Sex matters: The effects of biological sex on adipose tissue biology and energy metabolism

Adipose tissue is a complex and multi-faceted organ. It responds dynamically to internal and external stimuli, depending on the developmental stage and activity of the organism. The most common functional subunits of adipose tissue, white and brown adipocytes, regulate and respond to endocrine processes, which then determine metabolic rate as well as adipose tissue functions. While the molecular aspects of white and brown adipose biology have become clearer in the recent past, much less is known about sex-specific differences in regulation and deposition of adipose tissue, and the specific role of the so-called pink adipocytes during lactation in females. This review summarises the current understanding of adipose tissue dynamics with a focus on sex-specific differences in adipose tissue energy metabolism and endocrine functions, focussing on mammalian model organisms as well as human-derived data. In females, pink adipocytes trans-differentiate during pregnancy from subcutaneous white adipocytes and are responsible for milk-secretion in mammary glands. Overlooking biological sex variation may ultimately hamper clinical treatments of many aspects of metabolic disorders

“Like a wake-up call for humankind”: Views, challenges, and coping strategies related to public health measures during the first COVID-19 lockdown in Thailand

Following the first Thai COVID-19 case in January 2020, the Thai government introduced several non-pharmaceutical interventions (NPIs) in March 2020 (e.g., contact tracing, travel restrictions, closure of businesses, curfews, stay at home orders) to control COVID-19 transmissions. This study aimed to understand the views and experiences of a small number of Thai residents related to public health measures implemented during the first COVID-19 wave in Thailand. A total of 28 remote in-depth interviews with Thai residents (18–74 years old) were conducted between 8 May and 21 July 2020. Interviews were audio recorded, transcribed, and analysed using thematic analysis based on the Framework Method. Our results describe participants’ views, challenges, and coping strategies relating to COVID-19 restrictions. Most participants expressed support for the introduction of strict public health measures, while some criticized lacking enforcement or rational of certain measures. Participants identified four major challenges, namely financial hardship; social isolation and loneliness; stigma and shaming; and fear of COVID-19 infection. Strategies adopted to address these challenges included practical coping strategies (e.g., reducing risks and fear of COVID-19 infection; mitigating financial, social, and mental health impacts), and embedded socio-cultural ways of coping (e.g., turning to religion; practicing acceptance; kindness, generosity and sharing (‘Namjai’); ‘making merit’ (‘Tham-bun’)). The challenges identified from this study, in particular the role of stigma and discrimination, may be relevant to other infectious disease outbreaks beyond COVID-19. Findings from this study underscore the need for policies and interventions that mitigate the negative impacts of NPIs on the public, particularly on vulnerable groups, and highlight the importance of considering socio-cultural context to support community resilience in times of crisis. Our findings remain relevant in light of low COVID-19 vaccine availability and the potential need to implement further public health restrictions in Thailand and elsewhere against COVID-19 or future infectious disease threats

The Roborovski Dwarf Hamster Is A Highly Susceptible Model for a Rapid and Fatal Course of SARS-CoV-2 Infection

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated an unprecedented and yet-unresolved health crisis worldwide. Different mammals are susceptible to SARS-CoV-2; however, few species examined so far develop robust clinical disease that mirrors severe human cases or allows testing of vaccines and drugs under conditions of severe disease. Here, we compare the susceptibilities of three dwarf hamster species (Phodopus spp.) to SARS-CoV-2 and introduce the Roborovski dwarf hamster (P. roborovskii) as a highly susceptible COVID-19 model with consistent and fulminant clinical signs. Particularly, only this species shows SARS-CoV-2-induced severe acute diffuse alveolar damage and hyaline microthrombi in the lungs, changes described in patients who succumbed to the infection but not reproduced in any experimentally infected animal. Based on our findings, we propose the Roborovski dwarf hamster as a valuable model to examine the efficacy and safety of vaccine candidates and therapeutics, particularly for use in highly susceptible individuals

“AMR Dialogues”: a public engagement initiative to shape policies and solutions on antimicrobial resistance (AMR) in Thailand

Background: The use of antimicrobials in Thailand has been reported as one of the highest in the world in both the human and animal sectors. The objectives of this project are: (1) to improve understanding of the issue of antimicrobial resistance (AMR) among adult Thai communities and (2) to drive change through the national AMR policy to include context-specific and locally-driven solutions. Methods: The project contains two components conducted in parallel: the “AMR Dialogues” public engagement project and the embedded evaluation of the project. We will bring together AMR stakeholders and members of the public through a series of conversation events to co-create an AMR stakeholder map, engagement strategy, and context-specific solutions to reduce the burden of AMR. There will be a combination of regional in-person events (‘regional conversations’) and national online events (‘national conversations’) with members of the public and AMR stakeholders. The conversations will follow this sequence: introduce and explore issues related to AMR, brainstorm solutions and finally propose promising/feasible solutions to take forward. Evaluation of the project will be conducted to assess if the AMR Dialogues objectives have been achieved using feedback forms and qualitative methods. Ethics: Approval of the evaluation component of the project has been obtained from the ethics committee of the Thailand Institute for the Development of Human Subject Protection (IHRP2021059) and the Oxford University Tropical Research Ethics Committee (OxTREC 529-21). Dissemination: The results of these conversation events will inform the next Thailand National Strategic Plan on AMR. The learning and outcomes will be disseminated to AMR policy makers, academic audiences, and participants of all the conversation events. Thaiclinicaltrials.org registration: TCTR20210528003 (28/05/2021

Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters

Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines

A non-transmissible live attenuated SARS-CoV-2 vaccine

Live attenuated vaccines (LAVs) administered via the mucosal route may offer better control of the COVID-19 pandemic than non-replicating vaccines injected intramuscularly. Conceptionally, LAVs have several advantages, including presentation of the entire antigenic repertoire of the virus, and the induction of strong mucosal immunity. Thus, immunity induced by LAV could offer superior protection against future surges of COVID-19 cases caused by emerging SARS-CoV-2 variants. However, LAVs carry the risk of unintentional transmission. To address this issue, we investigated whether transmission of a SARS-CoV-2 LAV candidate can be blocked by removing the furin cleavage site (FCS) from the spike protein. The level of protection and immunity induced by the attenuated virus with the intact FCS was virtually identical to the one induced by the attenuated virus lacking the FCS. Most importantly, removal of the FCS completely abolished horizontal transmission of vaccine virus between cohoused hamsters. Furthermore, the vaccine was safe in immunosuppressed animals and showed no tendency to recombine in vitro or in vivo with a SARS-CoV-2 field strain. These results indicate that removal of the FCS from SARS-CoV-2 LAV is a promising strategy to increase vaccine safety and prevent vaccine transmission without compromising vaccine efficacy

Social, ethical and behavioural aspects of COVID-19.

Introduction: Vaccines and drugs for the treatment and prevention of COVID-19 require robust evidence generated from clinical trials before they can be used. Decisions on how to apply non-pharmaceutical interventions such as quarantine, self-isolation, social distancing and travel restrictions should also be based on evidence. There are some experiential and mathematical modelling data for these interventions, but there is a lack of data on the social, ethical and behavioural aspects of these interventions in the literature. Therefore, our study aims to produce evidence to inform (non-pharmaceutical) interventions such as communications, quarantine, self-isolation, social distancing, travel restrictions and other public health measures for the COVID-19 pandemic. Methods: The study will be conducted in the United Kingdom, Italy, Malaysia, Slovenia and Thailand. We propose to conduct 600-1000 quantitative surveys and 25-35 qualitative interviews per country. Data collection will follow the following four themes: (1) Quarantine and self-isolation (2) social distancing and travel restrictions (3) wellbeing and mental health (4) information, misinformation and rumours. In light of limitations of travel and holding in-person meetings, we will primarily use online/remote methods for collecting data. Study participants will be adults who have provided informed consent from different demographic, socio-economic and risk groups. Discussion: At the time of the inception of the study, United Kingdom, Italy, Malaysia, Slovenia and Thailand have initiated strict public health measures and varying degrees of "lockdowns" to curb the pandemic. These public health measures will change in the coming weeks and months depending on the number of cases of COVID-19 in the respective countries. The data generated from our study could inform these strategies in real time

Raising awareness of antimicrobial resistance: development of an 'antibiotic footprint calculator'

Non-academic partners can be vital in successful public engagement activities on antimicrobial resistance. With collaboration between academic and non-academic partners, we developed and launched an open-access web-based application, the 'antibiotic footprint calculator', in both Thai and English. The application focused on a good user experience, addressing antibiotic overuse and its impact, and encouraging immediate action. The application was unveiled in joint public engagement activities. From 1 Nov 2021 to 31 July 2022 (9 month period), 2554 players estimated their personal antibiotic footprint by using the application

The impact of COVID-19 non-pharmaceutical interventions on the lived experiences of people living in Thailand, Malaysia, Italy and the United Kingdom: A cross-country qualitative study.

This qualitative study explores the impact of non-pharmaceutical interventions (NPIs), including social distancing, travel restrictions and quarantine, on lived experiences during the first wave of the COVID-19 pandemic in Thailand (TH), Malaysia (MY), Italy (IT) and the United Kingdom (UK). A total of 86 interviews (TH: n = 28; MY: n = 18; IT: n = 20; UK: n = 20) were conducted with members of the public, including healthcare workers (n = 13). Participants across countries held strong views on government imposed NPIs, with many feeling measures lacked clarity. Most participants reported primarily negative impacts of NPIs on their lives, including through separation, isolation and grief over missed milestones; work-related challenges and income loss; and poor mental health and wellbeing. Nonetheless, many also experienced inadvertent positive consequences, including more time at home to focus on what they most valued in life; a greater sense of connectedness; and benefits to working life. Commonly employed coping strategies focused on financial coping (e.g. reducing spending); psycho-emotional coping (e.g. engaging in spiritual practices); social coping and connectedness (e.g., maintaining relationships remotely); reducing and mitigating risks (e.g., changing food shopping routines); and limiting exposure to the news (e.g., checking news only occasionally). Importantly, the extent to which participants' lived experiences were positive or negative, and their ability to cope was underpinned by individual, social and economic factors, with the analysis indicating some salient differences across countries and participants. In order to mitigate negative and unequal impacts of NPIs, COVID-19 policies will benefit from paying closer attention to the social, cultural and psychological-not just biological-vulnerabilities to, and consequences of public health measures