Human factors and data logging processes with the use of advanced technology for adults with type 1 diabetes (T1DM): A systematic integrative review

Background: People with T1DM are confronted with self-management tasks and strategies to reduce risks of long-term complications against the risk of hypoglycemic events. The potential of advanced and evolving technology to address these issues involves consideration of psychological and behavioral constructs alongside the usability of devices. Access and uptake of advanced technology is further influenced by economic factors and health care provider capacity to support such interventions. Previous reviews have focused upon either clinical outcomes or descriptively scoped the literature or have synthesized studies on adults with children and young people where human factors are different. Objective: The objective of this review was to describe the relationship between human factors and adherence with technology for data logging processes in adults (> 18 years) with T1DM and to explore the factors which influence this association. Methods: A systematic literature review. Results: 18 studies were included in the review following a literature search using the PRISMA guidelines and a quality appraisal process. This included 3320 participants with a mean age of 42 years. Overall, adults felt more satisfied with their treatment on transition to advanced technology (insulin pump and CGM), the most significant contributing factor was when BG levels were consistently < 7.00mmol/l (P =.009). However, participants spent considerable time on their diabetes self-care. There was evidence that logging of data was positively correlated with increasing age with the use of an app that provided meaningful feedback (regression coefficient = 55.8 recordings/ year; P = 0.009). Furthermore, there were benefits of CGM use for older adults in mediating complexities and their fears of hypoglycemia with reported significant differences in well-being (P= .009). Qualitative studies within the review aimed to explore the use and uptake of technology within the context of everyday lives. Participants experienced ‘frustrations’ with CGM, CSII, calibration of devices and alarms. In addition, there were implications for ‘body image’ when carrying and using a device. This takes into account wide variations in individual use and interaction with technology across a continuum of sociocultural contexts. This has implications for the way in which future technologies are designed. Conclusions: Many of the quantitative studies in the review were limited by small sample sizes. This may make it difficult to generalize findings to other contexts. This is further limited by a sample that was predominantly Caucasian, well-controlled and engaged with their self-care. However, the use of critical appraisal frameworks has highlighted areas where research into human factors and data logging processes of individuals could be improved. This includes engaging people in the design of the technology, and further exploration of the way in which significant others impact on the behavior and attitude of the individual towards technology use

Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine

Recent work shows that S-adenosylmethionine (AdoMet) helps maintain normal liver function as chronic hepatic deficiency results in spontaneous development of steatohepatitis and hepatocellular carcinoma. The mechanisms by which these nontraditional functions of AdoMet occur are unknown. Here, we use knockout mice deficient in hepatic AdoMet synthesis (MAT1A(-/-)) to study the proteome of the liver during the development of steatohepatitis. One hundred and seventeen protein spots, differentially expressed during the development of steatohepatitis, were selected and identified by peptide mass fingerprinting. Among them, 12 proteins were found to be affected from birth, when MAT1A(-/-) expression is switched on in WT mouse liver, to the rise of histological lesions, which occurs at approximately 8 months. Of the 12 proteins, 4 [prohibitin 1 (PHB1), cytochrome c oxidase I and II, and ATPase beta-subunit] have known roles in mitochondrial function. We show that the alteration in expression of PHB1 correlates with a loss of mitochondrial function. Experiments in isolated rat hepatocytes indicate that AdoMet regulates PHB1 content, thus suggesting ways by which steatohepatitis may be induced. Importantly, we found the expression of these mitochondrial proteins was abnormal in obob mice and obese patients who are at risk for nonalcoholic steatohepatitis

Oral dosing with papaya latex is an effective anthelmintic treatment for sheep infected with Haemonchus contortus

Background The cysteine proteinases in papaya latex have been shown to have potent anthelmintic properties in monogastric hosts such as rodents, pigs and humans, but this has not been demonstrated in ruminants. Methods In two experiments, sheep were infected concurrently with 5,000 infective larvae of Haemonchus contortus and 10,000 infective larvae of Trichostrongylus colubriformis and were then treated with the supernatant from a suspension of papaya latex from day 28 to day 32 post-infection. Faecal egg counts were monitored from a week before treatment until the end of the experiment and worm burdens were assessed on day 35 post-infection. Results We found that the soluble fraction of papaya latex had a potent in vivo effect on the abomasal nematode H. contortus, but not on the small intestinal nematode T. colubriformis. This effect was dose-dependent and at tolerated levels of gavage with papaya latex (117 μmol of active papaya latex supernatant for 4 days), the H. contortus worm burdens were reduced by 98%. Repeated treatment, daily for 4 days, was more effective than a single dose, but efficacy was not enhanced by concurrent treatment with the antacid cimetidine. Conclusions Our results provide support for the idea that cysteine proteinases derived from papaya latex may be developed into novel anthelmintics for the treatment of lumenal stages of gastro-intestinal nematode infections in sheep, particularly those parasitizing the abomasum

Methionine adenosyltransferase II beta subunit gene expression provides a proliferative advantage in human hepatoma

BACKGROUND & AIMS: Of the 2 genes (MAT1A, MAT2A) encoding methionine adenosyltransferase, the enzyme that synthesizes S-adenosylmethionine, MAT1A, is expressed in liver, whereas MAT2A is expressed in extrahepatic tissues. In liver, MAT2A expression associates with growth, dedifferentiation, and cancer. Here, we identified the beta subunit as a regulator of proliferation in human hepatoma cell lines. The beta subunit has been cloned and shown to lower the K(m) of methionine adenosyltransferase II alpha2 (the MAT2A product) for methionine and to render the enzyme more susceptible to S-adenosylmethionine inhibition. METHODS: Methionine adenosyltransferase II alpha2 and beta subunit expression was analyzed in human and rat liver and hepatoma cell lines and their interaction studied in HuH7 cells. beta Subunit expression was up- and down-regulated in human hepatoma cell lines and the effect on DNA synthesis determined. RESULTS: We found that beta subunit is expressed in rat extrahepatic tissues but not in normal liver. In human liver, beta subunit expression associates with cirrhosis and hepatoma. beta Subunit is expressed in most (HepG2, PLC, and Hep3B) but not all (HuH7) hepatoma cell lines. Transfection of beta subunit reduced S-adenosylmethionine content and stimulated DNA synthesis in HuH7 cells, whereas down-regulation of beta subunit expression diminished DNA synthesis in HepG2. The interaction between methionine adenosyltransferase II alpha2 and beta subunit was demonstrated in HuH7 cells. CONCLUSIONS: Our findings indicate that beta subunit associates with cirrhosis and cancer providing a proliferative advantage in hepatoma cells through its interaction with methionine adenosyltransferase II alpha2 and down-regulation of S-adenosylmethionine levels

Trust and contextual engagement with the PEPPER system: The qualitative findings of a clinical feasibility study

Background and aims. PEPPER (Patient Empowerment through Predictive PERsonalised decision support) is an EU-funded research project which aims to improve self-management of type 1 diabetes (T1D). The system comprises an AI insulin bolus recommender, coupled with a safety system. The aim of the qualitative arm of this clinical feasibility study was to examine the context of participants’ interaction with the PEPPER system and identify incidents where bolus recommendations were trusted and accepted. Methods. This was a multicentre (UK and Spain) non-randomised open-labelled 6-week pilot study. Thirteen adults with T1D participated in weekly telephone interviews to explore the context of their interactions and responses to PEPPER. Data was thematically analysed through conceptual frameworks for engagement with healthcare digital behaviour change interventions. Results. Participants reported their key interactions as responding to PEPPER bolus recommendations, inputting carbohydrate values, interpreting continuous glucose monitoring (CGM) values through visualization of personal data and dealing with safety alarms. Two themes were associated with trust and engagement with the system; ‘feeling monitored’ and ‘feeling in control’. The incidents where participants trusted PEPPER also enhanced personal expertise of T1D through insights provided by the safety system such as low glucose basal insulin for pump users. Benefits were balanced against technical challenges of the system, which were used to improve the PEPPER application and enhance user experience. Conclusion. Some participants suggested that even access to PEPPER for a temporary period could positively influence self-management strategies. Contextual interviewing is a valuable tool in mobile application development for diabetes decision support systems

Hyperhomocysteinemia in liver cirrhosis: mechanisms and role in vascular and hepatic fibrosis

Numerous clinical and epidemiological studies have identified elevated homocysteine levels in plasma as a risk factor for atherosclerotic vascular disease and thromboembolism. Hyperhomocysteinemia may develop as a consequence of defects in homocysteine-metabolizing genes; nutritional conditions leading to vitamin B(6), B(12), or folate deficiencies; or chronic alcohol consumption. Homocysteine is an intermediate in methionine metabolism, which takes place mainly in the liver. Impaired liver function leads to altered methionine and homocysteine metabolism; however, the molecular basis for such alterations is not completely understood. In addition, the mechanisms behind homocysteine-induced cellular toxicity are not fully defined. In the present work, we have examined the expression of the main enzymes involved in methionine and homocysteine metabolism, along with the plasma levels of methionine and homocysteine, in the liver of 26 cirrhotic patients and 10 control subjects. To gain more insight into the cellular effects of elevated homocysteine levels, we have searched for changes in gene expression induced by this amino acid in cultured human vascular smooth muscle cells. We have observed a marked reduction in the expression of the main genes involved in homocysteine metabolism in liver cirrhosis. In addition, we have identified the tissue inhibitor of metalloproteinases-1 and alpha1(I)procollagen to be upregulated in vascular smooth muscle cells and liver stellate cells exposed to pathological concentrations of homocysteine. Taken together, our observations suggest (1) impaired liver function could be a novel determinant in the development of hyperhomocysteinemia and (2) a role for elevated homocysteine levels in the development of liver fibrosis

Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma

BACKGROUND/AIMS: It has been known for at least 50 years that alterations in methionine metabolism occur in human liver cirrhosis. However, the molecular basis of this alteration is not completely understood. In order to gain more insight into the mechanisms behind this condition, mRNA levels of methionine adenosyltransferase (MAT1A), glycine methyltransferase (GNMT), methionine synthase (MS), betaine homocysteine methyltransferase (BHMT) and cystathionine beta-synthase (CBS) were examined in 26 cirrhotic livers, five hepatocellular carcinoma (HCC) tissues and ten control livers. METHODS: The expression of the above-mentioned genes was determined by quantitative RT-PCR analysis. Methylation of MAT1A promoter was assessed by methylation-sensitive restriction enzyme digestion of genomic DNA. RESULTS: When compared to normal livers MAT1A, GNMT, BHMT, CBS and MS mRNA contents were significantly reduced in liver cirrhosis. Interestingly, MAT1A promoter was hypermethylated in the cirrhotic liver. HCC tissues also showed decreased mRNA levels of these enzymes. CONCLUSIONS: These findings establish that the abundance of the mRNA of the main genes involved in methionine metabolism is markedly reduced in human cirrhosis and HCC. Hypermethylation of MAT1A promoter could participate in its reduced expression in cirrhosis. These observations help to explain the hypermethioninemia, hyperhomocysteinemia and reduced hepatic glutathione content observed in cirrhosis

Resistance to the cereal cyst nematode (Heterodera avenae) transferred from the wild grass Aegilops ventricosa to hexaploid wheat by a "stepping-stone" procedure

Transfer of resistance toHeterodera avenae, the cereal cyst nematode (CCN), by a stepping-stoneprocedure from the wild grassAegilops ventricosa to hexaploid wheat has been demonstrated. The number of nematodes per plant was lower, and reached a plateau much earlier, in the resistant introgression line H93-8 (1–2 nematodes per plant) than in the recipient H10-15 wheat (14–16 nematodes per plant). Necrosis (hypersensitive reaction) near the nematode, little cell fusion, and few, often degraded syncytia were observed in infested H93-8 roots, while abundant, well-formed syncytia were present in the susceptible H10-15 wheat. Line H93-8 was highly resistant to the two Spanish populations tested, as well as the four French races (Fr1-Fr4), and the British pathotype Hall, but was susceptible to the Swedish pathotypes HgI and HgIII. Resistance was inherited as though determined by a single quasi-dominant factor in the F2 generations resulting from crosses of H93-8 with H10-15 and with Loros, a resistant wheat carrying the geneCre1 (syn.Ccn1). The resistance gene in H93-8 (Cre2 orCcn2) is not allelic with respect to that in Loros. RFLPs and other markers, together with the cytogenetical evidence, indicate that theCre2 gene has been integrated into a wheat chromosome without affecting its meiotic pairing ability. Introduction ofCre2 by backcrossing into a commercial wheat backgroud increases grain yield when under challenge by the nematode and is not detrimental in the absence of infestation

The effects of knock-down resistance mutations and alternative splicing on voltage-gated sodium channels in Musca domestica and Drosophila melanogaster

© 2020 Elsevier Ltd Voltage-gated sodium channels (VGSCs) are a major target site for the action of pyrethroid insecticides and resistance to pyrethroids has been ascribed to mutations in the VGSC gene. VGSCs in insects are encoded by only one gene and their structural and functional diversity results from posttranscriptional modification, particularly, alternative splicing. Using whole cell patch clamping of neurons from pyrethroid susceptible (wild-type) and resistant strains (s-kdr) of housefly, Musca domestica, we have shown that the V50 for activation and steady state inactivation of sodium currents (INa+) is significantly depolarised in s-kdr neurons compared with wild-type and that 10 nM deltamethrin significantly hyperpolarised both of these parameters in the neurons from susceptible but not s-kdr houseflies. Similarly, tail currents were more sensitive to deltamethrin in wild-type neurons (EC15 14.5 nM) than s-kdr (EC15 133 nM). We also found that in both strains, INa+ are of two types: a strongly inactivating (to 6.8% of peak) current, and a more persistent (to 17.1% of peak) current. Analysis of tail currents showed that the persistent current in both strains (wild-type EC15 5.84 nM) was more sensitive to deltamethrin than was the inactivating type (wild-type EC15 35.1 nM). It has been shown previously, that the presence of exon l in the Drosophila melanogaster VGSC gives rise to a more persistent INa+ than does the alternative splice variant containing exon k and we used PCR with housefly head cDNA to confirm the presence of the housefly orthologues of splice variants k and l. Their effect on deltamethrin sensitivity was determined by examining INa+ in Xenopus oocytes expressing either the k or l variants of the Drosophila para VGSC. Analysis of tail currents, in the presence of various concentrations of deltamethrin, showed that the l splice variant was significantly more sensitive (EC50 42 nM) than the k splice variant (EC50 866 nM). We conclude that in addition to the presence of point mutations, target site resistance to pyrethroids may involve the differential expression of splice variants