A comprehensive method for the phenotypical and functional characterization of recalled human memory B and T cells specific to vaccine antigens.

Current methodologies for assessing vaccine effectiveness and longevity primarily center on measuring vaccine-induced neutralizing antibodies in serum or plasma. However, these methods overlook additional parameters such as the presence of memory B cells, even as antibody levels wane, and the pivotal role played by memory T cells in shaping antigen-specific memory B cell responses. Several studies have employed a combination of polyclonal activators, such as CpG and R848, along with various cytokines to provoke the recall of memory B cells from peripheral blood mononuclear cells (PBMCs) into antibody-secreting cells (ASCs). Other studies have examined the use of live attenuated viruses to stimulate antigen-specific memory T cells within PBMCs into effector T cells that produce Th1/Th2 cytokines. However, these studies have not fully elucidated the distinct effects of these polyclonal activators on individual subsets, nor have they evaluated whether the vaccine antigen alone is sufficient to trigger the recall of memory T cells. Thus, in this study, we directly compared the capacity of two B cell polyclonal activators to induce the transition of existing vaccine-specific memory cells present in peripheral blood samples into ASCs. Simultaneously, we also assessed the transition of existing memory T cells into effector subsets in response to vaccine antigens. Our findings demonstrate that both polyclonal activator combinations, CpG with IL-6 and IL-15, as well as R848 with IL-2, effectively induce the terminal differentiation of memory B cells into ASCs. Notably, CpG treatment preferentially expanded naïve and non-class-switched B cells, while R848 expanded class-switched memory cells, plasmablasts, and plasma cells. Consequently, R848 treatment led to a greater overall production of total and antigen-specific IgG immunoglobulins. Additionally, the exposure of isolated PBMCs to vaccine antigens alone proved sufficient for recalling the rare antigen-specific memory T cells into effector subsets, predominantly consisting of IFN-γ-producing CD4 T cells and TNF-ß-producing CD8 T cells. This study not only establishes a rationale for the selection of methods to expand and detect antigen-specific lymphocyte subsets but also presents a means to quantify vaccine effectiveness by correlating serum antibody levels with preexisting memory cells within peripheral blood samples.

A comprehensive trial on PFAS remediation: hemp phytoextraction and PFAS degradation in harvested plants.

Per- and polyfluoroalkyl substances (PFAS) are a class of recalcitrant, highly toxic contaminants, with limited remediation options. Phytoremediation - removal of contaminants using plants - is an inexpensive, community-friendly strategy for reducing PFAS concentrations and exposures. This project is a collaboration between the Mi'kmaq Nation, Upland Grassroots, and researchers at several institutions who conducted phytoremediation field trials using hemp to remove PFAS from soil at the former Loring Air Force base, which has now been returned to the Mi'kmaq Nation. PFAS were analyzed in paired hemp and soil samples using targeted and non-targeted analytical approaches. Additionally, we used hydrothermal liquefaction (HTL) to degrade PFAS in the harvested hemp tissue. We identified 28 PFAS in soil and found hemp uptake of 10 of these PFAS. Consistent with previous studies, hemp exhibited greater bioconcentration for carboxylic acids compared to sulfonic acids, and for shorter-chain compounds compared to longer-chain. In total, approximately 1.4 mg of PFAS was removed from the soil via uptake into hemp stems and leaves, with an approximate maximum of 2% PFAS removed from soil in the most successful area. Degradation of PFAS by HTL was nearly 100% for carboxylic acids, but a portion of sulfonic acids remained. HTL also decreased precursor PFAS and extractable organic fluorine. In conclusion, while hemp phytoremediation does not currently offer a comprehensive solution for PFAS-contaminated soil, this project has effectively reduced PFAS levels at the Loring site and underscores the importance of involving community members in research aimed at remediating their lands.

PFAS remediation in soil: An evaluation of carbon-based materials for contaminant sequestration.

The presence of per- and poly-fluoroalkyl substances (PFAS) in soils is a global concern as these emerging contaminants are highly resistant to degradation and cause adverse effects on human and environmental health at very low concentrations. Sequestering PFAS in soils using carbon-based materials is a low-cost and effective strategy to minimize pollutant bioavailability and exposure, and may offer potential long-term remediation of PFAS in the environment. This paper provides a comprehensive evaluation of current insights on sequestration of PFAS in soil using carbon-based sorbents. Hydrophobic effects originating from fluorinated carbon (C-F) backbone "tail" and electrostatic interactions deriving from functional groups on the molecules' "head" are the two driving forces governing PFAS sorption. Consequently, varying C-F chain lengths and polar functional groups significantly alter PFAS availability and leachability. Furthermore, matrix parameters such as soil organic matter, inorganic minerals, and pH significantly impact PFAS sequestration by sorbent amendments. Materials such as activated carbon, biochar, carbon nanotubes, and their composites are the primary C-based materials used for PFAS adsorption. Importantly, modifying the carbon structural and surface chemistry is essential for increasing the active sorption sites and for strengthening interactions with PFAS. This review evaluates current literature, identifies knowledge gaps in current remediation technologies and addresses future strategies on the sequestration of PFAS in contaminated soil using sustainable novel C-based sorbents.

Snacks contribute considerably to total dietary intakes among adults stratified by glycemia in the United States.

Little is known about the snacking patterns among adults with type 2 diabetes. The contribution of snacks to energy and nutrient intakes is important to further understand dietary patterns and glycemic control. The purpose of this study is to evaluate snack consumption among adults according to diabetes status in the United States. One NHANES 24-hour dietary recall for each participant collected between 2005-2016 was utilized for analysis (n = 23,708). Analysis of covariance was used to compare differences in nutrient and food groups intakes from snacks across levels of glycemic control, while controlling for age, race/ethnicity, income, marital status, and gender. Results of this analysis inform that adults with type 2 diabetes consume less energy, carbohydrates, and total sugars from snacks than adults without diabetes. Those with controlled type 2 diabetes consumed more vegetables and less fruit juice than other groups, yet adults with type 2 diabetes in general consumed more cured and luncheon meats than adults without diabetes or with prediabetes. Protein from all snacks for those without diabetes is higher than all other groups. This study elucidates common snacking patterns among US adults with diabetes and highlights the need for clinicians and policymakers to take snacking into consideration when evaluating and providing dietary recommendations.

A pilot intervention to improve uptake and equality of childhood influenza vaccination in an area of Wales, through the introduction of a mixed delivery model including nursery school immunisation sessions.

The schools-based influenza vaccination programme has seen consistently high uptake in Wales, however coverage in pre-school two and three-year olds is lower. One health board area (Cwm Taf University Health Board (UHB)) developed an intervention to offer live attenuated influenza vaccine (LAIV) for three-year olds attending nursery schools alongside the existing general practice (GP) programme. During the pilot, sessions were delivered by health visitors, working with school nurses. The mixed delivery model led to vaccination data being recorded in two separate data systems. To evaluate the impact of the pilot on overall vaccine uptake, data linkage was carried out within the Secure Anonymised Information Linkage (SAIL) Databank. Overall influenza vaccine uptake was calculated for each health board in Wales for two and three-year olds for the 2015-16, 2016-17, and 2017-18 influenza programmes. Uptake in two-year olds in Cwm Taf UHB and also uptake in three-year olds in other health boards in Wales were the comparison groups. Uptake of influenza vaccine in the 2015-16 (pre-intervention) period was 41.0% for three-year olds in Cwm Taf UHB. Following the intervention, coverage increased to 70.7% and 71.5% for 2016-17 and 2017-18 respectively. The same increases in uptake were not seen in two-year olds in Cwm Taf UHB or in three-year olds in non-intervention health boards. In Cwm Taf UHB resident three-year olds in 2015-16 there was an inequality gap in the uptake of 17.4 percentage points between the most and least deprived areas. Uptake increased across all deprivation quintiles in 2016-17 and 2017-18; and the inequality gap decreased to 10.3 and 13.4 percentage points respectively. Influenza vaccination uptake and equality of uptake in three-year olds can be improved by adopting a mixed delivery model across nursery school based immunisation sessions with the additional option of influenza vaccination at GPs.

Effectiveness of Hoffman's Exercise in Postnatal Mothers With Grade 1 Inverted Nipples.

BACKGROUND: Breastfeeding provides perfect nutrition for infants. The inverted nipples in mothers make breastfeeding more challenging. Besides surgical approaches, non-pharmacological interventions are also gaining importance. RESEARCH AIM: To evaluate the effectiveness of Hoffman's exercise on breastfeeding among postnatal mothers with grade I inverted nipples. METHOD: A quantitative approach with a parallel arm randomized controlled trial was used in the study. Postnatal mothers were screened for inverted nipples using a pinch test. Participants with at least one inverted nipple (Grade 1) were randomly allocated into two groups: the experimental group (supported with Hoffman's exercise; n = 28, 50.9% ) and the control group (without Hoffman's exercise; n = 27, 49.1%). The pre-test data, including demographics, nipple length, and breastfeeding assessment, were collected. Breastfeeding assessment was evaluated using the Bristol Breastfeeding Assessment Tool (BBAT). On the 3rd day, the post-test data, including nipple length and Breastfeeding Assessment, were collected among the groups. RESULTS: The BBAT assessment was significantly higher in the post-test compared to that of the pre-test in the participants provided with Hoffman's exercise. The nipple length was found to be higher in participants provided with Hoffman's exercise. Furthermore, the variables-including age, gravida, nipple problems, and delivery type-were not found to have any significant effect with either pre-test or post-test levels of breastfeeding. CONCLUSIONS: Hoffman's exercise was found to be an effective method to improve breastfeeding in Grade 1 nipple-inverted among post-natal mothers. This nipple exercise is inexpensive, easy to follow, and results in the successful initiation of breastfeeding. CLINICAL TRIAL REGISTRY AND REGISTRATION NUMBER: CTRI/2019/05/019279, May 23, 2019 (retrospectively registered).

Protocol for a feasibility study of a cancer symptom awareness campaign to support the rapid diagnostic centre referral pathway in a socioeconomically deprived area: Targeted Intensive Community-based campaign To Optimise Cancer awareness (TIC-TOC).

INTRODUCTION: Rapid diagnostic centres (RDCs) are being implemented across the UK to accelerate the assessment of vague suspected cancer symptoms. Targeted behavioural interventions are needed to augment RDCs that serve socioeconomically deprived populations who are disproportionately affected by cancer, have lower cancer symptom awareness and are less likely to seek help for cancer symptoms. The aim of this study is to assess the feasibility and acceptability of delivering and evaluating a community-based vague cancer symptom awareness intervention in an area of high socioeconomic deprivation. METHODS AND ANALYSIS: Intervention materials and messages were coproduced with local stakeholders in Cwm Taf Morgannwg, Wales. Cancer champions will be trained to deliver intervention messages and distribute intervention materials using broadcast media (eg, local radio), printed media (eg, branded pharmacy bags, posters, leaflets), social media (eg, Facebook) and attending local community events. A cross-sectional questionnaire will include self-reported patient interval (time between noticing symptoms to contacting the general practitioner), cancer symptom recognition, cancer beliefs and barriers to presentation, awareness of campaign messages, healthcare resource use, generic quality of life and individual and area-level deprivation indicators. Consent rates and proportion of missing data for patient questionnaires (n=189) attending RDCs will be measured. Qualitative interviews and focus groups will assess intervention acceptability and barriers/facilitators to delivery. ETHICS AND DISSEMINATION: Ethical approval for this study was given by the London-West London & GTAC Research Ethics (21/LO/0402). This project will inform a potential future controlled study to assess intervention effectiveness in reducing the patient interval for vague cancer symptoms. The results will be critical to informing national policy and practice regarding behavioural interventions to support RDCs in highly deprived populations.

Investigating the optimal handling of uncertain pregnancy episodes in the CPRD GOLD Pregnancy Register: a methodological study using UK primary care data.

OBJECTIVES: To investigate why episodes of pregnancy identified from electronic health records may be incomplete or conflicting (overlapping), and provide guidance on how to handle them. SETTING: Pregnancy Register generated from the Clinical Practice Research Datalink (CPRD) GOLD UK primary care database. PARTICIPANTS: Female patients with at least one pregnancy episode in the Register (01 January 1937-31 December 2017) which had no recorded outcome or conflicted with another episode. DESIGN: We identified multiple scenarios potentially explaining why uncertain episodes occur. Criteria were established and systematically applied to determine whether episodes had evidence of each scenario. Linked Hospital Episode Statistics were used to identify pregnancy events not captured in primary care. RESULTS: Of 5.8 million pregnancy episodes in the Register, 932 604 (16%) had no recorded outcome, and 478 341 (8.5%) conflicted with another episode (251 026 distinct conflicting pairs of episodes among 210 593 women). 826 146 (89%) of the episodes without outcome recorded in primary care and 215 577 (86%) of the conflicting pairs were consistent with one or more of our proposed scenarios. For 689 737 (74%) episodes with recorded outcome missing and 215 544 (86%) of the conflicting pairs (at least one episode), supportive evidence (eg, antenatal records, linked hospital records) suggested they were true and current pregnancies. Furthermore, 516 818 (55 %) and 160 936 (64%), respectively, were during research quality follow-up time. For a sizeable proportion of uncertain episode, there is evidence to suggest that historical outcomes being recorded by the general practitioner during an ongoing pregnancy may offer explanation (73 208 (29.2%) and 349 874 (37.5%)). CONCLUSIONS: This work provides insight to users of the CPRD Pregnancy Register on why uncertain pregnancy episodes exist and indicates that most of these episodes are likely to be real pregnancies. Guidance is given to help researchers consider whether to include/exclude uncertain pregnancies from their studies, and how to tailor approaches to minimise underestimation and bias.

Safety of Percutaneous vs Open Tracheostomy on Intubated Patients in ICU Setting: Which One is Better?

To study the safety of percutaneous vs open tracheostomy approaches on patients requiring long term ventilation in ICU setting. It is a prospective study done over a period of 2 years on 105 patients requiring long term ventilation in ICU set up in a tertiary care hospital. Patients were subjected to either open approach or percutaneous tracheostomy bedside in ICU itself. Then patients were followed during their hospital stay to look for any tracheostomy related complications. Data regarding age, gender, indications of long term ventilation and complications were compiled and analysis was done. It was found that most of the patients were of male gender (88.6%) in the age group of 50-59 years of age. The most common cause for tracheostomy was head injury secondary to road traffic accident, seen in 79 out of 105 cases. On comparing complications rate, there was no statistically significant difference in both the groups. However rate of peristomal infection is more with open approach group (P < 0.05). Percutaneous tracheostomy can be performed safely in ICU as a bedside procedure. There is significant reduction in peristomal infection with percutaneous tracheostomy and there is no significant difference in other complications between the two groups. Thus percutaneous tracheostomy is as safe as an open approach tracheostomy in properly selected cases.

Nutrition risk prevalence and nutrition care recommendations for hospitalized and critically-ill patients with COVID-19.

BACKGROUND: Nutritional status is an often-overlooked component in infectious disease severity. Hospitalized or critically ill patients are at higher risk of malnutrition, and rapid assessment and treatment of poor nutritional status can impact clinical outcomes. As it relates to the COVID-19 pandemic, an estimated 5% of these patients require admission to an ICU. Per clinical practice guidelines, nutrition therapy should be a core component of treatment regimens. On account of the urgent need for information relating to the nutritional support of these patients, clinical practice guidance was published based on current critical care guidelines. However, a growing body of literature is now available that may provide further direction for the nutritional status and support in COVID-19 patients. This review, intended for the health care community, provides a heretofore lacking in-depth discussion and summary of the current data on nutrition risk and assessment and clinical practice guidelines for medical nutrition therapy for hospitalized and critically ill patients with COVID-19.

Social determinants of pertussis and influenza vaccine uptake in pregnancy: a national cohort study in England using electronic health records.

OBJECTIVE: To examine the social determinants of influenza and pertussis vaccine uptake among pregnant women in England. DESIGN: Nationwide population-based cohort study. SETTING: The study used anonymised primary care data from the Clinical Practice Research Datalink and linked Hospital Episode Statistics secondary care data. PARTICIPANTS: Pregnant women eligible for pertussis (2012-2015, n=68 090) or influenza (2010/2011-2015/2016, n=152 132) vaccination in England. MAIN OUTCOME MEASURES: Influenza and pertussis vaccine uptake. RESULTS: Vaccine uptake was 67.3% for pertussis and 39.1% for influenza. Uptake of both vaccines varied by region, with the lowest uptakes in London and the North East. Lower vaccine uptake was associated with greater deprivation: almost 10% lower in the most deprived quintiles compared with the least deprived for influenza (34.5% vs 44.0%), and almost 20% lower for pertussis (57.7% vs 76.0%). Lower uptake for both vaccines was also associated with non-white ethnicity (lowest among women of black ethnicity), maternal age under 20 years and a greater number of children in the household. The associations between all social factors and vaccine uptake were broadly unchanged in fully adjusted models, suggesting the social determinants of uptake were largely independent of one another. Among 3111 women vaccinated against pertussis in their first eligible pregnancy and pregnant again, 1234 (40%) were not vaccinated in their second eligible pregnancy. CONCLUSIONS: Targeting promotional campaigns to pregnant women who are younger, of non-white ethnicity, with more children, living in areas of greater deprivation or the London or North East regions, has potential to reduce vaccine-preventable disease among infants and pregnant women, and to reduce health inequalities. Vaccination promotion needs to be sustained across successive pregnancies. Further research is needed into whether the effectiveness of vaccine promotion strategies may vary according to social factors.

Post-vaccination HPV seroprevalence among female sexual health clinic attenders in England.

BACKGROUND: The National HPV Immunisation Programme was introduced in England in September 2008 using the HPV16/18 bivalent vaccine. We conducted serological surveillance to explore vaccination coverage levels. We also conducted a case-control study to investigate a hypothesised cross-protective effect of the HPV16/18 vaccine against genital warts. METHODS: Residual serum specimens from 16 to 20 year-old women attending six specialist sexual health services (SSHS) between 2011 and 2015 in England were tested for antibodies against HPV16 and HPV18 using a virus-like particle (VLP)-based multiplex serology assay. Patients were classified as having vaccine-induced seropositivity if they were seropositive for both HPV types and either had high antibody levels for at least one HPV type, or moderately high levels for both HPV types. Differences in vaccine-induced seropositivity by patient characteristics were investigated using logistic regression. Vaccine-induced seropositivity was then compared for patients with genital warts (cases) and matched patients without (controls). RESULTS: Of 3,973 serum specimens collected, 3,870 (97.4%) had a valid result. The proportion of women with vaccine-induced seropositivity decreased with age (from 78.1% in 16-year-olds to 52.6% in 20-year-olds). Vaccine-induced seropositivity was lower among women born outside the UK, from more deprived areas and with a history of chlamydia diagnosis. A difference in uptake by ethnic group was also seen but this was largely confounded by differences in deprivation and country of birth. Among 537 cases and 1,515 controls, there was little evidence of a protective effect of the bivalent HPV vaccine against genital warts (adjusted odds ratio 0.93; 95% CI: 0.74-1.18). DISCUSSION: Vaccine-induced seropositivity in this high-risk population was in line with vaccination coverage in the general population although was lower in some at-risk sub-groups. This study does not provide evidence to support a cross-protective effect of the HPV16/18 vaccine against genital warts.

The identification and validity of congenital malformation diagnoses in UK electronic health records: A systematic review.

PURPOSE: To describe the methods used to identify and validate congenital malformation diagnoses recorded in UK electronic health records, and the results of validation studies. METHODS: Medline and Embase were searched for publications between 1987 and 2019 that involved identifying congenital malformations from UK electronic health records using diagnostic codes. The methods and code-lists used to identify congenital malformations, and the methods and results of validations, were examined. RESULTS: We retrieved 54 eligible studies; 36 identified congenital malformations from primary care data and 18 from secondary care data alone or in combination with birth and/or death records. Identification in secondary care data relied on codes from the 'Q' chapter for congenital malformations in ICD-10. In contrast, studies using primary care data frequently used additional codes outside of the 'P' chapter for congenital malformation diagnoses in Read, although the exact codes used were not always clear. Eight studies validated diagnoses identified in primary care data. The positive predictive value was highest (80%-100%) for congenital malformations overall, major malformations, and heart defects although the validity of the reference standard used was often uncertain. It was lowest for neural tube defects (71%) and developmental hip dysplasia (56%). CONCLUSIONS: Studies identifying congenital malformations from primary care data provided limited details about the methods used. The few validation studies were limited to diagnoses recorded in primary care. Further assessments of all measures of validity in both data sources and of other malformation subgroups are needed, using robust reference standards and adhering to reporting guidelines.

Seasonal Influenza Vaccination During Pregnancy and the Risk of Major Congenital Malformations in Live-born Infants: A 2010-2016 Historical Cohort Study.

BACKGROUND: Available evidence indicates that seasonal inactivated influenza vaccination during pregnancy protects both the mother and her newborn and is safe. Nevertheless, ongoing safety assessments are important in sustaining vaccine uptake. Few studies have explored safety in relation to major congenital malformations (MCMs), particularly in the first trimester when most organogenesis occurs. METHODS: Anonymized UK primary care data (the Clinical Practice Research Datalink), including a recently developed Pregnancy Register, were used to identify live-born singletons delivered between 2010 and 2016. Maternal influenza vaccination was determined using primary care records and stratified by trimester. Ascertainment of MCMs from infant primary care records was maximized by linkage to hospitalization data and death certificates. The relationship between vaccination and MCMs recorded in the year after delivery and in early childhood was then assessed using multivariable Cox regression. RESULTS: A total of 78 150 live-birth pregnancies were identified: 6872 (8.8%) were vaccinated in the first trimester, 11 678 (14.9%) in the second, and 12 931 (16.5%) in the third. Overall, 5707 live births resulted in an infant with an MCM recorded in the year after delivery and the adjusted hazard ratio when comparing first-trimester vaccination to no vaccination was 1.06 (99% CI, .94-1.19; P = .2). Results were similar for second- and third-trimester vaccination and for analyses considering MCMs recorded beyond the first birthday. CONCLUSIONS: In this large, population-based historical cohort study there was no evidence to suggest that seasonal influenza vaccine was associated with MCMs when given in the first trimester or subsequently in pregnancy.

Impact of Early Incorporation of Nutrition Interventions as a Component of Cancer Therapy in Adults: A Review.

Malnutrition is prevalent among oncology patients and can adversely affect clinical outcomes, prognosis, quality of life, and survival. This review evaluates current trends in the literature and reported evidence around the timing and impact of specific nutrition interventions in oncology patients undergoing active cancer treatment. Previous research studies (published 1 January 2010-1 April 2020) were identified and selected using predefined search strategy and selection criteria. In total, 15 articles met inclusion criteria and 12/15 articles provided an early nutrition intervention. Identified studies examined the impacts of nutrition interventions (nutrition counseling, oral nutrition supplements, or combination of both) on a variety of cancer diagnoses. Nutrition interventions were found to improve body weight and body mass index, nutrition status, protein and energy intake, quality of life, and response to cancer treatments. However, the impacts of nutrition interventions on body composition, functional status, complications, unplanned hospital readmissions, and mortality and survival were inconclusive, mainly due to the limited number of studies evaluating these outcomes. Early nutrition interventions were found to improve health and nutrition outcomes in oncology patients. Future research is needed to further evaluate the impacts of early nutrition interventions on patients' outcomes and explore the optimal duration and timing of nutrition interventions.

Cellular Mercury Coordination Environment, and Not Cell Surface Ligands, Influence Bacterial Methylmercury Production.

The conversion of inorganic mercury (Hg(II)) to methylmercury (MeHg) is central to the understanding of Hg toxicity in the environment. Hg methylation occurs in the cytosol of certain obligate anaerobic bacteria and archaea possessing the hgcAB gene cluster. However, the processes involved in Hg(II) biouptake and methylation are not well understood. Here, we examined the role of cell surface thiols, cellular ligands with the highest affinity for Hg(II) that are located at the interface between the outer membrane and external medium, on the sorption and methylation of Hg(II) by Geobacter sulfurreducens. The effect of added cysteine (Cys), which is known to greatly enhance Hg(II) biouptake and methylation, was also explored. By quantitatively blocking surface thiols with a thiol binding ligand (qBBr), we show that surface thiols have no significant effect on Hg(II) methylation, regardless of Cys addition. The results also identify a significant amount of cell-associated Hg-S3/S4 species, as studied by high energy-resolution X-ray absorption near edge structure (HR-XANES) spectroscopy, under conditions of high MeHg production (with Cys addition). In contrast, Hg-S2 are the predominant species during low MeHg production. Hg-S3/S4 species may be related to enhanced Hg(II) biouptake or the ability of Hg(II) to become methylated by HgcAB and should be further explored in this context.

Safety of inadvertent administration of live zoster vaccine to immunosuppressed individuals in a UK-based observational cohort analysis.

OBJECTIVES: To investigate the safety of live attenuated varicella zoster vaccination when administered to immunosuppressed individuals. DESIGN: Prospective observational cohort study. SETTING: The study used anonymised data from the Clinical Practice Research Datalink (CPRD), comprising a representative sample of routinely collected primary care data in England between 2013 and 2017 and and linked Hospital Episode Statistics data. PARTICIPANTS: 168 767 individuals age-eligible for varicella zoster vaccination registered at a general practice in England contributing data to CPRD. MAIN OUTCOME MEASURES: Electronic health records indicating immunosuppression, zoster vaccination, diagnoses of specific varicella-zoster virus (VZV)-related disease and non-specific rash/encephalitis compatible with VZV-related disease. RESULTS: Between 1 September 2013 and 31 August 2017, a period of immunosuppression was identified for 9093/168 767 (5.4%; 95% CI: 5.3%-5.5%) individuals age-eligible for zoster vaccination. The overall rate of vaccination while immunosuppressed was 1742/5251 (33.2 per 100 adjusted person years at risk; 95% CI: 31.9%-34.5%). Follow-up of the 1742 individuals who were inadvertently vaccinated while immunosuppressed identified only two cases of VZV-related disease within 8 weeks of vaccination (0.1%; 95% CI: 0.01%-0.4%), both primary care diagnoses of 'shingles', neither with a related hospital admission. CONCLUSIONS: Despite evidence of inadvertent vaccination of immunosuppressed individuals with live zoster vaccination, there is a lack of evidence of severe consequences including hospitalisation. This should reassure primary care staff and encourage vaccination of mildly immunosuppressed individuals who do not meet current thresholds for contraindication. These findings support a review of the extent to which live zoster vaccination is contraindicated among the immunosuppressed.

Progress toward the development of a microchip electrophoresis separation-based sensor with electrochemical detection for on-line in vivo monitoring of catecholamines.

The development of a separation-based sensor for catecholamines based on microdialysis (MD) coupled to microchip electrophoresis (ME) with electrochemical (EC) detection is described. The device consists of a pyrolyzed photoresist film working electrode and a poly(dimethylsiloxane) microchip with a flow-gated sample injection interface. The chip was partially reversibly sealed to the glass substrate by selectively exposing only the top section of the chip to plasma. This partially reversible chip/electrode integration process not only allows the reuse of the working electrode but also greatly enhanced the reproducibility of electrode alignment with the separation channel. The developed MD-ME-EC system was then tested using l-DOPA, 3-O-MD, HVA, DOPAC, and dopamine standards, which were separated in less than 100 seconds using a background electrolyte consisting of 15 mM sodium phosphate (pH 7.4), 15 mM sodium dodecyl sulfate, and 2.5 mM boric acid. A potential of +1.0 V vs. Ag/AgCl was used for amperometric detection of the analytes. The device was evaluated for on-line monitoring of the conversion of l-DOPA to dopamine in vitro and for monitoring dopamine release in an anesthetized rat in vivo following high K+ stimulation. The system was able to detect stimulated dopamine release in vivo but not endogenous levels of dopamine.

Racial discrimination and ethnic racial identity in adolescence as modulators of HPA axis activity.

We review evidence of racial discrimination as a critical and understudied form of adversity that has the potential to impact stress biology, particularly hypothalamic-pituitary-adrenal (HPA) axis activity. We highlight ethnic racial identity (ERI) as a positive regulatory influence on HPA axis activity, as indexed by levels of salivary cortisol. In past research by our group, Black individuals with high adolescent discrimination had low adult cortisol levels (hypocortisolism). Here, we present new analyses showing that ERI, measured prospectively from ages 12 through 32 in 112 Black and white individuals, is related to better-regulated cortisol levels in adulthood, particularly for Black participants. We also describe ongoing research that explores whether the promotion of ERI during adolescence can reduce ethnic-racial disparities in stress biology and in emotional health and academic outcomes.