Oleaginous Microbial Lipids' Potential in the Prevention and Treatment of Neurological Disorders.

The products of oleaginous microbes, primarily lipids, have gained tremendous attention for their health benefits in food-based applications as supplements. However, this emerging biotechnology also offers a neuroprotective treatment/management potential for various diseases that are seldom discussed. Essential fatty acids, such as DHA, are known to make up the majority of brain phospholipid membranes and are integral to cognitive function, which forms an important defense against Alzheimer's disease. Omega-3 polyunsaturated fatty acids have also been shown to reduce recurrent epilepsy seizures and have been used in brain cancer therapies. The ratio of omega-3 to omega-6 PUFAs is essential in maintaining physiological function. Furthermore, lipids have also been employed as an effective vehicle to deliver drugs for the treatment of diseases. Lipid nanoparticle technology, used in pharmaceuticals and cosmeceuticals, has recently emerged as a biocompatible, biodegradable, low-toxicity, and high-stability means for drug delivery to address the drawbacks associated with traditional medicine delivery methods. This review aims to highlight the dual benefit that lipids offer in maintaining good health for disease prevention and in the treatment of neurological diseases.

PLACK syndrome is potentially treatable with intralipids.

We describe an 11-year-old girl with PLACK Syndrome (peeling skin, leukonychia, acral punctate keratosis, cheilitis, and knuckle pads), who was found to have a novel homozygous variant in CAST, the pathogenicity of which was confirmed using blood-derived RNA. There is no established treatment for PLACK syndrome. However, we demonstrate for the first time that this condition is associated with low levels of vitamin A and essential fatty acids, which prompted us to consider a potential treatment strategy. Indeed, we initiated this patient on intravenous lipid infusion (Vitalipid®; an emulsion of fat-soluble vitamins and lipofundin-MCT/LCT 20%) and the response was dramatic. Following the fourth monthly course of treatment, pruritis disappeared and the skin lesions showed remarkable objective improvement. PLACK syndrome is a very rare genodermatosis and only six families have been described to date with pathogenic CAST variants. This is the first report of an objective response to a therapeutic agent, which suggests that PLACK is a potentially treatable condition. The remarkable response we report and the relative safety of the intervention should prompt healthcare providers who care for PLACK syndrome patients to explore this as a potential treatment strategy in future studies.

Souvenaid for Alzheimer's disease.

BACKGROUND: Souvenaid is a dietary supplement with a patented composition (Fortasyn Connect™)which is intended to be used by people with Alzheimer's disease (AD). It has been designed to support the formation and function of synapses in the brain, which are thought to be strongly correlated with cognitive function. If effective, it might improve symptoms of Alzheimer's disease and also prevent the progression from prodromal Alzheimer's disease to dementia. We sought in this review to examine the evidence for this proposition. OBJECTIVES: To assess the effects of Souvenaid on incidence of dementia, cognition, functional performance, and safety in people with Alzheimer's disease. SEARCH METHODS: We searched ALOIS, i.e. the specialised register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), Web of Science (ISI Web of Science), Cinahl (EBSCOhost), Lilacs (BIREME), and clinical trials registries up to 24 June 2020. We also reviewed citations of reference lists of landmark papers, reviews, and included studies for additional studies and assessed their suitability for inclusion in the review. SELECTION CRITERIA: We included randomised, placebo-controlled trials which evaluated Souvenaid in people diagnosed with mild cognitive impairment (MCI) due to AD (also termed prodromal AD) or with dementia due to AD, and with a treatment duration of at least 16 weeks. DATA COLLECTION AND ANALYSIS: Our primary outcome measures were incidence of dementia, global and specific cognitive function, functional performance, combined cognitive-functional outcomes and adverse events. We selected studies, extracted data, assessed the quality of trials and intended to conduct meta-analyses according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. We present all outcomes grouped by stage of AD. MAIN RESULTS: We included three randomised, placebo-controlled trials investigating Souvenaid in 1097 community-dwelling participants with Alzheimer's disease. One study each included participants with prodromal AD, mild AD dementia and mild-to-moderate AD dementia. We rated the risks of bias of all trials as low. One study (in prodromal AD) was funded by European grants. The other two studies were funded by the manufacturer of Souvenaid. One trial investigated the incidence of dementia in people with prodromal AD at baseline, and found little to no difference between the Souvenaid group and the placebo group after 24 months (RR 1.09, 95% CI 0.82 to 1.43; 1 trial, 311 participants; moderate quality of evidence). In prodromal AD, and in mild and mild-to-moderate Alzheimer's disease dementia, Souvenaid probably results in little or no difference in global or specific cognitive functions (moderate quality of evidence). Everyday function, or the ability to perform activities of daily living, were measured in mild and mild-to-moderate AD dementia. Neither study found evidence of a difference between the groups after 24 weeks of treatment (moderate quality of evidence). Two studies investigated combined cognitive-functional outcomes with the Clinical Dementia Rating Sum of Boxes and observed conflicting results. Souvenaid probably results in slight improvement, which is below estimates of meaningful change, in participants with prodromal Alzheimer's disease after 24 months (moderate quality of evidence), but probably has little to no effect in mild-to-moderate Alzheimer's disease dementia after 24 weeks (moderate quality of evidence). Adverse effects observed were low in all trials, and the available data were insufficient to determine any connection with Souvenaid. AUTHORS' CONCLUSIONS: Two years of treatment with Souvenaid probably does not reduce the risk of progression to dementia in people with prodromal AD. There is no convincing evidence that Souvenaid affects other outcomes important to people with AD in the prodromal stage or mild-to-moderate stages of dementia. Conflicting evidence on combined cognitive-functional outcomes in prodromal AD and mild AD dementia warrants further investigation. Adverse effects of Souvenaid seem to be uncommon, but the evidence synthesised in this review does not permit us to make a definitive statement on the long-term tolerability of Souvenaid. The effects of Souvenaid in more severe AD dementia or in people with AD at risk of nutritional deficiencies remain unclear.

Sources, Production, and Clinical Treatments of Milk Fat Globule Membrane for Infant Nutrition and Well-Being.

Research on milk fat globule membrane (MFGM) is gaining traction. The interest is two-fold; on the one hand, it is a unique trilayer structure with specific secretory function. On the other hand, it is the basis for ingredients with the presence of phospho- and sphingolipids and glycoproteins, which are being used as food ingredients with valuable functionality, in particular, for use as a supplement in infant nutrition. This last application is at the center of this Review, which aims to contribute to understanding MFGM's function in the proper development of immunity, cognition, and intestinal trophism, in addition to other potential effects such as prevention of diseases including cardiovascular disease, impaired bone turnover and inflammation, skin conditions, and infections as well as age-associated cognitive decline and muscle loss. The phospholipid composition of MFGM from bovine milk is quite like human milk and, although there are some differences due to dairy processing, these do not result in a chemical change. The MFGM ingredients, as used to improve the formulation in different clinical studies, have indeed increased the presence of phospholipids, sphingolipids, glycolipids, and glycoproteins with the resulting benefits of different outcomes (especially immune and cognitive outcomes) with no reported adverse effects. Nevertheless, the precise mechanism(s) of action of MFGM remain to be elucidated and further basic investigation is warranted.

Lamotrigine Toxicosis Treated with Intravenous Lipid Emulsion Therapy in a Dog.

A female spayed dachshund/mixed-breed dog was evaluated following ingestion of lamotrigine tablets with subsequent rapid onset of vomiting, diarrhea, and generalized tremoring. On initial examination, the dog was moderately obtunded and nonambulatory with intermittent myoclonus and hyperesthesia. Electrocardiogram revealed sinus tachycardia with prolongation of the QT interval. Intravenous lipid emulsion (ILE) infusion was initiated, with reduction in tremoring and improved patient mentation being noted after ∼20 min of therapy. An elevated cardiac troponin I value measured at 1.02 ng/mL the day after presentation. Serum toxicological assay revealed marked reduction in serum lamotrigine levels following ILE and continued reduction during hospitalization. The dog's clinical signs resolved, corrected QT interval returned to normal, and the patient was discharged 38 hr after presentation. Individual cases of lamotrigine toxicosis have not been fully reported in veterinary literature. This case report documents the rapid onset of clinical signs including neurologic dysfunction, cardiac arrhythmias, and transient corrected QT prolongation. Serial serum concentrations of lamotrigine showed a rapid reduction with ILE therapy and corresponded with clinical recovery, suggesting efficacy of ILE treatment in this case.

Intralipid and haemodialysis in caffeine overdose.

A 26-year-old woman presented after an intentional ingestion of 20 g of caffeine. She suffered a profound respiratory alkalosis with metabolic acidosis, hypokalaemia and sustained polymorphic ventricular tachycardia. She was treated with intravenous intralipid and haemodialysis, and her arrhythmia was controlled using magnesium sulphate. Once invasively ventilated and unable to hyperventilate the patient became acidotic and required intravenous bicarbonate to correct her acid-base status. Two days following the overdose the patient was extubated, haemodialysis was stopped and norepinephrine was weaned off. The patient was discharged after a further 7 days. Serial caffeine levels were taken during this patient's care; the highest measured caffeine concentration 7 hours after ingestion was 147.1 mg/L. The known lethal dose of caffeine is 80 mg/L. Intralipid and haemodialysis represent a new and viable treatment in life-threatening caffeine overdose. Intravenous magnesium may terminate unstable arrhythmias in caffeine-poisoned patients.

Preconditioning rats with three lipid emulsions prior to acute lung injury affects cytokine production and cell apoptosis in the lung and liver.

BACKGROUND: Critically ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition. We sought to study whether preconditioning with representative of lipid emulsions for one week could benefit rats from ALI. METHODS: Using a lipopolysaccharide (LPS)-induced ALI rat model and techniques such as polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. RESULTS: PGE2 production in the serum was highest in the LPS group, followed with Intralipid group, and the PGE2 level of these two groups was significantly (P < 0.05) higher than the rest. Intralipid conditioning caused significantly less production of LTB4 than the LPS, Clinoleic, or Omegaven group. In contrast to Intralipid, rats pretreated with Clinoleic or Omegaven significantly decreased their production of inflammatory mediators (IL-1 ß, IL-6 and TNF-α), had less apoptosis in the lung tissues, and Omegaven greatly improved liver function upon lipopolysaccharide (LPS) challenge. CONCLUSIONS: In an ALI setting, preconditioning with Omegaven or Clinoleic was better than Intralipid in decreasing the intensity of the cytokine storm and apoptosis caused by LPS challenge, and Omegaven in addition had the potential to improve liver function. The results from the present study set a basis for further investigation of the molecular mechanisms of ALI, including the up- and downstream pathways of proinflammatory factor production, in search of (small) molecules intervening with the pathogenesis of ALI in order to translate relevant research findings into clinical benefit for patients with ALI. The use of Omegaven or Clinoleic, particularly in patients with ALI, is still characterized by uncertainty due to a lack of relevant studies. Future investigations must specifically focus on the route of administration and mode of application (enteral vs. parenteral/bolus vs. continuous), determining an optimal dose of Omegaven or Clinoleic, and the defining the best timepoint(s) for administration. Critically ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition. The effect of lipid emulsion via parenteral nutrition on liver function was first time evaluated in rats in an ALI setting. The comparison of three forms of lipid emulsion in a rat model of acute lung injury was first time studied. The fish oil-based lipid emulsion decrease in PGE 2 and increase in LTB 4 was first time reported.

An Observational Study of Smoflipid vs Intralipid on the Evolution of Intestinal Failure-Associated Liver Disease in Infants With Intestinal Failure.

BACKGROUND: SMOFlipid has a more diverse lipid profile than traditional Intralipid and has become the standard lipid for patients in our intestinal rehabilitation program. Our objective was to compare outcomes in neonates with intestinal failure (IF) who received SMOFlipid against those receiving Intralipid. METHODS: This was a retrospective cohort study of infants with IF with a minimum follow-up of 12 months in 2008-2016. Patients were stratified into 2 groups: group 1 received SMOFlipid; group 2 was a historical cohort who received Intralipid. The primary outcome was liver function evaluated using conjugated bilirubin (CB) levels. Statistical analysis included the Mann-Whitney U and χ2 tests, with an α value < 0.05 considered significant. Approval was obtained from our institutional review board. RESULTS: Thirty-seven patients were evaluated (17 = SMOFlipid, 20 = Intralipid). SMOFlipid patients were less likely to reach CB of 34 (24% vs 55%, P = 0.05), 50 µmol/L (11.8% vs 45%; P = 0.028), and did not require Omegaven (0% vs 30%; P = 0.014). CB level at 3 months after initiation of parenteral nutrition (PN) was lower in patients receiving SMOFlipid (0 vs 36 µmol/L; P = 0.01). Weight z-scores were improved for patients receiving SMOFlipid at 3 months (-0.932 vs -2.092; P = 0.028) and 6 months (-0.633 vs -1.614; P = 0.018). There were no differences in PN-supported patients or demographics between the groups. CONCLUSION: Use of SMOFlipid resulted in decreased development of IF-associated liver disease in patients with IF when assessed using biochemical tests.

Effect of empiric intravenous intralipid therapy on pregnancy outcome in women with unexplained recurrent implantation failure undergoing intracytoplasmic sperm injection-embryo transfer cycle: a randomized controlled trial.

To evaluate the effect of empiric intralipid infusion therapy on pregnancy outcomes for patients with unexplained recurrent implantation failure (RIF) undergoing intracytoplasmic sperm injection (ICSI). A total of 142 patients with a history of unexplained RIF (3 or more cycles) were included in this randomized controlled trial. Patients were randomized into two groups, study group (n = 71) and control group (n = 71). The study group received intralipid 20% infusion on the day of embryo transfer (ET) and a second dose on the day of pregnancy test. The clinical pregnancy rate in the study group was 36.6% (n = 26) compared to 28.2% (n = 20) in the control group (OR 1.47, CI 0.72-2.98, p = .282). The live birth rate in the study group was 18.3% (n = 13) and 14.1% (n = 10) in the control group (OR 1.37, CI 0.55-3.36, p=.49). No side effects of intralipid therapy were reported in the study period. There was improvement in the pregnancy rate among women with unexplained RIF who received empiric intralipid infusion therapy; however, this improvement did not reach statistical significance.

A Comparison of Smoflipid® and Intralipid® in the Early Management of Infants with Intestinal Failure.

PURPOSE: Cholestasis is problematic for infants with intestinal failure (IF). The soy-based lipid Intralipid® (IL) has been implicated. An alternative, Smoflipid® (SMOF), is increasingly used. However, its role in cholestasis prevention is unclear. This study compares the incidence and degree of cholestasis between infants with IF receiving SMOF or IL. METHODS: Infants with IF receiving SMOF or IL during the first 8 weeks of parenteral nutrition (PN) support between 2014 and 2017 were reviewed. Clinical characteristics, cholestasis incidence (conjugated bilirubin (Cbili) >2 mg/dL for >2 weeks), and nutritional parameters were compared using Welch's t-test. RESULTS: 91% (21/23) of IL and 76% (16/21) of SMOF babies became cholestatic (p = 0.18). There was no significant difference in median peak Cbili, but SMOF babies normalized more quickly (p = 0.04). Median z-scores for weight were similar throughout the study. SMOF patients getting full PN had a lower incidence of cholestasis compared to IL patients (78% vs. 92%, p = 0.057), but those with cholestasis had similar peak Cbili, time to resolution, and growth. CONCLUSION: Early use of Smoflipid® did not reduce the incidence of cholestasis compared to Intralipid® in infants with IF, but hyperbilirubinemia did resolve more quickly. SMOF may be most beneficial for infants tolerating no enteral nutrition. LEVEL OF EVIDENCE: Level III Retrospective Comparative Treatment Study. TYPE OF STUDY: Retrospective Review.

The LipiDiDiet trial: what does it add to the current evidence for Fortasyn Connect in early Alzheimer's disease?

Nutritional factors can influence the risk of developing Alzheimer's disease (AD) and its rate of progression, and there is, therefore, increasing interest in nutrition as a modifiable risk factor for the disease. Synaptic loss is an important feature of early AD, and the formation of new synapses is dependent on key nutritional elements that are known to be deficient in patients with AD. The daily medical food, Souvenaid, contains Fortasyn Connect, a multinutrient combination developed to specifically address these deficiencies, comprising docosahexaenoic acid, eicosapentaenoic acid, uridine monophosphate, choline, phospholipids, selenium, folic acid, and vitamins B12, B6, C, and E. Although yielding heterogeneous findings, clinical studies of Fortasyn Connect provide preliminary evidence of clinically relevant benefits on cognitive outcomes in prodromal and early AD. The LipiDiDiet trial investigated the effects of Fortasyn Connect on cognition and related measures in prodromal AD, and is the first randomized, controlled, double-blind, multicenter trial study of a non-pharmacological intervention in this setting. The primary efficacy endpoint was change over 24 months in a composite score of cognitive performance using a neuropsychological test battery. Fortasyn Connect had no significant effect on this endpoint, but demonstrated a significant benefit on secondary endpoints, including domains of cognition affected by AD (attention, memory, executive function) and hippocampal atrophy, suggesting a potential benefit on disease progression. Other studies have demonstrated benefits for Fortasyn Connect on nutritional markers and levels of plasma homocysteine. Taken together, current evidence indicates that Fortasyn Connect may show benefit on domains of cognition affected by AD and nutritional measures that influence risk factors for its progression; that it has greater potential for benefit earlier rather than later in the disease; and that it is safe and well tolerated, alone or in combination with AD medications. Further research into its potential role in AD management is therefore warranted.

The effect of administration of intravenous intralipid on pregnancy outcomes in women with implantation failure after IVF/ICSI with non-donor oocytes: A randomised controlled trial.

OBJECTIVE: Does the administration of intravenous intralipid in women with previous implantation failure at the time of embryo transfer improve pregnancy outcomes in terms of biochemical pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, and ongoing pregnancy rate? STUDY DESIGN: This was a single blinded randomised controlled trial of 105 subjects with previous failed IVF undergoing self donor oocyte IVF/ICSI from January 2017 to May 2018. Randomisation was by computer generated sequence after oocyte pickup. Results were analysed for 102 women, excluding three women due to poor embryo quality. Women in the study arm(n = 52) received 2 doses of 20% intravenous intralipid (Fresenius Kabi), 4 ml diluted in 250 ml normal saline by slow infusion. The first dose was given immediately after oocyte recovery, and the second dose was given on the day of embryo transfer, 1 h prior to the transfer. The control group (n = 50) received normal saline. Flexible ovarian stimulation protocols were used. All the women received routine luteal phase support with micronised vaginal progesterone. RESULTS: 102 women underwent analysis, 52 in the study group and 50 in control group. There was no significant difference in the baseline characteristics. There was a significant difference in the biochemical pregnancy rate in the intralipid group (40.38%) versus control (16%) [(p = 0.006), RR = 2.5 (1.23-5.16 CI)], clinical pregnancy rate [(34.62% vs 14%), p = 0.006, RR = 2.5(1.13-5.40 CI)], implantation rate [(16.6% vs 6.6%), p = 0.012, RR = 2.5(1.18 to 5.41 CI)], and take home baby rate [28.8% vs 10%, p = 0.024, RR = 2.8(1.1-7.3)]. The adjusted odds ratio for clinical pregnancy in women who received intralipid vs placebo was 3.1 (1.02-9.70 95% CI), p = 0.046. No adverse effects of intralipid were observed. CONCLUSION: This study shows a statistically significant increase in implantation rate and live birth rate in women who receive intravenous intralipid with prior implantation failure after IVF/ICSI. These findings concur with other studies; however, literature is limited. The effect of intralipid on the immunological abnormalities in women who experience recurrent implantation failure needs to be investigated further.

SMOFlipid Protects Preterm Neonates against Perinatal Nutrition-Associated Cholestasis.

OBJECTIVE: Intravenous lipid infusions improve both short- and long-term outcomes of premature neonates. However, prolonged infusion of lipids has been implicated in the development of parenteral nutrition-associated cholestasis (PNAC). We speculated that the multicomponent SMOFlipid would be hepatoprotective against PNAC. STUDY DESIGN: This is a retrospective review comparing the incidence and severity of direct hyperbilirubinemia in preterm infants <1,500 g who were hospitalized for a minimum of 2 weeks during a 20-month period in which all preterm infants on total parenteral nutrition (TPN) received fat as Lipofundin with the following 20-month period in which all preterm infants on TPN received SMOFlipid. RESULTS: Infants in the SMOFlipid period had a lower incidence of PNAC (6 vs. 13%; p = 0.022), lower peak direct bilirubin levels (3.2 vs. 7.1 mg/dL; p = 0.018), and a shorter length of stay (51 vs. 60 days; p = 0.019). The relative risk of developing direct hyperbilirubinemia during the Lipofundin period was 2.22 (1.1-4.3) as compared with period 1; p = 0.018; NNT-14. CONCLUSION: SMOFlipid was hepatoprotective in our population of preterm neonates <1,500 g receiving long-term TPN as compared with those receiving Lipofundin, despite similar levels of exposure to both intravenous lipid load and duration in the two groups.

Efficacy of phospholipidated curcumin in nonalcoholic fatty liver disease: a clinical study.

Curcumin is a safe and dietary phytochemical that can improve different pathophysiologic features of non-alcoholic fatty liver disease (NAFLD). Here, we investigated the efficacy of phospholipidated curcumin supplementation in NAFLD patients. In this single-arm study, 36 patients were recruited. Each patient received three capsules a day (each containing 500 mg of phospholipidated curcumin [overall content of curcuminoids per capsule: 100 mg]) for a period of 8 weeks. The results indicated that phospholipidated curcumin supplementation reduced NAFLD severity and ameliorated ultrasonographic and biochemical measures (including liver transaminases and lipid profile) associated with disease progression.

Home parenteral nutrition with an omega-3-fatty-acid-enriched MCT/LCT lipid emulsion in patients with chronic intestinal failure (the HOME study): study protocol for a randomized, controlled, multicenter, international clinical trial.

BACKGROUND: Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited. METHODS/DESIGN: The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs. DISCUSSION: Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03282955. Registered on 14 September 2017.

Effect of dietary interventions in mild cognitive impairment: a systematic review.

Diet has been investigated in relation to its ability to promote cognitive function. However, evidence is currently limited and has rarely been systematically reviewed, particularly in a mild cognitive impairment (MCI) population. This review examined the effect of diet on cognitive outcomes in MCI patients. A total of five databases were searched to find randomised controlled trial (RCT) studies, with diet as the main focus, in MCI participants. The primary outcome was incident dementia and/or Alzheimer's disease (AD) and secondary outcomes included cognitive function across different domains using validated neuropsychological tests. Sixteen studies met the inclusion criteria. There was a high degree of heterogeneity relating to the nature of the dietary intervention and cognitive outcomes measured, thus making study comparisons difficult. Supplementation with vitamin E (one study, n 516), ginkgo biloba (one study, n 482) or Fortasyn Connect (one study, n 311) had no significant effect on progression from MCI to dementia and/or AD. For cognitive function, the findings showed some improvements in performance, particularly in memory, with the most consistent results shown by B vitamins, including folic acid (one study, n 266), folic acid alone (one study, n 180), DHA and EPA (two studies, n 36 and n 86), DHA (one study, n 240) and flavonol supplementation (one study, n 90). The findings indicate that dietary factors may have a potential benefit for cognitive function in MCI patients. Further well-designed trials are needed, with standardised and robust measures of cognition to investigate the influence of diet on cognitive status.

Phantom menace: novel psychoactive substances and the UK Armed Forces.

Novel psychoactive substances (NPS) encompass a large group of synthesised compounds specifically designed to mimic traditional recreational drugs. Current UK Armed Forces compulsory drug testing does not screen for these substances, making them tempting to the small proportion of UK Armed Forces personnel who indulge in recreational drug use. The acute and chronic sequelae of NPS misuse are widely variable and associated with high morbidity. In this paper, we discuss NPS pharmacology and clinical presentation. We describe toxidromes and management of patients who have misused NPS.Finally, we reflect on the legal, ethical and military consequences of NPS misuse for both the service person misusing NPS and the Military Physician providing their care.

Zinc phthalocyanine-soybean phospholipid complex based drug carrier for switchable photoacoustic/fluorescence image, multiphase photothermal/photodynamic treatment and synergetic therapy.

For the purpose of precision theranostic of tumor, multifunctional drug delivery systems are always receiving great attentions. Here, we developed a zinc phthalocyanine-soybean phospholipid (ZnPc-SPC) complex based drug delivery system with doxorubicin (Dox) as loading cargo to achieve additional chemotherapy while the carrier itself could serve as multifunctional and switchable theranostic agent. In the early phase, the ZnPc-SPC complex assembled to nanostructure displaying photothermal therapy (PTT) and photoacoustic (PA) properties while in the late phase, the prepared NPs dis-assembled into ZnPc-SPC complex again performing photodynamic therapy (PDT) and low-background fluorescence (FL) image. With the decoration of folate receptors α (FRα) targeted MTX, Dox-loaded, MTX-decorated self-assembled ZnPc-SPC complex NPs (DZSM) was formed. In vitro and in vivo evaluations both indicated that DZSM presented high selectivity for FRα over-expressed tumor cells, excellent switchable PA/FL image, significant multiphase PTT/PDT effect, as well as great synergetic therapy potential, leading to notable inhibition of tumor growth.

A role for nutritional intervention in addressing the aging neuromuscular junction.

The purpose of this review is to discuss the structural and physiological changes that underlie age-related neuromuscular dysfunction and to summarize current evidence on the potential role of nutritional interventions on neuromuscular dysfunction-associated pathways. Age-related neuromuscular deficits are known to coincide with distinct changes in the central and peripheral nervous system, in the neuromuscular system, and systemically. Although many features contribute to the age-related decline in neuromuscular function, a comprehensive understanding of their integration and temporal relationship is needed. Nonetheless, many nutrients and ingredients show promise in modulating neuromuscular output by counteracting the age-related changes that coincide with neuromuscular dysfunction. In particular, dietary supplements, such as vitamin D, omega-3 fatty acids, ß-hydroxy-ß-methylbutyrate, creatine, and dietary phospholipids, demonstrate potential in ameliorating age-related neuromuscular dysfunction. However, current evidence seldom directly assesses neuromuscular outcomes and is not always in the context of aging. Additional clinical research studies are needed to confirm the benefits of dietary supplements on neuromuscular function, as well as to define the appropriate population, dosage, and duration for intervention.

Effect of intralipid on myocardial injury during valve replacement surgery with concomitant radiofrequency ablation: A randomized controlled trial.

BACKGROUND: This study aimed to evaluate the effect of intralipid postconditioning (ILPC) on myocardial damage in patients undergoing valve replacement surgery with concomitant radiofrequency ablation (RFA) for atrial fibrillation (AF). METHODS: Randomized patient and assessor-blind controlled trial conducted in adult patients undergoing valve replacement surgery with concomitant RFA. Sixty-nine patients were randomly assigned to ILPC group (n = 34) or control group (n = 35): ILPC group received an intravenous infusion of 20% intralipid (2 mL/kg) just 10 minutes before aortic cross-unclamping, and control group received an equivalent volume of normal saline. Serum cardiac troponin-T (cTnT) and creatine kinase-MB (CK-MB) was measured before surgery and at 4, 12, 24, 48, and 72 hours after surgery. The primary endpoints were the 72-hour area under the curve (AUC) for cTnT and CK-MB. RESULTS: The total 72-hour AUC of cTnT (P = .33) and CK-MB (P = .52) were comparable between 2 groups. The left ventricle ejection fraction at discharge (P = .011) was higher in the ILPC group than that in the control group, while the AF recurrence did not differ significantly between 2 groups. CONCLUSIONS: There was no observed beneficial effect of ILPC on myocardial injury documented by the cardiac biomarkers in patients undergoing valve replacement surgery with concomitant RFA, and the effect of intralipid against myocardial I/R injury is undetectable within the background of massive biomarker release following ablation owing to localized myocardial necrosis. Besides, there are no other published data about the cardioprotective role of intralipid in patients undergoing this procedure and benefits of this protection need further studies to validate.