Publications by authors named "Martin Kidd"

100 Publications

Mycobacterium tuberculosis-stimulated whole blood culture to detect host biosignatures for tuberculosis treatment response.

Tuberculosis (Edinb) 2021 Apr 10;128:102082. Epub 2021 Apr 10.

DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Host markers to monitor the response to tuberculosis (TB) therapy hold some promise. We evaluated the changes in concentration of Mycobacterium tuberculosis (M.tb)-induced soluble biomarkers during early treatment for predicting short- and long-term treatment outcomes. Whole blood samples from 30 cured and 12 relapsed TB patients from diagnosis, week 1, 2, and 4 of treatment were cultured in the presence of live M.tb for seven days and patients followed up for 24 weeks after the end of treatment. 57 markers were measured in unstimulated and antigen-stimulated culture supernatants using Luminex assays. Top performing multi-variable models at diagnosis using unstimulated values predicted outcome at 24 months after treatment completion with a sensitivity of 75.0% (95% CI, 42.8-94.5%) and specificity of 72.4% (95% CI, 52.8-87.3%) in leave-one-out cross validation. Month two treatment responder classification was correctly predicted with a sensitivity of 79.2% (95% CI, 57.8-92.9%) and specificity of 92.3% (95% CI, 64.0-99.8%). This study provides evidence of the early M.tb-specific treatment response in TB patients but shows that the observed unstimulated marker models are not outperformed by stimulated marker models. Performance of unstimulated predictive host marker signatures is promising and requires validation in larger studies.
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http://dx.doi.org/10.1016/j.tube.2021.102082DOI Listing
April 2021

A Plasma 5-Marker Host Biosignature Identifies Tuberculosis in High and Low Endemic Countries.

Front Immunol 2021 24;12:608846. Epub 2021 Feb 24.

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

Several host inflammatory markers have been proposed as biomarkers for diagnosis and treatment response in Tuberculosis (TB), but few studies compare their utility in different demographic, ethnic, and TB endemic settings. Fifty-four host biomarkers were evaluated in plasma samples obtained from presumed TB cases recruited at the Oslo University Hospital in Norway, and a health center in Cape Town, South Africa. Based on clinical and laboratory assessments, participants were classified as having TB or other respiratory diseases (ORD). The concentrations of biomarkers were analyzed using the Luminex multiplex platform. Out of 185 study participants from both study sites, 107 (58%) had TB, and 78 (42%) ORD. Multiple host markers showed diagnostic potential in both the Norwegian and South African cohorts, with I-309 as the most accurate single marker irrespective of geographical setting. Although study site-specific biosignatures had high accuracy for TB, a site-independent 5-marker biosignature (G-CSF, C3b/iC3b, procalcitonin, IP-10, PDGF-BB) was identified diagnosing TB with a sensitivity of 72.7% (95% CI, 49.8-82.3) and specificity of 90.5% (95% CI, 69.6-98.8) irrespective of geographical site. A 5-marker host plasma biosignature has diagnostic potential for TB disease irrespective of TB setting and should be further explored in larger cohorts.
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http://dx.doi.org/10.3389/fimmu.2021.608846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958880PMC
February 2021

Evaluation of Host Serum Protein Biomarkers of Tuberculosis in sub-Saharan Africa.

Front Immunol 2021 25;12:639174. Epub 2021 Feb 25.

Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom.

Accurate and affordable point-of-care diagnostics for tuberculosis (TB) are needed. Host serum protein signatures have been derived for use in primary care settings, however validation of these in secondary care settings is lacking. We evaluated serum protein biomarkers discovered in primary care cohorts from Africa reapplied to patients from secondary care. In this nested case-control study, concentrations of 22 proteins were quantified in sera from 292 patients from Malawi and South Africa who presented predominantly to secondary care. Recruitment was based upon intention of local clinicians to test for TB. The case definition for TB was culture positivity for ; and for other diseases (OD) a confirmed alternative diagnosis. Equal numbers of TB and OD patients were selected. Within each group, there were equal numbers with and without HIV and from each site. Patients were split into training and test sets for biosignature discovery. A nine-protein signature to distinguish TB from OD was discovered comprising fibrinogen, alpha-2-macroglobulin, CRP, MMP-9, transthyretin, complement factor H, IFN-gamma, IP-10, and TNF-alpha. This signature had an area under the receiver operating characteristic curve in the training set of 90% (95% CI 86-95%), and, after adjusting the cut-off for increased sensitivity, a sensitivity and specificity in the test set of 92% (95% CI 80-98%) and 71% (95% CI 56-84%), respectively. The best single biomarker was complement factor H [area under the receiver operating characteristic curve 70% (95% CI 64-76%)]. Biosignatures consisting of host serum proteins may function as point-of-care screening tests for TB in African hospitals. Complement factor H is identified as a new biomarker for such signatures.
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http://dx.doi.org/10.3389/fimmu.2021.639174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947659PMC
February 2021

TERT rs2736100 and TERC rs16847897 genotypes moderate the association between internalizing mental disorders and accelerated telomere length attrition among HIV+ children and adolescents in Uganda.

BMC Med Genomics 2021 Jan 6;14(1):15. Epub 2021 Jan 6.

Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.

Background: Internalizing mental disorders (IMDs) (depression, anxiety and post-traumatic stress disorder) have been associated with accelerated telomere length (TL) attrition; however, this association has not been investigated in the context of genetic variation that has been found to influence TL. We have previously reported an association between IMDs and accelerated TL attrition among Ugandan HIV+ children and adolescents. This study investigated the moderating effects of selected single nucleotide polymorphisms in the telomerase reverse transcriptase gene (TERT) (rs2736100, rs7726159, rs10069690 and rs2853669) and the telomerase RNA component gene (TERC) (rs12696304, rs16847897 and rs10936599) on the association between IMDs and TL, among Ugandan HIV+ children (aged 5-11 years) and adolescents (aged 12-17 years).

Results: We found no significant interaction between IMDs as a group and any of the selected SNPs on TL at baseline. We observed significant interactions of IMDs with TERT rs2736100 (p = 0.007) and TERC rs16847897 (p = 0.012), respectively, on TL at 12 months.

Conclusions: TERT rs2736100 and TERC rs16847897 moderate the association between IMDs and TL among Ugandan HIV+ children and adolescents at 12 months. Understanding the nature of this association may shed light on the pathophysiological mechanisms underlying advanced cellular aging in IMDs.
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http://dx.doi.org/10.1186/s12920-020-00857-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789327PMC
January 2021

Effectiveness of a psychological intervention delivered by general nurses for alcohol use disorders in people living with HIV in Zimbabwe: a cluster randomized controlled trial.

J Int AIDS Soc 2020 12;23(12):e25641

Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.

Introduction: There have been very few randomized clinical trials of interventions for alcohol use disorders (AUD) in people living with HIV (PLWH) in African countries. This is despite the fact that alcohol use is one of the modifiable risk factors for poor virological control in PLWH on antiretroviral therapy.

Methods: Sixteen clinic clusters in Zimbabwe were selected through stratified randomization and randomized 1: 1 to Intervention and Control arms. Inclusion criteria for individual participants were being adult, living with HIV and a probable alcohol use disorder as defined by a score of 6 (women) or 7 (men) on the Alcohol Use Disorders Identification Test (AUDIT). In the Intervention clusters, participants received 8 to 10 sessions of Motivational Interviewing blended with brief Cognitive Behavioural Therapy (MI-CBT). In the control clusters, participants received four Enhanced Usual Care (EUC) sessions based on the alcohol treatment module from the World Health Organisation mhGAP intervention guide. General Nurses from the clinics were trained to deliver both treatments. The primary outcome was a change in AUDIT score at six-month post-randomization. Viral load, functioning and quality of life were secondary outcomes. A random-effects analysis-of-covariance model was used to account for the cluster design.

Results: Two hundred and thirty-four participants (n = 108 intervention and n = 126 control) were enrolled across 16 clinics. Participants were recruited from November 2016 to November 2017 and followed through to May 2018. Their mean age was 43.3 years (SD = 9.1) and 78.6% (n = 184) were male. At six months, the mean AUDIT score fell by -6.15 (95% CI -6.32; -6.00) in the MI-CBT arm, compared to a fall of - 3.09 95 % CI - 3.21; -2.93) in the EUC arm (mean difference -3.09 (95% CI -4.53 to -1.23) (p = 0.05). Viral load reduced and quality of life and functioning improved in both arms but the difference between arms was non-significant.

Conclusions: Interventions for hazardous drinking and AUD comprising brief, multiple alcohol treatment sessions delivered by nurses in public HIV facilities in low-income African countries can reduce problematic drinking among PLWH. Such interventions should be integrated into the primary care management of AUD and HIV and delivered by non-specialist providers. Research is needed on cost-effectiveness and implementation of such interventions, and on validation of cut-points for alcohol use scales in low resource settings, in partnership with those with lived experience of HIV and AUD.
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http://dx.doi.org/10.1002/jia2.25641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733606PMC
December 2020

Attitudes among South African university staff and students towards disclosing secondary genetic findings.

J Community Genet 2021 Jan 20;12(1):171-184. Epub 2020 Nov 20.

South African Research Chairs Initiative: PTSD programme, Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town, 8000, South Africa.

The present study represents an initial step in understanding diverse academic perspectives on the disclosure of secondary findings (SFs) from genetic research conducted in Africa. Using an online survey completed by 674 university students and academic staff in South Africa, we elicited attitudes towards the return of SFs. Latent class analysis (LCA) was performed to classify sub-groups of participants according to their overall attitudes to returning SFs. We did not find substantial differences in attitudes towards the return of findings between staff and students. Overall, respondents were in favour of the return of SFs in genetics research, depending on the type. The majority of survey respondents (80%) indicated that research participants should be given the option of deciding whether to have genetic SFs returned. LCA revealed that the largest group (53%) comprised individuals with more favourable attitudes to the return of SFs in genetics research. Those with less favourable attitudes comprised only 4% of the sample. This study provides important insights that may, together with further empirical evidence, inform the development of research guidelines and policy to assist healthcare professionals and researchers.
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http://dx.doi.org/10.1007/s12687-020-00494-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846629PMC
January 2021

The Effect of Different Oak Products Used during Fermentation and Ageing on the Sensory Properties of a White Wine over Time.

Foods 2020 Sep 2;9(9). Epub 2020 Sep 2.

DGB (PTY) Ltd., Lady Loch Weg, Wellington 7654, South Africa.

The sensorial evaluation of Chenin blanc wine produced with different types of oak wood treatments over time has not been investigated before. The main aim of this study was to assess the sensory profile, using a trained panel, of a South African Chenin blanc wine fermented and matured in old barrels, three types of new oak barrels, two types of oak staves as well as a stainless steel tank over time, which has not been done before. Results indicate mainly separation between the stainless-steel tank/old barrel treatments from the stave and new barrel treatments, with separation between the latter two treatments also being found. More fruity descriptors were used in the stainless-steel tank and old barrel treatments, with oak-related descriptors being used in the stave and new barrel treatments. Separation between among the new barrel and stave treatments were also noted, which was still reflected during bottle maturation. These results indicate that winemakers need to take cognizance of the sensorial differences induced by barrel and stave maturation in white wines and how these evolve over time.
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http://dx.doi.org/10.3390/foods9091220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555073PMC
September 2020

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

J Dual Diagn 2020 10 8;16(4):402-408. Epub 2020 Aug 8.

Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

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. 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. 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. 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.
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http://dx.doi.org/10.1080/15504263.2020.1802541DOI Listing
October 2020

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

S Afr J Psychiatr 2020 24;26:1421. Epub 2020 Jun 24.

Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

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.
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http://dx.doi.org/10.4102/sajpsychiatry.v26i0.1421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343936PMC
June 2020

The effects of acute serotonin challenge on executive planning in patients with obsessive-compulsive disorder (OCD), their first-degree relatives, and healthy controls.

Psychopharmacology (Berl) 2020 Oct 8;237(10):3117-3123. Epub 2020 Jul 8.

SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

Rationale: Obsessive-compulsive disorder (OCD) is characterized by executive function impairment and by clinical responsivity to selective serotonin reuptake inhibitors (SSRIs). Executive planning deficits constitute a candidate endophenotype for OCD. It is not known whether this endophenotype is responsive to acute serotonin manipulation.

Objective: The study aimed to investigate the effects of acute SSRI administration on executive function in patients with OCD, first-degree relatives of patients with OCD, and healthy controls.

Methods: A randomized double-blind cross-over study assessed the effects of single-dose escitalopram (20 mg) and placebo on executive planning in 24 patients with OCD, 13 clinically unaffected first-degree relatives of patients with OCD, and 28 healthy controls. Performance on a Tower of London task measuring executive planning was assessed 4 h after oral administration of the pharmacological challenge/placebo and compared across and within groups using a mixed model analysis of variance.

Results: On the outcome measure of interest, i.e., the mean number of choices to obtain the correct solution, there was a marginally significant effect of group (F(2, 59) = 3.1; p = 0.052), with patients (least square (LS) mean 1.43; standard error [SE] 0.06; 95% confidence interval (CI), 1.31-1.55) and their relatives (LS mean 1.46; SE 0.08; 95% CI, 1.30-1.62) performing worse than matched healthy controls (LS mean 1.26; SE 0.05; 95% CI, 1.15-1.37) on placebo. There was a trend towards a significant group × treatment interaction (F(2, 58) = 2.8, p = 0.069), with post hoc tests showing (i) patients (p = 0.009; LS mean difference 0.23; SE 0.08) and relatives (p = 0.03; LS mean difference 0.22; SE 0.10) were more impaired compared to controls and (ii) escitalopram was associated with improved executive planning in patients with OCD (p = 0.013; LS mean difference 0.1; SE 0.04), but not other groups (both p > 0.1; controls: LS mean difference - 0.03; SE 0.04; relatives: LS mean difference 0.02; SE 0.05).

Conclusion: Our findings are consistent with a view that there is impaired executive planning in OCD and that this constitutes a behavioural endophenotype. In patients with OCD, but not in relatives, acute SSRI administration ameliorated this deficit. Further investigation is needed to understand common and differential involvement of neurochemical systems in patients with OCD and their relatives.
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http://dx.doi.org/10.1007/s00213-020-05597-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116135PMC
October 2020

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

AIDS Res Ther 2020 05 19;17(1):20. Epub 2020 May 19.

Family Clinical Research Unit, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, University of Stellenbosch, Tygerberg, South Africa.

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.
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http://dx.doi.org/10.1186/s12981-020-00278-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236356PMC
May 2020

How useful are clinical details in blunt trauma referrals for computed tomography of the abdomen?

SA J Radiol 2020 22;24(1):1837. Epub 2020 Apr 22.

Division of Radiodiagnosis, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Background: The relevance of clinical data included in blunt trauma referrals for abdominal computed tomography (CT) is not known.

Objectives: To analyse the clinical details provided on free-text request forms for abdominal CT following blunt trauma and assess their association with imaging evidence of intra-abdominal injury.

Method: A single-institution, retrospective study of abdominal CT scans was performed for blunt trauma between 01 January and 31 March 2018. Computed tomography request forms were reviewed with their corresponding CT images. Clinical details provided and scan findings were captured systematically. The relationship between individual clinical features and CT evidence of abdominal injury was tested using one-way cross tabulation and Fisher's exact test.

Results: One hundred thirty-nine studies met inclusion criteria. A wide range of clinical details was communicated. Only clinical abdominal examination findings ( = 0.05), macroscopic haematuria ( < 0.01), pelvic fracture or hip dislocation ( = 0.04) and positive focused assessment with sonography in trauma ( < 0.01) demonstrated an associated trend with abdominal injury.

Conclusion: Key abdominal examination and basic imaging findings remain essential clinical details for the appropriate evaluation of CT abdomen requests in the setting of blunt trauma. Methods to improve consistent communication of relevant clinical details are likely to be of value.
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http://dx.doi.org/10.4102/sajr.v24i1.1837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203534PMC
April 2020

Adolescent human immunodeficiency virus self-management: Associations with treatment adherence, viral suppression, sexual risk behaviours and health-related quality of life.

South Afr J HIV Med 2020 29;21(1):1054. Epub 2020 Apr 29.

Department of Public Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Background: With the advent of access to antiretroviral treatment (ART), human immunodeficiency virus (HIV) has become a chronic disease and self-management is an important component of its care. Research to date has not explored associations between adolescent HIV self-management and treatment adherence, viral suppression, sexual risk behaviour and health-related quality of life (HRQoL).

Objectives: To explore the associations between adolescent HIV self-management and treatment adherence, viral suppression, sexual risk behaviour and HRQoL.

Methods: A quantitative cross-sectional study of 385 adolescents living with HIV (ALHIV) aged 13-18 years, who were recruited from 11 healthcare facilities between March and August 2017 in the Cape Metropole of the Western Cape, South Africa, provided the data that were examined in this self-completed questionnaire. Validated scales were used to measure key variables. The most recent viral load (VL) was obtained from the participants' clinic folder, taking into account that VL is done annually.

Results: Adolescents who reported higher HIV self-management were more likely to be adherent to treatment ( = 4.435 [336], < 0.01), virally suppressed ( = 2.376 [305], = 0.02) and to practise consistent condom use ( = 1.947 [95], = 0.54). Structural equation modelling (SEM) indicated a significant relationship between self-management and HRQoL ( = 0.43, < 0.01), whilst non-adherent treatment taking behaviour, correlated with elevated VL log values. No significant correlation was found between self-management and sexual risk behaviour.

Conclusion: Targeting adolescents' skills related to HIV self-management in the clinical setting may improve adolescents' treatment taking behaviour, viral suppression rates and their HRQoL.
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http://dx.doi.org/10.4102/sajhivmed.v21i1.1054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203195PMC
April 2020

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

Pediatr Res 2021 01 4;89(1):118-126. Epub 2020 Apr 4.

Section on Genetics and Endocrinology (SEGEN), Intramural Research Program (IRP), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD, USA.

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 (UPC-MS/MS). We hypothesized that UPC-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 UPC-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 C (11β-hydroxyandrostenedione, 11keto-androstenedione, 11β-hydroxytestosterone, 11keto-testosterone):C (androstenedione, testosterone) steroid ratio was decreased by 1.75-fold in PCOS patients compared to HVs. Downstream steroid metabolites 11β-hydroxyandrosterone and 11keto-androsterone were also measurable. The C11-oxy C 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 UPC-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.
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http://dx.doi.org/10.1038/s41390-020-0870-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541460PMC
January 2021

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

Ophthalmic Plast Reconstr Surg 2020 Sep/Oct;36(5):444-450

Division of Head and Neck Pathology, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.

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.
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http://dx.doi.org/10.1097/IOP.0000000000001585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423458PMC
March 2021

Identification of Potential Biomarkers in Peripheral Blood Supernatants of South African Patients with Syphilitic and Herpetic Uveitis.

Ocul Immunol Inflamm 2021 Feb 7;29(2):299-307. Epub 2019 Nov 7.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

: To identify potential diagnostic biomarkers for herpetic and syphilitic uveitis.: Blood samples were collected from 92 uveitis patients. Concentrations of 47 biomarkers were evaluated in unstimulated Quantiferon supernatants using the Luminex platform.: Results showed 11 patients (12%) had herpetic uveitis, 11 (12%) syphilis, 40 (43.5%) other infectious causes, 16 (17.4%) established noninfectious causes and 14 (15.2%) were idiopathic. Biomarker analysis revealed three proteins (Apo-A1, Apo-CIII, CRP) that differed between syphilis and other causes. A three-marker biosignature (CCL4/MIP-1β, Apo-CIII and CRP) separated syphilis from other groups with AUC = 0.83 (95% CI: 0.68-0.98). Apo-CIII and CRP differed between herpetic cases and other groups ( < .05). A three-analyte biosignature (Apo-A1, SAP and CRP) separated the herpetic group from other groups with AUC = 0.79 (95% CI: 0.65-0.93).: We have identified candidate biomarkers with potential to differentiate between herpetic, syphilitic and other causes of uveitis. These results warrant further investigation in larger future studies.
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http://dx.doi.org/10.1080/09273948.2019.1674341DOI Listing
February 2021

A multivariate approach to evaluating the chemical and sensorial evolution of South African Sauvignon Blanc and Chenin Blanc wines under different bottle storage conditions.

Food Res Int 2019 11 24;125:108515. Epub 2019 Jun 24.

Department of Viticulture and Oenology, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa. Electronic address:

Volatile compound composition contributes to the aroma profile of wine and is susceptible to change due to oxidation which may occur during storage and transportation, especially at high temperatures. Changes in sensory attributes may also occur, altering the sensory profile of wine. Classical univariate analysis only looks at the deviations for one factor at a time and may overlook the overall effect of treatments. In this study, changes in South African Sauvignon Blanc and Chenin Blanc wine sensory profile, volatile and antioxidant-related parameters resulting from storage under different temperatures (room temperature, 15 °C and 25 °C) and durations (0, 3 and 9 months) were investigated using a multivariate approach. Bottled, unwooded wines of both cultivars from six wineries were used. As expected, the chemical evolution of the wines was characterised by increases in absorbance at 420 nm (browning), colour density and hue with prolonged storage at high temperatures. To be able to compare the evolution of the sample sets regardless of the initial (T0/control) wine profile and composition, multivariate regression analysis in the form of regression vector (RV) coefficients were used to assess the correlations in the sensory and chemical changes relative to the control in each set. Using Pivot©Profile for the first time in this type of stability assessment and applying a new algorithm for data handling in addition to the classical one, this study showed that prolonged exposure to higher temperatures resulted in the change from fruity to toasted aroma attributes.
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http://dx.doi.org/10.1016/j.foodres.2019.108515DOI Listing
November 2019

Distinct serum biosignatures are associated with different tuberculosis treatment outcomes.

Tuberculosis (Edinb) 2019 09 12;118:101859. Epub 2019 Aug 12.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address:

Biomarkers for TB treatment response and outcome are needed. This study characterize changes in immune profiles during TB treatment, define biosignatures associated with treatment outcomes, and explore the feasibility of predictive models for relapse. Seventy-two markers were measured by multiplex cytokine array in serum samples from 78 cured, 12 relapsed and 15 failed treatment patients from South Africa before and during therapy for pulmonary TB. Promising biosignatures were evaluated in a second cohort from Uganda/Brazil consisting of 17 relapse and 23 cured patients. Thirty markers changed significantly with different response patterns during TB treatment in cured patients. The serum biosignature distinguished cured from relapse patients and a combination of two clinical (time to positivity in liquid culture and BMI) and four immunological parameters (TNF-β, sIL-6R, IL-12p40 and IP-10) at diagnosis predicted relapse with a 75% sensitivity (95%CI 0.38-1) and 85% specificity (95%CI 0.75-0.93). This biosignature was validated in an independent Uganda/Brazil cohort correctly classifying relapse patients with 83% (95%CI 0.58-1) sensitivity and 61% (95%CI 0.39-0.83) specificity. A characteristic biosignature with value as predictor of TB relapse was identified. The repeatability and robustness of these biomarkers require further validation in well-characterized cohorts.
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http://dx.doi.org/10.1016/j.tube.2019.101859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839616PMC
September 2019

Internalizing Mental Disorders and Accelerated Cellular Aging Among Perinatally HIV-Infected Youth in Uganda.

Front Genet 2019 2;10:705. Epub 2019 Aug 2.

Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.

Internalizing mental disorders (IMDs) in HIV+ children and adolescents are associated with impaired quality of life and non-adherence to anti-retroviral treatment. Telomere length is a biomarker of cellular aging, and shorter telomere length has been associated with IMDs. However, the nature of this association has yet to be elucidated. We determined the longitudinal association between IMDs and relative telomere length (rTL) and the influence of chronic stress among Ugandan perinatally HIV-infected youth (PHIY). IMDs (depressive disorders, anxiety disorders, and post-traumatic stress disorder) and IMDs were assessed using the locally adapted Child and Adolescent Symptom Inventory-5. In 368 PHIY with any IMD and 368 age- and sex-matched PHIY controls without any psychiatric disorder, rTL was assessed using quantitative polymerase chain reaction. Hierarchical cluster analysis was used to generate the three chronic stress classes (mild, moderate, and severe). -tests were used to assess the difference between baseline and 12 month rTL and the mean difference in rTL between cases and controls both at baseline and at 12 months. Linear regression analysis was used to model the effects of chronic stress on the association between IMDs and rTL, controlling for age and sex. We observed longer rTL among cases of IMDs compared with controls ( < 0.001). We also observed a statistically significant reduction in rTL between baseline and 12 months in the combined sample of cases and controls ( < 0.001). The same statistical difference was observed when cases and controls were individually analyzed ( < 0.001). We found no significant difference in rTL between cases and controls at 12 months ( = 0.117). We found no significant influence of chronic stress on the association between IMDs and rTL at both baseline and 12 months. rTL is longer among cases of IMDs compared with age- and sex-matched controls. We observed a significant attrition in rTL over 12 months, which seems to be driven by the presence of any IMDs. There is a need for future longitudinal and experimental studies to understand the mechanisms driving our findings.
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http://dx.doi.org/10.3389/fgene.2019.00705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688656PMC
August 2019

Prospective evaluation of host biomarkers other than interferon gamma in QuantiFERON Plus supernatants as candidates for the diagnosis of tuberculosis in symptomatic individuals.

J Infect 2019 09 15;79(3):228-235. Epub 2019 Jul 15.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Po Box 241, Cape Town 8000, South Africa. Electronic address:

Background: There is an urgent need for new tools for the diagnosis of TB. We evaluated the usefulness recently described host biomarkers in supernatants from the newest generation of the QuantiFERON test (QuantiFERON Plus) as tools for the diagnosis of active TB.

Methods: We recruited individuals presenting at primary health care clinics in Cape Town, South Africa with symptoms requiring investigation for TB disease, prior to the establishment of a clinical diagnosis. Participants were later classified as TB or other respiratory diseases (ORD) based on the results of clinical and laboratory tests. Using a multiplex platform, we evaluated the concentrations of 37 host biomarkers in QuantiFERON Plus supernatants from study participants as tools for the diagnosis of TB.

Results: Out of 120 study participants, 35(29.2%) were diagnosed with active TB, 69(57.5%) with ORD whereas 16(13.3%) were excluded. 14(11.6%) of the study participants were HIV infected. Although individual host markers showed potential as diagnostic candidates, the main finding of the study was the identification of a six-marker biosignature in unstimulated supernatants (Apo-ACIII, CXCL1, CXCL9, CCL8, CCL-1, CD56) which diagnosed TB with sensitivity and specificity of 73.9%(95% CI; 51.6-87.8) and 87.6%(95% CI; 77.2-94.5), respectively, after leave-one-out cross validation. Combinations between TB-antigen specific biomarkers also showed potential (sensitivity of 77.3% and specificity of 69.2%, respectively), with multiple biomarkers being significantly different between TB patients, Quantiferon Plus Positive and Quantiferon Plus negative individuals with ORD, regardless of HIV status.

Conclusions: Biomarkers detected in QuantiFERON Plus supernatants may contribute to adjunctive diagnosis of TB.
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http://dx.doi.org/10.1016/j.jinf.2019.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692655PMC
September 2019

Prospective evaluation of host biomarkers other than interferon gamma in QuantiFERON Plus supernatants as candidates for the diagnosis of tuberculosis in symptomatic individuals.

J Infect 2019 09 15;79(3):228-235. Epub 2019 Jul 15.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Po Box 241, Cape Town 8000, South Africa. Electronic address:

Background: There is an urgent need for new tools for the diagnosis of TB. We evaluated the usefulness recently described host biomarkers in supernatants from the newest generation of the QuantiFERON test (QuantiFERON Plus) as tools for the diagnosis of active TB.

Methods: We recruited individuals presenting at primary health care clinics in Cape Town, South Africa with symptoms requiring investigation for TB disease, prior to the establishment of a clinical diagnosis. Participants were later classified as TB or other respiratory diseases (ORD) based on the results of clinical and laboratory tests. Using a multiplex platform, we evaluated the concentrations of 37 host biomarkers in QuantiFERON Plus supernatants from study participants as tools for the diagnosis of TB.

Results: Out of 120 study participants, 35(29.2%) were diagnosed with active TB, 69(57.5%) with ORD whereas 16(13.3%) were excluded. 14(11.6%) of the study participants were HIV infected. Although individual host markers showed potential as diagnostic candidates, the main finding of the study was the identification of a six-marker biosignature in unstimulated supernatants (Apo-ACIII, CXCL1, CXCL9, CCL8, CCL-1, CD56) which diagnosed TB with sensitivity and specificity of 73.9%(95% CI; 51.6-87.8) and 87.6%(95% CI; 77.2-94.5), respectively, after leave-one-out cross validation. Combinations between TB-antigen specific biomarkers also showed potential (sensitivity of 77.3% and specificity of 69.2%, respectively), with multiple biomarkers being significantly different between TB patients, Quantiferon Plus Positive and Quantiferon Plus negative individuals with ORD, regardless of HIV status.

Conclusions: Biomarkers detected in QuantiFERON Plus supernatants may contribute to adjunctive diagnosis of TB.
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http://dx.doi.org/10.1016/j.jinf.2019.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692655PMC
September 2019

A factor analytic study of the Childhood Trauma Questionnaire-Short Form in an all-female South African sample with and without HIV infection.

Child Abuse Negl 2019 06 10;92:157-166. Epub 2019 Apr 10.

South African Research Chairs Initiative (SARChI), PTSD Program, Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Background: The Childhood Trauma Questionnaire-Short Form (CTQ-SF) is widely used around the world but no norms have been established for South African users of the CTQ. The CTQ has been employed in South Africa but not yet validated. The present study aims to address this gap. There is great need in both clinical and research settings for an assessment tool that adequately measures childhood trauma, a sensitive and challenging construct to measure.

Objective: This study explores the psychometric properties of the CTQ-SF in an all-female cohort living with and without HIV infection in South Africa, the first study of its kind in this population.

Participants And Setting: The CTQ-SF was administered to 314 women (170 HIV uninfected; 144 HIV infected) in Cape Town, South Africa.

Method: Internal consistency of the CTQ-SF was determined by Cronbach alpha coefficients. Using Lisrel, a confirmatory factor analysis (CFA) was performed, followed by an exploratory factor analysis (EFA) to explore an alternative factor structure model in this cohort.

Results: For the group as a whole, the model fit was acceptable but not good. However, for the sub-sample of women living with HIV, the CFA revealed poor model fit. The EFA revealed a three-factor model, with mostly stable factor loadings for four of the five subscales. However, the Physical Neglect (PN) subscale cross loaded on two of the three factors.

Conclusion: Our findings revealed an alternative factor structure from the original model in this study cohort. The PN subscale does not have stable factor loadings and is not homogenous. The original instrument may therefore benefit from revision for use in this population. Measures such as the CTQ can be informative for preventative strategies in HIV-infected or at-risk youth and for clinical interventions aimed at mitigating the negative psychological sequelae of childhood maltreatment.
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http://dx.doi.org/10.1016/j.chiabu.2019.04.002DOI Listing
June 2019

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

AIDS Behav 2020 Feb;24(2):592-606

Human Sciences Research Council, Cape Town, South Africa.

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.
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http://dx.doi.org/10.1007/s10461-019-02490-zDOI Listing
February 2020

Basic In-Mouth Attribute Evaluation: A Comparison of Two Panels.

Foods 2018 Dec 21;8(1). Epub 2018 Dec 21.

Department of Viticulture and Oenology, Stellenbosch University, ZA-7600 Stellenbosch, South Africa.

Astringency is often difficult to evaluate accurately in wine because of its complexity. This accuracy can improve through training sessions, but it can be time-consuming and expensive. A way to reduce these costs can be the use of wine experts, who are known to be reliable evaluators. Therefore, the aim of this work was to compare the sensory results and the panel performance obtained using trained panelists versus wine experts (winemakers). Judges evaluated twelve red wines for in-mouth basic perception (sweet, sour, bitter, astringent, and burning sensation) following the same tasting protocol and with the samples being presented in two different tasting modalities. Panels' performance and relationship between the chemical composition and the sensory perception were investigated. Both panels showed similar consistency and repeatability, and they were able to accurately measure the astringency of the wines. However, the significant correlations between sensory scores and chemical composition varied with the panel and the tasting modality. From our results, we could see that winemakers tended to discriminate better between the samples when the differences were very small.
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http://dx.doi.org/10.3390/foods8010003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352104PMC
December 2018

A statistical exploration of data to identify the role of cultivar and origin in the concentration and composition of yeast assimilable nitrogen.

Food Chem 2019 Mar 12;276:528-537. Epub 2018 Oct 12.

Department of Viticulture and Oenology, Faculty of AgriSciences, Stellenbosch University, Private Bax X1, Matieland 7602, South Africa. Electronic address:

The study was undertaken to gain insight into the nitrogen status of grape juices currently used to make commercial wines in South Africa. This was done as yeast assimilable nitrogen (YAN) is most often suspected as the cause for problematic fermentations and has major implications for the organoleptic qualities of the final product. Using exploratory statistical methods, this study explored the possibility of identifying the role of cultivar and grape-growing district in the determination of the concentration and composition of YAN. However, as the dataset was found to be non-parametric and heteroscedastic, paired with unequal sample sizes, data analysis was approached with caution. Through the use of various suitable statistical analyses, cultivar was shown to play the more important role in determining the concentration and composition of YAN.
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http://dx.doi.org/10.1016/j.foodchem.2018.10.063DOI Listing
March 2019

Prognostic Value of Motor Timing in Treatment Outcome in Patients With Alcohol- and/or Cocaine Use Disorder in a Rehabilitation Program.

Front Psychol 2018 22;9:1945. Epub 2018 Oct 22.

Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.

Individuals with Substance Use Disorder (SUD) often have cognitive deficits in multiple domains, including motor timing deficits, with recovery times of up to 1 year. Cognitive deficits influence treatment outcomes and abstinence. To our knowledge, timing deficits have not been investigated with regard to treatment outcome and relapse. This prospective study tested the prognostic value of motor timing in SUD with regard to treatment outcome. The study sample consisted of 74 abstinent in-patients at a private treatment programme for drug/alcohol dependence at the Momentum Mental Healthcare clinic in Somerset West, South Africa, diagnosed with alcohol and/or cocaine dependence. Participants were tested at three points: (i) Within 72 hours of the start of the treatment programme (ii) after completion of the treatment programme at 8 weeks (measure of treatment response) through filling out self-report questionnaires and experimental motor task testing, and (iii) a third visit followed through a telephonic interview at 12-months (measure of relapse). Motor timing alone predicted 27 percent of the variance in alcohol self-efficacy score change, and 25 percent variance in cocaine self-efficacy change scores at treatment completion. Specifically, spatial errors, synchronization errors and inter- response interval errors of a spatial tapping task at baseline predicted self-efficacy in alcohol self-efficacy. Cocaine self-efficacy was predicted by spatial errors and contact times of a spatial tapping task at very high tempi (300 ms) only. The high rate of dropout at 12 months post-treatment did not allow for further analysis of the prognostic value of motor timing on relapse. The results of this investigation show us that motor timing holds prognostic value with regard to treatment outcomes. Motor timing predictors for relapse require further investigation going forward.
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http://dx.doi.org/10.3389/fpsyg.2018.01945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204653PMC
October 2018

Magnetic resonance imaging of sacroiliitis in children: reply to Jalalvandi and Naderi.

Pediatr Radiol 2019 02 5;49(2):281. Epub 2018 Nov 5.

Bristol Royal Hospital for Children, University Hospitals Bristol NHS Foundation Trust, 24 Upper Maudlin Street, Bristol, BS2 8BJ, UK.

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http://dx.doi.org/10.1007/s00247-018-4287-5DOI Listing
February 2019

Cognitive-perceptual deficits and symptom correlates in first-episode schizophrenia.

S Afr J Psychiatr 2017 31;23:1049. Epub 2017 Aug 31.

Department of Statistics and Actuarial Sciences, Stellenbosch University, South Africa.

Background: Thought disorder and visual-perceptual deficits have been well documented, but their relationships with clinical symptoms and cognitive function remain unclear. Cognitive-perceptual deficits may underscore clinical symptoms in schizophrenia patients.

Aim: This study aimed to explore how thought disorder and form perception are related with clinical symptoms and cognitive dysfunction in first-episode schizophrenia.

Setting: Forty-two patients with a first-episode of schizophrenia, schizophreniform or schizoaffective disorder were recruited from community clinics and state hospitals in the Cape Town area.

Methods: Patients were assessed at baseline with the Rorschach Perceptual Thinking Index (PTI), the Positive and Negative Syndrome Scale (PANSS) and the MATRICS Cognitive Consensus Battery (MCCB). Spearman correlational analyses were conducted to investigate relationships between PTI scores, PANSS factor analysis-derived domain scores and MCCB composite and subscale scores. Multiple regression models explored these relationships further.

Results: Unexpectedly, poor form perception (X- %) was inversely correlated with the severity of PANSS positive symptoms ( = -0.42, = 0.02). Good form perception (XA%) correlated significantly with speed of processing ( = 0.59, < 0.01), working memory ( = 0.48, < 0.01) and visual learning ( = 0.55, < 0.01). PTI measures of thought disorder did not correlate significantly with PANSS symptom scores or cognitive performance.

Conclusions: Form perception is associated with positive symptoms and impairment in executive function during acute psychosis. These findings suggest that there may be clinical value in including sensory-perceptual processing tasks in cognitive remediation and social cognitive training programmes for schizophrenia patients.
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http://dx.doi.org/10.4102/sajpsychiatry.v23i0.1049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138160PMC
August 2017

The effects of childhood maltreatment and anxiety proneness on neuropsychological test performance in non-clinical older adolescents.

J Affect Disord 2019 01 11;243:133-144. Epub 2018 Sep 11.

Department of Psychiatry, Stellenbosch University, P.O. Box 241, Cape Town 8000, South Africa. Electronic address:

Background: The effect of childhood maltreatment (CM) on neuropsychological performance is well established, but the effect of anxiety proneness (AP) on such performance has been underexplored. We assessed the predictive ability of CM and AP, and their interaction, in non-clinical adolescents, for a range of previously documented neuropsychological deficits.

Methods: Multiple linear regression models were used to assess the unique and combined influences of CM and AP on neuropsychological performance in 104 non-clinical adolescents, who underwent both neuropsychiatric and neuropsychological assessment.

Results: The interaction of CM and AP was associated with poorer performance in executive functioning skills, processing speed, and estimated IQ. CM and AP were uniquely associated with verbal working memory performance, while verbal and visual memory performance and learning, and visuo-spatial ability, were not associated with either CM, AP or the interaction of CM and AP.

Limitations: The use of self-report measures to determine participants' levels of CM, AP, and depression. The CTQ-SF, a retrospective self-report measure, may have introduced recall bias. The neuropsychological evaluation was not conducted in the Xhosa language, the first language of most African participants. Most instruments utilized have not been validated in a South African adolescent sample. The impact of important moderator variables (e.g., age of onset of maltreatment) was not assessed.

Conclusions: Increased levels of CM and AP may be risk markers for poor performance in several key neuropsychological domains. Our findings underscore the importance of assessing the impact of both CM and anxiety-related temperamental traits on neuropsychological performance.
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http://dx.doi.org/10.1016/j.jad.2018.09.009DOI Listing
January 2019

No gene-by-environment interaction of BDNF polymorphism and childhood maltreatment on anxiety sensitivity in a mixed race adolescent sample.

Eur J Psychotraumatol 2018 22;9(1):1472987. Epub 2018 May 22.

Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.

: Anxiety disorders in youth are attributable to multiple causal mechanisms, comprising biological vulnerabilities, such as genetics and temperament, and unfavourable environmental influences, such as childhood maltreatment (CM). : A gene-environment (G x E) interaction study was conducted to determine the interactive effect of the BDNF polymorphism and CM to increase susceptibility to anxiety sensitivity (AS) in a sample of mixed race adolescents. : Participants ( 308, mean age = 15.8 years) who were all secondary school students and who completed measures for AS and CM were genotyped for the BDNF polymorphism. Hierarchical multiple regression analysis was conducted to assess G x E influences on AS. Age and gender were included in the models as covariates as age was significantly associated with AS total score ( .05), and females had significantly higher AS scores than males ( .05). : A main effect of CM on AS was evident ( .05), however, no main effect of BDNF genotype on AS was observed ( .05). A non-significant G x E effect on AS was revealed ( .05). : Our results suggest that CM does not have a moderating role in the relationship between the BDNF genotype and the increased risk of anxiety-related phenotypes, such as AS. Given the exploratory nature of this study, findings require replication in larger samples and adjustment for population stratification to further explore the role of BDNF and CM on AS in mixed race adolescents.
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http://dx.doi.org/10.1080/20008198.2018.1472987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5965035PMC
May 2018