Evidence for vagal sensory neural involvement in influenza pathogenesis and disease.

Influenza A virus (IAV) is a common respiratory pathogen and a global cause of significant and often severe morbidity. Although inflammatory immune responses to IAV infections are well described, little is known about how neuroimmune processes contribute to IAV pathogenesis. In the present study, we employed surgical, genetic, and pharmacological approaches to manipulate pulmonary vagal sensory neuron innervation and activity in the lungs to explore potential crosstalk between pulmonary sensory neurons and immune processes. Intranasal inoculation of mice with H1N1 strains of IAV resulted in stereotypical antiviral lung inflammation and tissue pathology, changes in breathing, loss of body weight and other clinical signs of severe IAV disease. Unilateral cervical vagotomy and genetic ablation of pulmonary vagal sensory neurons had a moderate effect on the pulmonary inflammation induced by IAV infection, but significantly worsened clinical disease presentation. Inhibition of pulmonary vagal sensory neuron activity via inhalation of the charged sodium channel blocker, QX-314, resulted in a moderate decrease in lung pathology, but again this was accompanied by a paradoxical worsening of clinical signs. Notably, vagal sensory ganglia neuroinflammation was induced by IAV infection and this was significantly potentiated by QX-314 administration. This vagal ganglia hyperinflammation was characterized by alterations in IAV-induced host defense gene expression, increased neuropeptide gene and protein expression, and an increase in the number of inflammatory cells present within the ganglia. These data suggest that pulmonary vagal sensory neurons play a role in the regulation of the inflammatory process during IAV infection and suggest that vagal neuroinflammation may be an important contributor to IAV pathogenesis and clinical presentation. Targeting these pathways could offer therapeutic opportunities to treat IAV-induced morbidity and mortality.

A Hybrid Auricular Framework of Autologous Rib Cartilage and a Porous Polyethylene Implant for Reconstruction of Congenital Microtia: A Modification of Nagata's Technique.

Background: An implant (porous polyethylene) is an alternative to rib cartilage for microtia reconstruction but carries a risk of extrusion. Objective: To evaluate the outcome of a hybrid framework of implant with rib cartilage for microtia reconstruction. Methods: Patients who underwent Nagata's technique for microtia reconstruction were reviewed for complications and aesthetic score. In stage 1, a rib cartilage framework or a hybrid framework of implant with rib cartilage was used. In stage 2, the framework was elevated and supported by an implant for projection. Postoperative outcomes were reported for both groups. Results: Forty-four ears of 40 patients underwent surgery. Eleven ears received a rib auricular framework and 33 ears a hybrid auricular framework. The mean postoperative follow-up for the rib and hybrid groups was 76.3 and 43.1 months, respectively. No supporting postauricular implant extruded, whereas stainless-steel wires extruded in seven ears (15.9%). Five (15.2%) hybrid frameworks were removed due to infection or extrusion. Mean operating time was 2 h shorter in the hybrid group. Aesthetic outcomes were similar for both groups. Conclusion: A hybrid framework of rib and implant that requires less harvested cartilage is feasible for microtia reconstruction, but caution should be used due to its higher explantation rate.

Elevated BMI reduces the humoral response to SARS-CoV-2 infection.

Objective: Class III obesity (body mass index [BMI] ≥ 40 kg m-2) significantly impairs the immune response to SARS-CoV-2 vaccination. However, the effect of an elevated BMI (≥ 25 kg m-2) on humoral immunity to SARS-CoV-2 infection and COVID-19 vaccination remains unclear. Methods: We collected blood samples from people who recovered from SARS-CoV-2 infection approximately 3 and 13 months of post-infection (noting that these individuals were not exposed to SARS-CoV-2 or vaccinated in the interim). We also collected blood samples from people approximately 5 months of post-second dose COVID-19 vaccination (the majority of whom did not have a prior SARS-CoV-2 infection). We measured their humoral responses to SARS-CoV-2, grouping individuals based on a BMI greater or less than 25 kg m-2. Results: Here, we show that an increased BMI (≥ 25 kg m-2), when accounting for age and sex differences, is associated with reduced antibody responses after SARS-CoV-2 infection. At 3 months of post-infection, an elevated BMI was associated with reduced antibody titres. At 13 months of post-infection, an elevated BMI was associated with reduced antibody avidity and a reduced percentage of spike-positive B cells. In contrast, no significant association was noted between a BMI ≥ 25 kg m-2 and humoral immunity to SARS-CoV-2 at 5 months of post-secondary vaccination. Conclusions: Taken together, these data showed that elevated BMI is associated with an impaired humoral immune response to SARS-CoV-2 infection. The impairment of infection-induced immunity in individuals with a BMI ≥ 25 kg m-2 suggests an added impetus for vaccination rather than relying on infection-induced immunity.

The swan genome and transcriptome, it is not all black and white.

BACKGROUND: The Australian black swan (Cygnus atratus) is an iconic species with contrasting plumage to that of the closely related northern hemisphere white swans. The relative geographic isolation of the black swan may have resulted in a limited immune repertoire and increased susceptibility to infectious diseases, notably infectious diseases from which Australia has been largely shielded. Unlike mallard ducks and the mute swan (Cygnus olor), the black swan is extremely sensitive to highly pathogenic avian influenza. Understanding this susceptibility has been impaired by the absence of any available swan genome and transcriptome information. RESULTS: Here, we generate the first chromosome-length black and mute swan genomes annotated with transcriptome data, all using long-read based pipelines generated for vertebrate species. We use these genomes and transcriptomes to show that unlike other wild waterfowl, black swans lack an expanded immune gene repertoire, lack a key viral pattern-recognition receptor in endothelial cells and mount a poorly controlled inflammatory response to highly pathogenic avian influenza. We also implicate genetic differences in SLC45A2 gene in the iconic plumage of the black swan. CONCLUSION: Together, these data suggest that the immune system of the black swan is such that should any avian viral infection become established in its native habitat, the black swan would be in a significant peril.

Effect of Tendon Strip (FCR vs APL) on Outcome of CMC Thumb Joint Arthroplasty With Pyrocarbon Disk Interposition.

BACKGROUND: Pyrocarbon disk interposition for carpometacarpal (CMC) thumb joint osteoarthritis can be performed with a flexor carpi radialis (FCR) or abductor pollicis longus (APL) tendon strip. With the FCR technique, a ligament reconstruction is performed in addition to disk fixation, whereas with the APL technique the disk is simply secured in place. Our aim is to compare long-term postoperative outcomes between both techniques. METHODS: In this observational study, we included 106 patients in 2 centers operated on between 2006 and 2011. We assigned patients to the FCR group or the APL group based on the respective tendon strip used. As a primary outcome, we analyzed postoperative key pinch. In addition, we analyzed postoperative tip pinch and tripod pinch, grip strength, range of motion, thumb height maintenance, and patient-reported outcome measures (PROMs). RESULTS: The analysis showed clinically important stronger key pinch for the APL group (ß = 1.28 kg). Tip pinch and grip strength showed higher outcome for the FCR group (ß = 1.22 kg and 5.14 kg, respectively). Palmar abduction was in favor of the FCR group and opposition in favor of the APL group, but these were interpreted as not clinically relevant. Radiological thumb height maintenance and PROMs showed no clinical difference. CONCLUSIONS: Pyrocarbon disk interposition arthroplasty for CMC thumb joint osteoarthritis can be secured with an APL or FCR tendon strip. At long-term follow-up, use of an APL tendon strip results in significantly higher key pinch and better opposition. Tip pinch, grip strength, and palmar abduction were better after use of the FCR tendon strip. The choice of the tendon strip can be based on outcomes considered most important for the individual patient.

Aspiration Thrombectomy for Posterior Circulation Stroke: A Systematic Review and Meta-Analysis.

PURPOSE: This study aims to analyze the efficacy of aspiration thrombectomy for large vessel occlusion of the posterior circulation, with an emphasis on comparison with stent retriever thrombectomy. METHODS: A systematic review and meta-analysis were performed to analyze the outcomes of aspiration thrombectomy for acute posterior circulation stroke. For those studies that included data for both aspiration and stent-retriever thrombectomy, we additionally performed a second meta-analysis comparing their outcomes against each other. RESULTS: A total of 17 articles were included. For the primary outcomes, the weighted pooled rate of mortality was 26.71% (95% confidence interval [CI] 19.35%-34.71%), modified Ranking Score (mRS) 0-2 at 3 months was 36.71 (95% CI 32.02%-41.52%), and successful recanalization 89.26% (95% CI 83.12%-94.31%). Primary stent retriever thrombectomy was inferior to primary aspiration thrombectomy for the outcomes of successful recanalization (odds ratio [OR] 0.57, 95% CI 0.36-0.91, P = 0.018), complete recanalization (OR 0.65, 95% CI 0.42-0.1.00, P = 0.048), procedure time (mean difference 28.17, 95% CI 9.47-46.87), and rate of embolization to new territory (OR 5.01, 95% CI 1.20-20.87, P = 0.027). No significant difference was seen for other outcomes. Further subgroup analysis suggests that for the outcome of recanalization, this may be dependent on the availability of second-line stent retriever thrombectomy. LIMITATIONS: The included studies were observational in nature. There was unresolved heterogeneity in some of the outcomes. CONCLUSIONS: There was no statistically significant difference seen for the primary outcomes of mortality and favorable outcome (mRS score 0-2) at 3 months. While superior rates of successful recanalization, complete recanalization, faster procedural time, and improved safety profile for primary aspiration thrombectomy were seen compared to primary stent retriever thrombectomy, this did not translate into superior clinical outcomes.

Therapy for acute basilar artery occlusion: a systematic review and meta-analysis.

Purpose: This study aims to analyse the efficacy of different treatment methods for acute basilar artery occlusion, with an emphasis placed on evaluating the latest treatment methods. Method:  A systematic review and meta-analysis was performed to analyse the current data on the therapies available for treating acute basilar artery occlusion. Results: A total of 102 articles were included. The weighted pooled rate of mortality was 43.16% (95% CI 38.35-48.03%) in the intravenous thrombolysis group, 45.56% (95% CI 39.88-51.28) in the intra-arterial thrombolysis group, and 31.40% (95% CI 28.31-34.56%) for the endovascular thrombectomy group. The weighted pooled rate of Modified Ranking Score (mRS) 0-2 at 3 months was 31.40 (95% CI 28.31-34.56%) in the IVT group, 28.29% (95% CI 23.16-33.69%) in the IAT group, and 35.22% (95% CI 32.39-38.09%) for the EVT group. Meta-analyses were also done for the secondary outcomes of recanalization and symptomatic haemorrhage. There was no difference between stent retriever and thrombo-aspiration thrombectomy on subgroup analysis in both clinical outcome and safety profile. Limitations: The included studies were observational in nature. There was significant heterogeneity in some of the outcomes. Conclusions:  Superior outcomes and better recanalization rates for acute basilar occlusion were seen with patients managed with endovascular thrombectomy when compared with either intravenous and/or intraarterial thrombolysis. No superiority of stent-retrievers over thrombo-aspiration thrombectomy was seen.

A delicate balancing act: immunity and immunopathology in human H7N9 influenza virus infections.

PURPOSE OF REVIEW: A delicate balance exists between a protective and detrimental immune response to an invading viral pathogen. Here, we review the latest advancements in our understanding of immunity and immunopathology during H7N9 influenza A virus (IAV) infections and its relevance to disease management and diagnosis. RECENT FINDINGS: Recent studies have highlighted the role of specific leukocytes in the pathogenesis of H7N9 IAV infections and potential diagnostic role that host cytokine profiles can play in forecasting disease severity. Furthermore, alterations in diet have emerged as a possible preventive measure for severe IAV infections. SUMMARY: The recent emergence and continued evolution of H7N9 IAVs have emphasized the threat that these avian viruses pose to human health. Understanding the role of the host immune response in both disease protection and pathogenesis is an essential first step in the creation of novel therapeutic and preventive measures for H7N9 IAV infections.

Surveillance for malaria elimination in Swaziland: a national cross-sectional study using pooled PCR and serology.

BACKGROUND: To guide malaria elimination efforts in Swaziland and other countries, accurate assessments of transmission are critical. Pooled-PCR has potential to efficiently improve sensitivity to detect infections; serology may clarify temporal and spatial trends in exposure. METHODOLOGY/PRINCIPAL FINDINGS: Using a stratified two-stage cluster, cross-sectional design, subjects were recruited from the malaria endemic region of Swaziland. Blood was collected for rapid diagnostic testing (RDT), pooled PCR, and ELISA detecting antibodies to Plasmodium falciparum surface antigens. Of 4330 participants tested, three were RDT-positive yet false positives by PCR. Pooled PCR led to the identification of one P. falciparum and one P. malariae infection among RDT-negative participants. The P. falciparum-infected participant reported recent travel to Mozambique. Compared to performing individual testing on thousands of samples, PCR pooling reduced labor and consumable costs by 95.5%. Seropositivity was associated with age ≥20 years (11·7% vs 1·9%, P<0.001), recent travel to Mozambique (OR 4.4 [95% CI 1.0-19.0]) and residence in southeast Swaziland (RR 3.78, P<0.001). CONCLUSIONS: The prevalence of malaria infection and recent exposure in Swaziland are extremely low, suggesting elimination is feasible. Future efforts should address imported malaria and target remaining foci of transmission. Pooled PCR and ELISA are valuable surveillance tools for guiding elimination efforts.