Understanding the experiences of ketogenic metabolic therapy for people living with varying levels of depressive symptoms: a thematic analysis.

Background: Evidence suggests that a ketogenic diet (KD) may help to alleviate psychiatric symptoms, including depression and anxiety. Positive changes have been reported such as improvements in cognition, concentration, and sleep, a reduction in hunger, and an increase in well-being, energy, confidence, and resilience. This research aims to understand the impact of a non-calorie-restricted KD on depression and aspects of psychological well-being in those with varying degrees of depressive symptoms. Though there are a few studies directly exploring the experiences of those following a KD, this will be the first study to explore the narrative from a mental health and psychological well-being viewpoint. Method: A sample of nine participants who had followed a non-calorie restricted KD intervention of 50 g of carbohydrates or less per day for at least 12 weeks were recruited. Participants were split into 'healthy adults' group who had no to low depressive symptoms and 'depressive symptoms' group who had mild to moderate depressive symptoms. A reflexive thematic analysis was considered suitable for this study. Findings: Five core themes and 24 subthemes were created. These were, (1) Poor health prior to program; (2) Hunger and cravings-the food and mood connection; (3) Psychological well-being improvements; (4) It becomes a lifestyle; and (5) Implementation difficulties. Participants experienced mental health improvements such as increased self-esteem, confidence, motivation, and achievement. Some experienced more control in life and a greater sense of reward. Those with depressive symptoms who initially reported low self-worth and hopelessness later reported increased self-esteem and renewed meaning and purpose in life. The findings from this study reflect the previous reports that the diet implementation can be difficult initially, but soon becomes easy to follow and turns into a lifestyle. Conclusion: In the literature, there are very few qualitative studies that explore the accounts and lived experiences of those following a KD. From the participants' accounts in this study, it appears that the benefits and positive outcomes of this diet outweigh any negative side-effects experienced. This is encouraging for those who are looking for adjunctive therapies to address and improve their depressive symptoms and overall mental health.

Unveiling Discrepant and Rare Dihydropyrimidine Dehydrogenase (DPYD) Results Using an In-House Genotyping Test: A Case Series.

Fluoropyrimidine chemotherapy is a primary component of many solid tumor treatment regimens, particularly those for gastrointestinal malignancies. Approximately one-third of patients receiving fluoropyrimidine-based chemotherapies experience serious adverse effects. This risk is substantially higher in patients carrying DPYD genetic variants, which cause reduced fluoropyrimidine metabolism and inactivation (ie, dihydropyridine dehydrogenase [DPD] deficiency). Despite the known relationship between DPD deficiency and severe toxicity risk, including drug-related fatalities, pretreatment DPYD testing is not standard of care in the United States. We developed an in-house DPYD genotyping test that detects 5 clinically actionable variants associated with DPD deficiency, and genotyped 827 patients receiving fluoropyrimidines, of which 49 (6%) were identified as heterozygous carriers. We highlight 3 unique cases: (1) a patient with a false-negative result from a commercial laboratory that only tested for the c.1905 + 1G>A (*2A) variant, (2) a White patient in whom the c.557A>G variant (typically observed in people of African ancestry) was detected, and (3) a patient with the rare c.1679T>G (*13) variant. Lastly, we evaluated which DPYD variants are detected by commercial laboratories offering DPYD genotyping in the United States and found 6 of 13 (46%) did not test for all 5 variants included on our panel. We estimated that 20.4% to 81.6% of DPYD heterozygous carriers identified on our panel would have had a false-negative result if tested by 1 of these 6 laboratories. The sensitivity and negative predictive value of the diagnostic tests from these laboratories ranged from 18.4% to 79.6% and 95.1% to 98.7%, respectively. These cases underscore the importance of comprehensive DPYD genotyping to accurately identify patients with DPD deficiency who may require lower fluoropyrimidine doses to mitigate severe toxicities and hospitalizations. Clinicians should be aware of test limitations and variability in variant detection by commercial laboratories, and seek assistance by pharmacogenetic experts or available resources for test selection and result interpretation.

A Monometallic Bis(cyaphido) Complex.

The first example of a bis(cyaphido) complex, trans-[Ru(dppe)2(C≡P)2], is described, unequivocally demonstrating the synthetic accessibility and stability of complexes that feature more than one cyaphido ligand. Synthesis is achieved from the precedent cation [Ru(dppe)2(C≡P)]+ via sequential coordination and desilylation of the phosphaalkyne Me3SiC≡P. The heteroleptic analogue trans-[Ru(dppe)2(C≡N)(C≡P)] is also prepared from the same cation and NaCN; both cyaphido complexes are structurally characterized, enabling the first direct comparison of cyaphide with cyanide, its isoelectronic and isolobal counterpart. This demonstrates an enhanced π-acidity for -C≡P over -C≡N, while computational studies reveal also a higher π-donor character for the cyaphido ligand.

Depth variation in benthic community response to repeated marine heatwaves on remote Central Indian Ocean reefs.

Coral reefs are increasingly impacted by climate-induced warming events. However, there is limited empirical evidence on the variation in the response of shallow coral reef communities to thermal stress across depths. Here, we assess depth-dependent changes in coral reef benthic communities following successive marine heatwaves from 2015 to 2017 across a 5-25 m depth gradient in the remote Chagos Archipelago, Central Indian Ocean. Our analyses show an overall decline in hard and soft coral cover and an increase in crustose coralline algae, sponge and reef pavement following successive marine heatwaves on the remote reef system. Our findings indicate that the changes in benthic communities in response to elevated seawater temperatures varied across depths. We found greater changes in benthic group cover at shallow depths (5-15 m) compared with deeper zones (15-25 m). The loss of hard coral cover was better predicted by initial thermal stress, while the loss of soft coral was associated with repeated thermal stress following successive warming events. Our study shows that benthic communities extending to 25 m depth were impacted by successive marine heatwaves, supporting concerns about the resilience of shallow coral reef communities to increasingly severe climate-driven warming events.

Genome characterization of the novel lytic phage vB_AbaAut_ChT04 and the antimicrobial activity of its lysin peptide against Acinetobacter baumannii isolates from different time periods.

Acinetobacter baumannii is an important opportunistic pathogen, usually associated with immunocompromised individuals with a prolonged period of stay in a hospital. Currently, the incidence of multi-drug resistant A. baumannii (MDR-AB) and extensively drug-resistant A. baumannii (XDR-AB) is increasing rapidly in Thailand, mirroring the trend worldwide. Novel therapeutic approaches for the treatment of A. baumannii infection using bacteriophages are being evaluated, and the use of phage-derived peptides is being tested as alternative approach to fighting infection. In this study, we isolated and determined the biological features of a lytic A. baumannii phage called vB_AbaAut_ChT04 (vChT04). The vChT04 phage was classified as a member of the family Autographiviridae of the class Caudoviricetes. It showed a short latent period (10 min) and a large burst size (280 PFU cell-1), and it was able to infect 52 out of 150 clinical MDR-AB strains tested (34.67%). Most of the phage-sensitive strains were A. baumannii strains that had been isolated during the same year that the phage was isolated. The phage showed activity across a broad pH (pH 5.0-8.0) and temperature (4-37°C) range. Whole-genome analysis revealed that the vChT04 genome comprises 41,158 bp with a 39.3% GC content and contains 48 open reading frames (ORFs), 28 of which were assigned putative functions based on homology to previously identified phage genes. Comparative genomic analysis demonstrated that vChT04 had the highest similarity to phage vB_AbaP_WU2001, which was isolated in the southern part of Thailand. An endolysin gene found in the vChT04 genome was used to synthesize an antimicrobial peptide (designated as PLysChT04) and its antimicrobial activity was evaluated using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. The MIC and MBC values of peptide PLysChT04 against MDR-AB and XDR-AB were 312.5-625 µg/mL, and it was able to inhibit both phage-susceptible and phage-resistant isolates collected over different time periods. PLysChT04 showed good efficacy in killing drug-resistant A. baumannii and other bacterial strains, and it is a promising candidate for development as an alternative therapeutic agent targeting A. baumannii infections.

Ferromagnetic resonators synthesized by metal-organic decomposition epitaxy.

Metal-organic decomposition epitaxy is an economical wet-chemical approach suitable to synthesize high-quality low-spin-damping films for resonator and oscillator applications. This work reports the temperature dependence of ferromagnetic resonances and associated structural and magnetic quantities of yttrium iron garnet nanofilms that coincide with single-crystal values. Despite imperfections originating from wet-chemical deposition and spin coating, the quality factor for out-of-plane and in-plane resonances approaches 600 and 1000, respectively, at room temperature and 40 GHz. These values increase with temperature and are 100 times larger than those offered by commercial devices based on complementary metal-oxide semiconductor voltage-controlled oscillators at comparable production costs.

An extension of the BioAssay Ontology to include pharmacokinetic/pharmacodynamic terminology for the enrichment of scientific workflows.

With the capacity to produce and record data electronically, Scientific research and the data associated with it have grown at an unprecedented rate. However, despite a decent amount of data now existing in an electronic form, it is still common for scientific research to be recorded in an unstructured text format with inconsistent context (vocabularies) which vastly reduces the potential for direct intelligent analysis. Research has demonstrated that the use of semantic technologies such as ontologies to structure and enrich scientific data can greatly improve this potential. However, whilst there are many ontologies that can be used for this purpose, there is still a vast quantity of scientific terminology that does not have adequate semantic representation. A key area for expansion identified by the authors was the pharmacokinetic/pharmacodynamic (PK/PD) domain due to its high usage across many areas of Pharma. As such we have produced a set of these terms and other bioassay related terms to be incorporated into the BioAssay Ontology (BAO), which was identified as the most relevant ontology for this work. A number of use cases developed by experts in the field were used to demonstrate how these new ontology terms can be used, and to set the scene for the continuation of this work with a look to expanding this work out into further relevant domains. The work done in this paper was part of Phase 1 of the SEED project (Semantically Enriching electronic laboratory notebook (eLN) Data).

Effect of different adjuvant formulations on the antibody response of horses to porcine zona pellucida proteins.

Immunization with porcine zona pellucida (PZP) proteins is being used successfully to induce infertility in wildlife including horses. However, widespread adoption of this method to control the growth of horse populations requires further refinement in order to induce long-term infertility, reduce the frequency and severity of injection site reactions, and make the vaccines easier to administer. The next generation of PZP-based vaccines will likely be a controlled-release formulation with different adjuvants from the Freund's adjuvants used in existing vaccines. We evaluated the response of equine peripheral blood mononuclear cells to a cationic nanoparticle adjuvant, Nano-11, alone and with the TLR agonists poly(I:C) and CpG ODN as a screen to develop an adjuvant system suitable for immunization of horses. The secretion of IL-1ß, TNF and CXCL10 were used as readouts. The combination of poly(I:C) with Nano-11 significantly increased the secretion of IL-1ß and TNF in comparison with Nano-11 only, with little effect of further addition of CpG ODN. The efficacy of the Nano-11/poly(I:C) adjuvant to enhance the immune response to native PZP proteins was determined in horses. Horses were immunized twice with the licensed Zonastat-H vaccine or PZP with Nano-11/poly(I:C) emulsified in silicone oil. A third group received PZP with the saponin adjuvant QA-21 emulsified in silicone oil. The horse sera collected monthly after the injections had increased anti-PZP IgG antibodies with the strongest response observed with Zonastat-H. We conclude that Nano-11/poly(I:C) is a potential candidate for the development of a controlled release formulation of a next generation PZP-based immunocontraception.

Fertility Control and the Welfare of Free-Roaming Horses and Burros on U.S. Public Lands: The Need for an Ethical Framing.

To be effective and publicly acceptable, management of free-roaming horses and burros in the United States and elsewhere needs a consistent ethical framing of the animals and the land they occupy. In the U.S., the two laws that largely govern wild horse and burro management, the 1971 Wild Free-Roaming Horse and Burro Act and the 1976 Federal Land Policy and Management Act ("FLPMA"), rest on conflicting foundations, the former based on an ethic of care and the latter on largely utilitarian principles. These conflicts specifically fuel debates over the selection of appropriate fertility control agents for horse and burro management. Because land-use and management decisions are largely controlled by the FLPMA, and because the ethical treatment of animals is typically considered under conditions established by their use, both the larger debate about equids and land management and the specific debate about fertility control are dominated by cost/benefit calculations and avoid broader ethical considerations. In our view, the long-term health and ethical treatment of free-roaming horses and burros, the lands they occupy, and the wildlife and people they share it with will require the replacement of the resource-use model with a more holistic, care-based approach.

Linking variation in planktonic primary production to coral reef fish growth and condition.

Within low-nutrient tropical oceans, islands and atolls with higher primary production support higher fish biomass and reef organism abundance. External energy subsidies can be delivered onto reefs via a range of physical mechanisms. However, the influence of spatial variation in primary production on reef fish growth and condition is largely unknown. It is not yet clear how energy subsidies interact with reef depth and slope. Here we test the hypothesis that with increased proximity to deep-water oceanic nutrient sources, or at sites with shallower reef slopes, parameters of fish growth and condition will be higher. Contrary to expectations, we found no association between fish growth rate and sites with higher mean chlorophyll-a values. There were no differences in fish δ 15N or δ 13C values between depths. The relationship between fish condition and primary production was influenced by depth, driven by increased fish condition at shallow depths within a primary production 'hotspot' site. Carbon δ 13C was depleted with increasing primary production, and interacted with reef slope. Our results indicate that variable primary production did not influence growth rates in planktivorous Chromis fieldi within 10-17.5 m depth, but show site-specific variation in reef physical characteristics influencing fish carbon isotopic composition.

Central tropical Pacific convection drives extreme high temperatures and surface melt on the Larsen C Ice Shelf, Antarctic Peninsula.

Northern sections of the Larsen Ice Shelf, eastern Antarctic Peninsula (AP) have experienced dramatic break-up and collapse since the early 1990s due to strong summertime surface melt, linked to strengthened circumpolar westerly winds. Here we show that extreme summertime surface melt and record-high temperature events over the eastern AP and Larsen C Ice Shelf are triggered by deep convection in the central tropical Pacific (CPAC), which produces an elongated cyclonic anomaly across the South Pacific coupled with a strong high pressure anomaly over Drake Passage. Together these atmospheric circulation anomalies transport very warm and moist air to the southwest AP, often in the form of "atmospheric rivers", producing strong foehn warming and surface melt on the eastern AP and Larsen C Ice Shelf. Therefore, variability in CPAC convection, in addition to the circumpolar westerlies, is a key driver of AP surface mass balance and the occurrence of extreme high temperatures.

Gut microbiota of wild fish as reporters of compromised aquatic environments sleuthed through machine learning.

Human-generated negative impacts on aquatic environments are rising. Despite wild fish playing a key role in aquatic ecologies and comprising a major global food source, physiological consequences of these impacts on them are poorly understood. Here we address the issue through the lens of interrelationship between wild fish and their gut microbiota, hypothesizing that fish microbiota are reporters of the aquatic environs. Two geographically separate teleost wild-fish species were studied (Lake Erie, Ohio, and Caribbean Sea, US Virgin Islands). At each geolocation, fresh fecal samples were collected from fish in areas of presence or absence of known aquatic compromise. Gut microbiota was assessed via microbial 16S-rRNA gene sequencing and represents the first complete report for both fish species. Despite marked differences in geography, climate, water type, fish species, habitat, diet, and gut microbial compositions, the pattern of shifts in microbiota shared by both fish species was nearly identical due to aquatic compromise. Next, these data were subjected to machine learning (ML) to examine reliability of using the fish-gut microbiota as an ecomarker for anthropogenic aquatic impacts. Independent of geolocation, ML predicted aquatic compromise with remarkable accuracy (>90%). Overall, this study represents the first multispecies stress-related comparison of its kind and demonstrates the potential of artificial intelligence via ML as a tool for biomonitoring and detecting compromised aquatic conditions.

Long-term survival and toxicity in patients with neuroendocrine tumors treated with 177 Lu-octreotate peptide radionuclide therapy.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) has shown favorable results in neuroendocrine tumors (NETs). Long-term safety and efficacy data for 177 Lu-octreotate PRRT, particularly in combination with chemotherapy, is lacking. METHODS: The authors conducted a retrospective review of the long-term toxicity and survival outcomes of 104 patients with advanced NETs treated on 4 phase 2 clinical trials with Lutetium-177-octreotate (177 Lu-octreotate) PRRT, mostly in combination with chemotherapy. Median follow-up was 68 months, which represents the longest follow-up study of 177 Lu-octreotate PRRT for NETs to date. RESULTS: Median progression-free survival (PFS) was 37 months, and median overall survival (OS) was 71 months. Five- and 10-year OS were 62% and 29%, and 5- and 10-year PFS were 36% and 21%, respectively, demonstrating 177 Lu-octreotate can provide durable responses. PRRT was well tolerated with 1.9% of patients developing chronic renal impairment and 1% of patients developing long-term thrombocytopenia. Interestingly, there was a relatively high rate of myelodysplasia (MDS)/leukemia (6.7%), possibly attributable to the longer follow-up (with all except 1 case occurring more than 4 years after PRRT treatment) or to the addition of concurrent chemotherapy. CONCLUSIONS: Lutetium-177-Octreotate PRRT remains an efficacious and well tolerated treatment in long-term follow-up. For clinicians deciding on the timing of PRRT for individual patients, the 6.7% long-term risk of MDS/leukemia needs to be balanced against the 21% PFS at 10 years.

Sample Selection Bias Due to Differential Mortality: A Supplementary Measure of Old-Age Poverty.

Traditional "head count" measures of poverty at advanced older ages understate the risk of falling into poverty because of survivorship bias due to the income-mortality gradient, which indicates that people in poverty have higher mortality rates than people with higher income. Survivorship bias is a form of sample selection bias. This paper presents a supplementary measure for poverty at older ages, based on an adaption of a model for correcting survivorship bias in rate of return data for mutual funds. Using U.S. longitudinal data from the Health and Retirement Study (HRS) for 1996 and 2002-2012 for the same cohort, we develop a new estimate of poverty at older ages that suggests that traditional cross-sectional measures understate the risk of falling into poverty by roughly a quarter. This finding has important implications for social programs that relate to the causes and consequences of the selectivity bias.

Predictors of suicide attempts in male UK gamblers seeking residential treatment.

BACKGROUND: Disordered gambling can have serious negative consequences for the individual and those around them. Previous research has indicated that disordered gamblers are at an increased risk of suicidal thoughts, ideation and attempts. The current study sought to utilise data from a clinical sample to identify factors that are associated with prior suicide attempts. METHODS: The sample included 621 patients entering a gambling-specific residential facility in the UK. A series of Chi-Square analyses and binary logistic regressions were run to identify clinical and sociodemographic variables associated with suicide attempts. RESULTS: Of the 20 variables analysed using Chi-square statistics, five were significantly associated with the outcome variable (lifetime attempted suicide): loss of family relationships, loss of home, prior depression, prior suicidal thoughts, and medication use. Regression analysis showed that individuals were more likely to have reported suicide attempts if they had experienced loss of family relationships (1.65 times), loss of a home (1.87 times), prior depression (3.2 times), prior suicidal thoughts (6.14 times), or were taking medication (1.95 times) compared to those not reporting such individual events. CONCLUSIONS: Disordered gamblers are vulnerable to suicide; a number of factors have been identified in the current study that predict an increased likelihood of attempted suicide. The factors mainly revolve around loss: not financial loss, but rather disintegration of an individual's support network and deterioration in the individual's mental health. Findings indicate that isolation and negative affect associated with gambling are most influential in attempted suicide and should therefore be more strongly considered when creating and providing the legislative, educational and treatment environments for those experiencing gambling related harm.

Atoll-dependent variation in depth zonation of benthic communities on remote reefs.

The distribution and organisation of benthic organisms on tropical reefs are typically heterogenous yet display distinct zonation patterns across depth gradients. However, there are few datasets which inform our understanding of how depth zonation in benthic community composition varies spatially among and within different reef systems. Here, we assess the depth zonation in benthic forereef slope communities in the Central Indian Ocean, prior to the back-to-back bleaching events in 2014-2017. We compare benthic communities between shallow (5-10 m) and deep (20-25 m) sites, at two spatial scales: among and within 4 atolls. Our analyses showed the variation in both major functional groups and hard coral assemblages between depth varied among atolls, and within-atoll comparisons revealed distinct differences between shallow and deep forereef slope communities. Indicator taxa analyses characterising the hard coral community between depths revealed a higher number of coral genera characteristic of the deep forereef slopes (10) than the shallow forereef slopes (6). Only two coral genera consistently associated with both depths across all atolls, and these were Acropora and Porites. Our results reveal spatial variation in depth zonation of benthic communities, potentially driven by biophysical processes varying across depths and atolls, and provide a baseline to understand and measure the impacts of future global climate change on benthic communities across depths.

Adaptive strategies of sponges to deoxygenated oceans.

Ocean deoxygenation is one of the major consequences of climate change. In coastal waters, this process can be exacerbated by eutrophication, which is contributing to an alarming increase in the so-called 'dead zones' globally. Despite its severity, the effect of reduced dissolved oxygen has only been studied for a very limited number of organisms, compared to other climate change impacts such as ocean acidification and warming. Here, we experimentally assessed the response of sponges to moderate and severe simulated hypoxic events. We ran three laboratory experiments on four species from two different temperate oceans (NE Atlantic and SW Pacific). Sponges were exposed to a total of five hypoxic treatments, with increasing severity (3.3, 1.6, 0.5, 0.4 and 0.13 mg O2  L-1 , over 7-12-days). We found that sponges are generally very tolerant of hypoxia. All the sponges survived in the experimental conditions, except Polymastia crocea, which showed significant mortality at the lowest oxygen concentration (0.13 mg O2  L-1 , lethal median time: 286 h). In all species except Suberites carnosus, hypoxic conditions do not significantly affect respiration rate down to 0.4 mg O2  L-1 , showing that sponges can uptake oxygen at very low concentrations in the surrounding environment. Importantly, sponges displayed species-specific phenotypic modifications in response to the hypoxic treatments, including physiological, morphological and behavioural changes. This phenotypic plasticity likely represents an adaptive strategy to live in reduced or low oxygen water. Our results also show that a single sponge species (i.e., Suberites australiensis) can display different strategies at different oxygen concentrations. Compared to other sessile organisms, sponges generally showed higher tolerance to hypoxia, suggesting that sponges could be favoured and survive in future deoxygenated oceans.

Safety Evaluation for Restorin® NMN, a NAD+ Precursor.

NAD+ is an abundant molecule in the body and vital to all living cells. NAD+ levels decline with age, and this decline correlates with age-related diseases. Therefore, sustaining NAD+ levels offers potential benefits to healthspan and longevity. Here we conducted toxicity studies to evaluate the safety of Restorin® NMN, a high purity form of the direct NAD+ precursor, ß-nicotinamide mononucleotide (NMN). Based on the preliminary toxicity study and a 14-days repeated dose toxicity study at a higher dose level exposure, Restorin® NMN was administered orally to Sprague-Dawley rats for 91 days followed by a 14-days recovery period. The oral doses of 500, 1,000, and 2000 mg/kg/day were compared. There were no test item-related findings that could be considered adverse events in animals dosed at 500 mg/kg/day. The findings in the Restorin® NMN high dose group (2000 mg/kg/day) were similar to the reference item (Nicotinamide Riboside Chloride) dosed at 1740 mg/kg/day: reduced body weight, reductions in body weight gains, and diminished food consumption. In conclusion, the No-Observed-Adverse-Effect-Level (NOAEL) for Restorin® NMN is 1,000 mg/kg/day in female rats and 500 mg/kg/day in male rats, and the Low-Observed-Adverse-Effect-Level (LOAEL) for Resotrin® NMN is 2000 mg/kg/day.

Protection outcomes for fish trophic groups across a range of management regimes.

Understanding how Marine Protected Areas (MPAs) improve conservation outcomes across anthropogenic pressures can improve the benefits derived from them. Effects of protection for coral reefs in the western and central Indian Ocean were assessed using size-spectra analysis of fish and the relationships of trophic group biomass with human population density. Length-spectra relationships quantifying the relative abundance of small and large fish (slope) and overall productivity of the system (intercept) showed inconsistent patterns with MPA protection. The results suggest that both the slopes and intercepts were significantly higher in highly and well-protected MPAs. This indicates that effective MPAs are more productive and support higher abundances of smaller fish, relative to moderately protected MPAs. Trophic group biomass spanning piscivores and herbivores, decreased with increasing human density implying restoration of fish functional structure is needed. This would require addressing fisher needs and supporting effective MPA management to secure ecosystem benefits for coastal communities.