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Healthcare (Basel, Switzerland) Oct 2022Metabolic syndrome (MetSyn) is a precursor for several cardiometabolic diseases. The prevalence of MetSyn is higher in postmenopausal women compared to premenopausal... (Review)
Review
Metabolic syndrome (MetSyn) is a precursor for several cardiometabolic diseases. The prevalence of MetSyn is higher in postmenopausal women compared to premenopausal women. The role of vitamin D in postmenopausal women is not clearly understood. Hypovitaminosis D is more prevalent in postmenopausal women compared to premenopausal women. For this review, Pubmed, Cochrane, SCOPUS, Embase, and Google Scholar databases were searched up to August 2022. Findings from one randomized controlled trial (RCT) and ten cross-sectional studies were included in this review. Several cross-sectional studies (8 out of 10 reviewed) unequivocally demonstrated an inverse association between serum 25-hydroxyvitamin D concentrations and MetSyn. However, RCTs are severely lacking in the effect of vitamin D intake on the biomarkers of MetSyn and the prevalence of MetSyn. Therefore, caution should be used in recommending mega doses of vitamin D supplements for postmenopausal women because of the potential adverse effects associated with this vitamer.
PubMed: 36292473
DOI: 10.3390/healthcare10102026 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2023Preterm infants risk deficits of long-chain polyunsaturated fatty acids (LCPUFAs) that may contribute to morbidities and hamper neurodevelopment. We aimed to determine... (Randomized Controlled Trial)
Randomized Controlled Trial
Modification of serum fatty acids in preterm infants by parenteral lipids and enteral docosahexaenoic acid/arachidonic acid: A secondary analysis of the Mega Donna Mega trial.
BACKGROUND & AIM
Preterm infants risk deficits of long-chain polyunsaturated fatty acids (LCPUFAs) that may contribute to morbidities and hamper neurodevelopment. We aimed to determine longitudinal serum fatty acid profiles in preterm infants and how the profiles are affected by enteral and parenteral lipid sources.
METHODS
Cohort study analyzing fatty acid data from the Mega Donna Mega study, a randomized control trial with infants born <28 weeks of gestation (n = 204) receiving standard nutrition or daily enteral lipid supplementation with arachidonic acid (AA):docosahexaenoic acid (DHA) (100:50 mg/kg/day). Infants received an intravenous lipid emulsion containing olive oil:soybean oil (4:1). Infants were followed from birth to postmenstrual age 40 weeks. Levels of 31 different fatty acids from serum phospholipids were determined by GC-MS and reported in relative (mol%) and absolute concentration (μmol l) units.
RESULTS
Higher parenteral lipid administration resulted in lower serum proportion of AA and DHA relative to other fatty acids during the first 13 weeks of life (p < 0.001 for the 25th vs the 75th percentile). The enteral AA:DHA supplement increased the target fatty acids with little impact on other fatty acids. The absolute concentration of total phospholipid fatty acids changed rapidly in the first weeks of life, peaking at day 3, median (Q1-Q3) 4452 (3645-5466) μmol l, and was positively correlated to the intake of parenteral lipids. Overall, infants displayed common fatty acid trajectories over the study period. However, remarkable differences in fatty acid patterns were observed depending on whether levels were expressed in relative or absolute units. For example, the relative levels of many LCPUFAs, including DHA and AA, declined rapidly after birth while their absolute concentrations increased in the first week of life. For DHA, absolute levels were significantly higher compared to cord blood from day 1 until postnatal week 16 (p < 0.001). For AA, absolute postnatal levels were lower compared to cord blood from week 4 throughout the study period (p < 0.05).
CONCLUSIONS
Our data show that parenteral lipids aggravate the postnatal loss of LCPUFAs seen in preterm infants and that serum AA available for accretion is below that in utero. Further research is needed to establish optimal postnatal fatty acid supplementation and profiles in extremely preterm infants to promote development and long-term health.
CLINICAL TRIAL REGISTRY
ClinicalTrials.gov, identifier: NCT03201588.
Topics: Infant; Infant, Newborn; Humans; Docosahexaenoic Acids; Fatty Acids; Arachidonic Acid; Cohort Studies; Infant, Extremely Premature; Phospholipids
PubMed: 37120902
DOI: 10.1016/j.clnu.2023.04.020 -
The New England Journal of Medicine Oct 2022Docosahexaenoic acid (DHA) is a component of neural tissue. Because its accretion into the brain is greatest during the final trimester of pregnancy, infants born before...
BACKGROUND
Docosahexaenoic acid (DHA) is a component of neural tissue. Because its accretion into the brain is greatest during the final trimester of pregnancy, infants born before 29 weeks' gestation do not receive the normal supply of DHA. The effect of this deficiency on subsequent cognitive development is not well understood.
METHODS
We assessed general intelligence at 5 years in children who had been enrolled in a trial of neonatal DHA supplementation to prevent bronchopulmonary dysplasia. In the previous trial, infants born before 29 weeks' gestation had been randomly assigned in a 1:1 ratio to receive an enteral emulsion that provided 60 mg of DHA per kilogram of body weight per day or a control emulsion from the first 3 days of enteral feeds until 36 weeks of postmenstrual age or discharge home, whichever occurred first. Children from 5 of the 13 centers in the original trial were invited to undergo assessment with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at 5 years of corrected age. The primary outcome was the full-scale intelligence quotient (FSIQ) score. Secondary outcomes included the components of WPPSI.
RESULTS
A total of 1273 infants underwent randomization in the original trial; of the 656 surviving children who had undergone randomization at the centers included in this follow-up study, 480 (73%) had an FSIQ score available - 241 in the DHA group and 239 in the control group. After imputation of missing data, the mean (±SD) FSIQ scores were 95.4±17.3 in the DHA group and 91.9±19.1 in the control group (adjusted difference, 3.45; 95% confidence interval, 0.38 to 6.53; P = 0.03). The results for secondary outcomes generally did not support that obtained for the primary outcome. Adverse events were similar in the two groups.
CONCLUSIONS
In infants born before 29 weeks' gestation who had been enrolled in a trial to assess the effect of DHA supplementation on bronchopulmonary dysplasia, the use of an enteral DHA emulsion until 36 weeks of postmenstrual age was associated with modestly higher FSIQ scores at 5 years of age than control feeding. (Funded by the Australian National Health and Medical Research Council and Nu-Mega Ingredients; N3RO Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820.).
Topics: Child; Child, Preschool; Humans; Infant; Infant, Newborn; Australia; Bronchopulmonary Dysplasia; Dietary Supplements; Docosahexaenoic Acids; Emulsions; Follow-Up Studies; Infant, Premature; Intelligence; Enteral Nutrition; Wechsler Scales; Cognition
PubMed: 36300974
DOI: 10.1056/NEJMoa2206868 -
PloS One 2021γ-Aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the human brain. It has been shown that altered GABA concentration plays an important role in a... (Clinical Trial)
Clinical Trial
γ-Aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the human brain. It has been shown that altered GABA concentration plays an important role in a variety of psychiatric and neurological disorders. The main purpose of this study was to propose a combination of PRESS and MEGA-PRESS acquisitions for absolute GABA quantification and to compare GABA estimations obtained using total choline (tCho), total creatine (tCr), and total N-acetyl aspartate (tNAA) as the internal concentration references with water referenced quantification. The second aim was to demonstrate the fitting approach of MEGA-PRESS spectra with QuasarX algorithm using a basis set of GABA, glutamate, glutamine, and NAA in vitro spectra. Thirteen volunteers were scanned with the MEGA-PRESS sequence at 3T. Interleaved water referencing was used for quantification, B0 drift correction and to update the carrier frequency of RF pulses in real time. Reference metabolite concentrations were acquired using a PRESS sequence with short TE (30 ms) and long TR (5000 ms). Absolute concentration were corrected for cerebrospinal fluid, gray and white matter water fractions and relaxation effects. Water referenced GABA estimations were significantly higher compared to the values obtained by metabolite references. We conclude that QuasarX algorithm together with the basis set of in vitro spectra improves reliability of GABA+ fitting. The proposed GABA quantification method with PRESS and MEGA-PRESS acquisitions enables the utilization of tCho, tCr, and tNAA as internal concentration references. The use of different concentration references have a good potential to improve the reliability of GABA estimation.
Topics: Adult; Algorithms; Female; Gyrus Cinguli; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; gamma-Aminobutyric Acid
PubMed: 33449935
DOI: 10.1371/journal.pone.0240641 -
Critical Care (London, England) Oct 2023Mega-dose sodium ascorbate (NaAscorbate) appears beneficial in experimental sepsis. However, its physiological effects in patients with septic shock are unknown. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Mega-dose sodium ascorbate (NaAscorbate) appears beneficial in experimental sepsis. However, its physiological effects in patients with septic shock are unknown.
METHODS
We conducted a pilot, single-dose, double-blind, randomized controlled trial. We enrolled patients with septic shock within 24 h of diagnosis. We randomly assigned them to receive a single mega-dose of NaAscorbate (30 g over 1 h followed by 30 g over 5 h) or placebo (vehicle). The primary outcome was the total 24 h urine output (UO) from the beginning of the study treatment. Secondary outcomes included the time course of the progressive cumulative UO, vasopressor dose, and sequential organ failure assessment (SOFA) score.
RESULTS
We enrolled 30 patients (15 patients in each arm). The mean (95% confidence interval) total 24-h UO was 2056 (1520-2593) ml with placebo and 2948 (2181-3715) ml with NaAscorbate (mean difference 891.5, 95% confidence interval [- 2.1 to 1785.2], P = 0.051). Moreover, the progressive cumulative UO was greater over time on linear mixed modelling with NaAscorbate (P < 0.001). Vasopressor dose and SOFA score changes over time showed faster reductions with NaAscorbate (P < 0.001 and P = 0.042). The sodium level, however, increased more over time with NaAscorbate (P < 0.001). There was no statistical difference in other clinical outcomes.
CONCLUSION
In patients with septic shock, mega-dose NaAscorbate did not significantly increase cumulative 24-h UO. However, it induced a significantly greater increase in UO and a greater reduction in vasopressor dose and SOFA score over time. One episode of hypernatremia and one of hemolysis were observed in the NaAscorbate group. These findings support further cautious investigation of this novel intervention. Trial registration Australian New Zealand Clinical Trial Registry (ACTRN12620000651987), Date registered June/5/2020.
Topics: Humans; Shock, Septic; Ascorbic Acid; Australia; Sepsis; Double-Blind Method; Vasoconstrictor Agents
PubMed: 37828547
DOI: 10.1186/s13054-023-04644-x -
Human Vaccines & Immunotherapeutics Dec 2023The rapid increase in antibiotic resistance presents a dire situation necessitating the need for alternative therapeutic agents. Among the current alternative therapies,... (Review)
Review
The rapid increase in antibiotic resistance presents a dire situation necessitating the need for alternative therapeutic agents. Among the current alternative therapies, phage therapy (PT) is promising. This review extensively summarizes preclinical PT approaches in various models. PT has been evaluated in several recent clinical trials. However, there are still several unanswered concerns due to a lack of appropriate regulation and pharmacokinetic data regarding the application of phages in human therapeutic procedures. In this review, we also presented the current state of PT and considered how animal models can be used to adapt these therapies for humans. The development of realistic solutions to circumvent these constraints is critical for advancing this technology.
Topics: Animals; Humans; Phage Therapy; Bacterial Infections; Bacteriophages; Drug Resistance, Multiple, Bacterial; Models, Animal; Anti-Bacterial Agents
PubMed: 36935353
DOI: 10.1080/21645515.2023.2175519 -
Nutrients Jan 20247-MEGA is a food product made from purified Alaska pollack fish oil containing palmitoleic acid (16:1), commonly referred to as omega-7. We sought to quantitatively... (Comparative Study)
Comparative Study Randomized Controlled Trial
7-MEGA is a food product made from purified Alaska pollack fish oil containing palmitoleic acid (16:1), commonly referred to as omega-7. We sought to quantitatively evaluate whether this substance inhibits skin aging. A total of 101 middle-aged females were randomly allocated to the intervention ( = 50) or placebo group ( = 51). Each participant was advised to take either 500 mg of 7-MEGA or a placebo twice daily for 12 weeks. The primary outcomes were the degree of improvement in wrinkles and the degree of moisture filling after consumption for 12 weeks compared to baseline. The secondary outcomes were improvement in skin wrinkles; moisture changes at 4 and 8 weeks from baseline; changes in transdermal water loss, skin elasticity, the melanin index, the erythema index, and the Global Photo Damage Score. We found a significant improvement in skin wrinkles and elasticity at 12 weeks in the 7-MEGA-consuming group compared to that in the placebo group; skin moisture, elasticity, and the melanin index were also improved. No supplement-related adverse reactions were observed and 7-MEGA was identified as safe. 7-MEGA was effective for human skin function in terms of wrinkles, moisture, elasticity, and melanin production and may be useful as a skin nutritional supplement.
Topics: Female; Humans; Middle Aged; Dietary Supplements; Elasticity; Melanins; Skin; Skin Aging; Double-Blind Method
PubMed: 38257104
DOI: 10.3390/nu16020212 -
Amyotrophic Lateral Sclerosis &... May 2021To evaluate safety, dose response, and preliminary efficacy of over 12 weeks in patients with amyotrophic lateral sclerosis (ALS). Patients (≤2 years since... (Randomized Controlled Trial)
Randomized Controlled Trial
To evaluate safety, dose response, and preliminary efficacy of over 12 weeks in patients with amyotrophic lateral sclerosis (ALS). Patients (≤2 years since diagnosis) with slow upright vital capacity (SVC) of ≥60% were randomized 1:1:1:1 to 150, 300, or 450 mg twice daily (bid) or placebo; active treatment was 12 weeks with 4-week follow-up. Primary endpoint was change in percent predicted SVC at 12 weeks; secondary measures included ALS Functional Rating Scale-Revised (ALSFRS-R) and muscle strength mega-score. Patients ( = 458) were enrolled; 85% completed 12-week treatment. The primary analysis failed to reach statistical significance ( = 0.11); secondary endpoints showed no statistically significant effects (ALSFRS-R, = 0.09; muscle strength mega-score, = 0.31). Post hoc analyses pooling all active -treated patients compared against placebo showed trends toward benefit in all endpoints (progression rate for SVC, ALSFRS-R, and muscle strength mega-score (nominal p values of 0.10, 0.01 and 0.20 respectively)). was well tolerated, with nausea and fatigue being the most common side effects. A dose-dependent decrease in estimated glomerular filtration rate was noted, and transaminase elevations were seen in approximately 5% of patients. Both hepatic and renal abnormalities trended toward resolution after study drug discontinuation. Although the primary efficacy analysis did not demonstrate statistical significance, there were trends favoring for all three endpoints, with effect sizes generally regarded as clinically important. Tolerability was good; modest hepatic and renal abnormalities were reversible. The impact of on patients with ALS should be assessed in a pivotal Phase 3 trial. (ClinicalTrials.gov Identifier: NCT03160898).
Topics: Amyotrophic Lateral Sclerosis; Double-Blind Method; Humans; Muscle Strength
PubMed: 32969758
DOI: 10.1080/21678421.2020.1822410 -
Expert Opinion on Drug Delivery Mar 2019Docetaxel (DTX) is one of the most important chemotherapeutic agents and has been widely used for treatment of various types of cancers. However, the clinical... (Review)
Review
INTRODUCTION
Docetaxel (DTX) is one of the most important chemotherapeutic agents and has been widely used for treatment of various types of cancers. However, the clinical chemotherapy of DTX gives many undesirable side effects due to the usage of organic solvent in the injection and its low selectivity for tumor cells. With the evolution of pharmaceutical technologies, great efforts have been paid to develop new DTX formulations to overcome these problems.
AREAS COVERED
This review provided an overview of the preparation and activities of new DTX formulations, which were classified by administration methods, including injection, oral, transdermal and rectal administration. Besides, up to date information of the clinical status of new DTX formulations was summarized. We also discussed the challenges and perspectives of the future development of DTX formulations.
EXPERT OPINION
There have been numerous studies on new DTX-based formulations in recent years, and many of them exhibited significantly enhanced anti-tumor and targeting activity compared with DTX in preclinical studies. However, only a few entered clinical trials, and none has been approved into market. The clinical translation of experimental drug faces many hurdles, including the limited knowledge of nanomedicine and oncology, safety issues, controllable and reproducible production.
Topics: Animals; Antineoplastic Agents; Docetaxel; Drug Compounding; Humans; Nanomedicine; Nanoparticles; Neoplasms; Technology, Pharmaceutical
PubMed: 30773947
DOI: 10.1080/17425247.2019.1583644 -
Small Business Economics 2022Employer business startups contribute disproportionately to job creation, innovation, and productivity growth. This contribution is dynamic and complex involving much... (Review)
Review
Employer business startups contribute disproportionately to job creation, innovation, and productivity growth. This contribution is dynamic and complex involving much trial and error. Most startups fail or do not grow but a small fraction grow rapidly contributing substantially to economic performance. In the USA, there has been a decline in startup rate and the share of activity accounted for by young firms over the last couple of decades. This decline has accelerated and become pervasive in the post-2000 period even in innovative-intensive sectors. The flip side of this change is an accompanying increase in the share of activity accounted for by mega (10,000 +) firms in the post-2000 period. While both benign and adverse factors may underlie these structural changes, the post-2000 period has also exhibited a decline in productivity growth along with indicators of business dynamism. The global pandemic has had a major adverse impact on health, morbidity, daily life, and economic activity. However, there has been a surge in new business applications that may signal a turning point in entrepreneurial activity.
PubMed: 38624942
DOI: 10.1007/s11187-021-00542-0