Free energy calculations for membrane morphological transformations and insights to physical biology and oncology.

In this chapter, we aim to bridge basic molecular and cellular principles surrounding membrane curvature generation with rewiring of cellular signals in cancer through multiscale models. We describe a general framework that integrates signaling with other cellular functions like trafficking, cell-cell and cell-matrix adhesion, and motility. The guiding question in our approach is: how does a physical change in cell membrane configuration caused by external stimuli (including those by the extracellular microenvironment) alter trafficking, signaling and subsequent cell fate? We answer this question by constructing a modeling framework based on stochastic spatial continuum models of cell membrane deformations. We apply this framework to explore the link between trafficking, signaling in the tumor microenvironment, and cell fate. At each stage, we aim to connect the results of our predictions with cellular experiments.

The role of extended reality in optometry education: a narrative review.

The evolution of digitally based pedagogies, such as extended reality (XR) - a group of simulated learning environments that include virtual simulation, virtual reality, and augmented reality - has prompted optometry educators to seek evidence to guide the implementation of these teaching and learning activities within their curricula. Looking more broadly across the medical and allied health fields, there is a wealth of evidence to guide the incorporation of XR, as it is increasingly being integrated into the curricula of other select health professions disciplines. Educators from these disciplines continue to explore and embed XR in practice. This narrative review summarises the findings and appraises the literature on the use of XR in optometry education. It identifies the learning domains in which XR has been implemented in optometry education and proposes areas for further investigation. The review questions the technology-focused approach that has driven the literature within the review and calls for richer pedagogical foundations with suggestions for future research agendas. As such, this narrative review provides optometry educators with new ways of understanding XR and its relationship with the curriculum.

Asymmetric crowders and membrane morphology at the nexus of intracellular trafficking and oncology.

A definitive understanding of the interplay between protein binding/migration and membrane curvature evolution is emerging but needs further study. The mechanisms defining such phenomena are critical to intracellular transport and trafficking of proteins. Among trafficking modalities, exosomes have drawn attention in cancer research as these nano-sized naturally occurring vehicles are implicated in intercellular communication in the tumor microenvironment, suppressing anti-tumor immunity and preparing the metastatic niche for progression. A significant question in the field is how the release and composition of tumor exosomes are regulated. In this perspective article, we explore how physical factors such as geometry and tissue mechanics regulate cell cortical tension to influence exosome production by co-opting the biophysics as well as the signaling dynamics of intracellular trafficking pathways and how these exosomes contribute to the suppression of anti-tumor immunity and promote metastasis. We describe a multiscale modeling approach whose impact goes beyond the fundamental investigation of specific cellular processes toward actual clinical translation. Exosomal mechanisms are critical to developing and approving liquid biopsy technologies, poised to transform future non-invasive, longitudinal profiling of evolving tumors and resistance to cancer therapies to bring us one step closer to the promise of personalized medicine.

Acupuncture knowledge, attitudes, beliefs and health service needs after traumatic brain injury: a cross-sectional survey.

BACKGROUND: Acupuncture is a promising treatment for common symptoms after traumatic brain injury (TBI). Our objectives were to explore knowledge, attitudes and beliefs about acupuncture, identify health service needs and assess the perceived feasibility of weekly acupuncture visits among individuals with TBI. METHODS: We surveyed adults 18 years of age and older with TBI who received care at the University of Washington. Respondents were asked to complete 143 questions regarding acupuncture knowledge, attitudes and beliefs, injury-related symptoms and comorbidities, and to describe their interest in weekly acupuncture. RESULTS: Respondents (n = 136) reported a high degree of knowledge about acupuncture as a component of Traditional Chinese Medicine, needle use and safety, but were less knowledgeable regarding that the fact that most conditions require multiple acupuncture treatments to achieve optimal therapeutic benefit. Respondents were comfortable talking with healthcare providers about acupuncture (63.4%), open to acupuncture concurrent with conventional treatments (80.6%) and identified lack of insurance coverage as a barrier (50.8%). Beliefs varied, but respondents were generally receptive to using acupuncture as therapy. Unsurprisingly, respondents with a history of acupuncture (n = 60) had more acupuncture knowledge than those without such a history (n = 66) and were more likely to pursue acupuncture without insurance (60%), for serious health conditions (63.3%) or alongside conventional medical therapy (85.0%). Half of all respondents expressed interest in participating in weekly acupuncture for up to 12 months and would expect almost a 50% improvement in symptoms by participating. CONCLUSION: Adults with TBI were receptive and interested in participating in weekly acupuncture to address health concerns. These results provide support for exploring the integration of acupuncture into the care of individuals with TBI.

Evaluating Mineral Biomarkers as Mediators and Moderators of Behavioural Improvements in a Randomized Controlled Trial of Multinutrients for Children with ADHD.

Essential minerals are cofactors for synthesis of neurotransmitters supporting cognition and mood. An 8-week fully-blind RCT of multinutrients for ADHD demonstrated three times as many children (age 6-12) had significantly improved behavior ("treatment responders") on multinutrients (54%) compared to placebo (18%). The aim of this secondary study was to evaluate changes in fasted plasma and urinary mineral concentrations following the intervention, and their role as mediators and moderators of treatment response. Fourteen essential or trace minerals were measured in plasma and/or urine at baseline and week 8 from 86 participants (49 multinutrient, 37 placebo). Two-sample t-tests/Mann-Whitney U-tests compared 8-week change between treatment and placebo groups, which were also evaluated as potential mediators. Baseline levels were evaluated as potential moderators, using logistic regression models with clinical treatment response as the outcome. After 8 weeks, plasma boron, chromium (in females only), lithium, molybdenum, selenium, and vanadium, and urinary iodine, lithium, and selenium increased more with multinutrients than placebo, while plasma phosphorus decreased. These changes did not mediate treatment response. However, baseline urinary lithium trended toward moderation: participants with lower baseline urinary lithium were more likely to respond to multinutrients (p=0.058). Additionally, participants with higher baseline iron were more likely to be treatment responders regardless of treatment group (p=0.036.) These results show that multinutrient treatment response among children with ADHD is independent of their baseline plasma mineral levels, while baseline urinary lithium levels show potential as a non-invasive biomarker of treatment response requiring further study.

Virtually delivered Mindfulness-Oriented Recovery Enhancement (MORE) reduces daily pain intensity in patients with lumbosacral radiculopathy: a randomized controlled trial.

Introduction: Lumbosacral radiculopathy (LR), also known as sciatica, is a common type of radiating neurologic pain involving burning, tingling, and numbness in the lower extremities. It has an estimated lifetime prevalence as high as 43%. Objectives: The objective of this randomized controlled trial was to evaluate the impact of virtually delivered Mindfulness-Oriented Recovery Enhancement (MORE) on patients with LR during the COVID-19 pandemic. Methods: Potentially eligible patients were identified using electronic health record queries and phone screenings. Participants were then randomized to MORE or treatment-as-usual (TAU) for 8 weeks, with pain intensity assessed daily. At baseline and follow-up visits, participants completed questionnaires assessing the primary outcome, disability, as well as quality of life, depression, mindful reinterpretation of pain, and trait mindfulness. Results: In our study, patients undergoing virtual delivery of MORE had greater improvements in daily pain intensity (P = 0.002) but not in disability (P = 0.09), depression (P = 0.26), or quality of life (P = 0.99 and P = 0.89, SF-12 physical and mental component scores, respectively), relative to TAU patients. In addition, patients in MORE experienced significantly greater increases in mindful reinterpretation of pain (P = 0.029) and trait mindfulness (P = 0.035). Conclusion: Among patients with lumbar radiculopathy, MORE significantly reduced daily pain intensity but did not decrease disability or depression symptoms. Given the long duration of symptoms in our sample, we hypothesize the discrepancy between changes in daily pain intensity and disability is due to fear avoidance behaviors common in patients with chronic pain. As the first trial of a mindfulness intervention in patients with LR, these findings should inform future integrative approaches to LR treatment, particularly when considering the increasing use of virtual interventions throughout the COVID-19 pandemic.

Use of once-daily oral semaglutide and associated clinical outcomes among adults with type 2 diabetes in routine clinical practice in Canada: A multicentre, prospective real-world study (PIONEER REAL Canada).

AIM: PIONEER REAL Canada examined real-world clinical outcomes associated with the use of once-daily oral semaglutide in adults with type 2 diabetes. MATERIALS AND METHODS: This was a 34- to 44-week, multicentre, prospective, open-label, non-interventional study in adults who were treatment-naive to injectable glucose-lowering medication and initiated oral semaglutide in routine clinical practice. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to the end of the study (EoS). Secondary endpoints assessed at EoS were change from baseline in body weight (BW); the proportion of participants reaching HbA1c levels <7% and the composite endpoints, HbA1c reduction ≥1% point with BW reduction ≥3% and ≥5%; and treatment satisfaction measured using Diabetes Treatment Satisfaction Questionnaires (DTSQ) status and change. Primary analyses were based on the in-study observation period. RESULTS: In total, 182 participants initiated oral semaglutide (mean age, 58.6 years; HbA1c, 8.0%; BW, 93.7 kg). The estimated changes (95% confidence interval) from baseline to EoS in HbA1c and BW were -1.09% points (-1.24, -0.94; p < .0001) and -7.17% (-8.24, -6.11; p < .0001), respectively. At EoS, 53.7% of participants had HbA1c levels <7%; 39.3% and 31.6% reached HbA1c reduction ≥1% point plus BW reduction ≥3% and ≥5%, respectively. Treatment satisfaction significantly increased (DTSQ status, +4.47 points; DTSQ change, 11.83 points; both p < .0001). At EoS, 75.3% of participants remained on oral semaglutide (55.5% received oral semaglutide 14 mg). No new safety signals were identified for oral semaglutide. CONCLUSIONS: In PIONEER REAL Canada, participants treated with oral semaglutide in routine clinical practice experienced clinically relevant reductions in HbA1c and BW and increased treatment satisfaction.

Relationships between Habitual Polyphenol Consumption and Gut Microbiota in the INCLD Health Cohort.

While polyphenol consumption is often associated with an increased abundance of beneficial microbes and decreased opportunistic pathogens, these relationships are not completely described for polyphenols consumed via habitual diet, including culinary herb and spice consumption. This analysis of the International Cohort on Lifestyle Determinants of Health (INCLD Health) cohort uses a dietary questionnaire and 16s microbiome data to examine relationships between habitual polyphenol consumption and gut microbiota in healthy adults (n = 96). In this exploratory analysis, microbial taxa, but not diversity measures, differed by levels of dietary polyphenol consumption. Taxa identified as exploratory biomarkers of daily polyphenol consumption (mg/day) included Lactobacillus, Bacteroides, Enterococcus, Eubacterium ventriosum group, Ruminococcus torques group, and Sutterella. Taxa identified as exploratory biomarkers of the frequency of polyphenol-weighted herb and spice use included Lachnospiraceae UCG-001, Lachnospiraceae UCG-004, Methanobrevibacter, Lachnoclostridium, and Lachnotalea. Several of the differentiating taxa carry out activities important for human health, although out of these taxa, those with previously described pro-inflammatory qualities in certain contexts displayed inverse relationships with polyphenol consumption. Our results suggest that higher quantities of habitual polyphenol consumption may support an intestinal environment where opportunistic and pro-inflammatory bacteria are represented in a lower relative abundance compared to those with less potentially virulent qualities.

Gut enterotype-dependent modulation of gut microbiota and their metabolism in response to xanthohumol supplementation in healthy adults.

Xanthohumol (XN), a polyphenol found in the hop plant (Humulus lupulus), has antioxidant, anti-inflammatory, prebiotic, and anti-hyperlipidemic activity. Preclinical evidence suggests the gut microbiome is essential in mediating these bioactivities; however, relatively little is known about XN's impact on human gut microbiota in vivo. We conducted a randomized, triple-blinded, placebo-controlled clinical trial (ClinicalTrials.gov NCT03735420) to determine safety and tolerability of XN in healthy adults. Thirty healthy participants were randomized to 24 mg/day XN or placebo for 8 weeks. As secondary outcomes, quantification of bacterial metabolites and 16S rRNA gene sequencing were utilized to explore the relationships between XN supplementation, gut microbiota, and biomarkers of gut health. Although XN did not significantly change gut microbiota composition, it did re-shape individual taxa in an enterotype-dependent manner. High levels of inter-individual variation in metabolic profiles and bioavailability of XN metabolites were observed. Moreover, reductions in microbiota-derived bile acid metabolism were observed, which were specific to Prevotella and Ruminococcus enterotypes. These results suggest interactions between XN and gut microbiota in healthy adults are highly inter-individualized and potentially indicate that XN elicits effects on gut health in an enterotype-dependent manner.

Economic impacts of marine debris encounters on commercial shrimping.

The commercial shrimping industry is subjected to myriad stressors that have led to financial hardships among industry members. One of these stressors is marine debris; however, there is limited understanding of the type and magnitude of impacts. Quantitative methods of estimating the economic impacts of marine debris on the commercial shrimping industry were developed. From June to December 2019, participating shrimpers submitted 393 daily summaries, including shrimping activities, marine debris encounters, damages, and impacts. The impacts of marine debris encounters were assessed from reports of daily damages to fishing assets, daily lost fishing time, daily loss-catch ratios, and daily catch losses. The results of this study demonstrate substantial negative economic impacts on commercial shrimpers related to marine debris encounters. About 17 % of shrimp caught were lost due to marine debris encounters, resulting in foregone total sales and job impacts of $3.2 million and 33 jobs in shrimping and associated businesses.

Affinity- and activity-based probes synthesized from structurally diverse hops-derived xanthohumol flavonoids reveal highly varied protein profiling in Escherichia coli.

Xanthohumol, the principle prenylflavonoid found in hops (Humulus lupulus) and a reported anti-inflammatory agent, has great potential for pharmaceutical interventions related to inflammatory disorders in the gut. A suite of probes was prepared from xanthohumol and its structural isomer isoxanthohumol to enable profiling of both protein affinity binding and catalytic enzyme reactivity. The regiochemistry of the reactive group on the probes was altered to reveal how probe structure dictates protein labeling, and which probes best emulate the natural flavonoids. Affinity- and activity-based probes were applied to Escherichia coli, and protein labeling was measured by chemoproteomics. Structurally dependent activity-based probe protein labeling demonstrates how subtle alterations in flavonoid structure and probe reactive groups can result in considerably different protein interactions. This work lays the groundwork to expand upon unexplored cellular activities related to xanthohumol interactions, metabolism, and anti-inflammatory mechanisms.

Associations Between Monthly Cannabis Use and Myocardial Infarction in Middle-Aged Adults: NHANES 2009 to 2018.

Mechanistic research suggests using Cannabis sativa L. (cannabis or marijuana) may increase the risk of cardiometabolic disease, but observational studies investigating associations between cannabis use and myocardial infarction (MI) have reported inconsistent results. Cross-sectional National Health and Nutrition Examination Survey data from five 2-year cycles between 2009 and 2018 and representing 9,769 middle-aged adults (35 to 59 years old) were analyzed. Multivariable logistic regression models accounting for sampling weights and adjusting for cardiovascular risk factors were used to assess associations between a history of monthly cannabis use before MI and a subsequent MI. A quarter of respondents (n = 2,220) reported a history of monthly use >1 year before an MI. A history of MI was reported by 2.1% of all respondents and 3.2.% of those who reported a history of monthly use. In fully adjusted multivariable models, and compared with never use, a history of monthly cannabis use preceding an MI was not associated with an MI (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.35 to 1.71). However, when stratified by recent use, the odds of MI were threefold greater (OR 2.98, 95% CI 1.08 to 8.60) when no use was reported within the past month than when use was reported within the past month. Duration of monthly use was also not significantly associated with MI, including monthly use >10 years (OR 0.78, 95% CI 0.30 to 2.01). In conclusion, in a representative sample of middle-aged US adults, a history of monthly cannabis use >1 year before an MI was not associated with a subsequent physician-diagnosed MI, except for threefold greater odds when cannabis was not used within the past month.

Trends in Cannabis Use, Blood Pressure, and Hypertension in Middle-Aged Adults: Findings From NHANES, 2009-2018.

BACKGROUND: Observational studies investigating associations between cannabis use and blood pressure (BP)/hypertension are inconsistent. METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) were analyzed for five 2-year cycles between 2009 and 2018 representing 9,783 middle-aged adults (35-59 years). Hypertension was defined as systolic BP (SBP) ≥130, diastolic BP (DBP) ≥80, or a BP medication. Sample-weighted multivariable logistic regression models were used to assess associations between cannabis use and BP and hypertension. RESULTS: One quarter of respondents (n = 2,228) reported a history of monthly cannabis use for more than 1 year, which was consistent over the study period (P for trend = 0.75). Approximately 48% (n = 4,831) met the definition of hypertension. While a significant positive trend was seen over time for mean SBP and DBP (P = <0.01 for both), no significant trend was seen in prevalent hypertension (P for trend = 0.23). In adjusted models, compared with never use, a history of monthly cannabis use for more than 1 year was not associated with increased BP (mean SBP: 124.5 mm Hg (95% confidence interval [CI], 122.4-126.6) vs. 122.6 (95% CI, 120.9-124.2); DBP: 74.7 mm Hg (95% CI, 73.1-76.2) vs. 74.1 (95% CI, 72.8-75.4)), or prevalent hypertension (odds ratio = 0.88 (95% CI, 0.62-1.24)). Results from analyses of duration of monthly use, and recency and frequency of recent use were similar. CONCLUSIONS: A history of monthly cannabis use for more than 1 year was not independently associated with either increased BP or prevalent hypertension in a nationally representative sample of middle-aged US adults.

LASSNet: A Four Steps Deep Neural Network for Left Atrial Segmentation and Scar Quantification.

Accurate quantification of left atrium (LA) scar in patients with atrial fibrillation is essential to guide successful ablation strategies. Prior to LA scar quantification, a proper LA cavity segmentation is required to ensure exact location of scar. Both tasks can be extremely time-consuming and are subject to inter-observer disagreements when done manually. We developed and validated a deep neural network to automatically segment the LA cavity and the LA scar. The global architecture uses a multi-network sequential approach in two stages which segment the LA cavity and the LA Scar. Each stage has two steps: a region of interest Neural Network and a refined segmentation network. We analysed the performances of our network according to different parameters and applied data triaging. 200+ late gadolinium enhancement magnetic resonance images were provided by the LAScarQS 2022 Challenge. Finally, we compared our performances for scar quantification to the literature and demonstrated improved performances.

Observed Improvement in Cognition During a Personalized Lifestyle Intervention in People with Cognitive Decline.

BACKGROUND: Alzheimer's disease (AD) is a chronic condition marked by progressive objective cognitive impairment (OCI). No monotherapy has substantially altered disease progression, suggesting the disease is multifactorial and may require a multimodal therapeutic approach. OBJECTIVE: We sought to determine if cognitive function in a sample with OCI would change in response to a multimodal, individualized care plan based on potential contributors to cognitive decline (e.g., nutritional status, infection, etc.). METHODS: Participants (n = 34) were recruited from the San Diego, CA area. The multimodal intervention included lifestyle changes (i.e., movement, diet, and stress management), nutraceutical support, and medications. It was delivered pragmatically over four clinical visits, and outcome measures were gathered at four study visits, occurring at baseline, one, three, and six months (primary endpoint). Study participants received weekly phone calls for nutrition support throughout study participation. Outcome measures included the Cambridge Brain Sciences (CBS) battery, and the Montreal Cognitive Assessment (MoCA). RESULTS: At 6 months, mean MoCA scores improved from 19.6±3.1 to 21.7±6.2 (p = 0.013). Significant improvement was observed in mean scores of the CBS memory domain [25.2 (SD 23.3) to 35.8 (SD 26.9); p < 0.01] and CBS overall composite cognition score [24.5 (SD 16.1) to 29.7 (SD 20.5); p = 0.02]. All CBS domains improved. CONCLUSION: Multiple measures of cognitive function improved after six months of intervention. Our results support the feasibility and impact of a multimodal, individualized treatment approach to OCI, warranting further research.

Reporting of adverse effects of pomegranate in clinical studies: a systematic review.

OBJECTIVES: Numerous studies have shown the pharmacological effects of pomegranate, such as: anti-cancer, cholesterol-lowering, anti-diabetic, and antihypertensive features. Pomegranate consumption has also revealed some adverse effects. This systematic review aimed to explore the adverse effects of pomegranate reported in clinical studies. CONTENT: The keywords "pomegranate", "Punica granatum", "side effect", "clinical trial", and "case report or case series" were searched for in valid databases. Reports about adverse effects of pomegranate were also collected from several international registries. SUMMARY: This systematic review included a total of 66 clinical articles. Eleven articles have reported side effects of pomegranate. Twenty-one articles have recorded no side effects in the pomegranate group while 34 articles have not mentioned any side effects for this plant. The study also included 7 case report studies. The most common side effects included gastrointestinal problems, flu-like symptoms, and urinary problems. In case report studies, the most significant reported side effect was allergic reaction. OUTLOOK: In summary, pomegranate and its extract seem to be safe according to the reported adverse effects. Meanwhile, conducting more robust controlled trials with pomegranate products and documentation of any probable side effect is warranted.

Participant Perspectives on Community Qigong for People with Multiple Sclerosis.

Introduction: Multiple sclerosis (MS) is a progressive neurodegenerative disorder affecting motor and nonmotor function including physical and cognitive decline, fatigue, anxiety, and depression. Qigong is a mind-body self-care practice with the potential to address MS symptoms. Publicly available community qigong classes may provide opportunities for people with MS to access qigong, but little is known about the risks and benefits. A mixed methods study of community qigong was conducted for people with MS. In this article, the results of this qualitative analysis to identify benefits and challenges faced by people with MS attending community qigong classes were presented. Methods: Qualitative data were collected from an exit survey of 14 study participants with MS who enrolled in a pragmatic trial of community qigong classes for 10 weeks. Participants were new to community-based classes offered but some had experience with qigong/tai chi/other martial arts or yoga. Data were analyzed using reflexive thematic analysis. Results and Discussion: Seven common themes were identified from this analysis: (1) physical function, (2) motivation/energy, (3) learning, (4) dedicating time for self, (5) meditation/centering/focus, (6) relaxation/stress relief, and (7) psychological/psychosocial. These themes reflected both positive and negative experiences with community qigong classes and home practice. Self-reported benefits centered around improved flexibility, endurance, energy, and focus; stress relief; and psychological/psychosocial benefits. Challenges included physical discomfort including short-term pain, balance difficulty, and heat intolerance. Conclusion: The qualitative findings provide evidence to support qigong as a self-care practice that may benefit people with MS. The challenges identified in the study will help to inform future clinical trials of qigong for MS. Trial Registration: ClinicalTrials.gov (CTR#: NCT04585659).

A closer look at yoga nidra- early randomized sleep lab investigations.

OBJECTIVES: We aimed to examine trial feasibility plus physiological and psychological effects of a guided meditation practice, Yoga Nidra, in adults with self-reported insomnia. METHODS: Twenty-two adults with self-reported insomnia were recruited to attend two visits at our research center. At Visit 1 (V1), participants were asked to lie quietly for ninety minutes. The primary outcome was change in electroencephalography (EEG). Heart rate variability (HRV), respiratory rate and self-reported mood and anxiety were also measured. At Visit 2 (V2), the same protocol was followed, except half of participants were randomized to practice Yoga Nidra for the first 30-min. RESULTS: There were no between-group changes (V1-V2) in alpha EEG power at O1 (Intervention: 13 ± 70%; Control: -20 ± 40%), HRV or sleep onset latency in response to Yoga Nidra. Respiratory rate, however, showed statistically significant difference between groups (Yoga Nidra -1.4 breaths per minute (bpm) change during and - 2.1 bpm afterwards vs. Control +0.2 bpm during and + 0.4 bpm after; p = .03 for both during and after). The intervention displayed good acceptability (well-tolerated) and credibility (perceived benefit ratings) with implementation success (target sample size reached; 5% dropout rate). CONCLUSIONS: This preliminary clinical trial provides early evidence that Yoga Nidra is a well-tolerated, feasible intervention for adults reporting insomnia. Decreased respiratory rate in response to Yoga Nidra needs to be confirmed in more definitive studies. TRIAL REGISTRATION INFORMATION: This trial was registered on ClinicalTrials.gov as "A Closer Look at Yoga Nidra: Sleep Lab Analyses" (NCT#03685227).