What is the impact of acquired immunity on the transmission of schistosomiasis and the efficacy of current and planned mass drug administration programmes?

Schistosomiasis causes severe morbidity in many countries with endemic infection with the schistosome digenean parasites in Africa and Asia. To control and eliminate the disease resulting from infection, regular mass drug administration (MDA) is used, with a focus on school-aged children (SAC; 5-14 years of age). In some high transmission settings, the World Health Organization (WHO) also recommends the inclusion of at-risk adults in MDA treatment programmes. The question of whether ecology (age-dependant exposure) or immunity (resistance to reinfection), or some combination of both, determines the form of observed convex age-intensity profile is still unresolved, but there is a growing body of evidence that the human hosts acquire some partial level of immunity after a long period of repeated exposure to infection. In the majority of past research modelling schistosome transmission and the impact of MDA programmes, the effect of acquired immunity has not been taken into account. Past work has been based on the assumption that age-related contact rates generate convex horizontal age-intensity profiles. In this paper, we use an individual based stochastic model of transmission and MDA impact to explore the effect of acquired immunity in defined MDA programmes. Compared with scenarios with no immunity, we find that acquired immunity makes the MDA programme less effective with a slower decrease in the prevalence of infection. Therefore, the time to achieve morbidity control and elimination as a public health problem is longer than predicted by models with just age-related exposure and no build-up of immunity. The level of impact depends on the baseline prevalence prior to treatment (the magnitude of the basic reproductive number R0) and the treatment frequency, among other factors. We find that immunity has a larger impact within moderate to high transmission settings such that it is very unlikely to achieve morbidity and transmission control employing current MDA programmes

Motor contagion: the contribution of trajectory and end-points

Increased involuntary arm movement deviation when observing an incongruent human arm movement has been interpreted as a strong indicator of motor contagion. Here, we examined the contribution of trajectory and end-point information on motor contagion by altering congruence between the stimulus and arm movement. Participants performed cyclical horizontal arm movements whilst simultaneously observing a stimulus representing human arm movement. The stimuli comprised congruent horizontal movements or vertical movements featuring incongruent trajectory and end-points. A novel, third, stimulus comprised curvilinear movements featuring congruent end-points, but an incongruent trajectory. In Experiment 1, our dependent variables indicated increased motor contagion when observing the vertical compared to horizontal movement stimulus. There was even greater motor contagion in the curvilinear stimulus condition indicating an additive effect of an incongruent trajectory comprising congruent end-points. In Experiment 2, this additive effect was also present when facing perpendicular to the display, and thus with end-points represented as a product of the movement rather than an external spatial reference. Together, these findings support the theory of event coding (Hommel et al., Behav Brain Sci 24:849–878, 2001), and the prediction that increased motor contagion takes place when observed and executed actions share common features (i.e., movement end-points)

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Top-down social modulation of interpersonal observation-execution.

Cyclical upper limb movement can involuntarily deviate from its primary movement axis when the performer concurrently observes incongruent biological motion (i.e. interpersonal observation-execution). The current study examined the social modulation of such involuntary motor interference using a protocol that reflected everyday social interactions encountered in a naturalistic social setting. Eighteen participants executed cyclical horizontal arm movements during the observation of horizontal (congruent) or curvilinear (incongruent) biological motion. Both prior to, and during the interpersonal observation-execution task, participants also received a series of social words designed to prime a pro-social or anti-social attitude. The results showed greater orthogonal movement deviation, and thus interference, for the curvilinear compared to horizontal stimuli. Importantly, and opposite to most of the previous findings from work on automatic imitation and mimicry, there was a greater interference effect for the anti-social compared to pro-social prime condition. These findings demonstrate the importance of interpreting the context of social primes, and strongly support predictions of a comparison between the prime construct and the self-concept/-schema and the top-down response modulation of social incentives

Examining ecological validity in social interaction: problems of visual fidelity, gaze, and social potential

Social interaction is an essential part of the human experience, and much work has been done to study it. However, several common approaches to examining social interactions in psychological research may inadvertently either unnaturally constrain the observed behaviour by causing it to deviate from naturalistic performance, or introduce unwanted sources of variance. In particular, these sources are the differences between naturalistic and experimental behaviour that occur from changes in visual fidelity (quality of the observed stimuli), gaze (whether it is controlled for in the stimuli), and social potential (potential for the stimuli to provide actual interaction). We expand on these possible sources of extraneous variance and why they may be important. We review the ways in which experimenters have developed novel designs to remove these sources of extraneous variance. New experimental designs using a ‘two-person’ approach are argued to be one of the most effective ways to develop more ecologically valid measures of social interaction, and we suggest that future work on social interaction should use these designs wherever possible

Protective effect of leptin against ischemia-reperfusion injury in the rat small intestine

BACKGROUND: The small intestine is extremely sensitive to ischemia-reperfusion (I/R) injury and a range of microcirculatory disturbances which contribute to tissue damage. Previous studies have shown that leptin plays an important physiological role in the microvasculature. The aim of this study was to evaluate the protective effects of leptin in I/R – induced mucosal injury in the small intestine. METHODS: Forty rats were divided into 5 groups (n = 8). Group I was subjected to a sham operation. Following mesenteric ischemia in group II (control); physiologic saline 1 cm(3), in group III; leptin 100 μg/kg, and physiologic saline 1 cm(3), in group IV; N(G)-L-arginine methyl ester (L-NAME) 20 mg/kg, and physiologic saline 1 cm(3), in group V; leptin 100 μg/kg, L-NAME 20 mg/kg, and physiologic saline 1 cm(3 )were given intra-peritoneally. In these groups, an I/R procedure was performed by occlusion of the superior mesenteric artery for 45 min followed by 120 min reperfusion. After reperfusion, the small intestines were resected for malondialdehyde (MDA) and nitric oxide (NO) concentration and histopathologic properties. Mucosal lesions were scored between 0 and 5. Tissue MDA and NO concentration and histopathologic grades were compared statistically. RESULTS: Tissue MDA level significantly increased (P < 0.05), tissue NO level significantly decreased in group V animals, compared to group III animals respectively (P < 0.001). Histopathologically, intestinal injury significantly decreased in the leptin treated ischemic group. CONCLUSION: Leptin can be used safely in mesenteric occlusive diseases, since it induces NO formation and release in mesenteric vessels

Psychosocial Needs of Children in Foster Care and the Impact of Sexual Abuse

Children in family foster care, especially those who have experienced sexual abuse, require a safe and nurturing environment in which their psychosocial needs are met. However, there is limited knowledge on how youth prioritize various needs and what impact previous experiences have on these needs. In this study, we asked youth (formerly) in family foster care to indicate their psychosocial needs, and analyzed if youth with a history of sexual abuse have different needs. A Q methodological study was conducted with 44 youth (age 16–28). Fifteen of them reported sexual abuse during their childhood. Using by-person factor analyses, respondents who share similar subjective views were grouped together. Qualitative interpretations of the factors show differences and similarities between and within the two groups, related to help from others, being independent, processing the past, and working toward the future. Although the needs of youth with and without experiences of sexual abuse seem mostly similar, one group of sexually abused youth specifically indicated not wanting an emotional connection to foster parents, but instead a strictly instrumental, professional relationship. This study captured the diverse perspectives of youth themselves, revealing that children in foster care differ with regard to what they consider as (most) important safety, belonging, self-esteem and self-actualization needs

Co-dependence of the neural and humoral pathways in the mechanism of remote ischemic conditioning

The cardioprotection afforded by remote ischaemic conditioning (RIC) is mediated via a complex mechanism involving sensory afferent nerves, the vagus nerve, and release of a humoral blood-borne factor. However, it is unknown whether release of the protective factor depends on vagal activation or occurs independently. This study aimed to evaluate the co-dependence of the neural and humoral pathways of RIC, focussing on the vagus nerve and intrinsic cardiac ganglia. In the first study, anesthetised rats received bilateral cervical vagotomy or sham-surgery immediately prior to RIC (4 × 5 min limb ischemia-reperfusion) or sham-RIC. Venous blood plasma was dialysed across a 12-14 kDa membrane and dialysate perfused through a naïve-isolated rat heart prior to 35-min left anterior descending ischemia and 60-min reperfusion. In the second study, anesthetised rats received RIC (4 × 5-min limb ischemia-reperfusion) or control (sham-RIC). Dialysate was prepared and perfused through a naïve-isolated rat heart in the presence of the ganglionic blocker hexamethonium or muscarinic antagonist atropine, prior to ischemia-reperfusion as above. Dialysate collected from RIC-treated rats reduced infarct size in naïve rat hearts from 40.7 ± 6.3 to 23.7 ± 3.1 %, p < 0.05. Following bilateral cervical vagotomy, the protection of RIC dialysate was abrogated (42.2 ± 3.2 %, p < 0.05 vs RIC dialysate). In the second study, the administration of 50-μM hexamethonium (45.8 ± 2.5 %) or 100-nM atropine (36.5 ± 3.4 %) abrogated the dialysate-mediated protection. Release of a protective factor following RIC is dependent on prior activation of the vagus nerve. In addition, this factor appears to induce cardioprotection via recruitment of intrinsic cardiac ganglia

Determination of Beta-Defensin Genomic Copy Number in Different Populations: A Comparison of Three Methods

There have been conflicting reports in the literature on association of gene copy number with disease, including CCL3L1 and HIV susceptibility, and β-defensins and Crohn's disease. Quantification of precise gene copy numbers is important in order to define any association of gene copy number with disease. At present, real-time quantitative PCR (QPCR) is the most commonly used method to determine gene copy number, however the Paralogue Ratio Test (PRT) is being used in more and more laboratories.In this study we compare a Pyrosequencing-based Paralogue Ratio Test (PPRT) for determining beta-defensin gene copy number with two currently used methods for gene copy number determination, QPCR and triplex PRT by typing five different cohorts (UK, Danish, Portuguese, Ghanaian and Czech) of DNA from a total of 576 healthy individuals. We found a systematic measurement bias between DNA cohorts revealed by QPCR, but not by the PRT-based methods. Using PRT, copy number ranged from 2 to 9 copies, with a modal copy number of 4 in all populations.QPCR is very sensitive to quality of the template DNA, generating systematic biases that could produce false-positive or negative disease associations. Both triplex PRT and PPRT do not show this systematic bias, and type copy number within the correct range, although triplex PRT appears to be a more precise and accurate method to type beta-defensin copy number

Natural Polymorphism in BUL2 Links Cellular Amino Acid Availability with Chronological Aging and Telomere Maintenance in Yeast

Aging and longevity are considered to be highly complex genetic traits. In order to gain insight into aging as a polygenic trait, we employed an outbred Saccharomyces cerevisiae model, generated by crossing a vineyard strain RM11 and a laboratory strain S288c, to identify quantitative trait loci that control chronological lifespan. Among the major loci that regulate chronological lifespan in this cross, one genetic linkage was found to be congruent with a previously mapped locus that controls telomere length variation. We found that a single nucleotide polymorphism in BUL2, encoding a component of an ubiquitin ligase complex involved in trafficking of amino acid permeases, controls chronological lifespan and telomere length as well as amino acid uptake. Cellular amino acid availability changes conferred by the BUL2 polymorphism alter telomere length by modulating activity of a transcription factor Gln3. Among the GLN3 transcriptional targets relevant to this phenotype, we identified Wtm1, whose upregulation promotes nuclear retention of ribonucleotide reductase (RNR) components and inhibits the assembly of the RNR enzyme complex during S-phase. Inhibition of RNR is one of the mechanisms by which Gln3 modulates telomere length. Identification of a polymorphism in BUL2 in this outbred yeast population revealed a link among cellular amino acid availability, chronological lifespan, and telomere length control