Sharp increase in gonorrhoea notifications among young people, EU/EEA, July 2022 to June 2023.

Gonorrhoea cases increased steeply in women aged 20 to 24 years across 15 EU/EEA countries in July to December 2022 and January to June 2023 with, respectively, 73% and 89% more cases reported than expected, based on historical data from 2015 to 2019. Smaller increases among men due to heterosexual transmission were observed in nine EU/EEA countries. Interventions to raise awareness among young people about sexually transmitted infection risks are needed, emphasising the benefit of safe sexual practices and testing.

Keep Calm: Does parental preoperative anxiety affect post-tonsillectomy pain scores in children?

PURPOSE: To understand if high parental anxiety leads to increased post-tonsillectomy pain in children. METHODS: Prospective study including parents of children aged 3-10 years old submitted to tonsillectomy with or without adenoidectomy. To evaluate anxiety, parents were asked to fill the State-Trait Anxiety Inventory form-Y, with postoperative pain being evaluated with the Wong-Baker FACES pain scale at postoperative days 1, 3 and 7. Parents were also asked to register the number of days during which children took analgesic and the number of analgesic intakes needed. RESULTS: 41 parents were enrolled, of which 95.1% (n = 39) were female with a mean age of 35.64 years (SD 5.751), with 41 children also being enrolled, of which 85.4% of children (n = 35) underwent tonsillectomy and adenoidectomy. 43.9% (n = 18) of parents presented State anxiety scores above the cut-off level and 53.7% (n = 22) above the Trait anxiety scores above the cut-off. Children of parents with high State anxiety presented statistically higher pain scores in both the third (p = 0.035) and the seventh postoperative days (p = 0.006), with significantly longer use of analgesic medication (p = 0.043) being found, as well as a statistically higher number of analgesic intakes (p = 0.045) (Table 4). CONCLUSION: The present study establishes an association between preoperative parental anxiety, postoperative pain scores and the need for longer analgesic use in children undergoing tonsillectomy. This reinforces the importance of reducing parental anxiety and opens the door for further strategies to better post-tonsillectomy outcomes.

Multiplexed Nanopore-Based Nucleic Acid Sensing and Bacterial Identification Using DNA Dumbbell Nanoswitches.

Multiplexed nucleic acid sensing methods with high specificity are vital for clinical diagnostics and infectious disease control, especially in the postpandemic era. Nanopore sensing techniques have developed in the past two decades, offering versatile tools for biosensing while enabling highly sensitive analyte measurements at the single-molecule level. Here, we establish a nanopore sensor based on DNA dumbbell nanoswitches for multiplexed nucleic acid detection and bacterial identification. The DNA nanotechnology-based sensor switches from an "open" into a "closed" state when a target strand hybridizes to two sequence-specific sensing overhangs. The loop in the DNA pulls two groups of dumbbells together. The change in topology results in an easily recognized peak in the current trace. Simultaneous detection of four different sequences was achieved by assembling four DNA dumbbell nanoswitches on one carrier. The high specificity of the dumbbell nanoswitch was verified by distinguishing single base variants in DNA and RNA targets using four barcoded carriers in multiplexed measurements. By combining multiple dumbbell nanoswitches with barcoded DNA carriers, we identified different bacterial species even with high sequence similarity by detecting strain specific 16S ribosomal RNA (rRNA) fragments.

Impact of cervicovaginal microbiome on the risk of cervical abnormalities development.

The vaginal microbiome has emerged as potentially influencing the natural history of Human Papillomavirus (HPV) infections and their clinical impact. We aimed to characterize the vaginal microbiome in samples from 807 high-risk HPVs (Hr-HPV) positive women with a mean age of 41.45 ± 10.79 years who participated in the Regional Cervical Cancer Screening Program from the Northern Region of Portugal. Microbiome analysis was performed with commercial kits for the detection of 21 microorganisms. The most frequent microorganisms were Ureaplasma parvum (52.5%), Gardnerella vaginalis (GV) (34.5%), Atopobium vaginae (AV) (32.6%), Lacto (30.7%), and Mycoplasma hominis (MH) (23.5%). The distribution according to age reveals that MH, Mega1, GV, BVab2, AV, and Mob were more prevalent in women older than 41 years of age (p < 0.050), while Lacto is significantly decreased in this group (23.5% vs. 39.4%, p < 0.001; RR = 0.47). The risk analysis showed that Hr-HPV-16/-18 and Hr-HPV-9val genotypes are associated with an increased risk of developing cervical abnormalities, while Lacto (p < 0.001; odd ratio [OR] = 0.33), GV (p = 0.0111; OR = 0.41), AV (p = 0.033; OR = 0.53) and Mob (p = 0.022; OR = 0.29) are associated with protection. Similar results were found for the risk of development atypical squamous cells cannot exclude HSIL/high-grade squamous intraepithelial lesion. Overall, the multivariate analysis confirmed that lactobacillus and bacteria associated with bacterial vaginosis (GV, AV, and Mob) are associated with protection against the development of cervical abnormalities. This study provides important data to be included in the future management of risk stratification for Hr-HPV-positive women.

Mucosal-associated invariant T-cell tumor infiltration predicts long-term survival in cholangiocarcinoma.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is a malignancy arising from biliary epithelial cells of intra- and extrahepatic bile ducts with dismal prognosis and few nonsurgical treatments available. Despite recent success in the immunotherapy-based treatment of many tumor types, this has not been successfully translated to CCA. Mucosal-associated invariant T (MAIT) cells are cytotoxic innate-like T cells highly enriched in the human liver, where they are located in close proximity to the biliary epithelium. Here, we aimed to comprehensively characterize MAIT cells in intrahepatic (iCCA) and perihilar CCA (pCCA). APPROACH AND RESULTS: Liver tissue from patients with CCA was used to study immune cells, including MAIT cells, in tumor-affected and surrounding tissue by immunohistochemistry, RNA-sequencing, and multicolor flow cytometry. The iCCA and pCCA tumor microenvironment was characterized by the presence of both cytotoxic T cells and high numbers of regulatory T cells. In contrast, MAIT cells were heterogenously lost from tumors compared to the surrounding liver tissue. This loss possibly occurred in response to increased bacterial burden within tumors. The residual intratumoral MAIT cell population exhibited phenotypic and transcriptomic alterations, but a preserved receptor repertoire for interaction with tumor cells. Finally, the high presence of MAIT cells in livers of iCCA patients predicted long-term survival in two independent cohorts and was associated with a favorable antitumor immune signature. CONCLUSIONS: MAIT cell tumor infiltration associates with favorable immunological fitness and predicts survival in CCA.

Impact of high-risk Human Papillomavirus genotyping in cervical disease in the Northern region of Portugal: Real-world data from regional cervical cancer screening program.

Cervical cancer prevention is based on primary prevention with vaccines against Human Papillomavirus (HPV) and secondary prevention by screening with High-Risk-HPV (Hr-HPV) detection. Since 2017, cervical cancer screening in women aged 25-60 years has been performed in Portugal using Hr-HPV detection, followed by cytology in Hr-HPV-positive cases. Herein we report the prevalence of Hr-HPV genotypes and cytological abnormalities among 462 401 women (mean age: 43.73 ± 10.79; median age: 45; range: 24-66 years) that participated in the Regional Cervical Cancer Screening Program of the Northern Region of Portugal, performed between August 2016 and December 2021. Overall, we describe a prevalence rate of 12.50% for Hr-HPV varying from 20.76% at age 25% to 8.32% at age 64. The five most common Hr-HPV genotypes identified were HPV-68 (16.09%), HPV-31 (15.30%), HPV-51 (12.96%), HPV-16 (11.06%), and HPV-39 (11.01%). The prevalence of Hr-HPV included in the nonavalent vaccine (HPV-9valent) was 55.00% ranging from 47.78% to 59.18% across different age groups. Considering positive Hr-HPV cases, 65.68% had a Negative for Intraepithelial Lesion or Malignancy (NILM) cytology, 20.83% atypical squamous cells of undetermined significance (ASC-US), 8.85% Low-Grade Squamous Intraepithelial Lesion (LSIL), 1.65% High-Grade Squamous Intraepithelial Lesion (HSIL), 2.85% ASC-H, 0.09% Atypical Glandular Cells, 0.02% Adenocarcinomas, and 0.02% Squamous Cell Carcinoma (SCC). Our analysis revealed that HPV-9val genotypes were responsible for 52.13% NILM, 59.21% ASC-US, 55.06% LSIL, 90.14% HSIL, 83.50% ASC-H, and 100.00% SCC. Furthermore, multiple Hr-HPV infections (risk ratio [RR] = 1.46; 95% confidence interval [CI] 1.34-1.58), HPV-16/18 (RR = 5.16; 95% CI 4.75-5.93), or HPV-9val genotypes (RR = 5.23; 95% CI 4.68-5.85) were associated with a significant risk of developing > HSIL (p < 0.001). To date, this is the largest study on Hr-HPV genotyping in cervical cancer screening that includes data from a complete cycle of the screening program. Our findings suggest a high prevalence of HPV-9valent genotypes and a significant association with an increased risk of developing > HSIL. This constitutes important data for health authorities, which may help define the future of vaccination and cervical cancer screening strategies.

Nutrient sensing modulates malaria parasite virulence.

The lifestyle of intracellular pathogens, such as malaria parasites, is intimately connected to that of their host, primarily for nutrient supply. Nutrients act not only as primary sources of energy but also as regulators of gene expression, metabolism and growth, through various signalling networks that enable cells to sense and adapt to varying environmental conditions. Canonical nutrient-sensing pathways are presumed to be absent from the causative agent of malaria, Plasmodium, thus raising the question of whether these parasites can sense and cope with fluctuations in host nutrient levels. Here we show that Plasmodium blood-stage parasites actively respond to host dietary calorie alterations through rearrangement of their transcriptome accompanied by substantial adjustment of their multiplication rate. A kinome analysis combined with chemical and genetic approaches identified KIN as a critical regulator that mediates sensing of nutrients and controls a transcriptional response to the host nutritional status. KIN shares homology with SNF1/AMPKα, and yeast complementation studies suggest that it is part of a functionally conserved cellular energy-sensing pathway. Overall, these findings reveal a key parasite nutrient-sensing mechanism that is critical for modulating parasite replication and virulence.

Ulva rigida Valorization into Poly(3-hydroxybutyrate), Organic Acids and Functional Ingredients.

Halomonas elongata 1H9T is a moderate halophilic strain able to produce poly(3-hydroxybutyrate) (P(3HB)), a biodegradable plastic, and gluconic acid, a valuable organic acid with wide industrial applications. In this work, the green alga Ulva rigida was used as platform to produce cultivation substrates for microbial conversion as well as functional ingredients, targeting its full valorization. The liquor obtained by autohydrolysis presented the highest concentration of oligosaccharides and protein, being an interesting feedstock to produce functional ingredients. The acid and/or enzymatic hydrolysis liquors are adequate as substrates for microbial processes. Shake flask assays with H. elongata revealed that the N-rich liquor produced after acidic treatment was the best suited for cell growth while the N-poor liquor produced by the enzymatic treatment of acid-pretreated algae residues produced the highest P(3HB) titers of 4.4 g/L. These hydrolysates were used in fed-batch cultivations as carbon and protein sources for the co-production of gluconic acid and polymer achieving titers of 123.2 g/L and 7.2 g/L, respectively. Besides gluconic acid, the Krebs cycle intermediate 2-oxoglutaric acid, also called alpha-ketoglutaric acid (KGA), was produced. Therefore, the co-production of P(3HB) and acids may be of considerable interest as an algal biorefinery valorization strategy.

Fc-mediated effector function contributes to the in vivo antiviral effect of an HIV neutralizing antibody.

Treatment of HIV infection with either antiretroviral (ARV) therapy or neutralizing monoclonal antibodies (NAbs) leads to a reduction in HIV plasma virus. Both ARVs and NAbs prevent new rounds of viral infection, but NAbs may have the additional capacity to accelerate the loss of virus-infected cells through Fc gamma receptor (FcγR)-mediated effector functions, which should affect the kinetics of plasma-virus decline. Here, we formally test the role of effector function in vivo by comparing the rate and timing of plasma-virus clearance in response to a single-dose treatment with either unmodified NAb or those with either reduced or augmented Fc function. When infused into viremic simian HIV (SHIV)-infected rhesus macaques, there was a 21% difference in slope of plasma-virus decline between NAb and NAb with reduced Fc function. NAb engineered to increase FcγRIII binding and improve antibody-dependent cellular cytotoxicity (ADCC) in vitro resulted in arming of effector cells in vivo, yet led to viral-decay kinetics similar to NAbs with reduced Fc function. These studies show that the predominant mechanism of antiviral activity of HIV NAbs is through inhibition of viral entry, but that Fc function can contribute to the overall antiviral activity, making them distinct from standard ARVs.

Legionnaires' disease in the EU/EEA*: increasing trend from 2017 to 2019.

BackgroundThe burden of Legionnaires' disease (LD) in the European Union/European Economic Area (EU/EEA) has increased during the last decade, with notification rates increasing from 1.2 to 1.4/100,000 population in 2012-16, to 1.8-2.2 within 2017-19.AimTo measure weekly excess cases during 2017-19 based on previous trends and determine whether a significant change in trend occurred, and to examine any differences in age, sex or level of imported infections.MethodsWe collated 2012-19 annual surveillance data from The European Surveillance System (TESSy) reported by EU/EEA countries. A retrospective prediction by a dynamic regression model was created from 2012-16 data to assess excess cases in 2017-19. Interrupted time series (ITS) analysis was performed to determine if a significant change in trend occurred in 2017-19 compared with the previous 5 years.ResultsWe found a 33.9% increase in cases in 2017-19 compared with the number predicted. The ITS also found a significant trend increase in 2017-19 compared with 2012-16. A significant trend increase was observed from 2017 most strongly among older age groups (> 60 years) and non-imported cases.ConclusionOur study showed a significant increasing trend in LD cases in the EU/EEA during 2017-19 compared with the previous 5 years. The distribution of cases per week suggests an overall amplification of the seasonal trends. These findings underscore that LD continues to be an infectious disease of public health concern in the EU/EEA, warranting further research into determinants of the increase.

Effect of neuraminidase inhibitor (oseltamivir) treatment on outcome of hospitalised influenza patients, surveillance data from 11 EU countries, 2010 to 2020.

BackgroundTimely treatment with neuraminidase inhibitors (NAI) can reduce severe outcomes in influenza patients.AimWe assessed the impact of antiviral treatment on in-hospital deaths of laboratory-confirmed influenza patients in 11 European Union countries from 2010/11 to 2019/20.MethodsCase-based surveillance data from hospitalised patients with known age, sex, outcome, ward, vaccination status, timing of antiviral treatment, and hospitalisation were obtained. A mixed effect logistic regression model using country as random intercept was applied to estimate the adjusted odds ratio (aOR) for in-hospital death in patients treated with NAIs vs not treated.ResultsOf 19,937 patients, 31% received NAIs within 48 hours of hospital admission. Older age (60-79 years aOR 3.0, 95% CI: 2.4-3.8; 80 years 8.3 (6.6-10.5)) and intensive care unit admission (3.8, 95% CI: 3.4-4.2) increased risk of dying, while early hospital admission after symptom onset decreased risk (aOR 0.91, 95% CI: 0.90-0.93). NAI treatment initiation within 48 hours and up to 7 days reduced risk of dying (0-48 hours aOR 0.51, 95% CI: 0.45-0.59; 3-4 days 0.59 (0.51-0.67); 5-7 days 0.64 (0.56-0.74)), in particular in patients 40 years and older (e.g. treatment within 48 hours: 40-59 years aOR 0.43, 95% CI: 0.28-0.66; 60-79 years 0.50 (0.39-0.63); ≥80 years 0.51 (0.42-0.63)).ConclusionNAI treatment given within 48 hours and possibly up to 7 days after symptom onset reduced risk of in-hospital death. NAI treatment should be considered in older patients to prevent severe outcomes.

Spatiotemporal spread of tick-borne encephalitis in the EU/EEA, 2012 to 2020.

BackgroundTick-borne encephalitis (TBE) is a vaccine-preventable disease involving the central nervous system. TBE became a notifiable disease on the EU/EEA level in 2012.AimWe aimed to provide an updated epidemiological assessment of TBE in the EU/EEA, focusing on spatiotemporal changes.MethodsWe performed a descriptive analysis of case characteristics, time and location using data of human TBE cases reported by EU/EEA countries to the European Centre for Disease Prevention and Control with disease onset in 2012-2020. We analysed data at EU/EEA, national, and subnational levels and calculated notification rates using Eurostat population data. Regression models were used for temporal analysis.ResultsFrom 2012 to 2020, 19 countries reported 29,974 TBE cases, of which 24,629 (98.6%) were autochthonous. Czechia, Germany and Lithuania reported 52.9% of all cases. The highest notification rates were recorded in Lithuania, Latvia, and Estonia (16.2, 9.5 and 7.5 cases/100,000 population, respectively). Fifty regions from 10 countries, had a notification rate ≥ 5/100,000. There was an increasing trend in number of cases during the study period with an estimated 0.053 additional TBE cases every week. In 2020, 11.5% more TBE cases were reported than predicted based on data from 2016 to 2019. A geographical spread of cases was observed, particularly in regions situated north-west of known endemic regions.ConclusionA close monitoring of ongoing changes to the TBE epidemiological situation in Europe can support the timely adaption of vaccination recommendations. Further analyses to identify populations and geographical areas where vaccination programmes can be of benefit are needed.

How Industry 4.0 and Sensors Can Leverage Product Design: Opportunities and Challenges.

The fourth industrial revolution, also known as Industry 4.0, has led to an increased transition towards automation and reliance on data-driven innovations and strategies. The interconnected systems and processes have significantly increased operational efficiency, enhanced organizational capacity to monitor and control functions, reduced costs, and improved product quality. One significant way that companies have achieved these benefits is by integrating diverse sensor technologies within these innovations. Given the rapidly changing market conditions, Industry 4.0 requires new products and business models to ensure companies adjust to the current and future changes. These requirements call for the evolutions in product design processes to accommodate design features and principles applicable in the current dynamic business environment. Thus, it becomes imperative to understand how these innovations can leverage product design to maximize benefits and opportunities. This research paper employs a Systematic Literature Review with Bibliometric Analysis (SLBA) methodology to explore and synthesize data on how Industry 4.0 and sensors can leverage product design. The results show that various product design features create opportunities to be leveraged to guarantee the success of Industry 4.0 and sensor technologies. However, the research also identifies numerous challenges that undermine the ongoing transition towards intelligent factories and products.

Comparison of 3D Sensors for Automating Bolt-Tightening Operations in the Automotive Industry.

Machine vision systems are widely used in assembly lines for providing sensing abilities to robots to allow them to handle dynamic environments. This paper presents a comparison of 3D sensors for evaluating which one is best suited for usage in a machine vision system for robotic fastening operations within an automotive assembly line. The perception system is necessary for taking into account the position uncertainty that arises from the vehicles being transported in an aerial conveyor. Three sensors with different working principles were compared, namely laser triangulation (SICK TriSpector1030), structured light with sequential stripe patterns (Photoneo PhoXi S) and structured light with infrared speckle pattern (Asus Xtion Pro Live). The accuracy of the sensors was measured by computing the root mean square error (RMSE) of the point cloud registrations between their scans and two types of reference point clouds, namely, CAD files and 3D sensor scans. Overall, the RMSE was lower when using sensor scans, with the SICK TriSpector1030 achieving the best results (0.25 mm ± 0.03 mm), the Photoneo PhoXi S having the intermediate performance (0.49 mm ± 0.14 mm) and the Asus Xtion Pro Live obtaining the higher RMSE (1.01 mm ± 0.11 mm). Considering the use case requirements, the final machine vision system relied on the SICK TriSpector1030 sensor and was integrated with a collaborative robot, which was successfully deployed in an vehicle assembly line, achieving 94% success in 53,400 screwing operations.

Chiari Type 1 Malformation: An Unusual Cause of Tinnitus.

Chiari Malformations are a group of conditions defined in 1891 with 5 degrees being described. These malformations present with several symptoms such as cervical protrusion and are associated with hydrocephalus. Also, they can also present with different clinical signs and symptoms, such as deafness and tinnitus. We present a case of a 45-year-old man with unilateral tinnitus evaluated in otolaryngology office. No other symptoms on otolaryngological physical exam were detected in the audiogram performed it was described a significant unilateral sensorineural hearing loss. During the study of this patient, Magnetic Resonance Imaging was requested, showing a type I Chiari malformation. The patient was then observed by Ophthalmology, Neurology, and Neurosurgery. No other neurological symptoms of malformation Chiari syndrome or cranial nerve abnormalities were presented at the respective exam. The surgical management of these pathologies takes into account an adequate CSF and venous blood flow - that was seen in this patient, therefore, there was no surgical indication for decompression. The patient maintains its follow-up in the otolaryngology, neurology, and neurosurgery office, and tinnitus was minimized after prosthetic adaptation was recommended to optimize the quality of life, which was achieved.

The Removal of Airborne Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Other Microbial Bioaerosols by Air Filtration on Coronavirus Disease 2019 (COVID-19) Surge Units.

Airborne severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in a coronavirus disease 19 (COVID-19) ward before activation of HEPA-air filtration but not during filter operation; SARS-CoV-2 was again detected following filter deactivation. Airborne SARS-CoV-2 was infrequently detected in a COVID-19 intensive care unit. Bioaerosol was also effectively filtered.

Opsonization-Enhanced Antigen Presentation by MR1 Activates Rapid Polyfunctional MAIT Cell Responses Acting as an Effector Arm of Humoral Antibacterial Immunity.

Mucosa-associated invariant T (MAIT) cells are innate-like antimicrobial T cells recognizing a breadth of important pathogens via presentation of microbial riboflavin metabolite Ags by MHC class Ib-related (MR1) molecules. However, the interaction of human MAIT cells with adaptive immune responses and the role they may play in settings of vaccinology remain relatively little explored. In this study we investigated the interplay between MAIT cell-mediated antibacterial effector functions and the humoral immune response. IgG opsonization of the model microbe Escherichia coli with pooled human sera markedly enhanced the capacity of monocytic APC to stimulate MAIT cells. This effect included greater sensitivity of recognition and faster response kinetics, as well as a markedly higher polyfunctionality and magnitude of MAIT cell responses involving a range of effector functions. The boost of MAIT cell responses was dependent on strongly enhanced MR1-mediated Ag presentation via increased FcγR-mediated uptake and signaling primarily mediated by FcγRI. To investigate possible translation of this effect to a vaccine setting, sera from human subjects before and after vaccination with the 13-valent-conjugated Streptococcus pneumoniae vaccine were assessed in a MAIT cell activation assay. Interestingly, vaccine-induced Abs enhanced Ag presentation to MAIT cells, resulting in more potent effector responses. These findings indicate that enhancement of Ag presentation by IgG opsonization allows innate-like MAIT cells to mount a faster, stronger, and qualitatively more complex response and to function as an effector arm of vaccine-induced humoral adaptive antibacterial immunity.

Dengue virus infections among European travellers, 2015 to 2019.

BackgroundDengue is a disease with major impacts on public health in tropical and subtropical countries. In Europe, in the past decade, few autochthonous outbreaks were described.AimWe aimed to identify factors associated with frequency of dengue virus infection among European travellers and at assessing how surveillance data could support preparedness against autochthonous outbreaks within Europe.MethodsWe performed a descriptive analysis of travel-related dengue cases reported by European countries from 2015 through 2019. Using flight passenger data, we calculated travellers' infection rates (TIR). We investigated the following associations: (i) between TIR and incidence rate in selected countries of infection and (ii) between number of travel-related cases and occurrence of autochthonous outbreaks within Europe.ResultsThere were 11,478 travel-related dengue cases and the TIR was 2.8 cases per 100,000 travellers. Most cases were infected in Asia (71%), predominantly in south-eastern Asia. The TIR was highest among travellers returning from Asia (6.1/100,000). There was an association between the incidence rate in the country of infection and the TIR but no association between the number of travel-related cases and occurrence of autochthonous outbreaks in Europe.ConclusionsThe likelihood of infection in travellers is a function of the ongoing epidemiological situation in the country of exposure. The number of travel-related cases alone is not sufficient to estimate the likelihood of autochthonous outbreaks where vectors are present in Europe. Additional contributing factors such as adequate vectorial capacity and suitable environmental conditions are required.

Age-specific associations between underlying health conditions and hospitalisation, death and in-hospital death among confirmed COVID-19 cases: a multi-country study based on surveillance data, June to December 2020.

BackgroundUnderlying conditions are risk factors for severe COVID-19 outcomes but evidence is limited about how risks differ with age.AimWe sought to estimate age-specific associations between underlying conditions and hospitalisation, death and in-hospital death among COVID-19 cases.MethodsWe analysed case-based COVID-19 data submitted to The European Surveillance System between 2 June and 13 December 2020 by nine European countries. Eleven underlying conditions among cases with only one condition and the number of underlying conditions among multimorbid cases were used as exposures. Adjusted odds ratios (aOR) were estimated using 39 different age-adjusted and age-interaction multivariable logistic regression models, with marginal means from the latter used to estimate probabilities of severe outcome for each condition-age group combination.ResultsCancer, cardiac disorder, diabetes, immunodeficiency, kidney, liver and lung disease, neurological disorders and obesity were associated with elevated risk (aOR: 1.5-5.6) of hospitalisation and death, after controlling for age, sex, reporting period and country. As age increased, age-specific aOR were lower and predicted probabilities higher. However, for some conditions, predicted probabilities were at least as high in younger individuals with the condition as in older cases without it. In multimorbid patients, the aOR for severe disease increased with number of conditions for all outcomes and in all age groups.ConclusionWhile supporting age-based vaccine roll-out, our findings could inform a more nuanced, age- and condition-specific approach to vaccine prioritisation. This is relevant as countries consider vaccination of younger people, boosters and dosing intervals in response to vaccine escape variants.

From Cancer Therapy to Winemaking: The Molecular Structure and Applications of ß-Glucans and ß-1, 3-Glucanases.

ß-glucans are a diverse group of polysaccharides composed of ß-1,3 or ß-(1,3-1,4) linked glucose monomers. They are mainly synthesized by fungi, plants, seaweed and bacteria, where they carry out structural, protective and energy storage roles. Because of their unique physicochemical properties, they have important applications in several industrial, biomedical and biotechnological processes. ß-glucans are also major bioactive molecules with marked immunomodulatory and metabolic properties. As such, they have been the focus of many studies attesting to their ability to, among other roles, fight cancer, reduce the risk of cardiovascular diseases and control diabetes. The physicochemical and functional profiles of ß-glucans are deeply influenced by their molecular structure. This structure governs ß-glucan interaction with multiple ß-glucan binding proteins, triggering myriad biological responses. It is then imperative to understand the structural properties of ß-glucans to fully reveal their biological roles and potential applications. The deconstruction of ß-glucans is a result of ß-glucanase activity. In addition to being invaluable tools for the study of ß-glucans, these enzymes have applications in numerous biotechnological and industrial processes, both alone and in conjunction with their natural substrates. Here, we review potential applications for ß-glucans and ß-glucanases, and explore how their functionalities are dictated by their structure.