Predictability of Painful Stimulation Modulates the Somatosensory-Evoked Potential in the Rat

Somatosensory-evoked potentials (SEPs) are used in humans and animals to increase knowledge about nociception and pain. Since the SEP in humans increases when noxious stimuli are administered unpredictably, predictability potentially influences the SEP in animals as well. To assess the effect of predictability on the SEP in animals, classical fear conditioning was applied to compare SEPs between rats receiving SEP-evoking electrical stimuli either predictably or unpredictably. As in humans, the rat’s SEP increased when SEP-evoking stimuli were administered unpredictably. These data support the hypothesis that the predictability of noxious stimuli plays a distinctive role in the processing of these stimuli in animals. The influence of predictability should be considered when studying nociception and pain in animals. Additionally, this finding suggests that animals confronted with (un)predictable noxious stimuli can be used to investigate the mechanisms underlying the influence of predictability on central processing of noxious stimuli.     

Population-Level Impact of Same-Day Microscopy and Xpert MTB/RIF for Tuberculosis Diagnosis in Africa

Objective

To compare the population-level impact of two World Health Organization-endorsed strategies for improving the diagnosis of tuberculosis (TB): same-day microscopy and Xpert MTB/RIF (Cepheid, USA).

Methods

We created a compartmental transmission model of TB in a representative African community, fit to the regional incidence and mortality of TB and HIV. We compared the population-level reduction in TB burden over ten years achievable with implementation over two years of same-day microscopy, Xpert MTB/RIF testing, and the combination of both approaches.

Findings

Same-day microscopy averted an estimated 11.0% of TB incidence over ten years (95% uncertainty range, UR: 3.3%–22.5%), and prevented 11.8% of all TB deaths (95% UR: 7.7%–27.1%). Scaling up Xpert MTB/RIF to all centralized laboratories to achieve 75% population coverage had similar impact on incidence (9.3% reduction, 95% UR: 1.9%–21.5%) and greater effect on mortality (23.8% reduction, 95% UR: 8.6%–33.4%). Combining the two strategies (i.e., same-day microscopy plus Xpert MTB/RIF) generated synergistic effects: an 18.7% reduction in incidence (95% UR: 5.6%–39.2%) and 33.1% reduction in TB mortality (95% UR: 18.1%–50.2%). By the end of year ten, combining same-day microscopy and Xpert MTB/RIF could reduce annual TB mortality by 44% relative to the current standard of care.

Conclusion

Scaling up novel diagnostic tests for TB and optimizing existing ones are complementary strategies that, when combined, may have substantial impact on TB epidemics in Africa.     

Habitat of the corn leafhopper (Hemiptera: Cicadellidae) during the dry (winter) season in Mexico

Although the corn leafhopper Dalbulus maidis (DeLong and Wolcott) is the most important vector of maize pathogens in Latin America, little is known about how and where it overwinters (passes the dry season), particularly in Mexico. The objectives of this study were (1) to monitor the abundance of D. maidis adults throughout the dry season in maize and maize-free habitats and (2) to determine where and how D. maidis adults, exposed or nonexposed to the maize pathogen Spiroplasma kunkelii Whitcomb, overwinter in a maize-free habitat. Work for the first objective was done during the two consecutive dry seasons of 1999-2000 and 2000-2001; the second objective was done during the dry seasons of 2003-2004 and 2005-2006. During the dry winter seasons, D. maidis was prevalent as long as maize was present in irrigated areas. The leafhopper was found in 52 of the 58 irrigated maize fields sampled in Mexico at the end of the dry seasons of 1999-2000 and 2000-2001. However, leafhopper adults were not found in nonirrigated maize-free habitats at high elevation during the dry winter season (February, March, and April), although leafhopper adults were prevalent on perennial wild grasses in January after maize harvest. Additional experiments revealed, however, that corn leafhopper adults, although few in number, survived the entire dry season in these nonirrigated maize-free fields. Also, no detectable difference in survival existed between leafhoppers exposed and those not exposed to S. kunkelli during the two dry seasons in the maize-free habitat.     

Preventing Acute Malnutrition among Young Children in Crises: A Prospective Intervention Study in Niger

Background

Finding the most appropriate strategy for the prevention of moderate acute malnutrition (MAM) and severe acute malnutrition (SAM) in young children is essential in countries like Niger with annual “hunger gaps.” Options for large-scale prevention include distribution of supplementary foods, such as fortified-blended foods or lipid-based nutrient supplements (LNSs) with or without household support (cash or food transfer). To date, there has been no direct controlled comparison between these strategies leading to debate concerning their effectiveness. We compared the effectiveness of seven preventive strategies—including distribution of nutritious supplementary foods, with or without additional household support (family food ration or cash transfer), and cash transfer only—on the incidence of SAM and MAM among children aged 6–23 months over a 5-month period, partly overlapping the hunger gap, in Maradi region, Niger. We hypothesized that distributions of supplementary foods would more effectively reduce the incidence of acute malnutrition than distributions of household support by cash transfer.

Methods and Findings

We conducted a prospective intervention study in 48 rural villages located within 15 km of a health center supported by Forum Santé Niger (FORSANI)/Médecins Sans Frontières in Madarounfa. Seven groups of villages (five to 11 villages) were allocated to different strategies of monthly distributions targeting households including at least one child measuring 60 cm–80 cm (at any time during the study period whatever their nutritional status): three groups received high-quantity LNS (HQ-LNS) or medium-quantity LNS (MQ-LNS) or Super Cereal Plus (SC+) with cash (€38/month [US$52/month]); one group received SC+ and family food ration; two groups received HQ-LNS or SC+ only; one group received cash only (€43/month [US$59/month]). Children 60 cm–80 cm of participating households were assessed at each monthly distribution from August to December 2011. Primary endpoints were SAM (weight-for-length Z-score [WLZ]<−3 and/or mid-upper arm circumference [MUAC]<11.5 cm and/or bipedal edema) and MAM (−3≤WLZ<−2 and/or 11.5≤MUAC<12.5 cm). A total of 5,395 children were included in the analysis (615 to 1,054 per group). Incidence of MAM was twice lower in the strategies receiving a food supplement combined with cash compared with the cash-only strategy (cash versus HQ-LNS/cash adjusted hazard ratio [HR] = 2.30, 95% CI 1.60–3.29; cash versus SC+/cash HR = 2.42, 95% CI 1.39–4.21; cash versus MQ-LNS/cash HR = 2.07, 95% CI 1.52–2.83) or with the supplementary food only groups (HQ-LNS versus HQ-LNS/cash HR = 1.84, 95% CI 1.35–2.51; SC+ versus SC+/cash HR = 2.53, 95% CI 1.47–4.35). In addition, the incidence of SAM was three times lower in the SC+/cash group compared with the SC+ only group (SC+ only versus SC+/cash HR = 3.13, 95% CI 1.65–5.94). However, non-quantified differences between groups, may limit the interpretation of the impact of the strategies.

Conclusions

Preventive distributions combining a supplementary food and cash transfer had a better preventive effect on MAM and SAM than strategies relying on cash transfer or supplementary food alone. As a result, distribution of nutritious supplementary foods to young children in conjunction with household support should remain a pillar of emergency nutritional interventions. Additional rigorous research is vital to evaluate the effectiveness of these and other nutritional interventions in diverse settings.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01828814","term_id":"NCT01828814"}}NCT01828814 Please see later in the article for the Editors'' Summary     

Opposite effects on facial morphology due to gene dosage sensitivity

Sequencing technology is increasingly demonstrating the impact of genomic copy number variation (CNV) on phenotypes. Opposing variation in growth, head size, cognition and behaviour is known to result from deletions and reciprocal duplications of some genomic regions. We propose normative inversion of face shape, opposing difference from a matched norm, as a basis for investigating the effects of gene dosage on craniofacial development. We use dense surface modelling techniques to match any face (or part of a face) to a facial norm of unaffected individuals of matched age, sex and ethnicity and then we reverse the individual’s face shape differences from the matched norm to produce the normative inversion. We demonstrate for five genomic regions, 4p16.3, 7q11.23, 11p15, 16p13.3 and 17p11.2, that such inversion for individuals with a duplication or (epi)-mutation produces facial forms remarkably similar to those associated with a deletion or opposite (epi-)mutation of the same region, and vice versa. The ability to visualise and quantify face shape effects of gene dosage is of major benefit for determining whether a CNV is the cause of the phenotype of an individual and for predicting reciprocal consequences. It enables face shape to be used as a relatively simple and inexpensive functional analysis of the gene(s) involved.     

Targeting Prolyl Endopeptidase with Valproic Acid as a Potential Modulator of Neutrophilic Inflammation

A novel neutrophil chemoattractant derived from collagen, proline-glycine-proline (PGP), has been recently characterized in chronic obstructive pulmonary disease (COPD). This peptide is derived via the proteolytic activity of matrix metalloproteases (MMP''s)-8/9 and PE, enzymes produced by neutrophils and present in COPD serum and sputum. Valproic acid (VPA) is an inhibitor of PE and could possibly have an effect on the severity of chronic inflammation. Here the interaction site of VPA to PE and the resulting effect on the secondary structure of PE is investigated. Also, the potential inhibition of PGP-generation by VPA was examined in vitro and in vivo to improve our understanding of the biological role of VPA. UV- visible, fluorescence spectroscopy, CD and NMR were used to determine kinetic information and structural interactions between VPA and PE. In vitro, PGP generation was significantly inhibited by VPA. In vivo, VPA significantly reduced cigarette-smoke induced neutrophil influx. Investigating the molecular interaction between VPA and PE showed that VPA modified the secondary structure of PE, making substrate binding at the catalytic side of PE impossible. Revealing the molecular interaction VPA to PE may lead to a better understanding of the involvement of PE and PGP in inflammatory conditions. In addition, the model of VPA interaction with PE suggests that PE inhibitors have a great potential to serve as therapeutics in inflammatory disorders.     

Histopathological Features of Aspirated Thrombi after Primary Percutaneous Coronary Intervention in Patients with ST-Elevation Myocardial Infarction

Background

Plaque disruption with superimposed thrombus is the predominant mechanism responsible for the onset of acute coronary syndromes. Studies have shown that plaque disruption and thrombotic occlusion are frequently separated in time. We established the histopathological characteristics of material aspirated during primary percutaneous coronary intervention (PCI) in a large consecutive ST-elevation myocardial infarction (STEMI) population.

Methodology/Principal Findings

Thrombus aspiration during primary PCI was performed in 1,362 STEMI patients. Thrombus age was classified as fresh (<1 day), lytic (1–5 days), or organized (>5 day). Further, the presence of plaque was documented. The histopathological findings were related to the clinical, angiographic, and procedural characteristics. Material could be aspirated in 1,009 patients (74%). Components of plaque were found in 395 of these patients (39%). Fresh thrombus was found in 577 of 959 patients (60%) compared to 382 patients (40%) with lytic or organized thrombi. Distal embolization was present in 21% of patients with lytic thrombus compared to 12% and 15% of patients with fresh or organized thrombus.

Conclusions/Significance

Material could be obtained in 74% of STEMI patients treated with thrombus aspiration during primary PCI. In 40% of patients thrombus age is older than 24 h, indicating that plaque disruption and thrombus formation occur significantly earlier than the onset of symptoms in many patients.     

Are There Ethnic Inequalities in Revascularisation Procedure Rate after an ST-Elevation Myocardial Infarction?

Background

Previously, ethnic inequalities in prognosis after a first acute myocardial infarction were observed in the Netherlands. This might be due to differences in revascularisation rate between ethnic minority groups and ethnic Dutch. Therefore, we investigated inequalities in revascularisation rate after occurrence of an ST-elevation myocardial infarction (STEMI) between first generation ethnic minority groups (henceforth, migrants) and ethnic Dutch.

Methods

All STEMI events between 2006 and 2011 were identified in a subset of the Achmea Health Database, which records medical care to persons insured at the Achmea health insurance company, a major health insurance company in the central part of the Netherlands. Ethnic Dutch and migrants from Suriname (Hindustani Surinamese and non-Hindustani Surinamese), Morocco, and Turkey were included (n = 1,765). Multivariable Cox proportional hazards regression analyses were used to identify ethnic inequalities in revascularisation rate (percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG)) after a STEMI event.

Results

On average, 73.2% of STEMI events were followed by a revascularisation procedure. After adjustment for confounders (age, sex, degree of urbanization) no significant differences in revascularisation rate were found between the ethnic Dutch population and Hindustani Surinamese (HR: 1.04; 0.85–1.27), non-Hindustani Surinamese (HR: 0.98; 0.63–1.51), Moroccan (HR: 0.94; 0.77–1.14), and Turkish migrants (HR: 1.04; 0.88–1.24). Additional adjustment for comorbidity and neighborhood income did not change our findings.

Conclusion

Our study suggests no ethnic inequalities in revascularisation rate after a STEMI event. This finding is in agreement with the universally accessible health care system in the Netherlands.