The Simultaneous Application of Transcranial Magnetic Stimulation and Virtual Reality to Treat Cognitive Deficits Among Stroke Patients: A Randomized Controlled Trial.

Background and objective Integrating virtual reality (VR) and transcranial magnetic stimulation (TMS) offers a promising strategy for stroke rehabilitation, as it specifically focuses on reorganizing neural connections and activating brain activity in the cortex. The main goal is to create equitable connections between the brain's two hemispheres to enhance the execution of voluntary movements by stimulating the central executive network (CEN) to strengthen both motor and cognitive abilities. This study aims to propose a therapeutic approach that can improve cognitive recovery and overall quality of life in patients after a stroke. Methods A total of 69 participants were enrolled in the study based on certain inclusion and exclusion criteria. The patients underwent pre-assessment and were randomly allocated into three groups: Group 1 received simultaneous repetitive TMS (rTMS) and virtual reality treatment (VRT), Group 2 received rTMS combined with sham VRT, and Group 3 received sham stimulation with VRT, in a 1:1:1 ratio using opaque, sealed, and stapled envelopes (SNOSE). Post-assessment was carried out using the same measures: the National Institutes of Health Stroke Scale (NIHSS), Addenbrooke's Cognitive Test (ACE III), and Montreal Cognitive Assessment (MOCA). Statistical analysis was conducted to determine the specific outcomes. Data analysis was carried out using IBM SPSS Statistics version 29 (IBM Corp., Armonk, NY), employing student's t-test for within-group comparisons and repeated measures ANOVA for between-group comparisons. The significance level was set at 5%. Results The results demonstrated statistical significance in NIHSS scores across all treatment groups (p<0.001). Regarding cognitive outcomes, improvements were observed in memory, language, and overall cognitive performance (ACE III) within all groups (p<0.05), with significant between-group outcomes (p = 0.009, p = 0.01, p = 0.004, respectively), suggesting variations in treatment effects across cognitive domains. However, no significant differences between groups were found in terms of fluency and visuospatial skills (p = 0.49, p = 0.13), indicating no treatment effects in these domains. Conclusions Based on our findings, the combined intervention involving rTMS and VRT, compared to sham treatments, demonstrates promising outcomes in alleviating stroke severity and improving specific cognitive functions such as memory, language, and overall cognitive performance. Additionally, the combined administration offers a more effective therapy than when they are administered separately.

Evaluation of antioxidant, anti-inflammatory and anticancer activities of diosgenin enriched Paris polyphylla rhizome extract of Indian Himalayan landraces.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional medicinal plants have gained attention as a potential therapeutic agent to combat cancer and inflammation. Diosgenin rich fresh extracts of Paris polyphylla rhizome from Indian Himalaya is traditionally used as wound healing, anti-bleeding, anti-inflammatory and anti-cancer agent by the folk healers. AIM OF THE STUDY: Present study was aimed to prepare two types of extracts from Paris polyphylla rhizome of Indian Himalayan landraces - 1. ethanolic extract of Paris polyphylla rhizome (EEPPR) and 2. Diosgenin enriched Paris polyphylla rhizome extract (DPPE), quantification of diosgenin content, and to evaluate their in vitro anti-oxidant, in vivo anti-inflammatory and in vitro cytotoxicity and anti-cancer activities of the DPPE. MATERIALS AND METHODS: Diosgenin content of EEPPR was quantified through GC-MS while diosgenin content of DPPE was quantified through HPTLC, and the diosgenin yield from EEPPR and DPPE were compared. In vitro antioxidant activities of DPPE were performed using DPPH, NOD, RP and SOD assay while in vivo anti-inflammatory activity of DPPE were evaluated in dextran induced hind paw edema in rats. In vitro cytotoxicity and anti-cancer activities of DPPE were evaluated in human breast cancer cell lines (MCF-7, MDA-MB-231), cervical cancer cell lines (HeLa) and Hep-2 cell lines. RESULTS: EEPPR obtained through cold extraction method using 70% ethanol showed maximum diosgenin content of 17.90% quantified through GC-MS while similar compounds pennogenin (3.29%), 7ß-Dehydrodiosgenin (1.90%), 7-Ketodiosgenin acetate (1.14%), and 7 ß-hydroxydiosgenin (0.55%) were detected in low concentration, and thus confirmed diosgenin as major and lead phytochemical. However, DPPE obtained through both cold and repeated hot extraction with the same solvent (70% ethanol) showed diosgenin content of 60.29% which is significantly higher (p < 0.001) than the diosgenin content in EEPPR. DPPE demonstrated significant in vitro antioxidant activities by dose-dependently quenched (p < 0.001) SOD free radicals by 76.66%, followed by DPPH (71.43%), NOD (67.35%), and RP (63.74%) at a max concentration of 2 µg/µl of ascorbic acid and test drugs with remarkable IC50 values (p < 0.01). Further, DPPE also showed potent anti-inflammatory activities by dose-dependently suppressed dextran induced paw edema in rats (p < 0.01) from 2 h to 4 h. DPPE suppressed the proliferation of MCF-7, MDA-MB-231, Hep-2 and HeLa cell lines. Maximum activity was observed in MCF-7 cells. The DPPE also induced apoptosis in MCF-7 cell lines as measured by AO/PI and DAPI staining, as well as DNA laddering, cell cycle analysis and phosphatidylserine externalization assay. The growth-inhibitory effect of DPPE on MCF-7 breast cancer cells was further confirmed from the colony-formation assay. DPPE upregulated expression of Bax and downregulated Bcl-2 and survivin mRNA transcripts. CONCLUSION: DPPE obtained through both cold and repeated hot extraction using ethanol showed significantly higher content of diosgenin than the diosgenin content detected in EEPPR. However, diosgenin yield of both the extracts (EEPPR & DPPE) clearly confirmed diosgenin as major and lead phytochemical of Paris polyphylla rhizome of Indian Himalayan landraces. Further, DPPE also demonstrated potent in vitro anti-oxidative and in vivo anti-inflammatory activities and showed in vitro cytotoxicity and significant anti-cancer (apoptosis) effects in MCF-7 breast cancer cells.

Surface morphology of immunocompetent cells isolated from spleen of Bufo himalayanus (Günther).

Immunocompetent cells were isolated from spleen of B. himalayanus and studied surface morphology of the three different cell types--(i) plastic adherent; (ii) nylon wool adherent; and (iii) nylon wool non-adherent cells. As revealed by scanning electron microscopy, they resembled the macrophages, B and T cells, respectively. Presence of such cell types indicated that Bufo himalayanus possessed a well-organized immune system. Further work is needed to characterize the functional efficacy of these immunocompetent cells found in B. himalayanus.

Matrix miniplate versus locking miniplate in the management of displaced mandibular angle fractures.

AIM: The purpose of this study was to determine and compare various postoperative parameters like ease of operability, plate adaptability, stability etc., associated with use of matrix miniplate versus locking miniplate in the treatment of displaced mandibular angle fractures. MATERIALS AND METHODS: The study was carried out in the Department of Oral and Maxillofacial surgery, King George's Medical College, GM and Associated Hospital, Lucknow. Total 50 patients were treated and included in the study. These were divided into two groups of 25 each and were treated with two of the standard techniques, i.e., one is matrix miniplate osteosynthesis and other is locking miniplate osteosynthesis. These patients were evaluated for postoperative complications and the differences between the two Groups were assessed. RESULTS: Patients treated by matrix miniplate showed better recovery phase postoperatively as compared to locking miniplate group. CONCLUSION: Based on this study matrix mini plate osteosynthesis may be considered as the better alternative method available for the treatment of displaced mandibular angle fractures.

Use of 3-d plate in displaced angle fracture of mandible.

Introduction Mandibular angle fractures can be treated by various methods, but even the most popular methods may not be able to give satisfactory results, as the pterygomasseteric sling and masticatory forces can result in displaced angle fracture. These displaced fragments cannot be satisfactorily retained by single miniplate fixation. The aim of this study is to assess treatment of displaced angle fracture with 3-D miniplate fixation. This study can also be considered as a therapeutic study with level V evidence. Materials and Methods This study was designed to assess the feasibility of 3-D matrix miniplate fixation in displaced angle fractures. Eighteen patients with displaced angle fractures were included in this study. Matrix miniplate fixation was done transorally under general anesthesia. Results All these cases were treated successfully, and common complications like infection (5.5% of patients), wound dehiscence (11%), paresthesia (16.7%), and malocclusion (11%) were observed in our study. Conclusions Three-dimensional miniplate fixation in displaced angle fractures provides better stability and function.

Coarse-grained modeling study of nonpeptide RGD ligand density and PEG molecular weight on the conformation of poly(γ-glutamyl-glutamate) paclitaxel conjugates.

Molecular shape, flexibility, and surface hydrophilicity are thought to influence the ability of nanoparticles to cross biological barriers during drug delivery. In this study, coarse-grained (CG) molecular dynamics (MD) simulations were used to study these properties of a polymer-drug construct in potential clinical development: poly(γ-glutamyl-glutamate)-paclitaxel-poly(ethylene glycol) nonpeptide RGD (PGG-PTX-PEG-npRGD), a linear glutamyl-glutamate polymer with paclitaxel and poly(ethylene glycol)-nonpeptide RGD side groups. It was hypothesized that the PEG molecular weight (MW) (500 Da; 1,000 Da; and 2,000 Da) and nonpeptide RGD ligand density (4, 8, 12, and 16 per molecule), respectively, may have advantageous effects on the shape, flexibility, and surface hydrophilicity of PGG-PTX-PEG-npRGD. Circular dichroism spectroscopy was used to suggest initial structures for the all-atom (AA) models of PGG-PTX-PEG-npRGD, which were further converted to CG models using a commercially available mapping algorithm. Due to its semi-flexibility, PGG-PTX-PEG-npRGD is not limited to one specific conformation. Thus, CG MD simulations were run until statistical equilibrium, at which PGG-PTX-PEG-npRGD is represented as an ensemble of statistically similar conformations. The size of a PGG-PTX-PEG-npRGD molecule is not affected by the PEG MW or the nonpeptide RGD density, but higher PEG MW results in increased surface density of a PGG-PTX-PEG-npRGD molecule. Most PGG-PTX-PEG-npRGD shapes are globular, although filamentous shapes were also observed in the PEG500 and PEG1000 molecules. PEG500 and PEG1000 molecules are more flexible than PEG2000 systems. A higher presence of npRGD ligands results in decrease surface hydrophilicity of PGG-PTX-PEG-npRGD. These results indicate that the PGG-PTX-PEG1000-npRGD(4) and PGG-PTX-PEG1000-npRGD(8) molecules are the most efficacious candidates and are further recommended for experimental preclinical studies.

Synthesis, characterization, and biological evaluation of poly(L-γ-glutamyl-glutamine)- paclitaxel nanoconjugate.

The purpose of this study was to develop a novel, highly water-soluble poly(L-γ-glutamyl-glutamine)-paclitaxel nanoconjugate (PGG-PTX) that would improve the therapeutic index of paclitaxel (PTX). PGG-PTX is a modification of poly(L-glutamic acid)- paclitaxel conjugate (PGA-PTX) in which an additional glutamic acid has been added to each glutamic side chain in the polymer. PGG-PTX has higher water-solubility and faster dissolution than PGA-PTX. Unlike PGA-PTX, PGG-PTX self-assembles into nanoparticles, whose size remains in the range of 12-15 nm over the concentration range from 25 to 2,000 µg/mL in saline. Its critical micellar concentration in saline was found to be ~25 µg/mL. The potency of PGG-PTX when tested in vitro against the human lung cancer H460 cell line was comparable to other known polymer-PTX conjugates. However, PGG-PTX possesses lower toxicity compared with PGA-PTX in mice. The maximum tolerated dose of PGG-PTX was found to be 350 mg PTX/kg, which is 2.2-fold higher than the maximum tolerated dose of 160 mg PTX/kg reported for the PGA-PTX. This result indicates that PGG-PTX was substantially less toxic in vivo than PGA-PTX.