The First Patient in Poland Treated for SMA with Nusinersen During Pregnancy.

The accessibility of effective SMA (spinal muscular atrophy) treatment is resulting in a growing number of affected women reaching fertility age and deciding to conceive. Pregnancy in women with SMA is associated with a high risk of rapid progression of symptoms, including increased weakness, growing paresis, or even onset of respiratory failure requiring ventilation support. Muscle weakness frequently leads to disability, which in a high percentage is irreversible.

A 20-year serological survey of Toxoplasma gondii and Neospora caninum infection in dogs with neuromuscular disorders from urban areas in Argentina.

Toxoplasma gondii and Neospora caninum infections may be associated with neuromuscular disorders in dogs. The aim of this study was to assess the seroprevalence to these protozoan parasites in dogs with neuromuscular disease from urban areas of Buenos Aires province, Argentina, over a period of 20 years, and to evaluate the association of seropositivity and antibody titres with different variables such as sex, breed and age. For this, a total of 7238 serum samples from urban owned dogs were analysed by the indirect fluorescence antibody test (IFAT) for specific IgG antibodies.

Metallacarboranes in Medicinal Chemistry: Current Advances and Future Perspectives.

Metallacarboranes, exemplified by cobalt bis(dicarbollide) ([COSAN]), have excelled their historical metallocene analogue label to become promising in drug design, medical studies, and fundamental biological research. Serving as a unique platform for conjugation with biomolecules, they also constitute an auspicious building block for biologically active derivatives and a carrier for cellular transport of membrane-impermeable cargos. Modified [COSAN] exhibits specific antimicrobial, antiviral, and anticancer actions showing promise for preclinical trials.

Seroprevalence of Toxoplasma gondii and Neospora caninum in family farming goats from the Luracatao Valley, Salta, Argentina.

Toxoplasma gondii and Neospora caninum infections are important causes of abortion in ruminants. The objective of this study was to determine the seroprevalence and frequency of T. gondii and N.

Genetic characterization of Toxoplasma gondii from human and chicken isolates from Argentina.

This study aimed to determine the nPCR-RFLP genotypes of newly obtained T. gondii isolates from human congenital toxoplasmosis cases in Argentina and to determine their allelic profiles for virulence genes ROP18/ROP5. In addition, the ROP18/ROP5 profiles were also determined for previously characterized T.

Research on the Pathogenesis of Cognitive and Neurofunctional Impairments in Patients with Noonan Syndrome: The Role of Rat Sarcoma-Mitogen Activated Protein Kinase Signaling Pathway Gene Disturbances.

Noonan syndrome (NS) is one of the most common genetic conditions inherited mostly in an autosomal dominant manner with vast heterogeneity in clinical and genetic features. Patients with NS might have speech disturbances, memory and attention deficits, limitations in daily functioning, and decreased overall intelligence. Here, 34 patients with Noonan syndrome and 23 healthy controls were enrolled in a study involving gray and white matter volume evaluation using voxel-based morphometry (VBM), white matter connectivity measurements using diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI).

Dynamics of anti-Toxoplasma gondii antibodies and seroconversion during pregnancy and lactation in naturally infected goats.

The objective of this work was to evaluate the dynamics of anti-T. gondii antibodies and seroconversion in naturally infected goats from the last third of pregnancy to 100 days of lactation and relate it to hematological and dehydration parameters. Blood samples were obtained from 56 goats in the different physiological states (pregnancy, kidding and lactation) as in different years (2019, 2021 and 2022).

Structural Patterns Enhancing the Antibacterial Activity of Metallacarborane-Based Antibiotics.

Healthcare systems heavily rely on antibiotics to treat bacterial infections, but the widespread presence of multidrug-resistant bacteria puts this strategy in danger. Novel drugs capable of overcoming current resistances are needed if our ability to treat bacterial infections is to be maintained. Boron clusters offer a valuable possibility to create a new class of antibiotics and expand the chemical space of antibiotics beyond conventional carbon-based molecules.

COVID-19-related premature ovarian insufficiency: case report and literature review.

Objective: The aim of this study is to present the case report of a 36-year-old woman developing premature ovarian insufficiency (POI) after COVID-19 and review the literature referring to the possible impact of SARS-CoV-2 infection on female reproduction.

Methods: A 36-year-old nulligravida with normal menstrual cycles, non-smoker, with a normal body mass index and no pelvic surgery or oncological treatment in her medical history presented to the Infertility Center of the Institute of Mother and Child in Warsaw after a year of unsuccessful attempts to get pregnant. During diagnostic process she was affected by COVID-19 with a mild manifestation and thereafter she presented amenorrhea with intense hot flushes.

Prenatal and Neonatal Ultrasound and Magnetic Resonance Imaging Diagnosis of Sprengel's Deformity with Unusual Associations.

Introduction: Sprengel's deformity is a rare congenital anomaly of the shoulder rim. It is the most common congenital anomaly of the shoulder, associated with cosmetic deformity and abnormal shoulder function. Nonsurgical management can be considered for mild cases.

Mutation of valine 53 at the interface between extracellular and transmembrane domains of the β principal subunit affects the GABA receptor gating.

GABA receptors (gamma-aminobutyric acid type A receptors) are pentameric ligand-gated ion channels mediating inhibition in adult mammalian brains. Their static structure has been intensely studied in the past years but the underlying molecular activatory mechanisms remain obscure. The interface between extracellular and transmembrane domains has been recognized as a key player in the receptor gating.

Newborn screening and gene therapy in SMA: Challenges related to vaccinations.

Spinal muscular atrophy (SMA) affects one in 7,500-10,000 newborns. Before the era of disease-modifying therapies, it used to be the major genetic cause of mortality in infants. Currently, there are three therapies approved for SMA, including two molecules modifying the splicing of the SMN2 gene and one gene therapy providing a healthy copy of the SMN gene with a viral vector.

Expanding the genetics and phenotypic spectrum of Lysine-specific demethylase 5C (KDM5C): a report of 13 novel variants.

Lysine-specific demethylase 5C (KDM5C) has been identified as an important chromatin remodeling gene, contributing to X-linked neurodevelopmental disorders (NDDs). The KDM5C gene, located in the Xp22 chromosomal region, encodes the H3K4me3-me2 eraser involved in neuronal plasticity and dendritic growth. Here we report 30 individuals carrying 13 novel and one previously identified KDM5C variants.

Destabilization of mutated human PUS3 protein causes intellectual disability.

Pseudouridine (Ψ) is an RNA base modification ubiquitously found in many types of RNAs. In humans, the isomerization of uridine is catalyzed by different stand-alone pseudouridine synthases (PUS). Genomic mutations in the human pseudouridine synthase 3 gene (PUS3) have been identified in patients with neurodevelopmental disorders.

Bullous diseases caused by gene mutations: from epidermolytic hyperkeratosis to a novel variant of epidermolysis bullosa simplex.

Introduction: Mutations in the gene encoding keratin 1 cause epidermolytic hyperkeratosis characterized by blistering in the neonatal period followed by ichthyotic hyperkeratosis in childhood and adolescent life. We observed a spectrum of clinical manifestations of blistering disorders caused by different mutations in the same gene.

Aim: To analyse the phenotypic spectrum of blistering disorders caused by the mutations.

Eleven years of Toxoplasma gondii serological follow-up in a goat herd and association of toxoplasmosis with reproductive losses.

Toxoplasmosis is considered one of the most important causes of abortion in small ruminants. The aim of this study was to evaluate the relationship between Toxoplasma gondii antibody titres and reproductive losses over an 11 year period in a goat farm located in Buenos Aires province, Argentina. Blood samples were obtained from 85 goats, representing three breeds, during the last third of gestation (n = 165 gestations), in consecutive pregnancies (2008-2019), and from 51 goats during kidding to analyze seroconversion.

Wide Fontanels, Delayed Speech Development and Hoarse Voice as Useful Signs in the Diagnosis of KBG Syndrome: A Clinical Description of 23 Cases with Pathogenic Variants Involving the Gene or Submicroscopic Chromosomal Rearrangements of 16q24.3.

KBG syndrome is a neurodevelopmental autosomal dominant disorder characterized by short stature, macrodontia, developmental delay, behavioral problems, speech delay and delayed closing of fontanels. Most patients with KBG syndrome are found to have a mutation in the gene or a chromosomal rearrangement involving this gene. We hereby present clinical evaluations of 23 patients aged 4 months to 26 years manifesting clinical features of KBG syndrome.

Case Report: Further Delineation of Neurological Symptoms in Young Children Caused by Compound Heterozygous Mutation in the Gene.

protein is a unique ion channel that converts mechanical impulses into cellular signals in somatosensory neurons and is involved in various mechanotransduction pathways. The recessive loss-of-function pathogenic variants are associated with distal arthrogryposis with impaired proprioception and touch (DAIPT). Here we present three new DAIPT patients.

Floppy infant syndrome as a first manifestation of LMNA-related congenital muscular dystrophy.

LMNA-related congenital muscular dystrophy (L-CMD) is the most severe phenotypic form of skeletal muscle laminopathies. This paper reports clinical presentation of the disease in 15 Polish patients from 13 families with genetically confirmed skeletal muscle laminopathy. In all these patients floppy infant syndrome was the first manifestation of the disease.

The haploinsufficiency syndrome associated with de novo nonsense variant (P.GLN1981*).

The Mediator complex subunit 13-like is a part of the large Mediator complex. Recently, a large number of patients were diagnosed with mutations in this gene, which makes it one of the most frequent causes of syndromic intellectual disability. In this work, we report a patient with a novel likely pathogenic variant c.

Differential Response of Lung Cancer Cells, with Various Driver Mutations, to Plant Polyphenol Resveratrol and Vitamin D Active Metabolite PRI-2191.

Plant polyphenols and vitamins D exhibit chemopreventive and therapeutic anticancer effects. We first evaluated the biological effects of the plant polyphenol resveratrol (RESV) and vitamin D active metabolite PRI-2191 on lung cancer cells having different genetic backgrounds. RESV and PRI-2191 showed divergent responses depending on the genetic profile of cells.

Pathogenic Mutations and Putative Phenotype-Affecting Variants in Polish Myofibrillar Myopathy Patients.

Myofibrillar myopathies (MFM) are heterogeneous hereditary muscle diseases with characteristic myopathological features of Z-disk dissolution and aggregates of its degradation products. The onset and progression of the disease are variable, with an elusive genetic background, and around half of the cases lacking molecular diagnosis. Here, we attempted to establish possible genetic foundations of MFM by performing whole exome sequencing (WES) in eleven unrelated families of 13 patients clinically diagnosed as MFM spectrum.

Successful Salvage Treosulfan-Based Megachemotherapy With Allogeneic Stem Cell Transplantation in Nonsyndromic, Therapy-Resistant Disseminated Juvenile Xanthogranuloma: A Case Report.

Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder classified as non-Langerhans cell histiocytosis; although it is usually a benign and self-limiting disease, it can be fatal in some cases, especially with systemic dissemination. We present a case report of a boy with therapy-resistant disseminated JXG who was treated with systemic chemotherapy and received 3 allogeneic hematopoietic stem cell transplantations (allo-HSCTs) from an unrelated donor. The post-transplant period was complicated by acute graft vs host disease and lymphoproliferative disease caused by Epstein-Barr virus.

Mutations of αF45 residue of GABA receptor loop G reveal its involvement in agonist binding and channel opening/closing transitions.

GABA receptors (GABARs) mediate inhibitory neurotransmission in the mammalian brain. Recently, numerous GABAR static structures have been published, but the molecular mechanisms of receptor activation remain elusive. Loop G is a rigid β-strand belonging to an extensive β-sheet that spans the regions involved in GABA binding and the interdomain interface which is important in receptor gating.