Cholinesterase Inhibitory Activity, GC-MS Profiling and In Silico Studies on the Selected Artemisia Essential Oils

In this study, the essential oils (EOs) from&nbsp;Artemisia campestris,&nbsp;A. herba-alba, and&nbsp;A. judaica, obtained by hydrodistillation and characterized by gas chromatography-mass spectrometry, were investigated for their inhibitory potential against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using a microtiter-based assay, molecular docking, molecular dynamics (MD) simulations, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling analysis.Major monoterpenes were docked into the active sites of AChE and BChE, and key complexes were subjected to 100&nbsp;ns MD simulations and molecular mechanics generalized born surface area binding free energy calculations. In silico ADMET analysis was further performed to assess pharmacokinetic properties and drug-likeness of the most active compounds.The EOs exhibited a concentration-dependent cholinesterase inhibition.&nbsp;A. judaica&nbsp;showed the strongest AChE inhibition (half-maximal inhibitory concentration [IC50] = 17.84&nbsp;µg/mL), while&nbsp;A. campestris&nbsp;was the most effective against BChE (IC50&nbsp;= 9.82&nbsp;µg/mL). Docking results revealed favorable interactions between key constituents, such as camphor and piperitone, and critical active site residues of the enzymes. MD simulations confirmed the structural stability and favorable binding of these ligands, as evidenced by low root mean square deviation fluctuations and consistent hydrogen bonding. ADMET predictions supported their oral bioavailability and low toxicity potential.These results highlight the cholinesterase inhibitory potential of three&nbsp;Artemisia-derived EOs and may provide an initial molecular basis for Alzheimer's disease management.</p

From Primary Amenorrhea to the Desert Hedgehog Gene: Novel Homozygous Variant in 46,XY Gonadal Dysgenesis

AbstractIntroduction46,XY gonadal dysgenesis is a rare difference of sex development in which individuals have female external genitalia despite a 46,XY karyotype. Pathogenic variants in genes involved in testis determination and differentiation may underlie the condition and should be considered in the evaluation of primary amenorrhea.CaseA 14-year-old girl presented with primary amenorrhea. Hormonal evaluation revealed hypergonadotropic hypogonadism, and imaging demonstrated absence of the uterus and ovaries. Gonadectomy specimens demonstrated testicular tissue. Genetic analysis identified a novel homozygous missense likely pathogenic variant in the Desert Hedgehog (DHH) gene (NM_021044.4:c.983T>C; p.Leu328Pro).ConclusionThe DHH gene plays a critical role in testis differentiation, and pathogenic variants may result in 46,XY gonadal dysgenesis. Hormone replacement therapy and long-term multidisciplinary follow-up are essential components of management

Surface properties of additively manufactured biobased dental cast resins cleaned with nonhazardous postprocessing solutions

Statement of problem: Biobased dental cast resins and nonhazardous postprocessing cleaning solutions have been introduced in efforts to improve the sustainability of additive manufacturing. However, the combined effects of these components on the surface roughness (Ra) and microhardness of additively manufactured dental casts have not been investigated. Purpose: The purpose of this in vitro study was to evaluate the Ra and microhardness of biobased dental cast resins cleaned with different postprocessing cleaning solutions and to compare them with those of a conventional dental cast resin cleaned with isopropyl alcohol (IPA). Material and methods: Disk-shaped specimens (Ø10×2 mm) were fabricated from 3 biobased dental cast resins, plant-based resin gray (AC), soy-based resin (EX), and FotoDent biobased model resin (FD), and cleaned using methyl ether solvent (MES), IPA, or a water-based cleaning solution (n=12). Additional 12 specimens were fabricated from a conventional dental cast resin (KeyModel Ultra Ivory [KM]) and cleaned with IPA to serve as the control group. After fabrication, the Ra and Vickers microhardness values of all specimens were measured, and representative laser microscope images were made. Test groups were compared with generalized linear model and Bonferroni-corrected post hoc tests, whereas comparisons with the control group were made with 1-way analysis of variance and post hoc Dunnett tests (α=.05). Results: For both outcomes, a statistically significant interaction was observed between biobased cast resin and cleaning solution, and significant differences were found between the test and control groups (P≤.009). The water-based solution led to the highest Ra for AC (P≤.001). When MES and IPA were used, FD had the highest Ra (P≤.001). FD also had higher Ra than EX when the water-based solution was used (P=.031). Except for FD and AC cleaned with the water-based solution (P≥.086), all test groups had lower Ra than the control group (P≤.003). MES cleaning led to the highest hardness for EX and FD (P<.001), whereas IPA cleaning led to the highest hardness for AC (P≤.042). EX resin had the highest hardness, regardless of the cleaning solution (P<.001). KM had lower hardness than all test groups (P<.001). AC showed pronounced irregularities with MES and water-based solutions, EX appeared similar across solutions, FD had heterogeneous debris after IPA cleaning, and KM exhibited superficial scratches. Conclusions: FD resin generally exhibited higher roughness, while the water-based solution increased AC resin’s roughness. EX resin showed the highest microhardness across all cleaning solutions. Microhardness was the highest after IPA cleaning for AC and after MES cleaning for the other biobased resins. Most test groups had lower roughness than the control, while all showed higher microhardness

Şarj Edilebilir İşitme Cihazlarının Tercih Edilme Nedenlerinin Değerlendirilmesi

ŞarjEdilebilir İşitme Cihazlarının Tercih Edilme Nedenlerinin DeğerlendirilmesiDr. Öğr. Üyesi Tuğçe Gül Çağlar1, Dr. Öğr.Üyesi Leyla Türe 21.&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Lokman Hekim Üniversitesi,Sağlık Bilimleri Fakültesi, Odyoloji Bölümü, Ankara/ Türkiye [email protected] Orcid : 0000-0001-6599-09202.&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;İstanbul Kent Üniversitesi,Sağlık Bilimleri Fakültesi, DKT Bölümü, İstanbul/ Tü[email protected] Orcid: 0000-0003-1506-0754Özet:Giriş: Şarj edilebilir işitmecihazları, geleneksel pilli modellere kıyasla kullanım kolaylığı ve çevreselsürdürülebilirlik açısından önemli avantajlar sunan çağdaş işitme teknolojileriarasında yer almaktadır. Bu cihazlar çoğunlukla lityum-iyon batarya ileçalışmakta olup, sık pil değişimi gerektirmeden gece boyunca şarj edilerek günboyu kesintisiz kullanım imkânı sağlamaktadır. Özellikle işitme kaybı bulunanbireyler için geliştirilen bu sistemler, dijital sinyal işleme teknolojileriaracılığıyla çevresel sesleri analiz ederek konuşma anlaşılırlığını artırmaktave arka plan gürültüsünü azaltmaktadır. Bunun yanı sıra Bluetooth bağlantıözellikleri sayesinde akıllı cihazlarla entegrasyon sağlayarak kullanıcıdeneyimini ileri düzeye taşımaktadır. Literatürde yer alan çalışmalar, şarjedilebilir işitme cihazlarının kullanım kolaylığı ve uzun vadeli ekonomikavantajları nedeniyle giderek daha fazla tercih edildiğini ortaya koymaktadır(World Health Organization, 2021; European Hearing Instrument ManufacturersAssociation, 2022).&nbsp; Amaç: &nbsp;Bu çalışmanın amacı, işitme cihazı kullanımıiçin başvuran bireylerin pilli ve şarj edilebilir işitme cihazları arasındakitercihlerini belirlemek ve bu tercihlerin dağılımını ortaya koymaktır. Ayrıca,kullanıcıların yeni nesil işitme teknolojilerine yönelim düzeyinindeğerlendirilmesi hedeflenmektedir.Materyaller ve Yöntemler:Bu çalışmada, son altı ay içerisinde işitme cihazı temini amacıyla işitmecihazı firmalarına başvuran toplam 938 bireyden anket yöntemiyle veritoplanmıştır. Katılımcılara, tercih ettikleri işitme cihazı türüne ilişkinsorular yöneltilmiş ve elde edilen veriler analiz edilmiştir.Bulgular:Çalışmaya katılan bireylerin 800’ünün pilli işitme cihazını, 138’inin ise şarj edilebilirişitme cihazını tercih ettiği belirlenmiştir.Sonuç:Elde edilen bulgular, işitme kaybı olan bireylerin yeni teknolojilere uyumsağlama eğiliminde olduklarını göstermektedir. Bununla birlikte, şarjedilebilir cihazların sunduğu avantajlara rağmen, pilli işitme cihazlarınınhalen daha yüksek oranda tercih edildiği saptanmıştır. Bu durum, kullanıcıalışkanlıkları, maliyet algısı ve teknolojiye erişim gibi faktörlerleilişkilendirilebilir.&nbsp;Anahtar Kelimeler: İşitme Cihazı, Şarj edilebilir işitme cihazları,Pilli işitme cihazları, Cihaz tercihi, Teknoloji</p

Mental health challenges, preventive behaviors, and perspective on telepsychiatry in patients with chronic mental illness during the pandemic

Objective: This study examines the challenges faced by patients with schizophrenia (SCZ) and bipolar disorder (BD) during the coronavirus disease 2019 (COVID-19) pandemic, including healthcare accessibility, treatment adherence, social support, illness course, vegetative symptoms, concerns about COVID-19, protective healthcare behavior, sources of COVID-19-related information, and attitudes toward telepsychiatry. Method: A dual-interview method was employed with 200 patients: 100 interviews were conducted by telephone and 100 face-to-face in the outpatient clinic (50 SCZ and 50 BD patients in each group), enabling a comparative analysis of interview modalities. Results: Among the patients, 22% experienced difficulties reaching their doctors or hospitals, 6.5% were unable to access medications, and 7.5% reported insufficient social support. Avoidance of hospital visits due to COVID-19 concerns was higher in the telephone group than in the outpatient group (61% vs. 31%, p=0.001). Exacerbations occurred in 27% of participants, and treatment nonadherence was observed in 25.5%. Nonadherence, insufficient social support, insomnia, and appetite and weight loss were significantly associated with exacerbations. Nonadherence was highest among patients receiving sodium valproate (40%), whereas clozapine (17.1%) and lithium (20%) were associated with better adherence. Adoption of COVID-19 protective behaviors ranged from 83% to 95%, while only 23% used online resources, with slightly higher use among outpatients. Most patients (92.5%) were unaware of telepsychiatry; however, after receiving an explanation, willingness to use it was higher in the telephone group, except among patients with SCZ or delusional symptoms. Conclusion: This study highlights the need for tailored healthcare strategies for individuals with chronic mental illnesses. Lack of familiarity with telepsychiatry may contribute to disruptions in the continuity of psychiatric care during crises, underscoring the importance of integrating telehealth services and improving access pathways

Recent developments of novel nanotechnology-based drug delivery systems for dermal and transdermal applications

Topical and transdermal drug delivery faces continuous challenges, primarily due to the formidable barrier function of the stratum corneum (SC), which limits the bioavailability of therapeutics. Nanotechnology-based drug delivery systems (NDDS) have emerged as powerful strategies to overcome these limitations, offering improved drug permeation, sustained release, and enhanced solubility for hydrophobic compounds. This review provides a critical and concise analysis of the latest advancements in NDDS, specifically those employed for both dermal (localized) and transdermal (systemic) delivery. Key nanosystems, including lipid-based, polymeric nanoparticles, vesicular structures, nanoemulsions, nanofibers, dendrimers and micelles are explored, highlighting how their unique physicochemical properties facilitate optimized drug performance. Crucially, the design strategies that selectively target the dermis versus those engineered for transdermal penetration are compared and contrasted. Furthermore, the often-overlooked clinical aspects, including the current understanding of the in vivo fate, biocompatibility, and safety profile of these nanocarriers within the skin layers, are addressed. This comprehensive evaluation provides a foundation for future development of safer and more effective nanomedicines for cutaneous applications

Liraglutide Modulates Zinc Release and Improves Mitochondrial Function in Insulin-Resistant Senescent Cardiomyocytes

Aging and insulin resistance are intertwined factors in the development of metabolic diseases such as type 2 diabetes and cardiovascular disorders. Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has shown promising cardioprotective effects in preclinical and clinical studies of metabolic diseases. Yet, its action on insulin-resistant aged subjects is not clearly defined. This study aimed to investigate the effects of liraglutide on intracellular zinc levels, including its modulation of oxidative stress, mitochondrial function, and Endoplasmic Reticulum (ER) stress in a novel insulin-resistant senescent model. Insulin resistance and senescence were confirmed by reduced glucose uptake and increased β-Galactosidase Staining and increased p-H2A.X (Ser139) levels after 24 h of co-incubation with bovine serum albumin (BSA) conjugated palmitic acid (PA; 50 µM) and 278 mM D-galactose (D-Gal) in human AC16 cells. Our findings showed upregulated expression of ER and mitochondrial proteostasis markers in the early minutes of liraglutide treatment. In addition, chronic but not acute liraglutide treatment significantly increased intracellular zinc levels, accompanied by improved mitochondrial membrane potential and reduced reactive oxygen species in the insulin-resistant senescent model. Casein kinase 2 inhibition completely abolished liraglutide-induced zinc elevation and mitochondrial improvements in the chronic context, highlighting the role of casein kinase 2 in the subcellular signaling of liraglutide. These findings indicate that liraglutide alters intracellular zinc and modulates endoplasmic reticulum–mitochondria communication, giving insight into its therapeutic potential in metabolic cardiomyopathies linked to insulin resistance and aging

ABR findings in inner ear anomaly subgroups: Influence of cochlear nerve deficiency

Purpose: This study aimed to investigate auditory brainstem response (ABR) findings across subgroups of inner ear anomalies and to compare the ABR profiles in cases with cochlear nerve deficiency (CND). Methods: A total of 189 ears from 109 individuals with various inner ear anomalies were evaluated. Radiological findings were used to classify each ear into specific anomaly subgroups and to assess cochlear nerve status. ABR outcomes were then analyzed accordingly. Results: CND was consistently observed in complete labyrinthine aplasia, rudimentary otocyst, cochlear aplasia, and common cavity malformations, with absent ABR wave V and cochlear microphonic (CM) responses. Cochlear hypoplasia and incomplete partition subtypes showed variable ABR and CM responses. In cochlear aperture anomalies, CND was consistently observed, with absent wave V but detectable CM of variable latency. Wave V responses differed significantly between normal and CND ears (p < 0.001), whereas CM responses did not (p = 0.055). Conclusions: This study delineates ABR characteristics specific to inner ear anomaly subgroups and highlights the influence of CND on ABR outcomes. The findings underscore the potential of detailed ABR analysis to serve as a valuable tool for guiding auditory rehabilitation decisions and emphasize its relevance in shaping future clinical practice guidelines