Low incidence of severe respiratory syncytial virus infections in lung transplant recipients despite the absence of specific therapy.

BACKGROUND: Respiratory syncytial virus (RSV) infections in lung transplant recipients (LTRs) have been associated with significant morbidity and mortality. Immunoglobulins, ribavirin, and palivizumab are suggested treatments for both pre-emptive and therapeutic purposes. However, in the absence of randomized, placebo-controlled trials, efficacy is controversial and there is toxicity as well as cost concerns. METHODS: We retrospectively reviewed cases of lower respiratory tract RSV infections in adult LTRs. Diagnosis was based on clinical history, combined with a positive polymerase chain reaction (PCR) and/or viral cultures of bronchoalveolar lavage (BAL) specimens. RESULTS: Ten symptomatic patients were identified (7 men and 3 women, age range 28 to 64 years). All were hospitalized for community-acquired respiratory tract infections. Two patients had a concomitant acute Grade A3 graft rejection, and 1 patient had a concomitant bacterial pneumonia. Eight patients did not receive a specific anti-RSV treatment because of clinical stability and/or improvement at the time of RSV diagnosis. Only 2 patients (1 with Grade A3 allograft rejection and 1 requiring mechanical ventilation) received ribavirin and palivizumab. All patients recovered without complications and with no persistent RSV infection. However, bronchiolitis obliterans (BOS) staging worsened in 6 patients during the mean follow-up of 45 months. CONCLUSIONS: Our data suggest that mild RSV infections in LTRs might evolve favorably in the absence of specific anti-viral therapy. However, this observation needs confirmation in a large clinical trial specifically investigating the development of BOS in untreated vs treated patients.

Induced normothermia attenuates cerebral metabolic distress in patients with aneurysmal subarachnoid hemorrhage and refractory Fever.

BACKGROUND AND PURPOSE: The purpose of this study was to analyze whether fever control attenuates cerebral metabolic distress after aneurysmal subarachnoid hemorrhage (SAH). METHODS: Eighteen SAH patients, who underwent intracranial pressure (ICP) and cerebral microdialysis monitoring and were treated with induced normothermia for refractory fever (body temperature >or=38.3 degrees C, despite antipyretics), were studied. Levels of microdialysate lactate/pyruvate ratio (LPR) and episodes of cerebral metabolic crisis (LPR >40) were analyzed during fever and induced normothermia, at normal and high ICP (>20 mm Hg). RESULTS: Compared to fever, induced normothermia resulted in lower LPR (40+/-24 versus 32+/-9, P<0.01) and a reduced incidence of cerebral metabolic crisis (13% versus 5%, P<0.05) at normal ICP. During episodes of high ICP, induced normothermia was associated with a similar reduction of LPR, fewer episodes of cerebral metabolic crisis (37% versus 8%, P<0.01), and lower ICP (32+/-11 versus 28+/-12 mm Hg, P<0.05). CONCLUSIONS: Fever control is associated with reduced cerebral metabolic distress in patients with SAH, irrespective of ICP.

Raeder's paratrigeminal syndrome due to spontaneous dissection of the cervical and petrous internal carotid artery.

The combination of pain, ipsilateral oculosympathetic defect (ptosis and miosis), and ipsilateral trigeminal dysfunction constitutes Raeder's syndrome. We describe a patient with an acute presentation of Raeder's syndrome due to spontaneous internal carotid artery dissection. True trigeminal dysfunction due to carotid dissection is rare, and the potential mechanisms for its involvement are reviewed in this paper. Finally, we remind clinicians to consider dissection in the differential diagnosis of Raeder's syndrome because of its potential for ischemic cerebral neurologic sequelae and suggest early cranial and neck imaging in the evaluation of such patients.

Dysfunctional SEMA3E signaling underlies gonadotropin-releasing hormone neuron deficiency in Kallmann syndrome.

Individuals with an inherited deficiency in gonadotropin-releasing hormone (GnRH) have impaired sexual reproduction. Previous genetic linkage studies and sequencing of plausible gene candidates have identified mutations associated with inherited GnRH deficiency, but the small number of affected families and limited success in validating candidates have impeded genetic diagnoses for most patients. Using a combination of exome sequencing and computational modeling, we have identified a shared point mutation in semaphorin 3E (SEMA3E) in 2 brothers with Kallmann syndrome (KS), which causes inherited GnRH deficiency. Recombinant wild-type SEMA3E protected maturing GnRH neurons from cell death by triggering a plexin D1-dependent (PLXND1-dependent) activation of PI3K-mediated survival signaling. In contrast, recombinant SEMA3E carrying the KS-associated mutation did not protect GnRH neurons from death. In murine models, lack of either SEMA3E or PLXND1 increased apoptosis of GnRH neurons in the developing brain, reducing innervation of the adult median eminence by GnRH-positive neurites. GnRH neuron deficiency in male mice was accompanied by impaired testes growth, a characteristic feature of KS. Together, these results identify SEMA3E as an essential gene for GnRH neuron development, uncover a neurotrophic function for SEMA3E in the developing brain, and elucidate SEMA3E/PLXND1/PI3K signaling as a mechanism that prevents GnRH neuron deficiency.

Données actualisées sur la physiopathologie, les phénotypes et les traitements de la maladie de Still de l'adulte [Pathophysiology, subtypes, and treatments of adult-onset Still's disease: An update].

Adult-onset Still's disease is a rare and difficult to diagnose multisystemic disorder considered as a multigenic autoinflammatory syndrome. Its immunopathogenesis seems to be at the crossroads between inflammasomopathies and hemophagocytic lymphohistiocytosis, the most severe manifestation of the disease. According to recent insights in the pathophysiology and thanks to cohort studies and therapeutic trials, two phenotypes of adult-onset Still's disease may be distinguished: a systemic pattern, initially highly symptomatic and with a higher risk to exhibit life-threatening complications such as reactive hemophagocytic lymphohistiocytosis, where interleukin-1 blockade seems to be very effective, a chronic articular pattern, more indolent with arthritis in the foreground and less severe systemic manifestations, which would threat functional outcome and where interleukin-6 blockade seems to be more effective. This review focuses on these data.

Dysregulated ADAM10-Mediated Processing of APP during a Critical Time Window Leads to Synaptic Deficits in Fragile X Syndrome.

The Fragile X mental retardation protein (FMRP) regulates neuronal RNA metabolism, and its absence or mutations leads to the Fragile X syndrome (FXS). The β-amyloid precursor protein (APP) is involved in Alzheimer's disease, plays a role in synapse formation, and is upregulated in intellectual disabilities. Here, we show that during mouse synaptogenesis and in human FXS fibroblasts, a dual dysregulation of APP and the α-secretase ADAM10 leads to the production of an excess of soluble APPα (sAPPα). In FXS, sAPPα signals through the metabotropic receptor that, activating the MAP kinase pathway, leads to synaptic and behavioral deficits. Modulation of ADAM10 activity in FXS reduces sAPPα levels, restoring translational control, synaptic morphology, and behavioral plasticity. Thus, proper control of ADAM10-mediated APP processing during a specific developmental postnatal stage is crucial for healthy spine formation and function(s). Downregulation of ADAM10 activity at synapses may be an effective strategy for ameliorating FXS phenotypes.

Associations between fruit and vegetable consumption and psychological distress: results from a population-based study.

BACKGROUND: Several studies observed associations of various aspects of diet with mental health, but little is known about the relationship between following the 5-a-day recommendation for fruit and vegetables consumption and mental health. Thus, we examined the associations of the Swiss daily recommended fruit and vegetable intake with psychological distress. METHODS: Data from 20,220 individuals aged 15+ years from the 2012 Swiss Health Survey were analyzed. The recommended portions of fruit and vegetables per day were defined as 5-a-day (at least 2 portions of fruit and 3 of vegetables). The outcome was perceived psychological distress over the previous 4 weeks (measured by the 5-item mental health index [MHI-5]). High distress (MHI-5 score ≤ 52), moderate distress (MHI-5 > 52 and ≤ 72) and low distress (MHI-5 > 72 and ≤ 100) were differentiated and multinomial logistic regression analyses adjusted for known confounding factors were performed. RESULTS: The 5-a-day recommendation was met by 11.6 % of the participants with low distress, 9.3 % of those with moderate distress, and 6.2 % of those with high distress. Consumers fulfilling the 5-a-day recommendation had lower odds of being highly or moderately distressed than individuals consuming less fruit and vegetables (moderate vs. low distress: OR = 0.82, 95 % confidence interval [CI] 0.69-0.97; high vs. low distress: OR = 0.55, 95 % CI 0.41-0.75). CONCLUSIONS: Daily intake of 5 servings of fruit and vegetable was associated with lower psychological distress. Longitudinal studies are needed to further determine the causal nature of this relationship.

Markers of iron metabolism and metabolic syndrome in Swiss adults

Plusieurs études populationnelles ont montré l'existence d'une association entre des taux sanguins élevés de transferrine et le syndrome métabolique (SM). Bien que cette association soit bien établie, restent encore à être décrites les associations entre le SM et les autres marqueurs sanguins du métabolisme du fer, tels que le fer, la transferrine (Tsf), la capacité totale de fixation de la transferrine (CTF) ou la saturation de la transferrine (SaTsf) sanguins. Le but de notre étude a été d'identifier les associations entre les différents marqueurs du métabolisme du fer (fer, ferritine, Tsf, CTF et SaTsf) et le SM. Les données de l'étude CoLaus, récoltées entre 2003 et 2006, ont été utilisées. Le SM était défini selon les critères du National Cholesterol Education Program Adult Panel III. L'analyse statistique a été faite en stratifiant selon le genre ainsi que le status ménopausal chez les femmes. Des 6733 participants, 1235 (18%) ont été exclus de fait d'absence de données concernant les variables qui nous intéressaient, ou chez qui nous avons soupçonné une possible hémochromatose non diagnostiquée (SaTsf> 50%). Des 5498 participants restant (âge moyen ± écart-type: 53 ± 11 ans), 2596 étaient des hommes, 1285 des femmes pré- et 1617 des femmes postménopausées. La prévalence du SM était de 29,4% chez les hommes, 8,3% et 25,5% chez les femmes pré- et postménopausées, respectivement. Dans les trois groupes, la prévalence du SM était la plus haute dans les quartiles les plus élevés de ferritine, Tsf et CTF, ainsi que dans le quartile le plus bas de SaTsf. Après ajustement sur l'âge, l'indice de masse corporelle, la protéine C réactive, la consommation de tabac et/ou d'alcool, la prise de suppléments en fer et les marqueurs hépatiques, l'appartenance au quartile le plus élevé de ferritine, Tsf ou CTF était associée à un risque plus important de SM chez les hommes et les femmes postménopausées : Odds ratio (OR) et [intervalle de confiance à 95%] pour la ferritine 1.44 [1.07-1.94] et 1.47 [0.99-2.17]; pour la Tsf et la CTF, OR=1.43 [1.06-1.91] et 2.13 [1.44-3.15] pour les hommes et les femmes postménopausées, respectivement. Au contraire, l'appartenance au quartile le plus élevé de la SaTsf était associé à un risque moins important de SM: OR=0.77 [0.57-1.05] et 0.59 [0.39-0.90] pour les hommes et les femmes postménopausées, respectivement. Il n'y avait aucune association entre les marqueurs sanguins du métabolisme du fer et le SM chez les femmes préménopausées, ni entre le fer sanguin et le SM chez les trois groupes. En conclusion, la majorité des marqueurs sanguins du métabolisme du fer, mais pas le fer lui-même, sont associés de manière indépendante au SM chez les hommes et les femmes postménopausées. -- Context: Excessive iron storage has been associated with metabolic syndrome (MS). Objective: To assess the association between markers of iron metabolism and MS in a healthy population. Design: Cross-sectional study conducted between 2003 and 2006. Setting: Population-based study in Lausanne, Switzerland. Patients: 5,498 participants aged 35-75 years, stratified by sex and menopausal status. Participants with transferrin saturation (TSAT) >50% were excluded. Intervention: None. Main Outcome Measures: serum iron, ferritin, transferrin, total iron binding capacity (TIBC) and TSAT. MS was defined according to ATP-III criteria. Results: Prevalence of MS was 29.4% in men, 8.3% in premenopausal and 25.5% in postmenopausal women. On bivariate analysis, the highest prevalence of MS occurred in the highest quartiles of serum ferritin, transferrin and TIBC, and in the lowest quartile of TSAT. After multivariate adjustment for age, body mass index, C-reactive protein, smoking, alcohol, liver markers and iron supplementation, men and postmenopausal women in the highest quartile of serum ferritin, transferrin and TIBC had a higher risk of presenting with MS: for ferritin, Odds ratio and [95% CI]=1.44 [1.07-1.94] for men and 1.47 [0.99-2.17] for postmenopausal women; for transferrin and TIBC, OR=1.43 [1.06-1.91] and 2.13 [1.44-3.15], Participants in the highest quartile of TSAT had a lower risk of MS: OR=0.77 [0.57-1.05] for men and 0.59 [0.39-0.90] for postmenopausal women. No association was found between iron and MS and between markers of iron metabolism and MS in premenopausal women. Conclusion: Ferritin, transferrin, TIBC are positively and TSAT is negatively associated with MS in men and postmenopausal women.

Prevalence of sleep apnoea syndrome in the middle to old age general population.

On the basis of a large populationbased sample who underwent full polysomnography at home (HypnoLaus cohort), we recently reported that 49·7% of men and 23·4% of women aged 40 years or older had an apnoea-hypopnoea index of 15 events per h or more1 according to the American Academy of Sleep Medicine (AASM) 2013 scoring criteria. When excessive daytime sleepiness (ie, Epworth score >10 [maximum score 24]) was included in the definition with an apnoea-hypopnoea index of 5 events per h or more, the prevalence was 12·5% in men and 5·9% in women. This high prevalence of sleep disordered breathing reinforced the idea that the treatment decision should not only be based the apnoeahypopnoea index, but should also take into account associated symptoms and cardiovascular and metabolic comorbidities. After this Article was published, several readers contacted us to ask for the prevalence of sleep apnoea syndrome in our sample according to the International Classification of Sleep Disorders (ICSD-3) criteria. These criteria include either the presence of an apnoea-hypopnoea index of 5 events per h or more associated with obstructive sleep apnoearelated symptoms or cardiovascular and metabolic comorbidities, or an apnoea-hypopnoea index of 15 events per h or more (figure).