Signal detection of drugs associated with obstructive and central sleep apnoea.

We aim to discover new safety signals of drug-induced sleep apnoea (SA), a global health problem affecting approximately 1 billion people worldwide. We first conducted a series of sequence symmetry analyses (SSA) in a cohort composed from all patients who received a first SA diagnosis or treatment between 2006 and 2018 in the Echantillon Généraliste des Bénéficaires (EGB), a random sample of the French healthcare database. We used two primary outcomes to estimate the sequence ratio (SR) for all drug classes available in France: a sensitive one (diagnosis or treatment of SA) and a specific one (Positive Airway Pressure (PAP) therapy). We then performed disproportionality analyses using the "Bayesian neural network method" on all cases of sleep apnoea (MedDRA high level term) reported up to November 2023 in the World Health Organisation (WHO) pharmacovigilance database. Among the 728,167 individuals, 46,193 had an incident diagnosis or treatment for SA and 17,080 had started an incident treatment by PAP therapy. Fifty-eight drug classes had a significant SR, with 7 considered highly plausible: opium alkaloids and derivatives, benzodiazepine derivatives, other centrally acting agents, other anxiolytics, carbamic acid esters, quinine and derivatives and antivertigo preparations; with consistent signals found for the first 3 drug classes in the disproportionality analysis. In this signal detection study, we found that opioids, benzodiazepines (but not Z-drugs) and myorelaxing agents are associated with the onset or aggravation of SA. Moreover, a new safety signal for antivertigo preparations such as betahistine emerged and needs to be further explored.

Association of Glasgow Prognostic Score with frailty, mortality and adverse health outcomes in older patients with cancer: A prospective cohort study.

INTRODUCTION: To balance benefits and risks of cancer treatment in older patients, prognostic information is needed. The Glasgow Prognostic Score (GPS), composed of albumin and C-reactive protein (CRP), might provide such information. This study first aims to investigate the association between GPS and frailty, functional decline, and health-related quality of life (HRQoL) decline as indicators of health problems in older patients with cancer. The second aim is to study the predictive value of GPS for mortality, in addition to clinical predictors. MATERIALS AND METHODS: This prospective cohort study included patients aged ≥70 years with a solid malignant tumor who underwent a geriatric assessment and blood sampling before treatment initiation. GPS was calculated using serum albumin and CRP measured in batch, categorized into normal (0) and abnormal GPS (1-2). Outcomes were all-cause mortality and a composite outcome of decline in daily functioning and/or HRQoL, or mortality at one year follow-up. Daily functioning was assessed by Activities of Daily Living and Instrumental Activities of Daily Living questionnaires and HRQoL by the EQ-5D-3L and EQ-VAS questionnaires. RESULTS: In total, 192 patients with a median age of 77 years (interquartile range 72.3-81.0) were included. Patients with abnormal GPS were more often frail compared to those with normal GPS (79 % vs. 63 %, p = 0.03). Patients with abnormal GPS had higher mortality rates after one year compared to those with normal GPS (48 % vs. 23 %, p < 0.01) in unadjusted analysis. Abnormal GPS was associated with increased mortality risk (hazard ratio 2.8, 95 % CI 1.7-4.8). The area under the receiver operating characteristics curve of age, distant metastasis, tumor site, comorbidity, and malnutrition combined was 0.73 (0.68-0.83) for mortality prediction, and changed to 0.78 (0.73-0.86) with GPS (p = 0.10). The composite outcome occurred in 88 % of patients with abnormal GPS versus 83 % with normal GPS (p = 0.44). DISCUSSION: Abnormal GPS was associated with frailty and mortality. The addition of GPS to clinical predictors showed a numerically superior mortality prediction in this cohort of older patients with cancer, although not statistically significant. While GPS may improve the stratification of future older patients with cancer, larger studies including older patients with similar tumor types are necessary to evaluate its clinical usefulness. TRIAL REGISTRATION: The TENT study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107. Date of registration: 22-10-2019.

A corpus of GA4GH phenopackets: case-level phenotyping for genomic diagnostics and discovery.

The Global Alliance for Genomics and Health (GA4GH) Phenopacket Schema was released in 2022 and approved by ISO as a standard for sharing clinical and genomic information about an individual, including phenotypic descriptions, numerical measurements, genetic information, diagnoses, and treatments. A phenopacket can be used as an input file for software that supports phenotype-driven genomic diagnostics and for algorithms that facilitate patient classification and stratification for identifying new diseases and treatments. There has been a great need for a collection of phenopackets to test software pipelines and algorithms. Here, we present Phenopacket Store. Version 0.1.19 of Phenopacket Store includes 6668 phenopackets representing 475 Mendelian and chromosomal diseases associated with 423 genes and 3834 unique pathogenic alleles curated from 959 different publications. This represents the first large-scale collection of case-level, standardized phenotypic information derived from case reports in the literature with detailed descriptions of the clinical data and will be useful for many purposes, including the development and testing of software for prioritizing genes and diseases in diagnostic genomics, machine learning analysis of clinical phenotype data, patient stratification, and genotype-phenotype correlations. This corpus also provides best-practice examples for curating literature-derived data using the GA4GH Phenopacket Schema.

[Position paper of the Austrian Society for Rheumatology and the Austrian Society for Pneumology on the diagnosis and treatment of sarcoidosis 2024]. / Positionspapier der ÖGR und ÖGP zur Diagnose und Therapie der Sarkoidose 2024.

In many cases sarcoidosis is a multisystemic disease that requires interdisciplinary medical cooperation in the diagnostics, treatment and medical care during follow-up. Due to the often chronic course, it is of utmost importance to include patients with their priorities and wishes at an early stage and extensively in disease management and to establish a shared decision making whenever possible. In the process of writing this joint position paper, the expert group on interstitial and orphan lung diseases of the Austrian Society for Pulmonology and the working group on rheumatological lung disorders of the Austrian Society for Rheumatology and Rehabilitation sought to include patient advocacy groups as well as experts for rare organ manifestations of sarcoidosis. This position paper is not only meant to reflect current scientific and clinical standards but should also focus the national expertise and by networking and exchange to be a first step to strengthen cooperation between stakeholders to ultimately improve care for patients with sarcoidosis.

Patent Foramen Ovale and Oxygenation in Patients with Cystic Fibrosis.

INTRODUCTION: Patent foramen ovale (PFO) affects about 25% of the population. We studied outcomes in cystic fibrosis (CF). METHODS: We conducted a case-control study of patients with CF (PwCF) and age and sex-matched controls who underwent agitated saline contrast (bubble) echocardiography, 1998-2020. We assessed PFO impacts using linear, logistic, quasipoisson and proportional hazards models. RESULT: 59 of 64 PwCF and 88 of 93 controls underwent bubble studies to investigate unexplained hypoxemia or dyspnea. PwCF had higher mean pulmonary artery pressure (PAP, 6.9 mm Hg, 95% Confidence Interval [CI] = 2.35-11.4), reduced tricuspid annular plane systolic excursion (TAPSE, -3.78 mm, CI = -5.64 to -1.93) and similar right ventricular diastolic sizes. Absent hypoxemia, PFO incidence was similar between PwCF and controls; with hypoxemia, PFO was more common in CF (Odds Ratio [OR] = 5.00, CI = 1.32-19.0). In CF, oxygen supplementation occurred at a percent predicted forced expiratory volume in 1 s (FEV1%) 22.5 points higher with PFO. Adjusted for FEV1%, PFO was associated with 0.59 more prior year pulmonary exacerbations (CI = 0.20-0.98) and shorter time to next exacerbation (Hazard Ratio = 1.86, CI = 1.06-3.26). Associations between PFO and hypoxemia or exacerbations were insensitive to PAP, TAPSE and CF transmembrane regulator protein modulator treatments. PFO was not associated with CF time to death or lung transplantation (median 1.87 years) adjusted for age, sex, FEV1% and prior year exacerbation counts. CONCLUSION: PFO in CF is associated with hypoxemia at higher FEV1% and more pulmonary exacerbations but not survival.

Pasta Incorporating Olive Pomace: Impact on Nutritional Composition and Consumer Acceptance of a Prototype.

The food industry is encouraged to develop new sustainable foodstuffs, and agri-food by-products can serve as valuable ingredients in these formulations. In this work, olive pomace (OP), a by-product of olive oil production, was incorporated as an ingredient in pasta. The changes in the nutritional composition and consumer acceptance were assessed, aiming to scale up the production. OP contains dietary fibre (55%), fat (9%), α-tocopherol (43 mg/kg), and oleic acid (76%) after moisture elimination. For that, the following two drying procedures were tested: 40 °C for 48 h (OP40) and 70 °C for 24 h (OP70). Both samples were sieved to remove the stone pieces. Drying at 70 °C (OP70) was the fastest method, revealed a better nutritional profile than OP40, and was the product selected for the incorporation into the pasta. The enriched pasta, containing 7.5% of OP70, was compared to a control. It showed an improved nutritional value with higher contents of fat, ash, fibre, vitamin E, oleic acid, phenolics, and flavonoids, a composition related to potential health benefits. Consumers appreciated the appearance, colour, shine, and aroma of the obtained pasta, making it a prototype with commercial viability. However, several improvements need to be implemented, namely, at the textural levels. Corrective actions, such as the optimisation of the amount of incorporated OP, the use of other ingredients for flavour masking, and textural adjustments, are advisable, thereby making this product more appealing and accepted by a larger number of consumers. This prototype can be a good approach for the circular economy, environmental sustainability, and food security.

[Limited cognitive assessment in primary care: are GP referrals to the memory clinic always appropriate?] / Weinig cognitieve diagnostiek in de eerste lijn.

OBJECTIVE: To investigate whether referrals of general practitioners (GPs) to the memory clinic align with the regional and national dementia guidelines. DESIGN: For this single center retrospective study, data was collected from electronic patient files. METHOD: GP referrals to the memory clinic over a 1-year period were categorized and evaluated according to the regional and national guidelines. RESULTS: 310 GP referrals were included with the most common referral motivations: "Additional somatic or psychiatric factors" (77; 24,8%) and "Straightforward dementia diagnosis" (70; 22,6%). A total of 51,0% of referrals were not in line with regional guidelines: either because of non-compliant referral reasons; or limited cognitive assessment without clinical findings and/or cognitive testing. CONCLUSION: Half of GP referrals to the memory clinic were not in line with the national and regional guidelines. Referrals were often not preceded by clinical findings and/or cognitive testing. Aiming for effective care, cognitive assessments in primary care should be encouraged and with appropriate assistance.

Robots are both anthropomorphized and dehumanized when harmed intentionally.

The harm-made mind phenomenon implies that witnessing intentional harm towards agents with ambiguous minds, such as robots, leads to augmented mind perception in these agents. We conducted two replications of previous work on this effect and extended it by testing if robots that detect and simulate emotions elicit a stronger harm-made mind effect than robots that do not. Additionally, we explored if someone is perceived as less prosocial when harming a robot compared to treating it kindly. The harm made mind-effect was replicated: participants attributed a higher capacity to experience pain to the robot when it was harmed, compared to when it was not harmed. We did not find evidence that this effect was influenced by the robot's ability to detect and simulate emotions. There were significant but conflicting direct and indirect effects of harm on the perception of mind in the robot: while harm had a positive indirect effect on mind perception in the robot through the perceived capacity for pain, the direct effect of harm on mind perception was negative. This suggests that robots are both anthropomorphized and dehumanized when harmed intentionally. Additionally, the results showed that someone is perceived as less prosocial when harming a robot compared to treating it kindly.

Screen Use at Bedtime and Sleep Duration and Quality Among Youths.

Importance: Although questionnaire-based cross-sectional research suggests that screen time before bed correlates with poor sleep, self-reported data seem unlikely to capture the complexity of modern screen use, requiring objective night-by-night measures to advance this field. Objective: To examine whether evening screen time is associated with sleep duration and quality that night in youths. Design, Setting, and Participants: This repeated-measures cohort study was performed from March to December 2021 in participant homes in Dunedin, New Zealand. Participants included healthy youths aged 11 to 14.9 years. Data were analyzed from October to November 2023. Exposure: Objectively measured screen time, captured using wearable or stationary video cameras from 2 hours before bedtime until the first time the youth attempted sleep (shut-eye time) over 4 nonconsecutive nights. Video data were coded using a reliable protocol (κ = 0.92) to quantify device (8 options [eg, smartphone]) and activity (10 options [eg, social media]) type. Main Outcomes and Measures: Sleep duration and quality were measured objectively via wrist-worn accelerometers. The association of screen use with sleep measures was analyzed on a night-by-night basis using mixed-effects regression models including participant as a random effect and adjusted for weekends. Results: Of the 79 participants (47 [59.5%] male; mean [SD] age, 12.9 [1.1] years), all but 1 had screen time before bed. Screen use in the 2 hours before bed had no association with most measures of sleep health that night (eg, mean difference in total sleep time, 0 minutes [95% CI, -3 to 20 minutes] for every 10 minutes more total screen time). All types of screen time were associated with delayed sleep onset but particularly interactive screen use (mean difference, 10 minutes; 95% CI, 4 to 16 minutes for every additional 10 minutes of interactive screen time). Every 10 minutes of additional screen time in bed was associated with shorter total sleep time (mean difference, -3 minutes; 95% CI, -6 to -1 minute). The mean difference in total sleep time was -9 minutes (95% CI, -16 to -2 minutes) for every 10 minutes of interactive screen use and -4 minutes (95% CI, -7 to 0 minutes) for passive screen use. In particular, gaming (mean difference, -17 minutes; 95% CI, -28 to -7 minutes for every 10 minutes of gaming) and multitasking (mean difference, -35 minutes; 95% CI, -67 to -4 minutes on nights with vs without multitasking) were associated with less total sleep time. Conclusions and Relevance: In this repeated-measures cohort study, use of an objective method showed that screen time once in bed was associated with impairment of sleep, especially when screen time was interactive or involved multitasking. These findings suggest that current sleep hygiene recommendations to restrict all screen time before bed seem neither achievable nor appropriate.

Doing the Right Thing? General Practitioners' Considerations in Achieving a Timely Dementia Diagnosis.

OBJECTIVES: Timely detection and diagnosis of dementia are beneficial for providing appropriate, anticipatory care and preventing acute situations. However, initiating diagnostic testing is a complex and dynamic process that requires general practitioners (GPs) to balance competing priorities. Previously identified barriers, such as a lack of time, knowledge, and resources, may not fully represent the challenges involved in this process. Therefore, this study aimed to examine GPs' more implicit considerations on starting the diagnostic trajectory for dementia. METHODS: A qualitative study was conducted using semi-structured interviews with 14 Dutch GPs who were purposively selected through maximum variation sampling. The interview transcripts were inductively analyzed in multiple rounds by a multidisciplinary research team using thematic analysis. RESULTS: GPs' considerations on starting the diagnostic trajectory for dementia can be summarized in three main themes that are interconnected: (1) 'the presumed patient's willingness', that is, facing a dilemma of wanting to respect patient autonomy in cases of denial or an absence of a diagnostic request, while at the same time identifying a problem and feeling the urgency to act; (2) 'the GP's attempt not to harm', that is, balancing between not wanting to harm the patient and/or relatives with the burdensome label of dementia and with the possible negative consequences of a late diagnosis; and (3) 'time, trust, and interprofessional collaboration influence timeliness of diagnostic work-up', that is, time available for consultations, time as a diagnostic factor, GP's diagnostic confidence, and trustful physician-patient relationship. CONCLUSIONS: This study revealed that important ethical dilemmas regarding patient autonomy and the principle of doing no harm lie behind practical GP barriers to initiating diagnostic testing for dementia. Time, trust, and interprofessional collaboration were found to facilitate GPs in determining the right decision and timing with each individual patient and their relatives. Future research could explore the value of diagnostic decision aids that explicitly involve patients and their relatives in this balancing act.

Nourishing the Infant Gut Microbiome to Support Immune Health: Protocol of SUN (Seeding Through Feeding) Randomized Controlled Trial.

BACKGROUND: The introduction of complementary foods during the first year of life influences the diversity of the gut microbiome. How this diversity affects immune development and health is unclear. OBJECTIVE: This study evaluates the effect of consuming kumara or kumara with added banana powder (resistant starch) compared to a reference control at 4 months post randomization on the prevalence of respiratory tract infections and the development of the gut microbiome. METHODS: This study is a double-blind, randomized controlled trial of mothers and their 6-month-old infants (up to n=300) who have not yet started solids. Infants are randomized into one of 3 groups: control arm (C), standard kumara intervention (K), and a kumara intervention with added banana powder product (K+) to be consumed daily for 4 months until the infant is approximately 10 months old. Infants are matched for sex using stratified randomization. Data are collected at baseline (prior to commencing solid food) and at 2 and 4 months after commencing solid food (at around 8 and 10 months of age). Data and samples collected at each timepoint include weight and length, intervention adherence (months 2 and 4), illness and medication history, dietary intake (months 2 and 4), sleep (diary and actigraphy), maternal dietary intake, breast milk, feces (baseline and 4 months), and blood samples (baseline and 4 months). RESULTS: The trial was approved by the Health and Disability Ethics Committee of the Ministry of Health, New Zealand (reference 20/NTA/9). Recruitment and data collection did not commence until January 2022 due to the COVID-19 pandemic. Data collection and analyses are expected to conclude in January 2024 and early 2025, respectively. Results are to be published in 2024 and 2025. CONCLUSIONS: The results of this study will help us understand how the introduction of a specific prebiotic complementary food affects the microbiota and relative abundances of the microbial species, the modulation of immune development, and infant health. It will contribute to the expanding body of research that aims to deepen our understanding of the connections between nutrition, gut microbiota, and early-life postnatal health. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620000026921; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378654. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56772.

Feline eosinophilic sclerosing fibroplasia associated with T-/natural killer-cell lymphoma.

Feline eosinophilic sclerosing fibroplasia (FESF) is a proliferative, inflammatory disease of the gastrointestinal tract and other sites, uncommonly diagnosed in the cat. This entity of uncertain etiology typically presents as a progressive mass lesion, mimicking a neoplastic process. In this case series, we present 17 cases of FESF associated with intralesional lymphoma. Histologic and immunohistochemical characterization of this unique lymphoma revealed that the neoplastic lymphocytes were immunopositive for CD56 and/ or CD3, suggesting a natural killer cell, natural killer T-cell, or T-cell origin. This case series represents the first description of this lymphoma subtype, for which the term eosinophilic sclerosing lymphoma is proposed.

A Holistic Approach to Producing Anti-Vibrio Metabolites by an Endosymbiotic Dinoflagellate Using Wastewater from Shrimp Rearing.

The aquaculture industry requires green solutions to solve several environmental challenges, including adequate wastewater remediation and natural drug applications to treat bacteria- and virus-related diseases. This study investigated the feasibility of cultivating the dinoflagellate Durusdinium glynnii in aquaculture wastewater from shrimp rearing in a synbiotic system (AWW-SS), with different dilutions of f/2 medium (FM). Interestingly, D. glynnii demonstrated enhanced growth in all AWW-SS treatments compared to the control (FM). The highest growth rates were achieved at AWW-SS:FM dilutions of 75:25 and 50:50. The removal of total nitrogen and total phosphorus reached 50.1 and 71.7%, respectively, of the crude AWW-SS. Biomass extracts of D. glynnii grown with AWW-SS were able to inhibit the growth of the bacteria Vibrio parahaemolyticus (inhibition zone of 10.0 ± 1.7 mm) and V. vulnificus (inhibition zone of 11.7 ± 1.5 mm). The presented results demonstrate that the dinoflagellate D. glynnii is a potential candidate for the development of circularity for sustainable aquaculture production, particularly by producing anti-Vibrio compounds at a near-zero cost.

The measurement of young children's nocturnal sleep health and the development of the Perception of Infant and Toddler Sleep Scale (PoITSS) in Aotearoa New Zealand whanau (families).

OBJECTIVES: To modify an existing questionnaire Brief Infant Sleep Questionnaire - Revised (BISQ-R) to ensure that it is suitable to measure nocturnal sleep health in a diverse sample of young children from Aotearoa New Zealand whanau (families), and to develop a "Perception of Infant and Toddler Sleep Scale" (PoITSS) to use as a primary outcome measurement in an upcoming trial. METHODS: Items from the BISQ-R were adapted for use among ethnically diverse whanau, and tested online with caregivers of 0-2 year old children. A PoITSS score was generated by scaling the responses from three of the questionnaire items to create a value between 0 (very poor) and 10 (very good). Caregivers provided qualitative feedback about the ease of interpreting and answering questionnaire items. RESULTS: Caregivers of 957 children (35% Maori, 12% Pacific) completed the questionnaire. Few differences in children's nocturnal sleep were observed by demographic characteristics. The mean PoITSS score was 6.9 (SD 2.3) and was slightly higher among Maori children (mean difference 0.4, 95% CI 0.1, 0.7). Test-retest indicated good reliability (ICC=0.81). While the majority (86%) of caregivers did not find it difficult to answer any of the items which formed the PoITSS, qualitative feedback indicated that simple modifications to some items would help ensure that they would be well understood by most caregivers. CONCLUSIONS: Items from the BISQ-R were successfully adapted, and the PoITSS scale was shown to be appropriate, for use in ethnically diverse Aotearoa New Zealand whanau with young children.

Nicorandil antiallodynic activity in a model of neuropathic pain is associated with the activation of ATP-dependent potassium channels and opioidergic pathways, and reduced production of cytokines and neutrophils recruitment in paw, sciatic nerve, and dorsal root ganglia.

BACKGROUND: Recently, we demonstrated that nicorandil inhibits mechanical allodynia induced by paclitaxel. In the present study, we evaluated the effect induced by nicorandil in a model of neuropathic pain induced by chronic constriction injury (CCI) in mice. We also investigated putative mechanisms underlying such an effect. METHODS: CCI was induced by three ligatures of the left sciatic nerve. Mechanical allodynia was evaluated by measuring the paw withdrawal threshold with an electronic von Frey apparatus. Concentrations of cytokines and myeloperoxidase activity were determined in the paw tissue, sciatic nerve, and dorsal root ganglia (DRG). RESULTS: Oral administration of two doses of nicorandil (150 mg/kg po), but not equimolar doses of nicotinamide or nicotinic acid, attenuated mechanical allodynia induced by CCI. Nicorandil activity was reduced by previous administration of glibenclamide (40 mg/kg) or naltrexone (5 mg/kg or 10 mg/kg). Two doses of nicorandil (150 mg/kg, po) reduced tumor necrosis factor-α, interleukin-1ß and interleukin-6, but not CXCL-1, concentrations in the paw tissue of CCI mice. Two doses of nicorandil (150 mg/kg, po) reduced concentrations of all these mediators in the sciatic nerve and DRG. Two doses of nicorandil (150 mg/kg, po) also reduced the myeloperoxidase activity in the paw tissue, sciatic nerve, and DRG. CONCLUSIONS: Nicorandil exhibits antiallodynic activity in a model of neuropathic pain induced by CCI. Inhibition of cytokines production and reduction of neutrophils recruitment in paw tissue, sciatic nerve, and DRG as well as activation of ATP-dependent potassium channels and opioidergic pathways, underlie nicorandil antiallodynic activity.

Uncovering communication strategies used in language-discordant consultations with people who are migrants: Qualitative interviews with healthcare providers.

BACKGROUND: Global migration has led to a sharp increase in the number of language-discordant consultations (LDCs) in healthcare. Evidence on how healthcare providers (HCPs) meet migrant patients' needs while mitigating language barriers is lacking. DESIGN: Using purposive and snowball sampling, we recruited twenty-seven Dutch HCPs (Mage = 45.07, SD = 11.46) and conducted semi-structured interviews to collect qualitative, open-ended data for identifying the communication strategies used with migrant patients in LDCs. We analysed the transcripts using deductive and inductive approaches (e.g., constant comparative method from Grounded Theory). Final pattern codes (i.e., key themes) were discussed among the research team until mutual agreement had been achieved. RESULTS: Five key themes emerged from the analyses: HCPs often 'got-by' with (1) instrumental and (2) affective communication strategies used in language-concordant consultations to start medical consultations. When some instrumental communication strategies were deemed ineffective (e.g., lingua franca, gesturing, etc.) to bridge language barriers, HCPs turned to (3) incorporating digital tools (e.g., Google Translate). When HCPs were unable to communicate with migrant patients at all, (4) informal, ad-hoc and professional interpreters were involved. Finally, HCPs often (5) involved additional support to engage migrant patients to engage in treatment-related behaviours. DISCUSSION AND CONCLUSIONS: Our results highlight the importance of raising awareness among HCPs about using various combinations of different strategies. The development of a guideline indicating the optimal combination of communication strategies for different medical consultation goals may be useful in reshaping the current communication behaviour of HCPs in LDCs. PATIENT OR PUBLIC CONTRIBUTION: HCPs were the study population involved in this qualitative study. Refugee health advisors, general practitioners and linguistic specialists (i.e., members of the Right2Health consortium) with experience with the Dutch healthcare system were involved throughout the development of this research. This includes a review of the research question, participant information sheet and interview topic guide as well as providing interpretations of the data and feedback to this manuscript.

Recommendations for the implementation of a national lung cancer screening program in Portugal-A consensus statement.

Lung cancer (LC) is a leading cause of cancer-related mortality worldwide. Lung Cancer Screening (LCS) programs that use low-dose computed tomography (LDCT) have been shown to reduce LC mortality by up to 25 % and are considered cost-effective. The European Health Union has encouraged its Member States to explore the feasibility of LCS implementation in their respective countries. The task force conducted a comprehensive literature review and engaged in extensive discussions to provide recommendations. These recommendations encompass the essential components required to initiate pilot LCS programs following the guidelines established by the World Health Organization. They were tailored to align with the specific context of the Portuguese healthcare system. The document addresses critical aspects, including the eligible population, methods for issuing invitations, radiological prerequisites, procedures for reporting results, referral processes, diagnostic strategies, program implementation, and ongoing monitoring. Furthermore, the task force emphasized that pairing LCS with evidence-based smoking cessation should be the standard of care for a high-quality screening program. This document also identifies areas for further research. These recommendations aim to guarantee that the implementation of a Portuguese LCS program ensures high-quality standards, consistency, and uniformity across centres.

PTEN loss shapes macrophage dynamics in high grade serous ovarian carcinoma.

High-grade serous ovarian carcinoma (HGSC) remains a disease of poor prognosis that is unresponsive to current immune checkpoint inhibitors. Although PI3K pathway alterations, such as PTEN loss, are common in HGSC, attempts to target this pathway have been unsuccessful. We hypothesized that aberrant PI3K pathway activation may alter the HGSC immune microenvironment and present a targeting opportunity. Single-cell RNA sequencing identified populations of resident macrophages specific to Pten-null omental tumors in murine models, which were confirmed by flow cytometry. These macrophages derived from peritoneal fluid macrophages and had a unique gene expression program, marked by high expression of the enzyme heme oxygenase-1 (HMOX1). Targeting resident peritoneal macrophages prevented the appearance of HMOX1hi macrophages and reduced tumor growth. Furthermore, direct inhibition of HMOX1 extended survival in vivo. RNA sequencing identified IL33 in Pten-null tumor cells as a likely candidate driver leading to the appearance of HMOX1hi macrophages. Human HGSC tumors also contained HMOX1hi macrophages with a corresponding gene expression program. Moreover, the presence of these macrophages correlated with activated tumoral PI3K/mTOR signaling and poor overall survival in HGSC patients. In contrast, tumors with low numbers of HMOX1hi macrophages were marked by increased adaptive immune response gene expression. These data suggest targeting HMOX1hi macrophages as a potential therapeutic strategy for treating poor prognosis HGSC.

Multicenter study of the performance of NTM Elite agar for the detection of nontuberculous mycobacteria from patients with cystic fibrosis.

The performance of a novel selective agar was evaluated against the performance of conventional mycobacterial cultures, i.e., a combination of the mycobacterial growth indicator tube (MGIT) with Löwenstein-Jensen (LJ), for the detection of nontuberculous mycobacteria (NTM) in sputum samples from people with cystic fibrosis (pwCF). Two hundred eighty-three sputum samples (231 fresh sputum and 52 spiked sputum) from 143 pwCF were collected. They were inoculated without prior decontamination on NTM Elite agar (30°C ± 2°C for 28 days) and inoculated on both MGIT and LJ (35°C-37°C for 6-8 weeks) after N-acetyl-L-cysteine-2% sodium hydroxide decontamination. NTM were identified by Matrix-Assisted Laser Desorption Ionization/Time of Flight Mass Spectrometry and/or PCR, and whole-genome sequencing. A total of 67 NTM were recovered overall by the combination of all culture media. NTM Elite agar allowed the recovery of 65 NTM (97%), compared to 22 for the conventional MGIT and LJ media combination (32.8%), including 22 NTM for MGIT (32.8%) and 3 NTM with the LJ medium (4.5%). For Mycobacterium abscessus complex, the sensitivity of NTM Elite agar was 95% compared with a sensitivity of 30% for the conventional MGIT and LJ media combination. Overall, 17.3% of cultures on NTM Elite agar were contaminated with other micro-organisms vs 46.3% on MGIT and 77% on LJ. This study shows that the novel selective agar (NTM Elite agar) significantly outperforms the conventional MGIT and LJ media combination in terms of sensitivity, selectivity, and ease of culture, without the requirement of an L3 laboratory.IMPORTANCENontuberculous mycobacteria (NTM) are significant pulmonary pathogens in patients with pre-existing structural lung conditions such as cystic fibrosis, bronchiectasis, or chronic obstructive pulmonary disease. Mycobacterium avium complex and Mycobacterium abscessus complex (MABSC) are the most frequently isolated organisms. Compared to the recommended culture method for NTM, which combines solid and liquid culture media, NTM Elite agar enables a faster/easier diagnosis and speeds up identification and susceptibility testing as the final reading is at 28 days instead of 6-8 weeks for the conventional mycobacterial cultures. In addition, for the NTM Elite agar, no decontamination stage before inoculation is necessary, unlike the conventional mycobacterial cultures. NTM Elite agar is derived from a formulation of medium adapted to rapidly growing mycobacteria (RGM). The medium enables the growth of RGM while suppressing other flora. It is supported with published clinical data showing the benefits of this medium.

Transcriptional regulation of the postnatal cardiac conduction system heterogeneity.

The cardiac conduction system (CCS) is a network of specialized cardiomyocytes that coordinates electrical impulse generation and propagation for synchronized heart contractions. Although the components of the CCS, including the sinoatrial node, atrioventricular node, His bundle, bundle branches, and Purkinje fibers, were anatomically discovered more than 100 years ago, their molecular constituents and regulatory mechanisms remain incompletely understood. Here, we demonstrate the transcriptomic landscape of the postnatal mouse CCS at a single-cell resolution with spatial information. Integration of single-cell and spatial transcriptomics uncover region-specific markers and zonation patterns of expression. Network inference shows heterogeneous gene regulatory networks across the CCS. Notably, region-specific gene regulation is recapitulated in vitro using neonatal mouse atrial and ventricular myocytes overexpressing CCS-specific transcription factors, Tbx3 and/or Irx3. This finding is supported by ATAC-seq of different CCS regions, Tbx3 ChIP-seq, and Irx motifs. Overall, this study provides comprehensive molecular profiles of the postnatal CCS and elucidates gene regulatory mechanisms contributing to its heterogeneity.