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The consumption of alcohol is associated with well-known health harms and many governments worldwide are actively engaged in devising approaches to reduce them. To this end, a common proposed strategy aims at reducing alcohol consumption. This approach has led to the development of non-alcoholic drinks, which have been especially welcome by younger, wealthier, health-conscious consumers, who have been turning away from alcohol to look toward alternatives. However, a drawback of non-alcoholic drinks is that they do not facilitate social interaction in the way alcohol does, which is the main reason behind social drinking. Therefore, an alternative approach is to develop functional drinks that do not use alcohol yet mimic the positive, pro-social effects of alcohol without the associated harms. This article will discuss (1) current knowledge of how alcohol mediates its effects in the brain, both the desirable, e.g., antistress to facilitate social interactions, and the harmful ones, with a specific focus on the pivotal role played by the gamma-aminobutyric acid (GABA) neurotransmitter system and (2) how this knowledge can be exploited to develop functional safe alternatives to alcohol using either molecules already existing in nature or synthetic ones. This discussion will be complemented by an analysis of the regulatory challenges associated with the novel endeavour of bringing safe, functional alternatives to alcohol from the bench to bars.

Background: 2022 marks a decade since the profession of podiatry secured independent prescribing rights in the UK. Widely viewed as a significant milestone, its advent appeared to herald a new age of practice, with increased autonomy, a broader scope of practice and improved patient care. Access to any medicine within the British National Formulary (with a few notable exceptions) seemed to signal an end to the perennial difficulties and frequent disappointments in obtaining ease of access to medicines necessary for effective practice., Main Body: Recent attempts to expand the scope of prescribing practice to include access to a broader range of controlled drugs (CDs) have led to unanticipated complications which may even threaten existing rights. These issues highlight the limitations of current independent prescribing and the continuing inability of podiatrists to access certain key medicines, primarily controlled drugs. Reliance on specified 'lists' of approved medicines, whether a controlled drug list for prescribers or the use of statutory exemptions by non-prescriber podiatrists, remain inflexible and difficult to change. The data underpinning much of this paper is derived from the work undertaken by the authors as representatives of podiatry on NHS England's Chief Professions' Officers' Medicines project, in particular involving submissions to the Commission on Human Medicines and the Advisory Council on the Misuse of Medicines, spanning the years 2017-2021. It describes a complex process, and highlights a misalignment between two legislative frameworks that threaten to unravel existing rights., Short Conclusion: Ongoing difficulties relating to controlled drugs illustrate the problematic nature of current supply, administration and prescribing rights in podiatry. Efforts to keep pace with periodic legal reclassifications of medicines are constrained by limited and inflexible legal mechanisms, and formal approval for extended access via prescribing remains unpredictable and complex. For prescriber and non-prescriber 1  ( 1 Non- prescriber podiatrists are those who are neither supplementary or independent prescribers, but do enjoy existing administration and supply rights to certain medicines.) podiatrists alike, the profession of podiatry faces a new challenge to its ability to access medicines, and to realise its full clinical potential., (© 2022. The Author(s).)

Retinoic acid receptors (RARs) α, β, and γ are members of the nuclear receptor superfamily. Compounds which bind to and activate the RARs are termed retinoids which regulate a wide variety of biological processes such as vertebrate embryonic morphogenesis and organogenesis, cell growth arrest, differentiation, and apoptosis, as well as their disorders. Although many synthetic selective RARα, RARβ, and RARγ agonists have been designed and prepared, these have generally been lipophilic acids without good drug-like properties and with low oral bioavailability. Recently this has been changing and drug design approaches to highly potent and selective RARα and RARβ agonists with low lipophilicity that are orally bioavailable and less toxic have been developed, that have a range of potential therapeutic uses. This review covers these new advances., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective : To identify the potential challenges and barriers to the implementation of Advanced Physiotherapy Practice (APP) in Ghana. Methods : A basic interpretive qualitative study design was conducted, with a semi-structured focus group comprising eight physiotherapists and a one-to-one interview with the director of orthopedic surgery in the second largest hospital in Ghana. Participants were sampled purposefully to ensure they had a clear understanding of APP. Discussions were audio recorded, transcribed, coded and thematic analysis was performed. Findings : Four key themes were identified as potential challenges to the implementation of APP in Ghana. Theme 1 Jurisdictional Disputes: Physiotherapists believed doctors will not accept the practice, while the doctor interviewed was willing to accept the practice. Theme 2: Management Support: Support from management was identified as a potential barrier to APP implementation due to workplace culture and liability. Theme 3 Change in Law and Policy: APP could be hindered if there is no legislative support and policies in place. Theme 4 Postgraduate Training: This was identified as key to the implementation of APP since there is no such level of training in Ghana. Conclusion : Barriers to health-care programs are often not identified and addressed prior to their implementation in developing countries, leading to program failure. Addressing these four barriers and challenges could ensure the successful implementation of APP in Ghana. APP has the potential to improve access to rural health-care delivery and augment the shortage of health professionals in developing countries.

Background: Escaping from emotional pain is a recognized driver in suicidal patients' desire to die. Formal scales of emotional pain are rarely used during routine contact between patients and their care team. No study has explored facilitators and inhibitors of emotional pain communication between staff and suicidal patients during regular care., Aims: To identify factors impeding or facilitating emotional pain communication between patients at risk of suicide and mental health professionals., Method: Nine patients with a history of a medically serious suicide attempt and 26 mental health (NHS) staff participated in individualized and focus group interviews, respectively., Results: A typological model was created, describing how patients either speak out or inhibit communication, and professionals may hear the communication or fail to do so. Four permutations are possible: unspoken/unheard, spoken/unheard, spoken/heard, and unspoken/heard. We found 14 subthemes of impediments and facilitators, which include misaligned, alienated and, co-bearing., Limitations: No male patients participated., Conclusion: Numerous factors influence whether emotional pain communication is responded to, missed, or ignored. Patients may try more than one way to communicate. Some patients fear that being able to speak out results in their emotional pain being taken less seriously. Knowledge of this model should improve the care of suicidal patients.

Background: The health professions have progressed and evolved considerably over the last few decades in response to demographic, technological, societal and political changes. They continue to do so as the volume and complexity of population health needs steadily increase. Role boundary expansion is among the key changes to the health professions, including podiatry to meet demand. Nonetheless podiatry's role boundary expansion has not been achieved swiftly or without resistance from neighbouring and dominant professions. This paper seeks to explain the nature of this resistance with respect to the sociology of the professions literature and to shed light on some of the factors and processes at play when role boundary changes arise in health care., Discussion: Six of the most contemporaneously relevant sociology of the professions theories are summarised: Taxonomic, Marxian, Bourdieusian, Foucauldian, Boundary Work and Neo-Weberian paradigms., Conclusion: This review highlights that some paradigms are more relevant than others in the current socio-political landscape. It also illustrates that there is a common theme underlying each approach to defining the professions and their boundaries: competition. This may help health professionals, including podiatrists, to understand and manage the challenges and resistance experienced when professions attempt to expand role boundaries to meet increasing and changing population health needs., Competing Interests: None required as the research method was a review of the literature.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Provision of podiatry services, like other therapies in the UK, is an area that lacks guidance by the National Institute for Health and Care Excellence. Many individuals living with arthritis in the UK are not eligible to access NHS podiatry services. The primary aim of this investigation was to understand the views of podiatry clinicians on their experiences of referral, access, provision and treatment for foot problems for patients who have arthritis., Methods: Focus groups were undertaken to explore, in-depth, individual views of podiatrists working in the UK to gain feedback on experiences of barriers and facilitators to referral, access, provision and treatment for foot problems for individuals living with arthritis. A purposive sampling strategy was adopted and two, semi-structured, focus group interviews conducted, involving 12 podiatrists from both NHS and independent sectors. To account for geographical variations one focus group took place in each of 2 predetermined 'zones' of the UK; Yorkshire and Hampshire. Thematic analysis was employed to identify key meanings and report patterns within the data., Results: The key themes derived from the podiatry clinician focus groups suggest a variety of factors influencing demand for, and burden of, foot pain within the UK. Participants expressed frustration on having a service that accepts and treats patients according to their condition, rather than their complaint. Additionally, concern was conveyed over variations in the understanding of stakeholders' views of what podiatry is and what podiatrists aim to achieve for patients., Conclusion: Podiatrists interviewed believed that many individuals living with arthritis in the UK are not eligible to access NHS podiatry services and that this may be, in part, due to confusion over what is known about podiatry and access criteria. Essentially, podiatrists interviewed called for a timely renaissance of current systems, to newer models of care that meet the foot care needs of individual patients' circumstances and incorporate national multi-disciplinary guidance. Through this project, we have formulated key recommendations that are directed towards improving what other stakeholders (including GPs, commissioners and users of podiatry services) know about the effectiveness of podiatry and also to futureproof the profession of podiatry., Competing Interests: Full ethical approval was gained (IRAS: 15/SW/0251). All participants provided written informed consent. Governance for the study was approved by the Faculty of Health Sciences, University of Southampton Ethics Committee via the ERGO (Ethics and Research Governance Online) online approval system.Dr. Alan Borthwick is Editor UK and Prof Catherine Bowen is the Deputy Editor UK of the Journal of Foot and Ankle Research. It is journal policy that editors are removed from the peer review and editorial decision-making processes for papers they have co-authored. The remaining authors declare no conflicts of interest in relation to this work.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Research focusing on management of foot health has become more evident over the past decade, especially related to chronic conditions such as diabetes. The level of methodological rigour across this body of work however is varied and outputs do not appear to have been developed or translated into clinical practice. The aim of this systematic review was to assess the latest guidelines, standards of care and current recommendations relative to people with chronic conditions to ascertain the level of supporting evidence concerning the management of foot health., Methods: A systematic search of electronic databases (Medline, Embase, Cinahl, Web of Science, SCOPUS and The Cochrane Library) for literature on recommendations for foot health management for people with chronic conditions was performed between 2000 and 2016 using predefined criteria. Data from the included publications was synthesised via template analysis, employing a thematic organisation and structure. The methodological quality of all included publications was appraised using the Appraisal for Research and Evaluation (AGREE II) instrument. A more in-depth analysis was carried out that specifically considered the levels of evidence that underpinned the strength of their recommendations concerning management of foot health., Results: The data collected revealed 166 publications in which the majority (102) were guidelines, standards of care or recommendations related to the treatment and management of diabetes. We noted a trend towards a systematic year on year increase in guidelines standards of care or recommendations related to the treatment and management of long term conditions other than diabetes over the past decade. The most common recommendation is for preventive care or assessments (e.g. vascular tests), followed by clinical interventions such as foot orthoses, foot ulcer care and foot health education. Methodological quality was spread across the range of AGREE II scores with 62 publications falling into the category of high quality (scores 6-7). The number of publications providing a recommendation in the context of a narrative but without an indication of the strength or quality of the underlying evidence was high (79 out of 166)., Conclusions: It is clear that evidence needs to be accelerated and in place to support the future of the Podiatry workforce. Whilst high level evidence for podiatry is currently low in quantity, the methodological quality is growing. Where levels of evidence have been given in in high quality guidelines, standards of care or recommendations, they also tend to be strong-moderate quality such that further strategically prioritised research, if performed, is likely to have an important impact in the field.

Background: Despite significant advancements in new treatment modalities for rheumatoid arthritis with biological therapies, foot complications remain a disabling and common feature of the disease . In this study the aim was to explore and describe the personal experiences of people with rheumatoid arthritis in receipt of biologic treatments in a bid to understand the impact of this form of medication on their mobility., Methods: An interpretative phenomenological analysis (IPA) was undertaken to explore in depth the individual experience of rheumatoid disease through personal accounts of the patient journey spanning both 'before' and 'after' the instigation of biologic therapy. A purposive sampling strategy was adopted and in-depth semi structured interviews used to facilitate rich, detailed interview data exploring the lived experiences of individuals undertaking biological therapy and the changes to mobility experienced as a result. Thematic analysis was employed with an IPA framework to identify key meanings, and report patterns within the data., Results: Five people with rheumatoid arthritis participated in the study. The mean disease duration was 20.2 years (range: 6 -32) and all were being treated with biologic therapies. Four key themes emerged from the data: 1) Life before biologic treatment, depicted in accounts as a negative experience characterised by painful and disabling symptoms and feelings of hopelessness. 2) Life with biologic treatment, often experienced as a life changing transition, restoring function and mobility and offering renewed hope. 3) Sense of self, in which the impact of rheumatoid disease and the subsequent changes arising from biologic therapy reveal a profound impact on feelings of personal identity both pre and post biologic therapy; an effect of footwear on self-image emerges as a dominant sub theme; 4) Unmet footcare needs were evident in the patient narrative, where the unrelenting if diminished impact of foot pain on mobility was viewed in the context of problematic access to foot health services., Conclusion: Whilst the findings from this study mirror those within the existing literature, which report improvements in physical function related to biological therapy, foot problems clearly remained an unremitting feature of life for patients with rheumatoid disease, even when in receipt of biologics.

2,5-Diketopiperazines (2,5-DKPs) have been found to occur in a wide range of food and beverages, and display an array of chemesthetic effects (bitter, astringent, metallic, and umami) that can contribute to the taste of a variety of foods. These smallest cyclic peptides also occur as natural products and have been found to display a variety of bioactivities from antibacterial, antifungal, to anthroprotective effects and have the potential to be used in the development of new functional foods. An overview of the synthesis of these small chiral molecules and their molecular properties is presented. The occurrence, taste, and bioactivity of all simple naturally occurring 2,5-DKPs to date have been reviewed and those found in food from yeasts, fungi, and bacteria that have been used in food preparation or contamination, as well as metabolites of sweeteners and antibiotics added to food are also reviewed.

Background: The design, medicinal chemistry, pharmacokinetics and development of the highly selective α2-adrenoceptor antagonist fluparoxan are reviewed., Method: The drug's activity and selectivity in vitro, its efficacy in animals and its excellent oral pharmacokinetics and central α2-adrenoceptor antagonist activity in man, are evaluated as well as its ability to increase extracellular levels of noradrenaline, dopamine and acetylcholine in vivo., Conclusion: Furthermore, its potential for the treatment of central neurodegenerative diseases is highlighted, in particular its improvement of cognitive dysfunction in schizophrenia and in models of Alzheimer's disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Demographic changes and a predicted rise in the prevalence of chronic illness have led to a range of health policies in the UK (and elsewhere) focused on workforce flexibility and extended roles for the allied health professions. Whilst much academic attention has been paid to extended specialised roles for allied health professionals such as podiatrists, little work has addressed the likely impact of these policy changes on non-specialist, 'generalist' podiatry practice. This study aimed to explore expert professional views on the impact of role flexibility on generalist podiatry practice., Methods: Expert podiatry practitioners drawn from within the professional body, the Society of Chiropodists and Podiatrists/College of Podiatry were recruited to 3 focus groups and 4 individual semi structured interviews and the data subject to a thematic analysis., Results: Three key themes emerged, reflecting concerns about the future of generalist podiatry practice in the NHS, a perceived likelihood that generalist care will move inexorably towards private sector provision, and a growth in support worker grades undermining the position of generalist practice in the mainstream health division of labour. Up skilling generalist practitioners was viewed as the strongest defence against marginalisation., Conclusions: An emphasis on enhanced and specialised roles in podiatry by NHS commissioners and profession alike may threaten the sustainability of generalist podiatry provision in the state funded NHS. Non-specialist general podiatry may increasingly become the province of the private sector.

Professional specialisation is broadly considered to result from increased complexity in professional knowledge and to be linked to specialist education, formalised credentials and registration. However, the degree of formal organisation may vary across professions. In healthcare, although medical specialisation is linked to rigorous selection criteria, formal training programmes and specialist registration, some forms of specialisation in the allied health professions are much less formal. Drawing on Weber's concept of charismatic authority, the establishment of a specialist role in podiatry, the 'diabetes specialist podiatrist', in the absence of codified or credentialed authority, is explored. 'Charismatic' leaders in podiatry, having attracted a following of practitioners, were able to constitute a speciality area of practice in the absence of established career pathways and acquire a degree of legitimacy in the medical field of diabetology., (© 2012 The Authors. Sociology of Health & Illness © 2012 Foundation for the Sociology of Health & Illness/JohnWiley & Sons Ltd. Published by John Wiley & Sons Ltd.)

Background: Although dermatology, as a medical subject, has been a facet of the training and education of podiatrists for many years, it is, arguably, only in recent years that the speciality of podiatric dermatology has emerged within the profession. Some indication of this gradual development may be identified through a content analysis of the podiatric literature in the UK, spanning a 21 year timeframe., Method: 6 key professional journals were selected for content analysis in order to provide a picture of the emergence and development of podiatric dermatology over a period extending from 1989 to 2010. Both syntactical and thematic unitization were deployed in the analysis, revealing both manifest and latent content. Categories were devised using a prior coding, a codebook produced to define relevant concepts and category characteristics, and the coding scheme subject to an assessment of reliability., Results: 1611 units appeared in the 6 journals across a 21 year timeframe. 88% (n = 1417) occurred in one journal (Podiatry Now and its predecessors). Modal categories within all journals included course adverts (n = 673), commercial adverts (n = 562) and articles by podiatrists (n = 133). There was an overall rise from 40 per annum in 1989, to over 100 in 2010. A wider range of dermatological topics were addressed, ranging from fungal nail infections to melanoma., Conclusions: It is evident from this analysis that there has been an increasing focus on dermatology as a topic within the main podiatric journals in the UK over the last 21 years, primarily reflecting a rise in commercial advertising and an increase in academic dermatology related publications. Whilst earlier publications tended to focus on warts and fungal infections, more recent publications address a broader spectrum of topics. Changes in prescribing rights may be relevant to these findings, as may the enhanced professional and regulatory body requirements on continuing professional development.

Occupational therapy theory and philosophy are broadly considered to be based on Western cultural values. In contrast, the application of theory and practice in the Sultanate of Oman, historically based on traditional Middle Eastern and Islamic cultural values, provides a case exemplar, which highlights both paradigmatic differences and cultural dissonance. Drawing on the experiences of occupational therapists working in Oman, this study found that the application of therapeutic goals aimed at patient independence and autonomy were difficult to achieve in an environment where family duty and responsibility for care were highly prized. Dressing and cooking assessments were challenging, and issues related to gender proved problematic. Therapists found the need to adapt practice to acknowledge these differences, and to adopt pragmatic problem-solving strategies, without resolving the underpinning philosophical contradictions. Occupational therapy in Oman is under-researched; further work is needed to confirm the cross-cultural validity of specific assessments and practice models., (Copyright © 2012 John Wiley & Sons, Ltd.)

Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa inhibitors, incorporating neutral and basic monoaryl P4 groups, ultimately producing potent inhibitors with effective levels of anticoagulant activity and extended oral pharmacokinetic profiles. However, time dependant inhibition of Cytochrome P450 3A4 was a particular issue with this series., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating basic biaryl P4 groups, producing highly potent inhibitors with significant anticoagulant activities and encouraging oral pharmacokinetic profiles.

Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating biaryl P4 groups, producing highly potent inhibitors with encouraging oral pharmacokinetic profiles and significant but sub-optimal anticoagulant activities.

The healthcare professions have never been static in terms of their own disciplinary boundaries, nor in their role or status in society. Healthcare provision has been defined by changing societal expectations and beliefs, new ways of perceiving health and illness, the introduction of a range of technologies and, more recently, the formal recognition of particular groups through the introduction of education and regulation. It has also been shaped by both inter-professional and profession-state relationships forged over time. A number of factors have converged that place new pressures on workforce boundaries, including an unmet demand for some healthcare services; neo-liberal management philosophies and a greater emphasis on consumer preferences than professional-led services. To date, however, there has been little analysis of the evolution of the workforce as a whole. The discussion of workforce change that has taken place has largely been from the perspective of individual disciplines. Yet the dynamic boundaries of each discipline mean that there is an interrelationship between the components of the workforce that cannot be ignored. The purpose of this paper is to describe four directions in which the existing workforce can change: diversification; specialisation and vertical and horizontal substitution, and to discuss the implications of these changes for the workforce.

The stereospecific synthesis of a series of alpha-methylpyrrolidine-5,5-trans-lactam inhibitors of human cytomegalovirus (HCMV) protease is described. Examination of the SAR in this series has defined the size and chirality of the alpha-substituent, optimized the acyl substituent on the lactam nitrogen, and defined the steric constraint of this functionality. The SAR of the functionality on the pyrrolidine nitrogen of the trans-lactam has been investigated, and this has led to the discovery of potent serine protease inhibitors that are highly selective for the viral enzyme over the mammalian enzymes elastase, thrombin, and acetylcholine esterase. The mechanism of action of our lead compounds has been established by mass spectrometry, and enzymatic degradation of HCMV deltaAla protease acylated with these inhibitors showed that Ser 132 is the active site nucleophile. The crystal structure of HCMV protease was obtained and used to model the conformationally restricted, chiral (S)-proline-alpha-methyl-5,5-trans-lactams into the active site groove of the enzyme, enabling us to direct and rationalize the SAR in this series. The activity against HCMV deltaAla protease is the greatest with inhibitors based on the dansyl-(S)-proline alpha-methyl-5,5-trans-lactam template, which have low nanomolar activity against the viral enzyme.