Therapeutic Potential of Platelet-Rich Plasma in Fracture Healing: A Comprehensive Review.

Fracture healing is a dynamic process essential for the restoration of bone integrity and function. However, factors such as patient age, comorbidities, and the severity of the fracture can impede this process, leading to delayed healing or nonunion. Platelet-rich plasma (PRP) has emerged as a promising therapeutic option for enhancing fracture healing. PRP is an autologous blood product containing a concentrated mixture of platelets, growth factors, and cytokines known to promote tissue regeneration and repair. This comprehensive review provides an overview of the fracture healing process, emphasizing the importance of timely and efficient bone repair. We discuss the mechanisms underlying the purported efficacy of PRP in fracture healing, drawing upon both preclinical and clinical evidence. Preclinical studies in animal models have demonstrated the ability of PRP to accelerate fracture healing, stimulate osteogenesis, and enhance bone regeneration. Clinical studies have yielded mixed results, with some reporting positive outcomes in terms of accelerated healing and improved functional outcomes, while others have shown no significant benefits over standard treatments. Factors influencing the efficacy of PRP, such as timing of administration, PRP concentration, and patient-specific variables, are also examined. Furthermore, safety considerations and potential adverse effects associated with PRP therapy are discussed. Despite the promising preclinical findings, challenges remain in standardizing PRP formulations, optimizing administration protocols, and addressing unanswered questions regarding its long-term efficacy and safety. This review aims to provide insights into the therapeutic potential of PRP in fracture healing, informing future research directions and guiding clinical practice.

Population infection estimation from wastewater surveillance for SARS-CoV-2 in Nagpur, India during the second pandemic wave.

Wastewater-based epidemiology (WBE) has emerged as an effective environmental surveillance tool for predicting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease outbreaks in high-income countries (HICs) with centralized sewage infrastructure. However, few studies have applied WBE alongside epidemic disease modelling to estimate the prevalence of SARS-CoV-2 in low-resource settings. This study aimed to explore the feasibility of collecting untreated wastewater samples from rural and urban catchment areas of Nagpur district, to detect and quantify SARS-CoV-2 using real-time qPCR, to compare geographic differences in viral loads, and to integrate the wastewater data into a modified Susceptible-Exposed-Infectious-Confirmed Positives-Recovered (SEIPR) model. Of the 983 wastewater samples analyzed for SARS-CoV-2 RNA, we detected significantly higher sample positivity rates, 43.7% (95% confidence interval (CI) 40.1, 47.4) and 30.4% (95% CI 24.66, 36.66), and higher viral loads for the urban compared with rural samples, respectively. The Basic reproductive number, R0, positively correlated with population density and negatively correlated with humidity, a proxy for rainfall and dilution of waste in the sewers. The SEIPR model estimated the rate of unreported coronavirus disease 2019 (COVID-19) cases at the start of the wave as 13.97 [95% CI (10.17, 17.0)] times that of confirmed cases, representing a material difference in cases and healthcare resource burden. Wastewater surveillance might prove to be a more reliable way to prepare for surges in COVID-19 cases during future waves for authorities.

Successful Surgical Management of a Giant Cell Tumor in the Proximal Tibia: A Case Report.

Giant cell tumors (GCTs) of the bone present unique challenges in management due to their locally aggressive nature and potential for recurrence. This case report describes the successful surgical management of a GCT located in the proximal tibia of a 28-year-old female. The patient presented with six months of pain and swelling following a traumatic injury to the knee. Diagnostic imaging confirmed the presence of a GCT, leading to preoperative prophylactic embolization to reduce intraoperative bleeding. Surgical excision of the tumor was performed, followed by reconstruction using autologous fibula grafts and plate fixation. Postoperative care included analgesia, antibiotics, and physiotherapy. Regular follow-up demonstrated satisfactory clinical outcomes without evidence of recurrence. This case highlights the importance of a multidisciplinary approach combining surgical expertise, preoperative planning, and postoperative rehabilitation to achieve favorable outcomes in managing GCTs.

Optimizing Acetabular Positioning: A Comprehensive Review of Contemporary Strategies in Total Hip Arthroplasty.

Total hip arthroplasty (THA) is a widely practiced surgical intervention to alleviate pain and reinstate functionality in individuals afflicted with hip joint pathology. The positioning of the acetabulum assumes paramount significance in determining the efficacy of THA, exerting profound influences on biomechanical dynamics, stability, and the durability of outcomes over time. This comprehensive review meticulously evaluates contemporary methodologies for optimizing acetabular positioning in THA, encompassing advanced technologies such as computer-assisted navigation systems, patient-specific instrumentation, robotic-assisted surgical approaches, image-based planning techniques, and intraoperative fluoroscopy. Crucially, key discoveries underscore the pivotal role of precise acetabular alignment in mitigating complications such as dislocation, component wear, and impingement. Moreover, the implications for clinical practice accentuate the imperative of continuous education and training to ensure effective deployment of sophisticated methodologies. Recommendations for furthering research and enhancing practice development underscore the necessity of scrutinizing long-term prognoses, assessing cost-effectiveness, and embracing technological innovations perpetually refining THA outcomes. Collaborative endeavors among researchers, practitioners, and industry stakeholders emerge as indispensable drivers of advancement in this domain, fostering an environment conducive to elevating the standard of care for individuals undergoing THA.

Unveiling Enigma: Navigating the Diagnostic Labyrinth of an Atypical Medial Clavicular Enchondroma.

Benign cartilaginous lesions called enchondromas usually appear in the long bones of the limbs. This case report, however, draws attention to an uncommon and unusual appearance of enchondroma near the medial end of clavicle. Because of the unusual location, the diagnostic process was very complex, which presented a challengefor the physicians. We provide the clinical, radiological and histological results that finally allowed for an accurate diagnosis. This example highlights the need of taking into account atypical location for benign lesions and highlights the necessity of a thorough diagnostic approach in unexpected clinical settings. Since the occurrence of clavicular enchondromas is a rare entity and can at times mislead the clinician, healthcare providers must be vigilant enough to guarantee a prompt and accurate diagnosis for timely intervention.

A Comprehensive Review of Platelet-Rich Plasma and Its Emerging Role in Accelerating Bone Healing.

This comprehensive review delves into the emerging role of platelet-rich plasma (PRP) in accelerating bone healing. PRP, a blood-derived product rich in platelets and growth factors, has garnered attention for its regenerative potential. The review begins by defining PRP and providing a historical background, highlighting its significance in expediting bone healing. PRP's composition and preparation methods, including centrifugation techniques and commercial kits, are explored. Mechanistically, PRP operates by releasing growth factors, chemotaxis, and angiogenesis, elucidating its cellular effects. Applications in fracture healing and orthopaedic surgeries, such as joint arthroplasty and spinal fusion, are discussed, emphasising the promising outcomes in clinical trials. Safety considerations, patient selection criteria, and the need for PRP preparation and application standardisation are underscored. The review outlines ongoing research trends, potential technological advancements, and unexplored areas in paediatric applications and inflammatory bone disorders. The implications for clinical practice involve informed decision-making, optimised protocols, and interdisciplinary collaboration. In conclusion, the future of PRP in bone healing holds exciting prospects, with the potential for precision medicine, integration with emerging therapies, expanded applications, and enhanced technological innovations shaping its trajectory in orthopaedics and regenerative medicine.

Navigating the Therapeutic Landscape: A Comprehensive Review of Platelet-Rich Plasma and Bone Marrow Aspirate Concentrate in Knee Osteoarthritis.

This comprehensive review provides an in-depth analysis of platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) as potential treatments for knee osteoarthritis. It explores their mechanisms of action, clinical efficacy, safety considerations, and the importance of personalised treatment approaches. The review highlights promising findings regarding the ability of PRP and BMAC to alleviate symptoms, improve joint function, and potentially slow disease progression. It emphasises the need for further research into long-term outcomes, direct comparative studies, protocol standardisation, biomarker identification, and cost-effectiveness assessments to enhance clinical practice. While the review does not directly compare PRP and BMAC, it provides valuable insights into their respective roles in knee osteoarthritis management. The review aims to contribute to evidence-based advancements in regenerative therapies for knee osteoarthritis by addressing critical research priorities and refining treatment strategies.

Reconstructive Surgical Intervention for Malunited Distal End Radius and Ulna Fracture: A Case Report Demonstrating Improved Patient Outcomes.

This case report explores the efficacy of reconstructive surgical intervention in addressing malunited fractures of the distal end of the radius and ulna. The study presents a detailed analysis of a specific case, highlighting the surgical techniques employed and their impact on patient outcomes. The report emphasizes the importance of precision in addressing malunited fractures and showcases how the intervention led to improved patient outcomes. By documenting this case, the study contributes valuable insights into the field of orthopedic surgery, providing a basis for further research and enhancing the understanding of optimal approaches to managing such complex fractures.

Challenges and Triumphs: Unusual Presentation of Tuberculosis in the Cuboid Bone Successfully Managed Through Surgical and Medical Intervention.

This case report describes the unusual presentation of tuberculosis (TB) affecting the cuboid bone in a 16-year-old male patient. The patient presented with a one-year history of progressive foot pain, a discharging sinus, evening rise of temperature, weight loss, and loss of appetite. Clinical examination revealed soft tissue swelling and the presence of caseous material oozing from the sinus. Emergency debridement and curettage were performed, and bone cementing was carried out. An intraoperative sample was sent for a culture sensitivity test, histological analysis, and cartridge-based nucleic acid amplification test (CBNAAT). Histopathological examination, CBNAAT, and culture and sensitivity tests confirmed the diagnosis of Mycobacterium tuberculosis infection. Post-operatively, anti-tuberculous treatment was started. The patient fully recovered from TB of the cuboid.

Unveiling Neglected Pin-Site Tuberculosis: An Uncommon Encounter Due to Surgical Distal-End Radius Fracture Management With K-Wires.

In this case report, a 29-year-old man underwent surgery to treat a fracture to the left distal end of his radius using closed reduction and K-wire fixation. The patient was advised to follow up in the outpatient department after six weeks for cast and K-wire removal. Still, the patient failed to do so and was doing alternate day dressing of the K-wires. After six months he slipped and fell from his cot while sleeping, sustaining an injury to the left wrist. Initially, he developed a swelling over the wrist, which suddenly increased in size and ruptured. Thick white caseous material was leaking out from the wounds. The patient underwent debridement and K-wire removal. An intraoperative sample was sent for a bacterial culture sensitivity test, histological analysis, and cartridge-based nucleic acid amplification test (CB-NAAT/GeneXpert). Postoperatively, anti-tuberculous treatment was started. The patient fully recovered from tuberculosis and had a complete range of movements after treatment.

Navigating Foot Tuberculosis in a Leprosy Survivor: A Case Managed Solely With Medical Strategies.

We present a case report of a 66-year-old male patient with a known history of leprosy who presented with pain and swelling in his right foot for the past 1.5 years. Fine needle aspiration cytology (FNAC) revealed non-inflammatory exudate, and Mycobacterium tuberculosis (MTB) was identified in the sample by the cartridge-based nucleic acid amplification test (CBNAAT). The patient was managed conservatively with anti-Koch's treatment (AKT), and a follow-up was conducted for 12 months to monitor the treatment response and overall progress. This highlights the importance of early diagnosis and appropriate medical management, along with a long-term follow-up, among patients with ankle tuberculosis, to reduce the need for surgical intervention.

Harnessing Healing Power: A Comprehensive Review on Platelet-Rich Plasma in Compound Fracture Care.

This comprehensive review explores the applications of platelet-rich plasma (PRP) in the context of compound fracture care, providing a thorough examination of its biological mechanisms, preparation techniques, and clinical implications. The analysis highlights PRP's potential in accelerating bone healing, enhancing soft tissue repair, reducing inflammation and infection risks, and managing pain during fracture recovery. The review underscores the importance of ethical and regulatory considerations in integrating PRP into orthopaedic practice, emphasising informed consent, transparent patient communication, and ongoing monitoring of ethical concerns. Looking ahead, the implications for the future of compound fracture care suggest a transformative shift with the potential for personalised medicine approaches and emerging technologies. However, the conclusion calls for a balanced perspective, acknowledging the promising applications of PRP while emphasising the need for responsible and ethical use. The collaborative efforts of healthcare professionals, researchers, and regulatory bodies are crucial in navigating this evolving landscape and harnessing the healing power of PRP to redefine orthopaedic care for individuals with compound fractures.

A Comprehensive Review on Platelet-Rich Plasma Activation: A Key Player in Accelerating Skin Wound Healing.

Platelet-rich plasma (PRP) activation is emerging as a promising and multifaceted tool for accelerating skin wound healing. This review extensively examines PRP's role in wound healing, focusing on its composition, mechanisms of action, activation methods, and clinical applications. PRP's potential to enhance both chronic and acute wound healing and its applications in cosmetic and aesthetic procedures are explored. Furthermore, this review investigates safety concerns, including adverse reactions, infection risks, and long-term safety implications. Looking to the future, emerging technologies, combination therapies, personalized medicine approaches, and regulatory developments are discussed, pointing towards an important and transformative era in wound healing and regenerative medicine. With its wide-ranging implications for healthcare, PRP activation has the potential to become a ubiquitous and essential therapeutic option, improving patient outcomes and reducing healthcare costs.

Simvastatin prevents BMP-2 driven cell migration and invasion by suppressing oncogenic DNMT1 expression in breast cancer cells.

Both epigenetic and genetic changes in the cancer genome act simultaneously to promote tumor development and metastasis. Aberrant DNA methylation, a prime epigenetic event, is often observed in various cancer types. The elevated DNA methyltransferase 1 (DNMT1) enzyme creates DNA hypermethylation at CpG islands to drive oncogenic potential. This study emphasized to decipher the molecular mechanism of endogenous regulation of DNMT1 expression for finding upstream signaling molecules. Cancer database analyses found an upregulated DNMT1 expression in most cancer types including breast cancer. Overexpression of DNMT1 showed an increased cell migration, invasion, and stemness potential whereas 5-azacytidine (DNMT1 inhibitor) and siRNA mediated knockdown of DNMT1 exhibited inhibition of such cancer activities in breast cancer MDA-MB-231 and MCF-7 cells. Infact, cancer database analyses further found a positive correlation of DNMT1 transcript with both cholesterol pathway regulatory genes and BMP signaling molecules. Experimental observations documented that the cholesterol-lowering drug, simvastatin decreased DNMT1 transcript as well as protein, whereas BMP-2 treatment increased DNMT1 expression in breast cancer cells. In addition, expression of various key cholesterol regulatory genes was found to be upregulated in response to BMP-2 treatment. Moreover, simvastatin inhibited BMP-2 induced DNMT1 expression in breast cancer cells. Thus, this study for the first time reveals that both BMP-2 signaling and cholesterol pathways could regulate endogenous DNMT1 expression in cancer cells.

Metformin prevents osteoblast-like potential and calcification in lung cancer A549 cells.

In spite of recent advances made in understanding its progression, cancer is still a leading cause of death across the nations. Molecular pathophysiology of these cancer cells largely differs depending on cancer types and even within the same tumor. Pathological mineralization/calcification is seen in various tissues including breast, prostate, and lung cancer. Osteoblast-like cells derived after trans-differentiation of mesenchymal cells usually drive calcium deposition in various tissues. This study aims to explore the presence of osteoblast-like potential in lung cancer cells and its prevention. ALP assay, ALP staining, nodule formation, RT-PCR, RT-qPCR, and western blot analysis experiments were carried out in lung cancer A549 cells to achieve said objective. Expressions of various osteoblast markers (e.g., ALP, OPN, RUNX2, and Osterix) along with osteoinducer genes (BMP-2 and BMP-4) were observed in A549 cells. Moreover, ALP activity and ability leading to nodule formation revealed the presence of osteoblast-like potential in lung cancer cells. Here, BMP-2 treatment increased expressions of osteoblast transcription factors such as RUNX2 and Osterix, enhanced ALP activity, and augmented calcification in this cell line. It was also observed that antidiabetic metformin inhibited BMP-2 mediated increase in osteoblast-like potential and calcification in these cancer cells. The current study noted that metformin blocked BMP-2 mediated increase in epithelial to mesenchymal transition (EMT) in A549 cells. The above findings for the first time unravel that A549 cells possess osteoblast-like potential which drives lung cancer calcification. Metformin might prevent BMP-2 induced osteoblast-like phenotype of the lung cancer cells with concomitant inhibition of EMT to inhibit lung cancer tissue calcification.

Point Prevalence Study (PPS) of Antibiotic Usage and Bacterial Culture Rate (BCR) among Secondary Care Hospitals of Small Cities in Central India: Consolidating Indian Evidence.

Objective Indian hospitals (especially government-run public sector hospitals) have a nonexistent antimicrobial stewardship program (AMSP). After successfully initiating AMSPs in tertiary care hospitals of India, the Indian Council of Medical Research envisages implementing AMSP in secondary care hospitals. This study is about the baseline data on antibiotic consumption in secondary care hospitals. Materials and Methods It was a prospective longitudinal observational chart review type of study. Baseline data on antibiotic consumption was captured by a 24-hour point prevalence study of antibiotic usage and bacterial culture rate. The prescribed antibiotics were classified according to the World Health Organization (WHO) Access, Watch, and Reserve classification. All data were collated in Microsoft Excel and summarized as percentages. Results Out of the 864 patients surveyed, overall antibiotic usage was 78.9% (71.5% in low-priority areas vs. 92.2% in high-priority areas). Most of the antibiotic usage was empirical with an extremely low bacterial culture rate (21.9%). Out of the prescribed drugs, 53.1% were from the WHO watch category and 5.5% from the reserve category. Conclusion Even after 5 years of the launch of the national action plan on AMR (NAP-AMR) of India, AMSP is still non-existent in small- and medium-level hospitals in urban cities. The importance of trained microbiologists in the health care system is identified as a fulcrum in combating antimicrobial resistance (AMR); however, their absence in government-run district hospitals is a matter of grave concern and needs to be addressed sooner than later.

RNA-Seq of untreated wastewater to assess COVID-19 and emerging and endemic viruses for public health surveillance.

Background: The COVID-19 pandemic showcased the power of genomic sequencing to tackle the emergence and spread of infectious diseases. However, metagenomic sequencing of total microbial RNAs in wastewater has the potential to assess multiple infectious diseases simultaneously and has yet to be explored. Methods: A retrospective RNA-Seq epidemiological survey of 140 untreated composite wastewater samples was performed across urban (n = 112) and rural (n = 28) areas of Nagpur, Central India. Composite wastewater samples were prepared by pooling 422 individual grab samples collected prospectively from sewer lines of urban municipality zones and open drains of rural areas from 3rd February to 3rd April 2021, during the second COVID-19 wave in India. Samples were pre-processed and total RNA was extracted prior to genomic sequencing. Findings: This is the first study that has utilised culture and/or probe-independent unbiased RNA-Seq to examine Indian wastewater samples. Our findings reveal the detection of zoonotic viruses including chikungunya, Jingmen tick and rabies viruses, which have not previously been reported in wastewater. SARS-CoV-2 was detectable in 83 locations (59%), with stark abundance variations observed between sampling sites. Hepatitis C virus was the most frequently detected infectious virus, identified in 113 locations and co-occurring 77 times with SARS-CoV-2; and both were more abundantly detected in rural areas than urban zones. Concurrent identification of segmented virus genomic fragments of influenza A virus, norovirus, and rotavirus was observed. Geographical differences were also observed for astrovirus, saffold virus, husavirus, and aichi virus that were more prevalent in urban samples, while the zoonotic viruses chikungunya and rabies, were more abundant in rural environments. Interpretation: RNA-Seq can effectively detect multiple infectious diseases simultaneously, facilitating geographical and epidemiological surveys of endemic viruses that could help direct healthcare interventions against emergent and pre-existent infectious diseases as well as cost-effectively and qualitatively characterising the health status of the population over time. Funding: UK Research and Innovation (UKRI) Global Challenges Research Fund (GCRF) grant number H54810, as supported by Research England.

Role of Cholesterol and its Biosynthetic Precursors on Membrane Organization and Dynamics: A Fluorescence Approach.

Cholesterol is the most representative sterol present in membranes of higher eukaryotes, and is the end product of a long and multistep biosynthetic pathway. Lathosterol and zymosterol are biosynthetic precursors of cholesterol in Kandutsch-Russell and Bloch pathways, respectively. Lathosterol differs with cholesterol merely in the position of the double bond in the sterol ring, whereas zymosterol differs with cholesterol in position and number of double bonds. In this work, we have monitored the effect of cholesterol and its biosynthetic precursors (lathosterol and zymosterol) on membrane organization and dynamics in fluid and gel phase membranes. Toward this goal, we have utilized two fluorescent membrane probes, DPH and its cationic derivative TMA-DPH. Our results using these probes show that cholesterol and its biosynthetic precursors (lathosterol and zymosterol) exhibit similar trend in maintaining membrane organization and dynamics (as reported by fluorescence anisotropy and apparent rotational correlation time), in fluid phase POPC membranes. Notably, although lathosterol and zymosterol show similar trend in maintaining membrane organization and dynamics, the corresponding change for cholesterol is different in gel phase DPPC membranes. These results demonstrate that the position and number of double bonds in sterols is an important determinant in maintaining membrane physical properties. Our results assume significance since accumulation of precursors of cholesterol have been reported to be associated with severe pathological conditions.

Cholesterol-Dependent Dynamics of the Serotonin1A Receptor Utilizing Single Particle Tracking: Analysis of Diffusion Modes.

G protein-coupled receptors (GPCRs) are signaling hubs in cell membranes that regulate a wide range of physiological processes and are popular drug targets. Serotonin1A receptors are important members of the GPCR family and are implicated in neuropsychiatric disorders. Cholesterol is a key constituent of higher eukaryotic membranes and is believed to contribute to the segregated distribution of membrane constituents into domains. To explore the role of cholesterol in lateral dynamics of GPCRs, we utilized single particle tracking (SPT) to monitor diffusion of serotonin1A receptors under acute and chronic cholesterol-depleted conditions. Our results show that the short-term diffusion coefficient of the receptor decreases upon cholesterol depletion, irrespective of the method of cholesterol depletion. Analysis of SPT trajectories revealed that relative populations of receptors undergoing various modes of diffusion change upon cholesterol depletion. Notably, in cholesterol-depleted cells, we observed an increase in the confined population of the receptor accompanied by a reduction in diffusion coefficient for chronic cholesterol depletion. These results are supported by our recent work and present observations that show polymerization of G-actin in response to chronic cholesterol depletion. Taken together, our results bring out the interdependence of cholesterol and actin cytoskeleton in regulating diffusion of GPCRs in membranes.