"Congenital cytomegalovirus in Sub-Saharan Africa-a narrative review with practice recommendations".

Cytomegalovirus (CMV) is the most common cause of congenital infection internationally, occurring in 0.67% of births, and increasingly recognised as a major public health burden due to the potential for long-term neurodevelopmental and hearing impairment. This burden includes estimates of 10% of childhood cerebral palsy and up to 25% of childhood deafness. In Sub-Saharan Africa, where CMV-seroprevalence is almost ubiquitous, prevalence of congenital CMV (cCMV) is higher than the global average, and yet there is a dearth of research and initiatives to improve recognition, diagnosis and treatment. This narrative review outlines the epidemiology and clinical presentation of cCMV, discusses issues of case identification and treatment in Sub-Saharan Africa, and recommends a framework of strategies to address these challenges. Considering the significant burden of cCMV disease in this setting, it is undoubtably time we embark upon improving diagnosis and care for these infants.

Discrepancies in Management of Congenital Cytomegalovirus in Preterm Infants: An International Survey.

We performed an international survey regarding management of infants with congenital cytomegalovirus (cCMV) born at less than 32 weeks gestation or with birth weight under 1500 g. Replies from 51 level 3 neonatal intensive care units across 13 countries demonstrated striking discrepancies in screening practices, testing for cCMV, further investigations of confirmed cases, indications for initiation, and duration of treatment.

Delays in diagnosis and treatment initiation for congenital cytomegalovirus infection - Why we need universal screening.

Introduction: Congenital cytomegalovirus (cCMV) is the leading cause of neurodevelopmental and hearing impairment from in-utero infection. Late diagnosis results in limited treatment options and may compromise long-term outcome. Methods: A retrospective audit of infants with cCMV referred to a Tertiary Pediatric Infectious Diseases center from 2012-2021. Data collected included timing of diagnostics, treatment initiation and reasons for delays. Results: 90 infants with confirmed cCMV were included, 46/90 (51%) were symptomatic at birth. Most common reasons for diagnostics in asymptomatic infants were failed newborn hearing screening (17/44, 39%) and antenatal risk-factors (14/44, 32%). Median age at cCMV diagnosis was 3 (range 0-68) and 7 (0-515) days, with median referral age 10 (1-120) and 22 (2-760) days for symptomatic and asymptomatic infants respectively. There was a significant risk of delay in diagnosis (>21 days) for asymptomatic infants [RR 2.93 (1.15-7.45); p = 0.02]. Of asymptomatic infants who received treatment, 13/24 (54%) commenced it within 28 days of life, a significant delay in treatment compared to 30/36 (83%) symptomatic infants [RR 2.75 (1.18-6.43); p = 0.02]. The commonest reason for delayed treatment initiation was delayed first diagnostic test for both symptomatic 4/6 (67%) and asymptomatic infants 9/11 (82%). Conclusions: Delays in diagnosis and treatment for cCMV are unacceptably frequent and significantly higher in asymptomatic infants. Our study highlights the need for increased awareness among healthcare professionals, reconsideration of age-targets for Newborn Hearing Screening, and research that addresses the barriers to implementation of universal screening, which would ultimately facilitate prompt diagnosis and management of all infants with cCMV.

Early ART-initiation and longer ART duration reduces HIV-1 proviral DNA levels in children from the CHER trial.

BACKGROUND: Reduction of the reservoir of latent HIV-infected cells might increase the possibility of long-term remission in individuals living with HIV. We investigated factors associated with HIV-1 proviral DNA levels in children receiving different antiretroviral therapy (ART) strategies in the children with HIV early antiretroviral therapy (CHER) trial. METHODS: Infants with HIV < 12 weeks old with CD4% ≥ 25% were randomized in the CHER trial to early limited ART for 40 or 96 weeks (ART-40 W, ART-96 W), or deferred ART (ART-Def). For ART-Def infants or following ART interruption in ART-40 W/ART-96 W, ART was started/re-started for clinical progression or CD4% < 25%. In 229 participants, HIV-1 proviral DNA was quantified by PCR from stored peripheral blood mononuclear cells from children who had received ≥ 24 weeks ART and two consecutive undetectable HIV-1 RNA 12-24 weeks apart. HIV-1 proviral DNA was compared between ART-Def and ART-96 W at week 96, and in all arms at week 248. Factors associated with HIV-1 proviral DNA levels were evaluated using linear regression. FINDINGS: Longer duration of ART was significantly associated with lower HIV-1 proviral DNA at both 96 (p = 0.0003) and 248 weeks (p = 0.0011). Higher total CD8 count at ART initiation was associated with lower HIV-1 proviral DNA at both 96 (p = 0.0225) and 248 weeks (p = 0.0398). Week 248 HIV-1 proviral DNA was significantly higher in those with positive HIV-1 serology at week 84 than those with negative serology (p = 0.0042). INTEPRETATION: Longer ART duration is key to HIV-1 proviral DNA reduction. Further understanding is needed of the effects of "immune-attenuation" through early HIV-1 exposure. FUNDING: Wellcome Trust, National Institutes of Health, Medical Research Council.

Direct and Ambient Light Pollution Alters Recruitment for a Diurnal Plant-Pollinator System.

Artificial light at night (ALAN) functions as a novel environmental stimulus that has the potential to disrupt interactions among species. Despite recent efforts to explain nocturnal pollinators' responses to this stimulus, the likelihood and associated mechanisms of attraction toward artificial light and potential consequences on fitness for diurnal pollinators are still largely unclear. Here, we took advantage of the obligate mutualism between yucca moths (Tegeticula maculata maculata) and yucca plants (Hesperoyucca whipplei) to understand how direct light exposure and skyglow can influence a pairwise plant-pollinator interaction. To surmise whether adult moths exhibit positive phototaxis, we deployed a set of field-placed light towers during the peak of yucca flowering and compared the number of moths caught in traps between dark-controlled and light-treated trials. Adult moth abundance was much higher when light was present, which suggests that ALAN may alter this diurnal moth's activity patterns to expand their temporal niche into the night. To evaluate ALAN effects on yucca fruit set and moth larva recruitment, we measured skyglow exposure above yucca plants and direct light intensity from a second set of light towers. Both larva and fruit recruitment increased with skyglow, and fruit set also increased with direct lighting, but the relationship was weaker. Contrarily, larva recruitment did not change when exposed to a gradient of direct light, which may instead reflect effects of ALAN on moth physiology, such as disrupted female oviposition, or misdirecting behaviors essential to oviposition activity. Our results suggest that ALAN can positively influence the fitness of both plants and moths in this tightly co-evolved mutualism, but the benefits to each species may depend on whether night lighting is direct or indirect. Whether such effects and mechanisms could relate to susceptibility to the presence of ALAN on this or other plant-pollinator relationships will remain an important focus of future research.

A Qualitative Study of the Views of Patients With Medically Unexplained Symptoms on The BodyMind Approach®: Employing Embodied Methods and Arts Practices for Self-Management.

The arts provide openings for symbolic expression by engaging the sensory experience in the body they become a source of insight through embodied cognition and emotion, enabling meaning-making, and acting as a catalyst for change. This synthesis of sensation and enactive, embodied expression through movement and the arts is capitalized on in The BodyMind Approach® (TBMA). It is integral to this biopsychosocial, innovative, unique intervention for people suffering medically unexplained symptoms (MUS) applied in primary healthcare. The relevance of embodiment and arts practices in TBMA are discussed in relation to the views of participants in the pursuit of self-management. If widely employed TBMA could have an enormous impact, reach, and significance for patients and global health services. This original pre-clinical trial of qualitative research reports on the perceptions of participant patients with generic MUS, a world-wide issue usually treated by either psychological therapy or physiotherapy. TBMA is not a therapy but a health education program founded upon the concept of an integration of psychological elements with physiological, bodily, and sensory experiences. Thematic analysis of qualitative data sets from open-ended questions in semi-structured interviews and a written questionnaire post intervention is presented. Five aspects which appear to be key to learning self-management were derived from analyzing the data: (1) body with mind connections; (2) importance of facilitation; (3) potential benefits; (4) preparedness for change; (5) self-acceptance/compassion. This article advances the discourse on the nature of self-management for MUS through changing the mind-set and the relationship participants have with their bodily symptom/s through employing embodied methods and arts practices, challenging current, and solely verbal, psychological conceptual frameworks. Rigor lies in the method of data analysis using cross verification of credibility between reported findings and scrutiny by stakeholders. We conclude that facilitated TBMA groups employing embodied methods and arts practices can act as a method for developing the self-management of MUS and improving wellbeing.

Comparison of Lymphocyte Subset Populations in Children From South Africa, US and Europe.

Background: Typically, African healthcare providers use immunological reference intervals adopted from Europe and the United States (US). This may be inappropriate in a setting with many differences including exposure to different environmental stimuli and pathogens. We compared immunological reference intervals for children from Europe and the US with South African children to explore whether healthy children living in settings with high rates of infectious diseases have different baseline immunological parameters. Methodology: Blood was taken from 381 HIV-uninfected children aged between 2 weeks and 13 years of age from a Child Wellness Clinic in an informal settlement in Cape Town to establish local hematological and lymphocyte reference intervals for South African children. Flow-cytometry quantified percentage and absolute counts of the B-cells, NK-cells, and T-cells including activated, naïve, and memory subsets. These parameters were compared to three separate studies of healthy children in Europe and the US. Results: Increased activated T-cells, and natural killer cells were seen in the younger age-groups. The main finding across all age-groups was that the ratio of naïve/memory CD4 and CD8 T-cells reached a 1:1 ratio around the first decade of life in healthy South African children, far earlier than in resource-rich countries, where it occurs around the fourth decade of life. Conclusions: This is the largest data set to date describing healthy children from an African environment. These data have been used to create local reference intervals for South African children. The dramatic decline in the naïve/memory ratio of both CD4 and CD8 T-cells alongside increased activation markers may indicate that South African children are exposed to a wider range of environmental pathogens in early life than in resource-rich countries. These marked differences illustrate that reference intervals should be relevant to the population they serve. The implications for the developing pediatric immune system requires further investigation.

Medically Unexplained Symptoms and Attachment Theory: The BodyMind Approach®.

This article discusses how The BodyMind Approach® (TBMA) addresses insecure attachment styles in medically unexplained symptoms (MUS). Insecure attachment styles are associated with adverse childhood experiences (ACEs) and MUS (Adshead and Guthrie, 2015) and affect sufferers' capacity to self-manage. The article goes on to make a new hypothesis to account for TBMA's effectiveness (Payne and Brooks, 2017), that is, it addresses insecure attachment styles, which may be present in some MUS sufferers, leading to their capacity to self-manage. Three insecure attachment styles (dismissive, pre-occupied and fearful) associated with MUS are discussed. TBMA is described and explanations provided of how TBMA has been specifically designed to support people's insecure attachment styles. Three key concepts to support insecure attachment styles involved in the content of TBMA are identified and debated: (a) emotional regulation; (b) safety; and (c) bodymindfulness. There is a rationale for the design of TBMA as opposed to psychological interventions for this population. The programme's structure, facilitation and content, takes account of the three insecure attachment styles above. Examples of how TBMA works with their specific characteristics are presented. TBMA has been tested and found to be effective during delivery in the United Kingdom National Health Service (NHS). Improved self-management has potential to reduce costs for the NHS and in General Practitioner time and resources.

Corrigendum: Different Strokes for Different Folks: The BodyMind Approach as a Learning Tool for Patients With Medically Unexplained Symptoms to Self-Manage.

[This corrects the article DOI: 10.3389/fpsyg.2018.02222.].

Naive B Cell Output in HIV-Infected and HIV-Uninfected Children.

In this study, we aimed to quantify KREC (kappa-deleting recombination excision circle) levels and naive B cell output in healthy HIV-uninfected children, compared with HIV-infected South African children, before and after starting ART (antiretroviral therapy). Samples were acquired from a Child Wellness Clinic (n = 288 HIV-uninfected South African children, 2 weeks-12 years) and the Children with HIV Early Antiretroviral Therapy (CHER) trial (n = 153 HIV-infected South African children, 7 weeks-8 years). Naive B cell output was estimated using a mathematical model combining KREC levels to reflect B cell emigration into the circulation, flow cytometry measures of naive unswitched B cells to quantify total body naive B cells, and their rates of proliferation using the intracellular marker Ki67. Naive B cell output increases from birth to 1 year, followed by a decline and plateau into late childhood. HIV-infected children on or off ART had higher naive B cell outputs than their uninfected counterparts (p = .01 and p = .04). This is the first study to present reference ranges for measurements of KRECs and naive B cell output in healthy and HIV-infected children. Comparison between HIV-uninfected healthy children and HIV-infected children suggests that HIV may increase naive B cell output. Further work is required to fully understand the mechanisms involved and clinical value of measuring naive B cell output in children.