Eden

Creative writing.Bachelor of Art

Comparing dietary strategies to manage cardiovascular risk in primary care: a narrative review of systematic reviews

BACKGROUND: Nutrition care in general practice is crucial for cardiovascular disease (CVD) prevention and management, although comparison between dietary strategies is lacking.AIM: To compare the best available (most recent, relevant, and high-quality) evidence for six dietary strategies that are effective for primary prevention/absolute risk reduction of CVD.DESIGN AND SETTING: A pragmatic narrative review of systematic reviews of randomised trials focused on primary prevention of cardiovascular events.METHOD: Studies about: 1) adults without a history of cardiovascular events; 2) target dietary strategies postulated to reduce CVD risk; and 3) direct cardiovascular or all-cause mortality outcomes were included. Six dietary strategies were examined: energy deficit, Mediterranean-like diet, sodium reduction (salt reduction and substitution), the Dietary Approaches to Stop Hypertension (DASH) diet, alcohol reduction, and fish/fish oil consumption. Reviews were selected based on quality, recency, and relevance. Quality and certainty of evidence was assessed using GRADE.RESULTS: Twenty-five reviews met inclusion criteria; eight were selected as the highest quality, recent, and relevant. Three dietary strategies showed modest, significant reductions in cardiovascular events: energy deficit (relative risk reduction [RRR] 30%, 95% confidence interval [CI] = 13 to 43), Mediterranean-like diet (RRR 40%, 95% CI = 20 to 55), and salt substitution (RRR 30%, 95% CI = 7 to 48). Still, some caveats remain on the effectiveness of these dietary strategies. Salt reduction, DASH diet, and alcohol reduction showed small, significant reductions in blood pressure, but no reduction in cardiovascular events. Fish/fish oil consumption showed little or no effect; supplementation of fish oil alone showed small reductions in CVD events.CONCLUSION: For primary prevention, energy deficit, Mediterranean-like diets, and sodium substitution have modest evidence for risk reduction of CVD events. Strategies incorporated into clinical nutrition care should ensure guidance is person centred and tailored to clinical circumstances.</p

Romantic Partner Interference and Psychological Reactance in the Context of Caregiving for an Aging Family Member

Negotiating romantic relational dynamics is inherent to family caregiving situations, which continue to be on the rise in the United States. However, despite evidence that family caregiving duties are linked to a variety of negative relational outcomes, limited research examines communication processes that contribute to or alleviate the burden of caregiver duties on romantic relationships. Guided by psychological reactance theory (PRT), this study examined the link between romantic partner interference with family caregiving duties and the reactance process, as well as directness of communication about irritation as a type of freedom restoration behavior associated with reactance. Adults caring for aging family members recruited from MTurk (N = 187) completed an online survey as part of a larger study of romantic partner communication surrounding family caregiving. Results using PROCESS serial mediation indicated that greater partner interference was related to heightened perceptions of freedom threat, which was positively associated with the experience of reactance, which in turn was associated with communication about irritation. However, the association between reactance and directness of communication about irritation was negative, the opposite direction of what was hypothesized. Implications for PRT and interventions with caregivers and their romantic partners are discussed

The Addition of Arachidin 1 or Arachidin 3 to Human Rotavirus-infected Cells Inhibits Viral Replication and Alters the Apoptotic Cell Death Pathway

Rotavirus (RV) infections are a leading cause of severe gastroenteritis in infants and children under the age of five. There are two vaccines available in the United States and one in India that can be administered early in childhood, however they only protect against specific strains1. From our previous work, both arachidin-1 (A1) and arachidin-3 (A3) from peanut (Arachis hypogaea) hairy root cultures significantly inhibit simian RV replication2,3,4. The purpose of this study was to determine if a human intestinal cell line, HT29.f8, infected with a human RV, Wa, was affected by A1 and A3. Cell viability assays were utilized to determine if A1 and A3 affect the HT29.f8 cells with/without RV infections. At eighteen hours post infection (hpi), supernatants from the RV-infected HT29.f8 cells with/without the arachidins were used in plaque forming assays to quantify and compare the amount of infectious RV particles that are produced during an infection. Transmission electron microscopy (TEM) was used to visualize cell ultrastructure and individual RV particles. Additionally, tunable resistive pulse sensing technology (TRPS) using the qNano system by IZON was employed to quantify and measure virus particle sizes, and display the size distribution of RV particles. Likewise, quantitative real time polymerase chain reactions (qRT-PCR) were performed to determine if A1 and A3 regulated cell death pathways in the HT29.f8 cell line. This data will guide our future studies to determine the antiviral mechanism(s) of action of A1 and A3

Recommendations for improving follow-up care for mesothelioma patients: A qualitative study comprising documentary analysis, interviews and consultation meetings

Objectives. The study aim was to explore experiences of patients with pleural mesothelioma of follow-up care in three National Health Service (NHS) Trusts to develop recommendations for practice. Design. The study design was qualitative and comprised three interlinked phases: a documentary analysis, interviews and consultation meetings. Altheide and Johnson’s Analytic Realism theoretical framework guided the thematic data analysis process. Setting. The study was conducted in three NHS Trusts in South England. Two were secondary care settings and the third was a tertiary centre. Participants. The secondary care trusts saw 15–20 patients with new mesothelioma per year and the tertiary centre 30–40. The tertiary centre had a designated mesothelioma team. Twenty-one patients met the inclusion criteria: >18 years, mesothelioma diagnosis and in follow-up care. Non-English speaking participants, those unable to provide written informed consent or those whom the clinical team felt would find participation too distressing were excluded. All participants were white, 71% were 70–79 years old and 71% were men. Three consultation meetings were conducted with key stakeholders including mesothelioma nurse specialists, patients with mesothelioma, carers and local clinical commissioning group members. Main outcome measures. Specific outcomes were to gain a detailed understanding of mesothelioma follow-up care pathways and processes and to develop coproduced recommendations for practice. Results. Mesothelioma pathways were not always distinct from lung cancer care pathways. All trusts provided follow-up information and resources but there was varied information on how to access local support groups, research or clinical trial participation. Five themes were developed relating to people; processes; places; purpose and perception of care. Coproduced recommendations for improving mesothelioma follow-up pathways were developed following the consultation meetings. Conclusions. This study has developed recommendations which identify the need for patients with pleural mesothelioma to access consistent, specialist, streamlined mesothelioma care, centred around specialist mesothelioma nurses and respiratory consultants, with input from the wider multidisciplinary team

A qualitative exploration of the relevance of training provision in planning for implementation of managed alcohol programs within a third sector setting

Background: Managed Alcohol Programs (MAPs) are a harm reduction strategy for people experiencing homelessness and alcohol dependence. Despite a growing evidence base, resistance to MAPs is apparent due to limited knowledge of alcohol harm reduction and the cultural preference for abstinence-based approaches. To address this, service managers working in a not-for-profit organization in Scotland designed and delivered a program of alcohol-specific staff training as part of a larger study exploring the potential implementation of MAPs during the COVID-19 pandemic. Methods: Semi-structured interviews were conducted with 15 service managers and staff regarding their experiences of the training provided. Data were analyzed using Framework Analysis, and Lewin’s model of organizational change was applied to the findings to gain deeper theoretical insight into data relating to staff knowledge, training, and organizational change. Findings: Participants described increased knowledge about alcohol harm reduction and MAPs, as well as increased opportunities for conversations around cultural change. Findings highlight individual- and organizational-level change is required when implementing novel harm reduction interventions like MAPs. Conclusion: The findings have implications for the future implementation of MAPs in homelessness settings. Training can promote staff buy-in, facilitate the involvement of staff within the planning process, and change organizational culture.</p

Misregulation of mitochondria-lysosome contact dynamics in Charcot-Marie-Tooth Type 2B disease Rab7 mutant sensory peripheral neurons

Inter-organelle contact sites between mitochondria and lysosomes mediate the crosstalk and bidirectional regulation of their dynamics in health and disease. However, mitochondria-lysosome contact sites and their misregulation have not been investigated in peripheral sensory neurons. Charcot-Marie-Tooth type 2B disease is an autosomal dominant axonal neuropathy affecting peripheral sensory neurons caused by mutations in the GTPase Rab7. Using live super-resolution and confocal time-lapse microscopy, we showed that mitochondria-lysosome contact sites dynamically form in the soma and axons of peripheral sensory neurons. Interestingly, Charcot-Marie-Tooth type 2B mutant Rab7 led to prolonged mitochondria-lysosome contact site tethering preferentially in the axons of peripheral sensory neurons, due to impaired Rab7 GTP hydrolysis-mediated contact site untethering. We further generated a Charcot-Marie-Tooth type 2B mutant Rab7 knock-in mouse model which exhibited prolonged axonal mitochondria-lysosome contact site tethering and defective downstream axonal mitochondrial dynamics due to impaired Rab7 GTP hydrolysis as well as fragmented mitochondria in the axon of the sciatic nerve. Importantly, mutant Rab7 mice further demonstrated preferential sensory behavioral abnormalities and neuropathy, highlighting an important role for mutant Rab7 in driving degeneration of peripheral sensory neurons. Together, this study identifies an important role for mitochondria-lysosome contact sites in the pathogenesis of peripheral neuropathy

MHC-I genotype and tumor mutational burden predict response to immunotherapy.

BackgroundImmune checkpoint blockade (ICB) with antibodies inhibiting cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein-1 (PD-1) (or its ligand (PD-L1)) can stimulate immune responses against cancer and have revolutionized the treatment of tumors. The influence of host germline genetics and its interaction with tumor neoantigens remains poorly defined. We sought to determine the interaction between tumor mutational burden (TMB) and the ability of a patient's major histocompatibility complex class I (MHC-I) to efficiently present mutated driver neoantigens in predicting response ICB.MethodsComprehensive genomic profiling was performed on 83 patients with diverse cancers treated with ICB to determine TMB and human leukocyte antigen-I (HLA-I) genotype. The ability of a patient's MHC-I to efficiently present mutated driver neoantigens (defined by the Patient Harmonic-mean Best Rank (PHBR) score (with lower PHBR indicating more efficient presentation)) was calculated for each patient.ResultsThe median progression-free survival (PFS) for PHBR score &lt; 0.5 vs. ≥ 0.5 was 5.1 vs. 4.4 months (P = 0.04). Using a TMB cutoff of 10 mutations/mb, the stable disease &gt; 6 months/partial response/complete response rate, median PFS, and median overall survival (OS) of TMB high/PHBR high vs. TMB high/PHBR low were 43% vs. 78% (P = 0.049), 5.8 vs. 26.8 months (P = 0.03), and 17.2 months vs. not reached (P = 0.23), respectively. These findings were confirmed in an independent validation cohort of 32 patients.ConclusionsPoor presentation of driver mutation neoantigens by MHC-I may explain why some tumors (even with a high TMB) do not respond to ICB

Metastable Nanostructured Metallized Fluoropolymer Composites for Energetics

Fluoropolymers have long served as potent oxidizers for metal-based pyrolant designs for the preparation of energetic materials. Commercial perfluoropolyethers (PFPEs), specifically known as Fomblins®, are well-known to undergo accelerated thermal degradation in the presence of native metals and Lewis acids producing energetically favorable metal fluoride species. This study employs the use of PFPEs to coat nano-aluminum (n-Al) and under optimized stoichiometric formulations, harness optimized energy output. The PFPEs serve as ideal oxidizers of n-Al because they are non-volatile, viscous liquids that coat the particles thereby maximizing surface interactions. The n-Al/PFPE blended combination is required to interface with an epoxy-based matrix in order to engineer a moldable/machinable, structurally viable epoxy composite without compromising bulk thermal/mechanical properties. Computational modeling/simulation supported by thermal experimental studies showed that the n-Al/PFPE blended epoxy composites produced an energetic material that undergoes latent thermal metal-mediated oxidation. Details of the work include the operationally simple, scalable synthetic preparation, thermal properties from DSC/TGA, and SEM/TEM of these energetic metallized nanocomposite systems. Post-burn analysis using powder XRD of this pyrolant system confirms the presence of the predominating exothermic metal-mediated oxidized AlF3 species in addition to the production of Al2O3 and Al4C3 during the deflagration reaction. Details of this first epoxy-based energetic nanocomposite entrained with a thermally reactive formulation of PFPE coated n-Al particles are presented herein

Arachidin-1 and Arachidin-3 Modulation of Rotavirus-infected MA104 Cells

Rotavirus (RV) causes severe life-threatening diarrhea in young children and immunocompromised individuals. There are several licensed attenuated vaccines for young children, but there are no vaccines or antiviral therapeutics for immunocompromised patients of any age. Previously, our laboratory demonstrated that arachidin 1 (A1) and arachidin 3 (A3) decreases the number of infectious simian RV particles and RV non-structural protein 4 (NSP4) in a human intestinal cell line which suggests effects on RV replication. This study examined the effects of the arachidins on the human RV (Wa)-infected African green monkey kidney cell line, MA104. The addition of either A1 or A3 did not decrease the viability of MA104 cells, however plaque forming assays measured significant decreases in the number of infectious RV particles with the addition of the arachidins. Correspondingly, western blot analyses revealed a change in the presence of VP6 and NSP4 (structural and nonstructural RV proteins, respectively). This implies that like the simian RV, Wa replication is also affected by both A1 and A3. Additionally, tunable resistive pulse sensing technology (TRPS) measured changes in the population distribution of released nanoparticles between 60-140 nanometers. Additionally, TEM morphometric analyses showed ultrastructural changed in RV-infected cells treated with A1 or A3. This included nucleus to cytoplasm ratios that were determined by TEM and whole cell fluorescent assays that disclosed significant nuclear size alterations with the addition of RV which implied modifications of the apoptosis and autophagy pathways. Moreover, the increased presence of autophagic vesicles seen with RV+A1 reinforced the model of a switch from the apoptosis to the autophagy pathway. In addition, immunoblot assays reveal the presence of cannabinoid 1 and 2 receptors on MA104 cells. These receptors bind A1 and A3 and are important in signaling in the endocannabinoid system. This implies a role for Witcher et al.: Arachidin-1 and Arachidin-3 Modulation of Rotavirus-infected MA10 2 A1 and A3 in modulating cannabinoid receptor cell signaling in RV-infected cells which indicates a mechanism of action of A1 and A3 with potential RV therapeutic activity