Systems-level analyses dissociate genetic regulators of reactive oxygen species and energy production.

Respiratory chain dysfunction can decrease ATP and increase reactive oxygen species (ROS) levels. Despite the importance of these metabolic parameters to a wide range of cellular functions and disease, we lack an integrated understanding of how they are differentially regulated. To address this question, we adapted a CRISPRi- and FACS-based platform to compare the effects of respiratory gene knockdown on ROS to their effects on ATP. Focusing on genes whose knockdown is known to decrease mitochondria-derived ATP, we showed that knockdown of genes in specific respiratory chain complexes (I, III, and CoQ10 biosynthesis) increased ROS, whereas knockdown of other low ATP hits either had no impact (mitochondrial ribosomal proteins) or actually decreased ROS (complex IV). Moreover, although shifting metabolic conditions profoundly altered mitochondria-derived ATP levels, it had little impact on mitochondrial or cytosolic ROS. In addition, knockdown of a subset of complex I subunits-including NDUFA8, NDUFB4, and NDUFS8-decreased complex I activity, mitochondria-derived ATP, and supercomplex level, but knockdown of these genes had differential effects on ROS. Conversely, we found an essential role for ether lipids in the dynamic regulation of mitochondrial ROS levels independent of ATP. Thus, our results identify specific metabolic regulators of cellular ATP and ROS balance that may help dissect the roles of these processes in disease and identify therapeutic strategies to independently target energy failure and oxidative stress.

Activin A-Expressing Polymorphonuclear Myeloid-Derived Suppressor Cells Infiltrate Skeletal and Cardiac Muscle and Promote Cancer Cachexia.

Cachexia is a major cause of death in cancer and leads to wasting of cardiac and skeletal muscle, as well as adipose tissue. Various cellular and soluble mediators have been postulated in driving cachexia; however, the specific mechanisms behind this muscle wasting remain poorly understood. In this study, we found polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) to be critical for the development of cancer-associated cachexia. Significant expansion of PMN-MDSCs was observed in the cardiac and skeletal muscles of cachectic murine models. Importantly, the depletion of this cell subset, using depleting anti-Ly6G Abs, attenuated this cachectic phenotype. To elucidate the mechanistic involvement of PMN-MDSCs in cachexia, we examined major mediators, that is, IL-6, TNF-α, and arginase 1. By employing a PMN-MDSC-specific Cre-recombinase mouse model, we showed that PMN-MDSCs were not maintained by IL-6 signaling. In addition, PMN-MDSC-mediated cardiac and skeletal muscle loss was not abrogated by deficiency in TNF-α or arginase 1. Alternatively, we found PMN-MDSCs to be critical producers of activin A in cachexia, which was noticeably elevated in cachectic murine serum. Moreover, inhibition of the activin A signaling pathway completely protected against cardiac and skeletal muscle loss. Collectively, we demonstrate that PMN-MDSCs are active producers of activin A, which in turn induces cachectic muscle loss. Targeting this immune/hormonal axis will allow the development of novel therapeutic interventions for patients afflicted with this debilitating syndrome.

Impact of comorbid opioid use disorder and major depressive disorder on healthcare utilization outcomes in patients with peripheral artery disease: A National Readmission Database analysis.

BACKGROUND: Prior research has demonstrated that individuals with peripheral artery disease (PAD) often have comorbid opioid use disorder (OUD) and major depressive disorder (MDD), with limited data regarding their impact on readmission outcomes, length of stay, and cost. This study aimed to investigate these healthcare utilization outcomes in patients with PAD who have comorbid OUD and MDD. METHODS: Data were obtained from the National Readmission Database from 2011 through 2018. The study population included all hospitalizations with PAD as the primary or secondary diagnosis, from which hospitalizations with OUD and MDD were extracted using appropriate ICD-9/10 diagnosis codes. Primary outcomes were 30-day and 90-day readmission, total cost, and total length of stay within the calendar year. We created hierarchical multivariable logistic regression models examining OUD with and without MDD, with a random effect for healthcare facility location. RESULTS: From 2011 to 2018, 13,265,817 weighted admissions with PAD were identified. These admissions were segmented into four categories: No OUD/No MDD (12,056,466), OUD/No MDD (323,762), No OUD/MDD (867,641), and OUD/MDD (17,948). The group with No OUD/No MDD was used as the reference group for all subsequent comparisons. Regarding 30-day and 90-day readmissions, patients with OUD/MDD had odds of 1.14 (95% CI 1.10, 1.18) and 1.09 (95% CI 1.06, 1.13), respectively. Patients with OUD/No MDD bore the highest median cost of $64,354 (IQR $30,797-137,074), and patients with OUD/MDD marked the lengthiest median stay of 6.01 days (IQR 2.01-13.30). CONCLUSION: This study found a significant association between these comorbidities and outcomes and therefore calls for targeted interventions and pain management strategies.

High Prevalence of Anorectal Dysfunction in Ambulatory Patients with Chronic Constipation, Regardless of Colon Transit Time.

BACKGROUND: Classification of chronic constipation (CC) into its three subtypes of slow transit constipation, defecation disorder and normal transit constipation, may improve its multifaceted management. We assessed the merits of the London classification in patients with CC, who were studied by both wireless motility capsule (WMC) and high-resolution anorectal manometry (HR-ARM), examining their relative utilities in decision-making.s PATIENTS AND METHODS: Retrospective, community-based study of prospectively collected data on patients with CC by Rome IV criteria, who underwent WMC and HR-ARM, Balloon Expulsion Test, and Rectal Sensory Testing. Clinical assessment was made by standard questionnaires. On WMC, standard criteria for colonic transit time (CTT) were used (normal CTT < 59 h). The hierarchical London classification was used for HR-ARM analyses. RESULTS: Of 1261 patients with CC, 166 (91 M; ages 22-86) received technically satisfactory WMC and HR-ARM, formed the analyzed study cohort, of whom 84 had normal CTT and 82 had prolonged CTT (> 59 h). Patients with slow CTT were significantly older and had longer duration and more severe disease. Using the London classification criteria for disorders of anorectal function, we noted a high prevalence of anorectal dysfunction, regardless of CTT. Except for lower rate of anal hypertonicity in patients with slow CTT, disorders of recto-anal coordination, and rectal sensation were seen at a comparable rate in patients with CC, regardless of CTT. CONCLUSION: There is a significant overlap of anorectal disorders in patients with slow CTT. There is questionable specificity and utility of WMC and HR-ARM in assessing patients with CC. More work is needed to demonstrate the value of these studies as surrogate markers of the disease and its response to multifaceted therapy.

'Nostalgic food heals for us': A qualitative exploration of experiences with nostalgia, food, and mood.

ISSUE ADDRESSED: Nostalgia-the bittersweet reliving of the past-has been linked to social connection and psychological wellbeing. Although food consumption is often an intrinsically social experience, relatively little research has examined how individuals experience and understand how food consumption relates to feelings of nostalgia, food and mood. METHODS: In the current study, semi-structured interviews were conducted with eight Australians from varying cultural backgrounds to explore their experiences with nostalgia, food and mood. RESULTS: Reflexive thematic analysis identified three key themes from the data: (i) The bittersweet experiences of food-evoked nostalgia-individuals' descriptions of food-evoked nostalgia and how it impacted their mood both positively and negatively (ii) social connection and identity continuity-participants' description of food-evoked nostalgia and how this provides an opportunity for social connection and identity continuity throughout life, which positively influences mood, and (iii) the role and relationship of food-evoked nostalgia and mood-individual descriptions of the important role that nostalgic food plays in their life, in addition to their relationship with food, and how this impacts mood. CONCLUSIONS: Understanding the positive component of nostalgic foods allowed individuals to bolster positive mood states with food-evoked nostalgia, increasing their quality of life. SO WHAT?: Understanding the link between food-evoked nostalgia and mood has significant implications, suggesting that negative mood states altered by nostalgic foods may result in positive mood states. Appropriate use of food-evoked nostalgia may increase the quality of life for individuals experiencing low mood states.

Effects of pregnancy and lactation on muscle-tendon morphology.

Pregnancy and lactation hormones have been shown to mediate anatomical changes to the musculoskeletal system that generates animal movement. In this study, we characterize changes in the medial gastrocnemius muscle, its tendon and aponeuroses that are likely to have an effect on whole animal movement and energy expenditure, using the rat model system, Rattus norvegicus. We quantified muscle architecture (mass, cross-sectional area, and pennation angle), muscle fiber type and diameter, and Young's modulus of stiffness for the medial gastrocnemius aponeuroses as well as its contribution to Achilles tendon in three groups of three-month-old female rats: virgin, primiparous pregnant, and primiparous lactating animals. We found that muscle mass drops by 23% during lactation but does not change during pregnancy. We also found that during pregnancy muscle fibers switch from Type I to IIa and during lactation from Type IIb to Type I. The stiffness of connective tissues that has a demonstrated role in locomotion, the aponeurosis and tendon, also changed. Pregnant animals had a significantly less stiff aponeurosis. However, tendon stiffness was most affected during lactation, with a significant drop in stiffness and interindividual variation. We propose that the energetic demands of locomotion may have driven the evolution of these anatomical changes in muscle-tendon units during pregnancy and lactation to ensure more energy can be allocated to fetal development and lactation.

Lower extremity symptoms and ankle-brachial index screening as predictors of cardiovascular outcomes in Black adults.

BACKGROUND: The prevalence of peripheral artery disease (PAD) and leg symptoms are higher in Black than White adults. We studied the effects of self-reported lower extremity symptoms and ankle-brachial indices (ABI) groups on outcomes. METHODS: Black participants in the Jackson Heart Study with baseline ABI and PAD symptom assessments (exertional leg pain by the San Diego Claudication questionnaire) were included. Abnormal ABI was < 0.90 or > 1.40. Participants were divided into (1) normal ABI, asymptomatic, (2) normal ABI, symptomatic, (3) abnormal ABI, asymptomatic, and (4) abnormal ABI, symptomatic to examine their associations with MACE (stroke, myocardial infarction, fatal coronary heart disease) and all-cause mortality, using Kaplan-Meier survival curves and stepwise Cox proportional hazard models adjusting for Framingham risk factors. RESULTS: Of 4586 participants, mean age was 54.6 ± 12.6 years, with 63% women. Compared with participants with normal ABI who were asymptomatic, participants with abnormal ABI and leg symptoms had highest risk of MACE (adjusted HR 2.28; 95% CI 1.62, 3.22) and mortality (aHR 1.82; 95% CI 1.32, 2.56). Participants with abnormal ABI without leg symptoms had higher risk for MACE (aHR 1.49; 95% CI 1.06, 2.11) and mortality (aHR 1.44; 95% CI 1.12, 1.99). Participants with normal ABI and no leg symptoms did not have higher risks. CONCLUSION: Among Black adults, the highest risk for adverse outcomes were in symptomatic participants with abnormal ABIs, followed by asymptomatic participants with abnormal ABIs. These findings underscore the need for further studies to screen for PAD and develop preventative approaches in Black adults with asymptomatic disease.

Variability in Antithrombotic Therapy after Infrainguinal Lower Extremity Bypass.

BACKGROUND: Antiplatelet monotherapy is recommended after infrainguinal lower extremity bypass (LEB). However, there is a paucity of high-quality data to guide therapy, and antiplatelet therapy is often prescribed in combination with anticoagulation. We therefore aimed to assess the variability in the use of antithrombotic therapy after infrainguinal LEB. METHODS: The Vascular Quality Initiative dataset (2015-2021) was retrospectively reviewed to determine discharge patterns of antithrombotic therapy for all patients undergoing infrainguinal LEB. Monotherapy on discharge was defined as either single antiplatelet therapy (SAPT) or single anticoagulant (SAC). Combination therapy was dual antiplatelet therapy (DAPT), anticoagulant + antiplatelet (ACAP), or triple therapy. Hierarchical multivariable logistic regression with random effects for physician and center was used to identify predictors of combination therapy. Median odds ratios (MOR) were derived to quantify degree of variability in antithrombotic therapy. RESULTS: There were 29,507 patients undergoing infrainguinal LEB (monotherapy = 10,634 vs. combination therapy = 18,873). SAPT (90.6%) was the most common form of monotherapy, while DAPT (57.7%) and ACAP (34.6%) were the most common combination therapies. Patients undergoing LEB to popliteal targets were more likely to be prescribed monotherapy (SAC or SAPT) than to infra-popliteal targets (60.6% vs. 56.6%, P < 0.001). Combination therapy (DAPT, ACAP, or triple therapy) was more often used in patients with tibial or plantar arteries as the bypass target. Patients undergoing bypass using autogenous vein were more likely to receive monotherapy compared with those receiving other conduits (64.8% vs. 52.9%, P < 0.001), while patients with prosthetic grafts were more likely to receive combination therapy (37.9% vs. 28.2%, P < 0.001). There were no significant differences in postoperative bleeding (P = 0.491) or 30-day mortality (P = 0.302) between the two groups. Prior peripheral vascular interventions (PVI) (odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.79-1.99), concomitant PVI (OR: 1.83, 95% CI: 1.66-2.02), prosthetic graft use (OR: 1.74, 95% CI: 1.64-1.85), prior percutaneous coronary intervention (OR: 1.53, 95% CI: 1.43-1.65), plantar distal target (OR: 1.46, 95% CI: 1.29-1.65), alternative conduits (OR: 1.39, 95% CI: 1.25-1.53), and tibial distal targets (OR: 1.36, 95% CI: 1.28-1.44) were independent predictors of combination therapy in a multivariable regression model. Upon adjusting for patient-level factors, there was significant physician-level (MOR: 1.65, 95% CI 1.61-1.67) and center-level (MOR: 1.64, 95% CI 1.57-1.69) variability in the selection of antithrombotic therapy. CONCLUSIONS: Significant physician- and center-level variability in the use of antithrombotic regimens after infrainguinal bypass reflects the paucity of available evidence to guide therapy. Pragmatic trials are needed to assess antithrombotic strategies and guide recommendations aimed at optimizing cardiovascular and graft-specific outcomes after LEB.

A systematic review of influences and outcomes of body image in postpartum via a socioecological framework.

BACKGROUND: Women in the postpartum period come under multi-level pressure to return to pre-pregnancy body shape and size. This pressure can lead to reduced body image satisfaction, self-esteem, and mood. In this systematic review we explored the influences and outcomes of body dissatisfaction during the postpartum period. METHODS: Four databases were searched using keywords: postpart* OR postnatal OR peripart* OR 'new mother' OR 'breast feed*' AND 'body image' OR 'body dissatisf*' OR 'body satisf*' OR 'body attitude' OR 'body shape'. RESULTS: The influences and outcomes of body image dis/satisfaction in the postpartum period from 55 international studies were found to align within four of the five factors of the socioecological model. Intrapersonal factors: weight and body shape concerns, mental health and stressors, attitudes and behaviours, and protective coping skills and interventions. Interpersonal factors: social support (partner, family, and friends) and sexual functioning. Institutional factors: experiences with the healthcare system and returning to work. Societal factors: culture and ethnicity, media influences and social norms such as the thin ideal. CONCLUSIONS: A focus on intrapersonal factors alone is insufficient to understand women's experiences of body dis/satisfaction during the postpartum period. This suggests a need for better education and policy practices in pre-natal and postpartum care directed at body image and education to dispel societal norms such as the thin ideal. Doing so shifts the focus to include interpersonal, institutional, and societal influences alongside intrapersonal experiences. Research is needed to explore the utility and efficacy of broader approaches for women during this vulnerable life period.

Real-world antithrombotic treatment variability in patients undergoing peripheral vascular intervention: Insights from the VQI registry.

For those undergoing peripheral vascular interventions (PVI), guidelines indicate the use of dual antiplatelet therapy (DAPT) is reasonable (Class IIb), but recommendations have not reached the highest level of evidence. In the largest effort to date, we found that antithrombotic prescription was dominated by single antiplatelet therapy (SAPT) (51.4%) before PVI, which switched to DAPT (57.7%) following PVI, with some patients still remaining on no therapy (8%). High site variability in prescription rates (median odds ratio: 1.40, 95% confidence interval: 1.32, 1.48) was not much explained by patient and provider factors, revealing a need for the creation and integration of the newest trial data and for interventions at the health system or practice level to help physicians determine the optimal medical therapy following PVI.

Antiplatelet regimens following carotid artery revascularization.

Dual antiplatelet therapy (DAPT) is indicated following carotid artery stenting (CAS) and single antiplatelet therapy (SAPT) following carotid endarterectomy (CEA), but it remains unknown how providers adhere to these guidelines in real-world clinical practice. Using the Vascular Quality Initiative New England data, we found that of 12,257 patients, 82% patients were discharged on DAPT following CAS and 66% were discharged on SAPT following CEA. While a high percentage of patients undergoing CAS appropriately receive DAPT, the use of SAPT following CEA exists with more variability and lower adherence rates.

Patient-level and external factors in the use of drug-coated balloons and drug-eluting stents in femoropopliteal endovascular interventions.

OBJECTIVE: Drug-coated balloons (DCB) and drug-eluting stents (DES) have been rapidly adopted for femoropopliteal endovascular interventions due to their favorable patency rates. It is unclear whether choice of using drug coated devices versus bare metal stents (BMS) or plain balloon angioplasty (POBA) as primary treatment in femoropopliteal disease is mostly associated with patient-level factors, safety concerns, or by operator preferences. This study sought to evaluate factors associated with their use in a contemporary dataset. METHODS: All femoropopliteal lesions treated with endovascular interventions between 2016 and 2019 from the Vascular Quality Initiative registry were included. For each procedure, a primary treatment was identified based on the following hierarchy: DES > DCB > BMS > POBA. A hierarchical logistic regression model predicting DCB or DES use included patient-level characteristics, key events (period after Centers for Medicare and Medicaid Services reimbursement change, January 2018 [vs before] and period after Katsanos meta-analysis December 2018 [vs before]), and random effects for site and operator. Operator-level variability for DCB and DES use was summarized with an adjusted median odds ratio (MOR). RESULTS: A total of 57,753 femoropopliteal endovascular procedures were included. Poor functional status (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.90-0.94), prior anticoagulant use (OR, 0.92; 95% CI, 0.87-0.97), higher Rutherford classification (OR, 0.86; 95% CI, 0.84-0.88), chronic kidney disease stage 4 or 5 (OR, 0.92; 95% CI, 0.86-0.98), and the period after the Katsanos meta-analysis publication (OR, 0.3; 95% CI, 0.29-0.32) were associated with a lower odds of DCB or DES use; whereas female sex (OR, 1.12; 95% CI,1.08-1.17), prior lesion treatment (OR, 1.17; 95% CI, 1.11-1.22), diabetes (OR, 1.07; 95% CI, 1.02-1.12), Trans-Atlantic Inter-Society Consensus class B (OR, 1.16; 95% CI, 1.09-1.24) and C (OR, 1.2; 95% CI, 1.12-1.28), and the period after the Centers for Medicare and Medicaid Services reimbursement change (OR, 1.08; 95% CI, 1.03-1.14) were associated with a higher odds of DCB or DES use. Significant variability in use was found across operators (adjusted MOR, 2.70; 95% CI, 2.55-2.85) and centers (adjusted MOR, 2.89; 95% CI, 2.50-3.27). CONCLUSIONS: DCB or DES use in femoropopliteal disease demonstrates wide variability across operators and is linked strongly with external factors, followed by anatomic lesion characteristics and a history of previous interventions. Future work needs to focus on tailoring DCB or DES use to patient and lesion characteristics and to develop appropriate use guidelines integrating these factors.

Is dietary quality associated with depression? An analysis of the Australian longitudinal study of women's health data.

Depression is a chronic and complex condition experienced by over 300 million people worldwide. While research on the impact of nutrition on chronic physical illness is well documented, there is growing interest in the role of dietary patterns for those experiencing symptoms of depression. This study aims to examine the association of diet quality (Dietary Questionnaire for Epidemiological Studies version 2) and depressive symptoms (Centre for Epidemiological Studies for Depression short form) of young Australian women over 6 years at two time points, 2003 (n 9081, Mean age = 27·6) and 2009 (n 8199, Mean age = 33·7) using secondary data from the Australian Longitudinal Study on Women's Health. A linear mixed-effects model found a small and significant inverse association of diet quality on depressive symptoms (ß = -0·03, 95 % CI (-0·04, -0·02)) after adjusting for covarying factors such as BMI, social functioning, alcohol and smoking status. These findings suggest that the continuation of a healthy dietary pattern may be protective of depressive symptoms. Caution should be applied in interpreting these findings due to the small effect sizes. More longitudinal studies are needed to assess temporal relationships between dietary quality and depression.

Perceived Pain and Smoking Interrelations Among Veterans with Chronic Pain Enrolled in a Smoking Cessation Trial.

INTRODUCTION: The Pain and Smoking Inventory (PSI) measures patients' perceived interrelations of their pain and smoking behavior, and it comprises three conceptually distinct domains: smoking to cope with pain (PSI-Cope), pain as a motivator of smoking (PSI-Motivate), and pain as a barrier to cessation (PSI-Barrier). Associations between PSI scores and pain interference and self-efficacy to quit smoking, two measures that can affect cessation outcomes, remain unclear. METHODS: We conducted a secondary analysis of baseline data from 371 veterans with chronic pain (88% male, Medianage =60) enrolled in a randomized smoking cessation trial. We used sequential multivariate regression models to examine associations between the three PSI domains and pain interference / self-efficacy. RESULTS: Of 371 veterans who completed baseline surveys, 88% were male, with a median age of 60 years. PSI-Motivate scores were positively associated with pain interference (beta [B]: 0.18, 95% confidence interval [CI]: 0.02 to 0.34). PSI-Barrier subscores were negatively associated with self-efficacy (B: -0.23, 95% CI: -0.36 to -0.10). CONCLUSION: Findings suggest that individuals who hold maladaptive perceptions of pain-smoking interrelations could be more likely to endorse higher pain interference and lower self-efficacy-two established predictors of cessation outcomes. Moreover, each PSI subscale demonstrated unique relationships with the dependent variables, and our results provided support for a three-factor structure. These findings further demonstrate that the PSI comprises three conceptually and empirically distinct domains; future research should evaluate the clinical utility of assessing each domain in relation to cessation outcomes.

Differential Effects of Intuitive and Disordered Eating on Physical and Psychological Outcomes for Women with Young Children.

OBJECTIVES: Pressure to lose weight can increase the risk of developing disordered eating behaviours, negative body image and depressive symptomatology. Eating intuitively may counteract these negative outcomes. This research examined the unique relationship between intuitive eating and disordered eating on body mass index (BMI), body image and depressive symptoms for women of young children. METHODS: A survey of women with a child aged between six and 48 months, included the Intuitive Eating Scale, Eating Attitudes Test-26, Body Shape Questionnaire and Edinburgh Postnatal Depression Scale. Multivariate analysis of variance (MANOVA) was conducted as an omnibus test to estimate the effect of intuitive and disordered eating on BMI, negative body image and depressive symptoms. RESULTS: Of the 419 sample (M age = 32.06), 32% were classified with disordered and 32% with intuitive eating. MANOVA and regression analysis found disordered eating positively associated with depressive symptoms, (ß = 0.303) and negative body image (ß = 0.318). Intuitive eating was associated with lower depressive symptoms (ß = - 0.183) and negative body image (ß = - 0.615). Disordered eating (ß = - 0.194) and intuitive eating (ß = - 0.586) both contributed to lower BMI, with the association stronger for intuitive eating. CONCLUSION: The early parenting period involves a high risk for developing disordered eating behaviours. Eating patterns are modifiable factors, illustrating the potential for positive and preventive health outcomes through adopting intuitive eating behaviours. There is an opportunity for healthcare professionals to promote physical and psychological health including for women in the early parenting period.

Effects of N-terminus modified Hx-amides on DNA binding affinity, sequence specificity, cellular uptake, and gene expression.

Five X-HxIP (Hx-amides) 6a-e, in which the N-terminus p-anisyl moiety is modified, were designed and synthesised with the purpose of optimising DNA binding, improving cellular uptake/nuclear penetration, and enhancing the modulation of the topoisomerase IIα (TOP2A) gene expression. The modifications include a fluorophenyl group and other heterocycles bearing different molecular shapes, size, and polarity. Like their parent compound HxIP 3, all five X-HxIP analogues bind preferentially to their cognate sequence 5'-TACGAT-3', which is found embedded on the 5' flank of the inverted CCAAT box-2 (ICB2) site in the TOP2A gene promoter, and inhibit protein complex binding. Interestingly, the 4-pyridyl analog 6a exhibits greater binding affinity for the target DNA sequence and abolishes the protein:ICB2 interaction in vitro, at a lower concentration, compared to the prototypical compound HxIP 3. Analogues 6b-e, display improved DNA sequence specificity, but reduced binding affinity for the cognate sequence, relative to the unmodified HxIP 3, with polyamides 6b and 6e being the most sequence selective. However, unlike 3 and 6b, 6a was unable to enter cells, access the nucleus and thereby affect TOP2A gene expression in confluent human lung cancer cells. These results show that while DNA binding affinity and sequence selectivity are important, consideration of cellular uptake and concentration in the nucleus are critical when exerting biological activity is the desired outcome. By characterising the DNA binding, cellular uptake and gene regulatory properties of these small molecules, we can elucidate the determinants of the elicited biological activity, which can be impacted by even small structural modifications in the polyamide molecular design.

Unexpected entanglement dynamics in semidilute blends of supercoiled and ring DNA.

Blends of polymers of different topologies, such as ring and supercoiled, naturally occur in biology and often exhibit emergent viscoelastic properties coveted in industry. However, due to their complexity, along with the difficulty of producing polymers of different topologies, the dynamics of topological polymer blends remains poorly understood. We address this void by using both passive and active microrheology to characterize the linear and nonlinear rheological properties of blends of relaxed circular and supercoiled DNA. We characterize the dynamics as we vary the concentration from below the overlap concentration c* to above (0.5c* to 2c*). Surprisingly, despite working at the dilute-semidilute crossover, entanglement dynamics, such as elastic plateaus and multiple relaxation modes, emerge. Finally, blends exhibit an unexpected sustained elastic response to nonlinear strains not previously observed even in well-entangled linear polymer solutions.

Evidence of avian influenza virus in seabirds breeding on a Norwegian high-Arctic archipelago.

BACKGROUND: Wild aquatic birds serve as the natural reservoir for avian influenza virus (AIV), a disease with significant implications for avian and mammalian health. Climate change is predicted to impact the dynamics of AIV, particularly in areas such as the Arctic, but the baseline data needed to detect these shifts is often unavailable. In this study, plasma from two species of gulls breeding on the high-Arctic Svalbard archipelago were screened for antibodies to AIV. RESULTS: AIV antibodies were found in black-legged kittiwake (Rissa tridactyla) samples from multiple years, as well as in glaucous gulls (Larus hyperboreous) samples. CONCLUSIONS: Despite small sample sizes, evidence of exposure to AIV was found among Svalbard gulls. A wider survey of Svalbard avian species is warranted to establish knowledge on the extent of AIV exposure on Svalbard and to determine whether active infections are present.

Striving for the thin ideal post-pregnancy: a cross-sectional study of intuitive eating in postpartum women.

Objective: To conduct a cross-sectional study of women in the postpartum period to identify relationships between intuitive eating, body image satisfaction, eating attitudes and depressive symptomology.Methods: Women with at least one child born in the previous 6-48 months were recruited via Facebook to complete an online survey which included: sociodemographic and health questions, the Intuitive Eating Scale, the Body Shape Questionnaire, the Multi-dimensional Body-Self Relations Questionnaire, the Eating Attitudes Test-26 and the Edinburgh Postnatal Depression Scale. Descriptive statistics were calculated for all variables and hierarchical regressions used to examine associations between intuitive eating styles, body image satisfaction, eating attitudes and depressive symptomology.Results: Of the 419 women (mean age 32 ± 5.3 years), 32% were classified with intuitive eating styles and were more likely to have higher body image satisfaction (F = 476.80, p < .001), less disordered eating attitudes (F = 30.74, p < .001) and lower depressive symptomology (F = 4.14, p = .042).Conclusions: The postpartum period is a time of high risk for developing/maintaining eating styles that may negatively impact psychological health and well-being. Providing education to new mothers about the benefits of intuitive eating could positively influence their health and well-being.

No evidence of avian influenza antibodies in two species of raptor nestlings inhabiting Norway.

BACKGROUND: Since 2016, incursions of highly pathogenic avian influenza virus (HPAIV) H5N8 clade 2.3.4.4b have caused unprecedented clinical signs and mortality in white-tailed eagles (WTE; Haliaeetus albicilla) across Europe and have been found to be infecting other raptor species, such as the northern goshawk (NG; Accipiter gentilis). Before this study, no screening of Norwegian raptors had been undertaken. RESULTS: Plasma samples from 43 white-tailed eagle and 29 northern goshawk nestlings, from several locations across Norway were screened for antibodies to avian influenza viruses. No antibodies, and thus, no evidence of AIV exposure, were found in these Norwegian raptors. No clinical signs of AIV were observed in 43 white tailed eagles and 29 northern goshawks. CONCLUSIONS: There are currently no indications that white-tailed eagles and northern goshawks inhabiting Norway are threatened by the recent HPAIV outbreaks in other areas of Europe. Ongoing monitoring should, however, be maintained to detect potential future outbreaks.