The (re)emergence of aerosol delivery: Treatment of pulmonary diseases and its clinical challenges.

Aerosol delivery represents a rapid and non-invasive way to directly reach the lungs while escaping the hepatic first-pass effect. The development of pulmonary drugs for respiratory diseases such as cystic fibrosis, lung infections, pulmonary fibrosis or lung cancer requires an enhanced understanding of the relationships between the natural physiology of the respiratory system and the pathophysiology of these conditions. This knowledge is crucial to better predict and thereby control drug deposition.

The brain interactome of a permissive prion replication substrate.

Bank voles are susceptible to prion strains from many different species, yet the molecular mechanisms underlying the ability of bank vole prion protein (BVPrP) to function as a universal prion acceptor remain unclear. Potential differences in molecular environments and protein interaction networks on the cell surface of brain cells may contribute to BVPrP's unusual behavior. To test this hypothesis, we generated knock-in mice that express physiological levels of BVPrP (M109 isoform) and employed mass spectrometry to compare the interactomes of mouse (Mo) PrP and BVPrP following mild in vivo crosslinking of brain tissue.

Effects of periodontal disease on the proteomic profile of the periodontal ligament.

Periodontal disease affects over 1 billion people globally. This study investigated how periodontitis affects the protein profile of the periodontal ligament (PDL) in rats. Eight Holtzman rats were divided into the control and experimental periodontitis groups.

Hyperacute Effects of Mitral Transcatheter Edge-to-Edge Repair on Left Ventricular Volumes and Functions.

Transcatheter edge-to-edge repair (TEER) is an effective intervention for high-risk patients with severe symptomatic mitral regurgitation (MR), but its acute impact on left ventricular (LV) function has not been well studied using advanced echocardiographic techniques. This study investigated the immediate effects of TEER on LV volumes and functions, as well as their influence on mid-term outcomes, using high-resolution 3D transesophageal echocardiography. In 80 patients undergoing TEER for severe MR (mean age 79±8 years, 49% with primary MR), LV end-diastolic volume (LVEDV) and stroke volume significantly decreased (161±61 to 147±54 ml and 69±18 to 50±15 ml, respectively), while end-systolic volume increased (92±60 to 97±45 ml; p<0.

Balloon atrioseptostomy for transposition of the great arteries in Europe: characteristics and outcomes.

Introduction And Objectives: Balloon atrial septostomy (BAS) improves oxygenation in neonates with transposition of the great arteries (TGA) and restrictive foramen ovale. Currently, there is a global shortage of dedicated BAS catheters, while new unmarked catheters have recently become available at some European centers. This study aimed to characterize BAS outcomes using the currently available BAS catheters in Europe.

John the Baptist in Leonardo Da Vinci's Painting - What's in a Smile?

The smile is a complex human facial expression, most commonly associated with joy. We present a detailed view on Leonardo Da Vinci's painting of Saint John the Baptist, between 1516 to 1516, which illustrates a smiling saint, which has evoked multiple explanations and theories. Discussing Da Vinci's concept of painting as science media and the two merely contradictory painting techniques chiaroscuro and sfumato, we attempt to approach this picture.

Risk of colorectal cancer associated with frequency of colorectal polyp diagnosis in relatives.

Background & Aims: We aimed to evaluate the association of frequency of polyp diagnosis in relatives with the risk of overall and early-onset colorectal cancer (CRC).

Methods: We leveraged data from nationwide Swedish family cancer datasets (1964-2018) to calculate standardized incidence ratios (SIRs) for individuals with a family history of polyp by frequency of polyp diagnosis in family members.

Results: We followed up 11,676,043 individuals for up to 54 years.

Impact of smoking on biological treatment response in patients from the German Severe Asthma (GAN) Registry.

Background: Clinical studies of biologics in severe asthma exclude smokers or ex-smokers (ExS) with over 10 pack-years (py). Thus, the effectiveness of this therapy in ex-smokers with severe asthma is not well understood.

Objectives: To assess the impact of smoking on clinical efficiency of biologics in patients with severe asthma from the German Asthma Net (GAN), a comprehensive international registry.

Accounting for differential exclusions in the NordICC trial discloses stronger-than-reported effects of screening colonoscopy.

Objective: Recently, results on colorectal cancer (CRC) incidence and mortality reduction by the offer of screening colonoscopy were reported for the first time from a randomized controlled trial (RCT), the Nordic-European Initiative on Colorectal Cancer (NordICC) trial. Despite randomization, there was a substantially lower proportion of post-randomization exclusions of CRC cases due to cancer registry-recorded date of diagnosis before recruitment in the invited group than in the usual-care group. We aimed to evaluate the impact of such differential exclusions on the trial's effect estimates on CRC risk.

Compartment model of strategy-dependent time delays in replicator dynamics.

Real-world processes often exhibit temporal separation between actions and reactions - a characteristic frequently ignored in many modelling frameworks. Adding temporal aspects, like time delays, introduces a higher complexity of problems and leads to models that are challenging to analyse and computationally expensive to solve. In this work, we propose an intermediate solution to resolve the issue in the framework of evolutionary game theory.

The UBR domain of plant Ubr1 homolog PRT6 accommodates basic and hydrophobic amino termini for substrate recognition.

N-degrons are amino-terminal degradation signals. Non-acetylated first residues with bulky side chains were the first discovered N-degrons. In yeast, their ability to destabilize a protein depends on ubiquitin ligase Ubr1, which has a binding site for basic first residues, the UBR box, and one for hydrophobic first residues, the N domain.

Endometriosis and risk of depression among oral contraceptive users: a pooled analysis of cohort studies from 13 countries.

Study Question: Does endometriosis affect the mental health of women using oral contraceptives?

Summary Answer: Among oral contraceptive users, women with endometriosis have a higher risk of depression compared to those without endometriosis, although the absolute risk increase is small.

What Is Known Already: Previous studies have suggested a potential link between endometriosis and mental health issues, but the impact of endometriosis on depression among oral contraceptive users remains unclear.

Study Design, Size, Duration: A secondary pooled cohort study utilizing data from two longitudinal patient-centric studies (INAS-VIPOS and PRO-E2) was conducted across 11 European countries, Colombia and Australia.

Active Components in Internet-Based Cognitive-Behavioral Therapy for Social Anxiety Disorder: A Randomized Full Factorial Trial.

Introduction: Many studies have demonstrated that social anxiety disorder (SAD) can be effectively treated with psychotherapy, particularly cognitive-behavioral therapy (CBT), including internet-based CBT (ICBT). Despite evidence-based treatments, many individuals do not sufficiently benefit from them. Identifying the active components could help improve the effectiveness of SAD treatment.

Improving the bioactivity of cellulose acetate hemodialysis membranes through nanosilver modification.

The effectiveness and safety of hemodialysis can be hindered by protein accumulation, mechanical instability of membranes and bacterial infection during the dialytic therapy. Herein, we show that cellulose acetate membranes modified with the low-fouling polymers (namely polyvinylpyrrolidone and polyethylene glycol), followed by the in situ reduction of different densities of silver oxide(I) nanoparticles, can effectively address these limitations. These improvements comprise the enhanced resistance to the protein fouling, improved antimicrobial capabilities against S.

Molecular dynamics simulations to decipher the hotspots at the allosteric site of human 5-lipoxygenase.

Human 5-lipoxygenase (LOX) is a non-heme, Fe-containing LOX which catalyses the conversion of arachidonic acid (AA) to leukotriene A (LTA). LTA is subsequently converted to cysteinyl-LTs and LTB that cause bronchoconstriction and act as chemotactic and chemokinetic agent on human leukocytes, respectively. Leukotrienes play significant roles in inflammation in asthma, cardiovascular diseases, allergic rhinitis, atopic dermatitis, inflammatory bowel disease, rheumatoid arthritis, psoriasis and many more.

Low-grade infections in nonunion of the femur and tibia without clinical suspicion of infection - Incidence, microbiology, treatment, and outcome.

Treatment algorithms for fracture nonunion depend on the presence or absence of bacterial infection. However, it is often impossible to identify infection preoperatively. While some infections may present with clinical signs of infection, low-grade infections lack infection signs and have a clinical presentation similar to aseptic nonunion.

Perfusion-MRI for differentiating cerebral metastatic lesions and gliomas: An evidence-based review.

Background: Lesions affecting the brain are variable and have multiple pathologies. Brain metastasis is a common entity of lesions that can be misleading in diagnosis. Brain metastasis affects the patient's life and survival in about 40% of cases; all patients with metastatic brain lesions are indicated for surgery, so proper diagnosis is crucial for each patient.

Asian Thoracic Oncology Research Group expert consensus statement on the peri-operative management of non-small cell lung cancer.

The peri-operative management of non-small cell lung cancer (NSCLC) in earlier stage disease has seen significant advances in recent years with the incorporation of immune checkpoint inhibitors and targeted therapy. However, many unanswered questions and challenges remain, including the application of clinical trial data to routine clinical practice. Recognising the unique demographic profile of Asian patients with NSCLC and heterogeneous healthcare systems, the Asian Thoracic Oncology Research Group (ATORG) convened a consensus meeting in Singapore on 26 April 2024 to discuss relevant issues spanning diagnostic testing to post-neoadjuvant treatment considerations and future directions.

Land carbon sink function variation across bedrock types in Southwest China.

Terrestrial ecosystem carbon sinks are a natural deposit that absorbs carbon from the atmosphere. A stable land carbon sink facilitates more reliable predictions of carbon sequestration under changing climate conditions. In contrast, a highly variable land carbon sink will introduce significant uncertainty into model predictions.

Seasonal variation in myasthenia gravis incidence.

Introduction: Environmental factors may contribute to myasthenia gravis (MG) development, sometimes with seasonal patterns of exposure. However, whether seasonality has an impact on MG incidence remains unclear. We aimed to investigate the association between seasonality and MG onset.

The role of artificial intelligence in gynecologic and obstetric emergencies.

Objective: To investigate the potential of artificial intelligence (AI) in emergency medicine, focusing on its utility in triaging and managing acute gynecologic and obstetric emergencies.

Methods And Materials: This feasibility study assessed Chat-GPT's performance in triaging and recommending management interventions for gynecologic and obstetric emergencies, using ten fictive cases. Five common conditions were modeled for each specialty.

Are horned cows in loose housing more stressed than hornless cows? a cross-sectional study in organic dairy farms.

In commercial dairy farming, the majority of cows are dehorned or genetically hornless. It is argued that this reduces the risk of injurious and stressful social conflicts. On the other hand, in horned herds, management and housing may be better adapted to the cows, e.

Gender Gap? A Survey among Plastic Surgeons in Germany.

Introduction: There is an ongoing increase in the percentage of females in the field of Plastic Surgery in Germany. Currently, 29,1% of fellows and 46% of residents in Germany are female. Several studies have pointed out the various obstacles that female doctors, especially female plastic surgeons, are confronted with in their professional life.