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Probiotic membrane vesicles:emerging tools for disease treatment
No full textProbiotics are widely recognized for their health benefits, particularly in disease prevention and treatment. Recent research suggests that their therapeutic effects may be linked to the bacterial membrane vesicles (bMVs) they release. These nanoscale vesicles, secreted during probiotic growth and metabolism, facilitate intercellular communication through efficient material transport and signaling. With their biocompatibility and targeting properties, probiotic bMVs hold promise for medical applications. This review examines their biogenesis, bioactive components, functions, and role in disease treatment, while also discussing future research directions to unlock their full therapeutic potential
The arrow of time in Parkinson's disease
No full textBackground: Parkinson's disease (PD) is a system-level disorder that implicates brain network dynamics across multiple scales. Detecting the ‘arrow of time’, or temporal reversibility of the brain's information processing flow enables quantification of equilibrium in the brain and inferences on the hierarchical organization. Therefore we aimed to explore disturbances in resting-state equilibrium levels as well as changes in the hierarchical organization due to PD. Methods: Structural and functional MRI of 29 PD patients and 19 healthy controls were acquired and analyzed. Empirical non-reversibility was computed as the distance between time-shifted forward- and artificially-reversed time series. Levels of equilibrium were subsequently assessed globally and within two cortico-subcortical motor networks implicated in PD. Moreover, whole-brain generative computational models consisting of 1051 Hopf oscillators were constructed to evaluate effective connectivities and alterations of the functional hierarchical organization. Results: We found that PD is characterized by disrupted equilibrium regimes, marked by distinct effective connectivity patterns, particularly within the motor networks. Additionally, we observed a flatter hierarchical organization in PD, with the cerebellum and thalamus exerting increased influence. Conclusion: The arrow of time methodology effectively identifies distinct and informative characteristics of PD. Our analyses suggest that PD shifts the brain towards less efficient, non-equilibrium dynamics that impair intrinsic flexibility and disrupt motor coordination. Thus, these findings not only provide insight into widespread system alterations in PD that could serve as potential biomarkers, but also lay the groundwork for next-generation stimulation techniques aimed at restoring balance in the Parkinsonian brain
Surgical Repair Of Macular Fold In X-Linked Retinoschisis Initially Misdiagnosed As Familial Exudative Vitreoretinopathy
No full textPurpose:The purpose of this study was to describe the presentation and surgical management of a young boy initially believed to have familial exudative vitreoretinopathy who was ultimately diagnosed with an unusually aggressive form of X-linked retinoschisis that included rapidly progressive bullous retinoschisis and tractional macular fold.Methods:Retrospective case report.Results:A 19-month-old boy with straightening of major arcades, peripheral retinal ischemia, and in the left eye, a large macular fold was initially diagnosed as familial exudative vitreoretinopathy. During follow-up, he developed a rapidly progressive bullous retinoschisis in the left eye involving the inferior macula extending superiorly up to the macular fold. This revised the working diagnosis to X-linked retinoschisis, which was confirmed by genetic testing. Pars plana vitrectomy, inner flap retinectomy, unrolling of the macular fold and inner flap retinectomy, and C3F8 gas tamponade were performed. This resolved the macular fold. The patient showed good anatomical results without surgical complications up to 18 months of postoperative follow-up.Conclusion:X-linked retinoschisis can rarely present in young children with macular fold and peripheral ischemia, mimicking familial exudative vitreoretinopathy. Rapidly progressive bullous retinoschisis in this setting can be treated with pars plana vitrectomy, inner wall retinectomy, and removal of the vitreous traction to improve visual prognosis
Number of Publications on New Clinical Prediction Models:A Bibliometric Review
No full textBACKGROUND: Concerns have been expressed about the abundance of new clinical prediction models (CPMs) proposed in the literature. However, the extent of this proliferation in prediction research remains unclear. OBJECTIVE: This study aimed to estimate the total and annual number of CPM development-related publications available across all medical fields. METHODS: Using a validated search strategy, we conducted a systematic search of literature for prediction model studies published in Pubmed and Embase between 1995 and the end of 2020. By taking random samples for each year, we identified eligible studies that developed a multivariable model (ie, diagnostic or prognostic) for individual-level prediction of a health outcome across all medical fields. Exclusion criteria included development of models with a single predictor, studies not involving humans, methodological studies, conference abstracts, articles with unavailable full text, and those not available in English. We estimated the total and annual number of published regression-based multivariable CPM development articles, based on the total number of publications, proportion of included articles, and the search sensitivity. Furthermore, we used an adjusted Poisson regression to extrapolate our results to the period 1950-2024. Additionally, we estimated the number of articles that developed CPMs using techniques other than regression (eg, machine learning). RESULTS: From a random sample of 10,660 articles published between 1995 and 2020, 109 regression-based CPM development articles were included. We estimated that 82,772 (95% CI 65,313-100,231) CPM development articles using regression were published, with an acceleration in model development from 2010 onward. With the addition of articles that developed non-regression-based CPMs, the number increased to 147,714 (95% CI 125,201-170,226). After extrapolation to the years 1950-2024, the number of articles increased to 156,673 and 248,431 for regression-based models and total CPMs, respectively. CONCLUSIONS: Based on a representative sample of publications from the literature, we estimated that nearly 250,000 articles reporting the development of CPMs across all medical fields were published until 2024. CPM development-related publications continue to increase in number. To prevent research waste and close the gap between research and clinical practice, focus should shift away from developing new CPMs to facilitating model validation and impact assessment of the plethora of existing CPMs. Limitations of this study include restriction of search to articles available in English and development of the validated search strategy prior to the popularity of artificial intelligence and machine learning models
Current Approaches of Nuclear Molecular Imaging in Breast Cancer
No full textIn this narrative review, we aim to summarize recent advancements in nuclear molecular imaging techniques and their applications in BCa management. The main focus of this review is on the most relevant clinical investigations from the past 2-3 years that highlight the enhanced diagnostic and therapeutic value of these imaging modalities. A variety of radiolabeled probes introduced in molecular imaging is explored, detailing their roles in the accurate diagnosis and characterization of BCa, as well as their integration into radioligand therapy and theragnostic strategies
Early prediction of long-term cognitive function, emotional distress, and health-related quality of life in cardiac arrest survivors
No full textBackground: Cardiac arrest survivors are at risk of long-term disturbances in cognition, emotional distress, and health-related quality of life (QoL). Early prediction can guide tailored treatment. We evaluated whether early clinical measures predict long-term outcomes. Methods: In a longitudinal multicenter cohort study, we prospectively included patients who regained consciousness after cardiac arrest. Potential predictors during hospitalization were scores on the Hospital Anxiety and Depression Scale (HADS), Montreal Cognitive Assessment (MoCA), and Barthel Index, and presence of delirium and transient coma >24 h. These were related to cognitive function (MoCA), emotional distress (HADS), and health-related QoL (EQ-5D-5L) at twelve months using multivariate mixed-effects models, with age and sex as covariates. Likelihood ratios were calculated for cognitive impairment (MoCA < 26). Results: We included 100 patients; 20 % showed cognitive impairment at twelve months and 8 % and 10 % showed signs of anxiety and depression, respectively. Early MoCA showed a borderline significant positive relation with twelve-month MoCA (β = 0.21, p = 0.05). The likelihood ratio for early MoCA < 26 predicting cognitive impairment at twelve months was LR+ 1.29 (95 % CI: 0.40–4.20) and LR- 0.60 (95 % CI: 0.18–1.94). Early HADS was associated with twelve-month HADS (β = 0.47, 95 % CI: 0.33–0.60, p < 0.001), with age negatively associated (β = −0.10, 95 % CI: −0.18 to −0.02, p = 0.019). No other significant relations were found. Conclusion: MoCA and HADS scores during hospitalization relate to long-term cognitive and emotional outcomes after cardiac arrest. These measures may help identify patients who could benefit from cognitive rehabilitation or psychosocial support.</p
Short-term benefit of early rhythm control for atrial fibrillation:the EAST-AFNET 4 trial
No full textFull-length gene polymorphism of the non-classical HLA-E in Estonian individuals
No full textEstonia is a small country in the Baltic region of Northern Europe with 1.3 million inhabitants. As a coastal area, the population of Estonia was subjected to migration influences. Due to this admixture of populations, HLA gene diversity in Estonia is interesting to study with regard to allele frequencies, haplotypes, and polymorphism. In this study, we focused on HLA-E polymorphism within the Estonian population and compared these with the polymorphism identified in other populations. Full-length HLA-E sequencing of 143 individuals originating from Estonia show dimorphism frequencies at amino acid position 107 (0.55 R vs 0.45 G) comparable to other populations. Within the study population, 16 different HLA-E alleles were identified, including four novel alleles. These 16 alleles encode four different protein variants. Despite a strong differentiation between the South-East and the rest of the Estonian country, no allele frequency differences for HLA-E between these regions were identified. Comparing the allele and SNP frequencies to frequencies found in the different neighboring countries revealed no major differences, except for the SNP encoding for HLA-E*01:06. Association analysis between classical HLA class I genes and polymorphism at amino acid position 107 of HLA-E revealed higher frequencies of HLA-A*01 with R107 and HLA-A*03 and HLA-C*04 with G107. In summary, our study provides new insights into HLA-E variation within the Estonian population and demonstrates that its level of polymorphism is comparable to those observed in other global populations
Socio-Economic Inequalities in Stillbirth and Preterm Birth Rates Across Europe:A Population-Based Study
No full textOBJECTIVE: To estimate socio-economic (SES) inequalities in stillbirth and preterm birth rates across European countries using population-based routine data. DESIGN: Cross-sectional study of national-level perinatal health and SES indicators (mother's education/occupation or area-level deprivation). SETTING: Twenty-four countries in the Euro-Peristat network. POPULATION: Seventeen million births in 2015-2019. METHODS: Rates of stillbirth, singleton very preterm birth (VPB) and singleton moderate/late preterm birth (MLPB) were derived from routine national birth data collected with a common protocol. MAIN OUTCOME MEASURE: Percentage of excess adverse outcomes associated with SES and concentration indices. RESULTS: Median rates of adverse outcomes were higher in the lowest versus highest SES groups [Stillbirth: 4.9 (interquartile range (IQR):4.30-5.80)] versus 2.7 (IQR:2.25-3.14) per 1000 births; VPB: 1.0 (IQR: 0.87-1.12) versus 0.6 (IQR: 0.59-0.66) per 100 live births; MLPB: 5.8 (IQR: 5.27-6.40) versus 4.4 (IQR:4.13-4.65) per 100 live births. Excess adverse outcomes associated with lower SES varied greatly, particularly for stillbirth (range-3%, 51%) versus VPB (7%, 27%) and MLPB (5%, 20%). Concentration indices further highlighted varying socio-economic inequalities across countries. Median concentration indices were similar for countries with both lower and higher levels of adverse events, with median CIs of -0.12 for countries with both high and low levels of stillbirth. CONCLUSION: We identified widespread but varying inequalities between countries. These seemed to be unrelated to the rate of adverse outcomes. This suggests the need for policy strategies directly targeted to the prevention of stillbirth and preterm birth in low SES populations. Our findings demonstrate the feasibility of monitoring inequalities internationally using routine data to identify effective action