Swiss School of Archaeology in Greece
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Vertebral Bone Density Abnormalities in Fetal Ultrasound: A Distinctive Clinical Sign of Spondylocarpotarsal Synostosis Syndrome MYH3-Related.
No full textUltrasound diagnosis of fetal skeletal conditions remains challenging. MYH3 is a gene that encodes the embryonic myosin heavy chain; it is important for skeletal and muscular development and is strongly expressed during fetal development. Variants in MYH3 are involved in distal arthrogryposes 2A and 2B3 and in spondyocarpotarsal synostosis syndrome with contractures and pterygia, contractures of proximal and distal joints, variable spine anomalies and vertebral, carpal and tarsal fusions.
We describe a case in which prenatal ultrasonography detected abnormal bone density in the fetal spine. The fetus showed abnormal spinal segmentation, characterised by demineralisation and lacunar morphological tracts. x-rays and histological examination confirmed the ultrasonographic findings. We describe a unique ultrasonographic phenotype of fetal spine that has not yet been described in the literature. This is likely associated with two MYH3 variants. Therefore, we believe that abnormal spinal segmentation should be considered a relevant ultrasound finding.
Fetal ultrasound, together with radiological investigations, clinical examination of the fetal phenotype and histological investigations are essential in directing molecular genetic testing to identify rare diseases. We review the literature and describe a prenatal case with abnormal bone density in the spine. Whole-exome sequencing (WES) analysis in the fetus was performed to explore variants compatible with ultrasound signs
Determining major adverse cardiovascular event risk of beta-blocker discontinuation after acute coronary syndromes.
No full textBeta-blocker therapy reduced mortality and cardiovascular events following acute coronary syndromes (ACS) in the pre-reperfusion era. In the contemporary era of early mechanical reperfusion and modern secondary prevention, the benefit of beta-blockers after ACS without reduced left ventricular ejection fraction (LVEF) has been questioned. This review was based on PubMed database searches from inception to January 2025.
The recent REDUCE-AMI and ABYSS trials were the first adequately powered contemporary randomized trials evaluating beta-blockers after ACS without reduced LVEF. Contemporary observational evidence is also discussed. Implications for different LVEF categories (41-49% versus ≥ 50%), ACS subtypes, beta-blocker therapy duration, optimal dose, and interaction with other secondary prevention therapies are addressed.
We estimate that there is sufficient evidence to abandon routine beta-blocker prescription in post-ACS patients with preserved LVEF ≥ 50%. Beta-blocker prescription should be individualized with shared decision-making, balancing the risk of cardiovascular event against potential benefits of deprescription. Factors favoring beta-blocker discontinuation include adverse effects, polypharmacy, >1-3 years of stability post-ACS, and specific comorbidities (e.g. heart failure with preserved LVEF). Factors favoring beta-blocker prescription/continuation (besides established indications such as LVEF ≤ 40%, arrhythmias, angina, and refractory hypertension) include good tolerance, LVEF 41-49%, and non-adherence to other secondary prevention therapies
An ISR-independent role of GCN2 prevents excessive ribosome biogenesis and mRNA translation.
No full textThe integrated stress response (ISR) is a corrective physiological programme to restore cellular homeostasis that is based on the attenuation of global protein synthesis and a resource-enhancing transcriptional programme. GCN2 is the oldest of four kinases that are activated by diverse cellular stresses to trigger the ISR and acts as the primary responder to amino acid shortage and ribosome collisions. Here, using a broad multi-omics approach, we uncover an ISR-independent role of GCN2. GCN2 inhibition or depletion in the absence of discernible stress causes excessive protein synthesis and ribosome biogenesis, perturbs the cellular translatome, and results in a dynamic and broad loss of metabolic homeostasis. Cancer cells that rely on GCN2 to keep protein synthesis in check under conditions of full nutrient availability depend on GCN2 for survival and unrestricted tumour growth. Our observations describe an ISR-independent role of GCN2 in regulating the cellular proteome and translatome and suggest new avenues for cancer therapies based on unleashing excessive mRNA translation
Evolutionary dynamics in the genome of ocular Chlamydia trachomatis strains from Northern Tanzania following mass drug administration.
No full textTrachoma, caused by Chlamydia trachomatis (Ct), remains a leading cause of preventable infection-induced blindness worldwide. We conducted a 4-year longitudinal study in three trachoma-endemic villages in Northern Tanzania, tracking infection dynamics and factors influencing trachomatous scarring progression and persistence pre- and post-mass drug administration (MDA) interventions. We analysed 118 whole genomes of Ct originating from ocular swabs of children. Sample collection was conducted at 3-month intervals over 4 years, encompassing 15 timepoints. We studied Ct phylogeny and patterns of SNP accumulation within sequences in the Ct genotype A (CtA) and Ct genotype B (CtB) phylogenetic clades, with the association of clinical signs of trachoma and scarring progression. Of the samples analysed, 71 (60.2%) were identified as CtA and 47 (39.8%) as CtB. We observed a significant shift in genotype prevalence: CtB predominated in pre-MDA samples (36 out of 40, 90%), whilst CtA became the dominant genotype after the first MDA round (67 out of 78, 85.9%) (P<0.0001). Phylogenetic analysis revealed two distinct CtA clades: clade 1 (29 sequences) was primarily found pre-MDA and shared a common ancestor with Tanzanian CtA reference genomes, whilst clade 2 (42 sequences) emerged post-MDA and exhibited a characteristic ~6 kbp reduction in the plasticity zone (PZ). Similarly, CtB sequences formed two distinct clades, both sharing ancestry with a Tanzanian CtB reference genome. Notably, we identified variable genome reduction in the PZ (~4 and ~10 kbp) amongst 13 CtB sequences distributed across both clades. We documented a significant shift in Ct genotype distribution following the first round of MDA, characterized by the emergence of CtA strains with distinct genetic profiles compared to pre-MDA strains. The observed reductions in Ct genome size suggest ongoing evolutionary processes shaping these bacterial populations. Additional research is needed to understand the dynamic changes in Ct lineage composition before and after antibiotic interventions and to determine how variations in genome size influence Ct biology and its susceptibility to azithromycin treatment
Isolated Anterior T-Wave Inversion in Elite Athletes: Prevalence and Clinical Relevance by Sex and Sporting Discipline
No full textCardiac screening of elite athletes is common internationally. Female athletes are reported to have a higher proportion of abnormal screening ECGs compared with male athletes, despite lower rates of sudden cardiac death. T-wave inversion in leads V2 and V3 (TWIV2-3) is considered abnormal for athletes aged ≥16 years, but there are knowledge gaps in prevalence and clinical outcomes.
Data were obtained from the ARENA (Australasian Registry of ECGs of National Athletes) project and combined with previous athlete cohort studies from Australia and New Zealand. Sporting disciplines included Olympic sports (summer and winter), Australian football, cricket, football (soccer), and netball. Logistic regression calculated adjusted odds ratios with 95% CIs for the odds of isolated TWIV2-3 adjusting for sex and sporting discipline.
Of 4423 athletes (40% female athletes; mean age, 19.7±4.5 years), isolated TWIV2-3 was found in 36 athletes aged ≥16 years (27 [1.5%] female athletes, 9 [0.3%] male athletes). Isolated TWIV2-3 was more common in female athletes compared with male athletes (adjusted odds ratio, 4.2 [95% CI, 2.0-9.5]) and endurance compared with nonendurance athletes (adjusted odds ratio, 4.8 [95% CI, 2.5-9.5]). Follow-up investigations were available in 34 of 36, including echocardiogram (n=30), magnetic resonance imaging (n=3), stress ECG (n=2), or subsequent normal ECG (n=13). After 6.4±2.6 years of follow-up, no athletes with isolated TWIV2-3 were diagnosed with cardiac disease. Overall, female athletes had a higher proportion of abnormal ECGs compared with male athletes (4.2% versus 2.6%, P=0.004). If TWIV2-3 was considered a normal finding in female athletes, female and male athletes would have similar proportions of abnormal ECGs (2.6% versus 2.6%, P=0.95).
Isolated TWIV2-3 was 4 times more common in female athletes and 5 times more common in endurance athletes. This finding was not associated with cardiac pathology
Oxidative stress and nitric oxide metabolism responses during prolonged high-altitude exposure in preterm born adults
No full textPrematurely-born individuals tend to exhibit higher resting oxidative stress, although evidence suggests they may be more resistant to acute hypoxia-induced redox balance alterations. We aimed to investigate the redox balance changes across a 3-day hypobaric hypoxic exposure at 3375 m in healthy adults born preterm (gestational age ≤ 32 weeks) and their term-born (gestational age ≥ 38 weeks) counterparts.
Resting venous blood was obtained in normoxia (prior to altitude exposure), immediately upon arrival to altitude, and the following 3 mornings. Antioxidant (superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and ferric reducing antioxidant power (FRAP)), pro-oxidant (xanthine oxidase (XO) and myeloperoxidase (MPO)) enzyme activity, oxidative stress markers (advanced oxidation protein product (AOPP) and malondialdehyde (MDA)), nitric oxide (NO) metabolites (nitrites, nitrates, and total nitrite and nitrate (NOx)), and nitrotyrosine were measured in plasma.
SOD increased only in the preterm group (p < 0.05). Catalase increased at arrival in preterm group (p < 0.05). XO activity increased at Day 3 for the preterm group, while it increased acutely (arrival and Day 1) in control group. MPO increased in both groups throughout the 3 days (p < 0.05). AOPP only increased at arrival in the preterm (p < 0.05) whereas it decreased at arrival up to Day 3 (p < 0.05) for control. MDA decreased in control group from arrival onward. Nitrotyrosine decreased in both groups (p < 0.05). Nitrites increased on Day 3 (p < 0.05) in control group and decreased on Day 1 (p < 0.05) in preterm group.
These data indicate that antioxidant enzymes seem to increase immediately upon hypoxic exposure in preterm adults. Conversely, the blunted pro-oxidant enzyme response to prolonged hypoxia exposure suggests that these enzymes may be less sensitive in preterm individuals. These findings lend further support to the potential hypoxic preconditioning effect of preterm birth.
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Association between the intensity of statin therapy and physical activity 1 year after acute coronary syndrome: a multicentre prospective cohort study in Switzerland.
No full textTo assess the association between the intensity of statin therapy and the level of physical activity in patients 1 year after an acute coronary syndrome (ACS).
Prospective cohort study from the Special Program University Medicine-Acute Coronary Syndromes.
Four university hospital centres in Switzerland.
2274 patients with a main diagnosis of ACS between 2009 and 2017 who were available for a 1-year follow-up visit 1 year after hospital discharge.
Self-reported physical activity was assessed with the International Physical Activity Questionnaire. The level of physical activity in metabolic equivalent-minutes per week (MET-min/week) was first stratified into sedentary and physically active categories and then analysed continuously among physically active patients. Analyses were performed using a propensity score weighting approach.
One year after ACS, 1222 (53.7%) patients were on high-intensity statin therapy, 890 (39.1%) were on low/moderate-intensity statin therapy and 162 (7.1%) were not on statin therapy. Compared with non-statin users, low-/moderate-intensity statin users and high-intensity statin users were more likely to be physically active than sedentary, with a fully adjusted OR of 2.86 (95% CI 1.12 to 7.26) and 4.52 (95% CI 1.68 to 12.20), respectively. Among physically active patients, physical activity level was similar across all statin user categories, with median levels of 2792.5, 2712.0 and 2839.5 MET-min/week in non-statin, moderate/low-statin and high-statin users, respectively (p=0.307).
One year after ACS, neither low-/moderate-intensity nor high-intensity statin uses were associated with reduced self-reported physical activity compared with non-statin use. The concern that statin therapy may impair physical activity among ACS patients was not confirmed in this study
Asparagine deprivation enhances T cell antitumour response in patients via ROS-mediated metabolic and signal adaptations.
No full textPreclinical studies have shown that asparagine deprivation enhances T cell antitumour responses. Here we apply compassionate use of L-asparaginase, usually employed to treat blood malignancies, on patients with recurrent metastatic nasopharyngeal carcinoma. The use of L-asparaginase notably enhances immune-checkpoint blockade therapy in patients by strengthening CD8 + T cell fitness. Our study shows that this combination is a promising avenue for clinical application and provides further mechanistic insight into how asparagine restriction rewires T cell metabolism
Prenatal evaluation, diagnosis and management of fetal corpus callosal abnormalities: international Delphi consensus
No full textThe corpus callosum (CC) is an interhemispheric structure that facilitates communication between the two cerebral hemispheres. Anomalies of the CC are frequent and associated with a wide spectrum of altered neurodevelopmental outcomes. However, variability in diagnostic criteria and the lack of standardized management strategies create challenges for clinicians and anxiety for expectant parents. This study aimed to establish an international consensus on the prenatal evaluation, diagnosis and management of fetal CC abnormalities using a structured Delphi methodology.
A three-round Delphi process was conducted among an international panel of fetal medicine experts, identified based on clinical expertise and publication history. Structured statements regarding CC evaluation, diagnosis and management were developed through expert input and a scoping literature review. The statements were iteratively refined and scored by the panel using a five-point Likert scale in the first two rounds. During the final round, consensus was defined as > 70% agreement among participants.
Fifty-five experts participated in the first round, with 43 (78.2%) experts completing the entire process. Key consensus findings included the incorporation of obtaining a sagittal view of the brain in routine ultrasound screening (72.4% agreement), without requiring measurement even when an anomaly is suspected (93.1% agreement), but instead with recommended referral to a specialist (100% agreement). For diagnostic ultrasound, three-dimensional ultrasound imaging (72.4% agreement) and transvaginal ultrasound evaluation (82.8% agreement) were recommended, with targeted measurements of CC length in the case of a subjective impression of abnormal size (82.8% agreement). However, it was agreed that there is no consensus on the reference chart or cut-off values to be used for defining abnormal CC length (86.2% and 89.3% agreement, respectively). In terms of management, it was agreed that both an invasive genetic workup and magnetic resonance imaging (MRI) should be offered in case of suspected dysgenesis of the CC (100% agreement). MRI should be performed if the CC appears to be too short (100% agreement), thin (100% agreement) or thick (92.0% agreement). In the case of an isolated CC with heterogeneous echogenicity, an infectious workup is recommended (86.2% agreement).
This study provides a structured framework for the evaluation and management of fetal CC abnormalities. By standardizing approaches to imaging and management, the recommendations aim to improve diagnostic accuracy, optimize patient outcomes and reduce unnecessary interventions. Further prospective studies are needed to validate these recommendations and assess their impact on clinical care. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
© 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology
Pain in Hospital: A Real-Word Data Analysis.
No full textThe study aim was to describe the prevalence of pain, its assessment, and its associated characteristics in a university hospital in the French-speaking part of Switzerland.
Despite many advances in its management, pain is still a common and persistent symptom in hospitals. Nurses have a central role in its management. Pain assessment is essential for optimal management; it is nonetheless made insufficiently and randomly.
The design was a monocentric correlational descriptive study.
This study was based on the secondary analysis of routine data from 22,987 computerised health records of the medical and surgical wards between 1 November 2017 and 31 March 2019.
The results showed that the prevalence of pain was high in medical and surgical wards. Almost one-fifth of the participants suffered from severe pain at least once during their hospital stay. There was no association between the presence of pain and hospital ward, but the likelihood of having severe pain increased if the participant was hospitalised in a medical ward. Close personalised pain monitoring should be promoted to prevent the onset of severe pain. No Patient or Public Contribution