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Introduction The fragility and sensitivity of the skin in people with albinism (PWA) have necessitated extensive research across molecular genetics, dermatology, and cosmetology. These efforts aim to address the increased susceptibility of albino skin to sun damage and dermatological conditions. Purpose This study investigates the dermatological efficacy of two galenic formulations, one based on Mathesia and the other on Curcuma longa L. (Zingiberaceae) oil, assessing their antimicrobial, anti-inflammatory, and photoprotective properties for the skin of PWA. Methods Using freeze-drying techniques for Mathesia and slight modifications of Sahouli et al.'s method for extracting Curcuma longa L. oil, we developed two creams. Their macroscopic properties, pH levels, and tyrosine concentrations were analyzed. UV-visible spectrophotometry determined their sun protection factor (SPF). An antibiogram test assessed their antimicrobial activity, and a clinical test evaluated their efficacy on PWA with and without skin conditions. Results The study revealed that both creams had good texture and appropriate pH levels. However, neither cream provided sufficient photoprotection for the sensitive skin of PWA. The Mathesia-based cream demonstrated a higher antimicrobial efficacy compared to the turmeric oil-based and neutral creams. Clinical tests showed 75% of participants had very satisfactory results, with the turmeric oil-based cream showing the most significant overall efficacy. Conclusion The creams exhibited beneficial antimicrobial and anti-inflammatory properties but were inadequate for UV protection of albino skin. Future research should focus on increasing active ingredient concentrations or exploring alternative plants to enhance tyrosine content and SPF values, potentially offering better protection and therapeutic effects for PWA.

Introduction Sickle cell disease is a hereditary condition primarily identified in tropical areas. It is marked by significant anemia, vaso-occlusive seizures, and a heightened vulnerability to both viral and bacterial infections. Additionally, sickle cell disease is distinguished by the depletion of mineral elements during crises. Purpose The purpose of this investigation was to identify the mineral composition of ten plants, namely Alchornea cordifolia, Alternanthera bettzickiana, Annona senegalensis, Cyttaranthus congolensis, Dissotis brazzae, Justicia secunda, Harungana madagascariensis, Hura crepitans, Hypoxis angustifolia, and Vigna unguiculata, traditionally utilized by practitioners in the management of sickle cell disease. Methods In this study, the biological material consists of the leaves, bark, and seeds of ten plant species. These plants were collected in Kwilu, and the mineral composition was assessed through fluorescence spectrometric analysis. The detection and quantification of the mineral elements were done by X-ray fluorescence spectrometric method with an XEPOS fluorescence spectrometer. The analysis of the results was carried out through Excel. R Studio and SPSS software packages were used for the statistical analyses. Results The study identified a total of twenty-three mineral elements in each of these plants, including Potassium (K), Phosphorus (P), Calcium (Ca), Sodium (Na), Magnesium (Mg), Sulphur (S), Chlorine (Cl), as well as trace elements like Aluminum (Al), Silicon (Si), Vanadium (V), Chromium (Cr), Manganese (Mn), Iron (Fe), Nickel (Ni), Copper (Cu), Zinc (Zn), Selenium (Se), Bromine (Br), Molybdenum (Mo), Tin (Sn), Iodine (I), Barium (Ba), and Lead (Pb). Notably, Iron, Zinc, Selenium, Copper, Calcium, Magnesium, and Manganese were found to be mineral elements associated with sickle cell disease. Potassium and Calcium exhibited higher concentrations, while Lead, Tin, Bromine, Copper, and Nickel were present in trace amounts. Conclusion The results obtained confirm that these plants contain some mineral elements such as Fe, Zn, Mg, and Se that are useful for sickle-cell patients.

Abstract The NMDA subtype of glutamate receptor serves as an attractive drug target for the treatment of disorders evolving from hyper‐ or hypoglutamatergic conditions. Compounds that optimize the function of NMDA receptors are of great clinical significance. Here, we present the pharmacological characterization of a biased allosteric modulator, CNS4. Results indicate that CNS4 sensitizes ambient levels of agonists and reduces higher‐concentration glycine & glutamate efficacy in 1/2AB receptors, but minimally alters these parameters in diheteromeric 1/2A or 1/2B receptors. Glycine efficacy is increased in both 1/2C and 1/2D, while glutamate efficacy is decreased in 1/2C and unaltered in 1/2D. CNS4 does not affect the activity of competitive antagonist binding at glycine (DCKA) and glutamate (DL‐AP5) sites; however, it decreases memantine potency in 1/2A receptors but not in 1/2D receptors. Current–voltage (I‐V) relationship studies indicate that CNS4 potentiates 1/2A inward currents, a phenomenon that was reversed in the absence of permeable Na+ ions. In 1/2D receptors, CNS4 blocks inward currents based on extracellular Ca2+ concentration. Further, CNS4 positively modulates glutamate potency on E781A_1/2A mutant receptors, indicating its role at the distal end of the 1/2A agonist binding domain interface. Together, these findings reveal that CNS4 sensitizes ambient agonists and allosterically modulates agonist efficacy by altering Na+ permeability based on the GluN2 subunit composition. Overall, the pharmacology of CNS4 aligns with the need for drug candidates to treat hypoglutamatergic neuropsychiatric conditions such as loss function GRIN disorders and anti‐NMDA receptor encephalitis.

N-Methyl-D-aspartate (NMDA) subtype of glutamate receptors is expressed in the human lungs and central nervous system. NMDA receptor potentiation could increase calcium ion influx and promote downstream signaling mechanisms associated with cellular contractions that are disrupted in severe acute respiratory syndrome. Pharmacological effects generated by triggering glutamate receptor function in the brain, coupled with concurrent stimulation of the respiratory tract, may produce a synergetic effect, improving the airway smooth muscle function. A novel multipronged intervention to simultaneously potentiate NMDA receptors expressed both in the central nervous system and airway muscles would be helpful for the treatment of severe acute respiratory syndrome that deteriorates peripheral and central nervous system function before causing death in humans.

Abstract Precisely controlled synaptic glutamate concentration is essential for the normal function of the N‐methyl D‐aspartate (NMDA) receptors. Atypical fluctuations in synaptic glutamate homeostasis lead to aberrant NMDA receptor activity that results in the pathogenesis of neurological and psychiatric disorders. Therefore, glutamate concentration‐dependent NMDA receptor modulators would be clinically useful agents with fewer on‐target adverse effects. In the present study, we have characterized a novel compound (CNS4) that potentiates NMDA receptor currents based on glutamate concentration. This compound alters glutamate potency and exhibits no voltage‐dependent effect. Patch‐clamp electrophysiology recordings confirmed agonist concentration‐dependent changes in maximum inducible currents. Dynamic Ca2+ and Na+ imaging assays using rat brain cortical, striatal and cerebellar neurons revealed CNS4 potentiated ion influx through native NMDA receptor activity. Overall, CNS4 is novel in chemical structure, mechanism of action and agonist concentration‐biased allosteric modulatory effect. This compound or its future analogs will serve as useful candidates to develop drug‐like compounds for the treatment of treatment‐resistant schizophrenia and major depression disorders associated with hypoglutamatergic neurotransmission.

N-methyl D-aspartate receptors (NMDAR) play crucial role in normal brain function and pathogenesis of neurodegenerative and psychiatric disorders. Functional tetra-heteromeric NMDAR contains two obligatory GluN1 subunits and two identical or different non-GluN1 subunits that include six different gene products; four GluN2 (A–D) and two GluN3 (A–B) subunits. The heterogeneity of subunit combination facilities the distinct function of NMDARs. All GluN subunits contain an extracellular N-terminal Domain (NTD) and ligand binding domain (LBD), transmembrane domain (TMD) and an intracellular C-terminal domain (CTD). Interaction between the GluN1 and co-assembling GluN2/3 subunits through the LBD has been proven crucial for defining receptor deactivation mechanisms that are unique for each combination of NMDAR. Modulating the LBD interactions has great therapeutic potential. In the present work, by amino acid point mutations and electrophysiology techniques, we have studied the role of LBD interactions in determining the effect of well-characterized pharmacological agents including agonists, competitive antagonists, and allosteric modulators. The results reveal that agonists (glycine and glutamate) potency was altered based on mutant amino acid sidechain chemistry and/or mutation site. Most antagonists inhibited mutant receptors with higher potency; interestingly, clinically used NMDAR channel blocker memantine was about three-fold more potent on mutated receptors (N521A, N521D, and K531A) than wild type receptors. These results provide novel insights on the clinical pharmacology of memantine, which is used for the treatment of mild to moderate Alzheimer's disease. In addition, these findings demonstrate the central role of LBD interactions that can be exploited to develop novel NMDAR based therapeutics.

Many adults diagnosed with autism spectrum disorder (ASD) face challenges in establishing and maintaining employment. These difficulties may be related to ASD symptomology or employer attitudes; however, vocational rehabilitation (VR) can provide employment-related resources. This study sought to understand how adults with ASD view their integration into workplace communities and VR services. Qualitative data were collected from 24 U.S. adults with ASD, and analysis identified themes surrounding the importance of workplace contributions, interesting work, and positive workplace relationships contributing to feeling integrated into the workplace community. Responses were also examined for perspectives on the role of VR in supporting workplace integration. Findings indicate the importance of attending to individual employment preferences and the need for long-term VR follow-along services to explore opportunities for employment growth. Implications and future recommendations for research and practice are also discussed. [ABSTRACT FROM AUTHOR]

NMDA receptors are a family of glutamate-gated ion channels that regulate various CNS functions such as synaptic plasticity and learning. However hypo- or hyper-activation of NMDA receptors is critically involved in many neurological and psychiatric conditions such as pain, stroke, epilepsy, neurodegeneration, schizophrenia, and depression. Thus, it is important to identify mechanisms (such as by targeted ubiquitination) that regulate the levels of individual subtypes of NMDA receptors. In this study, we used a series of tagged, carboxy terminal constructs of GluN2D to identify associating proteins from rat brain. Of seven different GluN2D C-terminal fragments used as bait, only the construct containing amino acids 983-1097 associated with an E3 ubiquitin ligase, Nedd4. A direct interaction between GluN2D and Nedd4 was confirmed both in vivo and in vitro. This association is mediated by an interaction between GluN2D's C-terminal PPXY motif and the 2nd and 3rd WW domains of Nedd4. Of the four GluN2 subunits, Nedd4 directly interacted with GluN2D and also weakly with GluN2A. Nedd4 coexpression with GluN2D enhances GluN2D ubiquitination and reduces GluN1/GluN2D NMDA receptor responses. These results identify Nedd4 as a novel binding partner for GluN2D and suggest a mechanism for the regulation of NMDA receptors that contain GluN2D subunits through ubiquitination-dependent downregulation. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'.