Low socioeconomic status is associated with prolonged times to assessment and treatment, sepsis and infectious death in pediatric Fever in el salvador

Background

Infection remains the most common cause of death from toxicity in children with cancer in low- and middle-income countries. Rapid administration of antibiotics when fever develops can prevent progression to sepsis and shock, and serves as an important indicator of the quality of care in children with acute lymphoblastic leukemia and acute myeloid leukemia. We analyzed factors associated with (1) Longer times from fever onset to hospital presentation/antibiotic treatment and (2) Sepsis and infection-related mortality.

Method

This prospective cohort study included children aged 0–16 years with newly diagnosed acute leukemia treated at Benjamin Bloom Hospital, San Salvador. We interviewed parents/caregivers within one month of diagnosis and at the onset of each new febrile episode. Times from initial fever to first antibiotic administration and occurrence of sepsis and infection-related mortality were documented.

Findings

Of 251 children enrolled, 215 had acute lymphoblastic leukemia (85.7%). Among 269 outpatient febrile episodes, median times from fever to deciding to seek medical care was 10.0 hours (interquartile range [IQR] 5.0–20.0), and from decision to seek care to first hospital visit was 1.8 hours (IQR 1.0–3.0). Forty-seven (17.5%) patients developed sepsis and 7 (2.6%) died of infection. Maternal illiteracy was associated with longer time from fever to decision to seek care (P = 0.029) and sepsis (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.09–8.63; P = 0.034). More infectious deaths occurred in those with longer travel time to hospital (OR 1.36, 95% CI 1.03–1.81; P = 0.031) and in families with an annual household income InterpretationIlliteracy, poverty, and longer travel times are associated with delays in assessment and treatment of fever and with sepsis and infectious mortality in pediatric leukemia. Providing additional education to high-risk families and staying at a nearby guest house during periods of neutropenia may decrease sepsis and infectious mortality.     

Shifting the life-history paradigm: discovery of novel habitat use by hawksbill turtles

Adult hawksbill turtles (Eretmochelys imbricata) are typically described as open-coast, coral reef and hard substrate dwellers. Here, we report new satellite tracking data on female hawksbills from several countries in the eastern Pacific that revealed previously undocumented behaviour for adults of the species. In contrast to patterns of habitat use exhibited by their Caribbean and Indo-Pacific counterparts, eastern Pacific hawksbills generally occupied inshore estuaries, wherein they had strong associations with mangrove saltwater forests. The use of inshore habitats and affinities with mangrove saltwater forests presents a previously unknown life-history paradigm for adult hawksbill turtles and suggests a potentially unique evolutionary trajectory for the species. Our findings highlight the variability in life-history strategies that marine turtles and other wide-ranging marine wildlife may exhibit among ocean regions, and the importance of understanding such disparities from an ecological and management perspective.     

Processing of triplex-directed psoralen DNA interstrand crosslinks by recombination mechanisms

Gene targeting via homologous recombination (HR) is an important application in biotechnology and medicine. However, in mammalian cells HR is much less efficient than random integration. Triplex-forming oligonucleotides (TFOs) linked to DNA damaging agents (e.g. psoralen) can stimulate HR, providing the potential to improve gene therapy applications. To elucidate factors affecting TFO-directed psoralen interstrand crosslink (ICL)-induced recombination, we constructed a series of plasmids with duplicated supF reporter genes, each containing an inactivating deletion, to measure HR frequencies in mammalian cells. Our results indicated that TFO-directed ICL-induced recombination frequencies were higher in the plasmids with larger distances between duplicated supF genes than with a smaller separation distance. However, the position of the ICL relative to the reporter genes did not affect HR frequencies. Recombination spectra were altered by the distance between supF copies. Although single-strand annealing (SSA) recombinants were predominant in all plasmid substrates, the plasmid with the shortest interval (60 bp) revealed a significant proportion of gene conversions (GCs). GCs occurred exclusively in the gene containing the shortest deletion, regardless of the distance between supF genes, ICL position or deletion orientation. Our analyses indicated that SSA is the predominant mechanism of ICL processing of these substrates in mammalian cells.     

The influence of habitat on travel speed, intermittent locomotion, and vigilance in a diurnal rodent

We studied effects of habitat structure on routine travel velocities, intermittent locomotion, and vigilance by the degu (Octodondegus), a diurnal rodent of central Chile. We predicted thattravel speed, pauses during locomotion, and vigilance wouldbe greater in open (riskier) than in shrub (safer) habitats.Video recordings of marked individuals in the wild were used to measure speed and other variables of spontaneous locomotionnot triggered by predatory attack or any other noticeable stimulusduring nonforaging periods. Time spent vigilant while foragingwas also measured. Because degus use bare-ground runways fordistant movements (e.g., between burrow openings and/or foodpatches), data on locomotion decisions were not confounded by effects of obstructive vegetation cover and/or resource abundance.When moving across the habitat between different feeding places,degus showed an intermittent pattern of locomotion, interruptingrunning events with short pauses. As predicted, travel speedand the duration of pauses between locomotion bursts were significantlygreater in open habitats. Further, the duration of locomotionbursts between feeding sites or between feeding sites and burrowswas significantly longer in open habitats. Our assumption that pauses and velocities are independent decisions was supportedby the lack of correlation between pauses and speeds duringlocomotion events. During foraging, degus devoted more timeto vigilance in open than in shrub habitats. The static positionadopted by degus during pauses, the speeds attained during movements, and the concordance between pausing behavior andvigilance across habitats suggest that pausing has an antipredatoryrole and is not limited to orientation and/or physiologicalrecovery. Our results support the view that degus perceivehigher predation risk in open areas and that flexible movement behavior reflects an adaptive antipredator response.     

Molecular evidence and clinical importance of β‐arrestins expression in patients with acromegaly

β‐arrestins seem to have a role in endocytosis and desensitization of somatostatin receptor subtype 2 (sst2) and could be associated with the responsiveness to somatostatin receptor ligands (SRL) in patients with acromegaly. To investigate the in vivo correlation between β‐arrestins 1 and 2 with sst2, sst5 and dopamine receptor subtype 2 (D2) expressions, and the association of β‐arrestins with response to first‐generation SRL and invasiveness in somatotropinomas. β‐arrestins 1 and 2, sst2, sst5 and D2 mRNA expressions were evaluated by quantitative real‐time RT‐PCR on tumoral tissue of 96 patients. Moreover, sst2 and sst5 protein expressions were also evaluated in 40 somatotropinomas by immunohistochemistry. Response to SRL, defined as GH <1 μg/l and normal IGF‐I levels, was assessed in 40 patients. The Knosp‐Steiner criteria were used to define invasiveness. Median β‐arrestin 1, β‐arrestin 2, sst2, sst5 and D2 mRNA copy numbers were 478; 9375; 731; 156 ; and 3989, respectively. There was a positive correlation between β‐arrestins 1 and 2 (R = 0.444, P < 0.001). However, no correlation between β‐arrestins and sst2, sst5 (mRNA and protein levels) or D2 was found. No association was found between β‐arrestins expression and SRL responsiveness or tumour invasiveness. Although previous data suggest a putative correlation between β‐arrestins and sst2, our data clearly indicated that no association existed between β‐arrestins and sst2, sst5 or D2 expression, nor with response to SRL or tumour invasiveness. Therefore, further studies are required to clarify whether β‐arrestins have a role in the response to treatment with SRL in acromegaly.     

Distinct Mechanisms of Nuclease-Directed DNA-Structure-Induced Genetic Instability in Cancer Genomes

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Relative toxicity of native Chilean Bacillus thuringiensis strains against Scrobipalpuloides absoluta (Lepidoptera: Gelechiidae)

The larva of Scrobipalpuloides absoluta , a South American moth, is the most devastating insect pest of tomato production in Chile. The potential for using bacterial insecticides was studied analysing the relative toxicity of native Bacillus thuringiensis (BT) isolates belonging to the Chilean collection. The polymerase chain reaction (PCR) technique was used in order to facilitate the prescreening. Mixtures of homologous specific primers to regions within genes encoding CryI , CryIII and CryIV crystal proteins were employed to generate a PCR product profile of each BT isolate. Four isolates were selected and further characterized by means of SDS-PAGE, Western blot and bioassays on fourth-instar S. absoluta larvae. Relative toxicities were evaluated by LD₅₀ determinations. The entomocidal activity of isolate 121e, an autoagglutinating strain, was threefold higher than toxin synthesized by B. thuringiensis var. kurstaki . This native strain was also active against Culex pipiens larvae, although much less than towards S. absoluta .     

Chondrocyte proliferation in a new culture system

Objective:  This study has aimed to study different culture systems that might stimulate an increase in cell proliferation of normal and osteoarthritis chondrocytes from articular cartilage in rat model.
Material and Methods:  Three culture systems using chondrocytes embedded in alginate beads were tested: chondrocytes cultured in Dulbecco's modified Eagle's medium (DMEM) as control, a co-culture system consisting of a monolayer of de-differentiated chondrocytes as a source of mitotic factors, and an enriched medium containing culture medium obtained from a monolayer of chondrocytes and DMEM. Normal and osteoarthritis chondrocytes were stained with 5-carboxyfluorescein diacetate succinimidyl ester and were cultured in each of the three systems. After 5 days of culture cell, proliferation was detected by flow cytometry. Chondrocyte phenotype was confirmed by collagen type II and MMP-3 expression. To determine possible molecules released into the medium by the cultured chondrocyte monolayer and which would probably be involved in cell proliferation, a study of mRNA and expression of transforming growth factor-β1 (TGF-β1), fibroblastic growth factor-2 (FGF-2), epidermal growth factor (EGF), platelet derived growth factor-A (PDGF-A) and insulin-like growth factor-1 (IGF-1) proteins was conducted.
Results and Conclusions:  Chondrocytes in the co-culture system or in enriched medium showed an increase in proliferation; only when osteoarthritis chondrocytes were cultured in enriched medium would they display a statistically significant increase in their proliferation rate and in their viability. When chondrocytes from the monolayer were analysed, differential mRNA expression of TGF-β1 and IGF-1 was found during all passages, which suggests that these two growth factors might be involved in chondrocyte proliferation.