The effect of health insurance and socioeconomic status on women's choice in birth attendant and place of delivery across regions in Indonesia: a multinomial logit analysis.

BACKGROUND: Evidence suggests that women gave birth in diverse types of health facilities and were assisted by various types of health providers. This study examines how these choices are influenced by the Indonesia national health insurance programme (Jaminan Kesehatan Nasional (JKN)), which aimed to provide equitable access to health services, including maternal health. METHODS: Using multinomial logit regression models, we examined patterns and determinants of women's choice for childbirth, focusing on health insurance coverage, geographical location and socioeconomic disparities. We used the 2018 nationally representative household survey dataset consisting of 41 460 women (15-49 years) with a recent live birth. RESULTS: JKN coverage was associated with increased use of higher-level health providers and facilities and reduced the likelihood of deliveries at primary health facilities and attendance by midwives/nurses. Women with JKN coverage were 13.1% and 17.0% (p<0.05) more likely to be attended by OBGYN/general practitioner (GP) and to deliver at hospitals, respectively, compared with uninsured women. We found notable synergistic effects of insurance status, place of residence and economic status on women's choice of type of birth attendant and place of delivery. Insured women living in Java-Bali and in the richest wealth quintile were 6.4 times more likely to be attended by OBGYN/GP and 4.2 times more likely to deliver at a hospital compared with those without health insurance, living in Eastern Indonesia, and in the poorest income quantile. CONCLUSION: There are large variations in the choice of birth attendant and place of delivery by population groups in Indonesia. Evaluation of health systems reform initiatives, including the JKN programme and the primary healthcare strengthening, is essential to determine their impact on disparities in maternal health services.

Virtual nature experiences and mindfulness practices while working from home during COVID-19: Effects on stress, focus, and creativity.

In this study, we focus on the impact of daily virtual nature experiences combined with mindfulness practices on remote workers' creativity, stress, and focus over an extended period (9 weeks) during the COVID-19 pandemic. Our results show a positive effect of virtual reality (VR) nature experience on increasing focus and reducing stress. When VR nature and mindfulness practices were combined, we also found an increase in convergent thinking task performance. Our findings demonstrate that 10-minute daily exposure to VR nature and mindfulness practices could compensate for some of the adverse effects of working remotely by improving some aspects of workers' well-being and creativity.

Protection of palmitic acid treatment in RAW264.7 cells and BALB/c mice during Brucella abortus 544 infection.

BACKGROUND: We previously elucidated the protective mechanism of Korean red ginseng oil (RGO) against Brucella abortus infection, and our phytochemical analysis revealed that palmitic acid (PA) was an abundant component of RGO. Consequently, we investigated the contribution of PA against B. abortus. OBJECTIVES: We aimed to investigate the efficacy of PA against B. abortus infection using a murine cell line and a murine model. METHODS: Cell viability, bactericidal, internalization, and intracellular replication, western blot, nitric oxide (NO), and superoxide (O2⁻) analyses and flow cytometry were performed to determine the effects of PA on the progression of B. abortus infection in macrophages. Flow cytometry for cytokine analysis of serum samples and bacterial counts from the spleens were performed to determine the effect of PA in a mouse model. RESULTS: PA did not affect the growth of B. abortus. PA treatment in macrophages did not change B. abortus uptake but it did attenuate the intracellular survivability of B. abortus. Incubation of cells with PA resulted in a modest increase in sirtuin 1 (SIRT1) expression. Compared to control cells, reduced nitrite accumulation, augmented O2⁻, and enhanced pro-inflammatory cytokine production were observed in PA-treated B. abortus-infected cells. Mice orally treated with PA displayed a decreased serum interleukin-10 level and enhanced bacterial resistance. CONCLUSIONS: Our results suggest that PA participates in the control of B. abortus within murine macrophages, and the in vivo study results confirm its efficacy against the infection. However, further investigations are encouraged to completely characterize the mechanisms involved in the inhibition of B. abortus infection by fatty acids.

The effect of dietary supplementation with high- or low-dose omega-3 fatty acid on inflammatory pathology after traumatic brain injury in rats.

This study investigated dietary supplementation as a prophylactic for neuroinflammation following traumatic brain injury (TBI) in a preclinical model. Adult male Sprague-Dawley rats received 30 days of supplementation with either water or two dietary supplements. The first consisted of high-dose omega-3 fatty acid (O3FA) (supplement A) along with vitamin D3 and vitamin E. The second had the same ingredients at different doses with an addition of cannabidiol (supplement B). Rats were subjected to an impact TBI and then euthanized 7 days post-injury and neuroinflammation quantified by histological detection of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, and CD68, a marker of microglial activity. There was a trend toward increased GFAP staining in injured, unsupplemented animals as compared to sham, unsupplemented animals, consistent with increased activation of astrocytes in response to trauma which was reversed by supplement A but not by supplement B. The pattern of CD68 staining across groups was similar to that of GFAP staining. There was a trend toward an increase in the injured unsupplemented group, relative to sham which was reversed by supplement A but not by supplement B. CD68 staining in injured animals was concentrated in the perivascular domain. The consistency between trends across different measures of neuroinflammation showing benefits of high-dose O3FA supplementation following TBI suggests that the observed effects are real. These findings are preliminary, but they justify further study to determine the functional benefits associated with improvements in histological outcomes and understand associated dose-response curves.

A pre-trial evaluation of blinding for a Chinese herbal medicine trial.

BACKGROUND: Blinding is considered an important methodological characteristic in clinical trials to minimise bias and maximise the validity of a trial. Unlike pharmaceutical substances, most herbal medicines have distinctive sensory specifications, including odour and taste, which can be quite challenging when developing a placebo control to match the specific characteristics of herbal substances being examined. The present study was, therefore, designed to evaluate whether the participants could differentiate an active herbal capsule (Ganopoly combination) from a placebo material capsule. The aim of this study was to develop a suitable placebo substance for encapsulation to be used in a future herbal medicine clinical trial. METHODS: The current study was improved upon the previous investigation, and several modifications were made to the placebo substance in order to mimic the herbal substance characteristics. Prior to conducting the study, a refined placebo substance was developed using commonly consumed culinary agents. Sixty-two healthy volunteers participated in the study and were randomly provided one of the two substances. Individuals were asked to evaluate the three sensory characteristics of the allocated capsule (visual appearance, odour, and taste), and determine whether they believed the substance to be a 'herbal' or a 'placebo' substance. RESULTS: The study provided evidence on the success of blinding for only two sensory characteristics, namely, visual appearance (95% CI -0.15, 0.34) and odour (95% CI -0.34, 0.15). In contrast, the findings related to the taste indicated that participants correctly guessed the herbal substance compared to the placebo substance to a significantly higher proportion than would have been expected by chance alone (95% CI 0.14, 0.60). CONCLUSION: The failure to blind participants for taste highlights the difficulties in preparing placebo herbal substances that match as closely as possible to a real herbal substance. Blinding is particularly challenging where herbal medicines have different sensory characteristics.

Acute and Residual Effects of IASTM and Roller Massage Stick on Hamstring Range of Motion.

PURPOSE: Fascial adhesions can reduce range of motion (ROM). Different techniques of varying costs have been studied to release these adhesions and restore normal ROM, but none have compared instrument-assisted soft tissue mobilization (IASTM) with a roller massage stick. The objective was to compare the acute and residual effects of IASTM and a roller massage stick on active and passive hamstring ROM after a single treatment. DESIGN: Prospective cohort study in a university laboratory. METHODS: Sixteen (8M, 8F) recreationally active individuals (age 23.38±2.45 yrs). IASTM using Graston instruments and a roller massage stick were randomly applied to the hamstrings of the dominant or non-dominant leg for 3.5 minutes. Active and passive ROM were measured pre-intervention, immediately post-intervention, and 48-hrs post-intervention. RESULTS: There was a main effect for time showing a significant increase in active and passive ROM from pre-intervention to immediate post-intervention (p<0.05) and from pre-intervention to 48-hr post-intervention (p<0.05). However, no interaction effect between treatment and time was found in either active or passive ROM (p>0.05). CONCLUSIONS: IASTM and the roller massage stick were equally effective immediately and over time, but the roller massage stick is more affordable.

Mindfulness and hemodynamics in asians: a literature review.

INTRODUCTION: Mindfulness interventions have been increasingly incorporated into clinical settings. Evidence supporting mindfulness practices are predominantly established in Western populations. Neurophysiological evidence has not been established to support the effectiveness of mindfulness practice in Asian populations. Greater understanding of the neurophysiological mechanisms underlying mindfulness would enable hemodynamics as measured by fNIRS to be used to monitor mindfulness practice as an adjunct to psychotherapy with Asian clients. METHOD: Research relating to fNIRS and hemodynamics for mindfulness in Asians was reviewed. The inclusion criteria for this review were recent publications in peer-reviewed journals from 2008 to 2018, with the search terms 'fNIRS', 'hemodynamics' and 'mindfulness', for studies in Asia. FINDINGS: Databases included Medline, PubMed, PSYCINFO, Google Scholar and SCOPUS. Initial searches yielded 86 results. Five duplicated articles were removed, and remaining abstracts were screened; and assessed for eligibility against the structured performa. Three full text papers which fit the inclusion criteria were included in the current review. CONCLUSION: This review highlighted the paucity of rigorous empirically validated research for hemodynamics as measured with fNIRS for mindfulness practice in Asia.

Impact of the NHS Health Check on inequalities in cardiovascular disease risk: a difference-in-differences matching analysis.

BACKGROUND: We assessed impacts of a large, nationwide cardiovascular disease (CVD) risk assessment and management programme on sociodemographic group inequalities in (1) early identification of hypertension, type 2 diabetes (T2D) and chronic kidney disease (CKD); and (2) management of global CVD risk among high-risk individuals. METHODS: We obtained retrospective electronic medical records from the Clinical Practice Research Datalink for a randomly selected sample of 138 788 patients aged 40-74 years without known CVD or diabetes, who were registered with 462 practices between 2009 and 2013. We estimated programme impact using a difference-in-differences matching analysis that compared changes in outcome over time between attendees and non-attendees. RESULTS: National Health Service Health Check attendance was 21.4% (29 672/138 788). A significantly greater number of hypertension and T2D incident cases were identified in men than women (eg, an additional 4.02%, 95% CI 3.65% to 4.39%, and 2.08%, 1.81% to 2.35% cases of hypertension in men and women, respectively). A significantly greater number of T2D incident cases were identified among attendees living in the most deprived areas, but no differences were found for hypertension and CKD across socioeconomic groups. No major differences in CVD risk management were observed between sociodemographic subgroups (eg, programme impact on 10-year CVD risk score was -1.13%, -1.48% to -0.78% in male and -1.53%, -2.36% to -0.71% in female attendees). CONCLUSION: During 2009-2013, the programme had low attendance and small overall impacts on early identification of disease and risk management. The age, sex and socioeconomic subgroups appeared to have derived similar level of benefits, leaving existing inequalities unchanged. These findings highlight the importance of population-wide interventions to address inequalities in CVD outcomes.

Lichen planus and lichenoid dermatoses: Conventional and emerging therapeutic strategies.

Having reviewed the diverse clinical subtypes of lichenoid disease and the postulated molecular basis thereof in the first article in this 2-part continuing medical education series, we discuss herein the existing and emerging treatment strategies in the most common clinical forms of lichenoid inflammation and provide an overview of their pharmacodynamics and evidence base. The scope of this review is not to exhaustively discuss treatment modalities for all lichenoid variants discussed in the previous article of this series. Instead, the focus will be on frequently encountered subtypes of lichen planus and on linking mechanisms of disease with mechanisms of drug action. Future directions and potential avenues for translational research will also be discussed.

An experimental study in distinguishing an authentic herbal substance from sham herbal substances.

OBJECTIVES: An unblinded randomised trial can result in biased treatment effect estimates and lead to erroneous conclusions on the efficacy of the therapeutic intervention. Unlike pharmaceutical substances, Chinese herbal medicines have special characteristics including texture, colour, odour and taste as the origin of these constituents are different. In addition, its distinctive odour makes blinding of Chinese herbal medicine RCTs very difficult, as the placebo substance needs to match the special characteristics of the herbal substance being investigated. For these reasons, two studies were undertaken to evaluate whether a participant could distinguish a herbal intervention capsule (Ganopoly combination) when compared to three types of capsules containing culinary materials following a visual, odour and taste evaluation. DESIGN: Study One, was a pilot involving eleven participants (n = 11) while Study Two, involved eighty one participants (n = 81) and was conducted to make improvements on Study One. For both studies, participants were asked to identify which of four capsules were a herbal substance following a visual, smell and taste evaluation. RESULTS: For study One it was found that for both odour (p = .484) and visual appearance (p = .077) the number of participants selecting the herbal substance was not significantly different from what may have been selected by chance. This was not the case for taste where significantly more participants selected capsule B as the herbal substance (p = .004). For Study Two test it was found that all three evaluations for odour, visual appearance and taste significantly more participants selected the herbal substance (p < .0001 in all cases). This indicates that the participant guesses were not evenly distributed across the four choices and suggests a failure to blind. CONCLUSION: The failure to blind participants highlights the difficulties in preparing sham herbal substances that look, smell and taste like the real herbal substance.

Interaction of Brain-Derived Neurotrophic Factor Val66Met genotype and history of stress in regulation of prepulse inhibition in mice.

The Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism results in reduced activity-dependent BDNF release and has been implicated in schizophrenia. However, effects of the polymorphism on functional dopaminergic and N-methyl-d-aspartate (NMDA) receptor-associated activity remain unclear. We used prepulse inhibition, a measure of sensorimotor gating which is disrupted in schizophrenia, and assessed the effects of acute treatment with the dopamine receptor agonist, apomorphine (APO), and the NMDA receptor antagonist, MK-801. We used adult humanized hBDNFVal66Met 'knockin' mice which express either the Val/Val, Val/Met or Met/Met genotype. An interaction of BDNF with stress was modelled by chronic young-adult treatment with corticosterone (CORT). At 1 or 3mg/kg, APO had no effect in Val/Val mice but significantly reduced PPI at the 100ms inter-stimulus interval (ISI) in Val/Met and Met/Met mice. However, after CORT pretreatment, APO significantly reduced PPI in all genotypes similarly. At 0.1 or 0.25mg/kg, MK-801 significantly disrupted PPI at the 100ms ISI independent of genotype or CORT pretreatment. There were differential effects of APO and MK-801 on PPI at the 30ms ISI and startle between the genotypes, irrespective of CORT pretreatment. These results show that the BDNF Val66Met Val/Met and Met/Met genotypes are more sensitive than the Val/Val genotype to the effect of APO on PPI. A history of stress, here modelled by chronic CORT administration, increases effects of APO in Val/Val mice.

Disgust but not Health Anxiety Graphic Warning Labels Reduce Motivated Attention in Smokers: A Study of P300 and Late Positive Potential Responses.

Background: Graphic health warning labels (GHWLs) on tobacco products attempt to leverage avoidance-promoting emotions, such as anxiety and disgust, to encourage cessation. Prior studies have relied on self-report or attentional metrics that may not accurately illuminate GHWLs' ability to motivate change. This report evaluates the impact of disgust- and anxiety-based GHWLs on electroencephalograph (EEG) measures of motivated attention among two groups of smokers-those that report higher versus lower cigarette dependence. We hypothesized that both anxiety and disgust GHWLs would reduce appetitive attention, as indexed by lowered P300 (P3) and late positive potential (LPP) activations. Methods: Sixty-one smokers provided demographic and smoking history before completing an oddball paradigm consisting of three counterbalanced stimuli blocks. Each block (100 trials) contained a neutral, GHWL-anxiety, or GHWL-disgust frequent image and a smoking cue as the oddball image (20%). Oddball trials for each block were averaged, P3 and LPP were identified at midline electrode positions (Fz, Cz, and Pz), and mean amplitude was analyzed. Results: Separate mixed-model ANOVAs of P3 and LPP reactivity revealed disgust-focused GHWLs reduced motivated attentional processing. Conversely, the anxiety-focused GHWL appeared to increase the salience of the smoking cue (Fz only). Less-dependent smokers showed lower P3 reactivity than those with higher dependence at Fz, but greater P3 reactivity at Cz and Pz. Conclusion: These results extend prior work in demonstrating that disgust, but not anxiety-based GHWLs, may reduce EEG-assessed motivated attention to smoking cues. Disgust may thus represent a more fruitful target for public health cessation efforts. Implications: Most GHWL evaluations have focused on fear (or anxiety) elicitation rather than disgust, an emotion that may have a unique link to smoking, having evolved specifically to facilitate the avoidance of contaminants via oral incorporation. Analyses of P300 and LPP responses to GHWLs suggest that disgust-focused images interfere with the EEG-indexed attentional processing of smoking cues and do so better than health anxiety-focused messages. However, interaction effects at different electrode sites indicated that GHWLs have complex effects in more versus less-dependent smokers and that an understanding of how smoking cues and anti-smoking imagery become associated over time is needed to identify relevant targets for public health efforts.

Effect of Electrode Montage and Head Position on Air-Conducted Ocular Vestibular Evoked Myogenic Potential.

PURPOSE: The purpose of this investigation was to identify the optimal recording parameters for evoking the ocular vestibular evoked myogenic potential (oVEMP) using air-conduction stimuli. METHOD: Subjects were 17 otologically and neurologically intact adults (age: M = 24.18 years, SD = 1.91 years). The oVEMP responses were elicited using a 500-Hz tone burst air-conduction stimulus presented at an intensity of 95 dB nHL. The setting was a balance function laboratory that was part of a large tertiary care otology clinic. RESULTS: The oVEMP electrode montage and body position that yielded the largest oVEMP amplitude was the belly-tendon montage (Sandhu, George, & Rea, 2013), recorded with the subject in the sitting position. The N1 latency recorded with the belly-tendon montage was significantly shorter than that recorded for the infraorbital montage in both the sitting and supine positions. CONCLUSION: The belly-tendon recording montage with the subject sitting yields significantly larger oVEMP amplitudes and shorter N1 latencies than do traditional bipolar infraorbital recordings.

Coumestrol Down-Regulates Melanin Production in Melan-a Murine Melanocytes through Degradation of Tyrosinase.

Pigmentation reflects skin darkening caused by melanin production, but excessive melanin synthesis may cause problems, such as melasma, solar lentigo, dark spots, and freckles. Considerable effort has been devoted to alleviating these undesired symptoms through the development of safe and effective depigmenting agents. Coumestrol, a plant-derived natural isoflavone with an estrogen-like structure and actions, is known to have anti-aging ability, but its potential depigmenting efficacy has not been evaluated. In the present study, we investigated the effects of coumestrol on melanin synthesis in normal melan-a murine melanocytes. Coumestrol significantly reduced melanin synthesis in a concentration-dependent manner up to a concentration of 25 µM without causing cytotoxicity. It also brightened tissue in an artificial skin model (MelanoDerm) that incorporates both human keratinocytes and melanocytes. Interestingly, although coumestrol did not inhibit tyrosinase activity or transcript level in melan-a cells, it clearly decreased the expression level of tyrosinase protein at a concentration of 25 µM. This coumestrol-induced reduction in tyrosinase protein levels was prevented by pretreatment with the proteasome inhibitor MG-132 or the lysosomal proteolysis inhibitor chloroquine. Collectively, our findings indicate that coumestrol exerts an inhibitory effect on melanin synthesis in melan-a cells, at least in part, through degradation of tyrosinase. These findings suggest that coumestrol is a good candidate for use in depigmentary reagents from a cosmetic and clinical perspective.

Carbapenemase-producing Enterobacteriaceae in the UK: a national study (EuSCAPE-UK) on prevalence, incidence, laboratory detection methods and infection control measures.

OBJECTIVES: To estimate UK prevalence and incidence of clinically significant carbapenemase-producing Enterobacteriaceae (CPE), and to determine epidemiological characteristics, laboratory methods and infection prevention and control (IPC) measures in acute care facilities. METHODS: A 6 month survey was undertaken in November 2013-April 2014 in 21 sentinel UK laboratories as part of the European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) project. Up to 10 consecutive, non-duplicate, clinically significant and carbapenem-non-susceptible isolates of Escherichia coli or Klebsiella pneumoniae were submitted to a reference laboratory. Participants answered a questionnaire on relevant laboratory methods and IPC measures. RESULTS: Of 102 isolates submitted, 89 (87%) were non-susceptible to ≥1 carbapenem, and 32 (36%) were confirmed as CPE. CPE were resistant to most antibiotics, except colistin (94% susceptible), gentamicin (63%), tigecycline (56%) and amikacin (53%). The prevalence of CPE was 0.02% (95% CI = 0.01%-0.03%). The incidence of CPE was 0.007 per 1000 patient-days (95% CI = 0.005-0.010), with north-west England the most affected region at 0.033 per 1000 patient-days (95% CI = 0.012-0.072). Recommended IPC measures were not universally followed, notably screening high-risk patients on admission (applied by 86%), using a CPE 'flag' on patients' records (70%) and alerting neighbouring hospitals when transferring affected patients (only 30%). Most sites (86%) had a laboratory protocol for CPE screening, most frequently using chromogenic agar (52%) or MacConkey/CLED agars with carbapenem discs (38%). CONCLUSIONS: The UK prevalence and incidence of clinically significant CPE is currently low, but these MDR bacteria affect most UK regions. Improved IPC measures, vigilance and monitoring are required.

Depletion of the Human Ion Channel TRPM2 in Neuroblastoma Demonstrates Its Key Role in Cell Survival through Modulation of Mitochondrial Reactive Oxygen Species and Bioenergetics.

Transient receptor potential melastatin 2 (TRPM2) ion channel has an essential function in modulating cell survival following oxidant injury and is highly expressed in many cancers including neuroblastoma. Here, in xenografts generated from neuroblastoma cells in which TRPM2 was depleted with CRISPR/Cas9 technology and in in vitro experiments, tumor growth was significantly inhibited and doxorubicin sensitivity increased. The hypoxia-inducible transcription factor 1/2α (HIF-1/2α) signaling cascade including proteins involved in oxidant stress, glycolysis, and mitochondrial function was suppressed by TRPM2 depletion. TRPM2-depleted SH-SY5Y neuroblastoma cells demonstrated reduced oxygen consumption and ATP production after doxorubicin, confirming impaired cellular bioenergetics. In cells in which TRPM2 was depleted, mitochondrial superoxide production was significantly increased, particularly following doxorubicin. Ectopic expression of superoxide dismutase 2 (SOD2) reduced ROS and preserved viability of TRPM2-depleted cells, however, failed to restore ATP levels. Mitochondrial reactive oxygen species (ROS) were also significantly increased in cells in which TRPM2 function was inhibited by TRPM2-S, and pretreatment of these cells with the antioxidant MitoTEMPO significantly reduced ROS levels in response to doxorubicin and protected cell viability. Expression of the TRPM2 pore mutant E960D, in which calcium entry through TRPM2 is abolished, also resulted in significantly increased mitochondrial ROS following doxorubicin treatment, showing the critical role of TRPM2-mediated calcium entry. These findings demonstrate the important function of TRPM2 in modulation of cell survival through mitochondrial ROS, and the potential of targeted inhibition of TRPM2 as a therapeutic approach to reduce cellular bioenergetics, tumor growth, and enhance susceptibility to chemotherapeutic agents.

Beetroot juice does not enhance altitude running performance in well-trained athletes.

We hypothesized that acute dietary nitrate (NO3(-)) provided as concentrated beetroot juice supplement would improve endurance running performance of well-trained runners in normobaric hypoxia. Ten male runners (mean (SD): sea level maximal oxygen uptake, 66 (7) mL·kg(-1)·min(-1); 10 km personal best, 36 (2) min) completed incremental exercise to exhaustion at 4000 m and a 10-km treadmill time-trial at 2500 m simulated altitude on separate days after supplementation with ∼7 mmol NO3(-) and a placebo at 2.5 h before exercise. Oxygen cost, arterial oxygen saturation, heart rate, and ratings of perceived exertion (RPE) were determined during the incremental exercise test. Differences between treatments were determined using means [95% confidence intervals], paired sample t tests, and a probability of individual response analysis. NO3(-) supplementation increased plasma nitrite concentration (NO3(-), 473 (226) nmol·L(-1) vs. placebo, 61 (37) nmol·L(-1), P < 0.001) but did not alter time to exhaustion during the incremental test (NO3(-), 402 (80) s vs. placebo 393 (62) s, P = 0.5) or time to complete the 10-km time-trial (NO3(-), 2862 (233) s vs. placebo, 2874 (265) s, P = 0.6). Further, no practically meaningful beneficial effect on time-trial performance was observed as the 11 [-60 to 38] s improvement was less than the a priori determined minimum important difference (51 s), and only 3 runners experienced a "likely, probable" performance improvement. NO3(-) also did not alter oxygen cost, arterial oxygen saturation, heart rate, or RPE. Acute dietary NO3(-) supplementation did not consistently enhance running performance of well-trained athletes in normobaric hypoxia.

Flavokawains B and C, melanogenesis inhibitors, isolated from the root of Piper methysticum and synthesis of analogs.

The ethanolic extract of the root of Piper methysticum was found to inhibit melanogenesis in MSH-activated B16 melanoma cells. Flavokawains B and C were isolated from this extract based on their anti-melanogenesis activity and found to inhibit melanogenesis with IC50 values of 7.7µM and 6.9µM, respectively. Flavokawain analogs were synthesized through a Claisen-Schmidt condensation of their corresponding acetophenones and benzaldehydes and were evaluated in terms of their tyrosinase inhibitory and anti-melanogenesis activities. Compound 1b was the most potent of these with an IC50 value of 2.3µM in melanogenesis inhibition assays using MSH-activated B16 melanoma cells.