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Fluorinated polyimides incorporated with triptycene units have gained growing attention over the last decade since they present potentially interesting selectivities and a higher free volume with respect to their triptycene-free counterparts. This work examines the transport of single-gas and mixed-gas N2 and CH4 in the triptycene-based 6FDA-BAPT homopolyimide and in a block 15,000 g mol−1/15,000 g mol−1 6FDA-mPDA/BAPT copolyimide by using molecular dynamics (MD) simulations. The void-space analyses reveal that, while the free volume consists of small-to-medium holes in the 6FDA-BAPT homopolyimide, there are more medium-to-large holes in the 6FDA-mPDA/BAPT copolyimide. The single-gas sorption isotherms for N2 and CH4 over the 0–70 bar range at 338.5 K show that both gases are more soluble in the block copolyimide, with a higher affinity for methane. CH4 favours sites with the most favourable energetic interactions, while N2 probes more sites in the matrices. The volume swellings remain limited since neither N2 nor CH4 plasticise penetrants. The transport of a binary-gas 2:1 CH4/N2 mixture is also examined in both polyimides under operating conditions similar to those used in current natural gas processing, i.e., at 65.5 bar and 338.5 K. In the mixed-gas simulations, the solubility selectivities in favour of CH4 are enhanced similarly in both matrices. Although diffusion is higher in 6FDA-BAPT/6FDA-mPDA, the diffusion selectivities are also close. Both triptycene-based polyimides under study favour, to a similar extent, the transport of methane over that of nitrogen under the conditions studied. [ABSTRACT FROM AUTHOR]

Suppliers and large buyers of electricity often sign load-following forward contracts (LFFCs). A LFFC obligates an electricity supplier to deliver at a pre-specified unit price a fraction of the buyer’s ultimate demand for electricity. We show that relative to more standard (“swap”) forward contracts, LFFCs can reduce the variation in the wholesale price of electricity. However, LFFCs also can increase the expected wholesale price and thereby reduce expected consumer surplus and total surplus. [ABSTRACT FROM AUTHOR]

Background: Frontline providers mostly outside specific emergency areas deliver emergency care around the world, yet often they do not receive dedicated training in managing emergency conditions. When designed for low-resource settings, emergency care training has been shown to improve provider skills, facilitate efficient use of available resources, and reduce death and disability by ensuring timely access to life-saving care. Methods: The WHO/ICRC Basic Emergency Care (BEC) Course with follow up longitudinal mentorship for 6 months was implemented in rural Neno District Malawi from September 2019-April 2020. We completed a mixed-methods analysis of the course and mentorship included mentor and participant surveys and feedback, mentorship quantification, and participant examination results. Simple descriptive statistics and boxplot visuals were used to describe participant demographics and mentorship quantification with a Wilcoxon signed-rank test to evaluate pre- and post-test scores. Qualitative feedback from participants and mentors were inductively analyzed using Dedoose. Results: The median difference of BEC course examination percentage score between participants before the BEC course and immediately following the course was 18.0 (95% CI 14.0–22.0; p<0.001). Examination scores from the one-year post-test was lower but sustained above the pre-course test score with a median difference of 11.9 (95% CI 4.0–16.0; p<0.009). There were 174 mentorship activities with results suggesting that a higher number of mentorship touches and hours of mentor-mentee interactions may assist in sustained knowledge test scores. Reported strengths included course delivery approach leading to improved knowledge with mentorship enhancing skills, learning and improved confidence. Suggestions for improvement included more contextualized training and increased mentorship. Conclusion: The BEC course and subsequent longitudinal mentorship were feasible and acceptable to participants and mentors in the Malawian low resource context. Follow-up longitudinal mentorship was feasible and acceptable and is likely important to cementing the course concepts for long-term retention of knowledge and skills. [ABSTRACT FROM AUTHOR]

This article addresses the role of nationalism and identity in relation to the experience of Italians in Australia, and more specifically, North Queensland, during World War One. Through a comparative study with the experience of Italians in the United States during World War One it is possible to comprehend further how the events of World War One impacted the Italian communities of Australia. World War One was a seminal event for the Italian communities in Australia as, unlike World War Two, the fact Italy and Australia were fighting on the same side gave Italians a sense of place in their new country they had not experienced before. However, when the Italian government attempted to forcibly conscript overseas Italians to fight on the Italian front, a policy they were helped with by the Australian government, it brought about challenging questions concerning citizenship, identity and the rights of immigrants residing in Australia. [ABSTRACT FROM AUTHOR]

The objective of this paper is to update and summarize the arguments behind the Integrated Heritage Rehabilitation (IHR) for Wooden Cities methodology. Building in the Coastal Temperate Rainforest ecoregion relied on native species, and is still characteristic of the towns in southern Chile, including the city of Valdivia. However, the historic town's urban fabric is vulnerable to natural disasters and neoliberal market practices. Regulations and instruments for architectural restoration hinder IHR since their primary focus lies in social sciences, excluding the fundamental architectonic technical aspects, as well as a broader understanding of the context. Through an analysis of a set of historic buildings restored with public funds, the relationship between social sciences, engineering, architecture, and the theories of public use and landscape is patent. It is evident that there is a need to establish effective practices to extend the service life of buildings through cultural heritage management. Eight key points were identified, that connect history with the material conditions, which today are lacking in the Chilean Public Service. For the restoration processes to be integrated, evaluations must include new dimensions, such as the economic relationship and the material or tangible management, as well as the integration with the surrounding original architectural identity and the ease with which it can be culturally associated. From the harmonization of these eight points within the heritage regulatory framework, an improvement of the integrated rehabilitation of heritage buildings in the southern Chilean towns is expected, with priority given to timber conservation and public contribution. [ABSTRACT FROM AUTHOR]

The average number of hours we spend at work varies dramatically by country. Previous research focuses on tax policy, social security, and labor market regulation to explain the differences. This paper builds on previous work by focusing on politics. Specifically, it examines the relationship between democracy and the average number of hours worked per person employed. Using data on the supply of labor from the Penn World Tables 9.1, I find there is an important difference between democracies and dictatorships: as GDP/capita increases, individuals in democracies spend fewer hours at work than their counterparts in dictatorships. The results are robust to various specifications of the model that account for selection bias and data that are missing not at random (MNAR). These findings imply that the elections, civil rights, and the political liberties associated with democracy influence the amount of time people spend at work. [ABSTRACT FROM AUTHOR]

Background and objective. Multiple mastopexy techniques have been described, however, reports of long-term results in different techniques are scarce. The inverted-T and periaerolar techniques continue to be the most used, reason why we describe our experience with the long-term comparison of the two techniques. Methods. A longitudinal, comparative, observational, retrospective study comparing aesthetic satisfaction, speed of recovery and the probability of long-term associated complications was carried out in 97 mastopexy cases: 48 operated with the inverted-T technique and 49 with the periareolar technique. The homogenization of the data was analyzed with the x² and Fisher tests and the odds ratio (OR, 95% CI) was used as a measure of association between the surgical technique used and the probability of presenting complications. Results. At 5 years, of 48 patients who declared satisfaction of 100-80% all were operated with the inverted-T technique (p <0.001). For both the inverted T technique and the periareolar technique, the p-value according to the Friedman test for related samples was <0.000. Conclusions. In our experience, the periareolar mastopexy pattern has less satisfaction and more long-term complications than the inverted-T technique, from which we conclude that the periareolar mastopexy pattern is recommended in patients with grade I mammary ptosis and/or with small volume breast implants; mastopexy with the inverted-T technique has more satisfaction and fewer long-term complications like widening of the nipple-areola complex and breast asymmetry. [ABSTRACT FROM AUTHOR]

The American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions have recently released their joint guideline on coronary artery revascularization [[1]]. Considering that only 26% of patients in the revascularization arm underwent CABG, one can hardly consider this trial as an adequate comparison of CABG plus OMT versus OMT alone. The largest trial to date is the ISCHEMIA trial, which randomized patients with SIHD to revascularization or OMT in patients with moderate to severe ischaemia. [Extracted from the article]

We previously reported that growth promoter-induced skeletal muscle hypertrophy co-ordinately upregulated expression of genes associated with an integrated stress response (ISR), as well as potential ISR regulators. We therefore used Adeno-Associated Virus (AAV)-mediated overexpression of these genes, individually or in combination, in mouse skeletal muscle to test whether they induced muscle hypertrophy. AAV of each target gene was injected into mouse Tibialis anterior (TA) and effects on skeletal muscle growth determined 28 days later. Individually, AAV constructs for Arginase-2 (Arg2) and Activating transcription factor-5 (Atf5) reduced hindlimb muscle weights and upregulated expression of genes associated with an ISR. AAV-Atf5 also decreased Myosin heavy chain (MyHC)-IIB mRNA, but increased MyHC-IIA and isocitrate dehydrogenase-2 (Idh2) mRNA, suggesting ATF5 is a novel transcriptional regulator of Idh2. AAV-Atf5 reduced the size of both TA oxidative and glycolytic fibres, without affecting fibre-type proportions, whereas Atf5 combined with Cebpg (CCAAT enhancer binding protein-gamma) only reduced the size of glycolytic fibres and tended to increase the proportion of oxidative fibres. It is likely that persistent Atf5 overexpression maintains activation of the ISR, thereby reducing protein synthesis and/or increasing protein degradation and possibly apoptosis, resulting in inhibition of muscle growth, with overexpression of Arg2 having a similar effect. [ABSTRACT FROM AUTHOR]

This paper uses simple electricity market models to demonstrate the workings of, and problems with, Ontario's zonal price/two-schedule electricity market design. The roles played by zonal prices, Shadow LMP prices, and out-of-market congestion payments are explained. This market design is compared and contrasted to the much better-known single-schedule designs with LMP pricing used in neighboring U.S. markets. The ways in which congestion payments can, and have been, gamed is highlighted and shown to be special cases of counter-trading "inc-dec games". The bizarre outcomes for interjurisdictional trading arising from Ontario's use of congestion pricing on its interties combined with uniform pricing on the internal grid are demonstrated. Some gaming problems identified in other markets are reviewed compared to Ontario's situation. Finally, the paper recaps the system operator's efforts to remedy the various problems with the market while preparing a fundamental redesign. [ABSTRACT FROM AUTHOR]

• Oil exposure causes successional changes of the soil microbial community. • After oil exposure, time and soil pH are key drivers of the microbial consortia. • The recovery of microbial diversity and soil stability depends on the oil removal. • High abundance of the genus Sphingomonas correlate with oil biodegradation enhance. [ABSTRACT FROM AUTHOR]

Background: Idiopathic Anaphylaxis (IA) is the most common anaphylactic syndrome in adults. Mental health problems associated with IA are not well recognised. We aimed to assess if patients diagnosed with IA were more likely to experience mental health problems compared to a normative Australian population. We additionally hypothesised that the number of anaphylactic episodes would correlate with symptoms of anxiety. Methods: A total of 34 patients with at least one episode of IA were recruited from an adult immunology clinic. Patients were recruited as part of a separate study evaluating alternative aetiologies in IA. Mental health problems were measured using the Depression, Anxiety and Stress Scale (DASS-21). An extension of the survey included questions specifically focused on the psychological impact of IA. Results: Compared to population norms, those with IA had significantly higher levels of mental health problems. Statistically significant DASS-21 scores were identified for depression 4.24 vs. 2.57 (p < 0.001), anxiety 4.76 vs. 1.74 (p < 0.012), stress 7.35 vs. 3.95 (p < 0.001) and total score 16.35 vs. 8.00 (p < 0.001). There was no association between two or more episodes of anaphylaxis and increased anxiety levels (β = 0.52, CI -2.59–3.62, p = 0.74). Conclusions: This is the first paper to demonstrate that patients living with idiopathic anaphylaxis are more symptomatic for mental illness than those in the community. Screening for mental illness and referral for psychological support should be undertaken in people with IA. [ABSTRACT FROM AUTHOR]

We define a notion of height for rational points with respect to a vector bundle on a proper algebraic stack with finite diagonal over a global field, which generalizes the usual notion for rational points on projective varieties. We explain how to compute this height for various stacks of interest (for instance: classifying stacks of finite groups, symmetric products of varieties, moduli stacks of abelian varieties, weighted projective spaces). In many cases, our uniform definition reproduces ways already in use for measuring the complexity of rational points, while in others it is something new. Finally, we formulate a conjecture about the number of rational points of bounded height (in our sense) on a stack X, which specializes to the Batyrev-Manin conjecture when X is a scheme and to Malle's conjecture when X is the classifying stack of a finite group. [ABSTRACT FROM AUTHOR]

Myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) is diagnosed by serum MOG‐immunoglobulin G (MOG‐IgG) in association with typical demyelination. 111/1127 patients with paired CSF/serum samples were seropositive for MOG‐IgG. Only 7/1016 (0.7%) seronegative patients had CSF‐restricted MOG‐IgG. While 3/7 patients had longitudinally extensive transverse myelitis, four had a confirmed alternate diagnosis (three multiple sclerosis, one CNS vasculitis). In a national referral setting, CSF‐restricted MOG‐IgG had a low sensitivity (2.63%, 95%CI 0.55–7.50%) and low positive predictive value (1.97%, 95%CI 0.45–8.13%). We strongly recommend serum as the preferred diagnostic biospecimen, and urge caution in the interpretation of CSF‐restricted MOG‐IgG in patients without clinico‐radiological features consistent with MOGAD. [ABSTRACT FROM AUTHOR]

Anti-IgLON5 (IgLON5-IgG)-associated disease is a newly defined clinical entity. This literature review aims to evaluate its pathogenesis, which remains a pivotal question. Features that favour a primary neurodegenerative mechanism include the non-inflammatory tauopathy neuropathological signature and overrepresentation of microtubule-associated protein tau (MAPT) H1/H1 genotype as seen in other sporadic tauopathies. In contrast, the cell-surface localisation of IgLON5, capability of anti-IgLON5 antibodies to exert direct in vitro pathogenicity and disrupt IgLON5 interactions with its binding partners, human leukocyte antigen (HLA)-DRB1*10:01 and HLA-DQB1*05:01 allele preponderance with high affinity binding of IgLON5 peptides, and responsiveness to immunotherapy favour a primary autoimmune process. The presentation and course of anti-IgLON5-associated disease is heterogenous; hence, we hypothesise that a multitude of immune mechanisms are likely simultaneously operational in this disease cohort. [ABSTRACT FROM AUTHOR]

To compare the efficacy and safety of the proposed aflibercept biosimilar SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration, this randomized, double-masked, parallel-group, multicenter study was conducted in 14 countries from 13 August 2020 to 8 September 2022. Patients with neovascular age-related macular degeneration. With subfoveal, juxtafoveal, or extrafoveal choroidal neovascularization were aged 50 years or older. Intravitreal injection of SCD411 or aflibercept (2.0 mg) were administered every 4 weeks for the first three injections and every 8 weeks until week 48. The primary efficacy endpoint was the change in best-corrected visual acuity from baseline to week 8 with an adjusted equivalence margin of ± 3.0 letters. Patients were randomly assigned to receive either SCD411 (n = 288) or reference aflibercept (n = 288). A total of 566 participants (98.3%) completed week 8 of the study. The least-squares mean difference of change in best-corrected visual acuity from baseline to week 8 (SCD411—aflibercept) was − 0.4 letters (90% confidence interval = − 1.6 to 0.9). The incidence of ocular (69 of 287 [24.0%] vs. 71 of 286 [24.8%]) and serious ocular (5 of 287 [1.7%] vs. 3 of 286 [1.0%]) treatment-emergent adverse effects were similar between the SCD411 and aflibercept groups. Immunogenicity analysis revealed a low incidence of neutralizing antibody formation in both groups. In conclusion, SCD411 has equivalent efficacy compared with reference aflibercept in patients with neovascular age-related macular degeneration and has a comparable safety profile. The results support the potential use of SCD411 for the treatment of neovascular age-related macular degeneration. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) is an arthropod-borne virus (arbovirus) transmitted by Aedes mosquitoes. The human infection usually manifests as a febrile and incapacitating arthritogenic illness, self-limiting and non-lethal. However, since 2013, CHIKV spreading through the tropics and to the Americas was accompanied by an increasing number of cases of atypical disease presentation, namely severe neuropathies and neonatal infection due to intrapartum vertical transmission. The pathophysiological mechanisms underlying these conditions have not been fully elucidated. However, arbovirus intrahost genetic diversity is thought to be linked to viral pathogenesis. To determine whether particular viral variants could be somehow associated, we analyzed the intrahost genetic diversity of CHIKV in three infected patients with neurological manifestations and three mothers infected during the intrapartum period, as well as their babies following vertical transmission. No statistically supported differences were observed for the genetic variability (nucleotide substitutions/gene length) along the genome between the groups. However, the newborn and cerebrospinal fluid samples (corresponding to virus passed through the placenta and/or the blood–brain barrier (BBB)) presented a different composition of their intrahost mutant ensembles compared to maternal or patient serum samples, even when concurrent. This finding could be consistent with the unidirectional virus transmission through these barriers, and the effect of selective bottlenecks during the transmission event. In addition, a higher proportion of defective variants (insertions/deletions and stop codons) was detected in the CSF and maternal samples and those were mainly distributed within the viral non-structural genes. Since defective viral genomes in RNA viruses are known to contribute to the outcome of acute viral infections and influence disease severity, their role in these atypical cases should be further investigated. Finally, with the in silico approach adopted, we detected no relevant non-conservative mutational pattern that could provide any hint of the pathophysiological mechanisms underlying these atypical cases. The present analysis represents a unique contribution to our understanding of the transmission events in these cases and generates hypotheses regarding underlying mechanisms, that can be explored further. [ABSTRACT FROM AUTHOR]

Worldwide, infections by influenza viruses are considered a major public health challenge. In this study, influenza B vaccine mismatches and clinical aspects of Victoria and Yamagata infections in Brazil were assessed. Clinical samples were collected from patients suspected of influenza infection. In addition, sociodemographic, clinical, and epidemiological information were collected by the epidemiological surveillance teams. Influenza B lineages were determined by real-time RT-PCR and/or Sanger sequencing. In addition, putative phylogeny–trait associations were assessed by using the BaTS program after phylogenetic reconstruction by a Bayesian Markov Chain Monte Carlo method (BEAST software package). Over 2010–2020, B/Victoria and B/Yamagata-like lineages co-circulated in almost all seasonal epidemics, with B/Victoria predominance in most years. Vaccine mismatches between circulating viruses and the trivalent vaccine strains occurred in five of the eleven seasons (45.5%). No significant differences were identified in clinical presentation or disease severity caused by both strains, but subjects infected by B/Victoria-like viruses were significantly younger than their B/Yamagata-like counterparts (16.7 vs. 31.4 years, p < 0.001). This study contributes to a better understanding of the circulation patterns and clinical outcomes of B/Victoria- and B/Yamagata-like lineages in Brazil and advocate for the inclusion of a quadrivalent vaccine in the scope of the Brazilian National Immunization Program. [ABSTRACT FROM AUTHOR]

PolyPOSS-imides are hybrid hyper-cross-linked networks based on inorganic octa(aminopropyl)silsesquioxane (POSS) cages covalently bonded via organic imide bridges. They were initially developed for separations under harsh conditions, but they cannot be used above 300 °C due to the decomposition of their –(CH 2) 3 – propyl linkers. Replacing the aliphatic-arm POSS with its phenyl-arm derivative, octa(aminophenyl)silsesquioxane (OAPS), should thus increase their resistance. However, OAPS has three possible isomers depending on the meta , para or ortho position of the –NH 2 group on the phenyl ring. To pre-screen the most interesting structures before attempting synthesis, molecular dynamics (MD) simulations were recently used to compare twenty-two model networks based on the OAPS isomers, the initial POSS and several imide precursors at high temperatures. Six phenyl-arm polyOAPS-PMDA and polyOAPS-6FDA and two aliphatic-arm polyPOSS-PMDA and polyPOSS-6FDA were selected for further analyses of their CH 4 and CO 2 sorption isotherms at 35 °C. All of them have an average number of ~5 links per cage and cross-linking densities of ~3.8. In terms of connectivities and free-volume morphologies, both the meta OAPS and para OAPS networks are found to be open structures with many low-energy sites and high penetrant solubilities. On the other hand, the ortho functionalization leads to denser morphologies associated to lower solubilities, which makes it closer to the POSS networks. Differences are enhanced when the inorganic precursor is associated to a rigid organic linker such as PMDA. The iterative GCMC (Grand Canonical Monte Carlo)-MD sorption-relaxation technique was used to predict the single-gas uptakes of CH 4 and CO 2 in the networks over an extended 0–60 bar pressure range at 35 °C. The sorption capacities varied in the order para OAPS > meta OAPS > ortho OAPS > POSS for the inorganic precursor, and PMDA > 6FDA for the organic precursor (except for the ortho OAPS). All correlate directly to the accessible free-volume, but the CO 2 /CH 4 ideal sorption selectivities remained essentially the same over the whole pressure range. Compared to POSS, OAPS showed less swelling at equivalent penetrant concentrations in the matrix. It is also more resistant to other mechanical deformations such as isotropic dilation or uniaxial tension. This confirms that the polyOAPS-imides can indeed be used under harsher conditions than the current polyPOSS-imides, without loss of the CO 2 /CH 4 sorption selectivities. [Display omitted] • PolyOAPS/POSS-imides are investigated for gas separations under harsh conditions. • Phenyl-arm OAPS (meta, para and ortho isomers) is compared to aliphatic-arm POSS. • Network structures and free-volume morphologies depend on the OAPS isomer. • PolyOAPS-imides have high CH 4 and CO 2 sorption capacities but retain selectivity. • PolyOAPS-imides are better suited to harsh conditions than polyPOSS-imides. [ABSTRACT FROM AUTHOR]

Reconstruction of hydrological fluctuations in arid regions has proven challenging due to a lack of reliable chronologic constraints on sparse geological archives. The aim of this study was to establish an independent record of hydrologic changes in the hyper-arid Tarim Basin (TB; northwest China) with high spatiotemporal resolution. We present comprehensive radiocarbon and tree-ring data sets of subfossilized plant remains in the TB compiled from geomorphological investigations of the paleochannels of the Tarim River (TR), the longest endorheic river in China, crossing the world's second-largest shifting sand desert. Results show that the late medieval configuration of the TR basin was characterized by enhanced hydrological connectivity, as indicated by the formation of significant riparian forests in the desert regions at ca. 1170 CE. A distinct low-flow interval (ca. 1500-1650 CE) is identified for the first time, refining the period of a wetter-than-present TB. The present-day organization of streams in the lower TR was proto-formed after the dry period, possibly led by episodic flood-induced diversion. Our study describes the centennial-scale dynamics in the TR flow over the past millennium, offering a robust long-term context for hydrological assessment in the extensive drylands of the Asian interior. [ABSTRACT FROM AUTHOR]

The Coronavirus Disease 2019 (COVID-19) pandemic has disproportionately impacted people who use drugs (PWUD). This study explored relationships between drug use, COVID-19 testing, vaccination, and infection. This cross-sectional study was conducted in Miami, Florida between March 2021 and October 2022 as part of the National Institutes of Health (NIH) Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) initiative and the Miami Adult Studies on HIV (MASH) cohort. Users of cannabis, cocaine/crack, heroin/fentanyl, methamphetamines, hallucinogens, and/or prescription drug misuse in the previous 12 months were considered PWUD. Sociodemographic data, COVID-19 testing history, and vaccination-related beliefs were self-reported. Vaccinations were confirmed with medical records and positivity was determined with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. Statistical analyses included chi-square tests and logistic regression. Of 1,780 participants, median age was 57 years, 50.7% were male, 50.2% Non-Hispanic Black, and 66.0% reported an annual income less than $15,000. Nearly 28.0% used drugs. PWUD were less likely than non-users to self-report ever testing positive for SARS-CoV-2 (14.7% vs. 21.0%, p = 0.006). However, 2.6% of participants tested positive for SARS-CoV-2, with no significant differences between PWUD and non-users (3.7% vs. 2.2%, p = 0.076). PWUD were more likely than non-users to experience difficulties accessing testing (10.2% vs. 7.1%, p = 0.033), vaccine hesitancy (58.9% vs. 43.4%, p = 0.002) and had lower odds of receiving any dose of a COVID-19 vaccine compared to non-users (aOR, 0.63; 95% CI, 0.49–0.81; p<0.001). PWUD presented with greater difficulties accessing COVID-19 testing, greater vaccine hesitancy, and lower odds of vaccination. Testing and immunization plans that are tailored to the needs of PWUD and consider access, trust-building campaigns, and education may be needed. [ABSTRACT FROM AUTHOR]

Next-generation humanised mouse models and single-cell RNA sequencing (scRNAseq) approaches enable in-depth studies into human immune cell biology. Here we used NSG-SGM3 mice engrafted with human umbilical cord haematopoietic stem cells to investigate how human immune cells respond to and/or are changed by traumatic spinal cord injury (SCI). We hypothesised that the use of such mice could help advance our understanding of spinal cord injury-induced immune depression syndrome (SCI-IDS), and also how human leukocytes change as they migrate from the circulation into the lesion site. Our scRNAseq experiments, supplemented by flow cytometry, demonstrate the existence of up to 11 human immune cell (sub-) types and/or states across the blood and injured spinal cord (7 days post-SCI) of humanised NSG-SGM3 mice. Further comparisons of human immune cell transcriptomes between naïve, sham-operated and SCI mice identified a total of 579 differentially expressed genes, 190 of which were 'SCI-specific' (that is, genes regulated only in response to SCI but not sham surgery). Gene ontology analysis showed a prominent downregulation of immune cell function under SCI conditions, including for T cell receptor signalling and antigen presentation, confirming the presence of SCI-IDS and the transcriptional signature of human leukocytes in association with this phenomenon. We also highlight the activating influence of the local spinal cord lesion microenvironment by comparing the transcriptomes of circulating versus infiltrated human immune cells; those isolated from the lesion site were enriched for genes relating to both immune cell activity and function (e.g., oxidative phosphorylation, T cell proliferation and antigen presentation). We lastly applied an integrated bioinformatics approach to determine where immune responses in humanised NSG-SGM3 mice appear congruent to the native responses of human SCI patients, and where they diverge. Collectively, our study provides a valuable resource and methodological framework for the use of these mice in translational research. [ABSTRACT FROM AUTHOR]

Objective. Autoimmune inner ear disease (AIED) is a rare disorder characterized by rapidly progressive, sensorineural hearing loss that demonstrates good responsiveness to corticosteroid and immunosuppressive therapy. The pathophysiology is likely driven by chronic trafficking of immune cells into the inner ear, targeting inner ear proteins to coordinate inflammation. Suppression or modulation of the immune response can minimize cochleitis allowing for potential recovery of hearing. It is an otologic emergency requiring a multidisciplinary approach to management to commence immunosuppressive therapy. This can be achieved using steroids, immunomodulators, plasmapheresis, intravenous immunoglobulin, or biologic agents. Treatment decisions are further complicated in pregnancy and require supervision by an obstetrician and maternal-fetal medicine (MFM) specialist. Concerns include safe dosing of steroids and potential for transplacental migration of immune complexes. We provide the first comprehensive literature review on AIED and its implications in pregnancy. We frame our discussion in the context of the second reported case of primary AIED in pregnancy and the first to show excellent response to immunosuppressive therapy. Methods. We reviewed the presented case and literature on AIED. Results. A 27-year-old, pregnant, HSP-70 positive woman was diagnosed with AIED and had excellent recovery of hearing and balance following a combination of steroid treatment, augmented by oral immunomodulators, plasmapheresis, and IVIG. Conclusion. AIED is a diagnostic challenge, and treatment considerations are complex when encountered in pregnancy. Management requires multidisciplinary involvement between otolaryngologists, immunologists, and obstetricians to balance maternal and fetal health outcomes. [ABSTRACT FROM AUTHOR]