Volume-based enteral feeding for ward patients with acute neurological conditions: a pilot prospective cohort study.

BACKGROUND: Patients requiring enteral nutrition (EN) after neurological insults experience feeding interruptions, contributing to inadequate nutrition delivery. This prospective cohort study investigated if volume-based enteral feeding (VBF) improved the delivery of prescribed EN volume in ward patients with acute neurological conditions. METHODS: Over two sequential periods, the usual care group received standard continuous rate-based feeding, and the intervention group received VBF with bi-daily EN rate adjustments to achieve target daily volume. The primary outcome was percentage of prescribed daily EN formula volume delivered. Differences in energy and protein provision, weight, malnutrition and safety were explored. An evaluation survey captured nurse acceptability of the protocol. RESULTS: The intervention group (n = 32) achieved greater median interquartile range (IQR) EN adequacy of prescribed volume at 92% (88-97) compared to 67% (54-78) for usual care (n = 35) (p < 0.001). VBF compared to rate-based feeding resulted in patients receiving more kilojoules (131 [121-138] kJ/kg vs. 84 [64-99] kJ/kg; p < 0.001) and protein (1.3 [1.2-1.5] g/kg vs. 0.9 [0.6-1.1] g/kg; p < 0.001). There were no differences in gastrointestinal intolerance between groups. Compliance to the VBF protocol was 90%, and 78% of staff reported high confidence using the protocol. The intervention group had less median weight loss at discharge (-1.4 [0.1 to -4.3] kg) than usual care (-3.6 [-1.3 to 8.4] kg; p < 0.011), but no differences in malnutrition status were observed. CONCLUSION: A VBF protocol delivered greater EN volume, energy and protein following neurological injury. The VBF protocol was feasible with high acceptability from nursing staff.

Dietary intake and nutritional status of people with epilepsy: A systematic review.

PURPOSE: In people with epilepsy achieving optimal dietary intake may be hampered by psychological and physical comorbidities associated with seizures, medication use, socioeconomic disadvantage and the use of therapeutic diets. This systematic review aimed to evaluate the reported dietary intake and nutritional status of children and adults with epilepsy. METHODS: A systematic literature search was completed across Ovid MEDLINE, EMBASE and CINAHL (all from inception to 4 November 2021). We included studies that reported dietary intake in adults and children diagnosed with epilepsy compared with local reference ranges, control groups or general populations. Studies using interventions and therapeutic diets were excluded. Risk of bias was assessed using the Study Quality Assessment Tools by the National Heart, Lung and Blood Institute. A descriptive analysis was performed due to the heterogenous nature of the data. RESULTS: The initial search returned 1214 articles. Full-text screening was completed for 98 studies and 19 studies met eligibility criteria and were included for extraction. These comprised of seven paediatric studies, eight adult studies and four studies that included both adult and paediatric cohorts. Sample size of cases in each study ranged from 17 to 3,220. Vitamin A, C, D and folate were the most frequently reported vitamins. Calcium, iron and zinc were the most commonly reported minerals. Most studies showed that people with epilepsy had poorer dietary intake and nutritional status compared with control groups or reference standards. CONCLUSION: There were limited studies on dietary intake and nutritional status in people with epilepsy. Most available studies suggested poorer status compared to non-epilepsy controls. The development of a validated dietary assessment tool specifically for epilepsy cohorts would enable comparison of findings across studies, and aid with appropriately tailoring nutrition advice to individuals with epilepsy.

Modified low ratio ketogenic therapy in the treatment of adults with super-refractory status epilepticus.

BACKGROUND: Induction of ketosis by manipulation of nutrition intake has been proposed as an adjunctive treatment for super-refractory status epilepticus (SRSE). However, the classical 4:1 ketogenic ratio may not meet the nutrition needs, specifically protein for critically ill adults. The aim of this study was to analyze the outcomes of adults with SRSE who received a lower ketogenic ratio of 2:1 grams of fat to non-fat grams, including 20%-30% of energy from medium chain triglycerides. METHODS: We reviewed patients aged ≥18 years with SRSE treated with ketogenic therapy between July 2015 and December 2020 at two quaternary teaching hospitals in Melbourne, Australia. Data collected from medical records included patient demographics, nutrition prescription, clinical outcomes, and ketogenic therapy-related complications. The primary outcome of the study was to assess tolerability of ketogenic therapy. RESULTS: Twelve patients (female = 7) were treated with ketogenic therapy for SRSE. Patients received between 4 and 8 antiseizure medications and 1-5 anesthetic agents prior to commencement of ketogenic therapy. Blood beta-hydroxybutyrate concentrations were variable (median = 0.5 mmol/L, range: 0.0-6.1 mmol/L). SRSE resolved in 10 cases (83%) after a median of 9 days (range: 2-21 days) following commencement of ketogenic therapy. Ketogenic therapy-associated complications were reported in five patients, leading to cessation in two patients. CONCLUSION: Despite the challenge in maintaining ketosis during critical illness, low ratio 2:1 ketogenic therapy incorporating medium chain triglycerides is tolerable for adults with SRSE. Further studies are required to determine the optimal timing, nutrition prescription and duration of ketogenic therapy for SRSE treatment.

Practical Considerations for Ketogenic Diet in Adults With Super-Refractory Status Epilepticus.

PURPOSE OF REVIEW: Ketogenic diet therapy can be used as an adjuvant treatment of super-refractory status epilepticus (SRSE). However, the drug and metabolic interactions with concomitant treatments present a challenge for clinicians. In this review, we focus on the practical considerations of implementing ketogenic dietary therapy in the acute setting, including the dietary composition, potential drug-diet interactions, and monitoring during ketogenic treatment. RECENT FINDINGS: This report describes the ketogenic diet therapy protocol implemented for the treatment of SRSE and a review of the current evidence to support clinical practice. SUMMARY: The control of SRSE is critical in reducing morbidity and mortality. There is emerging evidence that ketogenic diet may be a safe and effective treatment option for these patients.

A benchmarking study of home enteral nutrition services.

BACKGROUND & AIMS: Patients receiving home enteral nutrition (HEN) via an enteral feeding tube often have complex healthcare requirements. There is limited information regarding how HEN care is provided within Australia and New Zealand. This study aimed to investigate the characteristics of HEN services and the provision of nutrition care to individuals receiving HEN within Australia and New Zealand. METHODS: A cross-sectional study, surveying lead HEN dietitians for HEN services was conducted from the period 09 July 2019 to 20 September 2019 inclusive. An online survey was used to obtain data relating to the demographics, funding and clinical resources of respondents' HEN services. Services were benchmarked against a HEN service implementation checklist adapted from the Agency for Clinical Innovation (ACI). RESULTS: Responses were received from 107 HEN services, with an estimated combined population of 7122 HEN patients. Services were predominantly government-funded (n = 102, 95.3%) and operated from acute hospitals (n = 57, 53.3%). The reported combined cost of all HEN equipment to the patient ranged from $0-$77 per week or $0-$341 per month. Fifty-two services were reported to have a dedicated HEN dietitian/coordinator, which was positively associated with the undertaking of quality improvement activities (p = 0.019). Mean compliance to the ACI HEN implementation checklist was 70.4% (±15.7%) with a range of 13.0-98.2%. Mean compliance was significantly higher in services with a HEN dietitian/coordinator than services without one (75.5% (±12.0%) vs 64.3% (±16.6%); p < 0.001). CONCLUSIONS: This study provides detailed information regarding the characteristics of HEN services and nutrition care provided to enterally-fed patients across Australia and New Zealand. The majority of HEN services are not adhering to the ACI HEN service guidelines and there is considerable variation in cost burden for consumers indicating inequitable delivery of care to patients.

Open-label long-term treatment of add-on triheptanoin in adults with drug-resistant epilepsy.

OBJECTIVE: To investigate feasibility, safety, and tolerability of long-term (48 weeks) add-on treatment with triheptanoin (UX007), the triglyceride of heptanoate, in adults with drug-resistant epilepsy. METHODS: This extension study was offered to adult participants with drug-resistant epilepsy who completed a 12-week randomized controlled trial of add-on medium-chain triglycerides (MCT) vs triheptanoin. Participants were asked to titrate triheptanoin to their maximum tolerated dose over 3 weeks, followed by 48-week maintenance before tapering or treatment extension. The primary aims were to assess retention and safety of the triheptanoin treatment, and secondary aims to assess the tolerated doses and changes in seizure frequency. RESULTS: Eleven adults were enrolled and ten people were analyzed (because one patient was diagnosed as having nonepileptic seizures while on the study). Two adults finished the study and extended their treatment. Eight participants withdrew from the study, due to lack of efficacy (n = 3), unknown reasons (n = 2), belief of weight gain (n = 1), wanting to try a different treatment (n = 1), and a colonoscopy (n = 1). Diarrhea in two people and bloating in one person were deemed possibly related to treatment, but other adverse events were not. The duration of maintenance treatment dose was 27-513 days (median 247 days, range 27-513 days), and 0.49 -1.1 mL/kg triheptanoin was taken per day (0.77 ± 0.19 mL/kg, mean ± standard deviation, 40-100 mL/d). Two participants experienced >90% and three people >50% reduction in seizure frequency, and all had focal seizures. The median seizure reduction was 48% (average 38%). SIGNIFICANCE: Our results indicate antiseizure effects of triheptanoin on focal seizures in 5 out of 10 adults. However, only two people finished and extended the 48-week add-on treatment phase, despite lack of safety or tolerability issues.More studies focused on improved treatment formulations, the potential of lower dosages, and efficacy are needed. Trial registration number: ACTRN12615000406505.

Randomized trial of add-on triheptanoin vs medium chain triglycerides in adults with refractory epilepsy.

OBJECTIVE: To investigate the feasibility, safety, and tolerability of add-on treatment of the triglycerides of heptanoate (triheptanoin) vs the triglycerides of octanoate and decanoate (medium chain triglycerides [MCTs]) in adults with treatment-refractory epilepsy. METHODS: After an 8-week prospective baseline period, people with drug-resistant epilepsy were randomized in a double-blind fashion to receive triheptanoin or MCTs. Treatment was titrated over 3 weeks to a maximum of 100 mL/d to be distributed over 3 meals and mixed into food, followed by 12-week maintenance before tapering. The primary aims were to assess the following: (a) safety by comparing the number of intervention-related adverse events with triheptanoin vs MCT treatment and (b) adherence, measured as a percentage of the prescribed treatment doses taken. RESULTS: Thirty-four people were randomized (17 to MCT and 17 to triheptanoin). There were no differences regarding (a) the number of participants completing the study (11 vs 9 participants), (b) the time until withdrawal, (c) the total number of adverse events or those potentially related to treatment, (d) median doses of oils taken (59 vs 55 mL/d, P = 0.59), or (e) change in seizure frequency (54% vs 102%, P = 0.13). Please note that people with focal unaware seizures were underrepresented in the triheptanoin treatment arm (P = 0.04). The most common adverse events were gastrointestinal disturbances (47% and 62.5% of participants). Five people taking on average 0.73 mL/kg body weight MCTs (0.64 mL/kg median) and one person taking 0.59 mL/kg triheptanoin showed >50% reduction in seizure frequency, specifically focal unaware seizures. SIGNIFICANCE: Add-on treatment with MCTs or triheptanoin was feasible, safe, and tolerated for 12 weeks in two-thirds of people with treatment-resistant epilepsy. Our results indicate a protective effect of MCTs on focal unaware seizures. This warrants further study.

Study of the Physicochemical Properties of Fish Oil Solid Lipid Nanoparticle in the Presence of Palmitic Acid and Quercetin.

ω-3 polyunsaturated fatty acids, naturally found in fish oil, are highly desirable for their associated health benefits. However, they are highly prone to oxidation and degradation. We examined the feasibility of simultaneously adding a solid lipid (palmitic acid) and an antioxidant (quercetin) into a whey-protein-isolate-stabilized solid lipid nanoparticle emulsion for encapsulating fish oil. The goal was to find a rational and new formulation containing both solid lipid and antioxidant that can encapsulate fish oil and give it the best physicochemical stability. Our results show that adding palmitic acid improved the physical stability of the emulsions by decreasing the size of the oil-in-water droplets. On the basis of the thiobarbituric acid reactive substances assay, we found out that at low concentrations of palmitic acid the addition of quercetin played a dominant role in increasing the oxidation stability of fish oil. On the contrary, at high concentrations of palmitic acid, it was palmitic acid that dominated the oxidation inhibition by the solidification of the encapsulates' core.

A novel dual-color bifocal imaging system for single-molecule studies.

In this paper, we report the design and implementation of a dual-color bifocal imaging (DBI) system that is capable of acquiring two spectrally distinct, spatially registered images of objects located in either same or two distinct focal planes. We achieve this by separating an image into two channels with distinct chromatic properties and independently focusing both images onto a single CCD camera. The two channels in our device are registered with subpixel accuracy, and long-term stability of the registered images with nanometer-precision was accomplished by reducing the drift of the images to ∼5 nm. We demonstrate the capabilities of our DBI system by imaging biomolecules labeled with spectrally distinct dyes and micro- and nano-sized spheres located in different focal planes.

Effects of α-tubulin K40 acetylation and detyrosination on kinesin-1 motility in a purified system.

Long-range transport in cells is achieved primarily through motor-based transport along a network of microtubule tracks. Targeted transport by kinesin motors can be correlated with posttranslational modifications (PTMs) of the tubulin subunits in specific microtubules. To directly examine the influence of specific PTMs on kinesin-1 motility, we generated tubulin subunits that were either enriched in or lacking acetylation of α-tubulin lysine 40 (K40) or detyrosination of the α-tubulin C-terminal tail. We show that K40 acetylation does not result in significant changes in kinesin-1's landing rate or motility parameters (velocity and run length) across experimental conditions. In contrast, detyrosination causes a moderate increase in kinesin-1's landing rate. The fact that the effects of detyrosination are dampened by prior K40 acetylation indicates that the combination of PTMs may be an important aspect of the functional output of microtubule heterogeneity. Importantly, our results indicate that the moderate influences that single PTMs have on kinesin-1 in vitro do not explain the strong correlation between specific PTMs and kinesin-1 transport in cells. Thus, additional mechanisms for regulating kinesin-1 transport in cells must be explored in future work.

Paclitaxel-conjugated PAMAM dendrimers adversely affect microtubule structure through two independent modes of action.

Paclitaxel (Taxol) is an anticancer drug that induces mitotic arrest via microtubule hyperstabilization but causes side effects due to its hydrophobicity and cellular promiscuity. The targeted cytotoxicity of hydrophilic paclitaxel-conjugated polyamidoamine (PAMAM) dendrimers has been demonstrated in cultured cancer cells. Mechanisms of action responsible for this cytotoxicity are unknown, that is, whether the cytotoxicity is due to paclitaxel stabilization of microtubules, as is whether paclitaxel is released intracellularly from the dendrimer. To determine whether the conjugated paclitaxel can bind microtubules, we used a combination of ensemble and single microtubule imaging techniques in vitro. We demonstrate that these conjugates adversely affect microtubules by (1) promoting the polymerization and stabilization of microtubules in a paclitaxel-dependent manner, and (2) bundling preformed microtubules in a paclitaxel-independent manner, potentially due to protonation of tertiary amines in the dendrimer interior. Our results provide mechanistic insights into the cytotoxicity of paclitaxel-conjugated PAMAM dendrimers and uncover unexpected risks of using such conjugates therapeutically.

Kinesin assembly and movement in cells.

Long-distance transport in eukaryotic cells is driven by molecular motors that move along microtubule tracks. Molecular motors of the kinesin superfamily contain a kinesin motor domain attached to family-specific sequences for cargo binding, regulation, and oligomerization. The biochemical and biophysical properties of the kinesin motor domain have been widely studied, yet little is known about how kinesin motors work in the complex cellular environment. We discuss recent studies on the three major families involved in intracellular transport (kinesin-1, kinesin-2, and kinesin-3) that have begun to bridge the gap in knowledge between the in vitro and in vivo behaviors of kinesin motors. These studies have increased our understanding of how kinesin subunits assemble to produce a functional motor, how kinesin motors are affected by biochemical cues and obstacles present on cellular microtubules, and how multiple motors on a cargo surface can work collectively for increased force production and travel distance.

Recording single motor proteins in the cytoplasm of mammalian cells.

Biomolecular motors are central to the function and regulation of all cellular transport systems. The molecular mechanisms by which motors generate force and motion along cytoskeletal filaments have been mostly studied in vitro using a variety of approaches, including several single-molecule techniques. While such studies have revealed significant insights into the chemomechanical transduction mechanisms of motors, important questions remain unanswered as to how motors work in cells. To understand how motor activity is regulated and how motors orchestrate the transport of specific cargoes to the proper subcellular domain requires analysis of motor function in vivo. Many transport processes in cells are believed to be powered by single or very few motor molecules, which makes it essential to track, in real time and with nanometer resolution, individual motors and their associated cargoes and tracks. Here we summarize, contrast, and compare recent methodological advances, many relying on advanced fluorescent labeling, genetic tagging, and imaging techniques, that lay the foundation for groundbreaking approaches and discoveries. In addition, to illustrate the impact and capabilities for these methods, we highlight novel biological findings where appropriate.