Farmer perceptions, knowledge, and management of fall armyworm in maize production in Uganda.

Spodoptera frugiperda (J.E. Smith), fall armyworm (FAW), a polyphagous Noctuid pest, was first reported in Uganda in 2016. Farmers were trained to identify and manage the pest, but there was a lack of information on farmer knowledge, perceptions and practices deployed to control it. Therefore, we conducted a survey to assess maize farmers' knowledge, perceptions and management of the pest during the invasion. We interviewed 1,289 maize farmers from 10 maize-growing agro-ecological zones (AEZ) of Uganda using well-structured questionnaires. The data were analyzed using R version 4.2.3. The respondents faced many constraints, including pests, drought, poor soils and labor constraints. Among the pests, FAW was ranked by most (85%) of the respondents as the number one pest problem in maize, and some farmers reported having noticed it way back in 2014. By 2018, more than 90% of the farmers had seen or heard about FAW, and about 80% saw FAW in their fields. The most common FAW symptoms reported by maize farmers were windowing, near tunnel damage, and holes on the cobs. The developmental stages of FAW identified by farmers included eggs (10%), young larvae (78.7%), mature larvae (73.5%) and adult moths (6.7%). Insecticides were the major control tactic, although some farmers used plant extracts, hand-picking, sand, and ash. Farmers sourced information on FAW from various sources, including fellow farmers, radio/TV, extension agents, input dealers, print media, research and NGO extension. There is a need to package clear and uniform information for the farmers and to develop and promote a sustainable solution for FAW management, including harnessing biological control and cultural practices.

Beyond the Hippocampus: Amygdala and Memory Functioning in Older Adults.

BACKGROUND: Medial temporal lobe atrophy has been linked to decline in neuropsychological measures of explicit memory function. While the hippocampus has long been identified as a critical structure in learning and memory processes, less is known about contributions of the amygdala to these functions. We sought to investigate the relationship between amygdala volume and memory functioning in a clinical sample of older adults with and without cognitive impairment. METHODS: A serial clinical sample of older adults that underwent neuropsychological assessment at an outpatient neurology clinic was selected for retrospective chart review. Patients were included in the study if they completed a comprehensive neuropsychological assessment within six months of a structural magnetic resonance imaging scan. Regional brain volumes were quantified using Neuroreader® software. Associations between bilateral hippocampal and amygdala volumes and memory scores, derived from immediate and delayed recall conditions of a verbal story learning task and a visual design reconstruction task, were examined using mixed-effects general linear models, controlling for total intracranial volume, scanner model, age, sex and education. Partial correlation coefficients, adjusted for these covariates, were calculated to estimate the strength of the association between volumes and memory scores. RESULTS: A total of 68 (39F, 29M) participants were included in the analyses, with a mean (SD) adjusted age of 80.1 (6.0) and educational level of 15.9 (2.5) years. Controlling for age, sex, education, and total intracranial volume, greater amygdala volumes were associated with better verbal and visual memory performance, with effect sizes comparable to hippocampal volume. No significant lateralized effects were observed. Partial correlation coefficients ranged from 0.47 to 0.33 (p<.001). CONCLUSION: These findings contribute to a growing body of knowledge identifying the amygdala as a target for further research in memory functioning. This highlights the importance of considering the broader functioning of the limbic system in which multiple subcortical structures contribute to memory processes and decline in older adults.

Probing the optical properties and toxicological profile of zinc tungstate nanorods.

Zinc tungstate is a semiconductor known for its favorable photocatalytic, photoluminescence, and scintillation properties, coupled with its relatively low cost, reduced toxicity, and high stability in biological and catalytic environments. In particular, zinc tungstate evinces scintillation properties, namely the ability to emit visible light upon absorption of energetic radiation such as x rays, which has led to applications not only as radiation detectors but also for biomedical applications involving the delivery of optical light to deep tissue, such as photodynamic therapy and optogenetics. Here, we report on the synthesis of zinc tungstate nanorods generated via an optimized but facile method, which allows for synthetic control over the aspect ratio of the as-synthesized anisotropic motifs via rational variation of the solution pH. We investigate the effect of aspect ratio on their resulting photoluminescent and radioluminescent properties. We further demonstrate the potential of these zinc tungstate nanorods for biomedical applications, such as photodynamic therapy for cancer treatment, by analyzing their toxicological profile within cell lines and neurons.

Air pollution, genetic factors, and chronic rhinosinusitis: A prospective study in the UK Biobank.

BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent upper respiratory condition that manifests in two primary subtypes: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). While previous studies indicate a correlation between air pollution and CRS, the role of genetic predisposition in this relationship remains largely unexplored. We hypothesized that higher air pollution exposure would lead to the development of CRS, and that genetic susceptibility might modify this association. METHODS: This cohort study involving 367,298 adult participants from the UK Biobank, followed from March 2006 to October 2021. Air pollution metrics were estimated at residential locations using land-use regression models. Cox proportional hazard models were employed to explore the associations between air pollution exposure and CRS, CRSwNP, and CRSsNP. A polygenic risk score (PRS) was constructed to evaluate the joint effect of air pollution and genetic predisposition on the development of CRS. RESULTS: We found that the risk of CRS increased under long-term exposure to PM2.5 [the hazard ratios (HRs) with 95 % CIs: 1.59 (1.26-2.01)], PM10 [1.64 (1.26-2.12)], NO2 [1.11 (1.04-1.17)], and NOx [1.18 (1.12-1.25)], respectively. These effects were more pronounced among participants with CRSwNP, although the differences were not statistically significant. Additionally, we found that the risks for CRS and CRSwNP increased in a graded manner among participants with higher PRS or higher exposure to PM2.5, PM10, or NOx concentrations. However, no multiplicative or additive interactions were observed. CONCLUSIONS: Long-term exposure to air pollution increases the risk of CRS, particularly CRSwNP underscoring the need to prioritize clean air initiatives and environmental regulations.

Respiratory Health Associated with Systemic Metal Exposure in Post 9/11 Veterans in the Department of Veterans Affairs Toxic Embedded Fragment Registry.

OBJECTIVE: Adverse respiratory outcomes in post-9/11 Veterans with elevated urinary metal measures and enrolled in the VA's Toxic Embedded Fragment registry were compared to those without elevated urinary metals. METHODS: Veterans completed questionnaires, pulmonary physiology tests (pulmonary function and oscillometry) and provided urine samples for analysis of 13 metals. Respiratory symptoms, diagnoses and physiology measures were compared in Veterans with ≥1 urine metal elevation to those without metal elevations, adjusted for covariates, including smoking. RESULTS: Among 402 study participants, 24% had elevated urine metals, often just exceeding upper limits of reference values. Compared to Veterans without elevated metals, those with elevated metals had had higher FEV1 values but similar frequencies of respiratory symptoms and diagnoses and abnormalities on pulmonary physiology tests. CONCLUSIONS: Mild systemic metal elevations in post 9/11 Veterans are not associated with adverse respiratory health outcomes.

Adult-onset asthma, allergy, and aspirin hypersensitivity associate with self-reported food avoidance.

Background: The adoption of avoidance diets by adult-onset asthmatics has not previously been studied. We hypothesized that avoidance diets would associate with adult-onset asthma, allergy, and aspirin-exacerbated respiratory disease (AERD). Methods: A total of 1247 subjects with adult-onset asthma (age range: 31-91) from the Finnish national registry, and age- and sex-matched controls (n = 1970) participated in a questionnaire study in 1997. We estimated the association between asthma/allergy/AERD and avoidance diets, adjusting for potential confounding factors and validated the results in two retrospective cohorts of 5080 rhinitis/rhinosinusitis patients and 167 AERD patients from 2019 to 2020. Results: The presence of asthma positively associated with adoption of any avoidance diet (adjusted OR [CI95%] 1.24 [1.02-1.51], p = 0.029) as did allergic disease and self-reported AERD within the asthmatic group (1.79 [1.29-2.48], p = 0.001 and 1.69 [1.15-2.49], p = 0.007, respectively). Asthmatics and allergic asthmatics were more likely to report avoidance of fish, fruits and vegetables, and spices (p ≤ 0.03) compared to controls and non-allergic asthmatics. The adjusted OR for multiple diets among AERD patients was 2.57 [1.34-4.95] p = 0.005. In the validation, 26.2% of the allergic asthmatics and 10.8% of AERD patients had documented avoidance diets. Conclusions: Our study shows a positive association between avoidance diets and adult-onset asthma, and with allergic disease or AERD within asthmatic patients. Although we lack information on the reason patients chose to observe a specific diet, our results reinforce the importance of asking patients about their diet and if needed, giving dietary advice for adult asthma patients to help them avoid the adoption of unnecessarily restrictive diets.

Are predatory mites effective as biological control agents to suppress Oligonychus ilicis (Acari: Tetranychidae) in blueberry plantings?

Southern red mite, Oligonychus ilicis McGregor (Acari: Tetranychidae), is an important polyphagous spider mite pest that causes economic damage to many ornamentals, coffee, and fruit crops. Blueberry growers in the Southeastern United States, including Florida and Georgia, have experienced severe losses due to outbreaks of O. ilicis. Predatory mites are an important management tool used for controlling spider mites; however, predators have not been studied and successfully evaluated in blueberry systems. Amblyseius swirskii Athias-Henriot, Phytoseiulus persimilis Athias-Henriot, and Neoseiulus californicus (McGregor) (Acari: Phytoseiidae) are among the most economically important arthropod agents used in augmentative biological control worldwide. To evaluate the potential of these 3 commercially available predatory mites for use in blueberry plantings, we conducted experiments under controlled laboratory conditions and in the greenhouse. In preliminary laboratory experiments, P. persimilis and N. californicus significantly reduced the number of O. ilicis motile stages below those found in the untreated control, indicating the potential for these 2 predatory mite species to suppress O. ilicis populations. Amblyseius swirskii did not perform well controlling O. ilicis motiles in the laboratory. Under greenhouse conditions, N. californicus and P. persimilis significantly reduced the number of eggs after 7 days of release and the number of motile stages after 14 days of release. This is the first report of using phytoseiid mites to suppress O. ilicis in blueberry systems in the United States. Further studies on predator behavior, feeding preferences, and acaricide compatibility with predators are required to investigate the possibility of using P. persimilis, and N. californicus as biological control agents of O. ilicis in blueberry systems.

Real-world persistence of multiple sclerosis disease-modifying therapies.

BACKGROUND AND PURPOSE: Treatment persistence is the continuation of therapy over time. It reflects a combination of treatment efficacy and tolerability. We aimed to describe real-world rates of persistence on disease-modifying therapies (DMTs) for people with multiple sclerosis (pwMS) and reasons for DMT discontinuation. METHODS: Treatment data on 4366 consecutive people with relapse-onset multiple sclerosis (MS) were pooled from 13 UK specialist centres during 2021. Inclusion criteria were exposure to at least one MS DMT and a complete history of DMT prescribing. PwMS in blinded clinical trials were excluded. Data collected included sex, age at MS onset, age at DMT initiation, DMT treatment dates, and reasons for stopping or switching DMT. For pwMS who had received immune reconstituting therapies (cladribine/alemtuzumab), discontinuation date was defined as starting an alternative DMT. Kaplan-Meier survival analyses were used to express DMT persistence. RESULTS: In 6997 treatment events (1.6 per person with MS), median time spent on any single maintenance DMT was 4.3 years (95% confidence interval = 4.1-4.5 years). The commonest overall reasons for DMT discontinuation were adverse events (35.0%) and lack of efficacy (30.3%). After 10 years, 20% of people treated with alemtuzumab had received another subsequent DMT, compared to 82% of people treated with interferon or glatiramer acetate. CONCLUSIONS: Immune reconstituting DMTs may have the highest potential to offer a single treatment for relapsing MS. Comparative data on DMT persistence and reasons for discontinuation are valuable to inform treatment decisions and in personalizing treatment in MS.

Persistence and evolution of Pseudomonas aeruginosa following initiation of highly effective modulator therapy in cystic fibrosis.

Today, more than 90% of people with cystic fibrosis (pwCF) are eligible for the highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy called elexacaftor/tezacaftor/ivacaftor (ETI) and its use is widespread. Given the drastic respiratory symptom improvement experienced by many post-ETI, clinical studies are already underway to reduce the number of respiratory therapies, including antibiotic regimens, that pwCF historically relied on to combat lung disease progression. Early studies suggest that bacterial burden in the lungs is reduced post-ETI, yet it is unknown how chronic Pseudomonas aeruginosa populations are impacted by ETI. We found that pwCF remain infected throughout their upper and lower respiratory tract with their same strain of P. aeruginosa post-ETI, and these strains continue to evolve in response to the newly CFTR-corrected airway. Our work underscores the continued importance of CF airway microbiology in the new era of highly effective CFTR modulator therapy. IMPORTANCE: The highly effective cystic fibrosis transmembrane conductance regulator modulator therapy Elexakaftor/Tezacaftor/Ivacaftor (ETI) has changed cystic fibrosis (CF) disease for many people with cystic fibrosis. While respiratory symptoms are improved by ETI, we found that people with CF remain infected with Pseudomonas aeruginosa. How these persistent and evolving bacterial populations will impact the clinical manifestations of CF in the coming years remains to be seen, but the role and potentially changing face of infection in CF should not be discounted in the era of highly effective modulator therapy.

Surgical Navigation in the Anterior Skull Base Using 3-Dimensional Endoscopy and Surface Reconstruction.

Importance: Image guidance is an important adjunct for endoscopic sinus and skull base surgery. However, current systems require bulky external tracking equipment, and their use can interrupt efficient surgical workflow. Objective: To evaluate a trackerless surgical navigation system using 3-dimensional (3D) endoscopy and simultaneous localization and mapping (SLAM) algorithms in the anterior skull base. Design, Setting, and Participants: This interventional deceased donor cohort study and retrospective clinical case study was conducted at a tertiary academic medical center with human deceased donor specimens and a patient with anterior skull base pathology. Exposures: Participants underwent endoscopic endonasal transsphenoidal dissection and surface model reconstruction from stereoscopic video with registration to volumetric models segmented from computed tomography (CT) and magnetic resonance imaging. Main Outcomes and Measures: To assess the fidelity of surface model reconstruction and accuracy of surgical navigation and surface-CT model coregistration, 3 metrics were calculated: reconstruction error, registration error, and localization error. Results: In deceased donor models (n = 9), high-fidelity surface models of the posterior wall of the sphenoid sinus were reconstructed from stereoscopic video and coregistered to corresponding volumetric CT models. The mean (SD; range) reconstruction, registration, and localization errors were 0.60 (0.24; 0.36-0.93), 1.11 (0.49; 0.71-1.56) and 1.01 (0.17; 0.78-1.25) mm, respectively. In a clinical case study of a patient who underwent a 3D endoscopic endonasal transsphenoidal resection of a tubercular meningioma, a high-fidelity surface model of the posterior wall of the sphenoid was reconstructed from intraoperative stereoscopic video and coregistered to a volumetric preoperative fused CT magnetic resonance imaging model with a root-mean-square error of 1.38 mm. Conclusions and Relevance: The results of this study suggest that SLAM algorithm-based endoscopic endonasal surgery navigation is a novel, accurate, and trackerless approach to surgical navigation that uses 3D endoscopy and SLAM-based algorithms in lieu of conventional optical or electromagnetic tracking. While multiple challenges remain before clinical readiness, a SLAM algorithm-based endoscopic endonasal surgery navigation system has the potential to improve surgical efficiency, economy of motion, and safety.

Biologic Therapy in Pediatric Chronic Rhinosinusitis: A Systematic Review.

OBJECTIVE: Provide clinicians with current evidence for biologic therapy in children with chronic rhinosinusitis with nasal polyposis (CRSwNP). DATA SOURCES: PubMed, MEDLINE, Cochrane, and clinical trial registries. REVIEW METHODS: Key search terms related to biologic therapy in pediatric CRSwNP were identified via a structured query of current medical literature and clinical trial databases. CONCLUSIONS: There is a dearth of active clinical trials and research studies for biologics targeting pediatric CRSwNP. There is an ongoing compassionate-use clinical trial involving Dupilumab for children with nasal polyps as well as only 1 published work specifically focused on Dupilumab for pediatric CRSwNP in the setting of aspirin-exacerbated respiratory disease. IMPLICATIONS FOR PRACTICE: For children with atopic dermatitis, asthma, and chronic idiopathic urticaria, biologic therapies such as Omalizumab, Dupilumab, and Mepolizumab have gained Food and Drug Administration approval. The role of biologic therapy in pediatric CRSwNP demonstrates significant promise in the comprehensive management of the unified airway. Additional Phase III trials are necessary to broaden clinical indications for children with comorbid conditions and complex sinonasal disease.

Determinants of viral load suppression failure among HIV adults on ARV attending health care facilities: a retrospective study in Tanga region, Tanzania.

BACKGROUND: Availability and accessibility of Antiretroviral drugs (ARV's) improve the lives of People living with HIV (PLHIV) by improving client's immune system to overcome infections and prevent the development of AIDS and other HIV complications. Combination therapy, early initiation of ART, newer ART drugs, single dosage and drug affordability significantly contribute in the reduction of viral multiplication and suppression of HIV to undetectable plasma levels. METHODS: A retrospective longitudinal study design study was conducted from 1st October, 2018 to 30th June 2022 in all supported HIV care and treatment health facilities in Tanga region which were supported by Amref Health Africa, Tanzania. The participants were HIV adult patients aged 15 years and above on ART and attended the clinic at least once after ART initiation. Viral load suppression levels are defined with viral load <1,000 HIV RNA copies/ml (viral load suppression). Cox proportional hazard regression models were employed to identify risk factors for virological failure. P values were two-sided, and we considered a P<0.05 to be statistically significant. RESULTS: Fifty-nine thousand five hundred three adult clients >15 years whom were on ART were included in the analysis to determine the level of plasma Viral Load suppression after being on ART. Female 41,304 (69.4%) and male 18,199 (30.6%). Only four percent (2,290) were found to be unsuppressed i.e having plasma Viral Load >1,000cp/ml while 96% (57,213) were virally suppressed. Several factors were independently associated with virologic failure that included; age between 15 - <25 years (HR: 2.82, 95% CI 1.96 - 4.04), BMI <18.5 (HR: 1.69, 95% CI 1.23 - 2.30), advanced WHO stage IV (HR: 1.60, 95% CI 1.12 - 2.24), CD4 cell count <350 (HR: 2.61, 95% CI 2.12 - 3.23), poor adherence (HR: 1.98, 95% CI 1.80 - 2.18) and not using DTG based drug (HR: 11.8, 95% CI 9.74 - 14.3). CONCLUSION: Virologic failure was observed in this study among clients with young age, advanced WHO stage IV, not using DTG based regimen, poor drug adherence and second line regime. To improve Viral Load Suppression among these clients; the existing HIV intervention strategies should be taken care by targeting the identified risk factors.

Effects of highly effective modulator therapy on the dynamics of the respiratory mucosal environment and inflammatory response in cystic fibrosis.

BACKGROUND: While the widespread initiation of elexacaftor/tezacaftor/ivacaftor (ETI) has led to dramatic clinical improvements among persons with cystic fibrosis (pwCF), little is known about how ETI affects the respiratory mucosal inflammatory and physiochemical environment, or how these changes relate to lung function. METHODS: We performed a prospective, longitudinal study of adults with CF and chronic rhinosinusitis (CF-CRS) followed at our CF center (n = 18). Endoscopic upper respiratory tract (paranasal sinus) aspirates from multiple visit dates, both pre- and post-ETI initiation, were collected and tested for cytokines, metals, pH, and lactate levels. Generalized estimating equations were used to identify relationships between ETI and upper respiratory tract (URT) biomarker levels, and between URT biomarkers and lung function or clinical sinus parameters. RESULTS: ETI was associated with decreased upper respiratory mucosal cytokines B-cell activating factor (BAFF), IL-12p40, IL-32, IL-8, IL-22 and soluble tumor necrosis factor-1 (sTNFR1), and an increase in a proliferation-inducing ligand (APRIL) and IL-19. ETI was also associated with decreased URT levels of copper, manganese, and zinc. In turn, lower URT levels of BAFF, IL-8, lactate, and potassium were each associated with ~1.5% to 4.3% improved forced expiratory volume in 1 s (FEV1), while higher levels of IFNγ, iron, and selenium were associated with ~2% to 10% higher FEV1. CONCLUSIONS: Our observations suggest a dampening of inflammatory signals and restriction in microbial nutrients in the upper respiratory tract with ETI. These findings improve our understanding of how ETI impacts the mucosal environment in the respiratory tract, and may give insight into the improved infectious and inflammatory status and the resulting clinical improvements seen in pwCF.

Addressing sexual health concerns in Tanzania: perceived barriers among healthcare professionals and students in the "training for health professionals" study.

Little is known about the factors that may prevent healthcare professionals as key stakeholders from exploring sexual health issues in Tanzania. This study examined healthcare professionals' perspectives on the barriers to addressing sexual health concerns in practice. In June 2019, we conducted an exploratory qualitative study involving 18 focus group discussions among healthcare professionals (n = 60) and students (n = 61) in the health professions (midwifery, nursing, medicine) in Dar es Salaam, Tanzania. Study participants and design were purposively selected and stratified. We used a focus group discussion guide in Kiswahili. Data were transcribed in Kiswahili and translated into English. A thematic analysis approach was used for data analysis. Two themes were developed: (1) differences between health care professional and patient socio-demographic characteristics; (2) health care system and patients' backgrounds, such as communication barriers, lack of confidentiality and privacy within health facilities, type of clinical presentation and complaint, patient behaviours, and their clinical background. Several key barriers prevented sexual health communication between healthcare professionals and patients, affecting the quality of sexual health service delivery. Additional sexual health clinical training is warranted for health professions students and professionals to optimise sexual health care delivery in a culturally conservative country like Tanzania.

Lucanthone, a Potential PPT1 Inhibitor, Perturbs Stemness, Reduces Tumor Microtube Formation, and Slows the Growth of Temozolomide-Resistant Gliomas In Vivo.

Glioblastoma (GBM) is the most frequently diagnosed primary central nervous system tumor in adults. Despite the standard of care therapy, which includes surgical resection, temozolomide chemotherapy, radiation and the newly added tumor-treating fields, median survival remains only ∼20 months. Unfortunately, GBM has a ∼100% recurrence rate, but after recurrence there are no Food and Drug Administration-approved therapies to limit tumor growth and enhance patient survival, as these tumors are resistant to temozolomide (TMZ). Recently, our laboratory reported that lucanthone slows GBM by inhibiting autophagic flux through lysosome targeting and decreases the number of Olig2+ glioma stem-like cells (GSC) in vitro and in vivo. We now additionally report that lucanthone efficiently abates stemness in patient-derived GSC and reduces tumor microtube formation in GSC, an emerging hallmark of treatment resistance in GBM. In glioma tumors derived from cells with acquired resistance to TMZ, lucanthone retains the ability to perturb tumor growth, inhibits autophagy by targeting lysosomes, and reduces Olig2 positivity. We also find that lucanthone may act as an inhibitor of palmitoyl protein thioesterase 1. Our results suggest that lucanthone may function as a potential treatment option for GBM tumors that are not amenable to TMZ treatment. SIGNIFICANCE STATEMENT: We report that the antischistosome agent lucanthone impedes tumor growth in a preclinical model of temozolomide-resistant glioblastoma and reduces the numbers of stem-like glioma cells. In addition, it acts as an autophagy inhibitor, and its mechanism of action may be via inhibition of palmitoyl protein thioesterase 1. As there are no defined therapies approved for recurrent, TMZ-resistant tumor, lucanthone could emerge as a treatment for glioblastoma tumors that may not be amenable to TMZ both in the newly diagnosed and recurrent settings.

Residential and inpatient treatment of substance use disorders in Sub-Saharan Africa: a scoping review.

BACKGROUND: With substance use rates increasing in Sub-Saharan Africa (SSA), an understanding of the accessibility and effectiveness of rehabilitative services for people who use alcohol and other drugs (AOD) is critical in the global efforts to diagnose and treat substance use disorders (SUD). This scoping review seeks to address the gaps in knowledge related to the types of research that have been conducted regarding inpatient or residential SUD treatment in SSA, the settings in which the research was conducted, and the study countries. METHODS: A search of three databases, PubMED, Scopus, and African Index Medicus, was conducted for publications related to the treatment of SUD in inpatient or residential settings in SSA. Articles were screened at the title/abstract level and at full text by two reviewers. Articles eligible for inclusion were original research, conducted in SSA, published in English, included populations who received or were currently receiving treatment for SUD in inpatient or residential settings, or documented demand for SUD services. RESULTS: This scoping review included 82 studies originating from 6 countries in SSA. Three themes emerged within the literature: access and demand for inpatient and residential SUD treatment, quality and outcomes of SUD treatment, and descriptions of the services offered and staffing of these facilities. Barriers to access include financial barriers, limited availability of services, and geographic concentration in cities. Women were shown to access residential and inpatient SUD treatment at lower rates than men, and certain racial groups face unique language and financial barriers in accessing services. Studies indicate mixed success of inpatient and residential SUD treatment in sustained SUD remission for patients. CONCLUSION: There are significant gaps in the literature, driven by a lack of longitudinal studies focused on patient outcomes following treatment and the use of a narrow definition of treatment success. Both structural and non-structural barriers, such as stigma and discrimination, are barriers to access. Further research is needed to evaluate approaches to mitigate these barriers and expand access to residential and inpatient SUD treatment.

Prevalence of type 2 inflammatory signatures and efficacy of dupilumab in patients with chronic rhinosinusitis with nasal polyps from two phase 3 clinical trials: SINUS-24 and SINUS-52.

BACKGROUND: This post hoc analysis of the international SINUS-24/-52 trials (NCT02912468/NCT02898454) aimed to assess dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) according to different definitions of type 2 inflammatory signature. METHODS: Six definitions of type 2 inflammation were used: ≥150 eosinophils/µL or total immunoglobulin E (IgE) ≥100 IU/mL with a coexisting type 2 condition; ≥150 eosinophils/µL or total IgE ≥100 IU/mL; ≥150 eosinophils/µL; ≥250 eosinophils/µL or total IgE ≥100 IU/mL; coexisting asthma or ≥300 eosinophils/µL; presence of a coexisting type 2 condition. Odds ratios (ORs; dupilumab vs. placebo) for achieving clinically meaningful improvement (≥1 point) from baseline to week 24 (pooled SINUS-24/-52) and week 52 (SINUS-52) were calculated for nasal polyp score (NPS; range 0-8), nasal congestion/obstruction score (NC; 0-3), and loss of smell score (LoS; 0-3). RESULTS: At baseline (n = 724), most patients displayed a type 2 inflammatory signature across definitions (64.2%-95.3%). At week 24, ORs for clinically meaningful improvement ranged from 11.9 to 14.9 for NPS across type 2 definitions, 6.5-9.6 for NC, and 12.2-17.8 for LoS (all p < 0.0001). OR ranges were similar or greater at week 52: 19.0-36.6, 7.6-12.1, and 9.2-33.5, respectively (all p < 0.0001). CONCLUSION: Most patients with CRSwNP in the SINUS study had type 2 inflammation. Dupilumab demonstrated robust efficacy across definitions of type 2 inflammation, consistent with its profile as an inhibitor of Interleukin-4 and Interleukin-13 signaling, key and central drivers of type 2 inflammation in CRSwNP. KEY POINTS: This study assessed type 2 inflammation prevalence and dupilumab efficacy in chronic rhinosinusitis with nasal polyps according to algorithm-defined type 2 inflammation Dupilumab efficacy was similar across all type 2 definitions.

Local cytokine levels associate with SNOT-22 and UPSIT scores in chronic rhinosinusitis.

KEY POINTS: Elevated IL-5, IL-13, IL-33, and CCL2 correlate with lower UPSIT scores in CRS and AERD patients. Elevated IL-5, IL-13, TNF-α, CCL2, and CXCL-8 correlate with higher SNOT-22 scores in CRS and AERD patients.

Not just snot: Local inflammatory profiles in patients with aspirin-exacerbated respiratory disease differ from patients with aspirin-tolerant chronic rhinosinusitis.

KEY POINTS: IL-5, CCL2, and CXCL8 in sinus mucous are higher in patients with AERD relative to aspirin-tolerant patients with CRS These mediators are pleiotropic, leading to widescale inflammatory processes contributing to AERD AERD is not only a T2 disease but heterogeneous: this may explain the refractory nature of AERD.

Nasal polyp antibody-secreting cells display proliferation signature in aspirin-exacerbated respiratory disease.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) causes nasal obstruction and olfactory dysfunction. Aspirin-exacerbated respiratory disease (AERD) is the triad of CRSwNP, asthma, and respiratory reactions to COX-1 inhibitors. Patients with AERD have elevated nasal IL-5 levels and high numbers of antibody-secreting cells (ASCs), including plasma cells and plasmablasts, in their polyp tissue; in addition, their nasal polyp (NP) IgE levels are correlated with disease severity and recurrence of nasal polyposis. OBJECTIVE: We sought to explore differences in the transcriptomic profile, activation markers, and IL-5Rα expression and function of NP ASCs from patients with AERD and CRSwNP. METHODS: NP tissue was collected from patients with AERD and CRSwNP and digested into single-cell suspensions. NP cells were analyzed for protein expression by mass cytometry. For IL-5Rα functional studies, plasma cells were purified and cultured in vitro with or without IL-5 and analyzed by bulk RNA sequencing. RESULTS: Compared with polyp tissue from patients with CRSwNP, polyp tissue from patients with AERD contained significantly more ASCs and had increased ASC expression of IL-5Rα. ASCs from patients with AERD expressed higher protein levels of B-cell activation and regulatory markers (CD40, CD19, CD32, and CD38) and the proliferation marker Ki-67. ASCs from patients with AERD also expressed more IL5RA, IGHE, and cell cycle- and proliferation-related transcripts (CCND2, MKI67, CDC25A, and CDC25B) than did ASCs from patients with CRSwNP. Stimulation of plasma cells from patients with AERD with IL-5 induced key cell cycle genes (CCND2 and PTP4A3), whereas IL-5 stimulation of ASCs from patients with CRSwNP induced few transcriptomic changes. CONCLUSION: NP tissue ASCs from patients with AERD express higher levels of functional IL-5Rα and markers associated with cell cycling and proliferation than do ASCs from patients with aspirin-tolerant CRSwNP.