Callous-unemotional traits, low cortisol reactivity and physical aggression in children: findings from the Wirral Child Health and Development Study

Callous-unemotional (CU) traits are thought to confer risk for aggression via reduced amygdala responsivity to distress cues in others. Low cortisol reactivity is thought to confer risk for aggression via reduced arousal and this effect may be confined to boys. We tested the hypothesis that the association between childhood CU traits and aggression would be greatest in the absence of the inhibitory effects of cortisol reactivity, and that this effect would be sex dependent. Participants were 283 members of a stratified subsample within an epidemiological longitudinal cohort (WCHADS). Cortisol reactivity to a social stressor was assessed at 5 years. CU traits were reported by mothers at 5 years, and physical aggression by mothers and teachers at age 7. Results showed that CU traits were associated with elevated aggression at 7 years controlling for earlier aggression. There was no main effect of cortisol reactivity on regression. The association between CU traits and aggression was moderated by cortisol reactivity (p = .011) with a strong association between CU traits and aggression in the presence of low reactivity, and a small and non-significant association in the presence of high reactivity. This association was further moderated by child sex (p = .041) with the joint effect of high CU traits and low cortisol reactivity seen only in boys (p = .016). We report first evidence that a combined deficit in inhibitory processes associated with CU traits and low cortisol reactivity increases risk for childhood aggression, in a sex-dependent manner

The Burden of Trachoma in South Sudan: Assessing the Health Losses from a Condition of Graded Severity

Trachoma is an infectious disease that is endemic to the Republic of South Sudan. In the absence of appropriate treatment recurrent re-infection in an individual will lead to progressively severe states of trachoma, eventually leading to the loss of visual acuity and finally blindness. Here we distinguish between three separate states of disease: trachoma with normal vision, trachoma with low vision and trachoma with blindness. The first of these states, trachoma with normal vision, is the least severe and the impact of this state on a population has not been well investigated. Trachoma, even before any loss of vision, comes with a great deal of pain and social consequences, and thus disability. In this study we employ data from South Sudan and estimate the burden caused by trachoma with normal vision for the first time. In doing so, we also reveal the extent of the gaps in our knowledge surrounding the natural history of trachoma and highlight areas of research that require urgent attention

Genetics of callous-unemotional behavior in children

Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase ‘missing heritability’ was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU

An ethic of connectedness: enacting moral school leadership through people and programs

As educators, we grapple with a myriad of dilemmas and often have difficulty resolving issues that relate to curriculum and instruction, funding, facilities and supervision, to name a few. Depending on the leader(s), a variety of ethics come in to play when making decisions. The ethic of connectedness refers to community building and welfare as central to moral thought and practice (Bradley, 2007). Responsibility to community building and welfare begins in the schools and must be an acculturated practice within the schools so future generations possess the knowledge, skills and dispositions that ensure a connectedness to their society (Marzano et al., 2005; Barth 2006; Collinson et al., 2006). This article will explore the importance of an ethic of connectedness to effective school leadership and the experience of a Pennsylvania school district in nurturing and building a connectedness within the school community.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Abdominal wall paresis as a complication of laparoscopic surgery

Purpose: Abdominal wall nerve injury as a result of trocar placement for laparoscopic surgery is rare. We intend to discuss causes of abdominal wall paresis as well as relevant anatomy. Methods: A review of the nerve supply of the abdominal wall is illustrated with a rare case of a patient presenting with paresis of the internal oblique muscle due to a trocar lesion of the right iliohypogastric nerve after laparoscopic appendectomy. Results: Trocar placement in the upper lateral abdomen can damage the subcostal nerve (Th12), caudal intercostal nerves (Th7-11) and ventral rami of the thoracic nerves (Th7-12). Trocar placement in the lower abdomen can damage the ilioinguinal (L1 or L2) and iliohypogastric nerves (Th12-L1). Pareses of abdominal muscles due to trocar placement are rare due to overlap in innervation and relatively small sizes of trocar incisions. Conclusion: Knowledge of the anatomy of the abdominal wall is mandatory in order to avoid the injury of important structures during trocar placement

Catabolic efficiency of aerobic glycolysis: The Warburg effect revisited

<p>Abstract</p> <p>Background</p> <p>Cancer cells simultaneously exhibit glycolysis with lactate secretion and mitochondrial respiration even in the presence of oxygen, a phenomenon known as the Warburg effect. The maintenance of this mixed metabolic phenotype is seemingly counterintuitive given that aerobic glycolysis is far less efficient in terms of ATP yield per moles of glucose than mitochondrial respiration.</p> <p>Results</p> <p>Here, we resolve this apparent contradiction by expanding the notion of metabolic efficiency. We study a reduced flux balance model of ATP production that is constrained by the glucose uptake capacity and by the solvent capacity of the cell's cytoplasm, the latter quantifying the maximum amount of macromolecules that can occupy the intracellular space. At low glucose uptake rates we find that mitochondrial respiration is indeed the most efficient pathway for ATP generation. Above a threshold glucose uptake rate, however, a gradual activation of aerobic glycolysis and slight decrease of mitochondrial respiration results in the highest rate of ATP production.</p> <p>Conclusions</p> <p>Our analyses indicate that the Warburg effect is a favorable catabolic state for all rapidly proliferating mammalian cells with high glucose uptake capacity. It arises because while aerobic glycolysis is less efficient than mitochondrial respiration in terms of ATP yield per glucose uptake, it is more efficient in terms of the required solvent capacity. These results may have direct relevance to chemotherapeutic strategies attempting to target cancer metabolism.</p

CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells

<p>Abstract</p> <p>Background</p> <p>Interactions between CXCR4 and its ligand CXCL12 have been shown to be involved in cancer progression in colorectal cancer (CRC). We performed a comparative CXCL12/CXCR4 expression analysis and assessed the effect of external CXCL12 stimulation on migration of CRC cells without and with CXCR4 inhibition.</p> <p>Methods</p> <p>Expression of CXCL12/CXCR4 was assessed by quantitative real-time PCR, ELISA and immunohistochemistry in resection specimens of 50 CRC patients as well as in the corresponding normal tissues and in three human CRC cell lines with different metastatic potential (Caco-2, SW480 and HT-29). Migration assays were performed after stimulation with CXCL12 and CXCR4 was inhibited by siRNA and neutralizing antibodies.</p> <p>Results</p> <p>In CRC tissues CXCL12 was significantly down-regulated and CXCR4 was significantly up-regulated compared to the corresponding normal tissues. In cell lines CXCR4 was predominantly expressed in SW480 and less pronounced in HT-29 cells. CXCL12 was only detectable in Caco-2 cells. CXCL12 stimulation had no impact on Caco-2 cells but significantly increased migration of CXCR4 bearing SW480 and HT-29 cells. This effect was significantly abrogated by neutralizing anti-CXCR4 antibody as well as by CXCR4 siRNAs (P < 0.05).</p> <p>Conclusions</p> <p>CXCR4 expression was up-regulated in CRC and CXCL12 stimulation increased migration in CXCR4 bearing cell lines. Migration was inhibited by both neutralizing CXCR4 antibodies and CXCR4 siRNAs. Thus, the expression and functionality of CXCR4 might be associated with the metastatic potential of CRC cells and CXCL12/CXCR4 interactions might therefore constitute a promising target for specific treatment interventions.</p

Young Offenders’ Emotion Recognition Dysfunction Across Emotion Intensities: Explaining Variation Using Psychopathic Traits, Conduct Disorder and Offense Severity

Antisocial individuals have problems recognizing negative emotions (e.g. Marsh & Blair in Neuroscience and Biobehavioral Reviews 32:454–465, 2009); however, due to issues with sampling and different methods used, previous findings have been varied. Sixty-three male young offenders and 37 age-, IQ- and socio-economic status-matched male controls completed a facial emotion recognition task, which measures recognition of happiness, sadness, fear, anger, disgust, and surprise and neutral expressions across 4 emotional intensities. Conduct disorder (YSR), and psychopathic and callous/unemotional traits (YPI) were measured, and offenders’ offense data were taken from the Youth Offending Service’s case files. Relative to controls, offenders were significantly worse at identifying sadness, low intensity disgust and high intensity fear. A significant interaction for anger was also observed, with offenders showing reduced low- but increased high-intensity anger recognition in comparison with controls. Within the young offenders levels of conduct disorder and psychopathic traits explained variation in sadness and disgust recognition, whereas offense severity explained variation in anger recognition. These results suggest that antisocial youths show specific problems in recognizing negative emotions and support the use of targeted emotion recognition interventions for problematic behavior

What Will Happen If We Do Nothing To Control Trachoma: Health Expectancies for Blinding Trachoma in Southern Sudan

Summary measures of population health attempt to express disease burden in terms of a common “currency” and are useful in establishing public health priorities. Disability adjusted life years (DALYs), a health gap measure, have previously been used to estimate burden due to trachoma; however, their methods and results have limitations. This study demonstrates the application of the health expectancies to estimate burden due to trachoma. The study illustrates the future burden associated with doing nothing to control trachoma in Southern Sudan: a substantial proportion of remaining life expectancy spent with trichiasis and low vision or blindness for both men and women, with a disproportionate burden falling on women. The results presented are intuitively meaningful for policy makers and a non-technical audience and compare favourably with other indicators such as mortality and incidence rates or DALYs, which are not generally easily understood. Unless action is taken by further delivery of trachoma control interventions, then populations in Southern Sudan can expect to spend a substantial proportion of their life with low vision or blindness due to trachoma