Impaired cognition in narcolepsy: clinical and neurobiological perspectives.

In addition to well-known symptoms such as sleepiness and cataplexy, many people with narcolepsy have impaired cognition, reporting inattention, poor memory, and other concerns. Unfortunately, research on cognition in narcolepsy has been limited. Strong evidence demonstrates difficulties with sustained attention, but evidence for executive dysfunction and impaired memory is mixed.

Author Correction: Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice.

In the version of this article initially published, the Simons Foundation was missing from the list of sources of support to P.T.T.

Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice.

Cerebellar abnormalities, particularly in Right Crus I (RCrusI), are consistently reported in autism spectrum disorders (ASD). Although RCrusI is functionally connected with ASD-implicated circuits, the contribution of RCrusI dysfunction to ASD remains unclear. Here neuromodulation of RCrusI in neurotypical humans resulted in altered functional connectivity with the inferior parietal lobule, and children with ASD showed atypical functional connectivity in this circuit.

Update on monitoring and adverse effects of first generation disease modifying therapies and their recently approved versions in relapsing forms of multiple sclerosis.

Purpose Of Review: As of April 2015, 13 disease modifying therapies (DMTs) have been approved by the Food and Drug Administration. The older agents continue to be utilized across the globe, especially in developing countries where many newer DMTs are still not available. Even though first generation DMTs have modest efficacy they have long term safety profile, and are considered safer than the second generation DMTs.

Update on monitoring and adverse effects of approved second-generation disease-modifying therapies in relapsing forms of multiple sclerosis.

Purpose Of Review: There has been a considerable increase in the number of disease-modifying therapies (DMTs) in recent years. It appears that the number of approved DMTs is going to continue to increase in the coming years. The growing number of DMTs has provided a challenge to the clinician to tailor their therapeutic recommendations based on patients' needs and preferences.

Intractable and highly active relapsing multiple sclerosis - role of alemtuzumab.

Alemtuzumab is a humanized recombinant monoclonal antibody that was recently approved by the US Food and Drug Administration and the European Medicines Agency for the management of relapsing forms of multiple sclerosis (MS). It has been utilized for the management of chronic lymphocytic leukemia, bone marrow and renal transplantation, or graft versus host disease. Because of its immunomodulatory properties, it was brought into clinical development in MS.

Mutant surfactant A2 proteins associated with familial pulmonary fibrosis and lung cancer induce TGF-β1 secretion.

Mutations in the genes encoding the lung surfactant proteins are found in patients with interstitial lung disease and lung cancer, but their pathologic mechanism is poorly understood. Here we show that bronchoalveolar lavage fluid from humans heterozygous for a missense mutation in the gene encoding surfactant protein (SP)-A2 (SFTPA2) contains more TGF-β1 than control samples. Expression of mutant SP-A2 in lung epithelial cells leads to secretion of latent TGF-β1, which is capable of autocrine and paracrine signaling.

Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells.

SIV infection of natural host species such as sooty mangabeys results in high viral replication without clinical signs of simian AIDS. Studying such infections is useful for identifying immunologic parameters that lead to AIDS in HIV-infected patients. Here we have demonstrated that acute, SIV-induced CD4(+) T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3(+)CD4(-)CD8(-) T cells (double-negative T cells) partially compensates for CD4(+) T cell function in these animals.

Gamma/Delta T cell mRNA levels decrease at mucosal sites and increase at lymphoid sites following an oral SIV infection of macaques.

The oral and esophageal mucosa have been identified as possible sites of HIV/SIV entry following oral infection. Here, gamma/delta (gammadelta) T cells, a multi-functional T cell subset, were assessed at oral/esophageal mucosa and lymphoid sites at the earliest times (1-14 days) post-oral SIV inoculation utilizing quantitative RT-PCR. During these earliest times post-infection, decreased gammadelta TCR mRNA levels were observed at the oral gingiva and esophageal mucosa, while increased levels were observed within regional lymph nodes (cervical and retropharyngeal).