"Treated as second class citizens" - the lived experience of obesity-related stigma: an IMI2 SOPHIA study.

PURPOSE: Obesity-related stigma impacts on and shapes the physical and psychosocial wellbeing of individuals living with obesity. Often absent from the literature in the field is the voice(s) of those living with obesity capturing the nuances of the lived experiences of obesity-related stigma. METHODS: This study adopted a qualitative approach encompassing individual (n = 15) and photovoice method (n = 12), with a purposeful sample of patients accessing treatment for obesity within the healthcare setting during 2021. Analysis was undertaken using thematic analysis. RESULTS: Key themes developed from the analysis related to experiencing obesity-related stigma as exposure to external judgement, societal exclusion and felt environmental stigmatization. Exposure to external judgement was described as judgemental comments resulting in hypervigilance to societal judgement. Participants reported how being overlooked and ignored by others had various negative effects and compounded obesity-related stigma through societal exclusion. Public spaces lacking suitable equipment further made obesity-related stigma visible through felt environmental stigmatization when pursuing hobbies and in everyday life. CONCLUSIONS: Obesity-related stigma had a profoundly negative impact on participants in this study, particularly in shaping social interaction, limiting life experiences and impacting psychosocial wellbeing.

The implications of defining obesity as a disease: a report from the Association for the Study of Obesity 2021 annual conference.

Unlike various countries and organisations, including the World Health Organisation and the European Parliament, the United Kingdom does not formally recognise obesity as a disease. This report presents the discussion on the potential impact of defining obesity as a disease on the patient, the healthcare system, the economy, and the wider society. A group of speakers from a wide range of disciplines came together to debate the topic bringing their knowledge and expertise from backgrounds in medicine, psychology, economics, and politics as well as the experience of people living with obesity. The aim of their debate was not to decide whether obesity should be classified as a disease but rather to explore what the implications of doing so would be, what the gaps in the available data are, as well as to provide up-to-date information on the topic from experts in the field. There were four topics where speakers presented their viewpoints, each one including a question-and-answer section for debate. The first one focused on the impact that the recognition of obesity could have on people living with obesity regarding the change in their behaviour, either positive and empowering or more stigmatising. During the second one, the impact of defining obesity as a disease on the National Health Service and the wider economy was discussed. The primary outcome was the need for more robust data as the one available does not represent the actual cost of obesity. The third topic was related to the policy implications regarding treatment provision, focusing on the public's power to influence policy. Finally, the last issue discussed, included the implications of public health actions, highlighting the importance of the government's actions and private stakeholders. The speakers agreed that no matter where they stand on this debate, the goal is common: to provide a healthcare system that supports and protects the patients, strategies that protect the economy and broader society, and policies that reduce stigma and promote health equity. Many questions are left to be answered regarding how these goals can be achieved. However, this discussion has set a good foundation providing evidence that can be used by the public, clinicians, and policymakers to make that happen.

At home and at risk: The experiences of Irish adults living with obesity during the COVID-19 pandemic.

Background: People living with obesity are at elevated risk of hospitalisation, serious illness and mortality due to COVID-19. Little is known about their experience of living with obesity during the pandemic and its associated stay-at-home orders. This study sought to understand the experiences of people living with obesity during the COVID-19 pandemic. Methods: A stratified sample of Irish adults (n = 15) living with obesity engaged in open, phenomenological, interviews and a participatory photovoice methodology to capture both verbal and visual accounts of their experiences during the COVID-19 pandemic. Interviews, conducted throughout 2021, were transcribed verbatim and analysed thematically. Findings: Two overarching themes were identified. A) The pandemic and associated stay-at-home orders had a positive impact on the health and well-being of some participants; a negative impact on others; and this impact changed over time as the pandemic progressed. B) People living with obesity reported feeling stigmatised and 'othered' by their 'at risk' categorisation. Public health messaging and public discourse relating to obesity resulted in some people feeling segregated and punished by society. Interpretation: Changes in lifestyle initiated by the pandemic's stay-at-home orders had a varied impact on the health behaviours and outcomes of people with obesity. This variance offers helpful insight into the psychosocial aspects of obesity. Furthermore, the 'othering' effect of public health messaging during the pandemic warrants caution in light of the already stigmatised nature of this disease. Funding: This study is part of the SOPHIA project which received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 875534.

The effect of phenytoin on embryonic heart rate in Vivo.

Phenytoin is a known human teratogen with unknown etiology. Several mechanisms have been proposed including disturbances in folate metabolism, induction of embryonic hypoxia following phenytoin-induced bradycardia, free radical formation following re-oxygenation and phenytoin-induced maternal hyperglycemia. Using high frequency ultrasound, we demonstrated that phenytoin induced a dramatic decrease in the heart rate of embryos. This coincided with a moderate transient decrease in maternal heart rate and blood glucose levels. Embryonic heart rate had not fully recovered 24 h later in some embryos despite normal maternal physiological parameters. In a separate study, extent of hypoxia was measured using the marker pimonidazole. Phenytoin-exposed embryos did not demonstrate increased hypoxia compared to control embryos at 2, 4, 8 or 24 h dosing. Together our results show that phenytoin induces malformations as a result of a combination of insults: embryonic bradycardia, maternal bradycardia and maternal hyperglycemia. However, this does not appear to result in measurable embryonic hypoxia in our animal model.

The lived experience of patients with obesity: A systematic review and qualitative synthesis.

Although the deleterious effects of obesity have been well documented in terms of morbidity and mortality, less is known about what it is like to live with this complex and chronic disease. This study systematically reviewed and synthesized peer-reviewed studies relating to the lived experience of patients with obesity. A total of 12,388 records were screened, resulting in the inclusion of 32 final studies. Meta-ethnographic synthesis of these 32 studies generated five "third-order constructs" or themes: the development of obesity; a life limited; stigma, judgment, shame, and blame; treatment and; experiences of specific or minority groups. These constructs describe, from the patient's perspective, the factors associated with the development and maintenance of obesity; the effects of the disease on their day-to-day lives; the impact of the stigma and judgment many patients are subjected to; and their experience of accessing, or trying to access, treatment for their healthcare needs. This synthesis reveals the dearth of studies that focus solely on the experience of the patient and highlights the tendency for participant-informed, rather than participatory, methods in obesity research. It concludes with a call for further participatory research into the experiences of people living with obesity.

The lived experience of people with obesity: study protocol for a systematic review and synthesis of qualitative studies.

BACKGROUND: Obesity is a prevalent, complex, progressive and relapsing chronic disease characterised by abnormal or excessive body fat that impairs health and quality of life. It affects more than 650 million adults worldwide and is associated with a range of health complications. Qualitative research plays a key role in understanding patient experiences and the factors that facilitate or hinder the effectiveness of health interventions. This review aims to systematically locate, assess and synthesise qualitative studies in order to develop a more comprehensive understanding of the lived experience of people with obesity. METHODS: This is a protocol for a qualitative evidence synthesis of the lived experience of people with obesity. A defined search strategy will be employed in conducting a comprehensive literature search of the following databases: PubMed, Embase, PsycInfo, PsycArticles and Dimensions (from 2011 onwards). Qualitative studies focusing on the lived experience of adults with obesity (BMI >30) will be included. Two reviewers will independently screen all citations, abstracts and full-text articles and abstract data. The quality of included studies will be appraised using the critical appraisal skills programme (CASP) criteria. Thematic synthesis will be conducted on all of the included studies. Confidence in the review findings will be assessed using GRADE CERQual. DISCUSSION: The findings from this synthesis will be used to inform the EU Innovative Medicines Initiative (IMI)-funded SOPHIA (Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy) study. The objective of SOPHIA is to optimise future obesity treatment and stimulate a new narrative, understanding and vocabulary around obesity as a set of complex and chronic diseases. The findings will also be useful to health care providers and policy makers who seek to understand the experience of those with obesity. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020214560 .

Fetal hypoxia and hyperglycemia in the formation of phenytoin-induced cleft lip and maxillary hypoplasia.

OBJECTIVE: Phenytoin exposure during the first trimester of pregnancy increases the risk of maxillary hypoplasia and cleft lip. The etiology of phenytoin embryopathy is unknown. Interestingly, phenytoin is also known to induce hyperglycemia in humans as well as rats. This study uses a rat model of fetal phenytoin syndrome to examine the role of hyperoxia, hyperglycemia, and arachidonic acid deficiency in the development of cleft lip and maxillary hypoplasia. METHODS: Pregnant rats were dosed with phenytoin during the critical period of lip development (day 11 of pregnancy) with or without supplemental oxygen, insulin, or arachidonic acid. The fetuses from all studies were examined at term. RESULTS: The frequency of cleft lip and maxillary hypoplasia was reduced by treating dams at the time of phenytoin exposure with either increased oxygen or insulin. However, in fetuses from phenytoin-treated dams dosed with arachidonic acid, the incidence of severe lip deformities remained the same although there was an increase in normal and mildly affected fetuses. Interestingly, this occurred in embryos from hyperglycemic dams. SIGNIFICANCE: Together, the results from these experiments suggest phenytoin-induced malformations may be a multifactorial process as malformations were not solely linked to a hyperglycemic state of the dam.

A high prevalence of chronic gastrointestinal symptoms in adults with cystic fibrosis is detected using tools already validated in other GI disorders.

Background: People with cystic fibrosis (CF) report a variety of gastrointestinal (GI) symptoms, independent of pancreatic enzyme insufficiency (PEI), reminiscent of other chronic GI disorders. There are currently no accepted or validated assessment tools and neither the range, frequency nor severity of GI symptoms has been systematically described in CF. We present results of a cross-sectional study using established tools and compare them to current measures of quality of life (QOL). Methods: Consecutive patients attending specialist CF appointments were asked to complete questionnaires including the GI Symptom Rating Scale (GSRS); Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) and Cystic Fibrosis Questionnaire (CFQ-R). Questionnaire terminology was altered to replace references to 'IBS' with 'GI symptoms'. Results: In total, 107 patients were recruited (mean age, 27.8 ± 9.6 years; 60 female), and 94 (88%) had PEI. Body mass index was 22.1 ± 3.6 kg/m2, forced expiratory volume in one second was 59 + 27.7% predicted. Fifty-three (49.5%) were p.Phe508del homozygous. Overall 69/107 (65%) reported significant GI symptoms independent of PEI or adherence to pancreatic enzyme replacement therapy (PERT), with the four most frequent being attributable to the lower GI tract: bloating/distension, flatulence, abdominal pain and borborygmi (gurgling). There was no numerical correlation between any CFQ-R domain (particularly Digestion domain) and GSRS or SSS. Conclusion: This is the first systematic study measuring GI symptoms in CF using validated GI tools. Symptoms are not related to PERT or genotype and appear to be captured well by the GSRS. Further research will study longitudinal changes with treatment, and therapeutic trials in CF may use these tools to demonstrate a positive impact on 'non-respiratory' symptoms and QOL.

Misconceptions and persistence: resources for targeting student alternative conceptions in biotechnology.

Conceptual understanding and reasoning of nonscience major students enrolled in a course on biotechnology were evaluated before and after instruction. The instrument for analysis of student understanding was the Biotechnology Instrument for Knowledge Elicitation (BIKE). The BIKE targets 11 key concepts, as determined by experts in the field. A statistically significant score improvement was observed in each of the 11 concept areas after completion of the course, Biotechnology in Society (N = 117). Student responses to both the pretest and posttest were highly informative and revealed several common misconceptions that could have been overlooked in a closed form testing scenario. These alternative conceptions and recommended clarifications have been presented here. Our goal in documenting and distributing these is to better equip educators in biology and biochemistry to anticipate student preconceptions, design targeted interventions, and improve student conceptual reasoning in topics pertaining to biology and biotechnology. © 2018 International Union of Biochemistry and Molecular Biology, 46(6):602-611, 2018.

Reminiscence therapy for dementia: an abridged Cochrane systematic review of the evidence from randomized controlled trials.

INTRODUCTION: Reminiscence therapy (RT) is a popular psychosocial intervention widely used in dementia care. It involves discussion of past events and experiences, using tangible prompts to evoke memories or stimulate conversation. Areas covered: The aim of this review is to evaluate the effectiveness of RT for people with dementia. It includes studies from the specialized register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS). Searches yielded 185 records of which 22 (n = 1972) were eligible for inclusion. The meta-analysis comprised of data from 16 studies (n = 1749 participants). The review included four large multicenter high-quality studies and several smaller studies of reasonable quality. Outcomes of interest were quality of life, communication, depression, and cognition at posttreatment and later follow-up. Expert commentary: RT has the potential to improve psychosocial outcomes for people with dementia. Effects are small and can be inconsistent, varying across intervention modality and setting. Individual approaches were associated with improved cognition and mood. Group approaches were linked to improved communication. The impact on quality of life appeared most promising in care home settings. Diversity in reminiscence approaches makes it difficult to compare them, and the field would benefit from the development, evaluation, use, and sharing of standardized approaches.

Reminiscence therapy for dementia.

BACKGROUND: This updated Cochrane Review of reminiscence therapy (RT) for dementia was first published in 1998, and last updated in 2005. RT involves the discussion of memories and past experiences with other people using tangible prompts such as photographs or music to evoke memories and stimulate conversation. RT is implemented widely in a range of settings using a variety of formats. OBJECTIVES: To assess the effects of RT on people living with dementia and their carers, taking into account differences in its implementation, including setting (care home, community) and modality (group, individual). SEARCH METHODS: We searched ALOIS (the Cochrane Dementia and Cognitive Improvement Group's Specialized Register) on 6 April 2017 using the search term 'reminiscence.' SELECTION CRITERIA: We included all randomised controlled trials of RT for dementia in which the duration of the intervention was at least four weeks (or six sessions) and that had a 'no treatment' or passive control group. Outcomes of interest were quality of life (QoL), cognition, communication, behaviour, mood and carer outcomes. DATA COLLECTION AND ANALYSIS: Two authors (LOP and EF) independently extracted data and assessed risk of bias. Where necessary, we contacted study authors for additional information. We pooled data from all sufficiently similar studies reporting on each outcome. We undertook subgroup analysis by setting (community versus care home) and by modality (individual versus group). We used GRADE methods to assess the overall quality of evidence for each outcome. MAIN RESULTS: We included 22 studies involving 1972 people with dementia. Meta-analyses included data from 16 studies (1749 participants). Apart from six studies with risk of selection bias, the overall risk of bias in the studies was low.Overall, moderate quality evidence indicated RT did not have an important effect on QoL immediately after the intervention period compared with no treatment (standardised mean difference (SMD) 0.11, 95% confidence interval (CI) -0.12 to 0.33; I2 = 59%; 8 studies; 1060 participants). Inconsistency between studies mainly related to the study setting. There was probably a slight benefit in favour of RT in care homes post-treatment (SMD 0.46, 95% CI 0.18 to 0.75; 3 studies; 193 participants), but little or no difference in QoL in community settings (867 participants from five studies).For cognitive measures, there was high quality evidence for a very small benefit, of doubtful clinical importance, associated with reminiscence at the end of treatment (SMD 0.11, 95% CI 0.00 to 0.23; 14 studies; 1219 participants), but little or no difference at longer-term follow-up. There was a probable slight improvement for individual reminiscence and for care homes when analysed separately, but little or no difference for community settings or for group studies. Nine studies included the widely used Mini-Mental State Examination (MMSE) as a cognitive measure, and, on this scale, there was high quality evidence for an improvement at the end of treatment (mean difference (MD) 1.87 points, 95% CI 0.54 to 3.20; 437 participants). There was a similar effect at longer-term follow-up, but the quality of evidence for this analysis was low (1.8 points, 95% CI -0.06 to 3.65).For communication measures, there may have been a benefit of RT at the end of treatment (SMD -0.51 points, 95% CI -0.97 to -0.05; I2 = 62%; negative scores indicated improvement; 6 studies; 249 participants), but there was inconsistency between studies, related to the RT modality. At follow-up, there was probably a slight benefit of RT (SMD -0.49 points, 95% CI -0.77 to -0.21; 4 studies; 204 participants). Effects were uncertain for individual RT, with very low quality evidence available. For reminiscence groups, evidence of moderate quality indicated a probable slight benefit immediately (SMD -0.39, 95% CI -0.71 to -0.06; 4 studies; 153 participants), and at later follow-up. Community participants probably benefited at end of treatment and follow-up. For care home participants, the results were inconsistent between studies and, while there may be an improvement at follow-up, at the end of treatment the evidence quality was very low and effects were uncertain.Other outcome domains examined for people with dementia included mood, functioning in daily activities, agitation/irritability and relationship quality. There were no clear effects in these domains. Individual reminiscence was probably associated with a slight benefit on depression scales, although its clinical importance was uncertain (SMD -0.41, 95% CI -0.76 to -0.06; 4 studies; 131 participants). We found no evidence of any harmful effects on people with dementia.We also looked at outcomes for carers, including stress, mood and quality of relationship with the person with dementia (from the carer's perspective). We found no evidence of effects on carers other than a potential adverse outcome related to carer anxiety at longer-term follow-up, based on two studies that had involved the carer jointly in reminiscence groups with people with dementia. The control group carers were probably slightly less anxious (MD 0.56 points, 95% CI -0.17 to 1.30; 464 participants), but this result is of uncertain clinical importance, and is also consistent with little or no effect. AUTHORS' CONCLUSIONS: The effects of reminiscence interventions are inconsistent, often small in size and can differ considerably across settings and modalities. RT has some positive effects on people with dementia in the domains of QoL, cognition, communication and mood. Care home studies show the widest range of benefits, including QoL, cognition and communication (at follow-up). Individual RT is associated with probable benefits for cognition and mood. Group RT and a community setting are associated with probable improvements in communication. The wide range of RT interventions across studies makes comparisons and evaluation of relative benefits difficult. Treatment protocols are not described in sufficient detail in many publications. There have been welcome improvements in the quality of research on RT since the previous version of this review, although there still remains a need for more randomised controlled trials following clear, detailed treatment protocols, especially allowing the effects of simple and integrative RT to be compared.

Glycine N-acyltransferase-like 3 is responsible for long-chain N-acylglycine formation in N18TG2 cells.

Long-chain fatty acid amides are signaling lipids found in mammals and other organisms; however, details of the metabolic pathways for the N-acylglycines and primary fatty acid amides (PFAMs) have remained elusive. Heavy-labeled precursor and subtraction lipidomic experiments in mouse neuroblastoma N18TG2 cells, a model cell line for the study of fatty acid amide metabolism, establish the biosynthetic pathways for the N-acylglycines and the PFAMs. We provide evidence that the N-acylglycines are formed by a long-chain specific glycine-conjugating enzyme, glycine N-acyltransferase-like 3 (GLYATL3). siRNA knockdown of GLYATL3 in the N18TG2 cells resulted in a decrease in the levels of the N-acylglycines and the PFAMs. This is the first report of an enzyme responsible for long-chain N-acylglycine production in cellula. The production of the PFAMs in N18TG2 cells was reported to occur by the oxidative cleavage of the N-acylglycines, as catalyzed by peptidylglycine α-amidating monooxygenase (PAM). siRNA knockdown of PAM resulted in an accumulation of [(13)C18]N-oleoylglycine and decreased levels of [(13)C18]oleamide when the N18TG2 cells were grown in the presence of [(13)C18]oleic acid. The addition of [1-(13)C]palmitate to the N18TG2 cell growth media led to the production of a family of [1-(13)C]palmitoylated fatty acid amides, consistent with the biosynthetic pathways detailed herein.

Functional characterization of AlgL, an alginate lyase from Pseudomonas aeruginosa.

Alginate lyase (AlgL) catalyzes the cleavage of the polysaccharide alginate through a ß-elimination reaction. In Pseudomonas aeruginosa, algL is part of the alginate biosynthetic operon, and although it is required for alginate biosynthesis, it is not clear why. Steady-state kinetic studies were performed to characterize its substrate specificity and revealed that AlgL operates preferentially on nonacetylated alginate or its precursor mannuronan. Mature alginate is secreted as a partially acetylated polysaccharide, so this observation is consistent with suggestions that AlgL serves to degrade mislocalized alginate that is trapped in the periplasmic space. The k(cat)/K(m) for the reaction increased linearly with the number of residues in the substrate, from 2.1 × 10(5) M(-1) s(-1) for the substrate containing 16 residues to 7.9 × 10(6) M(-1) s(-1) for the substrate with 280 residues. Over the same substrate size range, k(cat) varied between 10 and 30 s(-1). The variation in k(cat)/K(m) with substrate length suggests that AlgL operates in a processive manner. AlgL displayed a surprising lack of stereospecificity, in that it was able to catalyze cleavage adjacent to either mannuronate or guluronate residues in alginate. Thus, the enzyme is able to remove the C5 proton from both mannuronate and guluronate, which are C5 epimers. Exhaustive digestion of alginate by AlgL generated dimeric and trimeric products, which were characterized by (1)H nuclear magnetic resonance spectroscopy and mass spectrometry. Rapid-mixing chemical quench studies revealed that there was no lag in dimer or trimer production, indicating that AlgL operates as an exopolysaccharide lyase.

Primary fatty acid amide metabolism: conversion of fatty acids and an ethanolamine in N18TG2 and SCP cells.

Primary fatty acid amides (PFAM) are important signaling molecules in the mammalian nervous system, binding to many drug receptors and demonstrating control over sleep, locomotion, angiogenesis, and many other processes. Oleamide is the best-studied of the primary fatty acid amides, whereas the other known PFAMs are significantly less studied. Herein, quantitative assays were used to examine the endogenous amounts of a panel of PFAMs, as well as the amounts produced after incubation of mouse neuroblastoma N(18)TG(2) and sheep choroid plexus (SCP) cells with the corresponding fatty acids or N-tridecanoylethanolamine. Although five endogenous primary amides were discovered in the N(18)TG(2) and SCP cells, a different pattern of relative amounts were found between the two cell lines. Higher amounts of primary amides were found in SCP cells, and the conversion of N-tridecanoylethanolamine to tridecanamide was observed in the two cell lines. The data reported here show that the N(18)TG(2) and SCP cells are excellent model systems for the study of PFAM metabolism. Furthermore, the data support a role for the N-acylethanolamines as precursors for the PFAMs and provide valuable new kinetic results useful in modeling the metabolic flux through the pathways for PFAM biosynthesis and degradation.

Biosynthesis, degradation and pharmacological importance of the fatty acid amides.

The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologically occurring fatty acid amides. In this review, we will outline which fatty acid amides have been isolated from mammalian sources, detail what is known about how these molecules are made and degraded in vivo, and highlight their potential for the development of novel therapeutics.