Anti-obesity effect of Neoagaro-oligosaccharides with overweight and obese subjects: a 16-week, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: This trial aimed to evaluate the anti-obesity effects and safety of Neoagaro-oligosaccharides (NAOs) in humans in a 16 week, randomized, double-blind, placebo-controlled clinical trial. METHODS: One hundred overweight or obese subjects with a body mass index of 23 to 34.9 kg/m2 and a percent body fat of > 25% for males or > 30% for females were enrolled. NAOs or placebo products were administered at 3 g (twice a day, four capsules once) each for 16 weeks. Efficacy and safety biomarkers were measured before and after intervention. RESULTS: After 16 weeks of intervention, the group administered with NAOs had statistically significant decreases in visceral fat area and visceral-subcutaneous fat area ratio compared to the placebo group. The NAOs group suppressed the increase in weight and BMI compared to the placebo group, which was significant between groups. High-density lipoprotein- cholesterol was increased in the group administered with NAOs, which showed a significant trend compared to the placebo group. Clinical changes were not observed for any safety biomarkers. CONCLUSIONS: These results suggest that NAOs have a beneficial effect on obesity. Thus, NAOs could be used as an anti-obesity supplement without side effects. TRIAL REGISTRATION: cris.nih.go.kr: (KCT0006640, 07/10/2021).

Supplementary Effects of Allium hookeri Extract on Glucose Tolerance in Prediabetic Subjects and C57BL/KsJ-db/db Mice.

Allium hookeri (AH) has been used as a nutritional and medicinal food in Asia for many years. Our previous studies have described its anti-diabetic, anti-obesity, and anti-inflammatory activities in animal models and prediabetes. This study investigated whether AH could improve glycemia by modulating insulin secretion in prediabetic subjects through an in-depth study. Eighty prediabetic subjects (100 ≤ fasting plasma glucose < 140 mg/dL) were randomly assigned to a placebo (n = 40) group or an ethanol AH extract (500 mg/day, n = 40) group for 12 weeks. Dietary intake and physical activity, blood glucose (an oral glucose tolerance test for 120 min), insulin (insulin response to oral glucose for 120 min), area under the curve (AUC) of glucose or insulin after oral glucose intake, insulin sensitivity markers, C-peptide, adiponectin, glycated hemoglobin A1c (HbA1c) levels, hematological tests (WBC, RBC, hemoglobin, hematocrit, and platelet count), blood biochemical parameters (ALP, AST, total bilirubin, total protein, albumin, gamma-GT, BUN, creatinine, LD, CK, and hs-CRP), and urine parameters (specific gravity and pH) were examined at both baseline and 12 weeks after supplementation with placebo or AH capsules. Fifty-eight participants (placebo group: 20 men and 10 women; AH group: 13 men and 15 women) completed the study. AH supplementation moderately reduced postprandial blood glucose at 60 min (-6.14 mg/dL, p = 0.061), postprandial insulin levels at 90 min (-16.69 µU/mL, p = 0.017), the glucose AUC at 90 min (-412.52 mg*min/dL, p = 0.021), as well as the insulin AUC at 90 min (-978.77 µU*min/mL, p = 0.021) and 120 min (-1426.41 µU*min/mL, p = 0.015) when compared with the placebo group. However, there were no effects of AH on dietary intake and physical activity; HOMA index; HbAlc; C-peptide; or adiponectin, hematological-, blood biochemical-, and urinary markers. To confirm the effects of AH extract on blood glucose insulin sensitivity, C57BL/6J or C57BL/KsJ-db/db mice were used (n = 8/group). Body weight, fasting plasma glucose level, lipid profiles, liver and renal function, pancreatic histology, and insulin immunoreactivity were assessed. In the diabetic db/db mice, hyperglycemia, which was accompanied by an increase in insulin secretion in diabetic mice, was significantly reduced by AH treatment, resulting in the alleviation of ß-cell overcompensation and insulin resistance. We confirmed that AH supplementation can effectively control blood glucose and insulin levels by improving insulin sensitivity and may be a potential agent for glycemic control in subjects with prediabetes and type 2 diabetes mellitus.

Use of combined treatment of 3rd-generation cephalosporin, azithromycin and antiviral agents on moderate SARs-CoV-2 patients in South Korea: A retrospective cohort study.

OBJECTIVES: To assess efficacy and safety of the combined treatment of antibiotics (3rd-generation cephalosporin and azithromycin) and antiviral agents (lopinavir/ritonavir or hydroxychloroquine) on moderate COVID-19 patients in South Korea. METHODS: A retrospective cohort study of the 358 laboratory-confirmed SARS-CoV-2 (COVID-19) patients was conducted. 299 patients met inclusion criteria for analysis. Propensity score matching (PSM) and Cox regression method were used to control and adjust for confounding factors. Mild to moderate COVID-19 patients were managed with either CA/LoP (cephalosporin, azithromycin, and lopinavir/ritonavir) (n = 57), CA/HQ (cephalosporin, azithromycin, and hydroxychloroquine) (n = 25) or standard supportive care (n = 217). We analyzed the association between treatment group and standard supportive group in terms of three endpoints: time to symptom resolution, time to viral clearance, and hospital stay duration. Using propensity-score matching analysis, three rounds of propensity-matching analysis were performed to balance baseline characteristics among three cohorts. RESULTS: Kaplan-Meier curves fitted using propensity score-matched data revealed no significant differences on time to symptom resolution, time to viral clearance, hospital stay duration among the three treatment arms (CA/LoP vs Standard, log-rank p-value = 0.2, 0.58, and 0.74 respectively for the three endpoints) (CA/HQ vs Standard, log-rank p-value = 0.46, 0.99, and 0.75 respectively). Similarly, Cox regression analysis on matched cohorts of CA/LoP and standard supportive group showed that hazard ratios of time to symptom resolution (HR: 1.447 [95%-CI: 0.813-2.577]), time to viral clearance(HR: 0.861, [95%-CI: 0.485-1.527]), and hospital stay duration (HR: 0.902, [95%-CI: 0.510-1.595]) were not significant. For CA/HQ and standard supportive group, hazard ratios of the three endpoints all showed no statistical significance (HR: 1.331 [95%-CI:0.631-2.809], 1.005 [95%-CI:0.480-2.105], and 0.887, [95%-CI:0.422-1.862] respectively). No severe adverse event or death was observed in all groups. CONCLUSIONS: Combined treatment of 3rd cephalosporin, azithromycin and either low-dose lopinavir/ritonavir or hydroxychloroquine was not associated with better clinical outcomes in terms of time to symptom resolution, time to viral clearance, and hospital stay duration compared to standard supportive treatment alone. Microbiological evidence should be closely monitored when treating SARS-CoV-2 patients with antibiotics to prevent indiscreet administration of empirical antimicrobial treatments.

Efficacy and Safety of Sesame Oil Cake Extract on Memory Function Improvement: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Pilot Study.

The goal of treatment for mild cognitive impairment (MCI) is to reduce the existing clinical symptoms, delay the progression of cognitive impairment and prevent the progression to Alzheimer's disease (AD). At present, there is no effective drug therapy for AD treatment. However, early intake of dietary supplements may be effective in alleviating and delaying the MCI. This study aims to evaluate the effects of sesame oil cake extract (SOCE) supplementation on cognitive function in aged 60 years or older adults with memory impairment. A total of 70 subjects received either SOCE (n = 35) or placebo (n = 35) for 12 weeks based on random 1:1 assignment to these two groups. Cognitive function was evaluated by a computerized neurocognitive function test (CNT), and changes in the concentrations of plasma amyloid ß (Aß) proteins and urine 8-OHdG (8-hydroxy-2'-deoxyguanosine) were investigated before and after the experiment. Verbal learning test index items of the CNT improved markedly in the SOCE group compared to the placebo group (p < 0.05). Furthermore, plasma amyloid-ß (1-40) and amyloid-ß (1-42) levels in the SOCE group decreased significantly compared to that in the placebo group (p < 0.05). There was no statistically significant difference in urine 8-OHdG between the two groups (p > 0.05). Collectively, intake of SOCE for 12 weeks appears to have a beneficial effect on the verbal memory abilities and plasma ß-amyloid levels of older adults with memory impairment.

Anti-growth and pro-apoptotic effects of dasatinib on human oral cancer cells through multi-targeted mechanisms.

Dasatinib is an inhibitor of Src that has anti-tumour effects on many haematological and solid cancers. However, the anti-tumour effects of dasatinib on human oral cancers remain unclear. In this study, we investigated the effects of dasatinib on different types of human oral cancer cells: the non-tumorigenic YD-8 and YD-38 and the tumorigenic YD-10B and HSC-3 cells. Strikingly, dasatinib at 10 µM strongly suppressed the growth and induced apoptosis of YD-38 cells and inhibited the phosphorylation of Src, EGFR, STAT-3, STAT-5, PKB and ERK-1/2. In contrast, knockdown of Src blocked the phosphorylation of EGFR, STAT-5, PKB and ERK-1/2, but not STAT-3, in YD-38 cells. Dasatinib induced activation of the intrinsic caspase pathway, which was inhibited by z-VAD-fmk, a pan-caspase inhibitor. Dasatinib also decreased Mcl-1 expression and S6 phosphorylation while increased GRP78 expression and eIF-2α phosphorylation in YD-38 cells. In addition, to its direct effects on YD-38 cells, dasatinib also exhibited anti-angiogenic properties. Dasatinib-treated YD-38 or HUVEC showed reduced HIF-1α expression and stability. Dasatinib alone or conditioned media from dasatinib-treated YD-38 cells inhibited HUVEC tube formation on Matrigel without affecting HUVEC viability. Importantly, dasatinib's anti-growth, anti-angiogenic and pro-apoptotic effects were additionally seen in tumorigenic HSC-3 cells. Together, these results demonstrate that dasatinib has strong anti-growth, anti-angiogenic and pro-apoptotic effects on human oral cancer cells, which are mediated through the regulation of multiple targets, including Src, EGFR, STAT-3, STAT-5, PKB, ERK-1/2, S6, eIF-2α, GRP78, caspase-9/3, Mcl-1 and HIF-1α.

Effectiveness and Safety of Hwangchil-Unripe Bokbunja Extract Mixture on Blood Pressure: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

From 25% to 50% of adults are affected by prehypertension. Prehypertension increases the risk of hypertension and affects the heart and systemic vascular system. Food mixed tree essence of Dendropanax morbifera called Hwangchil in Korean and immature fruit of Rubus coreanus, called Bokbunja (HDR-2), have been studied for safety and effectiveness against prehypertension studies. This study was a randomized double-blind placebo-controlled multicenter clinical trial lasting 19 months from October 2017 to May 2019. The 88 subjects who enrolled in the study were divided into two groups. The treatment group was provided HDR-2 and the other group took a placebo. Both HDR-2 and placebo were in the form of capsules, and the dose was 900 mg per day. Subjects took HDR-2 or placebo capsules once a day for 8 weeks before dinner. The primary observational indicators were systolic blood pressure (SBP) and diastolic blood pressure (DBP), and the secondary observational indicators were mean arterial pressure (MAP), mean pulse pressure, pulse rate, angiotensin-converting enzyme activity, renin activity, aldosterone, and highly sensitive-C reactive protein. The number of measurements was three times: the first visit in the screening week, the second visit in 4 weeks, and the third visit was after 8 weeks. Significant study results showed that the SBP and MAP of the HDR-2 group after 8 weeks were lower than those of the placebo group. Adverse events were not significantly different between the two groups. In conclusion, these results suggest that HDR-2 may be a useful intervention for the management of prehypertension. The protocol was registered in the Korean Clinical Trial Registration system (http://cris.nih.go.kr; registration number: KCT0004300).

Patterns of viral clearance in the natural course of asymptomatic COVID-19: Comparison with symptomatic non-severe COVID-19.

OBJECTIVES: The aim of this study was to elucidate patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in the natural course of asymptomatic coronavirus disease 2019 (COVID-19). METHODS: Consecutive patients with non-severe COVID-19 were included retrospectively. Asymptomatic patients with a normal body temperature and no evidence of pneumonia throughout the disease course were assigned to the asymptomatic group. The reverse transcription PCR (RT-PCR) assay was repeated every two to five days after the first follow-up RT-PCR assay. Negative conversion was defined as two consecutive negative RT-PCR assay results within a 24-h interval. Rebound of the cycle threshold (Ct) value was defined as negative from the single RT-PCR assay and positive from the following assay. RESULTS: Among a total of 396 patients identified (median age 42.5 years (interquartile range (IQR) 25.0-55.0 years), 35.6% male), 68 (17.2%) were assigned to the asymptomatic group and 328 (82.8%) to the symptomatic group. The time until negative conversion was significantly shorter in the asymptomatic group than in the symptomatic group: median 14.5 days (IQR 11.0-21.0 days) and 18.0 days (IQR 15.0-22.0 days), respectively (p = 0.001). Rebound of Ct values was observed in 78 patients (19.7%). CONCLUSIONS: Time until negative conversion is shorter in asymptomatic COVID-19 than in symptomatic COVID-19. Rebound of Ct values is not uncommon.

Risk factors for disease progression in COVID-19 patients.

BACKGROUND: Coronavirus disease (COVID-19) is rapidly spreading worldwide. Although 10-20% of patients with COVID-19 have severe symptoms, little is known about the risk factors related to the aggravation of COVID-19 symptoms from asymptomatic or mild to severe disease states. METHODS: This retrospective study included 211 patients who were asymptomatic or with mild presentations of COVID-19. We evaluated the differences in demographic and clinical data between the cured (discharged to home) and transferred (aggravated to severe-stage COVID-19) groups. RESULTS: A multivariate logistic analysis showed that body temperature, chills, initial chest X-ray findings, and the presence of diabetes were significantly associated with predicting the progression to severe stage of COVID-19 (p < 0.05). The odds ratio of transfer in patients with COVID-19 increased by 12.7-fold for abnormal findings such as haziness or consolidation in initial chest X-ray, 6.32-fold for initial symptom of chills, and 64.1-fold for diabetes. CONCLUSIONS: Even if patients are asymptomatic or have mild symptoms, clinicians should closely observe patients with COVID-19 presenting with chills, body temperature > 37.5 °C, findings of pneumonia in chest X-ray, or diabetes.

The effects of steamed ginger ethanolic extract on weight and body fat loss: a randomized, double-blind, placebo-controlled clinical trial.

Steamed ginger ethanolic extract (SGE) is a product with a high 6-shogaol contents and is thought to be more potent than other ginger products. We conducted a 12-week, randomized, double-blind, placebo-controlled clinical trial to determine the effects of SGE on weight and body fat loss. Eighty healthy obese participants were recruited and randomly divided into the SGE and placebo groups. The outcome measures comprised indicators of efficacy (body weight, body mass index, body composition, and blood markers) and safety. Following the supplementation period, mean body weight, body mass index, and body fat level were significantly lower in the SGE group than in the placebo group. No clinically significant changes were observed for any safety parameter. These results suggest that SGE is a potent anti-obesity agent that does not cause significant side effects. Therefore, SGE supplementation combined with lifestyle modification could be effective in the management of body weight and fat mass.

[Reliability and Validity of the Korean Version of the Perinatal Post-Traumatic Stress Disorder Questionnaire].

PURPOSE: The Perinatal Post-Traumatic Stress Disorder Questionnaire (PPQ) was designed to measure post-traumatic symptoms related to childbirth and symptoms during postnatal period. The purpose of this study was to develop a translated Korean version of the PPQ and to evaluate reliability and validity of the Korean PPQ. METHODS: Participants were 196 mothers at one to 18 months after giving childbirth and data were collected through e-mails. The PPQ was translated into Korean using translation guideline from World Health Organization. For this study Cronbach's alpha and split-half reliability were used to evaluate the reliability of the PPQ. Exploratory Factor Analysis (EFA), Confirmatory Factor Analysis (CFA), and known-group validity were conducted to examine construct validity. Correlations of the PPQ with Impact of Event Scale (IES), Beck Depression Inventory II (BDI-II), and Beck Anxiety Inventory (BAI) were used to test a criterion validity of the PPQ. RESULTS: Cronbach's alpha and Spearman-Brown split-half correlation coefficient were 0.91 and 0.77, respectively. EFA identified a 3-factor solution including arousal, avoidance, and intrusion factors and CFA revealed the strongest support for the 3-factor model. The correlations of the PPQ with IES, BDI-II, and BAI were .99, .60, and .72, respectively, pointing to criterion validity of a high level. CONCLUSION: The Korean version PPQ is a useful tool for screening and assessing mothers' experiencing emotional distress related to child birth and during the postnatal period. The PPQ also reflects Post Traumatic Stress Disorder's diagnostic standards well.

Factors associated with development of complications after endoscopic foreign body removal.

BACKGROUND/AIMS: We analyzed the clinical characteristics of patients who underwent endoscopic foreign body removal and the risk factors of complications. PATIENTS AND METHODS: The medical records of 415 patients treated from January 2000 to August 2011 for suspected foreign bodies were retrospectively reviewed. Patient characteristics, endoscopic findings, clinical outcomes, and risk factors of complications were analyzed. RESULTS: Foreign bodies were detected endoscopically in 315 patients. Fish bone fragment (36.9%) and coins (15.3%) were the most common type of foreign bodies in adults and children, respectively. Complications associated with endoscopic procedure occurred in 26 patients (8.3%); 20 of the patients were treated conservatively and the other six patients underwent surgical treatment. Perforation (14%) was the most common complication. By univariate and multivariate analysis, the risk factors associated with complication after endoscopic foreign body removal were long duration from ingestion to endoscopy ( P = 0.009) and existence of initial mucosal injury ( P = 0.018). CONCLUSIONS: Most foreign bodies were successfully removed by endoscopy without complication, but long duration from ingestion to endoscopy and mucosal injury were risk factors of complications of endoscopic foreign body removal. Patients with these risk factors could require more careful treatment.

Dietary effect of lactoferrin-enriched fermented milk on skin surface lipid and clinical improvement of acne vulgaris.

OBJECTIVE: Lactoferrin, a whey milk protein after removing precipitated casein, has a prominent activity against inflammation in vitro and systemic effects on various inflammatory diseases have been suggested. The objective was to determine dietary effects of lactoferrin-enriched fermented milk on patients with acne vulgaris, an inflammatory skin condition. METHODS: Patients 18 to 30 y of age were randomly assigned to ingest fermented milk with 200 mg of lactoferrin daily (n = 18, lactoferrin group) or fermented milk only (n = 18, placebo group) in a 12-wk, double-blind, placebo-controlled study. Acne lesion counts and grade were assessed at monthly visits. The condition of the skin by hydration, sebum and pH, and skin surface lipids was assessed at baseline and 12 wk. RESULTS: Acne showed improvement in the lactoferrin group by significant decreases in inflammatory lesion count by 38.6%, total lesion count by 23.1%, and acne grade by 20.3% compared with the placebo group at 12 wk. Furthermore, sebum content in the lactoferrin group was decreased by 31.1% compared with the placebo group. The amount of total skin surface lipids decreased in both groups. However, of the major lipids, amounts of triacylglycerols and free fatty acids decreased in the lactoferrin group, whereas the amount of free fatty acids decreased only in the placebo group. The decreased amount of triacylglycerols in the lactoferrin group was significantly correlated with decreases in serum content, acne lesion counts, and acne grade. No alterations in skin hydration or pH were noted in either group. CONCLUSION: Lactoferrin-enriched fermented milk ameliorates acne vulgaris with a selective decrease of triacylglycerols in skin surface lipids.

Early treadmill training promotes motor function after hemorrhagic stroke in rats.

Rehabilitation after a stroke is very important because it has beneficial effects on brain function, including the promotion of plasticity. However, an optimal time window for rehabilitation interventions after hemorrhagic stroke has not been clearly defined. The aim of this study was to determine whether early exercise training initiated 24h after an intracerebral hemorrhage (ICH) might enhance neurologic recovery more than exercise initiated 1 week after ICH without hematoma expansion and edema volume increase. We subjected adult male Sprague-Dawley rats to experimental ICH by the intrastriatal administration of bacterial collagenase. The rats were randomly divided into the following 2 groups: early training group (treadmill exercise started 24h post-ICH; n=18) and late training group (treadmill exercise started 1-week post-ICH; n=18). Two weeks after surgery we performed neurologic tests (rota-rod, modified limb-placing, and adhesive-dot removal tests), and measured hematoma volumes and brain water content. In the late training group, compared with the pre-ICH performance on the rota-rod test (98.3+/-69.4s), the animals had significantly worse performance after the post-ICH rehabilitation (40.5+/-52.6s; p<0.01, paired t-test). In the early training group however, the motor performance after the post-ICH rehabilitation (56.4+/-73.5s) was not significantly different from the baseline pre-ICH performance (79.8+/-33.9s; p=0.24). There were no significant differences between the two groups with respect to the other neurologic tests. Early exercise did not increase hematoma size or brain water content. Early treadmill training could be performed safely, and enhanced motor recovery in a rat model of ICH. Further studies are required to translate the results into clinical significance.