scholarly journals The Erythrocytic Hypothesis of Brain Energy Crisis in Sporadic Alzheimer Disease: Possible Consequences and Supporting Evidence

2020 ◽  
Vol 9 (1) ◽  
pp. 206
Author(s):  
Elena Kosenko ◽  
Lyudmila Tikhonova ◽  
Gubidat Alilova ◽  
Amparo Urios ◽  
Carmina Montoliu
Keyword(s):  
Systemic Disease ◽  
Amyloid Plaque ◽  
Energy Crisis ◽  
Current Evidence ◽  
Unknown Etiology ◽  
Supporting Evidence ◽  
Fatal Form ◽  
New Hypothesis ◽  
Brain Energy ◽  
Sporadic Alzheimer Disease

Alzheimer’s disease (AD) is a fatal form of dementia of unknown etiology. Although amyloid plaque accumulation in the brain has been the subject of intensive research in disease pathogenesis and anti-amyloid drug development; the continued failures of the clinical trials suggest that amyloids are not a key cause of AD and new approaches to AD investigation and treatment are needed. We propose a new hypothesis of AD development based on metabolic abnormalities in circulating red blood cells (RBCs) that slow down oxygen release from RBCs into brain tissue which in turn leads to hypoxia-induced brain energy crisis; loss of neurons; and progressive atrophy preceding cognitive dysfunction. This review summarizes current evidence for the erythrocytic hypothesis of AD development and provides new insights into the causes of neurodegeneration offering an innovative way to diagnose and treat this systemic disease.

scholarly journals Evaluation of nasal mucociliary clearance in rheumatoid arthritis: a comparative analysis using saccharin test

2017 ◽  
Vol 5 (11) ◽  
pp. 5026 ◽  
Author(s):  
Shelja Deswal ◽  
Jyoti Yadav ◽  
Mohit Deswal ◽  
Harpreet Singh
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Duration ◽  
Mucociliary Clearance ◽  
Systemic Disease ◽  
Unknown Etiology ◽  
Control Group ◽  
Ciliary Activity ◽  
Multisystem Disease ◽  
Organic Particles ◽  
Nasal Mucociliary Clearance

Background: Rheumatoid arthritis (RA) is a chronic multisystem disease of unknown etiology characterized by persistent inflammatory synovitis, usually involving peripheral joints in a symmetric distribution. RA is a systemic disease often associated with cutaneous and organ-specific extra-articular manifestations the mucociliary clearance system protects the lower respiratory system by trapping and removing inhaled pathogenic viruses and bacteria, in addition to nontoxic and toxic particulates (e.g., pollen, ash, mineral dust, mold spores, and organic particles), from the lungs. Effective clearance requires both ciliary activity and the appropriate balance of periciliary fluid and mucus.Methods: This was a case control study conducted in the Department of Physiology, Pt. B.D. Sharma PGIMS, Rohtak in 50 females of age group 30-50 years. Control group comprised of 25 healthy volunteer females while study group comprised of 25 rheumatoid arthritis female patients with disease duration of more than five years. Proven cases of RA (as per 1987 ACR criteria) were taken with disease duration of more than five years from Rheumatology clinic of Pt. B.D. Sharma PGIMS, Rohtak. Nasal mucociliary clearance time was evaluated by saccharin method.Results: The results of our study showed abnormal mucociliary clearance in rheumatoid arthritis patients.Conclusions: The study shows an abnormal mucociliary clearance in rheumatoid arthritis patients. Impairment of mucociliary clearance seems to be the result of qualitative and quantitative alterations in respiratory secretions.

scholarly journals Rheumatoid arthritis activity scores in patients with and without fibromyalgia syndrome

2021 ◽  
Vol 41 (4) ◽  
pp. 246-252
Author(s):  
Yunus Durmaz ◽  
Ilker Ilhanli
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Fibromyalgia Syndrome ◽  
Conflicts Of Interest ◽  
Systemic Disease ◽  
Response To Treatment ◽  
Unknown Etiology ◽  
Tender Joint Count ◽  
Tender Joint ◽  
Cross Sectional

BACKGROUND: Fibromyalgia syndrome (FM) is a systemic disease of unknown etiology, which can cause widespread musculoskeletal pain. In patients with rheumatoid arthritis (RA), FM can cause an additional symptom burden, which can affect some variables on the RA disease activity score 28 (DAS28), a tool that evaluates 28 joints in RA patients. OBJECTIVE: Compare the results of four different versions of the DAS28 and the parameters used to determine disease activity scores in RA patients with and without FM, and determine whether there are treatment differences between RA patients with and without FM. DESIGN: Retrospective, cross-sectional. SETTING: Tertiary hospital. PATIENTS AND METHODS: We identified patients diagnosed with RA between 1 September 2016 and 1 February 2020 and identified patients with and without FM. MAIN OUTCOME MEASURES: Differences between variables in the DAS28 calculations (tender joint count [TJC], patient global assessment [PGA], and others), between patients with and without FM, and differences between patients with and without FM who were using or not using biological agents. SAMPLE SIZE: 381, including 322 females (84.5%). RESULTS: The frequency of FM in RA patients was 25.7% (89 females, 24.6%). In RA patients with FM, the TJC and PGA median values were significantly higher than in patients without FM ( P <.05). The use of corticosteroids and biological therapy in patients with FM was more frequent than in patients without FM ( P <.05). Compared to patients without FM, patients with FM switched treatment more often because of non-response to treatment ( P =.01) Median values of the DAS28 scores (calculated by four different versions of the instrument) in RA patients with FM were higher than in patients without FM ( P <.05). CONCLUSION: The presence of FM in RA patients may affect the subjective variables in different versions of DAS28 scores, causing the disease activity to score higher on the instrument, erroneously indicating worse disease than is actually present. LIMITATIONS: A single center, retrospective study. CONFLICTS OF INTEREST: None.

COVID-19 in pediatrics: The current knowledge and practice

2021 ◽  
Vol 21 ◽  
Author(s):  
Esmaeil Mehraeen ◽  
Shahram Oliaei ◽  
SeyedAhmad SeyedAlinaghi ◽  
Amirali Karimi ◽  
Pegah Mirzapour ◽  
...  
Keyword(s):  
Systematic Review ◽  
Current Knowledge ◽  
Systemic Disease ◽  
Severe Disease ◽  
Reliability And Validity ◽  
Current Evidence ◽  
Original Research ◽  
Consensus Statements ◽  
Knowledge And Practice ◽  
Novel Coronavirus

Introduction: SARS-CoV-2 is the novel coronavirus that causes severe acute respiratory syndrome and could afflict individuals from all walks of life. Children are usually asymptomatic or represent non-specific mild to moderate symptoms; therefore, they often remain undiagnosed and could be potential reservoirs and silent carriers of the virus. Despite the global attention to COVID-19 and its importance in public health, some clinical and paraclinical aspects of this disease in children are still unclear. Thus, we conducted a comprehensive systematic review of available literature to reflect on the current knowledge and practice of the disease among children. Methods: This study was a systematic review of current evidence conducted in October 2020. We performed a systematic search using the keywords in online databases. The investigation adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to ensure the reliability and validity of extracted literature and results. Results: We selected and reviewed 23 most related studies out of 1744 identified paper in an initial online search based on the inclusion and exclusion criteria of the present review; of whom, 13 were original research studies, and 10 were a letter to the editors, commentaries, viewpoints, consensus statements, and perspectives. Although due to the origin of the current pandemic, China was the country with the most publications (14 articles), data from several countries have beenincluded in this review. Conclusion: COVID-19 can also affect children and cause systemic disease with several internal organ involvements. However, the prevalence, severity, and diversity of the symptoms in children are less than in adults. Cough and fever appear to be some of the most common symptoms, followed by other symptoms such as gastrointestinal manifestations. Comorbidities increase the risk of severe COVID-19 in children, and those without underlying conditions are very unlikely to suffer from severe disease. Mental health issues such as anxiety and depression due to the isolated situation caused by pandemics are common findings in children of early ages and should be seriously considered in current practice.

Cardiac Sarcoidosis: Cytokine Patterns in the Course of the Disease

2003 ◽  
Vol 127 (9) ◽  
pp. 1207-1210 ◽  
Author(s):  
Michael Schoppet ◽  
Sabine Pankuweit ◽  
Bernhard Maisch
Keyword(s):  
Time Course ◽  
Mononuclear Cells ◽  
Cardiac Sarcoidosis ◽  
Systemic Disease ◽  
Healing Process ◽  
Unknown Etiology ◽  
Enzyme Linked Immunosorbent Assay ◽  
Rapid Decline ◽  
Peripheral Blood Mononuclear ◽  
Multiple Organs

Abstract Sarcoidosis is a chronic systemic disease of unknown etiology, which is characterized by noncaseating epitheloid granulomas usually in multiple organs. Here we describe changes in cytokine mRNA expression by peripheral blood mononuclear cells (PBMCs) and changes of cytokine protein levels in plasma over a time course of 12 months in a patient with sarcoidosis confined to the heart as diagnosed by endomyocardial biopsy. Mitogen-stimulated PBMCs exhibited a more TH1 cytokine profile at onset of symptoms before immunosuppressive therapy was initiated, with a change to a TH0 response in the course of the disease as evidenced by multiplex-polymerase chain reaction. In plasma, high levels of interleukin-6 could be detected by an enzyme-linked immunosorbent assay system, with rapid decline correlating with immunosuppression and improving clinical course. These changes may point to a role of TH1 and TH2 cytokines in the pathogenesis and the healing process of cardiac sarcoidosis.

Sarcoidosis

Chest Imaging ◽  
2019 ◽  
pp. 441-446
Author(s):  
Juliana Bueno
Keyword(s):  
Chest Radiography ◽  
Asymptomatic Patient ◽  
Systemic Disease ◽  
Imaging Study ◽  
Epithelioid Cell ◽  
Unknown Etiology ◽  
Imaging Findings ◽  
Clinical Context ◽  
Pathological Confirmation ◽  
Necrotizing Granulomas

Sarcoidosis is a systemic disease of unknown etiology, characterized by noncaseating epithelioid cell granulomas. Patients with sarcoidosis are frequently asymptomatic and may be diagnosed incidentally because of an abnormal imaging study. Sarcoidosis is a diagnosis of exclusion that warrants pathological confirmation in all cases. The distribution of granulomas in the lungs is characteristic and correlates with imaging findings; non-necrotizing granulomas classically exhibit a perilymphatic distribution. On chest radiography, the presence of bilateral hilar and right paratracheal lymphadenopathy, particularly in a young asymptomatic patient, should raise the possibility of sarcoidosis. On CT, a perilymphatic distribution (peribronchovascular, subpleural, septal) of abnormalities in the appropriate clinical context is highly specific for sarcoidosis.

scholarly journals The Bewildering Effect of AMPK Activators in Alzheimer’s Disease: Review of the Current Evidence

2020 ◽  
Vol 2020 ◽  
pp. 1-18 ◽  
Author(s):  
Brhane Teklebrhan Assefa ◽  
Gebrehiwot Gebremedhin Tafere ◽  
Dawit Zewdu Wondafrash ◽  
Meles Tekie Gidey
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Plaque ◽  
Current Evidence ◽  
Negative Effects ◽  
Disease Modifying Therapy ◽  
Tau Aggregation ◽  
And Oxidative Stress ◽  
Remarkable Progress

Alzheimer’s disease is a multifactorial neurodegenerative disease characterized by progressive cognitive dysfunction. It is the most common form of dementia. The pathologic hallmarks of the disease include extracellular amyloid plaque, intracellular neurofibrillary tangles, and oxidative stress, to mention some of them. Despite remarkable progress in the understanding of the pathogenesis of the disease, drugs for cure or disease-modifying therapy remain somewhere in the distance. From recent time, the signaling molecule AMPK is gaining enormous attention in the AD drug research. AMPK is a master regulator of cellular energy metabolism, and recent pieces of evidence show that perturbation of its function is highly ascribed in the pathology of AD. Several drugs are known to activate AMPK, but their effect in AD remains to be controversial. In this review, the current shreds of evidence on the effect of AMPK activators in Aβ accumulation, tau aggregation, and oxidative stress are addressed. Positive and negative effects are reported with regard to Aβ and tauopathy but only positive in oxidative stress. We also tried to dissect the molecular interplays where the bewildering effects arise from.

scholarly journals Clinical Presentations, Pathogenesis, and Therapy of Sarcoidosis: State of the Art

2020 ◽  
Vol 9 (8) ◽  
pp. 2363
Author(s):  
Francesca Polverino ◽  
Elisabetta Balestro ◽  
Paolo Spagnolo
Keyword(s):  
Clinical Course ◽  
State Of The Art ◽  
Systemic Disease ◽  
Unknown Etiology ◽  
Therapeutic Approaches ◽  
Epidemiologic Factors ◽  
Adaptive Immune ◽  
Clinical Presentations ◽  
Specific Organ ◽  
Noncaseating Granulomas

Sarcoidosis is a systemic disease of unknown etiology characterized by the presence of noncaseating granulomas that can occur in any organ, most commonly the lungs. Early and accurate diagnosis of sarcoidosis remains challenging because initial presentations may vary, many patients are asymptomatic, and there is no single reliable diagnostic test. Prognosis is variable and depends on epidemiologic factors, mode of onset, initial clinical course, and specific organ involvement. From a pathobiological standpoint, sarcoidosis represents an immune paradox, where an excessive spread of both the innate and the adaptive immune arms of the immune system is accompanied by a state of partial immune anergy. For all these reasons, the optimal treatment for sarcoidosis remains unclear, with corticosteroid therapy being the current gold standard for those patients with significantly symptomatic or progressive pulmonary disease or serious extrapulmonary disease. This review is a state of the art of clinical presentations and immunological features of sarcoidosis, and the current therapeutic approaches used to treat the disease.

Ruptured Mycotic Aneurysm of the Distal Circulation in a Patient with Mucormycosis Without Direct Skull Base Extension: Case Report

2018 ◽  
Vol 16 (3) ◽  
pp. E101-E107 ◽  
Author(s):  
Shivani D Rangwala ◽  
Ben A Strickland ◽  
Robert C Rennert ◽  
Kristine Ravina ◽  
Joshua Bakhsheshian ◽  
...  
Keyword(s):  
Skull Base ◽  
Intracranial Aneurysms ◽  
Systemic Disease ◽  
Cerebral Aneurysms ◽  
Artery Aneurysm ◽  
Pathological Examination ◽  
Unknown Etiology ◽  
Intracranial Surgery ◽  
Pulmonary Mucormycosis ◽  
Base Extension

Abstract BACKGROUND AND IMPORTANCE Infectious intracranial aneurysms are a rare subset of intracranial aneurysms caused by bacterial, fungal, or viral sources. Intracranial aneurysms of fungal etiology carry a high mortality risk and typically occur in immunocompromised patients via direct extension of skull base infections, or more rarely, after intracranial surgery. CLINICAL PRESENTATION We present the case of a 27-yr-old female with systemic lupus erythematous and primary pulmonary mucormycosis, who suffered a subarachnoid hemorrhage from a ruptured fusiform distal middle cerebral artery aneurysm. Despite undergoing a successful extracranial-to-intracranial bypass and aneurysm excision, the patient ultimately died following progressive disseminated infection and a secondary intracranial hemorrhage of unknown etiology. Pathological examination of the excised artery confirmed Mucor infection. CONCLUSION To the best of our knowledge, this case represents one of the first mycotic cerebral aneurysms from mucormycosis in a patient without an underlying skull base infection or previous intracranial surgery. Despite optimal surgical management, clinical outcomes for mycotic cerebral aneurysms are largely dependent on the success of medical therapies at controlling systemic disease.

scholarly journals Immunotherapy in Advanced Gastric Cancer: An Overview of the Emerging Strategies

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Helena Magalhães ◽  
Mário Fontes-Sousa ◽  
Manuela Machado
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Median Overall Survival ◽  
Systemic Disease ◽  
Treatment Strategies ◽  
Public Health Problem ◽  
Molecular Classification ◽  
Current Evidence ◽  
Curative Intent

Gastric cancer (GC) remains a public health problem, being the fifth most common cancer worldwide. In the western countries, the majority of patients present with advanced disease. Additionally, 65 to 75% of patients treated with curative intent will relapse and develop systemic disease. In metastatic disease, systemic treatment still represents the state of the art, with less than a year of median overall survival. The new molecular classification of GC was published in 2014, identifying four distinct major subtypes of gastric cancer, and has encouraged the investigation of new and more personalized treatment strategies. This paper will review the current evidence of immunotherapy in advanced gastric cancer.

scholarly journals Screening for autistic spectrum disorder in early childhood

2021 ◽  
Vol 21 (S1) ◽  
Author(s):  
Sophie Jullien
Keyword(s):  
Young Children ◽  
Universal Screening ◽  
Autistic Spectrum Disorder ◽  
Spectrum Disorder ◽  
Screening Tools ◽  
Current Evidence ◽  
Supporting Evidence ◽  
Autistic Spectrum ◽  
Manual Search ◽  
Children With Asd

AbstractWe looked at existing recommendations and supporting evidence on the effectiveness of screening young children for autistic spectrum disorder (ASD) for improving short- and long-term outcomes.We conducted a literature search up to the 8th of November 2019 by using key terms and manual search in selected sources. We summarized the recommendations and the strength of the recommendation when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported.There are discrepancies among the recommendations given by different institutions on universal screening for ASD in children. Some recommend that all children should be screened with an ASD-specific instrument during well-child visits at ages 18 and 24 months in conjunction with ongoing developmental surveillance and broadband developmental screening; some conclude that the current evidence is insufficient to assess the balance of benefits and harms of screening for ASD in young children for whom no concerns of ASD have been raised by their parents or a clinician; and others recommend against universal screening, but for a screening among children with high risks.There is adequate evidence that ASD screening tools applied to children between 12 and 36 months accurately identify those with ASD. There is some evidence showing benefit of early interventions applied to children with ASD, from children identified with developmental concern by their family, teacher or clinicians. We found no evidence on the effectiveness of interventions applied to children with ASD detected through screening.

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