Strategies for the incorporation of organosolv lignin in hydroxypropyl methylcellulose-based films: A comparative study.

Organosolv lignin extracted from vine pruning residues was added to hydroxypropyl methylcellulose (HPMC)-based films using three strategies: i) lignin incorporated into the film (lignin-based film), ii) lignin nanoparticles (LNPs) incorporated into the film (LNPs-based film), and iii) lignin coated on HPMC films' surface (lignin-coated film). The films obtained were evaluated in terms of morphology, water barrier and mechanical properties, and antioxidant capacity. Results showed that LNPs incorporation did not affect the films´ water vapour permeability (WVP). Nonetheless, the lignin-based and lignin-coated films improved the water barrier properties of HPMC-based films, achieving a 31.5 and 36 % reduction of WVP, respectively. The morphological evaluation, performed by scanning electron microscopy, revealed films' morphology changes with the lignin incorporation, which was more evident in the lignin-based films. Fourier transform infrared spectroscopy (FTIR) showed minor changes in the film's structure using the different lignin incorporation methods. The mechanical properties were improved, including a significant increase in the tensile strength in the lignin-based and lignin-coated films. All films showed high radical scavenging activity (RSA) after 24 h, with a gradual increase in the lignin-coated films over time. The lignin-coated films showed to be the most promising incorporation strategy to improve the HPMC-based film's properties.

Multidrug-Resistant Escherichia coli Accumulated by Freshwater Bivalves: An Underestimated Risk for Public Health?

As bioindicators, freshwater bivalves are crucial for the assessment of the contamination impact on different levels of biological integration. Escherichia coli is used as a bioindicator of water fecal contamination, representing a critical global concern, especially with the rise of multidrug-resistant (MDR) strains. Phylogenetic diversity, pathotypic characterization, and antibiotic resistance profiles of E. coli isolated from freshwater bivalves (Anodonta anatina) were assessed. Samples were collected from the Tua River in Northern Portugal, from two different sites, Chelas and Barcel, representing different degrees of contamination. Antimicrobial susceptibility testing was performed by the disk diffusion method, and characterizations of the phylogenetic groups and pathotypes were assessed by PCR-multiplex and real-time PCR-multiplex, respectively. Results showed that 60% of isolates were characterized as MDR, including resistance to carbapenems, considered the last resort against multidrug-resistant bacteria. Within this study, it was also possible to verify the antimicrobial resistance (AMR) profile differences between the two sampling sites, with bivalve isolates from the Chelas site showing a higher percentage of antibiotic resistance. Among the E. coli isolates, the highest prevalence (55%) was observed in group B1, followed by group D or E (15%), group A (10%), and group E or Clade I (10%). None of the isolates were classified as diarrheagenic E. coli (DEC). This work highlights the potential transmission of antimicrobial-resistant bacteria through bivalves in the food chain. The 'One Health' approach is crucial for combating antimicrobial resistance, namely in edible freshwater species, emphasizing active surveillance to protect human, animal, and environmental health against the spread of antibiotic-resistant bacteria in aquatic environments.

Paradoxical Brain Herniation: An Unexpected Diagnosis.

Paradoxical herniation is a dreadful neurosurgical complication often underdiagnosed, which typically becomes evident over the course of weeks to months after the initial intervention. Here we present a unique case with manifestations in the post-operative period. A patient initially referred to neurosurgery for a meningioma underwent an uneventful surgical excision, followed by the transient placement of a lumbar drain for 48 hours. On the first post-operative day, the patient exhibited progressively altered neurological status, with corresponding imaging revealing a transfalcine herniation, necessitating emergent decompressive craniectomy. Despite the medical and surgical interventions, there were continuous signs of neurological and imaging worsening, with increase in herniation, which led to the diagnosis suspicion of a paradoxical brain herniation. Consequently, a rapid reversal of neurological deficits was observed after applying maneuvers to augment the intracranial pressure, followed by cranioplasty. This case illustrates the utmost importance of clinical suspicion for the uncommon complications of neurointerventions.

The use of phosphodiesterase inhibitors in the treatment of female sexual dysfunction: scoping review.

Objective: The purpose of this study was to analyze the available evidence regarding the efficacy of iPDE5 in the treatment of female sexual dysfunction (FSD). Methods: A comprehensive literature search was conducted in March 2023 through the main scientific databases. Results: A total of 53 articles were identified, out of which, 6 met the predefined inclusion criteria. All of these were randomized controlled trials. Among the included studies, 4 demonstrated the effectiveness of sildenafil in improving sexual response and addressing FSD, while 2 studies failed to establish its efficacy in this context. Conclusion: Overall, the efficacy of sildenafil in the treatment of FSD remains controversial and inconclusive based on the available evidence. Further research is necessary to clarify the therapeutic potential of iPDE5 in addressing FSD and to better understand the factors that influence treatment outcomes.

Effect of Arm-Ergometry Versus Treadmill Supervised Exercise on Cardiorespiratory Fitness and Walking Distances in Patients With Peripheral Artery Disease: The ARMEX Randomized Clinical Trial.

PURPOSE: To compare arm-ergometry and treadmill supervised exercise training on cardiorespiratory fitness and walking distances in patients with peripheral artery disease (PAD). METHODS: ARMEX was a single-center, single-blinded, parallel group, non-inferiority trial enrolling symptomatic patients with PAD. Patients were randomized (1:1 ratio) to a 12-wk arm-ergometry (AEx) or standard treadmill (TEx) supervised exercise training protocol. The powered primary end point was the change in peak oxygen uptake (VO 2 ) at 12 wk, measured on a treadmill cardiopulmonary exercise test (CPX). Secondary outcomes included changes in VO 2 at the first ventilatory threshold (VT-1), ventilatory efficiency (ratio of minute ventilation [VE] to carbon dioxide production [VCO 2 ], VE/VCO 2 ), walking distances by CPX and 6-min walking test (6MWT), and self-reported walking limitations. RESULTS: Fifty-six patients (66 ± 8 yr; 88% male) were randomized (AEx, n = 28; TEx, n = 28). At 12 wk, VO 2peak change was not significantly different between groups (0.75 mL/kg/min; 95% CI, -0.94 to 2.44; P = .378), despite a significant increase only in AEx. VO 2 at VT-1 improved in both groups without between-group differences, and VE/VCO 2 slope improved more in AEx. The TEx attained greater improvements in walking distance by CPX (121.08 m; 95% CI, 24.49-217.66; P = .015) and 6MWT (25.08 m; 95% CI, 5.87-44.29; P = .012) and self-perceived walking distance. CONCLUSIONS: Arm-ergometry was noninferior to standard treadmill training for VO 2peak , and treadmill training was associated with greater improvements in walking distance. Our data support the use of treadmill as a first-line choice in patients with PAD to enhance walking capacity, but arm-ergometry could be an option in selected patients.

Dynamically Normalized Pupillometry for Detecting Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVES: Delayed cerebral ischemia (DCI) is a major driver of morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Quantitative pupillometry has been shown to be of prognostic value after acute neurological injury. However, the evidence for the use of pupillometric features for the detection of DCI has been conflicting. The aim of this study was to investigate the prognostic value of frequent pupillometric monitoring for DCI detection. DESIGN: Observational cohort study from a prospective aSAH registry. SETTING: Tertiary referral center. PATIENTS: Adult patients with confirmed aSAH admitted to the ICU between March 2019 and December 2023. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred fourteen patients were included, of which 31 (27.2%) suffered from DCI. All patients underwent frequent pupillometry (every 3 hr). We determined the absolute value of the neurological pupil index (NPi) and constriction velocity (CV), and their value normalized to the maximal recorded value between the admission and the pupillometry measure to account for personalized baselines. The association between pupillometry values and the occurrence of DCI within 6-24 hours was investigated. Normalized CV had the best discriminative performance to identify DCI within 8 hours, with an area under the receiver operating characteristic curve of 0.82 (95% CI, 0.69-0.91). NPi, as well as non-normalized metrics, were not significantly associated with DCI. CONCLUSIONS: Normalized CV has a clinically and statistically significant association with the occurrence of DCI after aSAH. Frequent quantitative pupillometry could improve the multimodal monitoring of patients after aSAH with the goal of improving the identification of patients likely to benefit from therapeutic interventions.

Three-Dimensional Melted Electrowriting Drug Coating Fibers for the Prevention of Device-Associated Infections: A Pilot Study.

Medical device-related infections (DRIs), especially prevalent among critically ill patients, impose significant health and economic burdens and are mainly caused by bacteria. Severe infections often necessitate device removal when antibiotic therapy is inefficient, delaying recovery. To tackle this issue, PCL drug-eluting coated meshes were explored, and they were printed via melt electrowriting (MEW). These meshes were coated with gentamicin sulfate (GS) and tetracycline hydrochloride (TCH) and underwent FTIR analysis to confirm drug integration. Antimicrobial activity was assessed via agar diffusion assays and biofilm formation assays against bacterial strains: Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 43300, and Staphylococcus epidermidis ATCC 35984. FTIR analysis evidenced the presence of the drugs in the meshes. TCH displayed broad-spectrum antimicrobial activity against all strains, whereas GS was effective against all except S. aureus. These findings indicate the potential of cost-effective ultra-fine drug coating fibers for medical device applications, offering infection prevention during implantation. This preliminary study demonstrates the feasibility of producing drug-eluting fibers for DRI prevention through a non-toxic, fast, and cost-efficient technique, paving the way for enhanced patient care and reduced healthcare costs.

Isolation and Identification of Lichen Photobionts Collected from Different Environments in North of Portugal and Evaluation of Bioactivities of Their Extracts.

Lichens are organisms constituted by a symbiotic relationship between a fungus (mycobiont) and a photoautotrophic partner (photobiont). Lichens produce several bioactive compounds; however, the biotechnological exploitation of this organism is hampered by its slow growth. To start studying the possibility of exploiting lichens as alternative sources of bioactive compounds, eighteen lichens were collected in the north of Portugal in order to isolate and study the bioactivity of their photobionts. It was possible to isolate and cultivate only eight photobionts. Three of them, LFR1, LFA2 and LCF3, belong to the Coelastrella genus, the other two (LFA1 and LCF1) belong to the Chlorella genus and for the remaining three photobionts, LFS1, LCA1 and LCR1, it was impossible to isolate their microalgae. These only grow in consortium with bacteria and/or cyanobacteria. All extracts showed antioxidant activity, mainly at a concentration of 10 mg.mL-1. LFS1, a consortium extract, showed the highest antioxidant power, as well as the highest concentration of phenolic compounds (5.16 ± 0.53 mg of gallic acid equivalents (GAE).g-1). The extracts under study did not show significant antibacterial activity against Escherichia coli, Listeria or Salmonella. The Coelastrella sp. and LFA1 extracts showed the highest hyaluronidase inhibition. The LFR1 extract at a concentration of 5 mg.mL-1 showed the highest anti-inflammatory activity (79.77 ± 7.66%). The extracts of Coelastrella sp. and LFA1 also showed greater antidiabetic activity, demonstrating the high inhibitory power of α-amylase and α-glucosidase. LFR1 at a concentration of 5 mg.mL-1, due to its selective cytotoxicity inhibiting the growth of cancer cells (Caco-2 cells), is a promising anticancer agent.

Enhancing cannabidiol bioaccessibility using ionic liquid as emulsifier to produce nanosystems: Characterization of structures, cytotoxicity assessment, and in vitro digestion.

The emulsifying potential of a biocompatible ionic liquid (IL) to produce lipid-based nanosystems developed to enhance the bioaccessibility of cannabidiol (CBD) was investigated. The IL (cholinium oleate) was evaluated at concentrations of 1 % and 2 % to produce nanoemulsions (NE-IL) and nanostructured lipid carriers (NLC-IL) loaded with CBD. The IL concentration of 1 % demonstrated to be sufficient to produce both NE-IL and NLC-IL with excellent stability properties, entrapment efficiency superior to 99 %, and CBD retention rate of 100 % during the storage period evaluated (i.e. 28 days at 25 °C). The in vitro digestion evaluation demonstrated that the NLC-IL provided a higher stability to the CBD, while the NE-IL improved the CBD bioaccessibility, which was mainly related to the composition of the lipid matrices used to obtain each nanosystem. Finally, it was observed that the CBD cytotoxicity was reduced when the compound was entrapped into both nanosystems.

Correlation Between Pedal Acceleration Time and Transcutaneous Oxygen Pressures - A Prognostic Tool for Wound Healing in the Diabetic Foot Population.

BACKGROUND: Pedal arch interrogation by ultrasound through systolic acceleration time measurement (Pedal Acceleration Time [PAT]) is a recently described technique that offers valuable insights into foot hemodynamics. Previous studies have demonstrated a correlation between PAT and the ankle-brachial index and PAT has been proposed as a prognostic tool for wound healing in patients with peripheral artery disease. This study aims to assess the correlation between PAT and Transcutaneous Pressure of Oxygen (TcPO2) in the diabetic foot population. METHODS: In this single-center cross-sectional study PAT and TcPO2 were measured in diabetic patients with ischemic foot ulcers. The assessment of wound status was performed between the 12th and 16th week after the first evaluation. The primary outcome was to assess the correlation between the values obtained for PAT and TcPO2. The secondary outcome was to establish a cut-off value for wound healing. RESULTS: Sixty limbs with ischemic foot ulcers were evaluated. The results showed a correlation between PAT and TcPO2 [F (1.52) = 16.928; R2 = 0.246; P < 0.001]. The receiver operating characteristics curve analysis showed an optimal cut-off value at PAT >186 ms for predicting a nonhealing ulcer with a 96% specificity (area under the curve = 0.774; confidence interval 0.648-0.872; P < 0.001). CONCLUSIONS: PAT showed a significant correlation with TcPO2 with high specificity to identify nonhealing foot ulcers due to insufficient foot perfusion with a potential prognostic value in the diabetic foot population.

Performance of ß-carotene-loaded nanostructured lipid carriers under dynamic in vitro digestion system: Influence of the emulsifier type.

A better understanding of how emulsifier type could differently influence the behavior of nanostructured lipid carriers (NLC) under the gastrointestinal digestion process, as well as at the cellular level, is of utmost importance for the NLC-based formulations' optimization and risk assessment in the food field. In this study, NLC composed by fully hydrogenated soybean and high-oleic sunflower oils were prepared using soy lecithin (NLC Lß) or Tween 80 (NLC Tß) as an emulsifier. ß-Carotene was entrapped within NLC developed as a promising strategy to overcome ß-carotene's low bioavailability and stability. The effect of emulsifier type on the digestibility of ß-carotene-loaded NLC was evaluated using an in vitro dynamic digestion model mimicking peristalsis motion. The influence of ß-carotene-loaded NLC on cell viability was assessed using Caco-2 cells in vitro. NLC Tß remained stable in the gastric compartment, presenting particle size (PS) similar to the initial NLC (PS: 245.68 and 218.18 nm, respectively), while NLC Lß showed lower stability (PS > 1000 nm) in stomach and duodenum phases. NLC Tß also provided high ß-carotene protection and delivery capacity (i.e., ß-carotene bioaccessibility increased 10-fold). Based on the results of digestion studies, NLC Tß has shown better physical stability during the passage through the in vitro dynamic gastrointestinal system than NLC Lß. Moreover, the developed NLC did not compromise cell viability up to 25 µg/mL of ß-carotene. Thus, the NLC developed proved to be a biocompatible structure and able to incorporate and protect ß-carotene for further food applications. PRACTICAL APPLICATION: The findings of this study hold significant implications for industrial applications in terms of developing nanostructured lipid carriers from natural raw materials widely available and used to produce other lipid-based products in the food industry, as an alternative to synthetic ones. In this respect, the ß-carotene-loaded NLC developed in this study would find a great industrial application in the food industry, which is in constant search to develop functional foods capable of increasing the bioavailability of bioactive compounds.

Comparison of Different Pretreatment Processes Envisaging the Potential Use of Food Waste as Microalgae Substrate.

A significant fraction of the food produced worldwide is currently lost or wasted throughout the supply chain, squandering natural and economic resources. Food waste valorization will be an important necessity in the coming years. This work investigates the ability of food waste to serve as a viable nutritional substrate for the heterotrophic growth of Chlorella vulgaris. The impact of different pretreatments on the elemental composition and microbial contamination of seven retail food waste mixtures was evaluated. Among the pretreatment methods applied to the food waste formulations, autoclaving was able to eliminate all microbial contamination and increase the availability of reducing sugars by 30%. Ohmic heating was also able to eliminate most of the contaminations in the food wastes in shorter time periods than autoclave. However, it has reduced the availability of reducing sugars, making it less preferable for microalgae heterotrophic cultivation. The direct utilization of food waste containing essential nutrients from fruits, vegetables, dairy and bakery products, and meat on the heterotrophic growth of microalgae allowed a biomass concentration of 2.2 × 108 cells·mL-1, being the culture able to consume more than 42% of the reducing sugars present in the substrate, thus demonstrating the economic and environmental potential of these wastes.

How do people in prison access palliative care? A scoping review of models of palliative care delivery for people in prison in high-income countries.

BACKGROUND: An ageing prison population with complex health needs combined with punitive sentencing practices means palliative care for incarcerated individuals is increasingly important. However, there is limited evidence regarding the models of care delivery in high-income countries, and their associated challenges and benefits. AIM: To develop a typology of models of palliative care provision for incarcerated individuals, synthesise evidence of their outcomes and describe facilitators of and challenges in delivering different models of palliative and end-of-life care in prisons. DESIGN: Scoping review following Arksey and O'Malley, with narrative synthesis. The protocol was registered prospectively (reviewregistry1260). DATA SOURCES: MEDLINE, EMBASE, CINAHL, PsycINFO, the Social Sciences Citation Index and grey literature were searched on 15th March 2023. The Mixed Methods Appraisal Tool (MMAT) was used for quality appraisal. RESULTS: A total of 16,865 records were screened; 22 peer-reviewed articles and 18 grey literature sources met the inclusion criteria. Three models were identified: Embedded Hospice, Outsourcing Care and Community Collaboration. The Embedded Hospice model shows potential benefits for patients and prisons. Outsourcing Care may miss opportunities for comprehensive care. Collaborative Care relies on proactive prison-community relationships that could be formalised for improvement. Psychosocial and bereavement needs of those dying in prison and their caregivers lack sufficient documentation. CONCLUSION: Further research is needed to evaluate prison hospice costs and examine how prison hospices impact compassionate release usage. Beyond the USA, policies might formalise care pathways and recognise best practices. Further investigation to address psychosocial needs of people in prison with life-limiting illnesses and post-death bereavement support is required.

Predictors of damage accrual and its impact on health-related quality of life of thrombotic antiphospholipid syndrome: Independent validation of the damage index for antiphospholipid syndrome (DIAPS).

OBJECTIVES: We aim to independently assess the validity of the damage index for antiphospholipid syndrome (DIAPS) in thrombotic antiphospholipid syndrome (APS) patients by exploring the prevalence and risk factors of organ damage and evaluating its impact on health-related quality of life (HR-QoL). METHODS: Cross-sectional study including all thrombotic APS patients (Sydney criteria) attending a Portuguese tertiary centre. Damage was assessed using the DIAPS, and HR-QoL using the 3- and 5-level EuroQol HR-QoL (EQ-D5-3L and 5L), and Visual Analogue Scale (VAS) applied via a phone questionnaire. Spearman's correlation between DIAPS and the HR-QoL scales was performed. Risk factors for damage accrual and HR-QoL impairment were explored using univariate and multivariate logistic regression. RESULTS: Among the 108 patients (female, 65.7%; white, 90.7%; primary APS, 75.9%; median disease duration, 6 years), damage (DIAPS≥1) developed in 48.2% of patients (mean ± SD DIAPS, 3.08 ± 1.83). DIAPS's neuropsychiatric domain was the most affected (24.2%), followed by the peripheral vascular domain (20.3%). No clinical, demographic nor laboratory parameters were significantly associated with damage. Regarding HR-QoL, pain/discomfort, anxiety/depression and usual activities domains were the most frequently impaired in both scales. DIAPS's domains correlated similarly with the EQ-5D-3L and 5L scales' individual domains. Female sex, medical disorders, secondary APS and type of presenting thrombosis (arterial) increased the risk of HR-QoL impairment. Total DIAPS was associated with higher odds of mobility, self-care and pain/discomfort impairment in both EQ-5D-3L and 5L scales but lost its independent risk in multivariable analysis. CONCLUSION: This external validation of DIAPS reinforces the ability of the score to correlate with HR-QoL while also highlighting risk factors for HR-QoL impairment other than damage accrual.

Incorporation of curcumin-loaded solid lipid nanoparticles into yogurt: Tribo-rheological properties and dynamic in vitro digestion.

The incorporation of nanostructures loaded with bioactive compounds into food matrices is a promising approach to develop new functional foods with improved nutritional, health profiles and good sensorial properties. The rheological and tribological properties of yogurt enriched with curcumin-loaded solid lipid nanoparticles (SLN) were evaluated. Also, the TCA solubility index, the bioaccessibility of curcumin and cell viability were assessed after dynamic in vitro digestion. The presence of SLN in yogurt did not affect its rheological properties; however, SLN addition increased the lubrication capability of yogurt. After in vitro digestion, yogurt with added SLN (yogurt_SLN) presented a lower TCA solubility index (22 %) than the plain yogurt (39 %). The bioaccessibility and stability of curcumin were statistically similar for yogurt_SLN (30 % and 42 %, respectively) and SLN alone (20 % and 39 %, respectively). Regarding cell viability results, the intestinal digesta filtrates of both controls (i.e., SLN alone and plain yogurt) did not affect significantly the cell viability, while the yogurt_SLN presented a possible cytotoxic effect at the concentrations tested. In general, the incorporation of SLN into yogurt seemed to promote the mouthfeel of the yogurt and did not adversely affect the bioaccessibility of curcumin. However, the interaction of SLN and yogurt matrix seemed to have a cytotoxic effect after in vitro digestion, which should be further investigated. Despite that, SLN has a high potential to be used as nanostructure in a functional food as a strategy to increase the bioactive compounds' bioaccessibility.

Early-Onset Dystonia and Visual Impairment Preceding Epileptic Encephalopathy Associated with PIGA Gene Mutation.

The association between dystonia and early-onset epileptic encephalopathy (EOEE) may have a genetic basis. Phosphatidylinositol glycan biosynthesis class A protein (PIGA) germline mutations have been described in the last decade and associated with refractory EOEEs. Dysmorphisms and visceral abnormalities have also been reported. Here, we present the case of a now 8-month-old child who was evaluated for dystonia, visual impairment, and developmental delay at 2 months of age, followed by refractory focal seizures when he was 4 months old. The remaining examination was normal, besides an accelerated linear growth. His brain magnetic resonance and an extensive metabolic investigation failed to show any abnormalities. At 7 months of age, the exome sequencing found a hemizygous PIGA pathogenic variant-c.1352T > C (p.(Ile451Thr). Seizures improved after the association of carbamazepine with levetiracetam and the beginning of the ketogenic diet. To our knowledge, this is the first time the phenotype associated with this specific mutation is described. Our patient had the singularity of manifesting with remarkable dystonia, over 2 months before the onset of seizures. We also point to the utility of the gene sequencing approach in the diagnosis of patients with dystonia and EOEEs, since identification of the genetic cause may help in patient's management and families' empowerment.

The use of phosphodiesterase inhibitors in the treatment of female sexual dysfunction: scoping review

Abstract Objective The purpose of this study was to analyze the available evidence regarding the efficacy of iPDE5 in the treatment of female sexual dysfunction (FSD). Methods A comprehensive literature search was conducted in March 2023 through the main scientific databases. Results A total of 53 articles were identified, out of which, 6 met the predefined inclusion criteria. All of these were randomized controlled trials. Among the included studies, 4 demonstrated the effectiveness of sildenafil in improving sexual response and addressing FSD, while 2 studies failed to establish its efficacy in this context. Conclusion Overall, the efficacy of sildenafil in the treatment of FSD remains controversial and inconclusive based on the available evidence. Further research is necessary to clarify the therapeutic potential of iPDE5 in addressing FSD and to better understand the factors that influence treatment outcomes.

Systems biology analysis reveals distinct molecular signatures associated with immune responsiveness to the BNT162b COVID-19 vaccine.

BACKGROUND: Human immune responses to COVID-19 vaccines display a large heterogeneity of induced immunity and the underlying immune mechanisms for this remain largely unknown. METHODS: Using a systems biology approach, we longitudinally profiled a unique cohort of female high and low responders to the BNT162b vaccine, who were known from previous COVID-19 vaccinations to develop maximum and minimum immune responses to the vaccine. We utilized high dimensional flow cytometry, bulk and single cell mRNA sequencing and 48-plex serum cytokine analyses. FINDINGS: We revealed early, transient immunological and molecular signatures that distinguished high from low responders and correlated with B and T cell responses measured 14 days later. High responders featured a distinct transcriptional activity of interferon-driven genes and genes connected to enhanced antigen presentation. This was accompanied by a robust cytokine response related to Th1 differentiation. Both transcriptome and serum cytokine signatures were confirmed in two independent confirmatory cohorts. INTERPRETATION: Collectively, our data contribute to a better understanding of the immunogenicity of mRNA-based COVID-19 vaccines, which might lead to the optimization of vaccine designs for individuals with poor vaccine responses. FUNDING: German Center for Infection Research, German Center for Lung Research, German Research Foundation, Excellence Strategy EXC 2155 "RESIST" and European Regional Development Fund.

Deep Neck Infection: A Case of Retropharyngeal Abscess.

The incidence of retropharyngeal abscesses has been decreasing since the introduction of antibiotic therapy, and it is currently a rare diagnosis in adults, although there are some recent cases in the literature. Given its seriousness, if not treated promptly, the infection can progress rapidly and its complications can be fatal, making it a serious health problem. A 79-year-old woman presented at her primary care center with complaints of persistent odynophagia for about two weeks and rapidly progressive dysphagia in five days, initially for solids and later for solids and liquids. On observation, she had difficulty swallowing saliva and presented a painful mass in the bilateral anterior submental and anterior cervical region. Due to the rapid progression of symptoms and the findings of the physical examination, the patient was referred to the emergency department for a suspected abscess or cervical mass. In the emergency department, a cervical CT scan was performed, which revealed a retropharyngeal abscess measuring approximately 7 x 6 x 4 cm, involving the right carotid artery and internal jugular vein, with compression of the internal jugular vein. The patient was admitted to the otorhinolaryngology department, where intravenous antibiotic therapy with third-generation cephalosporin and clindamycin was initiated. She underwent exploration in the operating room to determine the cause of the abscess and transoral drainage of the already spontaneously draining abscess. After completing antibiotic therapy, a follow-up CT scan showed complete resolution of the abscess without suggestive masses of neoplasm or foreign bodies, therefore, the cause of the abscess has not been identified.  The most frequent cause of retropharyngeal abscess in adults is dental septic foci and another commonly described cause is the ingestion of foreign bodies such as fish bones or chicken bones. Early diagnosis of this condition is crucial, as delays in treatment initiation can lead to the progression of infection into the deep cervical spaces, resulting in serious complications such as mediastinitis, pericarditis, jugular vein thrombosis, sepsis, laryngeal edema, conditions with a high degree of morbidity and mortality. Therefore, it is important for any doctor to be aware of warning signs and symptoms in patients who present such symptoms, especially primary care doctors, who are the first gateway to health services and to whom patients often turn first. This case report shows the importance of suspicion and subsequent referral for timely diagnosis and treatment.

Prospective Clinical Evaluation of the Singularity™ Air Laryngeal Mask in Adult Patients.

A laryngeal mask is one of the most widely used airway management devices. The SingularityTM Air is a second-generation laryngeal mask whose shaft angle can be adjusted after insertion. Since the device's performance has been assessed on mannequins only, this study aimed to evaluate SingularityTM Air's effectiveness in the clinical setting. The prospective single-center cohort study included 100 adults undergoing elective surgery under general anesthesia and suitable for airway securing with a laryngeal mask. The primary endpoint was the oropharyngeal leak pressure, and the secondary endpoints were the ease of insertion and the patient's comfort. Laryngeal mask insertion was successful in 97%, and mechanical ventilation was possible in 96% of patients. After insertion, the median (IQR) oropharyngeal leak pressure was 25 (18-25) cm H2O, which remained stable at 25 (25-25) cm H2O after 20 min. The median (IQR) time for successful manual bag ventilation was 42 (34-50) seconds. Nineteen patients complained of side effects (e.g., sore throat, difficulty swallowing), but none persisted. The SingularityTM Air performed well in a clinical setting, and its oropharyngeal leak pressure was comparable to that of other masks reported in the literature. The time for successful manual ventilation was slightly longer, and patients reported more temporary side effects.