Abstract In Parkinson’s disease, synucleinopathy is hypothesized to spread from the enteric nervous system, via the vagus nerve, to the CNS. Here, we compare, in baboon monkeys, the pathological consequences of either intrastriatal or enteric injection of α-synuclein-containing Lewy body extracts from patients with Parkinson’s disease. This study shows that patient-derived α-synuclein aggregates are able to induce nigrostriatal lesions and enteric nervous system pathology after either enteric or striatal injection in a non-human primate model. This finding suggests that the progression of α-synuclein pathology might be either caudo-rostral or rostro-caudal, varying between patients and disease subtypes. In addition, we report that α-synuclein pathological lesions were not found in the vagal nerve in our experimental setting. This study does not support the hypothesis of a transmission of α-synuclein pathology through the vagus nerve and the dorsal motor nucleus of the vagus. Instead, our results suggest a possible systemic mechanism in which the general circulation would act as a route for long-distance bidirectional transmission of endogenous α-synuclein between the enteric and the central nervous systems. Taken together, our study provides invaluable primate data exploring the role of the gut-brain axis in the initiation and propagation of Parkinson’s disease pathology and should open the door to the development and testing of new therapeutic approaches aimed at interfering with the development of sporadic Parkinson’s disease.

Epidemiological studies have demonstrated that there is a correlation between oral lichen planus and chronic hepatitis C virus (HCV) infection. HCV RNA has been recently detected in epithelial cells from oral lichen planus lesions by reverse-transcription polymerase chain reaction (RT-PCR). However, this technique does not discriminate which types of cells are infected by the virus or if the viralThe hepatitis C virus (HCV) is the etiological agent of most cases of posttransfusional hepatitis. 1 The viral genome consists of a 9.4-kb-long single-stranded RNA molecule of positive polarity. 2 HCV is thought to replicate in the liver through an RNA intermediate of negative polarity. 3 HCV causes acute and chronic hepatitis in humans. 4 Chronic HCV infection is characterized by a wide spectrum of liver damage ranging from mild chronic hepatitis to cirrhosis, and even hepatocellular carcinoma. 5 On the other hand, several dermatological diseases such as cutaneous necrotizing vasculitis, mixed cryoglobulinemia, porphiria cutanea tarda, and lichen planus have been associated with HCV infection. 6 Lichen planus is a mucocutaneous disease characterized by a band-inflammatory infiltrate enriched in CD4-positive cells, vacuolating degeneration of the basal epithelial layer, and the presence of acidophilic bodies that may represent apoptotic keratinocytes. 7 Its etiology is unknown and may be caused by a cell-mediated immunological response to induced antigenic changes in the skin and mucosa epithelium. 8 The association between HCV infection and lichen planus comes from epidemiological studies that have shown that the prevalence of antibodies against HCV antigens (anti-HCV) is higher in patients with lichen planus than in the general population. [9][10][11] Recently, the presence of positive and negative HCV-RNA strands (which is evidence of viral replication) has been demonstrated by reverse-transcription polymerase chain reaction (RT-PCR) in mucosa biopsies from anti-HCV-positive patients with oral lichen planus. 12 However, because of the high sensitivity of the RT-PCR technique, these PCR products may come from blood that contaminates the biopsies. Furthermore, the presence of HCV RNA in epithelial oral cells has not been demonstrated by in situ hybridization. To establish a role for HCV in the pathology of lichen planus, morphological evidence of HCV replication in the cells of the lesion is needed.For this reason, in this report, we have analyzed the presence of positive and negative HCV-RNA strands by in situ hybridization in paraffin-embedded mucosa biopsies from patients diagnosed as having oral lichen planus and from patients with a chronic HCV infection, but without evidence of suffering oral lichen planus. PATIENTS AND METHODSPatients. Paraffin-embedded oral mucosa biopsies from 23 patients clinically diagnosed as having oral lichen planus were analyzed in this study. Oral mucosa biopsies from the jugal mucosa were obtained to confirm the clinical diagnosis. After the histological examination, the remaining tiss...

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Among the many unknowns regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 is the way in which sex and gender affect the risk of acquiring the virus, illness presentation, disease management and outcomes. Sex, a biological attribute, and gender, a social construct, may both influence an individual's susceptibility, vulnerability and exposure to infectious disease. 1 Immune function differs between sexes and has been shown to affect an individual's likelihood of acquiring infection upon ex posure, or developing complications. [2][3][4] Indeed, early research has shown that these sex differences in immune response may lead to worse COVID-19 outcomes for males in terms of ability to recover from severe infection. 5 Gender, which comprises roles, norms and behaviours that may vary by sex, is associated with an individual's likelihood of exposure 6,7 (Box 1). Several institutions, including the Canadian Institutes of Health Research, have appealed to researchers to include sex and gender variables in data analysis, to improve the effectiveness of health interventions and promote gender and health equity goals. 8 In previous coronavirus epidemics (severe acute respiratory syndrome and Middle East respiratory syndrome), male sex was associated with worse outcomes; 9,10 similarly, early evidence related to COVID-19 appears to largely show increased mortality among males. 11 However, the prevalence of reported cases varies between men and women by country, suggesting that social, economic and cultural factors may influence either acquisition of SARS-CoV-2 or patterns of testing for suspected infection. We, a consortium of European and Canadian researchers (www.mcgill.ca/going -fwd4gender/), sought to assess the influence of gender-related factors on the relative male-female burden of COVID-19, to further understanding of the risks and impact of the COVID-19 pandemic. How might gender influence observed sex differences in epidemiologic research on COVID-19?Gender-related factors may influence an individual's likelihood of exposure to SARS-CoV-2, but they may also influence whether an individual tries to obtain a test and whether they are given one. These factors are presented in a conceptual framework in Figure 1.Gender identity refers to the way in which individuals identify and express their gender as men, women or gender-diverse. How power, opportunities and resources are distributed among men and women within the political, educational and social institutions of a society reflect the institutionalization of gender. 7 Institutionalized gender norms may directly affect health through differential access to health care, food education and income, according to gender. 7,12-14 Furthermore, they shape social norms that define, reproduce and often justify different opportunities and expectations for women and men, such as social and family roles, job segregation and limitations, dress codes and health practices. Gender roles and norms may be related to sex but are also influen...