Development of Vaccines against Visceral Leishmaniasis

Leishmaniasis is a neglected disease resulting in a global morbidity of 2,090 thousand Disability-Adjusted Life Years and a mortality rate of approximately 60,000 per year. Among the three clinical forms of leishmaniasis (cutaneous, mucosal, and visceral), visceral leishmaniasis (VL) accounts for the majority of mortality, as if left untreated VL is almost always fatal. Caused by infection with Leishmania donovani or L. infantum, VL represents a serious public health problem in endemic regions and is rapidly emerging as an opportunistic infection in HIV patients. To date, no vaccine exists for VL or any other form of leishmaniasis. In endemic areas, the majority of those infected do not develop clinical symptoms and past infection leads to robust immunity against reinfection. Thus the development of vaccine for Leishmania is a realistic public health goal, and this paper summarizes advances in vaccination strategies against VL

Experiences of Postpartum Women With Nurse-Delivered Education and Postpartum

Postpartum depression affects many women globally, yet largely remains underdiagnosed. It is thus important for nurses to have all available tools when delivering education and care to the postpartum patient. Yet, there is a lack of information on the experiences of postpartum women related to postpartum education and postpartum depression. The purposes of this quantitative study, for which Beck\u27s postpartum theory was the framework, were to explore postpartum women\u27s perceptions of education experiences and to determine if a correlation exists between the satisfaction with education and scores on the Edinburgh Postnatal Depression Scale. Sixty study participants who were 6-8 weeks postpartum completed the questionnaire, with 22 participants meeting the inclusion criteria of being between the ages of 18-40 and not formally diagnosed with depression or postpartum depression in the past. Study participants completed a demographics survey, the modified client satisfaction tool, and the Edinburgh Postnatal Depression Scale on the Survey Monkey website. Data from the modified client satisfaction tool analyzed with a scatter plot revealed that there was an uneven distribution of satisfaction scores. Spearman\u27s rho correlation analysis revealed no statically significant correlation between the satisfaction of study participants and the development of postpartum depressive symptoms. The findings may encourage future researchers to examine whether there is a connection between low satisfaction and the development of postpartum depressive symptoms. The implications for social change include providing a greater understanding of postpartum depression and how healthcare workers and families can better support postpartum patients

Host reticulocytes provide metabolic reservoirs that can be exploited by malaria parasites

Human malaria parasites proliferate in different erythroid cell types during infection. Whilst Plasmodium vivax exhibits a strong preference for immature reticulocytes, the more pathogenic P. falciparum primarily infects mature erythrocytes. In order to assess if these two cell types offer different growth conditions and relate them to parasite preference, we compared the metabolomes of human and rodent reticulocytes with those of their mature erythrocyte counterparts. Reticulocytes were found to have a more complex, enriched metabolic profile than mature erythrocytes and a higher level of metabolic overlap between reticulocyte resident parasite stages and their host cell. This redundancy was assessed by generating a panel of mutants of the rodent malaria parasite P. berghei with defects in intermediary carbon metabolism (ICM) and pyrimidine biosynthesis known to be important for P. falciparum growth and survival in vitro in mature erythrocytes. P. berghei ICM mutants (pbpepc-, phosphoenolpyruvate carboxylase and pbmdh-, malate dehydrogenase) multiplied in reticulocytes and committed to sexual development like wild type parasites. However, P. berghei pyrimidine biosynthesis mutants (pboprt-, orotate phosphoribosyltransferase and pbompdc-, orotidine 5′-monophosphate decarboxylase) were restricted to growth in the youngest forms of reticulocytes and had a severe slow growth phenotype in part resulting from reduced merozoite production. The pbpepc-, pboprt- and pbompdc- mutants retained virulence in mice implying that malaria parasites can partially salvage pyrimidines but failed to complete differentiation to various stages in mosquitoes. These findings suggest that species-specific differences in Plasmodium host cell tropism result in marked differences in the necessity for parasite intrinsic metabolism. These data have implications for drug design when targeting mature erythrocyte or reticulocyte resident parasites

Developing a coding taxonomy to analyze dental regulatory complaints

Background: As part of their mandate to protect the public, dental regulatory authorities (DRA) in Canada are responsible for investigating complaints made by members of the public. To gain an understanding of the nature of and trends in complaints made to the Royal College of Dental Surgeons of Ontario (RCDSO), Canada’s largest DRA, a coding taxonomy was developed for systematic analysis of complaints. Methods: The taxonomy was developed through a two-pronged approach. First, the research team searched for existing complaints frameworks and integrated data from a variety of sources to ensure applicability to the dental context in terms of the generated items/complaint codes in the taxonomy. Second, an anonymized sample of complaint letters made by the public to the RCDSO (n = 174) were used to refine the taxonomy. This sample was further used to assess the feasibility of use in a larger content analysis of complaints. Inter-coder reliability was also assessed using a separate sample of letters (n = 110). Results: The resulting taxonomy comprised three domains (Clinical Care and Treatment, Management and Access, and Relationships and Conduct), with seven categories, 23 sub-categories, and over 100 complaint codes. Pilot testing for the feasibility and applicability of the taxonomy’s use for a systematic analysis of complaints proved successful. Conclusions: The resulting coding taxonomy allows for reliable documentation and interpretation of complaints made to a DRA in Canada and potentially other jurisdictions, such that the nature of and trends in complaints can be identified, monitored and used in quality assurance and improvement

Particulate oxidative burden as a predictor of exhaled nitric oxide in children with asthma

Background: Epidemiological studies have provided strong evidence that fine particulate matter (PM2.5; aerodynamic diameter ≤ 2.5 μm) can exacerbate asthmatic symptoms in children. Pro-oxidant components of PM2.5 are capable of directly generating reactive oxygen species. Oxidative burden is used to describe the capacity of PM2.5 to generate reactive oxygen species in the lung. Objective: In this study we investigated the association between airway inflammation in asthmatic children and oxidative burden of PM2.5 personal exposure. Methods: Daily PM2.5 personal exposure samples (n = 249) of 62 asthmatic school-aged children in Montreal were collected over 10 consecutive days. The oxidative burden of PM2.5 samples was determined in vitro as the depletion of low-molecular-weight antioxidants (ascorbate and glutathione) from a synthetic model of the fluid lining the respiratory tract. Airway inflammation was measured daily as fractional exhaled nitric oxide (FeNO). Results: A positive association was identified between FeNO and glutathione-related oxidative burden exposure in the previous 24 hr (6.0% increase per interquartile range change in glutathione). Glutathione-related oxidative burden was further found to be positively associated with FeNO over 1-day lag and 2-day lag periods. Results further demonstrate that corticosteroid use may reduce the FeNO response to elevated glutathione-related oxidative burden exposure (no use, 15.8%; irregular use, 3.8%), whereas mold (22.1%), dust (10.6%), or fur (13.1%) allergies may increase FeNO in children with versus children without these allergies (11.5%). No association was found between PM2.5 mass or ascorbate-related oxidative burden and FeNO levels. Conclusions: Exposure to PM2.5 with elevated glutathione-related oxidative burden was associated with increased FeNO

Increased Oxidative Burden Associated with Traffic Component of Ambient Particulate Matter at Roadside and Urban Background Schools Sites in London

As the incidence of respiratory and allergic symptoms has been reported to be increased in children attending schools in close proximity to busy roads, it was hypothesised that PM from roadside schools would display enhanced oxidative potential (OP). Two consecutive one-week air quality monitoring campaigns were conducted at seven school sampling sites, reflecting roadside and urban background in London. Chemical characteristics of size fractionated particulate matter (PM) samples were related to the capacity to drive biological oxidation reactions in a synthetic respiratory tract lining fluid. Contrary to hypothesised contrasts in particulate OP between school site types, no robust size-fractionated differences in OP were identified due high temporal variability in concentrations of PM components over the one-week sampling campaigns. For OP assessed both by ascorbate (OPAA m−3) and glutathione (OPGSH m−3) depletion, the highest OP per cubic metre of air was in the largest size fraction, PM1.9–10.2. However, when expressed per unit mass of particles OPAA µg−1 showed no significant dependence upon particle size, while OPGSH µg−1 had a tendency to increase with increasing particle size, paralleling increased concentrations of Fe, Ba and Cu. The two OP metrics were not significantly correlated with one another, suggesting that the glutathione and ascorbate depletion assays respond to different components of the particles. Ascorbate depletion per unit mass did not show the same dependence as for GSH and it is possible that other trace metals (Zn, Ni, V) or organic components which are enriched in the finer particle fractions, or the greater surface area of smaller particles, counter-balance the redox activity of Fe, Ba and Cu in the coarse particles. Further work with longer-term sampling and a larger suite of analytes is advised in order to better elucidate the determinants of oxidative potential, and to fuller explore the contrasts between site types.\ud \u

Zum Einfluß der Dexamethason-Dosis auf Chemotherapie-induzierte akute Nausea und Emesis

20 mg Dexamethason oder eine dessen Wirkung äquivalente Dosis eines Corticosteroids- in Verbindung mit einem 5-HT3-Rezeptorantagonisten- erscheint derzeit als Goldstandardt der Prophylaxe zytostatisch induzierter Emesis. Neben der negativen Auswirkung auf die Tumorbiologie, sei es ein beschleunigtes Zellwachstum oder eine verminderte Tumorzellvernichtung durch die körpereigene Immunabwehr, besteht begründeter Verdacht, daß eine hohe Cortisol-Dosierung am Tag der Chemotherapie vermehrt Nausea und Emesis in der verzögerten Phase begünstigt. Deshalb erscheint es sinnvoll, den Stellenwert einer mittleren Steroiddosierung in der Prophylaxe der akuten Emesis zu überprüfen. In einer prospektiven, einfachblinden randomisierten Studie wurden zwei Dexamethason-Dosierungen -20 mg Dexamethason gegen 8 mg Dexamethason- jeweils in Verbindung mit dem 5-HT3-Rezeptorantagonisten Tropisetron in Cisplatin-haltigen Therapien anhand objektiver und subjektiver Parameter verglichen. Nach einer Zwischenanalyse von 121 Fällen (69 Patientinnen), in der keine signifikanten Unterschiede zwischen den beiden Behandlungsstrategien festgestellt werden konnten, wurde die Untersuchung beendet. Hohe Dexamethason-Dosierungen (20 mg) als antiemetische Prophylaxe ergeben weder in der Anzahl der Emesis-Episoden, noch bei den subjektiven Parameter der Rotterdam Symptoms Checklist Vorteile gegenüber einer mittleren (8 mg) Dosis. Dagegen wird gezeigt, daß das endogene Cortisol, vor der Chemotherapie und nach der Dexamethason- Applikation untersucht, die Ausprägung von Nausea und Emesis mitbeeinflußt. Die Patientinnen, deren Cortisol-Werte vor Therapiebeginn unterhalb des errechneten Medians von 169 [ng / ml] liegen, leiden im Vergleich mit den Patientinnen, deren Wert oberhalb dieser Schwelle liegen, verstärkt unter Übelkeit (p = 0,038). Weiterhin tritt bei den Patientinnen, deren Serum-Cortisol an Tag 2 unterhalb des Medians von 21 [ng/ml] liegt, subjektiv erheblichere Übelkeit (p = 0,020) und Emesis (p = 0,046) auf. Aufgrund dieser Ergebnisse ist die antiemetische Prophylaxe mit der Dosis 8 mg Dexamethason der Dosis 20 mg Dexamethason vorzuziehen, um in Verbindung mit einem 5-HT3 Rezeptorantagonisten in hoch emetogenen Chemotherapien von nicht-hämatologischen Tumoren Übelkeit und Erbrechen zu verhindern

What factors influence the rediscovery of lost tetrapod species?

We created a database of lost and rediscovered tetrapod species, identified patterns in their distribution and factors influencing rediscovery. Tetrapod species are being lost at a faster rate than they are being rediscovered, due to slowing rates of rediscovery for amphibians, birds and mammals, and rapid rates of loss for reptiles. Finding lost species and preventing future losses should therefore be a conservation priority. By comparing the taxonomic and spatial distribution of lost and rediscovered tetrapod species, we have identified regions and taxa with many lost species in comparison to those that have been rediscovered—our results may help to prioritise search effort to find them. By identifying factors that influence rediscovery, we have improved our ability to broadly distinguish the types of species that are likely to be found from those that are not (because they are likely to be extinct). Some lost species, particularly those that are small and perceived to be uncharismatic, may have been neglected in terms of conservation effort, and other lost species may be hard to find due to their intrinsic characteristics and the characteristics of the environments they occupy (e.g. nocturnal species, fossorial species and species occupying habitats that are more difficult to survey such as wetlands). These lost species may genuinely await rediscovery. However, other lost species that possess characteristics associated with rediscovery (e.g. large species) and that are also associated with factors that negatively influence rediscovery (e.g. those occupying small islands) are more likely to be extinct. Our results may foster pragmatic search protocols that prioritise lost species likely to still exist.Israel Science Foundation http://dx.doi.org/10.13039/501100003977Leibniz‐Institut für Gewässerökologie und BinnenfischereiAlexander von Humboldt‐StiftungPontificia Universidad Católica del Ecuador http://dx.doi.org/10.13039/501100011749Peer Reviewe

Loop Diuretics Have Anxiolytic Effects in Rat Models of Conditioned Anxiety

A number of antiepileptic medications that modulate GABAA mediated synaptic transmission are anxiolytic. The loop diuretics furosemide (Lasix) and bumetanide (Bumex) are thought to have antiepileptic properties. These drugs also modulate GABAA mediated signalling through their antagonism of cation-chloride cotransporters. Given that loop diuretics may act as antiepileptic drugs that modulate GABAergic signalling, we sought to investigate whether they also mediate anxiolytic effects. Here we report the first investigation of the anxiolytic effects of these drugs in rat models of anxiety. Furosemide and bumetanide were tested in adult rats for their anxiolytic effects using four standard anxiety models: 1) contextual fear conditioning; 2) fear-potentiated startle; 3) elevated plus maze, and 4) open-field test. Furosemide and bumetanide significantly reduced conditioned anxiety in the contextual fear-conditioning and fear-potentiated startle models. At the tested doses, neither compound had significant anxiolytic effects on unconditioned anxiety in the elevated plus maze and open-field test models. These observations suggest that loop diuretics elicit significant anxiolytic effects in rat models of conditioned anxiety. Since loop diuretics are antagonists of the NKCC1 and KCC2 cotransporters, these results implicate the cation-chloride cotransport system as possible molecular mechanism involved in anxiety, and as novel pharmacological target for the development of anxiolytics. In view of these findings, and since furosemide and bumetanide are safe and well tolerated drugs, the clinical potential of loop diuretics for treating some types of anxiety disorders deserves further investigation