An Unusual Cause of Increasing Excessive Daytime Sleepiness in a CPAP-treated Obstructive Sleep Apnea Patient.

The onset of narcolepsy type 1 (NT1) occurs after 50 years of age in less than 2% of the cases. In older adults, the diagnosis is often delayed due to the presence of neurological degenerative and inflammatory comorbidities and overlapping sleep disorders. We report the case of a 63-year-old man with a 5-year history of excessive daytime sleepiness (EDS) and a 2-year diagnosis of obstructive sleep apnea syndrome (OSAS), which. OSAS was confirmed by respiratory polygraphy that showed an apnea-hypopnea index (AHI) of 71 events/hour of sleep associated with significant nocturnal hypoxemia (lowest oxygen saturation: 53%), which lead to the initiation of continuous positive airway pressure (CPAP) treatment. Cognitive complaints, unexplained spells of dizziness, and lack of improvement in EDS with CPAP led to further diagnostic investigation of infectious, inflammatory, and neurodegenerative disorders. Low hypocretin levels in the cerebrospinal fluid (CSF) confirmed the diagnosis of NT1, and the patient's symptoms improved with the treatment with pitolisant. Though exceptional in older adults, NT1 should be suspected in the presence of atypical EDS with neurological complaints, unexplained dizzy spells, or OSAS that resists the CPAP treatment. Low levels of hypocretin in the CSF are highly specific and rule out other neurological and sleep disorders.

The Nebulous Association between Cognitive Impairment and Falls in Older Adults: A Systematic Review of the Literature.

BACKGROUND: In older people, dementia is a well-established risk factor for falls. However, the association and the causal relationship between falls and the earlier stages of cognitive impairment remains unclear. The purpose of the study was to review the literature data on the association between falls and cognitive impairment, no dementia, including Mild Cognitive Impairment. METHODS: According to PRISMA guidelines, we searched five electronic databases (EMBASE, Web of Science, Medline, CINAHL, and PsychINFO) for articles published between January 2011 and August 2022 on observational studies of older people with a cognitive assessment and/or cognitive impairment diagnosis and a recording of falls. Their quality was reviewed according to the STROBE checklist. RESULTS: We selected 42 of the 4934 initially retrieved publications. In 24 retrospective studies, a statistically significant association between falls and cognitive status was found in only 15 of the 32 comparisons (47%). Of the 27 cross-sectional analyses in prospective studies, only eight (30%) were positive and significant. We counted four longitudinal analyses, half of which suggested a causal relationship between falls and cognitive impairment. The investigational methods varied markedly from one study to another. CONCLUSION: It is still not clear whether falls are associated with cognitive impairment, no dementia. Data in favor of a causal relationship are scarce. Further studies are needed to clarify their relationship.

Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8(+) T cells.

CD8(+) T-cell memory phenotype and function are acquired after antigen-driven activation. Memory-like cells may also arise in absence of antigenic exposure in the thymus or in the periphery. Eomesodermin (Eomes) is a key transcription factor for the development of these unconventional memory cells. Herein, we show that type I interferon signalling in CD8(+) T cells directly activates Eomes gene expression. Consistent with this observation, the phenotype, function and age-dependent expansion of 'virtual memory' CD8(+) T cells are strongly affected in absence of type I interferon signalling. In addition, type I interferons induce a sustained expansion of 'virtual memory' CD8(+) T cells in an Eomes-dependent fashion. We further show that the development of 'innate thymic' CD8(+) T cells is dependent on the same pathway. In conclusion, we demonstrate that type I interferon signalling in CD8(+) T cells drives Eomes expression and thereby regulates the function and homeostasis of memory-like CD8(+) T cells.

Interferon regulatory factor 3 in adaptive immune responses.

Interferon regulatory factor (IRF) 3 plays a key role in innate responses against viruses. Indeed, activation of this transcription factor triggers the expression of type I interferons and downstream interferon-stimulated genes in infected cells. Recent evidences indicate that this pathway also modulates adaptive immune responses. This review focuses on the different mechanisms that are implicated in this process. We discuss the role of IRF3 within antigen-presenting cells and T lymphocytes in the polarization of the cellular immune response and its implication in the pathogenesis of immune disorders.

Interferon regulatory factor 3 controls interleukin-17 expression in CD8 T lymphocytes.

IFN regulatory factor (IRF) 3 plays a key role in innate responses against viruses. Herein we assessed its contribution to T-cell activation. We observed that poly(I:C)-induced IRF3 activation in CD8 T cells represses IL-17 expression in a type I IFN-independent fashion. Even in the absence of poly(I:C), polyclonally activated naïve IRF3(-/-) CD8 T cells expressed high levels of IL-17 and IL-23R in comparison with wild-type cells. Furthermore, IRF3(-/-) OT1 cells adoptively transferred into wild-type hosts also produced higher IL-17 levels upon immunization than their wild-type counterparts. This phenotype could be reversed by ectopic expression of IRF3, confirming that this effect is intrinsic to T cells. We show that IRF3 directly interacts with RORγt in the cytoplasm through its IRF interaction domain and limits its ability to bind and transactivate the IL-17 promoter. These observations uncover an unexpected role of IRF3 in the control of CD8 T-cell polarization.

Ovarian response to stimulation of HIV-positive patients during IVF treatment: a matched, controlled study.

BACKGROUND: Our aim was to compare the ovarian response of HIV-positive and -negative patients during IVF. METHODS: Setting - HIV and IVF reference university hospital. Twenty-seven HIV-infected patients who had undergone IVF between March 2000 and March 2005 were matched with 77 HIV-negative patients for age, aetiology of infertility, whether it was primary or secondary infertility, duration of infertility, history of pelvic surgery and type of pituitary inhibition. Outcome - poor responders were defined using one of the following criteria: a cancelled cycle (for insufficient ovarian response), less than four mature follicles (> or = 16 mm), peak serum levels of E2 lower than 1000 pg/ml. RESULTS: There were no differences between the two groups of patients for the matched criteria. The proportion of African women and of women with a history of pelvic inflammatory disease was significantly higher among HIV patients than among the control group. With the exception of a lower number of transferred embryos among HIV-positive patients versus HIV-negative ones (1.3 versus 1.9; P = 0.035), there was no significant difference between the two groups of patients regarding ovarian response parameters. CONCLUSION: HIV-infected patients who are in good general condition and who are matched to a control group present a similar ovarian response to stimulation, suggesting the existence of a similar ovarian reserve.