The Malaria-High Blood Pressure Hypothesis.

RATIONALE: Several studies have demonstrated links between infectious diseases and cardiovascular conditions. Malaria and hypertension are widespread in many low- and middle-income countries, but the possible link between them has not been considered. OBJECTIVE: In this article, we outline the basis for a possible link between malaria and hypertension and discuss how the hypothesis could be confirmed or refuted. METHODS AND RESULTS: We reviewed published literature on factors associated with hypertension and checked whether any of these were also associated with malaria. We then considered various study designs that could be used to test the hypothesis. Malaria causes low birth weight, malnutrition, and inflammation, all of which are associated with hypertension in high-income countries. The hypothetical link between malaria and hypertension can be tested through the use of ecological, cohort, or Mendelian randomization studies, each of which poses specific challenges. CONCLUSIONS: Confirmation of the existence of a causative link with malaria would be a paradigm shift in efforts to prevent and control hypertension and would stimulate wider research on the links between infectious and noncommunicable disease

Clinical and Epidemiological Implications of 24-Hour Ambulatory Blood Pressure Monitoring for the Diagnosis of Hypertension in Kenyan Adults: A Population-Based Study.

BACKGROUND: The clinical and epidemiological implications of using ambulatory blood pressure monitoring (ABPM) for the diagnosis of hypertension have not been studied at a population level in sub-Saharan Africa. We examined the impact of ABPM use among Kenyan adults. METHODS AND RESULTS: We performed a nested case-control study of diagnostic accuracy. We selected an age-stratified random sample of 1248 adults from the list of residents of the Kilifi Health and Demographic Surveillance System in Kenya. All participants underwent a screening blood pressure (BP) measurement. All those with screening BP ≥140/90 mm Hg and a random subset of those with screening BP <140/90 mm Hg were invited to undergo ABPM. Based on the 2 tests, participants were categorized as sustained hypertensive, masked hypertensive, "white coat" hypertensive, or normotensive. Analyses were weighted by the probability of undergoing ABPM. Screening BP ≥140/90 mm Hg was present in 359 of 986 participants, translating to a crude population prevalence of 23.1% (95% CI 16.5-31.5%). Age standardized prevalence of screening BP ≥140/90 mm Hg was 26.5% (95% CI 19.3-35.6%). On ABPM, 186 of 415 participants were confirmed to be hypertensive, with crude prevalence of 15.6% (95% CI 9.4-23.1%) and age-standardized prevalence of 17.1% (95% CI 11.0-24.4%). Age-standardized prevalence of masked and white coat hypertension were 7.6% (95% CI 2.8-13.7%) and 3.8% (95% CI 1.7-6.1%), respectively. The sensitivity and specificity of screening BP measurements were 80% (95% CI 73-86%) and 84% (95% CI 79-88%), respectively. BP indices and validity measures showed strong age-related trends. CONCLUSIONS: Screening BP measurement significantly overestimated hypertension prevalence while failing to identify ≈50% of true hypertension diagnosed by ABPM. Our findings suggest significant clinical and epidemiological benefits of ABPM use for diagnosing hypertension in Kenyan adults

Influences on academics' approaches to development: voices from below

The purpose of this qualitative case study research was to explore faculty-based academics’ views on what influences their behaviours and attitudes towards their development. Informed by critical realist ontology, the data collection was carried out through narrative interviews with academics in two contrasting English Universities. Findings, or areas for reflection, have emerged about the constraints and enablements academics perceive in respect of their professional development. In particular, themes such as the significance of professional status; misaligned initiatives and priorities; the influence of supportive networks; and emergent personal, individual concerns have surfaced. The conclusion is drawn that the significance of agency raises the importance of responding to the ‘voices from below’

Future textile visions: smart textiles for health and wellness.

A report prepared for the Scottish Government on behalf of the Scottish Academy of Fashion, which examines the potential of new textiles solutions for health applications. Following a Sandpit event hosted by the Scottish Academy of Fashion on 13th and 14th January 2011, a number of projects emerged one of which was Molecular Imprinted Textiles (MIT). The interest of this group was to apply nano-technology to extend the value of textiles by making it possible to add or extract information over the lifetime of garments. A workshop was held on 19th October 2011 by the MIT Group at Edinburgh College of Art to explore concepts based on related technologies. An emerging conversation was focused on the potential of technologies that could be incorporated into textiles specifically for medical applications. The Future Textiles Project (FTV) developed as a result of the earlier dialogue, with the aim of exploring the potential for developing new textiles products designed to address specific medical conditions. The report details some of the most prominent areas of medical need and some of the technologies that may be applied. It does not suggest specific concepts, but rather examines the methodologies that could be profitably adopted for developing new concepts in this field based on a cross-disciplinary user-focused approach. The premise for this project is based on the identification of human needs that provide the focus for subsequent technology development. The report focuses on the potential of Scottish businesses, making use of current research across a number of fields in order to develop new products, which have life-changing implications. Smart (or technologically enhanced) textiles have the potential to control temperature, incorporate antimicrobial properties, provide insulation, breathability, compression, re-shaping, moisture absorption, articulation enabling mobility, constrain movement and improve circulation. They can be used as a diagnostic tool to deliver drugs and respond to changing body states. This project considers new methodologies for rapid product development looking for synergies between business and academic research

Longitudinal characterization of TK6 cells sequentially adapted to animal product-free, chemically defined culture medium: considerations for genotoxicity studies

© 2023 The Author(s). 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/Introduction: In vitro approaches are an essential tool in screening for toxicity of new chemicals, products and therapeutics. To increase the reproducibility and human relevance of these in vitro assessments, it is advocated to remove animal-derived products such as foetal bovine serum (FBS) from the cell culture system. Currently, FBS is routinely used as a supplement in cell culture medium, but batch-to-batch variability may introduce inconsistency in inter- and intra-lab assessments. Several chemically defined serum replacements (CDSR) have been developed to provide an alternative to FBS, but not every cell line adapts easily and successfully to CDSR-supplemented medium, and the long-term effect on cell characteristics remains uncertain. Aim: The aim of this study was to adapt the TK6 cell line to animal-product free CDSR-supplemented medium and evaluate the long-term effects on cell health, growth, morphology, phenotype, and function. This included a provisional assessment to determine the suitability of the transitioned cell line for standardised genotoxicity testing using the “in vitro mammalian cell micronucleus test” (OECD TG 487). Materials and methods: Gradual adaptation and direct adaptation methodologies were compared by assessing the cell proliferation, size and viability every passage until the cells were fully adapted to animal-free CDSR. The metabolic activity and membrane integrity was assessed every 4-8 passages by PrestoBlue and CytoTox-ONE™ Homogeneous Membrane Integrity Assay respectively. A detailed morphology study by high content imaging was performed and the expression of cell surface markers (CD19 and CD20) was conducted via flow cytometry to assess the potential for phenotypic drift during longer term culture of TK6 in animal-free conditions. Finally, functionality of cells in the OECD TG 487 assay was evaluated. Results: The baseline characteristics of TK6 cells cultured in FBS-supplemented medium were established and variability among passages was used to set up acceptance criteria for CDSR adapted cells. TK6 were adapted to CDSR supplemented medium either via direct or gradual transition reducing from 10% v/v FBS to 0% v/v FBS. The cell growth rate was compromised in the direct adaptation and therefore the gradual adaptation was preferred to investigate the long-term effects of animal-free CDSR on TK6 cells. The new animal cells showed comparable (p > 0.05) viability and cell size as the parent FBS-supplemented cells, with the exception of growth rate. The new animal free cells showed a lag phase double the length of the original cells. Cell morphology (cellular and nuclear area, sphericity) and phenotype (CD19 and CD20 surface markers) were in line (p > 0.05) with the original cells. The new cells cultured in CDSR-supplemented medium performed satisfactory in a pilot OECD TG 487 assay with compounds not requiring metabolic activation. Conclusion: TK6 cells were successfully transitioned to FBS- and animal product-free medium. The new cell cultures were viable and mimicked the characteristics of FBS-cultured cells. The gradual transition methodology utilised in this study can also be applied to other cell lines of interest. Maintaining cells in CDSR-supplemented medium eliminates variability from FBS, which in turn is likely to increase the reproducibility of in vitro experiments. Furthermore, removal of animal derived products from cell culture techniques is likely to increase the human relevance of in vitro methodologies.Peer reviewe

Risk algorithm using serial biomarker measurements doubles the number of screen-detected cancers compared with a single-threshold rule in the United Kingdom collaborative trial of ovarian cancer screening

PURPOSE: Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates. PATIENTS AND METHODS: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves. RESULTS: After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P = .0027) higher than that for a single-threshold rule (0.869). CONCLUSION: Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded

Dendritic cell subsets in the intestinal lamina propria: ontogeny and function

The intestinal mucosa is exposed to large amounts of foreign antigen (Ag) derived from commensal bacteria, dietary Ags, and intestinal pathogens. Dendritic cells (DCs) are believed to be involved in the induction of tolerance to harmless Ags and in mounting protective immune responses to pathogens and, as such, to play key roles in regulating intestinal immune homeostasis. The characterization of classical DCs (cDCs) in the intestinal lamina propria has been under intense investigation in recent years but the use of markers (including CD11c, CD11b, MHC class II), which are also expressed by intestinal MΦs, has led to some controversy regarding their definition. Here we review recent studies that help to distinguish cDCs subsets from monocyte-derived cells in the intestinal mucosa. We address the phenotype and ontogeny of these cDC subsets and highlight recent findings indicating that these subsets play distinct roles in the regulation of mucosal immune responses in vivo

Health Is Still Social: Contemporary Examples in the Age of the Genome

Holtz and colleagues argue that social medicine, including an understanding of the social roots of disease, is as important now as it has ever been

Barriers to management of opioid withdrawal in hospitals in England: a document analysis of hospital policies on the management of substance dependence.

BACKGROUND: People who use illicit opioids are more likely to be admitted to hospital than people of the same age in the general population. Many admissions end in discharge against medical advice, which is associated with readmission and all-cause mortality. Opioid withdrawal contributes to premature discharge. We sought to understand the barriers to timely provision of opioid substitution therapy (OST), which helps to prevent opioid withdrawal, in acute hospitals in England.MethodsWe requested policies on substance dependence management from 135 National Health Service trusts, which manage acute hospitals in England, and conducted a document content analysis. Additionally, we reviewed an Omitted and Delayed Medicines Tool (ODMT), one resource used to inform critical medicine categorisation in England. We worked closely with people with lived experience of OST and/or illicit opioid use, informed by principles of community-based participatory research. RESULTS: Eighty-six (64%) trusts provided 101 relevant policies. An additional 44 (33%) responded but could not provide relevant policies, and five (4%) did not send a definitive response. Policies illustrate procedural barriers to OST provision, including inconsistent application of national guidelines across trusts. Continuing community OST prescriptions for people admitted in the evening, night-time, or weekend was often precluded by requirements to confirm doses with organisations that were closed during these hours. 42/101 trusts (42%) required or recommended a urine drug test positive for OST medications or opioids prior to OST prescription. The language used in many policies was stigmatising and characterised people who use drugs as untrustworthy. OST was not specifically mentioned in the reviewed ODMT, with 'drugs used in substance dependence' collectively categorised as posing low risk if delayed and moderate risk if omitted. CONCLUSIONS: Many hospitals in England have policies that likely prevent timely and effective OST. This was underpinned by the 'low-risk' categorisation of OST delay in the ODMT. Delays to continuity of OST between community and hospital settings may contribute to inpatient opioid withdrawal and increase the risk of discharge against medical advice. Acute hospitals in England require standardised best practice policies that account for the needs of this patient group