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Objectives: To evaluate the natural history and to highlight the possible masqueraders causing diagnostic delay and iatrogenic interventions in Fibrodysplasia Ossificans Progressiva (FOP). Methods: Patient details with suspected FOP were retrieved from the patient registry from 2012 through 2021. Clinical records, X-rays, clinical photographs, and molecular testing results were captured. Follow-up was recorded where available. Results: A total of 16 patients with a clinical diagnosis of FOP were found. Twelve patients with both clinical and molecular records were included in this study. The median age of onset and diagnosis was 1.5 y and 6.5 y respectively with a median diagnostic delay of 3.5 y. The disease course was progressive in ten patients. Seven out of twelve patients were subjected to invasive procedures due to misdiagnosis, which exacerbated their disease progression. Conclusions: Clinical suspicion followed by molecular testing is straightforward for a confirmed diagnosis of FOP. It is not only diagnostic, cost-effective, and saves time but also avoids unnecessary interventions in these patients. [ABSTRACT FROM AUTHOR]

The sustainability of social–ecological systems within river deltas globally is in question as rapid development and environmental change trigger "negative" or "positive" tipping points depending on actors' perspectives, e.g. regime shift from abundant sediment deposition to sediment shortage, agricultural sustainability to agricultural collapse or shift from rural to urban land use. Using a systematic review of the literature, we show how cascading effects across anthropogenic, ecological, and geophysical processes have triggered numerous tipping points in the governance, hydrological, and land-use management of the world's river deltas. Crossing tipping points had both positive and negative effects that generally enhanced economic development to the detriment of the environment. Assessment of deltas that featured prominently in the review revealed how outcomes of tipping points can inform the long-term trajectory of deltas towards sustainability or collapse. Management of key drivers at the delta scale can trigger positive tipping points to place social–ecological systems on a pathway towards sustainable development. [ABSTRACT FROM AUTHOR]

The sodium dependent SLC13 family transporters comprise of five genes SLC13A1, SLC13A2 (NaDC1), SLC13A3 (NaDC3), SLC13A4 and SLC13A5 (NaCT). Among them, NaDC1, NaDC3 and NaCT are sodium dependent transporters belonging to family of dicarboxylates (succinate, malate, α-ketoglutarate) and tricarboxylates (citrate). The mouse and the human NaCT structures have still not been crystallized, therefore structural information is taken from the related bacterial transporter of VcINDY. Citrate in the cytosol works as a precursor for the fatty acid synthesis, cholesterol, and low-density lipoproteins. The excess citrate from the matrix is translocated to the cytosol for fatty acid synthesis through these transporters and thus controls the energy balance by downregulating the glycolysis, tricarboxylic acid (TCA), and fatty acid breakdown. These transporters play an important role in regulating various metabolic diseases including cancer, diabetes, obesity, fatty liver diseases and CNS disorders. These di and tricarboxylate transporters are emerging as new targets for metabolic disorders such as obesity and diabetes. The mutation in the function of the NaCT causes several neurological diseases including neonatal epilepsy and impaired brain development whereas mutation of genes coding for citrate transport present in the liver may provide positive effect. Therefore, continued efforts from the earlier work on citrate transporters are required for the development of citrate inhibitors. This review discusses the structure, function, and regulation of the NaCT transporter. The review also highlights citrate role in diagnosing diseases such as cancer, diabetes, fatty liver, and diabetes. The therapeutic perspective of synthetic inhibitors against NaCT transporters is succinctly summarized. [ABSTRACT FROM AUTHOR]

Purpose: Re-implantation of the tumor bearing autograft following extracorporeal radiation therapy (ECRT) has been established as an oncologically safe biological reconstruction technique following resection of bone sarcomas. However, factors affecting the ECRT graft-host bone incorporation have not been fully investigated. An insight into the factors that influence graft incorporation can circumvent the complications and increase graft survival. Methods: A total of 96 osteotomies in 48 patients with intercalary resections of primary extremity bone sarcomas (mean age 15.8 years, mean follow-up 42.1 months) were analyzed retrospectively for factors ECRT autograft-host bone union. Results: On univariate analysis, age < 20 years, metaphyseal osteotomy site, V-shaped diaphyseal osteotomy, and use of additional plate at diaphyseal osteotomy had a significantly faster time to union, while gender, tumour type, bone involved, resection length, chemotherapy, type of fixation, and use of intra-medullary fibula did not influence union time. In multivariate analysis, V-shaped diaphyseal osteotomy and use of additional plate at diaphyseal ostetomy were the independent factors with favourable time to union. None of the analyzed factors was found to have a significant effect on the union rate. The major complications were non-union in 11.4% patients, graft failure in 2.1%, infection in 12.5%, and soft tissue local recurrences in 14.5% patients. Conclusion: Modified diaphyseal osteotomy and augmentation of the stability of the reconstruction using additional small plates enhance the incorporation of ECRT autograft. [ABSTRACT FROM AUTHOR]

Proteolysis-targeting technology is a new emerging technique to target mutated, denatured, and misfolded proteins that accumulate in various parts of the body. The accumulation of these aggregated harmful proteins, such as β-amyloid (Aβ), tau, mHTT, polyglutamates, and other proteins in the brain, are some of the reasons for the development of neurodegenerative diseases. Aβ accumulation and hyperphosphorylation are the common signals for the progression of Alzheimer's disease (AD). Developing conventional small molecule inhibitors to target these accumulating proteins is a difficult task due to the undruggable/indestructible nature of certain protein molecules. However, the removal of these aggregates as a defense mechanism by different protein quality control systems in our body is a normal physiological process. Advancements in the field of medicinal chemistry has led to the development of various chemical mediated targeted protein degradation techniques, which target disease causing protein of interest (POI) through ubiquitin-proteasome system (UPS) to dissolve/degrade the misfolded proteins. Such methods involve the development of molecular glues, proteolysis targeting chimeras (PROTACs), autophagosome conjugated compounds, and hydrophobic tagging. This article covers a recent update on designing of PROTACs using different linkers, their mechanism of action, pharmacokinetics, in addition to advantages and disadvantages of PROTACs as therapeutic modalities to treat AD. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OGS) is the most common primary bone tumor in children and adolescents which requires a multidisciplinary approach to management. Although chemotherapy and surgery can cure more than half of localized OGS cases, the unique challenges faced by resource-limited countries like India make this outcome difficult to achieve. Various questions in the management of OGS including role of high-dose methotrexate (HDMTX) in neoadjuvant setting, triplet vs doublet chemotherapy, intensification of chemotherapy based on response in setting of doublet, and indigenous prosthesis in setting of limb salvage need to be defined. Similarly, in the metastatic and recurrent setting, questions regarding intent of treatment, indications of chemotherapy, timing of surgery, and role of targeted therapies need clarification. Lack of randomized trials from India makes definite conclusions difficult, but an attempt can be made to define the best approach in the Indian scenario from available evidence. Hence, a critical review of literature from India and the West was done to define possible management approaches and highlight the lacuna for future research. [ABSTRACT FROM AUTHOR]

Soil with heavy metals contamination, mainly lead (Pb), cadmium (Cd), and chromium (Cr) is a progressively worldwide alarming environmental problem. Recently, biochar has been used as a soil amendment to remediate contaminated soils, but little work has been done to compare with other organic amendments like compost. We investigated biochar and compost's comparative effect on Pb, Cd, and Cr immobilization in soil, photosynthesis, and growth of maize plants. Ten kg soil was placed in pots and were spiked with Pb, Cd, and Cr at concentrations 20, 10, 20 mg kg−1. The biochar and compost treatments included 0, 0.5, 1, 2, and 4% were separately applied to the soil. The crop from pots was harvested after 60 days. The results show that the highest reduction of AB-DTPA extractable Pb, Cd, and Cr in soil was 79%, 61% and 78% with 4% biochar, followed by 61%, 43% and 60% with 4% compost compared to the control, respectively. Similarly, the highest reduction in shoot Pb, Cd, and Cr concentration was 71%, 63% and 78%with 4% biochar, followed by 50%, 50% and 71% with 4% compost than the control, respectively. The maximum increase in shoot and dry root weight, total chlorophyll contents, and gas exchange characteristics were recorded with 4% biochar, followed by 4% compost than the control. The maximum increase in soil organic matter and total nitrogen (N) was recorded at 4% biochar application while available phosphorus and potassium in the soil at 4% compost application. It is concluded that both biochar and compost decreased heavy metals availability in the soil, reducing toxicity in the plant. However, biochar was most effective in reducing heavy metals content in soil and plant compared to compost. In the future, more low-cost, eco-friendly soil remediation methods should be developed for better soil health and plant productivity. [ABSTRACT FROM AUTHOR]

In this study, we explored the role of biochar (BC) and/or urease inhibitor (UI) in mitigating ammonia (NH3) and nitrous oxide (N2O) discharge from urea fertilized wheat cultivated fields in Pakistan (34.01°N, 71.71°E). The experiment included five treatments [control, urea (150 kg N ha−1), BC (10 Mg ha−1), urea + BC and urea + BC + UI (1 L ton−1)], which were all repeated four times and were carried out in a randomized complete block design. Urea supplementation along with BC and BC + UI reduced soil NH3 emissions by 27% and 69%, respectively, compared to sole urea application. Nitrous oxide emissions from urea fertilized plots were also reduced by 24% and 53% applying BC and BC + UI, respectively, compared to urea alone. Application of BC with urea improved the grain yield, shoot biomass, and total N uptake of wheat by 13%, 24%, and 12%, respectively, compared to urea alone. Moreover, UI further promoted biomass and grain yield, and N assimilation in wheat by 38%, 22% and 27%, respectively, over sole urea application. In conclusion, application of BC and/or UI can mitigate NH3 and N2O emissions from urea fertilized soil, improve N use efficiency (NUE) and overall crop productivity. [ABSTRACT FROM AUTHOR]

An important source of the destructive greenhouse gas, nitrous oxide (N2O) comes from the use of ammonium based nitrogen (N) fertilizers that release N2O in the incomplete conversion (nitrification) of NH4+ to NO3ˉ1. Biochar has been shown to decrease nitrification rates and N2O emission. However, there is little information from semi-arid environments such as in Pakistan where conditions favor N2O emissions. Therefore, the object was to conduct field experiment to determine the impact of biochar rates in the presence or absence of urea amended soils on yield-scaled N2O emissions, and wheat yield and N use efficiency (NUE). The experiment on wheat (Triticum aestivum L.), had a randomized complete block design with four replications and the treatments: control, sole urea (150 kg N ha−1), 5 Mg biochar ha−1 (B5), 10 Mg biochar ha−1 (B10), urea + B5 or urea + B10. In urea amended soils with B5 or B10 treatments, biochar reduced total N2O emissions by 27 and 35%, respectively, over the sole urea treatment. Urea + B5 or + B10 treatments had 34 and 46% lower levels, respectively, of yield scaled N2O over the sole urea treatment. The B5 and B10 treatments had 24–38%, 9–13%, 12–27% and 35–43%, respectively greater wheat above-ground biomass, grain yield, total N uptake, and NUE, over sole urea. The biochar treatments increased the retention of NH4+ which likely was an important mechanism for reducing N2O by limiting nitrification. These results indicate that amending soils with biochar has potential to mitigate N2O emissions in a semi-arid and at the same time increase wheat productivity. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative old age disease that is complex, multifactorial, unalterable, and progressive in nature. The currently approved therapy includes cholinesterase inhibitors, NMDA-receptor antagonists and their combination therapy provides only temporary symptomatic relief. Sincere efforts have been made by the researchers globally to identify new targets, discover, and develop novel therapeutic agents for the treatment of AD. This brief review article is intended to cover the recent advances in drug development and emerging therapeutic agents for AD acting at different targets. The article is compiled using various scientific online databases and by referring to clinicaltrials.gov and ALZFORUM (alzforum.org) websites. The upcoming therapies act on one or more targets including amyloids (secretases, Aβ42 production, amyloid deposition, and immunotherapy), tau proteins (tau phosphorylation/aggregation and immunotherapy) and neuroinflammation in addition to other miscellaneous targets. Despite the tremendous improvement in our understanding of the underlying pathophysiology of AD, only aducanumab was approved by FDA for the treatment of AD in 18 years i.e., since 2003. Hence, it is concluded that novel therapeutic strategies are required to discover and develop therapeutic agents to fight against the century old AD. [ABSTRACT FROM AUTHOR]

Brain endothelial cells play an important role in maintaining blood flow homeostasis in the brain. Cerebral ischemia is a major cause of endothelial dysfunction which can disrupt the blood–brain barrier (BBB). Oxygen–glucose deprivation (OGD)/reperfusion promote cell death and BBB breakdown in brain endothelial cells. Acetyl-11-keto-β-boswellic acid (AKBA), a biologically active phytoconstituent of the medicinal plant Boswellia serrata, has been shown to be protective against various inflammatory diseases as well as ischemic brain injury. The molecular mechanisms underlying these beneficial characteristics of AKBA are poorly understood. We subjected bEND.3 cells to OGD/reperfusion to investigate the protective role of AKBA in this model. We found that AKBA treatment attenuated endothelial cell death and oxidative stress assessed by means of TUNEL assay, cleaved-caspase-3, and dihydroethidium (DHE) staining. Furthermore, OGD downregulated tight junction proteins ZO-1 and Occludin levels, and increased the expressions of inflammatory cytokines TNF-α, ICAM-1, and complement C3a receptor (C3aR). We also noticed the increased phosphorylation of ERK 1/2 in bEND.3 cells in OGD group. AKBA treatment significantly attenuated expression levels of these inflammatory proteins and prevented the degradation of ZO-1 and Occludin following OGD. In conclusion, AKBA treatment provides protection against endothelial cell dysfunction following OGD by attenuating oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Neoplasms arising from scapula are rare. We herein, present a rare case of Ewing's sarcoma of scapula in a 9-year-old male child. Extensive literature search reveals that less than 20 similar cases have been reported so far. The index case had been treated with multimodal therapies—chemotherapy, surgery, and radiotherapy. This case is reported to highlight the rarity of the case and discuss the review of literature comprehensively. [ABSTRACT FROM AUTHOR]

Background: Factors influencing publication of manuscripts in reputed journals have never been studied to the best of our knowledge. This study was conducted to evaluate the trend in publication within the Indian Journal of Orthopaedics (IJO). Materials and Methods: A cross-sectional study was conducted by accessing the online database of the IJO. All the issues available online were included. Published articles were classified into one of the following thirteen categories: (i) Basic Sciences (ii) trauma (upper limb and lower limb) (iii) infections (iv) pediatric orthopedics (v) arthroplasty (vi) arthroscopy (vii) spine surgery (viii) musculoskeletal oncology (ix) hand and microvascular surgery (x) adult reconstruction (including the Ilizarov technique) (xi) general orthopedics and miscellaneous (xii) letter to editor (xiii) book review. A scatter diagram was plotted to study the individual trends. Results: A total of 2213 articles from 110 issues published between 1967 and 2014 were studied. Total number of articles per issue have increased overthe years. Publications in the fields of trauma, adult reconstruction, arthroscopy and hand and microvascular surgery have increased steadily. Arthroplasty and spine surgery have recorded dramatic increase in publication. On the other hand, publications in the rest of the fields have declined of which the greatest fall is noted in the field of musculoskeletal oncology. Conclusions: Trend in publication with the IJO has changed over years with more articles being published in arthroplasty and Spine surgery. Despite advances, publication in the field of musculoskeletal oncology has fallen. [ABSTRACT FROM AUTHOR]