Safety Evaluations of Long-Term and Excessive Intakes of Bifidobacterium longum CLA8013: A Placebo-Controlled, Randomized, Double-Blind Study

Heat-killed Bifidobacterium longum CLA8013 has been demonstrated to improve the frequency of defecation, straining, and pain during defecation in human placebo-controlled, double-blind, parallel-group studies. We conducted a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety of both long-term and excessive intakes of heat-killed B. longum CLA8013, when used as a food with functional claims. In both tests, 30 healthy volunteers were divided into two groups: an active group that ingested heat-killed B. longum CLA8013 and a placebo group. In the long-term intake safety study, participants in the active group ingested 25 billion cells/day for 12 weeks. In the excessive intake safety study, participants in the active group ingested 125 billion cells/day for 4 weeks. Physical, hematological, biochemical, and urine examinations were conducted, and adverse events were evaluated in both studies. The studies revealed no abnormalities in any of the safety tests. In conclusion, no safety-related issues were identified with long-term or excessive intake of heat-killed B. longum CLA8013.

Effect of Zn deficiency and excessive bicarbonate on the allocation and exudation of organic acids in two Moraceae plants

The effect of zinc(Zn) deficiency and excessive bicarbonate on the allocation and exudation of organic acids in plant organs(root, stem, and leaf) and root exudates of two Moraceae plants(Broussonetia papyrifera and Morus alba) were investigated. Two Moraceae plants were hydroponically grown and cultured in nutrient solution in four different treatments with 0.02 mM Zn or no Zn,combined with no or 10 mM bicarbonate. The variations of organic acids in different plant organs were similar to those of root exudates in the four treatments except B. papyrifera, which was in a treatment that was a combination of 0.02 mM Zn and no bicarbonate. The response characteristics in the production, translocation, and allocation of organic acids in the plant organs and root exudates varied with species and treatments. Organic acids in plant organs and root exudates increased under Zn-deficient conditions,excessive bicarbonate, or both. An increase of organic acids in the leaves resulted in an increase of root-exuded organic acids. B. papyrifera translocated more oxalate and citrate from the roots to the rhizosphere than M. alba under the dual influence of 10 mM bicarbonate and Zn deficiency. Organic acids of leaves may be derived from dark respiration and photorespiration. By comparison, organic acids in stems, roots, and root exudates may be derived from dark respiration and organic acid translocation from the leaves. These results provide evidence for the selective adaptation of plants to environments with low Zn levels or high bicarbonate levels such as a karst ecosystem.

Excessive Weight Gain during Pregnancy and Prognosis of Childbirth in Douala (Cameroun)

The objective was to describe the maternofetal outcome of childbirth in women with excessive weight gain during pregnancy. We conducted a cross-sectional analytical study over a period of 03 months in the Obstetrics Department of Laquintinie Hospital in Douala (HLD). Our study population consisted of any pregnant in labor or waiting for a caesarean section. We compared two groups of pregnant women with excessive weight gain during pregnancy (exposed) and those without excessive weight gain during pregnancy (unexposed). We recorded 240 pregnant women who gave birth at the HLD maternity, 59 of whom had excessive weight gain during pregnancy, which gave us a proportion of 24.6%. The only sociodemographic characteristic associated with excessive weight gain during pregnancy was the married marital status of the pregnant women (OR: 2.0 (1.1 - 3.8) P = 0.023). Pregnant women with maternal complications associated with excessive weight gain had an average elevated uterine height of 35.4 (P = 0.007). The increase in caesarean section rate (P = 0.094) and the onset of pregnancy-related hypertension (HTA) showed differences close to significance (P = 0.063). Mean birth weight was higher (P = 0.023) in pregnant women with excessive weight gain during pregnancy. Ultimately, excessive weight gain during pregnancy has deleterious effects on the course of pregnancy and childbirth. It promotes the onset of pregnancy HTA and macrosomia.

Life Cycle Assessment-based method of Excessive Commodity Packaging on Energy Conservation and Emissions Reduction

Based on a Life Cycle Assessment model, the effect of the whole life cycle of excessive commodity packaging on the environment was analyzed by eBalance Evaluation LCA software from production through circulation. The cost evaluation system and environment impact model of its three main processes, that is, material production, product machining and waste manufacturing, were established to identify the main environmental impact corresponding indicators and the influence on energy conservation and emissions reduction of excessive packaging life cycle. And packaging of moon-cakes was taken as an example to analyze the difference between the ordinary packaging and excessive packaging of moon-cakes in terms of life cycle assessment and costs analysis. Meanwhile some measures are put forward to conserve energy and reduce emissions.

Outcome of cesarean delivery in women with excessive weight gain during pregnancy

The objective of this study was to assess the effects of excessive weight gain during pregnancy on the outcome of cesarean delivery. It was a cohort study comparing the outcome of cesarean delivery between 56 pregnant women with excessive weight gain during pregnancy and 75 pregnant women with no excessive weight gain during pregnancy, consecutively recruited at the Yaoundé Gyneco-Obstetric and Pediatric Hospital, Cameroon. In women delivered by cesarean section, excessive weight gain during pregnancy was found to predispose to: time interval from parietal incision to fetal extraction of more than five minutes, duration of cesarean section more than 60 minutes, blood loss more than 1000 ml during surgery, post-operative maternal complications, especially sepsis, fetal weight >3.5 kg and macrosomia. A systematic screening of excessive weight gain should be offered to all pregnant women, so as to prevent the adverse effects of excessive gestational weight gain on cesarean outcome.

Safety Evaluation of Excessive Intake of <i>Lactococcus lactis</i>Subsp. <i>lactis</i>JCM 5805: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial

Background/Aims: Administration of a lactic acid bacterial strain, Lactococcus lactis subsp. lactis JCM 5805 (LC-Plasma), is reported to prevent viral infection via activation of plasmacytoid dendritic cells in mouse and human studies. As it is assumed that LC-Plasma is taken in excess when it is commercially provided as a supplement, we conducted a trial using capsules to give 250 mg LC-Plasma (5 times the effective anti-viral dose) every day for four weeks to healthy volunteers to investigate the safety of excessive intake of LC-Plasma. Trial Design: A randomized, double-blind, placebo-controlled, parallel-group trial was conducted. Methods: Forty healthy subjects were randomly assigned to the LC-Plasma group (daily intake of five capsules containing 50 mg heat-killed LC-Plasma cells per capsule) or the placebo group (daily intake of five placebo capsules with no LC-Plasma). Physical, hematological, biochemical and urinary examinations and medical interviews were used to evaluate safety. Results: No abnormal differences were observed after excessive intake of LC-Plasma capsules when compared to the intake of placebo capsules. Conclusions: There are no safety concerns associated with the excessive intake of heat-killed LC-Plasma capsules.

Original Research: Pupillary Constriction Velocity and Latency to Predict Excessive Daytime Sleepiness

Background: Excessive daytime sleepiness (EDS) is common in adults. A need exists for an easier and faster objective clinical measures of EDS. The autonomic nervous system controls pupil size and prior pupillometry studies have demonstrated associations with sleepiness. We used a novel portable device to assess pupillometry and prospectively evaluated a sleep clinic cohort. Methods: Following IRB approval Pupillometry (The ForSiteTM, NeurOptics, Irvine, CA), was performed on 113 sleep clinic patients. Constriction and dilation velocity and latencies, minimum and maximum aperture were obtained along with Epworth Sleepiness Score (ESS), 10 point Visual Analog Scale (VAS), BMI, gender, age and AHI. Three sets of measures were obtained and analyzed with ANOVA, t-test, Linear Regression and Pearson correlation coefficients (SAS, Cary, NC). Results: Both constriction velocity and latency correlated with VAS (n = 88, r = 0.28, p = 0.007 and r = 0.31, p = 0.004). Only constriction velocity correlated with AHI (n = 78, r = -0.27, p = 0.016). Multivariate linear regression which includes VAS and age predicted constriction velocity (r = 0.36, p = 0.002) and latency (r = 0.38, p = 0.001). Using Pearson correlation, AHI and VAS combined were associated with constriction velocity (-0.273 (0.016), and 0.284 (0.007), respectively). Using a maximum constriction velocity threshold value (age adjusted) of 2.8, VAS ≥ 6 was predicted with a sensitivity of 83% and specificity of 84%. Conclusions: Pupillary constriction velocity and latency predict self-reported VAS state of sleepiness. While both are affected by age, only constriction velocity is affected by apnea severity. These data suggest that a portable pupillometer may provide a method to identify individuals with abnormal sleepiness.

Insomnia and Excessive Daytime Sleepiness in Parkinson’s Disease Patient—A Review Article

Sleep-wake disorders play an important role among non-motor symptoms in Parkinson’s Disease, being a constant subject of research in recent years. There are a multitude of sleep-wake disturbances that worsen the patient’s quality of life, insomnia and excessive daytime sleepiness being two of the most frequent complaints. The aim of this review is to highlight the most relevant clinical trials conducted during the last 5 years, focusing on the problematic of insomnia and daytime sleepiness correlated with Parkinson’s Disease and its treatment. Three electronic databases (Pubmed, Science Direct and Google Scholar) were searched during March and April 2020 for articles on this topic, finally selecting 21 most relevant articles that we have included in this review. Interesting aspects regarding correlation between sleep-wake disorders and Parkinson’s disease were found, showing that non-motor symptoms may be independent of the disease itself. We discussed the most recent advances in treatment opportunities and the adverse effects, with insomnia and daytime sleepiness among the most common complaints. Besides newly developed pharmacological therapy, consisting in mostly dopaminergic agonists or levodopa adjuvant drugs. Other possibly effective therapies on sleep-wake disorders such as deep brain stimulation, dietary changes, bright light therapy and alternative medicine protocols are also reviewed. Insomnia and excessive daytime sleepiness are common complaints in Parkinson’s disease patients, being either self-standing non-motor symptoms or adverse effects of the antiparkinsonian medication, diminishing patient’s quality of life. The effervescence of research on this topic shows promising results, with new clinical trials still to come in the near future.

Excessive participation in on-line internet action games by two American teenagers: Case report, description of extent of overuse, and adverse consequences

In the past 15 years, there have been more than 40 articles in the medical literature about excessive participation in on-line internet action games by adolescents and young adults. The following case reports provide detailed information on two boys, ages 16 and 20 years respectively, who are compulsive and enthusiastic internet gamers, to the exclusion of family communication, school activities, academic performance, participation in sports and dating. They have not mastered any of the usual goals of adolescent development.

Factors Associated with Excessive Daytime Sleepiness in Obstructive Sleep Apnea Syndrome under CPAP Treatment

The purpose of this study was to assess factors associated with subjective sleep evaluation, chiefly excessive daytime sleepiness (EDS) in obstructive sleep apnea syndrome (OSAS) adult outpatients under continuous positive airway pressure (CPAP) treatment. One thousand and forty-eight OSAS outpatients (mean age: 51.4% male: 90.5%) who were treated by CPAP were consecutively collected. Age, sex, CPAP compliance (CPAP usage as their device of nights with application-time of at least 4 hours per night objectively;%usage ≥ 4 h/d), and Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) of the patients showing EDS (Japanese version of the Epworth Sleepiness Scale;JESS ≥ 11) were compared cross-sectionally with those of the patients who did not show EDS (JESS < 11). Nineteen point two % of all patients showed EDS subjectively. Two hundred one patients were classified to an EDS(+) group and an 847 patients were classified to EDS(–) group. Age and global PSQI-J scores were significantly different between the two groups. Logistic regression showed that EDS was significantly associated with global PSQI-J scores, but not with age. Among PSQI-J components, overall sleep quality, duration of sleep, sleep disturbance, and day dysfunction due to sleepiness were significantly higher in the EDS(+) group. Especially, 19.4% of patient in the EDS(+) group reported actual sleep time during the past month to be less than 5 hours/day. Although functional relationship should be further evaluated, insufficient sleep is the main factor associated with EDS in the OSAS patients under CPAP treatment.

Intervention Strategies of Excessive Masturbation for a 19-Years Youth: Experience of Counseling Intervention

Introduction: Excessive masturbation has for long been reported to affect youths with intervention strategies to intervene with this problem remaining unclear. This study aimed at determining the underlying factors for excessive masturbation, its effects and intervention strategies used. Methods: This was a case study design for a youth aged 19 years;affected by excessive masturbation. Data were collected through individual counseling and intervention. It involved 15 counseling sessions which were run in nine months in a three weeks interval. The sessions involved narration and exploration of the causes and effects of masturbation. Counseling intervention was built in a vicious circle. Results: Several factors, effects and intervention strategies were identified, reported and discussed in this study. Main causes were such as stories from friends and pornographic videos. Effects were multiple risk behaviors and health problems. Counseling model for individual was developed. Conclusion: The study indicates that there are multiple causes and effects of excessive masturbation. Since masturbation is secretly done, the effects are not widely known to many people. Most of these effects are long-term which affects a person psychologically, physically, socially and morally.

Local Government Behavior behind China's Excessive Investment under Decentralization——Theoretical and Empirical Analysis Based on Manufacturing Sector

This paper investigates the effect of local government intervention on capital deepening of manufacturing sector by using interprovincial panel data sets of 28 Chinese provinces,municipalities and autonomous regions between 1994 and 2011.Theoretical research indicates that as a transitional economy,China's local government intervention in corporate investment behaviors will cause excessive investment,thus bringing about a long-term and sustained tendency of capital deepening in manufacturing sector.Empirical test further discovers that in a certain range,the phenomenon of capital deepening in manufacturing sector is not an inevitable result endogenous to economic development and technology progress,and that investment behaviors of manufacturing sector are largely subject to the external institutional environment.Fiscal decentralization has indeed promoted capital deepening of manufacturing sector.Financial credit expansion and interventions in SOEs are major instruments for local governments to intervene in the capital deepening of manufacturing sector and such an influence is particularly significant for China's central,western and northeast regions.Therefore,clarifying government functions and improving local government performance review mechanism are of great significance to the healthy development of China's manufacturing sector.

The Determination of Excessive Defense by Judicial Practice and Its Rethinking——Based on an Analysis of 722 Criminal Judgments

Concerning the determination of excessive defense,the main problems are the judicial practice of determining excessive defense only based on the resul of harm inflicted on a perpetrator;identifying excessive harm generally as an intentional crime;limiting the scope of exemption from punishmen of excessive defense relatively narrowly as well as repeated appraisals and indirect punishments.For the improvement of judicial determination of excessive defense,the following efforts should be made.First,from the perspective of ex ante,determining the necessary limits as the standard of whether the act of defense was necessary to stop unlawful infringement Second,paying due attention to the influence of the awareness of defense on the form of culpability and in general circumstances determining excessive defense as a negligent crime.Third,giving sufficient consideration of the extent to which the possibility of anticipation decreased when the defender was faced with unlawful infringement and expanding the scope of exemption from punishment for excessive defense.Fourth,avoiding repeated appraisals and indirect punishments by analyzing the factual grounds and essentia foundations of the circumstances of lesser or greater punishments.

A Systematic Review of Excessive Speed Monitoring and Control System for Accident Prevention on Cameroon Highways

Road safety is still an important issue with road accidents among the leading causes of death accounting for more than 1.2 million fatalities and 50 million injuries globally per year. Of these casualties, speeding is a substantial contributing factor. Nowadays, speed reduction is mainly achieved through speed law enforcement measures. The review is aimed at examining the different enforcement approaches used to control and monitor excessive speeds on highways at large and particularly in Cameroon. A systematic search was performed in Science Direct, Elsevier, google scholar, scientific research, and Springer, ResearchGate, Scopus, and PubMed databases. Furthermore, references of selected articles were reviewed to maximize the rate of articles found. The details of the research articles were generated using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow chart. The results show that of 658 retried articles, duplicates of 458 were excluded and 200 were screened. A total of 61 and 40 articles were screened from abstract and full pdf text respectively. Finally, 15 relevant studies were included in the study. The review revealed that the included articles on speed enforcement on the highway were limited to sanctioning defaulters for fine payments.

Excessive 5-year weight gain predicts metabolic syndrome development in healthy middle-aged adults

AIM:To quantitatively examine the impacts of an easyto-measure parameter-weight gain-on metabolic syndrome development among middle-aged adults. METHODS:We conducted a five-year interval observational study.A total of 1384 middle-aged adults not meeting metabolic syndrome(MetS)criteria at the initial screening were included in our analysis.Baseline data such as MetS-components and lifestyle factors were collected in 2002.Body weight and MetS-components were measured in both 2002 and 2007.Participants were classified according to proximal quartiles of weight gain(WG)in percentages(%WG≤1%,1%< %WG≤5%,5%<%WG≤10%and%WG>10%, defined as:control,mild-WG,moderate-WG and severe-WG groups,respectively)at the end of the follow-up. Multivariate models were used to assess the association between MetS outcome and excessive WG in the total population,as well as in both genders. RESULTS:In total,175(12.6%)participants fulfilled MetS criteria within five years.In comparison to the control group,mild-WG adults had an insignificant risk for MetS development while adults having moderate-WG had a 3.0-fold increased risk for progression to MetS [95%confidence interval(CI),1.8-5.1],and this risk was increased 5.4-fold(95%CI,3.0-9.7)in subjects having severe-WG.For females having moderate-and severe-WG,the risk for developing MetS was 3.6(95% CI,1.03-12.4)and 5.5(95%CI,1.4-21.4),respectively. For males having moderate-and severe-WG,the odds ratio for MetS outcome was respectively 3.0(95%CI, 1.6-5.5)and 5.2(95%CI,2.6-10.2). CONCLUSION:For early-middle-aged healthy adults with a five-year weight gain over 5%,the severity of weight gain is related to the risk for developing metabolic syndrome.

Excessive parasympathetic responses to sympathetic challenges: a treatable, hidden, dynamic autonomic imbalance

Background:A common assumption with autonomic assessment is that one branch opposes the other.With independent measures of parasympathetic (P) and sympathetic (S) ac tivity,based on concurrent time-frequency analysis of respiratory activity and heart rate variability,this assumption has been challenged.Clinical observations of unprovoked P-excess during S-stimulation have been associated with treatable,abnormal responses.Method:Serial autonomic profiling of 12,967 patients was performed using the P&S method (ANX-3.0 Autonomic Monitor by ANSAR Medical Technologies,Inc.,Philadelphia,PA) over a five-year period.Treatment protocols are very low-dose and depend on patient history.For cardiovascular disease patients,Carvedilol was prescribed.For non-CVD patients,Nortriptyline was prescribed.In some cases where end-organ effects were not yet presented or relieved,patients were weaned of therapy once PE was relieved.Alternative therapies included Specific Chiropractic Adjustment,better known in the literature as Chiropractic Manipulative Therapy and intensive zero-impact,cardiovascular exercise.Results:PE patients present with normal HR and BP and no other apparent symptoms at rest.However,they reported symptoms of:sleep difficulties,palpitations,poor peripheral circulation,general malaise,depression (often with anxiety or ADD-like symptoms),frequent headache or migraines,menopause difficulties in women,hypothyroidism,cognitive difficulties,gastrointestinal upset,persistent weight-gain,and dizziness after standing.Conclusion:Normalizing PE,regardless of method,stabilizes the patient,relieves symptoms,improves quality of life,and improves patient outcomes.

Prenatal cadmium exposure impairs neural tube closure via inducing excessive apoptosis in neuroepithelium

Birth defects have become a public health concern.The hazardous environmental factors exposure to embryos could increase the risk of birth defects.Cadmium,a toxic environmental factor,can cross the placental barrier during pregnancy.Pregnant woman may be subjected to cadmium before taking precautionary protective actions.However,the link between birth defects and cadmium remains obscure.Cadmium exposure can induce excessive apoptosis in neuroepithelium during embryonic development progresses.Cadmium exposure activated the p53 via enhancing the adenosine 5‘-monophosphate(AMP)-activated protein kinase(AMPK)and reactive oxygen species'(ROS)level.And cadmium decreases the level of Paired box 3(Pax3)and murine double minute 2(Mdm2),disrupting the process of p53 ubiquitylation.And p53 accumulation induced excessive apoptosis in neuroepithelium during embryonic development progresses.Excessive apoptosis led to the failure of neural tube closure.The study emphasizes that environmental materials may increase the health risk for embryos.Cadmium caused the failure of neural tube closure during early embryotic day.Pregnant women may be exposed by cadmium before taking precautionary protective actions,because of cadmium concentration-containing foods and environmental tobacco smoking.This suggests that prenatal cadmium exposure is a threatening risk factor for birth defects.

Engineering cannabidiol synergistic carbon monoxide nanocomplexes to enhance cancer therapy via excessive autophagy

Although carbon monoxide(CO)-based treatments have demonstrated the high cancer efficacy by promoting mitochondrial damage and core-region penetrating ability,the efficiency was often compromised by protective autophagy(mitophagy).Herein,cannabidiol(CBD)is integrated into biomimetic carbon monoxide nanocomplexes(HMPOC@M)to address this issue by inducing excessive autophagy.The biomimetic membrane not only prevents premature drugs leakage,but also prolongs blood circulation for tumor enrichment.After entering the acidic tumor microenvironment,carbon monoxide(CO)donors are stimulated by hydrogen oxide(H_(2)O_(2))to disintegrate into CO and Mn^(2+).The comprehensive effect of CO/Mn^(2+)and CBD can induce ROS-mediated cell apoptosis.In addition,HMPOC@Mmediated excessive autophagy can promote cancer cell death by increasing autophagic flux via classⅢPI3K/BECN1 complex activation and blocking autolysosome degradation via LAMP1 downregulation.Furthermore,in vivo experiments showed that HMPOC@M+laser strongly inhibited tumor growth and attenuated liver and lung metastases by downregulating VEGF and MMP9 proteins.This strategy may highlight the pro-death role of excessive autophagy in TNBC treatment,providing a novel yet versatile avenue to enhance the efficacy of CO treatments.Importantly,this work also indicated the applicability of CBD for triple-negative breast cancer(TNBC)therapy through excessive autophagy.

Tanned or Sunburned:How Excessive Light Triggers Plant Cell Death

Plants often encounter light intensities exceeding the capacity of photosynthesis(excessive light)mainly due to biotic and abiotic factors,which lower C02 fixation and reduce light energy sinks.Under excessive light,the photosynthetic electron transport chain generates damaging molecules,hence leading to photooxidative stress and eventually to cell death.In this review,we summarize the mechanisms linking the excessive absorption of light energy in chloroplasts to programmed cell death in plant leaves.We highlight the importance of reactive carbonyl species generated by lipid photooxidation,their detoxification,and the integrating role of the endoplasmic reticulum in the adoption of phototolerance or cell-death pathways.Finally,we invite the scientific community to standardize the conditions of excessive light treatments.

Dynamic response mechanism and precursor characteristics of gneiss rockburst under different initial burial depths

To investigate the influence mechanism of geostress on rockburst characteristics,three groups of gneiss rockburst experiments were conducted under different initial geostress conditions.A high-speed photography system and acoustic emission(AE)monitoring system were used to monitor the entire rockburst process in real time.The experimental results show that when the initial burial depth increases from 928 m to 1320 m,the proportion of large fracture scale in rockburst increases by 154.54%,and the AE energy increases by 565.63%,reflecting that the degree and severity of rockburst increase with the increase of burial depth.And then,two mechanisms are proposed to explain this effect,including(i)the increase of initial geostress improves the energy storage capacity of gneiss,and then,the excess energy which can be converted into kinetic energy of debris ejection increases,consequently,a more pronounced violent ejection phenomenon is observed at rockburst;(ii)the increase of initial geostress causes more sufficient plate cracks of gneiss after unloading ofσh,which provides a basis for more severe ejection of rockburst.What’s more,a precursor with clear physical meaning for rockburst is proposed under the framework of dynamic response process of crack evolution.Finally,potential value in long term rockburst warning of the precursor obtained in this study is shown via the comparison of conventional precursor.