abnormal accumulation
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The microtubule-associated protein tau (MAPT) plays an important role in Alzheimer’s disease and primary tauopathy diseases. The abnormal accumulation of tau contributes to the development of neurotoxicity, inflammation, neurodegeneration, and cognitive deficits in tauopathy diseases. Tau synergically interacts with amyloid-beta in Alzheimer’s disease leading to detrimental consequence. Thus, tau has been an important target for therapeutics development for Alzheimer’s disease and primary tauopathy diseases. Tauopathy animal models recapitulating the tauopathy such as transgenic, knock-in mouse and rat models have been developed and greatly facilitated the understanding of disease mechanisms. The advance in PET and imaging tracers have enabled non-invasive detection of the accumulation and spread of tau, the associated microglia activation, metabolic, and neurotransmitter receptor alterations in disease animal models. In vivo microPET studies on mouse or rat models of tauopathy have provided significant insights into the phenotypes and time course of pathophysiology of these models and allowed the monitoring of treatment targeting at tau. In this study, we discuss the utilities of PET and recently developed tracers for evaluating the pathophysiology in tauopathy animal models. We point out the outstanding challenges and propose future outlook in visualizing tau-related pathophysiological changes in brain of tauopathy disease animal models.

As a primary cause of dementia and death in older people, Alzheimer’s disease (AD) has become a common problem and challenge worldwide. Abnormal accumulation of tau proteins in the brain is a hallmark pathology of AD and is closely related to the clinical progression and severity of cognitive deficits. Here, we found that overexpression of phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) effectively promoted the degradation of tau, thereby rescuing neuron loss, synaptic damage, and cognitive impairments in a mouse model of tauopathy with AAV-full-length human Tau (hTau) injected into the hippocampal CA1 area (hTau mice). Overexpression of PINK1 activated autophagy, and chloroquine but not MG132 reversed the PINK1-induced decrease in human Tau levels and cognitive improvement in hTau mice. Furthermore, PINK1 also ameliorated mitochondrial dysfunction induced by hTau. Taken together, our data revealed that PINK1 overexpression promoted degradation of abnormal accumulated tau via the autophagy–lysosome pathway, indicating that PINK1 may be a potential target for AD treatment.

Cardiac tamponade is a life-threatening compression of the heart caused by abnormal accumulation of pericardial fluid. Important elements affecting its disposition and treatment are the rate of fluid accumulation relative to pericardial stretch and the effectiveness of compensatory mechanisms before critical hemodynamic compromise occurs. It is a clinical diagnosis and waiting for the threshold of steep rise in cardiac transmural pressure to critical levels may lead to catastrophic outcomes which is why early drainage has to be strongly considered in suspected cases.

<p><strong>Background:</strong> Laryngeal edema is defined as abnormal accumulation of fluid and swelling in the tissues of the larynx commonly associated with laryngeal injuries and allergic causes. The objective of this study is for the prompt recognition and management of laryngeal edema caused by an anaphylaxis reaction after receiving the COVID-19 vaccination from Pfizer-BioNTech, which is extremely important in view of its high morbidity and mortality rate.</p><p><strong>Methods:</strong> A retrospective case reviews was conducted for all health care workers in Sabah who were administered COVID-19 vaccination from Pfizer-BioNTech from February 2021-April 2021.</p><p><strong>Results:</strong> The mean age of study population in present study was found to be 33 years. Total of 42 patients were admitted during the period of 6 weeks out of 5000 health care workers who were vaccinated. Females constituted 64.3% of the study population while males constituted 35.7%. The clinical signs of laryngeal edema were dysphagia; the sensation of a lump in the throat; a feeling of tightness in the throat; voice changes, including hoarseness and roughness; and dyspnea within the period of 3 to 5 minutes post Pfizer COVID-19 vaccination. All patients received appropriate management using standard guidelines.</p><p><strong>Conclusions:</strong> The administration of the COVID-19 vaccination from Pfizer-BioNTech is life-threatening, however, its identification may aid in prompt emergency management in the future. Referral to an otorhinolaryngologist is necessary for patients who experience immediate or severe reactions.</p>

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder, one of the main characteristics of which is the abnormal accumulation of amyloid peptide (Aβ) in the brain. Whereas β-secretase supports Aβ formation along the amyloidogenic processing of the β-amyloid precursor protein (βAPP), α-secretase counterbalances this pathway by both preventing Aβ production and triggering the release of the neuroprotective sAPPα metabolite. Therefore, stimulating α-secretase and/or inhibiting β-secretase can be considered a promising anti-AD therapeutic track. In this context, we tested andrographolide, a labdane diterpene derived from the plant Andrographis paniculata, as well as 24 synthesized derivatives, for their ability to induce sAPPα production in cultured SH-SY5Y human neuroblastoma cells. Following several rounds of screening, we identified three hits that were subjected to full characterization. Interestingly, andrographolide (8,17-olefinic) and its close derivative 14α-(5′,7′-dichloro-8′-quinolyloxy)-3,19-acetonylidene (compound 9) behave as moderate α-secretase activators, while 14α-(2′-methyl-5′,7′-dichloro-8′-quinolyloxy)-8,9-olefinic compounds 31 (3,19-acetonylidene) and 37 (3,19-diol), whose two structures are quite similar although distant from that of andrographolide and 9, stand as β-secretase inhibitors. Importantly, these results were confirmed in human HEK293 cells and these compounds do not trigger toxicity in either cell line. Altogether, these findings may represent an encouraging starting point for the future development of andrographolide-based compounds aimed at both activating α-secretase and inhibiting β-secretase that could prove useful in our quest for the therapeutic treatment of AD.

AbstractAmyloid transthyretin (ATTR) amyloidosis is characterized by the abnormal accumulation of ATTR fibrils in multiple organs. However, the structure of ATTR fibrils from the eye is poorly understood. Here, we used cryo-EM to structurally characterize vitreous body ATTR fibrils. These structures were distinct from previously characterized heart fibrils, even though both have the same mutation and type A pathology. Differences were observed at several structural levels: in both the number and arrangement of protofilaments, and the conformation of the protein fibril in each layer of protofilaments. Thus, our results show that ATTR protein structure and its assembly into protofilaments in the type A fibrils can vary between patients carrying the same mutation. By analyzing and matching the interfaces between the amino acids in the ATTR fibril with those in the natively folded TTR, we are able to propose a mechanism for the structural conversion of TTR into a fibrillar form.

The purpose of this review is to provide the latest information on POEMS syndrome. The authors conducted a literature search of available sources describing the issue of POEMS syndrome with special focus on syndrome and made a comparison and evaluation of relevant findings. The results of this review indicate that POEMS syndrome is associated with a group of disorders known as monoclonal gammopathies or plasma cell dyscrasias. These disorders are characterized the uncontrolled growth of a single clone (monoclonal) of plasma cells, which results in the abnormal accumulation of M-proteins (also known as immunoglobulin) in the blood which has a significant impact on the quality of life of both the patients and his/her family. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. Therefore, early and proper diagnosis and treatment are necessary in order to reduce or even eliminate both symptoms and social burden of the patient.

Abstract Lumbar epidural lipomatosis (LEL) is characterized by the abnormal accumulation of unencapsulated adipose tissue in the spinal epidural space. Symptomatic LEL occurs in middle aged and elderly patients, and it is most often seen in males. The purpose of this study was to elucidate the histopathological and cytogenetic characteristics of the epidural lipomatosis in patients with symptomatic LEL. Six patients undergoing decompressive spinal surgery (mean age, 69.4 years) were enrolled between 2013 and 2017. Three cases were steroid-induced and 3 cases were diagnosed as idiopathic LEL. We compared the differences in histological morphology between the subcutaneous fat tissue and epidural fat tissue in each patient. We also analyzed the karyotype of resected epidural lipomatous tissue using the G-band method. The epidural adipocytes were histologically more irregular and smaller compared with the subcutaneous adipocytes in all cases. The mean size of subcutaneous adipocytes and epidural adipocytes was 5,485.6 ± 2,584.1 µm2 and 2,705.4 ± 1,069.1 µm2, respectively. In cytogenetic analysis of the epidural adipocytes, loss of the Y chromosome (LOY) was found in all 6 cases. The mechanisms related to the development of LEL are not well understood. In this study, the size of the lipid component of epidural adipocytes was significantly smaller than that of subcutaneous adipocytes in LEL. Cytogenetically, LOY was frequently recognized. Although this may be an effect rather than a cause, LOY may be related to morphologic changes in and proliferation of adipocytes in LEL. LOY might partially contribute to the pathological mechanism or expression of LEL.

Meningomyelocele, one of the neural tube defect (NTD) variants, is a condition in which meninges and neural tissue protrudes through a defect in vertebral arch and forms a cyst-like sac with an incidence of 0.5–11/1000 live births. Hydrocephalus is a major problem for majority of patients with meningomyelocele due to the abnormal accumulation of cerebrospinal fluid (CSF) in the ventricles of the brain. Meticulous preoperative evaluation with planning of the anesthetic technique, especially in regard to managing the airway, plays a crucial role in successful surgical management of these cases. Here, we report a case of lumbosacral meningomyelocele with hydrocephalus underwent a multimodal treatment approach for providing a comprehensive plan of care.

Hemochromatosis is defined as abnormal accumulation of iron in various organs of the body such as liver, pancreas, skin, joints, heart due to raised gut absorption of iron due to low hepcidin yield. Hemochromatosis is secondary to thalassemia major in this case. In the absence of other concurrent processes, cardiac hemochromatosis is identified as the presence of cardiac dysfunction owing to increased iron accumulation in the heart leading to heart failure. Unique: Cardiac involvement in secondary hemochromatosis due to thalassemia major. Take Away lesson: Regular monitoring of serum iron, ferritin, echocardiographic monitoring among thalassemia major patients is essential. Despite the fact that heart failure due to iron overload could be fatal, early diagnosis and intervention could prevent and treat the disease.