40,478 results match your criteria onset progression

Sex influences the effects of APOE genotype and Alzheimer's diagnosis on neuropathology and memory.

Psychoneuroendocrinology 2021 Apr 29;129:105248. Epub 2021 Apr 29.

Djavad Mowafaghian Centre for Brain Health and Department of Psychology, University of British Columbia, Vancouver, BC, Canada; Women's Health Research Institute of British Columbia, Vancouver, BC, Canada; Djavad Mowafaghian Centre for Brain Health and Department of Physical Therapy, University of British Columbia, Vancouver, BC, Canada.

Alzheimer's disease (AD) is characterized by severe cognitive decline and pathological changes in the brain (brain atrophy, hyperphosphorylation of tau, and deposition of amyloid-beta protein). Females have greater neuropathology (AD biomarkers and brain atrophy rates) and cognitive decline than males, however these effects can depend on diagnosis (amnestic mild cognitive impairment (aMCI) or AD) and APOE genotype (presence of ε4 alleles). Using the ADNI database (N = 630 females, N = 830 males), we analyzed the effect of sex, APOE genotype (non-carriers or carriers of APOEε4 alleles), and diagnosis (cognitively normal (CN), early aMCI (EMCI), late aMCI (LMCI), probable AD) on cognition (memory and executive function), hippocampal volume, and AD biomarkers (CSF levels of amyloid beta, tau, and ptau). Read More

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Very Late-onset Neuromyelitis Optica Spectrum Disorders.

Eur J Neurol 2021 May 7. Epub 2021 May 7.

Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.

Background: Neuromyelitis optica spectrum disorder (NMOSD) often presents in the elderly with an insidious onset of symptoms and aggressive progression. There have been anecdotal cases of very late-onset (VLO)-NMOSD, but case series reports are rare. The aim of this retrospective study was to clarify the clinical features of VLO-NMOSD. Read More

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Efficacy and Safety of Tripterygium Glycoside in the Treatment of Diabetic Nephropathy: A Systematic Review and Meta-Analysis Based on the Duration of Medication.

Front Endocrinol (Lausanne) 2021 20;12:656621. Epub 2021 Apr 20.

School of Life and Science, Beijing University of Chinese Medicine, Beijing, China.

Aim: The aim of this study was to assess the clinical efficacy and safety of Tripterygium-derived glycosides (TG) after 3-month and 6-month of treatments of diabetic nephropathy (DN) and to resolve the conflict between medicine guidance and clinical practice for TG application.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials involving TG application in treating DN. We extensively searched PubMed, Cochrane Library, CNKI, VIP, Wan-Fang, CBM, Chinese Clinical Trial Registry, and WHO International Clinical Trial Registration Platform till November 2020, along with grey literature for diabetes and all other relevant publications to gather eligible studies. Read More

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Cytochrome P450-epoxygenated fatty acids inhibit Müller glial inflammation.

Sci Rep 2021 May 6;11(1):9677. Epub 2021 May 6.

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA.

Free fatty acid dysregulation in diabetics may elicit the release of inflammatory cytokines from Müller cells (MC), promoting the onset and progression of diabetic retinopathy (DR). Palmitic acid (PA) is elevated in the sera of diabetics and stimulates the production of the DR-relevant cytokines by MC, including IL-1β, which induces the production of itself and other inflammatory cytokines in the retina as well. In this study we propose that experimental elevation of cytochrome P450 epoxygenase (CYP)-derived epoxygenated fatty acids, epoxyeicosatrienoic acid (EET) and epoxydocosapentaenoic acid (EDP), will reduce PA- and IL-1β-induced MC inflammation. Read More

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Dynamic miRNA changes during the process of epileptogenesis in an infantile and adult-onset model.

Sci Rep 2021 May 6;11(1):9649. Epub 2021 May 6.

CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.

Temporal lobe epilepsy (TLE) is the most common epilepsy type. TLE onset in infancy aggravates features like severity, drug responsiveness, or development of comorbidities. These aggravations may arise from altered micro RNA (miRNA) expression specific to the early onset of the disease. Read More

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Identification of germ cell-specific Mga variant mRNA that promotes meiosis via impediment of a non-canonical PRC1.

Sci Rep 2021 May 6;11(1):9737. Epub 2021 May 6.

Division of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1, Yamane Hidaka, Saitama, 350-1241, Japan.

A non-canonical PRC1 (PRC1.6) prevents precocious meiotic onset. Germ cells alleviate its negative effect by reducing their amount of MAX, a component of PRC1. Read More

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The Use of Motor-Evoked Potentials in Clinical Trials in Multiple Sclerosis.

J Clin Neurophysiol 2021 May;38(3):166-170

Service of Clinical Neurophysiology, University Regional Hospital of Malaga, Malaga, Spain.

Summary: Motor-evoked potentials (MEPs) can be used to assess the integrity of the descending corticospinal tract in the laboratory. Evoked potentials (EPs) have been widely used in the past for the diagnosis of multiple sclerosis (MS), but they are now becoming more useful in assessing the prognosis of the disease. Motor-evoked potentials have been included in EP scales that have demonstrated good correlations with clinical disability. Read More

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Diabetes Mellitus and the Development of Lumbar Canal Stenosis: Is There Any Relevance?

Asian Spine J 2021 May 7. Epub 2021 May 7.

Fortis Hospital, Mohali, India.

Study Design: Retrospective study.

Purpose: To assess the relationship between the severity of lumbar canal stenosis (LCS) and type-II diabetes mellitus (DM).

Overview Of Literature: DM is a multiorgan disorder that has an effect on all types of connective tissues. Read More

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Colonization of the Caenorhabditis elegans gut with human enteric bacterial pathogens leads to proteostasis disruption that is rescued by butyrate.

PLoS Pathog 2021 May 6;17(5):e1009510. Epub 2021 May 6.

Department of Microbiology & Cell Science, University of Florida, Gainesville, Florida, United States of America.

Protein conformational diseases are characterized by misfolding and toxic aggregation of metastable proteins, often culminating in neurodegeneration. Enteric bacteria influence the pathogenesis of neurodegenerative diseases; however, the complexity of the human microbiome hinders our understanding of how individual microbes influence these diseases. Disruption of host protein homeostasis, or proteostasis, affects the onset and progression of these diseases. Read More

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Fast Algorithms for Conducting Large-Scale GWAS of Age-at-Onset Traits Using Cox Mixed-Effects Models.

Genetics 2020 May;215(1):41-58

Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, North Carolina.

Age-at-onset traits are of paramount importance in studies of age-related diseases and behavioral genetics. Cox mixed-effects models (CMEMs) are widely used when sample dependence is taken into account. However, the application of CMEMs in genome-wide association. Read More

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Microbial Ecosystem in Diabetes Mellitus: Consideration of the Gastrointestinal System.

Diabetes Metab Syndr Obes 2021 28;14:1841-1854. Epub 2021 Apr 28.

Pharmacology and Toxicology Unit, Department of Pharmacy, College of Health Sciences, Debre Berhan University, Debre Berhan, Ethiopia.

Intestinal microbiota is established to be a crucial element in the control of human health, and keeping the symbiotic relationship between the human body and intestinal microbes will have paramount importance. A number of investigations illustrated that many chronic diseases are associated with intestinal micro-ecological disorders implying intestinal floras as an important component among the environmental factors, and perturbations in their composition are correlated with metabolic disorders, including obesity and diabetes mellitus (DM). Increased evidence suggests that alterations in the gut microbial ecosystem have been involved in part in the pathogenesis of both type 1 and type 2 DM. Read More

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Delayed production of neutralizing antibodies correlates with fatal COVID-19.

Nat Med 2021 May 5. Epub 2021 May 5.

Department of Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT, USA.

Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). However, the exact features of antibody responses that govern COVID-19 disease outcomes remain unclear. In this study, we analyzed humoral immune responses in 229 patients with asymptomatic, mild, moderate and severe COVID-19 over time to probe the nature of antibody responses in disease severity and mortality. Read More

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Neurovascular Interactions in Malaria.

Neuroimmunomodulation 2021 May 5:1-10. Epub 2021 May 5.

Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro, Brazil.

Malaria is caused by Plasmodium infection and remains a serious public health problem worldwide, despite control efforts. Malaria can progress to severe forms, affecting multiple organs, including the brain causing cerebral malaria (CM). CM is the most severe neurological complication of malaria, and cognitive and behavior deficits are commonly reported in surviving patients. Read More

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Activation of Insulin-Like Growth Factor-2 Ameliorates Retinal Cell Damage and Exerts Protection in in vitro Model of Diabetic Retinopathy.

Neuroimmunomodulation 2021 May 5:1-10. Epub 2021 May 5.

Department of Ophthalmology, The First Hospital of Hebei Medical University, Shijiazhuang, China.

Background: The major event in the development of diabetes-related blindness and vision impairment is the onset of retinal cell damage. Overall awareness of insulin-like growth factor-2 (IGF2) mechanisms emphasizes its protective behavior in retinal cells that help to provide new information about the development of treatment for retinal complications.

Objectives: This study analyzes the effect of in vitro changes associated with the cell survival and rescue mechanism in IGF2 inhibition and activation using chromeceptin and IGF2 peptides in ARPE-19 cells cultured in high glucose conditions. Read More

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Neuroinflammation in Mood Disorders: Role of Regulatory Immune Cells.

Neuroimmunomodulation 2021 May 5:1-9. Epub 2021 May 5.

Institute of Education and Research, Santa Casa BH, Belo Horizonte, Brazil.

Mood disorders are associated with chronic low-grade systemic (sterile) inflammation, with increased plasma levels of pro-inflammatory mediators targeting all tissues including the brain. Importantly, pro-inflammatory cytokines (ex., tumor-necrosis factor alpha [TNF-α], interleukin [IL]-6) regulate mood behavior and cognition by influencing neurotransmitter levels, activating stress-responsive endocrine axes, among other effects. Read More

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Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3.

Mov Disord 2021 May 5. Epub 2021 May 5.

IXICO Plc, London, United Kingdom.

Background: Given that new therapeutic options for spinocerebellar ataxias are on the horizon, there is a need for markers that reflect disease-related alterations, in particular, in the preataxic stage, in which clinical scales are lacking sensitivity.

Objective: The objective of this study was to quantify regional brain volumes and upper cervical spinal cord areas in spinocerebellar ataxia type 3 in vivo across the entire time course of the disease.

Methods: We applied a brain segmentation approach that included a lobular subsegmentation of the cerebellum to magnetic resonance images of 210 ataxic and 48 preataxic spinocerebellar ataxia type 3 mutation carriers and 63 healthy controls. Read More

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Rhododendrol-induced leukoderma update II: Pathophysiology, mechanisms, risk evaluation, and possible mechanism-based treatments in comparison with vitiligo.

J Dermatol 2021 May 5. Epub 2021 May 5.

Department of Integrative Medical Science for Allergic Disease, Fujita Health University School of Medicine, Nagoya, Japan.

A small proportion of individuals utilizing cosmetics containing rhododendrol developed leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol-induced leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism-based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Read More

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[Nonfusion procedures in pediatric scoliosis].

Orthopade 2021 May 5. Epub 2021 May 5.

Klinik für Orthopädie (Friedrichsheim), Universitätsklinikum Frankfurt, Marienburgstr. 2, 60528, Frankfurt am Main, Deutschland.

The treatment of early onset scoliosis (EOS) in children is a complex and demanding challenge in the treatment of spinal deformities. Conservative treatment with physiotherapy is indicated in mild forms with a Cobb angle from 10° and additionally a corset treatment with a Cobb angle of more than 20°. After exhaustion of the conservative measures or a progression of spinal scoliosis of 10° or deformities of more than 35°, a surgical approach should be considered in order to prevent respiratory insufficiency as well as severe postural and thoracic deformities. Read More

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Sensitivity of Uni- vs Bilateral Spike-Wave Discharges to Ethosuximide and Carbamazepine in the Fluid Percussion Injury Rat Model of Traumatic Brain Injury.

J Neurophysiol 2021 May 5. Epub 2021 May 5.

Department of Psychology and Neuroscience, University of Colorado Boulder, United Statesgrid.266190.a.

Unilateral-onset spike-wave discharges (SWDs) following fluid percussion injury (FPI) in rats have been used for nearly two decades as a model for complex partial seizures in human post-traumatic epilepsy (PTE). This study determined if SWDs with a unilateral versus bilateral cortical onset differed. In this experiment, 2-month old rats received severe FPI (3 atm) or sham surgery, and were instrumented for chronic video-electrocorticography (ECoG) recording (up to 9 months). Read More

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Scoliosis in Friedreich's ataxia: longitudinal characterization in a large heterogeneous cohort.

Ann Clin Transl Neurol 2021 May 5. Epub 2021 May 5.

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Objective: The objective of this study was to characterize the incidence and progression of scoliosis in the natural history of Friedreich's ataxia (FRDA) and document the factors leading to the requirement for corrective surgery.

Methods: Data on the prevalence of scoliosis and scoliosis surgery from up to 17 years of follow-up collected during a large natural history study in FRDA (1116 patients at 4928 visits) were summarized descriptively and subjected to time to event analyses.

Results: Well over 90% of early or typical FRDA patients (as determined by age of onset) developed intermediate to severe scoliosis, while patients with a later onset (>14 years) had no or much lower prevalence of scoliosis. Read More

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Longitudinal phenotypic study of late-onset retinal degeneration due to a founder variant c.562C>A p.(Pro188Thr) in the gene.

Ophthalmic Genet 2021 May 5:1-12. Epub 2021 May 5.

Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium.

: Late-onset retinal degeneration (L-ORD) is a rare autosomal dominant retinal dystrophy related to gene variants.: Twenty-six patients (21-81 years) with L-ORD due to c.562C>A p. Read More

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Vaginal mucositis related to immunotherapy in endometrial cancer.

Gynecol Oncol Rep 2021 May 31;36:100742. Epub 2021 Mar 31.

Rutgers Cancer Institute of New Jersey, United States.

Immunotherapy, specifically immune checkpoint inhibitors (ICPi), has revolutionized our approach to treating all solid tumors, including gynecologic malignancies. Compared to standard chemotherapy, the adverse events associated with immunotherapies, are often mild and localized, although more severe systemic responses can also occur. While dermatitisdermatitis is a most commonly reported side effect of ICPi therapy, cutaneous toxicities have a range of clinical manifestations and can provide a challenge in an otherwise favorable treatment protocol. Read More

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Modulation of microRNome by Human Cytomegalovirus and Human Herpesvirus 6 Infection in Human Dermal Fibroblasts: Possible Significance in the Induction of Fibrosis in Systemic Sclerosis.

Cells 2021 Apr 29;10(5). Epub 2021 Apr 29.

Department of Chemical, Pharmaceutical and Agricultural Sciences and LTTA, University of Ferrara, 44121 Ferrara, Italy.

Human cytomegalovirus (HCMV) and Human herpesvirus 6 (HHV-6) have been reportedly suggested as triggers of the onset and/or progression of systemic sclerosis (SSc), a severe autoimmune disorder characterized by multi-organ fibrosis. The etiology and pathogenesis of SSc are still largely unknown but virological and immunological observations support a role for these beta-herpesviruses, and we recently observed a direct impact of HCMV and HHV-6 infection on the expression of cell factors associated with fibrosis at the cell level. Since miRNA expression has been found profoundly deregulated at the tissue level, here we aimed to investigate the impact on cell microRNome (miRNome) of HCMV and HHV-6 infection in in vitro infected primary human dermal fibroblasts, which represent one of the main SSc target cells. Read More

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Facilitates ErbB2-Mammary Adenocarcinoma in Mice.

Cancers (Basel) 2021 Apr 30;13(9). Epub 2021 Apr 30.

Pennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg Institute, Wynnewood, PA 19096, USA.

HER2, which is associated with clinically aggressive disease, is overexpressed in 15-20% of breast cancers (BC). The host immune system participates in the therapeutic response of HER2 breast cancer. Identifying genetic programs that participate in ErbB2-induced tumors may provide the rational basis for co-extinction therapeutic approaches. Read More

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The detrimental effect of iron on OA chondrocytes: Importance of pro-inflammatory cytokines induced iron influx and oxidative stress.

J Cell Mol Med 2021 May 3. Epub 2021 May 3.

Department of spine surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Iron overload is common in elderly people which is implicated in the disease progression of osteoarthritis (OA), however, how iron homeostasis is regulated during the onset and progression of OA and how it contributes to the pathological transition of articular chondrocytes remain unknown. In the present study, we developed an in vitro approach to investigate the roles of iron homeostasis and iron overload mediated oxidative stress in chondrocytes under an inflammatory environment. We found that pro-inflammatory cytokines could disrupt chondrocytes iron homeostasis via upregulating iron influx transporter TfR1 and downregulating iron efflux transporter FPN, thus leading to chondrocytes iron overload. Read More

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Long noncoding RNA CTD-2245E15.3 promotes anabolic enzymes ACC1 and PC to support non-small cell lung cancer growth.

Cancer Res 2021 May 3. Epub 2021 May 3.

Biochemistry, Nanjing University

Long noncoding RNAs (lncRNA) have been shown to play critical regulatory roles in the onset and progression of human cancers. However, the functions of a large proportion of lncRNAs are still unexplored. Here we describe a novel lncRNA, CTD-2245E15. Read More

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Plasma neurofilament light in Huntington's disease: A marker for disease onset, but not symptom progression.

Parkinsonism Relat Disord 2021 Apr 28;87:32-38. Epub 2021 Apr 28.

Department of Epidemiology, University of California Irvine, Irvine, CA, USA; Institute for Interdisciplinary Salivary Bioscience Research, University of California Irvine, Irvine, CA, USA. Electronic address:

Objective: To investigate whether plasma NfL levels correlate with clinical symptom severity in premanifest (PM) and manifest HD (HD) individuals, and whether a NfL cut-point could distinguish PM from HD patients with reasonable accuracy.

Method: 98 participants (33 control, 26 PM, 39 HD), underwent blood sample collection and clinical assessment, using both UHDRS and non-UHDRS measures, at one academic HD Center. Years to onset (YTO), probability of disease onset in 5 years, and predicted years until 60% onset probability were also calculated. Read More

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Multi-omics comparisons of different forms of centronuclear myopathies and the effects of several therapeutic strategies.

Mol Ther 2021 Apr 30. Epub 2021 Apr 30.

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR7104, INSERM U1258, Université de Strasbourg, 67404 Illkirch, France. Electronic address:

Omics analyses are powerful methods to obtain an integrated view of complex biological processes, disease progression or therapy efficiency. However, few studies have compared different disease forms and different therapy strategies to define the common molecular signatures representing the most significant implicated pathways. Here, we used RNA sequencing and mass spectrometry data to profile the transcriptomes and proteomes of mouse models for three forms of centronuclear myopathies (CNM), untreated or treated with either a drug (tamoxifen), antisense oligonucleotides reducing the level of dynamin 2 (DNM2), or following modulation of dynamin 2 or amphiphysin 2 (BIN1) through genetic crosses. Read More

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[Consensus statement of the Hungarian Clinical Neurogenic Society about the therapy of adult SMA patients].

Ideggyogy Sz 2021 Mar;74(3-4):79-86

Semmelweis Egyetem, Genomikai Medicina és Ritka Betegségek Tanszék; European Reference Network, Neuromuscular Disorders Szakértôi Központ, Budapest.

Background And Purpose: Background - Spinal muscular atrophy (SMA) is an autosomal recessive, progressive neuromuscular disorder resulting in a loss of lower motoneurons. Recently, new disease-modifying treatments (two drugs for splicing modification of SMN2 and one for SMN1 gene replacement) have become available. Purpose - The new drugs change the progression of SMA with neonatal and childhood onset. Read More

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Progression of the first stage of labour, in low risk nulliparas in a South Asian population: a prospective observational study.

J Obstet Gynaecol 2021 May 2:1-5. Epub 2021 May 2.

Department of Obstetrics and Gynaecology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.

We compared the labour pattern in the active phase of labour, defined at 4 cm versus 6 cm cervical dilatation, in a South Asian population. This was a prospective observational study where 500 low risk nulliparous women were recruited. Our aim was to study, the average labour pattern curve of all parturients. Read More

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