Precursors of exhausted T cells are preemptively formed in acute infection.

T cell exhaustion limits effector T cell function in chronic infection and tumors. The development of these hypofunctional T cells and of their precursors was considered to require stimulatory conditions met only upon persisting exposure to antigen and inflammation. In sharp contrast, we found similar T cell populations in the early phase of acute infections.

Clinical Pharmacokinetics and Pharmacodynamics of Baxdrostat.

Patients with hypertension are at an increased risk of cardiovascular disease and death. Resistant hypertension, or hypertension that is unsuccessfully treated with multiple antihypertensive medications, further exacerbates the complications and negative outcomes for patients. A new pathway, via aldosterone synthesis inhibition, is currently being studied as a method to reduce blood pressure values in patients who are currently taking other antihypertensive medications.

Virtual surgical planning in microsurgical head and neck reconstruction: The Newcastle experience.

Head and neck microvascular reconstruction is a complex but powerful tool following immediate cancer ablation or delayed sequalae after cancer treatment. Virtual surgical planning (VSP), using computer-aided design or computer-aided manufacturing has emerged as a potentially beneficial adjunct to head and neck reconstruction. The aim of this study was to assess the outcomes of VSP technology using the KLS Martin custom-made cutting guides and low-profile plates in head and neck microvascular reconstruction in our centre.

Objective sleep monitoring at home in older adults: A scoping review.

Inadequate sleep in older adults is linked to health issues such as frailty, cognitive impairment and cardiovascular disorders. Maintaining regular sleep patterns is important for healthy aging, making effective sleep monitoring essential. While polysomnography is the gold-standard for diagnosing sleep disorders, its regular use in home settings is limited.

Avoiding "a piece of paper on the wall that everyone ignores": A qualitative study on the barriers for implementing open fracture guidelines.

Background: Ortho-plastic evidence-based clinical guidelines for open fractures have demonstrated to standardise care and improve outcomes for patients admitted following lower extremity trauma. Despite its benefits, very few countries have introduced such guidance. The aim of this study was to explore the attitudes, barriers and limitations to the development and implementation of guidelines for lower limb open fractures METHODS: Twelve renowned orthopaedic and plastic surgeons, based in countries with no guidelines at present, underwent semi-structured interviews.

Quality of Life after Open Extremity Trauma (QUINTET) study: An international, multicentric, observational, cohort study of quality of life following lower extremity open fractures.

Introduction: Open lower limb fractures are severe injuries with long-lasting consequences. Limited research has been conducted on the impact of these injuries on quality of life (QoL), internationally.

Methods: The Quality of Life after Open Extremity Trauma (QUINTET) study was designed as an international, multicentric, observational, cohort study of patients presented with open lower limb fractures.

Large-scale medieval urbanism traced by UAV-lidar in highland Central Asia.

Aerial light detection and ranging (lidar) has emerged as a powerful technology for mapping urban archaeological landscapes, especially where dense vegetation obscures site visibility. More recently, uncrewed aerial vehicle/drone lidar scanning has markedly improved the resolution of three-dimensional point clouds, allowing for the detection of slight traces of structural features at centimetres of detail across large archaeological sites, a method particularly useful in areas such as mountains, where rapid deposition and erosion irregularly bury and expose archaeological remains. Here we present the results of uncrewed aerial vehicle-lidar surveys in Central Asia, conducted at two recently discovered archaeological sites in southeastern Uzbekistan: Tashbulak and Tugunbulak.

Insulin oxidation and oxidative modifications alter glucose uptake, cell metabolism, and inflammatory secretion profiles.

Insulin participates in glucose homeostasis in the body and regulates glucose, protein, and lipid metabolism. Chronic hyperglycemia triggers oxidative stress and the generation of reactive oxygen species (ROS), leading to oxidized insulin variants. Oxidative protein modifications can cause functional changes or altered immunogenicity as known from the context of autoimmune disorders.

Levels and trends of persistent organic pollutants in human populations living in the Arctic.

The Arctic Monitoring Assessment Program (AMAP) is tasked with monitoring and assessing the status of environmental contaminants in the Arctic, documenting levels and trends, and producing science-based assessments. The objectives of this paper are to present the current levels of persistent organic pollutants (POPs) across the Arctic, and to identify trends and knowledge gaps as detailed in the most recent AMAP Human Health Assessment Report. Many Arctic populations continue to have elevated levels of these contaminants, and the highest levels of POPs were observed in populations from Greenland, Faroe Islands, and Nunavik (Canada), as well as populations in the coastal Chukotka district (Russia) for legacy POPs only.

Tissue-engineered cellulose tubes for microvascular and lymphatic reconstruction: A translational and feasibility study.

Background: Lymphedema microsurgery is an emerging treatment modality, with dissimilar long-term outcomes. One of the main technical challenges in lymphatic microsurgery is the identification and availability of suitable donor vessels for anastomosis. Tissue engineering using biomaterials has demonstrated promise in addressing vessel quality issues in other fields, but its application in microsurgery is still limited.

mTORC1 activation in presumed classical monocytes: observed correlation with human size variation and neuropsychiatric disease.

Background: Gain of function disturbances in nutrient sensing are likely the largest component in human age-related disease. Mammalian target of rapamycin complex 1 (mTORC1) activity affects health span and longevity. The drugs ketamine and rapamycin are effective against chronic pain and depression, and both affect mTORC1 activity.

Insulin icodec: A novel once-weekly treatment for diabetes.

Aims: To summarize the results of clinical studies of insulin icodec, an investigational insulin analog designed for once-weekly administration, in adults with type 1 and type 2 diabetes.

Methods: Thirteen published articles describing clinical studies of insulin icodec were identified in PubMed, and data pertinent to key study outcomes were selected for inclusion in this review.

Results: In insulin-naïve and insulin-treated individuals, icodec demonstrated efficacy in glycaemic control superior or noninferior to that of insulins glargine U100, glargine U300 and degludec.

The "Flapbot": A Global Perspective on the Validity and Usability of a Flap Monitoring Chatbot.

Background:  The Flapbot chatbot assists in free-flap monitoring, emphasizing accessibility, user-friendliness, and global reliability. This study assesses Flapbot's worldwide validity and usability and uses qualitative analysis to identify areas for future enhancement.

Methods:  Flapbot, built on Google's DialogFlow, was evaluated by international plastic surgeons.

Reactive Species Risk Assessment Using Optimized HET-CAM Safety Evaluation of Feed Gas-Modified Gas Plasma Technology and Anticancer Drugs.

Clinical therapies, including dermatology and oncology, require safe application. In vitro experiments allow only limited conclusions about in vivo effects, while animal studies in, e.g.

Characterization of Immune Cell Infiltration and Collagen Type III Disorganization in Human Secondary Lymphedema: A Case-control Study.

Background: Secondary lymphedema (SL) affects 120 million people globally, posing a lifelong burden for up to 37% of cancer survivors. Chronic inflammation and progressive fibrosis are key drivers of SL, yet detailed characterization of immune cell subpopulations across lymphedema stages is lacking. This study aimed to investigate the immunologic profile of lymphedematous skin and its association with extracellular matrix changes, which could serve as clinical biomarkers or therapeutic targets.

One health in the Arctic - connections and actions.

There is growing awareness and recognition of the importance of the One Health paradigm to address existing environmental threats and recognise emerging ones at an early stage among Arctic residents, public health agencies, and wildlife resource managers. The One Health approach, emphasising the interconnectedness of human, animal, and ecosystem health, plays a pivotal role in addressing these multifaceted issues. Warming climate and permafrost thaw may influence both contaminant exposure and the spread of zoonotic infectious diseases and have impacts on water and food security.

Meropenem Disposition in Neonatal and Pediatric Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy.

This study aimed to characterize the impact of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics (PK) of meropenem in neonates and children and to provide recommendations for meropenem dosing in this specific population of patients. Therapeutic drug monitoring (152 meropenem plasma concentrations) data from 45 patients (38 received ECMO) with a body weight (BW) of 7.88 (3.