Publications by authors named "Martha Holmes"

Introduction: Short-read amplicon sequencing studies have typically focused on 1-2 variable regions of the 16S rRNA gene. Species-level resolution is limited in these studies, as each variable region enables the characterisation of a different subsection of the microbiome. Although long-read sequencing techniques take advantage of all 9 variable regions by sequencing the entire 16S rRNA gene, they are substantially more expensive.

View Article and Find Full Text PDF

HIV exposed-uninfected (HEU) infants and children are at risk of developmental delays as compared to HIV uninfected unexposed (HUU) populations. The effects of exposure to in utero HIV and ART regimens on the HEU the developing brain are not well understood. In a cohort of 2-week-old newborns, we used diffusion tensor imaging (DTI) tractography and graph theory to examine the influence of HIV and ART exposure in utero on neonate white matter integrity and organisation.

View Article and Find Full Text PDF

Introduction: School-aged children experience crucial developmental changes in white matter (WM) in adolescence. The human immunodeficiency virus (HIV) affects neurodevelopment. Children living with perinatally acquired HIV (CPHIVs) demonstrate hearing and neurocognitive impairments when compared to their uninfected peers (CHUUs), but investigations into the central auditory system (CAS) WM integrity are lacking.

View Article and Find Full Text PDF

HIV exposed-uninfected (HEU) infants and children are at risk of developmental delays as compared to uninfected unexposed (HUU) populations. The effects of exposure to HIV and ART regimens on the HEU the developing brain are not well understood. In a cohort of 2-week-old newborns, we used diffusion tensor imaging (DTI) tractography and graph theory to examine the influence of HIV and ART exposure on neonate white matter integrity and organisation.

View Article and Find Full Text PDF

Hearing loss places a substantial burden on medical resources across the world and impacts quality of life for those affected. Further, it can occur peripherally and/or centrally. With many possible causes of hearing loss, there is scope for investigating the underlying mechanisms involved.

View Article and Find Full Text PDF
Article Synopsis
  • - Successful programs in South Africa have significantly reduced the rate of infant HIV infection from 8% in 2008 to less than 1% in 2018/2019, increasing the number of HIV-exposed but uninfected (HEU) children, although their neurodevelopmental outcomes are not as strong compared to unexposed children.
  • - The study focused on 120 infants, including 79 HEU babies, to assess the impact of maternal HIV and antiretroviral treatment (ART) on brain development, specifically examining differences in subcortical brain regions via imaging.
  • - Results indicated that HEU infants had smaller volumes in certain brain areas, particularly the left putamen and caudate
View Article and Find Full Text PDF

Background: Life-long early ART (started before age 2 years), often with periods of treatment interruption, is now the standard of care in pediatric HIV infection. Although cross-sectional studies have investigated HIV-related differences in cortical morphology in the setting of early ART and ART interruption, the long-term impact on cortical developmental trajectories is unclear. This study compares the longitudinal trajectories of cortical thickness and folding (gyrification) from age 5 to 9 years in a subset of children perinatally infected with HIV (CPHIV) from the Children with HIV Early antiRetroviral therapy (CHER) trial to age-matched children without HIV infection.

View Article and Find Full Text PDF

Children with perinatally acquired HIV (CPHIV) have poor cognitive outcomes despite early combination antiretroviral therapy (cART). While CPHIV-related brain alterations can be investigated separately using proton magnetic resonance spectroscopy ( H-MRS), structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and functional MRI (fMRI), a set of multimodal MRI measures characteristic of children on cART has not been previously identified. We used the embedded feature selection of a logistic elastic-net (EN) regularization to select neuroimaging measures that distinguish CPHIV from controls and measured their classification performance via the area under the receiver operating characteristic curve (AUC) using repeated cross validation.

View Article and Find Full Text PDF

ART interruption in children can occur especially in resource-limited settings for reasons including poor adherence, stock-outs, ART intolerance of non-pediatric formulas and pill size, as well as ultimately to test for HIV remission. Although early ART initiation is now standard of care in pediatric HIV management, very little is known on the effect of early ART initiation or subsequent interruption on brain development. This study aimed to investigate the effect of ART interruption on brain cortical thickness (CT) and folding in a subset of children from the Children with HIV Early antiRetroviral therapy (CHER) trial cohort who all started ART before 18 months of age.

View Article and Find Full Text PDF

Even with the increased access and early initiation of combination antiretroviral therapy, children with perinatally acquired human immunodeficiency virus (CPHIV) continue to demonstrate white matter alterations. Children perinatally HIV-exposed, but uninfected (CHEU) alike show differences in white matter integrity compared with children who are HIV-unexposed and uninfected (CHUU). Mapping white matter connections that link gray matter regions that form resting-state (RS) functional networks may demonstrate whether structural and functional connectivity alterations in HIV infection and exposure may be related.

View Article and Find Full Text PDF

Treatment guidelines recommend that children with perinatal HIV infection (PHIV) initiate antiretroviral therapy (ART) early in life and remain on it lifelong. As part of a longitudinal study examining the long-term consequences of PHIV and early ART on the developing brain, 89 PHIV children and a control group of 85 HIV uninfected children (HIV-) received neuroimaging at ages 5, 7, 9 and 11 years, including single voxel magnetic resonance spectroscopy (MRS) in three brain regions, namely the basal ganglia (BG), midfrontal gray matter (MFGM) and peritrigonal white matter (PWM). We analysed age-related changes in absolute metabolite concentrations using a multivariate approach traditionally applied to ecological data, the Correlated Response Model (CRM) and compared these to results obtained from a multilevel mixed effect modelling (MMEM) approach.

View Article and Find Full Text PDF

The neurological changes in children living with perinatal HIV (PHIV) on antiretroviral therapy (ART) can be studied at a metabolic level through proton magnetic resonance spectroscopy. While previous studies in children have largely focused on individual metabolite changes, investigating patterns within and across regions of interest can aid in identifying metabolic markers of HIV infection. In this study 76 children with PHIV from the Children with HIV Early AntiRetroviral (CHER) trial, 30 children who were HIV-exposed-uninfected (HEU) and 30 children who were HIV-unexposed (HU), were scanned at the age of 11.

View Article and Find Full Text PDF

Abnormalities of the basal ganglia are frequently seen in HIV-infected (HIV+) children despite antiretroviral treatment (ART) initiation during childhood. Assessment of metabolites associated with neuronal integrity or with glial proliferation can present a sensitive description of metabolic events underlying basal ganglia structural changes. We used magnetic resonance spectroscopy to examine differences in creatine, choline, -acetylaspartate (NAA), glutamate, and myo-inositol between HIV+ children and HIV-unexposed controls, as well as between HIV-exposed uninfected (HEU) children and HIV-unexposed controls at age 7 and at age 9.

View Article and Find Full Text PDF

Although HIV has been shown to impact brain connectivity in adults and youth, it is not yet known to what extent long-term early antiretroviral therapy (ART) may alter these effects, especially during rapid brain development in early childhood. Using both independent component analysis (ICA) and seed-based correlation analysis (SCA), we examine the effects of HIV infection in conjunction with early ART on resting state functional connectivity (FC) in 7 year old children. HIV infected (HIV+) children were from the Children with HIV Early Antiretroviral Therapy (CHER) trial and all initiated ART before 18 months; uninfected children were recruited from an interlinking vaccine trial.

View Article and Find Full Text PDF

Even with the increased roll out of combination antiretroviral therapy (cART), paediatric HIV infection is associated with neurodevelopmental delays and neurocognitive deficits that may be accompanied by alterations in brain structure. Few neuroimaging studies have been done in children initiating ART before 2 years of age, and even fewer in children within the critical stage of brain development between 5 and 11 years. We hypothesized that early ART would limit HIV-related brain morphometric deficits at age 7.

View Article and Find Full Text PDF

Sub-Saharan Africa is home to 90% of HIV infected (HIV+) children. Since the advent of antiretroviral therapy (ART), HIV/AIDS has transitioned to a chronic condition where central nervous system (CNS) damage may be ongoing. Although, most guidelines recommend early ART to reduce CNS viral reservoirs, the brain may be more vulnerable to potential neurotoxic effects of ART during the rapid development phase in the first years of life.

View Article and Find Full Text PDF

Due to changes in guidelines and access to treatment, more children start combination antiretroviral therapy (ART) in infancy. With few studies examining the long-term effects of perinatal HIV infection and early ART on neurodevelopment, much is still unknown about brain maturation in the presence of HIV and ART. Follow-up studies of HIV infected (HIV+) children are important for monitoring brain development in the presence of HIV infection and ART.

View Article and Find Full Text PDF

Longitudinal magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) studies reveal significant changes in brain structure and structural networks that occur together with cognitive and behavioral maturation in childhood. However, the underlying cellular changes accompanying brain maturation are less understood. Examining regional age-related changes in metabolite levels provides insight into the physiology of neurodevelopment.

View Article and Find Full Text PDF

Objective: Investigating consequences of early or late antiretroviral therapy (ART) initiation in infancy on young brain development using magnetic resonance spectroscopy.

Design: Most pediatric HIV/ART-related neurological studies are from neuropsychological/clinical perspectives. Magnetic resonance spectroscopy can elucidate the mechanisms underpinning neurocognitive outcomes by quantifying the brain's chemical condition through localized metabolism to provide insights into health and development.

View Article and Find Full Text PDF

As the recent Ebola outbreak demonstrates, visibility is central to the shaping of political, medical, and socioeconomic decisions. The symposium in this issue of the Journal of Bioethical Inquiry explores the uneasy relationship between the necessity of making diseases visible, the mechanisms of legal and visual censorship, and the overall ethics of viewing and spectatorship, including the effects of media visibility on the perception of particular "marked" bodies. Scholarship across the disciplines of communication, anthropology, gender studies, and visual studies, as well as a photographer's visual essay and memorial reflection, throw light on various strategies of visualization and (de)legitimation and link these to broader socioeconomic concerns.

View Article and Find Full Text PDF

Temporal-lobe epilepsy (TLE) involves seizures that typically originate in the hippocampus. There is evidence that seizures involve anatomically and functionally connected brain networks within and beyond the temporal lobe. Many studies have explored the effect of TLE on gray matter and resting-state functional connectivity in the brain.

View Article and Find Full Text PDF

The majority of patients with temporal lobe epilepsy (TLE) experience disturbances of episodic memory from structural damage or dysfunction of the hippocampus. The objective of this study was to use functional Magnetic Resonance Imaging (fMRI) to identify regions where resting state connectivity to the left hippocampus (LH) is correlated with neuropsychological measures of verbal memory retention in TLE patients. Eleven left TLE (LTLE) patients and 15 control subjects participated in resting state fMRI scans.

View Article and Find Full Text PDF

Ultra-high field 7T magnetic resonance imaging (MRI) offers potentially unprecedented spatial resolution of functional activity within the human brain through increased signal and contrast to noise ratios over traditional 1.5T and 3T MRI scanners. However, the effects physiological and imaging artifacts are also greatly increased.

View Article and Find Full Text PDF