Toxicity Assessment of Environmental Liquid Crystal Monomers: A Bacteriological Investigation on Escherichia coli and Staphylococcus epidermidis.

The widespread existence of liquid crystal monomers (LCMs) in various environmental matrices has been demonstrated, yet studies on the toxicological effects of LCMs are considerably scarce and are urgently needed to be conducted to assess the adverse impacts on ecology and human health. Here, we conducted a bacteriological study on two representative human commensal bacteria, Escherichia coli (E. coli) and Staphylococcus epidermidis (S. epidermidis), to investigate the effect of LCMs at human-relevant dosage and maximum environmental concentration on growth, metabolome, enzymatic activity, and mRNA expression. Microbial growth results exhibited that the highest inhibition ratio of LCMs on S. epidermidis reached 33.6% in our set concentration range, while the corresponding data on E. coli was only 14.3%. Additionally, LCMs showed more dose-dependent toxicity to S. epidermidis rather than E. coli. A novel in vivo solid-phase microextraction (SPME) fiber was applied to capture the in vivo metabolites of microorganisms. In vivo metabolomic analyses revealed that dysregulated fatty acid metabolism-related products of both bacteria accounted for >50% of the total number of differential substances, and the results also showed the species-specific and concentration-dependent metabolic dysregulation in LCM-exposed bacteria. The determination of enzymatic activity and mRNA relative expression levels related to oxidative stress confirmed our speculation that the adverse effects were related to the oxidative metabolism of fatty acids. This study complements the gaps in toxicity data for LCMs against bacteria and provides a new and important insight regarding metabolic dysregulation induced by environmental LCMs in human commensal bacteria.

Cardiac autonomic neuropathy modified the association between obesity and hypoglycemia in type 2 diabetes.

BACKGROUND: Previous studies have shown that increasing body mass index (BMI) was associated with decreased hypoglycemia in type 2 diabetes, but it remains uncertain whether this finding could be applied to patients with and without cardiac autonomic neuropathy (CAN). METHODS: The study included 7789 participants with type 2 diabetes from action to control cardiovascular risk in diabetes (ACCORD) trail. CAN was defined as SDNN < 8.2 ms and RMSSD < 8.0 ms. Obesity was defined as BMI ≥ 30 kg/m2. Outcomes were identified as severe hypoglycemia requiring any assistance (HAA) or requiring medical assistance (HMA). We assessed the association between obesity and severe hypoglycemia in type 2 diabetes with or without CAN using COX regression models adjusted for baseline characteristics. RESULTS: Over a median follow-up of 4.7 years, a total of 893 participants developed HAA and 584 participants developed HMA. Compared with non-obesity, obesity was associated with lower risk of severe hypoglycemia (HAA: hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.38-0.68, P < 0.001; HMA: HR 0.57, 95% CI 0.40-0.82, P = 0.002) in CAN present group, but not in CAN absent group (HAA: HR 0.98, 95% CI 0.83-1.16, P = 0.830; HMA: HR 0.97, 95% CI 0.79-1.19, P = 0.754). Similarly, increasing BMI was associated with reduced severe hypoglycemic events in participants with CAN, but not in participants without CAN. CONCLUSIONS: CAN modifies the association between obesity and hypoglycemia in type 2 diabetes. Type 2 diabetic individuals with CAN who are under weight control should pay attention to hypoglycemic events. TRIAL REGISTRY: http://www. CLINICALTRIALS: gov . Unique identifier: NCT00000620.

Interplay of heart rate variability and resting heart rate on mortality in type 2 diabetes.

AIMS: Heart rate variability (HRV) and resting heart rate (RHR) are usually analyzed and interpreted separately. We aimed to assess the interplay of HRV and RHR on mortality in type 2 diabetes. METHODS: The study included 7,529 participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. HRV metrics included standard deviation of all normal-to-normal intervals (SDNN) and root mean square of successive differences between normal-to-normal intervals (rMSSD). Abnormal values were defined based on <25th percentile for HRV and >75th percentile for RHR. Interactions of HRV status and RHR status were tested on multiplicative and additive scales. Results were validated in a subset of patients with type 2 diabetes (n = 745) from the Multi-Ethnic Study of Atherosclerosis. RESULTS: Low SDNN was associated with increased all-cause mortality in the high RHR group (HR 1.60; 95% CI 1.29-1.97), but not in the normal RHR group. Compared with those who had neither low SDNN nor high RHR, the presence of either low SDNN or high RHR was not significantly associated with an increased risk of all-cause mortality. In contrast, the combination of low SDNN and high RHR was associated with a significantly increased risk of all-cause mortality (HR 1.68; 95% CI 1.43-1.97). Significant multiplicative and additive interactions were found between HRV status and RHR status on risk of all-cause mortality (all Pinteraction < 0.05). Similar findings were observed for cardiovascular mortality, in analyses using rMSSD, and in the Multi-Ethnic Study of Atherosclerosis. CONCLUSIONS: The association between HRV and mortality risk is modified by RHR levels. Furthermore, low HRV and high RHR have interdependent and synergistic associations with mortality risk.

New Insights into Rate Control: Time in Target Range of Resting Heart Rate and Major Adverse Outcomes in Atrial Fibrillation.

Background: Few studies have examined the relationship between the fluctuation of heart rate control over time and cardiovascular outcomes in patients with atrial fibrillation. Our study sought to evaluate the independent association between time in target range (TIR) of resting heart rate and cardiovascular outcomes in the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) study. Methods: Target range of resting heart was defined as less than 80 beats per minute (bpm) for both rate and rhythm control groups. Time in target range was estimated over the first 8 months of follow-up using Rosendaal interpolation method. The association between TIR of resting heart rate and cardiovascular outcomes was estimated using adjusted Cox proportional hazards regression models. Results: Time in target range of resting heart rate (months 0 through 8) was 71 ± 34% in the rate control group and 83 ± 27% in the rhythm control group. Each 1-SD increase in TIR of resting heart rate was significantly associated with lower risk of major adverse cardiovascular events after full adjustment for demographics, medical history and history of prior heart surgery, as well as all-cause mortality. Conclusions: Time in target range of resting heart rate independently predicts the risk of cardiovascular outcomes in patients with atrial fibrillation. Long-term maintenance of heart rate on target is of great importance for patients with atrial fibrillation.