Frequency of Drug Resistance Gene Amplification in Clinical Leishmania Strains

Experimental studies about Leishmania resistance to metal and antifolates have pointed out that gene amplification is one of the main mechanisms of drug detoxification. Amplified genes code for adenosine triphosphate-dependent transporters (multidrug resistance and P-glycoproteins P), enzymes involved in trypanothione pathway, particularly gamma glutamyl cysteine synthase, and others involved in folates metabolism, such as dihydrofolate reductase and pterine reductase. The aim of this study was to detect and quantify the amplification of these genes in clinical strains of visceral leishmaniasis agents: Leishmania infantum, L. donovani, and L. archibaldi. Relative quantification experiments by means of real-time polymerase chain reaction showed that multidrug resistance gene amplification is the more frequent event. For P-glycoproteins P and dihydrofolate reductase genes, level of amplification was comparable to the level observed after in vitro selection of resistant clones. Gene amplification is therefore a common phenomenon in wild strains concurring to Leishmania genomic plasticity. This finding, which corroborates results of experimental studies, supports a better understanding of metal resistance selection and spreading in endemic areas

Leishmaniose en Equateur : 4. Infestation naturelle du chien par Leishmania panamensis

Dans deux stations de la plaine côtière d'Equateur, région endémique de leishmaniose à #Leishmania panamensis, 34 chiens ont été contrôlés aux plans clinique, sérologique et parasitologique; des tests d'immunofluorescence indirecte et d'électrosynérèse, des ponctions ganglionnaires, des biopsies de lésions ont été pratiqués. De deux chiens présentant des lésions suspectes, un seul avait des lésions de la truffe et du scrotum infectées par des #Leishmania. La souche isolée a été rapportée à #L. panamensis (complexe #L. guyanensis). L'atteinte leishmanienne était strictement tégumentaire. Dans la zone d'étude, le chien semble un hôte accidentel. (Résumé d'auteur

Investigating Ramp Wave Propagation inside Silica Glass with Laser Experiments and Molecular Simulations

Under elastic shock compression silica glass exhibits a very specific behaviour. A shock propagating inside a material is usually seen as the propagation of a discontinuity. However in silica glass, shocks are unstable and lead to the propagation of a ramp wave where the shock front becomes gradually larger over time. Ramp waves were already reported in the literature, however their origin remain uncertain. This work presents an original study combining laser shock-induced experiments and molecular dynamics simulation aiming to improve the understanding of the mechanisms involved. Experimental ramp waves were directly observed using shadowgraphy technique allowing for an estimation of the head and tail velocities. Molecular dynamics simulations were carried out in order to reproduce ramp waves and to gain insight into the material properties. Ramp waves were observed for both elastic and plastic shockwaves. In the latter case, the plastic waves were preceded by an elastic ramp precursor. The sound speed, related to the material compressibility, was found to decrease with increasing pressure, as observed experimentally for quasi-static hydrostatic loading, thus providing an explanation for the instabilities that lead to the propagation of ramp waves

Rare association of Visceral leishmaniasis with Hodgkin's disease: A case report

We present here a case of young male with complaints of fever and swelling in the neck for eight months. History of progressive weakness associated with weight loss was present. Physical examination revealed pallor, multiple enlarged cervical lymph nodes and hepatosplenomegaly. Investigations showed pancytopenia, hyperglobinemia and Leishman-Donovan bodies on bone marrow aspiration. Serological test confirmed diagnosis of visceral leishmaniasis. However, cervical lymph node aspiration and biopsy were suggestive of Mixed cellularity Hodgkin's disease. This made it a very rare case of Leishmaniasis as an opportunistic infection in a patient of pre-chemotherapy Hodgkin's disease. There was marked improvement in haematological profile and regression of hepatosplenomegaly with Amphotericin B treatment followed by favourable response to chemotherapy. The case emphasizes the suspicion for leishmaniasis as a masquerader and as an opportunistic infection in haematological malignancies

Maternal obesity support services: a qualitative study of the perspectives of women and midwives

Background - Twenty percent of pregnant women in the UK are obese (BMI ≥ 30 kg/m2), reflecting the growing public health challenge of obesity in the 21st century. Obesity increases the risk of adverse outcomes during pregnancy and birth and has significant cost implications for maternity services. Gestational weight management strategies are a high priority; however the evidence for effective, feasible and acceptable weight control interventions is limited and inconclusive. This qualitative study explored the experiences and perceptions of pregnant women and midwives regarding existing support for weight management in pregnancy and their ideas for service development. Methods - A purposive sample of 6 women and 7 midwives from Doncaster, UK, participated in two separate focus groups. Transcripts were analysed thematically. Results - Two overarching themes were identified, 'Explanations for obesity and weight management' and 'Best care for pregnant women'. 'Explanations' included a lack of knowledge about weight, diet and exercise during pregnancy; self-talk messages which excused overeating; difficulties maintaining motivation for a healthy lifestyle; the importance of social support; stigmatisation; and sensitivity surrounding communication about obesity between midwives and their clients. 'Best care' suggested that weight management required care which was consistent and continuous, supportive and non-judgemental, and which created opportunities for interaction and mutual support between obese pregnant women. Conclusions - Women need unambiguous advice regarding healthy lifestyles, diet and exercise in pregnancy to address a lack of knowledge and a tendency towards unhelpful self-talk messages. Midwives expressed difficulties in communicating with their clients about their weight, given awareness that obesity is a sensitive and potentially stigmatising issue. This indicates more could be done to educate and support them in their work with obese pregnant women. Motivation and social support were strong explanatory themes for obesity and weight management, suggesting that interventions should focus on motivational strategies and social support facilitation

P19 H-Ras Induces G1/S Phase Delay Maintaining Cells in a Reversible Quiescence State

This is an open-access article distributed under the terms of the Creative Commons Attribution License.[Background]: Three functional c-ras genes, known as c-H-ras, c-K-ras, and c-N-ras, have been largely studied in mammalian cells with important insights into normal and tumorigenic cellular signal transduction events. Two K-Ras mRNAs are obtained from the same pre-mRNA by alternative splicing. H-Ras pre-mRNA can also be alternatively spliced in the IDX and 4A terminal exons, yielding the p19 and p21 proteins, respectively. However, despite the Ras gene family’s established role in tumorigenic cellular signal transduction events, little is known about p19 function. Previous results showed that p19 did not interact with two known p21 effectors, Raf1 and Rin1, but was shown to interact with RACK1, a scaffolding protein that promotes multi-protein complexes in different signaling pathways (Cancer Res 2003, 63 p5178). This observation suggests that p19 and p21 play differential and complementary roles in the cell.[Principal Findings]: We found that p19 regulates telomerase activity through its interaction with p73a/b proteins. We also found that p19 overexpression induces G1/S phase delay; an observation that correlates with hypophosphorylation of both Akt and p70SK6. Similarly, we also observed that FOXO1 is upregulated when p19 is overexpressed. The three observations of (1) hypophosphorylation of Akt, (2) G1/S phase delay and (3) upregulation of FOXO1 lead us to conclude that p19 induces G1/S phase delay, thereby maintaining cells in a reversible quiescence state and preventing entry into apoptosis. We then assessed the effect of p19 RNAi on HeLa cell growth and found that p19 RNAi increases cell growth, thereby having the opposite effect of arrest of the G1/S phase or producing a cellular quiescence state.[Significance]: Interestingly, p19 induces FOXO1 that in combination with the G1/S phase delay and hypophosphorylation of both Akt and p70SK6 leads to maintenance of a reversible cellular quiescence state, thereby preventing entry into apoptosis.This work was supported by Fundacion de Investigacion Medica Mutua Madrileña Automovilista (Fundacion MMA), the Plan Nacional (MEC) BFU2005-00701 and the Fundacion Eugenio Rodriguez Pascual. M.C. was a recipient of a Fmed MMA fellowship.Peer reviewe

Continuity of midwifery care and gestational weight gain in obese women: a randomised controlled trial

Background: The increased prevalence of obesity in pregnant women in Australia and other developed countries is a significant public health concern. Obese women are at increased risk of serious perinatal complications and guidelines recommend weight gain restriction and additional care. There is limited evidence to support the effectiveness of dietary and physical activity lifestyle interventions in preventing adverse perinatal outcomes and new strategies need to be evaluated. The primary aim of this project is to evaluate the effect of continuity of midwifery care on restricting gestational weight gain in obese women to the recommended range. The secondary aims of the study are to assess the impact of continuity of midwifery care on: women&rsquo;s experience of pregnancy care; women&rsquo;s satisfaction with care and a range of psychological factors.Methods/Design: A two arm randomised controlled trial (RCT) will be conducted with primigravid women recruited from maternity services in Victoria, Australia. Participants will be primigravid women, with a BMI&ge;30 who are less than 17 weeks gestation. Women allocated to the intervention arm will be cared for in a midwifery continuity of care model and receive an informational leaflet on managing weight gain in pregnancy. Women allocated to the control group will receive routine care in addition to the same informational leaflet. Weight gain during pregnancy, standards of care, medical and obstetric information will be extracted from medical records. Data collected at recruitment (self administered survey) and at 36 weeks by postal survey will include sociodemographic information and the use of validated scales to measure secondary outcomes.Discussion: Continuity of midwifery care models are well aligned with current Victorian, Australian and many international government policies on maternity care. Increasingly, midwifery continuity models of care are being introduced in low risk maternity care, and information on their application in high risk populations is required. There is an identified need to trial alternative antenatal interventions to reduce perinatal risk factors for women who are obese and the findings from this project may have application in other maternity services. In addition this study will inform a larger trial that will focus on birth and postnatal outcomes.<br /