The association of maternal HIV status during pregnancy on longitudinal neuro-immune regulation, and neurodevelopment in HIV-exposed uninfected children

Introduction: It has long been established that the Human Immunodeficiency Virus (HIV) and its effects, such as its impact on the immune system and then the numerous consequences on other biological systems including the central nervous system (CNS), have had a significant effect worldwide. This is particularly relevant in South Africa, where the prevalence of adults living with HIV remains high. However, with the improved access to antiretroviral therapy (ART), more children are now being born uninfected with HIV while still being exposed to the virus in utero. Exposure to HIV in utero may still negatively affect the developing brain of these children. However, the biological mechanisms involved in the neurodevelopmental outcomes in HIV-exposed uninfected (HEU) children are still largely unknown. Evidence from clinical studies showed that HEU children have an altered immune regulation compared to their unexposed counterparts, and this is hypothesised to play a role in neurodevelopmental outcomes in HEU children. The aim of this study was to evaluate the longitudinal relationship between the inflammatory environment of pregnant mothers living with HIV on ART and their children and the association of the inflammatory environment with neurodevelopmental outcomes in HEU children. Methods: This study was performed in a sub-sample of the Drakenstein Child Health Study (DCHS), a South African birth cohort of 1137 mother-infant pairs. This sub-study included mothers at ≈26 weeks gestation (n=267), their infants at 6-10 weeks (n=222) and children at 24-28 months (n=267). Maternal HIV status was determined at ≈26 weeks gestation. This sub-study included n=190 HIV negative mother-infant pairs and n=77 HIV positive mother-infant pairs. Serum inflammatory markers (Granulocyte-macrophage colony-stimulating factor (GM CSF), Interferon-γ (IFN-γ), Interleukin IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumour necrosis factor-α (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL/Lcn2) and metalloproteinase-9 (MMP-9)) were analyzed in all study participants with a multiplex bead array and ELISA. The Bayley Scales of Infant and Toddler Development (Bayley-III) were used to assess the neurodevelopmental domains: cognitive, motor, language, social-emotional behaviour and adaptive behaviour at 24-28 months of age. Results: Mothers living with HIV on ART had significantly lower levels of the inflammatory markers GM-CSF and MMP9 compared to mothers without HIV. Serum levels of inflammatory markers IFN-γ and IL-1β were significantly lower in HEU infants at 6-10 weeks compared to HIV-unexposed uninfected (HUU) infants. At 24-28 months of age, HEU children also proved to have significantly lower serum levels of the inflammatory markers IFN-γ, IL-1β, IL-2 and IL-4 compared with HUU children. Increased levels of the inflammatory markers; GM-CSF, IFN-γ, IL-10, IL-12p70, IL-1β, IL-2, IL-4, IL-6 and Lcn2 in HEU infants at 6-10 weeks of age was associated with impaired motor neurodevelopment at 24-28 months of age. Conclusion: This is the first study to evaluate the longitudinal associations of immune markers with neurodevelopment in HEU children. The results show that maternal HIV infection was associated with lower levels of inflammatory markers in mothers and their children. Our results further indicate that an altered immune system in HEU infants, specifically at the earliest stages of life, was associated with impaired motor function at 2 years of age. These findings may provide further insights into the involvement of immune regulation, linking maternal HIV status and neurodevelopment in South African HEU children

Association of maternal and infant inflammation with neurodevelopment in HIV-exposed uninfected children in a South African birth cohort.

HIV-exposed uninfected (HEU) children may have altered immune regulation and poorer neurodevelopment outcomes compared to their HIV-unexposed (HU) counterparts. However, studies investigating the association of maternal and infant inflammation with neurodevelopment in HEU children are limited and longitudinal data are lacking. This study investigated serum inflammatory markers in women living with HIV vs. HIV-uninfected women during pregnancy and in their children, as well as associations with neurodevelopmental outcomes at two years of age in an African birth cohort study. A sub-group of mother-child dyads from the Drakenstein Child Health Study had serum inflammatory markers measured at ?26?week's gestation (n?=?77 HIV-infected mothers; n?=?190 HIV-uninfected mothers), at 6-10?weeks (n?=?63 HEU infants and n?=?159 HU infants) and at 24-28?months (n?=?77 HEU children and n?=?190 HU children). Serum inflammatory markers [granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-? (IFN-?), interleukin IL-1?, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor-? (TNF-?), neutrophil gelatinase-associated lipocalin (NGAL) and metalloproteinase-9 (MMP-9)] were analyzed with a multiplex bead array and ELISA assays. The Bayley Scales of Infant and Toddler Development, third edition, was used to assess neurodevelopment at 24-28?months. After correcting for multiple comparisons, HIV infection during pregnancy was associated with lower serum levels of inflammatory markers in mothers at 26?weeks gestation (GM-CSF and MMP-9, p?<?0.05) and HEU children at 6-10?weeks (IFN-? and IL-1?, p?<?0.01), and at 24-28?months (IFN-?, IL-1?, IL-2 and IL-4, p?<?0.05) compared to HIV-uninfected mothers and HU children. In HEU infants at 6-10?weeks, inflammatory markers (GM-CSF, IFN-?, IL-10, IL-12p70, IL-1?, IL-2, IL-4, IL-6 and NGAL, all p?<?0.05) were associated with poorer motor function at two years of age. This is the first study to evaluate the associations of follow-up immune markers in HEU children with neurodevelopment. These findings suggest that maternal HIV infection is associated with immune dysregulation in mothers and their children through two years of age. An altered immune system in HEU infants is associated with poorer follow-up motor neurodevelopment. These data highlight the important role of the immune system in early neurodevelopment and provide a foundation for future research

The application of antimicrobial stewardship knowledge to nursing practice : A national survey of United Kingdom pre-registration nursing students

© 2024 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/AIM: To assess student nurses understanding and skills in the application of antimicrobial stewardship knowledge to practice. DESIGN: Quantitative. METHODS: Cross-sectional survey. RESULTS: Five hundred and twenty three student nurses responded across 23 UK universities. Although students felt prepared in competencies in infection prevention and control, patient-centred care and interprofessional collaborative practice, they felt less prepared in competencies in which microbiological knowledge, prescribing and its effect on antimicrobial stewardship is required. Problem-based learning, activities in the clinical setting and face-to-face teaching were identified as the preferred modes of education delivery. Those who had shared antimicrobial stewardship teaching with students from other professions reported the benefits to include a broader understanding of antimicrobial stewardship, an understanding of the roles of others in antimicrobial stewardship and improved interprofessional working. CONCLUSION: There are gaps in student nurses' knowledge of the basic sciences associated with the antimicrobial stewardship activities in which nurses are involved, and a need to strengthen knowledge in pre-registration nurse education programmes pertaining to antimicrobial management, specifically microbiology and antimicrobial regimes and effects on antimicrobial stewardship. Infection prevention and control, patient-centred care and interprofessional collaborative practice are areas of antimicrobial stewardship in which student nurses feel prepared. Interprofessional education would help nurses and other members of the antimicrobial stewardship team clarify the role nurses can play in antimicrobial stewardship and therefore maximize their contribution to antimicrobial stewardship and antimicrobial management. IMPLICATIONS FOR THE PROFESSION: There is a need to strengthen knowledge from the basic sciences, specifically pertaining to antimicrobial management, in pre-registration nurse education programmes. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. IMPACT: What Problem Did the Study Address? Nurses must protect health through understanding and applying antimicrobial stewardship knowledge and skills (Nursing and Midwifery Council 2018); however, there is no research available that has investigated nurses understanding and skills of the basic sciences associated with the antimicrobial stewardship activities in which they are involved. What Were the Main Findings? There are gaps in student nurses' knowledge of the basic sciences (specifically microbiology and prescribing) associated with the antimicrobial stewardship activities in which nurses are involved. Problem-based learning, and activities in the clinical setting, were reported as useful teaching methods, whereas online learning, was seen as less useful. Where and on Whom Will the Research Have an Impact? Pre-registration nurse education programmes. REPORTING METHOD: The relevant reporting method has been adhered to, that is, STROBE.Peer reviewe

Delivery of antimicrobial stewardship competencies in UK pre-registration nurse education programmes: a national cross-sectional survey

Background: Registered nurses perform numerous functions critical to the success of antimicrobial stewardship but only 63% of pre-registration nursing programmes include any teaching about stewardship. Updated nursing standards highlight nurses require antimicrobial stewardship knowledge and skills. Aim: To explore the delivery of key antimicrobial stewardship competencies within updated pre-registration nursing programmes. Method: A cross-sectional survey design. Data was collected between March and June 2021. Findings: Lecturers from 35 universities responsible for teaching antimicrobial stewardship participated. The provision of antimicrobial stewardship teaching and learning was inconsistent across programmes with competencies in infection prevention and control, patient centred care, and interprofessional collaborative practice taking precedent over those pertaining to the use, management, and monitoring of antimicrobials. On-line learning and teaching surrounding hand hygiene, personal protective equipment, and immunisation theory was reported to have increased during the pandemic. Only a small number of respondents reported that students shared taught learning with other healthcare professional groups. Conclusion: There is a need to ensure consistency in antimicrobial stewardship across programmes, and greater knowledge pertaining to the use, management and monitoring of antimicrobials should be included. Programmes need to adopt teaching strategies and methods that allow nurses to develop interprofessional skill in order to practice collaboratively

The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiency

<p>Abstract</p> <p>Background</p> <p>Genetic variation may underlie phenotypic variation in chronic obstructive pulmonary disease (COPD) in subjects with and without alpha 1 antitrypsin deficiency (AATD). Genotype specific sub-phenotypes are likely and may underlie the poor replication of previous genetic studies. This study investigated subjects with AATD to determine the relationship between specific phenotypes and <it>TNFα </it>polymorphisms.</p> <p>Methods</p> <p>424 unrelated subjects of the PiZZ genotype were assessed for history of chronic bronchitis, impairment of lung function and radiological presence of emphysema and bronchiectasis. A subset of subjects with 3 years consecutive lung function data was assessed for decline of lung function. Four single nucleotide polymorphisms (SNPs) tagging <it>TNFα </it>were genotyped using TaqMan^®genotyping technologies and compared between subjects affected by each phenotype and those unaffected. Plasma TNFα levels were measured in all PiZZ subjects.</p> <p>Results</p> <p>All SNPs were in Hardy-Weinberg equilibrium. A significant difference in rs361525 genotype (p = 0.01) and allele (p = 0.01) frequency was seen between subjects with and without chronic bronchitis, independent of the presence of other phenotypes. TNFα plasma level showed no phenotypic or genotypic associations.</p> <p>Conclusion</p> <p>Variation in <it>TNFα </it>is associated with chronic bronchitis in AATD.</p

IL6 and CRP haplotypes are associated with COPD risk and systemic inflammation: a case-control study

<p>Abstract</p> <p>Background</p> <p>Elevated circulating levels of C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen (FG) have been repeatedly associated with many adverse outcomes in patients with chronic obstructive pulmonary disease (COPD). To date, it remains unclear whether and to what extent systemic inflammation is primary or secondary in the pathogenesis of COPD.</p> <p>The aim of this study was to examine the association between haplotypes of <it>CRP</it>, <it>IL6 </it>and <it>FGB </it>genes, systemic inflammation, COPD risk and COPD-related phenotypes (respiratory impairment, exercise capacity and body composition).</p> <p>Methods</p> <p>Eighteen SNPs in three genes, representing optimal haplotype-tagging sets, were genotyped in 355 COPD patients and 195 healthy smokers. Plasma levels of CRP, IL-6 and FG were measured in the total study group. Differences in haplotype distributions were tested using the global and haplotype-specific statistics.</p> <p>Results</p> <p>Raised plasma levels of CRP, IL-6 and fibrinogen were demonstrated in COPD patients. However, COPD population was very heterogeneous: about 40% of patients had no evidence of systemic inflammation (CRP < 3 mg/uL or no inflammatory markers in their top quartile). Global test for haplotype effect indicated association of <it>CRP </it>gene and CRP plasma levels (P = 0.0004) and <it>IL6 </it>gene and COPD (P = 0.003). Subsequent analysis has shown that <it>IL6 </it>haplotype H2, associated with an increased COPD risk (p = 0.004, OR = 4.82; 1.64 to 4.18), was also associated with very low CRP levels (p = 0.0005). None of the genes were associated with COPD-related phenotypes.</p> <p>Conclusion</p> <p>Our findings suggest that common genetic variation in <it>CRP </it>and <it>IL6 </it>genes may contribute to heterogeneity of COPD population associated with systemic inflammation.</p

The genetics of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease caused by the interaction of genetic susceptibility and environmental influences. There is increasing evidence that genes link to disease pathogenesis and heterogeneity by causing variation in protease anti-protease systems, defence against oxidative stress and inflammation. The main methods of genomic research for complex disease traits are described, together with the genes implicated in COPD thus far, their roles in disease causation and the future for this area of investigation

The BARCODE1 Pilot: a feasibility study of using germline single nucleotide polymorphisms to target prostate cancer screening

Funder: FP7 Ideas: European Research Council; Id: http://dx.doi.org/10.13039/100011199; Grant(s): ERC‐2013‐AdG‐339208Objectives: To assess the feasibility and uptake of a community‐based prostate cancer (PCa) screening programme selecting men according to their genetic risk of PCa. To assess the uptake of PCa screening investigations by men invited for screening. The uptake of the pilot study would guide the opening of the larger BARCODE1 study recruiting 5000 men. Subjects and Methods: Healthy males aged 55–69 years were invited to participate via their general practitioners (GPs). Saliva samples were collected via mailed collection kits. After DNA extraction, genotyping was conducted using a study specific assay. Genetic risk was based on genotyping 130 germline PCa risk single nucleotide polymorphisms (SNPs). A polygenic risk score (PRS) was calculated for each participant using the sum of weighted alleles for 130 SNPs. Study participants with a PRS lying above the 90th centile value were invited for PCa screening by prostate magnetic resonance imaging (MRI) and biopsy. Results: Invitation letters were sent to 1434 men. The overall study uptake was 26% (375/1436) and 87% of responders were eligible for study entry. DNA genotyping data were available for 297 men and 25 were invited for screening. After exclusions due to medical comorbidity/invitations declined, 18 of 25 men (72%) underwent MRI and biopsy of the prostate. There were seven diagnoses of PCa (38.9%). All cancers were low‐risk and were managed with active surveillance. Conclusion: The BARCODE1 Pilot has shown this community study in the UK to be feasible, with an overall uptake of 26%. The main BARCODE1 study is now open and will recruit 5000 men. The results of BARCODE1 will be important in defining the role of genetic profiling in targeted PCa population screening. Patient Summary: What is the paper about?: Very few prostate cancer screening programmes currently exist anywhere in the world. Our pilot study investigated if men in the UK would find it acceptable to have a genetic test based on a saliva sample to examine their risk of prostate cancer development. This test would guide whether men are offered prostate cancer screening tests. What does it mean for patients?: We found that the study design was acceptable: 26% of men invited to take part agreed to have the test. The majority of men who were found to have an increased genetic risk of prostate cancer underwent further tests offered (prostate MRI scan and biopsy). We have now expanded the study to enrol 5000 men. The BARCODE1 study will be important in examining whether this approach could be used for large‐scale population prostate cancer screening