Nocturnal Levels Research Articles

Nocturnal oxygen saturation is associated with all-cause mortality: a community-based study.

Observational studies have demonstrated the association between the single-point measurement of oxygen saturation (SpO2) level and mortality in the general population. This study aimed to evaluate whether nocturnal SpO2 level could predict all-cause mortality in a community-based population. The study samples were obtained from the Sleep Heart Health Study, which included 2,280 men and 2,606 women (mean age, 63.8 ± 11.1 years). A pulse oximeter based on overnight in-home polysomnography was used to monitor SpO2 levels during total sleep time (SpO2-TOTAL). Multivariable Cox proportional hazards analysis was performed to examine the association between nocturnal SpO2 and all-cause mortality. During the follow-up period of 10.7 ± 3.0 years, 1,110 (22.7%) people died. After adjusting for confounding factors, multivariable Cox regression analysis showed that the average SpO2-TOTAL (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.90-0.96, P < .001) was associated with all-cause mortality. These findings remained stable in individuals with low and high apnea-hypopnea index levels. Additionally, maximum SpO2-TOTAL (HR, 0.91; 95% CI, 0.87-0.96; P = .001) and minimum SpO2-TOTAL (HR, 0.98; 95% CI, 0.97-0.99; P = .001) could predict all-cause mortality. A significant association between nocturnal hypoxemia and all-cause mortality was also observed. Our findings highlight the importance of monitoring nocturnal SpO2 level and improving hypoxemia in the general populations. Yan B, Gao Y, Zhang Z, Shi T, Chen Q. Nocturnal oxygen saturation is associated with all-cause mortality: a community-based study. J Clin Sleep Med. 2024;20(2):229-235.

Assessing spatiotemporal patterns of mesocarnivores along an urban‐to‐rural gradient

AbstractRapid increases in human development and activity are affecting the spatial and temporal dynamics of mammalian mesocarnivore communities. We used 40 motion‐sensitive cameras along an urban‐to‐rural gradient, and single‐season occupancy models, to evaluate the habitat use of a local mesocarnivore guild (coyote [Canis latrans], bobcat [Lynx rufus], red fox [Vulpes vulpes], gray fox [Urocyon cinereoargenteus], and raccoon [Procyon lotor]) near Newburgh, New York, USA, during May–September 2021. Additionally, we fit circular kernel density estimations to assess how mesocarnivores may alter their diel and nocturnal activity patterns in response to human development. Red foxes were positively associated with urban areas and were also significantly more active at night in semiurban areas versus rural and urban locations. Coyotes demonstrated some adaptability to urban areas, being generally more nocturnal as urbanization increased but were also more likely to use higher elevation sites and areas with more natural habitat cover. We did not find support for a spatial shield hypothesis, as red foxes and raccoons were often detected in the same semiurban and urban sites as coyotes. Bobcats generally avoided human‐dominated areas, whereas raccoons were ubiquitous throughout the gradient and exhibited similar daily and nocturnal activity levels in all land cover types. Overall, our results document how anthropogenic disturbance may alter mesocarnivore community structure and landscape use, providing information for managing urban carnivore populations and mitigating human–wildlife conflict, particularly at the local scale.

Effectiveness of Continuous Positive Airway Pressure in Treating Hypertension in Obstructive Sleep Apnea: A Traditional Review.

Almost one billion individuals worldwide suffer from obstructive sleep apnea (OSA). The most widely used treatment for OSA has been continuous positive airway pressure (CPAP), but its effect on blood pressure (BP) has been challenged. Our review aims to evaluate the effects of treating OSA with CPAP on BP and BP-related morbidities in adult hypertensive patients. Medical subject headings (MeSH) terminology was used to search the PubMed Central, MEDLINE, and PubMed databases for articles on the use of CPAP in OSA patients with hypertension. We selected various forms of academic writing, encompassing complete texts that were published in the English language. The study included a total of 21 papers. OSA is a serious health concern associated with a higher risk of cardiovascular disease, kidney disease, pulmonary hypertension, and aortic stiffness, which is brought on by the periodic hypoxia caused by nocturnal respiratory episodes. For individuals with moderate-to-severe OSA, CPAP therapy has been shown to have a considerable long-term benefit with a median drop of 11 mm Hg, and high adherence results in a decrease in diastolic BP. CPAP therapy directly lowers BP in OSA patients with a body mass index (BMI) of more than 30 kg/m2 and has also demonstrated improvement in early signs of atherosclerosis with lower nocturnal systolic BP levels. OSA patients with resistant hypertension also experienced lower BP after using CPAP for a year. Therefore, our findings suggest that obesity, hypersomnolence, high nocturnal BP, prolonged CPAP usage, and resistant hypertension may all have a major impact on the BP response to CPAP therapy in individuals with severe OSA.

Glucose metabolism profile recorded by flash glucose monitoring system in patients with hypopituitarism during prednisone replacement.

Commonly used glucocorticoids replacement regimens in patients with hypopituitarism have difficulty mimicking physiological cortisol rhythms and are usually accompanied by risks of over-treatment, with adverse effects on glucose metabolism. Disorders associated with glucose metabolism are established risk factors of cardiovascular events, one of the life-threatening ramifications. To investigate the glycometabolism profile in patients with hypopituitarism receiving prednisone (Pred) replacement, and to clarify the impacts of different Pred doses on glycometabolism and consequent adverse cardiovascular outcomes. Twenty patients with hypopituitarism receiving Pred replacement [patient group (PG)] and 20 normal controls (NCs) were recruited. A flash glucose monitoring system was used to record continuous glucose levels during the day, which provided information on glucose-target-rate, glucose variability (GV), period glucose level, and hypoglycemia occurrence at certain periods. Islet β-cell function was also assessed. Based on the administered Pred dose per day, the PG was then regrouped into Pred > 5 mg/d and Pred ≤ 5 mg/d subgroups. Comparative analysis was carried out between the PG and NCs. Significantly altered glucose metabolism profiles were identified in the PG. This includes significant reductions in glucose-target-rate and nocturnal glucose level, along with elevations in GV, hypoglycemia occurrence and postprandial glucose level, when compared with those in NCs. Subgroup analysis indicated more significant glucose metabolism impairment in the Pred > 5 mg/d group, including significantly decreased glucose-target-rate and nocturnal glucose level, along with increased GV, hypoglycemia occurrence, and postprandial glucose level. With regard to islet β-cell function, PG showed significant difference in homeostasis model assessment (HOMA)-β compared with that of NCs; a notable difference in HOMA-β was identified in Pred > 5 mg/d group when compared with those of NCs; as for Pred ≤ 5 mg/d group, significant differences were found in HOMA-β, and fasting glucose/insulin ratio when compared with NCs. Our results demonstrated that Pred replacement disrupted glycometabolic homeostasis in patients with hypopituitarism. A Pred dose of > 5 mg/d seemed to cause more adverse effects on glycometabolism than a dose of ≤ 5 mg/d. Comprehensive and accurate evaluation is necessary to consider a suitable Pred replacement regimen, wherein, flash glucose monitoring system is a kind of promising and reliable assessment device. The present data allows us to thoroughly examine our modern treatment standards, especially in difficult cases such as hormonal replacement mimicking delicate natural cycles, in conditions such as diabetes mellitus that are rapidly growing in worldwide prevalence.

Ketogenic diet acutely improves gas exchange and sleep apnoea in obesity hypoventilation syndrome: A non-randomized crossover study.

Obesity hypoventilation syndrome (OHS) causes hypercapnia which is often refractory to current therapies. We examine whether hypercapnia in OHS can be improved by a ketogenic dietary intervention. We conducted a single-arm crossover clinical trial to examine the impact of a ketogenic diet on CO2 levels in patients with OHS. Patients were instructed to adhere to 1 week of regular diet, 2 weeks of ketogenic diet, followed by 1 week of regular diet in an ambulatory setting. Adherence was assessed with capillary ketone levels and continuous glucose monitors. At weekly visits, we measured blood gases, calorimetry, body composition, metabolic profiles, and sleep studies. Outcomes were assessed with linear mixed models. A total of 20 subjects completed the study. Blood ketones increased from 0.14 ± 0.08 during regular diet to 1.99 ± 1.11 mmol/L (p < 0.001) after 2 weeks of ketogenic diet. Ketogenic diet decreased venous CO2 by 3.0 mm Hg (p = 0.008), bicarbonate by 1.8 mmol/L (p = 0.001), and weight by 3.4 kg (p < 0.001). Sleep apnoea severity and nocturnal oxygen levels significantly improved. Ketogenic diet lowered respiratory quotient, fat mass, body water, glucose, insulin, triglycerides, leptin, and insulin-like growth factor 1. Rebound hypercapnia was observed after resuming regular diet. CO2 lowering was dependent on baseline hypercapnia, and associated with circulating ketone levels and respiratory quotient. The ketogenic diet was well tolerated. This study demonstrates for the first time that a ketogenic diet may be useful for control of hypercapnia and sleep apnoea in patients with obesity hypoventilation syndrome.

Changes in Glucose Intolerance after Treatment with Antithyroid Drugs in Patients with Graves' Disease Using Continuous Glucose Monitoring: A Pilot Study.

Objective Graves' disease (GD) is known to cause glucose intolerance. The present study used continuous glucose monitoring (CGM) in 15 patients newly diagnosed with GD to evaluate changes in glucose trends following improvement in the thyroid function. Methods At the time of the diagnosis of GD, each participant wore a CGM monitor for seven days, and the data recorded on days 3 to 5 were analyzed. The clinical status before treatment with antithyroid drugs was evaluated. Following successful treatment with antithyroid drugs and improvement of free thyroxine (fT4) to within the normal range, CGM was used again to evaluate the same variables after treatment. Results The primary outcome, the standard deviation (SD) of glucose, improved from a baseline value of 28.9±4.9 to a post-treatment value of 22.2±5.1 mg/dL (p=0.001). Other variables also improved after treatment, including the mean amplitude of glycemic excursion (MAGE), daily average glucose level, nocturnal average glucose level (0:00-05:59), maximum and minimum glucose, percent time with glucose at >140 mg/dL, and percent time with glucose at >180 mg/dL; however, the coefficient of variation (CV) and percent time with glucose at <70 mg/dL did not improve. A univariate analysis showed the significant correlation of the SD with TSH receptor antibody (TRAb) and 1,5-Anhydro-D-Glucitol (1,5-AG). Conclusions Our results showed that CGM-based markers of mean glucose and glucose variability improved with the improvement of the thyroid function in newly diagnosed GD patients treated with antithyroid drugs.

Nocturnal blood pressure surge in seconds is associated with arterial stiffness independently of conventional nocturnal blood pressure variability in suspected obstructive sleep apnea patients.

Nocturnal blood pressure (BP) surge in seconds (sec-surge), which is characterized as acute transient BP elevation over several tens of seconds is induced by obstructive sleep apnea (OSA) and OSA-related sympathetic hyperactivity. The authors assessed the relationship between sec-surge and arterial stiffness in 34 nocturnal hypertensive patients with suspected OSA (mean age 63.9±12.6years, 32.4% female). During the night, they had beat-by-beat (BbB) BP and cuff-oscillometric BP measurements, and brachial-ankle pulse wave velocity (baPWV) was assessed as an arterial stiffness index. Multiple linear regression analysis revealed that the upward duration (UD) of sec-surge was significantly associated with baPWV independently of nocturnal oscillometric systolic BP variability (β=.365, p=.046). This study suggests that the UD of sec-surge, which can only be measured using a BbB BP monitoring device, may be worth monitoring in addition to nocturnal BP level.

Seasonal patterns of body temperature in response to experimental photoperiod variation in a non-hibernating ground squirrel.

Unlike numerous other members of the holarctic Tribe Marmotini of the squirrel family (Sciuridae) that typically exhibit spontaneous bouts of torpor that progress into an annual season of hibernation, members of the genus Ammospermophilus (antelope ground squirrels) do not enter torpor, and they remain active throughout the year in nature. We have experimentally evaluated seasonal patterns of variation in the circadian rhythm of body temperature in captive A. leucurus over a two-and-a-half-year period by exposing groups to either a constant daily photoperiod of 12h light or a seasonally changing photoperiod that cycled between a summer maximum of 16h per day and a winter minimum of 8h; ambient air temperature was maintained at 26°C. All squirrels showed continuous, year-round diurnal locomotor activity, and the group exposed to seasonally changing photoperiod adjusted onset and end of activity to changes in duration of the photoperiod. Animals in both groups showed a marked circadian rhythm of core body temperature with a typical daytime level of about 38°C and nighttime level of about 35°C for most of each year, but the group exposed to naturally changing daylength surprisingly reduced the level of its circadian oscillation by about 2°C at the winter seasonal extreme of shortest daily illumination to a daytime level about 36°C and a nocturnal level of about 33°C. Despite this modest experimentally induced reduction in the level of the circadian rhythm of body temperature, we conclude that A. leucurus shows an overall stable annual pattern of circadian rhythmicity of its core body temperature that is consistent with a lack of any other evidence that the species engages in torpor or hibernation.

Glucose variability in maintenance hemodialysis patients with type 2 diabetes: Comparison of dialysis and nondialysis days.

Hemodialysis (HD) induces several physiological changes that can affect plasma glucose levels in patients with diabetes and in turn their glycemic control. Studies using continuous glucose monitoring (CGM) to assess glucose variations on dialysis days compared with nondialysis days report conflicting results. Here, we used CGM to examine glucose variations induced by HD in patients with type 2 diabetes. Patients with type 2 diabetes undergoing maintenance HD were included. CGM (Ipro2®, Medtronic) was performed at baseline and Week 4, 8, 12, and 16 for up to 7 days at each visit. CGM profiles on days where participants received HD were compared with days without HD using a linear mixed model. Twenty-seven patients were included. The median number of CGM days performed was 8 (interquartile range [IQR] 6-10) for dialysis days and 16 (IQR 12-17) for nondialysis days. The median sensor glucose was 9.4 (95% confidence interval [CI] 8.8-10.2) mmol/L on dialysis days compared with 9.5 (95% CI 8.9-10.2) mmol/L on nondialysis days (p=0.58). Nocturnal mean sensor glucose was higher on dialysis days compared with nondialysis days: 8.8 (95% CI 8.0-9.6) mmol/L versus 8.4 (95% CI 7.7-9.2) mmol/L (p=0.029). Similar median sensor glucose values were found for days on and off HD. Nocturnal glucose levels were modestly increased on dialysis days. Our findings indicate that antidiabetic treatment does not need to be differentiated on dialysis versus nondialysis days in patients with type 2 diabetes undergoing maintenance HD.

Melatonin: Both a Messenger of Darkness and a Participant in the Cellular Actions of Non-Visible Solar Radiation of Near Infrared Light.

Throughout the history of melatonin research, almost exclusive focus has been on nocturnally-generated pineal melatonin production, which accounts for its circadian rhythm in the blood and cerebrospinal fluid; these light/dark melatonin cycles drive the daily and seasonal photoperiodic alterations in organismal physiology. Because pineal melatonin is produced and secreted primarily at night, it is referred to as the chemical expression of darkness. The importance of the other sources of melatonin has almost been ignored. Based on current evidence, there are at least four sources of melatonin in vertebrates that contribute to the whole-body melatonin pool. These include melatonin produced by (1) the pineal gland; (2) extrapineal cells, tissues, and organs; (3) the microbiota of the skin, mouth, nose, digestive tract, and vagina as well as (4) melatonin present in the diet. These multiple sources of melatonin exhibit differentially regulated mechanisms for its synthesis. Visible light striking the retina or an intense physical stimulus can suppress nocturnal pineal melatonin levels; in contrast, there are examples where extrapineal melatonin levels are increased during heavy exercise in daylight, which contains the whole range of NIR radiation. The cumulative impact of all cells producing augmented extrapineal melatonin is sufficient to elevate sweat concentrations, and potentially, if the exposure is sustained, to also increasing the circulating values. The transient increases in sweat and plasma melatonin support the premise that extrapineal melatonin has a production capacity that exceeds by far what can be produced by the pineal gland, and is used to maintain intercellular homeostasis and responds to rapid changes in ROS density. The potential regulatory mechanisms of near infrared light (NIR) on melatonin synthesis are discussed in detail herein. Combined with the discovery of high levels of melanopsin in most fat cells and their response to light further calls into question pineal centric theories. While the regulatory processes related to microbiota-derived melatonin are currently unknown, there does seem to be crosstalk between melatonin derived from the host and that originating from microbiota.

PS-C12-4: OPEN-ANGLE GLAUCOMATOUS OPTIC DAMAGE ASSOCIATED WITH DAYTIME AND NOCTURNAL DIPS IN BLOOD PRESSURE

Background: Impaired ocular perfusion pressure via systemic hypoperfusion plays a pivotal role in the pathogenesis of open-angle glaucoma (OAG). Extreme dips in mean arterial pressure (MAP) during 24-h are associated with OAG, however, whether this is driven by diurnal or nocturnal dips remains undocumented. We aimed this study to investigate the association of OAG damage with daytime and nocturnal dips in MAP. Methods: We conducted a retrospective longitudinal study that included 110 primary OAG patients who underwent 24-h ambulatory blood pressure monitoring. OAG damage was defined as changes in mean deviation (MD) of visual field tests during follow-up. MAP variability independent of the mean (VIMmap) was computed for daytime and nighttime. Dips were the five daytime and three nighttime lowest drops in MAP. We also calculated the night-to-day ratio and defined low diurnal and nocturnal MAP levels. We applied mixed models to evaluate changes in MD (expressed as decibels [dB]) during follow-up in relation to diurnal and nocturnal variability and dips in MAP. Results: The mean age was 64.0y (53% women). The median follow-up was nine years. In adjusted mixed models, every + 3 mmHg increase in daytime VIMmap was associated with a -2.57 dB longitudinal change in MD (P &lt; 0.001). The longitudinal changes in MD associated with daytime dip measures ranged from -2.56 dB (95% confidence interval [CI], -3.61 to -1.51; P &lt; 0.001) to -3.19 dB (95% CI, -4.53 to -1.84; P &lt; 0.001). For nighttime measures, the MD changed -0.71 dB (CI, -1.24 to -0.17; P = 0.009) per every -5 decrease in the nighttime MAP level. Nocturnal MAP level &lt; 74 mmHg and every 0.05 decrease in the night-to-day ratio were related to -7.23 (P = 0.003) and -0.96 (P = 0.011) changes in MD. Nighttime VIMmapP and nocturnal dips were not associated with changes in MD (P &gt; 0.097). Conclusions: Extreme daytime dips in MAP relate to OAG damage independently of the MAP level. Whereas, the association between OAG damage and nocturnal measures is driven by the nocturnal MAP level rather than variability or dips in MAP. The assessment of diurnal patterns in MAP might offer an opportunity to understand the pathogenesis of OAG. This is also critical as the perfusion pressure to the eyes is physiological 30% lower than at the brachial level in the standing or sitting positions. Therefore, a physiological lower perfusion pressure combined with extreme diurnal dips in MAP would exacerbate the hypoperfusion state in the optic nerve, leading to further glaucoma damage.

Effects of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on substrate metabolism in prediabetic insulin resistant individuals: A randomized, double-blind crossover trial

Aims/hypothesisSodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment in type 2 diabetes mellitus patients results in glucosuria, causing an energy loss, and triggers beneficial metabolic adaptations. It is so far unknown if SGLT2i exerts beneficial metabolic effects in prediabetic insulin resistant individuals, yet this is of interest since SGLT2is also reduce the risk for progression of heart failure and chronic kidney disease in patients without diabetes. MethodsFourteen prediabetic insulin resistant individuals (BMI: 30.3 ± 2.1 kg/m2; age: 66.3 ± 6.2 years) underwent 2-weeks of treatment with dapagliflozin (10 mg/day) or placebo in a randomized, placebo-controlled, cross-over design. Outcome parameters include 24-hour and nocturnal substrate oxidation, and twenty-four-hour blood substrate and insulin levels. Hepatic glycogen and lipid content/composition were measured by MRS. Muscle biopsies were taken to measure mitochondrial oxidative capacity and glycogen and lipid content. ResultsDapagliflozin treatment resulted in a urinary glucose excretion of 36 g/24-h, leading to a negative energy and fat balance. Dapagliflozin treatment resulted in a higher 24-hour and nocturnal fat oxidation (p = 0.043 and p = 0.039, respectively), and a lower 24-hour carbohydrate oxidation (p = 0.048). Twenty-four-hour plasma glucose levels were lower (AUC; p = 0.016), while 24-hour free fatty acids and nocturnal β-hydroxybutyrate levels were higher (AUC; p = 0.002 and p = 0.012, respectively) after dapagliflozin compared to placebo. Maximal mitochondrial oxidative capacity was higher after dapagliflozin treatment (dapagliflozin: 87.6 ± 5.4, placebo: 78.1 ± 5.5 pmol/mg/s, p = 0.007). Hepatic glycogen and lipid content were not significantly changed by dapagliflozin compared to placebo. However, muscle glycogen levels were numerically higher in the afternoon in individuals on placebo (morning: 332.9 ± 27.9, afternoon: 368.8 ± 13.1 nmol/mg), while numerically lower in the afternoon on dapagliflozin treatment (morning: 371.7 ± 22.8, afternoon: 340.5 ± 24.3 nmol/mg). Conclusions/interpretationDapagliflozin treatment of prediabetic insulin resistant individuals for 14 days resulted in significant metabolic adaptations in whole-body and skeletal muscle substrate metabolism despite being weight neutral. Dapagliflozin improved fat oxidation and ex vivo skeletal muscle mitochondrial oxidative capacity, mimicking the effects of calorie restriction. Trial registrationClinicalTrials.gov NCT03721874.

Progression of functional and structural glaucomatous damage in relation to diurnal and nocturnal dips in mean arterial pressure.

Systemic hypoperfusion plays a pivotal role in the pathogenesis of primary open-angle glaucoma (POAG). Extreme dips in mean arterial pressure (MAP) due to high 24-h variability are associated with POAG, however, whether this is driven by diurnal or nocturnal dips remains undocumented. We aimed this study to investigate the association of POAG damage with variability and dips in the diurnal and nocturnal MAP. We conducted a retrospective longitudinal study that included 110 POAG patients who underwent 24-h ambulatory blood pressure monitoring. Our outcomes included (i) functional [visual field defects expressed as mean deviation (MD)] and (ii) structural (optic disc cupping obtained from cup-to-disc ratio) glaucoma damage. MAP variability independent of the mean (VIMmap) was computed for diurnal and nocturnal MAP. Dips were the five diurnal and three nocturnal lowest drops in MAP. We also calculated the night-to-day ratio. We applied mixed models to evaluate the progression of visual field defects and optic disc cupping in relation to diurnal and nocturnal MAP measures. The mean age was 64.0 y (53% women). The median follow-up was 9 years. In adjusted mixed models, functional progression of glaucoma damage was associated with VIMmap (-2.57 dB change in MD per every 3 mmHg increase in VIMmap; P < 0.001) and diurnal MAP dips (changes in the MD ranged from -2.56 to -3.19 dB; P < 0.001). Every 5 mmHg decrease in the nocturnal MAP level was associated with -1.14 dB changes in MD [95% confidence interval (CI), -1.90 to -0.40] and 0.01 larger optic disc cupping (95% CI, 0.01-0.02). Lower night-to-day ratio was also related to both outcomes (P ≤ 0.012). Functional glaucoma damage worsened if nocturnal hypotension was combined with high variability or extreme dips in the diurnal MAP (P ≤ 0.022). Progression of glaucoma damage in POAG associates with high variability and extreme dips in the diurnal MAP. Structural glaucoma damage seems more vulnerable to nocturnal hypotension. Ambulatory blood pressure monitoring allows the assessment of sporadic diurnal and persistent nocturnal hypotension episodes. These phenotypes might offer an opportunity to improve the risk-stratification of open-angle glaucoma (OAG).

The increased cortisol levels with preserved rhythmicity in aging and its relationship with dementia and metabolic syndrome.

In the aging process, the cumulative exposure to stress with increased cortisol levels is considered to be associated to the senescence itself and its related disorders. To evaluate the role of cortisol in elderly subjects, with or without dementia, by the means of the AGICO study. The AGICO study enrolled patients from ten Geriatric Units in Italy in 2012-2017 (Study Director Prof Paolo Falaschi, S. Andrea Hospital of Rome). Every subject received a comprehensive geriatric assessment (including the Mini-Mental State Examination, MMSE), the neurological examination (with a computed tomography scan or magnetic resonance imaging of the brain), the assessment of the metabolic syndrome (MetS), the evaluation of the cortisol activity by two consecutive urine collections (diurnal and nocturnal). The MMSE was inversely related to the standardized diurnal and nocturnal urinary cortisol levels (p < 0.025 and p < 0.01, respectively) and the age was positively related (p < 0.01 and p < 0.001, respectively). The ratio between the standardized diurnal and nocturnal urinary cortisol levels was 1.50 ± 1.2 (mean ± standard deviation) and it was not modified by the age or dementia. The standardized diurnal and nocturnal urinary cortisol levels were significantly higher in patients with dementia (MMSE < 24) (p < 0.01). In the analysis of the subgroups with MetS, the highest concentrations of diurnal and nocturnal cortisol were found in patients with both dementia and MetS (p < 0.025 and p < 0.01, respectively). The AGICO study showed that the stress response significantly and progressively increases with age. The cortisol increase in aging is related to the presence of both dementia and metabolic syndrome.

Tree visitation and potential seed dispersal of keystone Ficus species by vertebrates in an urban mosaic landscape in eastern South Africa

Globally with the human population increase, urban expansion has increased, impacting biodiversity and ecosystem functions. Visitation of fruiting trees by vertebrate frugivores can influence the persistence of fleshy fruited trees and so further maintain frugivore communities in transformed landscapes. Figs (Ficus spp.) have been recognised as keystone plant resources that support diverse frugivorous vertebrate communities. Our main objective was to identify the frugivorous vertebrates visiting fruiting Ficus trees in an urban mosaic landscape of Durban, Ethekwini Municipality, KwaZulu-Natal, South Africa, using camera traps focused on focal fig trees. We quantified the diurnal and nocturnal frugivore visitation rates and levels of interactions. We analysed frugivore visits to 12 individual trees of five Ficus species between 2019 and 2020. During 3888 h, we recorded a total of 4,071 videos from camera traps with 10,016 visits and levels of interactions of three main vertebrate taxa (8958 fruit bat visits, 808 bird visits and 250 monkey visits). These were in five Ficus species (F. burkei, F. lutea, F. natalensis, F. sur and F. sycomorus). Of the bird species visiting, we identified a total of 34 species, but some species were unidentified. We recorded a total of 8958 visits by Wahlberg's epauletted fruit bats Epomophorus wahlbergi, and 250 visits by vervet monkeys Chlorocebus pygerythrus. The latter tended to stay for prolonged periods in the trees feeding. Our data showed the importance of fruiting fig trees for vertebrate frugivores in the urban mosaic landscape. This highlights the conservation implications of figs as keystone resources in the urban mosaic landscape. Our findings support the planting and conservation of native Ficus tree species in transformed urban mosaic landscapes for the persistence of forest species biodiversity.

Melatonin: Manager of psychosomatic and metabolic disorders in polymorbid cardiovascular pathology.

ObjectivesTo investigate the relationship between changes in circadian patterns of melatonin and clinical manifestations of polymorbid cardiovascular pathology (PCVP) in young men and to analyze the effectiveness of their complex treatment.Materials and methodsWe made the immunohistochemical (IHC) analysis of epiphysis tissues from autopsies of 25 men aged 32–44 with PCVP and metabolic syndrome (MS) who had died as a result of ischemic cardiomyopathy (IC) and 25 persons after the car accident as a control group. Then, 93 young men aged 35–44 with PCVP, metabolic syndrome, and depressive spectrum disorders (DSD) were divided into three groups: (1) standard therapy; (2) standard therapy and psychotherapy sessions; (3) standard therapy in combination with psychotherapeutic and psychophysiological visual and auditory correction sessions. The control group included 24 conditionally healthy male volunteers. Before and after the treatment, we studied the anthropometric status, lipid and carbohydrate metabolism indicators, the level of urinary 6-hydroxymelatonin sulfate, the degree of nocturnal decrease in blood pressure (BP), and the relationship of these indicators with circadian variations of melatonin excretion.ResultsYoung polymorbid patients who died from IC have a lower expression of melatonin type 1 and 2 receptors. All patients with PCVP showed a decrease in the nocturnal melatonin excretion fraction and a correlation with higher severity of depressive (r = −0.72) and anxiety (r = −0.66) symptoms. Reduced values of the 6-hydroxymelatonin sulfate (6-SM) in the 1st (r = 0.45), 2nd (r = 0.39), and 3rd (r = 0.51) groups before treatment was associated with periods of increased BP. The achievement of melatonin excretion reference values and normalization of biochemical parameters of carbohydrate and lipid metabolism, daily BP profile, and psychophysiological state were noted in all three patients’ groups, with a more pronounced effect in group 3.ConclusionLow nocturnal melatonin excretion levels are associated with greater severity of clinical symptoms and a higher risk of death in patients with PCVP. Therefore, comprehensive therapy may be more effective for correcting this disease.

Changes in the Metabolic Profile of Melatonin Synthesis-Related Indoles during Post-Embryonic Development of the Turkey Pineal Organ.

Research on age-dependent changes in pineal activity has been limited almost exclusively to melatonin (MLT). This study determined, for the first time, the alterations occurring in the metabolic profile of MLT synthesis-related indoles during the post-embryonic development period in birds. Turkeys reared under a 12 h light/dark cycle were euthanized at 2 h intervals for 24 h at the ages of 2, 7, 14, and 28 days and 10, 20, 30, and 45 weeks. The results showed prominent changes in the metabolic profile of indoles during development and could be distinguished in four stages. The first stage, from hatching to the age of 2 weeks, was characterized by a decrease in the 5-hydroxytryptophan concentration and an increase in the concentrations of serotonin (5-HT), MLT, 5-methoxyindoleacetic acid, and 5-methoxytryptamine (5-MTAM). During the second stage, around the age of 1 month, the concentrations of N-acetylserotonin (NAS) and MLT reached a maximum. The synthesis and degradation of 5-HT were also the highest. The third stage, around the age of 10 weeks, was characterized by decreased levels of 5-HT (approximately 50%) and 5-hydroxyindoleacetic acid and a high level of 5-MTAM. The last stage, covering the age of 20 to 45 weeks, was characterized by a large decrease in the synthesis, content, and degradation of 5-HT. Despite these changes, there were no prominent differences in the nocturnal levels of NAS and MLT between the third and fourth stages. The concentrations of all tryptophan derivatives showed daily fluctuations until the age of 45 weeks.

Association of Circulating Platelet Extracellular Vesicles and Pulse Wave Velocity with Cardiovascular Risk Estimation.

Elevated circulating platelet-derived extracellular vesicles (EVs) have been reported in conditions associated with thrombotic risk. The present study aimed to assess the relationship between circulating platelet-derived EV levels, cardiovascular risk stratification and vascular organ damage, as assessed by pulse wave velocity (PWV). A total of 92 patients were included in the present analysis. Platelet EV were evaluated by flow cytometry (CD41+/Annexin v+). The cardiovascular risk was determined using the 2021 ESC guideline stratification and SCORE2 and SCORE-OP. PWV was performed as a surrogate to assess macrovascular damage. Risk stratification revealed significant group differences in EV levels (ANOVA, p = 0.04). Post hoc analysis demonstrated significantly higher levels of EVs in the very high-risk group compared with the young participants (12.53 ± 8.69 vs. 7.51 ± 4.67 EV/µL, p = 0.03). Linear regression models showed SCORE2 and SCORE-OP (p = 0.04) was a predictor of EV levels. EVs showed a significant association with macrovascular organ damage measured by PWV (p = 0.01). PWV progressively increased with more severe cardiovascular risk (p < 0.001) and was also associated with SCORE2 and SCORE-OP (p < 0.001). Within the pooled group of subjects with low to moderate risk and young participants (<40 years), those with EV levels in the highest tertile had a trend towards higher nocturnal blood pressure levels, fasting glucose concentration, lipid levels, homocysteine and PWV. Levels of platelet-derived EVs were highest in those patients with very high CV risk. Within a pooled group of patients with low to moderate risk, an unfavourable cardiometabolic profile was present with higher EV levels.

Nocturnal urine 6-hydroxy sulfate melatonin is associated with the outcome of subjects with sepsis

Abstract Background It is imperative to identify potential biomarkers for early diagnosis and intervention of severe sepsis. This study investigated the relationship between melatonin secretion and outcome of sepsis after 28-day admission. Methods Patients with sepsis were randomly divided into an eye mask group and a control group. Blood and urine samples were collected from day 0 to 4. Relevant clinical data and 28-day survival data were obtained. Serum melatonin and urine 6-hydroxy sulfate melatonin (6-SMT) levels were measured. Results The outcome of sepsis did not differ between the eye mask and control groups. Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were significantly higher and monocyte human leukocyte antigen-DR (mHLA-DR), serum melatonin, nocturnal urine 6-SMT, and 24-hour urine 6-SMT levels were significantly lower in the nonsurvivors than in the survivors. The outcome at day 28 after admission was significantly associated with APACHE II and SOFA scores and mHLA-DR, nocturnal urine 6-SMT, and 24-hour urine 6-SMT levels. The areas under the receiver operating characteristic curve were 0.785, 0.740, 0.774, and 0.858 for APACHE II score, SOFA score, mHLA-DR expression, and nocturnal urine 6-SMT amount, respectively. The optimal thresholds for mHLA-DR and nocturnal urine 6-SMT were 30.13% and 43.60%, respectively. Nocturnal urine 6-SMT level was significantly and positively correlated with mHLA-DR expression. Conclusion Nocturnal urine 6-SMT level may be a feasible biomarker to predict the outcome of patients with sepsis. The use of a night-time eye mask has no significant effect on the outcome of sepsis. Clinical trials This study was registered at clinicaltrials.gov (NCT02304224).

Hydroclimatology and Hydrometeorology of Flooding Over the Eastern Tibetan Plateau

AbstractThe hydroclimatology and hydrometeorology of flooding over the Third Pole region is poorly understood, despite its societal and environmental significance. Here we examine extreme rainfall and flooding over the eastern Tibetan Plateau (TP) based on empirical analyses of long‐term, in‐situ rainfall and stream gaging observations as well as the ECMWF Reanalysis fields. We develop a flood catalog that consists of 168 extreme rainfall‐runoff floods over the eastern TP, and characterize the synoptic conditions for flood‐producing storms based on the principal component analysis. We show the transitional pattern form Asian summer monsoons to midlatitude systems as the most frequent synoptic conditions for flooding over the eastern TP. The interplay between complex terrains and moisture transport determines the contrasting flood characteristics (in terms of intensity and spatial pattern) under different synoptic environments. We carry out high‐resolution Weather Research and Forecasting modeling analysis for four flood‐producing storms over the eastern TP. We highlight the interaction of complex terrains and nocturnal low level jets as the key mesoscale ingredients in dictating a pronounced diurnal cycle of extreme rainfall over the southeastern portion of TP. Our results establish the link between large‐scale synoptic environment, mesoscale process, and regional flood hydrology over the eastern TP, and therefore contribute to improved flood risk management practices over the Third Pole region under a changing climate.