Diplopia is a common symptom of interdisciplinary significance that can lead to marked impairment of function. Its causes range from harmless to life-threatening conditions that must be precisely distinguished. For this CME review article, a PubMed search was conducted in an interdisciplinary collaboration of ophthalmologists and neurologists. Systematic history-taking and a structured clinical examination are the basis for topographic-anatomical diagnosis and the differentiation of peripheral and central causes. It is important to distinguish monocular from binocular diplopia. Monocular diplopia persists when one eye is covered and is not dangerous. Binocular diplopia may arise from disturbances at a variety of anatomical levels that can result from many different causes: disturbances of fusion in strabismus, diseases of the eye muscles such as thyroid eye disease or mitochondropathies, orbital trauma, impaired neuromuscular transmission in myasthenia gravis, fascicular or nuclear lesions of the three nerves that supply the extraocular muscles (oculomotor, trochlear, and abducens), supranuclear lesions "above" the cranial nerve nuclei, and cerebellar diseases. The most common causes, together accounting for ca. 70% of cases, are decompensated latent strabismus and cranial nerve palsies, followed by orbital, brainstem, and cerebellar diseases. Diplopia can be accurately diagnosed through a systematic approach that includes precise history-taking and clinical examination of eye position and eye movements. On this basis, there can be a targeted and specific search for the various underlying causes. When the patient's leading symptom is isolated diplopia, the ophthalmologist is generally the specialist to whom the primary care physician should turn next.

Gout and type 2 diabetes mellitus (T2DM) are prevalent metabolic disorders with a significant bidirectional association. The review article focuses on the interplay between serum uric acid and glucose/lipid metabolism, innate immunity, inflammation, and gut microbiota, proposing simultaneous treatment strategies. Gout, caused by monosodium urate crystal deposition due to hyperuricaemia, and T2DM, induced by high-fat, high-sugar diets disrupting metabolic balance, share common pathological mechanisms. Elevated uric acid levels contribute to lipid and glucose metabolic disorders, activate inflammatory pathways like the nucleotide-binding oligomerization domain-like receptor 3 inflammasome, and trigger innate immune responses. The gut microbiota also plays a significant role in both metabolic diseases, with dysbiosis affecting uric acid excretion and insulin resistance. This review article highlights promising therapeutic approaches, including the use of sodium-glucose cotransporter-2 inhibitors which reduce serum uric acid and lowers gout risk alongside glycaemic control. Additionally, targeting inflammatory pathways such as interleukin-1β offers potential benefits for both conditions. Combined pharmacological therapies, dietary adjustments, and gut microbiota interventions present new directions for simultaneous management. This review article provides a comprehensive analysis of the links between gout and T2DM, offering novel insights for clinical practice and future research.

Practical and translational therapeutic elements for GBM therapy.

Environmental pollutants and biomolecules detection using ZIF-67 and its composites as electrode modifier: A review.

Renal safety is an important consideration for treatment selection in chronic hepatitis B (CHB) because of the ageing population and increasing prevalence of medical comorbidities. However, the renal safety profiles of first-line nucleos(t)ide analogues (NUCs) for CHB-tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) have not been comprehensively reviewed. To evaluate the renal safety of ETV, TDF, and TAF in general and special populations with CHB. In this narrative review, relevant studies in PubMed were identified using a range of keywords, followed by manual screening of reference lists to capture additional sources. Based on current randomised and real-world evidence, TDF may cause more nephrotoxic effects than ETV in patients with pre-existing moderate-to-severe chronic kidney disease (CKD), but the two agents may have similar renal safety profiles among patients with no or mild baseline renal impairment. Randomised data showed that TAF is significantly less nephrotoxic than TDF in different clinical settings. Retrospective data from both treatment-naïve and -experienced patients, as well as special populations, including patients with renal impairment, kidney transplant, advanced age, and acute-on-chronic liver failure, indicated that TAF may be more likely to improve renal function compared to ETV. Current first-line NUCs show comparable renal safety profiles in CHB patients with no or mild kidney dysfunction, with growing evidence that favours TAF. Future prospective studies are needed to validate these findings, and more research should focus on CHB patients with diabetes mellitus who are at risk of CKD.

Steroidal alkaloids: Exploring new therapeutic frontiers in cardiovascular diseases.

Linking misophonia and tinnitus: Common and divergent neurobiological mechanisms.

Obsessive compulsive disorder (OCD) is a psychiatric disorder characterized by the persistence of obsessions and compulsions, which negatively impact functionality and may become chronic if left untreated. Although the efficacy of pharmacological treatment and Cognitive Behavioral Therapy (CBT) involving exposure and response prevention techniques has been proven in OCD, treatment discontinuation rates and residual symptoms following treatment have led researchers to explore different therapeutic approaches. One such approach gaining increasing interest is Acceptance and Commitment Therapy (ACT), a third-generation therapeutic model, which is proving to be an innovative and effective treatment for OCD. ACT primarily aims to guide individuals toward leading a life aligned with their chosen values, by accepting the pains that exist in the natural flow of life instead of avoiding them. In the treatment of OCD, with the ACT approach, interventions aimed at enhancing psychological flexibility have been shown to positively impact the prognosis of the disorder. In addition to engaging in compulsions to avoid the anxiety caused by obsessions, OCD patients may follow a wide variety of experiential avoidance strategies. With the ACT approach, these strategies can be reduced and the anxiety caused by obsessions and compulsions can be eliminated through the acceptance of negative internal experiences. This review article addresses experiential avoidance in OCD within the framework of ACT. Based on recent publications, the article discusses how ACT targets experiential avoidance in OCD treatment and the effects of interventions on the relationship between OCD symptom severity and psychological flexibility.

Psoriasis is an autoimmune and inflammatory conditions and characterized by red, inflammatory plaques and macules that develop due to poor differentiation and increased proliferation of keratin-produced by epidermal cells. Pathophysiology, including as immune cells, genetic predisposition, antimicrobial peptides, and non-coding RNAs. The traditional prescription drugs are not enough to control the condition because they have many drawbacks. They are link to large dosage of drugs and the potential for toxicity and the adverse effects, which can result in long- term poor patient compliance. Nanotechnology-based approaches aiming at a greater therapeutic effect in order to get beyond the aforementioned restrictions and allow tailored pharmaceuticals treatments for psoriasis and reduced toxicity in psoriasis topical treatment. This comprehensive review included the type, onset of disease and pathophysiology of psoriasis, conventional treatment, the need for nano based drug delivery systems for the treatment of psoriasis and also described the nanobased drug delivery approaches such as lipid based nanocarriers: - nanoemulsion, liposomes, ethosomes, transferosomes, cerosomes, NLC, SLN and polymer based nannocarriers such as: - hydrogels, nanosphere nanocapsules, dendrimers and also metallic nanocarriers: - gold and silver nanoparticles. The review was prepared through literature search using the databases ScienceDirect, PubMed, and Google Scholar. The review article offered information on the utilization of nano carriers while talking about the drawbacks of traditional psoriasis treatment. Throughout the skin's penetration and permeation process, the biodegradable nanoformulations usually result in targeted drug administrations. Additionally, it controls drug release, avoids toxicity, and protects labile compounds from degradation. Keywords: Psoriasis, Nanotechnology, Traditional medicines, Nanocarriers

Stereoisomers arising from the rotational restriction about a CN single bond, namely CN atropisomers, have recently attracted considerable attention in the field of synthetic organic chemistry. Diverse CN atropisomeric compounds have been prepared with high optical purity through catalytic enantioselective reactions, and they have been used in various asymmetric reactions as chiral building blocks and chiral ligands. CN atropisomers are attractive compounds from the viewpoint of not only synthetic organic chemistry but also medicinal chemistry. Recently, various CN atropisomeric bioactive compounds have been found, and their biological activity, the target selectivity, and the pharmacokinetics have been revealed to differ significantly between atropisomers. On the other hand, we feel that the chemistry community is still not fully aware of the fascinating biological properties of CN atropisomers. This review article comprehensively describes CN atropisomeric compounds exhibiting diverse biological activities as well as the synthesis or separation of atropisomers and their rotational stability.

Extracorporeal Shock Wave Therapy (ESWT) has emerged as a promising treatment modality in dentistry, offering non-invasive and effective solutions for various dental conditions. This review article aims to provide an overview of the current state of research on ESWT in dentistry, focusing on its applications, mechanisms of action and clinical outcomes. ESWT utilizes high-energy acoustic waves to stimulate biological tissues, promoting tissue regeneration, angiogenesis and pain relief. In dentistry, ESWT has been explored for the management of conditions such as periodontitis, peri-implantitis, Temporomandibular Joint Disorders (TMDs) and orofacial pain syndromes. Studies have demonstrated the efficacy of ESWT in reducing inflammation, promoting wound healing and improving clinical outcomes in these conditions. Furthermore, ESWT has shown promise in enhancing the outcomes of dental implant therapy by improving osseointegration and reducing implant failure rates. The non-invasive nature of ESWT, along with its minimal side effects and high patient acceptance, makes it a valuable adjunctive therapy in dental practice. ESWT thus represents a novel and effective approach in the management of various dental conditions. Further research is warranted to explore its full potential and establish standardized protocols for its use in dentistry.

Skin sebaceous glands (SGs) synthesize and secrete sebum, a mixture of lipids and cellular debris that defends the external body surface against physicochemical challenges. Recent data define the SG as a dynamic entity with potential functions beyond skin protection, including immunomodulatory actions and the regulation of energy metabolism. We postulate that the SG also has important, unrecognized roles in physiological and pathological processes in domestic animals. Conversely, data derived from domestic animals may have translational relevance for humans. This review article summarizes SG structural and functional features in the most widespread species domesticated for food (cattle, sheep, goats, and pigs), work (horses), and companionship (dogs and cats). Our survey reveals hitherto unrecognized roles of the SG in diverse pathophysiological processes. Among other fascinating facts, we learn that sebum has an exquisite and unique lipid composition in each of the considered species. Furthermore, sebum is essential for e.g., wool production but also a carrier for the most important cat protein causing allergic reactions in humans, and dogs and cats may develop a SG-related skin illness resembling acne that is potentially relevant as a model for the human disease. This critical review provides a foundation for future interdisciplinary studies in a largely neglected area with great potential for advancing animal welfare and human health.

Cell-autonomous and noncell-autonomous drivers of dopamine neuron vulnerability in Parkinson's disease.

This review article discusses the most common umbilical cord vessel anomalies and umbilical cord emergencies, as well as their implications on anesthetic management. Umbilical cord anomalies and emergencies pose significant risks to both the fetus and the mother. Fetal complications can include fetal heart tone issues, hypoxia, preterm delivery, unexpected neonatal ICU admissions, exsanguination, and fetal demise. Maternal complications can include emergency cesarean delivery and postpartum hemorrhage. Recognition of these anomalies and their potential complications is essential to the proper management of these patients. Anesthesia providers must be familiar with and available for patients with various umbilical cord pathologies to provide safe and effective care for the best maternal and neonatal outcomes if umbilical cord emergencies arise. Coordinated efforts should be in place for multidisciplinary emergency response systems.

A second language is referred to any language that learned and used by an individual besides their mother tongue. Teaching second is considered as a key challenge for the language teachers due to diverse learner needs, limited resources, and evolving pedagogical demands. This review article critically examines the major difficulties faced by teachers in second language classrooms, including linguistic diversity, varying levels of learner motivation and proficiency, inadequate teaching materials, and insufficient professional training. The study synthesizes findings from existing literature to identify common barriers that affect the effectiveness of second language teaching and learning. The review concludes that institutional support, improved teaching resources, and effective training programs are essential for helping language teachers overcome these challenges and enhance the quality of second language instruction.

Pharmaceuticals and personal care products (PPCPs) are emerging as the major contaminants of great concern in the world water matrices due to their high numbers, distribution, and bioaccumulation possibilities. The review has examined around 80+ peer-reviewed articles (2014-2026) in the Web of Science, Scopus, and Google Scholar databases, based on the AOP-NBS synergy to pharmaceutical remediation. Systematic searches were done by using cluster of keywords such as advanced oxidation, nature-based solutions, emerging contaminants, and mineralization efficiency as the performance and sustainability of current hybrid treatments. The present review article, the existing and possible remediation techniques of the pharmaceutical waste water have been discussed. The study concludes that the conventional wastewater treatment plants (WWTPs) are far from efficient in eliminating complex active pharmaceutical ingredients (APIs). Consequently, the integration of advanced oxidation process (AOPs) and nature-based solution is a most essential requirement to attain superior removal efficiencies. An example is hybrid treatment wetlands that used local zeolite that has shown almost 100 percent (93.6-99.9) removal of various antibiotics such as ciprofloxacin and ofloxacin. On the other hand, some of the non-biodegradable compounds such as carbamazepine and diclofenac are observed to be resistant to most treatment regimens with their presence in some systems only clearing 1.1%. The research emphasizes the importance of the hybrid technologies- the combination of biological technologies with AOPs to enhance the biodegradability and the nearly total mineralization. Moreover, the shift to a so-called circular economy based on recovery of resources (up to 80 percent regarding certain materials) and application of the principles of Industry is determined as the important direction of the future. This article offers a strategic guideline in selecting treatment units depending on the nature of wastewater with the aim to reduce the adverse impact of PPCPs on aquatic organisms and human health.

Patient-reported outcomes (PROs) for cemiplimab monotherapy versus chemotherapy from the EMPOWER-Lung 1 phase 3 clinical trial (ClinicalTrials.gov identifier NCT03088540) in patients who had advanced non-small cell lung cancer with programmed cell death-ligand 1 expression ≥50% were previously reported. This review article characterizes PRO findings for cemiplimab monotherapy versus chemotherapy overall and in prespecified subgroups of patients from the EMPOWER-Lung 1 clinical trial. Patients were randomly assigned 1:1 to receive either cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy, and multiple PROs, including the European Organization for Research and Treatment of Cancer Quality of Life-Core 30 questionnaire, were administered in the EMPOWER-Lung 1 trial. PRO analyses using mixed model for repeated measures analysis to estimate least-squares mean changes in PRO scores from baseline and Cox proportional hazards models for the time to deterioration using a 10-point threshold have been reported and are summarized herein. Generally, the mixed model for repeated measures analysis of global health status/quality of life (GHS/QoL) significantly favored cemiplimab versus chemotherapy in the overall study population and in prespecified subgroup populations. Statistically significant differences in the overall change from baseline in GHS/QoL favoring cemiplimab versus chemotherapy were observed overall and in multiple subgroups, including patients who had brain metastasis (p=.0110), an Eastern Cooperative Oncology Group performance status of 1 (p=.0017), squamous (p=.0247) and nonsquamous (p=.0073) histology, and patients aged 65 years and older (p=.0069). Statistically significant delays in the time to deterioration favoring cemiplimab were observed in GHS/QoL for the subgroup with programmed cell death-ligand 1 expression ≥90% (p=.0152) and the subgroup younger than 65 years (p=.0195). Collectively, the current data support the GHS/QoL benefit of first-line cemiplimab monotherapy versus chemotherapy overall and in multiple subpopulations of patients with programmed cell death-ligand 1 expression ≥50% advanced non-small cell lung cancer.

This contribution explores the possibility that cultural landscapes can move and what the consequences of this might be for (our thinking about) borders, in particular the borders between nation states. Mainstream landscape research assumes that each cultural landscape has a unique, exclusive and inalienable relationship with a specific area. However, since the 1980s, with the increasing influence of humanistic and new cultural geographies in landscape research, this assumption has been regularly questioned. If cultural landscapes are understood not only as physical manifestations of human ecosystems and cultures, but also as “ways of seeing” and “landscape ideas”, then people also carry landscapes with them in their minds and hearts and can physically realise them elsewhere. In the following review paper, both views are explored through a series of case studies. The relationships between (moving) cultural landscapes and borders receive special attention.

The current standard of maintenance care for patients with moderate-to-severe asthma is the use of inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) medications; some patients may also require additional therapies including long-acting muscarinic antagonists or biologics to establish disease control. Presently, there is a striking discrepancy between the positive outcomes reported in randomised clinical trials (RCTs) of these therapies and real-world outcomes that may be independent of treatment adherence. Patients with asthma included in RCTs are selected using stringent eligibility criteria, for example they have never been heavy smokers. Because current recommendations rely on results from such exclusive RCTs, this calls into question the extent to which these recommendations are applicable in daily practice. Therefore, generalising information from RCTs can be a difficult task for a number of reasons, including differences between ICS/LABAs, varied responses to medications among patients and the limited time busy general practitioners have to bridge the care gaps that exist. Factors in choosing a desirable ICS/LABA may include (a) considerations in clinical decision-making; (b) differences in pharmacokinetic and pharmacodynamic properties of ICS/LABA molecules, therapeutic index; (c) individual patient factors which may influence or facilitate successful adherence to treatment; (d) ease of inhaler use; (e) underlying inflammation; and (f) balancing efficacy and long-term safety, including adverse events and long-term exacerbation risk, based on data from both RCTs and real-world evidence. This review article discusses factors that healthcare professionals may utilise when selecting an ICS/LABA treatment for their patients, by considering data from RCTs and real-world evidence in addition to geographical/environmental, personal, and disease factors, which may also influence the decision process, such as availability and affordability.

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes severe acute and chronic infections, particularly in immunocompromised patients, those with cystic fibrosis, burn wounds, and structural lung disease. It has numerous virulence factors, including biofilm formation, quorum-sensing (QS) systems, exotoxins, and degradative enzymes, which make it pathogenic. All these factors combine to enhance tenaciousness, tissue destruction, and antimicrobial resistance. These virulence factors are being explored to inhibit multidrug-resistant microbes that are not susceptible to conventional antibiotics. Recent research has shown that synthetic molecules (such as enzyme antagonists, QS inhibitors, and novel chemical scaffolds), natural compounds (such as phytochemicals derived from plants, essential oils, and microbial metabolites), and synergistic combinations represent promising anti-virulence strategies. The use of nanomaterial-based synergistic delivery systems is vital for enhancing efficacy and targeted delivery. This review paper discusses the intriguing therapeutic properties of natural and synthetic agents, as well as their synergistic inhibitory effects, against various virulence factors that influence the strategies of multidrug-resistant bacteria, such as P. aeruginosa. Overall, these inhibitors enhance bactericidal activity by targeting multiple microbial pathways, with an emphasis on biofilm and QS systems, thereby addressing the problems of resilience and resistance development associated with conventional antibiotics. There are still issues with maximizing biocompatibility, pharmacokinetics, and clinical translation despite encouraging in vitro and preclinical results. This multifaceted strategy offers a lasting remedy for antibiotic-resistant P. aeruginosa infections, representing a paradigm shift from conventional bactericidal approaches to virulence attenuation. However, the possible adaptations of the pathogen and compensatory mutations to anti-virulence strategies need careful consideration.