Synthesis, Characterization, and Study of Biological, Laser, and Molecular Docking Activity of Oxazolidinone‐5‐one Compounds Derived From 5‐methyl 1,3,4‐thiadiazole‐2‐amine

ABSTRACT In this study, 5‐methyl 1,3,4‐thiadiazole‐2‐amine was used as the synthon of various Schiff bases, which were prepared by reacting the amine with benzaldehyde substituents and then reacting with chloroacetic acid to form oxazolidin‐5‐one five‐membered rings. This compound has good biological activity, and physical and spectroscopic methods confirmed the structure of the prepared compound. Examples include infrared spectroscopy, proton nuclear magnetic resonance spectroscopy ( 1 H‐NMR), mass spectrometry, melting point and purity determination, and tracking of reaction progress via thin layer chromatography (TLC). Gram‐negative Escherichia coli (Gram‐ve) and Gram‐positive Staphylococcus aureus (Gram+ve), two bacterial isolates renowned for their antibiotic resistance, were used to assess the bioavailability of the produced compounds (HA6‐HA15), and the results were compared with the antibiotic amoxicillin as a control. The level of selectivity was excellent. A helium‐neon laser (visible laser) was used to measure the laser activity of several of the produced compounds (HA7, HA10, HA11, HA13, and HA15). Each compound was exposed to radiation for four durations (15, 30, 45, and 60 s). Using MOE (2015) software, the molecular binding of HA9 and H15, two of the produced compounds, to Escherichia coli was investigated.

In Vitro Release Study of Celecoxib‐Loaded Fractionated Medium Chain Triglycerides Nanoemulgel Formulation for Enhanced Transdermal Delivery

ABSTRACT Celecoxib (CXB) is a lipophilic drug classified as a Biopharmaceutical Classification System (BCS) Class II compound, characterized by poor aqueous solubility and low oral bioavailability, which hinders its ability to penetrate through the stratum corneum. To address these concerns, nanoemulgel (NEG) has emerged as a promising carrier for enhancing transdermal delivery of lipophilic drugs. This study aimed to develop, characterize, and investigate the release profile of the CXB‐loaded NEG incorporating fractionated medium chain triglycerides (FMCTs) as the carrier oil, which mainly contains caprylic and capric acids, which are known for their superior solubilizing capacity and skin penetration enhancement. Herein, the CXB‐loaded nanoemulsion (NE) was prepared with a combination of oil, surfactants and water using the spontaneous emulsification method. The resulting CXB‐NE was then characterized according to its particle size, polydispersity index, zeta potential to evaluate its physicochemical properties. The optimized formulation was incorporated with Carbopol 940 gel to develop CXB‐NEG, which was evaluated for in vitro release study. The results showed that CXB‐NEG F1 formulated with a blend of MCT and PKOlein demonstrated a smaller particle size (146.80 nm) compared to CXB‐NEG F2 containing MCT alone (161.90 nm). Both formulations exhibited good stability with PDI less than 0.30 and zeta potential exceeding −30 mV. Notably, CXB release from NEG‐F1 was approximately 10‐fold higher (50.35%) than the release from conventional gel (5.03%), followed by NEG‐F2 with 42.60% release. These findings suggested that incorporating a blend of MCT and PKOlein in CXB‐NEG F1 enhances particle size reduction, stability, and drug release performance. These enhancements improve skin permeation, supporting the formulation's suitability for transdermal delivery and indicating the effectiveness of FMCTs as permeation enhancers.

Synthesis of Hg(II) Complexes with S‐(Thiophene‐2‐yl)2‐((2‐Hydroxyphenyl)amino) Ethanethiol for Antibacterial Studies

ABSTRACT This study focused on the unique synthesis and characterization of macromolecular complexes using thiophene‐2‐thiol as a core structure. The ligand S‐(thiophene‐2‐yl)‐2‐((2‐hydroxyphenyl)amino)ethanethiol (AZ2) was developed as a precursor for constructing macromolecular metal complexes. Specifically, two novel complexes, [Hg(AZ2)(dppf)]Cl 2 and [Hg(AZ2)(PPh 3 ) 2 ]Cl 2 , were synthesized through reactions involving mercuric chloride and phosphine‐based reagents. Comprehensive structural characterization of the macromolecular assemblies was performed using advanced physical and spectroscopic techniques, such as infrared (IR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy for 1 H, 13 C, and 31 P nuclei. The biological evaluation of these macromolecular complexes against antibiotic‐resistant bacteria, including Escherichia coli (Gram‐negative) and Staphylococcus aureus (Gram‐positive), revealed significant antimicrobial activity. When compared to amoxicillin, the standard antibiotic control, the macromolecular complexes exhibited enhanced inhibitory potency, underscoring their potential as effective agents against resistant bacterial strains.

Early Onset Dystonia, Parkinsonism, and Spasticity in Siblings with VAC14 ‐Associated Neurodegeneration: A Case Report and Literature Review

Current Perspectives and Practices in Infection‐Related Movement Disorders ( IRMD ): Insights from a Survey of Members of the International Parkinson and Movement Disorder Society

Abstract Background Infection‐related movement disorders (IRMD) represent an important group of secondary movement disorders whose prevalence, patterns, treatment and outcomes remain poorly understood. Objectives To survey members of the International Parkinson and Movement Disorder Society regarding prevailing practices in IRMD. Methods A cross‐sectional online survey was conducted. Results Of 95 responses received, 75 (78.9%) were from the Asia‐Oceania (AO) region and were further analyzed. The highest number of responses was from India (67/75, 89.3%). The most frequent phenotypes included ataxia (64, 85.3%), chorea (49, 65.3%), myoclonus (55, 73.3%) and parkinsonism (43, 57.3%). Tuberculosis‐related (61, 81.3%), subacute sclerosing panencephalitis (50, 66.7%), and dengue‐related movement disorders (49, 65.3%) were most frequent. Variable outcomes were observed by 46 (61.3%) respondents and 66 (88%) indicated that up to 50% of patients experienced persistence of IRMD. Conclusions This survey provides critical insights into prevailing practices in the field of IRMD from the AO region.

Anticholinergic Burden and Botulinum Toxin Needs after Deep Brain Stimulation in Adult and Pediatric Patients with Dystonia

Abstract Background Anticholinergic medications and botulinum neurotoxin injections are established treatments for dystonia, yet they carry potential side effects and practical challenges. Deep brain stimulation (DBS) is offered in case of poor response to these approaches. Objectives To assess the need for anticholinergic medications and botulinum neurotoxin injections in adult and pediatric patients at two specialized Canadian centers before and after DBS over the past 10 years. Methods 58 patients were included analyzing data before, 6 and 12 months after DBS. Clinical assessment included the Toronto Western Spasmodic Torticollis Rating Scale and Fahn‐Marsden Dystonia Rating Scale. Anticholinergic burden was determined by the Anticholinergic Drug Scale (ADS). Results Severity of cervical dystonia and ADS scores reduction were statistically significant after DBS. Anticholinergic medication and Botulinum Neurotoxin injections were discontinued a year after surgery in 28.8% and 72.4% of the patients, respectively. Conclusion Simplification of anti‐dystonia treatments is another added benefit of DBS.

Practices, Resources and Challenges in Parkinson's Disease Management in Asia: Movement Disorders in Asia Study Group Report

Abstract Background The prevalence of Parkinson's disease (PD) is increasing markedly in Asia, highlighting the urgent need to understand the current practices and challenges in delivering comprehensive PD care in this region. Objectives We aimed to determine the resources and facilities for comprehensive management of PD in Asia focusing on regions (South East Asia, Middle East, Indian Subcontinent, East Asia, and Central Asia) and income levels (high‐income countries‐HIC, upper middle‐income countries‐UMIC, lower middle‐income countries‐LMIC). Method A survey‐based questionnaire was deployed to the MDS affiliate societies or key neurologists in 32 countries in Asia. Results Thirty countries/territories participated in the survey. HICs have better availability of and accessibility to most health care professionals. Central Asia has the lowest availability of and accessibility to health care professionals. PD nurses are least available (33.3%) and least easily accessible (6.7%). Levodopa and anticholinergics are the most available (100%), accessible (100%) and affordable (100%) antiparkinsonian medications. Device‐aid therapies are more available and accessible in East Asian countries/territories, compared to other regions. Accessibility to allied health professionals is poor (43%). Genetic testing is available in 18 (60%) countries/territories, mostly in HIC ( P  = 0.031). Community engagement and public health awareness campaigns are available in 21 (70%) countries/territories. Brain bank is available in seven (24.1%) countries/territories, mostly in HIC. Telemedicine is utilized in 21 (70%) countries/territories. Conclusion This is the first survey‐based study to highlight regional and income‐based disparities on infrastructures required for comprehensive PD care in Asia. Regional collaborations between HIC and MIC may address some of these disparities.

Whole Exome Sequencing in Patients With Developmental Delay/Intellectual Disability ( DD / ID ), Epilepsy and the First Turkish Patient Diagnosed With BCL11A ‐Related Intellectual Disability

ABSTRACT Introduction Whole‐exome sequencing (WES) is considered an important tool in investigating the etiology of developmental delay/intellectual disability (DD/ID) and epilepsy. Genetic diagnosis with WES has become an important tool in patients with DD/ID and epilepsy. Methods In this study, we present the findings of WES conducted between August 2021 and December 2024 on children with DD/ID and epilepsy. We evaluated clinically important variants identified by WES in 65 pediatric patients by retrospective analysis. Results Sixty‐five patients with DD/ID were included in the study, 34 of whom (52.3%) were male. The most common symptom was epilepsy (45 patients, 69.2%), and the second most common symptom was DD/ID in 39 patients (60%). A total of 19 pathogenic/likely pathogenic variants (31.2%) with confirmation made in the parents and probands, 9 variants were determined to be de novo. In this study, the number of patients diagnosed was determined as 19 (31.2%). We detected a de novo likely pathogenic heterozygous c.142 T>C (p.Cys48Arg) variant in the BCL11A gene in the first reported Turkish patient with BCL11A‐related intellectual disability. Other previously unreported de novo variants identified: ASXL3 gene, NM_030632.2 c.3613G>T p.(Glu1205Ter), ANKRD11 gene, NM_001256182.2 c.4750G>T, SHANK3 gene, NM_001372044.2 c.4711_4712del. Conclusion The cases we present contribute to the expansion of the spectrum of genetic variants in genetically heterogeneous patient groups such as DD/ID and epilepsy. These previously unreported variants advance our molecular understanding and broaden the clinical spectrum of these rare genetic disorders.

7T 19 F / 1 H MRI with perfluorocarbon‐labeled immune cells in pigs: Pilot results with a dedicated twin‐array system with pTX support

Abstract Purpose Cardiac inflammation plays a key role in many diseases. However, its underlying mechanisms and progression remain poorly understood. Using an ultra‐high field (UHF) may increase the sensitivity of MRI of inflammatory processes with 19 F‐labeled immune cells. The high Larmor frequency of 19 F (∼95% of that for 1 H‐nuclei) leads to similar technical hurdles in acquiring MR images at UHF that originate from the heterogeneity of B 1 + . We aimed to develop a system of transmit/receive (Tx/Rx) arrays exploiting parallel transmit (pTX) technology for B 1 + ‐shimming to acquire a combination of high‐quality anatomical 1 H MR‐images of a pig heart and 19 F images of labeled immune cells at 7T. Method The 16‐element twin‐arrays for 1 H and 19 F nuclei were designed using electromagnetic simulations with a focus on optimal B 1 ‐shimming and g‐factor in the region of the pig heart. pTX support allows for the subject‐specific B 1 ‐shimming for 1 H cardiac MRI and transfer of settings for the B 1 ‐shimming to the 19 F twin‐array. Results The twin‐array system was implemented and tested in a pig‐thorax‐‐shaped phantom, in‐vivo in a myocardial infarction pig model, and in an excised heart. A transfer of static B 1 + shimming setting between the 1 H to 19 F arrays was demonstrated. The parallel imaging acceleration of up to a factor 4 was possible with a g‐factor <1.3 for both arrays. The 7T MRI of 19 F‐labeled immune cells in the heart of the pig was demonstrated both in‐vivo and ex‐vivo. Conclusion The 7T MRI of perfluorocarbon‐labeled immune cells in a large‐animal myocardial infarction model becomes feasible using a novel dedicated twin‐arrays system.

DNA barcode analyses and taxonomy reveal two new species of Inocybe from Pine and Oak forests of Pakistan

Here we describe two new species of Inocybe from pine forests of Pakistan; I. hazarensis and I. shimlaensis . Morphological and molecular data show that these species have not been described before and hence need to be described as new. Both species are smooth‐spored and pruinose only in the apical part of the stipe. Inocybe hazarensis is characterized by rather small size, brown to dark brown, dense radial fibrils to rimose to glabrous pileus with prominent umbo, finely fibrillose at apex only becoming pruinose to strigose, along rest of length of stipe, slightly bulbous stipe base, narrow basidiospore spores and smaller clavate, oblong, ovoid, narrowly utriform cheilocystidia. Inocybe shimlaensis is characterized by brown to golden pileus, low and broad umbo, radially fibrillose, rimose to granulose, with brown appressed‐squamulose stipe with only apex pruinose and submarginate base. Anatomically, it has small (6.8 × 4.4 μm) basidiospores and smaller conical to fusiform cheilocystidia. Phylogenetic estimation based on DNA sequences from the internal transcribed spacer (ITS) region and large subunit (LSU) of the nuclear ribosomal DNA (rDNA) genes is congruent with the morphological characters that help to delimit these as new species of Inocybe .