Does Platelet-Rich Plasma Deserve a Role in Accelerating the Recovery of Reflex Sympathetic Dystrophy Following Distal Radius Fracture?

Introduction: This study was to evaluate the efficacy of multiple platelet-rich plasma injections in reflex sympathetic dystrophy following distal radius fracture after previous various treatments have failed. Materials and methods: This comparative prospective study was designed for 64 patients of reflex sympathetic dystrophy developed following distal radius fracture, from January 2009 to December 2020 were enrolled in this study. This cohort of patient was given either four multiple subcutaneous platelet-rich plasma injections at weekly interval (n = 32) or two injections in a month with 15 days interval (n = 32). The primary outcome measure assessed with patient rated wrist evaluation questionnaire score. The secondary outcome was a visual analogue scale pain score. The final follow up was at 2 years. p ≤ 0.05 is considered statistically. Results: The patient rated wrist evaluation score for usual and specific activities and EQ-VAS for pain level showed statistically significant greater improvement in group A (42 ± 21%) compared to group B (19 ± 24%), (p = 0.37). Patients also had improvement in wrist movements with no statistically significant differences in both groups. The standard difference in means of all three functional scores was almost similar between both groups A and B (standard difference in means = 0.032; 95% CI 0.236-0.830; p = 0.495), considered clinically meaningful. Conclusion: This study results suggest autologous platelet-rich plasma injections seem to be safe, cost effective, efficacious algorithm treatment for reflex sympathetic dystrophy following distal radius fracture patients where previous treatments have failed.

Clobetasol propionate, a Nrf-2 inhibitor, sensitizes human lung cancer cells to radiation-induced killing via mitochondrial ROS-dependent ferroptosis.

Combining radiotherapy with Nrf-2 inhibitor holds promise as a potential therapeutic strategy for radioresistant lung cancer. Here, the radiosensitizing efficacy of a synthetic glucocorticoid clobetasol propionate (CP) in A549 human lung cancer cells was evaluated. CP exhibited potent radiosensitization in lung cancer cells via inhibition of Nrf-2 pathway, leading to elevation of oxidative stress. Transcriptomic studies revealed significant modulation of pathways related to ferroptosis, fatty acid and glutathione metabolism. Consistent with these findings, CP treatment followed by radiation exposure showed characteristic features of ferroptosis in terms of mitochondrial swelling, rupture and loss of cristae. Ferroptosis is a form of regulated cell death triggered by iron-dependent ROS accumulation and lipid peroxidation. In combination with radiation, CP showed enhanced iron release, mitochondrial ROS, and lipid peroxidation, indicating ferroptosis induction. Further, iron chelation, inhibition of lipid peroxidation or scavenging mitochondrial ROS prevented CP-mediated radiosensitization. Nrf-2 negatively regulates ferroptosis through upregulation of antioxidant defense and iron homeostasis. Interestingly, Nrf-2 overexpressing A549 cells were refractory to CP-mediated ferroptosis induction and radiosensitization. Thus, this study identified anti-psoriatic drug clobetasol propionate can be repurposed as a promising radiosensitizer for Keap-1 mutant lung cancers.

Txnrd1 as a prognosticator for recurrence, metastasis and response to neoadjuvant chemotherapy and radiotherapy in breast cancer patients.

Thioredoxin reductase 1 (Txnrd1) is known to have prognostic significance in a subset of breast cancer patients. Despite the pivotal role of Txnrd1 in regulating several cellular and physiological processes in cancer progression and metastasis, its clinical significance is largely unrecognized. Here, we undertook a retrospective comprehensive meta-analysis of 13,322 breast cancer patients from 43 independent cohorts to assess prognostic and predictive roles of Txnrd1. We observed that Txnrd1 has a positive correlation with tumor grade and size and it is over-expressed in higher-grade and larger tumors. Further, hormone receptor-negative and HER2-positive tumors exhibit elevated Txnrd1 gene expression. Patients with elevated Txnrd1 expression exhibit significant hazards for shorter disease-specific and overall survival. While Txnrd1 has a positive correlation with tumor recurrence and metastasis, it has a negative correlation with time to recurrence and metastasis. Txnrd1High patients exhibit 2.5 years early recurrence and 1.3 years early metastasis as compared to Txnrd1Low cohort. Interestingly, patients with high Txnrd1 gene expression exhibit a pathologic complete response (pCR) to neoadjuvant chemotherapy, but they experience early recurrence after radiotherapy. Txnrd1High MDA-MB-231 cells exhibit significant ROS generation and reduced viability after doxorubicin treatment compared to Txnrd1Low MCF7 cells. Corroborating with findings from meta-analysis, Txnrd1 depletion leads to decreased survival, enhanced sensitivity to radiation induced killing, poor scratch-wound healing, and reduced invasion potential in MDA-MB-231 cells. Thus, Txnrd1 appears to be a potential predictor of recurrence, metastasis and therapy response in breast cancer patients.

Distinct spectral signatures unfold ECM stiffness-triggered biochemical changes in breast cancer cells.

Cancer progression often accompanies the stiffening of extracellular matrix (ECM) in and around the tumor, owing to extra deposition and cross-linking of collagen. Stiff ECM has been linked with poor prognosis and is known to fuel invasion and metastasis, notably in breast cancer. However, the underlying biochemical or metabolic changes and the cognate molecular signatures remain elusive. Here, we explored Raman spectroscopy to unveil the spectral fingerprints of breast cancer cells in response to extracellular mechanical cues. Using stiffness-tuneable hydrogels, we showed that cells grown on stiff ECM displayed morphological changes with high proliferation. We further demonstrated that Raman Spectroscopy, a label-free and non-invasive technique, could provide comprehensive information about the biochemical environment of breast cancer cells in response to varying ECM stiffness. Raman spectroscopic analysis classified the cells into distinct clusters based on principal component-based linear discriminant analysis (PC-LDA). Multivariate curve resolution-alternating least squares (MCR-ALS) analysis indicated that cells cultured on stiff ECM exhibited elevated nucleic acid content and lesser lipids. Interestingly, increased intensity of Raman bands corresponding to cytochrome-c was also observed in stiff ECM conditions, suggesting mitochondrial modulation. The key findings harboured by spectral profiles were also corroborated by transmission electron microscopy, confirming altered metabolic status as reflected by increased mitochondria number and decreased lipid droplets in response to ECM stiffening. Collectively, these findings not only give the spectral signatures for mechanoresponse but also provide the landscape of biochemical changes in response to ECM stiffening.

Efficacy and safety of fixed dose combination of Sitagliptin, metformin, and pioglitazone in type 2 Diabetes (IMPACT study): a randomized controlled trial.

BACKGROUND: Due to the progressive decline in ß-cell function, it is often necessary to utilize multiple agents with complementary mechanisms of action to address various facets and achieve glycemic control. Thus, this study aimed to evaluate the efficacy and safety of a fixed-dose combination (FDC) of metformin/sitagliptin/pioglitazone (MSP) therapy vs. metformin/sitagliptin (MS) in type 2 diabetes mellitus (T2DM). METHODS: In this phase 3, multicenter, double-blind study, patients with T2DM who exhibited inadequate glycemic control with HbA1c of 8.0-11.0% while taking ≥1500 mg/day metformin for at least 6 weeks were randomized to receive either FDC of MSP (1000/100/15 mg) or MS (1000/100 mg) per day for 24 weeks. The primary outcome measure was the change in HbA1c, and secondary outcomes included changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and body weight from baseline to 24 weeks along with safety and tolerability. RESULTS: Among the 236 patients randomized, 207 (87.71%) successfully completed the study. All baseline characteristics were comparable between the FDC of MSP and MS groups. There was a subsequent significant reduction of HbA1c in FDC of MSP (- 1.64) vs. MS (- 1.32); between groups was [- 0.32% (95% CI, - 0.59, - 0.05)], P = 0.0208. Similar reductions were found in FPG [- 13.2 mg/dL (95% CI, - 22.86, - 3.71)], P = 0.0068, and PPG [- 20.83 mg/dL (95% CI, - 34.11, - 7.55)], P = 0.0023. There were no significant changes in body weight. A total of 27 adverse effects (AEs) and one severe AE were reported, none of which were related to the study drug. CONCLUSION: The FDC of MSP demonstrated significant efficacy in managing glycemic indices and could serve as a valuable tool for physicians in the management of Indian patients with T2DM. TRIAL REGISTRATION: Clinical Trials Registry of India, CTRI/2021/10/037461.

Mitochondrial-targeted curcumin inhibits T-cell activation via Nrf2 and inhibits graft-versus-host-disease in a mouse model.

Anti-inflammatory and immune suppressive agents are required to moderate hyper-activation of lymphocytes under disease conditions or organ transplantation. However, selective disruption of mitochondrial redox has not been evaluated as a therapeutic strategy for suppression of T-cell-mediated pathologies. Using mitochondrial targeted curcumin (MitoC), we studied the effect of mitochondrial redox modulation on T-cell responses by flow cytometry, transmission electron microscopy, transcriptomics, and proteomics, and the role of Nrf2 was studied using Nrf2- /- mice. MitoC decreased mitochondrial TrxR activity, enhanced mitochondrial ROS (mROS) production, depleted mitochondrial glutathione, and suppressed activation-induced increase in mitochondrial biomass. This led to suppression of T-cell responses and metabolic reprogramming towards Treg differentiation. MitoC induced nuclear translocation and DNA binding of Nrf2, leading to upregulation of Nrf2-dependent genes and proteins. MitoC-mediated changes in mitochondrial redox and modulation of T-cell responses are abolished in Nrf2- /- mice. Restoration of mitochondrial thiols abrogated inhibition of T-cell responses. MitoC suppressed alloantigen-induced lymphoblast formation, inflammatory cytokines, morbidity, and mortality in acute graft-versus-host disease mice. Disruption of mitochondrial thiols but not mROS increase inculcates an Nrf2-dependent immune-suppressive disposition in T cells for the propitious treatment of graft-versus-host disease.

Repurposing of FDA approved kinase inhibitor bosutinib for mitigation of radiation induced damage via inhibition of JNK pathway.

Radiotherapy is a common modality for cancer treatment. However, it is often associated with normal tissue toxicity in 20-80% of the patients. Radioprotectors can improve the outcome of radiotherapy by selectively protecting normal cells against radiation toxicity. In the present study, compound libraries containing 54 kinase inhibitors and 80 FDA-approved drugs were screened for radioprotection of lymphocytes using high throughput cell analysis. A second-generation FDA-approved kinase inhibitor, bosutinib, was identified as a potential radioprotector for normal cells. The radioprotective efficacy of bosutinib was evinced from a reduction in radiation induced DNA damage, caspase-3 activation, DNA fragmentation and apoptosis. Oral administration of bosutinib protected mice against whole body irradiation (WBI) induced morbidity and mortality. Bosutinib also reduced radiation induced bone-marrow aplasia and hematopoietic damage in mice exposed to 4 Gy and 6 Gy dose of WBI. Mechanistic studies revealed that the radioprotective action of bosutinib involved interaction with cellular thiols and modulation of JNK pathway. The addition of glutathione and N-acetyl cysteine significantly reduced the radioprotective efficacy of bosutinib. Moreover, bosutinib did not protect cancer cells against radiation induced toxicity. On the contrary, bosutinib per se exhibited anticancer activity against human cancer cell lines. The results highlight possible use of bosutinib as a repurposable radioprotective agent for mitigation of radiation toxicity in cancer patients undergoing radiotherapy.

Is There a Case for Case-Based Learning in Pharmacology?

Background In a didactic lecture (DL), students listen, take notes, and passively accept the knowledge. Case-based learning (CBL) uses clinical cases for active learning and productive outcome. Although some studies have shown that DL is less effective than CBL, the results were inconclusive. Hence, this study aimed to evaluate the effectiveness of CBL in pharmacology. Methodology This study involved 80 second-year medical students divided into two groups. The results of post-test scores and retention test one month later were compared between the groups using multiple-choice questions. Results DL showed statistically significant better outcomes in immediate learning compared to CBL in both groups (p = 0.000 and 0.002). Although there were slightly better retention scores for CBL compared to DL in both groups, it was not statistically significant. Conclusions DL showed significantly better immediate learning outcomes compared to CBL, with no difference in long-term outcomes for both teaching-learning methods. Hence, DL continues to be the gold standard for teaching pharmacology.

Evaluation of anterior tooth-ridge angulation, root position and labial bone perforation using dental cone-beam computed tomography: An observational study.

Purpose: The objective of this study was to use cone-beam computed tomography (CBCT) scans to measure and correlate the maxillary and mandibular tooth-ridge angulation (TRA) and labial bone perforation (LBP) in anterior teeth. Materials and Methods: A standardized technique was used to orientate Planmeca CBCT images in 140 patients. On the sagittal section, TRA was defined as the angle between the long axis of the tooth and the alveolar housing of the corresponding tooth. The maxillary and mandibular anterior teeth's sagittal root locations were evaluated. Virtual implant software was used to analyze bone perforations using a predetermined taper implant system. Results: A total of 1680 teeth were scanned for this investigation, and 1338 teeth were selected for further analysis. In comparison to the mandible, the maxilla had a greater TRA. LBP was found to be 4.26% (57 teeth) more common in the mandibular arch (n = 39; 68.42 and) than in the maxillary arch (n = 18; 31.58%). When comparing both the sides, there was no significant difference in LBP. There was a significant relationship between TRA and LBP (P < 0.05). There was a significant association between all parameters. There was no statistically significant difference in TRA, sagittal root position (SRP), and LBP between the right and left teeth. Conclusions: The SRP type 1 is most typically present in the anterior teeth. The maxillary anterior teeth were placed at a 5°-10° angle, while the mandibular incisors were parallel to the alveolar ridge. The LBP was more characteristically present in the mandibular incisors. SRP and TRA were directly correlated with LBP. Clinically, bone perforations may be reduced using taper implants and abutments with a 5°-10° angle in maxillary anterior teeth, while straight implants are preferred in mandibular anterior teeth, which may be recommended.

Malabaricone C, a constituent of spice Myristica malabarica, exhibits anti-inflammatory effects via modulation of cellular redox.

The present study primarily focuses on the efficacy of Malabaricone C (Mal C) as an anti-inflammatory agent. Mal C inhibited mitogen-induced T-cell proliferation and cytokine secretion. Mal C significantly reduced cellular thiols in lymphocytes. N-acetyl cysteine (NAC) restored cellular thiol levels and abrogated Mal C-mediated inhibition of T-cell proliferation and cytokine secretion. Physical interaction between Mal C and NAC was evinced from HPLC and spectral analysis. Mal C treatment significantly inhibited concanavalin A-induced phosphorylation of ERK/JNK and DNA binding of NF-κB. Administration of Mal C to mice suppressed T-cell proliferation and effector functions ex vivo. Mal C treatment did not alter the homeostatic proliferation of T-cells in vivo but completely abrogated acute graft-versus-host disease (GvHD)-associated morbidity and mortality. Our studies indicate probable use of Mal C for prophylaxis and treatment of immunological disorders caused due to hyper-activation of T-cells.

A split-mouth randomised controlled trial comparing the clinical effects of MVISTA with chorion membrane or connective tissue graft in multiple gingival recessions.

Objectives: Modified form of VISTA (MVISTA), a novel surgical procedure, aims at comprehensive root coverage that maintains the inner continuity of the periosteum and papilla. This technique incorporates any regenerative graft material within the tunnel. The objective of study is to compare the MVISTA for treating multiple adjacent gingival recessions and chorion membranes or grafts of connective tissues. Materials and methods: This is a split-mouth type randomized trial. In this trial total of 18 patients were considered. The patients in this trial had multiple adjacent, gingival recessions of Miller's Classes I/II, and they were randomized to either the MVISTA with chorion membrane (test) or connective tissue graft (CTG) (control) group. A baseline and one year after surgery were considered for recording to mean root coverage (MRC), complete root coverage (CRC), and clinical periodontal parameters. An intragroup comparison was made. Results: The intragroup comparison of recession depth baseline and 12 months after-surgery record found a significant difference between the two groups (P = 0.00). In the postoperative condition, the depth of recession reduction was higher in the test group than in the control group. However, from a statistical perspective, the difference was insignificant (P > 0.05). At the end of the year, it was found that the width of the keratinized tissue had increased significantly (P < 0.05). The MRC in the test group was significantly higher (91.33 %±8.17 %) than that in the control group (89.46 %±11.22 %) (P > 000). At the end of 1 year, the test group showed 66.67 % CRC compared to 44.44 % in the control group. The gingival phenotype displayed statistically significant improvement in the test group (p = 0.004). PD and CAL showed statistically nonsignificant outcomes (P > 0.05). Conclusions: As far as multiple adjacent gingival recession treatment is concerned, MVISTA with chorion membrane treatment enhanced the gingival phenotype, restored complete root coverage (66.6%), and increased the width of keratinized tissue. CTG and CM demonstrated good root coverage results; the latter might be used as a substitute graft to treat multiple recessions.

Withaferin A, a steroidal lactone, selectively protects normal lymphocytes against ionizing radiation induced apoptosis and genotoxicity via activation of ERK/Nrf-2/HO-1 axis.

Increasing use of ionizing radiation (IR) in medicine, industry, agriculture and research ensues potential health hazards if not used properly or contained effectively. However, radioprotectors which are effective in clinical and/or accidental radiation exposures are still elusive. In this direction, we have explored the radioprotective potential of Withaferin A, a plant withanolide, which was recently shown to be safe and well tolerated in cancer patients in a clinical trial and is also known to be a radio-sensitizer in cancer cells. Our results show that, Withaferin A (WA) protected only normal lymphocytes, but not cancer cells, against IR-induced apoptosis and offered radioprotection even when added post-radiation exposure. WA treatment led to significant inhibition of IR-induced caspase-3 activation and decreased IR-induced DNA damage to lymphocytes and bone-marrow cells. WA reduced intracellular ROS and GSH levels and only thiol based anti-oxidants could abrogate the radio-protective effects of WA, indicating a crucial role of cellular/protein thiols in its biological activity. The inability of WA-glutathione adduct to offer radioprotection further underscored the role of cellular thiols. WA induced pro-survival transcription factor, Nrf-2, and expression of cytoprotective genes HO-1, catalase, SOD, peroxiredoxin-2 via ERK. Further, WA administration could rescue mice against radiation induced mortality, DNA damage, increase in micro-nucleated polychromatic erythrocytes (mn-PCEs) and increased ratio of polychromatic erythrocytes (PCEs) to Normochromatic Erythrocytes (NCEs) in bone-marrow, demonstrating its potent in vivo the radio-protective efficacy. In conclusion, WA selectively protects normal cells against IR-induced apoptosis via activation of cytoprotective Nrf-2 pathway.

Jack of all trades: Genome assembly of Wild Jack and comparative genomics of Artocarpus.

Artocarpus (Moraceae), known as breadfruits for their diverse nutritious fruits, is prized for its high-quality timber, medicinal value, and economic importance. Breadfruits are native to Southeast Asia but have been introduced to other continents. The most commonly cultivated species are Artocarpus heterophyllus (Jackfruit) and Artocarpus altilis (Breadfruit). With numerous smaller but nutritionally comparable fruits on a larger tree, Artocarpus hirsutus, also called "Wild Jack" or "Ayani", is an elusive forest species endemic to Indian Western Ghats. In this study, we sequenced and assembled the whole genome of Artocarpus hirsutus sampled from the sacred groves of Coorg, India. To decipher demographic and evolutionary history, we compared our Wild Jack genome with previously published Jackfruit and Breadfruit genomes. Demographic history reconstruction indicates a stronger effect of habitat rather than phylogeny on the population histories of these plants. Repetitive genomic regions, especially LTR Copia, strongly affected the demographic trajectory of A. heterophyllus. Upon further investigation, we found a recent lineage-specific accumulation of LTR Copia in A. heterophyllus, which had a major contribution to its larger genome size. Several genes from starch, sucrose metabolism, and plant hormone signal transduction pathways, in Artocarpus species had signatures of selection and gene family evolution. Our comparative genomic framework provides important insights by incorporating endemic species such as the Wild Jack.

The Joining of Copper to Stainless Steel by Solid-State Welding Processes: A Review.

Joining immiscible materials such as copper and stainless steel together is a significant concern due to distinct mechanical and metallurgical properties across the joint line, such as melting points, the coefficient of linear thermal expansion, and thermal conductivity. The joint properties of copper to stainless steel welds are in great demand for various mechanical components of the international thermonuclear experimental reactor, ultra-high vacuum system, plan wave linear-accelerator or linac structure, and heat exchanger. These dissimilar-metals joints offer excellent flexibility in design and production, leading to a robust structure for many cutting-edge applications. Hence, the present article reviews the copper to stainless steel joining mechanism under different solid-state processing conditions. The present understanding says that defect-free strong joints between the dissimilar metals are systematically possible. Apart from this understanding, the authors have identified and highlighted the gaps in the research exploration to date. Moreover, a sustainable methodology to achieve a desirable weld of copper to stainless steel depends on favorable processing conditions.

A real world multi center study on efficacy and safety of natalizumab in Indian patients with multiple sclerosis.

BACKGROUND: Natalizumab (NTZ) is increasingly being used in Indian multiple sclerosis (MS) patients. There are no reports on its safety and efficacy, especially with respect to the occurrence of progressive multifocal leukoencephalopathy (PML). OBJECTIVES: To describe the patient characteristics, treatment outcomes, and adverse events, especially the occurrence of PML in NTZ-treated patients. METHODS: A multicentre ambispective study was conducted across 18 centres, from Jan 2012 to Dec 2021. Patients at and above the age of 18 years treated with NTZ were included. Descriptive and comparative statistics were applied to analyze data. RESULTS: During the study period of 9 years, 116 patients were treated with NTZ. Mean age of the cohort was 35.6 ± 9.7 years; 83/116 (71.6%) were females. Relapse rate for the entire cohort in the year before NTZ was 3.1 ± 1.51 while one year after was 0.20±0.57 (p = 0.001; CI 2.45 -3.35). EDSS of the entire cohort in the year before NTZ was 4.5 ± 1.94 and one year after was 3.8 ± 2.7 (p = 0.013; CI 0.16-1.36). At last follow up (38.3 ± 22.78 months) there were no cases of PML identified. CONCLUSIONS: Natalizumab is highly effective and safe in Indian MS patients, with no cases of PML identified at last follow up.

Effectiveness of methylene blue photosensitizers compared to that of corticosteroids in the management of oral lichen planus: a systematic review and meta-analysis.

This study aimed to systematically review the effectiveness of methylene blue (MB) photosensitizers in the management of symptomatic oral lichen planus (OLP). Electronic online databases and manual searches were performed for randomized controlled trials (RCTs) published in English between January 2010 and February 2022. RCTs comparing photodynamic therapy (PDT) and corticosteroid therapy at baseline and follow-up period were identified. The Cochrane risk of bias tool was used to assess the quality of the included studies. A meta-analysis was performed regarding visual analog scale (VAS) scores, Thongprasom sign scores, lesion size, response to treatment, and exacerbation of lesions after therapy. The clinical severity was analyzed qualitatively. Five RCTs consisting of 180 samples fulfilled the inclusion and exclusion criteria. All parameters of VAS score, Thongprasom sign score, lesion size, and response to treatment were statistically non-significant. Our results indicate that both MB-PDT and corticosteroid therapy are effective for the management of OLP. Moreover, MB-PDT is an effective alternative treatment option for OLP when corticosteroids are contraindicated. However, conclusive evidence cannot be ascertained owing to the heterogeneity among the studies.

Thioredoxin reductase: An emerging pharmacologic target for radiosensitization of cancer.

Novel agents are required to increase the radiosensitivity of cancer and improve the outcome of radiotherapy. Thioredoxin (Trx) and thioredoxin reductase (TrxR) reduce the oxidized cysteine thiols in several proteins, which regulate cellular redox, survival, proliferation, DNA synthesis, transcription factor activity and apoptosis. TrxR is essential for maintaining a conducive redox state for tumor growth, survival and resistance to therapy. Therefore, it is an appealing pharmacological target for the radiosensitization of tumors. Ionizing radiation (IR) is known to cause cytotoxicity through ROS, oxidative stress and DNA damage. Inhibition of thioredoxin system augments IR induced oxidative stress and potentiates cytotoxic effects. However, TrxR also regulates several critical cellular processes in normal cells. Here, we highlight the pre-clinical research and pharmacological studies to surmise possible utility of different TrxR inhibitors for radiosensitization. This review provides a succinct perspective on the role of TrxR inhibitors during the radiotherapy of cancer.

An In Vitro Evaluation of Ice Apple as a Novel Storage Medium to Preserve the Viability of Human Periodontal Ligament Fibroblasts.

Aim: For a better prognosis of an avulsed tooth, it is important to store it in an appropriate storage medium prior to replantation. The purpose of this study was to evaluate the ability of ice apples to preserve the viability of periodontal ligament (PDL) fibroblasts. Materials and methods: Periodontal ligament (PDL) fibroblasts were procured from the roots of healthy premolars and cultured in Dulbecco's Modified Eagle's Medium (DMEM). They were preserved with-ice apple water (IAW), 30 and 10% ice apple fruit pulp extract (IAFPE), DMEM, negative control without any agent, and positive control DMEM supplemented with fetal bovine serum (FBS). Culture plates were incubated with investigational media at 37°C for 1, 3, and 24 hours. Each experiment was repeated thrice. Assessment of cell viability was done using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium reduction (MTT) assay. After every test period, storage media was removed; 60 µL of MTT solution was added to each well and incubated for 3 hours at 37°C. The supernatant was aspirated and the formazan blue crystals formed were solubilized using dimethyl sulphoxide (DMSO) (100 µL). Optical density was measured at a wavelength of 490 nm. The effects of the test storage media at each time period were evaluated by a one-way analysis of variance (ANOVA) test, and this was followed by post hoc Tukey's multiple comparison tests (p < 0.05). Results: A total of 10% IAFPE demonstrated the maximum capacity to maintain PDL cell viability in all three test periods (p = 0.001). Among the different forms of ice apple used in this study, IAFPE showed better results as compared to IAW (p = 0.001). Conclusion: Ice apple fruit pulp extract (IAFPE) at 10% concentration showed the maximum capacity to maintain PDL cell viability across all three test periods. Therefore, it can be considered a suitable alternative natural storage medium for avulsed teeth. However, further, more detailed studies are required in this field. How to cite this article: Bijlani S, Shanbhog RS. An In Vitro Evaluation of Ice Apple as a Novel Storage Medium to Preserve the Viability of Human Periodontal Ligament Fibroblasts. Int J Clin Pediatr Dent 2022;15(6):699-703.

Shoulder Injury Following Overzealous Manipulation in Adhesive Capsulitis by Untrained Professional Managed with Shoulder Arthroscopy.

Introduction: Adhesive capsulitis of shoulder is a commoner condition in middle aged population and is classified into primary and secondary types based on etiology. Treatment options depend on stages of disease which ranges from physical therapy, non-steroidal anti-inflammatory medications, intra-articular steroid injection, hydro-dilatation therapy, manipulation under anesthesia, and arthroscopic capsular release. However, the condition is generally mismanaged by untrained professionals in the periphery center leading to complications. We report one such case, which was then managed arthroscopically. Case Report: A 58-year-old female patient presented to our outpatient department with a severe painful left shoulder following overzealous manipulation by untrained professional and she was diagnosed with severe traumatic capsulosynovitis with a subscapularis tear, biceps tendon subluxation, and shoulder subluxation. We managed patient arthroscopically with extensive capsulosynovectomy, biceps tenotomy, and upper subscapularis repair. Postoperatively, she was immobilized for 6 weeks and was put on proper rehabilitation program. At the 2-year follow-up, the patient had an excellent outcome and had complete pain-free movements at the left shoulder with significant increase in pre-operative constant shoulder score of 12-82. Conclusion: ?Overzealous manipulation shoulder in frozen shoulder patients has serious complications and has to be avoided and therefore has to be done by trained professional gently under anesthesia. Shoulder arthroscopy plays a pivotal role in managing such complications successfully.

Effectiveness of hyaluronic acid in the management of oral lichen planus: a systematic review and meta-analysis.

Oral lichen planus (OLP) is a chronic inflammatory immune-mediated condition that has been identified as a potentially malignant oral disorder. Various therapies have been proposed for its management as alternative to corticosteroids. However, no definitive treatment has been identified that can result in complete remission or minimal recurrence. Hyaluronic acid has recently been used as an alternative therapy for the management of OLP. This study aimed to systematically review the effectiveness of Hyaluronic acid in the management of symptomatic OLP. Online electronic databases and manual searches were performed for randomized controlled trials (RCTs) published in English between January 2010 and April 2022. RCTs were identified that compared the efficacy of hyaluronic acid and other interventional therapies at baseline and during follow-up. The Cochrane Risk of Bias tool was used to assess the quality of the included studies. Visual analog scale (VAS) scores, Thongprasom sign scores, lesion size, degree of erythema, clinical severity, and disease severity were assessed both quantitatively and qualitatively. Seven studies were analyzed. Five studies reported a high risk of bias while the remaining two studies reported an unclear risk of bias. The overall quantitative assessment of size, symptoms, degree of erythema, and sign score in OLP lesions treated with HA was not statistically significant compared to that in the control group (P > 0.05). In addition, subgroup analysis comparing HA with placebo or corticosteroids did not yield statistically significant (P > 0.05) results. Qualitatively, both HA and tacrolimus resulted in an effective reduction in signs and symptoms. Clinical/disease severity index/scores were inconsistent. A high degree of heterogeneity was observed among the included studies. None of the included studies reported the side effects of HA. These findings suggest that corticosteroids, tacrolimus, placebo, and HA could be equally effective in OLP management. The clinical/disease severity index or score reduction cannot be determined with certainty. Thus, OLP can be treated with HA as an alternative therapy. Owing to limited clinical trials on HA, high heterogeneity, and high risk of bias in the included studies, definitive conclusions cannot be derived.