Incentives and individualized coaching improves completion rates of supervised exercise therapy for claudication.

OBJECTIVE: Supervised exercise therapy (SET) provides clinical benefit for patients suffering from intermittent claudication and has been widely recommended as first-line therapy before endovascular or surgical intervention. However, published rates of SET program completion range from 5% to 55%, with historic completion of 54% at our own institution. As such, we sought to identify if targeted patient-supportive interventions improve SET completion rates while still maintaining efficacious SET programming. METHODS: Patients who were diagnosed with intermittent claudication, as defined by ankle-brachial index (ABI) <0.9 without rest pain, were offered enrollment in a prospective quality improvement protocol for our 12-week SET for peripheral artery disease program. Program completion was defined as ≥24 of 36 offered sessions over 12 weeks. A three-pronged approach was utilized to improve completion during the study, including financial incentives up to $180, scheduled coaching with our advanced practitioner staff, and informational materials on the importance of SET programming and lifestyle modification. Patient-reported improvements in walking symptoms were tracked via regularly administered questionnaires. Functional measures of SET programming including total walking duration and distance, metabolic equivalent of task, and ABIs; vascular intervention within 12-months after enrollment was also collected and compared using univariate paired analysis. RESULTS: In total, seventy-three patients were enrolled in SET for peripheral artery disease programming over the study period. Utilizing our three-pronged coaching approach, 56 patients completed SET programming, increasing our SET completion rate to 76.7% over a 2-year study period. Compared with pre-SET baseline, patients who completed SET noted less pain, aching, cramps in calves when walking (P = .004), and less difficulty walking 1 block (P = .038). Additionally, patients significantly increased their metabolic equivalent of task (3.1 vs 2.6; P < .001), total walking duration (30 mins vs 13.5 mins; P < .001), and total walking distance (0.7 vs 0.3 miles; P < .001) from their pre-SET baseline. There were no changes in participant ABIs from enrollment to completion in participants. Patients who completed SET programming also delayed vascular intervention compared with those who did not complete SET or declined participation (213.5 vs 122.5 days from enrollment; P = .041). CONCLUSIONS: Targeted incentives, including cost-coverage vouchers and personalized coaching with instructional materials, successfully improved patient completion of a prescribed SET program. Patients who completed SET programming reported subjective improvement in walking symptoms and objective walking benefits. In addition, these patients had delayed time to vascular intervention, supporting current vascular guidelines advocating for effective SET therapy prior to offering vascular intervention for intermittent claudication.

Patient Reported Barriers for Participation in Supervised Exercise Therapy for Symptomatic Peripheral Artery Disease.

BACKGROUND: Supervised exercise therapy (SET) provides clinical benefit for patients suffering from intermittent claudication due to peripheral artery disease (PAD). However, enrollment in programs when offered remains low. We sought to identify patient-reported barriers to enrollment in SET as part of a prospective quality improvement program. METHODS: Patients who presented to clinic and were diagnosed with claudication were offered enrollment in a prospective quality improvement protocol, offered at 9 regional offices throughout our health system. Both patients who enrolled and declined enrollment were offered a 12-question questionnaire to identify potential barriers to enrollment. Additional data including gender, smoking status, ankle-brachial index (ABI), proximity to the nearest regional office, and disadvantage levels of neighborhoods (low: 1-3, medium: 4-7, and high: 8-10 area deprivation index [ADI]) was collected and compared by program participation using univariate analysis. RESULTS: Patients enrolled in the SET program (n = 66 patients) versus those who declined (n = 84 patients) were of similar age (medium age: 71.4 vs. 69.7 years, P = 0.694), baseline ABI (0.6 vs. 0.6, P = 0.944), smoking status (former 56.1% vs. 53.6%, P = 0.668), distance away from outpatient center (8.2 mi vs. 8.4 mi, P = 0.249), and had similar Connecticut state ADIs (2021 high-disadvantage: 35.4% vs. 33.3%, P = 0.549). Patients participating in the SET program were more likely to be male (78.8% vs. 56.0%, P = 0.003). Top self-reported barriers for patients who declined participation included transportation/distance (39.3%), preference for independent walking (56.0%), inability to commit to 3 sessions per week (52.4%), and lack of interest (20.2%). In addition, a higher proportion of patients who declined participation identified severe barriers of preference for independent walking (39.3% vs. 1.5%, P < 0.001), inability to commit to 3 sessions per week (26.2% vs. 3.0% P < 0.001), transportation/distance issues (23.8% vs. 7.6% P = 0.008), and cost (27.4% vs. 9.1%, P = 0.005) as significant barriers for participation in SET. CONCLUSIONS: Patients who declined participation in SET for PAD had similar disease status and access to care than participating counterparts. Top reported barriers to enrollment include a preference for independent walking, transportation/distance, commitment to 3x/week program, and cost, which highlight areas of focus for equitable access to these limb-saving services.

An orthosteric/allosteric bivalent peptide agonist comprising covalently linked protease-activated receptor-derived peptides mimics in vitro and in vivo activities of activated protein C.

BACKGROUND: Activated protein C (APC) has anticoagulant and cytoprotective cell-signaling activities, which often require protease-activated receptor (PAR) 1 and PAR3 and PAR cleavages at noncanonical sites (R46-N47 and R41-G42, respectively). Some PAR1-derived (P1) peptides and PAR3-derived (P3) peptides, eg, P1-47-66 and P3-42-65, mimic APC's cell signaling. In anti-inflammatory assays, these 2 peptides at low concentrations synergistically attenuate cellular inflammation. OBJECTIVES: To determine whether a P1 peptide covalently linked to a P3 peptide mimics APC's anti-inflammatory and endothelial barrier stabilization activities. METHODS: Anti-inflammatory assays employed stimulated THP-1 cells and caspase-1 measurements. Cultured human EA.hy926 or murine aortic endothelial cells (ECs) exposed to thrombin were monitored for transendothelial electrical resistance. Bivalent covalently linked P1:P3 peptides were studied for APC-like activities. RESULTS: In anti-inflammatory assays, P1-47-55 was as active as P1-47-66 and some P3 peptides (eg, P3-44-54 and P3-51-65) were as active as P3-42-65. The bivalent P1:P3 peptide comprising P1-47-55-(Gly[10 residues])-P3-51-65 (designated "G10 peptide") was more potently anti-inflammatory than the P1 or P3 peptide alone. In transendothelial electrical resistance studies of thrombin-challenged ECs, P1-47-55 and the G10 peptide mimicked APC's protective actions. In dose-response studies, the G10 peptide was more potent than the P1-47-55 peptide. In murine EC studies, the murine PAR-sequence-derived G10 peptide mimicked murine APC's activity. Anti-PAR1 and anti-PAR3 antibodies, but not anti-endothelial protein C receptor antibodies, abated G10's cytoprotection, showing that G10's actions involve PAR1:PAR3. G10 significantly increased survival in murine endotoxemia. CONCLUSION: The PAR-sequence-derived G10 peptide is a bivalent agonist that mimics APC's cytoprotective, anti-inflammatory, and endothelial barrier-stabilizing actions and APC's protection against endotoxemic mortality.

What Effect Do Goal Setting Interventions Have on Physical Activity and Psychological Outcomes in Insufficiently Active Adults? A Systematic Review and Meta-Analysis.

BACKGROUND: Goal setting is commonly used for promoting physical activity (PA) among insufficiently active individuals. Previous reviews have analyzed the effects of goal setting on PA, but the purpose of this systematic review was to examine the concurrent effects of goal setting on PA and psychological outcomes in insufficiently active individuals to support interventions aiming to produce sustained PA behavior change. METHODS: In this review (PROSPERO: CRD42021243970), we identified 13 studies with 1208 insufficiently active adults that reported the effects of goal-setting interventions (range 3-24 wk) on both PA and psychological outcomes (eg, self-efficacy, motivation, and affect). We used meta-analysis and narrative synthesis to analyze these effects. RESULTS: All goals used in the included studies were specific goals. Setting specific goals had a large, positive effect on PA (g [standard mean difference] = 1.11 [P < .001]; 95% confidence interval, 0.74-1.47), but only a small, positive effect on the combined psychological outcomes (g [standard mean difference] = 0.25 [P < .001]; 95% CI, 0.10-0.40). Moderator analyses revealed that interventions that did not reward participants had a significantly greater effect on PA than interventions that did provide rewards (g = 1.30 vs 0.60, respectively, P ≤ .003). No other significant moderators were found. CONCLUSION: Our review offers initial insight into the long-term effects of specific goals on PA and psychological outcomes in insufficiently active adults. Further research that examines the PA and psychological effects of goal-setting interventions and investigates a wider range of goal types could develop a stronger evidence base to inform intervention for insufficiently active individuals.

Determining factors of physical activity and sedentary behaviour in university students during the COVID-19 pandemic: A longitudinal study.

INTRODUCTION: Historically, university students demonstrate poor movement behaviours that could negatively impact current and future health. Recent literature has focused on identifying determinants of physical activity (PA) and sedentary behaviour (SB) in this population to inform the development of intervention strategies. However, the COVID-19 pandemic substantially restricted movement behaviours in this population, meaning findings of previous research may no longer be applicable within the current societal context. The present study explored the longitudinal relationships between pre-pandemic psychological, behavioural and anthropometric factors, and the movement behaviours of UK university students nine months following the outbreak of COVID-19. METHODS: Mental wellbeing (MWB), perceived stress (PS), body mass index (BMI), SB, and PA were assessed using an online self-report survey in 255 students prior to (October 2019) and nine months following (October 2020) the first confirmed case of COVID-19 in the UK. Path analysis was utilised to test relationships between pre-COVID mental wellbeing, perceived stress and BMI, and movement behaviours during the pandemic. RESULTS: The fit of the path analysis model was good (χ2 = 0.01; CMIN = 0.10, CFI = 1.00, RMSEA = 0.00). Pre-covid MWB and PS positively influenced PA (ß = 0.29; ß = 0.24; P < 0.01) but not SB (ß = -0.10; ß = 0.00; P = 0.79) during the pandemic. Additionally, pre-pandemic SB and PA positively influenced SB and PA during the pandemic respectively (SB: ß = 0.26; P < 0.01) (PA: ß = 0.55; P < 0.01). Pre-pandemic BMI did not influence any measured variable during the pandemic (PA: ß = 0.03 and P = 0.29; SB: ß = 0.06 and P = 0.56), and there was no mediating effect of PA on SB during the pandemic (ß = -0.26; P = 0.14). CONCLUSION: These findings indicate that pre-covid mental health and movement behaviours had a direct positive influence on PA during the pandemic, but not SB. This longitudinal study demonstrates the influence that prior psychological and behavioural factors have in determining university students' response to periods of elevated stress and uncertainty, furthering our understanding of determinants of health-related behaviours in students.

Investigation into the use of novel pretreatments in the fermentation of Alaria esculenta by Lactiplantibacillus plantarum and kombucha SCOBY.

High pressure processing (HPP), ultrasound probe (USP) and ultrasound bath (USB) were applied to Alaria esculenta as a fermentation pre-treatment. Seaweed was then fermented by Lactiplantibacillus plantarum (LAB) or symbiotic culture of bacteria and yeast (SCOBY). Physiochemical properties of fermented seaweed were measured. pH was significantly different (p < 0.05) across SCOBY-fermented samples with different pre-treatments but not LAB-fermented samples (p > 0.05). There was a significant difference (p < 0.05) in total viable count (TVC) with the highest count in HPP-treated samples, and lowest in control samples. Organic acids differed significantly (p < 0.05) across pre-treatments for both fermentation groups. 27 volatile compounds were detected in the samples, with alcohols and ketones the most prominent groups. The quantity of volatile compounds was not significantly lower (p > 0.05) from seaweed powder. The control sample had the highest levels of tropomyosin (15.92 mg/kg) followed by HPP samples.

Motivational profiles and their relation to wellbeing, burnout, and drop-out intentions in university football players in the UK: A mixed methods approach.

In this multi-study paper, we adopted a mixed methods approach to examine the motivational profiles of sub-elite student footballers participating in UK university sport, in relation to their wellbeing, burnout, and drop-out intentions. In Study 1 we used a cross-sectional survey design to collect quantitative measures of motivational regulations, wellbeing, burnout, and drop-out intentions in 260 (n = 129 female) and (n = 131 male) sub-elite university footballers from UK universities (Mage = 20.7 y, SD = 1.5 y). Latent profile analysis revealed five distinct motivational regulation profiles that we deemed ranged from less to more motivationally adaptive in the following order: High-controlled, Amotivated (n = 27), Very-low Motivation (n = 32), Average Motivation (n = 104), High-autonomous, High-controlled (n = 38), and High-autonomous, Low-controlled (n = 59). Wald chi-square tests revealed between-profile differences in wellbeing (χ2 = 115, p < .001), burnout (reduced accomplishment: χ2 = 74, p < .001, exhaustion: χ2 = 34, p < .001, devaluation: χ2 = 121, p < .001), and drop-out intentions (university football: χ2 = 40, p < .001, football in general: χ2 = 91, p < .001). Pairwise comparisons suggested more adaptive motivational profiles had higher wellbeing, and lower burnout and drop-out intentions, than less adaptive profiles. Subsequently, in Study 2 we qualitatively explored the experiences of footballers from the different motivational profiles. We purposefully sampled 2-4 participants from each of the five motivational profiles to take part in focus groups, resulting in a total of 15 participants (Mage = 21.6 y, SD = 1.41 y; n = 8 female, n = 7 male). Results revealed commonalities across the motivational profiles, including that while motivation was complex, individualized, dynamic and interactive in nature; a central, underlying motivator for all players was their passion for football. However, results also suggested that compared to those from less motivationally adaptive profiles, those from more adaptive profiles tended to perceive the environment more positively and tended to feel more valued by those around them. Thus, protecting players' passion for football and helping them feel more valued within their university-sport environment may support players in remaining in, or moving towards, more adaptive motivational regulation profiles and experiencing associated positive outcomes.

Pharmacological targeting of coagulation factor XI attenuates experimental autoimmune encephalomyelitis in mice.

Multiple sclerosis (MS) is the most common causes of non-traumatic disability in young adults worldwide. MS pathophysiologies include the formation of inflammatory lesions, axonal damage and demyelination, and blood brain barrier (BBB) disruption. Coagulation proteins, including factor (F)XII, can serve as important mediators of the adaptive immune response during neuroinflammation. Indeed, plasma FXII levels are increased during relapse in relapsing-remitting MS patients, and previous studies showed that reducing FXII levels was protective in a murine model of MS, experimental autoimmune encephalomyelitis (EAE). Our objective was to determine if pharmacological targeting of FXI, a major substrate of activated FXII (FXIIa), improves neurological function and attenuates CNS damage in the setting of EAE. EAE was induced in male mice using murine myelin oligodendrocyte glycoprotein peptides combined with heat-inactivated Mycobacterium tuberculosis and pertussis toxin. Upon onset of symptoms, mice were treated every other day intravenously with anti-FXI antibody, 14E11, or saline. Disease scores were recorded daily until euthanasia for ex vivo analyses of inflammation. Compared to the vehicle control, 14E11 treatment reduced the clinical severity of EAE and total mononuclear cells, including CD11b+CD45high macrophage/microglia and CD4+ T cell numbers in brain. Following pharmacological targeting of FXI, BBB disruption was reduced, as measured by decreased axonal damage and fibrin(ogen) accumulation in the spinal cord. These data demonstrate that pharmacological inhibition of FXI reduces disease severity, immune cell migration, axonal damage, and BBB disruption in mice with EAE. Thus, therapeutic agents targeting FXI and FXII may provide a useful approach for treating autoimmune and neurologic disorders.

Living with epilepsy during COVID-19 pandemic restrictions: A longitudinal perspective.

The purpose of our study was to explore how people with epilepsy fared during two of the most stringent 4-month society-wide COVID-19-related pandemic restrictions in Ireland, in 2020 and one year later in 2021. This was in the context of their seizure control, lifestyle factors, and access to epilepsy-related healthcare services. A 14-part questionnaire was administered to adults with epilepsy during virtual specialist epilepsy clinics in a University Hospital in Dublin, Ireland at the end of the two lockdowns. People with epilepsy were questioned on their epilepsy control, lifestyle factors, and quality of epilepsy-related medical care, compared to pre-COVID times. The study sample consisted of two separate cohorts of those diagnosed with epilepsy (100 (51.8%) in 2020, and 93 (48.2%) in 2021, with similar baseline characteristics. There was no significant change in seizure control or lifestyle factors from 2020 to 2021, except for deterioration in anti-seizure medication (ASM) adherence in 2021 compared to 2020 (p = 0.028). There was no correlation between ASM adherence and other lifestyle factors. Over the two years, poor seizure control was significantly associated with poor sleep (p < 0.001) and average seizure frequency in a month (p = 0.007). We concluded that there was no significant difference between seizure control or lifestyle factors between the two most stringent lockdowns in Ireland, in 2020 and 2021. Furthermore, people with epilepsy reported that throughout the lockdowns access to services was well maintained, and they felt well supported by their services. Contrary to the popular opinion that COVID lockdowns greatly affected patients with chronic diseases, we found that those with epilepsy attending our service remained largely stable, optimistic, and healthy during this time.

Biomolecules from Macroalgae-Nutritional Profile and Bioactives for Novel Food Product Development.

Seaweed is in the spotlight as a promising source of nutrition for humans as the search for sustainable food production systems continues. Seaweed has a well-documented rich nutritional profile containing compounds such as polyphenols, carotenoids and polysaccharides as well as proteins, fatty acids and minerals. Seaweed processing for the extraction of functional ingredients such as alginate, agar, and carrageenan is well-established. Novel pretreatments such as ultrasound assisted extraction or high-pressure processing can be incorporated to more efficiently extract these targeted ingredients. The scope of products that can be created using seaweed are wide ranging: from bread and noodles to yoghurt and milk and even as an ingredient to enhance the nutritional profile and stability of meat products. There are opportunities for food producers in this area to develop novel food products using seaweed. This review paper discusses the unique properties of seaweed as a food, the processes involved in seaweed aquaculture, and the products that can be developed from this marine biomass. Challenges facing the industry such as consumer hesitation around seaweed products, the safety of seaweed, and processing hurdles will also be discussed.

Embedding Physical Activity into Community-Based Peer Support Groups for those Severely Affected by Mental Illness.

Despite a growing evidence base on the effectiveness of community-based physical activity interventions for mental health, there is a lack of studies that focus on those affected by severe mental illness (SMI), who often experience poorer physical health, and are less physically active than the wider population. The use of peer support groups in this context is also understudied, despite benefits being documented in other contexts. This study examined the impact and process of a nationwide project to embed physical activity into peer support groups for those affected by SMI. Following the embedding of physical activity within peer support groups, interviews and focus groups were conducted to explore the experiences of those involved with the project and analysed using reflexive thematic analysis. The key findings related to: 1) the social aspects of embedding physical activity in the groups; 2) the focus on peer support and informal physical activity (rather than organised sport) being beneficial; 3) doing things differently and lessons to learn; and 4) the impact of the COVID-19 pandemic. Overall, we found that peer support is an important feature to include in projects encouraging those severely affected by mental illness to become more physically active.

Indicators for effective visiting primary care services: A case study.

OBJECTIVE: The objective of this study was to assess the clinical utility of a model of seven principles for effective visiting primary care services and to determine how it could be conceptualised as a tool for evaluation. SETTING: The research was undertaken in the context of visiting primary care services with an agency, Outback Futures, selected as a case study. PARTICIPANTS: Three executive staff with Outback Futures participated in the research. DESIGN: The case study design involved data collection by four group interviews conducted between July and November 2021. The interview data were analysed using thematic analysis. RESULTS: This case study is additional evidence for the clinical utility of the model of seven principles. The results reinforce the importance of a community-focussed approach to assess the impact of visiting service organisations on rural and remote communities. A comprehensive approach to evaluation is required to justify the investments made and safeguard the health and well-being of rural and remote residents. A self-assessment protocol has been established from the model for use by visiting services. Furthermore, three themes were drawn from the data: relationship is fundamental, the importance of co-design, and being effective as a visiting service is challenging. CONCLUSION: The model is appropriate for the case study organisation, and has clinical utility and implications for other visiting services. A self-assessment protocol has been developed. Future research should apply the model and protocol self-assessment tool in an effort to construct a consistent and credible approach to evaluation of visiting primary care services.

Defining the normal range of fractional exhaled nitric oxide in children: one size does not fit all.

Background: The normal range of fractional exhaled nitric oxide (F ENO) is influenced by demographic factors. However, single, fixed cut-off values are used for clinical interpretation in children despite rapid growth. We aimed to define the normal range of F ENO during childhood and evaluate its utility in a diagnostic setting. Method: F ENO percentile charts were developed using data from nonasthmatic children in a population-based birth cohort (Manchester Asthma and Allergy Study). Children were skin prick tested, F ENO measured at the ages of 8, 11, 13-16 and 18 years and clinical information collected. This chart was externally validated in the Study of Eczema and Asthma to Observe the Influence of Nutrition (SEATON) cohort before being prospectively tested in symptomatic, treatment-naïve patients with suspected asthma in a diagnostic setting (Rapid Access Diagnostics for Asthma study). Results: Height, weight, body mass index and age were predictive of F ENO in univariate analysis using 1220 F ENO measurements. Only height remained significant after adjustment in the overall, nonatopic and atopic populations, and was included in the predictive equations for 50th, 75th 90th and 98th percentiles. The proposed percentile lines corresponded to the 57th (95% CI 53rd-61st), 80th (76th-83rd), 90th (87th-92nd) and 98th (96th-99th) percentiles in the SEATON cohort (660 measurements). When tested in 73 symptomatic treatment-naïve children and young adults (median (interquartile range) age: 11 (8-14) years), an F ENO >90th percentile gave a 96% specificity and positive predictive value of 97%, identifying 59% of children who were subsequently diagnosed with asthma after extensive testing. Conclusion: We developed a height-based F ENO percentile chart which quantifies the probability of asthma in symptomatic children and merits further validation towards clinical implementation.

Unbiased approach to identify and assess efficacy of human SARS-CoV-2 neutralizing antibodies.

Coronavirus disease 2019 (COVID-19) continues to significantly impact the global population, thus countermeasure platforms that enable rapid development of therapeutics against variants of SARS-CoV-2 are essential. We report use of a phage display human antibody library approach to rapidly identify neutralizing antibodies (nAbs) against SARS-CoV-2. We demonstrate the binding and neutralization capability of two nAbs, STI-2020 and STI-5041, against the SARS-CoV-2 WA-1 strain as well as the Alpha and Beta variants. STI-2020 and STI-5041 were protective when administered intravenously or intranasally in the golden (Syrian) hamster model of COVID-19 challenged with the WA-1 strain or Beta variant. The ability to administer nAbs intravenously and intranasally may have important therapeutic implications and Phase 1 healthy subjects clinical trials are ongoing.

"From everything to nothing in a split second": Elite youth players' experiences of release from professional football academies.

Previous research has assessed the affects release from football academies has on psychological distress and athletic identity of players. However, there has been no qualitative research exploring players' experiences of the release process. This study retrospectively explored players' lived experiences of being released from a professional football academy, having completed a scholarship (from ages 16-18). Four male football players (age 21.6 ± 1.5 years) who had experienced release from professional academies participated in in-depth semi-structured interviews. Data were analyzed using Interpretative Phenomenological Analysis. Four super-ordinate themes were interpreted from the data: Foreshadowing release-"left out in the cold", The process of release, Support during the process of release and New beginnings-"there's a bigger world than just playing football every day". Players reported that their contract meeting was a traumatic experience, and they experienced psychological difficulties in the longer-term following release. Factors that compounded the players' release were: a lack of aftercare being provided by the players' professional clubs for their wellbeing, and a disuse of social support, which hindered their transition out of full-time football. Context relevant recommendations are made to help improve the release process for elite youth football players.

Discovery and intranasal administration of a SARS-CoV-2 broadly acting neutralizing antibody with activity against multiple Omicron subvariants.

BACKGROUND: The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern, in particular the newly emerged Omicron (B.1.1.529) variant and its BA.X lineages, has rendered ineffective a number of previously FDA emergency use authorized SARS-CoV-2 neutralizing antibody therapies. Furthermore, those approved antibodies with neutralizing activity against Omicron BA.1 are reportedly ineffective against the subset of Omicron subvariants that contain a R346K substitution, BA.1.1, and the more recently emergent BA.2, demonstrating the continued need for discovery and characterization of candidate therapeutic antibodies with the breadth and potency of neutralizing activity required to treat newly diagnosed COVID-19 linked to recently emerged variants of concern. METHODS: Following a campaign of antibody discovery based on the vaccination of Harbor H2L2 mice with defined SARS-CoV-2 spike domains, we have characterized the activity of a large collection of spike-binding antibodies and identified a lead neutralizing human IgG1 LALA antibody, STI-9167. FINDINGS: STI-9167 has potent, broad-spectrum neutralizing activity against the current SARS-COV-2 variants of concern and retained activity against each of the tested Omicron subvariants in both pseudotype and live virus neutralization assays. Furthermore, STI-9167 nAb administered intranasally or intravenously provided protection against weight loss and reduced virus lung titers to levels below the limit of quantitation in Omicron-infected K18-hACE2 transgenic mice. CONCLUSIONS: With this established activity profile, a cGMP cell line has been developed and used to produce cGMP drug product intended for intravenous or intranasal use in human clinical trials. FUNDING: Funded by CRIPT (no. 75N93021R00014), DARPA (HR0011-19-2-0020), and NCI Seronet (U54CA260560).

Female Sex is Associated with Worse Outcomes following Complex Fenestrated or Branched Endovascular Aortic Repair.

BACKGROUND: Sex-related discrepancies after standard endovascular aneurysm repair (EVAR) are noted to disproportionally affect females. A growing body of literature suggests similar disparities may extend to complex fenestrated or branched endovascular aneurysm repair (FBEVAR). However, recent examination of complex FBEVAR by a consortium of high-volume centers noted equivalent mortality among sexes. Whether similar results extend to non-trial data is unknown. METHODS: We examined all juxta-renal through type IV thoraco-abdominal aneurysms (sealing zones 6-8) which underwent elective FBEVAR within the Vascular Quality Initiative (VQI) database from January 2012 to December 2020. Urgent, symptomatic, ruptured, and staged cases were excluded, as were parallel stent grafts. Demographics, comorbid conditions, and technical factors were compared between sexes. Univariate analysis with Wilcoxon ranked sum tests and Chi-square tests of proportion were performed, followed by multivariate logistic regression for failure of target vessel technical success, reintervention, complications, and in-hospital mortality. RESULTS: Our analysis included 1,521 patients, 1,180 males (77.6%) and 341 females (22.4%). There were noted differences in pre-operative demographics, medical optimization, and technical aspects of the procedure. However, no difference was noted in proximal or distal sealing stents, number of fenestrations, or immediate endoleaks. On a multi variate logistic regression, female sex was an independent predictor of failure of target vessel technical success (odds ratio (OR) 3.339, 95% confidence interval (CI): 2.173-5.132, P < 0.001), reintervention (OR 2.192, 95% CI: 1.304-3.683, P = 0.003), complications (OR 1.747, 95% CI: 1.282-2.381, P < 0.001), and in-hospital mortality (OR 2.836, 95% CI: 1.510-5.328, P = 0.001). CONCLUSIONS: Females suffer worse outcomes after FBEVAR despite similar extent of disease, number of fenestrations, and incidence of immediate endoleak. Notable discrepancies were higher rates of chronic obstructive pulmonary disease (COPD) and lower rates of pre-operative aspirin, statin, and beta blocker therapy in females. Controlling for pre-operative demographics, female sex remained an independent predictor of worse outcomes. These discrepancies warrant further examination and should impact case planning for female patients undergoing complex aortic aneurysm repair.

Impacts of novel blanching treatments combined with commercial drying methods on the physicochemical properties of Irish brown seaweed Alaria esculenta.

Alaria esculenta is one of the most abundant edible brown seaweeds in Irelandandisconsidered an excellent source of nutrients, sought after by the food, nutraceutical and pharmaceutical industries. Seaweed is typically blanched and dried prior to consumption to enhance the end-product quality attributes and shelf life. Three blanching techniques were examined in this work; conventional hot water blanching, novel ultrasound blanching and microwave blanching. The L* and b*colour metrics were affected significantly (P < 0.01) by the processing methods. There were 76 volatile compounds detected in blanched and dehydrated Alaria esculenta. Freeze-dried samples after treatment with microwave alone (at 1000 W) and microwave (800 W) combined with ultrasound (at 50% amplitude) had the highest retention rate of volatile compounds (up to 98.61%). Regarding mineral content, drying methods significantly affected (P < 0.05) the content of Ca, Co, Cu and Fe, while blanching treatments significantly affected (P < 0.05) the content of Na, Cu, Fe and Mn.

International Recommendations for the Management of Adults Treated With Ketogenic Diet Therapies.

OBJECTIVE: To evaluate current clinical practices and evidence-based literature to establish preliminary recommendations for the management of adults using ketogenic diet therapies (KDTs). METHODS: A 12-topic survey was distributed to international experts on KDTs in adults consisting of neurologists and dietitians at medical institutions providing KDTs to adults with epilepsy and other neurologic disorders. Panel survey responses were tabulated by the authors to determine the common and disparate practices between institutions and to compare these practices in adults with KDT recommendations in children and the medical literature. Recommendations are based on a combination of clinical evidence and expert opinion regarding management of KDTs. RESULTS: Surveys were obtained from 20 medical institutions with >2,000 adult patients treated with KDTs for epilepsy or other neurologic disorders. Common side effects reported are similar to those observed in children, and recommendations for management are comparable with important distinctions, which are emphasized. Institutions differ with regard to recommended biochemical assessment, screening, monitoring, and concern for long-term side effects, and further investigation is warranted to determine the optimal clinical management. Differences also exist between screening and monitoring practices among adult and pediatric providers. CONCLUSIONS: KDTs may be safe and effective in treating adults with drug-resistant epilepsy, and there is emerging evidence supporting the use in other adult neurologic disorders and general medical conditions as well. Therefore, expert recommendations to guide optimal care are critical as well as further evidence-based investigation.

Revised model for evaluating visiting health care services in rural and remote settings.

OBJECTIVE: Visiting health care services were developed to improve access to essential health care in rural and remote areas. Evaluating these services requires a robust framework. The objective of this study was to assess the confirmability and credibility of a model of 7 principles for effective visiting health care services. SETTING: Three iterative online survey rounds administered between July and December 2020. PARTICIPANTS: A heterogeneous panel of 13 experts in rural and remote health care participated, including managers of health care services, senior clinical staff in rural and remote regions and research academics specialising in rural infrastructure. DESIGN: The model was appraised using the Delphi method involving iterative online survey rounds to facilitate anonymous and structured discussion between panel members. RESULTS: Findings indicate consensus between panel members and support for a revised model. The revised model includes 4 modifications: (a) proposal of a new principle titled Feasibility, (b) restructure of 2 existing principles, (c) refined shape of the model to more accurately reflect the nature of service delivery and (d) detailed definitions of each principle. CONCLUSION: This study presents a credible, revised version of the model of 7 principles for effective visiting services. This will enhance the quality of the health workforce across geographically large countries, like Australia, enabling organisations to more effectively and consistently evaluate the impact of their service on rural and remote communities.