Pilot study of a ketogenic diet in bipolar disorder.

BACKGROUND: Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. However, no clinical trials have been conducted to date. AIMS: To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder. METHOD: Euthymic individuals with bipolar disorder were recruited to a 6-8 week trial of a modified ketogenic diet, and a range of clinical, economic and functional outcome measures were assessed. Study registration number: ISRCTN61613198. RESULTS: Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet for 6-8 weeks. The outcomes data-set was 95% complete for daily ketone measures, 95% complete for daily glucose measures and 95% complete for daily ecological momentary assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (s.d. = 0.77, median = 1.1) during the intervention period, and 91% of all readings indicated ketosis, suggesting a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range, with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant taking SGLT2-inhibitor medication). CONCLUSIONS: The recruitment and retention of euthymic individuals with bipolar disorder to a 6-8 week ketogenic diet intervention was feasible, with high completion rates for outcome measures. The majority of participants reached and maintained ketosis, and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.

The Potential of Naturalistic Eye Movement Tasks in the Diagnosis of Alzheimer's Disease: A Review.

Extensive research has demonstrated that eye-tracking tasks can effectively indicate cognitive impairment. For example, lab-based eye-tracking tasks, such as the antisaccade task, have robustly distinguished between people with Alzheimer's disease (AD) and healthy older adults. Due to the neurodegeneration associated with AD, people with AD often display extended saccade latencies and increased error rates on eye-tracking tasks. Although the effectiveness of using eye tracking to identify cognitive impairment appears promising, research considering the utility of eye tracking during naturalistic tasks, such as reading, in identifying cognitive impairment is limited. The current review identified 39 articles assessing eye-tracking distinctions between people with AD, mild cognitive impairment (MCI), and healthy controls when completing naturalistic task (reading, real-life simulations, static image search) or a goal-directed task involving naturalistic stimuli. The results revealed that naturalistic tasks show promising biomarkers and distinctions between healthy older adults and AD participants, and therefore show potential to be used for diagnostic and monitoring purposes. However, only twelve articles included MCI participants and assessed the sensitivity of measures to detect cognitive impairment in preclinical stages. In addition, the review revealed inconsistencies within the literature, particularly when assessing reading tasks. We urge researchers to expand on the current literature in this area and strive to assess the robustness and sensitivity of eye-tracking measures in both AD and MCI populations on naturalistic tasks.

Massive Leiomyomatous Uterine Proliferation Following Kidney Transplantation: A Case Report and Literature Review.

Uterine fibroids are the most common benign uterine tumors affecting > 50% of premenopausal women. The incidence, burden and symptoms from uterine fibroids are higher in women of African descent compared to Caucasians. Despite increasing number of African American females being evaluated for and undergoing kidney transplantation (KT), perioperative management guidelines for uterine fibroids currently do not exist. We present a case of a 40 y/o African American female with known symptomatic uterine fibroids preoperatively and medically managed, who underwent a successful KT and 4 years later progressively developed massive leiomyomatous uterine proliferation, causing a complete lateral displacement of the transplanted kidney with severe hydronephrosis, transplant ureteral obstruction and secondary urinary tract infections with bacteremia. This obstruction required a percutaneous nephrostomy tube placement followed by an interval transabdominal hysterectomy, which was complicated by transplant ureteral transection requiring ureteral reimplantation, resulting in prolonged hospitalization, follow-up and outpatient antibiotic regimen. There is a need for management guidelines for uterine fibroids incidentally encountered during the KT evaluation process to avoid similar preventable post-KT complications in patient populations most commonly affected. Literature review and perioperative management/surveillance strategies are provided.

How could discharge management affect Florida spring fish assemblage structure?

Freshwater bodies are increasingly affected by reductions in water quantity and quality and by invasions of exotic species. To protect water quantity and maintain the ecological integrity of many water bodies in central Florida, a program of adopting Minimum Flows and Levels (MFLs) has begun for both lentic and lotic waters. The purpose of this study was to determine whether there were relationships between discharge and stage, water quality, and biological parameters for Volusia Blue Spring, a first magnitude spring (discharge > 380,000 m3 day-1 or 100 mgd) for which an MFL program was adopted in 2006. Over the course of fourteen years, we assessed fish density and diversity weekly, monthly, or seasonally with seine and snorkel counts. We evaluated annual changes in the assemblages for relationships with water quantity and quality. Low discharge and dissolved oxygen combined with high stage and conductivity produced a fish population with a lower density and diversity in 2014 than in previous years. Densities of fish taxonomic/functional groups also were low in 2014 and measures of water quantity were significant predictors of fish assemblage structure. As a result of the strong relationships between variation in discharge and an array of chemical and biological characteristics of the spring, we conclude that maintaining the historical discharge rate is important for preserving the ecological integrity of Volusia Blue Spring.

Effect of lyophilization and freeze-thawing on the stability of siRNA-liposome complexes.

The purpose of this research was to describe the application of lyophilization in the delivery of siRNA using cationic lipids by addressing the long-term formulation/stability issues associated with cationic lipids and to understand the mechanism of lyoprotection. siRNA liposomes complexes were formed in different potential cyro/lyoprotectants and subjected to either lyophilization or freeze thaw cycles. siRNA, liposomes and/or lipoplexes were tested for activity, SYBR Green I binding, cellular uptake and particle size. The lipoplexes when lyophilized in the presence of sugars as lyoprotectants could be lyophilized and reconstituted without loss of transfection efficacy but in ionic solutions they lost 65-75% of their functionality. The mechanism of this loss of activity was further investigated. The lyophilization process did not alter siRNA's intrinsic biological activity as was evident by the ability of lyophilized siRNA to retain functionality and SYBR green I binding ability. While the lipoplex size dramatically increased ( approximately 50-70 times) after lyophilization in the absence of non-ionic lyoprotectants. This increase in size correlated to the decrease in cellular accumulation of siRNA and a decrease in activity. In conclusion, siRNAs can be applied in cationic lipid lyophilized formulations and these complexes represent a potential method of increasing the stability of pre-formed complex.

Lateral line receptors: where do they come from developmentally and where is our research going?

The lateral line system is composed of both mechanoreceptors, which exhibit little variation in structure between taxonomic groups, and electroreceptors, which exhibit considerably more variation. Cathodally sensitive ampullary electroreceptors are the primitive condition and are found in agnathans, chondrichthyans, and most osteichthyans. Aquatic amphibians also have ampullary electroreceptors for at least part of their life cycle. The more recently evolved anodally sensitive ampullary electroreceptors and tuberous electroreceptors are only found in four groups of teleost fishes. The basic ontogenetic unit of lateral line development is the dorsolateral placode. Primitively, there are six pairs of placodes, which pass through sequential stages of development into lateral line receptors. There is no question about the origin of primitive mechanoreceptors or electroreceptors, however, we do not have a good understanding of the origin of teleost mechanoreceptors and their ampullary or tuberous electroreceptors; do they come exclusively from dorsolateral placodes or from neural crest or even general ectoderm? A second intriguing lateral line question is how certain teleost fish groups evolved tuberous electroreceptors. Electroreception appears to have re-evolved at least twice in teleosts after being lost during the neopterygian radiation. It has been suggested that the development of tuberous electroreceptors might be due to changes in placodal patterning or a change in the general ectoderm that placodes arise from. Unfortunately, our understanding of lateral line origins in fishes is very sketchy, and, if we are to answer such an evolutionary question, we first need more complete information about lateral line development in a variety of fishes, which can then be combined with gene expression data to better interpret lateral line receptor development.

Development of the lateral line system in the shovelnose sturgeon.

The lateral line systems of aquatic amphibians and all chondrichthyan and osteichthyan fish present a similar array of mechanoreceptors. However, electroreceptors, the second major component of the lateral line system, have clearly undergone more significant evolutionary change. Chondrichthyans and non-neopterygian fish possess primitive ampullary organ electroreceptors, whereas significantly different 'new' ampullary organs and tuberous electroreceptors are found in a few groups of teleosts (mormyrids, gymnotids and some catfish). The pairing of mechano- and electroreceptors in the lateral line system, as well as the morphologically and physiologically distinct electroreceptors of teleosts have inspired several recent studies on the origin and evolution of the lateral line receptors. We described the development of the lateral line system in sturgeon (Scaphirhynchus platorynchus) as part of an outgroup analysis of lateral line development in three taxa: vertebrates that have both mechanoreceptive neuromasts and primitive electroreceptors; neopterygian fish that only have mechanoreceptors; and teleosts that have re-evolved new electroreceptors. Development in Scaphirhynchus was consistent with previously studied taxa in that the lateral line system developed from a series of six dorsolateral placodes. Interestingly, we found that the octaval placode was bound rostrally and caudally by large placodal fields, out of which the six lateral line placodes arose. This finding supports recent suggestions for a common placodal primordium for all placodes. Each of the six placodes gave rise to the lateral line nerves before elongating into sensory ridges, which contained neuromast primordia. The ampullary organ fields of Scaphirhynchus arose from the lateral zones of the anterodorsal, anteroventral, otic and supratemporal sensory ridges, which is also consistent with recently studied taxa. Comparisons of the lateral line system of Scaphirhynchus and close relatives, Acipenser and Polyodon, indicate that variation in some aspects of lateral line receptor numbers and distribution are related to changes in head morphology and feeding strategy, whereas other changes, such as a reduction in receptor number without a change in placode field size, indicate changes in placode development.

Retinoic acid repatterns axolotl lateral line receptors.

The effects of all-trans retinoic acid on the development of the lateral line placodes of axolotls was studied. Late gastrula and early neurula were exposed to 10(-7) to 10(-5) M retinoic acid for one hour and then reared until they would normally be feeding larvae. As in other vertebrates, the extent of the developmental abnormalities is concentration dependent. Those embryos exposed to the highest concentration of retinoic acid failed to form much of the forebrain and midbrain, including the olfactory, optic and otic organs, which were reduced or absent. Although all lateral line placodes continued to generate fully formed receptors and cranial nerves, the production of neuromasts and the organization of these receptors into lines were markedly reduced. Equally important, all of the placodes at the highest concentration of retinoic acid failed to generate ampullary organs, thereby indicating a strong posteriorizing effect of retinoic acid on these placodes.