Alzheimer's disease (AD) is a serious medical challenge, representing an incurable and insidious disease. Current treatments can slow AD progression but cannot cure it. Promising new methods for AD therapy are essential for addressing the growing number of people with dementia, especially after the COVID-19 pandemic. The review highlights pioneering approaches to AD treatment based on innovative methods for the stimulation of brain drainage and clearance, in which the meningeal lymphatic vessels (MLVs) play a key role. Clinically promising noninvasive technologies using photobiomodulation for the effective clearance of metabolites, including amyloid beta (Aβ), and for the improvement of cognitive impairment during AD progression are discussed. An interesting part of the review is its analysis of innovative methods of improving the efficacy of anti-Aβ immunotherapy by stimulating MLV growth. The review is also focused on lifestyle, including sleep and physical exercises, discussing their support for the efficient lymphatic removal of waste products from the brain. Overall, the review provides an important, informative platform to excite the interest of a wide range of readers in the development of promising and clinically significant strategies for the treatment of AD, based on new strategies for the stimulation of brain drainage and clearance.

Autoimmune thyroiditis (AIT) is characterized by dysregulated endocrine-immune interactions, and vitamin D has been proposed as a potential immunomodulatory factor influencing vaccine-induced immune responses. This study investigated the association between serum vitamin D status and humoral responses to SARS-CoV-2 vaccination in patients with AIT, while exploring potential molecular mechanisms using network pharmacology, molecular docking and Molecular Dynamics (MD) simulations. Patients were stratified according to serum 25-hydroxyvitamin D levels as deficient, insufficient, or sufficient. Anti-spike receptor-binding domain (RBD) IgG titers, thyroid autoantibodies, and thyroid-stimulating hormone levels were measured. In parallel, vitamin D₃ related molecular targets were integrated with AIT-associated genes, followed by protein-protein interaction analysis, molecular docking and MD simulations were performed to assess the interactions between vitamin D₃ (cholecalciferol) and selected key proteins. An inverse correlation was observed between serum vitamin D levels and anti-RBD IgG titers (p = 0.0013), with higher antibody responses detected in vitamin D-deficient patients. Network pharmacology analysis highlighted CYP19A1, CYP17A1, and ESR1 as prioritized targets associated with steroid hormone biosynthesis and endocrine signaling pathways. Molecular docking showed compatible binding of vitamin D₃ to these proteins, while MD simulations supported the structural stability of the complexes over time. Collectively, these findings suggest that vitamin D status may influence post-vaccination humoral immune responses in AIT, potentially through modulation of endocrine-immune crosstalk. Further longitudinal and mechanistic studies are required to clarify causality and clinical relevance.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by endothelial dysfunction, vascular remodeling, and a sustained increase in pulmonary vascular resistance, causing cardiopulmonary damage. The apelin receptor (APJ), a member of the G protein-coupled receptor family, has emerged as an essential modulator of vascular homeostasis. Clinical and preclinical studies have demonstrated that its activation exerts beneficial effects on the progression of PAH. Its main actions include the restoration of endothelial function, reactivation of the BMPR2/SMAD axis, induction of nitric oxide-mediated vasodilation, inhibition of autophagy and the migration of the pulmonary artery smooth muscle cells (PASMCs). Furthermore, its expression and functionality are modulated by epitranscriptomic mechanisms, particularly by microRNAs involved in the post-transcriptional regulation of key genes for vascular homeostasis. These findings position the APJ as a relevant therapeutic target in PAH. However, the clinical application of its agonists still faces pharmacokinetic limitations that restrict their therapeutic use. Therefore, the aim of this review is to gather current information on APJ in the pathophysiology of PAH and focus attention on its potential as a therapeutic target.

Obstructive sleep apnoea (OSA) is a common medical condition with significant morbidity and mortality, but frequently undiagnosed. Clinical signs and symptoms may be identified by general dental practitioners during routine dental examinations and patient history taking. This article explores the clinical characteristics, aetiology, and prevalence of OSA, and outlines when a referral should be considered, including the essential details to include in the referral. Additionally, it examines the current clinical pathway following referral, detailing the assessment and planning process for maxillomandibular advancement surgery (MMA). The discussion outlines the indications, benefits, and risks of MMA and compares it with alternative treatment options. The goal of this paper is to equip general dental practitioners with the knowledge and confidence to make informed referrals, assist in communicating both conservative and potential surgical treatment options to their patients, and provide a clear outline of what to expect following a referral for OSA in the UK.

Fibrosis appears to be an out-of-control wound-healing response that drives a progressive formation of scar tissue in an organ. A key profibrotic cytokine, transforming growth factor beta-1 (TGF-β1), upregulates levels of the extracellular sialidase neuraminidase 3 (NEU3), and NEU3 in turn can activate latent TGF-β1 to release active TGF-β1 from the sequestering latency-associated peptide (LAP). In the mouse bleomycin model of pulmonary fibrosis, NEU3 is both necessary and sufficient for pulmonary fibrosis. In this report, we find that NEU3 protein levels increase both intracellularly and extracellularly in cultures of human lung fibroblasts within 5 min of TGF-β1 exposure. This effect is driven by an increase in translation and is independent of new transcription, supporting a model where TGF-β1 causes a pool of weakly translated NEU3 mRNA to increase translation. By participating in the feedback loop, latent TGF-β1 makes cells more sensitive to TGF-β1. LAP also stimulates NEU3 expression and acts synergistically with TGF-β1 to upregulate NEU3. The positive feedback loop is blocked by NEU3 inhibitors. The RNA helicase DEAD-box helicase 3 (DDX3) mediates NEU3 translation, and the DDX3 inhibitor RK-33 blocks the rapid upregulation of NEU3 by TGF-β1 and LAP. Exposure of cells to TGF-β1 but not LAP induces dephosphorylation of DDX3 within two minutes, suggesting that the mechanisms used by TGF-β1 and LAP to activate DDX3 to increase NEU3 levels may differ. Together, these results suggest that a rapid positive feedback loop involving TGF-β1, LAP, and NEU3 helps drive fibrosis.

Pulmonary hypertension (PH) is recognized for being a severe, chronic phenomenon that necessitates a careful multidisciplinary approach. Its frequent coexistence with multiple comorbidities highlights the need for tailored decision-making concerning treatment towards not only certain PH subtypes but also towards each individual patient as well. Pulmonary arterial hypertension (PAH) management has undergone extensive development, which enabled patients' life expectancy to be prolonged. The targeted treatment made a significant contribution to the improvement of the patients' quality of life, thereby reducing the illness burden. However, apart from the administration of drugs in the course of PAH, there is also the field for determining and addressing modifiable factors, which may influence everyday life and the final outcome of these individuals. Taking into consideration the fact that iron deficiency (ID) is the most prevalent nutritional deficit worldwide and that there exists a well-established, scientifically supported correlation between ID and the outcome and prognosis of left heart failure patients, multiple studies were conducted in order to verify a possible connection between ID and right heart failure as well. Indeed, the crossroads of iron and PAH, PH related to hypoxia, and pathophysiological mechanisms linking pulmonary vasculature and ID have been eagerly investigated over recent years. Therefore, research provided a considerable amount of data in this area, emphasizing the potential usefulness of iron homeostasis to serve as a prognostic factor. Nevertheless, due to extensive exploration of this matter, several issues have arisen that demand further study and clarification, with the use of a proper ID definition being one of the most crucial. Herein, we present a concise review of the most up-to-date literature regarding iron's homeostasis and pulmonary vascular bed through the prism of PAH and PH related to hypoxia.

To investigate the association between air pollution and the incidence of ischaemic and haemorrhagic strokes.

The bidirectional cohort study was conducted at the Neurology Department of Liaquat National Hospital, Karachi, from August 10, 2022, to February 5, 2024, and comprised newly hospitalised patients who experienced an acute onset of stroke, including both ischaemic and haemorrhagic types. Precise documentation of stroke onset dates and times was done. Air pollutant data, specifically the Air Quality Index and particulate matter 2.5 concentrations, was sourced from the relevant Swiss website, which provides extensive real-time and historical air quality measurements. For each patient, air quality data was collected for the three days preceding the stroke onset. The association between stroke type and exposure variables was explored, and the odds of stroke occurrence in relation to particulate matter 2.5 exposure were worked out. Data was analysed using SPSS version 27.

Of the 228 patients,149(65.4%) were males and 79(34.6%) were females. The overall mean age was 62.15±14.20 years. Stroke subtype and onset time had no significant association with air quality index readings or or with particulate matter 2.5 at days 1, 2 and 3 (p>0.05). Males exhibited a heightened propensity for experiencing ischaemic strokes compared to females (odds ratio: 1.179, p=0.606). Moreover, individuals afflicted with ischaemic heart disease demonstrated an elevated risk of suffering ischaemic strokes compared to those without the comorbidity (odds ratio: 2.986, p=0.051).

Short-term rise in air quality index readings and particulate matter 2.5 concentrations were found to have no association with the incidence of ischaemic and haemorrhagic strokes.

To analyse the birth characteristics and maternal risk factors associated with preterm infants.

The retrospective study was conducted at the Jinshan Branch of Shanghai Sixth People's Hospital, China, and comprised data related to mothers and their preterm infants delivered between January 1, 2011, and December 31, 2020. Information on maternal age, pregnancy complications, number of births, gestational age at delivery and neonatal outcomes was collected from hospital records to assess risk factors for preterm birth. Data was analysed using SPSS 25.

Among 9,953 total births, 454 (4.56%) were preterm. Of these, 57 (12.56%) were early preterm and 397 (87.44%) were late preterm. The mean gestational age was 34.97±1.60 weeks and the average birth weight was 2,596.87 ± 502.28 g. Independent risk factors included gestational hypertension 56 (12.30%), cholestasis 17 (3.74%), premature rupture of membranes (PROM) 134 (29.52%), hormone use during pregnancy 105 (23.13%), and twin pregnancies 80 (17.62%) (p<0.01).

Key maternal risk factors included gestational hypertension, intrahepatic cholestasis of pregnancy, premature rupture of membranes, and multiple gestations.

Vasculitic neuropathy (VN) is a disease in which vessel inflammation happens and injures peripheral nerves. Despite increasing awareness, features of VN in mainland China are still understudied.

To characterize the clinical, pathological features and outcomes of VN in mainland China, and evaluate clinicopathological correlations: METHODS: We retrospectively reviewed records of VN patients diagnosed pathologically between June 1999 and December 2024, including demographic data, clinical manifestations, biopsy features, and outcomes.

112 patients were totally included. All presented with axonal sensorimotor neuropathy, most commonly involving the tibial (90.63%) and peroneal (87.50%) nerves. Systemic VN (SVN) showed more frequent transmural inflammatory cell infiltration (ICI) than non-systemic VN (NSVN) (p = 0.046). Eosinophilic granulomatosis with polyangiitis (EGPA) was more common in VN without ICI than VN with ICI (p = 0.008). In SVN, the ICI-positive exhibited more severe distal upper limb weakness (p = 0.042) and higher thrombosis rates (p = 0.001) than ICI-negative. Of the 63 patients followed, 62 received glucocorticoids with or without immunosuppressants. Thirteen died from multi-organ complications (12 SVN and 1 NSVN), while others achieved remission. The 5-year all-survival rate was 80.23% (95% CI 66.83%- 88.66%).

This first large cohort of VN in mainland China delineates its clinical-pathological features. EGPA showed a lower diagnostic yield on biopsy, suggesting diverse mechanisms of vascular injury. Nerve biopsy remains the diagnostic gold standard. The overall prognosis of VN is relatively favorable, emphasizing the need for early recognition and treatment.

Recent studies have identified the HbA1c-to-hemoglobin ratio (HHR) as a potential indicator for increased mortality from all causes and cardiovascular diseases. This investigation sought to determine whether HHR could serve as a prognostic marker for neurological function at 90 days in patients undergoing endovascular thrombectomy procedures.

This study performed a retrospective evaluation of patients undergoing endovascular treatment (EVT) at Nanjing First Hospital from April 2022 to June 2024. The HHR was determined by dividing HbA1c levels by hemoglobin values. Poor clinical outcomes were characterized by modified Rankin Scale scores ranging from 3 to 6 at the 90-day follow-up. Multivariate logistic regression analysis was employed to examine the association between HHR values and posttreatment functional outcomes.

The study enrolled 353 participants (average age of 70.5 years with a standard deviation of 12.2 years; 218 were male), of whom 181 (51.3%) showed adverse clinical results after 90 days. Multivariate regression analysis revealed that higher HHR levels upon hospital admission independently predicted worse functional recovery (adjusted OR: 10.484; 95% confidence interval: 4.581-23.990; p = 0.001). Additional investigation using restricted cubic spline methodology confirmed a nonlinear, dose-dependent relationship between HHR values and negative prognosis likelihood (nonlinearity p value = 0.001). When implemented in a predictive framework, continuous HHR measurements exhibited a strong discriminatory capability, achieving a receiver operating characteristic curve value of 0.760 (95% CI: 0.710-0.810).

Increased HHR levels demonstrate an independent correlation with poorer 90-day recovery rates among ischemic stroke patients undergoing endovascular thrombectomy. This evidence positions HHR as a potentially valuable indicator for clinical prognosis assessment in such cases.