Clinical Outcomes Associated with a Remote Postpartum Hypertension Monitoring Program.

OBJECTIVE: To evaluate differences in health care utilization and guideline adherence for postpartum individuals with hypertensive disorders of pregnancy (HDP) who are engaged in a remote monitoring program, compared with usual care. METHODS: This was a retrospective cohort study of postpartum individuals with HDP who delivered between March 2019 and June 2023 at a single institution. The primary exposure was enrollment in a remote hypertension management program that relies on patient home blood pressure (BP) measurement and centralized nursing team management. Patients enrolled in the program were compared with those receiving usual care. Outcomes included postpartum readmission, office visit within 6 weeks postpartum, BP measurement within 10 days, and initiation of antihypertensive medication. We performed multivariable logistic and conditional regression in a propensity score matched cohort. Propensity scores, generated by modeling likelihood of program participation, were assessed for even distribution by group, ensuring standardized bias of less than 10% after matching. RESULTS: Overall, 12,038 eligible individuals (6,556 participants, 5,482 in the control group) were included. Program participants were more likely to be White, commercially insured, be diagnosed with preeclampsia, and have higher prenatal and inpatient postpartum BPs. Differences in baseline factors were well-balanced after implementation of propensity score. Program enrollment was associated with lower 6-week postpartum readmission rates, demonstrating 1 fewer readmission for every 100 individuals in the program (propensity score-matched adjusted risk difference [aRD] -1.5, 95% CI, -2.6 to -0.46; adjusted risk ratio [aRR] 0.78, 95% CI, 0.65-0.93). For every 100 individuals enrolled in the program, 85 more had a BP recorded within 10 days (propensity score-matched aRD 85.4, 95% CI, 84.3-86.6), and six more had a 6-week postpartum office visit (propensity score-matched aRD 5.7, 95% CI, 3.9-7.6). Program enrollment was also associated with increased initiation of an antihypertensive medication postpartum (propensity score-matched aRR 4.44, 95% CI, 3.88-5.07). CONCLUSION: Participation in a postpartum remote BP monitoring program was associated with fewer postpartum hospital readmissions, higher attendance at postpartum visits, improved guideline adherence, and higher rates of antihypertensive use.

HPV vaccine-related articles shared on Facebook from 2019 to 2021: Did COVID make a difference?

Objective: HPV vaccination is recommended for children beginning at age 9 to prevent several types of cancer. Many parents turn to Facebook for health information. This study describes changes in HPV vaccine-related articles shared on Facebook amidst the COVID-19 pandemic. Methods: HPV-related articles shared on Facebook (2019-2021) were collected using Buzzsumo, a social media analytics tool and analyzed using content analysis. Articles were categorized by valence, misinformation, evidence types, persuasive tactics, and framing. We quantified these data and tested for difference by article year. Results: Of the 138 included articles, 51% had positive valence towards the vaccine and 36% had negative valence. In 2021, there was a significant increase in positive messaging (72% vs. 44% in 2019/2020; p < 0.01) and misinformation decreased from 50% in 2019 to 24% in 2021 (p = 0.04). Persuasive strategies were more common in 2019 than in later years. Conclusion: Despite decreased engagement in 2021, more positive HPV vaccine messaging was observed, although a quarter of articles still contained misinformation. Our results can inform strategies for communicating with parents about the HPV vaccine. Innovation: Our study is the first to analyze HPV-related articles linked on Facebook and to assess for differences during the pandemic.

Integrative network analysis of miRNA-mRNA expression profiles during epileptogenesis in rats reveals therapeutic targets after emergence of first spontaneous seizure.

Epileptogenesis is the process by which a normal brain becomes hyperexcitable and capable of generating spontaneous recurrent seizures. The extensive dysregulation of gene expression associated with epileptogenesis is shaped, in part, by microRNAs (miRNAs) - short, non-coding RNAs that negatively regulate protein levels. Functional miRNA-mediated regulation can, however, be difficult to elucidate due to the complexity of miRNA-mRNA interactions. Here, we integrated miRNA and mRNA expression profiles sampled over multiple time-points during and after epileptogenesis in rats, and applied bi-clustering and Bayesian modelling to construct temporal miRNA-mRNA-mRNA interaction networks. Network analysis and enrichment of network inference with sequence- and human disease-specific information identified key regulatory miRNAs with the strongest influence on the mRNA landscape, and miRNA-mRNA interactions closely associated with epileptogenesis and subsequent epilepsy. Our findings underscore the complexity of miRNA-mRNA regulation, can be used to prioritise miRNA targets in specific systems, and offer insights into key regulatory processes in epileptogenesis with therapeutic potential for further investigation.

Design, Development, and Functional Validation of a 3D-Printed Passive Upper Limb Exoskeleton.

Motor disability in children is evident in diagnoses such as cerebral palsy, muscular dystrophy, multiple sclerosis, or spinal muscular atrophy, among others, due to altered movement and postural patterns. This becomes more evident as the child grows and can be treated with physical therapy. The effectiveness of early interventions in facilitating an improvement in daily life activities varies depending on the child's condition. In this context, the use of exoskeletons has emerged in recent years as a valuable resource for conducting more efficient therapy processes. This work describes the design (both structural and functional) and preliminary usability and functional validation of a 3D-printed passive upper limb exoskeleton. The goal is to provide clinicians with an efficient, low-cost device that is both easy to manufacture and assemble and, in a gamified environment, serves as an assistive device to physical therapy. The device features 5 degrees of freedom, enabling both a pro-gravity and an anti-gravity mode, controlled by a series of elastic bands. This gives rise to a dual operating mode, offering assistance or resistance to different arm, forearm, and shoulder-dependent movements. Usability validation conducted by exoskeleton users showed average results in all aspects rated above 3.8 out of 5, which implies levels of satisfaction between "quite satisfied" and "very satisfied". The analysis of metrics recorded during therapy, such as the Hand Path Ratio and Success Rate (capturing user movements using an inertial sensor in the gamified environment), as well as the range of motion, reveals quantifiable improvements which can be attributed to the use of the exoskeleton: the Hand Path Ratio tended to approach 1 throughout sessions in almost all the users, the Success Rate remained stable (as users consistently were capable of completing the assigned tasks), and the range of motion showed that all patients achieved improvements of more than 10 degrees in some of the tested movements). These functional validation processes involved the participation of 7 children with varying levels of upper limb neuro-motor impairments.

Barriers to and facilitators of implementing colorectal cancer screening evidence-based interventions in federally qualified health centers: a qualitative study.

BACKGROUND: There is an urgent need to increase colorectal cancer screening (CRCS) uptake in Texas federally qualified health centers (FQHCs), which serve a predominantly vulnerable population with high demands. Empirical support exists for evidence-based interventions (EBIs) that are proven to increase CRCS; however, as with screening, their use remains low in FQHCs. This study aimed to identify barriers to and facilitators of implementing colorectal cancer screening (CRCS) evidence-based interventions (EBIs) in federally qualified health centers (FQHCs), guided by the Consolidated Framework for Implementation Research (CFIR). METHODS: We recruited employees involved in implementing CRCS EBIs (e.g., physicians) using data from a CDC-funded program to increase the CRCS in Texas FQHCs. Through 23 group interviews, we explored experiences with practice change, CRCS promotion and quality improvement initiatives, organizational readiness, the impact of COVID-19, and the use of CRCS EBIs (e.g., provider reminders). We used directed content analysis with CFIR constructs to identify the critical facilitators and barriers. RESULTS: The analysis revealed six primary CFIR constructs that influence implementation: information technology infrastructure, innovation design, work infrastructure, performance measurement pressure, assessing needs, and available resources. Based on experiences with four recommended EBIs, participants described barriers, including data limitations of electronic health records and the design of reminder alerts targeted at deliverers and recipients of patient or provider reminders. Implementation facilitators include incentivized processes to increase provider assessment and feedback, existing clinic processes (e.g., screening referrals), and available resources to address patient needs (e.g., transportation). Staff buy-in emerged as an implementation facilitator, fostering a conducive environment for change within clinics. CONCLUSIONS: Using CFIR, we identified barriers, such as the burden of technology infrastructure, and facilitators, such as staff buy-in. The results, which enhance our understanding of CRCS EBI implementation in FQHCs, provide insights into designing nuanced, practical implementation strategies to improve cancer control in a critical setting.

Prognostic impact of quantitative flow ratio (QFR)-consistent complete revascularization in patients with myocardial infarction and multivessel coronary artery disease.

BACKGROUND: Complete revascularization is associated with improved outcomes in patients with myocardial infarction and multivessel coronary artery disease. Quantitative flow ratio (QFR) represents an emerging angiography-based tool for functional lesion assessment. The present study investigated the prognostic impact of QFR-consistent complete revascularization in patients with myocardial infarction and multivessel disease. METHODS: A total of 792 patients with myocardial infarction and multivessel disease were enrolled in the analysis. Post-hoc QFR analyses of 1320 non-culprit vessels were performed by investigators blinded to clinical outcomes. The primary endpoint was a composite of all-cause death, non-culprit vessel related non-fatal myocardial infarction, and ischemia-driven revascularization at two years after index myocardial infarction. Patients were stratified into a QFR-consistent PCI group (n=646) and a QFR-inconsistent PCI group (n=146), based on whether the intervention was congruent with the QFR-determined functional significance of the non-culprit lesions. RESULTS: The primary endpoint occurred in a total of 22 patients (3.4%) in the QFR-consistent PCI group and in 27 patients (18.5%) in the QFR-inconsistent group (HR 0.17, 95%CI 0.10-0.30, p<0.001).The difference in the primary endpoint was driven by reduced rates of non-fatal myocardial infarction (2.0% vs. 15.1%; HR 0.13, 95%CI 0.06-0.25; p<0.001) and ischemia-driven revascularization (1.2% vs. 5.5%; HR 0.21, 95%CI 0.08-0.57; p=0.001) in the QFR-consistent PCI group. CONCLUSIONS: Among patients with myocardial infarction and multivessel disease, a QFR-consistent complete revascularization was associated with a reduced risk of all-cause mortality, non-fatal myocardial infarction, and ischemia-driven revascularization. These findings underline the value of angiography-based functional lesion assessment for personalized revascularization strategies.

The contribution of community-based conservation models to conserving large herbivore populations.

In East Africa, community-based conservation models (CBCMs) have been established to support the conservation of wildlife in fragmented landscapes like the Tarangire Ecosystem, Tanzania. To assess how different management approaches maintained large herbivore populations, we conducted line distance surveys and estimated seasonal densities of elephant, giraffe, zebra, and wildebeest in six management units, including three CBCMs, two national parks (positive controls), and one area with little conservation interventions (negative control). Using a Monte-Carlo approach to propagate uncertainties from the density estimates and trend analysis, we analyzed the resulting time series (2011-2019). Densities of the target species were consistently low in the site with little conservation interventions. In contrast, densities of zebra and wildebeest in CBCMs were similar to national parks, providing evidence that CBCMs contributed to the stabilization of these migratory populations in the central part of the ecosystem. CBCMs also supported giraffe and elephant densities similar to those found in national parks. In contrast, the functional connectivity of Lake Manyara National Park has not been augmented by CBCMs. Our analysis suggests that CBCMs can effectively conserve large herbivores, and that maintaining connectivity through CBCMs should be prioritized.

Exploring the psychosocial burden of foot complications in diabetes: A cross-sectional survey and qualitative interview study in a United Kingdom coastal community.

BACKGROUND: Foot complications in diabetes are common and destructive, resulting in substantial healthcare costs and high rates of morbidity. Coastal areas have a significantly higher burden of disease. People with diabetes experience disproportionately high rates of psychological health issues, including anxiety, depression and diabetes distress. These can affect self-management and concordance with preventive measures and treatments of foot complications, negatively impacting on outcomes. Access to psychological health services is variable across the United Kingdom and there is a paucity of high-quality evidence for the effectiveness of treatments for diabetes distress. This study aimed to explore experiences of psychosocial burden and perceptions and experiences of psychosocial support, among patients with diabetes and foot complications living in a coastal area. METHODS: Patients were eligible to participate if they had experienced diabetes-related foot complications (amputation, ulceration and/or Charcot neuroarthropathy) within the last 5 years and scored positive for diabetes distress on a validated screening tool (DDS2). Eligible patients completed cross-sectional questionnaires describing symptoms of diabetes distress (DDS17), anxiety (GAD-7) and depression (PHQ-9) and to take part in a face-to-face, semi-structured interview. Questionnaires were analysed using frequencies and interviews were analysed using reflexive thematic analysis. RESULTS: A total of 183 patients completed the DDS2 screening questionnaire. Of these, 56 (30.6%) screened positive for diabetes distress. Twenty-seven patients completed DDS17, GAD-7 and PHQ-9 questionnaires. Eleven (40.7%) participants indicated high levels of diabetes distress and four (14.8%) indicated moderate distress. Seventeen participants (age range 52-81 years; 12 men) took part in an interview. Four key themes were identified: impact of living with foot problems; emotional consequences of foot problems; experiences and perceptions of psychological support; and strategies to cope with the emotional impact of foot problems. CONCLUSION: Diabetes distress was prevalent among patients with diabetes-related foot complications. Foot problems impacted on participants' daily activities, social lives and ability to work. Despite expressing feelings of ongoing fear, worry and depression relating to their foot problems, only one participant had accessed formal psychological support. Many participants relied on talking to podiatrists at routine appointments and described developing various strategies to cope. The psychosocial burden of living with foot complications in diabetes must not be overlooked by health professionals. Findings from this study can inform the design of future services and interventions.

Facebook's shared articles on HPV vaccination: analysis of persuasive strategies.

BACKGROUND: The current study analyzed articles shared on Facebook between 2019 and 2021 that discuss the HPV vaccine. Results address a gap in knowledge about the persuasive strategies used in HPV vaccine discourse on Facebook. METHODS: Using Buzzsumo.com, we collected 138 articles, shared on Facebook between 2019 and 2021, with the highest "engagement scores," or total number of reactions, comments, and shares. Using a content analysis methodology, three independent coders were trained in using the study codebook, achieved acceptable inter-rater reliability (Krippendorf's alpha = 0.811), and coded each article in Atlas.ti. RESULTS: Seventy-two articles had a positive valence toward the HPV vaccine, 48 had a negative valence, and 18 were mixed-valence or neutral. Pro-vaccine articles presented a variety of evidence types in support of benefits of HPV vaccination. Pro-vaccine articles primarily originated from national and local news sources. Anti-vaccine articles combined presentation of evidence with persuasive arguments and strategies, such as mistrust of institutions, fear appeals, ideological appeals, presenting a high number of arguments or detail, and minimizing the severity of HPV. Three sources were responsible for producing 62.5% of all anti-vaccine articles in the dataset. Mixed-valence or neutral articles mixed cancer prevention discourse with ideological appeals about protecting parental rights, and were mostly produced by local news outlets. CONCLUSION: The results of this study can help health communicators anticipate the types of discourses that vaccine-hesitant parents may have encountered online. Implications and suggestions for practice are discussed.

A toolkit for the dynamic study of air sacs in siamang and other elastic circular structures.

Biological structures are defined by rigid elements, such as bones, and elastic elements, like muscles and membranes. Computer vision advances have enabled automatic tracking of moving animal skeletal poses. Such developments provide insights into complex time-varying dynamics of biological motion. Conversely, the elastic soft-tissues of organisms, like the nose of elephant seals, or the buccal sac of frogs, are poorly studied and no computer vision methods have been proposed. This leaves major gaps in different areas of biology. In primatology, most critically, the function of air sacs is widely debated; many open questions on the role of air sacs in the evolution of animal communication, including human speech, remain unanswered. To support the dynamic study of soft-tissue structures, we present a toolkit for the automated tracking of semi-circular elastic structures in biological video data. The toolkit contains unsupervised computer vision tools (using Hough transform) and supervised deep learning (by adapting DeepLabCut) methodology to track inflation of laryngeal air sacs or other biological spherical objects (e.g., gular cavities). Confirming the value of elastic kinematic analysis, we show that air sac inflation correlates with acoustic markers that likely inform about body size. Finally, we present a pre-processed audiovisual-kinematic dataset of 7+ hours of closeup audiovisual recordings of siamang (Symphalangus syndactylus) singing. This toolkit (https://github.com/WimPouw/AirSacTracker) aims to revitalize the study of non-skeletal morphological structures across multiple species.

Induction and antiviral activity of ferret myxovirus resistance (Mx) protein 1 against influenza A viruses.

Myxovirus resistance (Mx) proteins are products of interferon stimulated genes (ISGs) and Mx proteins of different species have been reported to mediate antiviral activity against a number of viruses, including influenza A viruses (IAV). Ferrets are widely considered to represent the 'gold standard' small animal model for studying pathogenesis and immunity to human IAV infections, however little is known regarding the antiviral activity of ferret Mx proteins. Herein, we report induction of ferret (f)Mx1/2 in a ferret lung cell line and in airway tissues from IAV-infected ferrets, noting that fMx1 was induced to higher levels that fMx2 both in vitro and in vivo. Overexpression confirmed cytoplasmic expression of fMx1 as well as its ability to inhibit infection and replication of IAV, noting that this antiviral effect of fMx1was modest when compared to cells overexpressing either human MxA or mouse Mx1. Together, these studies provide the first insights regarding the role of fMx1 in cell innate antiviral immunity to influenza viruses. Understanding similarities and differences in the antiviral activities of human and ferret ISGs provides critical context for evaluating results when studying human IAV infections in the ferret model.

Postpartum Weight Change Association With Readmission and Blood Pressure Trend Among Individuals With Hypertensive Disorders of Pregnancy.

BACKGROUND: The aim of this study was to evaluate the association between early postpartum weight change and (1) hospital readmission and (2) 2-week blood pressure trajectory. METHODS AND RESULTS: This retrospective study cohort included 1365 individuals with a hypertensive disorder of pregnancy enrolled in a postpartum hypertension remote monitoring program. Exposure was percentage weight change from delivery to first weight recorded within 10 days postpartum. We first modeled likelihood of hospital readmission within 8 weeks postpartum using logistic regression adjusting for age, race, insurance, type of hypertensive disorder of pregnancy, early body mass index, gestational weight gain, mode of delivery, and any discharge antihypertensive medications. We then performed case-control analysis additionally matching in a 1:3 ratio on breastfeeding, early body mass index, discharge on antihypertensive medications, and days between weight measurements. Both analytic approaches were repeated, limiting to readmissions attributable to hypertension or heart failure. Finally, we compared blood pressure trajectories over first 2 weeks postpartum. Individuals who did not lose weight in the early postpartum period had more admissions compared with weight loss groups (group 3: 14.1% versus group 2: 5.8% versus group 1: 4.5%). These individuals had 4 times the odds of postpartum readmissions (adjusted odds ratio [aOR], 3.9 [95% CI, 1.8-8.6]) to 7 (aOR, 7.8 [95% CI, 2.3-26.5]) compared with those with the most weight loss. This association strengthened when limited to hypertension or heart failure readmissions. These individuals also had more adverse postpartum blood pressure trajectories, with significant differences by weight change group. CONCLUSIONS: Weight change is readily accessible and may identify individuals at high risk for postpartum readmission following a hypertensive disorder of pregnancy who could benefit from targeted interventions.

YABBY transcription factor family in the octoploid Fragaria × ananassa and five diploid Fragaria species.

YABBY genes encode specific TFs of seed plants involved in development and formation of leaves, flowers, and fruit. In the present work, genome-wide and expression analyses of the YABBY gene family were performed in six species of the Fragaria genus: Fragaria × ananassa, F. daltoniana, F. nilgerrensis, F. pentaphylla, F. viridis, and F. vesca. The chromosomal location, synteny pattern, gene structure, and phylogenetic analyses were carried out. By combining RNA-seq data and RT-qPCR analysis we explored specific expression of YABBYs in F. × ananassa and F. vesca. We also analysed the promoter regions of FaYABBYs and performed MeJA application to F. × ananassa fruit to observe effects on gene expression. We identified and characterized 25 YABBY genes in F. × ananassa and six in each of the other five species, which belong to FIL/YAB3 (YABBY1), YAB2 (YABBY2), YAB5 (YABBY5), CRC, and INO clades previously described. Division of the YABBY1 clade into YABBY1.1 and YABBY1.2 subclades is reported. We observed differential expression according to tissue, where some FaYABBYs are expressed mainly in leaves and flowers and to a minor extent during fruit development of F. × ananassa. Specifically, the FaINO genes contain jasmonate-responsive cis-acting elements in their promoters which may be functional since FaINOs are upregulated in F. × ananassa fruit under MeJA treatment. This study suggests that YABBY TFs play an important role in the development- and environment-associated responses of the Fragaria genus.

Immune imprinting in early life shapes cross-reactivity to influenza B virus haemagglutinin.

Influenza exposures early in life are believed to shape future susceptibility to influenza infections by imprinting immunological biases that affect cross-reactivity to future influenza viruses. However, direct serological evidence linked to susceptibility is limited. Here we analysed haemagglutination-inhibition titres in 1,451 cross-sectional samples collected between 1992 and 2020, from individuals born between 1917 and 2008, against influenza B virus (IBV) isolates from 1940 to 2021. We included testing of 'future' isolates that circulated after sample collection. We show that immunological biases are conferred by early life IBV infection and result in lineage-specific cross-reactivity of a birth cohort towards future IBV isolates. This translates into differential estimates of susceptibility between birth cohorts towards the B/Yamagata and B/Victoria lineages, predicting lineage-specific birth-cohort distributions of observed medically attended IBV infections. Our data suggest that immunological measurements of imprinting could be important in modelling and predicting virus epidemiology.

Persistent hypocalcemia post total thyroidectomy in a case of Hashimoto's thyroiditis.

INTRODUCTION: Thyroidectomy is a surgical procedure commonly employed in the management of thyroid disorders. Complications include, but not limited to, postoperative hypocalcemia. In order to effectively manage hypocalcemia following thyroidectomy, a comprehensive approach is essential. CASE PRESENTATION: We present an intriguing case of a patient who developed severe transient hypocalcemia that was resistant to conventional therapeutic interventions following a total thyroidectomy. DISCUSSION: Hypocalcemia post total thyroidectomy is a well-established complication which can lead to devastating consequences. Some of the contributing factors include failure of pre-operative optimization, autoimmune disease, malignancy, and prolonged surgical time. A comprehensive approach to identify the contributors is essential in managing the risk factors associated with hypocalcemia. CONCLUSION: This case highlights the importance of pre-operative elevation and management as well as the close monitoring and individualized treatment plans for patients at risk for post-thyroidectomy hypocalcemia. The successful management of severe hypocalcemia in this patient involved a multidisciplinary team approach and consideration of alternative treatment options.

Translating motivational interviewing for the HPV vaccine into a computable ontology model for automated AI conversational interaction.

Human papillomavirus (HPV) vaccinations are lower than expected. To protect the onset of head and neck cancers, innovative strategies to improve the rates are needed. Artificial intelligence may offer some solutions, specifically conversational agents to perform counseling methods. We present our efforts in developing a dialogue model for automating motivational interviewing (MI) to encourage HPV vaccination. We developed a formalized dialogue model for MI using an existing ontology-based framework to manifest a computable representation using OWL2. New utterance classifications were identified along with the ontology that encodes the dialogue model. Our work is available on GitHub under the GPL v.3. We discuss how an ontology-based model of MI can help standardize/formalize MI counseling for HPV vaccine uptake. Our future steps will involve assessing MI fidelity of the ontology model, operationalization, and testing the dialogue model in a simulation with live participants.

Concurrent inflammation-related brain reorganization in multiple sclerosis and depression.

BACKGROUND: Neuroinflammation affects brain tissue integrity in multiple sclerosis (MS) and may have a role in major depressive disorder (MDD). Whether advanced magnetic resonance imaging characteristics of the gray-to-white matter border serve as proxy of neuroinflammatory activity in MDD and MS remain unknown. METHODS: We included 684 participants (132 MDD patients with recurrent depressive episodes (RDE), 70 MDD patients with a single depressive episode (SDE), 222 MS patients without depressive symptoms (nMS), 58 MS patients with depressive symptoms (dMS), and 202 healthy controls (HC)). 3 T-T1w MRI-derived gray-to-white matter contrast (GWc) was used to reconstruct and characterize connectivity alterations of GWc-covariance networks by means of modularity, clustering coefficient, and degree. A cross-validated support vector machine was used to test the ability of GWc to stratify groups according to their depression symptoms, measured with BDI, at the single-subject level in MS and MDD independently. FINDINGS: MS and MDD patients showed increased modularity (ANOVA partial-η2 = 0.3) and clustering (partial-η2 = 0.1) compared to HC. In the subgroups, a linear trend analysis attested a gradient of modularity increases in the form: HC, dMS, nMS, SDE, and RDE (ANOVA partial-η2 = 0.28, p < 0.001) while this trend was less evident for clustering coefficient. Reduced morphological integrity (GWc) was seen in patients with increased depressive symptoms (partial-η2 = 0.42, P < 0.001) and was associated with depression scores across patient groups (r = -0.2, P < 0.001). Depressive symptoms in MS were robustly classified (88 %). CONCLUSIONS: Similar structural network alterations in MDD and MS exist, suggesting possible common inflammatory events like demyelination, neuroinflammation that are caught by GWc analyses. These alterations may vary depending on the severity of symptoms and in the case of MS may elucidate the occurrence of comorbid depression.

Dissemination of influenza B virus to the lower respiratory tract of mice is restricted by the interferon response.

The global burden of disease caused by influenza B virus (IBV) is substantial; however, IBVs remain overlooked. Understanding host-pathogen interactions and establishing physiologically relevant models of infection are important for the development and assessment of therapeutics and vaccines against IBV. In this study, we assessed an upper respiratory tract (URT)-restricted model of mouse IBV infection, comparing it to the conventional administration of the virus to the total respiratory tract (TRT). We found that URT infections caused by different strains of IBV disseminate to the trachea but resulted in limited dissemination of IBV to the lungs. Infection of the URT did not result in weight loss or systemic inflammation even at high inoculum doses and despite robust viral replication in the nose. Dissemination of IBV to the lungs was enhanced in mice lacking functional type I IFN receptor (IFNAR2), but not IFNγ. Conversely, in mice expressing the IFN-inducible gene Mx1, we found reduced IBV replication in the lungs and reduced dissemination of IBV from the URT to the lungs. Inoculation of IBV in both the URT and TRT resulted in seroconversion against IBV. However, priming at the TRT conferred superior protection from a heterologous lethal IBV challenge compared to URT priming, as determined by improved survival rates and reduced viral replication throughout the respiratory tract. Overall, our study establishes a URT-restricted IBV infection model, highlights the critical role of IFNs in limiting dissemination of IBV to the lungs, and also demonstrates that the lack of viral replication in the lungs may impact protection from subsequent infections. IMPORTANCE: Our study investigated how influenza B virus (IBV) spreads from the nose to the lungs of mice and the impact this has on disease and protection from re-infection. We found that when applied to the nose only, IBV does not spread very efficiently to the lungs in a process controlled by the interferon response. Priming immunity at the nose only resulted in less protection from re-infection than priming immunity at both the nose and lungs. These insights can guide the development of potential therapies targeting the interferon response as well as of intranasal vaccines against IBV.