A phase 2 study of ibrutinib in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma

Objective: We evaluated ibrutinib, a once-daily inhibitor of Bruton's tyrosine kinase, combined with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma who had received 1-3 prior therapies. Methods: This was a phase 2, single-arm, open-label, multicentre study (NCT02902965). The primary endpoint was progression-free survival (PFS). Results: Seventy-six patients were enrolled; 74 received ≥1 dose of study treatment. After median follow-up of 19.6 months, median PFS was 8.5 months (95% CI: 6.2-10.8); median overall survival was not reached. Overall response rate was 57% (95% CI: 45-68), and median duration of response was 9.5 months (95% CI: 6.9-10.6). Grade 3/4 AEs occurred in 73% of patients and fatal AEs occurred in 15% of patients. Incidence of major haemorrhage was 5%; one patient died from cerebral haemorrhage. After an observed increased incidence of serious (42%) and fatal (11%) infections, enrolment was suspended to implement risk-minimisation measures. The safety profile was otherwise consistent with known safety profiles of the individual drugs. Conclusion: Ibrutinib combined with bortezomib and dexamethasone elicited clinical responses. However, efficacy assessments conducted at potential restart of enrolment indicated that the targeted PFS could not be reached with additional patient enrolment, and the study was terminated

Comparison of new forms of creatine in raising plasma creatine levels

<p>Abstract</p> <p>Background</p> <p>Previous research has shown that plasma creatine levels are influenced by extracellular concentrations of insulin and glucose as well as by the intracellular creatine concentration. However, the form of creatine administered does not appear to have any effect although specific data on this is lacking. This study examined whether the administration of three different forms of creatine had different effects on plasma creatine concentrations and pharmacokinetics.</p> <p>Methods</p> <p>Six healthy subjects (three female and three male subjects) participated in the study. Each subject was assigned to ingest a single dose of isomolar amounts of creatine (4.4 g) in the form of creatine monohydrate (CrM), tri-creatine citrate (CrC), or creatine pyruvate (CrPyr) using a balanced cross-over design. Plasma concentration curves, determined over eight hours after ingestion, were subject to pharmacokinetic analysis and primary derived data were analyzed by repeated measures ANOVA.</p> <p>Results</p> <p>Mean peak concentrations and area under the curve (AUC) were significantly higher with CrPyr (17 and 14%, respectively) in comparison to CrM and CrC. Mean peak concentration and AUC were not significantly different between CrM and CrC. Despite the higher peak concentration with CrPyr there was no difference between the estimated velocity constants of absorption (ka) or elimination (kel) between the three treatments. There was no effect of treatment with CrPyr on the plasma pyruvate concentration.</p> <p>Conclusion</p> <p>The findings suggest that different forms of creatine result in slightly altered kinetics of plasma creatine absorption following ingestion of isomolar (with respect to creatine) doses of CrM, CrC and CrPyr although differences in ka could not be detected due to the small number of blood samples taken during the absorption phase. Characteristically this resulted in higher plasma concentrations of creatine with CrPyr. Differences in bioavailability are thought to be unlikely since absorption of CrM is already close to 100%. The small differences in kinetics are unlikely to have any effect on muscle creatine elevation during periods of creatine loading.</p

The immunobiology of primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease histologically characterized by the presence of intrahepatic and/or extrahepatic biliary duct concentric, obliterative fibrosis, eventually leading to cirrhosis. Approximately 75% of patients with PSC have inflammatory bowel disease. The male predominance of PSC, the lack of a defined, pathogenic autoantigen, and the potential role of the innate immune system suggest that it may be due to dysregulation of immunity rather than a classic autoimmune disease. However, PSC is associated with several classic autoimmune diseases, and the strongest genetic link to PSC identified to date is with the human leukocyte antigen DRB01*03 haplotype. The precise immunopathogenesis of PSC is largely unknown but likely involves activation of the innate immune system by bacterial components delivered to the liver via the portal vein. Induction of adhesion molecules and chemokines leads to the recruitment of intestinal lymphocytes. Bile duct injury results from the sustained inflammation and production of inflammatory cytokines. Biliary strictures may cause further damage as a result of bile stasis and recurrent secondary bacterial cholangitis. Currently, there is no effective therapy for PSC and developing a rational therapeutic strategy demands a better understanding of the disease

Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology characterised by inflammation and fibrosis of the biliary tree. The mean age at diagnosis is 40 years and men are affected twice as often as women. There is a reported annual incidence of PSC of 0.9–1.31/100,000 and point prevalence of 8.5–13.6/100,000. The onset of PSC is usually insidious and many patients are asymptomatic at diagnosis or have mild symptoms only such as fatigue, abdominal discomfort and pruritus In late stages, splenomegaly and jaundice may be a feature. In most, the disease progresses to cirrhosis and liver failure. Cholangiocarcinoma develops in 8–30% of patients. PSC is thought to be immune mediated and is often associated with inflammatory bowel disease, especially ulcerative colitis. The disease is diagnosed on typical cholangiographic and histological findings and after exclusion of secondary sclerosing cholangitis. Median survival has been estimated to be 12 years from diagnosis in symptomatic patients. Patients who are asymptomatic at diagnosis, the majority of whom will develop progressive disease, have a survival rate greater than 70% at 16 years after diagnosis. Liver transplantation remains the only effective therapeutic option for patients with end-stage liver disease from PSC, although high dose ursodeoxycholic acid may have a beneficial effect

Strength and hypertrophy responses to constant and decreasing rest intervals in trained men using creatine supplementation

<p>Abstract</p> <p>Background</p> <p>The purpose of the current study was to compare strength and hypertrophy responses to resistance training programs that instituted constant rest intervals (CI) and decreasing rest intervals (DI) between sets over the course of eight weeks by trained men who supplemented with creatine monohydrate (CR).</p> <p>Methods</p> <p>Twenty-two recreationally trained men were randomly assigned to a CI group (n = 11; 22.3 ± 1 years; 77.7 ± 5.4 kg; 180 ± 2.2 cm) or a DI group (n = 11; 22 ± 2.5 years; 75.8 ± 4.9 kg; 178.8 ± 3.4 cm). Subjects in both groups supplemented with CR; the only difference between groups was the rest interval instituted between sets; the CI group used 2 minutes rest intervals between sets and exercises for the entire 8-weeks of training, while the DI group started with a 2 minute rest interval the first two weeks; after which the rest interval between sets was decreased 15 seconds per week (i.e. 2 minutes decreasing to 30 seconds between sets). Pre- and post-intervention maximal strength for the free weight back squat and bench press exercises and isokinetic peak torque were assessed for the knee extensors and flexors. Additionally, muscle cross-sectional area (CSA) of the right thigh and upper arm was measured using magnetic resonance imaging.</p> <p>Results</p> <p>Both groups demonstrated significant increases in back squat and bench press maximal strength, knee extensor and flexor isokinetic peak torque, and upper arm and right thigh CSA from pre- to post-training (p ≤ 0.0001); however, there were no significant differences between groups for any of these variables. The total volume for the bench press and back squat were significantly greater for CI group versus the DI group.</p> <p>Conclusions</p> <p>We report that the combination of CR supplementation and resistance training can increase muscular strength, isokinetic peak torque, and muscle CSA, irrespective of the rest interval length between sets. Because the volume of training was greater for the CI group versus the DI group, yet strength gains were similar, the creatine supplementation appeared to bolster adaptations for the DI group, even in the presence of significantly less volume. However, further research is needed with the inclusion of a control group not receiving supplementation combined and resistance training with decreasing rest intervals to further elucidate such hypotheses.</p

Incubating Isolated Mouse EDL Muscles with Creatine Improves Force Production and Twitch Kinetics in Fatigue Due to Reduction in Ionic Strength

Creatine supplementation can improve performance during high intensity exercise in humans and improve muscle strength in certain myopathies. In this present study, we investigated the direct effects of acute creatine incubation on isolated mouse fast-twitch EDL muscles, and examined how these effects change with fatigue. muscle from mice aged 12–14 weeks was isolated and stimulated with field electrodes to measure force characteristics in 3 different states: (i) before fatigue; (ii) immediately after a fatigue protocol; and (iii) after recovery. These served as the control measurements for the muscle. The muscle was then incubated in a creatine solution and washed. The measurement of force characteristics in the 3 different states was then repeated. In un-fatigued muscle, creatine incubation increased the maximal tetanic force. In fatigued muscle, creatine treatment increased the force produced at all frequencies of stimulation. Incubation also increased the rate of twitch relaxation and twitch contraction in fatigued muscle. During repetitive fatiguing stimulation, creatine-treated muscles took 55.1±9.5% longer than control muscles to lose half of their original force. Measurement of weight changes showed that creatine incubation increased EDL muscle mass by 7%. sensitivity of contractile proteins as a result of ionic strength decreases following creatine incubation

Exercise and functional foods

Appropriate nutrition is an essential prerequisite for effective improvement of athletic performance, conditioning, recovery from fatigue after exercise, and avoidance of injury. Nutritional supplements containing carbohydrates, proteins, vitamins, and minerals have been widely used in various sporting fields to provide a boost to the recommended daily allowance. In addition, several natural food components have been found to show physiological effects, and some of them are considered to be useful for promoting exercise performance or for prevention of injury. However, these foods should only be used when there is clear scientific evidence and with understanding of the physiological changes caused by exercise. This article describes various "functional foods" that have been reported to be effective for improving exercise performance or health promotion, along with the relevant physiological changes that occur during exercise

Eurasian consumers' food safety beliefs and trust issues in the age of COVID ‐19: evidence from an online survey in 15 countries

Eurasian consumers' food safety beliefs and trust issues in the age of COVID ‐19: evidence from an online survey in 15 countries Igor Tomasevic Faculty of Agriculture University of Belgrade Belgrade Serbia German Institute of Food Technologies (DIL) Quakenbrück Germany Department of Dairy Technology and Functional Foods, Faculty of Food Sciences and Biotechnology University of Life Sciences in Lublin Lublin Poland https://orcid.org/0000-0002-1611-2264 Garegin Hambardzumyan Armenian National Agrarian University Yerevan Armenia Gayane Marmaryan Armenian National Agrarian University Yerevan Armenia Aleksandra Nikolic Faculty of Agriculture and Food Sciences University of Sarajevo Sarajevo Bosnia and Herzegovina Alen Mujcinovic Faculty of Agriculture and Food Sciences University of Sarajevo Sarajevo Bosnia and Herzegovina Weizheng Sun School of Food Science and Engineering South China University of Technology Guangzhou China https://orcid.org/0000-0001-5769-4275 Xiao‐Chen Liu School of Food Science and Engineering South China University of Technology Guangzhou China Danijela Bursać Kovačević Faculty of Food Technology and Biotechnology University of Zagreb Zagreb Croatia Anica Bebek Markovinović Faculty of Food Technology and Biotechnology University of Zagreb Zagreb Croatia Nino Terjung German Institute of Food Technologies (DIL) Quakenbrück Germany Volker Heinz German Institute of Food Technologies (DIL) Quakenbrück Germany Maria Papageorgiou Department of Food Science and Technology International Hellenic University Thessaloniki Greece Adriana Skendi Department of Food Science and Technology International Hellenic University Thessaloniki Greece Gunjan Goel Department of Microbiology Central University of Haryana Mahendragarh India https://orcid.org/0000-0002-8761-929X Mamta Raghav Department of Life Sciences RPS Degree College Mahendragarh India Antonella Dalle Zotte Department of Animal Medicine, Production and Health University of Padova Padova Italy Dimitar Nakov Faculty of Agriculture "Goce Delcev" University in Stip Shtip Republic of North Macedonia Faculty of Medical Sciences "Goce Delcev" University in Stip Shtip Republic of North Macedonia Valentina Velkoska Faculty of Agriculture "Goce Delcev" University in Stip Shtip Republic of North Macedonia Bartosz G. Sołowiej Department of Dairy Technology and Functional Foods, Faculty of Food Sciences and Biotechnology University of Life Sciences in Lublin Lublin Poland Anastasia A. Semenova V. M. Gorbatov Federal Research Center for Food Systems Moscow Russia Oksana A. Kuznetsova V. M. Gorbatov Federal Research Center for Food Systems Moscow Russia Miroslav Krocko Department of Technology and Quality of Animal Products, Faculty of Biotechnology and Food Sciences Institute of Food Sciences, Slovak University of Agriculture in Nitra Nitra Slovakia Viera Duckova Department of Technology and Quality of Animal Products, Faculty of Biotechnology and Food Sciences Institute of Food Sciences, Slovak University of Agriculture in Nitra Nitra Slovakia Jose M. Lorenzo Centro Tecnológico de la Carne de Galicia Ourense Spain https://orcid.org/0000-0002-7725-9294 Noemi Echegaray Centro Tecnológico de la Carne de Galicia Ourense Spain https://orcid.org/0000-0002-7393-2955 Emel Oz Department of Food Engineering, Agriculture Faculty Atatürk University Erzurum Türkiye https://orcid.org/0000-0003-3766-2713 Fatih Oz Department of Food Engineering, Agriculture Faculty Atatürk University Erzurum Türkiye https://orcid.org/0000-0002-5300-7519 Ilija Djekic Faculty of Agriculture University of Belgrade Belgrade Serbia Abstract BACKGROUND This investigation provides an important insight into Eurasian consumers' food safety beliefs and trust issues influenced by the COVID‐19 pandemic. An online survey was conducted in 15 European and Asian countries involving more than 4000 consumers. RESULTS It has confirmed that different socioeconomic characteristics, cultural aspects and education levels shape food safety perceptions within Eurasian countries. The COVID‐19 pandemic influenced their beliefs and trust in food safety, which is relatively low on average. However, it is significantly higher for European consumers (especially European Union ones) compared to their Asian counterparts. Both Asian and European respondents agreed that food fraud and climate changes represent a food safety issue. However, European consumers were less concerned regarding the food safety of genetically modified foods and meat and dairy analogs/hybrids. Asian consumers were, to a greater extent, worried about the risk of getting COVID‐19 from food, restaurants, food retail establishments and home food deliveries. CONCLUSION Eurasian consumers have put their greatest extent of trust, when food safety assurance is concerned, into food scientists and food producers holding a food safety certificate. Broadly, they are uncertain to what extent their federal governments and food inspectors are competent, able and efficient in ensuring food safety. Higher education of Eurasian consumers was followed by increased food safety confidence in all parts of the food chain. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. 07 13 2023 jsfa.12815 10.1002/jsfa.12815 2 10.1002/crossmark_policy onlinelibrary.wiley.com true 2023-02-27 2023-06-21 2023-07-13 http://creativecommons.org/licenses/by-nc-nd/4.0/ 10.1002/jsfa.12815 https://onlinelibrary.wiley.com/doi/10.1002/jsfa.12815 https://onlinelibrary.wiley.com/doi/pdf/10.1002/jsfa.12815 10.1097/PHH.0000000000001470 10.4315/JFP-21-096 10.1186/s12889-022-12568-4 10.1007/s10551-015-2690-5 10.1037/ipp0000074 10.1007/BF02249397 10.1016/j.foodqual.2017.09.012 10.1093/heapro/daw024 10.1016/S0195-6663(03)00112-0 10.1080/18692729.2017.1256987 10.1080/15287394.2016.1174008 10.1016/B978-0-12-381504-0.00041-X 10.1016/j.foodcont.2020.107800 Studies in Systems, Decision and Control Azzam Z 25 10.1016/j.appet.2021.105309 10.2139/ssrn.4053920 LimA XuJandYuYeds Consumer Food Demand Shifts in the COVID‐19 Pandemic: An Empirical Study Based on Retail Sales Data. Lecture Notes in Networks and Systems; 2023 Consumer Food Demand Shifts in the COVID‐19 Pandemic: An Empirical Study Based on Retail Sales Data. 10.3390/math10091394 Econ Pol Wkly Kaicker N 16 57 2022 Food consumption expenditures and the COVID‐19 pandemic in India 10.1016/j.appet.2022.106313 10.1016/j.foodcont.2020.107089 10.3390/foods11030432 10.1016/j.foodcont.2020.107238 10.1016/j.tifs.2003.08.004 Kodeks profesionalne etike Univerziteta u Beogradu Serbia 193 2016 10.1111/j.1365-2648.2004.03185.x 10.1016/j.foodcont.2022.109216 10.1016/j.appet.2022.106265 10.1016/B978-0-12-813148-0.00001-3 Basic statistics: a modern approach Hamburg M 548 1985 Fundamentals of Biostatistics Rosner B 2011 10.1016/j.jretconser.2011.08.007 10.1108/00070700210418767 Ageing Europe: looking at the lives of older people in the EU:2 020th edition Eurostat 2020 CIA Median Age‐The World Factbook: Central Intelligence Agency(2022). Available from:https://www.cia.gov/the-world-factbook/field/median-age/country-comparison. 10.1016/j.jpolmod.2015.05.002 Higher education across asia: an overview of issues and strategies ADB 66 2011 10.1016/j.tifs.2019.10.005 Rapid alert system for food and feed‐alert and cooperation network: 2021 annual report RASFF 2021 10.1016/j.foodres.2016.08.028 10.1007/s13593-022-00778-4 BhavanaTandRoshanD Europe meat substitute market by product type source and category: regional opportunity analysis and industry forecast 2021‐2027 allied market research(2021). Nils‐GerritW Plant‐based milk and dairy alternatives in Europe‐statistics & facts: Statista(2022). Available from:https://www.statista.com/topics/10162/milk-and-dairy-alternatives-in-europe/#topicOverview. Nils‐GerritW Retail sales value of milk and milk alternatives worldwide in 2020 by region: Statista(2021). Available from:https://www.statista.com/topics/10162/milk-and-dairy-alternatives-in-europe/#topicOverview. 10.1016/j.appet.2011.06.010 10.1007/978-3-030-12453-3_53 10.1108/CAER-08-2015-0102 10.1111/ijcs.12345 10.1371/journal.pone.0126060 10.1080/14636778.2012.743269 10.1016/j.meatsci.2019.107965 10.1016/j.tifs.2013.01.003 Coronavirus: no Evidence that Food Is a Source or Transmission Route EFSA 2020 10.1016/S0140-6736(20)30211-7 10.1016/j.foodcont.2015.07.028 10.1016/j.ijhm.2021.102960 10.1016/j.ijhm.2021.102988 10.1016/j.jretconser.2022.102972 10.1016/j.ijhm.2020.102821 10.1016/j.ijgfs.2021.100330 10.1016/j.gfs.2022.100658 10.1016/j.meatsci.2015.12.008 10.1016/j.tifs.2020.08.020 10.1111/ijcs.12184 EFSA Food Safety in the EU: report(2022). 10.3390/foods10102490 10.4102/hsag.v26i0.1407 10.1016/j.foodcont.2022.109377 10.1016/j.foodcont.2013.11.022 10.1016/j.ijhm.2021.102905 10.1002/agr.21414 10.1016/j.fct.2020.111170 10.1016/j.appet.2004.05.003 10.1016/j.jneb.2018.03.013 10.1016/j.emj.2017.02.00