A star shaped acoustofluidic mixer enhances rapid malaria diagnostics via cell lysis and whole blood homogenisation in 2 seconds.

Malaria is a life-threatening disease caused by a parasite, which can be transmitted to humans through bites of infected female Anopheles mosquitoes. This disease plagues a significant population of the world, necessitating the need for better diagnostic platforms to enhance the detection sensitivity, whilst reducing processing times, sample volumes and cost. A critical step in achieving improved detection is the effective lysis of blood samples. Here, we propose the use of an acoustically actuated microfluidic mixer for enhanced blood cell lysis. Guided by numerical simulations, we experimentally demonstrate that the device is capable of lysing a 20× dilution of isolated red blood cells (RBCs) with an efficiency of ∼95% within 350 ms (0.1 mL). Further, experimental results show that the device can effectively lyse whole blood irrespective of its dilution factor. Compared to the conventional method of using water, this platform is capable of releasing a larger quantity of haemoglobin into plasma, increasing the efficiency without the need for lysis reagents. The lysis efficiency was validated with malaria infected whole blood samples, resulting in an improved sensitivity as compared to the unlysed infected samples. Partial least squares-regression (PLS-R) analysis exhibits cross-validated R2 values of 0.959 and 0.98 from unlysed and device lysed spectral datasets, respectively. Critically, as expected, the root mean square error of cross validation (RMSECV) value was significantly reduced in the acoustically lysed datasets (RMSECV of 0.97), indicating the improved quantification of parasitic infections compared to unlysed datasets (RMSECV of 1.48). High lysis efficiency and ultrafast processing of very small sample volumes makes the combined acoustofluidic/spectroscopic approach extremely attractive for point-of-care blood diagnosis, especially for detection of neonatal and congenital malaria in babies, for whom a heel prick is often the only option for blood collection.

Prenatal drug exposure to illicit drugs alters working memory-related brain activity and underlying network properties in adolescence.

The persistence of effects of prenatal drug exposure (PDE) on brain functioning during adolescence is poorly understood. We explored neural activation to a visuospatial working memory (VSWM) versus a control task using functional magnetic resonance imaging (fMRI) in adolescents with PDE and a community comparison group (CC) of non-exposed adolescents. We applied graph theory metrics to resting state data using a network of nodes derived from the VSWM task activation map to further explore connectivity underlying WM functioning. Participants (ages 12-15 years) included 47 adolescents (27 PDE and 20 CC). All analyses controlled for potentially confounding differences in birth characteristics and postnatal environment. Significant group by task differences in brain activation emerged in the left middle frontal gyrus (BA 6) with the CC group, but not the PDE group, activating this region during VSWM. The PDE group deactivated the culmen, whereas the CC group activated it during the VSWM task. The CC group demonstrated a significant relation between reaction time and culmen activation, not present in the PDE group. The network analysis underlying VSWM performance showed that PDE group had lower global efficiency than the CC group and a trend level reduction in local efficiency. The network node corresponding to the BA 6 group by task interaction showed reduced nodal efficiency and fewer direct connections to other nodes in the network. These results suggest that adolescence reveals altered neural functioning related to response planning that may reflect less efficient network functioning in youth with PDE.

Prenatal drug exposure, behavioral problems, and drug experimentation among African-American urban adolescents.

PURPOSE: To examine how prenatal drug exposure (PDE) to heroin/cocaine and behavioral problems relate to adolescent drug experimentation. METHODS: The sample included African-American adolescents (mean age = 14.2 years, SD = 1.2) with PDE (n = 73) and a nonexposed community comparison (n = 61). PDE status was determined at delivery through toxicology analysis and maternal report. Internalizing/externalizing problems were assessed during adolescence with the Behavior Assessment System for Children, Second Edition. Drug experimentation was assessed by adolescent report and urine analysis. Logistic regression evaluated the likelihood of drug experimentation related to PDE and behavioral problems, adjusting for age, gender, PDE, perceived peer drug use, and caregiver drug use. Interaction terms examined gender modification. RESULTS: Sixty-seven subjects (50%) used drugs: 25 (19%) used tobacco/alcohol only and 42 (31%) used marijuana/illegal drugs. Ninety-four subjects (70%) perceived peer drug use. PDE significantly increased the risk of tobacco/alcohol experimentation (odds ratio = 3.07, 95% confidence interval [CI] 1.09-8.66, p = .034) but not after covariate adjustment (adjusted odds ratio [aOR] = 1.16, 95% CI .31-4.33, p > .05). PDE was not related to the overall or marijuana/illegal drug experimentation. The likelihood of overall drug experimentation was doubled per SD increase in externalizing problems (aOR = 2.28, 95% CI 1.33-3.91, p = .003) and, among girls, 2.82 times greater (aOR = 2.82, 95% CI 1.34-5.94, p = .006) per SD increase in internalizing problems. Age and perceived peer drug use were significant covariates. CONCLUSIONS: Drug experimentation was relatively common (50%), especially in the context of externalizing problems, internalizing problems (girls only), older age, and perceived peer drug use. Findings support the Problem Behavior Theory and suggest that adolescent drug prevention addresses behavioral problems and promotes prosocial peer groups.

Markers of Inflammation and Lineage on Exfoliated Colonic Cells In Pediatric Inflammatory Bowel Disease.

OBJECTIVES: The diagnosis (endoscopy, and biopsy) and continued clinical management of Inflammatory Bowel Disease (IBD), remain highly invasive, expensive, and inconvenient for the pediatric patient. The objective of this study was to see if colonocytes obtained from stools of subjects with IBD and normal controls would demonstrate higher levels of inflammatory markers (Cox 2 in CD45+ and CD45- cells) and if the inflammatory process and treatment effects would be reflected in an altered cytokine expression in the subjects compared to controls. SETTING: Outpatient hospital based pediatric gastroenterology clinic. METHODS AND MAIN OUTCOME MEASURES: Stool samples (~ 1 gm), were obtained from 18 children between the ages of 4 and 18 diagnosed with IBD, and from a normal first degree relative. Colonocytes were isolated using the Somatic Cell Sampling Recovery (SCSR) system and assessed for the expression of COX-2, CD-45, IgA, IgG, IL6, IL18, TGF ß, TNF, and IL16ß using flow cytometry. In addition, levels of COX-2 and cytokeratin 19 transcripts were measured by microwell plate hybridization assay. RESULTS: Expression of COX-2 and co-expression of IgA and IgG were significantly higher in the IBD cases compared to the controls. In ulcerative colitis, the expression of COX-2 and co-expression of COX-2 and CD45 were greater than that in patients with Crohn's disease. In contrast, cells expressing IgA and IgG were higher in Crohn's. Subjects on immunosuppressants and/or anti-inflammatory medications, expressed significantly lower levels of COX-2 and IL-18 compared to those who were not on treatment. CONCLUSIONS: This study indicates that the use of disease markers on exfoliated colonic cells can be used for non-invasive assessment of disease status, for follow-up of response to treatment and for forecasting flare-up of disease before its symptomatic manifestations.

The effect of prenatal drug exposure and caregiving context on children's performance on a task of sustained visual attention.

OBJECTIVES: Three groups of children from low-income, urban environments were examined to determine the effects of prenatal drug exposure (PDE) and caregiving environment on sustained visual attention (SVA) at 7 years of age. METHODS: Drug-exposed children remaining in maternal care (n = 43), drug-exposed children placed in nonmaternal care (n = 45), and community comparison (CC) children (n = 56) were administered a battery of neurocognitive tests, including the Conners' Continuous Performance Test (CPT). RESULTS: PDE children remaining in maternal care displayed more omission errors than CC children. PDE children in nonmaternal care had intermediate scores that did not differ significantly from PDE children in maternal care or CC children. There were no group differences with respect to commission errors or reaction time. CPT errors of omission and commission were significantly correlated with parent-reported attention problems and academic achievement scores. CONCLUSIONS: PDE in the context of care provided by a maternal caregiver with persistent drug use patterns may contribute to problems in children's SVA at school-age. As parental drug abuse can interfere with the provision of early care, children raised in a drug-using context may be highly vulnerable to problems with self-regulation, including sustained attention. SVA problems may contribute to subsequent academic and behavioral problems as demands for concentration and sustained effort increase throughout childhood. Children who have been prenatally exposed to drugs or raised in a drug-using household may benefit from early intervention services to avoid problems in SVA that may interfere with subsequent neurocognitive functioning and academic performance.

Children's cognitive-behavioral functioning at age 6 and 7: prenatal drug exposure and caregiving environment.

OBJECTIVE: The aim of this study was to examine how prenatal drug exposure (PDE) and caregiving environment relate to cognitive, academic, and behavioral performance at ages 6 and 7. METHODS: A longitudinal follow-up was conducted of 111 children with PDE and a community cohort of 62 non-drug-exposed children (N = 173). Children completed standardized tests of cognition (Stanford-Binet Intelligence Scales, Fourth Edition [SB-IV]) and academic performance (Wide Range Achievement Test 3). Caregivers completed ratings of child behavior problems (Child Behavior Checklist [CBCL]). Multivariate analyses were conducted, adjusting for gender, prenatal tobacco exposure, number of caregiver placement changes, and 3 caregiver variables assessed at age 7, including depressive symptoms, employment status, and public assistance status. RESULTS: After adjusting for perinatal and environmental variables, there were no significant exposure-group differences in cognition, academic performance, or behavior problems. In comparison with males, females had higher scores on overall IQ and 4 of 8 SB-IV subtests, fewer caregiver-reported attention and aggression problems, and higher reading achievement scores. There were no significant gender-by-group interactions. CONCLUSION: When analyses were adjusted for perinatal and environmental variables, most associations between PDE and cognitive-behavioral functioning were attenuated. Regardless of drug exposure history, males performed more poorly than females on multiple cognitive-behavioral indices. Both exposed and nonexposed children were from low-income families and obtained scores substantially below normative expectations.

Developmental outcome of drug-exposed children through 30 months: a comparison of Bayley and Bayley-II.

This study examined the effects of the Bayley Scales of Infant Development (BSID) version on developmental outcomes among drug-exposed children, some of whom received an intervention. Developmental outcome was evaluated with the BSID at 12 and 18 months and with the BSID-II at 24 and 30 months. In the repeated measures analyses, children scored higher on the BSID Mental Developmental Index (MDI; p < .01) and Psychomotor Developmental Index (PDI; p < .01) than on the BSID-II MDI and PDI. Version x Time (p < .01) and Version x Group (p < .01) interactions were also found for the MDI but not the PDI. PDI scores decreased on both the BSID and the BSID-II (p < .01). Over the first 2 years postpartum, mean MDI and PDI scores decreased among these high-risk, drug-exposed children.

Cumulative environmental risk in substance abusing women: early intervention, parenting stress, child abuse potential and child development.

OBJECTIVE: To assess the relationship between cumulative environmental risks and early intervention, parenting attitudes, potential for child abuse and child development in substance abusing mothers. METHOD: We studied 161 substance-abusing women, from a randomized longitudinal study of a home based early intervention, who had custody of their children through 18 months. The intervention group received weekly home visits in the first 6 months and biweekly visits from 6 to 18 months. Parenting stress and child abuse potential were assessed at 6 and 18 months postpartum. Children's mental and motor development (Bayley MDI and PDI) and language development (REEL) were assessed at 6, 12, and 18 months postpartum. Ten maternal risk factors were assessed: maternal depression, domestic violence, nondomestic violence, family size, incarceration, no significant other in home, negative life events, psychiatric problems, homelessness, and severity of drug use. Level of risk was recoded into four categories (2 or less, 3, 4, and 5 or more), which had adequate cell sizes for repeated measures analysis. DATA ANALYSIS: Repeated measures analyses were run to examine how level of risk and group (intervention or control) were related to parenting stress, child abuse potential, and children's mental, motor and language development over time. RESULTS: Parenting stress and child abuse potential were higher for women with five risks or more compared with women who had four or fewer risks; children's mental, motor, and language development were not related to level of risk. Children in the intervention group had significantly higher scores on the PDI at 6 and 18 months (107.4 vs. 103.6 and 101.1 vs. 97.2) and had marginally better scores on the MDI at 6 and 12 months (107.7 vs. 104.2 and 103.6 vs. 100.1), compared to the control group. CONCLUSION: Compared to drug-abusing women with fewer than five risks, women with five or more risks found parenting more stressful and indicated greater inclination towards abusive and neglectful behavior, placing their infants at increased risk for poor parenting, abuse and neglect. Early home-based intervention in high-risk families may be beneficial to infant development.

Drug-exposed infants and developmental outcome: effects of a home intervention and ongoing maternal drug use.

OBJECTIVE: To evaluate the effects of a home intervention and ongoing maternal drug use on the developmental outcome of drug-exposed infants. DESIGN: Longitudinal randomized cohort study of a home intervention with substance-abusing mothers and their infants. Mother-infant dyads were randomly assigned to a control or intervention group at 2 weeks' post partum. Control families received brief monthly tracking visits. Intervention families received weekly home visits from 0 to 6 months and biweekly visits from 6 to 18 months by trained lay visitors. PARTICIPANTS: One hundred eight low-income, inner-city, drug-exposed children (control, 54; intervention, 54) who underwent developmental testing at 6, 12, and 18 months post partum and who remained with their biological mothers through 18 months. MAIN OUTCOME MEASURES: Infant scores from the Bayley Scales of Infant Development (BSID) at 6, 12, and 18 months post partum. Maternal report of drug use during the pregnancy and ongoing drug use through 18 months post partum was assessed. RESULTS: In the repeated-measures analyses, intervention infants had significantly higher BSID Mental Developmental Index (MDI) and Psychomotor Developmental Index scores than control infants. Ongoing maternal cocaine and/or heroin use was associated with lower MDI scores. Finally, MDI scores decreased significantly in both groups. CONCLUSIONS: Ongoing maternal drug use is associated with worse developmental outcomes among a group of drug-exposed infants. A home intervention led to higher BSID scores among drug-exposed infants. However, BSID MDI scores decreased during the first 18 months post partum among inner-city, low-socioeconomic-status infants in the present study.

Ongoing maternal drug use, parenting attitudes, and a home intervention: effects on mother-child interaction at 18 months.

This prospective study examined the effects of ongoing maternal drug use, parenting attitudes, and a home-based intervention on mother-child interaction among drug-using women and their children. At 2 weeks postpartum, mothers and infants were randomly assigned to either an Intervention (n = 67) or Control (n = 64) Group. Intervention families received weekly visits until 6 months postpartum and biweekly visits from 6 to 18 months by trained lay visitors. The home intervention was designed to increase maternal empowerment and promote child development. Control families received brief monthly tracking visits. Mother-child interaction was evaluated at 18 months through observation of play. Mothers who continued to use cocaine and/or heroin had lower competence scores (p <.05); poor parenting attitude was also associated with lower competence scores during mother-child interaction (p <.05). Although the intervention had no measured effect, ongoing maternal drug use and poor parenting attitudes were associated with less optimal maternal behavior during mother-child interaction.