Prenatal diagnosis of Neu-Laxova syndrome: a case report

BACKGROUND: Neu-Laxova syndrome is a rare congenital abnormality involving multiple systems. We report a case of Neu-Laxova syndrome (NLS) diagnosed prenatally by ultrasound examination. CASE PRESENTATION: A 29-year-old gravida 3, para 2 woman was first seen in our antenatal clinic at 38 weeks' pregnancy. Except for the consanguinity and two previous abnormal stillborn babies her medical history was unremarkable. On ultrasound examination microcephaly, flat forehead, micrognathia, intrauterine growth restriction, generalized edema of the skin, hypoplastic chest, excessive soft tissue deposition of hands and feet, joint contractures and a penis without scrotal sacs were detected. She delivered a 2000 g male fetus. He died five minutes after delivery. Postmortem examination confirmed the diagnosis of Neu-Laxova syndrome. CONCLUSION: Because of the autosomal recessive inheritance of Neu-Laxova syndrome genetic counseling and early-serial ultrasound examination should be performed at risk families. Early diagnosis of the disease may offer termination of the pregnancy as an option

Utjecaj desflurana i sevoflurana na razine oksidativnog stresa u tkivima štakora

General anaesthetics are often used in patients who are under oxidative stress due to a critical illness or surgical trauma. Some anaesthetics may worsen oxidative stress and some may act as antioxidants. The aim of this study was to evaluate liver, brain, kidney, and lung tissue oxidative stress in rats exposed to desflurane and sevoflurane and in unexposed rats. The animals were divided in three groups: control (received only air); sevoflurane (8 %), and desflurane (4 %). After four hours of exposure, we evaluated the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Cu, and Zn. Exposure to either of the anaesthetics significantly increased lung MDA levels compared to control (Mann-Whitney U test; P<0.05), probably because it is the tissue directly exposed to anaesthetic gases. Oxidative stress and antioxidant activity in other tissues varied between the desflurane and sevoflurane groups. Our results suggest that anaesthesiologist should not only be aware of the oxidative or antioxidative potential of anaesthetics they use, but should also base their choices on organs which are the most affected by their oxidative actionkisikovih radikala tako i zbog smanjene aktivnosti obrambenih sustava koji se mogu oduprijeti njihovu djelovanju. Stoga su saznanja o antioksidativnom kapacitetu anestetika koji se primjenjuju prije nekoga kirurškog zahvata vrlo važna i od velikog su kliničkog značenja. Sevofl uran i desfl uran su inhalacijski anestetici koji se učestalo rabe u svrhu uvođenja bolesnika u anesteziju. Cilj ovog istraživanja bio je utvrditi razine oksidativnog stresa u različitim tkivima štakora i usporediti razlike u odgovoru tkiva na izlaganje navedenim anesteticima. U tu svrhu razine oksidativnog stresa izmjerili smo u jetri, mozgu, bubrezima i plućima štakora podijeljenih u tri eksperimentalne skupine. Kontrolna skupina udisala je samo zrak, dok su druge dvije skupine izložene 8 %-tnomu sevofl uranu te 4 %-tnomu desfl uranu tijekom 4 h. Nakon završetka obrade životinje su žrtvovane i uzimani su im uzorci tkiva za biokemijske analize. Mjerena je razina malondialdehida (MDA), aktivnst enzima superoksid dismutaze (SOD) i glutation peroksidaze (GSH-Px) te razine bakra i cinka. Izloženost anesteticima izazvala je oksidativni stres u plućima, na što upućuje značajno povišena razina MDA (Mann-Whitney U-test P<0.05) izmjerena u plućnom tkivu štakora obiju izloženih skupina u odnosu na kontrolu. Plućno je tkivo u odnosu na ostala tkiva podložnije štetnim utjecajima reaktivnih kisikovih radikala vjerojatno stoga što je ono prvo izloženo plinovitim anesteticima nakon njihova ulaska u organizam. Razine oksidativnog stresa i antioksidativne aktivnosti koje smo izmjerili u ostalim tkivima bile su različite te su ovisile o primijenjenom anestetiku. Na osnovi dobivenih rezultata možemo zaključiti da bi se zbog različitog odgovora tkiva izbor anestetika trebao provoditi na individualnoj osnovi

Neuromuscular disease genetics in under-represented populations: increasing data diversity

Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses ‘solved’ or ‘possibly solved’ ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% ‘solved’ and ∼13% ‘possibly solved’ outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally

Neuromuscular disease genetics in underrepresented populations : increasing data diversity

DATA AVAILABILITY : At the end of the study, participants de-identified exome and genome data will be archived in the European Molecular Biology Laboratory European Bioinformatics Institute’s European Genome-Phenome Archive (EMBL EBI EGA), with community access to this and selected de-identified REDCap data managed via an ICGNMD Data Access Committee.Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses 'solved' or 'possibly solved' ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% 'solved' and ∼13% 'possibly solved' outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally.This work was supported by a Medical Research Council strategic award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) MR/S005021/1. Additional ICGNMD support including travel and subsistence costs was received from the National Brain Appeal (UK Charity 290173) and University College London Global Engagement Funds. Fellowships for R.S.S.F. and K.N. were funded by the Guarantors of Brain (UK Charity 1197319). The authors acknowledge and are grateful for: conference bursaries from the World Muscle Society to R.S.S.F. S.R., K.N., O.Y.K., P.J.T., V.V.Y. S.V.D.M. and R.L. are members of the European Reference Network for Rare Neuromuscular Diseases (ERN EURO-MND). M.P.K.: National Institute of Neurological Disorders and Stroke (1K23NS112463), American Association of Neuromuscular & Electrodiagnostic Medicine Development Award and Allen Foundation. D.B.: National Institute of Neurological Disorders and Stroke (K23NS117310) and support from Biogen for the KCTN1 Natural History Study. G.M.R.: University College London and UCLH Biomedical Research Centre funding, Health Education England and University College London Hospitals NHS Foundation Trust Innovation Fund. R.M.F., R.W.T. and K.P.: Wellcome core support (203105/Z/16/Z). R.M.F. received additional support from the Lily Foundation and the Leigh Syndrome International Consortium. A.T.: EU Horizon 2020 research and innovation Solve-RD project, No. 779257. F.H.W., M.S., M.B. and A.V.: South African Medical Research Council award ‘The genetics of Neuromuscular Diseases in South African patient populations: the ICGNMD study’. K.T. is funded by a J. C. Bose Fellowship, Science and Engineering Research Board (SERB) Department of Science and Technology, India. P.G. is supported by the Centre for DNA Fingerprinting and Diagnostics (CDFD) Core Research Grant, Department of Biotechnology, Government of India. R.H.: Wellcome award 109915/Z/15/Z, UK Medical Research Council award MR/N025431/1, the Lily Foundation, Evelyn Trust Research Grant (Ref 19/14), Action for A-T and UK Research and Innovation Newton Fund (MR/NO27302/1). P.F.C.: Wellcome awards 212219/Z/18/Z and 224486/Z/21/Z, UK Medical Research Council awards MC_PC_21046, MR/S035699/1 and MR/ S01165X/1, LifeArc Philanthropic Fund, NIHR BioResource for Translational Research in Common and Rare Diseases, Alzheimer’s Society, NIHR BioResource for Genes and Cognition and Leverhulme Trust. R.D.S.P.: UK Medical Research Council MR/ S002065/1 and MC_PC_21046, and the Lily Foundation. H.H.: UK Medical Research Council, Wellcome, UCLH Biomedical Research Centre (NIHR-BRC), Rosetrees Trust, and SOLVE-RD. M.M.R.: Wellcome grant G104817, National Institute of Neurological Disorders and Stroke and Office of Rare Diseases grants U54NS065712 and 1UOINS109403-01 and Muscular Dystrophy Association grant.https://www.edusoft.ro/brain/index.php/brainam2024Paediatrics and Child HealthSDG-03:Good heatlh and well-bein

Genetic diversity and molecular epidemiology of the T strain of <em>Plum pox virus</em>

Very limited information is available on the origin, diversity and evolution of Plum pox virus (PPV) “Turkey” (T) strain. Phylogenetic analyses based on partial sequences of 421 isolates and complete genome sequences of 57 isolates, representing the geographical distribution of PPV‐T in Turkey revealed the existence of several monophyletic and, in some cases, geographically limited groups within the PPV‐T strain (Ankara‐Konya1‐Kayseri, Ankara‐Balkan, Istanbul, Konya2 and Balkan). PPV‐T diversity (0.018%) was found to be greater than that of PPV strains D and Rec but lower than the of the M strain when including the newly described and divergent M‐Istanbul isolates, suggesting a long evolutionary history for PPV‐T. The European part of Turkey in the Balkan, which is close to Bulgaria where PPV was identified for the first time, appears as a likely origin center for PPV‐T isolates. A colonization of various parts of Turkey by diverse isolates from that region, followed by secondary local spread is the most likely scenario for the diffusion of PPV‐T in Turkey

Photocatalytically Active Graphitic Carbon Nitride as an Effective and Safe 2D Material for In Vitro and In Vivo Photodynamic Therapy

Thanks to its photocatalytic property, graphitic carbon nitride (g-C3N4) is a promising candidate in various applications including nanomedicine. However, studies focusing on the suitability of g-C3N4 for cancer therapy are very limited and possible underlying molecular mechanisms are unknown. Here, it is demonstrated that photoexcitation of g-C3N4 can be used effectively in photodynamic therapy, without using any other carrier or additional photosensitizer. Upon light exposure, g-C3N4 treatment kills cancer cells, without the need of any other nanosystem or chemotherapeutic drug. The material is efficiently taken up by tumor cells in vitro. The transcriptome and proteome of g-C3N4 and light treated cells show activation in pathways related to both oxidative stress, cell death, and apoptosis which strongly suggests that only when combined with light exposure, g-C3N4 is able to kill cancer cells. Systemic administration of the mesoporous form results in elimination from urinary bladder without any systemic toxicity. Administration of the material significantly decreases tumor volume when combined with local light treatment. This study paves the way for the future use of not only g-C3N4 but also other 2D nanomaterials in cancer therapy