Evolution of Nervous Control from Primitive Organisms to Man A Symposium organized by the Section on Medical Sciences of the American Association for the Advancement of Science, and presented at the New York Meeting on December 29–30, 1956. Edited by Allan D. Bass. Pp. vii + 231. (Washington, D.C.: American Association for the Advancement of Science; London: Bailey Bros. and Swinfen, Ltd., 1959.) 52s.

The Central Nervous System

Obstructive sleep apnoea syndrome.

Introduction: Hsp60 (Cpn60) assembles into a tetradecamer that interacts with the co-chaperonin Hsp10 (Cpn10) to assist client polypeptides to fold, but it also has other roles, including participation in pathogenic mechanisms Area covered: Hsp60 chaperonopathies are pathological conditions, inherited or acquired, in which the chaperone plays a determinant etiologic-pathogenic role These diseases justify selection of Hsp60 as a target for developing agents that interfere with its pathogenic effects We provide information on how to proceed Expert opinion: The information available encourages the development of ways to improve Hsp60 activity (positive chaperonotherapy) when deficient or to block it (negative chaperonotherapy) when pathogenic Many questions are still unanswered and obstacles are obvious More information is needed to establish when and why autologous Hsp60 becomes a pathogenic autoantigen, or induces cytokine formation and inflammation, or favors carcinogenesis Clarification of these p

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Hsp60 chaperonopathies and chaperonotherapy: targets and agents

IL-1β, also known as “the master regulator of inflammation”, is a potent pro-inflammatory cytokine secreted by activated microglia in response to pathogenic invasions or neurodegeneration. It initiates a vicious cycle of inflammation and orchestrates various molecular mechanisms involved in neuroinflammation. The role of IL-1β has been extensively studied in neurodegenerative disorders; however, molecular mechanisms underlying inflammation induced by IL-1β are still poorly understood. The objective of our study is the comprehensive identification of molecular circuitry involved in IL-1β-induced inflammation in microglia through protein profiling. To achieve our aim, we performed the proteomic analysis of N9 microglial cells with and without IL-1β treatment at different time points. Expression of HSP60 in response to IL-1β administration was checked by quantitative real-time PCR, immunoblotting, and immunofluorescence. Interaction of HSP60 with TLR4 was determined by co-immunoprecipitation. Inhibition of TLR4 was done using TLR4 inhibitor to reveal its effect on IL-1β-induced inflammation. Further, effect of HSP60 knockdown and overexpression were assessed on the inflammation in microglia. Specific MAPK inhibitors were used to reveal the downstream MAPK exclusively involved in HSP60-induced inflammation in microglia. Total 21 proteins were found to be differentially expressed in response to IL-1β treatment in N9 microglial cells. In silico analysis of these proteins revealed unfolded protein response as one of the most significant molecular functions, and HSP60 turned out to be a key hub molecule. IL-1β induced the expression as well as secretion of HSP60 in extracellular milieu during inflammation of N9 cells. Secreted HSP60 binds to TLR4 and inhibition of TLR4 suppressed IL-1β-induced inflammation to a significant extent. Our knockdown and overexpression studies demonstrated that HSP60 increases the phosphorylation of ERK, JNK, and p38 MAPKs in N9 cells during inflammation. Specific inhibition of p38 by inhibitors suppressed HSP60-induced inflammation, thus pointed towards the major role of p38 MAPK rather than ERK1/2 and JNK in HSP60-induced inflammation. Furthermore, silencing of upstream modulator of p38, i.e., MEK3/6 also reduced HSP60-induced inflammation. IL-1β induces expression of HSP60 in N9 microglial cells that further augments inflammation via TLR4-p38 MAPK axis.

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HSP60 plays a regulatory role in IL-1β-induced microglial inflammation via TLR4-p38 MAPK axis

It has long been observed in clinical practice that a subset of patients with Lyme disease report a constellation of symptoms such as fatigue, cognitive difficulties, and musculoskeletal pain, which may last for a significant period of time. These symptoms, which can range from mild to severe, have been reported throughout the literature in both prospective and population-based studies in Lyme disease endemic regions. The etiology of these symptoms is unknown, however several illness-causing mechanisms have been hypothesized, including microbial persistence, host immune dysregulation through inflammatory or secondary autoimmune pathways, or altered neural networks, as in central sensitization. Evaluation and characterization of persistent symptoms in Lyme disease is complicated by potential independent, repeat exposures to B. burgdorferi, as well as the potential for co-morbid diseases with overlapping symptom profiles. Antibody testing for B. burgdorferi is an insensitive measure after treatment, and no other FDA-approved tests currently exist. As such, diagnosis presents a complex challenge for physicians, while the lived experience for patients is one marked by uncertainty and often illness invalidation. Currently, there are no FDA-approved pharmaceutical therapies, and the safety and efficacy of off-label and/or complementary therapies have not been well studied and are not agreed-upon within the medical community. Post-treatment Lyme disease represents a narrow, defined, mechanistically-neutral subset of this larger, more heterogeneous group of patients, and is a useful definition in research settings as an initial subgroup of study. The aim of this paper is to review the current literature on the diagnosis, etiology, risk factors, and treatment of patients with persistent symptoms in the context of Lyme disease. The meaning and relevance of existing patient subgroups will be discussed, as will future research priorities, including the need to develop illness biomarkers, elucidate the biologic mechanisms of disease, and drive improvements in therapeutic options.

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Post-treatment Lyme Disease as a Model for Persistent Symptoms in Lyme Disease.

Obstructive sleep apnea (OSA) is a highly prevalent disease, and is traditionally associated with increased cardiovascular risk. The role of comorbidities in OSA patients has emerged recently, and new conditions significantly associated with OSA are increasingly reported. A high comorbidity burden worsens prognosis, but some data suggest that CPAP might be protective especially in patients with comorbidities. Aim of this narrative review is to provide an update on recent studies, with special attention to cardiovascular and cerebrovascular comorbidities, the metabolic syndrome and type 2 diabetes, asthma, COPD and cancer. Better phenotypic characterization of OSA patients, including comorbidities, will help to provide better individualized care. The unsatisfactory adherence to CPAP in patients without daytime sleepiness should prompt clinicians to examine the overall risk profile of each patient in order to identify subjects at high risk for worse prognosis and provide the optimal treatment not only for OSA, but also for comorbidities.

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Obstructive sleep apnea and comorbidities: a dangerous liaison

To illustrate the characteristics of endurance exercise training and its positive effects on health.To provide an overview on the effects of endurance training on airway cells and bronchial reactivity.To summarise the current knowledge on respiratory health problems in elite athletes. Endurance exercise training exerts many positive effects on health, including improved metabol-ism, reduction of cardiovascular risk, and reduced all-cause and cardiovascular mortality. Intense endurance exercise causes mild epithelial injury and inflammation in the airways, but does not appear to exert detrimental effects on respiratory health or bronchial reactivity in recreational/non-elite athletes. Conversely, elite athletes of both summer and winter sports show increased susceptibility to development of asthma, possibly related to environmental exposures to allergens or poor conditioning of inspired air, so that a distinct phenotype of "sports asthma" has been proposed to characterise such athletes, who more often practise aquatic and winter sports. Overall, endurance training is good for health but may become deleterious when performed at high intensity or volume.

https://breathe.ersjournals.com/content/breathe/12/2/140.full.pdf

Endurance training: Is it bad for you?

In this work we analysed, by immunohistochemistry, a series of brain tumors to detect the levels and cellular distribution of Hsp60 and Hsp70. We found that Hsp60 levels were significantly higher than those of Hsp70 in neuroepithelial tumors, while levels of both molecules were not significantly different from each other in meningeal neoplasms. In particular, Hsp60 immunopositivity was present mainly at the cytoplasmic level, while Hsp70 immunopositivity was found both in the cytoplasm and in the nucleus of tumor cells. The levels of these molecules in healthy control cells were always very low. Finally, Hsp60 and Hsp70 levels did not correlate with the different types (WHO grade) of neoplasm. Our results are partially in agreement with previous studies and suggest that Hsp60 is not increased by a passive phenomenon (e.g., due to the stress caused by the peritumor environment on cancer cells) but may be actively implicated in tumor progression, e.g. inhibiting tumor cell death or antitumor immune system response, as already postulated in vitro. We also briefly discuss the most recent publications on the extramitochondrial localization of Hsp60 in tumor cells and its role in tumor progression.

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Different Immunohistochemical Levels of Hsp60 and Hsp70 in a Subset of Brain Tumors and Putative Role of Hsp60 in Neuroepithelial Tumorigenesis

Individuals with Chronic Obstructive Pulmonary Disease (COPD) experience sleep disturbances due to the impact of respiratory symptoms on sleep quality. We explored whether sleep disturbances in COP...

Sleep Disturbances in COPD are Associated with Heterogeneity of Airway Obstruction

Continuous positive airway pressure (CPAP) is the first-choice treatment for obstructive sleep-disordered breathing. Automatic bilevel ventilation can be used to treat obstructive sleep-disordered breathing when CPAP is ineffective, but clinical experience is still limited. To assess the outcome of titration with CPAP and automatic bilevel ventilation, the charts of 356 outpatients (obstructive sleep apnea, n = 242; chronic obstructive pulmonary disease + obstructive sleep apnea overlap, n = 80; obesity hypoventilation syndrome [OHS], n = 34; 103 females) treated for obstructive sleep-disordered breathing from January 2014 to April 2017 were reviewed. Positive airway pressure titration was considered successful in the case of sleep-disordered breathing resolution (apnea-hypopnea index 40 kg/m2 (odds ratio 6.16, confidence interval 1.50-25.17, p = 0.011) and CT90% >42% (odds ratio 5.87, confidence interval 1.39-24.83, p = 0.016). During follow-up, automatic bilevel ventilation treatment failed in seven patients (10%), and compliance was similar in CPAP (4.5 ± 2.2 hr) and automatic bilevel ventilation (5.2 ± 2.3 hr, p = 0.09) groups. Automatic bilevel ventilation was useful to treat sleep-disordered breathing, but failed in patients with severe OHS.

Pierpaolo Baiamonte

Papers

Obstructive sleep apnea and comorbidities: a dangerous liaison

Endurance training: Is it bad for you?

Different Immunohistochemical Levels of Hsp60 and Hsp70 in a Subset of Brain Tumors and Putative Role of Hsp60 in Neuroepithelial Tumorigenesis

Sleep Disturbances in COPD are Associated with Heterogeneity of Airway Obstruction

Use of autobilevel ventilation in patients with obstructive sleep apnea: An observational study.