Influence of glycemic control and hypoglycemia on the risk of fracture in patients with diabetes mellitus: a systematic review and meta-analysis of observational studies.

Individuals with diabetes mellitus (DM) have an increased risk of fracture. Glycemic control is crucial to the management of DM, but there are concerns pertaining to hypoglycemia development in the course of glycemic control target achievement. The extent to which glycemic control may affect the risk of fracture remains less defined. Hypoglycemia-induced falls have been suggested to contribute to an elevated risk of fracture in DM patients. In this meta-analysis of observational studies, we aimed to investigate the relative contribution of glycemic control, as measured by glycated hemoglobin (HbA1c), and hypoglycemia to the risk of fracture in DM. The PubMed and Web of Science databases were searched for relevant studies. A random-effects model was used to generate summary relative risks (RRs) and 95% confidence intervals (CIs). Both increased HbA1c levels (RR per 1% increase 1.08, 95% CI 1.03, 1.14; nstudies = 10) and hypoglycemia (RR 1.52, 95% CI 1.23, 1.88; nstudies = 8) were associated with an increased risk of fracture. The association between HbA1c levels and the risk of fracture was somewhat nonlinear, with a noticeably increased risk observed at an HbA1c level ≥ 8%. The positive associations of HbA1c levels and hypoglycemia with the risk of fracture did not reach statistical significance in the studies that adjusted for insulin use, hypoglycemia, or falls for the former and in those that adjusted for falls for the latter. In summary, both increased HbA1c levels and hypoglycemia may increase the risk of fracture in patients with DM. The positive association between HbA1c levels and the risk of fracture appears to be, in part, explained by hypoglycemia-induced falls, possibly due to insulin use. The avoidance of hypoglycemia in the course of achieving good glycemic control through the careful selection of glucose-lowering medications may contribute to fracture prevention by reducing the risk of falls related to treatment-induced hypoglycemia.

Systematic review and meta-analysis of the association between dairy consumption and the risk of hip fracture: critical interpretation of the currently available evidence.

In the present meta-analysis, reductions in the risk of hip fracture with milk consumption were only observed among American adults, but not among Scandinavian adults, possibly because milk products are more commonly fortified with vitamin D in the former population than in Scandinavian countries. The reduction in the risk of hip fracture was also observed with yogurt consumption, which is often associated with healthy lifestyles and dietary patterns that contribute to improved bone health. INTRODUCTION: Although dairy products contain bone-beneficial nutrients, the association between dairy consumption and the risk of hip fracture remains equivocal. Fueling this uncertainty, the elevated risk of hip fracture in association with milk consumption was observed in a cohort of Swedish women. A systematic review and meta-analysis of prospective cohort studies was performed to critically evaluate the association, or lack thereof, between dairy consumption (milk, yogurt, and cheese) and the risk of hip fracture. METHODS: A random effects model was used to generate the summary relative risks (RRs) with their 95% confidence intervals (CIs) for the associations of interest. RESULTS: In the meta-analysis of the highest versus lowest category of consumption, higher consumption of yogurt (RR 0.78, 95% CI 0.68, 0.90), but not milk (RR 0.86, 95% CI 0.73, 1.02) or cheese (RR 0.85, 95% CI 0.66, 1.08), was associated with a lower risk of hip fracture. For milk, the reduced risk of fracture with higher milk consumption was observed in the USA (RR 0.75, 95% CI 0.65, 0.87), but not in Scandinavian countries (RR 1.00, 95% CI 0.85, 1.17). These findings were further supported by the fact that American studies (RR 0.93, 95% CI 0.88, 0.98; per 1 glass/day), but not Scandinavian studies (RR 1.01, 95% CI 0.95, 1.07; per 1 glass/day), demonstrated a linear association between milk consumption and the risk of hip fracture. CONCLUSIONS: The cumulative evidence from prospective cohort studies reassuringly suggests that the risk of hip fracture may not be elevated among people who consume milk, yogurt, and cheese, and that a greater consumption of milk or yogurt may even be associated with a lower risk of hip fracture depending on the factors that may differ across the population of interest.

[Analysis of project results of preventive medicine from the National Natural Science Foundation of China in 2017].

We analyzed the project results of preventive medicine from the National Natural Science Foundation of China (NSFC) finished in 2017 based on the project-ending reports and data on science fund sharing service network. A total of 406 projects in this field were completed in 2017. A total of 3 122 published articles supported by these projects, including 1 789 articles in science citation index (SCI) journals and 525 articles in Chinese core journals. In addition, there were 224 patent application/software copyright and 589 trained postgraduates. The top three sub-disciplines of project were non-communicable disease epidemiology, human nutrition and hygienic toxicology, accounting for 45.32% of the total number of completed projects. There were 12 institutions which had more than 10 finished projects, accounting for 41.87%. During the recent 5 years, the number of SCI articles and patents/software copyrights per project showed a general uptrend. It should be noted that the number of articles in Chinese core journals and postgraduates decreased in recent two years. Our analyses demonstrated that the project results should be guided by the new era policy of science fund to promote sustainable development of scientific research.

Antioxidant status of serum bilirubin, uric acid and albumin in pemphigus vulgaris.

BACKGROUND: Oxidative stress and low antioxidant status are implicated in the pathogenesis of inflammatory and autoimmune diseases. Pemphigus vulgaris (PV) is an extremely severe autoimmune bullous dermatosis characterized by intraepithelial bullae on the skin and mucosa, and its antioxidant status is not fully understood. AIM: To assess correlations between PV and serum antioxidant levels of bilirubin, uric acid (UA) and albumin. METHODS: We enrolled 116 patients newly diagnosed with PV who were admitted to the First Affiliated Hospital of Guangxi Medical University (Guangxi, China), and 108 healthy controls (HCs). Clinical characteristics and laboratory parameters of patients were retrospectively analysed. RESULTS: Our survey shows that compared with the HC groups, serum levels of bilirubin [total bilirubin (Tbil), direct bilirubin (Dbil) and indirect bilirubin (Ibil)], UA and albumin were significantly lower in patients with PV, regardless of sex. In all groups, serum Tbil, Dbil, Ibil, UA and albumin levels were lower for women than for men. Severity of pemphigus was slightly negatively associated with Tbil, Dbil and Ibil, but was not associated with UA or albumin. Moreover, when the data were adjusted for the covariances of age and sex separately, Tbil, Dbil, Ibil, UA and albumin were all relevant to PV. CONCLUSIONS: Our findings demonstrate that serum levels of bilirubin (Tbil, Dbil and Ibil), UA and albumin are reduced in patients with PV supporting the hypothesis that oxidative stress and antioxidant status are important in the pathogenic mechanism of PV.

[Effects of leucine on adipogenesis in 3T3-L1 preadipocytes during and after differentiation].

OBJECTIVE: To observe the effects of leucine on adipogenesis in 3T3-L1 preadipocyte during and after differentiation, and to investigate possible mechanisms. METHODS: Respectively, 0.0 (control), 0.5, 1.0 and 2.0 mmol/L leucine was added in 3T3-L1 cells and cell proliferation was measured by MTT. Then, 3T3-L1 preadipocyte was induced to differentiate. Leucine was added during whole differentiation period, or after differentiation for 4 days. The cells were stained with Oil Red O dye to observe lipid droplet. The culture media were collected and used to determine glycerol contents. Meanwhile, protein expressions related to lypolytic enzymes, leptin signaling pathway were determined by Western blot. RESULTS: MTT result showed that cell viabilities were (100.00±12.10)%, (102.73±12.38)%, (103.94±14.65)%, (108.70±5.05)% in 0.0, 0.5, 1.0 and 2.0 mmol/L leucine groups, respectively, there were no significant differences in cell proliferation among 4 groups (F=1.07, P=0.383). When 0.0, 0.5, 1.0 and 2.0 mmol/L leucine was added during differentiation, the relative number of lipid droplet was 1.00±0.06, 0.94±0.09, 0.82±0.08 and 0.79±0.04, respectively (F=11.74, P<0.001), and it was significantly lower in 1.0 and 2.0 mmol/L leucine groups than in control group (P=0.002 and P<0.001, respectively). There was no significant difference in lipid droplet when leucine was added after differentiation (F=0.16, P=0.924). When leucine was added during differentiation, the increment of glyceride contents in medium was (65.04 ± 11.75), (71.45 ± 23.71), (79.37 ± 17.63) and (110.32 ± 25.36) µmol/L, respectively (F=2.92, P=0.100). And it was significantly higher in 2.0 mmol/L leucine group (110.32 ± 25.36) µmol/L than in control group (65.04 ± 11.75) µmol/L (t=2.73, P=0.026). No significant difference of the increment of glyceride contents among 4 groups was observed when leucine was added after differentiation (F=0.80, P=0.528). Western blot results showed that leucine treatment during differentiation upregulated expression level of hormone-sensitive lipase phosphorylation (after 0.0 and 2.0 mmol/L leucine treatment,the protein levels were 1.00 ± 0.08 vs. 2.54 ± 0.27, P<0.001) , and downregulated the protein expression levels of perilipin A, leptin and leptin-related pathway, such as leptin receptor, Janus kinase 2 and suppressor of cytokine signaling-3 (after 0.0 and 2.0 mmol/L leucine was added, the protein levels were (1.00 ± 0.03) vs. (0.31 ± 0.07) , (1.00 ± 0.08) vs. (0.22±0.07) , (1.00±0.07) vs. (0.21 ± 0.04) , (1.00 ± 0.03) vs. (0.35 ± 0.05) , (1.00 ± 0.06) vs. (0.34 ± 0.05) , P<0.001). Leucine treatment after differentiation had no effects on these protein expressions (all P>0.05). CONCLUSION: Leucine inhibits adipogenesis during 3T3-L1 preadipocyte differentiation by the regulation of lypolytic enzymes and leptin signaling pathway; however, leucine has no effect on adipogenesis when differentiation completed.

Lactotripeptides intake and blood pressure management: a meta-analysis of randomised controlled clinical trials.

BACKGROUND AND AIMS: Lactotripeptides (LTPs, including IPP and VPP) have held promise in the framework of lifestyle modification for prevention and control of hypertension - a cardiovascular risk factor, as LTPs are reported to have an inhibitory effect on angiotensin-converting enzyme. While the number of clinical trials to test the efficacy of LTP continues to increase, the results have been inconsistent, especially in the last few years. The purpose of the present meta-analysis is to precisely estimate the pooled mean effect of LTPs on conventional blood pressure (BP) generally and on 24-h ambulatory BP (ABP) particularly, as well as the change of BP in relation to baseline BP, race, and study design, to better reflect the evolving field. DATA SYNTHESIS: In general analysis of 24 studies with 28 trials on 1919 human subjects, there are small reductions in both systolic BP (SBP) and diastolic BP (DBP) with the pooled mean effects of 1.66 (95% confidence interval (CI): -2.48 and -0.84) and 0.76 mmHg (-1.31 and -0.20) in response to LTP administration. In analysis of 24-h ABP response to LTP intervention, the reductions of SBP and DBP are 1.30 (-2.49 and -0.11) and 0.57 mmHg (-1.49 and 0.35). In subgroup analysis, the anti-hypertensive efficacy appears to be related to baseline BP, ethnic differences, treatment duration and double versus not double-blind design. CONCLUSIONS: The present findings indicate that the BP-lowering effect of LTP is statistically significant, though small in magnitude. More clinical investigations (especially randomized double-blind trials with ABP) are warranted to determine the anti-hypertensive efficacy of LTP conclusively.

Dynapenic Abdominal Obesity and Risk of Heart Disease among Middle-Aged and Older Adults: A Prospective Cohort Study.

OBJECTIVES: The vicious cycle of dynapenia and abdominal obesity may have synergistic detrimental impacts on health. We aim to investigate the prospective association between dynapenic abdominal obesity and the risk of heart disease among middle-aged and older adults. DESIGN: A prospective cohort study. SETTING: English Longitudinal Study of Ageing, 2002-2019. PARTICIPANTS: A total of 4734 participants aged 50 years and older were included. MEASUREMENTS: Individuals were divided into non-dynapenia/non-abdominal obesity (ND/NAO), non-dynapenia/abdominal obesity (ND/AO), dynapenia/non-abdominal obesity (D/NAO), and dynapenia/abdominal obesity (D/AO) according to grip strength and waist circumference at baseline. The Cox proportional hazards models were used to obtain the hazard ratios (HRs) of incident heart disease associated with dynapenia and abdominal obesity after adjusting for potential confounding factors. RESULTS: During a median follow-up of 9.5 years, 1040 cases of heart disease were recorded. Compared with ND/NAO group, the multivariable HRs were 1.05 (0.92, 1.21) for ND/AO group, 1.31 (0.96, 1.81) for D/NAO group, and 1.39 (1.03, 1.88) for D/AO group. The significant association of D/AO with incident heart disease was detected in women but not in men [HR = 1.55 (1.07, 2.24) and 1.06 (0.60, 1.88), respectively]. Among middle-aged adults, significant associations of D/NAO and D/AO with incident heart disease were observed [HR = 2.46 (1.42, 4.29) and 1.74 (1.02, 2.97), respectively]. CONCLUSION: Both D/NAO and D/AO might increase the risk of developing heart disease, highlighting the importance of dynapenia and obesity early screening for heart disease prevention.

Soy isoflavone intake inhibits bone resorption and stimulates bone formation in menopausal women: meta-analysis of randomized controlled trials.

OBJECTIVE: To clarify the effects of isoflavone intake on bone resorption and bone formation. METHODS: We identified randomized controlled trials related to urinary deoxypyridinoline (Dpyr, a bone resorption marker) and serum bone-specific alkaline phosphatase (BAP, a bone formation marker) listed on MEDLINE (January 1966-April 2006), the Cochrane Controlled Trials Register, EMBASE (1985-January 2006), Science Citation Index and PUBMED (updated till April 2006). RESULTS: Nine studies with a total of 432 subjects were selected for meta-analysis. The urinary Dpyr concentration in subjects who consumed isoflavones decreased significantly by -2.08 nmol/mmol (95% confidence interval (CI): -3.82 to -0.34 nmol/mmol) in comparison with that in subjects who did not consume isoflavones. Isoflavone intake vs placebo intake significantly increased serum BAP by 1.48 microg/l (95% CI: 0.22-2.75 mug/l). Decreases in the urinary Dpyr concentration with isoflavone intake of <90 mg/day and with treatment lasting less than 12 weeks were -2.34 nmol/mmol (95% CI: -4.46 to -0.22 nmol/mmol) and -2.03 nmol/mmol (95% CI: -3.20 to -0.85 nmol/mmol), respectively. CONCLUSIONS: Isoflavone intervention significantly inhibits bone resorption and stimulates bone formation. These favorable effects occur even if <90 mg/day of isoflavones are consumed or the intervention lasts less than 12 weeks.

Effects of Milk Proteins Supplementation in Older Adults Undergoing Resistance Training: A Meta-Analysis of Randomized Control Trials.

BACKGROUND: Older adults experience age-related physiological changes that affect body weight and body composition. In general, nutrition and exercise have been identified as potent stimulators of protein synthesis in skeletal muscle. Milk proteins are excellent sources of all the essential amino acids and may represent an ideal protein source to promote muscle anabolism in older adults undergoing resistance training. However, several randomized control trials (RCTs) have yielded mixed results on the effects of milk proteins supplementation in combination with resistance training on body weight and composition. METHODS: PubMed, Web of Science and Cochrane databases were searched for literature that evaluated the effects of milk proteins supplementation on body weight and composition among older adults (age ≥ 60 years) undergoing resistance training up to September 2016. A random-effects model was used to calculate the pooled estimates and 95% confidence intervals (CIs) of effect sizes. RESULTS: The final analysis included 10 RCTs involving 574 participants (mean age range from 60 to 80.8 years). Overall, the combination of milk proteins supplementation and resistance training did not have significant effect on fat mass (0.30, 95% CI -0.25, 0.86 kg) or body weight (1.02, 95% CI: -0.01, 2.04 kg). However, a positive effect of milk proteins supplementation paired with resistance training on fat-free mass was observed (0.74, 95% CI 0.30, 1.17 kg). Greater fat-free mass gains were observed in studies that included more than 55 participants (0.73, 95% CI 0.30, 1.16 kg), and in studies that enrolled participants with aging-related medical conditions (1.60, 95% CI 0.92, 2.28 kg). There was no statistical evidence of publication bias among the studies. CONCLUSION: Our findings provide evidence that supplementation of milk protein, in combination with resistance training, is effective to elicit fat-free mass gain in older adults.

Effect of body mass index on overall survival of patients with allogeneic hematopoietic stem cell transplantation.

BACKGROUND/OBJECTIVES: The present work was performed to investigate the association between body mass index (BMI) before transplantation and the overall survival (OS) of patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). SUBJECTS/METHODS: Data from 310 adults who were diagnosed with acute leukemia and underwent allo-HSCT between March 2001 and December 2011 were analyzed. According to the suggested BMI categories for Asian population, patients with BMIs of ⩾23 and ⩾25 kg/m2 were identified as overweight and obese, respectively. Cox proportional hazards models was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The median follow-up time among the patients was 19.7 months (interquartile range=8.1-37.7). A total of 93 (34.8%) people died within the follow-up period. After adjusting for the potential confounders, normal-weight, overweight and obese patients showed significantly lower HRs than those of underweight patients, with a significant trend of OS improvement upon increasing BMI (P=0.019). Overweight and obese patients survived longer, with a significantly decreased HR by ~40% (HR=0.60; 95% CI: 0.38-0.95) compared with underweight and normal-weight patients. CONCLUSIONS: An increased OS was seen in allo-HSCT patients with BMI⩾23 kg/m2 compared to those with lower BMI. Further work are still needed to investigate of the effects of BMI or body composition on the survival of allo-HSCT patients.

Effect of whey protein on blood lipid profiles: a meta-analysis of randomized controlled trials.

Previous studies have suggested that whey supplementation may have beneficial effects on lipid profiles, although results were inconsistent. A literature search was performed in March 2015 for randomized controlled trials observing the effects of whey protein and its derivatives on circulating levels of triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). A meta-analysis was subsequently conducted. The meta-analysis results of 13 trials showed that whey supplementation significantly reduced the circulating TG level by 0.11 mmol/l (95% CI: -0.21, 0 mmol/l), whereas the whey protein had no effects on circulating TC (-0.11 mmol/l, 95% CI: -0.27, 0.05 mmol/l), LDL-C (-0.08 mmol/l, 95% CI: -0.23, 0.07 mmol/l) and HDL-C (0.01 mmol/l, 95% CI: -0.04, 0.05 mmol/l). Subgroup analysis showed that significant TG reduction disappeared in participants with low body mass index, low supplemental whey dose or under exercise training/energy restriction during the trial. No evidence of heterogeneity across studies and publication bias was observed. In conclusion, our findings demonstrated that the effects of whey protein supplementation were modest, with an overall lowering effect on TG but no effect on TC, LDL-C and HDL-C.

Central obesity and risks of pre- and postmenopausal breast cancer: a dose-response meta-analysis of prospective studies.

Epidemiologic evidence has shown inconsistent findings regarding the relationships between abdominal fatness, as measured by waist circumferences (WC) or waist-to-hip ratio (WHR), and risks of pre- and postmenopausal breast cancer (BC). A dose-response meta-analysis of prospective studies was conducted to address these issues. Potentially eligible studies were identified by searching PubMed and EMBASE databases, and by carefully reviewing the bibliographies of retrieved publications and related reviews. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. When the most fully adjusted RRs were combined, both WC (14 studies, RR per 10-cm increase = 1.06, 95% CI: 1.04-1.09, I2 = 29.9%) and WHR (15 studies, RR per 0.1-unit increase = 1.07, 95% CI: 1.01-1.14, I2 = 52.9%) were significantly positively associated with postmenopausal BC, but neither WC (eight studies, RR per 10-cm increase = 1.05, 95% CI: 0.99-1.10, I2 = 0%) nor WHR (11 studies, RR per 0.1-unit increase = 1.07, 95% CI: 0.95-1.21, I2 = 59.7%) were associated with premenopausal BC. The WHR-postmenopausal BC association lost statistical significance after correcting publication bias (RR per 0.1-unit increase = 1.06, 95% CI: 0.99-1.13). When considering BMI-adjusted RRs, WC was associated with both pre- (five studies, RR per 10-cm increase = 1.09, 95% CI: 1.02-1.16, I2 = 0%) and postmenopausal BC (seven studies, RR per 10-cm increase = 1.05, 95% CI: 1.02-1.08, I2 = 6.3%), whereas WHR was not associated with either pre- (seven studies, RR per 0.1-unit increase = 1.12, 95% CI: 0.94-1.34, I2 = 70.9%) or postmenopausal BC (eight studies, RR per 0.1-unit increase = 1.05, 95% CI: 0.98-1.13, I2 = 57.3%). Among non-current (former or never) users of hormone replacement therapy, the summary RR per 10-cm increase of postmenopausal BC associated with WC was 1.08 (95% CI: 1.03-1.05, I2 = 69.2%, seven studies; BMI-adjusted RR = 1.05, 95% CI: 1.02-1.09, I2 = 22.8%, four studies). This meta-analysis indicates that central obesity measured by WC, but not by WHR, is associated with modestly increased risks of both pre- and postmenopausal BC independent of general obesity.

Milk/dairy products consumption, galactose metabolism and ovarian cancer: meta-analysis of epidemiological studies.

Ovarian cancer is the fifth most common cause of cancer death among women and the leading cause of gynaecological cancer death in the United States. Milk/dairy products consumption was considered to be a risk factor for ovarian cancer mainly because milk carbohydrate-lactose and galactose metabolism is toxic to oocytes. However, recent evidence does not support this hypothesis completely. We collected epidemiological studies related to the association between milk/dairy products consumption or galactose metabolism (lactose, galactose, galactose-1-phosphate uridyltransferase, lactose/transferase) and ovarian cancer published between January 1966 and August 2003 and found 27 items from 22 independent studies. Twenty studies were case-control studies and the other two were cohort studies. A meta-analysis method was conducted to estimate relative risk combining all relative data. In general, we did not find any association between milk/dairy products or galactose metabolism and ovarian cancer risk in this meta-analysis. The consumption of whole milk and butter, which contain relatively high amounts of fat, was positively (relative risk > 1.2), but not significantly, associated with an increased risk.

Is milk responsible for male reproductive disorders?

The role of environmental compounds with estrogenic activity in the development of male reproductive disorders has been a source of great concern. Among the routes of human exposure to estrogens, we are particularly concerned about cows' milk, which contains considerable amounts of estrogens. The major sources of animal-derived estrogens in the human diet are milk and dairy products, which account for 60-70% of the estrogens consumed. Humans consume milk obtained from heifers in the latter half of pregnancy, when the estrogen levels in cows are markedly elevated. The milk that we now consume may be quite unlike that consumed 100 years ago. Modern genetically-improved dairy cows, such as the Holstein, are usually fed a combination of grass and concentrates (grain/protein mixes and various by-products), allowing them to lactate during the latter half of pregnancy, even at 220 days of gestation. We hypothesize that milk is responsible, at least in part, for some male reproductive disorders.

The experience of Japan as a clue to the etiology of testicular and prostatic cancers.

In Japan dramatic lifestyle changes occurred after World War 2. To examine the experience of Japan as a clue to the etiology, trends in the mortality rates of testicular and prostatic cancers from 1947 to 1998 were related to changes in dietary practices. The male population born before 1945 had a peak in death from testicular cancer in their thirties or forties, whereas those born after 1946 had a peak in their twenties. The death rate of prostatic cancer increased 25-fold almost linearly after the war. The intake of milk, meat, and eggs increased 20-, 9-, and 7-fold, respectively, after the war. In connection with the development and growth of testicular and prostatic cancers in Japan, particular attention should be paid to milk, because the increase in its consumption in this country is a recent occurrence and because milk contains considerable amounts of estrogens plus saturated fats.

[Mechanism of pineal and suprachiasmatic regulation on circadian rhythm of body temperature in rats].

OBJECTIVE: To investigate the mechanism of circadian rhythm of skin and core temperature as regulated by pineal and suprachiasmatic nucleus (SCN) in rats. METHOD: Pineal destruction and melatonin interference test were employed. RESULT: The two nuclei functioned differently in the maintenance of the temperature rhythm. Changes of the temperature level were nucleus related, i.e., up-regulated by pineal and down-regulated by SCN. In terms of initiation and daily running of the rhythmic oscillation, pineal is probably the central clock of the skin temperature rhythm, while SCN mainly controls the core temperature rhythm. CONCLUSION: The two nuclei interlink by way of neuroendocrine signals to balance over the oscillatory system of the circadian temperature.