Lung cell transplantation for pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a major cause of death with few treatment options. Here, we demonstrate the therapeutic efficacy for lung fibrosis of adult lung cell transplantation using a single-cell suspension of the entire lung in two distinct mouse systems: bleomycin treatment and mice lacking telomeric repeat-binding factor 1 expression in alveolar type 2 (AT2) cells (SPC-Cre TRF1fl/fl), spontaneously developing fibrosis. In both models, the progression of fibrosis was associated with reduced levels of host lung progenitors, enabling engraftment of donor progenitors without any additional conditioning, in contrast to our previous studies. Two months after transplantation, engrafted progenitors expanded to form numerous donor-derived patches comprising AT1 and AT2 alveolar cells, as well as donor-derived mesenchymal and endothelial cells. This lung chimerism was associated with attenuation of fibrosis, as demonstrated histologically, biochemically, by computed tomography imaging, and by lung function measurements. Our study provides a strong rationale for the treatment of lung fibrosis using lung cell transplantation.

Bolometric IR photoresponse based on a 3D micro-nano integrated CNT architecture.

A new 3D micro-nano integrated M-shaped carbon nanotube (CNT) architecture was designed and fabricated. It is based on vertically aligned carbon nanotube arrays composed of low-density, mainly double-walled CNTs with simple lateral external contacts to the surroundings. Standard optical lithography techniques were used to locally tailor the width of the vertical block structure. The complete sensor system, based on a broadband blackbody absorber region and a high-resistance thermistor region, can be fabricated in a single chemical vapor deposition process step. The thermistor resistance is mainly determined by the high junction resistances of the adjacent aligned CNTs. This configuration also provides low lateral thermal conductivity and a high temperature coefficient of resistance (TCR). These properties are advantageous for new bolometric sensors with high voltage responsivity and broadband absorption from the infrared (IR) to the terahertz spectrum. Preliminary performance evaluations have shown current and voltage responsivities of 2 mA/W and 30 V/W, respectively, in response to IR (980 nm) absorption for a 20 × 20 µm2 device. The device exhibits an exceptionally fast response time of ≈0.15 ms, coupled with a TCR of -0.91 %/K. These attributes underscore its high operating speed and responsivity, respectively. In particular, the device maintains excellent thermal stability and reliable operation at elevated temperatures in excess of 200 °C, extending its potential utility in challenging environmental conditions. This design allows for further device miniaturization using optical lithography techniques. Its unique properties for mass production through large-scale integration techniques make it important for real-time broadband imaging systems.

Femoral neck fracture fixation in rhombic versus inverted triangle configuration in young adults: A systematic review.

Objective: This review evaluated the outcomes of rhombic versus inverted triangle configuration fixation of femoral neck fractures. Methods: Six databases, PubMed, Embase, Scopus, Web of Science, Cochrane Library databases, and China National Knowledge Infrastructure (CNKI), were comprehensibly searched for the comparative studies of two configurations (rhombic versus inverted triangle) of neck femur fracture fixation. Ultimately seven studies were included in this systematic review for qualitative and quantitative analysis. A meta-analysis was performed with the software RevMan 5.4.1. Results: Fewer nonunion (OR 0.46 with 95 % CI 0.23, 0.94; p = 0.03), and early full weight bearing (MD -3.09 with 95 % CI -5.41, -0.77; p = 0.009) were seen in the rhombic than in the inverted configuration; however, a better hip function (MD 3.72 with 95 % CI 0.99, 6.44; p = 0.008), and lesser less blood loss (MD 3.84 with 95 % CI 1.19, 6.49; p = 0.004) during surgery were found in the inverted triangle configuration. There was no difference between the two fixation configurations regarding the duration of surgery, fracture union time, overall complications, femoral neck shortening, length of hospital stay, fluoroscopy times, and incision size. Conclusion: The rhomboid configuration showed fewer non-union, early weight bearing, better hip function and comparable complications rate than the inverted triangle configuration; however, there was more blood loss intraoperatively than inverted triangle configuration. Hence, the addition of a fourth screw in the rhombic configuration have an added advantage over the inverted triangle configuration in femoral neck fracture.

A rare primary sacral glomus tumor presenting as intradural-extramedullary tumor: A Case report and review of literature.

Background: Glomus tumors are very infrequent in the spine where they can grow intraosseously at any level. We were able to identify only eight such cases in the literature, with only one occurring in the sacrum. Here, a 48-year-old male with sacral S1/S2 radiculopathy was found to have a rare glomangioma/glomus tumor of the sacral region. Case Description: A 48-year-old male presented with left-sided S2 radiculopathy characterized by left lower extremity weakness/paresis. The magnetic resonance showed an intradural extramedullary mass measuring 1.8 × 1.9 × 4.3 cm at S1-S2 extending through the left foramen, inhomogeneously enhanced with contrast. He underwent an S1-S2 durotomy with gross total excision of the mass. Pathologically, it proved to be a glomus tumor. Two months postoperatively, he ambulated without the support and demonstrated no tumor recurrence at 1 postoperative year. Conclusion: Glomus tumors involving the sacral region are rare and can be successfully excised resulting in good clinical outcomes.

Molecular Docking and Molecular Dynamics Simulations of Synthesized Thiazole-Isatin-1,2,3-triazole Hybrids as Promising Inhibitors for DNA Gyrase and 14α-Sterol Demethylase.

In the present work, a new class of thiazole-isatin-1,2,3-triazole hybrids (5a-5p) and precursor alkyne hybrids (6a-6d) has been reported with their in-silico studies. After structural identifications using different spectroscopic technique such as FTIR, 1H and 13C NMR and HRMS, the synthesized hybrids were explored for their biological potential using molecular docking and molecular dynamics calculations. Molecular docking results revealed that compound 5j showed maximum binding energy i.e. -10.3 and -12.6 kcal/mol against antibacterial and antifungal enzymes; 1KZN (E. coli) and 5TZ1 (C. albicans), respectively.Top of FormBottom of Form Molecular dynamics simulations for the best molecule (100 ns) followed by PBSA calculations  suggested a stable complex of 5j with 5TZ1 with binding energy of -118.760 kJ/mol as compared to 1KZN (-94.593 kJ/mol). The mean RMSD values for the 1KZN with 5j complex remained approximately 0.175 nm throughout all the time span of 100 ns in the production stages and is in the acceptable range.  Whereas, 5TZ1 with 5j complex, RMSD values exhibited variability within the range of 0.15 to 0.25 nm.

Investigating the Potential of 2-Ethylbutyl-(Phenoxy)phosphoryl-D-Alaninate Against RNA-Dependent RNA Polymerase (RdRp) of SARS-CoV-2.

There was an emergency call globally when COVID-19 was detected in December 2019. The SARS-CoV-2 virus, a modified virus, is what causes this contagious disease. Although research is being conducted throughout the world, the main target is still to find the promising candidate to target RNA-dependent RNA polymerase (RdRp) to provide possible drug against COVID-19. Aim of this work is to find a molecule to inhibit the translational process of viral protein synthesis. Density Functional Theory calculations revealed information about the formation of the desired ligand (RD). Molecular docking of RD with RdRp was performed and compared with some reported molecules and the data revealed that RD had the best docking score with RdRp (-6.7 kcal/mol). Further, molecular dynamics (MD) simulations of RD with RdRp of SARS-CoV-2 revealed the formation of stable complex with a maximum number of seven hydrogen bonds. Root mean square deviations values are in acceptable range and root mean square fluctuations has less fluctuation indicate stable complex formation. Further, based on MM-GBSA calculation, RD formed a stable complex with RdRp of nCoV with ΔG° of -12.28 kcal·mol-1.

Analytic and In Silico Methods to Understand the Interactions between Dinotefuran and Haemoglobin.

This work lies in the growing concern over the potential impacts of pesticides on human health and the environment. Pesticides are extensively used to protect crops and control pests, but their interaction with essential biomolecules like haemoglobin (Hb) remains poorly understood. Spectrofluorometric, electrochemical, and in silico investigations have been chosen as potential methods to delve into this issue, as they offer valuable insights into the molecular-level interactions between pesticides and haemoglobin. The research aims to address the gaps in knowledge and contribute to developing safer and more sustainable pesticide practices. The interaction was studied by spectroscopic techniques (UV-Visible & Fluorescence), in silico studies (molecular docking & molecular dynamics simulations) and electrochemical techniques (cyclic voltammetry and tafel). The studies showed effective binding of dinotefuran with the Hb which will cause toxicity to human. The formation of a stable molecular complex between ofloxacin and Haemoglobin was shown via molecular docking and the binding energy was found to be -5.37 kcal/mol. Further, molecular dynamics simulations provide an insight for the stability of the complex (Hb-dinotefuran) for a span of 250 ns with a binding free energy of -53.627 kJ/mol. Further, cyclic voltammetry and tafel studies show the interaction of dinotefuran with Hb effectively.

An insight for the inhibition of anxiolytic and anti-convulsant effects in zebrafish using the curcumins via exploring molecular docking and molecular dynamics simulations.

In the contemporary landscape, anxiety and seizures stand as major areas of concern, prompting researchers to explore potential drugs against them. While numerous drugs have shown the potential to treat these two neurological conditions, certain adverse effects emphasize the need for development of safer alternatives. This study seeks to employ an in silico approach to evaluate natural compounds, particularly curcumins, as potential inhibitors of GABA-AT to mitigate anxiety and seizures. The proposed methodology includes generating a compound library, minimizing energy, conducting molecular docking using AutoDock, molecular dynamics simulations using Amber, and MM-GBSA calculations. Remarkably, CMPD50 and CMPD88 exhibited promising binding affinities of - 9.0 kcal/mol and - 9.1 kcal/mol with chains A and C of GABA-AT, respectively. Further, MM-GBSA calculations revealed binding free energies of - 10.88 kcal/mol and - 10.72 kcal/mol in CMPD50 and CMPD88, respectively. ADME analysis showed that these compounds contain drug-likeness properties and might be considered as potential drug candidates. The findings from this study will have practical applications in the field of drug discovery for the development of safer and effective drugs for treatment of anxiety and seizures. Overall, this study will lay the groundwork for providing valuable insights into the potential therapeutic effects of curcumins in alleviating anxiety and seizures, establishing a computational framework for future experimental validation.

Short segment posterior fixation of unstable thoracolumbar vertebral fractures with fractured vertebra augmentation with intermediate pedicle screw - a clinicoradiological analysis.

INTRODUCTION: Unstable thoracolumbar burst fractures are routinely encountered in orthopedic practice. Recently, short-segment fixation with pedicle screw augmentation of the fractured vertebra for unstable thoracolumbar burst fractures has gained popularity. Nonetheless, the maintenance of the kyphotic correction during the follow-up period remains controversial. This study aimed to examine the clinical-radiological outcomes, complications, and functional outcomes of fractured vertebrae augmentation with intermediate pedicle screws in short-segment instrumentation in acute thoracolumbar spine fractures. METHODS: This retrospective study was conducted in the Department of Orthopedics, All India Institute of Medical Sciences, Jodhpur, using medical records from January 2021 to October 2022. Parameters such as local kyphosis correction, loss of kyphotic correction at final follow-up, anterior body height correction (%), and loss of correction (%) at final follow-up were measured as primary outcomes. Various other parameters such as operative time, blood loss, length of hospital stay, and visual analog scale were measured as secondary outcomes. RESULTS: The mean correction obtained via surgery in the immediate postoperative period was 13.7±2.3 degrees. The mean loss of correction at the final follow-up was 4.1±2.0 degrees, and the mean final local kyphotic angle was 7.2±2.4 degrees (P<0.05). The mean correction obtained via surgery in the immediate postoperative period was 37.2%±9.0%. The mean loss of correction at the final follow-up was 10.5%±5.3%, and the mean final anterior vertebral body height maintained was 72%±11.0% (P<0.05). CONCLUSION: Short-segment posterior fixation with pedicle screw augmentation achieves good correction of local kyphotic angle and anterior vertebral height in the immediate postoperative period, but some loss of correction at final follow-up is common. In our study, the loss of correction corresponded directly to the load-sharing score.

Drug product Formulation and Fill/Finish Manufacturing Process Considerations for AAV-Based Genomic Medicines.

Adeno-associated viruses (AAVs) have become the delivery medium of choice for a variety of genomic medicine applications i.e., gene therapy, gene editing/regulation, and ex-vivo cell therapy. AAVs are protein-DNA complexes which have unique stability characteristics that are susceptible to various stress exposure conditions commonly seen in the drug product (DP) life cycle. This review takes a comprehensive look at AAV DP formulation and process development considerations that could impact critical quality attributes (CQAs) during manufacturing, packaging, shipping, and clinical use. Additional aspects related to AAV development reviewed herein are: (1) Different AAV serotypes with unique protein sequences and charge characteristics potentially leading to discrete stability profiles; (2) Manufacturing process challenges and optimization efforts to improve yield, recovery and purity especially during early development activities; and (3) Defining and identifying CQAs with analytical methods which are constantly evolving and present unique characterization challenges for AAV-based products.

Discovery of a Novel Yadav-Kunal Reflex in Context of Upper Motor Neuron Lesions: A Report of Three Cases.

Introduction: Numerous reflexive responses have been documented as alterations to the Babinski sign within upper motor neuron lesions. However, scant attention has been given to reflexes beyond these, which exhibit independence from the extensor plantar response. These reflexes predominantly form polysynaptic arcs, with nociceptive stimuli acting as afferents. Case Report: The reflex was serendipitously discovered in an 18-year-old female patient who presented with spastic paraplegia with bowel and bladder involvement, as a consequence of an aneurysmal bone cyst of the D3 (dorsal) vertebrae, and the same was named after the authors as "Yadav-Kunal reflex" which can be defined as: "In individuals with spastic paraparesis, forcibly plantarflexing the toes will result in sudden jerky flexion of the knee and hip on the same side." This novel reflex was further investigated and validated in two additional patients with spastic paraplegia: one, a 45-year-old female with D9-D10 Pott's spine and bowel and bladder involvement, and the other, a 65-year-old male with D10-D11 compressive myelopathy and bowel and bladder involvement. This reflex was meticulously tracked until the abatement of spasticity following surgical intervention. Notably, its manifestation was evident in individuals experiencing spastic paraparesis, dissipating concomitantly with the resolution of spasticity - a direct clinical correlation. Conversely, the reflex was conspicuously absent in cases of flaccid paraplegia. Conclusion: Spasticity, characterized by an increase in muscle tone on swift stretching movements, is a manifestation of a stretch reflex disorder. This condition is primarily induced by lesions affecting upper motor neurons. The activation of muscle spindles in toe dorsiflexors (primarily governed by the L5 nerve) occurs during forceful elongation caused by plantarflexion.

Multifocal lower limb hemangioendothelioma in a young female: a case report and review of the literature.

A 26-year-old female presented with pain and swelling of distal thigh and distal leg. She was diagnosed with multifocal epitheloid hemangioendothelioma (EHE) and was successfully treated with wide resection of femoral and tibial lesions followed by their reconstruction using vascularised fibular graft and local bone grafting. One year into follow-up, the patient remained asymptomatic with full Range Of Motion (ROM) and full weight bearing walking. This case illustrates a unique multifocal presentation of hemangioendothelioma and early surgical intervention leading to complete recovery, highlighting the importance of early diagnosis and intervention to help improve prognosis and quality of life of the patient.

Functional outcome and analysis of factors affecting health-related quality of life of surgically managed pelvic ring fractures: a cross-sectional study.

INTRODUCTION: Pelvic ring fractures, particularly those involving the posterior pelvis, pose significant challenges due to their inherent instability. The posterior pelvic ring is critical in providing structural support and stability to the pelvis. This study evaluates the functional outcomes and health-related Quality of life (HRQOL) of patients who underwent internal fixation for unstable pelvic fractures. Various factors influencing the outcomes are also investigated. MATERIAL AND METHODS: A single-center cross-sectional study was conducted on patients with unstable sacral fractures treated with posterior tension band plate or sacroiliac plating with or without symphyseal plating between 2016 and 2020. Patient demographics, injury mechanisms, associated injuries, surgical details, complications, and return-to-work data were collected. HRQOL was assessed using specific pelvic fracture instruments and general HRQOL questionnaires. Logistic regression analysis was performed to identify factors associated with lower SF-12 and SF-36 scores RESULTS: The study included 54 patients, predominantly males (55.6%), aged 18-70 years, with high-energy trauma mechanisms, such as road traffic accidents and occupational injuries. The majority of patients had lateral compression pelvic fractures. Overall, the functional outcomes were favorable, with excellent or good outcomes observed in 86.1% of cases. Patients with associated injuries, such as abdominal, chest, or head injuries, were likelier to have lower SF-12 physical component scores. Sexual satisfaction scores remained stable for most patients post-surgery. DISCUSSION: This study highlights the favorable functional outcomes and HRQOL for patients undergoing fixation for unstable pelvic ring fractures. Younger, working-age males were the most commonly affected demographic. Associated injuries significantly affected physical HRQOL scores. Despite high-energy trauma, patients generally reported satisfactory sexual function post-surgery.

Antibacterial activity of hydrophobicity modulated cationic polymers with enzyme and pH-responsiveness.

The membrane lipid compositions of prokaryotic and eukaryotic cells are inherently different in many aspects, although some similarities exist in their structure and composition. Therefore, selective targeting of membrane lipids with a compound of therapeutic value, such as an antibacterial copolymer, is often challenging. Hence, developing an ideal copolymer with antibacterial properties demands hydrophobicity/hydrophilicity balance with a high biosafety profile. To integrate hydrophobic/hydrophilic balance and cationic charge in an alternating antibacterial copolymer with enzyme and pH-responsiveness, a lysine appended styrenic monomer was copolymerized with a fatty acid (octanoic acid (OA) or myristic acid (MA)) tethered maleimide monomer via reversible addition-fragmentation chain transfer (RAFT) polymerization. A range of microscopic analyses, including dynamic light scattering (DLS), confirmed the formation of nanoaggregates (size ∼30-40 nm) by these polymers in aqueous solution with positive zeta potential (cationic surface charge). Hydrophobic Nile red (NR) dye was successfully encapsulated in the nanoaggregates, and the in vitro release kinetics of the NR dye were monitored at different pHs and in the presence or absence of esterase/lipase. The in vitro release kinetics of NR revealed ∼85% dye release in the presence of pH 5.5 and lipase, suggesting their suitability for pH/enzyme-triggered therapeutic payload delivery. The standard broth microdilution assay showed significant bactericidal activity against both Gram-positive (Bacillus subtilis) and Gram-negative (Escherichia coli) bacteria with an MIC50 value <30 µg mL-1. The effect of polymeric nanoaggregates on bacterial morphology and in vitro survival was further confirmed by field emission scanning electron microscopy (FESEM), agar gel disk diffusion assay, and bacterial live/dead cell count. The significantly low hemolytic activity against red blood cells (RBCs) (HC50 >103 µg mL-1) and nontoxic effect on human intestinal epithelial cells (INT 407) (EC50 >500 µg mL-1) ensure that the polymer nanoaggregates are safe for in vivo use and can serve as a potent antibacterial polymer.

Does the pararectus approach have better outcomes and fewer complications than the modified Stoppa approach for the fixation of acetabular fractures in adults: A systematic review and meta-analysis?

BACKGROUND: The pararectus approach is a minimally invasive surgical approach for anterior acetabulum fracture, with an advantage of the medial window of the modified Stoppa approach (MSA). However, it is unclear whether the pararectus approach is superior to MSA. We aimed this systematic review and meta-analysis to compare the outcomes and complications of pararectus and MSA. METHODS: We performed a data search by conducting an electronic search across databases of PubMed, Embase, Scopus, Cinahl, CNKI, and Cochrane Library and included seven comparative studies for analysis. Statistical analysis was performed using the RevMan software 5.4.1. The risk of bias was evaluated using the Cochrane Collaboration's risk of bias tool for RCTs and the MINORS tool for non-RCTs. RESULTS: Two randomized control trials (RCTs), one prospective study, and four retrospective studies were included. Meta-analysis revealed a better Matta's reduction quality [OR 1.58, 95% CI 1.06, 2.37; p = 0.03] and radiological outcome [OR 2.18, 95% CI 1.03, 4.60; p = 0.04] in MSA than in pararectus approach. However, the pararectus approach has less intraoperative blood loss [MD - 9.79 (95% CI - 176.75, - 6.83; p = 0.03)] and a shorter hospital stay [MD - 2.61 (95% CI - 5.03, - .18; p = 0.04)] than MSA. Both approaches have failed to show a difference concerning overall complication rates [OR 0.66 (95% CI 0.28, 1.55; p = 0.34)], postoperative infection, DVT, duration of surgery [MD - 15.09 (95% CI - 35.38, 5.20; p = 0.15)], functional outcome, and incision length. CONCLUSION: The pararectus approach offers an advantage with lesser operative blood loss and shorter hospital stay, whilst MSA stands out with better reduction quality and radiological outcomes. Nevertheless, both approaches exhibit no difference in complication rates, duration of surgery, incision length, and functional outcome. Hence, the pararectus approach can be considered an alternative to MSA; however, the existing literature fails to demonstrate a distinct advantage over MSA.

Pathological fracture treated with total femoral replacement in a case of chondrosarcoma involving the entire-length femoral shaft.

INTRODUCTION AND IMPORTANCE: We here present a case of chondrosarcoma of the diaphysis of the femur with extensive involvement of the length of the bone and with the pathological fracture at the mid-shaft level. Total femur replacement was done in this case with a bipolar head and repair of abductors and hip flexors to the implanted prosthesis. CASE PRESENTATION: An elderly female in her late 60s presented to the trauma department with sudden onset pain and inability to bear weight on her left lower limb following a trivial slip and fall. The Radiographs revealed a pathological spiral mid-shaft displaced fracture of the femur with an extensive mixed lesion throughout the femur. Magnetic Resonance imaging revealed involvement of more than 90% of the femur with lesion extension into the quadriceps and hamstrings. Histopathology confirmed grade-II conventional chondrosarcoma. Metastatic work-up showed no distant spread. Wide-local resection and total femur endo-prosthetic reconstruction were done. No recurrence or infection was evident at the 18-month follow-up. In elderly non-metastatic pathological fractures, limb salvage with endo-prosthetic reconstruction can be a preferred treatment. CLINICAL DISCUSSION: This case is unique in describing a rare presentation of chondrosarcoma of the diaphysis of the femur, which eventually landed in a pathological fracture. The fracture may increase the tumour's aggressiveness, but wide-margin resection should be the mainstay treatment for primary or recurrent chondrosarcoma, irrespective of pathological fracture. CONCLUSION: In well-indicated cases (no distant spread - N0M0 disease), Total Femur Replacement (TFR) is an excellent option for limb salvage in tumours with extensive involvement of the femur.

Malignant giant cell tumour of distal ulna.

Giant cell tumour (GCT) accounts for 5% of all primary bone tumours. GCT in the distal third of ulna is quite rare. We present a case of recurrent GCT in distal third of ulna with malignant features involving tenosynovium. The case was treated by wide resection of tumour and on follow up, patient recovered well with no evidence of further recurrence. Considering the features, according to the literature reviewed, is the first case of its type.

Gelatin-decorated Graphene oxide: A nanocarrier for delivering pH-responsive drug for improving therapeutic efficacy against atherosclerotic plaque.

The progressive inflammatory disease atherosclerosis promotes myocardial infarction, stroke, and heart attack. Anti-inflammatory drugs treat severe atherosclerosis. They are inadequate bioavailability and cause adverse effects at higher doses. A new nanomaterial coupled pH-apperceptive drug delivery system for atherosclerotic plaque is outlined here. We have synthesized a Graphene Oxide-Gelatin-Atorvastatin (GO-Gel-ATR) nanodrug characterized by spectroscopic and imaging techniques. The encapsulation efficiency of GO-Gel-ATR (79.2%) in the loading process is observed to be better than GO-ATR (66.8%). The internal milieu of the plaque cells has a pH of 6.8. The GO-Gel-ATR displays sustained and cumulative release profile at pH 6.8 compared to ATR and GO-ATR. Our proposed nanocomposite demonstrated high cytocompatibility up to 100µg/mL in foam cells induced by Oxidized-Low Density Lipoprotein (Ox-LDL) and Lipopolysaccharides (LPS) compared to normal macrophages for 24 and 48 h. The uptake efficacy of the nanodrugs is shown to be enhanced in foam cells compared to normal macrophage. Oil red O staining of foam cells with and without drugs confirmed therapeutic efficacy. Foam cells treated with nanocomposite had more lipids efflux than ATR. The finding of the in-vitro study reveals that the GO-Gel-ATR nanocomposite carriers have the potential to deliver anti-atherosclerotic drugs effectively and inhibit atherosclerotic plaque progression.