Can 3-dimensional cranial ultrasound be used to successfully reconstruct a 2-dimensional image without compromising on image quality in a neonatal population?

BACKGROUND: Cranial ultrasound is frequently performed in neonatal intensive care units and acquiring 2-dimensional (D) images requires significant training. Three-D ultrasound images can be acquired semi-automatically. OBJECTIVE: This proof-of-concept study aimed to demonstrate that 3-D study image quality compares well with 2-D. If this is successful, 3-D images could be acquired in remote areas and read remotely by experts. MATERIALS AND METHODS: This was a prospective study of 20 neonates, who underwent both routine 2-D and 3-D cranial ultrasounds. Images were reconstructed into standard views extracted from the 3-D volume and evaluated by three radiologists blinded to the acquisition method. The radiologists assessed for the presence of anatomical landmarks and overall image quality. RESULTS: More anatomical structures were identified in the 3-D studies (P<0.01). There was a trend that 3-D ultrasound demonstrated better image quality in the coronal plane, and 2-D in the sagittal plane, only reaching statistical significance for two coronal views and two sagittal views. CONCLUSION: Overall, this study has demonstrated that 3-D cranial ultrasound performs similarly to 2-D and could be implemented into neonatal practice.

Four Steps To My Future (4STMF): acceptability, feasibility and exploratory outcomes of a universal school-based mental health and well-being programme, delivered to young adolescents in South Africa.

OBJECTIVE: Mental health disorders affect many children in South Africa, where vulnerability is high, and treatment is limited. We sought to determine the feasibility and acceptability of a universally delivered classroom-based programme for the promotion of mental health in young adolescents. METHOD: We pilot tested an 8 session, cognitive-behavioural therapy-based programme, 4 Steps To My Future (4STMF) in two schools. Participants were grade 5 learners (n = 222; Meanage = 10.62 (Standard deviation = 0.69)). 4STMF was delivered in class time by trained psychology postgraduates. Feasibility (rates of parental opt-out, child assent, assessment completion at baseline and follow-up, programme completion, session attendance and programme fidelity), acceptability (teacher feedback and focus groups with learners), as well as demographic data and data on a battery of a psychological measures were collected at baseline, postintervention and at one-month follow-up. RESULTS: Most eligible learners at both schools agreed to participate (85% - school 1; 91% - school 2) with more than 80% completing postintervention measures. Learner session attendance and programme fidelity were high. Teachers rated facilitators highly on confidence, preparedness, enthusiasm and classroom management and observed children to be enjoying the programme. Focus group data suggest that learners liked the programme, could recall the content and had shared some of the content with their family. An exploratory analysis of outcomes showed significant pre-post differences on self-esteem at school 1 and on emotion regulation at school 1 and school 2, maintained at follow-up. CONCLUSIONS: This pilot study has shown that 4STMF can acceptably and feasibly be delivered, at classroom level, as a universal school-based prevention programme to young adolescent learners in South African primary schools. The programme could fit in with school context, could be delivered by nonspecialists, showed significant improvements on self-esteem and emotion regulation and was liked by the learners.

Neuropsychological Test Norms for the Assessment of HIV-Associated Neurocognitive Impairment Among South African Adults.

Reliable and valid neurocognitive (NC) test batteries that assess multiple domains of cognitive functioning are vital tools in the early detection of HIV-associated NC impairment. The HIV Neurobehavioral Research Center's International Neurobehavioral Battery (HNRC Battery) is one such diagnostic tool and has shown cultural validity in several international neuroHIV studies. However, no published norms are currently available for the full HNRC Battery in South Africa. To accurately interpret NC test results, appropriate reference norms are required. In light of this challenge, data were collected from 500 healthy, HIV-uninfected participants to develop demographically corrected South African norms. When demographically corrected United States of America (U.S.) norms were applied to the performance scores of our neurologically intact, HIV-negative sample, an impairment rate of 62.2% was observed compared to a 15.0% impairment rate when the newly generated South African norms were applied. These results reiterate the findings of other low- and middle-income countries, highlighting the need for localized, country-specific norms when interpreting NC performance.

A cross-national validation of the Internet Severity and Activities Addiction Questionnaire (ISAAQ).

Problematic usage of the internet (PUI) is of increasing concern in a digitalized world. While several screening tools have been developed to assess PUI, few have had their psychometric properties evaluated, and existing scales are also not typically designed to quantify both the severity of PUI and the nature of diverse problematic online activities. The Internet Severity and Activities Addiction Questionnaire (ISAAQ), consisting of a severity scale (ISAAQ Part A) and an online activities scale (ISAAQ part B) was previously developed to address these limitations. This study undertook psychometric validation of ISAAQ Part A using data from three countries. The optimal one-factor structure of ISAAQ Part A was determined in a large dataset from South Africa, then validated against datasets from the United Kingdom and United States. The scale had high Cronbach's alpha (≥0.9 in each country). A working operational cut-off point was determined to distinguish between those with some degree of problematic use and those without (ISAAQ Part A), and insight was given into the types of potentially problematic activities that may encompass PUI (ISAAQ Part B).

Genetic and Clinical Predictors of Ataxia in Pediatric Primary Mitochondrial Disorders.

Evaluation of ataxia in children is challenging in clinical practice. This is particularly true for highly heterogeneous conditions such as primary mitochondrial disorders (PMD). This study aims to explore cerebellar and brain abnormalities identified on MRI as potential predictors of ataxia in patients with PMD and, likewise, to determine the effect of the patient's genetic profile on these predictors as well as determination of the temporal relationship of clinical ataxia with MRI findings. We evaluated clinical, radiological, and genetic characteristics of 111 PMD patients younger than 21 years of age at The Children's Hospital of Philadelphia. Data was extracted from charts. Blinded radiological evaluations were carried out by experienced neuroradiologists. Multivariate logistic regression and generalized equation estimates were used for analysis. Ataxia was identified in 41% of patients. Cerebellar atrophy or putaminal involvement with mitochondrial DNA (mtDNA) mutations (OR 1.18, 95% CI 1.1-1.3, p < 0.001) and nuclear DNA mutation with no atrophy of the cerebellum (OR 1.14, 95% CI 1.0-1.3, p = 0.007) predicted an increased likelihood of having ataxia per year of age. Central tegmental tract predicted the presence of ataxia independent of age and pathogenic variant origin (OR 9.8, 95% CI 2-74, p = 0.009). Ataxia tended to precede the imaging finding of cerebellar atrophy. Cerebellar atrophy and putaminal involvement on MRI of pediatric-onset PMD may predict the presence of ataxia with age in patients with mtDNA mutations. This study provides predicted probabilities of having ataxia per year of age that may help in family counseling and future research of the population.

Validation of host cerebrospinal fluid protein biomarkers for early diagnosis of tuberculous meningitis in children: a replication and new biosignature discovery study.

Purpose: The diagnosis of tuberculous meningitis (TBM) in children is often delayed due to diagnostic difficulties. New tools are urgently needed to improve the diagnosis of the disease in this vulnerable group. The present study aimed to validate the accuracy of recently identified host cerebrospinal (CSF) biomarkers as candidates for the diagnosis of TBM in children.Materials and methods: We collected CSF samples from 87 children aged 3 months to 13 years, that were consecutively admitted at a tertiary hospital in Cape Town, South Africa, on suspicion of having TBM. We evaluated the concentrations of 67 selected host protein biomarkers using a multiplex platform.Results: Previously identified 3-marker (VEGF-A + IFN-γ + MPO) and 4-marker (IFN-γ + MPO + ICAM-1 + IL-8) signatures diagnosed TBM with AUCs of 0.89 (95% CI, 0.81-0.97) and 0.87 (95% CI, 0.79-0.95) respectively; sensitivities of 80.6% (95% CI, 62.5-92.5%) and 81.6% (95% CI, 65.7-92.3%), and specificities of 86.8% (71.9-95.6%) and 83.7% (70.4-92.7%) respectively. Furthermore, a new combination between the analytes (CC4b + CC4 + procalcitonin + CCL1) showed promise, with an AUC of 0.98 (95% CI, 0.94-1.00).Conclusions: We have shown that the accuracies of previously identified candidate CSF biomarkers for childhood TBM was reproducible. Our findings augur well for the future development of a simple bedside test for the rapid diagnosis of TBM in children.

Pain perception and physiological correlates in body-focused repetitive behavior disorders.

BACKGROUND: Behaviors typical of body-focused repetitive behavior disorders such as trichotillomania (TTM) and skin-picking disorder (SPD) are often associated with pleasure or relief, and with little or no physical pain, suggesting aberrant pain perception. Conclusive evidence about pain perception and correlates in these conditions is, however, lacking. METHODS: A multisite international study examined pain perception and its physiological correlates in adults with TTM (n = 31), SPD (n = 24), and healthy controls (HCs; n = 26). The cold pressor test was administered, and measurements of pain perception and cardiovascular parameters were taken every 15 seconds. Pain perception, latency to pain tolerance, cardiovascular parameters and associations with illness severity, and comorbid depression, as well as interaction effects (group × time interval), were investigated across groups. RESULTS: There were no group differences in pain ratings over time (P = .8) or latency to pain tolerance (P = .8). Illness severity was not associated with pain ratings (all P > .05). In terms of diastolic blood pressure (DBP), the main effect of group was statistically significant (P = .01), with post hoc analyses indicating higher mean DBP in TTM (95% confidence intervals [CI], 84.0-93.5) compared to SPD (95% CI, 73.5-84.2; P = .01), and HCs (95% CI, 75.6-86.0; P = .03). Pain perception did not differ between those with and those without depression (TTM: P = .2, SPD: P = .4). CONCLUSION: The study findings were mostly negative suggesting that general pain perception aberration is not involved in TTM and SPD. Other underlying drivers of hair-pulling and skin-picking behavior (eg, abnormal reward processing) should be investigated.

Steroid hormone analysis of adolescents and young women with polycystic ovarian syndrome and adrenocortical dysfunction using UPC2-MS/MS.

BACKGROUND: We recently identified 35 women with polycystic ovarian syndrome (PCOS) who exhibited features of micronodular adrenocortical hyperplasia. Steroid hormone analysis can be more accurate using state-of-the-art ultra-performance convergence chromatography-tandem mass spectrometry (UPC2-MS/MS). We hypothesized that UPC2-MS/MS may be used to better define hormonally this distinct subgroup of patients with PCOS. METHODS: Plasma from PCOS patients (n = 35) and healthy volunteers (HVs, n = 19) who all received dexamethasone testing was analyzed. Samples were grouped per dexamethasone responses and followed by UPC2-MS/MS analysis. When insufficient, samples were pooled from patients with similar responses to allow quantification over the low end of the assay. RESULTS: The C11-oxy C19 (11ß-hydroxyandrostenedione, 11keto-androstenedione, 11ß-hydroxytestosterone, 11keto-testosterone):C19 (androstenedione, testosterone) steroid ratio was decreased by 1.75-fold in PCOS patients compared to HVs. Downstream steroid metabolites 11ß-hydroxyandrosterone and 11keto-androsterone were also measurable. The C11-oxy C21 steroids, 11-hydroxyprogesterone and 11keto-dihydroprogesterone levels, were 1.2- and 1.7-fold higher in PCOS patients compared to HVs, respectively. CONCLUSIONS: We hypothesized that UPC2-MS/MS may accurately quantify steroids, in vivo, and identify novel metabolites in a subgroup of patients with PCOS and adrenal abnormalities. Indeed, it appears that adrenal C11-oxy steroids have the potential of being used diagnostically to identify younger women and adolescents with PCOS who also have some evidence of micronodular adrenocortical hyperplasia. IMPACT: Adrenal C11-oxy steroids may be clinically important in identifying young patients with PCOS and adrenal abnormalities. The steroids presented in our manuscript have not yet been considered in the clinical setting so far, and we believe that this study could represent a first focused step towards the characterization of a distinct subgroup of women with PCOS who may in fact be treated differently than the average patient with PCOS. This paper can change the understanding of PCOS as one disorder: it is in fact a heterogeneous condition. In addition, for the subgroup of patients with PCOS associated with adrenocortical dysfunction, our paper provides novel hormonal markers that can be used diagnostically. Finally, the paper also adds to the basic pathophysiological understanding of adrenocortical-ovarian interactions in steroidogenesis of young women and adolescent girls with PCOS.

Measuring Adolescent HIV Self-management: An Instrument Development Study.

Adolescent HIV self-management is a complex phenomenon that has been poorly researched. A mixed-method explorative sequential research design was used to develop an instrument to measure adolescent HIV self-management in the context of the Western Cape, South Africa. The development and validation was undertaken in four phases: (i) individual interviews and focus groups with adolescents aged 13 to 18, their caregivers and healthcare workers (n = 56); (ii) item identification; (iii) item refinement through cognitive interviewing (n = 11), expert review (n = 11) and pilot testing (n = 33); and (iv) psychometric evaluation (n = 385). The final scale consists of five components with 35 items encompassing the construct of adolescent HIV self-management. The developed scale had acceptable reliability (0.84) and stability (0.76). Factor analysis indicated a good model-fit that support the structural validity (RMSEA = 0.052, p = 0.24; RMR = 0.065; CFI = 0.9). Higher self-management was associated with better HIV-related and general health outcomes, which supports the criterion- and convergent validity of the instrument.

Diffusion tensor imaging point to ongoing functional impairment in HIV-infected children at age 5, undetectable using standard neurodevelopmental assessments.

BACKGROUND: Perinatal HIV infection negatively impacts cognitive functioning of children, main domains affected are working memory, processing speed and executive function. Early ART, even when interrupted, improves neurodevelopmental outcomes. Diffusion tension imaging (DTI) is a sensitive tool assessing white matter damage. We hypothesised that white matter measures in regions showing HIV-related alterations will be associated with lower neurodevelopmental scores in specific domains related to the functionality of the affected tracts. METHODS: DTI was performed on children in a neurodevelopmental sub study from the Children with HIV Early Antiretroviral (CHER) trial. Voxel-based group comparisons to determine regions where fractional anisotropy and mean diffusion differed between HIV+ and uninfected children were done. Locations of clusters showing group differences were identified using the Harvard-Oxford cortical and subcortical and John Hopkins University WM tractography atlases provided in FSL. This is a second review of DTI data in this cohort, which was reported in a previous study. Neurodevelopmental assessments including GMDS and Beery-Buktenica tests were performed and correlated with DTI parameters in abnormal white matter. RESULTS: 38 HIV+ children (14 male, mean age 64.7 months) and 11 controls (4 male, mean age 67.7 months) were imaged. Two clusters with lower fractional anisotropy and 7 clusters with increased mean diffusion were identified in the HIV+ group. The only neurodevelopmental domain with a trend of difference between the HIV+ children and controls (p = 0.08), was Personal Social Quotient which correlated to improved myelination of the forceps minor in the control group. As a combined group there was a negative correlation between visual perception and radial diffusion in the right superior longitudinal fasciculus and left inferior longitudinal fasciculus, which may be related to the fact that these tracts, forming part of the visual perception pathway, are at a crucial state of development at age 5. CONCLUSION: Even directed neurodevelopmental tests will underestimate the degree of microstructural white matter damage detected by DTI. The visual perception deficit detected in the entire study population should be further examined in a larger study.

PD-L1 and PD-L2 Expression Levels Are Low in Primary and Secondary Adenoid Cystic Carcinomas of the Orbit: Therapeutic Implications.

PURPOSE: To determine if there is a biologic rationale for using checkpoint inhibitor drugs targeting programmed cell death ligand 1 (PD-L1) and PD-L2 in the treatment of adenoid cystic carcinoma of the orbit. METHODS: Twenty-three cases of adenoid cystic carcinoma involving the orbit (13 primary lacrimal gland, 5 secondarily extending into the orbit, and 5 unspecified) were examined histopathologically. Immunohistochemistry for PD-L1, PD-L2, and CD8 was performed. Charts were reviewed for clinical correlations. RESULTS: Expression of PD-L1 and of PD-L2 was overall low in adenoid cystic carcinoma (mean expression 1.4 ± 0.9 of 5 for PD-L1, mean 0.83 ± 1.1 of 5 for PD-L2), and tumor-infiltrating CD8-positive T-lymphocytes were sparse (mean 1.1 ± 0.51 of 3). Only 13 of the 23 (57%) cases expressed PD-L1 as a combined positive score ≥1 of cells. No associations were found between expression levels of these markers and patient sex, tumor site of origin, Tumor, Node, Metastasis stage, or patient outcome. A significant association was observed between stromal PD-L1 expression and tumor histopathologic subtype (p = 0.05), and between tumor PD-L1 expression and prior exposure to radiation (p = 0.03). CONCLUSIONS: Checkpoint inhibitor drugs may have limited impact in the treatment and clinical course of orbital adenoid cystic carcinoma based on the low frequency of CD8 infiltrate and low expression of PD-L1 and PD-L2. Pretreatment with radiation, however, may improve tumor response to checkpoint inhibitor drugs.

Self-Induced Vomiting and Other Impulsive Behaviors in Alcohol Use Disorder: A Cross-sectional Descriptive Study.

OBJECTIVE: To determine the prevalence of self-induced vomiting (SIV) in a sample of patients with Alcohol Use Disorder (AUD), and to explore whether such behavior is associated with a comorbid eating disorder psychopathology and other clinical symptomatology, such as impulsivity. Methods: This cross-sectional descriptive study was carried out at the Alcohol Rehabilitation Unit at Stikland Psychiatric Hospital, South Africa. All consecutive inpatient admissions between April and June 2017 were invited to participate in an hour-long data interview. The Alcohol Use Disorders Identification Test (AUDIT), Bulimic Investigatory Test, Edinburgh (BITE), and the Barratt Impulsiveness Scale (BIS-11) were used to collect data from 104 adults. Results: A total of 29% of patients with AUD reported SIV. The main reason stated for SIV was to prevent hangover (66%). There were no significant differences in BITE and BIS110 scores between participants who reported SIV and those who did not. Conclusions: Almost a third of patients with AUD reported SIV. BITE scores indicated no relationship between eating disorders and alcohol-related SIV in this sample. Our findings also did not support an etiological role for impulsivity in alcohol-related SIV.

Eating disorders and substance use at a South African tertiary hospital over a 21-year period.

BACKGROUND: Eating disorders (EDs) and substance-related disorders pose a challenge when they co-occur and have implications for patient management. Clinical information on EDs and substance-related disorders as independent disorders is fairly well established in South Africa, but our understanding of the coexistence of these disorders is limited. AIM: To determine the prevalence, the concurrent nature and the possible trends of substance use among patients diagnosed with EDs at a South African tertiary hospital over a 21-year period. SETTING: The ED unit at Tygerberg Hospital, Cape Town, South Africa. METHODS: We performed a retrospective chart review of 162 patients who were treated for EDs between January 1993 and December 2014. RESULTS: The prevalence of ED subtypes was 40.1% bulimia nervosa (BN), 33.3% EDs not otherwise specified (EDNOS) and 26.5% anorexia nervosa. Most participants (71.0%) used at least one substance. Alcohol was the most prevalent substance of choice (54.8%). Most patients had an additional psychiatric disorder (62.3%), of which major depressive disorder was the most prevalent (46.3%). Apart from the use of alcohol and cannabis, which remained consistent, the use of most other substances as well as the prevalence of BN declined during the study period. CONCLUSION: Understanding the prevalence and trends of EDs and the corresponding patterns of substance misuse is essential to improve service provision. This study emphasises the need to better understand the ongoing and changing behavioural trends in EDs to improve patient management.

Suicide ideation and attempts in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) places individuals at risk for suicidality. Inconsistencies regarding the associated features of suicidality and OCD remain. METHODS: Regression analysis determined the extent to which psychiatric comorbidity, illness severity, OCD symptom dimensions, childhood trauma history, and the Val66Met (rs6265) polymorphism of the brainderived neurotrophic factor (BDNF) gene predict lifetime suicidal ideation and attempts in adults with OCD. RESULTS: Among the 496 participants, 51.8% reported suicidal ideation and 16.5% reported ≥1 suicide attempts. Females and individuals with borderline personality disorder (BPD) were at higher risk of presenting with suicide attempts (female: odds ratio [OR] = 2.75; 95% confidence interval [CI], 1.28 to 5.94; BPD: OR = 7.35; 95% CI, 3.25 to 16.61). Major depressive disorder (MDD), BPD, and avoidant personality disorder (AVPD) were significant predictors of suicidal ideation (MDD: OR = 2.4; 95% CI, 1.5 to 3.86; BPD: OR = 2.8; 95% CI, 1.36 to 5.73; AVPD: OR = 1.96; 95% CI, 1.02 to 3.75). No significant association was observed between BDNF Val66Met and suicidality. CONCLUSIONS: Suicidality is common among patients with OCD. Several variables were associated with risk, including female sex, depression, and personality pathology. Further research into the underlying mechanisms is warranted. Emphasis is placed on assessment of suicidality risk and addressing modifiable features associated with suicidality to ensure better outcomes.

Fractional anisotropy of white matter, disability and blood iron parameters in multiple sclerosis.

Multiple sclerosis (MS) is a disorder related to myelin damage, which can be investigated by neuroimaging techniques such as fractional anisotropy (FA), a measure of microstructural white matter properties. The objectives of this study were to investigate (1) the relationship between FA and disability using an extremes of outcome approach, and (2) whether blood iron parameters were associated with FA and/or disability. Patients diagnosed with MS (n = 107; 14 males and 93 females) had iron parameter tests and disability determinations using the Expanded Disability Status Scale (EDSS). FA was recorded in 48 white matter tracts in 11 of the female patients with MS and 12 female controls. RESULTS: In patients with high disability scores the mean FA was significantly lower (0.34 ± 0.067) than in the control group (0.45 ± 0.036; p = 0.04), while patients with low disability had mean FA values (0.44 ± 0.014) similar to controls (p = 0.5). Positive associations were found between FA and the iron parameters serum iron, ferritin and percentage transferrin saturation (%Tfsat) in all the white matter tracts. For % Tfsat, the associations were highly significant in 14 tracts (p < 0.01; r-values 0.74-0.84) and p < 0.001 (r = 0.83) in the superior fronto occipital fasciculus (LH). In the whole patient group a trend was found towards an inverse association between the EDSS and the %Tfsat (r = -0.26, p = 0.05) after excluding male gender and smoking as confounders, suggesting reduced disability in the presence of higher blood iron parameters. Additionally, significant inverse associations between disease duration and haemoglobin (p = 0.04) as well as %Tfsat (p = 0.02) suggested that patients with MS may experience a decrease in blood iron concentrations over time.

Predictive Indicators to Identify High-Risk Paediatric Febrile Neutropenia in Paediatric Oncology Patients in a Middle-Income Country.

PURPOSE: To validate a clinical risk prediction score (Ammann score) to predict adverse events (AEs) in paediatric febrile neutropenia (FN). PATIENTS AND METHODS: Patients <16 years of age were enrolled. A risk prediction score (based on haemoglobin ≥ 9 g/dl, white cell count (WCC) < 0.3 G/l, platelet count <50 G/l and chemotherapy more intensive than acute lymphoblastic leukaemia maintenance therapy) was calculated and AEs were documented. RESULTS: In total, 100 FN episodes occurred in 52 patients, male:female ratio was 1.8:1 and median age was 56 months. At reassessment, AEs occurred in 18 of 55 (45%) low-risk FN episodes (score < 9) and 21 of 42 (55%) high-risk episodes (score ≥9) (sensitivity 60%, specificity 65%, positive predictive value 53%, negative predictive value 71%). Total WCC and absolute monocyte count (AMC) were significantly associated with AEs. CONCLUSION: This study identified total WCC and AMC as significantly associated with AEs but failed to validate the risk prediction score.

Diagnostic performance of a seven-marker serum protein biosignature for the diagnosis of active TB disease in African primary healthcare clinic attendees with signs and symptoms suggestive of TB.

BACKGROUND: User-friendly, rapid, inexpensive yet accurate TB diagnostic tools are urgently needed at points of care in resource-limited settings. We investigated host biomarkers detected in serum samples obtained from adults with signs and symptoms suggestive of TB at primary healthcare clinics in five African countries (Malawi, Namibia, South Africa, The Gambia and Uganda), for the diagnosis of TB disease. METHODS: We prospectively enrolled individuals presenting with symptoms warranting investigation for pulmonary TB, prior to assessment for TB disease. We evaluated 22 host protein biomarkers in stored serum samples using a multiplex cytokine platform. Using a pre-established diagnostic algorithm comprising of laboratory, clinical and radiological findings, participants were classified as either definite TB, probable TB, questionable TB status or non-pulmonary TB. RESULTS: Of the 716 participants enrolled, 185 were definite and 29 were probable TB cases, 6 had questionable TB disease status, whereas 487 had no evidence of TB. A seven-marker biosignature of C reactive protein, transthyretin, IFN-γ, complement factor H, apolipoprotein-A1, inducible protein 10 and serum amyloid A identified on a training sample set (n=491), diagnosed TB disease in the test set (n=210) with sensitivity of 93.8% (95% CI 84.0% to 98.0%), specificity of 73.3% (95% CI 65.2% to 80.1%), and positive and negative predictive values of 60.6% (95% CI 50.3% to 70.1%) and 96.4% (95% CI 90.5% to 98.8%), respectively, regardless of HIV infection status or study site. CONCLUSIONS: We have identified a seven-marker host serum protein biosignature for the diagnosis of TB disease irrespective of HIV infection status or ethnicity in Africa. These results hold promise for the development of a field-friendly point-of-care screening test for pulmonary TB.

Neuropsychological manifestations in children with Sydenham's chorea after adjunct intravenous immunoglobulin and standard treatment.

This was an exploratory study comparing neuropsychological manifestations of Sydenham's chorea (SC), 6 months after initiation of treatment, in children who had received intravenous immunoglobulins as an adjunct to standard treatment, with those who had received standard treatment. We included a non-SC control group for comparison. We hypothesized that compared to controls, children with SC who had received prior intravenous immunoglobulins would demonstrate less pronounced impairments compared to those who had received standard care. We conducted a cross-sectional analysis of 17 children with -SC who had received treatment 6 months previously (9 treated with standard of care and 8 augmented with intravenous immunoglobulins) and 17 non-SC, medically well controls. The standard treatment group (n = 9) exhibited significant behavioral difficulties, including significantly poorer co-operation (p = 0.009) compared with the other augmented immunoglobulins and non-SC control groups, and increased impulsivity (p = 0.016) compared with non-SC controls. The standard treatment group scored significantly lower than the other two groups on a measure of executive functioning (p = 0.03). Children with SC may be more at risk for neuropsychological difficulties than non-SC, medically well children. Intravenous immunoglobulins may mitigate some of these impairments.

Molecular mechanisms of D-cycloserine in facilitating fear extinction: insights from RNAseq.

D-cycloserine (DCS) has been shown to be effective in facilitating fear extinction in animal and human studies, however the precise mechanisms whereby the co-administration of DCS and behavioural fear extinction reduce fear are still unclear. This study investigated the molecular mechanisms of intrahippocampally administered D-cycloserine in facilitating fear extinction in a contextual fear conditioning animal model. Male Sprague Dawley rats (n = 120) were grouped into four experimental groups (n = 30) based on fear conditioning and intrahippocampal administration of either DCS or saline. The light/dark avoidance test was used to differentiate maladapted (MA) (anxious) from well-adapted (WA) (not anxious) subgroups. RNA extracted from the left dorsal hippocampus was used for RNA sequencing and gene expression data was compared between six fear-conditioned + saline MA (FEAR + SALINE MA) and six fear-conditioned + DCS WA (FEAR + DCS WA) animals. Of the 424 significantly downregulated and 25 significantly upregulated genes identified in the FEAR + DCS WA group compared to the FEAR + SALINE MA group, 121 downregulated and nine upregulated genes were predicted to be relevant to fear conditioning and anxiety and stress-related disorders. The majority of downregulated genes transcribed immune, proinflammatory and oxidative stress systems molecules. These molecules mediate neuroinflammation and cause neuronal damage. DCS also regulated genes involved in learning and memory processes, and genes associated with anxiety, stress-related disorders and co-occurring diseases (e.g., cardiovascular diseases, digestive system diseases and nervous system diseases). Identifying the molecular underpinnings of DCS-mediated fear extinction brings us closer to understanding the process of fear extinction.