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Effects of a dietary intervention on cardiometabolic risk and food consumption in a workplace.
Shrestha, A, Tamrakar, D, Ghinanju, B, Shrestha, D, Khadka, P, Adhikari, B, Shrestha, J, Waiwa, S, Pyakurel, P, Bhandari, N, et al
PloS one. 2024;(4):e0301826
Abstract
BACKGROUND Worksite-based health programs have shown positive impacts on employee health and have led to significant improvements in cardiovascular risk factor profiles. We aimed to determine the effect of cafeteria intervention on cardio-metabolic risk factors diet in a worksite setting (Dhulikhel Hospital) in Nepal. METHODS In this one-arm pre-post intervention study, we recruited 277 non-pregnant hospital employees aged 18-60 with prediabetes or pre-hypertension. The study was registered in clinicaltrials.gov (NCT03447340; 2018/02/27). All four cafeterias in the hospital premises received cafeteria intervention encouraging healthy foods and discouraging unhealthy foods for six months. We measured blood pressure, fasting glucose level, glycated hemoglobin, cholesterol in the laboratory, and diet intake (in servings per week) using 24-hour recall before and six months after the intervention. The before and after measures were compared using paired-t tests. RESULTS After six months of cafeteria intervention, the median consumption of whole grains, mono/polyunsaturated fat, fruits, vegetable and nuts servings per week increased by 2.24(p<0.001), 2.88(p<0.001), 0.84(p<0.001) 2.25(p<0.001) and nuts 0.55 (p<0.001) servings per week respectively. The median consumption of refined grains decreased by 5.07 servings per week (p<0.001). Mean systolic and diastolic blood pressure decreased by 2 mmHg (SE = 0.6; p = 0.003) and 0.1 mmHg (SE = 0.6; p = 0.008), respectively. The low-density lipoprotein (LDL) was significantly reduced by 6 mg/dL (SE = 1.4; p<0.001). CONCLUSION Overall, we found a decrease in consumption of refined grains and an increase in consumption of whole grains, unsaturated fats, fruits, and nuts observed a modest reduction in blood pressure and LDL cholesterol following a 6-month cafeteria-based worksite intervention incorporating access to healthy foods.
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A Phase 2 Clinical Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of Different Prime-Boost Vaccination Schedules of 2013 and 2017 A(H7N9) Inactivated Influenza Virus Vaccines Administered With and Without AS03 Adjuvant in Healthy US Adults.
Rostad, CA, Atmar, RL, Walter, EB, Frey, S, Meier, JL, Sherman, AC, Lai, L, Tsong, R, Kao, CM, Raabe, V, et al
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2024;(6):1757-1768
Abstract
INTRODUCTION A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs. METHODS Healthy adults (n = 180), ages 19-50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with 2 different boost intervals (21 vs 120 days) and 2 dosages (3.75 or 15 μg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition and neutralizing antibody titers were assessed. RESULTS Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest hemagglutination inhibition geometric mean titer (95% confidence interval) observed against the 2017 A(H7N9) strain was 133.4 (83.6-212.6) among participants who received homologous, adjuvanted 3.75 µg + AS03/2017 doses with delayed boost interval. CONCLUSIONS Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. Clinical Trials Registration. NCT03589807.
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Efficacy of parsley seed-supplemented bread in improving serum osteopontin level and renal health in obese women: A nutritional intervention study.
Essa, HA, El Shebini, SM, Moaty, MIA, Ahmed, NH, Hussein, AMS, Mohamed, MS
Clinical nutrition ESPEN. 2024;:287-295
Abstract
BACKGROUND Obesity is a global epidemic and a major contributor to chronic kidney disease worldwide. This interventional study aimed to evaluate the effects of a unique parsley seed bread and a healthy balanced diet on serum osteopontin level and renal function in obese women. METHODS A total of 85 obese women (BMI, 35.68 ± 0.47 kg/m2) participated in an 8-week nutritional intervention comprising two phases. In the first phase, participants consumed 100 g of ground parsley seed bread along with a healthy balanced low caloric regimen for four weeks. In the second phase, Baladi bread was substituted for the supplement, providing an equal caloric intake, for another four weeks. Relevant Anthropometric measurements, blood pressure, dietary recall, and biochemical parameters (osteopontin, IL-1β, IL-10, kidney functions, and lipid parameters) were assessed before and after each intervention phase. RESULTS Following the initial intervention phase, there were significant improvements in all recorded mean anthropometric parameters (p ≤ 0.001). Lipid parameters and risk factors also significantly decreased (p < 0.05), while osteopontin, creatinine, and IL-1β levels decreased significantly. eGFR, creatinine clearance, IL-10 increased. However, these improved values returned to elevated levels after the omission of the supplement in the second phase. There was a significant negative correlation between osteopontin and creatinine, creatinine clearance, and IL-10. CONCLUSION The combined effect of the novel parsley seed-based intervention and a healthy balanced low-calorie regimen demonstrated improvements in osteopontin level associated with renal disorders, and inflammation, in addition to dyslipidemia in obese women. This suggests a promising approach for improving and protecting kidney disorders.
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[The influence of diet therapy and regular physical trainings on monocyte chemoattractant protein-1 (MCP-1) secretion by monocytes among obese patients with coronary heart disease].
Starodubova, AV, Shaposhnikova, NN, Varaeva, YR, Kirichenko, TV, Markina, YV, Tolstik, TV, Nikityuk, DV
Voprosy pitaniia. 2024;(2):63-72
Abstract
Chronic systemic inflammation is one of the leading pathogenetic pathways for the development of atherosclerosis in obese patients. In this regard, it seems promising to evaluate the effect of the diet and physical exertion on the proinflammatory activity of monocytes. The purpose of this research was to evaluate the effect of the diet and regular physical trainings on the secretion of monocyte chemotactic factor 1 (MCP-1) by monocytes in obese patients with coronary artery disease. Material and methods. 27 obese participants (body mass index >30 kg/m2) with a confirmed diagnosis of coronary heart disease were recruited. All participants were prescribed with 12 weeks of a specialized diet with a restriction of simple carbohydrates and salt, a 500-kcal daily energy deficit, and with inclusion of cruciferous (200 g per day), seasonal dark berries (70 g per day) and green tea (200 ml per day). The regular assisted physical trainings were also administered. The body composition, blood biochemical parameters and MCP-1 secretion rates in the primary culture of monocytes isolated from blood samples via the immunomagnetic separation method were assessed before and after the intervention. Results. As a result, after the 12-weeks intervention the reliable body weight loss (-4.0%), waist circumference (-4.2%), visceral fat (-5.4%), total cholesterol (-9.8%), LDL-cholesterol (-16.6%) and triglycerides (-26.0%), an improvement in the results of the 6-minute walk test (+10.33%) was achieved, as well as an LPS-stimulated monocytes secretion of MCP-1 decreased by 2.8 times (p=0.005). Conclusion. Overall, the results suggest that diet and regular physical activity in patients with obesity and coronary heart disease may decrease the functional "proinflammatory" activity of monocytes.
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Probiotic BC30 Improves Amino Acid Absorption from Plant Protein Concentrate in Older Women.
Walden, KE, Hagele, AM, Orr, LS, Gross, KN, Krieger, JM, Jäger, R, Kerksick, CM
Probiotics and antimicrobial proteins. 2024;16(1):125-137
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The ability of probiotics to influence the absorption of key nutrients and various forms of digestive enzymes has evolved into an emerging area of interest. It is currently well-established that probiotic outcomes are strain specific. In particular, the Weizmannia coagulans GBI-30, 6086 (BC30) strain, is a lactic acid producing, spore-forming bacterial species that has exhibited the ability to improve protein and amino acid absorption. The aim of this study was to assess the impact of adding BC30 to a plant protein concentrate on amino acid appearance into the bloodstream in a cohort of healthy, older women. This study was a randomised, double-blind, crossover study design. Healthy women (n = 30) between the ages of 50–70 years of age were recruited. Two supplementation periods that each spanned 2 weeks were completed and separated with a washout period of 3 weeks. Results showed that area under the curve values for three individual amino acids (alanine, tryptophan, and cysteine), essential amino acids, and total amino acids were greater when BC30 was co-ingested with a plant protein concentrate when compared to isolated ingestion of an identical dose of the plant protein concentrate in healthy, older women. Additionally, peak plasma concentrations of tryptophan, cysteine, essential amino acids, and total amino acids were also greater when BC30 was added to a plant protein concentrate. Authors concluded that their findings provide additional evidence that adding specific probiotic strains such as BC30 to various forms of protein can improve the appearance of amino acids in the blood.
Abstract
Weizmannia coagulans GBI-30, 6086 (BC30) has previously been shown to increase protein digestion in an in vitro model of the stomach and small intestine and amino acid appearance in healthy men and women after ingestion of milk protein concentrate. The impact of ingesting BC30 with other protein sources or in other demographics is largely unknown. The purpose of this study was to examine the impact of adding BC30 to a 20-g dose of a blend of rice and pea protein on postprandial changes in blood amino acids concentrations in healthy, older women. Healthy, older females (n = 30, 58.5 ± 5.2 years, 165.4 ± 6.8 cm, 65.6 ± 8.8 kg, 23.7 ± 3.2 kg/m2) completed two separate 14-day supplementation protocols separated by a 3-week washout period. Participants were instructed to ingest a 20-g protein dose of a blend of rice and pea protein concentrates (ProDiem Plant Protein Solutions, Kerry) with (PPCBC30) or without (PPC) the addition of 1 × 109 CFU BC30 (Kerry). Body composition and demographics were assessed upon arrival to the laboratory. Upon ingestion of their final assigned supplemental dose, blood samples were taken at 0 (baseline), 30-, 60-, 90-, 120-, 180-, and 240-min post-consumption and analyzed for amino acid concentrations. Alanine (p = 0.018), tryptophan (p = 0.003), cysteine (p = 0.041), essential amino acids (p = 0.050), and total amino acids (p = 0.039) all exhibited significantly (p ≤ 0.05) greater AUC with PPCBC30 when compared to PPC. In addition, tryptophan (p = 0.003), cysteine (p = 0.021), essential amino acids (p = 0.049), and total amino acids (p = 0.035) displayed significantly greater (p ≤ 0.05) concentration maximum (CMax) values in PPCBC30 when compared to PPC. Finally, time to reach CMax (TMax) was similar between conditions with 80% of all measured amino acids and amino acid combinations achieving CMax at a similar time (~ 60 min). Only phenylalanine TMax was found to be different (p = 0.01) between the two conditions with PPC displaying a greater proportion of TMax values after 30 min. Following qualitative (non-inferential) assessment, 88% of all measured outcomes achieved a higher AUC with PPCBC30 and 100% of all outcomes achieved a higher CMax with PPCBC30. In concert with previous findings in a younger mixed gender cohort with milk protein, the addition of BC30 to a daily 20-g dose of plant protein concentrate in healthy older women improved AUC and CMax values in several individual amino acids and amino acid combinations. Retrospectively registered on April 6, 2022, at ClinicalTrials.gov as NCT05313178.
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Exercise intervention in middle-aged and elderly individuals with insomnia improves sleep and restores connectivity in the motor network.
Chen, R, Wang, S, Hu, Q, Kang, N, Xie, H, Liu, M, Shan, H, Long, Y, Hao, Y, Qin, B, et al
Translational psychiatry. 2024;14(1):159
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Insomnia is highly prevalent in older adults. Exercise intervention has been recognized as a potential treatment to improve sleep. The most frequent exercise intervention includes aerobic and resistance exercise. The aim of this study was to identify the effects of a 12-week exercise program on sleep quality and brain functional connectivity in middle-aged and older adults with insomnia. This study was a randomised controlled trial. Ninety-two participants were randomly assigned to one of the two groups (exercise vs control group). Results showed that middle-aged and older adults with insomnia had decreases in both subjective and objective sleep quality. At the level of brain circuits, individuals with insomnia exhibited reduced connectivity within the extensive motor network. Following the exercise intervention, participants in the exercise group reported an improvement in sleep quality. Authors concluded that exercise intervention improved insomnia symptoms and motor network connectivity. Additionally, they underscore the potential to enhance sleep quality and promote brain plasticity in aging individuals through exercise intervention.
Abstract
Exercise is a potential treatment to improve sleep quality in middle-aged and elderly individuals. Understanding exercise-induced changes in functional plasticity of brain circuits that underlie improvements in sleep among middle-aged and older adults can inform treatment of sleep problems. The aim of the study is to identify the effects of a 12-week exercise program on sleep quality and brain functional connectivity in middle-aged and older adults with insomnia. The trial was registered with Chinese Clinical Trial Register (ChiCTR2000033652). We recruited 84 healthy sleepers and 85 individuals with insomnia. Participants with insomnia were assigned to receive either a 12-week exercise intervention or were placed in a 12-week waitlist control condition. Thirty-seven middle-aged and older adults in the exercise group and 30 in the waitlist group completed both baseline and week 12 assessments. We found that middle-aged and older adults with insomnia showed significantly worse sleep quality than healthy sleepers. At the brain circuit level, insomnia patients showed decreased connectivity in the widespread motor network. After exercise intervention, self-reported sleep was increased in the exercise group (P < 0.001) compared to that in the waitlist group. We also found increased functional connectivity of the motor network with the cerebellum in the exercise group (P < 0.001). Moreover, we observed significant correlations between improvement in subjective sleep indices and connectivity changes within the motor network. We highlight exercise-induced improvement in sleep quality and functional plasticity of the aging brain.
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Phase I trial of apatinib and paclitaxel+oxaliplatin+5-FU/levoleucovorin for treatment-naïve advanced gastric cancer.
Zhao, S, Su, L, Huang, F, Zhuo, C, Ye, Z, Li, H, Yin, Y, Gao, P, Zhu, Y, Lin, R
Cancer science. 2024;(5):1611-1621
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Abstract
Chinese guidelines recommend POF (paclitaxel, oxaliplatin, and 5-FU/levoleucovorin) as first-line treatment for advanced gastric cancer (AGC). Apatinib can augment the antitumor effect of paclitaxel, oxaliplatin, or fluorouracil in preclinical studies of AGC. A phase I clinical trial was conducted to evaluate the anticancer activity and maximum tolerated dose (MTD) of apatinib plus POF in treatment-naïve patients with AGC and to establish a recommended phase II dose. Participants received escalating doses of daily oral apatinib (250, 375, 500, 625, 750, and 850 mg) plus POF every 2 weeks using a conventional "3 + 3" study design. Among 21 treated patients, one experienced a dose-limiting toxicity (grade 3 skin ulceration at 850 mg). No MTD was reached. Apatinib 750 mg plus POF was recommended for phase II study. The most common grade 3-4 adverse events (AEs) were neutropenia (33.3%), mucositis (14.3%), and hand-foot syndrome (14.3%). Median progression-free and overall survival were 10.4 months (95% CI: 6.3, 14.6) and 18.4 months (95% CI: 9.8, 28.2), respectively. Apatinib up to 850 mg coadministered with POF was well tolerated with manageable AEs. The safety and anticancer activity of this regimen warrants its further investigation as first-line treatment for AGC in a larger study.
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Population pharmacokinetics of intraperitoneal irinotecan and SN-38 in patients with peritoneal metastases from colorectal origin.
Rietveld, PCS, Sassen, SDT, Guchelaar, NAD, van Eerden, RAG, de Boer, NL, van den Heuvel, TBM, Burger, JWA, Mathijssen, RHJ, Koch, BCP, Koolen, SLW
CPT: pharmacometrics & systems pharmacology. 2024;(6):1006-1016
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Peritoneal metastases (PM) are common in patients with colorectal cancer. Patients with PM have a poor prognosis, and for those who are not eligible for cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC), palliative chemotherapy is currently the only option. Recently, we conducted a phase I trial (INTERACT) in which irinotecan was administered intraperitoneally (IP) to 18 patients ineligible for CRS-HIPEC. The primary objective was to evaluate covariates influencing the PK profile of irinotecan and SN-38 after IP administration. Secondly, a population PK model was developed to support the further development of IP irinotecan by improving dosing in patients with PM. Patients were treated with IP irinotecan every 2 weeks in combination with systemic FOLFOX-bevacizumab. Irinotecan and SN-38 were measured in plasma (588 samples) and SN-38 was measured in peritoneal fluid (267 samples). Concentration-Time data were log-transformed and analyzed using NONMEM version 7.5 using FOCE+I estimation. An additive error model described the residual error, with inter-individual variability in PK parameters modeled exponentially. The final structural model consisted of five compartments. Weight was identified as a covariate influencing the SN-38 plasma volume of distribution and GGT was found to influence the SN-38 plasma clearance. This population PK model adequately described the irinotecan and SN-38 in plasma after IP administration, with weight and GGT as predictive factors. Irinotecan is converted intraperitoneal to SN-38 by carboxylesterases and the plasma bioavailability of irinotecan is low. This model will be used for the further clinical development of IP irinotecan by providing dosing strategies.
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Total and H-specific growth/differentiation factor 15 levels are unaffected by liraglutide or naltrexone/bupropion administration.
Konstantinidou, SK, Argyrakopoulou, G, Simati, S, Stefanakis, K, Kokkinos, A, Analitis, A, Mantzoros, CS
Diabetes, obesity & metabolism. 2024;(8):3147-3154
Abstract
AIM: To investigate growth/differentiation factor 15 (GDF-15) levels in response to antiobesity medications, namely, liraglutide (Lira) and naltrexone/bupropion (N/B), in individuals with overweight or obesity. MATERIALS AND METHODS This was a prospective, non-randomized clinical trial with a two-arm, parallel design. A total of 42 individuals with overweight or obesity without type 1 or type 2 diabetes mellitus were enrolled. The participants received either Lira 3 mg or N/B 32/360 mg, along with diet and exercise, according to comorbidities, cost and method of administration. Participants underwent clinical and laboratory measurements at baseline, as well as at the 3- and 6-month time points. Anthropometric measurements and body composition analysis via bioelectrical impendence analysis were performed. Total blood samples for GDF-15 and H-specific GDF-15 were collected in the fasting state and every 30 min for 3 h after the consumption of a standardized mixed meal. RESULTS Overall, participants' weight was reduced by 9.29 ± 5.34 kg at Month 3 and 11.52 ± 7.52 kg at Month 6. Total and H-specific GDF-15 levels did not show significant changes during the mixed meal compared to values before the meal when all participants were examined at baseline, and at 3 and 6 month follow-ups. No statistical significance was found when participants were examined by subgroup (Lira vs. N/B). No significant differences between treatment groups in postprandial area under the curve (AUC) or incremental AUC values were found at baseline or in the follow-up months with regard to total and H-specific GDF-15 levels. CONCLUSION Neither total nor H-specific GDF-15 levels are affected by Lira or N/B treatment in patients with overweight or obesity.
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Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab for locally advanced esophageal squamous cell carcinoma (ESCC): A phase II clinical trial.
Wang, L, Liu, L, Cao, Y, Chen, X, Liu, S, Li, X, Han, J, Wang, Q, Han, C
BMC cancer. 2024;(1):679
Abstract
OBJECTIVE To evaluate the feasibility, safety and efficacy of concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab in the treatment of locally advanced esophageal squamous cell cancer (ESCC). METHODS Eligible patients were histologically proven to have locally advanced ESCC, and were unable to tolerate or refuse concurrent chemoradiotherapy (CCRT). Enrolled patients underwent concurrent SIB-IMRT in combination with nimotuzumab. SIB-IMRT: For the planning target volume of clinical target volume (PTV-C), the prescription dose was 50.4 Gy/28fractions, 1.8 Gy/fraction, 5fractions/week, concurrently, the planning target volume of gross tumor (PTV-G) undergone an integrated boost therapy, with a prescription dose of 63 Gy/28fractions, 2.25 Gy/fraction, 5 fractions/week. Nimotuzumab was administered concurrently with radiotherapy, 200 mg/time, on D1, 8, 15, 22, 29, and 36, with a total accumulation of 1200 mg through intravenous infusion. The primary endpoint of the study was the safety and efficacy of the combined treatment regimen, and the secondary endpoints were 1-year, 2-year, and 3-year local control and survival outcomes. RESULTS (1) From December 2018 to August 2021, 35 patients with stage II-IVA ESCC were enrolled and 34 patients completed the full course of radiotherapy and the intravenous infusion of full-dose nimotuzumab. The overall completion rate of the protocol was 97.1%. (2) No grade 4-5 adverse events occurred in the entire group. The most common treatment-related toxicity was acute radiation esophagitis, with a total incidence of 68.6% (24/35). The incidence of grade 2 and 3 acute esophagitis was 25.7% (9/35) and 17.1% (6/35), respectively. The incidence of acute radiation pneumonitis was 8.6% (3/35), including one case each of Grades 1, 2, and 3 pneumonitis. Adverse events in other systems included decreased blood cells, hypoalbuminemia, electrolyte disturbances, and skin rash. Among these patients, five experienced grade 3 electrolyte disturbances during the treatment period (three with grade 3 hyponatremia and two with grade 3 hypokalemia). (3) Efficacy: The overall CR rate was 22.8%, PR rate was 71.4%, ORR rate was 94.2%, and DCR rate was 97.1%.(4) Local control and survival: The 1-, 2-, and 3-year local control (LC) rate, progression-free survival(PFS) rate, and overall survival(OS) rate for the entire group were 85.5%, 75.4%, and 64.9%; 65.7%, 54.1%, and 49.6%; and 77.1%, 62.9%, and 54.5%, respectively. CONCLUSIONS The combination of SIB-IMRT and nimotuzumab for locally advanced esophageal cancer demonstrated good feasibility, safety and efficacy. It offered potential benefits in local control and survival. Acute radiation esophagitis was the primary treatment-related toxicity, which is clinically manageable. This comprehensive treatment approach is worthy of further clinical exploration (ChiCTR1900027936).
