Mosaic vs. Single Image Analysis with Confocal Microscopy of the Corneal Nerve Plexus for Diagnosis of Early Diabetic Peripheral Neuropathy

The assessment of the corneal nerve fibre plexus with corneal confocal microscopy (CCM) is an upcoming but still experimental method in the diagnosis of early stage diabetic peripheral neuropathy (DPN). Using an innovative imaging technique—Heidelberg Retina Tomograph equipped with the Rostock Cornea Module (HRT-RCM) and EyeGuidance module (EG)—we were able to look at greater areas of subbasal nerve plexus (SNP) in order to increase the diagnostic accuracy. The aim of our study was to evaluate the usefulness of EG instead of single image analysis in diagnosis of early stage DPN

Cell cycle regulation of embryonic stem cells and mouse embryonic fibroblasts lacking functional Pax7

The transcription factor Pax7 plays a key role during embryonic myogenesis and in adult organisms in that it sustains the proper function of satellite cells, which serve as adult skeletal muscle stem cells. Recently we have shown that lack of Pax7 does not prevent the myogenic differentiation of pluripotent stem cells. In the current work we show that the absence of functional Pax7 in differentiating embryonic stem cells modulates cell cycle facilitating their proliferation. Surprisingly, deregulation of Pax7 function also positively impacts at the proliferation of mouse embryonic fibroblasts. Such phenotypes seem to be executed by modulating the expression of positive cell cycle regulators, such as cyclin E

Ammonia reduction by trees (ART). Summary report

The aim of Ammonia Reduction by Trees (ART) project was to provide new scientific evidence on tree planting for reducing the impact of ammonia emissions from farming to inform better advice, guidance and incentives for farmers on ammonia mitigation through treebelt planting

Clinico-radiological features, molecular spectrum, and identification of prognostic factors in developmental and epileptic encephalopathy due to inosine triphosphate pyrophosphatase (ITPase) deficiency

Developmental and epileptic encephalopathy 35 (DEE 35) is a severe neurological condition caused by biallelic variants in ITPA, encoding inosine triphosphate pyrophosphatase, an essential enzyme in purine metabolism. We delineate the genotypic and phenotypic spectrum of DEE 35, analyzing possible predictors for adverse clinical outcomes. We investigated a cohort of 28 new patients and reviewed previously described cases, providing a comprehensive characterization of 40 subjects. Exome sequencing was performed to identify underlying ITPA pathogenic variants. Brain MRI (magnetic resonance imaging) scans were systematically analyzed to delineate the neuroradiological spectrum. Survival curves according to the Kaplan–Meier method and log-rank test were used to investigate outcome predictors in different subgroups of patients. We identified 18 distinct ITPA pathogenic variants, including 14 novel variants, and two deletions. All subjects showed profound developmental delay, microcephaly, and refractory epilepsy followed by neurodevelopmental regression. Brain MRI revision revealed a recurrent pattern of delayed myelination and restricted diffusion of early myelinating structures. Congenital microcephaly and cardiac involvement were statistically significant novel clinical predictors of adverse outcomes. We refined the molecular, clinical, and neuroradiological characterization of ITPase deficiency, and identified new clinical predictors which may have a potentially important impact on diagnosis, counseling, and follow-up of affected individuals

Omission of Radiotherapy in Primary Mediastinal B-Cell Lymphoma: IELSG37 Trial Results

\ua9 2024 by American Society of Clinical Oncology. PURPOSE The role of consolidation radiotherapy in patients with primary mediastinal B-cell lymphoma (PMBCL) is controversial. METHODS The IELSG37 trial, a randomized noninferiority study, aimed to assess whether irradiation can be omitted in patients with PMBCL with complete metabolic response (CMR) after induction immunochemotherapy. The primary end point was progression-free survival (PFS) at 30 months after random assignment. Patients with CMR were randomly assigned to observation or consolidation radiotherapy (30 Gy). With a noninferiority margin of 10% (assuming a 30-month PFS of 85% in both arms), a sample size of 540 patients was planned with 376 expected to be randomly assigned. RESULTS The observed events were considerably lower than expected; therefore, primary end point analysis was conducted when ≥95% of patients were followed for ≥30 months. Of the 545 patients enrolled, 268 were in CMR after induction and were randomly assigned to observation (n = 132) or radiotherapy (n = 136). The 30-month PFS was 96.2% in the observation arm and 98.5% in the radiotherapy arm, with a stratified hazard ratio of 1.47 (95% CI, 0.34 to 6.28) and absolute risk difference of 0.68% (95% CI, -0.97 to 7.46). The 5-year overall survival (OS) was 99% in both arms. Nonrandomized patients were managed according to local policies. Radiotherapy was the only treatment in 86% of those with Deauville score (DS) 4 and in 57% of those with DS 5. The 5-year PFS and OS of patients with DS 4 (95.8% and 97.5%, respectively) were not significantly different from those of randomly assigned patients. Patients with DS5 had significantly poorer 5-year PFS and OS (60.3% and 74.6%, respectively). CONCLUSION This study, the largest randomized trial of radiotherapy in PMBCL, demonstrated favorable outcomes in patients achieving CMR with no survival impairment for those omitting irradiation

Genetic landscape of pediatric acute liver failure of indeterminate origin.

BACKGROUND AIMS Pediatric acute liver failure (PALF) is a life-threatening condition. In Europe, main causes are viral infections (12-16%) and inherited metabolic diseases (14-28%). Yet, in up to 50% of cases the underlying etiology remains elusive, challenging clinical management, including liver transplantation. We systematically studied indeterminate PALF cases referred for genetic evaluation by whole-exome sequencing (WES), and analyzed phenotypic and biochemical markers, and the diagnostic yield of WES in this condition. METHODS With this international, multicenter observational study, patients (0-18 y) with indeterminate PALF were analyzed by WES. Data on the clinical and biochemical phenotype were retrieved and systematically analyzed. RESULTS In total, 260 indeterminate PALF patients from 19 countries were recruited between 2011 and 2022, of whom 59 had recurrent PALF (RALF). WES established a genetic diagnosis in 37% of cases (97/260). Diagnostic yield was highest in children with PALF in the first year of life (46%), and in children with RALF (64%). Thirty-six distinct disease genes were identified. Defects in NBAS (n=20), MPV17 (n=8) and DGUOK (n=7) were the most frequent findings. When categorizing, most frequent were mitochondrial diseases (45%), disorders of vesicular trafficking (28%) and cytosolic aminoacyl-tRNA synthetase deficiencies (10%). One-third of patients had a fatal outcome. Fifty-six patients received liver transplants. CONCLUSION This study elucidates a large contribution of genetic causes in PALF of indeterminate origin with an increasing spectrum of disease entities. The high proportion of diagnosed cases and potential treatment implications argue for exome or in future rapid genome sequencing in PALF diagnostics

Hearing rehabilitation in SERAC1 related MEGD(H)EL syndrome – implications from a multi-center retrospective cohort study

Objective 3-methylglutaconic aciduria (MEG), dystonia-deafness (D), (hepatopathy (H)), encephalopathy (E), and Leigh-like-syndrome (L) (MEGD(H)EL) syndrome is a rare, severely disabling progressive mitochondrial disease associated with biallelic pathogenic variants in SERAC1. Knowledge about hearing loss (HL) and hearing rehabilitation is scarce but highly sought after for best possible care in the absence of causative treatment. Methods Retrospective cross-sectional study. Results This study analyzed the audiometric data of 36 MEGD(H)EL patients (14 unpublished). Bilateral HL was diagnosed in 31 individuals (86 %). Detailed audiometric data, available for 23 of 31 patients, did not allow for general statements on site and degree of HL. HL was mostly congenital (n = 14/31), pre-lingual in six and post-lingual in nine cases (median age 2 years, n = 15/31; age unknown in n = 2). In four of the five patients without HL, the severity of the other clinical-neurological symptoms was milder and less progressive, and their onset was significantly later than in the patients with HL. Five of 36 patients acquired spoken language, these were 4 of the 5 individuals without and one with HL. Twenty-two individuals received hearing rehabilitation with conventional hearing aids, followed by cochlear implant (CI) surgery in six. One of these six individuals acquired spoken language, which lessened in clarity as disease progressed. Conclusions Congenital HL represents a ubiquitous symptom in severe types of MEGD(H)EL syndrome, being absent in late onset milder forms. Regularly, severely affected MEGD(H)EL patients do not achieve spoken language, even with CI. Hence, hearing rehabilitation with CIs needs to be discussed very critically

UK Eutrophying and Acidifying Atmospheric Pollutants (UKEAP) Annual Report 2023

This annual report for 2023 was prepared by UK Centre for Ecology & Hydrology and Ricardo for the Environment Agency, the Department of Environment and Rural Affairs, the Department of Environment Northern Ireland, the Welsh Government and the Scottish Government. The Defra rural air pollutant monitoring networks project, (2021 – 2024: ECM48524), UK Eutrophying and Acidifying Atmospheric Pollutants (UKEAP) comprises the following measurement networks: • UK Environmental Monitoring and Evaluation Program (EMEP) monitoring supersites (Chilbolton Observatory and Auchencorth Moss) • National Ammonia Monitoring Network (NAMN – 113 sites, Dec 2023) • Acid Gases and Aerosol Network (AGANet – 28 sites, Dec 2023) • Precipitation chemistry Network (Precip-Net – 48 sites) • Rural nitrogen dioxide (NO2) diffusion tube network (NO2-Net – 24 sites) The report provides information on: • Updates on network operations during 2023. • Annual concentrations. • Interpretation of data and discussion of trends across the network. • A summary of the scientific research, publications and other activities related to the network. Key network changes for 2023: • In spring 2023, 16 sites were added to NAMN and 7 sites were added to PrecipNet. The additional sites were embedded Natural England’s Long Term Monitoring Network (LTMN)