.01) and peak atrial filling velocity (49.2 vs. 35.9, P<0.001) are higher, and isovolumic relaxation time is shorter (45 vs. 53 ms, P<0.001) than in closed duct peers. Isovolumic relaxation time is inversely correlated with the cardiac index (R = -0.78). These parameter changes can be interpreted as incipient left ventricular diastolic failure in extremely low birth weight infants in the presence of a preload challenge. The coincidence of higher peak velocities with a shortened isovolumic relaxation time is very likely a result of left atrial pressure elevation. Preload mismatch has to be considered in preterm infants with a persistent ductus arteriosus. The results of this study can be helpful to find the indication for PDA-closure and to adjust volume replacement therapy, and catecholamine medication to a level appropriate for the individual cardiac performance.


Yawning and hypothermia in rats: effects of dopamine D3 and D2 agonists and antagonists.
Identification of behaviors specifically mediated by the dopamine D2 and D3 receptors would allow for the determination of in vivo receptor selectivity and aide the development of novel therapeutics for dopamine-related diseases. These studies were aimed at evaluating the specific receptors involved in the mediation of D2/D3 agonist-induced yawning and hypothermia. The relative potencies of a series of D2-like agonists to produce yawning and hypothermia were determined. The ability of D3-selective and D2-selective antagonists to inhibit the induction of yawning and hypothermia were assessed and a series of D2/D3 antagonists were characterized with respect to their ability to alter yawning induced by a low and high dose of PD-128,907 and sumanirole-induced hypothermia. D3-preferring agonists induced yawning at lower doses than those required to induce hypothermia and the D2-preferring agonist, sumanirole, induced hypothermia at lower doses than were necessary to induce yawning. The rank order of D3 selectivity was pramipexole > PD-128,907 = 7-OH-DPAT = quinpirole = quinelorane > apomorphine = U91,356A. Sumanirole had only D2 agonist effects. PG01,037, SB-277,011A, and U99,194 were all D3-selective antagonists, whereas haloperidol and L-741,626 were D2-selective antagonists and nafadotride's profile of action was more similar to the D2 antagonists than to the D3 antagonists. D3 and D2 receptors have specific roles in the mediation of yawning and hypothermia, respectively, and the analysis of these effects allow inferences to be made regarding the selectivity of D2/D3 agonists and antagonists with respect to their actions at D2 and D3 receptors.


Is the mitochondrial outermembrane protein VDAC1 therapeutic target for Alzheimer's disease?
Mitochondrial dysfunction and synaptic damage have been described as early events in Alzheimer's disease (AD) pathogenesis. Recent research using AD postmortem brains, and AD mouse and cell models revealed that amyloid beta (Aβ) and tau hyperphosphorylation are involved in mitochondrial dysfunction and synaptic damage in AD. Further, recent research also revealed that the protein levels of mitochondrial outer membrane protein, voltage-dependent anion channel 1 (VDAC1), are elevated in the affected regions of AD postmortem brains and cortical tissues from APP transgenic mice. In addition, emerging research using AD postmortem brains and AD mouse models revealed that VDAC1 is linked to Aβ and phosphorylated tau, blocks the mitochondrial permeability transition (MPT) pores, disrupts the transport of mitochondrial proteins and metabolites, impairs gating of VDAC, and causes defects in oxidative phosphorylation, leading to mitochondrial dysfunction in AD neurons. The purpose of this article is to review research that has investigated the relationship between VDAC1 and the regulation of MPT pores in AD progression.


Arsenic exposure in pregnancy: a population-based study in Matlab, Bangladesh.
This study assessed the exposure of pregnant women to arsenic in Matlab, Bangladesh, an area with highly-elevated concentrations of arsenic in tubewells, by measuring concentrations of arsenic in urine. In a defined administrative area, all new pregnancies were identified by urine test in gestational week 6-8, and women were asked to participate in the assessment of arsenic exposure. Urine for analysis of arsenic was collected immediately and in gestational week 30. In total, 3,426 pregnant women provided urine samples during January 2002-March 2003. There was a considerable variation in urinary concentrations of arsenic (total range 1-1,470 microg/L, adjusted to specific gravity 1.012 g/mL), with an overall median concentration of 80 microg/L (25th and 75th percentiles were 37 and 208 microg/L respectively). Similar concentrations were found in gestational week 30, indicating no trend of decreasing exposure, despite the initiation of mitigation activities in the area. Arsenic exposure was negatively associated with socioeconomic classes and achieved educational level. There were marked geographical variations in exposure. The results emphasize the urgent need for efficient mitigation activities and investigations of arsenic-related reproductive effects.


Use of small-bore vs large-bore chest tubes for treatment of malignant pleural effusions.
To evaluate the efficacy of small-bore (12 French vanSonnenberg) catheters compared with standard large-bore chest tubes in the drainage and sclerotherapy of malignant pleural effusions. Retrospective review. An academic tertiary care hospital. Adult patients with documented neoplasms and malignant pleural effusions, treated between 1986 and 1995. All patients included in the study underwent drainage of malignant pleural effusions either by large-bore chest tube or by ultrasound-guided small-bore catheter. After drainage, pleurodesis was performed. Outcome as defined by recurrence of effusion was determined by blinded examination of all postpleurodesis chest radiographs. We identified 58 cases of malignant pleural effusion in which small-bore catheters were used and 44 in which large-bore chest tubes were used. The majority of patients had breast (n = 56, 55%) or lung cancer (n = 29, 28%). The median age was 65 years. Fifty-nine patients were actively being treated with chemotherapy at the time of pleurodesis. The following sclerosing agents were used: talc, 27 (26%); tetracycline, 72 (70%); bleomycin, 2 (2%); and interferon, 1 (1%). Actuarial probabilities of recurrence at 6 weeks and 4 months were 45% and 53% for the small tubes vs 45% and 51% for the large tubes. Univariate and multivariate analyses failed to demonstrate that tube size had any influence on the rate of recurrence. We were unable to detect any major differences in outcomes with the use of either size of chest tube. Our study suggests that small-bore catheters may be effective in the treatment of malignant pleural effusions and deserve further evaluation in prospectively designed trials.