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European Union enlargement Quo vadis?
No full textThe European Union has not enlarged for the longest period in its history since the first enlargement in 1973. In recent years, however, talk of ‘enlargement fatigue’ has been replaced by an emphasis on the geostrategic importance of enlargement, primarily in response to the Russian invasion of and war in Ukraine. This begs the question of whether at least some of the current nine candidates will accede to the Union in the foreseeable future. While the prospects for enlargement rely on candidates making meaningful progress in meeting the requirements to join the Union, they also require the European Union to agree to enlargement. We consider five key variables to assess the state of play with European Union enlargement: the Union commitment, Member State preferences, supranational activism, integration capacity, and public opinion
The role of inflammasomes in chronic oral inflammatory disease and oral cancer: a narrative review
No full textBackground: Chronic inflammation is a hallmark of many oral and systemic diseases and has long been recognised as a risk factor for cancer development. Central to inflammatory responses are inflammasomes—multiprotein complexes that, upon activation, trigger caspase-1–mediated release of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). Their emerging contribution to chronic oral inflammatory conditions has generated interest in understanding whether persistent inflammasome activity may also influence pathways involved in oral carcinogenesis. This review summarises current evidence on the role of inflammasomes in oral inflammatory diseases and explores their potential involvement in the transition from chronic inflammation to malignant transformation. Methods: A narrative review of the literature was conducted by searching major scientific databases for studies investigating inflammasome activation in oral tissues, inflammatory oral diseases, and mechanisms linking chronic inflammation to oral cancer. Eligible articles included experimental studies, animal models, observational clinical research, and review papers that provided mechanistic or associative insights. Due to heterogeneity in study designs, a qualitative synthesis was performed. Results: Available evidence indicates that inflammasomes, particularly NLRP3 and AIM2, contribute to the pathophysiology of pulpitis, periodontitis, and several systemic conditions that affect oral health. Preclinical and observational findings also suggest potential involvement of inflammasome-related pathways in early tumorigenic processes, although these associations require further clarification. Preliminary biomarker-based studies demonstrate that inflammasome components measurable in saliva, pulpal blood, or gingival crevicular fluid may offer minimally invasive indicators of inflammatory burden and oral health status. Conclusions: Inflammasomes appear to play a meaningful role in oral inflammatory diseases, and growing evidence links their persistent activation to mechanisms relevant to oral carcinogenesis. However, current findings are largely associative and derived primarily from experimental and early clinical research. Additional work is needed to define precisely how inflammasomes contribute to the progression from chronic oral inflammation toward malignant change and to evaluate whether targeting inflammasome pathways offers viable therapeutic or diagnostic potential
Intra-nasal and intra-pulmonary routes: strategies for managing COVID-19
No full textDrug delivery through intranasal (IN) and intrapulmonary (IP) routes has been extensively employed for the management of the coronavirus disease 19 (COVID-19) pandemic. In the post-pandemic era, it is necessary to effectively administer pharmaceuticals and vaccines to address the less severe manifestations of COVID-19. The IN delivery process involves direct application of medicinal substances via the nasal mucosa. Vaccines and anti-viral drugs are designed to provide localised immunity and mitigate the symptoms and severity of various diseases. The utilisation of inhalable formulations of anti-viral medications and immunomodulators can facilitate targeted drug delivery to specific affected lung tissues, thereby improving treatment outcomes and minimising adverse effects on the overall systemic physiology. This manuscript provides an overview of the most recent research and development on the use of IN and IP routes of administration for the management of COVID-19. It examines the potential advantages, obstacles, and consequences of the future healthcare strategies associated with these approaches
Effects of exposure to phthalates and a phthalate substitute on food sensitization in children in China: evidence from a population study
No full textBackgroundPhthalates are among the most ubiquitous environmental pollutants and endocrine disruptors. However, the effect of phthalates exposure on food allergies remains unclear.ObjectivesThis study examined the relationship between exposure to phthalates and a phthalate substitute and food sensitization in children.MethodsA study was conducted including 198 children with self-reported food allergy and 202 healthy children. Specific immunoglobulin E (sIgE) test and skin prick test were applied to evaluate the susceptibility to food sensitization. Urine samples were analyzed for 17 metabolites of phthalates and a phthalate substitute. Logistic regression and weighted quantile sum regression models were used to examine the correlations between exposure and food sensitization. Bayesian benchmark dose models were established to calculate benchmark dose values for these metabolites.ResultsIn single compound models, mono-2-ethyl-5-hydroxyhexyl terephthalate (MEHHTP) was associated with increased sensitization to almond, crab, shrimp, and total foods, and mono-2-methyl-2-hydroxypropyl phthalate (MHiBP) was associated with positive skin prick tests for wheat, peanut, and blue mussel (all p < 0.05). Mixed exposure only increased susceptibility for total foods sensitization with higher levels of sIgE (Odds Ratio = 1.25, 95 % confidence intervals: 1.01–1.56, p = 0.04), and MEHHTP had the dominant contribution.ConclusionPhthalates exposure is linked to a higher risk of food sensitization in children in China. Further studies are warranted to confirm these findings and the role of phthalate substitutes
Central contrast sensitivity as an outcome measure in randomized controlled trials in glaucoma-a systematic review
No full textPurpose: Standard automated perimetry (SAP) remains the gold standard functional test in glaucoma, used primarily for evaluating peripheral vision loss. Central contrast sensitivity (CCS) has emerged as a potential early functional marker of glaucomatous damage. This systematic review aimed to describe the different methods used to measure CCS in randomized controlled trials (RCT) involving glaucoma patients. Methods: We searched the MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, Epistemonikos, and ClinicalTrials.gov databases on 25 January 2023, and updated the search on 12 February 2025. Eligible studies comprised RCTs that reported CCS as an outcome in patients with glaucoma, suspected glaucoma, or ocular hypertension. No restrictions were placed on age, sex, ethnicity, geography, intervention, or publication year. Abstracts and full texts were screened independently by two reviewers. Descriptive statistics were used. No formal risk of bias assessment was performed, due to the descriptive nature of the review. Results: Of 1066 records screened, 31 studies met the eligibility criteria. The study sample size ranged from 7 to 207 (median: 23), with most studies involving primary open-angle glaucoma. Interventions were diverse, mainly involving topical medications, with timolol being the most frequent. Eleven CCS test methods were identified. Five studies did not report the method used. The CSV-1000 was the most commonly used test, being applied in 11 studies. Conclusions: CCS has been measured using a wide range of methods in glaucoma RCTs, with limited standardization. Most of the included studies were small, variably reported, and conducted over 10 years ago, suggesting a decreasing interest in CCS as an outcome measure in glaucoma RCTs
Variation within and between digital pathology and light microscopy for the diagnosis of histopathology slides: blinded crossover comparison study
No full textBackgroundDigital pathology refers to the conversion of histopathology slides to digital image files for examination on computer workstations as opposed to conventional microscopes. Prior to adoption, it is important to demonstrate pathologists provide equivalent reports when using digital pathology in comparison to bright-field and immunofluorescent light microscopy, the current standard of care.ObjectiveA multicentre comparison of digital pathology with light microscopy for reporting of histopathology slides, measuring variation within and between pathologists on both modalities.DesignA blinded crossover 2000-case study estimating clinical management concordance (identical diagnoses plus differences not affecting patient management). Each sample was assessed twice by four pathologists (once using light microscopy, once using digital pathology, the order randomly assigned and a 6-week gap between viewings). Random-effects logistic regression models, including crossed random-effects terms for case and pathologist, estimated percentage clinical management concordance. Findings were interpreted with reference to 98.3% concordance (Azam AS, Miligy IM, Kimani PKU, Maqbool H, Hewitt K, Rajpoot NM, Snead DRJ. Diagnostic concordance and discordance in digital pathology: a systematic review and meta-analysis. J Clin Pathol 2021;74:448–55. https://doi.org/10.1136/jclinpath-2020-206764).SettingSixteen consultant pathologists, four for each specialty, from six National Health Service laboratories. Experience ranged from 3 to 35 years. Some were early adopters of digital pathology, but the majority were new to digital pathology.InterventionsEight viewings per sample (four pathologists with light microscopy and with digital pathology), culminating in a consensus ground truth, enabling measurement of agreement within and between readers. Samples enrolled reflected routine practice, included cancer screening biopsies, and were enriched for areas of difficulty [e.g. dysplasia (7, 10, 11)]. State-of-the-art digital pathology equipment designed for diagnosis, and holding either Conformité Européene or Food and Drug Administration approval, was used.Main outcomeIntra-pathologist variation between reports issued on digital pathology and light microscopy, inter-pathologist variation against ground-truth diagnosis using light microscopy and digital pathology.Secondary outcomesPathologist-recorded reporting times, along with their confidence in diagnosis, analysis of eye-tracking evaluating examination techniques, and a qualitative study examining attitudes of pathologists and laboratory staff to digital pathology adoption.ResultsTwo thousand and twenty-four cases (608 breast, 607 gastrointestinal, 609 skin, 200 renal) were recruited, with breast and gastrointestinal including screening samples [207 (34%) breast, 250 (41%) gastrointestinal]. Overall, in light microscopy versus digital pathology comparisons, clinical management concordance levels were 99.95% (95% confidence interval 99.91 to 99.97). Similar results were observed within specialties [breast: 99.40% (95% confidence interval 99.06 to 99.62); gastrointestinal 99.96% (95% confidence interval 99.89 to 99.99); skin 99.99% (95% confidence interval 99.92 to 100.0); renal 99.99% (95% confidence interval 99.57 to 100.0)], and within screening cases [98.96% (95% confidence interval 98.42 to 99.32), breast 96.27% (94.63 to 97.43), gastrointestinal 99.93% (95% confidence interval 99.68 to 99.98)]. Reporting time between digital pathology and light microscopy was similar, but pathologists became faster on digital pathology with familiarity. Pathologists recorded high levels of confidence in their diagnosis with light microscopy, significantly higher than digital pathology.LimitationsCytology cases and specialty groups outside those tested were not examined. The study used two digital pathology scanning systems. Other systems available on the market were not tested.ConclusionsClinical management concordance levels between the two modalities exceed the reference 98.3% in breast, gastrointestinal, skin and renal specialties, and pooled breast and large bowel cancer screening cases. Subgroup analysis of clinically significant differences revealed a range of differences including areas where interobserver variability is known to be high, which were distributed between reads performed with both platforms and without apparent trends to either
Efficacy of a feed additive consisting of a copper(II)-betaine complex for all animal species (Biochem Zusatzstoffe Handels- und Produktionsges. mbH)
No full textFollowing a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the efficacy of copper(II)-betaine complex as a nutritional feed additive for all species and categories. In a previous opinion, the FEEDAP Panel characterised the feed additive and concluded that it is safe for the target animals, consumers, and the environment when used up to the maximum authorised levels of copper in the diets. With regard to the safety of users, the additive is considered irritant to the eyes and a skin and respiratory sensitiser. In the current submission, the applicant provided a new efficacy study in chickens for fattening to support the efficacy of the additive. The data submitted provided evidence that the additive is a bioavailable source of copper and thus, the FEEDAP Panel concludes that the additive is efficacious as a source of copper for all animal species.</p
Efficacy of a feed additive consisting of Enterococcus lactis NCIMB 11181 (Lactiferm®) for chickens for fattening or reared for laying, other poultry species for fattening or reared for laying and ornamental birds (Chr. Hansen A/S)
No full textFollowing a request from the European Commission, EFSA was asked to deliver a scientific opinion on the efficacy of Lactiferm®, a preparation containing viable cells of Enterococcus lactis NCIMB 11181, as a zootechnical feed additive (functional group: gut flora stabilisers). The additive is intended to be used in the feed (3 × 1010 CFU/kg complete feed) and water for drinking (1.5 × 1010 CFU/L) for chickens for fattening or reared for laying, other poultry species for fattening or reared for laying and ornamental birds. In a previous assessment, the FEEDAP Panel concluded that the additive is safe for the target species, consumers and the environment but could not conclude on its efficacy because only two out of the six trials submitted showed significant and positive effects on the zootechnical performance of chickens for fattening. The applicant provided two published studies, one pooled analysis of the data from two previously assessed trials and two long-term trials in chickens for fattening to address the data gaps in the efficacy assessment. Based on the results of the trials in the previous and current applications, the FEEDAP Panel concluded that Lactiferm® has the potential to be efficacious when supplemented either in the feed or water of chickens for fattening, and the conclusion was extended to chickens reared for laying and extrapolated to other poultry for fattening and reared for laying and ornamental birds.</p
Safety and efficacy of a feed additive consisting of endo-1,4-beta-xylanase EC 3.2.1.8 produced by Bacillus subtilis LMG S-15136 (Belfeed B MP/ML) for gestating sows (Puratos NV)
No full textFollowing a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of Belfeed B MP/ML as a feed additive for gestating sows when used at 10 IU/kg feed. The additive contains endo-1,4-b-xylanase produced by a genetically modified strain of Bacillus subtilis (LMG S-15136). The FEEDAP Panel concluded that the additive is safe for the target species at the proposed use level and that there are no concerns regarding the use of Belfeed B MP/ML for the consumers and for the environment. The two formulations of the additive were considered skin and eye irritants and respiratory sensitisers. The Panel concluded that the additive has the potential to be efficacious as a zootechnical additive in sows during the gestation period at 10 IU/kg feed.</p
Safety and efficacy of a feed additive consisting of guanidinoacetic acid and its preparation (GuanAMINO®) for chickens for fattening, chickens reared for laying, chickens reared for reproduction, turkeys for fattening, turkeys reared for reproduction (Evonik Operations GmbH)
No full textFollowing a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of guanidinoacetic acid (GAA) and its preparation (GuanAMINO®) as zootechnical additives for chickens for fattening, chickens reared for laying, chickens reared for reproduction, turkeys for fattening, turkeys reared for reproduction. The FEEDAP Panel concluded that GAA and its preparation GuanAMINO® are safe for chickens for fattening and reared for laying/reproduction and for turkeys for fattening and reared for reproduction when used up to the maximum proposed use level of 1200 mg guanidinoacetic acid/kg complete feed. The same conclusion applies for its use in water at 600 mg guanidinoacetic acid/L in water for drinking. However, considering the variability in water intake and the fact that no margin of safety was identified for chickens for fattening, attention should be paid to ensure that the exposure via water does not exceed the maximum safe level of the additive when administered via feed. The Panel concluded that the use of the additives under the proposed conditions of use is of no concern for the consumer and the environment. GAA and GuanAMINO® are not irritant to the skin or eyes and are not skin sensitisers. The FEEDAP Panel concludes that GAA and GuanAMINO® do not raise safety concerns for the user. The FEEDAP Panel considers that GAA and GuanAMINO® are efficacious in chickens for fattening, chickens reared for laying/reproduction and turkeys for fattening and reared for reproduction when guanidinoacetic acid is used at the minimum use level of 600 mg/kg complete feed or 300 mg/L water.</p