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BackgroundIn Europe, the combination of cabotegravir (CAB) with rilpivirine (RPV) has been approved as a dual injection long-acting (LA) therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections in adults since December 2020. Studies have shown that between 36 and 61% of people living with HIV (PLWHIV) prefer LA therapy. However, there are no real-world data on the number of people receiving LA therapy, in Germany or internationally. The aim of this study was to assess the current situation and trends in usage of LA therapy for the treatment of HIV-1 in Germany.MethodsBased on pharmacy prescription data derived from Insight Health, the monthly number of prescriptions for oral CAB, CAB-LA, and RPV-LA over the entire period of availability in Germany was analyzed and evaluated (May 2021 to December 2023). The number of 1st and 2nd initiation injections and subsequent maintenance injections was calculated on the basis of the prescriptions for oral CAB initiation.ResultsThe bimonthly schedule resulted in two growing cohorts from September 2021 with an estimated 14,523 CAB-LA prescriptions over the entire period. Accordingly, in December 2023, there were approximately 1,364 PLWHIV receiving LA therapy, of whom 1,318 were receiving maintenance therapy. Only treatments with bimonthly regimens were carried out. Accounting for people not covered by statutory health insurance (~13%), a total of ~1,600 PLWHIV were receiving LA therapy in Germany in December 2023. The average rounded annual cost of therapy in 2023 was €11,940 (maintenance therapy with initiation) and €10,950 (maintenance therapy without initiation).ConclusionTo our knowledge, this is the first study of real-world use and number of people receiving LA therapy. A strength of our study is the nearly complete coverage of people with statutory health insurance in Germany. The predicted demand for LA therapy does not match the actual number of people receiving LA therapy. Although the number of PLWHIV receiving LA therapy increased steadily, they accounted for just under 2% of the estimated total number of people receiving HIV therapy in Germany in 2023, almost 2 years after the market launch. No significant increase in prescriptions is expected; on the contrary, the trend is leveling off and is unlikely to change drastically in the near future. Hence, the need for this mode of therapy in Germany appears to be limited. Follow-up studies at regular intervals on the further course would be useful and are recommended, as well as investigations into the possible reasons for the slow uptake to inform public health experts and possibly broaden treatment options.

El síndrome metabólico es un desorden complejo que emerge como un reto clínico. Fue introducido desde hace muchos años, primero por investigadores italianos, quienes describieron un conjunto de factores de riesgo cardiovasculares que incluían la diabetes mellitus, la hipertensión arterial, la dislipidemia y la obesidad.

En este número de Acta Médica iniciamos una sección en la que pretendemos proporcionarles a nuestros colegas información que sea relevante para su práctica médica, presentada en formal de Simposio, que incluya algunos artículos de revisión por profesionales destacados en una determinada área, que esperemos les ayuden a resolver problemas de manejo diario.

Tobacco-free nicotine pouches are new nicotine products for oral consumption. They can contain very high nicotine amounts that have not been addressed with clinical studies yet. Thus, nicotine delivery, effects on craving, and side effects were assessed using pouches with up to 30 mg nicotine. In this single-center, five-arm, crossover study, 15 regular cigarette smokers consumed tobacco-free nicotine pouches from different brands with 6, 20, and 30 mg for 20 min. Comparators were nicotine-free pouches and tobacco cigarettes. At baseline and predefined time points over a study period of 240 min, plasma nicotine concentrations, effects on cigarette craving, and side effects were assessed. Cardiovascular parameters including arterial stiffness were measured using a MobilOGraph. Consumption of 30 mg nicotine pouches has led to a higher nicotine uptake compared with the cigarette (Cmax: 29.4 vs 15.2 ng/mL; AUC: 45.7 vs 22.1 ng/mL × h). Nicotine uptake in the acute phase was rapid during use of the 30 mg pouch and cigarette. Extraction rate of nicotine differed between pouches. Use of all products has reduced acute cigarette craving, even the nicotine-free pouch. During consumption of the cigarette and the pouches with 20 and 30 mg, heart rate increased about 27, 12, and 25 bpm, respectively. Parameters for arterial stiffness were elevated and all pouches have induced mouth irritations. The pouches with 30 mg nicotine had overall the strongest side effects and may induce addiction. As craving was also reduced by products with less nicotine, it is questionable whether such high nicotine contents should be allowed on the market. A limit of nicotine content is warranted. The nicotine release rate varies across products and needs to be known to estimate the nicotine delivery.

Introduction/Objectives: Despite U.S. Preventive Services Task Force and American Cancer Society endorsement of primary HPV screening, limited published data shows low uptake. Primary Aim: Assess cervical cancer screening rates over time, particularly primary HPV test uptake, among patients in a midwestern practice. Secondary Aim: Evaluate associations between sociodemographics and screening adherence. Methods: Cross-sectional study. Qualifying subjects and type of screening test used were identified by applying ICD-9, ICD-10, lab test, and CPT codes to the Unified Data Platform. Sociodemographics were found through the electronic health record. Results: Primary HPV uptake represented

Background According to epidemiological studies, psychosocial factors are known to be associated with disease activity, physical activity, pain, functioning, treatment help-seeking, treatment waiting times and mortality in people with rheumatoid arthritis (RA). Limited qualitative inquiry into the psychosocial factors that add to RA disease burden and potential synergistic interactions with biological parameters makes it difficult to understand patients’ perspectives from the existing literature.Aim This study aimed to gather in-depth patient perspectives on psychosocial determinants that drive persistently active disease in RA, to help guide optimal patient care.Methods Patient research partners collaborated on the research design and materials. Semistructured interviews and focus groups were conducted online (in 2021) with patients purposively sampled from diverse ethnicities, primary languages, employment status and occupations. Data were analysed using inductive thematic analysis.Results 45 patients participated across 28 semistructured interviews and three focus groups. Six main themes on psychosocial determinants that may impact RA management were identified: (1) healthcare systems experiences, (2) patient education and health literacy, (3) employment and working conditions, (4) social and familial support, (5) socioeconomic (dis)advantages, and (6) life experiences and well-being practices.Conclusion This study emphasises the importance of clinicians working closely with patients and taking a holistic approach to care that incorporates psychosocial factors into assessments, treatment plans and resources. There is an unmet need to understand the relationships between interconnected biopsychosocial factors, and how these may impact on RA management.

Summary: Background: Matrix metalloproteinases (MMPs) are implied in blood–brain barrier degradation and haemorrhagic transformation following ischaemic stroke, but their local relevance in the hyperacute disease phase is unknown. We aimed to examine ultra-early MMP-9 and MMP-2 release into collateral blood vessels, and to assess its prognostic value before therapeutic recanalisation by endovascular thrombectomy (EVT). Methods: We report a cross-sectional proof-of-concept study including patients undergoing EVT for large-vessel ischaemic stroke at the University Hospital Würzburg, Germany. We obtained liquid biopsies from the collateral circulation before recanalisation, and systemic control samples. Laboratory workup included quantification of MMP-9 and MMP-2 plasma concentrations by cytometric bead array, immunohistochemical analyses of cellular MMP-9 and MMP-2 expression, and detection of proteolytic activity by gelatine zymography. The clinical impact of MMP concentrations was assessed by stratification according to intracranial haemorrhagic lesions on postinterventional computed tomography (Heidelberg Bleeding Classification, HBC) and early functional outcome (modified Rankin Scale, mRS). We used multivariable logistic regression, receiver-operating-characteristic (ROC) curves, and fixed-level estimates of test accuracy measures to study the prognostic value of MMP-9 concentrations. Findings: Between August 3, 2018, and September 16, 2021, 264 matched samples from 132 patients (86 [65.2%] women, 46 [34.8%] men, aged 40–94 years) were obtained. Median (interquartile range, IQR) MMP-9 (279.7 [IQR 126.4–569.6] vs 441 [IQR 223.4–731.5] ng/ml, p

While Canadian maternal mortality rates suggest widespread access to high-quality care, perinatal health care outcomes and care experiences among pregnant people in Canada vary widely, particularly among communities that have been historically oppressed, excluded, and marginalized. The lack of patient-oriented research and measurement in perinatal services led to the RESPCCT (Research Examining the Stories of Pregnancy and Childbirth in Canada Today) Study which used a community participatory action research (CPAR) approach to examine experiences of pregnancy and childbirth care. In this paper, we describe co-creation of a person-centered survey instrument that measures respect, disrespect and mistreatment during pregnancy-related care of individuals with diverse identities, backgrounds and circumstances. The study was co-led by a Community Steering Council alongside a multi-disciplinary group of researchers and clinicians, and pilot tested by service users from across Canada. The final survey instrument includes items that assess respectful care across 17 domains, including validated measures of autonomy, respect, mistreatment, trauma, and discrimination. It also captures information about respondents' identities, backgrounds, circumstances, access to care, provider type, and outcomes. A total of 6096 individuals participated in the survey. We describe how we implemented CPAR best practices, strengths, challenges, and lessons learned for instrument development in reproductive justice research.

Abstract Understanding the microscopic variability of impurities in glacier ice on a quantitative level has importance for assessing the preservation of paleoclimatic signals and enables the study of macroscopic deformational as well as dielectric ice properties. Two‐dimensional imaging via laser‐ablation‐inductively‐coupled‐plasma‐mass‐spectrometry (LA‐ICP‐MS) can provide key insight into the localization of impurities in the ice. So far, these findings are mostly qualitative and gaining quantitative insights remains challenging. Recent advances in LA‐ICP‐MS high‐resolution imaging now allow ice grains and grain boundaries to be resolved individually. These resolutions require new adequate quantification strategies and, consequently, accurate calibration with matrix‐matched standards. Here, we present three different quantification methods, which provide a high level of homogeneity at the scale of a few tens of microns and are dedicated to imaging applications of ice cores. One of the proposed methods has a second application, offering laboratory experiments to investigate the displacement of impurities by grain growth, with important future potential to study ice‐impurity interactions. Standards were analyzed to enable absolute quantification of impurities in selected ice core samples. Calibrated LA‐ICP‐MS maps indicate similar spatial distributions of impurities in all samples, while impurity levels vary distinctly: Higher concentrations were detected in glacial periods and Greenland, and lower levels in interglacial periods and samples from central Antarctica. These results are consistent with ranges from complementary meltwater analysis. Further comparison with cm‐scale melting techniques calls for a more sophisticated understanding of the ice chemistry across spatial scales, to which calibrated LA‐ICP‐MS maps now contribute quantitatively.

Este artigo avalia sob quais condições a performatividade linguística participa da inclusão da pessoa com deficiência. Realizado por meio de revisão bibliográfica, o estudo revela que as diferenças resultantes da produção de identidades e critérios produtivistas, quando levados a efeito com excessivo vigor, geram discriminação. Assim, mais do que fortalecer identidades culturais, é preciso compreender que a diversidade é componente estrutural de qualquer cultura, e que a universalidade da categoria “pessoa humana” representa o pressuposto fundamental à inclusão social, direito cuja concretização envolve transformações estruturais nos códigos que performam os processos comunicativos.

It is important to know the limitations of the supercritical water gasification (SCWG) in terms of behavior of different biomasses, especially when determining whether SCWG is a suitable conversion process for a certain biomass. Ten different biomasses (eight different plant species, of which two were grown in two different sites) were processed to evaluate this aspect. Moist and dry, woody and grassy biomasses were gasified in the same experimental setup under similar conditions. Only small differences could be seen in the gasification experiments. The carbon gasification efficiency was 60.3 ± 5.1 %, the gas compositions were very similar. Solid deposits formed in all experiments in the same temperature zone of the reactor containing coke, salt building elements and heavy metals, sometimes leading to plugging. Nevertheless, an experimental duration of 6 h could be achieved for the dry biomasses. The experiment with the moist biomass Reed Canary Grass was ended early due to plugging of the feed tubing which is due to the different size reduction procedure for moist biomasses resulting in bigger biomass particles. This emphasizes the importance of sufficient size reduction prior to the experiment. Potassium addition as a homogeneous catalyst, in form of potassium hydroxide, has proven to be beneficial regarding gasification efficiency, but poses a threat regarding plugging due to salt deposits in the system.

Introduction Rural patients face barriers to accessing surgical care and often need to travel long distance for pre- or post-surgical consultations. Although adaptation to the COVID-19 pandemic has demonstrated the efficacy of virtual care, there is minimal data available to evaluate patient satisfaction with this modality and consequent health service utilization if virtual services are not available. Methods An online survey was conducted with participants living in rural British Columbia, Canada who had undergone surgery within 12 months of data collection and had either virtual or face-to-face pre- or post-surgical consultations. It was supplemented by an in-person survey administered in two rural sites to all patients who had a virtual visit prior to undergoing procedural care. A ten-point scale was used to assess satisfaction. Quantitative and qualitative data were collected and analyzed. Results Findings from the province-wide survey (n = 163) revealed no significant differences in average satisfaction ratings between people with in-person and virtual surgical consultations (8.03 versus 8.38, p = 0.26). However, most participants indicated that virtual appointments saved them time traveling, energy, and money and made them less dependent on others, accruing significant social benefit. In the community-focused sample (n = 71), 38% said they would not have had the procedure without a virtual visit option and 21% said that they would have delayed the procedure. Virtual consultations saved patients an average of 9 h (range 1–90). Participants traveled an average of 427 kilometers round trip to have the procedures. Conclusion Findings reveal costs and time saved in accessing care due to the introduction of pre- and post-operative virtual care visits, and further investments in virtual care are warranted. This will contribute to promoting equitable access to healthcare for rural residents.

Abstract Background The lack of water is a major constraint for microbial life in hyperarid deserts. Consequently, the abundance and diversity of microorganisms in common habitats such as soil are strongly reduced, and colonization occurs primarily by specifically adapted microorganisms that thrive in particular refugia to escape the harsh conditions that prevail in these deserts. We suggest that plants provide another refugium for microbial life in hyperarid deserts. We studied the bacterial colonization of Tillandsia landbeckii (Bromeliaceae) plants, which occur in the hyperarid regions of the Atacama Desert in Chile, one of the driest and oldest deserts on Earth. Results We detected clear differences between the bacterial communities being plant associated to those of the bare soil surface (PERMANOVA, R 2 = 0.187, p = 0.001), indicating that Tillandsia plants host a specific bacterial community, not only dust-deposited cells. Moreover, the bacterial communities in the phyllosphere were distinct from those in the laimosphere, i.e., on buried shoots (R 2 = 0.108, p = 0.001), indicating further habitat differentiation within plant individuals. The bacterial taxa detected in the phyllosphere are partly well-known phyllosphere colonizers, but in addition, some rather unusual taxa (subgroup2 Acidobacteriae, Acidiphilum) and insect endosymbionts (Wolbachia, “Candidatus Uzinura”) were found. The laimosphere hosted phyllosphere-associated as well as soil-derived taxa. The phyllosphere bacterial communities showed biogeographic patterns across the desert (R 2 = 0.331, p = 0.001). These patterns were different and even more pronounced in the laimosphere (R 2 = 0.467, p = 0.001), indicating that different factors determine community assembly in the two plant compartments. Furthermore, the phyllosphere microbiota underwent temporal changes (R 2 = 0.064, p = 0.001). Conclusions Our data demonstrate that T. landbeckii plants host specific bacterial communities in the phyllosphere as well as in the laimosphere. Therewith, these plants provide compartment-specific refugia for microbial life in hyperarid desert environments. The bacterial communities show biogeographic patterns and temporal variation, as known from other plant microbiomes, demonstrating environmental responsiveness and suggesting that bacteria inhabit these plants as viable microorganisms. Video Abstract

Abstract We aimed to assess the prognostic value of serum β-synuclein (β-syn), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in patients with moderate-to-severe acute ischemic stroke. We measured β-syn, GFAP and NfL in serum samples collected one day after admission in 30 adult patients with moderate-to-severe ischemic stroke due to middle cerebral artery (MCA) occlusion. We tested the associations between biomarker levels and clinical and radiological scores (National Institute of Health Stroke Scale scores, NIHSS, and Alberta Stroke Program Early CT Score, ASPECTS), as well as measures of functional outcome (modified Rankin Scale, mRS). Serum biomarkers were significantly associated with ASPECTS values (β-syn p = 0.0011, GFAP p = 0.0002) but not with NIHSS scores at admission. Patients who received mechanical thrombectomy and intravenous thrombolysis showed lower β-syn (p = 0.029) und NfL concentrations (p = 0.0024) compared to patients who received only mechanical thrombectomy. According to median biomarker levels, patients with high β-syn, NfL or GFAP levels showed, after therapy, lower clinical improvement (i.e., lower 24-h NIHSS change), higher NIHSS scores during hospitalization and higher mRS scores at 3-month follow-up. Elevated serum concentrations of β-syn (p = 0.016), NfL (p = 0.020) or GFAP (p = 0.010) were significantly associated with 3-month mRS of 3–6 vs. 0–2 even after accounting for age, sex and renal function. In patients with moderate-to-severe acute ischemic stroke, serum β-syn, NfL and GFAP levels associated with clinical and radiological scores at different timepoints and were able to predict short- and middle-term clinical outcomes.

This paper aims to analyse the concept of indigenous peoples in Indonesia and examines whether the concept is appropriate with an international legal framework. Analysing the concept is essential to legitimising indigenous rights under the international law regime. The discourse on indigenous in Indonesia emerged after the government rejected an international treaty on indigenous rights and was reluctant to adopt the UNDRIP into their national law. The government opposes this by arguing that the concept of indigenous peoples under the international legal framework is inappropriate for the Indonesian context. Consequently, indigenous peoples in Indonesia do not benefit from international norms that have recognised and protected their rights globally. This paper found that the concept of indigenous peoples in Indonesia has similarities and is appropriate to the international instrument (ILO169 and UNDRIP). Thus, ratifying the ILO treaty or adopting the UNDRIP into national law will benefit the indigenous in protecting their fundamental rights, including their collective rights to traditional lands under international norms.

Abstract Background Aim of the study was to compare success rate and functional outcome following pars plana vitrectomy (PPV) with conventional internal limiting membrane (ILM) peeling versus ILM flap technique for full-thickness idiopathic macular holes (FTMH). Methods Retrospective analysis of consecutive eyes with FTMH having undergone vitrectomy with sulfur hexafluoride (SF6) endotamponade 25% at the University Medical Center Rostock, Germany (2009–2020). Eyes were divided according to applied surgical technique (ILM peeling [group P] versus ILM flap [group F]). Inclusion criteria were macular hole base diameters (MH-BD) ≥ 400 μm plus axial length ≤ 26.0 mm. Each group was divided into two subgroups based on macular hole minimum linear diameter (MH-MLD): ≤ 400 μm and > 400 μm. Exclusion criteria were FTMH with MH-BD 26.0 mm or macular schisis. Demographic, functional, and anatomical data were obtained pre- and postoperatively. Preoperative MH-BD and MH-MLD were measured using optical coherence tomography (OCT; Spectralis®, Heidelberg Engineering GmbH, Heidelberg, Germany). Main outcome parameter were: primary closure rate, best-corrected visual acuity (BCVA), and re-surgery rate. Results Overall 117 eyes of 117 patients with FTMH could be included, thereof 52 eyes underwent conventional ILM peeling (group P) and 65 additional ILM flap (group F) technique. Macular hole closure was achieved in 31 eyes (59.6%) in group P and in 59 eyes (90.8%) in group F (p 400 μm: p = 0.241). Conclusion Anatomical results and surgical closure rate following ILM flap technique seems to be superior to conventional ILM peeling for treatment of FTMH.

Abstract Background Inherited defects in the base-excision repair gene MBD4 predispose individuals to adenomatous polyposis and colorectal cancer, which is characterized by an accumulation of C > T transitions resulting from spontaneous deamination of 5’-methylcytosine. Methods Here, we have investigated the potential role of MBD4 in regulating DNA methylation levels using genome-wide transcriptome and methylome analyses. Additionally, we have elucidated its function through a series of in vitro experiments. Results Here we show that the protein MBD4 is required for DNA methylation maintenance and G/T mismatch repair. Transcriptome and methylome analyses reveal a genome-wide hypomethylation of promoters, gene bodies and repetitive elements in the absence of MBD4 in vivo. Methylation mark loss is accompanied by a broad transcriptional derepression phenotype affecting promoters and retroelements with low methylated CpG density. MBD4 in vivo forms a complex with the mismatch repair proteins (MMR), which exhibits high bi-functional glycosylase/AP-lyase endonuclease specific activity towards methylated DNA substrates containing a G/T mismatch. Experiments using recombinant proteins reveal that the association of MBD4 with the MMR protein MLH1 is required for this activity. Conclusions Our data identify MBD4 as an enzyme specifically designed to repair deaminated 5-methylcytosines and underscores its critical role in safeguarding against methylation damage. Furthermore, it illustrates how MBD4 functions in normal and pathological conditions.

Abstract Pregnancy-Associated Plasma Protein A isoforms, PAPP-A and PAPP-A2, are metalloproteases that cleave insulin-like growth factor binding proteins (IGFBPs) to modulate insulin-like growth factor signaling. The structures of homodimeric PAPP-A in complex with IGFBP5 anchor peptide, and inhibitor proteins STC2 and proMBP have been recently reported. Here, we present the single-particle cryo-EM structure of the monomeric, N-terminal LG, MP, and the M1 domains (with the exception of LNR1/2) of human PAPP-A2 to 3.13 Å resolution. Our structure together with functional studies provides insight into a previously reported patient mutation that inactivates PAPP-A2 in a distal region of the protein. Using a combinational approach, we suggest that PAPP-A2 recognizes IGFBP5 in a similar manner as PAPP-A and show that PAPP-A2 cleaves IGFBP5 less efficiently due to differences in the M2 domain. Overall, our studies characterize the cleavage mechanism of IGFBP5 by PAPP-A2 and shed light onto key differences with its paralog PAPP-A.

Low-cost simulations providing accurate predictions of transport of airborne material in urban areas, vegetative canopies, and complex terrain are demanding because of the small-scale heterogeneity of the features influencing the mean flow and turbulence fields. Common models used to predict turbulent transport of passive scalars are based on the Lagrangian stochastic dispersion model. The Quick Environmental Simulation (QES) tool is a low-computational-cost framework developed to provide high-resolution wind and concentration fields in a variety of complex atmospheric-boundary-layer environments. Part of the framework, QES-Plume, is a Lagrangian dispersion code that uses a time-implicit integration scheme to solve the generalized Langevin equations which require mean flow and turbulence fields. Here, QES-Plume is driven by QES-Winds, a 3D fast-response model that computes mass-consistent wind fields around buildings, vegetation, and hills using empirical parameterizations, and QES-Turb, a local-mixing-length turbulence model. In this paper, the particle dispersion model is presented and validated against analytical solutions to examine QES-Plume’s performance under idealized conditions. In particular, QES-Plume is evaluated against a classical Gaussian plume model for an elevated continuous point-source release in uniform flow, the Lagrangian scaling of dispersion in isotropic turbulence, and a non-Gaussian plume model for an elevated continuous point-source release in a power-law boundary-layer flow. In these cases, QES-Plume yields a maximum relative error below 6 % when compared with analytical solutions. In addition, the model is tested against wind-tunnel data for a uniform array of cubical buildings. QES-Plume exhibits good agreement with the experiment with 99 % of matched zeros and 59 % of the predicted concentrations falling within a factor of 2 of the experimental concentrations. Furthermore, results also emphasize the importance of using high-quality turbulence models for particle dispersion in complex environments. Finally, QES-Plume demonstrates excellent computational performance.

Abstract Objective Pediatric rheumatology faces a looming supply-demand crisis. While strategies have been proposed to address the supply shortfall, investigation into the increased demand for pediatric rheumatic care has been limited. Herein, we analyze new patient visits to a large tertiary care pediatric rheumatology center to identify emerging trends in referrals and areas for potential intervention to meet this increased demand. Methods All patients referred to and seen by the University of Alabama at Birmingham Pediatric Rheumatology Division between January 2019 and December 2021 for a new patient evaluation were identified. Patient data was retrospectively abstracted, de-identified, and analyzed to develop trends in referrals and frequency of rheumatic disease, non-rheumatic disease, and specific diagnoses. Results During the study period, 2638 patients were referred to and seen in by the pediatric rheumatology division. Six hundred and ten patients (23.1%) were diagnosed with rheumatic disease. The most common rheumatic disease was juvenile idiopathic arthritis (JIA) at 45.6%, followed by primary Raynaud phenomenon (7.4%), recurrent fever syndromes (6.9%), vasculitides (6.7%), and inflammatory eye disease (6.2%). Of the 2028 patients (76.9%) diagnosed with a non-rheumatic condition, benign musculoskeletal pain was the most common (61.8%), followed by a combination of somatic conditions (11.6%), and non-inflammatory rash (7.7%). Conclusion In this analysis of new patient referrals to a large pediatric rheumatology center, the majority of patients were diagnosed with a non-rheumatic condition. As a worsening supply-demand gap threatens the field of pediatric rheumatology, increased emphasis should be placed on reducing non-rheumatic disease referrals.

Abstract Aims Mild cognitive impairment and dementia are common and serious co‐morbidities in people with chronic heart failure (HF) as they increase hospitalization rates, mortality and health care costs. Upon other factors, dysregulated cerebral perfusion might contribute to brain pathology. We aimed to evaluate the association of non‐invasively measured blood flow (BF) and pulsatility index (PI) of the internal carotid artery (ICA) with (i) chronic HF parameters, (ii) brain morphologic measures and (iii) cognitive impairment. Methods and results This post‐hoc analysis of the observational, prospective Cognition.Matters‐HF study included 107 chronic HF patients without atrial fibrillation or carotid artery stenosis (aged 63 ± 10 years; 19% women). Using extracranial sonography, we measured ICA‐BF and ICA‐PI 1.5 cm distal of the carotid bifurcation. Brain magnetic resonance imaging was performed on a 3‐Tesla scanner to quantify cerebral atrophy, hippocampal atrophy and white matter hyperintensities. Extensive neuropsychological testing tested the cognitive domains intensity of attention, visual/verbal memory and executive function (including its subdomains selectivity of attention, visual/verbal fluency and working memory) using a comprehensive test battery. (i) Neither ICA‐BF (median 630 (quartiles 570, 700) mL/min) nor ICA‐PI (1.05 (0.96. 1.23)) related to left ventricular ejection fraction, left atrial volume index or NT‐proBNP. (ii) Higher ICA‐PI (r = 0.25; P = 0.011), but not ICA‐BF (r = 0.08; P = 0.409), associated with increased volume of white matter hyperintensities beyond ageing, while neither ICA‐PI nor ICA‐BF related to cerebral or hippocampal atrophy indices. (iii) ICA‐BF, but not ICA‐PI, positively correlated with age‐adjusted T‐scores of executive function (r = 0.38; P

Abstract Background Transition from hospital to home is a vulnerable period for patients with COPD exacerbations, with a high risk for readmission and mortality. Twenty percent of patients with an initial hospitalization for a COPD exacerbation are readmitted to a hospital within 30 days, costing the health care system over $15 billion annually. While nebulizer therapy directed at some high-risk COPD patients may improve the transition from hospital to home, patient and social factors are likely to contribute to difficulties with their use. Current literature describing the COPD patient’s experience with utilizing nebulizer therapy, particularly during care transitions, is limited. Therefore, the objective of this study was to explore underlying COPD patient and social factors contributing to practical difficulties with nebulizer use at the care transition from hospital to home. Methods This was a qualitative study conducted between September 2020 and June 2022. Patients were included if they were ≥ 40 years old, had a current diagnosis of COPD, had an inpatient admission at a hospital, and were discharged directly to home with nebulizer therapy. Semi-structured, one-on-one interviews with patients were conducted covering a broad range of patient and social factors and their relationships with nebulizer use and readmission. Interviews were recorded and transcribed verbatim. A thematic analysis was performed using a mixed inductive and deductive approach. Results Twenty-one interviews were conducted, and subjects had a mean age of 64 ± 8.4 years, 62% were female, and 76% were White. The predominant interview themes were health care system interactions and medication management. The interviews highlighted that discharge counseling methods and depth of counseling from hospitals were inconsistent and were not always patient-friendly. They also suggested that patients could appropriately identify, set up, and utilize their nebulizer treatment without difficulties, but additional patient education is required for nebulizer clean up and maintenance. Conclusions Our interviews suggest that there is room for improvement within the health care system for providing consistent, effective discharge counseling. Also, COPD patients discharged from a hospital on nebulizer therapy can access and understand their treatment but require additional education for nebulizer clean up and maintenance.

Abstract The high-resolution paleoclimate records on the Iberian Margin provide an excellent archive to study the mechanism of abrupt climate events. Previous studies on the Iberian Margin proposed that the surface cooling reconstructed by the alkenone-unsaturation index coincided with surface water freshening inferred from an elevated percentage of tetra-unsaturated alkenones, C37:4%. However, recent data indicate that marine alkenone producers, coccolithophores, do not produce more C37:4 in culture as salinity decreases. Hence, the causes for high C37:4 are still unclear. Here we provide detailed alkenone measurements to trace the producers of alkenones in combination with foraminiferal Mg/Ca and oxygen isotope ratios to trace salinity variations. The results indicate that all alkenones were produced by coccolithophores and the high C37:4% reflects decrease in SST instead of freshening. Furthermore, during the millennial climate changes, a surface freshening did not always trigger a cooling, but sometimes happened in the middle of multiple-stage cooling events and likely amplified the temperature decrease.