Anatomy and physiology of the autonomic nervous system: Implication on the choice of diagnostic/monitoring tools in 2023.

The autonomic nervous system (ANS) harmoniously regulates all internal organic functions (heart rate, blood pressure, vasomotion, digestive tract motility, endocrinal secretions) and adapts them to the needs. It's the control of so-called vegetative functions, which allows homeostasis but also allostasis of our body. ANS is divided into two systems often understood as antagonistic and complementary: the sympathetic and the parasympathetic systems. However, we currently know of many situations of co-activation of the two systems. Long seen as acting through "reflex" control loops passing through the integration of peripheral information and the efferent response to the peripheral organ, more recent electrophysiological and brain functional imaging knowledge has been able to identify the essential role of the central autonomic network. This element complicates the understanding of the responses of the reflex loops classically used to identify and quantify dysautonomia. Finding the "ANS" tools best suited for the clinician in their daily practice is a challenge that we will attempt to address in this work.

Mechanically activated mesenchymal-derived bone cells drive vessel formation via an extracellular vesicle mediated mechanism.

Blood vessel formation is an important initial step for bone formation during development as well as during remodelling and repair in the adult skeleton. This results in a heavily vascularized tissue where endothelial cells and skeletal cells are constantly in crosstalk to facilitate homeostasis, a process that is mediated by numerous environmental signals, including mechanical loading. Breakdown in this communication can lead to disease and/or poor fracture repair. Therefore, this study aimed to determine the role of mature bone cells in regulating angiogenesis, how this is influenced by a dynamic mechanical environment, and understand the mechanism by which this could occur. Herein, we demonstrate that both osteoblasts and osteocytes coordinate endothelial cell proliferation, migration, and blood vessel formation via a mechanically dependent paracrine mechanism. Moreover, we identified that this process is mediated via the secretion of extracellular vesicles (EVs), as isolated EVs from mechanically stimulated bone cells elicited the same response as seen with the full secretome, while the EV-depleted secretome did not elicit any effect. Despite mechanically activated bone cell-derived EVs (MA-EVs) driving a similar response to VEGF treatment, MA-EVs contain minimal quantities of this angiogenic factor. Lastly, a miRNA screen identified mechanoresponsive miRNAs packaged within MA-EVs which are linked with angiogenesis. Taken together, this study has highlighted an important mechanism in osteogenic-angiogenic coupling in bone and has identified the mechanically activated bone cell-derived EVs as a therapeutic to promote angiogenesis and potentially bone repair.

The physical activity experience of prostate cancer patients: a multicentre peer motivation monitoring feasibility study. The Acti-Pair study.

BACKGROUND: Although the benefits of physical activity (PA) on health are recognised, prostate cancer patients do not follow PA recommendations. The barriers to PA, whether physical, environmental or organisational, are known. Furthermore, even when such barriers are overcome, this achievement is not systematically accompanied by a change in lifestyle habits. The proposal of a programme enabling the integration of PA in the patient's everyday life represents a new challenge in the personalized management of cancer patients. Peer-mentoring interventions have demonstrated their effectiveness in increasing adherence to PA by patients. This study aimed (1) to assess the feasibility of a peer-mentoring intervention: the Acti-Pair program in a local context and (2) to assess the effectiveness of the intervention in this context. METHODS AND ANALYSIS: A pre-post  design pilot study will be used to evaluate feasibility, potential effectiveness and implementation outcomes overs in prostate cancer patients. We performed a mixed quantitative and qualitative prospective study to assess means and process indicators and the implementation of the Acti-Pair program. This study will be performed in cancer centres of Loire district and will be comprised of three successive stages (1) diagnosis of the target population, (2) recruitment and training of peers, and (3) implementation of this intervention in the Loire department. DISCUSSION: This study will allow us to extend the peer-mentoring intervention to other contexts and assess the effectiveness of this intervention and its generalisability.

Oral health status and cardiovascular risk profile in Cameroonian military population.

BACKGROUND: Periodontal diseases (PD) seem to appear today as predictors of some cardiovascular diseases (CVD). There is a lack of data on the oral health among Cameroonian military population, and its relationship with CVD. PURPOSE: Investigate on the link between oral health of Cameroonian military from the Ngaoundéré garrison and their cardiovascular risk profile. PARTICIPANTS AND METHODS: A cross-sectional study at the Fifth Military Sector Health Center in Ngaoundéré was conducted. General health parameters assessment was done according to the World Health Organization STEPS manual for surveillance of risk factors for non-communicable chronic diseases and the Alcohol Use Disorders Identification Test. The periodontal status was assessed using Dutch Periodontal Screening Index. RESULTS: Two hundred and five participants who were officers and non-commissioned officers (aged 47 ± 08 and 32 ± 08 years respectively), with 86.4% of men were included. Smoking was associated to periodontitis (OR = 4.44 [1.73-11.43], p = 0.0031). Quality of oral hygiene was associated to high cardiovascular risk profile, poor/good (OR = 3.96 [1.07-14.57], p = 0.0386) and medium/good (OR = 3.44 [1.11-10.66], p = 0.0322). CONCLUSION: Lifestyle as tobacco consumption and poor oral hygiene were associated to CVD among military, and this call for change.

Care through cohort studies: sociological survey of the PROOF cohort study on vascular and cognitive aging.

BACKGROUND: The success of health research depends on the involvement of participants. Few studies have examined the participation of subjects in cohorts. Drawing on a sociological survey on a French cohort around aging, this study proposes to question the nature of interactions between researchers and subjects that would help to understand the motivations of subjects to participate and remain in health research studies. METHODS: Qualitative study combining participant observation within the research laboratory that conducted the cohort and semi-structured interviews with subjects included in the cohort and with members of the research team. RESULTS: This study highlights the existence of two-way care: from the laboratory to the subjects and from the cohort to researchers. Health research seems to correspond to a complex association between subjects concerned with aging and the expected benefits of exceptional monitoring. Research is incorporated into subjects' daily lives, allowing a shift in the purpose of research from overmedicalization to medical safety that subjects experienced as a form of care. CONCLUSIONS: In cohort studies, care is understood as a form of attention to the person through high-quality medical follow-up. Aging is turned into a matter of concern that subjects, in collaboration with researchers, strive to control.

Long-lasting active lifestyle and successful cognitive aging in a healthy elderly population: The PROOF cohort.

OBJECTIVES: The aim of this study was to determine whether cognitive reserve in the elderly affects the evolution of cognitive performance and what its relationship is with active lifestyles in later life. METHODS: Cognitive performance was evaluated at baseline and 8 years later in 543 participants of the PROOF cohort, initially aged 67 years. Subjects were categorized as Cognitively Elite (CE), Cognitively Normal (CN) or Cognitively Impaired (CI) at each evaluation. At follow-up, demographic data and lifestyle, including social, intellectual and physical behaviors, were collected by questionnaires. RESULTS: As much as 69% (n=375) remained unchanged, while 25.5% (n=138) decreased and 5.5% (n=30) improved. When present, the reduction in cognitive status was most often limited to one level, but was dependent on the initial level, affecting up to 73% of the initially CN, but only 58% of the initially CE. Cognitive stability was significantly associated with the degree of social engagement at follow-up (CE: P=0.009; CN: P=0.025). CONCLUSION: In the healthy elderly, high cognitive ability predicts both cognitive ability and social involvement in later life. Cognitive decline by only one level may also extend the time to reach impairment, underlining the importance of the so-called cognitive reserve.

Tyrosinemia type II: Mutation update, 11 novel mutations and description of 5 independent subjects with a novel founder mutation.

BACKGROUND: Tyrosinemia type II, also known as Richner-Hanhart Syndrome, is an extremely rare autosomal recessive disorder, caused by mutations in the gene encoding hepatic cytosolic tyrosine aminotransferase, leading to the accumulation of tyrosine and its metabolites which cause ocular and skin lesions, that may be accompanied by neurological manifestations, mostly intellectual disability. AIMS: To update disease-causing mutations and current clinical knowledge of the disease. MATERIALS AND METHODS: Genetic and clinical information were obtained from a collection of both unreported and previously reported cases. RESULTS: We report 106 families, represented by 143 individuals, carrying a total of 36 genetic variants, 11 of them not previously known to be associated with the disease. Variants include 3 large deletions, 21 non-synonymous and 5 nonsense amino-acid changes, 5 frameshifts and 2 splice variants. We also report 5 patients from Gran Canaria, representing the largest known group of unrelated families sharing the same P406L mutation. CONCLUSIONS: Data analysis did not reveal a genotype-phenotype correlation, but stressed the need of early diagnosis: All patients improved the oculocutaneous lesions after dietary treatment but neurological symptoms prevailed. The discovery of founder mutations in isolated populations, and the benefits of early intervention, should increase diagnostic awareness in newborns.

Point prevalence survey of healthcare-associated infections and use of antimicrobials in Irish intellectual disability long-term care facilities: 2013.

BACKGROUND: Healthcare-associated infections (HCAIs) and use of antimicrobials are prevalent in long-term care facilities (LTCFs), but few data are available on the burden of these issues in intellectual disability (ID) LTCFs. AIM: To assess the prevalence of HCAIs and use of antimicrobials in Irish ID-LTCFs to plan future HCAI prevention programmes. METHODS: A national point prevalence survey was conducted in Irish ID-LTCFs in May 2013 using a European protocol. All Irish ID-LTCFs with full-time residents were invited to participate in this voluntary survey. Data were collected locally and analysed at the national coordinating centre. RESULTS: Twenty-four Irish ID-LTCFs participated, with 1060 residents surveyed, representing 42% of ID-LTCF residents in Ireland. The crude HCAI prevalence rate was 4.3% (median 2.2, range 0-46.7), with respiratory tract infections (1.6%) and skin infections (1.6%) being the most prevalent types. Antimicrobials were prescribed for 10% of eligible residents (median 7.5, range 3.2-13.9), with 49% of all prescriptions indicated for prophylaxis. Prevention of urinary tract infections (38%), respiratory tract infections (36%) and skin infections (27%) were the most common reasons for prophylaxis. There was considerable variation in the prevalence of prescribing for prophylaxis across ID-LTCFs (range 2-29%), with only 17% of facilities having local antimicrobial guidelines in place. CONCLUSION: There is a considerable burden of HCAIs and use of antimicrobials, particularly for skin and respiratory tract infections, in Irish ID-LTCFs. Further surveillance in this population is needed to help guide preventive strategies for ID-LTCF residents at risk of these infections.

Subjective sleep and cognitive complaints in 65 year old subjects: a significant association. The PROOF cohort.

OBJECTIVE: The prevalence of subjective sleep and cognitive complaints increases with age. The purpose of this study was to investigate the link between subjective cognitive and sleep complaints in a population aged 65. DESIGN AND SETTING: analysis of a cohort of 1011 subjects aged 65 years old at time of inclusion. METHODS: Older people underwent a cognitive tests battery and a nocturnal polygraphy recording. Subjective cognitive difficulties were scored on the McNair and Kahn Scale. Subjective sleep complaints were evaluated according to the St. Mary's Hospital Sleep Questionnaire and the Epworth Sleepiness Scale score. RESULTS: In a 65 years old population, an association between subjective cognitive difficulties and poor sleep quality was observed. This remained significant after adjustment on gender, depression score, anxiety, educational level, medication intake, Apnea/Hypopnea index, Body Mass Index and Mini-Mental State Examination (OR = 2.1; p = 0.0002). Similar significant association was demonstrated between subjective cognitive difficulties and daytime sleepiness (OR = 2.6; p = 0.0007). CONCLUSION: There was a significant association between subjective cognitive and sleep complaints, and daytime sleepiness in our population of older people.

Healthcare-associated infections and antimicrobial use in long-term care facilities: the Irish experience with the HALT surveys.

In the context of an ageing European population, point prevalence surveys (PPS) of healthcare-associated infection and antimicrobial use in long-term care facilities (HALT) in Europe were commissioned by the European Centre for Disease Prevention and Control. Sixty-nine Irish long-term care facilities (LTCFs) took part in the first survey in 2010. A series of interventions to raise the profile of infection prevention and control and antimicrobial stewardship in Irish LTCFs followed. HALT was repeated in Ireland in 2011, with 108 participating LTCFs, and again in 2013 as part of the second European HALT survey, with 190 participating LTCFs. The latest Irish HALT report incorporates data from the three PPSs to date, and discusses the findings and the national implementation priorities recommended by the Irish multi-disciplinary steering group. Ireland contributed ∼10% of the total resident population in both of the European HALT PPSs. This, and the growing number of participating LTCFs, shows that healthcare professionals in Irish LTCFs are committed to improving the quality and safety of resident care.

Seven-year predictors of self-rated health and life satisfaction in the elderly: the PROOF study.

OBJECTIVES: To investigate the relationship between cognitive performance, affective state, metabolic syndrome and 7-year follow-up self-rated health (SRH) and perceived life satisfaction (PLS). DESIGN: Analysis of a prospective cohort study. SETTING: The PROOF study, including 1011 elderly community residents. PARTICIPANTS: Six hundred and fifty seven subjects completed metabolic syndrome (Met S) variables, neuropsychological and affective measurements at baseline, and then returned a 7-year follow-up questionnaire which included SRH and PLS. MEASUREMENTS: The prospective association between cognitive function, Met S and each of its components, and affective disorders and subsequent subjective health and quality of life was examined. Covariates included educational level and use of tobacco. The analyses were made in men and women separately. RESULTS: In multivariate models, the presence of Met S was significantly associated to weaker SRH (OR = 2.78, p = 0.009 in men and OR = 2.0, p = 0.02 in women). Higher triglycerides rate were associated with weaker SRH in men (OR = 2.23, p = 0.002) and higher fasting glucose in women (OR = 2.54, p = 0.006). Global Met S and abdominal obesity was significantly associated to weaker PLS in women only (respectively OR = 2.70, p = 0.0002 and OR = 1.9, p = 0.02). Depressive symptoms were significantly associated to both weaker SRH and PLS in men (OR = 1.30, p = 0.002; OR = 1.44, p < 0.0001 for SRH and PLS respectively) and in woman (OR = 1.09, p = 0.04; OR = 1.26, p < 0.0001 for SRH and PLS respectively). Anxiety was linked to both weaker SRH and PLS in women (OR = 1.17, p = 0.002 and 0R = 1.11, p = 0.03 for SRH and PLS respectively). Finally, lower executive function was associated with weaker PLS in men (OR = 0.43, p = 0.0005). CONCLUSION: metabolic syndrome and certain of its components, anxiety and depressive symptoms, are independent predictors of poorer subjective health and quality of life as assessed over a period of 7 years in a population of a non-demented aging community. Moreover, executive performance was linked to subsequent quality of life in men. Many of these factors being treatable, our findings point to the necessity of providing preventive care strategies by the management of cardiovascular risk factors and anxio-depressive symptoms.

Sleep fragmentation and sleep-disordered breathing in individuals living close to main roads: results from a population-based study.

BACKGROUND: Nighttime traffic noise is associated with sleep disturbances, but sleep fragmentation and sleep-disordered breathing (SDB) have not been demonstrated in individuals living near busy roads. METHODS: We asked 1383 participants to answer a health questionnaire and to undergo 24-h electrocardiogram (ECG). Nocturnal ECG records were used to calculate the very low frequency index (VLFI) interval, a surrogate marker of sleep fragmentation. Distances of participants' addresses to roadways were calculated using the VECTOR25© Swisstopo roads classification, a traffic noise proxy. Distances of homes within 100 or 50 m of major roads defined proximity to busy roads. Adjusted multivariate logistic regressions analyzed associations between the distance of home to main roads and VLFI or self-reported SDB. RESULTS: Distance of participants' homes to main roads was significantly associated with the VLFI in women (odds ratio [OR], 1.58 [confidence interval {CI}, 1.03-2.42]; P = .038) but not in men (OR, 1.35 [CI, 0.77-2.35]; P = .295). Women under hormonal replacement therapy (HRT) were at higher risk for increased VLFI when living close to main roads (OR, 2.10 [CI, 1.20-3.68]; P = .01) than untreated women (P = .584). Associations with self-reported SDB were not statistically relevant. CONCLUSIONS: In our large population, women living close to main roads were at significantly higher risk for sleep fragmentation than men. The 2-fold higher risk for menopausal women under HRT underscores the vulnerability of this group.

[Autonomic regulation and bradycardia during the neonatal period]. / Régulation autonomique et bradycardies néonatales.

The high frequency of bradycardia observed during the neonatal period requires cardiac monitoring but also understanding its intrinsic mechanisms, including responsiveness of the autonomic nervous system (ANS). Heart rate variability and spontaneous baroreflex analysis can help understand the autonomic dysregulation of cardiorespiratory control, possibly responsible for sudden infant death. In clinical neonatology practice, neonatal bradycardia does not warrant continuation of monitoring if it remains isolated, asymptomatic, and short (<10 s), followed by a rapid cardiac acceleration indicating an adapted sympathetic response. Further evaluation of ANS responsiveness is possible for newborns including analyzing the complexity of the heart rate and respiratory variability. This allows better targeting children with high risk after discharge. The real-time evaluation of autonomic regulation could become a valuable tool in clinical practice.

Sympathetic overactivity due to sleep fragmentation is associated with elevated diurnal systolic blood pressure in healthy elderly subjects: the PROOF-SYNAPSE study.

AIMS: Sleep fragmentation is a landmark of sleep disorders, because microarousals are systematically associated with sympathetic surges (i.e., sympathetic arousals). However, the impact of sympathetic sleep fragmentation on blood pressure (BP) remains understudied. We assessed the relationships between 24 h ambulatory BP monitoring, the autonomic arousal index (AAI) derived from pulse transit time, and heart rate variability indices. We hypothesized that repeated sympathetic arousals during sleep are associated with elevated BP in a large population of elderly volunteers. METHODS AND RESULTS: Volunteer subjects (n = 780, 57.4% women) with a mean age of 68.7 years and free of known sleep-disordered breathing, coronary heart diseases, and neurological disorders underwent polygraphy, 24 h ECG Holter monitoring, and 24 h ambulatory BP monitoring. Multivariate regressions showed that sleep fragmentation, expressed by AAI, was associated with elevated diurnal (P = 0.008) and 24 h (P = 0.005) systolic BP and higher risk for 24 h [odds ratio (OR): 1.70 (1.04-2.80), P = 0.036] systolic hypertension, independently of confounders such as sleep-disordered breathing, body mass index, sex, diabetes, hypercholesterolaemia, and self-reported sleep duration and quality. Increased AAI was associated with higher nocturnal and diurnal low-frequency power (P < 0.001) and low-to-high-frequency ratio (P < 0.001), suggesting nocturnal and diurnal sympathetic overactivity. CONCLUSION: In healthy elderly subjects, repetitive sympathetic arousals during sleep are associated with elevated systolic BP and higher risk of hypertension, after controlling for confounders. Sympathetic overactivity is the proposed underlying mechanism. CLINICAL TRIAL REGISTRATION: NCT00766584 and NCT00759304.

[Chronic cough in the elderly is associated with expiratory flow limitation]. / La toux chronique du sujet âgé est associée à une limitation expiratoire des débits.

As chronic respiratory symptoms and the presence of expiratory flow limitation (EFL) are commonly reported in the elderly, we investigated whether they were associated in a population of 75 years old volunteers. We analyzed the results of a prevalence survey of chronic respiratory symptoms and respiratory infections, and performed spirometry and measured EFL after application of a negative expiratory pressure at the mouth (NEP). EFL was present in 170 (46%) subjects, a chronic cough in 49 (13%), chronic sputum in 58 (29%) and a history of respiratory infection in 62 (17%). Chronic cough and the composite outcome "chronic cough or sputum" were significantly associated with the presence of EFL (respectively 60% vs. 43%, OR=2.04 [1.09 to 3.78], P=0.023, and 56% vs. 43%, OR=1.74 [1.05 to 2.87], P=0.04), after controlling for smoking or airway obstruction. History of respiratory infections were not associated with an increased prevalence of EFL. We concluded that the presence of a LED could be an interesting indicator of respiratory aging. Its detection could be advocated in elderly subjects presenting with respiratory symptoms.

Catheter-related infection in Irish intensive care units diagnosed with HELICS criteria: a multi-centre surveillance study.

BACKGROUND: Catheter-related infection (CRI) surveillance is advocated as a healthcare quality indicator. However, there is no national CRI surveillance programme or standardized CRI definitions in Irish intensive care units (ICUs). AIM: To examine the feasibility of multi-centre CRI surveillance in nine Irish ICUs, using Hospitals in Europe Link for Infection Control through Surveillance (HELICS) definitions (CRI 1, CRI 2 and CRI 3). METHODS: All non-tunnelled central venous catheters (CVCs) inserted in patients aged >18 years with an ICU stay ≥48 h were included over a three-month study period. FINDINGS: Feasibility was demonstrated by the 99.5% return rate for study forms. Data on 1209 CVCs in 614 patients over 7587 CVC-days showed 17 episodes of CRI, representing a national rate of 2.2 per 1000 CVC-days [95% confidence interval (CI) 1.2-3.3]. Rates of CRI 1, CRI 2 and CRI 3 were 0.13 (95% CI 0.00-0.39), 0.79 (95% CI 0.16-1.42) and 1.39 (95% CI 0.60-2.17) per 1000 CVC-days, respectively. CRI was associated with length of ICU stay (P < 0.001), number of CVCs inserted (P < 0.001) and total number of CVC-days per patient (P < 0.001). CRI was higher in CVCs inserted in operating theatres (incident rate ratio 3.9, 95% CI 1.3-11.5; P = 0.02) compared with CVCs inserted in ICUs. Participant feedback reported minimal difficulty with surveillance implementation, and data collection required approximately 1 h per patient per week. CONCLUSION: The study demonstrated that multi-centre ICU surveillance using HELICS CRI definitions was practical, feasible and provided clinically relevant information. CRI surveillance in ICUs, although labour intensive, is recommended to reduce CRI and allow ongoing evaluation of processes aimed at CRI reduction.

Healthcare-associated infection in Irish long-term care facilities: results from the First National Prevalence Study.

BACKGROUND: Prevalence of healthcare-associated infection (HCAI) and antimicrobial use in Irish long-term care facilities (LTCFs) has never been studied. AIM: To collect baseline data on HCAI prevalence and antibiotic use in Irish LTCFs to inform national LTCF policy and plan future HCAI prevention programmes. METHODS: A prevalence study of HCAI and antibiotic use was undertaken in Irish LTCFs. Participation was voluntary. Data on HCAI risk factors, signs and symptoms of infection and antimicrobial use were collected prospectively on a single day in each institution. FINDINGS: Sixty-nine Irish LTCFs participated and 4170 eligible residents were surveyed; 472 (11.3%) had signs/symptoms of infection (266, 6.4%) and/or were on antibiotics (426, 10.2%). A third of residents (1430, 34.3%) were aged ≥85 years and more than half disorientated (2110, 50.6%) with impaired mobility (2101, 50.4%). HCAI prevalence was 3.7% (range: 0-22.2%). The most common HCAI was urinary tract infection (UTI) (62 residents, 40% of HCAI). Presence of a urinary catheter was associated with UTI (P < 0.0000001). Antibiotics were prescribed for treatment (262 residents, 57.8%) and prophylaxis (182 residents, 40.2%) of infection. The most common indication for prophylaxis was UTI prevention (35.8% of total prescriptions). Fourteen (10.2%) residents on UTI prophylaxis had a urinary catheter. The most common indications for therapy included respiratory tract infections (35.1%), UTI (32.1%) and skin infection (21.8%). CONCLUSION: This study highlights the frequency of prophylactic antimicrobial prescribing and provides an important baseline to inform future preventive strategies.