Potentiation of the in vitro cytotoxic response to syngeneic lymphoma cells by soluble products of tuberculin-sensitive lymphoid cells stimulated with PPD

Spleen cells from rats immunized with the syngeneic (C58NT)D Gross virus induced lymphoma have previously been shown to differentiate into cytotoxic effector cells following restimulation with tumor cells in vitro. Previous work has also demonstrated that the addition of PPD-primed syngeneic spleen cells and PPD to cultures of (C58NT)D-primed spleen cells will potentiate the in vitro cytotoxic response to tumor antigens. In the studies presented here, the potentiating effect was found to be mediated by a soluble factor(s) released by nonadherent cells from BCG-primed rats. The release of this immunopotentiating factor(IPF) required the presence of PPD and varied with the concentration of PPD added. IPF was produced by BCG-primed spleen, lymph node, and thymus cells. Maximal production of IPF in PPD-stimulated cultures was obtained after 6–12 hr of incubation. Supernatants obtained after 30 hr of incubation lacked apparent IPF activity when tested initially, but activity was recovered after mild heat treatment. Recovery of IPF activity after heat exposure is best explained by the presence of a heat-labile inhibitor. IPF itself is stable to heat treatment to 56 °C for 40 min. IPF was also shown to be capable of enhancing immune responses to histocompatibility antigens in vitro.     

Plasmodium falciparum gametocyte carriage, emergence, clearance and population sex ratios in anaemic and non-anaemic malarious children

Anaemia in falciparum malaria is associated with an increased risk of gametocyte carriage, but its effects on transmission have not been extensively evaluated in malarious children. Plasmodium falciparum gametocyte carriage, emergence, clearance, population sex ratios (SR) (defined as the proportion of gametocytes that are male), inbreeding rates and temporal changes in SR were evaluated in 840 malarious children. Gametocyte carriage pre-treatment was at a level of 8.1%. Anaemia at enrolment was an independent risk factor for gametocyte carriage post-treatment. The emergence of gametocytes seven days post-treatment was significantly more frequent in anaemic children (7/106 vs. 10/696, p = 0.002). In the initially detected gametocytes, the proportion of children with a male-biased SR (MBSR) (> 0.5) was significantly higher in anaemic children (6/7 vs. 3/10, p = 0.027). Pre-treatment SR and estimated inbreeding rates (proportion of a mother's daughters fertilised by her sons) were similar in anaemic and non-anaemic children. Pre-treatment SR became more female-biased in non-anaemic children following treatment. However, in anaemic children, SR became male-biased. Anaemia was shown to significantly increase gametocyte emergence and may significantly alter the SR of emerging gametocytes. If MBSR is more infective to mosquitoes at low gametocytaemia, then these findings may have significant implications for malaria control efforts in endemic settings where malaria-associated anaemia is common.     

Adaptación y validación de la versión española de la escala de evaluación de dolor en personas con demencia avanzada: PAINAD-Sp

Introduction

Pain in elderly people is considered a major concern in nursing home facilities affecting between 49% and 83% of the residents. Progression of Alzheimer's Disease causes more communication difficulties in patients with advanced dementia and therefore more problems to understand even the most simple pain evaluation scales. Identification and implementation of appropriate pain management strategies depends on an adequate pain assessment.

Material and methods

The main objective of the study was to validate the Spanish version of the PAINAD Scale (PAINAD-Sp) and to assess its applicability in Spanish Geriatric Nursing Homes. The 20 patients diagnosed with severe dementia from a Geriatric Centre in Spain were observed by five observers with different professional profiles for 5 minutes to each participant, and PAINAD-Sp Scale was administered simultaneously to a Visual Analogical Scale-VAS. Three different observational conditions were established: resting condition, during presumably pleasant activity and during presumable painful activity.

Results

Cronbach's alpha ranged between 0.467 and 0.827 (average 0.692), and rose if Breathing item was deleted. Inter-rater reliability ranged between 0.587 and 0.956. Correlation between PAINAD-Sp Scale total measures and VAS was statistically significant (P<.05) in all measures and ranged from 0.517 to 0.868.

Conclusions

Findings in the study showed that the scale is useful to measure pain in non communicative patients suffering from dementia. The scale maintains good levels of reliability for different healthcare professionals even when they have little training.     

The ENU-induced powdery mildew resistant mutant pea (Pisum sativum L.) lines S(er1mut1) and F(er1mut2) harbour early stop codons in the PsMLO1 gene

Two pea (Pisum sativum L.) powdery mildew-resistant mutant lines, S(er1mut1) and F(er1mut2), were previously obtained by experimental chemical mutagenesis with ethylnitrosourea. Identification and subsequent analysis of the genomic sequence of the PsMLO1 gene revealed one single nucleotide mutation in each mutant line that leads to either a transversion or a transition, respectively, resulting in premature stop codons that drastically truncate the protein product of this gene in these two mutant lines. These results confirm the previous findings that PsMLO1 is the powdery mildew resistance gene er1. Only one additional mutation (transition) was observed in the S(er1mut1), downstream of the protein-truncating stop codon. Mutations were not identified in the intron regions of the gene. Specific molecular markers (cleaved amplified polymorphic sequences and sequence-tagged sites) were generated for the protein-truncating mutations, and these provide breeders with very efficient tools for marker-assisted selection when either of the two mutated lines are used in plant breeding programmes.     

Cost-Effectiveness Analysis of Option B+ for HIV Prevention and Treatment of Mothers and Children in Malawi

Background

The Ministry of Health in Malawi is implementing a pragmatic and innovative approach for the management of all HIV-infected pregnant women, termed Option B+, which consists of providing life-long antiretroviral treatment, regardless of their CD4 count or clinical stage. Our objective was to determine if Option B+ represents a cost-effective option.

Methods

A decision model simulates the disease progression of a cohort of HIV-infected pregnant women receiving prophylaxis and antiretroviral therapy, and estimates the number of paediatric infections averted and maternal life years gained over a ten-year time horizon. We assess the cost-effectiveness from the Ministry of Health perspective while taking into account the practical realities of implementing ART services in Malawi.

Results

If implemented as recommended by the World Health Organization, options A, B and B+ are equivalent in preventing new infant infections, yielding cost effectiveness ratios between US$ 37 and US$ 69 per disability adjusted life year averted in children. However, when the three options are compared to the current practice, the provision of antiretroviral therapy to all mothers (Option B+) not only prevents infant infections, but also improves the ten-year survival in mothers more than four-fold. This translates into saving more than 250,000 maternal life years, as compared to mothers receiving only Option A or B, with savings of 153,000 and 172,000 life years respectively. Option B+ also yields favourable incremental cost effectiveness ratios (ICER) of US$ 455 per life year gained over the current practice.

Conclusion

In Malawi, Option B+ represents a favorable policy option from a cost-effectiveness perspective to prevent future infant infections, save mothers'' lives and reduce orphanhood. Although Option B+ would require more financial resources initially, it would save societal resources in the long-term and represents a strategic option to simplify and integrate HIV services into maternal, newborn and child health programmes.