Seed amplification assay of nasal swab extracts for accurate and non-invasive molecular diagnosis of neurodegenerative diseases.

Nasal swabs are non-invasive testing methods for detecting diseases by collecting samples from the nasal cavity or nasopharynx. Dysosmia is regarded as an early sign of coronavirus disease 2019 (COVID-19), and nasal swabs are the gold standard for the detection. By nasal swabs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids can be cyclically amplified and detected using real-time reverse transcriptase-polymerase chain reaction after sampling. Similarly, olfactory dysfunction precedes the onset of typical clinical manifestations by several years in prion diseases and other neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. In neurodegenerative diseases, nasal swab tests are currently being explored using seed amplification assay (SAA) of pathogenic misfolded proteins, such as prion, α-synuclein, and tau. These misfolded proteins can serve as templates for the conformational change of other copies from the native form into the same misfolded form in a prion-like manner. SAA for misfolded prion-like proteins from nasal swab extracts has been developed, conceptually analogous to PCR, showing high sensitivity and specificity for molecular diagnosis of degenerative diseases even in the prodromal stage. Cyclic amplification assay of nasal swab extracts is an attractive and feasible method for accurate and non-invasive detection of trace amount of pathogenic substances for screening and diagnosis of neurodegenerative disease.

Clinical application of prion-like seeding in α-synucleinopathies: Early and non-invasive diagnosis and therapeutic development.

The accumulation and deposition of misfolded α-synuclein (α-Syn) aggregates in the brain is the central event in the pathogenesis of α-synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple-system atrophy. Currently, the diagnosis of these diseases mainly relies on the recognition of advanced clinical manifestations. Differential diagnosis among the various α-synucleinopathies subtypes remains challenging. Misfolded α-Syn can template its native counterpart into the same misfolded one within or between cells, behaving as a prion-like seeding. Protein-misfolding cyclic amplification and real-time quaking-induced conversion are ultrasensitive protein amplification assays initially used for the detection of prion diseases. Both assays showed high sensitivity and specificity in detection of α-synucleinopathies even in the pre-clinical stage recently. Herein, we collectively reviewed the prion-like properties of α-Syn and critically assessed the detection techniques of α-Syn-seeding activity. The progress of test tissues, which tend to be less invasive, is presented, particularly nasal swab, which is now widely known owing to the global fight against coronavirus disease 2019. We highlight the clinical application of α-Syn seeding in early and non-invasive diagnosis. Moreover, some promising therapeutic perspectives and clinical trials targeting α-Syn-seeding mechanisms are presented.

Awareness and Mental Health of Male Drug Addicts With Tuberculosis During the COVID-19 Pandemic.

Introduction: At present, the COVID-19 pandemic remains the most pressing global health issue. Given the significant amount of public awareness, the infection rate and rehabilitation efforts are governed not only by the compliance of transmission mitigation strategies but also by the understanding of coexisting diseases and COVID-19 in patients with chronic infectious diseases. The main goal of this study was to evaluate the differences in demographics, as well as awareness, risk perception, and emotional reactions, among imprisoned drug addicts with and without tuberculosis (TB) regarding their perceptions of and feelings toward the COVID-19 pandemic. The secondary goal of the study was also to measure how the psychological health and nutritional indices of the drug addicts with TB changed during their ongoing rehabilitation. Methods: A total of 265 male drug addicts, 45 of which were positive for TB and another 220 who were negative, were selected as subjects from a mandatory detoxification and rehabilitation center (MDRC). Data were collected through a combination of questionnaires (questions regarding COVID-19 awareness, emotional knowledge and responses, and SCL-90 tests), anthropometric examination, and laboratory blood tests, with which inferential and descriptive statistical analyses were performed. Results: During a period of 1 week in early 2021, the differences in the accuracy of the responses from the questions probing the awareness of COVID-19 symptoms, transmission, susceptible populations, what kind of mask should be worn, and preventive measures between TB addicts to non-TB addicts were 11.11 vs. 60.45%, 57.78 vs. 77.27%, 66.67 vs. 78.64%, 97.98 vs. 97.73%, and 93.33 vs. 65.91%, respectively. In the risk perception and emotional reaction sections of the questionnaire, there was a significant difference in the responses to "What you were more worried about was?" (p < 0.001) and "Alteration in your mood since the outbreak?" (p = 0.002) between the two cohorts. In the section assessing the 10 dimensions of the SCL-90 scale, there were significant differences between the TB addicts and the Chinese norm. In addition, the BMI (21.06 ± 2.65 kg/m2) and total serum protein (77.14 ± 6.12 g/L) levels of the TB addicts were normal, but the serum hemoglobin (117.02 ± 4.97 g/L) and albumin (42.08 ± 1.81 g/L) levels were significantly lower in the TB addicts compared to the norm (p < 0.001). Conclusion: The COVID-19 pandemic we are facing is both an epidemiologic and a psychological crisis. However, while the COVID-19 epidemic will eventually disappear (or become manageable, similar to the flu), the TB epidemic may still persist. To avoid the deleterious consequences of multiple simultaneous epidemics, complementary response measures to COVID-19 and TB can help curb the exacerbation of both situations and, therefore, save lives. Imprisoned drug addicts, especially those with TB, can master relevant knowledge on COVID-19.