Neuronal intranuclear hyaline inclusion disease is a neurodegenerative condition which can be a target for gene therapy

Mapping Intimacies ◽

10.31219/osf.io/upgqd ◽

2021 ◽

Author(s):

Moataz Dowaidar

Keyword(s):

Gene Therapy ◽

Clinical Symptoms ◽

Repeat Expansion ◽

Gene Identification ◽

Therapeutic Assessment ◽

Causative Gene ◽

Central Nervous System Disorders ◽

Number Of Patients ◽

Mechanism Research ◽

Or Gene

NIHID (neuronal intranuclear hyaline inclusion disease) is a neurodegenerative condition that is easy to detect but also easy to misdiagnose. Thanks to breakthroughs in MRI detection, the availability of skin biopsied pathology, and, most critically, the finding of the causative gene which can be targeted by gene therapy, the rate of NIID diagnosis before death has grown significantly in recent years. Symptoms linked with central nervous system disorders, autonomic and peripheral neuropathy, and myopathy may be experienced by patients with NIID. Regardless of how far clinical symptoms or gene identification have progressed in NOTCH2NLC gene-related repeat expansion disorders (NRED), it not only adds to our understanding of NIID, but it also adds to the number of challenges we must address. East Asia has seen a substantial number of patients with GGC repeat expansion in NOTCH2NLC. Clinicians should work together to develop a database of NIID clinical and biological samples, as well as perform additional clinical diagnostic, therapeutic assessment, and pathogenic mechanism research.

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B-cell function in severe combined immunodeficiency after stem cell or gene therapy: A review

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2010.02.012 ◽

2010 ◽

Vol 125 (4) ◽

pp. 790-797 ◽

Cited By ~ 39

Author(s):

Rebecca H. Buckley

Keyword(s):

Gene Therapy ◽

Stem Cell ◽

B Cell ◽

Cell Function ◽

Severe Combined Immunodeficiency ◽

Combined Immunodeficiency ◽

B Cell Function ◽

Or Gene

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MYRF haploinsufficiency causes 46,XY and 46,XX disorders of sex development: bioinformatics consideration

Human Molecular Genetics ◽

10.1093/hmg/ddz066 ◽

2019 ◽

Vol 28 (14) ◽

pp. 2319-2329 ◽

Cited By ~ 1

Author(s):

Kohei Hamanaka ◽

Atsushi Takata ◽

Yuri Uchiyama ◽

Satoko Miyatake ◽

Noriko Miyake ◽

...

Keyword(s):

Transcription Factor ◽

Target Genes ◽

De Novo ◽

Clinical Symptoms ◽

Disorders Of Sex Development ◽

Sequencing Data ◽

Causative Gene ◽

Sex Development ◽

And Migration ◽

Proliferation And Migration

AbstractDisorders of sex development (DSDs) are defined as congenital conditions in which chromosomal, gonadal or anatomical sex is atypical. In many DSD cases, genetic causes remain to be elucidated. Here, we performed a case–control exome sequencing study comparing gene-based burdens of rare damaging variants between 26 DSD cases and 2625 controls. We found exome-wide significant enrichment of rare heterozygous truncating variants in the MYRF gene encoding myelin regulatory factor, a transcription factor essential for oligodendrocyte development. All three variants occurred de novo. We identified an additional 46,XY DSD case of a de novo damaging missense variant in an independent cohort. The clinical symptoms included hypoplasia of Müllerian derivatives and ovaries in 46,XX DSD patients, defective development of Sertoli and Leydig cells in 46,XY DSD patients and congenital diaphragmatic hernia in one 46,XY DSD patient. As all of these cells and tissues are or partly consist of coelomic epithelium (CE)-derived cells (CEDC) and CEDC developed from CE via proliferaiton and migration, MYRF might be related to these processes. Consistent with this hypothesis, single-cell RNA sequencing of foetal gonads revealed high expression of MYRF in CE and CEDC. Reanalysis of public chromatin immunoprecipitation sequencing data for rat Myrf showed that genes regulating proliferation and migration were enriched among putative target genes of Myrf. These results suggested that MYRF is a novel causative gene of 46,XY and 46,XX DSD and MYRF is a transcription factor regulating CD and/or CEDC proliferation and migration, which is essential for development of multiple organs.

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The fast-track outpatient clinic significantly decreases hospitalisation rates among polymyalgia rheumatica patients

BMC Rheumatology ◽

10.1186/s41927-021-00210-6 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Stavros Chrysidis ◽

Philip Rask Lage-Hansen ◽

Nikoletta Svendsen ◽

Andreas P. Diamantopoulos

Keyword(s):

Polymyalgia Rheumatica ◽

Fast Track ◽

Clinical Symptoms ◽

Classification Criteria ◽

Duration Of Symptoms ◽

Prednisolone Dose ◽

South West ◽

Hospitalised Patients ◽

Number Of Patients ◽

The Impact

Abstract Objectives This study aimed to investigate the hospitalisation rates and the reasons for hospitalisation in patients with polymyalgia rheumatica (PMR). Furthermore, it aimed to clarify the impact of a newly established Fast Track Clinic (FTC) approach on hospitalisation rates in connection with PMR diagnosis. Methods Patients diagnosed with PMR at South-West Jutland Hospital, Denmark, between 2013 and 2018 were included retrospectively. Only patients fulfilling the 2012 EULAR/ACR classification criteria were included in our cohort. An FTC for patients suspected of having PMR was established in the rheumatologic department of South-West Jutland Hospital in January 2018. Results Over 6 years (2013 to 2017), 254 patients were diagnosed with PMR, 56 of them while hospitalised. Hospitalised patients were more likely to have a higher initial CRP mean ± standard deviation (SD) 99.53 ± 59.36 vs 45.82 ± 36.96 mg/lt (p < 0.0001) and a shorter duration of symptoms (p = 0.0018). After implementing the FTC, a significant decrease in hospitalisation rates (from 20.4% to 3,5%) and inpatient days of care (mean ± SD 4.15 ± 3.1 vs 1 ± 0) were observed. No differences between the two groups were observed regarding clinical symptoms, laboratory values and initial prednisolone dose. Conclusion A substantial number of patients are hospitalised in connection with the PMR diagnosis. The FTC approach can decrease the hospitalisation rates significantly among these patients. Trial registration Retrospectively registered.

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The Results of Giardiasis Treatment Using Giardicidal Drugs and their Combination with Probiotics in Children: A Retrospective Cohort Study

Вопросы современной педиатрии ◽

10.15690/vsp.v17i4.1923 ◽

2018 ◽

Vol 17 (4) ◽

pp. 301-306

Author(s):

Olga G. Kimirilova ◽

Gennady A. Kharchenko

Keyword(s):

Abdominal Pain ◽

Combination Therapy ◽

Clinical Symptoms ◽

Clinical Manifestations ◽

Saccharomyces Boulardii ◽

Lactase Deficiency ◽

Intestinal Dysbiosis ◽

Number Of Patients ◽

Freeze Dried ◽

Inpatient Settings

Background. Giardiasis in children remains an urgent problem, the significance of which is determined by the endemicity for many countries and regions, outbreaks of sporadic epidemics, polymorphism of clinical symptoms, and insufficient treatment efficacy. Objective. Our aim was to study the results of giardiasis treatment using giardicidal drugs or their combination with probiotics in children. Methods. We analyzed the frequency of Giardia lamblia elimination (the main outcome) as a result of giardiasis treatment (laboratory confirmed) in children aged from 3 months to 18 years who received giardicidal drugs (nifuratel, albendazole) or their combination with probiotics based on Saccharomyces boulardii (probiotic 1) and live freeze-dried lactic acid bacteria Lactobacillus acidophilus (L. gasseri), Bifidobacterium infantis, and Enterococcus faecium (probiotic 2) in outpatient or inpatient settings. Additionally, we registered the duration of the main symptoms of giardiasis (abdominal pain, diarrhea), the prevalence of intestinal dysbiosis and lactase deficiency. The considering period is from January 2015 to September 2017. Results. The results of giardiasis treatment were studied in 4 groups: monotherapy with nifuratel (n = 65) or albendazole (n = 64), a combination of nifuratel + probiotic 1 (n = 67) or albendazole + probiotic 2 (n = 64). The groups were comparable by sex, age, and clinical manifestations of the disease. The elimination of lamblia on the 14–16th day of monotherapy with giardicidal drugs was achieved in 56–60%, when combined with probiotics — in 84% of patients for each combination (df = 3, p < 0.001). Against the background of combination therapy, the disease symptoms (abdominal pain, diarrhea, vomiting) were reversed 1.5 times faster; the number of patients with lactase deficiency and intestinal dysbiosis decreased two and more times, under monotherapy with giardicidal drugs — 1.2 times (df = 3, p < 0.001). Conclusion. Giardiasis treatment in children using combination therapy, including giardicidal drugs and probiotics, is more effective than monotherapy with giardicidal drugs.

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10-Year Incidence of Diabetic Ketoacidosis at Type 1 Diabetes Diagnosis in Children Aged Less Than 16 Years From a Large Regional Center (Hangzhou, China)

Frontiers in Endocrinology ◽

10.3389/fendo.2021.653519 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wei Peng ◽

Jinna Yuan ◽

Valentina Chiavaroli ◽

Guanping Dong ◽

Ke Huang ◽

...

Keyword(s):

Type 1 Diabetes ◽

Abdominal Pain ◽

Diabetic Ketoacidosis ◽

Primary Care Physicians ◽

Clinical Symptoms ◽

Diabetes Diagnosis ◽

Regional Center ◽

Retrospective Audit ◽

Number Of Patients

BackgroundDiabetic ketoacidosis (DKA) is a potentially life-threatening complication of type 1 diabetes (T1D), and a leading cause of death in children aged <15 years with new-onset T1D.Aimsi) to assess the incidence of DKA in children and adolescents newly diagnosed with T1D over a 10-year period at a large regional center in China; and ii) to examine the clinical symptoms and demographic factors associated with DKA and its severity at diagnosis.MethodsWe carried out a retrospective audit of a regional center, encompassing all youth aged <16 years diagnosed with T1D in 2009–2018 at the Children’s Hospital, Zhejiang University School of Medicine (Hangzhou, China). DKA and its severity were classified according to ISPAD 2018 guidelines.Results681 children were diagnosed with T1D, 50.1% having DKA at presentation (36.0% mild, 30.0% moderate, and 33.9% severe DKA). The number of patients diagnosed with T1D progressively rose from approximately 39 cases/year in 2009–2010 to 95 cases/year in 2017–2018 (≈2.5-fold increase), rising primarily among children aged 5–9 years. DKA incidence was unchanged but variable (44.8% to 56.8%). At T1D diagnosis, 89% of patients reported polyuria and 91% polydipsia. Children presenting with DKA were more likely to report vomiting, abdominal pain, and particularly fatigue. DKA was most common among the youngest children, affecting 4 in 5 children aged <2 years (81.4%), in comparison to 53.3%, 42.7%, and 49.3% of patients aged 2–4, 5–9, and ≥10 years, respectively. Children with severe DKA were more likely to report vomiting, fatigue, and abdominal pain, but less likely to report polyuria, polydipsia, and polyphagia than those with mild/moderate DKA. Rates of severe DKA were highest in children aged <2 years (51.1%).ConclusionsThe number of children diagnosed with T1D at our regional center increased over the study period, but DKA rates were unchanged. With 9 of 10 children reporting polyuria and polydipsia prior to T1D diagnosis, increasing awareness of this condition in the community and among primary care physicians could lead to earlier diagnosis, and thus potentially reduce rates of DKA at presentation.

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Advanced Technologies in DNA-based Nanomedicine

Recent Advances in Drug Delivery and Formulation ◽

10.2174/2667387815666210212142526 ◽

2021 ◽

Vol 15 ◽

Author(s):

Ameneh Mohammadi ◽

Pooria Gill ◽

Pedram Ebrahimnejad ◽

Said Abediankenari ◽

Zahra Kashi

Keyword(s):

Drug Delivery ◽

Gene Therapy ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Dna Nanostructures ◽

Medical Sciences ◽

Rational Engineering ◽

Advanced Technologies ◽

Wide Range ◽

Or Gene

: The application of nanotechnology in medicine and pharmaceutical purpose suggested a novel procedure in the nanotechnology terminology as nanomedicine. There is a wide range of applications for nanotechnology in medicine, such as the use of nanocarriers in drug delivery systems. Recently a remarkable attention to DNA has been made through its amazing functionality and its nature as a nanomaterial in biological systems. Since DNA is a biocompatible, the use of DNA as a nanomaterial in medicine has shown a great perspective of rational engineering of DNA nanostructures. According to new approaches in treatment of diseases in gene levels, gene therapy, using DNA as a nanomedicine possesses an important role in the medical sciences as the researchers published enormous papers and patents in the fields, for instance, the applications of DNA and DNA-based nanostructures as drug or gene nanocarriers, DNA-based diagnostics and DNA nanovasccines. Here, some examples of DNA-based nanomedicine in the patent frame were reviewed.

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CURING HEMOGLOBINOPATHIES: CHALLENGES AND ADVANCES OF CONVENTIONAL AND NEW GENE THERAPY APPROACHES.

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2019.067 ◽

2019 ◽

Vol 11 (1) ◽

pp. e2019067 ◽

Cited By ~ 3

Author(s):

Irene Motta ◽

Valentina Ghiaccio ◽

Andrea Cosentino ◽

Laura Breda

Keyword(s):

Quality Of Life ◽

Health Care ◽

Gene Therapy ◽

Bone Marrow ◽

Iron Chelation ◽

Beta Thalassemia ◽

Allogenic Bone ◽

Number Of Patients ◽

Monogenic Diseases

Inherited hemoglobin disorders, including beta-thalassemia (BT) and sickle-cell disease (SCD) are the most common monogenic diseases worldwide, with a global carrier frequency of over 5%. With migration they are becoming more common worldwide, making their management and care an increasing concern for health care systems. BT is characterized by an imbalance in the α/β-globin chain ratio, ineffective erythropoiesis, chronic hemolytic anemia, and compensatory haemopoietic expansion. Globally, there are over 25,000 births each year with transfusion-dependent thalassemia (TDT). The current available treatment for TDT is lifelong transfusions and iron chelation therapy or allogenic bone marrow as curative option. SCD affects 300 million people worldwide and severely impacts the quality of life of patients, who experience unpredictable, recurrent acute and chronic severe pain, stroke, infections, pulmonary disease, kidney disease, retinopathy, and other complications. While survival has been dramatically extended, quality of life is markedly reduced by disease- and treatment-associated morbidity. The development of safe, tissue specific and efficient vectors, and efficient gene editing technologies have led to the development of several gene therapy trials for BT and SCD. Yet, the complexity of the approach presents its hurdles. Fundamental factors at play include the requirement for myeloablation on a patient with a benign disease, the age of the patient and consequent bone marrow microenvironment. A successful path from proof-of-concept studies to commercialization must render gene therapy a sustainable and accessible approach for a large number of patients. Furthermore, the cost of these therapies is a considerable challenge for the health care system. While new promising therapeutic options are emerging and many others are on the pipeline5, gene therapy can potentially cure patients. We herein provide an overview of the most recent potentially curative therapies for hemoglobinopathies and a summary of the challenges that these approaches entail.

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Sensitivity and specificity of different imaging modalities in diagnosing necrotising enterocolitis in a Polish population of preterm infants: a diagnostic test accuracy study protocol

BMJ Open ◽

10.1136/bmjopen-2019-033519 ◽

2020 ◽

Vol 10 (7) ◽

pp. e033519

Author(s):

Joanna Seliga-Siwecka ◽

Jakub Rutkowski ◽

Wojciech Margas ◽

Joanna Puskarz- Gąsowska ◽

Renata Bokiniec

Keyword(s):

Very Low Birth Weight ◽

Clinical Symptoms ◽

Newborn Infants ◽

Pneumatosis Intestinalis ◽

Abdominal Ultrasound ◽

Necrotising Enterocolitis ◽

Test Accuracy ◽

Detection Rates ◽

Vlbw Infants ◽

Number Of Patients

IntroductionNecrotising enterocolitis (NEC) is one of the most serious conditions in newborn infants, affecting up to 10% of very low birth weight (VLBW) infants. Mortality rates can rise as high as 60%.The suspected diagnosis is confirmed with typical findings on abdominal radiography (AR) such as pneumatosis intestinalis (PI), portal vein gas (PVG) and in extreme cases pneumoperitoneum. Abdominal ultrasound (AUS) can depict PI, PVG and pnuemoperitoneum (in some cases ahead of AR), but it also provides other crucial information such as bowel wall viability (thickness or thinning) and free abdominal fluid. These additional findings are helpful in diagnosing and managing NEC.Methods and analysisThe hypothesis being tested is that preforming an AR in patients with clinical symptoms of NEC, but inconclusive/normal AR will enhance detection rates, and expedite treatment in infants born at <32 weeks. Additionally, the time needed to initiate treatment, according to decision made based on AR or AR and AUS will also be compared. The use of AUS together with AR as an add-on test may increase the accuracy of diagnosing NEC and expedite life-saving treatment. We plan to recruit 200 VLBW infants, who are most prone to NEC. It will also be the first multicentre study evaluating the use of AUS as an add-on test, enabling us to recruit a significantly higher number of patients compared with published studies.Ethics and disseminationThe Bioethical Committee of the Medical University of Warsaw has approved the study (KB 130/2017). We plan to submit our findings to international peer-reviewed journals. Abstract will be submitted to local and international conferences.Trial registration numberNCT03188380; Protocol version: V.2.08.2019; Pre-results.

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