Biomimetic Non-ergodic Aging by Dynamic-to-covalent Transitions in Physical Hydrogels.

Hydrogels are soft materials engineered to suit a multitude of applications that exploit their tunable mechanochemical properties. Dynamic hydrogels employing noncovalent, physically cross-linked networks dominated by either enthalpic or entropic interactions enable unique rheological and stimuli-responsive characteristics. In contrast to enthalpy-driven interactions that soften with increasing temperature, entropic interactions result in largely temperature-independent mechanical properties. By engineering interfacial polymer-particle interactions, we can induce a dynamic-to-covalent transition in entropic hydrogels that leads to biomimetic non-ergodic aging in the microstructure without altering the network mesh size. This transition is tuned by varying temperature and formulation conditions such as pH, which allows for multivalent tunability in properties. These hydrogels can thus be designed to exhibit either temperature-independent metastable dynamic cross-linking or time-dependent stiffening based on formulation and storage conditions, all while maintaining structural features critical for controlling mass transport, akin to many biological tissues. Such robust materials with versatile and adaptable properties can be utilized in applications such as wildfire suppression, surgical adhesives, and depot-forming injectable drug delivery systems.

A reproducible, self-reported, field-based tool for monitoring ovarian hormone status and body weight variations in female athletes: the Answ'Her questionnaire.

BACKGROUND: Intra-individual factors like ovarian hormone profiles and body weight variations may influence sports practice and performance in female athletes and need to be characterized. The "Answ'Her" questionnaire was designed to develop a relevant and reproducible field-based tool to assess self-reported ovarian hormone status (natural menstrual cycle and hormonal contraceptive use) and body weight variations practices among female athletes. METHODS: French females with a regular sports practice responded (once: N.=210; twice: N.=86; thrice: N.=66) to this 73-item questionnaire reporting their ovarian hormone status, associated symptoms, perceived influence on sports practice, and body weight variations. Reproducibility was evaluated, then a descriptive cross-sectional analysis was conducted on athletes. RESULTS: Reproducibility was verified with 92% of Lin's correlation concordance coefficients above 0.7 and 100% of weighted agreements above 70%. Ultimately 185 female athletes (23.0±4.8 years) were included in the cross-sectional analysis. Whether they used hormonal contraceptive (46.5%) or not (53.5%), most of the athletes perceived a negative impact of their ovarian hormone status on sports practice (78.7%) and performance (84.7%). Overall, 77.3% of the athletes had experienced body weight variations that were significantly associated with an interruption of menses (>3 months) and menses irregularity over the last three years. CONCLUSIONS: The Answ'Her questionnaire is a simple and effective reproducible field-based tool for the self-reported characterisation of female athlete ovarian hormone status and body weight variations. It could be used for a unique and simple overview of the athlete situation but also in a longitudinal design to assess the athlete's evolution and/or effectiveness of implanted training strategies.

High-throughput mass spectrometry maps the sepsis plasma proteome and differences in patient response.

Sepsis, the dysregulated host response to infection causing life-threatening organ dysfunction, is a global health challenge requiring better understanding of pathophysiology and new therapeutic approaches. Here, we applied high-throughput tandem mass spectrometry to delineate the plasma proteome for sepsis and comparator groups (noninfected critical illness, postoperative inflammation, and healthy volunteers) involving 2612 samples (from 1611 patients) and 4553 liquid chromatography-mass spectrometry analyses acquired through a single batch of continuous measurements, with a throughput of 100 samples per day. We show how this scale of data can delineate proteins, pathways, and coexpression modules in sepsis and be integrated with paired leukocyte transcriptomic data (837 samples from n = 649 patients). We mapped the plasma proteomic landscape of the host response in sepsis, including changes over time, and identified features relating to etiology, clinical phenotypes (including organ failures), and severity. This work reveals subphenotypes informative for sepsis response state, disease processes, and outcome; identifies potential biomarkers; and advances opportunities for a precision medicine approach to sepsis.

Phthalate and phthalate replacement concentrations in relationship to adiposity in a multi-racial cohort of children.

BACKGROUND/OBJECTIVE: Phthalates and phthalate replacements are used in multiple everyday products, making many of them bioavailable to children. Experimental studies suggest that phthalates and their replacements may be obesogenic, however, epidemiologic studies remain inconsistent. Therefore, our objective was to examine the association between phthalates, phthalate replacements and childhood adiposity/obesity markers in children. SUBJECTS/METHODS: A cross-sectional study was conducted in 630 racial/ethnically diverse children ages 4-8 years. Urinary oxidative metabolites of DINCH and DEHTP, three low molecular weight (LMW) phthalates, and eleven high molecular weight (HMW) phthalates were measured. Weight, height, waist circumference and % body fat were measured. Composite molar sum groups (nmol/ml) were natural log-transformed. Linear regression models adjusted for urine specific gravity, sex, age, race-ethnicity, birthweight, breastfeeding, reported activity level, mother's education and pre-pregnancy BMI. RESULTS: All children had LMW and HMW phthalate metabolites and 88% had DINCH levels above the limit of detection. One unit higher in the log of DINCH was associated with 0.106 units lower BMI z-score [ß = -0.106 (95% CI: -0.181, -0.031)], 0.119 units lower waist circumference z-score [ß = -0.119 (95% CI: -0.189, -0.050)], and 0.012 units lower percent body fat [ß = -0.012 (95% CI: -0.019, -0.005)]. LMW and HMW group values were not associated with adiposity/obesity. CONCLUSIONS: We report an inverse association between child urinary DINCH levels, a non-phthalate plasticizer that has replaced DEHP in several applications, and BMI z-score, waist circumference z-score and % body fat in children. Few prior studies of phthalates and their replacements in children have been conducted in diverse populations. Moreover, DINCH has not received a great deal of attention or regulation, but it is a common exposure. In summary, understanding the ubiquitous nature of these chemical exposures and ultimately their sources will contribute to our understanding of their relationship with obesity.

Study protocol of a systematic review and metaanalysis of stress and burnout among general surgery residents.

Introduction: Chronic workplace stress and burnout are impediments to physicians' professional fulfillment, healthcare organizations' efficiency, and patient care quality/safety. General surgery residents are especially at risk due to the complexity of their training. We report the protocol of a metaanalysis of chronic stress and burnout among Accreditation Council for Graduate Medical Education (ACGME)-affiliated general surgery residents in the era after duty-hour reforms, plus downstream effects on their health and clinical performance. Methods: The proposed systematic review and metaanalysis (PROSPERO registration CRD42021277626) will synthesize/pool data from studies of chronic stress and burnout among general surgery residents at ACGME-affiliated programs. The timeframe under review is subdivided into three intervals: (a) after the 2003 duty-hour restrictions but before 2011 reforms, (b) after the 2011 reforms but before the coronavirus pandemic, and (c) the first 3 years after the pandemic's outbreak. Only studies reporting outcomes based on validated instruments will be included. Qualitative studies, commentaries/editorials, narrative reviews, and studies not published in English will be excluded. Multivariable analyses will adjust for sample characteristics and the methodological quality of included studies. Conclusions: The metaanalysis will yield evidence reflecting experiences of North American-based general surgery residents in the years after ACGME-mandated duty-hour restructuring.

Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in Synovial Sarcoma.

Synovial Sarcoma (SS) is driven by the SS18::SSX fusion oncoprotein and is ultimately refractory to therapeutic approaches. SS18::SSX alters ATP-dependent chromatin remodeling BAF (mammalian SWI/SNF) complexes, leading to the degradation of canonical (cBAF) complex and amplified presence of an SS18::SSX-containing non-canonical BAF (ncBAF or GBAF) that drives an SS-specific transcription program and tumorigenesis. We demonstrate that SS18::SSX activates the SUMOylation program and SSs are sensitive to the small molecule SAE1/2 inhibitor, TAK-981. Mechanistically, TAK-981 de-SUMOylates the cBAF subunit SMARCE1, stabilizing and restoring cBAF on chromatin, shifting away from SS18::SSX-ncBAF-driven transcription, associated with DNA damage and cell death and resulting in tumor inhibition across both human and mouse SS tumor models. TAK-981 synergized with cytotoxic chemotherapy through increased DNA damage, leading to tumor regression. Targeting the SUMOylation pathway in SS restores cBAF complexes and blocks the SS18::SSX-ncBAF transcriptome, identifying a therapeutic vulnerability in SS, positioning the in-clinic TAK-981 to treat SS.

Precision symptom phenotyping identifies early clinical and proteomic predictors of distinct COVID-19 sequelae.

BACKGROUND: Post-COVID conditions (PCC) are difficult to characterize, diagnose, predict, and treat due to overlapping symptoms and poorly understood pathology. Identifying inflammatory profiles may improve clinical prognostication and trial endpoints. METHODS: 1,988 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative post-COVID symptom scores were included in this analysis. Among participants who reported moderate-to-severe symptoms on surveys collected 6-months post-SARS-CoV-2 infection, principal component analysis (PCA) followed by K-means clustering identified distinct clusters of symptoms. RESULTS: Three symptom-based clusters were identified: a sensory cluster (loss of smell and/or taste), a fatigue/difficulty thinking cluster, and a difficulty breathing/exercise intolerance cluster. Individuals within the sensory cluster were all outpatients during their initial COVID-19 presentation. The difficulty breathing cluster had a higher likelihood of obesity and COVID-19 hospitalization compared to those with no/mild symptoms at 6-months post-infection. Multinomial regression linked early post-infection D-dimer and IL-1RA elevation to fatigue/difficulty thinking, and elevated ICAM-1 concentrations to sensory symptoms. CONCLUSIONS: We identified three distinct symptom-based PCC phenotypes with specific clinical risk factors and early post-infection inflammatory predictors. With further validation and characterization, this framework may allow more precise classification of PCC cases and potentially improve the diagnosis, prognostication, and treatment of PCC.

Stroke as a career option for neurologists.

Stroke is one of the most common acute neurological disorders and a leading cause of disability worldwide. Evidence-based treatments over the last two decades have driven a revolution in the clinical management and design of stroke services. We need a highly skilled, multidisciplinary workforce that includes neurologists as core members to deliver modern stroke care. In the UK, the dedicated subspecialty training programme for stroke medicine has recently been integrated into the neurology curriculum. All neurologists will be trained to contribute to each aspect of the stroke care pathway. We discuss how training in stroke medicine is evolving for neurologists and the opportunities and challenges around practising stroke medicine in the UK and beyond.

Transcutaneous auricular vagus nerve stimulation to acutely reduce emotional vulnerability and improve emotional regulation in borderline personality disorder (tVNS-BPD): study protocol for a randomized, single-blind, sham-controlled trial.

BACKGROUND: Borderline personality disorder (BPD) is considered a disorder of emotion regulation resulting from the expression of a biologically determined emotional vulnerability (that is, heightened sensitivity to emotion, increased emotional intensity/reactivity, and a slow return to emotional baseline) combined with exposure to invalidating environments. Vagal tone has been associated with activity in cortical regions involved in emotion regulation and a lower resting state of vagal tone has been observed in BPD patients relative to healthy controls. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has been shown to reduce temper outbursts in adults with Prader-Willi Syndrome, to enhance recognition of emotions in healthy students, and to improve depressive and anxiety symptoms. Furthermore, a single session of taVNS has been shown to acutely alter the recognition of facial expressions of negative valence in adolescents with MDD and increase emotion recognition in controls. However, the effect of taVNS on emotional vulnerability and regulation in individuals diagnosed with BPD has not been investigated. Our aims are to determine if taVNS is effective in acutely reducing emotional vulnerability and improve emotional regulation in BPD patients. METHODS: Forty-two patients will be randomized to a single session of taVNS or sham-taVNS while going through an affect induction procedure. It will consist of the presentation of one neutral and three negative affect-evoking 4-min-long videos in sequence, each of which is followed by a 4-min post-induction period during which participants will rate the quality and intensity of their current self-reported emotions (post-induction ratings) and the perceived effectiveness in managing their emotions during the video presentation. The rating of the current self-reported emotions will be repeated after every post-induction period (recovery ratings). Mixed models with individuals as random effect will be used to investigate the ratings at each stage of the study, taking into account the repeated measures of the same individuals at baseline, pre-induction, post-induction, and recovery. DISCUSSION: The study has potential to yield new insights into the role of vagal tone in emotion dysregulation in BPD and offer preliminary data on the effectiveness of taVNS as a possible non-invasive brain stimulation to treat a core symptom of BPD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05892900. Retrospectively registered on Jun 07, 2023.

Surveillance outcomes of respiratory pathogen infections during the 2021-2022 season among U.S. Military Health System beneficiaries, October 3, 2021-October 1, 2022.

The Department of Defense Global Respiratory Pathogen Surveillance Program conducts continuous surveillance for influenza, severe acute respiratory syndrome 2 (SARS-CoV-2), and other respiratory pathogens at 104 sentinel sites across the globe. These sites submitted 65,475 respiratory specimens for clinical diagnostic testing during the 2021-2022 surveillance season. The predominant influenza strain was influenza A(H3N2) (n=777), of which 99.9% of strains were in clade 3C.2a1b.2a2. A total of 21,466 SARSCoV-2-positive specimens were identified, and 12,225 of the associated viruses were successfully sequenced. The Delta variant predominated at the start of the season, until December 2021, when Omicron became dominant. Most circulating SARS-CoV-2 viruses were subsequently held by Omicron sublineages BA.1, BA.2, and BA.5 during the season. Clinical manifestation, obtained through a self-reported questionnaire, found that cough, sinus congestion, and runny nose complaints were the most common symptoms presenting among all pathogens. Sentinel surveillance can provide useful epidemiological data to supplement other disease monitoring activities, and has become increasingly useful with increasing numbers of individuals utilizing COVID-19 rapid self-test kits and reductions in outpatient visits for routine respiratory testing.

Androgen deprivation-induced senescence confers sensitivity to a senolytic strategy in prostate cancer.

We have previously demonstrated that androgen-dependent prostate cancer (PCa) cell lines enter a state of senescence following exposure to androgen deprivation therapies (ADT). ADT-induced senescence was found to be transient, as senescent cells develop castration resistance and re-emerge into a proliferative state even under continuous androgen deprivation in vitro. Moreover, the BCL-XL/BCL-2 inhibitor, ABT-263 (navitoclax), an established senolytic agent, promoted apoptosis of senescent PCa cells, suppressing proliferative recovery and subsequent tumor cell outgrowth. As this strategy has not previously been validated in vivo, we used a clinically relevant, syngeneic murine model of PCa, where mice were either castrated or castrated followed by the administration of ABT-263. Our results largely confirm the outcomes previously reported in vitro; specifically, castration alone results in a transient tumor growth suppression with characteristics of senescence, which is prolonged by exposure to ABT-263. Most critically, mice that underwent castration followed by ABT-263 experienced a statistically significant prolongation in survival, with an increase of 14.5 days in median survival time (56 days castration alone vs. 70.5 days castration + ABT-263). However, as is often the case in studies combining the promotion of senescence with a senolytic (the "one-two" punch approach), the suppression of tumor growth by the inclusion of the senolytic agent was transient, allowing for tumor regrowth once the drug treatment was terminated. Nevertheless, the results of this work suggest that the "one-two" punch senolytic strategy in PCa may effectively interfere with, diminish, or delay the development of the lethal castration-resistant phenotype.

Effects of a Preseason Neuromuscular Training Program vs. an Endurance-Dominated Program on Physical Fitness and Injury Prevention in Female Soccer Players.

BACKGROUND: The pre-season preparatory period is considered key for optimizing the physical fitness levels needed to withstand congested match periods and preventing injuries during the regular soccer season. This study contrasted the effects s of neuromuscular training (NMT) versus an endurance-dominated training (ET) program conducted during the preseason on measures of physical fitness and injury occurrence in female soccer players. METHODS: Twenty-four female soccer players aged 17.0 ± 1.3 years from a professional soccer club participated in this study. Players were randomly assigned to NMT (n = 12) or ET (n = 12) groups according to their playing position. The preseason intervention program lasted six weeks, with three weekly sessions with a duration of 45-60 min per session. Exercises in the NMT group included muscle strengthening exercises, plyometrics, agility and dynamic stability exercises, while the ET group practiced a traditional pre-season training program consisting of running and sprinting exercises, fartlek, and high-intensity interval training. The training volumes were similar in the two study groups. Anthropometric measurements, physical fitness tests (i.e., linear and change-of-direction speed, muscle strength and power tests) and the overall injury rate per 1000 h of exposure (training, match) were recorded throughout the season. RESULTS: No between group differences were found at pre (T1). Significant group-by-time interactions were observed for the 5, 10, and 30-m linear sprint speed tests (p < 0.001, 2.16 < d < 2.58), the T-test (p = 0.024, d = 1.03), the squat (p < 0.001, d = 4.04), and the countermovement jump test (p < 0.001, d = 2.21), the Loughborough soccer passing test (LSPT) (p = 0.019, d = 1.08), and the 1-RM back squat test (p < 0.001, d = 2.53). Post-hoc tests indicated that NMT provided larger improvements for SJ, CMJ, 1-RM back squat, the 5-m sprint, 10-m sprint, 30-m sprint, T-test and LSPT compared to ET (1.07 > d > 2.77). The injury rate across the season was significantly lower in the NMT (5.1/1000 h exposure) compared to ET (11.8/1000 h exposure) (p = 0.014). CONCLUSIONS: The findings support that six-weeks of preseason NMT versus ET induced larger performance improvements, and significantly reduced injury occurrence in elite female soccer players.

Preliminary Virtual Constraint-Based Control Evaluation on a Pediatric Lower-Limb Exoskeleton.

Pediatric gait rehabilitation and guidance strategies using robotic exoskeletons require a controller that encourages user volitional control and participation while guiding the wearer towards a stable gait cycle. Virtual constraint-based controllers have created stable gait cycles in bipedal robotic systems and have seen recent use in assistive exoskeletons. This paper evaluates a virtual constraint-based controller for pediatric gait guidance through comparison with a traditional time-dependent position tracking controller on a newly developed exoskeleton system. Walking experiments were performed with a healthy child subject wearing the exoskeleton under proportional-derivative control, virtual constraint-based control, and while unpowered. The participant questionnaires assessed the perceived exertion and controller usability measures, while sensors provided kinematic, control torque, and muscle activation data. The virtual constraint-based controller resulted in a gait similar to the proportional-derivative controlled gait but reduced the variability in the gait kinematics by 36.72% and 16.28% relative to unassisted gait in the hips and knees, respectively. The virtual constraint-based controller also used 35.89% and 4.44% less rms torque per gait cycle in the hips and knees, respectively. The user feedback indicated that the virtual constraint-based controller was intuitive and easy to utilize relative to the proportional-derivative controller. These results indicate that virtual constraint-based control has favorable characteristics for robot-assisted gait guidance.

Sex Differences in Cardiovascular Outcomes in Patients With Kidney Failure.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in patients with kidney failure, and their risk of cardiovascular events is 10 to 20 times higher as compared with the general population. METHODS AND RESULTS: We evaluated 508 822 patients who initiated dialysis between January 1, 2005 and December 31, 2014 using the United States Renal Data System with linked Medicare claims. We determined hospitalization rates for cardiovascular events, defined by acute coronary syndrome, heart failure, and stroke. We examined the association of sex with outcome of cardiovascular events, cardiovascular death, and all-cause death using adjusted time-to-event models. The mean age was 70±12 years and 44.7% were women. The cardiovascular event rate was 232 per thousand person-years (95% CI, 231-233), with a higher rate in women than in men (248 per thousand person-years [95% CI, 247-250] versus 219 per thousand person-years [95% CI, 217-220]). Women had a 14% higher risk of cardiovascular events than men (hazard ratio [HR], 1.14 [95% CI, 1.13-1.16]). Women had a 16% higher risk of heart failure (HR, 1.16 [95% CI, 1.15-1.18]), a 31% higher risk of stroke (HR, 1.31 [95% CI, 1.28-1.34]), and no difference in risk of acute coronary syndrome (HR, 1.01 [95% CI, 0.99-1.03]). Women had a lower risk of cardiovascular death (HR, 0.89 [95% CI, 0.88-0.90]) and a lower risk of all-cause death than men (HR, 0.96 [95% CI, 0.95-0.97]). CONCLUSIONS: Among patients undergoing dialysis, women have a higher risk of cardiovascular events of heart failure and stroke than men. Women have a lower adjusted risk of cardiovascular mortality and all-cause mortality.

Postoperative pain score does not correlate with injury severity in isolated tibial plateau fractures.

PURPOSE: Appropriate management of acute postoperative pain is critical for patient care and practice management. The purpose of this study was to determine whether postoperative pain score correlates with injury severity in tibial plateau fractures. METHODS: A retrospective review of prospectively collected data was completed at a single academic level one trauma center. All adult patients treated operatively for tibial plateau fractures who did not have concomitant injuries, previous injury to the ipsilateral tibia or knee joint, compartment syndrome, inadequate follow-up, or perioperative regional anesthesia were included (n = 88). The patients were split into groups based on the AO/OTA fracture classification (B-type vs C-type), energy mechanism, number of surgical approaches, need for temporizing external fixation, and operative time as a proxy for injury severity. The primary outcome measure was the visual analog scale (VAS) pain score (average in the first 24 h, highest in the first 24 h, two- and six-week postoperative appointments). Psychosocial and comorbid factors that may affect pain were studied and controlled for (history of diabetes, neuropathy, anxiety, depression, PTSD, and previous opioid prescription). Additionally, opioid use in the postoperative period was studied and controlled for (morphine milligram equivalents (MME) administered in the first 24 h, discharge MME/day, total discharge MME, and opioid refills). RESULTS: VAS scores were similar between groups at each time point except the two-week postoperative time point. At the two-week postoperative time point, the absolute difference between the groups was 1.3. The groups were significantly different in several injury and surgical variables as expected, but were similar in all demographic, comorbid, and postoperative opioid factors. CONCLUSIONS: There was no clinical difference in postoperative pain between AO/OTA 41B and 41C tibial plateau fractures. This supports the idea of providers uncoupling nociception and pain in postoperative patients. Providers should consider minimizing extended opioid use, even in more severe injuries.

General practitioner preferences for telehealth consultations in Australia: a pilot survey and discrete choice experiment.

AIM: To identify and quantify general practitioner (GP) preferences related to service attributes of clinical consultations, including telehealth consultations, in Australia. BACKGROUND: GPs have been increasingly using telehealth to deliver patient care since the onset of the 2019 coronavirus disease (COVID-19) pandemic. GP preferences for telehealth service models will play an important role in the uptake and sustainability of telehealth services post-pandemic. METHODS: An online survey was used to ask GPs general telehealth questions and have them complete a discrete choice experiment (DCE). The DCE elicited GP preferences for various service attributes of telehealth (telephone and videoconference) consultations. The DCE investigated five service attributes, including consultation mode, consultation purpose, consultation length, quality of care and rapport, and patient co-payment. Participants were presented with eight choice sets, each containing three options to choose from. Descriptive statistics was used, and mixed logit models were used to estimate and analyse the DCE data. FINDINGS: A total of 60 GPs fully completed the survey. Previous telehealth experiences impacted direct preferences towards telehealth consultations across clinical presentations, although in-person modes were generally favoured (in approximately 70% of all scenarios). The DCE results lacked statistical significance which demonstrated undiscernible differences between GP preferences for some service attributes. However, it was found that GPs prefer to provide a consultation with good quality care and rapport (P < 002). GPs would also prefer to provide care to their patients rather than decline a consultation due to consultation mode, length or purpose (P < 0.0001). Based on the findings, GPs value the ability to provide high-quality care and develop rapport during a clinical consultation. This highlights the importance of recognising value-based care for future policy reforms, to ensure continued adoption and sustainability of GP telehealth services in Australia.

It Was Like Going to a Battlefield: Lived Experience of Frontline Nurses Supporting Two Hospitals in Wuhan During the COVID-19 Pandemic.

Introduction: The literature indicates that pandemics significantly impact the mental health of frontline health workers. While the effects of COVID-19 on the mental health of frontline nurses have been studied, their lived experiences remain insufficiently explored. Objective: This study aims to investigate the lived experience of nurses who were deployed to support Wuhan during the COVID-19 pandemic. Methods: This study adopted a qualitative study design. A purposive sample of fifteen nurses were recruited from a group of nurses who supported Wuhan during COVID-19 pandemic. The data was collected during May and June 2020. Data collection occurred in May and June 2020, employing semistructured interviews conducted via telephone. Interpretative phenomenological analysis (IPA) was utilized to analyze the collected data by two independent researchers. This report follows the COREQ checklist. Results: Frontline nurses supporting Wuhan likened their experience to being on a battlefield. Four superordinate themes emerged: (1) mobilization for combating COVID-19; (2) rapid adaption to a dynamic high-stress environment; (3) navigating psychological distress; and (4) the journey home. Conclusion: This study offers comprehensive insights into the lived experience of nurses deployed from other provinces to assist COVID patients in Wuhan. The findings indicate that despite facing a variety of challenges, these frontline nurses were capable of rapid adaptation and successfully fulfilled their roles. Recommendations for future preparedness in public health emergencies are provided. Additionally, follow-up research is warranted to explore the long-term effects of frontline experience on the mental health of the nurses and their family members.

Managing idiopathic intracranial hypertension in the eye clinic.

Idiopathic intracranial hypertension (IIH) is a neuro-ophthalmological condition characterised by a raised intracranial pressure and papilloedema that causes disabling headaches. The main risk factors of female sex and living with obesity have been known for some time, however the knowledge of the underlying pathophysiology is evolving. Papilloedema can impact the visual function, and the majority of people are offered acetazolamide. Those with sight threatening disease need urgent management, though there is little high quality evidence to recommend any particular surgical intervention. Headache treatment is an unmet clinical need and simple medication overuse advice has the potential to reduce the chronification of migraine-like headaches. IIH is emerging as a systemic metabolic disease distinct from people living with obesity alone. While weight loss is the main stay of disease modifying therapy this is challenging to access and many healthcare professionals that manage the condition have no formal training or accessible pathways for weight management. The aim of this "how to do it" article is to present the latest advances in knowledge of IIH that we pragmatically included in routine clinical care for people living with the condition.

Metabolic pathway-based subtypes associate glycan biosynthesis and treatment response in head and neck cancer.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous malignancy that remains a significant challenge in clinical management due to frequent treatment failures and pronounced therapy resistance. While metabolic dysregulation appears to be a critical factor in this scenario, comprehensive analyses of the metabolic HNSCC landscape and its impact on clinical outcomes are lacking. This study utilized transcriptomic data from four independent clinical cohorts to investigate metabolic heterogeneity in HNSCC and define metabolic pathway-based subtypes (MPS). In HPV-negative HNSCCs, MPS1 and MPS2 were identified, while MPS3 was enriched in HPV-positive cases. MPS classification was associated with clinical outcome post adjuvant radio(chemo)therapy, with MPS1 consistently exhibiting the highest risk of therapeutic failure. MPS1 was uniquely characterized by upregulation of glycan (particularly chondroitin/dermatan sulfate) metabolism genes. Immunohistochemistry and pilot mass spectrometry imaging analyses confirmed this at metabolite level. The histological context and single-cell RNA sequencing data identified the malignant cells as key contributors. Globally, MPS1 was distinguished by a unique transcriptomic landscape associated with increased disease aggressiveness, featuring motifs related to epithelial-mesenchymal transition, immune signaling, cancer stemness, tumor microenvironment assembly, and oncogenic signaling. This translated into a distinct histological appearance marked by extensive extracellular matrix remodeling, abundant spindle-shaped cancer-associated fibroblasts, and intimately intertwined populations of malignant and stromal cells. Proof-of-concept data from orthotopic xenotransplants replicated the MPS phenotypes on the histological and transcriptome levels. In summary, this study introduces a metabolic pathway-based classification of HNSCC, pinpointing glycan metabolism-enriched MPS1 as the most challenging subgroup that necessitates alternative therapeutic strategies.