Parallel-group Comparative Study Research Articles

The role of preoperative immunonutrition on morbidity and immune response after cystectomy: protocol of a multicenter randomized controlled trial (INCyst Trial)

IntroductionCancer, malnutrition, and surgery negatively impact patient’s immune system. Despite standardized surgical technique and the development of new perioperative care protocols, morbidity after cystectomy remains a serious challenge for urologists. Most common postoperative complications, such as infections and ileus, often lead to longer length of stay and worse survival. The immune system and its interaction with the gut microbiota play a pivotal role in cancer immunosurveillance and in patient’s response to surgical stress. Malnutrition has been identified as an independent and modifiable risk factor for both mortality and morbidity. Immunonutrition (IN) may improve the nutritional status, immunological function, and clinical outcome of surgical patients. Aims of the study are (1) to evaluate the impact of IN on morbidity and mortality at 30 and 90 days after cystectomy and (2) to determine immune and microbiota signature that would predict IN effect.MethodsThis is a randomized, multicentric, controlled, pragmatic, parallel-group comparative study, supported by the Swiss National Science Foundation. A total of 232 patients is planned to be enrolled between April 2023 and June 2026. Three participating centers (Lausanne, Bern, and Riviera-Chablais) have been selected. All patients undergoing elective radical and simple cystectomy will be randomly assigned to receive 7 days of preoperative IN (Oral Impact®, Nestlé, Switzerland) versus standard of care (control group) and followed for 90 days after surgery. For the exploratory outcomes, blood, serum, urine, and stool samples will be collected in patients treated at Lausanne. In order to determine the impact of IN on immune fitness, patients enrolled at Lausanne will be vaccinated against influenza and the establishment of the vaccine-specific immune response will be followed. Analysis of the microbiota and expression of argininosuccinate synthetase 1 as potential biomarker will also be performed.Discussion and conclusionStrengths of the INCyst study include the randomized, multicenter, prospective design, the large number of patients studied, and the translational investigation. This study will challenge the added value of preoperative IN in patients undergoing cystectomy, assessing the clinical effect of IN on the onset of postoperative morbidity and mortality after cystectomy. Furthermore, it will provide invaluable data on the host immune response and microbiota composition.Trial registrationClinicalTrials.gov NCT05726786. Registered on March 9, 2023.

Continuous Glucose Monitor Metrics That Predict Neonatal Adiposity in Early and Later Pregnancy Are Higher in Obesity Despite Macronutrient-Controlled Eucaloric Diets.

Fasting glucose is higher in pregnancies with obesity (OB); less is known about postprandial (PP) and nocturnal patterns when the diet is eucaloric and fixed or about the continuous-glucose-monitor (CGM) metrics that predict neonatal adiposity (NB%fat). We hypothesized that continuous glucose monitors (CGMs) would reveal higher glycemia in OB vs. normal weight (NW) during Early (14-16 weeks) and Later (26-28 weeks) gestation despite macronutrient-controlled eucaloric diets and elucidate unique predictors of NB%fat. In a prospective, parallel-group comparative study, a eucaloric diet (NW: 25 kcal/kg; OB: 30 kcal/kg) was provided (50% carbohydrate [20% simple/30% complex; of total calories], 35% fat, 15% protein) to Early and Later gestation groups wearing a blinded CGM for three days. CGM metrics (mean fasting; 1 h and 2 h PP; daytime and nocturnal glucose; percent time-in-range (%TIR: 63-140 mg/dL); PP excursions; and area-under-the-curve [AUC]) were interrogated between groups and as predictors of NB%fat by dual X-ray absorptiometry(DXA). Fifty-four women with NW (BMI: 23 kg/m2; n = 27) and OB (BMI: 32; n = 27) provided their informed consent to participate. Early, the daytime glucose was higher in OB vs. NW (mean ± SEM) (91 ± 2 vs. 85 ± 2 mg/dL, p = 0.017), driven by 2 h PP glucose (95 ± 2 vs. 88 ± 2, p = 0.004). Later, those with OB exhibited higher nocturnal (89 ± 2 vs. 81 ± 2), daytime (95 ± 2 vs. 87 ± 2), 1 h (109 ± 3 vs. 98 ± 2), and 2 h PP (101 ± 3 vs. 92 ± 2) glucose (all p < 0.05) but no difference in %TIR (95-99%). Postprandial peak excursions for all meals were markedly blunted in both the Early (9-19 mg/dL) and Later (15-26 mg/dL). In OB, the Later group's 24 h AUC was correlated with NB%fat (r = 0.534, p = 0.02). Despite similar weight gain, infants of OB had higher birthweight (3528 ± 107 vs. 3258 ± 74 g, p = 0.037); differences in NB%fat did not reach statistical significance (11.0 vs. 8.9%; p > 0.05). Despite macronutrient-controlled eucaloric diets, pregnancies with OB had higher glycemia Early and Later in gestation; the Later 24 h glucose AUC correlated with NB%fat. However, glycemic patterns were strikingly lower than current management targets.

Efficacy and safety of switching to bilastine, an H1-antihistamine, in patients with refractory chronic spontaneous urticaria (H1-SWITCH): a multicenter, open-label, randomized, parallel-group comparative study.

For treating patients with refractory chronic spontaneous urticaria (CSU) resistant to standard doses of 2nd generation H1-antihistamines (H1AH) the International and Japanese guidelines recommend increasing H1AH dose. The latter also recommends switching to a different H1AH. This study explored if the efficacy of the standard dose of bilastine 20 mg is non-inferior to that of double-dose of H1AH in patients with refractory CSU. This phase IV, multicenter, open-label, randomized, parallel-group trial evaluated the efficacy and safety of switching treatment to bilastine compared to treatment with a 2-fold dose of H1AH in patients with CSU refractory to standard dose H1AH. The primary endpoint was the mean total symptom score (TSS) at Day 5-7 after the start of administration. Treatment efficacy and safety were evaluated in 128 patients (bilastine, n=64; 2-fold dose of H1AH, n=64). The mean TSS at Day 5-7 after the start of administration was smaller than the non-inferiority margin of 0.8, demonstrating non-inferiority of the bilastine switching group to the double-dose H1AH group (0.17 (95% CI -0.32, 0.67)). No difference in Japanese version of Epworth Sleepiness Scale (JESS), DLQI, and urticaria activity score over 7 consecutive days (UAS7) was observed between the two groups. There were no serious adverse events in either group. H1AH-related adverse events occurred in 5 subjects (8 cases) and 2 subjects (3 cases) in the double-dose H1AH and bilastine groups, respectively. Switching treatment to bilastine demonstrated non-inferiority to a double-dose of H1AH in terms of efficacy in patients with CSU refractory to standard dose H1AH with a favorable safety profile. https://jrct.niph.go.jp/latest-detail/jRCTs051180105, identifier jRCTs051180105.

Effect of trabeculectomy with mitomycin C versus ologen implant in reducing intraocular pressure: A comparative study in patients with primary open-angle glaucoma

: To compare the efficacy of mitomycin C (MMC) and Ologen implant (OLO) as adjuvants in Trabeculectomy in patients with POAG in eastern India.: It was a hospital based prospective randomized parallel group comparative study from November 2019 to April 2021. Forty eyes of forty patients of POAG with inadequate intraocular pressure (IOP) control were enrolled and randomly divided them into two groups of twenty. Group A (MMC) patients underwent MMC trabeculectomy, while Group B (OLO) patients underwent OLO trabeculectomy. All the cases were followed up post-operatively for six months, and the recorded IOP of each visit was analyses using software R 4.0.3 and R-studio.: The preoperative IOP for the OLO group was 34.0 mmHg (IQR: 30.75 – 38.0), while for the MMC intervention group it was 36.50 mmHg (IQR: 31- 42). The difference in IOP between the two groups was insignificant (p= 0.24). On the first postoperative day, the IOP in the MMC group was 10.05 ± 3.65 mmHg and in the OLO group it was 10.35 ± 2.13 mmHg. Seven days after surgery, the mean IOP in MMC group was 9.45 ± 3.0 mmHg, while it was 11.50 ± 2.52 mmHg in the OLO group. One month after surgery, the mean IOP in the MMC group was 11.15 ± 4.25 mmHg, whereas it was 11.50±5.02 mmHg in OLO group. At 3 months postoperatively, the mean IOP in the MMC group was 12.25± 5.17 mmHg, while it was 12.70± 1.84 mmHg in the OLO group. Six months after surgery, the mean IOP in the MMC group was 10.50± 2.72 mmHg, whereas in the OLO group it was 13.35± 2.94 mmHg. In both the groups, there was significant reduction of IOP (p value &amp;#60; 0.05) observed in all postoperative visits.: In trabeculectomy surgery on POAG eyes, the MMC and OLO implants both successfully lower IOP. Between the two groups, there was no statistically significant difference in the success rate.

Long-term safety study of the highly absorbable curcumin formulation TS-P1 in healthy Japanese adults: a randomized, placebo-controlled, double-blind, parallel-group comparative study

Long-term safety study of the highly absorbable curcumin formulation TS-P1 in healthy Japanese adults: a randomized, placebo-controlled, double-blind, parallel-group comparative study

Effect of Intake of Bifidobacteria and Dietary Fiber on Resting Energy Expenditure: A Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Comparison Study.

Bifidobacterium animalis subsp. lactis GCL2505 in combination with inulin has been shown to have several health benefits, including an improvement in the intestinal microbiota and a reduction in human visceral fat. Previous studies have suggested that the visceral fat reduction of GCL2505 and inulin may be achieved by improving daily energy expenditure. This parallel, placebo-controlled, randomized, double-blind study was conducted to evaluate the effects of GCL2505 and inulin on resting energy expenditure (REE) in overweight or mildly obese Japanese adults (n = 44). Participants ingested 1 × 1010 colony forming units of GCL2505 and 5.0 g of inulin daily for 4 weeks. REE score at week 4 was set as the primary endpoint. At week 4, the REE score of the GCL2505 and inulin group was significantly higher than that of the placebo group, with a difference of 84.4 kcal/day. In addition, fecal bifidobacteria counts were significantly increased in the GCL2505 and inulin group. Our results indicated that the intake of GCL2505 and inulin improves energy balance, which is known to be a major factor of obesity, by modulating the microbiota in the gut. This is the first report to demonstrate the effects of probiotics and dietary fiber on REE in humans.

5'-UMP inhibited muscle atrophy due to detraining: a randomized, double-blinded, placebo-controlled, parallel-group comparative study.

A short period of disuse of 1-2 weeks due to factors such as illness or injury can lead to muscle atrophy, affecting both athletic performance and health. Recent research has shown that uridine 5'-monophosphate (5'-UMP) can counteract disuse-induced muscle atrophy by increasing PGC-1α expression and inhibiting atrogin-1 expression. However, the effect of 5'-UMP on disuse muscle atrophy in humans remains unknown. Therefore, the aimed of this study was to explore the effects of 5'-UMP supplementation during detraining on short-term disuse muscle atrophy in healthy men. Following a 6-week resistance training program on upper arm, healthy men were randomized to either a UMP group (n = 11) or a placebo group (n = 10), taking their respective supplements during the 2-week detraining period. Muscle thickness, an indicator of muscle hypertrophy and atrophy, was measured at 3 positions (MT50, MT60, and MT70) at baseline, 1 week, and 2 weeks after detraining. Both groups showed a significant decrease in muscle thickness at MT70. The relative decrease was greater in the placebo group (2.4 ± 2.8%) than in the UMP group (0.0 ± 2.0%), significantly (p = 0.034) at 1 week. However, no significant difference was observed at MT50 and MT60. After the hypertrophy, 5'-UMP may prevent muscle atrophy due to the detraining within the first week.

Effects of a medium cut-off dialyzer on inflammation and cardiac and vascular function in hemodialysis patients with heart failure.

Expanded hemodialysis (HDx) could provide clearance of larger middle-molecule uremic toxins. We compared the effect of hemodialysis with medium cut-off membranes and high-flux (HFHD) membranes regarding changes in inflammation and vascular and left ventricular function. This was a single-center, prospective, parallel-group comparative study. Patients were divided into two groups (HDx: 25 patients and HFHD: 26 patients). All measurements were performed at baseline and 12 weeks. Serum c-reactive protein, interkelukin-18, pentraxin-3, β-2 microglobulin, and brain natriuretic peptide were measured. We used pulse wave velocity and augmentation index to assess arterial stiffness and echocardiography to evaluate left and right ventricular function. We enrolled 51 patients. Although serum c-reactive protein, interkelukin-18, pentraxin 3, and β-2 microglobulin were significantly decreased in the HDx group (p = 0.02, p < 0.001, p = 0.002, and p = 0.02, respectively), there was no significant change in HFHD group at 12th week. Serum c-reactive protein and interkelukin-18were significantly lower in the HDx group compared to the HFHD group in the 12th week (p = 0.007 and p = 0.03, respectively). We observed a significant decrease in pulse wave velocity in the HDx group at the end of the study (p = 0.03). Although there was no significant change in pulse wave velocity in the HFHD group, pulse wave velocity was similar between the HDx and HFHD groups in the 12th week. We detected a significant decrease in the mean isovolumetric relaxation time in the HDx group (p = 0.006). However, there was no significant difference in isovolumetric relaxation time between the HDx and HFHD groups in the 12th week. HDx provides better clearance of middle molecular uremic toxins and inflammatory biomarkers, and it may be associated with better central hemodynamic parameters and diastolic functions.

Ingestion of β-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults in a double-blind randomized, placebo-controlled study.

The study evaluated how ingestion of nicotinamide mononucleotide (NMN) for 12weeks by older adults affected blood nicotinamide adenine dinucleotide (NAD +) levels and physical function, particularly walking function. Information concerning sleep, and stress was also collected as secondary endpoints. In this randomized, placebo-controlled, double-blind, parallel-group comparison study, 60 participants were randomly allocated into a placebo group or NMN group. Members of the NMN group consumed 250mg/day NMN for 12weeks. Motor function tests, blood NAD metabolite analysis, and questionnaires were conducted at the start of the study and 4 and 12weeks after intake. This trial was registered at umin.ac.jp/ctr as UMIN000047871 on June 22nd, 2022.At primary outcome, at both 4weeks and 12weeks, the NMN and placebo groups had no significant differences in a stepping test. At secondary outcomes, after 12weeks of NMN intake, the NMN group had a significantly shorter 4-m walking time than the placebo group as well as significantly higher blood levels of NAD + and its metabolites. A significant negative correlation was observed between the change in the 4-m walking time and the change in blood NAD + , N1-methyl-2-pridone-5-carboxamide (2-PY), and N1-methyl-4-pridone-3-carboxamide (4-PY) at 12weeks. The NMN group had improved sleep quality at 12weeks relative to the placebo group as evidenced by lower scores for "Daytime dysfunction" and "Global PSQI" on the Pittsburgh Sleep Questionnaire. No adverse effects related to test substance consumption were observed. Together, these results indicate that NMN intake could increase blood NAD + levels, maintain walking speed, and improve sleep quality in older adults. Interventions involving NMN aimed at maintaining walking speed could contribute to extended healthy life expectancy.

Effects of Oleanolic Acid Derived from Wine Pomace on Periodontopathic Bacterial Growth in Healthy Individuals: A Randomized Placebo-Controlled Study.

Periodontal disease is caused by oral pathogenic bacteria and is associated with systemic disease and frailty. Therefore, its prevention is crucial in extending healthy life expectancy. This study aimed to evaluate the effect of orally administered oleanolic acid, extracted from wine pomace, on periodontopathic bacterial growth in healthy individuals. In this randomized, placebo-controlled, double-blind, parallel-group comparison study, 84 healthy adults were assigned to a placebo (n = 29), low-dose (n = 29, 9 mg oleanolic acid), or high-dose (n = 26, 27 mg oleanolic acid) groups. The number of oral bacteria in their saliva, collected before and 5 h after administration, was determined using the polymerase chain reaction-invader technique. The proportion of periodontopathic bacteria among the total oral bacteria in the saliva was calculated. Oleanolic acid significantly decreased the proportion of Porphyromonas gingivalis among the total oral bacteria in a dose-dependent manner (p = 0.005 (low-dose) and p = 0.003 (high-dose) vs. placebo, Williams' test). Moreover, high-dose oleanolic acid decreased the proportion of Tannerella forsythia (p = 0.064 vs. placebo, Williams' test). Periodontopathic bacteria are closely associated with the development and progression of periodontal disease; thus, the continuous daily intake of oleanolic acid derived from pomace may be helpful in maintaining a healthy oral microbiome by controlling the proportion of periodontopathic bacteria.

Effects of γ-aminobutyric acid (GABA) intake in combination with exercise on muscle strength in humans with decreased mobility: a randomized, double-blind, placebo-controlled, parallel-group study

Background: Aging-related declines in skeletal muscle mass, muscle strength, and physical function are related to instability, falls, and frailty in older people, resulting in the need for nursing care. Objective: To investigate the effect of oral γ-aminobutyric acid (GABA) intake and exercise on muscle parameters in healthy subjects whose muscle strength is beginning to decline with age. Methods: A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted. Fifty subjects (over 40 years old) were randomly divided into the GABA (100 mg/day) or placebo food intake group. Subjects orally consumed the respective study substance every day for 12 weeks. They performed daily “locomotion training” as devised by the Japanese Orthopedic Society. Muscle mass, fat mass, and knee extension muscle strength were measured. Results: The two groups had no significant differences in muscle and fat mass. Compared with the placebo food group, the GABA group showed a significant improvement in knee extension muscle strength in the left and right legs at pre-dose Week 0 (at Week 6, p = 0.02). In post hoc subgroup analysis by sex, when compared with the placebo food intake group, the GABA food intake group showed significant improvement in knee extension muscle strength of the right leg at Weeks 6 (p = 0.001) and 12 (p = 0.007), the left leg at Week 6 (p = 0.02), the stronger of the left and right legs at pre-dose Week 0 (at Week 6, p = 0.001), and the weaker of the left and right legs at pre-dose Week 0 (at Week 12, p = 0.013) in males. Conclusions: These results suggest that GABA intake combined with daily exercise is effective for maintaining knee extension muscle strength, which decreases with age. Furthermore, there were no safety issues with the intake of GABA-containing food during this study. Trial registration: UMIN-CTR: UMIN000050152. Keywords: γ-Aminobutyric acid, GABA, Muscle mass, Knee extension muscle strength, Aging

The effects of cyclodextrin on plaque accumulation in healthy Japanese adults: A randomized, placebo-controlled, double-blind, parallel-group comparison study

Background: Cyclo-isomalto-oligosaccharides (CI) have been reported to inhibit glucosyltransferases (GTF) in vitro. GTF is an enzyme related to oral plaque synthesis. However, there are few clinical studies to investigate the effect of CI on oral plaque via inhibiting GTF activity. Objective: The purpose of this study was to evaluate the inhibitory effect of consuming CI-Dextran mix on plaque accumulation in healthy Japanese adults. Methods: This randomized, placebo-controlled, double-blind, parallel-group comparison study was conducted from May 26, 2022, to September 16, 2022. Individuals who agreed to participate in the study were randomly assigned to the CI-Dextran mix group with 60 mg/day (n = 22), the CI-Dextran mix group with 600 mg/day (n = 11), or the placebo group (n = 22). The intervention period was three days, and the outcome of this study was the plaque index (PlI), an indicator of plaque accumulation. Results: Our results showed that the CI-Dextran mix group (600mg/day) had significantly lower post-intervention PlI values than the placebo group in a full analysis set (FAS). In individuals identified as prone to plaque accumulation among the FAS, both CI-Dextran mix groups showed significantly lower PlI values than the placebo group. No adverse events were observed during the study period, and consumption of the test food under the study conditions was considered safe. Conclusions: Our results clearly indicated that a high dose of CI-Dextran mix (600 mg/day) could significantly reduce plaque formation in healthy Japanese adults, while a marginal reduction was noted for the group taking a low dose (60 mg/day). In particular, intake of both doses (CI-Dextran mix 60 mg/day and 600 mg/day) in individuals who were prone to plaque accumulation, could significantly inhibit plaque formation. Keywords: CI-Dextran mix, cyclodextran, plaque inhibition, functional carbohydrates, isomaltooligosaccharide, Randomized Controlled Trial Trial registration: UMIN000047901. Foundation: Nissin Sugar Co., Ltd.

The effects of cyclodextrin on plaque accumulation in healthy Japanese adults: A randomized, placebo-controlled, double-blind, parallel-group comparison study

Background: Cyclo-isomalto-oligosaccharides (CI) have been reported to inhibit glucosyltransferases (GTF) in vitro. GTF is an enzyme related to oral plaque synthesis. However, there are few clinical studies to investigate the effect of CI on oral plaque via inhibiting GTF activity. Objective: The purpose of this study was to evaluate the inhibitory effect of consuming CI-Dextran mix on plaque accumulation in healthy Japanese adults. Methods: This randomized, placebo-controlled, double-blind, parallel-group comparison study was conducted from May 26, 2022, to September 16, 2022. Individuals who agreed to participate in the study were randomly assigned to the CI-Dextran mix group with 60 mg/day (n = 22), the CI-Dextran mix group with 600 mg/day (n = 11), or the placebo group (n = 22). The intervention period was three days, and the outcome of this study was the plaque index (PlI), an indicator of plaque accumulation. Results: Our results showed that the CI-Dextran mix group (600mg/day) had significantly lower post-intervention PlI values than the placebo group in a full analysis set (FAS). In individuals identified as prone to plaque accumulation among the FAS, both CI-Dextran mix groups showed significantly lower PlI values than the placebo group. No adverse events were observed during the study period, and consumption of the test food under the study conditions was considered safe. Conclusions: Our results clearly indicated that a high dose of CI-Dextran mix (600 mg/day) could significantly reduce plaque formation in healthy Japanese adults, while a marginal reduction was noted for the group taking a low dose (60 mg/day). In particular, intake of both doses (CI-Dextran mix 60 mg/day and 600 mg/day) in individuals who were prone to plaque accumulation, could significantly inhibit plaque formation. Keywords: CI-Dextran mix, cyclodextran, plaque inhibition, functional carbohydrates, isomaltooligosaccharide, Randomized Controlled Trial Trial registration: UMIN000047901. Foundation: Nissin Sugar Co., Ltd.

Skin Anti-Aging Efficacy of a Lactobacillus plantarum GT-17F Fermented Dendrobium officinale Ingredient: A Randomized, Double-Blind, Placebo-Controlled Clinical Study

We previously found that fermented extract of Dendrobium officinale using Lactobacillus plantarum GT-17F has a stronger antioxidant effect, especially in free radical scavenging. The result provided a basis for further studies to evaluate the effectiveness of fermented D. officinale in preventing UV-mediated damage and photoaging in humans. Therefore, in this study, we aimed to assess the anti-aging efficacy of D. officinale fermented with GT-17F strain in a clinical trial, which was conducted as a double-blind, placebo-controlled, randomized parallel-group comparative study with 99 volunteers with visible wrinkles. During the study, subjects were instructed to apply one pump of each essence, which contains fermented, unfermented, or no D. officinale extract, evenly to their face, both in the morning and evening, following their cleansing routine. At 28 days post-treatment, compared to baseline, subjects in the fermented extract group demonstrated significant improvements in stratum corneum water content, skin elasticity, skin glossiness, wrinkle area and ratio, erythema area, and erythema area ratio. In contrast, the unfermented extract group showed a significant difference only in improving erythema index levels in the skin. This comprehensive study has rigorously investigated the anti-aging effects of D. officinale and its fermented version on human skin, highlighting a notable contribution to dermatological research.

Effects of Daily Consumption of Scallop Oil Prepared from Internal Organs of Japanese Giant Scallop (Patinopecten yessoensis) on Serum Lipid Composition and Its Safety: A Randomized, Double-blind, Placebo-controlled, Parallel Group Comparison Study.

Scallop oil (SCO) prepared from the internal organs of the Japanese giant scallop (Patinopecten yessoensis) contains eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and phospholipids (PL). It was previously shown that SCO consumption improves cholesterol and triacylglycerols (TG) contents in mice. The present study demonstrated the effects of daily SCO consumption (1.2 g/day, containing 376 mg of EPA, 63 mg of DHA, and 150 mg of PL) for 12 weeks in human subjects. In this randomized, doubleblind, placebo-controlled, parallel group comparison study, 70 Japanese subjects with serum TG levels ≥120 but < 200 mg/dL were recruited and randomly assigned to the SCO or placebo group. All subjects ingested six capsules per day for 12 weeks. We conducted medical interviews, body composition measurements, vital sign examinations, and blood sampling at weeks 0 (baseline), 4, 8, and 12, and measured peripheral blood flow at weeks 0 and 12. In the case of subjects with higher serum TG levels, SCO consumption decreased the changes in serum TG and malondialdehyde-low density lipoprotein (MDA-LDL) levels compared with the placebo group. Safety assessment revealed no medically significant changes due to continuous SCO consumption. The findings indicate that 1.2 g/day of SCO consumption may be beneficial for reducing serum TG and MDA-LDL levels in persons with higher TG levels.

The Effects of Adlay Tea Intake on Immune Homeostasis and Vascular Endothelial Function in Healthy Adults: A Randomized, Double-Blind, Parallel-Group Comparative Study.

Excessive immune response and inflammation are associated with an increased risk of various diseases. In particular, excessive myeloperoxidase (MPO) activity in neutrophils causes inflammatory reactions and lifestyle-related diseases. Adlay has a long history of being used as a traditional Chinese medicine. Polyphenols present in adlay seeds are expected to have the effect of suppressing excessive immune and inflammatory responses. Here, we conducted a randomized, double-blind, parallel group, placebo-controlled study was conducted to evaluate the suppressing effects of adlay seeds extract on excessive immune responses. One hundred and twenty adults participated in the study and they were equally divided into an adlay tea intake group and a placebo group. MPO activity was significantly elevated in the placebo group after 8-wk ingestion, while no significant change was observed in the adlay group. Vascular endothelial functions improved in the adlay group, especially in subjects over 40 y old. These results indicate that adlay tea intake may suppress an excessive immune and inflammatory responses, and improve arterial stiffness. Since caffeic acid, p-coumaric acid, and ferulic acid detected in adlay tea are known to inhibit MPO activity, these polyphenols may be the major functional molecules. Collectively, adlay tea is considered to have a preventative effect against lifestyle-related diseases through improving vascular endothelial function by effects to maintain immune homeostasis of the contained polyphenols. This trial was registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000032263).

Zinc alleviates high fat diet-induced spermatogenic dysfunction in Wistar rats: role of oxidative stress, HMGB1 and inflammasome.

Whether chronic inflammation in the genital tract induced by obesity shares in spermatogenic dysfunction is not clearly known. We aimed to study the effect of high fat diet (HFD) on spermatogenesis, seminal oxidative stress (malondialdehyde (MDA)) and inflammatory markers (high mobility group box 1 (HMGB1), nucleotide-binding oligomerization domain, leucine rich repeat and pyrin-3 domain containing (NLRP3)) in the rat testes and the role of zinc on testicular dysfunction and chronic inflammation in high fat diet (HFD) fed rat testes. This parallel group comparative experimental study included 36 male wistar rats divided into 3 groups: group A (fed on normal control diet); group B (fed on high fat diet (HFD) only); and group C (fed on HFD with zinc supplementation 3.2 mg/kg/day orally). At the end of the 12th week, sperm count, viability and motility were assessed by computer-assisted seemen analysis (CASA), seminal malondialdehyde measured by calorimetry and histopathological examination of testicular sections was done. Immunohistochemical staining was done for HMGB1 and NLRP3 evaluation. Sperm count was lowest in group B. Groups A and C showed statistically significant higher mean sperm vitality, total and progressive motility scores (p < 0.001), while no difference was found between the groups A and C (p > 0.05). Seminal malondialdehyde level was significantly highest in group B. Tubular diameter, epithelial height and Johnsen score were significantly lowest in group B. Significantly higher HMGB1 and NLRP3 levels were demonstrated in group B (p < 0.001). Obesity is associated with testicular dysfunction, testicular oxidative stress and increased testicular HMGB1 and NLRP3. We suggest a beneficial effect of zinc on testicular function in HFD-rats.

Silk-derived sericin/fibroin mixture drink fermented with plant-derived Lactococcus lactis BM32-1 improves constipation and related microbiota: a randomized, double-blind, and placebo-controlled clinical trial.

We previously showed through clinical trials that one plant-derived lactic acid bacteria (LAB) can improve constipation. We preliminarily found that the plant-derived LAB Lactococcus lactis BM32-1 can grow in a mixture of sericin and fibroin, which are extracted from silk and have been reported to help promote health. Thus, in the present study, we evaluated the favorable effect of a sericin/fibroin mixture (S/F-M), which was extracted from silk prepared from cocoons reared in an aseptic rearing system using an artificial diet, fermented with the BM32-1 strain through a clinical trial. The trial was conducted at Hiroshima University from June to October 2022 as a double-blind, placebo-controlled, randomized parallel-group comparative study with 50 eligible subjects (aged 23-71) who had an average defecation frequency of less than 5 times per week. The subjects were instructed to drink 100 mL of fermented S/F-M or placebo every day. After the 12 weeks of the clinical trial period, the average defecation frequency increased significantly-1.4 times higher than that at baseline in the test group-as compared with the placebo group. Furthermore, the fecal microbiota was also compared before and after treatment, revealing that intake of the fermented S/F-M significantly multiplied the relative abundance of the genera Enterococcus and Clostridium, which have been reported to contribute to the amelioration of constipation by improving the gut microbiota and producing butyric acid, respectively. In conclusion, the S/F-M fermented using the BM32-1 strain improves defecation frequency through alteration of the gut microbiota.

Safety evaluation of high bioavailability curcumin in Healthy Japanese Adults: A Randomized, placebo-controlled, double-blind, parallel-group comparison study

Background: Curcumin is the principal component responsible for the pharmacological action of Curcuma longa. It has been proven to exhibit a diverse range of functions. It has been used in many fields as a spice, coloring agent, cosmetic, and food preservative.Objective: To evaluate the safety of the intake of highly bioavailable curcumin (CR-033P and TS-P1) in humans. Methods: We conducted two trials. The participants were healthy Japanese adults. Participants of tria1 1 (Long-term intake trial) took CR-033P or TS-P1 for 12 weeks (as curcumin 150 mg/day). Participants of Trial 2 (Excessive intake trial) took TS-P1 for 4 weeks (as curcumin 750 mg/day). The safety assessment involved monitoring the occurrence of side effects or adverse events, along with the analysis of urinalysis and blood parameters.Results: The safety analysis population of Trial 1 included 33 participants in the CR-033P group, 32 participants TS-P1, and 30 participants in the Placebo group. The safety analysis population of trial 2 included 22 participants in TS-P1 and 20 participants in the Placebo group. In both Trial 1 and Trial 2, few participants were observed to experience adverse events and however these were not adverse events related to the CR-033P or TS-P1. Results of urinalysis and blood analysis were confirmed to not exhibit medically problematic changes related to the CR-033P or TS-P1.Conclusions: These trials proved the safety of the long-term intake of CR-033P or TS-PI- (as curcumin 150mg/ day) and the safety of the excessive intake of TS- P1 for four weeks (as curcumin 750mg/ day). TS-P1 and CR-033P can be considered a safe curcumin supplement based on these results. Keywords: Curcumin, bioavailability, safety, high dose, long term dose, Healthy Japanese Adults, BMI, Blood pressure Trial registration: Trial 1: UMIN000046160, Trial 2: UMIN000048797. Foundation:Theravalues Corporation

Is intravenous valproate more efficacious than oral valproate for inpatients with bipolar I disorder with a manic or depressive episode and concomitant symptoms of opposite polarity?

Valproic acid (VPA) is a commonly prescribed mood stabilizer, available in both oral (OS) and intravenous (IV) formulations. However, few studies have compared their safety and efficacy. This retrospective study aimed to investigate the safety and efficacy of and IV-VPA in patients with Bipolar Disorder. Fifty patients with Bipolar Disorder experiencing a manic or depressive episode, with concomitant symptoms of opposite polarity, admitted to our inpatient unit and treated with IV-VPA were included in a retrospective, single-centre, non-randomized, open-label, parallel-group comparative study. Fifty patients experiencing a manic or depressive episode, with concomitant symptoms of opposite polarity, treated with oral-VPA and selected among those who were admitted to the inpatient unit prior to the introduction of IV-VPA in our clinical practice, were included as the control group (matched based on age, gender and clinical scales score at baseline). The Clinical Global Impression (CGI), Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A) scores were recorded at baseline, after 3 days of treatment and discharge from the inpatient unit. Patients were asked to respond on the basis of the symptoms present on the day the scale was administered. Response rate and the presence of adverse effects were also recorded. Both patients treated with oral and IV-VPA demonstrated significant improvements in all psychometric scales (p < 0.001). However, the IV group exhibited superior efficacy, with significantly lower scores on the CGI, YMRS, MADRS and HAM-A scales on Day 3 and at discharge from the inpatient unit. The IV-VPA treatment showed higher response rates on all psychometric scales, and no adverse effects were reported in either group. This retrospective study supports the use of IV-VPA as a more efficacious treatment option for patients with Bipolar Disorder, particularly in acute settings where rapid symptom improvement is crucial. Both oral and IV-VPA were found to be safe and well-tolerated.