The role of infants' mother-directed gaze, maternal sensitivity, and emotion recognition in childhood callous unemotional behaviours.

While some children with callous unemotional (CU) behaviours show difficulty recognizing emotional expressions, the underlying developmental pathways are not well understood. Reduced infant attention to the caregiver's face and a lack of sensitive parenting have previously been associated with emerging CU features. The current study examined whether facial emotion recognition mediates the association between infants' mother-directed gaze, maternal sensitivity, and later CU behaviours. Participants were 206 full-term infants and their families from a prospective longitudinal study, the Durham Child Health and Development Study (DCHDS). Measures of infants' mother-directed gaze, and maternal sensitivity were collected at 6 months, facial emotion recognition performance at 6 years, and CU behaviours at 7 years. A path analysis showed a significant effect of emotion recognition predicting CU behaviours (ß = -0.275, S.E. = 0.084, p = 0.001). While the main effects of infants' mother-directed gaze and maternal sensitivity were not significant, their interaction significantly predicted CU behaviours (ß = 0.194, S.E. = 0.081, p = 0.016) with region of significance analysis showing a significant negative relationship between infant gaze and later CU behaviours only for those with low maternal sensitivity. There were no indirect effects of infants' mother-directed gaze, maternal sensitivity or the mother-directed gaze by maternal sensitivity interaction via emotion recognition. Emotion recognition appears to act as an independent predictor of CU behaviours, rather than mediating the relationship between infants' mother-directed gaze and maternal sensitivity with later CU behaviours. This supports the idea of multiple risk factors for CU behaviours.

[Importance of cellular tight junction complexes in the development of periprosthetic leakage after prosthetic voice rehabilitation]. / Bedeutung zellulärer Tight-junction-Komplexe bei der Entwicklung einer periprothetischen Leckage bei stimmprothetischer Versorgung.

BACKGROUND: The use of voice prostheses is currently the gold standard in voice rehabilitation after total laryngectomy. This method combines low complication rates and excellent rehabilitation results; however, approximately 30% of patients show periprosthetic leakage or severe fistula enlargement after laryngectomy and prosthetic voice restoration within the first 4 years. The development of this enlargement is controversially discussed in the literature but recently published studies have shown that high esophageal reflux plays a key role in this process, which leads to an inflammatory reaction and disturbs the intercellular tight junctions in the sense of an epithelial mesenchymal transition (EMT). MATERIAL AND METHODS: A total of 44 patients underwent 24 h pH monitoring, a sample biopsy from the region of the fistula and a subsequent biomolecular examination for intracellular junction proteins as well as a correlation between the severity of reflux and tracheoesophageal fistula problems before and after antireflux therapy with proton pump inhibitors (PPI). RESULTS: Immunohistochemical staining revealed decreases in membrane E-cadherin and ß-catenin and a significant increase in the cytoplasmic fraction, depending on the severity of inflammation in the fistula tissue. In patients with an improvement of clinical fistula problems under oral PPI treatment an increase of membrane E-cadherin could be shown, whereas patients with persisting fistula enlargement demonstrated a further decrease of E-cadherin. CONCLUSION: The data indicate a central role of EMT in the development of fistula enlargement after total laryngectomy. Patients with periprosthetic leakage showed a loss of membrane bound E-cadherin and ß-catenin with an up-regulation of vimentin expression. In patients with mild or no leakage problems EMT could be resolved by aggressive antireflux treatment, whereas patients without any effect of PPI treatment on the fistula showed no reversal of EMT. These data contribute to the understanding of treatment resistant fistula enlargement after total laryngectomy.

Intergenerational effects of racism on amygdala and hippocampus resting state functional connectivity.

Racism is an insidious problem with far-reaching effects on the lives of Black, Indigenous, and People of Color (BIPOC). The pervasive negative impact of racism on mental health is well documented. However, less is known about the potential downstream impacts of maternal experiences of racism on offspring neurodevelopment. This study sought to examine evidence for a biological pathway of intergenerational transmission of racism-related trauma. This study examined the effects of self-reported maternal experiences of racism on resting state functional connectivity (rsFC) in n = 25 neonates (13 female, 12 male) birthed by BIPOC mothers. Amygdala and hippocampus are brain regions involved in fear, memory, and anxiety, and are central nodes in brain networks associated with trauma-related change. We used average scores on the Experiences of Racism Scale as a continuous, voxel-wise regressor in seed-based, whole-brain connectivity analysis of anatomically defined amygdala and hippocampus seed regions of interest. All analyses controlled for infant sex and gestational age at the 2-week scanning session. More maternal racism-related experiences were associated with (1) stronger right amygdala rsFC with visual cortex and thalamus; and (2) stronger hippocampus rsFC with visual cortex and a temporo-parietal network, in neonates. The results of this research have implications for understanding how maternal experiences of racism may alter neurodevelopment, and for related social policy.

[Abelson interactor 1 (Abi1) in colorectal cancer. From synaptic plasticity to tumor cell migration]. / Abelson interactor 1 (Abi1) im kolorektalen Karzinom. Von der synaptischen Plastizität zur Tumorzellmigration.

BACKGROUND: Invasion and metastatic dissemination of tumor cells defines the prognosis of patients with colorectal cancer (CRC). The Abelson interactor 1 (Abi1), a 65 kD substrate of the eponymous Abelson tyrosine kinase, interacts with phosphatidylinositol-3-kinase (PI3K) and heterogeneous nuclear ribonucleoprotein K (hnRNP K) and is a key regulator of cytoskeletal reorganization during synaptic maturation and cellular migration. AIM: The aim of this study was the analysis of Abi1 expression patterns and to elucidate the role in cytoskeletal reorganization in colorectal carcinoma cells. MATERIAL AND METHODS: The methods used in this study were immunohistochemistry; immunofluorescence microscopy; liposomal transfection and protein analysis by Western blotting. RESULTS: The results showed that Abi1 is expressed at the invasive front of colorectal carcinomas and localizes to the leading edge of lamellipodia in cultured colorectal carcinoma cells. A phosphorylated isoform of Abi1 that stains positively in these microcompartments disappears after treatment with the tyrosine kinase inhibitor STI571 (Glivec®). The RNA interference (RNAi) approach knockdown of Abi1 as well as treatment with STI571 induce a shift in cellular morphology from broad lamellipodia-like to thin filopodia-like cellular protrusions. DISCUSSION: The initial results support a central role for phosphorylated Abi1 in the formation of lamellipodia-like cellular protrusions as a prerequisite for cellular migration of colorectal carcinoma cells. As phosphorylation of Abi1 could be pharmaceutically targeted with STI571, this indicates a possible therapeutic option to prevent the gain of a metastatic phenotype in colorectal cancer. This possibility will be further evaluated in ongoing research.

Arsenic Concentrations in Ground and Surface Waters across Arizona Including Native Lands.

Parts of the Southwestern United States report arsenic levels in water resources that are above the United States Environmental Protection Agency's current drinking water limits. Prolonged exposure to arsenic through food and drinking water can contribute to significant health problems including cancer, developmental effects, cardiovascular disease, neurotoxicity, and diabetes. In order to understand exposure risks, water sampling and testing has been conducted throughout Arizona. This information is available to the public through often non-overlapping databases that are difficult to access and in impracticable formats. The current study utilized a systemic compilation of online databases to compile a spreadsheet containing over 33,000 water samples. The reported arsenic concentrations from these databases were collected from 1990-2017. Using ArcGIS software, these data were converted into a map shapefile and overlaid onto a map of Arizona. This visual representation shows that arsenic levels in surface and ground water exceed the United States Environmental Protection Agency's drinking water limits for many sites in several counties in Arizona, and there is an underrepresentation of sampling in several tribal jurisdictions. This information is useful for water managers and private well owners throughout the State for determining safe drinking water sources and limiting exposure to arsenic.

Endosulfan exposure disrupts pheromonal systems in the red-spotted newt: a mechanism for subtle effects of environmental chemicals.

Because chemicals introduced into the environment by humans can affect both long-term survivorship and reproduction of amphibians, discovering the specific mechanisms through which these chemicals act may facilitate the development of plans for amphibian conservation. We investigated the amphibian pheromonal system as a potential target of common environmental chemicals. By treating female red-spotted newts, Notophthalmus viridescens, to a commonly used insecticide, endosulfan, we found that the pheromonal system is highly susceptible to low-concentration exposure. The impairment of the pheromonal system directly led to disrupted mate choice and lowered mating success. There were no other notable physiologic or behavioral changes demonstrated by the animals at the insecticide concentrations administered. Our findings suggest that the amphibian pheromonal system is one of the systems subject to subtle negative effects of environmental chemicals.

Organization of proenkephalin in amphibians: cloning of a proenkephalin cDNA from the brain of the anuran amphibian, Spea multiplicatus.

Cloning of a proenkephalin cDNA from the pelobatid anuran amphibian, Spea multiplicatus, provides additional evidence that Leu-enkephalin, although present in the brain of anuran amphibians, is not encoded by the proenkephalin gene. The S. multiplicatus proenkephalin cDNA is 1375 nucleotides in length, and the open reading frame contains the sequences of seven opioid sequences. There are five copies of the Met-enkephalin sequence, as well as an octapeptide opioid sequence (YGGFMRNY) and a heptapeptide opioid sequence (YGGFMRF). In the proenkephalin sequence of S. multiplicatus the penultimate opioid is a Met-enkephalin sequence rather than the Leu-enkephalin present in mammalian sequences. The same order of opioid sequences also is observed for the proenkephalin sequence of the pipid anuran amphibian, Xenopus laevis. Hence, from a phylogenetic standpoint the organization of tetrapod proenkephalin has been remarkably conserved. What remains to be resolved is whether the Leu-enkephalin sequence found in mammalian proenkephalin is an ancestral trait or a derived trait for the tetrapods. Unlike the proenkephalin precursor of X. laevis, all of the opioid sequences in the S. multiplicatus proenkephalin cDNA are flanked by paired-basic amino acid proteolytic cleavage sites. In this regard the proenkephalin sequence for S. multiplicatus is more similar to mammalian proenkephalins than the proenkephalin sequence of X. laevis. However, a comparison of the proenkephalin sequences in human, X. laevis, and S. multiplicatus revealed several conserved features in the evolution of the tetrapod proenkephalin gene. By contrast, a comparison of tetrapod proenkephalin sequences with the partial sequence of a sturgeon proenkephalin cDNA indicates that the position occupied by the penultimate opioid sequence in vertebrate proenkephalins may be a highly variable locus in this gene.

An additional dimension to health inequalities: disease severity and socioeconomic position.

OBJECTIVE: To investigate the association between the severity of hip pain and disability, and a number of measures of socioeconomic position, using a range of individual and ecological socioeconomic indicators. DESIGN: Interviewer administered and self completed questionnaires on symptoms of pain and disability, general health and socioeconomic indicators, completed by people reporting hip pain in a cross sectional, postal, screening questionnaire. SETTING: 40 general practices from inner city, suburban and rural areas of south west England. PARTICIPANTS: 954 study participants who had reported hip pain in a postal questionnaire survey of 26,046 people aged 35 and over, selected using an age/sex stratified random probability sample. DATA: Individual indicators of socioeconomic position: social class based on occupation, maximum educational attainment, car ownership, gross household income, manual or non-manual occupation and living alone. Area level measures of socioeconomic position: Townsend scores for material deprivation at enumeration district level; urban or rural location based on the postcode of residence. Severity of hip disease, measured by the pain, disability and independence components of the New Zealand score for major joint replacement. Self reported comorbidity validated using general practice case notes and summary measures of general health. MAIN RESULTS: Increasing disease severity was strongly associated with increasing age and a variety of measures of general health, including comorbidity. The data provide considerable evidence for the systematic association of increased severity of hip disease with decreasing socioeconomic position. Measures of socioeconomic position that were systematically associated with increasing disease severity, standardised for age and sex, included educational attainment (relative index of inequality 1.95 (95% confidence intervals 1.29 to 2.62) and income (relative index of inequality 4.03 (95% confidence intervals 3.43 to 4.64). Those with access to a car (mean disease severity 15.5) had statistically significant lower severity of hip disease than those without (mean 17.5, p < 0.01). Similar results were found for access to higher or further education and living with others. For a given level of income, people with greater comorbidity had more severe hip pain and disability. The gradient in disease severity between rich and poor was steepest among those with the most comorbidity. CONCLUSIONS: People with lower socioeconomic position experience a greater severity of hip disease. The poorest sector of the population seem to be in double jeopardy: they not only experience a greater burden of chronic morbidity but also a greater severity of hip disease. This study has implications for health care provision, if the National Health Service is to live up to its principle of equal treatment for equal medical need.

The demand for private health care in the UK.

Policy change has eroded the entitlement of UK residents to free state-provided health care, with a resulting rise in the use of the private sector. This paper examines the choice between public and private health care. It models the use of private health care as a function of its costs and benefits relative to state care and no care. The results indicate a difference between users of private care and other care, and the importance of past use as a predictor of current use. But they also show considerable movement between the public and private sectors, indicating a complex relationship in public and private sector use.

The effects of regulation and competition in the NHS internal market: the case of general practice fundholder prices.

The 1989 reforms of the UK National Health Service introduced competition in supply within a tightly regulated framework. The paper examines whether this competition affects the prices posted by sellers of medical services. We argue that despite regulation market forces may have an impact on price. We test this using the posted prices for one of the two types of buyer, General Practice Fundholders. We find the regulatory rules are not observed, and some evidence of the impact of market forces on price.

Equity and the distribution of UK National Health Service resources.

This paper examines the extent to which the British NHS allocates health care according to need. The results, based on 1985 data, show that within morbidity groups the poor receive, on average, more health care than the rich. This does not necessarily indicate pro-poor inequity. There is some evidence of a positive relationship between income and health within any morbidity category. The results contradict those of an earlier study which found bias favouring the middle classes. It is argued that the methodology adopted in the present study is more appropriate for the examination of allocation according to need.

Income-related inequalities in health: some international comparisons.

This paper presents evidence on income-related inequalities in self-assessed health in nine industrialized countries. Health interview survey data were used to construct concentration curves of self-assessed health, measured as a latent variable. Inequalities in health favoured the higher income groups and were statistically significant in all countries. Inequalities were particularly high in the United States and the United Kingdom. Amongst other European countries, Sweden, Finland and the former East Germany had the lowest inequality. Across countries, a strong association was found between inequalities in health and inequalities in income.

Equity in the delivery of health care in Europe and the US.

This paper presents a comparison of horizontal equity in health care utilization in 10 European countries and the US. It does not only extend previous work by using more recent data from a larger set of countries, but also uses new methods and presents disaggregated results by various types of care. In all countries, the lower-income groups are more intensive users of the health care system. But after indirect standardization for need differences, there is little or no evidence of significant inequity in the delivery of health care overall, though in half of the countries, significant pro-rich inequity emerges for physician contacts. This seems to be due mainly to a higher use of medical specialist services by higher-income groups and a higher use of GP care among lower-income groups. These findings appear to be fairly general and emerge in countries with very diverse characteristics regarding access and provider incentives.

Equity in the finance of health care: some further international comparisons.

This paper presents further international comparisons of progressivity of health care financing systems. The paper builds on the work of Wagstaff et al. [Wagstaff, A., van Doorslaer E., et al., 1992. Equity in the finance of health care: some international comparisons, Journal of Health Economics 11, pp. 361-387] but extends it in a number of directions: we modify the methodology used there and achieve a higher degree of cross-country comparability in variable definitions; we update and extend the cross-section of countries; and we present evidence on trends in financing mixes and progressivity.

The redistributive effect of health care finance in twelve OECD countries.

The OECD countries finance their health care through a mixture of taxes, social insurance contributions, private insurance premiums and out-of-pocket payments. The various payment sources have very different implications for both vertical and horizontal equity and on redistributive effect which is a function of both. This paper presents results on the income redistribution consequences of the health care financing mixes adopted in twelve OECD countries by decomposing the overall income redistributive effect into a progressivity, horizontal inequity and reranking component. The general finding of this study is that the vertical effect is much more important than horizontal inequity and reranking in determining the overall redistributive effect but that their relative importance varies by source of payment. Public finance sources tend to have small positive redistributive effects and less differential treatment while private financing sources generally have (larger) negative redistributive effects which are to a substantial degree caused by differential treatment.

Intra- and extracellular dehydration-induced thirst-related behavior in an amphibian.

The behavioral response to dehydration is critical to an animal's survival. Because of their permeable skin, amphibians are particularly sensitive to dehydrating conditions. We tested the hypothesis that different forms of dehydration induce water absorption response (WR) behavior in the desert spadefoot toad, Scaphiopus couchii. First, we determined the behavioral response to intracellular dehydration by treating fully hydrated toads with increasing concentrations of hypertonic solutions of NaCl or sucrose via intraperitoneal injection (i.p.). Animals that were treated to induce intracellular dehydration with either solute exhibited a significant increase in WR behavior compared to vehicle-treated controls. To distinguish that the response was a result of an increased osmotic gradient between the intra- and extracellular compartments, we treated fully hydrated animals i.p. with urea, which freely passes into the intracellular compartment and increases overall animal osmolarity. Urea treatment did not induce WR behavior. To determine the response to extracellular dehydration, the blood volume of fully hydrated toads was reduced via cardiac puncture, and the WR behavior was measured. Animals who had a reduction in blood volume exhibited a significant increase in WR behavior compared to sham-punctured controls. Our results are the first to demonstrate that multiple forms of dehydration can induce thirst-related behavior in amphibians.

Agency and incentives in the NHS internal market.

This paper presents and assesses the structure of incentives created by the 1991 reforms to the U.K. National Health System. It argues that these reforms created a set of overlapping principal-agent relationships, in which the ownership of assets and the division of rewards from use of these assets is unclear. This lack of clarity and the form of performance monitoring used by the government as principal in these agency relationships seem likely to give limited incentives for improvements in efficiency in the medium term. The paper discusses possible means to improve incentives.

Common exonic missense variants in the C2 domain of the human KIBRA protein modify lipid binding and cognitive performance.

The human KIBRA gene has been linked to human cognition through a lead intronic single-nucleotide polymorphism (SNP; rs17070145) that is associated with episodic memory performance and the risk to develop Alzheimer's disease. However, it remains unknown how this relates to the function of the KIBRA protein. Here, we identified two common missense SNPs (rs3822660G/T [M734I], rs3822659T/G [S735A]) in exon 15 of the human KIBRA gene to affect cognitive performance, and to be in almost complete linkage disequilibrium with rs17070145. The identified SNPs encode variants of the KIBRA C2 domain with distinct Ca(2+) dependent binding preferences for monophosphorylated phosphatidylinositols likely due to differences in the dynamics and folding of the lipid-binding pocket. Our results further implicate the KIBRA protein in higher brain function and provide direction to the cellular pathways involved.