Autologous hematopoietic stem cell transplant at a tertiary care centre in India: achieving comparable outcomes with adaptations.

Autologous stem cell transplantation (ASCT) is the standard treatment for many high-risk solid tumors. Patients undergoing ASCT should be managed in a dedicated hematopoietic stem cell transplantation (HSCT) unit with isolation rooms, high-efficiency particulate air (HEPA) filters, and positive pressure. We report the outcomes of the first 20 pediatric patients who underwent ASCT in isolation rooms with no HEPA filters or positive pressure. Moreover, the isolation rooms were not part of a dedicated HSCT unit. Data from 20 patients were analyzed. All patients included in the study underwent ASCT after harvest and cryopreservation of the hematopoietic stem cells (HSC). Furthermore, all patients also underwent myeloablative conditioning. The most common indications for ASCT included high-risk neuroblastoma (HR-NB) (n=9) and refractory/relapsed Hodgkin's lymphoma (HL) (n=6). The median CD-34 positive HSC administered was 4.5 (0.8-21.9) million per kg. The median time to neutrophil and platelet engraftment was 16.5 (10-35) and 19 (10-87) days, respectively. Additionally, only one transplant-related mortality was observed and the mean time to discharge from the hospital was 27.6+8.3 days. The overall survival for all our patients was 75% at a median follow-up of 33.2 months (15 out of 20 patients survived), and the disease-free survival was 60% (median follow-up, 28.4 months). The overall survival for the patients with HL was 85.7% at a median of 45.3 months and for the HR-NB was 66.7% at a median of 34.9 months. This study provides evidence that ASCT can be safely performed in isolation rooms without HEPA filters and positive pressure if expertise and supportive care are available. In settings with limited resources, such a model could help establish low-cost HSCT units.

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches.

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.

Whole genome sequencing followed by functional analysis of genomic deletion encompassing ERCC8 and NDUFAF2 genes in a non-consanguineous Indian family reveals dysfunctional mitochondrial bioenergetics leading to infant mortality.

Genomic investigations on an infant who presented with a putative mitochondrial disorder led to identification of compound heterozygous deletion with an overlapping region of ∼142 kb encompassing two nuclear encoded genes namely ERCC8 and NDUFAF2. Investigations on fetal-derived fibroblast culture demonstrated impaired bioenergetics and mitochondrial dysfunction, which explains the phenotype and observed infant mortality in the present study. The genetic findings from this study extended the utility of whole-genome sequencing as it led to development of a MLPA-based assay for carrier screening in the extended family and the prenatal testing aiding in the birth of two healthy children.

Breaking the graft-versus-host-disease barrier: Mesenchymal stromal/stem cells as precision healers.

Mesenchymal Stromal/Stem Cells (MSCs) are multipotent, non-hematopoietic progenitor cells with a wide range of immune modulation and regenerative potential which qualify them as a potential component of cell-based therapy for various autoimmune/chronic inflammatory ailments. Their immunomodulatory properties include the secretion of immunosuppressive cytokines, the ability to suppress T-cell activation and differentiation, and the induction of regulatory T-cells. Considering this and our interest, we here discuss the significance of MSC for the management of Graft-versus-Host-Disease (GvHD), one of the autoimmune manifestations in human. In pre-clinical models, MSCs have been shown to reduce the severity of GvHD symptoms, including skin and gut damage, which are the most common and debilitating manifestations of this disease. While initial clinical studies of MSCs in GvHD cases were promising, the results were variable in randomized studies. So, further studies are warranted to fully understand their potential benefits, safety profile, and optimal dosing regimens. Owing to these inevitable issues, here we discuss various mechanisms, and how MSCs can be employed in managing GvHD, as a cellular therapeutic approach for this disease.

Mandibular primary intraosseous carcinoma arising from long-standing odontogenic keratocyst.

Primary intraosseous carcinoma (PIOC) of the jaw is a rare neoplasm arising from the lining epithelium of odontogenic cysts or de novo from odontogenic epithelial rests that has no communication with the surrounding mucosa of the upper aerodigestive tract. We present a case of PIOC ex-odontogenic keratocyst (PIOC ex-OKC) in a 35-year-old male. Histopathologic examination revealed a cystic lesion with a fibrous capsule lined by corrugated parakeratinized stratified squamous epithelium resting on a basal cell layer composed of columnar cells exhibiting palisaded hyperchromatic nuclei, features consistent with OKC. Surgical treatment consisted of bilateral crestal and crevicular incision, a reflection of the flap, breaking of all OKC locules, creation of a continuous cavity, and fitting of a decompression mold around the mandibular teeth. This case highlights the importance of knowing the features of PIOC and considering PIOC in the differential diagnosis of malignant tumors of odontogenic epithelium for timely surgical treatment.

Carbon quantum dot-nanocomposite hydrogel as Denovo Nexus in rapid chondrogenesis.

The incapability of cartilage to naturally regenerate and repair chronic muscular injuries urges the development of competent bionic rostrums. There is a need to explore faster strategies for chondrogenic engineering using mesenchymal stem cells (MSCs). Along these lines, rapid chondrocyte differentiation would benefit the transplantation demand affecting osteoarthritis (OA) and rheumatoid arthritis (RA) patients. In this report, a de novo nanocomposite was constructed by integrating biogenic carbon quantum dot (CQD) filler into synthetic hydrogel prepared from dimethylaminoethyl methacrylate (DMAEMA) and acrylic acid (AAc). The dominant structural integrity of synthetic hydrogel along with the chondrogenic differentiation potential of garlic peel derived CQDs led to faster chondrogenesis within 14 days. By means of extensive chemical and morphological characterization techniques, we illustrate that the hydrogel nanocomposite possesses lucrative features to influence rapid chondrogenesis. These results were further corroborated by bright field imaging, Alcian blue staining and Masson trichome staining. Thus, this stratagem of chondrogenic engineering conceptualizes to be a paragon in clinical wound care for the rapid manufacturing of chondrocytes.

Revisiting the Role of Amniotic Membrane Dressing in Acute Large Traumatic Wounds: A Randomized Feasibility Study at a Level 1 Trauma Centre.

Introduction: Acute large traumatic wounds require temporary dressing prior to the definitive soft tissue reconstruction, as the physiological derangement during the immediate postinjury period delays the definitive surgical intervention. Selecting an ideal dressing material from numerous available synthetic dressings and skin substitutes poses a challenge. Although amniotic membrane (AM) scaffold has a definitive role in promoting wound healing in burns and chronic wounds, however, its efficacy in acute large traumatic wound is lacking. The present trial aimed to evaluate the safety and efficacy of AM in wound bed preparation before the definitive soft-tissue reconstruction in acute large traumatic wounds. Methods: Sixty patients with acute large traumatic wounds (>10 cm × 10 cm) were divided into two groups (conventional dressing and AM dressing) using simple mixed block randomization. Wounds were assessed using the Bates Jensen Score at various timelines for the signs of early wound healing. The primary outcome was to evaluate the time taken for the wound bed preparation for definitive soft-tissue reconstruction. The secondary outcome was the pain assessment and complications, if any. Results: There was significant reduction in the wound exudate as well as peripheral tissue edema in the intervention group (P = 0.01). AM dressing was significantly less painful (P = 0.01). The incidence of wound infection and need for debridement was decreased in the intervention group. However, the time interval to definitive soft-tissue coverage was statistically insignificant and comparable in both the groups. No adverse reactions were seen in either group. Conclusion: AM dressings are safe and efficacious with significant reduction in wound exudates and peripheral edema. However, these dressings do not hasten the wound maturation as compared to conventional dressings. AM dressings can be used as a less painful alternative to conventional dressing in the management of large acute posttraumatic wounds.

Recent advances in tailoring stimuli-responsive hybrid scaffolds for cardiac tissue engineering and allied applications.

To recapitulate bio-physical properties and functional behaviour of native heart tissues, recent tissue engineering-based approaches are focused on developing smart/stimuli-responsive materials for interfacing cardiac cells. Overcoming the drawbacks of the traditionally used biomaterials, these smart materials portray outstanding mechanical and conductive properties while promoting cell-cell interaction and cell-matrix transduction cues in such excitable tissues. To date, a large number of stimuli-responsive materials have been employed for interfacing cardiac tissues alone or in combination with natural/synthetic materials for cardiac tissue engineering. However, their comprehensive classification and a comparative analysis of the role played by these materials in regulating cardiac cell behaviour and in vivo metabolism are much less discussed. In an attempt to cover the recent advances in fabricating stimuli-responsive biomaterials for engineering cardiac tissues, this review details the role of these materials in modulating cardiomyocyte behaviour, functionality and surrounding matrix properties. Furthermore, concerns and challenges regarding the clinical translation of these materials and the possibility of using such materials for the fabrication of bio-actuators and bioelectronic devices are discussed.

Modified-Hydroxyapatite-Chitosan Hybrid Composite Interfacial Coating on 3D Polymeric Scaffolds for Bone Tissue Engineering.

Three dimensional (3D) scaffolds have huge limitations due to their low porosity, mechanical strength, and lack of direct cell-bioactive drug contact. Whereas bisphosphonate drug has the ability to stimulate osteogenesis in osteoblasts and bone marrow mesenchymal stem cells (hMSC) which attracted its therapeutic use. However it is hard administration low bioavailability, and lack of site-specificity, limiting its usage. The proposed scaffold architecture allows cells to access the bioactive surface at their apex by interacting at the scaffold's interfacial layer. The interface of 3D polycaprolactone (PCL) scaffolds has been coated with alendronate-modified hydroxyapatite (MALD) enclosed in a chitosan matrix, to mimic the native environment and stupulate the through interaction of cells to bioactive layer. Where the mechanical strength will be provided by the skeleton of PCL. In the MALD composite's hydroxyapatite (HAP) component will govern alendronate (ALD) release behavior, and HAP presence will drive the increase in local calcium ion concentration increases hMSC proliferation and differentiation. In results, MALD show release of 86.28 ± 0.22. XPS and SEM investigation of the scaffold structure, shows inspiring particle deposition with chitosan over the interface. All scaffolds enhanced cell adhesion, proliferation, and osteocyte differentiation for over a week without in vitro cell toxicity with 3.03 ± 0.2 kPa mechanical strength.

Epidermoid cysts of the orofacial region: A clinico-pathological study of 13 cases with review of literature.

Background: Epidermoid cysts (ECs) are uncommon benign cystic lesions derived from the germinative epithelium. Head and neck ECs constitute only 7% of all ECs whereas only 1.6% are seen intraorally. The floor of the mouth is the commonest intraoral site whereas tongue, lips, buccal mucosa, and jaws are less commonly involved intraoral sites. To date, very few large case series of ECs of head and neck have been published. To the best of our knowledge, this is the third-largest case series of 11 intraoral ECs along with 2 extra-oral cases in the pre-auricular region. Aims: To highlight the typical and atypical features of ECs in the common as well as rare sites and draw attention to its consideration as a differential diagnosis for head and neck masses. Settings and Design: Archival data of 13 histopathological cases identified as ECs were analyzed from the Department of Oral Pathology at a tertiary dental hospital and college in New Delhi from 2007 to 2020. Materials and Methods: The demographic, clinical, radiographic, histopathological features, and treatment modalities were recorded and analyzed. Statistical Analysis Used: Appropriate statistical tests were used. Results: The study found strong male predilection in the ratio of 10:3 with an average age of presentation as 28 years. The pre-auricular region and floor of the mouth were the common sites involved followed by buccal mucosa, lips, and jaws. All patients presented with slowly growing swelling with dysphagia, dyspnea, and dysphonia seen in larger cysts on the floor of the mouth. Microscopically, all cases were lined with stratified squamous epithelium filled with laminated layers of keratin. Two cases showed the presence of melanin. One case showed recurrence even after complete surgical excision. Conclusion: ECs, though a rare entity, should be considered in differential diagnosis for head and neck masses and require close follow-up due to their potential for malignant transformation.

"Does the Exploration of the Temporomandibular Joint Using a Deep Subfascial Technique Result in a Superior Operative Outcome?"

PURPOSE: The literature is replete with various approaches for the temporomandibular joint (TMJ), each with its own distinct advantages and disadvantages. None of these approaches, however, have been associated with superior operative outcomes. The purpose of this study was to measure the efficacy of three operative approaches to TMJ, namely superficial, subfascial, and deep subfascial approaches. The aim was to contrast selected intraoperative and postoperative outcomes among these surgical approaches. METHODS: This was a prospective randomized clinical trial of subjects presenting to outpatient department. The primary predictor variables were three dissection planes of TMJ: Group-I (superficial), Group-II (subfascial), and Group-III (deep subfascial). The primary outcome variables were quality of surgical field employing fromme scale, dissection time in minutes, amount of blood loss in milliliters, and facial nerve function (FNF) using House-Brackmann scale. The secondary outcome variables were postoperative pain using visual-analog scale and swelling in millimeters measured on 1st, 3rd, and 7th postoperative days and quality of life using facial clinimetric evaluation questionnaire at 6-month follow-up. Age, gender, side, diagnosis, and type of surgery were the covariates. The data were analyzed using descriptive, comparative, and regression analysis. A P value of less than .05 was considered statistically significant. RESULT: The study included thirty subjects (8 males and 22 females) with various TMJ disorders ranging in age from 8 years to 65 years (mean 27.83 ± 10.52). On evaluation of intraoperative parameters, subfascial approach had statistically significant superior quality of surgical field (Group-I: 1.90 ± 0.57; Group-II: 1.10 ± 0.32; Group-III: 1.40 ± 0.52; P value = .006), statistically significant shortest dissection time (Group-I: 18.30 ± 3.74 min; Group-II: 13.240 ± 1.96 min; Group-III: 16.20 ± 1.99 min; with P value = .03), and statistically significant lower amount of blood loss compared with other groups (Group-I: 92.40 ± 4.74 ml: Group-II: 82.30 ± 3.77 ml; Group-III: 84.60 ± 3.06 ml; P value<.001). On assessment of postoperative parameters, only FNF of temporal branch showed statistically significant difference from 24 hours till 3 months with better outcome in deep subfascial approach. Mean scores of FNF at 24 hours and 1-week (Group-I: 4.20 ± 2.39; Group-II: 2.40 ± 2.27; Group-III: 1.50 ± 1.58 P = .02) and 1-month and 3-month (Group-I: 2.70 ± 1.82; Group-II: 1.20 ± 0.63; Group-III: 1.00 ± 0.00 P = .04). CONCLUSIONS: The subfascial approach significantly improved intraoperative outcomes and deep subfascial approach was comparatively safe with fewer incidence of facial nerve injury.

Effect of low-level laser therapy on post-extraction hemostasis in patients with hemophilia - A prospective cohort study.

Dental extraction in hemophiliacs can be complicated by perilous bleeding. Although developments in local hemostatics and factor replacement have made outpatient extraction feasible, there is no standard protocol for preventing hemorrhagic exigency. Low-level laser therapy (LLLT) has firmly established role in hemostasis due to its ability to seal vessels, but this function has not been conclusively established in hemophiliac patients. The objective of our study was to evaluate the effectiveness of LLLT as compared with the standard protocol alone in achieving post-extraction hemostasis. A prospective interventional cohort study was designed and consisted of 60 patients with hemophilia A or B, who reported to the Maulana Azad Institute of Dental Sciences, New Delhi between October 2021 and March 2022. These were divided equally into test and control groups, both following the standard protocol. In the test group, extraction sockets were exposed to LLLT. The study assessed time required, instance of rebleeding, and additional methods employed for hemostasis in each group. The results showed a 22.42% reduction in average time taken to achieve hemostasis in the test group as compared with the control group. The tranexamic acid pack was replaced in two cases in both groups after 60 min of procedure. Three cases in the control group required suturing, and one case required cauterization. Rebleeding occurred in four cases in the test group and in 13 cases among the controls. Postoperative factor was infused in three and 12 cases in the test and control groups, respectively. The authors believe that perioperative use of LLLT should be encouraged because it demonstrated a significantly reduced time for hemostasis among hemophilia patients.

Single Institute Audit of Maxillofacial Trauma Cases Before and During COVID-19 Pandemic.

Study Design: In the year 2020, we saw the emergence of severe acute respiratory syndrome coronavirus 2 causing COVID-19 into a full blown pandemic. This resulted in constraints on healthcare resources, and the attention was shifted to reduce cross contamination and prevent spreader events. Maxillofacial trauma care was also affected similarly, and most of the cases were managed by closed reduction whenever possible. A retrospective study was conducted to document our experience in treating maxillofacial trauma cases before and after nationwide lockdown due to COVID-19 pandemic in India. Objective: The objective of the study was to compare the effect of pandemic in reported pattern of mandibular trauma and the result of closed reduction procedures in the management of single or multiple fractures in mandible during this time period. Methods: The study was conducted in the Department of Oral and Maxillofacial Surgery, Maulana Azad institute of Dental Sciences, Delhi, for a period of 20 months, that is, 10 months before and after nationwide lock down which was effective from 23rd March 2020 due to COVID-19 pandemic. The cases were grouped into Group A (those reporting from 1st June 2019 to 31st March 2020) and Group B (those reporting from 1st April 2020 to 31st January 2021). Primary objectives were assessed and compared according to etiology, gender, location of the mandibular fractures, and treatment provided. Quality of life (QoL) associated with the treatment outcome by closed reduction was assessed after 2 months as a secondary objective using General Oral Health Assessment Index (GOHAI) in Group B. Results: A total of 798 patients sought treatment for mandibular fractures and included 476 patients in Group A and 322 in Group B. The groups showed similar age and male: female ratio. Cases showed a steep fall during first wave of pandemic, and most of the cases occurred as result of RTA followed by fall and assault. The fractures due to fall and assault showed an obvious rise during the lockdown period. There were 718 (89.97%) patients having exclusive mandibular fractures and 80 (10.03%) patients having involvement of both mandible and maxilla. Single fractures of mandible constituted 110 (23.11%) and 58 (18.01%) in Group A and B, respectively. 324 patients (68.07%) and 226 patients (70.19%) had multiple fractures involving mandible in respective groups. Parasymphysis of mandible was most commonly involved (24.31%) followed closely by unilateral condyle (23.48%) then Angle and Ramus of mandible (20.71%) with coronoid being the least fractured. During the initial 6 months after lockdown, all the cases were treated successfully using closed reduction. GOHAI QoL assessment conducted in cases having exclusive mandibular fracture (210 Multiple, 48 Single) showed favorable results with significant (P < .05) difference between the single and multiple fractures. Conclusions: After one and half years and recovering from the second wave of pandemic that hit the country, we have come to understand COVID-19 better and embraced better management protocol. The study reveals that IMF remains the gold standard for the management of most of the facial fractures in pandemic situations. It was evident from the QoL data that most of the patients were able to carry out their day-to-day functions adequately. As the country prepares for a third wave of pandemic, management of maxillofacial trauma by closed reduction will remain the norm for most unless indicated otherwise.

Biogenic Carbon Quantum Dots as a Neoteric Inducer in the Game of Directing Chondrogenesis.

The journey into the field of stem cell biology has been an endeavor of paramount advancement in biomedicine, establishing new horizons in the avenue of materiobiology. The creative drive of the scientific community focuses on ameliorating the utilization of stem cells, which is currently untapped on a large scale. With similar motivation, we present a nascent strategy of maneuvering biogenic carbon quantum dots (CQDs) to eclipse the toxic hurdles of chemical synthesis of carbon allotropes to serve as a biocompatible trident in stem cell biology employing a three-prong action of stem cell differentiation, imaging, and migration. The derivation of CQDs from garlic peels as a biogenic precursor abets in realizing the optophysical features of CQDs to image mesenchymal stem cells without hampering the biological systems with cytotoxicity. We report the versatility of biogenic CQDs to generate reactive oxygen species (ROS) to robustly influence stem cell migration and concomitantly chondrocyte differentiation from human Wharton's jelly mesenchymal stem cells (hWJ-MSCs). This was orchestrated without the use of chondrogenic induction factors, which was confirmed from the expression of chondrogenic markers (Col II, Col X, ACAN). Even the collagen content of cells incubated with CQDs was quite comparable with that of chondrocyte-induced cells. Thus, we empirically propose garlic peel-derived CQDs as a tangible advancement in stem cell biology from a materiobiological frame of reference to hone significant development in this arena.

Prognostic significance of matrix metalloproteinase 9 in COMET operated chronic ocular Stevens-Johnson syndrome.

PURPOSE: Molecular pathogenesis underlying persistent ocular surface inflammation in chronic Stevens-Johnson syndrome (SJS) still remains largely unexplored. The present study investigates the expression of matrix metalloproteinase 2 (MMP2), MMP3, MMP9, MMP11 and TIMP1 (tissue inhibittor of matrix metalloproteinase 1) in pannus tissues of chronic ocular SJS undergoing cultivated oral mucosal epithelial transplantation (COMET) and their prognostic relevance. METHODS: In this prospective study, 45 eyes with chronic SJS underwent COMET for visual and anatomical rehabilitation. Preoperative and postoperative clinical parameters were documented. MMP2, MMP3, MMP9, MMP11 and TIMP1 expression were assessed using immunohistochemistry and quantitative real time PCR. Inflammadry MMP9 assay was performed at 1-year follow-up. Kaplan-Meier curves and Cox proportional hazard models were used to correlate protein expression with clinicopathological parameters and COMET graft survival outcomes. RESULTS: MMP9 and MMP11 positivity was seen in both pannus epithelia (48% and 55%, respectively) and in stromal layer (57% and 33%, respectively) while MMP2 and MMP3 showed only pannus epithelial positivity in 35% and 51% cases, respectively. High MMP9 stromal expression was significantly associated with preoperative corneal keratinisation (p=0.011), conjunctival hyperaemia (p=0.014), symblepharon (p=0.028). High MMP9 and MMP3 epithelial expression were found to be independent risk factors for poor best-corrected visual acuity (BCVA) outcomes post-COMET (p=0.022 and p=0.048). Multivariate analysis revealed MMP9 to be the best prognostic marker (p=0.050). CONCLUSION: Our findings suggest that differential expression of MMPs and TIMP1 is seen in SJS in chronic stage. Emergence of MMP9 as a poor prognostic predictor of BCVA post COMET and postoperative MMP9 immunoassay positivity could be a useful tool in further studies to understand the unresolved ocular surface inflammation seen in SJS.

Association of Catechol-O-Methyltransferase Gene rs4680 Polymorphism and Levodopa Induced Dyskinesia in Parkinson's Disease: A Meta-Analysis and Systematic Review.

INTRODUCTION: Long-term levodopa therapy for Parkinson's disease (PD) can cause levodopa induced dyskinesia (LID). Genetic predisposition has a significant role to play in inter-individual heterogeneity in the clinical manifestation of LID. Despite accumulating evidence for the role of COMT gene polymorphism (rs4680) as a genetic basis for LID, to date results have been inconsistent. Early assessment of the Catechol-O-Methyltransferase (COMT) genotype might be helpful to stratify PD patients concerning their individual risk for LID. METHOD: In this meta-analysis, we have used 9 studies, which were selected through online databases. Statistical analysis was performed using R (v-3.6) software. 5 genetic models have been used in the present study: Allele model (A vs. G), Dominant model (AA+AG vs. GG), Homozygote model (AA vs. GG), Co-dominant/heterozygote model (AG vs. GG), and Recessive model (AA vs. AG + GG). RESULTS: The results indicated a significant association between COMT rs4680 (Val158Met) polymorphism and LID risk. The genotype AA of COMT rs4680 is a risk factor for LID in PD patients under the recessive model (AA vs GG+AG) in the random-effect model. Analysis based on ethnicity showed that COMT rs4680 SNP allele A is a risk factor for LID development in Asian PD patients, while GG genotype is a risk factor for LID development in non-Asian PD patients using different genetic models. CONCLUSION: The results of the present meta-analysis support that the COMT Val158Met polymorphism is a risk factor for the development of LID in PD patients having ethnic variations.

A facile 3D bio-fabrication of customized tubular scaffolds using solvent-based extrusion printing for tissue-engineered tracheal grafts.

Tracheal implantation remains a major therapeutic challenge due to the unavailability of donors and the lack of biomimetic tubular grafts. Fabrication of biomimetic tracheal scaffolds of suitable materials with matched rigidity, enhanced flexibility and biocompatibility has been a major challenge in the field of tracheal reconstruction. In this study, customized tubular grafts made up of FDA-approved polycaprolactone ( PCL ) and polyurethane ( PU ) were fabricated using a novel solvent-based extrusion 3D printing. The printed scaffolds were investigated by various physical, thermal, and mechanical characterizations such as contact angle measurement, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), radial compression, longitudinal compression, and cyclic radial compression. In this study, the native goat trachea was used as a reference for the fabrication of different types of scaffolds (cylindrical, bellow-shaped, and spiral-shaped). The mechanical properties of the goat trachea were also compared to find suitable formulations of PCL / PU . Spiral-shaped scaffolds were found to be an ideal shape based on longitudinal compression and torsion load maintaining clear patency. To check the long-term implantation, in vitro degradation test was performed for all the 3D printed scaffolds and it was found that blending of PU with PCL reduced the degradation behavior. The printed scaffolds were further evaluated for biocompatibility assay, live/dead assay, and cell adhesion assay using bone marrow-derived human mesenchymal stem cells (hMSCs). From biomechanical and biological assessments, PCL 70 / PU 30 of spiral-shaped scaffolds could be a suitable candidate for the development of tracheal regenerative applications.

Management of a Rare Tessier 30 Median Mandibular Cleft Anomaly: A Comprehensive Review.

Introduction: The median mandibular cleft (MMC) is a rare craniofacial anomaly manifesting as a cleft of the lower lip and mandible, which may extend to the neck to a variable extent and severity. Its management involves a timely, staged, and multidisciplinary approach. Unlike for maxillary cleft lip and palate, the literature on this anomaly is scarce and scattered. Also, guidelines for the management of mandibular cleft are not clearly outlined. This narrative review aims to consolidate the prevalence, classification, pathophysiology, and management of MMC. Materials and methods: A literature search was performed on PubMed, SCOPUS, and Web of Science for terms "Mandibular cleft" OR "Tessier 30." From the preliminary search, n = 68 articles were hand-filtered as per relevance to MMC from the title and abstract. Results: Among these articles, n = 56 were case reports, n = 2 were articles related to genetic associations, n = 4 syndromes associated, n = 3 discussed the classification of craniofacial clefts, and n = 3 were literature reviews. The findings from the literature are presented under subheadings embryonic origin, clinical presentation, diagnostic workup, and multidisciplinary management of MMC. Conclusion: Traditionally, MMC was treated by multistep surgical procedures; however, the contemporary approach promotes early and single-step correction of both soft and hard tissue defects for better growth outcomes. These cases demand comprehensive workup and timely management. Newer innovations, such as the use of BMPs and resorbable reduction plates, need further validation. How to cite this article: Katyal S, Mohanty S, Miglani S, et al. Management of a Rare Tessier 30 Median Mandibular Cleft Anomaly: A Comprehensive Review. Int J Clin Pediatr Dent 2023;16(6):875-881.

Bone marrow-derived extracellular vesicles modulate the abundance of infiltrating immune cells in the brain and exert an antiviral effect against the Japanese encephalitis virus.

Mesenchymal stem cells (MSCs) have regenerative capacity and have reported a beneficial effect on the Japanese encephalitis virus (JEV) in an encephalitis model. However, the MSCs do not cross the blood-brain barrier and have other disadvantages limiting their therapeutic utility scope. Recently, there has been a shift in concept from a cell-based to a cell-free approach using MSCs-derived extracellular vesicles (MSC-EVs). The MSC-EVs retain regenerative and immunomodulatory capacity as their parental cells. However, the role of MSC-EVs in limiting JEV pathology remains elusive. In this study, we have used Bone marrow (BM)-derived EV (BM-EVs) and assessed their effect on JEV replication and pathogenesis in primary neuronal stem cells and a murine model. The in vitro and in vivo studies suggested that BM-derived EVs delay JEV-induced symptoms and death in mice, improve the length of survival, accelerate neurogenesis in primary neuronal stem cells, reduce JEV-induced neuronal death, and attenuate viral replication. BM-EVs treatment upregulated interferon-stimulated genes. Flow cytometry analysis revealed a reduction in the frequency of macrophages. At the same time, CD4+ T cells and neutrophils were significantly augmented, accompanied by the alteration of cytokine expression with the administration of BM-EVs, reinforcing the immunomodulatory role of EVs during JEV-induced encephalitis. In conclusion, our study describes the beneficial role of BM-EVs in limiting JEV pathology by attenuating virus replication, enhancing antiviral response, and neurogenesis in primary neuronal stem cells. However, BM-EVs do not seem to protect BBB integrity and alter immune cell infiltration into the treated brain.

Plant-derived natural products for drug discovery: current approaches and prospects.

Nature has abundant source of drugs that need to be identified/purified for use as essential biologics, either individually or in combination in the modern medical field. These drugs are divided into small bio-molecules, plant-made biologics, and a recently introduced third category known as phytopharmaceutical drugs. The development of phytopharmaceutical medicines is based on the ethnopharmacological approach, which relies on the traditional medicine system. The concept of 'one-disease one-target drug' is becoming less popular, and the use of plant extracts, fractions, and molecules is the new paradigm that holds promising scope to formulate appropriate drugs. This led to discovering a new concept known as polypharmacology, where natural products from varying sources can engage with multiple human physiology targets. This article summarizes different approaches for phytopharmaceutical drug development and discusses the progress in systems biology and computational tools for identifying drug targets. We review the existing drug delivery methods to facilitate the efficient delivery of drugs to the targets. In addition, we describe different analytical techniques for the authentication and fingerprinting of plant materials. Finally, we highlight the role of biopharming in developing plant-based biologics.