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Nature Reviews. Endocrinology Oct 2019Turner syndrome is a rare condition in women that is associated with either complete or partial loss of one X chromosome, often in mosaic karyotypes. Turner syndrome is... (Review)
Review
Turner syndrome is a rare condition in women that is associated with either complete or partial loss of one X chromosome, often in mosaic karyotypes. Turner syndrome is associated with short stature, delayed puberty, ovarian dysgenesis, hypergonadotropic hypogonadism, infertility, congenital malformations of the heart, endocrine disorders such as type 1 and type 2 diabetes mellitus, osteoporosis and autoimmune disorders. Morbidity and mortality are increased in women with Turner syndrome compared with the general population and the involvement of multiple organs through all stages of life necessitates a multidisciplinary approach to care. Despite an often conspicuous phenotype, the diagnostic delay can be substantial and the average age at diagnosis is around 15 years of age. However, numerous important clinical advances have been achieved, covering all specialty fields involved in the care of girls and women with Turner syndrome. Here, we present an updated Review of Turner syndrome, covering advances in genetic and genomic mechanisms of disease, associated disorders and multidisciplinary approaches to patient management, including growth hormone therapy and hormone replacement therapy.
Topics: Disease Management; Female; Heart Defects, Congenital; Hormone Replacement Therapy; Human Growth Hormone; Humans; Turner Syndrome
PubMed: 31213699
DOI: 10.1038/s41574-019-0224-4 -
The Lancet. Neurology Oct 2022Diabetic peripheral neuropathy (DPN) occurs in up to half of individuals with type 1 or type 2 diabetes. DPN results from the distal-to-proximal loss of peripheral nerve... (Review)
Review
Diabetic peripheral neuropathy (DPN) occurs in up to half of individuals with type 1 or type 2 diabetes. DPN results from the distal-to-proximal loss of peripheral nerve function, leading to physical disability and sometimes pain, with the consequent lowering of quality of life. Early diagnosis improves clinical outcomes, but many patients still develop neuropathy. Hyperglycaemia is a risk factor and glycaemic control prevents DPN development in type 1 diabetes. However, glycaemic control has modest or no benefit in individuals with type 2 diabetes, probably because they usually have comorbidities. Among them, the metabolic syndrome is a major risk factor for DPN. The pathophysiology of DPN is complex, but mechanisms converge on a unifying theme of bioenergetic failure in the peripheral nerves due to their unique anatomy. Current clinical management focuses on controlling diabetes, the metabolic syndrome, and pain, but remains suboptimal for most patients. Thus, research is ongoing to improve early diagnosis and prognosis, to identify molecular mechanisms that could lead to therapeutic targets, and to investigate lifestyle interventions to improve clinical outcomes.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Metabolic Syndrome; Pain; Quality of Life
PubMed: 36115364
DOI: 10.1016/S1474-4422(22)00188-0 -
Endocrine Reviews Jan 2023Turner syndrome (TS) is a condition in females missing the second sex chromosome (45,X) or parts thereof. It is considered a rare genetic condition and is associated... (Review)
Review
Turner syndrome (TS) is a condition in females missing the second sex chromosome (45,X) or parts thereof. It is considered a rare genetic condition and is associated with a wide range of clinical stigmata, such as short stature, ovarian dysgenesis, delayed puberty and infertility, congenital malformations, endocrine disorders, including a range of autoimmune conditions and type 2 diabetes, and neurocognitive deficits. Morbidity and mortality are clearly increased compared with the general population and the average age at diagnosis is quite delayed. During recent years it has become clear that a multidisciplinary approach is necessary toward the patient with TS. A number of clinical advances has been implemented, and these are reviewed. Our understanding of the genomic architecture of TS is advancing rapidly, and these latest developments are reviewed and discussed. Several candidate genes, genomic pathways and mechanisms, including an altered transcriptome and epigenome, are also presented.
Topics: Female; Humans; Diabetes Mellitus, Type 2; Endocrine System Diseases; Infertility; Turner Syndrome
PubMed: 35695701
DOI: 10.1210/endrev/bnac016 -
European Heart Journal Nov 2022
2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS).
Topics: Humans; Radiation Oncology; Medical Oncology; Neoplasms; Heart; Hematology; Antineoplastic Agents
PubMed: 36017568
DOI: 10.1093/eurheartj/ehac244 -
Cardiology in ReviewAndersen-Tawil syndrome (ATS) is a very rare orphan genetic multisystem channelopathy without structural heart disease (with rare exceptions). ATS type 1 is inherited in... (Review)
Review
Andersen-Tawil syndrome (ATS) is a very rare orphan genetic multisystem channelopathy without structural heart disease (with rare exceptions). ATS type 1 is inherited in an autosomal dominant fashion and is caused by mutations in the KCNJ2 gene, which encodes the α subunit of the K+ channel protein Kir2.1 (in ≈ 50-60% of cases). ATS type 2 is in turn linked to a rare mutation in the KCNJ5-GIRK4 gene that encodes the G protein-sensitive-activated inwardly rectifying K+ channel Kir3.4 (15%), which carries the acetylcholine-induced potassium current. About 30% of cases are de novo/sporadic, suggesting that additional as-yet unidentified genes also cause the disorder. A triad of periodic muscle paralysis, repolarization changes in the electrocardiogram, and structural body changes characterize ATS. The typical muscular change is episodic flaccid muscle weakness. Prolongation of the QU/QUc intervals and normal or minimally prolonged QT/QTc intervals with a tendency to ventricular arrhythmias are typical repolarization changes. Bidirectional ventricular tachycardia is the hallmark ventricular arrhythmia, but also premature ventricular contractions, and rarely, polymorphic ventricular tachycardia of torsade de pointes type may be present. Patients with ATS have characteristic physical developmental dysmorphisms that affect the face, skull, limbs, thorax, and stature. Mild learning difficulties and a distinct neurocognitive phenotype (deficits in executive function and abstract reasoning) have been described. About 60% of affected individuals have all features of the major triad. The purpose of this review is to present historical aspects, nomenclature (observations/criticisms), epidemiology, genetics, electrocardiography, arrhythmias, electrophysiological mechanisms, diagnostic criteria/clues of periodic paralysis, prognosis, and management of ATS.
Topics: Andersen Syndrome; Humans; Long QT Syndrome; Mutation; Paralysis; Phenotype; Potassium Channels, Inwardly Rectifying; Tachycardia, Ventricular
PubMed: 32947483
DOI: 10.1097/CRD.0000000000000326 -
Nature Oct 2022Self-organizing neural organoids represent a promising in vitro platform with which to model human development and disease. However, organoids lack the connectivity...
Self-organizing neural organoids represent a promising in vitro platform with which to model human development and disease. However, organoids lack the connectivity that exists in vivo, which limits maturation and makes integration with other circuits that control behaviour impossible. Here we show that human stem cell-derived cortical organoids transplanted into the somatosensory cortex of newborn athymic rats develop mature cell types that integrate into sensory and motivation-related circuits. MRI reveals post-transplantation organoid growth across multiple stem cell lines and animals, whereas single-nucleus profiling shows progression of corticogenesis and the emergence of activity-dependent transcriptional programs. Indeed, transplanted cortical neurons display more complex morphological, synaptic and intrinsic membrane properties than their in vitro counterparts, which enables the discovery of defects in neurons derived from individuals with Timothy syndrome. Anatomical and functional tracings show that transplanted organoids receive thalamocortical and corticocortical inputs, and in vivo recordings of neural activity demonstrate that these inputs can produce sensory responses in human cells. Finally, cortical organoids extend axons throughout the rat brain and their optogenetic activation can drive reward-seeking behaviour. Thus, transplanted human cortical neurons mature and engage host circuits that control behaviour. We anticipate that this approach will be useful for detecting circuit-level phenotypes in patient-derived cells that cannot otherwise be uncovered.
Topics: Animals; Animals, Newborn; Autistic Disorder; Humans; Long QT Syndrome; Motivation; Neural Pathways; Neurons; Optogenetics; Organoids; Rats; Reward; Somatosensory Cortex; Stem Cells; Syndactyly
PubMed: 36224417
DOI: 10.1038/s41586-022-05277-w -
Handbook of Clinical Neurology 2023Muscle channelopathies encompass a wide range of mainly episodic conditions that are characterized by muscle stiffness and weakness. The myotonic conditions,... (Review)
Review
Muscle channelopathies encompass a wide range of mainly episodic conditions that are characterized by muscle stiffness and weakness. The myotonic conditions, characterized predominantly by stiffness, include myotonia congenita, paramyotonia congenita, and sodium channel myotonia. The periodic paralysis conditions include hypokalemic periodic paralysis, hyperkalemic periodic paralysis, and Andersen-Tawil syndrome. Clinical history is key, and diagnosis is confirmed by next-generation genetic sequencing of a panel of known genes but can also be supplemented by neurophysiology studies and MRI. As genetic testing expands, so have the spectrum of phenotypes seen including pediatric presentations and congenital myopathies. Management of these conditions requires a multidisciplinary approach with extra support needed when patients require anesthetics or when pregnant. Patients with Andersen-Tawil syndrome will also need cardiac input. Diagnosis is important as symptomatic treatment is available for all of these conditions but need to be tailored to the gene and variant of the patient.
Topics: Humans; Andersen Syndrome; Channelopathies; Paralysis, Hyperkalemic Periodic; Myotonic Disorders; Muscle, Skeletal; Paralysis; Mutation
PubMed: 37562884
DOI: 10.1016/B978-0-323-98818-6.00006-6 -
Trends in Endocrinology and Metabolism:... Jul 2019Polycystic ovary syndrome (PCOS) affects 8-13% of women. The Rotterdam diagnostic criteria include polycystic ovarian morphology (PCOM) on ultrasound, but given... (Review)
Review
Polycystic ovary syndrome (PCOS) affects 8-13% of women. The Rotterdam diagnostic criteria include polycystic ovarian morphology (PCOM) on ultrasound, but given recognized challenges, serum anti-Müllerian hormone (AMH) is proposed as an alternative. To inform international PCOS guidelines, a systematic review was completed. Key identified gaps include large international studies in well-defined populations across the lifespan, clustering of AMH with PCOS features, relationships to long-term health outcomes, and improved quality, assay standardization, and sample handling, all needed to determine cut offs. Here we identify research priorities to address these gaps and enhance AMH utility in PCOS. Once issues are addressed, AMH levels could replace more costly and less accessible ultrasound in PCOS diagnosis.
Topics: Anti-Mullerian Hormone; Female; Humans; Ovary; Polycystic Ovary Syndrome
PubMed: 31160167
DOI: 10.1016/j.tem.2019.04.006 -
Scientific Reports Nov 2020Upper crossed syndrome (UCS) refers to the altered muscle activations and movement patterns in scapulae along with some abnormal alignment in the upper quarter, which... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Upper crossed syndrome (UCS) refers to the altered muscle activations and movement patterns in scapulae along with some abnormal alignment in the upper quarter, which may contribute to the dysfunction of the cervicothoracic and glenohumeral joints. The present study aimed to investigate the effectiveness of a comprehensive corrective exercise program (CCEP) and subsequent detraining on alignment, muscle activation, and movement pattern in men with the UCS. This randomized controlled trial included 24 men. The intervention group conducted CCEP (8 weeks), followed by four weeks of detraining and the control group maintained normal daily activities. Electromyography of selected muscles, scapular dyskinesis test, head, shoulder, and thoracic spine angle were measured at baseline, post-test, and follow-up. There were significant differences for Group x time interaction and also for within-group from pre-test to post-test and follow-up in all outcomes. Also, significant differences were observed in three outcomes at post-test and follow-up between the CCEP and control group in favor of the CCEP. In Conclusion, the present study demonstrates that the CCEP for individuals with UCS is feasible and effective, improving muscle activation imbalance, movement patterns, and alignment. Importantly, these improvements were maintained after four weeks of detraining, suggesting lasting neuromuscular re-training adaptations.
Topics: Adult; Dyskinesias; Electromyography; Exercise; Exercise Therapy; Humans; Male; Movement; Muscles; Scapula; Shoulder; Shoulder Joint; Spine
PubMed: 33244045
DOI: 10.1038/s41598-020-77571-4 -
Ugeskrift For Laeger Mar 2023Bladder pain syndrome is rare and leads to increased morbidity and decreased quality of life. The patients are a heterogenous group with different clinical... (Review)
Review
Bladder pain syndrome is rare and leads to increased morbidity and decreased quality of life. The patients are a heterogenous group with different clinical presentations, and little is known of the different aspects of the syndrome. A thorough patient history and specialised diagnostics are required to offer these patients the best possible treatment. This review suggests an algorithm to manage these patients at all levels of the Danish health-care system. It is recommended that final diagnosis and multidisciplinary treatment should be centered at large regional hospitals.
Topics: Humans; Quality of Life; Cystitis, Interstitial; Delivery of Health Care; Syndrome; Algorithms
PubMed: 36999301
DOI: No ID Found