Browsing by Author "Conrad, Nailah"
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- ItemOpen AccessAssessing the impact of mHealth on the autonomy of diabetic patients: a systematic review(2023) Pincus, Shannon; Conrad, Nailah; Mthoko, HafeniBackground mHealth has emerged as a major modality for the provision of healthcare and it is generally proposed that mHealth interventions improve patient autonomy. Diabetes mellitus requires chronic management to mitigate a myriad of serious complications. mHealth uses features such as regular reminders to encourage patient engagement with health treatments. This may assist with chronic diabetes management. This systematic review aims to answer the research question: What is the impact of mHealth interventions on patient autonomy? Methods A systematic review was conducted, in accordance with the PRISMA-P 2020 checklist, to critically assess the literature from the following databases: PubMed, Scopus, Cochrane Library, Web of Science, EBSCO, Africawide, Academic Search Premier, CINAHL and APA PsycInfo. Both free text words and medical subject heading terms [MeSH] were used as required. Both randomised and nonrandomised studies were reviewed, and studies were considered eligible if they met the predetermined inclusion criteria as follows: populations over 18 years of age and diagnosed with diabetes mellitus type 1, diabetes mellitus type 2 or gestational diabetes, using an mHealth intervention where the outcome related to patient autonomy. A thematic analysis was conducted to critically assess the articles. Results Eighteen studies that met the eligibility criteria were included in this systematic review. 12 of the articles focused on patients with diabetes mellitus type 2, 3 focused on both types 1 and 2, 1 focused on gestational diabetes and 2 articles were unclear on the type of diabetes considered. The interventions used included interactive voice response interventions, text messages, phone calls and mHealth applications. Outcomes primarily focused on health literacy and various health outcomes such as medication adherence, healthy eating, exercise, and glycated haemoglobin (HbA1c). The thematic analysis revealed that there were challenges with conceptualising autonomy and mHealth, rather focusing on what seem to be components of autonomy, such as self-management. Despite this, the articles seem to suggest mHealth may have some value in improving patient autonomy. Discussion In critically assessing the literature it seemsthat mHealth does promote the components of autonomy of diabetic patients, especially through text-messaging based interventions that act as reminders and support patients. However, this is tempered by the issues surrounding the concept of autonomy. There is a lack of critical thought and interrogation around autonomy. The articles do not define autonomy or measure autonomy, rather focussing on the components of autonomy such as selfmanagement, health literacy and improved health outcomes. The complexities surrounding the concept of autonomy, such as the focus on rationality, diminish its utility in a healthcare setting. Instead, it is the components of autonomy that offer a better tool for driving behaviour change in diabetic patients. Conclusion mHealth may improve the components of autonomy (such as self-management, health literacy and improved health outcomes) in diabetic patients. Text-message based systems especially, are useful in promoting self-care behaviours as part of a self-management scheme. A deeper understanding of the concept of autonomy is essential to mitigate against the limitations of autonomy in its current state, namely the centrality of rationality. A discussion around alternative terminology and ways to measure improvements may be useful. This can then inform new mHealth designs that generate the best patient outcomes.
- ItemOpen AccessCharacterisation of the structural motifs Involved in the cleavage and secretion of human angiotensin-converting enzyme(2014) Conrad, Nailah; Sturrock, Edward D; Schwager, Sylva L UAngiotensin converting enzyme is an ectoprotein prone to regulated proteolytic solubilisation by an as yet unknown protease or sheddase. Proteolytic cleavage of membrane proteins is an essential cellular process that controls their expression and function, and modulates cellular and physiological processes. Testis ACE (tACE) is shed at a higher rate than somatic ACE and it has been proposed that regions in its ectodomain direct its shedding. Discrete secondary structures on the surface of the distal ectodomain of tACE were replaced with their N-domain counterparts to determine their role in the ectodomain shedding of ACE. None of the regions investigated proved to be an absolute requirement for shedding, but the mutant ACE proteins were subject to variations in shedding compared to wild-type tACE. To investigate the role of the proximal ectodomain in shedding the residues H610-L614 were mutated to alanines, causing a decrease in shedding. An extension of this mutation on the N-terminal side to seven alanines resulted in a reduction in ACE activity and, more importantly, it affected the processing of the protein to the membrane, resulting in expression of an underglycosylated form of ACE. When E608-H614 was mutated to the homologous region of the N-domain, processing was normal and shedding only marginally reduced. These data suggest that this region is more crucial for the processing of ACE than is for regulating shedding. Construction of a P628L mutation in tACE showed an increase in shedding. Furthermore, MALDI analysis of a tryptic digest established that the putative glycosylation site N620WT became glycosylated. Further mutagenesis of the P628L mutant to remove the newly formed glycosylation site, resulted in an even greater increase in shedding. Soluble fluorogenic peptides mimicking the ACE stalk were used in a cell-based assay to characterise the contribution of the stalk to ACE shedding. Hydrolysis of the wild-type peptide Abz-NSARSEGPQ-EDDnp was not responsive to phorbol ester or the hydroxamate inhibitor (TAPI), however, it was inhibited by EDTA. The aminopeptidase inhibitor bestatin did not inhibit cleavage or alter the cleavage site. Therefore the protease involved in the cleavage of the ACE stalk peptides is likely different to the sheddase responsible for ACE shedding. Substitution of the P1 and P1' sites of the peptides did not significantly influence the rate of cleavage. All the peptides were cleaved at the E-G bond, which is C-terminal to the physiological R-S cleavage site. Removal of the fluorogenic capping groups resulted in no cleavage of the peptides and lengthening of the peptide did not result in cleavage. This confirms the need for the ACE sheddase and its substrate to be anchored in the membrane and suggests the use of soluble peptide substrates in a cell assay has limited application for investigating the ectodomain shedding of ACE.
- ItemOpen AccessCharacterization of XVEF and XvCaM : two calcium-binding proteins isolated from the resurrection plant Xerophyta viscosa(2005) Conrad, NailahXerophyta viscosa (Baker) is a resurrection plant with the ability to survive desiccation and rehydrate upon watering with minimal tissue damage. XVEF was isolated by differential screening of aX viscosa dehydration stress cDNA library. Reconstruction of the full length XVEF cDNA was conducted utilizing overlap extension PCR. XVEF codes for a putative calcium-binding protein and sequence analysis indicated that it has a 708 bp ORF corresponding to a protein with a molecular mass of26.95 kDa, has a conserved calcium-binding EF-hand motif, potential phosphorylation sites, a pI of 6.49 and a putative conserved transmembrane domain spanning residues 90-107. Northern blot analyses of total RNA indicated that XVEF transcript increased 48 hours after 100/-lM ABA application and was present between 12 and 48 hours in response to a low temperature stress (4°C). A second gene, XvCaM, was isolated from a low temperature (4°C) cDNA stress library. Sequence analysis indicates that it has a 450 bp ORF corresponding to a 16.39 kDa protein, a pI of 3.90 and potential phosphorylation sites. It apparently encodes a calcium-binding protein with putatively three EF-hands which showed the highest similarity to plant calmodulins. XVCAM was heterologously expressed in E. coli as a fusion protein with a 6X His-tag and it was shown to be a functional protein that binds Ca2+ by utilizing a 45CaCh overlay assay. Northern blot analyses of XvCaM using total RNA under low (4°C) and high temperature treatment (42°C) showed constitutive expression levels of the transcript. Under the dehydration/rehydration treatment transcript levels decreased between 40% R WC dehydration and 26% RWC rehydration. The northern blot conducted with polysomal RNA isolated from 150 mM NaCI treatment also showed constitutive expression. Western blot analyses using anti-XVCAM polyclonal antibodies showed that the protein accumulated at 24 hours during the NaCI stress and at 15% RWC (dry) to 40% RWC (rehydration) during the dehydration/rehydration stress. The northern and western analyses results suggest that XVCAM undergoes post-translational modifications and XvCaM mRNA is possibly stored for rapid recovery processes upon rehydration. These results indicate that XVEF and XvCaM are possibly calcium-binding proteins most likely involved in modulating stress-responsive calcium-signaling cascades.
- ItemOpen AccessThe impact of digital health interventions in the treatment and management of perinatal depression: a systematic review(2023) Mahlalela, Nongcebo Nokukhanya; Fortuin, Jill; Conrad, NailahBackground Perinatal depression, a significant complication of pregnancy and the postpartum period is common amongst women within the reproductive age. Despite its significant contribution to the disease burden and being one of the leading factors of disability, mental healthcare for treating and managing perinatal depression remains a low priority globally (Almond, 2009; Dadi et al., 2020; Rahman et al., 2013). Digital health interventions (DHIs) are implemented to address the accessibility and cost barriers related to mental healthcare. This systematic review aims to examine the impact of the integration of DHIs and psychological approaches in decreasing the symptoms of perinatal depression amongst women aged between 16 and 55. An assessment of the effectiveness, acceptability, usability and cost-effectiveness of the mentioned DHIs will be conducted. Methodology The systematic search was conducted in six academic health databases: PubMed, Cochrane, CINHAL, PsycInfo, PsycArticles and Medline. The year of publication of the studies was between the first of January 2007 and the thirtyfirst of December 2020. Randomised control trials (RCT), quasi-experimental, and cohort studies assessing the effectiveness of DHIs in treating perinatal depression were included. The study participants were limited to pregnant and postpartum women aged 16 to 55. The psychological interventions include cognitive behavioural therapy (CBT), interpersonal psychotherapy (IPT), psychoeducation, peer support and counselling. Furthermore, the DHIs included mobile health applications and telephone-based and web-based solutions. The studies that met the inclusion criteria after screening were included for data extraction. Lastly, a narrative analysis was conducted to synthesise the results from the included studies. Results Out of 271 articles, 24 met the inclusion criteria, where randomised control trials (RCT) were the most predominant studies for eligibility (n = 21). The participants consisted of perinatal (n = 1), postpartum (n =18) and pregnant women (n =5). Surprisingly, only one study was conducted in a low-and-middle-income country (LMIC). Fifteen studies utilised web-based interventions: five used telephonebased solutions, while only four used mobile health applications. For the review outcomes, twenty studies assessed the effectiveness, while 13 assessed the acceptability. Notably, the outcomes of cost-effectiveness (n =2) and usability (n = 3) were assessed in only a few studies. Discussion The findings of the present review indicate the success of DHIs in treating perinatal depression, especially when integrated with the predominant psychological approaches such as CBT. However, the shortage of literature that evaluates its efficacy in LMICs highlights a significant research gap. Furthermore, due to its limited availability in literature, the outcomes of cost-effectiveness and usability need to be further assessed in future research. The systematic review protocol has been successfully registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number: CRD42021264253. Conclusion The integration of CBT, peer support and psychoeducation with digital health reports positive outcomes among the perinatal population. Despite the positive outcomes reported in the application of CBT, psychoeducation and peer support, disproportionate access to digital devices among the LMICs remains, calling for an increase in the implementation of telehealth instead of web-based interventions. Keywords Digital health, mHealth, eHealth, telemedicine, perinatal depression, low-andmiddle-income countries, mental health, maternal health.