Peripheral blood flow estimated by laser doppler flowmetry provides additional information about sleep state beyond that provided by pulse rate variability.

Pulse rate variability (PRV), derived from Laser Doppler flowmetry (LDF) or photoplethysmography, has recently become widely used for sleep state assessment, although it cannot identify all the sleep stages. Peripheral blood flow (BF), also estimated by LDF, may be modulated by sleep stages; however, few studies have explored its potential for assessing sleep state. Thus, we aimed to investigate whether peripheral BF could provide information about sleep stages, and thus improve sleep state assessment. We performed electrocardiography and simultaneously recorded BF signals by LDF from the right-index finger and ear concha of 45 healthy participants (13 women; mean age, 22.5 ± 3.4 years) during one night of polysomnographic recording. Time- and frequency-domain parameters of peripheral BF, and time-domain, frequency-domain, and non-linear indices of PRV and heart rate variability (HRV) were calculated. Finger-BF parameters in the time and frequency domains provided information about different sleep stages, some of which (such as the difference between N1 and rapid eye movement sleep) were not revealed by finger-PRV. In addition, finger-PRV patterns and HRV patterns were similar for most parameters. Further, both finger- and ear-BF results showed 0.2-0.3 Hz oscillations that varied with sleep stages, with a significant increase in N3, suggesting a modulation of respiration within this frequency band. These results showed that peripheral BF could provide information for different sleep stages, some of which was complementary to the information provided by PRV. Furthermore, the combination of peripheral BF and PRV may be more advantageous than HRV alone in assessing sleep states and related autonomic nervous activity.

Cardiovascular and renal disease manifestation and healthcare resource utilization in patients on first-line oral therapy for type 2 diabetes: A claims-based observational cohort study.

AIM: To examine incident cardiovascular disease (CVD) and chronic kidney disease (CKD) diagnosis and associated healthcare resource utilization (HCRU) in a real-world population of patients with type 2 diabetes (T2D) initiating first-line oral antidiabetes drug (OAD) therapy. MATERIALS AND METHODS: Adults with T2D without CVD/CKD initiating first-line OAD therapy from 2008 to 2018 IBM MarketScan claims data were included. Incident CVD/CKD diagnoses following OAD initiation and first diagnosis type were assessed. Risk of incident diagnosis of heart failure (HF) among patients with CKD and of CKD among patients with HF was evaluated. HCRU and costs were compared for the 12 months before and after the first CVD/CKD diagnosis. RESULTS: Of 12 286 016 patients, 1 286 287 met all the inclusion criteria. During follow-up (mean 752 days), 205 865 (16.0%) patients had CVD/CKD diagnoses; the most common first diagnosis was the composite cardiorenal outcome of HF and/or CKD (64.6%). Most first diagnoses were within 2 years of OAD initiation. For HF and CKD, diagnosis of one was associated with increased risk of subsequent diagnosis of the other (both P < .001). Average annualized visits per patient increased by 31% after the first CVD/CKD diagnosis and annualized payer and patient costs increased by 75% and 26%, respectively, compared with the 12 months prediagnosis. Costs increased for all diagnosis types. CONCLUSIONS: Most first CVD/CKD diagnoses occurred within 2 years after OAD initiation and were associated with increased HCRU and costs. Reducing CVD/CKD risk with T2D treatments that improve both cardiovascular and renal outcomes may attenuate the burden of illness.

Clinical Outcomes and Healthcare Resource Utilization in a Real-World Population Reflecting the DAPA-CKD Trial Participants.

INTRODUCTION: The DAPA-CKD trial assessed dapagliflozin in patients with chronic kidney disease (CKD) with or without type 2 diabetes (T2D). To aid interpretation of results, renal and cardiovascular outcomes plus healthcare resource utilization (HCRU) and costs were assessed in a real-world population similar to that of DAPA-CKD. METHODS: Henry Ford Health System (2006-2016) data were used to identify patients with CKD stages 2-4 [estimated glomerular filtration rate (eGFR) 25-75 ml/min/1.73 m2 at index and urine albumin-to-creatinine ratio (UACR) 0-5000 mg/g; n = 22,251]. Included patients had confirmatory eGFR ≥ 90 days post-index and no kidney transplant or progression to end-stage kidney disease during 12 months pre-index. The final population (n = 6557) was stratified by UACR (0-29, 30-199 and 200-5000 mg/g; the last comprising the DAPA-CKD-like cohort). Patients were followed for 5 years post-index. RESULTS: Adverse clinical outcomes incidence increased with UACR and was highest for the DAPA-CKD-like cohort (UACR 200-5000 mg/g) versus lower UACR categories (0-29 mg/g and 30-199 mg/g): renal composite outcome (progression to CKD stage 5, dialysis, transplant, ≥ 50% sustained eGFR decline): 26.0% versus 2.2% and 5.8%; heart failure (HF): 36.1% versus 13.9% and 24.6%; myocardial infarction: 11.3% versus 4.7% and 7.4%; stroke: 8.9% versus 4.0% and 5.7%; and mortality: 18.5% versus 6.0% and 11.7%, respectively. Within the DAPA-CKD-like cohort, patients with versus without T2D or HF had a higher frequency of adverse outcomes. The DAPA-CKD-like cohort also had significantly higher annualized per-patient healthcare costs ($39,222/year versus $19,547/year), hospital admission rate (0.55/year versus 0.20/year) and outpatient specialist visit rate (7.55/year versus 6.74/year) versus the lowest UACR category. CONCLUSION: The significant adverse renal and cardiovascular outcomes observed, particularly in the DAPA-CKD-like cohort, represent a substantial burden resulting in increased mortality, HCRU and costs, demonstrating the need for additional treatment options.

Combined acoustical and visual performance of noise barriers in mitigating the environmental impact of motorways.

This study investigated the overall performance of noise barriers in mitigating environmental impact of motorways, taking into consideration their effects on reducing noise and visual intrusions of moving traffic, but also potentially inducing visual impact themselves. A laboratory experiment was carried out, using computer-visualised video scenes and motorway traffic noise recordings to present experimental scenarios covering two traffic levels, two distances of receiver to road, two types of background landscape, and five barrier conditions including motorway only, motorway with tree belt, motorways with 3 m timber barrier, 5m timber barrier, and 5m transparent barrier. Responses from 30 participants of university students were gathered and perceived barrier performance analysed. The results show that noise barriers were always beneficial in mitigating environmental impact of motorways, or made no significant changes in environmental quality when the impact of motorways was low. Overall, barriers only offered similar mitigation effect as compared to tree belt, but showed some potential to be more advantageous when traffic level went high. 5m timber barrier tended to perform better than the 3m one at the distance of 300 m but not at 100 m possibly due to its negative visual effect when getting closer. The transparent barrier did not perform much differently from the timber barriers but tended to be the least effective in most scenarios. Some low positive correlations were found between aesthetic preference for barriers and environmental impact reduction by the barriers.

[Enhanced nisin production by overexpression of nisin immunity gene nisI in the nisin-producing strain].

OBJECTIVE: Our aim was to enhance nisin production by overexpression of nisin immunity gene nisI in nisin-producing strains. METHODS: Nisin immunity gene nisI with a strong promoter P59 was cloned into vector pHJ201 and introduced into Lacotococcus lactis NZ9800, resulting in a recombinant strain L. lactis NZ9800/pHMI. Then the differences between the recombinant strain and the control strain L. lactis NZ9800/pHJ201 were analyzed in several aspects, including their growth curves, nisin resistance level and antibacterial activity against indicator strain Microccus flavus NCIB 8166. RESULTS: The overexpression of nisI had no significant difference in growth rate between recombinant strain and contrast strain. However, it promoted recombinant strain tolerance 25% higer nisin resistance level and stronger antibacterial activity against M. flavus NCIB 8166, which was increased by 32% and 25% when fermented for 6 and 8 hours, respectively. CONCLUSION: These results indicated that overexpression of nisI gene in the nisin producing strain can effectively enhance nisin resistence level and thus improve nisin production.

[Improving heat and pH stability of nisin by site-directed mutagenesis].

OBJECTIVE: The aim of this study was to optimize the property of nisin through altering its specific amino acid by site-directed mutagenesis method. METHODS: On the basis of M21K nisinZ, a former reported nisinZ mutant that exhibited antimicrobial activity against Gram-negative bacteria, the 29th amino acid of it was mutated from serine to lysine. The mutant M21K/S29K nisZ gene was cloned into vector pMG36e and the recombinant plasmid was introduced into Lacotococcus lactis NZ9800. The resulting M21K/S29K nisinZ was then isolated and purified, and its antibacterial activity, antibacterial spectrum and stability were analyzed and compared to those of M21K nisinZ and nisinZ. RESULTS: Compared with wild-type nisinZ and M21K nisinZ, the M21K/S29K nisinZ displayed reduced antimicrobial activity, but showed significantly increased stabilities to heat and pH stress. Moreover, M21K/S29K nisinZ also exhibited antimicrobial activity against Gram-negative bacteria as M21K nisinZ did. CONCLUSION: By changing the 29th amino acid of nisin, we can optimize the property of nisin, especially its stability to heat and pH stress.

[Mitochondria aberration of Aspergillus flavus under citral stress circumstance].

Observation of mitochondrion in Aspergillus flavus damaged by citral under uransmission electron microscope, it was found that mitochondria had changes on number increase and shape aberrance as hyperplasia or hypertrophy, which resulted from the DNA replication system in mitochondria was damaged by citral. From the data that free radical in A. flavus which were determined by MDA method, it was showed that citral damaged mitochondria via induced free radical, which affected oxidation-reduction system and energy metabolism.

Acute and genetic toxicity of essential oil extracted from Litsea cubeba (Lour.) Pers.

Litsea cubeba oil is an aromatic essential oil extracted from the fresh fruits of Litsea cubeba (Lour.) Pers. It is used as a flavor enhancer in foods, cosmetics, and cigarettes; as a raw material in the manufacture of citral, vitamins A, E, and K, ionone, methyl ionone, and perfumes; and as an antimicrobial and insecticide. Based on the widespread use of L. cubeba oil, its insolubility in water, resulting in its partition in soil sediment, and its volatility when exposed to the atmosphere, risk of injury due to consumption and occupational exposure may be significant. In the present study, we studied the toxicity of L. cubeba oil with a battery of acute and genetic toxicity tests in Institute of Cancer Research mice and Sprague-Dawley rats. The oral, dermal, and inhalation 50% lethal dose and concentration (LD50 and LC50) of L. cubeba oil were determined. Results indicated that the oral LD50, the dermal LD50, and the inhalation LC50 are approximately 4,000 mg/kg of body weight, in excess of 5,000 mg/kg, and approximatively 12,500 ppm, respectively. We therefore conclude that L. cubeba oil is slightly toxic. In addition, the genetic toxicity of L. cubeba oil was assessed with Salmonella Typhimurium, by determination of the induction of micronuclei in bone marrow cells, and also by testing for chromosome aberration in spermatocyte cells of Institute of Cancer Research mice. The results of genetic toxicity testing of L. cubeba oil in vitro and in vivo were negative.

Effects of citral on Aspergillus flavus spores by quasi-elastic light scattering and multiplex microanalysis techniques.

Citral refined from Litsea cubeba oil has been found to have a strong influence on fungi, especially Aspergillus flavus. Multiplex microanalysis and quasi-elastic light scattering techniques were applied to study the effects of citral on Aspergillus flavus spores from the levels of membrane, organelle and intracellular macromolecule. It was found that citral injured the wall and the membrane of A. flavus spore, resulting in decrease of its elasticity. After entering the cell, citral not only influenced the genetic expression of mitochondrion reduplication and its morphology, but also changed the aggregation of protein-like macromolecules. As a result, cells, organelles and macromolecules lost their normal structures and functions, eventually leading to the loss of germination ability of A. flavus spores. Since Litsea cubeba oil as food additive and antifungal agent is safe and less poisonous, it is important to elucidate the inhibitory mechanisms of Litsea cubeba oil on the germination ability of A. flavus spore.

[Study on morphological change of aspergillus flavus damaged by citral with a multi-channel micro-spectrophotometer system].

Citral extracted from litsea cubeb oil was used as antibacterial drug; toxigenic and atoxigenic Aspergillus flavus cell (AFC) were used as its target. Multi-channel micro-spectrophotometer (MMSP) and micro-image analysis were applied. Under the pressure of citral, changes in AFC were measured, including items such as absorbance, area, perimeter, major axis length and minor axis length. We found that toxigenic AFC had two characteristic absorbent peaks at 410 nm and 665 nm, and that the waveforms of absorption spectrum of toxigenic and atoxigenic AFC migrated and their peak areas increased, and that four morphological parameters reduced with citral concentration increasing. The results suggest that citral damages selective permeability and structure of membrane to enter to cell, and acts on target molecule or organelle to bring changes in physiology and biochemistry. In real-time, in-situ and non-invasive situation, the dynamic changes in shape and intracellular macromolecule are fastly measured during the drugs damage a living cell, which not only provides these changes with necessary physical parameters, but also has an importance in theoretical research and experimental method.

[Study on quantitative test on the DNA damage of Aspergillus flavus caused by citral with a comet analysis system].

Comet assay provided a object method for DNA damage caused by physical and chemical factors. A new system of SCGE image analysis, which combines microphotodensitometry and microphotography with image analysis have been developed. Compared with the international popular, it has well at speed, convenience, exchange face of Chinese and English and print. We used it to directly determine the A. flavus' DNA damages for citral. The results show that test time was shorted 2/3 and accuracy was improved. It is probable that cell structural parameter, cell molecule and membrane could be test long, successive, movably and instantly. So the new system has a wide application.

[Study on biochemical mechanism of citral damage to the A. flavasi's mitochondria].

Adopted biochemical method and combinded with Scanning Electron Microscope(SEM) to observe, study the inhibition-growth mechanism to A. flavus when citral was permeated to the cell and damaged mitochondria, the result suggested that the mitochondria changed in many kinds of unrule shape and the oxidation-reduction system was destroyed, when the citral reached at the level of anaphylactic consistency to A. flavus. Compared with the control group, activities of MDH and SDH in experimental group non-reversibly decreased 27.1% and 23.8% respectively, and grandully lost. When respectively used the succinate, pyruvate and alpha-ketoglutarate as substrates, the respiration speed of mitochondria separatelly decreased 24.1%, 36.1%, 14.3%. It suggested that the citral could inhibit the biosynthesis of the mycelial DNA, RNA, lipoid and protein, so promoted to dath.