Ukrainian healthcare providers under siege during the first year of war: challenges and adaptations.

The overlapping COVID-19 crisis and the war starting in 2022 threaten front-line healthcare workers' mental health, well-being and job retention in Ukraine. This paper provides a synopsis of a panel discussion held by the Global Mental Health Humanitarian Coalition in May 2022 and expert consultations with clinicians between December 2022 and February 2023 on these challenges. The crises created new problems and exacerbated many pre-existing difficulties. We found that healthcare workers had needed to mobilise previously untapped strengths, including portable emergency medical documents and bespoke local psychosocial support services, amid the costs and pressures of ongoing healthcare reforms.

Treatment System Adaptations during War: Lessons from Ukrainian Addiction Treatment Providers.

Background: The war in Ukraine has posed significant challenges to the healthcare system. This paper draws upon expert consultations, held between December 2022 and February 2023, focused on HIV/AIDS, addiction, and mental health service delivery during the first year of this war, and following the Global Mental Health Humanitarian Coalition panel discussion in May 2022. Objectives: This commentary presents the experiences of frontline healthcare workers in Ukraine, challenges, and local adaptations to meet the increased mental health needs of healthcare providers. We aimed to document the adaptations made in the addiction healthcare system and to acknowledge the changes in vulnerabilities and lessons learned. Results: Burnout among healthcare providers delivering addiction, HIV/AIDS and mental health services became more visible after the second half of 2022. Challenges included increased workload, contextual threats, lack of job relocation strategies, and money-follow-the-patient policies. Recommendations: The lessons from the first year of war in Ukraine hold significant generalizability to other contexts. These include enabling bottom-up approaches to tailoring services and allowing healthcare providers to respond to the dynamics of war in an effective and active manner. Other recommendations include departmental-specific resources and strategies, particularly as vulnerable groups and challenges are unstable in humanitarian contexts. Conclusions: Globally and in Ukraine, healthcare workers need more than applause. Along with monetary incentives, other strategies to prevent burnout, ensure sustainable capacity building, job relocation opportunities, and bespoke adaptations are imperative to protect healthcare providers' wellbeing and overall public health.

Temporin L and aurein 2.5 have identical conformations but subtly distinct membrane and antibacterial activities.

Frogs such as Rana temporaria and Litoria aurea secrete numerous closely related antimicrobial peptides (AMPs) as an effective chemical dermal defence. Damage or penetration of the bacterial plasma membrane is considered essential for AMP activity and such properties are commonly ascribed to their ability to form secondary amphipathic, α-helix conformations in membrane mimicking milieu. Nevertheless, despite the high similarity in physical properties and preference for adopting such conformations, the spectrum of activity and potency of AMPs often varies considerably. Hence distinguishing apparently similar AMPs according to their behaviour in, and effects on, model membranes will inform understanding of primary-sequence-specific antimicrobial mechanisms. Here we use a combination of molecular dynamics simulations, circular dichroism and patch-clamp to investigate the basis for differing anti-bacterial activities in representative AMPs from each species; temporin L and aurein 2.5. Despite adopting near identical, α-helix conformations in the steady-state in a variety of membrane models, these two AMPs can be distinguished both in vitro and in silico based on their dynamic interactions with model membranes, notably their differing conformational flexibility at the N-terminus, ability to form higher order aggregates and the characteristics of induced ion conductance. Taken together, these differences provide an explanation of the greater potency and broader antibacterial spectrum of activity of temporin L over aurein 2.5. Consequently, while the secondary amphipathic, α-helix conformation is a key determinant of the ability of a cationic AMP to penetrate and disrupt the bacterial plasma membrane, the exact mechanism, potency and spectrum of activity is determined by precise structural and dynamic contributions from specific residues in each AMP sequence.

Minor sequence modifications in temporin B cause drastic changes in antibacterial potency and selectivity by fundamentally altering membrane activity.

Antimicrobial peptides (AMPs) are a potential source of new molecules to counter the increase in antimicrobial resistant infections but a better understanding of their properties is required to understand their native function and for effective translation as therapeutics. Details of the mechanism of their interaction with the bacterial plasma membrane are desired since damage or penetration of this structure is considered essential for AMPs activity. Relatively modest modifications to AMPs primary sequence can induce substantial changes in potency and/or spectrum of activity but, hitherto, have not been predicted to substantially alter the mechanism of interaction with the bacterial plasma membrane. Here we use a combination of molecular dynamics simulations, circular dichroism, solid-state NMR and patch clamp to investigate the extent to which temporin B and its analogues can be distinguished both in vitro and in silico on the basis of their interactions with model membranes. Enhancing the hydrophobicity of the N-terminus and cationicity of the C-terminus in temporin B improves its membrane activity and potency against both Gram-negative and Gram-positive bacteria. In contrast, enhancing the cationicity of the N-terminus abrogates its ability to trigger channel conductance and renders it ineffective against Gram-positive bacteria while nevertheless enhancing its potency against Escherichia coli. Our findings suggest even closely related AMPs may target the same bacterium with fundamentally differing mechanisms of action.