First recovery of bird acanthocephalan Sphaerirostris lanceoides in an Eurasian badger (Meles meles) in Italy

Esemplari di cistacanti parzialmente e completamente evertiti dell'acantocefalo Sphaerirostris lanceoides sono stati rilevati nell'intestino di 1 tra 5 tassi (Meles meles) raccolti in Italia e già deceduti al momento del loro ritrovamento. Questa è la prima segnalazione di S. lanceoides nel tasso

Synthetic Oligodeoxynucleotide CpG Motifs Activate Human Complement through Their Backbone Structure and Induce Complement-Dependent Cytokine Release

Bacterial and mitochondrial DNA, sharing an evolutionary origin, act as danger-associated molecular patterns in infectious and sterile inflammation. They both contain immunomodulatory CpG motifs. Interactions between CpG motifs and the complement system are sparsely described, and mechanisms of complement activation by CpG remain unclear. Lepirudin-anticoagulated human whole blood and plasma were incubated with increasing concentrations of three classes of synthetic CpGs: CpG-A, -B, and -C oligodeoxynucleotides and their GpC sequence controls. Complement activation products were analyzed by immunoassays. Cytokine levels were determined via 27-plex beads-based immunoassay, and CpG interactions with individual complement proteins were evaluated using magnetic beads coated with CpG-B. In whole blood and plasma, CpG-B and CpG-C (p 0.8 for all), led to time- and dose-dependent increase of soluble C5b-9, the alternative complement convertase C3bBbP, and the C3 cleavage product C3bc. GpC-A, -B, and -C changed soluble fluid-phase C5b-9, C3bBbP, and C3bc to the same extent as CpG-A, -B, and -C, indicating a DNA backbone–dependent effect. Dose-dependent CpG-B binding was found to C1q (r = 0.83; p = 0.006) and factor H (r = 0.93; p < 0.001). The stimulatory complement effect was partly preserved in C2-deficient plasma and completely preserved in MASP-2–deficient serum. CpG-B increased levels of IL-1β, IL-2, IL-6, IL-8, MCP-1, and TNF in whole blood, which were completely abolished by inhibition of C5 and C5aR1 (p < 0.05 for all). In conclusion, synthetic analogs of bacterial and mitochondrial DNA activate the complement system via the DNA backbone. We suggest that CpG-B interacts directly with classical and alternative pathway components, resulting in complement-C5aR1–dependent cytokine release

Emotional intelligence buffers the effect of physiological arousal on dishonesty

We studied the emotional processes that allow people to balance two competing desires: benefitting from dishonesty and keeping a positive self-image. We recorded physiological arousal (skin conductance and heart rate) during a computer card game in which participants could cheat and fail to report a certain card when presented on the screen to avoid losing their money. We found that higher skin conductance corresponded to lower cheating rates. Importantly, emotional intelligence regulated this effect; participants with high emotional intelligence were less affected by their physiological reactions than those with low emotional intelligence. As a result, they were more likely to profit from dishonesty. However, no interaction emerged between heart rate and emotional intelligence. We suggest that the ability to manage and control emotions can allow people to overcome the tension between doing right or wrong and license them to bend the rules

A mathematical model of mitochondrial swelling

<p>Abstract</p> <p>Background</p> <p>The <it>permeabilization </it>of mitochondrial membranes is a decisive event in apoptosis or necrosis culminating in cell death. One fundamental mechanism by which such permeabilization events occur is the calcium-induced mitochondrial permeability transition. Upon Ca²⁺-uptake into mitochondria an increase in inner membrane permeability occurs by a yet unclear mechanism. This leads to a net water influx in the mitochondrial matrix, mitochondrial swelling, and finally the rupture of the outer membrane. Although already described more than thirty years ago, many unsolved questions surround this important biological phenomenon. Importantly, theoretical modeling of the mitochondrial permeability transition has only started recently and the existing mathematical models fail to characterize the swelling process throughout the whole time range.</p> <p>Results</p> <p>We propose here a new mathematical approach to the mitochondrial permeability transition introducing a specific delay equation and resulting in an optimized representation of mitochondrial swelling. Our new model is in accordance with the experimentally determined course of volume increase throughout the whole swelling process, including its initial lag phase as well as its termination. From this new model biological consequences can be deduced, such as the confirmation of a positive feedback of mitochondrial swelling which linearly depends on the Ca²⁺-concentration, or a negative exponential dependence of the average swelling time on the Ca²⁺-concentration. Finally, our model can show an initial shrinking phase of mitochondria, which is often observed experimentally before the actual swelling starts.</p> <p>Conclusions</p> <p>We present a model of the mitochondrial swelling kinetics. This model may be adapted and extended to diverse other inducing/inhibiting conditions or to mitochondria from other biological sources and thus may benefit a better understanding of the mitochondrial permeability transition.</p

'Rumours' and clinical trials: a retrospective examination of a paediatric malnutrition study in Zambia, southern Africa

BACKGROUND: Many public health researchers conducting studies in resource-constrained settings have experienced negative 'rumours' about their work; in some cases they have been reported to create serious challenges and derail studies. However, what may appear superficially as 'gossip' or 'rumours' can also be regarded and understood as metaphors which represent local concerns. For researchers unaccustomed to having concerns expressed from participants in this manner, possible reactions can be to be unduly perturbed or conversely dismissive.This paper represents a retrospective examination of a malnutrition study conducted by an international team of researchers in Zambia, Southern Africa. The fears of mothers whose children were involved in the study and some of the concerns which were expressed as rumours are also presented. This paper argues that there is an underlying logic to these anxieties and to dismiss them simply as 'rumours' or 'gossip' would be to overlook the historic and socio-economic factors which have contributed to their production. METHODS: Qualitative interviews were conducted with the mothers whose children were involved in the study and with the research nurses. Twenty five face-to-face interviews and 2 focus group discussions (FGDs) were conducted with mothers. In addition, face-to-face interviews were conducted with research nurses participating in the trial. RESULTS: A prominent anxiety expressed as rumours by the mothers whose children were involved in the study was that recruitment into the trial was an indicator that the child was HIV-infected. Other anxieties included that the trial was a disguise for witchcraft or Satanism and that the children's body parts would be removed and sold. In addition, the liquid, milk-based food given to the children to improve their nutrition was suspected of being insufficiently nutritious, thus worsening their condition.The form which these anxieties took, such as rumours related to the stealing of body parts and other anxieties about a stigmatised condition, provide an insight into the historical, socio-economic and cultural influences in such settings. CONCLUSIONS: Employing strategies to understand local concerns should accompany research aims to achieve optimal success. The concerns raised by the participants we interviewed are not unique to this study. They are produced in countries where the historic, socio-economic and cultural settings communicate anxieties in this format. By examining this study we have shown that by contextualizing these 'rumours', the concerns they express can be constructively addressed and in turn result in the successful conduct of research aims

Reduction of Severe Acute Maternal Morbidity and Maternal Mortality in Thyolo District, Malawi: The Impact of Obstetric Audit

BACKGROUND: Critical incident audit and feedback are recommended interventions to improve the quality of obstetric care. To evaluate the effect of audit at district level in Thyolo, Malawi, we assessed the incidence of facility-based severe maternal complications (severe acute maternal morbidity (SAMM) and maternal mortality) during two years of audit and feedback. METHODOLOGY/PRINCIPAL FINDINGS: Between September 2007 and September 2009, we included all cases of maternal mortality and SAMM that occurred in Thyolo District Hospital, the main referral facility in the area, using validated disease-specific criteria. During two- to three-weekly audit sessions, health workers and managers identified substandard care factors. Resulting recommendations were implemented and followed up. Feedback was given during subsequent sessions. A linear regression analysis was performed on facility-based severe maternal complications. During the two-year study period, 386 women were included: 46 died and 340 sustained SAMM, giving a case fatality rate of 11.9%. Forty-five cases out of the 386 inclusions were audited in plenary with hospital staff. There was a reduction of 3.1 women with severe maternal complications per 1000 deliveries in the district health facilities, from 13.5 per 1000 deliveries in the beginning to 10.4 per 1000 deliveries at the end of the study period. The incidence of uterine rupture and major obstetric hemorrhage reduced considerably (from 3.5 to 0.2 and from 5.9 to 2.6 per 1000 facility deliveries respectively). CONCLUSIONS: Our findings indicate that audit and feedback have the potential to reduce serious maternal complications including maternal mortality. Complications like major hemorrhage and uterine rupture that require relatively straightforward intrapartum emergency management are easier to reduce than those which require uptake of improved antenatal care (eclampsia) or timely intravenous medication or HIV-treatment (peripartum infections)

A study of association between common variation in the growth hormone-chorionic somatomammotropin hormone gene cluster and adult fasting insulin in a UK Caucasian population

BACKGROUND: Reduced growth during infancy is associated with adult insulin resistance. In a UK Caucasian cohort, the CSH1.01 microsatellite polymorphism in the growth hormone-chorionic somatomammotropin hormone gene cluster was recently associated with increases in adult fasting insulin of approximately 23 pmol/l for TT homozygote males compared to D1D1 or D2D2 homozygotes (P = 0.001 and 0.009; n = 206 and 92, respectively), but not for females. TT males additionally had a 547-g lower weight at 1 year (n = 270; P = 0.008) than D2D2 males. We sought to replicate these data in healthy UK Caucasian subjects. We genotyped 1396 subjects (fathers, mothers and children) from a consecutive birth study for the CSH1.01 marker and analysed genotypes for association with 1-year weight in boys and fasting insulin in fathers. RESULTS: We found no evidence for association of CSH1.01 genotype with adult male fasting insulin concentrations (TT/D1D1 P = 0.38; TT/D2D2 P = 0.18) or weight at 1 year in boys (TT/D1D1 P = 0.76; TT/D2D2 P = 0.85). For fasting insulin, our data can exclude the previously observed effect sizes as the 95 % confidence intervals for the differences observed in our study exclude increases in fasting insulin of 9.0 and 12.6 pmol/l for TT relative to D1D1 and D2D2 homozygotes, respectively. Whilst we have fewer data on boys' 1-year weight than the original study, our data can exclude a reduction in 1-year weight greater than 557 g for TT relative to D2D2 homozygotes. CONCLUSION: We have not found association of the CSH1.01 genotype with fasting insulin or weight at 1 year. We conclude that the original study is likely to have over-estimated the effect size for fasting insulin, or that the difference in results reflects the younger age of subjects in this study relative to those in the previous study

Monitoring Virologic Responses to Antiretroviral Therapy in HIV-Infected Adults in Kenya: Evaluation of a Low-Cost Viral Load Assay

A key advantage of monitoring HIV viral load (VL) in persons receiving antiretroviral therapy (ART) is the ability to detect virologic failure before clinical deterioration or resistance occurs. Detection of virologic failure will help clarify the need for enhanced adherence counseling or a change to second- line therapy. Low-cost, locally performable alternates to expensive VL assays are needed where resources are limited.We monitored the response to 48-week ART in 100 treatment-naïve Kenyan adults using a low-cost VL measurement, the Cavidi reverse transcriptase (RT) assay and gold-standard assays, Roche RNA PCR and Bayer Versant HIV-1 RNA (bDNA) assays. In Altman-Bland plots, the mean difference in viral loads between the three assays was small (<0.5 log(10) copies/mL). However, the limits of agreement between the methods exceeded the biologically relevant change of 0.5 log copies/ml. Therefore, the RT assay cannot be used interchangeably with the other assays to monitor individual patients. The RT assay was 100% sensitive in detecting viral loads of > or =400 copies/ml compared to gold-standard assays. After 24 weeks of treatment, viral load measured by the RT assay was undetectable in 95% of 65 patients with undetectable RNA PCR VL (<400 copies/ml), 90% of 67 patients with undetectable bDNA VL, and 96% of 57 patients with undetectable VL in both RNA PCR and bDNA assays. The negative predictive value of the RT assay was 100% compared to either assay; the positive predictive value was 86% compared to RNA PCR and 70% compared to bDNA.The RT assay compared well with gold standard assays. Our study highlights the importance of not interchanging viral load assays when monitoring an individual patient. Furthermore, the RT assay may be limited by low positive predictive values when used in populations with low prevalence of virologic failure

Loss of KCNJ10 protein expression abolishes endocochlear potential and causes deafness in Pendred syndrome mouse model

BACKGROUND: Pendred syndrome, a common autosomal-recessive disorder characterized by congenital deafness and goiter, is caused by mutations of SLC26A4, which codes for pendrin. We investigated the relationship between pendrin and deafness using mice that have (Slc26a4(+/+)) or lack a complete Slc26a4 gene (Slc26a4(-/-)). METHODS: Expression of pendrin and other proteins was determined by confocal immunocytochemistry. Expression of mRNA was determined by quantitative RT-PCR. The endocochlear potential and the endolymphatic K(+ )concentration were measured with double-barreled microelectrodes. Currents generated by the stria marginal cells were recorded with a vibrating probe. Tissue masses were evaluated by morphometric distance measurements and pigmentation was quantified by densitometry. RESULTS: Pendrin was found in the cochlea in apical membranes of spiral prominence cells and spindle-shaped cells of stria vascularis, in outer sulcus and root cells. Endolymph volume in Slc26a4(-/- )mice was increased and tissue masses in areas normally occupied by type I and II fibrocytes were reduced. Slc26a4(-/- )mice lacked the endocochlear potential, which is generated across the basal cell barrier by the K(+ )channel KCNJ10 localized in intermediate cells. Stria vascularis was hyperpigmented, suggesting unalleviated free radical damage. The basal cell barrier appeared intact; intermediate cells and KCNJ10 mRNA were present but KCNJ10 protein was absent. Endolymphatic K(+ )concentrations were normal and membrane proteins necessary for K(+ )secretion were present, including the K(+ )channel KCNQ1 and KCNE1, Na(+)/2Cl(-)/K(+ )cotransporter SLC12A2 and the gap junction GJB2. CONCLUSIONS: These observations demonstrate that pendrin dysfunction leads to a loss of KCNJ10 protein expression and a loss of the endocochlear potential, which may be the direct cause of deafness in Pendred syndrome