Glucose Monitoring Metrics in Individuals With Type 1 Diabetes Using Different Treatment Modalities: A Real-World Observational Study.

OBJECTIVE: This study aimed to investigate the association between continuous glucose monitoring (CGM)-derived glycemic metrics and different insulin treatment modalities using real-world data. RESEARCH DESIGN AND METHODS: A cross-sectional study at Steno Diabetes Center Copenhagen, Denmark, included individuals with type 1 diabetes using CGM. Data from September 2021 to August 2022 were analyzed if CGM was used for at least 20% of a 4-week period. Individuals were divided into four groups: multiple daily injection (MDI) therapy, insulin pumps with unintegrated CGM (SUP), sensor-augmented pumps with low glucose management (SAP), and automated insulin delivery (AID). The MDI and SUP groups were further subdivided based on CGM alarm features. The primary outcome was percentage of time in range (TIR: 3.9-10.0 mmol/L) for each treatment group. Secondary outcomes included other glucose metrics and HbA1c. RESULTS: Out of 6,314 attendees, 3,184 CGM users were included in the analysis. Among them, 1,622 used MDI, 504 used SUP, 354 used SAP, and 561 used AID. Median TIR was 54.0% for MDI, 54.9% for SUP, 62,9% for SAP, and 72,1% for AID users. The proportion of individuals achieving all recommended glycemic targets (TIR >70%, time above range <25%, and time below range <4%) was significantly higher in SAP (odds ratio [OR] 2.4 [95% CI 1.6-3.5]) and AID (OR 9.4 [95% CI 6.7-13.0]) compared with MDI without alarm features. CONCLUSIONS: AID appears superior to other insulin treatment modalities with CGM. Although bias may be present because of indications, AID should be considered the preferred choice for insulin pump therapy.

Feasibility of Monitoring Patients Who Have Cancer With a Smart T-shirt: Protocol for the OncoSmartShirt Study.

BACKGROUND: Studies have shown that there may be dissimilar perceptions on symptoms or side effects between patients with cancer and health care professionals. This may lead to symptomatic patients notifying the clinic irregularly or not telling the clinic at all. Wearables could help identify symptoms earlier. Patients with low socioeconomic status and less self-awareness of their health may benefit from this. A new design of wearables is a smart t-shirt that, with embedded sensors, provides measurement flows such as electrocardiogram, thoracic and abdominal respiration, and temperature. OBJECTIVE: This study evaluates the feasibility of using a smart t-shirt for home monitoring of biometric sensor data in adolescent and young adult and elderly patients during cancer treatment. METHODS: The OncoSmartShirt study is an explorative study investigating the feasibility of using the Chronolife smart t-shirt during cancer treatment. This smart t-shirt is designed with multiple fully embedded sensors and electrodes that engender 6 different measurement flows continuously. A total of 20 Danish patients with cancer ≥18 years old in antineoplastic treatment at Department of Oncology Rigshospitalet Denmark will be recruited from all cancer wards, whether patients are in curative or palliative care. Of these 20 patients, 10 (50%) will be <39 years old, defined as adolescent and young adult, and 10 (50%) will be patients >65 years old, defined as elderly. Consenting patients will be asked to wear a smart t-shirt daily for 2 weeks during their treatment course. RESULTS: The primary outcome is to determine if it is feasible to wear a smart t-shirt throughout the day (preferably 8 hours per day) for 2 weeks. Inclusion of patients started in March 2022. CONCLUSIONS: The study will assess the feasibility of using the Chronolife smart t-shirt for home monitoring of vital parameters in patients with cancer during their treatment and bring new insights into how wearables and biometric data can be used as part of symptom or side-effect recognition in patients with cancer during treatment, with the aim to increase patients' quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05235594; https://beta.clinicaltrials.gov/study/NCT05235594. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/37626.

Climate change leads to higher NPP at the end of the century in the Antarctic Tundra: Response patterns through the lens of lichens.

Poikilohydric autotrophs are the main colonizers of the permanent ice-free areas in the Antarctic tundra biome. Global climate warming and the small human footprint in this ecosystem make it especially vulnerable to abrupt changes. Elucidating the effects of climate change on the Antarctic ecosystem is challenging because it mainly comprises poikilohydric species, which are greatly influenced by microtopographic factors. In the present study, we investigated the potential effects of climate change on the metabolic activity and net primary photosynthesis (NPP) in the widespread lichen species Usnea aurantiaco-atra. Long-term monitoring of chlorophyll a fluorescence in the field was combined with photosynthetic performance measurements in laboratory experiments in order to establish the daily response patterns under biotic and abiotic factors at micro- and macro-scales. Our findings suggest that macroclimate is a poor predictor of NPP, thereby indicating that microclimate is the main driver due to the strong effects of microtopographic factors on cryptogams. Metabolic activity is also crucial for estimating the NPP, which is highly dependent on the type, distribution, and duration of the hydration sources available throughout the year. Under RCP 4.5 and RCP 8.5, metabolic activity will increase slightly compared with that at present due to the increased precipitation events predicted in MIROC5. Temperature is highlighted as the main driver for NPP projections, and thus climate warming will lead to an average increase in NPP of 167-171% at the end of the century. However, small changes in other drivers such as light and relative humidity may strongly modify the metabolic activity patterns of poikilohydric autotrophs, and thus their NPP. Species with similar physiological response ranges to the species investigated in the present study are expected to behave in a similar manner provided that liquid water is available.

Using Biometric Sensor Data to Monitor Cancer Patients During Radiotherapy: Protocol for the OncoWatch Feasibility Study.

BACKGROUND: Patients with head and neck cancer (HNC) experience severe side effects during radiotherapy (RT). Ongoing technological advances in wearable biometric sensors allow for the collection of objective data (eg, physical activity and heart rate), which might, in the future, help detect and counter side effects before they become severe. A smartwatch such as the Apple Watch allows for objective data monitoring outside the hospital with minimal effort from the patient. To determine whether such tools can be implemented in the oncological setting, feasibility studies are needed. OBJECTIVE: This protocol describes the design of the OncoWatch 1.0 feasibility study that assesses the adherence of patients with HNC to an Apple Watch during RT. METHODS: A prospective, single-cohort trial will be conducted at the Department of Oncology, Rigshospitalet (Copenhagen, Denmark). Patients aged ≥18 years intended for primary or postoperative curatively intended RT for HNC will be recruited. Consenting patients will be asked to wear an Apple Watch on the wrist during and until 2 weeks after RT. The study will include 10 patients. Data on adherence, data acquisition, and biometric data will be collected. Demographic data, objective toxicity scores, and hospitalizations will be documented. RESULTS: The primary outcome is to determine if it is feasible for the patients to wear a smartwatch continuously (minimum 12 hours/day) during RT. Furthermore, we will explore how the heart rate and physical activity change over the treatment course. CONCLUSIONS: The study will assess the feasibility of using the Apple Watch for home monitoring of patients with HNC. Our findings may provide novel insights into the patient's activity levels and variations in heart rate during the treatment course. The knowledge obtained from this study will be essential for further investigating how biometric data can be used as part of symptom monitoring for patients with HNC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04613232; https://clinicaltrials.gov/ct2/show/NCT04613232. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/26096.

Development of a Brassica napus (Canola) Crop Containing Fish Oil-Like Levels of DHA in the Seed Oil.

Plant seeds have long been promoted as a production platform for novel fatty acids such as the ω3 long-chain (≥ C20) polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) commonly found in fish oil. In this article we describe the creation of a canola (Brassica napus) variety producing fish oil-like levels of DHA in the seed. This was achieved by the introduction of a microalgal/yeast transgenic pathway of seven consecutive enzymatic steps which converted the native substrate oleic acid to α-linolenic acid and, subsequently, to EPA, docosapentaenoic acid (DPA) and DHA. This paper describes construct design and evaluation, plant transformation, event selection, field testing in a wide range of environments, and oil profile stability of the transgenic seed. The stable, high-performing event NS-B50027-4 produced fish oil-like levels of DHA (9-11%) in open field trials of T3 to T7 generation plants in several locations in Australia and Canada. This study also describes the highest seed DHA levels reported thus far and is one of the first examples of a deregulated genetically modified crop with clear health benefits to the consumer.

Engineering Trienoic Fatty Acids into Cottonseed Oil Improves Low-Temperature Seed Germination, Plant Photosynthesis and Cotton Fiber Quality.

Alpha-linolenic acid (ALA, 18:3Δ9,12,15) and γ-linolenic acid \ (GLA, 18:3Δ6,9,12) are important trienoic fatty acids, which are beneficial for human health in their own right, or as precursors for the biosynthesis of long-chain polyunsaturated fatty acids. ALA and GLA in seed oil are synthesized from linoleic acid (LA, 18:2Δ9,12) by the microsomal ω-3 fatty acid desaturase (FAD3) and Δ6 desaturase (D6D), respectively. Cotton (Gossypium hirsutum L.) seed oil composition was modified by transforming with an FAD3 gene from Brassica napus and a D6D gene from Echium plantagineum, resulting in approximately 30% ALA and 20% GLA, respectively. The total oil content in transgenic seeds remained unaltered relative to parental seeds. Despite the use of a seed-specific promoter for transgene expression, low levels of GLA and increased levels of ALA were found in non-seed cotton tissues. At low temperature, the germinating cottonseeds containing the linolenic acid isomers elongated faster than the untransformed controls. ALA-producing lines also showed higher photosynthetic rates at cooler temperature and better fiber quality compared to both untransformed controls and GLA-producing lines. The oxidative stability of the novel cottonseed oils was assessed, providing guidance for potential food, pharmaceutical and industrial applications of these oils.

Metabolic engineering for enhanced oil in biomass.

The world is hungry for energy. Plant oils in the form of triacylglycerol (TAG) are one of the most reduced storage forms of carbon found in nature and hence represent an excellent source of energy. The myriad of applications for plant oils range across foods, feeds, biofuels, and chemical feedstocks as a unique substitute for petroleum derivatives. Traditionally, plant oils are sourced either from oilseeds or tissues surrounding the seed (mesocarp). Most vegetative tissues, such as leaves and stems, however, accumulate relatively low levels of TAG. Since non-seed tissues constitute the majority of the plant biomass, metabolic engineering to improve their low-intrinsic TAG-biosynthetic capacity has recently attracted significant attention as a novel, sustainable and potentially high-yielding oil production platform. While initial attempts predominantly targeted single genes, recent combinatorial metabolic engineering strategies have focused on the simultaneous optimization of oil synthesis, packaging and degradation pathways (i.e., 'push, pull, package and protect'). This holistic approach has resulted in dramatic, seed-like TAG levels in vegetative tissues. With the first proof of concept hurdle addressed, new challenges and opportunities emerge, including engineering fatty acid profile, translation into agronomic crops, extraction, and downstream processing to deliver accessible and sustainable bioenergy.

Ketoacidosis - Where Do the Protons Come From?

In extreme conditions ketosis can progress to ketoacidosis, a dangerous and potentially life-threatening condition. Ketoacidosis is most common in new or poorly treated type 1 diabetes. The acidosis is usually attributed to the 'acidic' nature of the ketone bodies (acetoacetate, 3-hydroxybutyrate, and acetone). However, acetoacetate and 3-hydroxybutyrate are produced not as acids but as their conjugate bases, and acetone is neither an acid nor a base. This raises the question of why severe ketosis is accompanied by acidosis. Here, we analyze steps in ketogenesis and identify four potential sources: adipocyte lipolysis, hydrolysis of inorganic pyrophosphate generated during synthesis of fatty acyl-coenzyme A (CoA), the reaction catalyzed by an enzyme in the ß-oxidation pathway (3-hydroxyacyl-CoA dehydrogenase), and increased synthesis of CoA.

Effect of tele-health care on quality of life in patients with severe COPD: a randomized clinical trial.

Background and objective: Telemonitoring (TM) of patients with COPD has gained much interest, but studies have produced conflicting results. We aimed to investigate the effect of TM with the option of video consultations on quality of life (QoL) in patients with severe COPD. Patients and methods: COPD patients at high risk of exacerbations were eligible for the 6-month study and a total of 281 patients were equally randomized to either TM (n=141) or usual care (n=140). TM comprised recording of symptoms, oxygen saturation, spirometry, and video consultations. Algorithms generated alerts if readings breached thresholds. Both groups filled in a health-related QoL questionnaire (15D©) and the COPD Assessment Test (CAT) at baseline and at 6 months. Within-group differences were analyzed by paired t-test. Results: Most of the enrolled patients had severe COPD (86% with Global Initiative for Chronic Obstructive Lung Disease stage 3 or 4 and 45% with admission for COPD within the last year, respectively). No difference in drop-out rate and mortality was found between the groups, and likewise there was no difference in 15D or CAT at baseline. At 6 months, a significant improvement of 0.016 in 15D score (p=0.03; minimal clinically important difference 0.015) was observed in the TM group (compared to baseline), while there was no improvement in the control group -0.003 (p=0.68). After stratifying 15D score at baseline to <0.75 or ≥0.75, respectively, there was a significant difference in the <0.75 TM group of 0.037 (p=0.001), which is a substantial improvement. No statistically significant changes were found in CAT score. Conclusion: Compared to the nonintervention group, TM as an add-on to usual care over a 6-month period improved QoL, as assessed by the 15D questionnaire, in patients with severe COPD, whereas no difference between groups was observed in CAT score.

Seed-specific RNAi in safflower generates a superhigh oleic oil with extended oxidative stability.

Vegetable oils extracted from oilseeds are an important component of foods, but are also used in a range of high value oleochemical applications. Despite being biodegradable, nontoxic and renewable current plant oils suffer from the presence of residual polyunsaturated fatty acids that are prone to free radical formation that limit their oxidative stability, and consequently shelf life and functionality. Many decades of plant breeding have been successful in raising the oleic content to ~90%, but have come at the expense of overall field performance, including poor yields. Here, we engineer superhigh oleic (SHO) safflower producing a seed oil with 93% oleic generated from seed produced in multisite field trials spanning five generations. SHO safflower oil is the result of seed-specific hairpin-based RNA interference of two safflower lipid biosynthetic genes, FAD2.2 and FATB, producing seed oil containing less than 1.5% polyunsaturates and only 4% saturates but with no impact on lipid profiles of leaves and roots. Transgenic SHO events were compared to non-GM safflower in multisite trial plots with a wide range of growing season conditions, which showed no evidence of impact on seed yield. The oxidative stability of the field-grown SHO oil produced from various sites was 50 h at 110°C compared to 13 h for conventional ~80% oleic safflower oils. SHO safflower produces a uniquely stable vegetable oil across different field conditions that can provide the scale of production that is required for meeting the global demands for high stability oils in food and the oleochemical industry.

Barriers for recruitment of patients with chronic obstructive pulmonary disease to a controlled telemedicine trial.

The aim of this analysis is to investigate reasons why patients with chronic obstructive pulmonary disease decline to participate in a controlled trial of telemedicine. Patients with previous chronic obstructive pulmonary disease exacerbations were invited to participate in a 6-month randomized telemedicine trial. For eligible patients, reasons for refusal were registered. Of 560 eligible patients, 279 (50%) declined to participate in the trial, 257 (92%) reported a reason: 53 (20.6%) technical concerns, 164 (63.8%) personal reasons, 17 (6.6%) preferred outpatient clinic visits, and 23 (8.9%) did not want to participate in clinical research. Compared to consenting patients, subjects declining participation were significantly older, more often female, had higher lung function (%predicted), lower body mass index, higher admission-rate for chronic obstructive pulmonary disease in the previous year, and were more often diagnosed with osteoporosis. Many eligible patients decline participating in a controlled tele-healthcare trial and, furthermore, a tailored approach for recruiting females and elderly patients appears appropriate.

Step changes in leaf oil accumulation via iterative metabolic engineering.

Synthesis and accumulation of plant oils in the entire vegetative biomass offers the potential to deliver yields surpassing those of oilseed crops. However, current levels still fall well short of those typically found in oilseeds. Here we show how transcriptome and biochemical analyses pointed to a futile cycle in a previously established Nicotiana tabacum line, accumulating up to 15% (dry weight) of the storage lipid triacylglycerol in leaf tissue. To overcome this metabolic bottleneck, we either silenced the SDP1 lipase or overexpressed the Arabidopsis thaliana LEC2 transcription factor in this transgenic background. Both strategies independently resulted in the accumulation of 30-33% triacylglycerol in leaf tissues. Our results demonstrate that the combined optimization of de novo fatty acid biosynthesis, storage lipid assembly and lipid turnover in leaf tissue results in a major overhaul of the plant central carbon allocation and lipid metabolism. The resulting further step changes in oil accumulation in the entire plant biomass offers the possibility of delivering yields that outperform current oilseed crops.

Genetic enhancement of palmitic acid accumulation in cotton seed oil through RNAi down-regulation of ghKAS2 encoding ß-ketoacyl-ACP synthase II (KASII).

Palmitic acid (C16:0) already makes up approximately 25% of the total fatty acids in the conventional cotton seed oil. However, further enhancements in palmitic acid content at the expense of the predominant unsaturated fatty acids would provide increased oxidative stability of cotton seed oil and also impart the high melting point required for making margarine, shortening and confectionary products free of trans fatty acids. Seed-specific RNAi-mediated down-regulation of ß-ketoacyl-ACP synthase II (KASII) catalysing the elongation of palmitoyl-ACP to stearoyl-ACP has succeeded in dramatically increasing the C16 fatty acid content of cotton seed oil to well beyond its natural limits, reaching up to 65% of total fatty acids. The elevated C16 levels were comprised of predominantly palmitic acid (C16:0, 51%) and to a lesser extent palmitoleic acid (C16:1, 11%) and hexadecadienoic acid (C16:2, 3%), and were stably inherited. Despite of the dramatic alteration of fatty acid composition and a slight yet significant reduction in oil content in these high-palmitic (HP) lines, seed germination remained unaffected. Regiochemical analysis of triacylglycerols (TAG) showed that the increased levels of palmitic acid mainly occurred at the outer positions, while C16:1 and C16:2 were predominantly found in the sn-2 position in both TAG and phosphatidylcholine. Crossing the HP line with previously created high-oleic (HO) and high-stearic (HS) genotypes demonstrated that HP and HO traits could be achieved simultaneously; however, elevation of stearic acid was hindered in the presence of high level of palmitic acid.

A call for comparative effectiveness research to learn whether routine clinical care decisions can protect from dementia and cognitive decline.

Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer's and other dementia. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer's Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia.

Do telemedical interventions improve quality of life in patients with COPD? A systematic review.

OBJECTIVE: Telehealth is an approach to disease management, which may hold the potential of improving some of the features associated with COPD, including positive impact on disease progression, and thus possibly limiting further reduction in quality of life (QoL). Our objective was, therefore, to summarize studies addressing the impact of telehealth on QoL in patients with COPD. DESIGN: Systematic review. METHODS: A series of systematic searches were carried out using the following databases: PubMed, EMBASE, Cochrane Controlled Trials Register, and ClinicalTrials.gov (last updated November 2015). A predefined search algorithm was utilized with the intention to capture all results related to COPD, QoL, and telehealth published since year 2000. OUTCOME MEASURES: Primary outcome was QoL, assessed by validated measures. RESULTS: Out of the 18 studies fulfilling the criteria for inclusion in this review, three studies found statistically significant improvements in QoL for patients allocated to telemedical interventions. However, all of the other included studies found no statistically significant differences between control and telemedical intervention groups in terms of QoL. CONCLUSION: Telehealth does not make a strong case for itself when exclusively looking at QoL as an outcome, since statistically significant improvements relative to control groups have been observed only in few of the available studies. Nonetheless, this does not only rule out the possibility that telehealth is superior to standard care with regard to other outcomes but also seems to call for more research, not least in large-scale controlled trials.

Dedicated Industrial Oilseed Crops as Metabolic Engineering Platforms for Sustainable Industrial Feedstock Production.

Feedstocks for industrial applications ranging from polymers to lubricants are largely derived from petroleum, a non-renewable resource. Vegetable oils with fatty acid structures and storage forms tailored for specific industrial uses offer renewable and potentially sustainable sources of petrochemical-type functionalities. A wide array of industrial vegetable oils can be generated through biotechnology, but will likely require non-commodity oilseed platforms dedicated to specialty oil production for commercial acceptance. Here we show the feasibility of three Brassicaceae oilseeds crambe, camelina, and carinata, none of which are widely cultivated for food use, as hosts for complex metabolic engineering of wax esters for lubricant applications. Lines producing wax esters >20% of total seed oil were generated for each crop and further improved for high temperature oxidative stability by down-regulation of fatty acid polyunsaturation. Field cultivation of optimized wax ester-producing crambe demonstrated commercial utility of these engineered crops and a path for sustainable production of other industrial oils in dedicated specialty oilseeds.

Down-regulation of crambe fatty acid desaturase and elongase in Arabidopsis and crambe resulted in significantly increased oleic acid content in seed oil.

High oleic oil is an important industrial feedstock that has been one of the main targets for oil improvement in a number of oil crops. Crambe (Crambe abyssinica) is a dedicated oilseed crop, suitable for industrial oil production. In this study, we down-regulated the crambe fatty acid desaturase (FAD) and fatty acid elongase (FAE) genes for creating high oleic seed oil. We first cloned the crambe CaFAD2, CaFAD3 and CaFAE1 genes. Multiple copies of each of these genes were isolated, and the highly homologous sequences were used to make RNAi constructs. These constructs were first tested in Arabidopsis, which led to the elevated oleic or linoleic levels depending on the genes targeted, indicating that the RNAi constructs were effective in regulating the expression of the target genes in nonidentical but closely related species. Furthermore, down-regulation of CaFAD2 and CaFAE1 in crambe with the FAD2-FAE1 RNAi vector resulted in even more significant increase in oleic acid level in the seed oil with up to 80% compared to 13% for wild type. The high oleic trait has been stable in subsequent five generations and the GM line grew normally in greenhouse. This work has demonstrated the great potential of producing high oleic oil in crambe, thus contributing to its development into an oil crop platform for industrial oil production.

A case study on the genetic origin of the high oleic acid trait through FAD2-1 DNA sequence variation in safflower (Carthamus tinctorius L.).

The safflower (Carthamus tinctorius L.) is considered a strongly domesticated species with a long history of cultivation. The hybridization of safflower with its wild relatives has played an important role in the evolution of cultivars and is of particular interest with regards to their production of high quality edible oils. Original safflower varieties were all rich in linoleic acid, while varieties rich in oleic acid have risen to prominence in recent decades. The high oleic acid trait is controlled by a partially recessive allele ol at a single locus OL. The ol allele was found to be a defective microsomal oleate desaturase FAD2-1. Here we present DNA sequence data and Southern blot analysis suggesting that there has been an ancient hybridization and introgression of the FAD2-1 gene into C. tinctorius from its wild relative C. palaestinus. It is from this gene that FAD2-1Δ was derived more recently. Identification and characterization of the genetic origin and diversity of FAD2-1 could aid safflower breeders in reducing population size and generations required for the development of new high oleic acid varieties by using perfect molecular marker-assisted selection.