REGIONAL WATER USE PRACTICES IN THE KWAHU EAST DISTRICT OF GHANA AND THE POTENTIAL INFLUENCE ON DIARRHEAL DISEASE

Background: In low income countries, the Daily Adjusted Life Years (DALYs) of unsafe water, sanitation, and hygiene is 530/100,000 and is the 6th leading cause of death in children. Ghana, located in West Africa, is greatly impacted by poor sanitation and unsafe water supply. The objective of this study is to assess local water use and sanitation practices in the Kwahu East district of Ghana and how they relate to diarrheal disease. Methods: A cross-sectional survey was administered to 236 households in the Kwahu East district. It was divided into four sections: demographics, water use practices, water related illness, and water related sanitation. Prevalence data for certain variables were calculated and simple t-tests compared difference in water practices for different demographic groups based on gender, age, and education status. Results: Surface water and pump-well/borehole were the main sources of water for this area. Household demographics played a role in determining the household water collector. Over 95% of the responders did not treat their water. Moreover, gender, education, and age played significant roles in the degree of knowledge about diarrheal disease. Conclusions: Gender, education, age, and household size are all key factors that impact water practices. The results of this study can be used for the development of culturally sustainable interventions directed towards the improvement of access to safe drinking water, and in turn, reduce waterborne illness

Short-term organoid culture for drug sensitivity testing of high-grade serous carcinoma.

ObjectiveCancer patient-derived organoids (PDOs) grow as three dimensional (3D) structures in the presence of extracellular matrix and have been found to represent the original tumor's genetic complexity. In addition, PDOs can be grown and subjected to drug sensitivity testing in a shorter time course and with lesser expense than patient-derived xenograft models. Many patients with recurrent ovarian cancer develop malignant effusions that become refractory to chemotherapy. Since these same patients often present for palliative aspiration of ascites or pleural effusions, there is a potential opportunity to obtain tumor specimens in the form of multicellular spheroids (MCS) present in malignant effusion fluids. Our objective was to develop a short duration culture of MCS from ovarian cancer malignant effusions in conditions selected to support organoid growth and use them as a platform for empirical drug sensitivity testing.MethodsIn this study, malignant effusion specimens were collected from patients with high-grade serous ovarian carcinoma (HGSOC). MCS were recovered and subjected to culture conditions designed to support organoid growth. In a subset of specimens, RNA-sequencing was performed at two time points during the short-term culture to determine changes in transcriptome in response to culture conditions. Organoid induction was also characterized in these specimens using Ki67 staining and histologic analysis. Drug sensitivity testing was performed on all specimens.ResultsOur model describes organoids formed within days of primary culture, which can recapitulate the histological features of malignant ascites fluid and can be expanded for at least 6 days. RNA-seq analysis of four patient specimens showed that within 6 days of culture, there was significant up-regulation of genes related to cellular proliferation, epithelial-mesenchymal transition, and KRAS signaling pathways. Drug sensitivity testing identified several agents with therapeutic potential.ConclusionsShort duration organoid culture of MCS from HGSOC malignant effusions can be used as a platform for empiric drug sensitivity testing. These ex vivo models may be helpful in screening new or existing therapeutic agents prior to individualized treatment options

Your Resting Brain CAREs about Your Risky Behavior

Research on the neural correlates of risk-related behaviors and personality traits has provided insight into mechanisms underlying both normal and pathological decision-making. Task-based neuroimaging studies implicate a distributed network of brain regions in risky decision-making. What remains to be understood are the interactions between these regions and their relation to individual differences in personality variables associated with real-world risk-taking.We employed resting state functional magnetic resonance imaging (R-fMRI) and resting state functional connectivity (RSFC) methods to investigate differences in the brain's intrinsic functional architecture associated with beliefs about the consequences of risky behavior. We obtained an individual measure of expected benefit from engaging in risky behavior, indicating a risk seeking or risk-averse personality, for each of 21 participants from whom we also collected a series of R-fMRI scans. The expected benefit scores were entered in statistical models assessing the RSFC of brain regions consistently implicated in both the evaluation of risk and reward, and cognitive control (i.e., orbitofrontal cortex, nucleus accumbens, lateral prefrontal cortex, dorsal anterior cingulate). We specifically focused on significant brain-behavior relationships that were stable across R-fMRI scans collected one year apart. Two stable expected benefit-RSFC relationships were observed: decreased expected benefit (increased risk-aversion) was associated with 1) stronger positive functional connectivity between right inferior frontal gyrus (IFG) and right insula, and 2) weaker negative functional connectivity between left nucleus accumbens and right parieto-occipital cortex.Task-based activation in the IFG and insula has been associated with risk-aversion, while activation in the nucleus accumbens and parietal cortex has been associated with both risk seeking and risk-averse tendencies. Our results suggest that individual differences in attitudes toward risk-taking are reflected in the brain's functional architecture and may have implications for engaging in real-world risky behaviors

Uncovering putative neural markers of risk avoidance

Risk avoidance is a hallmark of psychopathological conditions such as anxiety disorders. Yet few studies have examined its neural basis. The present work sought to identify the neural correlates of risk avoidance. While functional MRI scans were acquired, healthy adults (N = 23) played a Wheel of Fortune game during which they chose to bet or pass on each of 104 proposed gamble trials. Participants also completed the Cognitive Appraisal of Risky Events (CARE, Fromme et al., 1997), a self-report measure of “real world” risky behavior. As expected, decision-making was associated with activation, as measured by increased BOLD responses, of the striatum, insula, anterior cingulate cortex, dorsolateral prefrontal cortex, and parietal lobe. Risk avoidance during probabilistic trials (percent of trials passed) was significantly correlated with precuneus and striatal responses to trials with a certain outcome (No-Risk). Similarly, “real world” risk avoidance, as measured by the CARE, was significantly correlated with precuneus activity during No-Risk trials. Collectively, these data suggest that precuneus and striatal responses to decision-making under certainty represent putative neural markers of risk avoidance in the laboratory and in the “real world.” Further, they underline the need to extend neuroimaging research on risk avoidance, and associated anxiety disorders, to posterior cortical regions

The Intolerance of Uncertainty Scale for Children: A psychometric evaluation

Intolerance of uncertainty (IU) has contributed to our understanding of excessive worry and adult anxiety disorders, but there is a paucity of research on IU in child samples. This gap is due to the absence of a psychometrically sound measure of IU in youth. The present study adapted parallel child- and parent-report forms of the Intolerance of Uncertainty Scale (IUS) and examined the internal consistency, convergent validity, and classification properties of these forms in youth aged 7–17 (M=11.6 years, SD=2.6). Participating youth (N=197; 100 girls, 97 boys) either met diagnostic criteria for an anxiety disorder (n=73) or were nonreferred community participants (n=124). The child-report form (i.e., IUS for Children, orIUSC), and to a lesser extent the parent-report form, demonstrated strong internal consistency and convergentvalidity, evidenced by significant associations with anxiety and worry (and reassurance-seeking in the case ofthe child-report form). Children diagnosed with anxiety disorders scored higher than nonreferred communityyouth on both forms. Receiver operating characteristic (ROC) analysis demonstrated acceptable overall utility in distinguishing the 2 groups of youth. Findings provide preliminary support for use of the IUSC for continuous measurement of children’s ability to tolerate uncertainty

A Functional Magnetic Resonance Imaging Investigation of Uncertainty in Adolescents with Anxiety Disorders

Background: Pediatric anxiety disorders, although highly prevalent, are understudied with little known about their pathophysiology. Intolerance of uncertainty (IU) is a trait associated with worry, a key characteristic of these disorders. Neural responses to uncertainty in healthy subjects involve the same frontal–limbic circuits that are hyper-responsive in pediatric anxiety. As such, the present study examines the relationship between IU and neural responses to uncertainty in anxious adolescents. Methods: Sixteenadolescents(ages13–17)diagnosedwithgeneralizedanxietydisorderand/orsocialphobia(ANX)and13non-anxious control subjects completed a decision-making task while functional magnetic resonance imaging scans were acquired. Results: TheANXgroupendorsedgreatertask-relatedanxietyandlesscertaintythancontrolsubjectsonapost-taskquestionnaire.Compared with control subjects, the ANX group did not demonstrate hyper-responsivity of brain regions as hypothesized. Across groups, IU was positively correlated with activity in several frontal and limbic regions. Further analyses identified subgroups within the ANX group: those with high IU activated frontal/limbic regions, whereas those with low IU and less anxiety during the task deactivated the same regions in response to uncertainty. Conclusions: ResultssubstantiatethehypothesizedlinkbetweenIUandneuralresponsestouncertaintyinsomeadolescentswithanxiety disorders. Our findings, if replicated, suggest that trait measures, such as IU, can significantly improve our understanding of the neurobio- logical basis of pediatric anxiety disorders

The Intolerance of Uncertainty Scale for Children: A psychometric evaluation.

Intolerance of Uncertainty (IU) has contributed to our understanding of excessive worry and adult anxiety disorders, but there is a paucity of research on IU in child samples. This gap is due to the absence of a psychometrically sound measure of IU in youth. The present study adapted parallel child- and parent-report forms of the Intolerance of Uncertainty Scale (IUS) and examined the internal consistency, convergent validity, and classification properties of these forms in youth aged 7–17 (M = 11.6 years, SD = 2.6). Participating youth (N = 197; 100 females) either met diagnostic criteria for an anxiety disorder (N = 73) or were non-referred community participants (N = 124). The child-report form (i.e., IUS for Children, or IUSC), and to a lesser extent the parent-report form, demonstrated strong internal consistency and convergent validity, evidenced by significant associations with anxiety and worry (and reassurance-seeking in the case of the child-report form). Children diagnosed with anxiety disorders scored higher than non-referred community youth on both forms. ROC analysis demonstrated acceptable overall utility in distinguishing the two groups of youth. Findings provide preliminary support for use of the IUSC for continuous measurement of children’s ability to tolerate uncertainty

Functional connectivity of the human amygdala using resting state fMRI

The amygdala is composed of structurally and functionally distinct nuclei that contribute to the processing of emotion through interactions with other subcortical and cortical structures. While these circuits have been studied extensively in animals, human neuroimaging investigations of amygdala-based networks have typically considered the amygdala as a single structure, which likely masks contributions of individual amygdala subdivisions. The present study uses resting state functional magnetic resonance imaging (fMRI) to test whether distinct functional connectivity patterns, like those observed in animal studies, can be detected across three amygdala subdivisions: laterobasal, centromedial, and superficial. In a sample of 65 healthy adults, voxelwise regression analyses demonstrated positively-predicted ventral and negatively-predicted dorsal networks associated with the total amygdala, consistent with previous animal and human studies. Investigation of individual amygdala subdivisions revealed distinct differences in connectivity patterns within the amygdala and throughout the brain. Spontaneous activity in the laterobasal subdivision predicted activity in temporal and frontal regions, while activity in the centromedial nuclei predicted activity primarily in striatum. Activity in the superficial subdivision positively predicted activity throughout the limbic lobe. These findings suggest that resting state fMRI can be used to investigate human amygdala networks at a greater level of detail than previously appreciated, allowing for the further advancement of translational models