Invasive or noninvasive? A systematic review and network meta-analysis of acupuncture and acupressure to treat sleep disturbance in cancer patients.

BACKGROUND: Both acupuncture and acupressure have been suggested beneficial for reducing sleep disturbance in cancer patients. While acupuncture is invasive involving needle insertion, acupressure is noninvasive. Their comparative effectiveness is unclear, hindering clinical recommendations. AIMS: This study aimed to explore the comparative effectiveness of acupuncture and acupressure on sleep in cancer patients. METHODS: This is a systematic review and Bayesian network meta-analysis. Eight key English and Chinese databases were searched. Twenty-four randomized controlled trials involving 2002 cancer patients comparing the effects of six treatments (manual acupuncture, electroacupuncture, acupressure, sham, enhanced usual care, and no treatment) on sleep were found. RESULTS: Compared with enhanced supportive care, acupressure demonstrated the largest effect size for reducing self-reported sleep disturbance (standardized mean difference [SMD] = -2.67, 95% CrI: -3.46 to -1.90; GRADE = moderate), followed by acupuncture (SMD = -1.87, 95% CrI: -2.94 to -0.81, GRADE = moderate) and electroacupuncture (SMD = -1.60, 95% CrI: -3 to -0.21; GRADE = low). The surface under the cumulative ranking curve indicates that acupressure is most likely to rank highest. LINKING EVIDENCE TO ACTION: Based on available evidence, acupressure can be recommended as the optimal treatment for reducing sleep disturbance in cancer patients. More rigorous trials are warranted to confirm whether different forms of acupuncture or acupressure have different effects on sleep in cancer patients. Particularly, studies examining acupuncture interventions alone instead of in combination with other therapies are needed.

Outbreak of sexually transmitted, extensively drug-resistant Shigella sonnei in the UK, 2021-22: a descriptive epidemiological study.

BACKGROUND: Shigellosis, traditionally a foodborne and waterborne infection, causes substantial morbidity globally. It is now a leading cause of sexually transmitted gastroenteritis among gay, bisexual, and other men who have sex with men (MSM). We describe an ongoing outbreak of extensively drug-resistant (XDR) Shigella sonnei in the UK. METHODS: Routine laboratory surveillance (Second Generation Surveillance System, Gastrointestinal Data Warehouse) identified an exceedance of S sonnei clade 5 in England, first detected in September, 2021. Cases within this clade were subsequently reported from Scotland, Wales, and Northern Ireland. Confirmed cases in this outbreak were defined as individuals diagnosed with S sonnei clade 5 in the UK, with a specimen date between Sept 1, 2021, and Feb 9, 2022, who were genomically confirmed as part of a ten-single nucleotide polymorphism (SNP) linkage cluster. We used whole-genome sequencing with SNP typing to identify genomic clusters and antimicrobial-resistance determinants, analysing cases across the UK. We collected demographic, epidemiological, and clinical data from people infected with S sonnei clade 5 in England using questionnaires (standard and bespoke outbreak questionnaires). We used descriptive summary statistics to characterise cases. FINDINGS: 72 cases (70 [97%] male, median age 34 years [IQR 27-39]) belonging to the ten-SNP single linkage cluster of S sonnei clade 5 were identified between Sept 4, 2021, and Feb 9, 2022. Isolates were predominantly XDR, with 66 (92%) of 72 harbouring blaCTX-M-27, a plasmid-mediated gene for production of extended-spectrum ß-lactamases (ESBLs). Of 33 cases with clinical data, 19 (58%) received antibiotics and eight (24%) were hospitalised. 21 (78%) of 27 cases with completed bespoke outbreak questionnaires were HIV-negative MSM taking HIV pre-exposure prophylaxis (PrEP) who reported sexual contacts in the UK and Europe within the incubation period. INTERPRETATION: We highlight the rapid dissemination of XDR ESBL-producing S sonnei in sexual networks of MSM. We recommend strengthening shigella testing where clinically indicated, antimicrobial-resistance surveillance, and integrated health promotion messaging among all MSM, including PrEP users, to reduce the burden of shigellosis. FUNDING: National Institute for Health Research Health Protection Research Unit in Gastrointestinal Infections at the University of Liverpool in partnership with the UK Health Security Agency.

State legislative trends related to biomarker testing.

Comprehensive biomarker testing has become the standard of care for informing the choice of the most appropriate targeted therapy for many patients with advanced cancer. Despite evidence demonstrating the need for comprehensive biomarker testing to enable the selection of appropriate targeted therapies and immunotherapy, the incorporation of biomarker testing into clinical practice lags behind recommendations in National Comprehensive Cancer Network guidelines. Coverage policy differences across insurance health plans have limited the accessibility of comprehensive biomarker testing largely to patients whose insurance covers the recommended testing or those who can pay for the testing, and this has contributed to health disparities. Furthermore, even when insurance coverage exists for recommended biomarker testing, patients may incur burdensome out-of-pocket costs depending on their insurance plan benefits, which may also create barriers to testing. Prior authorization for biomarker testing for some patients can add an administrative burden and may delay testing and thus treatment if it is not done in a timely manner. Recently, three states (Illinois, Louisiana, and California) passed laws designed to improve access to biomarker testing at the state level. However, there is variability among these laws in terms of the population affected, the stage of cancer, and whether the coverage of testing is mandated, or the legislation addresses only prior authorization. Advocacy efforts by patient advocates, health care professionals, and professional societies are imperative at the state level to further improve coverage for and access to appropriate biomarker testing.

Feasibility of Aerobic Exercise and Tai-Chi Interventions in Advanced Lung Cancer Patients: A Randomized Controlled Trial.

BACKGROUND: A majority of lung cancer patients are diagnosed at advanced stages. Although there is considerable evidence of the benefits of aerobic exercise and tai-chi for lung cancer patients, little is known about the comparative effectiveness of the 2 exercise modes in advanced lung cancer patients. OBJECTIVES: To explore the feasibility and preliminary effects of aerobic exercise and tai-chi interventions on survival and well-being among advanced lung cancer patients. METHODS: In an assessor-blinded, exploratory randomized controlled trial, 30 advanced lung cancer patients were randomized to an aerobic exercise group, a tai-chi group (both attending 12-week, twice-weekly supervised sessions), or a self-management control group (receiving written exercise guidelines). The primary outcomes focused on feasibility including intervention completion, exercise adherence, and adverse events, while the secondary outcomes addressed preliminary effects and included 1-year survival, cancer symptoms (Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Score, Brief Fatigue Inventory), quality of life (EORTC QLQ-C30, QLQ-LC13), physical performance (6-minute walk test, up-and-go, sit-to-stand, 1-leg standing), activity levels (actigraph), and circadian rhythms (salivary cortisol). RESULTS: Intervention feasibility was established with a satisfactory completion rate at post-intervention for the aerobic exercise group (80%) and the tai-chi group (78%). The tai-chi group attained higher adherence than the exercise group in terms of attendance in supervised sessions (89% vs 75% of scheduled classes) and self-practice (225% vs 87% of the prescribed amount). Higher adherence to self-practice in the tai-chi group remained at the 6-month follow-up (81% vs 38% of the prescribed amount). No adverse event as a result of the intervention was reported. Effect-related outcomes did not show statistically significant changes in any group, except an improvement post-intervention in the up-and-go (-2.26, 95% CI: -4.04, -0.48) and sit-to-stand tests (4.52, 95% CI: 2.19, 6.85) in the aerobic exercise group. CONCLUSIONS: The findings support the feasibility of aerobic exercise and tai-chi interventions in advanced lung cancer patients. A future study with a larger sample from multiple sites is recommended to confirm the comparative effects of the 2 exercise interventions relative to the self-management group and to enhance the generalizability of the findings.

The effects of phosphocreatine disodium salts plus blueberry extract supplementation on muscular strength, power, and endurance.

BACKGROUND: Numerous studies have demonstrated the efficacy of creatine supplementation for improvements in exercise performance. Few studies, however, have examined the effects of phosphocreatine supplementation on exercise performance. Furthermore, while polyphenols have antioxidant and anti-inflammatory properties, little is known regarding the influence of polyphenol supplementation on muscular strength, power, and endurance. Thus, the purpose of the present study was to compare the effects of 28 days of supplementation with phosphocreatine disodium salts plus blueberry extract (PCDSB), creatine monohydrate (CM), and placebo on measures of muscular strength, power, and endurance. METHODS: Thirty-three men were randomly assigned to consume either PCDSB, CM, or placebo for 28 days. Peak torque (PT), average power (AP), and percent decline for peak torque (PT%) and average power (AP%) were assessed from a fatigue test consisting of 50 maximal, unilateral, isokinetic leg extensions at 180°·s- 1 before and after the 28 days of supplementation. Individual responses were assessed to examine the proportion of subjects that exceeded a minimal important difference (MID). RESULTS: The results demonstrated significant (p < 0.05) improvements in PT for the PCDSB and CM groups from pre- (99.90 ± 22.47 N·m and 99.95 ± 22.50 N·m, respectively) to post-supplementation (119.22 ± 29.87 N·m and 111.97 ± 24.50 N·m, respectively), but no significant (p = 0.112) change for the placebo group. The PCDSB and CM groups also exhibited significant improvements in AP from pre- (140.18 ± 32.08 W and 143.42 ± 33.84 W, respectively) to post-supplementation (170.12 ± 42.68 W and 159.78 ± 31.20 W, respectively), but no significant (p = 0.279) change for the placebo group. A significantly (p < 0.05) greater proportion of subjects in the PCDSB group exceeded the MID for PT compared to the placebo group, but there were no significant (p > 0.05) differences in the proportion of subjects exceeding the MID between the CM and placebo groups or between the CM and PCDSB groups. CONCLUSIONS: These findings indicated that for the group mean responses, 28 days of supplementation with both PCDSB and CM resulted in increases in PT and AP. The PCDSB, however, may have an advantage over CM when compared to the placebo group for the proportion of individuals that respond favorably to supplementation with meaningful increases in muscular strength.

Phytochemicals as Therapeutic Interventions in Peripheral Artery Disease.

Peripheral artery disease (PAD) affects over 200 million people worldwide, resulting in significant morbidity and mortality, yet treatment options remain limited. Among the manifestations of PAD is a severe functional disability and decline, which is thought to be the result of different pathophysiological mechanisms including oxidative stress, skeletal muscle pathology, and reduced nitric oxide bioavailability. Thus, compounds that target these mechanisms may have a therapeutic effect on walking performance in PAD patients. Phytochemicals produced by plants have been widely studied for their potential health effects and role in various diseases including cardiovascular disease and cancer. In this review, we focus on PAD and discuss the evidence related to the clinical utility of different phytochemicals. We discuss phytochemical research in preclinical models of PAD, and we highlight the results of the available clinical trials that have assessed the effects of these compounds on PAD patient functional outcomes.

Effect of qigong for sleep disturbance-related symptom clusters in cancer: a systematic review and meta-analysis.

OBJECTIVES: To examine the effects of qigong interventions on sleep disturbance-related symptom clusters for cancer patients and to explore the possible mediating role of fatigue and depression in affecting sleep. METHODS: In this systematic review and meta-analysis, a systematic search was conducted through October 2020 by searching multiple English and Chinese databases. Inclusion was limited to randomized controlled trials that measured the effect of qigong on sleep and fatigue/depressive symptoms in cancer patients. Eleven studies involving 907 cancer patients were included in the systematic review, whereas the meta-analysis included ten studies with 851 cancer patients. RESULTS: The most commonly investigated form of qigong was Taichi, and the intervention length ranged from 10 days to 6 months. All studies employed self-reported measurements. Overall, qigong significantly improved sleep (SMD = -1.28, 95% CI: -2.01, -0.55) and fatigue (SMD = -0.89, 95% CI: -1.59, -0.19) in cancer patients post-intervention, but not depressive symptoms (SMD = -0.69, 95% CI: -1.81, 0.42). Notably, the benefits on sleep and fatigue became non-significant after 3 months. Qigong's effect on sleep was significantly mediated by its effect on fatigue (ß = 1.27, SE = 0.24, p = 0.002), but not depressive symptoms (ß = 0.53, SE = 0.26, p = 0.106). CONCLUSIONS: Qigong can be recommended for improving sleep disturbance-fatigue symptom clusters in the cancer population, while qigong's benefit on sleep is likely based on its effect on reducing fatigue. Future qigong studies should adopt more rigorous design and employ strategies to maintain longevity of intervention benefits.

A Rare Case of Disseminated Coccidioidomycosis Presenting as Brachial Plexopathy.

Coccidioidomycosis, a fungal infection caused by inhaling spores of Coccidioides immitis/posadasii, is endemic to the southwestern states of the United States, Northern Mexico and some parts of Central and South America. It is primarily a pulmonary infection with less than 0.5% of symptomatic cases showing dissemination. Skin, lymph nodes and bone are the commonest sites. Neurological involvement is rare and commonly presents as strokes, abscesses or meningoencephalitis. We present the case of a previously healthy 23-year-old African American male, presented with a four-month history of progressive right upper extremity weakness that initially started with right shoulder pain followed by worsening weakness and loss of muscle mass. Electromyography (EMG) demonstrated right brachial plexopathy with moderate-to-severe active denervation changes. MRI cervical spine revealed a 9-cm contrast enhancing extradural mass extending through the neural foramen from C4-T1 roots and forming a 4-cm right apical lung mass subsequently seen on MRI of the brachial plexus. All trunks, divisions and cords were thickened, hyperintense and showed contrast enhancement on MRI. Neuromuscular ultrasound (NUS) demonstrated enlargement of peripheral nerves. Differentials prior to biopsy of the mass ranged from neurofibromas to pancoast lung tumors. Coccidioidomycosis did not figure on the initial list of differentials. Patient underwent subsequent biopsy of the extradural and lung masses that showed coccidiodes. Serum coccidioides antibody titers were elevated. The patient was treated with high-dose intravenous fluconazole and aggressive mass debridement. His weakness improved on four months follow-up evaluation with significant resolution of EMG abnormalities and decreased swelling on NUS.

Effects of Bang® Keto Coffee Energy Drink on Metabolism and Exercise Performance in Resistance-Trained Adults: A Randomized, Double-blind, Placebo-controlled, Crossover Study.

BACKGROUND: Energy drinks are often consumed by the general population, as well as by active individuals seeking to enhance exercise performance and augment training adaptations. However, limited information is available regarding the efficacy of these products. Thus, the purpose of this study was to determine the effects of a commercially available caffeine- and protein-containing energy drink on metabolism and muscular performance. METHODS: Sixteen resistance-trained males (n = 8; mean ± SD; age: 22.4 ± 4.9 years; body mass: 78.8 ± 14.0 kg; body fat: 15.3 ± 6.4%) and females (n = 8; age: 24.5 ± 4.8 years; body mass: 67.5 ± 11.9 kg; body fat: 26.6 ± 7.1%) participated in this randomized, double-blind, placebo-controlled, crossover study. Following a familiarization visit, participants completed two identical visits to the laboratory separated by 5-10 days, each of which consisted of indirect calorimetry energy expenditure (EE) assessments before and after consumption of the beverage (Bang® Keto Coffee; 130 kcal, 300 mg caffeine, 20 g protein) or placebo (30 kcal, 11 mg caffeine, 1 g protein) as well as after exercise testing. In addition, participants' subjective feelings of energy, fatigue, and focus as well as muscular performance (leg press one-repetition maximum and repetitions to fatigue, maximal isometric and isokinetic squat testing) were assessed. Multiple repeated measures ANOVAs with Tukey post-hoc tests were used to analyze data. Estimates of effect size were quantified via partial eta squared (ηP2) and Hedge's g. RESULTS: A significant interaction effect was identified for EE (p < 0.001, ηP2 = 0.52) but not respiratory exchange ratio (p = 0.17, ηP2 = 0.11). Following consumption of the beverage, EE was 0.18 [corrected] kcal·min- 1 greater than placebo at the post-beverage time point (p < 0.001) and 0.08 [corrected] kcal·min- 1 greater than placebo at the post-exercise time point (p = 0.011). However, no between-condition differences were detected for any subjective or muscular performance outcomes. CONCLUSIONS: The results of this study suggest that consumption of the energy drink had minimal effects on lower-body muscular performance and subjective factors in the context of a laboratory setting. However, the beverage was found to significantly increase energy expenditure compared to placebo immediately following ingestion as well as during the recovery period after an exercise bout, suggesting that active individuals may improve acute metabolic outcomes via consumption of a caffeine- and protein-containing energy drink. TRIAL REGISTRATION: This trial was prospectively registered at ClinicalTrials.gov (Identifier: NCT04180787 ; Registered 29 November 2019).

Effectiveness of aerobic exercise and mind-body exercise in cancer patients with poor sleep quality: A systematic review and meta-analysis of randomized controlled trials.

Exercise has promising effects on sleep disturbances and quality of life among cancer patients. Aerobic exercises (AE) and mind-body exercises (MBE) have different mechanisms for improving sleep, but whether they are effective remains unclear. This systematic review and meta-analysis is the first to examine the effectiveness of AE and MBE on sleep outcomes, specifically among cancer patients with sleep disturbances. A systematic search of several databases, from inception to January 2018, was conducted. The pooled effect sizes suggested that both AE (standardized mean difference (SMD) = 0.33, 95% confidence intervals (CI): 0.11, 0.54) and MBE (SMD = 0.18, 95% CI: 0.06, 0.30), improved sleep outcomes in cancer patients with poor sleep quality post-intervention. The effects remained significant after 3-6 months for AE, but not MBE. Due to the heterogeneity in AE, future studies should establish the optimal AE prescription. For MBE, future research should study essential components that make the intervention effect sustainable.

Phenolic Compounds and Metals in Some Edible Annonaceae Fruits.

The concentrations of 3,4-dihydroxybenzoic acid, caffeic acid, catechin, chlorogenic acid, epicatechin, gallic acid, p-coumaric acid, quercetin, rutin, ferulic acid, and the major metals in graviola (Annona muricata), atemoya (A. squamosa x A. cherimola), fruta do conde (A. squamosa), biribá (Rollinia mucosa), and the North American pawpaw (Asimina triloba) were determined by UPLC-ESI (-)-MS/MS. It enabled the identification and quantification of phenolic compounds. Catechin was only found in atemoya, at a concentration of 38.6 µg/g-dw. Only 3,4-dihydroxybenzoic acid was found in the fruit pulps of all five fruits analyzed. Atemoya stands out for not only having catechin but also for having much more epicatechin (239 µg/g-dw) than the other fruits. At the same time, graviola had more p-coumaric acid (62.6 µg/g-dw), and the North American pawpaw had more chlorogenic acid (48.1 µg/g-dw) than the other fruits. Metals were determined by ICP equipped with axially viewed plasma. All five fruit pulps had relatively high levels of potassium, with concentrations ranging from 7640 to 15,000 µg/g-dw, with pawpaw being the lowest and atemoya being the highest. The concentrations of other metals ranged from Ca 547 to 1110, Na 14.3 to 123, P 1210 to 1690, Mg 472 to 980, Mn 1.86 to 5.27, and Zn 5.55 to 7.32 µg/g-dw. All five fruits in the Annonaceae family that were analyzed in this study have several phenolic compounds in them and were good sources of potassium, calcium, phosphorus, and magnesium.

The Effects of Dietary Supplements that Overactivate the Nrf2/ARE System.

BACKGROUND: Inflammation is one of the most misunderstood aspects of human health. People have been encouraged to eat foods that have a high antioxidant capacity, and in vitro tests for total antioxidant capacity emerged. They were based on measuring the destruction of oxidized test compounds in direct reactions with the antioxidants in foods. Many dietary supplements arrived in the market. They contained purified antioxidants, such as resveratrol and EGCG that were and still are widely assumed by many to be quite healthy at any dose. METHODS: The literature on inflammation and the Nrf2/ARE antioxidant system was searched systematically. Articles from prestigious, peer-reviewed journals were obtained and read. The information obtained from them was used to write this review article. RESULTS: Over 150 articles and books were read. The information obtained from them showed that very few dietary antioxidants exert their effects by reacting directly with Reactive Oxygen and Nitrogen Species (RONS). Instead, most of the effective antioxidants activate the endogenous Nrf2/ARE antioxidant system. This helps prevent smoldering inflammation and the diseases that it can cause. However, when overactivated or activated constitutively, the Nrf2/ARE antioxidant system can cause some of these diseases, including many types of multidrug resistant cancer, autoimmune, neurodegenerative and cardiovascular diseases. CONCLUSION: Even though green tea, as well as many fruits, vegetables and spices are quite healthy, dietary supplements that deliver much higher doses of antioxidants may not be. People who are diagnosed with cancer and plan to start chemotherapy and/or radiotherapy should probably avoid such supplements. This is because multidrug resistant tumors can hijack and overactivate the Nrf2/ARE antioxidant system.

History of the Growing Burden of Cancer in India: From Antiquity to the 21st Century.

This review traces the growing burden of cancer in India from antiquity. We searched PubMed, Internet Archive, the British Library, and several other sources for information on cancer in Indian history. Paleopathology studies from Indus Valley Civilization sites do not reveal any malignancy. Cancer-like diseases and remedies are mentioned in the ancient Ayurveda and Siddha manuscripts from India. Cancer was rarely mentioned in the medieval literature from India. Cancer case reports from India began in the 17th century. Between 1860 and 1910, several audits and cancer case series were published by Indian Medical Service doctors across India. The landmark study by Nath and Grewal used autopsy, pathology, and clinical data between 1917 and 1932 from various medical college hospitals across India to confirm that cancer was a common cause of death in middle-aged and elderly Indians. India's cancer burden was apparently low as a result of the short life expectancy of the natives in those times. In 1946, a national committee on health reforms recommended the creation of sufficient facilities to diagnose and manage the increasing cancer burden in all Indian states. Trends from the Mumbai population-based cancer registry revealed a four-fold increase in patients with cancer from 1964 to 2012. Depending on the epidemiologic transition level, wide interstate variation in cancer burden is found in India. We conclude that cancer has been recognized in India since antiquity. India's current burden of a million incident cancers is the result of an epidemiologic transition, improved cancer diagnostics, and improved cancer data capture. The increase in cancer in India with wide interstate variations offers useful insights and important lessons for developing countries in managing their increasing cancer burdens.

Estimating the economic costs of algal blooms in the Canadian Lake Erie Basin.

Over the past two decades there has been a re-emergence of regular harmful algal blooms in Lake Erie due to increasing phosphorus loading, mainly from non-point agricultural sources. The Canadian and United States governments have jointly agreed to reduce phosphorus loadings to the lake in order to control the extent and severity of the blooms. Citizens on both sides of the border face a number of economic costs, both market and non-market, as a result of the blooms. This study values these costs for the Canadian portion of the Lake Erie basin economy using standard economic approaches that are widely applied within the world of cost-benefit analysis. The results suggest that algal blooms will impose equivalent annual costs equal to $272 million in 2015 prices over a 30-year period if left unchecked. The largest market costs will be imposed on the tourism industry ($110 million in equivalent annual costs) and the largest non-market costs will be borne by recreational users and those who place inherent value on the lake's quality ($115 million in equivalent annual costs). Management action to reduce phosphorus loadings is found to be justified on economic grounds if the 30-year net present value of the reduction program is less than $1294 million (2015 Canadian dollars).

Evaluation of the effects of passion fruit peel flour (Passiflora edulis fo. flavicarpa) on metabolic changes in HIV patients with lipodystrophy syndrome secondary to antiretroviral therapy

ABSTRACT This study evaluated the effects of using passion fruit peel flour together with diet therapy and counseling in 36 patients with HIV lipodystrophy who were in an ambulatory clinic in a university hospital. The patients were divided into two groups. One received 30 g of passion fruit peel flour daily for 90 days and diet therapy counseling. The other group received only diet therapy counseling. The metabolic changes were analyzed before and after the intervention, with a significance level predetermined at p ≤ 0.05. The use of passion fruit peel flour was effective in reducing total cholesterol and triacylglycerides after 30 days. The concentrations of LDL-C decreased, while HDL-C increased in the blood of lipodystrophy patients after 90 days passion fruit peel flour treatment. No significant differences in food consumption were seen between groups. The use of 30 g of passion fruit peel flour for 90 days together with diet therapy counseling was effective in improving plasma concentrations of total cholesterol, LDL-C, HDL-C and triacylglycerides.

Phytochemicals and botanical extracts regulate NF-κB and Nrf2/ARE reporter activities in DI TNC1 astrocytes.

The increase in oxidative stress and inflammatory responses associated with neurodegenerative diseases has drawn considerable attention towards understanding the transcriptional signaling pathways involving NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and Nrf2 (Nuclear Factor Erythroid 2-like 2). Our recent studies with immortalized murine microglial cells (BV-2) demonstrated effects of botanical polyphenols to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) and enhance Nrf2-mediated antioxidant responses (Sun et al., 2015). In this study, an immortalized rat astrocyte (DI TNC1) cell line expressing a luciferase reporter driven by the NF-κB or the Nrf2/Antioxidant Response Element (ARE) promoter was used to assess regulation of these two pathways by phytochemicals such as quercetin, rutin, cyanidin, cyanidin-3-O-glucoside, as well as botanical extracts from Withania somnifera (Ashwagandha), Sutherlandia frutescens (Sutherlandia) and Euterpe oleracea (Açaí). Quercetin effectively inhibited LPS-induced NF-κB reporter activity and stimulated Nrf2/ARE reporter activity in DI TNC1 astrocytes. Cyanidin and the glycosides showed similar effects but only at much higher concentrations. All three botanical extracts effectively inhibited LPS-induced NF-κB reporter activity. These extracts were capable of enhancing ARE activity by themselves and further enhanced ARE activity in the presence of LPS. Quercetin and botanical extracts induced Nrf2 and HO-1 protein expression. Interestingly, Ashwagandha extract was more active in inducing Nrf2 and HO-1 expression in DI TNC1 astrocytes as compared to Sutherlandia and Açaí extracts. In summary, this study demonstrated NF-kB and Nrf2/ARE promoter activities in DI TNC1 astrocytes, and further showed differences in ability for specific botanical polyphenols and extracts to down-regulate LPS-induced NF-kB and up-regulate the NRF2/ARE activities in these cells.

All-Cause Mortality and Progression Risks to Hepatic Decompensation and Hepatocellular Carcinoma in Patients Infected With Hepatitis C Virus.

BACKGROUND: A key question in care of patients with chronic hepatitis C virus (HCV) infection is beginning treatment immediately vs delaying treatment. Risks of mortality and disease progression in "real world" settings are important to assess the implications of delaying HCV treatment. METHODS: This was a cohort study of HCV patients identified from 4 integrated health systems in the United States who had liver biopsies during 2001-2012. The probabilities of death and progression to hepatocellular carcinoma, hepatic decompensation (hepatic encephalopathy, esophageal varices, ascites, or portal hypertension) or liver transplant were estimated over 1, 2, or 5 years by fibrosis stage (Metavir F0-F4) determined by biopsy at beginning of observation. RESULTS: Among 2799 HCV-monoinfected patients who had a qualifying liver biopsy, the mean age at the time of biopsy was 50.7 years. The majority were male (58.9%) and non-Hispanic white (66.9%). Over a mean observation of 5.0 years, 261 (9.3%) patients died and 34 (1.2%) received liver transplants. At 5 years after biopsy, the estimated risk of progression to hepatic decompensation or hepatocellular carcinoma was 37.2% in stage F4, 19.6% in F3, 4.7% in F2, and 2.3% in F0-F1 patients. Baseline biopsy stage F3 or F4 and platelet count below normal were the strongest predictors of progression to hepatic decompensation or hepatocellular carcinoma. CONCLUSIONS: The risks of death and progression to liver failure varied greatly by fibrosis stage. Clinicians and policy makers could use these progression risk data in prioritization and in determining the timing of treatment for patients in early stages of liver disease.

Neurotoxicity of Dietary Supplements from Annonaceae Species.

Dietary supplements containing plant materials of Annonaceae species (Annona muricata L., A. squamosa L., A. mucosa JACQ., A. squamosa × cherimola Mabb.) were extracted by hot, pressurized ethyl acetate and analyzed for their effect in vitro on Lund human mesencephalic neurons. Cell viability was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell death was determined by lactate dehydrogenase levels. Three supplements strongly decreased the cell viability at extract concentrations of 1 µg/mL, of which 1 decreased cell viability at 0.1 µg/µL. Also, strong neuronal toxicities of these supplements were found. Cell death was observed at concentrations of 10 µg/mL. The degree of toxicity was comparable to the ones found in Annonaceous fruit extracts. Two fruit pulps of Annonaceae (A. muricata and A. squamosa) showed a reduction in cell viability at lower concentrations. The fruit pulp extract of A. muricata revealed the strongest neurotoxic effect, with 67% cell death at a concentration of 1 µg/mL. A high reduction in cell viability coupled with pronounced cell death was found at 0.1 µg/mL for an Annonaceous seed extract. These results demonstrate that the intake of dietary supplements containing plant material from Annonaceae may be hazardous to health in terms of neurotoxicity.