High-dose rifampin improves bactericidal activity without increased intracerebral inflammation in animal models of tuberculous meningitis

Tuberculous meningitis (TB meningitis) is the most severe form of tuberculosis (TB), requiring 12 months of multidrug treatment for cure, and is associated with high morbidity and mortality. High-dose rifampin (35 mg/kg/d) is safe and improves the bactericidal activity of the standard-dose (10 mg/kg/d) rifampin-containing TB regimen in pulmonary TB. However, there are conflicting clinical data regarding its benefit for TB meningitis, where outcomes may also be associated with intracerebral inflammation. We conducted cross-species studies in mice and rabbits, demonstrating that an intensified high-dose rifampin-containing regimen has significantly improved bactericidal activity for TB meningitis over the first-line, standard-dose rifampin regimen, without an increase in intracerebral inflammation. Positron emission tomography in live animals demonstrated spatially compartmentalized, lesion-specific pathology, with postmortem analyses showing discordant brain tissue and cerebrospinal fluid rifampin levels and inflammatory markers. Longitudinal multimodal imaging in the same cohort of animals during TB treatment as well as imaging studies in two cohorts of TB patients demonstrated that spatiotemporal changes in localized blood-brain barrier disruption in TB meningitis are an important driver of rifampin brain exposure. These data provide unique insights into the mechanisms underlying high-dose rifampin in TB meningitis with important implications for developing new antibiotic treatments for infections.     

Rigidoporus corticola Colonization and Invasive Fungal Disease in Immunocompromised Patients,United States

We report 2 cases of Rigidoporus corticola (Oxyporus corticola) infection in humans in the United States. Clinical manifestations consisted of angioinvasive fungal sinusitis in 1 patient and pulmonary intracavitary fungus ball in the other patient. These cases illustrate previously undescribed clinicopathologic manifestations of infection by this filamentous basidiomycete in humans.     

Violence Committed Against Migrants in Transit: Experiences on the Northern Mexican Border

Thousands of Mexican and Central American migrants converge at the Mexico-United States border. Undocumented migrants in transit to the United States are vulnerable due to their lack of access to health care and legal assistance. This study attempts to provide evidence on the violent-related consequences that migration has on migrants. A mixed-method study was conducted between April 2006-May 2007 in shelters in Baja California, Mexicali and Tijuana, Mexico. 22 in depth interviews were performed and fifteen hundred and twelve migrants responded a questionnaire. Results from both in-depth interviews and the analysis of the quantitative data shows the different types of violence experiences by migrants which include threats, verbal abuse, and arbitrary detention based on ethnicity, as well as assaults, beatings and sexual violence. It is crucial to stress the importance and the need to evidence the condition in which migrants’ transit to the US and to effectively respond to the violence they experience.     

IL-1β at the crossroad between rheumatoid arthritis and type 2 diabetes: may we kill two birds with one stone?

Although in the past the prevention of joint destruction in rheumatoid arthritis (RA) was strongly emphasized, now a great interest is focused on associated comorbidities in these patients. Multiple data suggest that a large percentage of RA patients are affected by Type 2 Diabetes (T2D), whose incidence has reached epidemic levels in recent years, thus increasing the health care costs. A better knowledge about the pathogenesis of these diseases as well as the mechanisms of action of drugs may allow both policy designers and physicians to choose the most effective treatments, thus lowering the costs. This review will focus on the role of Interleukin (IL)-1β in the pathogenesis of both the diseases, the efficacy of IL-1 blocking molecules in controlling these diseases, and will provide information suggesting that targeting IL-1β, in patients affected by both RA and T2D, may be a promising therapeutic choice.     

‘Twin’ familial aneurysms of the anterior communicating artery

Abstract

Two sisters harbouringan intracranial aneurysm are described. Rather than merely adding new cases to the records of familial aneurysms, this communication reports clinical and radiological findings supporting the hypothesis of inheritance: (1) same anatomical location with involvement of the anterior communicating artery (ACoA), which is uncommon when dealing with familial aneurysms, and similar morphology of the lesions; (2) identical haemodynamic pattern; (3) similar timing of haemorrhage, occuring in both cases during the sixth decade.