Low-Dose Doxycycline Treatment Normalizes Levels of Some Salivary Metabolites Associated with Oral Microbiota in Patients with Primary Sjögren’s Syndrome

Saliva is a complex oral fluid, and plays a major role in oral health. Primary Sjögren’s syndrome (pSS), as an autoimmune disease that typically causes hyposalivation. In the present study, salivary metabolites were studied from stimulated saliva samples (n = 15) of female patients with pSS in a group treated with low-dose doxycycline (LDD), saliva samples (n = 10) of non-treated female patients with pSS, and saliva samples (n = 14) of healthy age-matched females as controls. Saliva samples were analyzed with liquid chromatography mass spectrometry (LC-MS) based on the non-targeted metabolomics method. The saliva metabolite profile differed between pSS patients and the healthy control (HC). In the pSS patients, the LDD treatment normalized saliva levels of several metabolites, including tyrosine glutamine dipeptide, phenylalanine isoleucine dipeptide, valine leucine dipeptide, phenylalanine, pantothenic acid (vitamin B5), urocanic acid, and salivary lipid cholesteryl palmitic acid (CE 16:0), to levels seen in the saliva samples of the HC. In conclusion, the data showed that pSS is associated with an altered saliva metabolite profile compared to the HC and that the LLD treatment normalized levels of several metabolites associated with dysbiosis of oral microbiota in pSS patients. The role of the saliva metabolome in pSS pathology needs to be further studied to clarify if saliva metabolite levels can be used to predict or monitor the progress and treatment of pSS

Low-Dose Doxycycline Treatment Normalizes Levels of Some Salivary Metabolites Associated with Oral Microbiota in Patients with Primary Sjögren’s Syndrome

Saliva is a complex oral fluid, and plays a major role in oral health. Primary Sjögren’s syndrome (pSS), as an autoimmune disease that typically causes hyposalivation. In the present study, salivary metabolites were studied from stimulated saliva samples (n = 15) of female patients with pSS in a group treated with low-dose doxycycline (LDD), saliva samples (n = 10) of non-treated female patients with pSS, and saliva samples (n = 14) of healthy age-matched females as controls. Saliva samples were analyzed with liquid chromatography mass spectrometry (LC-MS) based on the non-targeted metabolomics method. The saliva metabolite profile differed between pSS patients and the healthy control (HC). In the pSS patients, the LDD treatment normalized saliva levels of several metabolites, including tyrosine glutamine dipeptide, phenylalanine isoleucine dipeptide, valine leucine dipeptide, phenylalanine, pantothenic acid (vitamin B5), urocanic acid, and salivary lipid cholesteryl palmitic acid (CE 16:0), to levels seen in the saliva samples of the HC. In conclusion, the data showed that pSS is associated with an altered saliva metabolite profile compared to the HC and that the LLD treatment normalized levels of several metabolites associated with dysbiosis of oral microbiota in pSS patients. The role of the saliva metabolome in pSS pathology needs to be further studied to clarify if saliva metabolite levels can be used to predict or monitor the progress and treatment of pSS. </p

Infant motor development and physical activity and sedentary time at midlife

Abstract This study investigated whether the timing of infant motor development is associated with self-reported and accelerometer-measured physical activity (PA) and sedentary time (ST) in midlife. This population-based study consisted of 4098 people born in 1966 in Northern Finland (NFBC 1966). Data on nine infant motor developmental milestones included making sounds, holding up the head, grabbing objects, turning from back to tummy, sitting without support, standing with support, walking with support, standing without support, and walking without support. At the age of 46, PA at leisure time and sitting time was self-reported. PA and ST were also measured with a wrist-worn Polar Active accelerometer that was instructed to be worn on the non-dominant hand 24 h/d for 14 days. A multiple linear regression analysis was used to analyze the association between infant motor development and PA and ST in midlife. Later infant motor development was weakly associated with higher accelerometer-measured light PA, but not with moderate-to-vigorous PA. Later infant locomotor development was associated with lower accelerometer-measured ST (β −0.07, p = 0.012) and lower self-reported sitting time at work (β −0.06, p = 0.004) in women. In conclusion, later infant motor development was associated with higher light PA and lower sedentary time at middle age. PA is a multifactorial behavior influenced by various factors from early childhood to midlife. Further research is required before more general conclusions can be drawn

Compositional associations of sleep and activities within the 24-h cycle with cardiometabolic health markers in adults

Abstract Purpose: This study aimed to examine how compositions of 24-h time use and time reallocations between movement behaviors are associated with cardiometabolic health in a population-based sample of middle-age Finnish adults. Methods: Participants were 3443 adults 46 yr of age from the Northern Finland Birth Cohort 1966 study. Participants wore a hip-worn accelerometer for 14 d from which time spent in sedentary behavior (SB), light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) were determined. These data were combined with self-reported sleep to obtain the 24-h time-use composition. Cardiometabolic outcomes included adiposity markers, blood lipid levels, and markers of glucose control and insulin sensitivity. Multivariable-adjusted regression analysis, using a compositional data analysis approach based on isometric log-ratio transformation, was used to examine associations between movement behaviors with cardiometabolic outcomes. Results: More daily time in MVPA and LPA, relative to other movement behaviors, was consistently favorably associated with all cardiometabolic outcomes. For example, relative to time spent in other behaviors, 30 min·d−1 more MVPA and LPA were both associated with lower 2-h post–glucose load insulin level (−11.8% and −2.7%, respectively). Relative to other movement behaviors, more daily time in SB was adversely associated with adiposity measures, lipid levels, and markers of insulin sensitivity, and more daily time asleep was adversely associated with adiposity measures, blood lipid, fasting plasma glucose, and 2-h insulin. For example, 60 min·d−1 more SB and sleep relative to the remaining behaviors were both associated with higher 2-h insulin (3.5% and 5.7%, respectively). Conclusions: Altering daily movement behavior compositions to incorporate more MVPA at the expense of any other movement behavior, or more LPA at the expense of SB or sleep, could help to improve cardiometabolic health in midadulthood

Satellite imaging-based residential greenness and accelerometry measured physical activity at midlife:population-based Northern Finland Birth Cohort 1966 study

Abstract Background: Recently, the importance of light physical activity (LPA) for health has been emphasized, and residential greenness has been positively linked to the level of LPA and a variety of positive health outcomes. However, people spend less time in green environments because of urbanization and modern sedentary leisure activities. Aims: In this population-based study, we investigated the association between objectively measured residential greenness and accelerometry measured physical activity (PA), with a special interest in LPA and gender differences. Methods: The study was based on the Northern Finland Birth Cohort 1966 (5433 members). Participants filled in a postal questionnaire and underwent clinical examinations and wore a continuous measurement of PA with wrist-worn Polar Active Activity Monitor accelerometers for two weeks. The volume of PA (metabolic equivalent of task or MET) was used to describe the participant’s total daily activity (light: 2–3.49 MET; moderate: 3.5–4.99 MET; vigorous: 5–7.99 MET; very vigorous: ≥8 MET). A geographic information system (GIS) was used to assess the features of each individual’s residential environment. The normalized difference vegetation index (NDVI) was used for the objective quantification of residential greenness. Multiple linear regression and a generalized additive model (GAM) were used to analyze the association between residential greenness and the amount of PA at different intensity levels. Results: Residential greenness (NDVI) was independently associated with LPA (unadjusted β = 174; CI = 140, 209) and moderate physical activity (MPA) (unadjusted β = 75; CI = 48, 101). In the adjusted model, residential greenness was positively and significantly associated with LPA (adjusted β = 70; CI = 26, 114). In men, residential greenness was positively and significantly associated with LPA (unadjusted β = 224; CI = 173, 275), MPA (unadjusted β = 75; CI = 48, 101), and moderate to vigorous physical activity (MVPA) (unadjusted β = 89; CI = 25, 152). In women, residential greenness was positively related to LPA (unadjusted β = 142; CI = 96, 188) and inversely associated with MPA (unadjusted β = −22; CI = −36, −8), vigorous/very vigorous physical activity (VPA/VVPA) (unadjusted β = −49; CI = −84, −14), and MVPA (unadjusted β = −71; CI = −113, −29). In the final adjusted models, residential greenness was significantly associated only with the amount of LPA in men (adjusted β = 140; CI = 75, 204). Conclusions: Residential greenness was positively associated with LPA in both genders, but the association remained significant after adjustments only in men. Residential greenness may provide a supportive environment for promoting LPA

Intensity and temporal patterns of physical activity and cardiovascular disease risk in midlife

Abstract Physical activity (PA) and sedentary time (SED) are associated with the risk of cardiovascular disease (CVD), but the temporal patterns of these behaviors most beneficial for cardiovascular health remain unknown. We aimed to identify the intensity and temporal patterns of PA and SED measured continuously by an accelerometer and their relationship with CVD risk. At the age of 46 years, 4582 members (1916 men; 2666 women) of the Northern Finland Birth Cohort 1966 study underwent continuous measurement of PA with Polar Active (Polar Electro, Finland) accelerometers for one week. X-means clustering was applied based on 10 min average MET (metabolic equivalent) values during the measurement period. Ten-year risk of CVD was estimated using the Framingham risk model. Most of the participants had low risk for CVD. Four distinct PA clusters were identified that were well differentiable by the intensity and temporal patterns of activity (inactive, evening active, moderately active, very active). A significant difference in 10-year CVD risk across the clusters was found in men (p = 0.028) and women (p &lt; 0.001). Higher levels of HDL cholesterol were found in more active clusters compared to less active clusters (p &lt; 0.001) in both genders. In women total cholesterol was lower in the moderately active cluster compared to the inactive and evening active clusters (p = 0.001). Four distinct PA clusters were recognized based on accelerometer data and X-means clustering. A significant difference in CVD risk across the clusters was found in both genders. These results can be used in developing and promoting CVD prevention strategies

Variability of salivary metabolite levels in patients with Sjögren’s syndrome

Abstract Purpose: To investigate inter- and intra-individual variation in the levels and outputs (concentration multiplied by salivary flow rate) of salivary metabolites in patients with primary Sjögren’s syndrome (pSS). Methods: A total of 56 samples of stimulated saliva were collected from 14 female pSS patients during four laboratory visits within 20 weeks and analyzed using proton nuclear magnetic resonance spectroscopy. Single saliva samples from each of 15 controls were also analyzed. Results: Among 21 quantified metabolites, choline was significantly elevated in the pSS patients at each time point (P ≤ 0.015), taurine at the last three time points (P ≤ 0.013), alanine at the last two time points (P ≤ 0.007) and glycine at the last time point (P = 0.005). Inter-individual variation in metabolite concentrations was generally larger among the patients than among the controls, and significantly large variations were observed for glycine (P ≤ 0.007, all time points), choline (P ≤ 0.033, three last time points) and alanine (P = 0.028, baseline). Metabolite output analysis showed that choline had the lowest intra-patient variation. Conclusions: In spite of considerable intra- and inter-individual variation, levels and outputs of specific metabolites in patients with pSS differ from those in controls, and may be potentially applicable as new biological markers for monitoring of the response to treatment

Prolonged bouts of sedentary time and cardiac autonomic function in midlife

Abstract Excessive sedentary time (SED) and long SED bouts are associated with cardiovascular diseases (CVD) and increased mortality. Low heart rate variability (HRV), indicating autonomic dysfunction, increases mortality and CVD morbidity. Information about the association between prolonged SED and HRV is lacking. The aim was to assess the relationship between SED bouts and HRV. Physical activity (PA), SED, HRV, and cardiorespiratory fitness (CRF) were collected from a birth‐cohort sample (n = 4150) at 46 years. PA and SED were measured for 14 days with an activity monitor (Polar Active, Polar Electro, Finland). SED accumulating in bouts of at least 30 and 60 minutes (SED30, SED60) was calculated. Linear regression was used to study the relationship between prolonged SED and HRV accounting for CRF, PA, and health covariates. Higher SED60 and in women SED30 were associated with higher root mean square of differences in R‐R intervals (rMSSD) after adjustments (β = .082‐.104). In women, higher SED60 was associated with lower ratio between low‐ and high‐frequency powers (β = −.060). Sedentary bouts were not associated with resting HR or post‐exercise HR recovery. A positive relationship between SED bouts and rMSSD independent of PA and CRF was found, prolonged SED being positively associated with cardiac parasympathetic activity in midlife

Associations of fitness and physical activity with orthostatic responses of heart rate and blood pressure at midlife

Abstract Cardiorespiratory fitness (CRF) and physical activity (PA) are associated with autonomic function, but their associations to orthostatic autonomic responses are unclear in epidemiological setting. We hypothesized that higher CRF and PA would associate with higher immediate vagal responses and lower incidence of adverse findings during orthostatic test. At age of 46, 787 men and 938 women without cardiorespiratory diseases and diabetes underwent an orthostatic test (3‐minutes sitting, 3‐minutes standing) with recording of RR intervals (RRi) and blood pressure (BP) by finger plethysmography. Acute responses of RRi (30:15 ratio) and BP were calculated. CRF was measured by a submaximal step test and daily amount of moderate‐to‐vigorous PA (MVPA) for 2 weeks by wrist‐worn accelerometer. Lifelong PA was based on questionnaires at ages of 14, 31, and 46. High CRF was significantly associated with higher RRi 30:15 ratio (adjusted standardized β = 0.17, P &lt; 0.001) and milder acute decrease of systolic BP while standing (β = 0.10, P = 0.001), while MVPA was not (β = 0.04 for RRi 30:15 ratio and β = 0.05 for systolic BP acute response). High lifelong PA was significantly associated with higher RRi 30:15 ratio (β = 0.08, P = 0.002) but not with acute systolic BP response. Those in the lowest tertile of CRF had 9.2‐fold risk (P = 0.002) of having postural orthostatic tachycardia syndrome compared to more fit. Cardiorespiratory fitness and lifelong physical activity, but not current physical activity, were independently associated with higher cardiac vagal response to orthostasis. The present results underscore the importance fitness and lifelong physical activity in prevention of abnormal autonomic function and related cardiovascular risk