Discrimination between Alpha-Synuclein Protein Variants with a Single Nanometer-Scale Pore.

Alpha-synuclein is one of several key factors in the regulation of nerve activity. It is striking that single- or multiple-point mutations in the 140-amino-acid-long protein can change its structure, which leads to the protein's aggregation and fibril formation (which is associated with several neurodegenerative diseases, e.g., Parkinson's disease). We recently demonstrated that a single nanometer-scale pore can identify proteins based on its ability to discriminate between protease-generated polypeptide fragments. We show here that a variation of this method can readily discriminate between the wild-type alpha synuclein, a known deleterious point mutation of the glutamic acid at position 46 replaced with a lysine (E46K), and post-translational modifications (i.e., tyrosine Y39 nitration and serine 129 phosphorylation).

Sleep Disorders and Quality of Life in Patients With Cancer: Prospective Observational Study of the Rafael Institute.

BACKGROUND: Sleep disorders are a common occurrence in the general population. Yet today, it is clearly agreed that sleep disorders represent both a cancer risk factor and a biological consequence of the of the activation of the immuno-inflammatory system induced by cancer itself. OBJECTIVE: The aim of this study was to assess the impact of sleep disorders on quality of life and identify the type of disorder and its causes in order to offer an adapted and personalized care plan. METHODS: In a survey completed during the COVID-19 lockdown, 2000 hours of interviews were collected by remote consultations. During these calls, we administered a sleep questionnaire. This questionnaire was inspired by the STOP-BANG questionnaire and enquired about 6 items. The demographic details of each patient (eg, age and sex), the nature of the pathology, their past treatments, the ongoing cancer treatment, the mood, whether or not the patient is anxious or depressed, and the use of sleeping drug pills were analyzed. A univariate analysis was performed according to the presence or absence of fatigue. Chi-square test was applied to assess possible differences of variables' link to sleep disturbance between patients complaining of fatigue and those without fatigue. The same test was then used to analyze patients on hormone therapy and those with no hormone therapy for 2 types of cancer-breast cancer and prostate cancer. RESULTS: A total of 905 patients were prospectively included in this study. The average age was 66.7 (5 SD) years, and 606 (67%) patients were women; 142 patients declared being overweight. Breast cancer was the most frequently reported cancer. Nocturnal awakening was reported by 70% (n=633), fatigue by 50% (n=452), difficulty falling asleep by 38% (n=343), snoring reported by an independent observer in 38% (n=343), and apnea reported by an independent observer in 9% (n=81) of the patients. The univariate analysis showed that the feeling of tiredness was significantly greater in patients reporting difficulty falling asleep (P≥.99), pain (P<.001), and frequent awakening (P<.001), as well as in patients who were not receiving cancer treatment (P<.001). The univariate analysis showed that patients who were receiving breast cancer treatment and were under hormone therapy reported difficulty falling asleep (P=.04) and pain (P=.05). In a univariate analysis of patients treated for prostate cancer, being overweight was the only factor reported that had a statistically significant value. CONCLUSIONS: Our preliminary data support and are consistent with data in the literature regarding the importance of sleep disorders in oncology. This justifies the usefulness of a diagnosis and early treatment of sleep disorders in patients with cancer. The Rafael Institute sleep observatory will enable patients to be identified and treated.

Spontaneous regression of an orbital Langerhans cell histiocytosis after biopsy: A case report. Spontaneous regression of an orbital Langerhans cell histiocytosis.

Langerhans histiocytosis or Langerhans cell histiocytosis (LCH) is a rare benign pathology representing less than 1% of orbital tumors. It can cause either localized or generalized lesions, leading to the destruction of hard and soft tissues. Eosinophilic granuloma is the most benign form and the predominant clinical presentation of LCH. We report a case of eosinophilic granuloma with orbital involvement in an 18-year-old male patient. Orbital radiotherapy was initially planned, but finally it was not performed due to a spontaneous regression of the lesion after the incisional biopsy. The presented case supports an expectant attitude given the possibility of a spontaneous regression after the biopsy, especially in small lesions. However, long-term follow-up is essential given the risk of recurrence.

On possible trypsin-induced biases in peptides analysis with aerolysin nanopore.

Nanopore-based single-molecule analysis technique is a promising approach in the field of proteomics. In this Technical Brief, the interaction between the biological nanopore of Aerolysin (AeL) and peptides is investigated, focusing on potential biases depending on the AeL activation protocol. Our results reveal that residual trypsin, which may be unintentionally introduced in analyte solution when using a classical AeL activation protocol, can induce a significant formation of shorter peptides by enzymatic degradation of longer ones, which may lead to unwanted effects and/or misinterpretations. AeL free-trypsin activation protocol eliminates this bias and appears more appropriate for peptide/proteins analysis, specifically in the perspective of nanopore-based molecular fingerprinting or of low-abundance species characterization.

Impact of local treatment on survival from hematological malignancies causing spinal cord compression.

BACKGROUND: Various hematological malignancies, including multiple myeloma, plasmacytoma, aggressive lymphoma, and indolent lymphoma, rarely result in spinal cord compression. METHODS: Here, we retrospectively analyzed 32 patients with multiple myeloma (50%), plasmacytoma (13%), aggressive lymphoma (28%), and indolent lymphoma (9%), resulting in spinal cord compression (2004 and 2016). Patients averaged 57 years of age and presented with the indolent onset of spinal cord compression (91% of cases) resulting mostly in motor deficits (69%). RESULTS: Local treatment modalities included radiotherapy (RT) (28%) alone, decompressive surgery (28%) alone, or decompressive surgery with consolidation RT (40%). The 1-year overall survival was 70%, and the progression-free survival frequency was 62%. CONCLUSION: This study highlighted the importance of standardizing the indications for RT alone versus RT with surgery depending on the patient's underlying pathological diagnosis, neurological deficits, and radiological findings.