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Acetylcholine (ACh) neurotransmitter of the cholinergic system in the brain is involved in learning, memory, stress responses, and cognitive functioning. It is hydrolyzed into choline and acetic acid by two key cholinesterase enzymes, viz., acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A loss or degeneration of cholinergic neurons that leads to a reduction in ACh levels is considered a significant contributing factor in the development of neurodegenerative diseases (NDs) such as Alzheimer's disease (AD). Numerous studies have shown that cholinesterase inhibitors can raise the level of ACh and, therefore, enhance people's quality of life, and, at the very least, it can temporarily lessen the symptoms of NDs. 1,2,3-triazole, a five-membered heterocyclic ring, is a privileged moiety, that is, a central scaffold, and is capable of interacting with a variety of receptors and enzymes to exhibit a broad range of important biological activities. Recently, it has been clubbed with other pharmacophoric fragments/molecules in hope of obtaining potent and selective AChE and/or BuChE inhibitors. The present updated review succinctly summarizes the different synthetic strategies used to synthesize the 1,2,3-triazole moiety. It also highlights the anticholinesterase potential of various 1,2,3-triazole di/trihybrids reported in the past seven years (2015–2022), including a rationale for hybridization and with an emphasis on their structural features for the development and optimization of cholinesterase inhibitors to treat NDs. [ABSTRACT FROM AUTHOR]

In order to obtain potential anticancer agents, hybrid compounds have been synthesized by coupling thiazolidinone and pyrazole scaffolds. Among the synthesized compounds, 2-(1,3-diphenyl-1H-pyrazol-4-yl)-3-phenyl thiazolidin-4-one (4a) was found to be the most potent based on a docking (−9.307) and binding scores (−66.46), along with good ADME parameters. In vitro anticancer activity of compound 4a shows a maximum inhibition against lung cancer (NCI-H23) cell lines with a moderate inhibition rate of 31.01%. Molecular docking studies revealed that these hybrid compounds bind well to the active site of peroxisome proliferator-activated receptors-gamma (PPAR-gamma). Doxorubicin was used as a positive control. It can be concluded that 4a having pyrazole-thiazolidinone ring systems has the potential to be developed as an anticancer agent. [ABSTRACT FROM AUTHOR]

Canola (Brassica napus L.) is one of the economically important crops of Pakistan and mustard aphid, Lipaphis erysimi Kalt. (Hemiptera: Aphididae), is a serious threat to this crop. This experiment was conducted with an aim to screen out selected canola cultivars for their tolerance against L. erysimi infestation under glasshouse conditions. Experiment was carried out using completely randomized design with ten replications for each treatment during growing seasons of 2018 and 2019. Data were documented based on the tolerance indices (TI) and proportional plant dry weight change (DWT) to identify tolerance of canola crop. Results revealed that commercial cultivar 'Zahoor' comparatively performed well despite higher number of aphids found on itas compared its other counterparts "Abaseen, Omega and KS-75" and hence, was identified as tolerant to mustard aphid. This cultivar also exhibited strong vigor against mustard aphid and minimal symptoms of damages were observed. The yield losses based on DWT and TI in susceptible cultivar "Abaseen" was 40.79%, whereas it was 23.56% in Zahoor which confirmed the reduced percent yield losses in the later genotype. This study identified "Zahoor" as the most tolerant cultivar to mustard aphid followed by KS-75 and Omega hence, other susceptible cultivars should be replaced by Zahoor to attain higher and sustainable yield production in canola. [ABSTRACT FROM AUTHOR]

COVID-19 has had an impact on human quality of life and economics. Scientists have been identifying remedies for its prevention and treatment from all possible sources, including plants. Nigella sativa L. (NS) is an important medicinal plant of Islamic value. This review highlights the anti-COVID-19 potential, clinical trials, inventions, and patent literature related to NS and its major chemical constituents, like thymoquinone. The literature was collected from different databases, including Pubmed, Espacenet, and Patentscope. The literature supports the efficacy of NS, NS oil (NSO), and its chemical constituents against COVID-19. The clinical data imply that NS and NSO can prevent and treat COVID-19 patients with a faster recovery rate. Several inventions comprising NS and NSO have been claimed in patent applications to prevent/treat COVID-19. The patent literature cites NS as an immunomodulator, antioxidant, anti-inflammatory, a source of anti-SARS-CoV-2 compounds, and a plant having protective effects on the lungs. The available facts indicate that NS, NSO, and its various compositions have all the attributes to be used as a promising remedy to prevent, manage, and treat COVID-19 among high-risk people as well as for the therapy of COVID-19 patients of all age groups as a monotherapy or a combination therapy. Many compositions of NS in combination with countless medicinal herbs and medicines are still unexplored. Accordingly, the authors foresee a bright scope in developing NS-based anti-COVID-19 composition for clinical use in the future. [ABSTRACT FROM AUTHOR]

Potato (Solanum tuberosum L.) is an important vegetable food crop in Pakistan. Myzus persicae is an insect pest of potato, feeding on phloem tissues of leaves of potato plant and significantly reduces the yield of potato. Antixenosis experiments were performed to assess the resistance potential of eight different potato cultivars against M. persicae under glasshouse conditions for three different durations of time (12, 24 and 48 hours) during spring and autumn potato growing seasons of 2016. Both the experiments were conducted using a completely randomized design. Each experiment having eight treatments and each treatment was replicated 10 times. The replicated pots containing each of the eight potato cultivars were infested with 100 and 200 adult of M. persicae. Significant antixenosis effects among the tested potato cultivars were observed while the different durations of M. persicae infestation on potato cultivars also displayed significant antixenosis effects against M. persicae during the spring and autumn experiments in 2016. During both experiments, Sarpo Mira displayed the lowest number of adults per plant on release of 100 and 200 adults per plant. Sarpo Mira showed M. persicae infestation of 3.3 and 2.4 per plant per pot on release of 100 adults per plant during spring and autumn seasons, respectively while an infestation of 5.3 per plant 4.7 per plant on Sarpo Mira was observed on release of 200 adults of M. persicae during spring and autumn seasons, respectively. FD-70 had the highest number of M. persicae (13.7 per plant) in the pots released with 100 M. persicae during spring season while Asterix showed the highest number of M. persicae (13.8 per plant) in pots infested with 200 M. persicae during autumn season. Sarpo Mira also appeared to be the most resistant potato cultivar against M. persicae at 12, 24 and 48 hours post infestation of M. persicae. Overall, this study revealed the resistant potential of potato cultivar Sarpo Mira against M. persicae. [ABSTRACT FROM AUTHOR]

Furanone, a five-membered heteroaromatic ring containing oxygen atom, is of immense pharmaceutical importance. Presence of this nucleus in biologically active compounds of natural and synthetic origin has made it an indispensable motif for design and development of new therapeutic agents. In recent years synthesis of furanone derivatives and exploring their therapeutic actions has been the prime interest amongst researchers. Furanone containing compounds cover numerous therapeutic categories viz. Analgesic and anti-inflammatory, anticancer, anticonvulsant, antibacterial and antifungal, antioxidant, antiulcer and anti-TB, etc. There is a need to couple recent work done with previously available information on furanone, a well acknowledged scaffold, to help scientists to develop novel and new furanone based therapeutic agents at a faster pace. This updated review highlights the worth of numerous therapeutically active furanone based compounds developed by the medicinal chemists. SAR studies have also been derived which may be useful for rational designing of furanone derivatives with improved therapeutic index. Image 1 • 2(5H) furanone derivatives emerged as the most promising anti-inflammatory, anti-cancer and anti-microbial agents. • The review covers useful pharmacological activities of furanone derivatives along with SAR studies. • It provides an overview of research work carried out on furanones in past three decades. • Enlist the patents granted on furanones and drugs containing furanone nucleus. [ABSTRACT FROM AUTHOR]

In the Netherlands, the central government, water authorities, provinces and municipalities are working together on a new Delta Program on Flood Risk Management and Fresh Water Supply (DP). Its primary goal is to protect the Netherlands against floods and ensure the availability of fresh water, now and for future generations. The DP has developed a new, adaptive management concept: the Adaptive Delta Management (ADM) approach. ADM is defined as ‘a smart and intelligent way of taking account of uncertainties and dependencies in decision-making on Delta Management with a view to reducing the risk of overspending or underinvestment’. Important features of DP are: (i) involving multiple stakeholders in a joint decision-making process to enhance ownership, legitimacy and feasibility; (ii) taking a risk-based perspective; (iii) adopting a flexible approach in possible strategies by valuing flexibility with regard to the timing of implementation and (iv) interlinking various investment agendas and looking for opportunities for mainstreaming with planned investments. Along similar lines, a Bangladesh Delta Plan 2100 (BDP 2100) is being devised to achieve long-term sustainable socio-economic development and provide safety in the face of disasters through adaptive water governance in Bangladesh. It embodies a holistic, integrated vision, adaptive strategies and a long-term investment agenda for the Bangladesh Delta. The Plan is scheduled to be finalized in 2017. ADM is not an approach that can be transferred easily from one country to another as it demands a fundamental change in institutional capacity at multiple levels including new knowledge and skills, relationships and policy frameworks, and, hence, depends on the local socio-economic characteristics, culture and governance. This paper explores the challenges and opportunities for successful formulation and implementation of BDP 2100. [ABSTRACT FROM AUTHOR]

We report herein one-pot synthesis and the antibacterial and antitubercular activities of 2,5-disubstituted-1,3,4-oxadiazole compounds obtained by hybridization of a well-known antitubercular agent isoniazid ( INH) with four broad-spectrum antibiotics belonging to fluoroquinolone ( FQ) class. The work is aimed at designing and developing potential antimicrobial agents having synergistic action due to the coupling of INH and FQ through the biologically active 1,3,4-oxadiazole nucleus. The synthesized compounds are expected to have low toxicity as compared to INH due to the absence of free hydrazide group in the chemical structure of the prepared derivatives. The antibacterial activities of the 1,3,4 oxadiazole derivatives were also tested against several Gram-positive and Gram-negative pathogenic bacterial strains. The antitubercular activity was evaluated against M. tuberculosis H37Rv strain, and the results were compared with that of the positive control INH. The title compounds showed excellent antimicrobial and promising antitubercular activity in comparison to the parent fluoroquinolones and INH, respectively. [ABSTRACT FROM AUTHOR]

A number of pyridazinone derivatives bearing substituted benzylidene and heterocyclic/aromatic rings at 4th and 6th positions, respectively were synthesized in good to moderate yields and screened for antioxidant activity. Antioxidant activity of pyridazinone derivatives was evaluated by using several in vitro radical scavenging methods such as 1,1-diphenylpicrylhydrazyl (DPPH), hydrogen peroxide (H2O2), nitric oxide (NO), reducing power, and metal chelating assay etc. Molegro virtual docker software was used to study the binding affinity of the title compounds with the xanthine oxidoreductase enzyme. Amongst the tested compounds, 5a, 5d, 5g & 5j were found to exhibit excellent antioxidant activity at par with the positive control, ascorbic acid. The molecular docking studies of these compounds demonstrated a good selectivity profile with xanthine oxidoreductase receptors. A preliminary study of the structural-activity relationship showed that the presence of electron withdrawing group and heterocyclic ring on pyridazinone nucleus are associated with the best potency and selectivity profile. It could be proposed that xanthine oxidoreductase receptor may be involved in observed antioxidant activity of pyridazinone derivatives bearing aromatic ring and benzylidene substituents and thus the synthesized compounds are worthy of further exploration. [ABSTRACT FROM AUTHOR]

Metronidazole is an antiprotozoal drug which is also effective against anaerobic bacteria. It exhibits pronounced in-vitro and in-vivo activity against Trichomonas vaginalis and E. histolytica. Many different brands and dosage forms of Metronidazole are available in the gulf countries that place physicians and pharmacists in a dilemma of drug substitution in case of non availability of a particular brand. The present study was aimed to evaluate the pharmaceutical equivalence of four brands of 250 mg Metronidazole tablets marketed in Middle East countries. Four brands of Metronidazole tablets were purchased locally from the retail pharmacy outlets in Muscat, Oman and their solubility, partition coefficient (log P) and pharmaceutical quality were assessed by using in-vitro tests as per the United States Pharmacopoeia (USP) and unofficial standards as recommended by the manufacturers. Selected brands of Metronidazole were found to be highly soluble, highly permeable and also passed all the official and unofficial in- vitro quality control tests prescribed for the tablets except hardness test. All brands of Metronidazole tablets released more than 70% of their drug content within 45 minutes. Thus, based on the above results, it can be concluded that tested brands of Metronidazole tablets being eligible for biowaiver, are pharmaceutically equivalent and therefore can be considered for drug substitution for each other. [ABSTRACT FROM AUTHOR]

Human African trypanosomiasis (HAT or 'sleeping sickness') is a neglected tropical disease. If untreated, it is always fatal and leads to death. A few treatments are available for HAT, but most of them require a skilled professional, which increases the financial burden on the patient. Recently, fexinidazole (FEX) has been approved by the European Medicine Agency (EMA) and the United States Food and Drug Administration (USFDA) as the first all-oral therapy for the treatment of stage-1 (hemolymphatic) as well as stage-2 (meningoencephalitic) of HAT. Before the FEX approval, there were separate treatments for stage-1 and stage-2 of HAT. This study reviews the discovery, development timeline, inventions, and patent literature of FEX. It was first approved by EMA and USFDA in 2018 and 2021, respectively. FEX was also added to the World Health Organization's list of essential drugs in 2019. The patent literature search revealed many types of patents/patent applications (compound, salt, process, method of treatment, drug combinations, and compositions) related to FEX, which have been summarized in this article. The authors foresee a great scope to develop more inventions based on FEX (novel salts, polymorphs, drug conjugates, cyclodextrin complex, etc.) for the treatment of many protozoal diseases (Leishmaniasis and Chagas disease), inflammatory diseases, and other microbial infections. New combinations of FEX with other treatments of HAT may also provide fruitful results. This review might be useful to the scientists working on the HAT and other neglected diseases to develop novel inventions and innovations of therapeutic relevance. [ABSTRACT FROM AUTHOR]

Metronidazole is an antiprotozoal drug which is also effective against anaerobic bacteria. It exhibits pronounced in-vitro and in-vivo activity against Trichomonas vaginalis and E. histolytica. Many different brands and dosage forms of Metronidazole are available in the gulf countries that place physicians and pharmacists in a dilemma of drug substitution in case of non availability of a particular brand. The present study was aimed to evaluate the pharmaceutical equivalence of four brands of 250 mg Metronidazole tablets marketed in Middle East countries. Four brands of Metronidazole tablets were purchased locally from the retail pharmacy outlets in Muscat, Oman and their solubility, partition coefficient (log P) and pharmaceutical quality were assessed by using in-vitro tests as per the United States Pharmacopoeia (USP) and unofficial standards as recommended by the manufacturers. Selected brands of Metronidazole were found to be highly soluble, highly permeable and also passed all the official and unofficial in- vitro quality control tests prescribed for the tablets except hardness test. All brands of Metronidazole tablets released more than 70% of their drug content within 45 minutes. Thus, based on the above results, it can be concluded that tested brands of Metronidazole tablets being eligible for biowaiver, are pharmaceutically equivalent and therefore can be considered for drug substitution for each other. [ABSTRACT FROM AUTHOR]

Quercetin, a bioflavonol is widely found in nature and possesses diverse pharmacological properties. A heterocyclic 1,4 dioxane nucleus was incorporated in Quercetin to obtain two structural analogues of silybin. The aim of the study was to explore antihepatotoxic potential of Quercetin derivatives containing 1,4 dioxane heterocyclic ring in Carbon tetrachloride (CCl4) induced hepatotoxicity in female Wistar Albino rats. Two Quercetin derivatives (QD) were synthesized by reported method. QD were administered orally at dose of 10 mg/kg, once daily for 7 days to Wistar Albino rats. A single dose of CCl4 (1mL/kg) was used for inducing liver damage. Antihepatotoxic activity was evaluated by measuring levels of total proteins (TP), total albumin (TA), alkaline phosphatase (ALKP) and liver enzymes such as serum glutamate oxaloacetate (SGOT) and serum glutamate pyruvate transaminase (SGPT).QD exhibited potent antihepatotoxic activity with respect to standard drug silybon-70. However, it was observed that the Quercetin derivative having -CH2OH group in the dioxane ring exhibited better activity in comparision to unsubstituted 1,4 dixoane ring derivative. The exact mechanism by which QD protects the liver is unknown however the observed effects could be attributed to presence of 1,4 dioxane ring and due to the significant antioxidant activity of Quercetin flavone. [ABSTRACT FROM AUTHOR]

This study was aimed at the synthesis of few xanthone derivatives containing 1,4-dioxane ring system. The reaction of 3,4-dihydroxy xanthone derivatives (3a-c) with ethylene dibromide and epichlorohydrin under approriate reaction conditions afforded xanthone derivatives containing 1,4-dioxane ring system (4a-e). The structures of the synthesized compounds were confirmed on the basis of their chemical and spectral data. This work was also extended to study the possible antihepatotoxic activity of the newly synthesized compounds against carbon tetrachloride (CCl4)-induced hepatotoxicity in female Wistar albino rats by estimating the levels of biochemical parameters such as total proteins (TP), total albumin (TA), alkaline phosphatase (ALKP), serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT). Compound 4b [3,4-(2'-hydroxy methyl-1',4'-dioxano) xanthone] showed a potent antihepatotoxic activity comaparable to the standard reference drug Silybon-70®, whereas other compounds exhibited moderate activity. It was also observed that the unsubstituted xanthone derivatives possessing 1,4-dioxane ring have better antihepatotoxic activity in comparision to nitro-and bromo-substituted xanthone derivatives. [ABSTRACT FROM AUTHOR]

The ethanolic extract of Ficus carica leaves was screened for hepatoprotective and antioxidant activity in hepatotoxic Albino rats induced via carbon tetrachloride. The degree of protection was measured by estimating biochemical parameters such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), total protein (TP), total albumin (TA), alkaline phosphatase (ALKP) and the level of total serum bilirubin. The extract in addition reduced CCl4 induced lipid peroxidation in-vivo and in-vitro. The ethanolic extract (50 mg/kg, 100mg/kg, 200 mg/kg) exhibited significant hepatoprotection in carbon tetrachloride intoxicated rats in a dose dependant manner. The hepatoprotective effects of the extract were comparable with the standard drug silymarin (10 mg/kg body weight, IP). [ABSTRACT FROM AUTHOR]

The article presents a case study of an eight-year-old immunocompetent child who is suffering from calcaneal osteomyelitis caused by exophiala jeanselmei. The child received treatment from his primary care physician in the form of local dressings and broad-spectrum antibiotics. Clinical examination of the child revealed that his chest radiograph is normal.

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]

Natural compounds such as polyphenols play several positive roles in maintaining the oxidative and inflammatory capacity of cells, which leads to their potential use as anticancer therapeutics. There is promising evidence for the in vitro and in vivo anticancer activity of many polyphenols, including resveratrol and quercetin, specifically in the treatment of colorectal cancer (CRC). There is a clear association between resveratrol and quercetin in interfering with the mechanistic pathways involved in CRC, such as Wnt, P13K/AKT, caspase-3, MAPK, NF-κB, etc. These molecular pathways establish the role of resveratrol and quercetin in controlling cancer cell growth, inducing apoptosis, and inhibiting metastasis. The major bottleneck in the progression of the use of resveratrol and quercetin as anticancer therapeutics is their reduced bioavailability in vivo because of their rapid metabolism in humans. Recent advancements in various nanotechnological formulations are promising for overcoming these bioavailability issues. Various nanoformulations of resveratrol and quercetin have shown an optimistic impact on reducing the solubility and improving the stability of resveratrol and quercetin in vivo. A combinatorial approach using nanoformulations of resveratrol with quercetin could potentially increase the impact of resveratrol in controlling CRC cell proliferation. This review discusses the mechanism of resveratrol and quercetin, the two bioactive polyphenolics, in colon cancer, with an emphasis on various types of nanoformulations of the two molecules targeting colon cancer. It also explores the synergistic effect of combining resveratrol and quercetin in various nanoformulations, targeting colon cancer. This research delves into the enhanced pharmacokinetics and potential chemotherapeutic benefits of these bioactive polyphenolics when used together in innovative ways. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the knowledge and attitudes among pharmacists in Oman towards the specific use and knowledge of herbal drugs. Methods: The study was conducted on 100 pharmacists employed in Oman. The data was collected using two self- administered questionnaire containing 7 and 11 closed ended questions in each, respectively. Results: The mean age of pharmacists was 32.6 (SD=5.6) years. The majority of pharmacists were interested in herbal information and their herbal information mainly comes from their previous classes during college. Most of them have belief on the effectiveness of herbal products. Pharmacists were more knowledgeable on specific therapeutic indications of herbal products rather than on other areas such as drug- herb interaction or side effects. Conclusion: In summary, Pharmacists need to be informed on the therapeutic indications, drug interactions, dose, active constituent and precautions of herbal products. Concerned bodies must also provide them with regular continuing education programs apart from putting their effects to incorporate relevant topics in herbal medicine in pharmacy curriculum. [ABSTRACT FROM AUTHOR]

We present a 6-year-old child with a chondromyxoid fibroma (CMF) of the clavicle. In view of the atypical site, clinical features and imaging was not useful to pin point a diagnosis. The diagnosis was confirmed on histopathology. CMF is a rare benign bone tumor and only three cases of CMF clavicle are reported in world literature. Our patient is the first child reported with CMF of the clavicle. A very good result was obtained following an en-block resection of the clavicle. The report highlights the importance of keeping a diagnosis of CMF even at atypical sites like clavicle. [ABSTRACT FROM AUTHOR]

Abstract: We present a 27-year-old man with pure anterior dislocation of the ankle joint following a fall from height. There were no accompanying fractures in and around the ankle joint. The injury was initially missed on clinical examination in view of minimal ankle deformity. The patient was managed conservatively with closed reduction and plaster immobilisation. The case report highlights the importance of early diagnosis and management of anterior ankle dislocation to obtain good functional outcome. A review of the literature on this rare injury is also presented. [Copyright &y& Elsevier]

Ewing sarcoma (ES) of the spine is a rare childhood cancer with sparse literature on treatment outcomes. We aimed to describe survival outcomes and prognostic factors in patients with spinal ES treated at a single institute in a resource-challenged setting. We conducted a retrospective analysis of patients with spinal ES registered at a tertiary care oncology center between 2003–2019. Clinical patient data was retrieved from hospital records. Cox regression analysis was used to identify the association of baseline clinical parameters with event free survival (EFS) and overall survival (OS). A cohort of 85 patients was analyzed including 38 (45%) patients with metastatic disease. The median age was 15 years with 73% being male. Local therapy was administered in 62 (72.9%) patients with surgery alone in 8 (9.4%), radiotherapy alone in 36 (42.4%) and both in 18 (21.2%) patients. A higher proportion of males received local therapy than females (80.3% versus 59.1%; p = 0.049). The median EFS and OS were 20.1 and 28.6 months, respectively. On univariable analysis, age ≤ 15 years, female sex, serum albumin ≤3.5 g/dL and hemoglobin ≤11 g/dL were associated with inferior EFS while younger age, female sex, hypoalbuminemia and metastatic disease were associated with inferior OS. On multivariable analysis, only hypoalbuminemia was predictive for inferior EFS (HR:2.41; p = 0.005) while hypoalbuminemia (HR:2.06;p = 0.033) and female sex (HR:1.83; p = 0.046) were associated with inferior OS. We concluded that hypoalbuminemia confers poor prognosis in ES spine. Survival outcomes are poorer in females treated in our setting, possibly due to prevailing sex-based biases. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease that still has no permanent cure. The drugs prescribed in the present days are only for symptomatic relief for the patients. Many studies correlating the reduction in the incidence of AD with the diet consumed have been published. These studies showed that a diet rich in polyphenols is associated with a decrease in the incidence of AD. The present review is focused on the ability of pomegranate and its bioactive components to ameliorate the progression of AD and their ability to exert a neuroprotective effect. Various studies showing the ability of pomegranate in inhibiting enzymes, reducing reactive oxygen species, inhibition of microglial activation, inhibition of tau protein hyperphosphorylation, maintenance of synaptic plasticity, anti-inflammatory activity and its ability to inhibit Beta secretase-1 (BACE-1) has been reviewed in this article. In spite of the lack of studies on humans, there are compelling evidence indicating that pomegranate can reduce various risk factors involved in the causation of AD and thus can be used as a persistent nutraceutical to slow ageing and for providing neuroprotection for the treatment of AD. Highlights An overview of traditional and pharmacological uses of pomegranate (POM). Potential of POM in the treatment of neurodegenerative diseases especially in AD. Insight into the molecular mechanisms of neuroprotective effects of POM in AD. Clinical evaluation studies involving POM and its bioactive components. [ABSTRACT FROM AUTHOR]

Acyclovir (ACV) is a promising candidate for drug repurposing because of its potential to provide an effective treatment for viral infections and non-viral diseases, such as cancer, for which limited treatment options exist. However, its poor physicochemical properties limit its application. This study aimed to formulate and evaluate an ACV-loaded red clay nanodrug delivery system exhibiting an effective cytotoxicity. The study focused on the preparation of a complex between ACV and red clay (RC) using sucrose stearate (SS) (nanocomplex F1) as an immediate-release drug-delivery system for melanoma treatment. The synthesized nanocomplex, which had nanosized dimensions, a negative zeta potential and the drug release of approximately 85% after 3 h, was found to be promising. Characterization techniques, including FT-IR, XRD and DSC-TGA, confirmed the effective encapsulation of ACV within the nanocomplex and its stability due to intercalation. Cytotoxicity experiments conducted on melanoma cancer cell lines SK-MEL-3 revealed that the ACV release from the nanocomplex formulation F1 effectively inhibited the growth of melanoma cancer cells, with an IC50 of 25 ± 0.09 µg/mL. Additionally, ACV demonstrated a significant cytotoxicity at approximately 20 µg/mL in the melanoma cancer cell line, indicating its potential repurposing for skin cancer treatment. Based on these findings, it can be suggested that the RC-SS complex could be an effective drug delivery carrier for localized cancer therapy. Furthermore, the results of an in silico study suggested the addition of chitosan to the formulation for a more effective drug delivery. Energy and interaction analyses using various modules in a material studio demonstrated the high stability of the composite comprising red clay, sucrose stearate, chitosan and ACV. Thus, it could be concluded that the utilization of the red clay-based drug delivery system is a promising strategy to improve the effectiveness of targeted cancer therapy. [ABSTRACT FROM AUTHOR]

Pyrilla perpusilla (Walker) is one of the devastating pests which decrease yield directly and indirectly of sugarcane crop. For the safe management of P. perpusilla, field experiments were conducted to find the population of Pyrilla perpusilla on 12 different sugarcane varieties under field conditions at two different districts Charsadda and district Dera Ismail Khan of Khyber Pakhtunkhwa. Plot size 36×16 m (length × width) was selected in both localities for the cultivation of sugarcane varieties (CP77/400, Jhang 59, 2086, US-633, YT-55, CPF-252, CPF-246, CPF-251, CPF-247, CPF-250, CPF-248, and CPF-249) in Feb 2020. Each variety was planted in sub-plot size 3×2 meters having 3 rows and 5plants/row in randomized complete block design (RCBD) with three replications. The data was recorded from Mar-Nov from fresh and ratoon crops of the year 2020 and 2021, respectively. The leaves (top, middle, and bottom) of five plants in each subplot was observed randomly for data collection every fortnight in all replications. The total mean population of Pyrilla perpusilla (eggs cluster and nymphs/adults) was recorded from the leaves of the plants. The experimental results were of the view that could be used to conclude the research that the different varieties have different behaviour towards hosting the P. perpusilla. The population Pyrilla perpusilla (eggs clusters and nymphs/adults) were found highest on CPF-252 while least population of P. perpusilla was recorded on CPF-249 in both location and both years of the study (2020-2021) with its peak activity in the month of August. Significantly, positive correlation was recorded between P. perpusilla (eggs clusters and nymphs/adults) population infestation and average abiotic factors (temperature, humidity and rainfall). The correlation between leaf length and leaf width with P. perpusilla (eggs clusters and nymphs/adults) was significantly positive, the correlation of P. perpusilla (eggs clusters and nymphs/adults) with cane length was non-significant but positive while negative non-significant correlation was found between P. perpusilla (eggs clusters and nymphs/adults) population and cane diameter. The population of P. perpusilla on sugarcane variety CPF-249 was comparatively less which can be combine in future IPM programmes for the suppression of P. perpusilla infestation. [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]

An obituary for orthopedics William Fisher Enneking is presented.

Background: Osteosarcoma is a type of bone cancer that predominantly affects young individuals, including children and adolescents. The disease progresses through heterogeneous genetic alterations, and patients often develop pulmonary metastases even after the primary tumors have been surgically removed. Ubiquitin-specific peptidases (USPs) regulate several critical cellular processes, such as cell cycle progression, transcriptional activation, and signal transduction. Various studies have revealed the significance of USP37 in the regulation of replication stress and oncogenesis. Methods: In this study, the Cancer Genome Atlas (TCGA) database was analyzed to investigate USP37 expression. RNA sequencing was utilized to assess the impact of USP37 overexpression and depletion on gene expression in osteosarcoma cells. Various molecular assays, including colony formation, immunofluorescence, immunoprecipitation, and DNA replication restart, were employed to examine the physical interaction between USP37 and PCNA, as well as its physiological effects in osteosarcoma cells. Additionally, molecular docking studies were conducted to gain insight into the nature of the interaction between USP37 and PCNA. Furthermore, immunohistochemistry was performed on archived tissue blocks from osteosarcoma patients to establish a correlation between USP37 and PCNA expression. Results: Analysis of the TCGA database revealed that increased expression of USP37 was linked to decreased progression-free survival (PFS) in osteosarcoma patients. Next-generation sequencing analysis of osteosarcoma cells demonstrated that overexpression or knockdown of USP37 led to the expression of different sets of genes. USP37 overexpression provided a survival advantage, while its depletion heightened sensitivity to replication stress in osteosarcoma cells. USP37 was found to physically interact with PCNA, and molecular docking studies indicated that the interaction occurs through unique residues. In response to genotoxic stress, cells that overexpressed USP37 resolved DNA damage foci more quickly than control cells or cells in which USP37 was depleted. The expression of USP37 varied in archived osteosarcoma tissues, with intermediate expression seen in 52% of cases in the cohort examined. Conclusion: The results of this investigation propose that USP37 plays a vital role in promoting replication stress tolerance in osteosarcoma cells. The interaction between USP37 and PCNA is involved in the regulation of replication stress, and disrupting it could potentially trigger synthetic lethality in osteosarcoma. This study has expanded our knowledge of the mechanism through which USP37 regulates replication stress, and its potential as a therapeutic target in osteosarcoma merits additional exploration. [ABSTRACT FROM AUTHOR]

A pharmaceutical formulation with favorable pharmacokinetic parameters is more likely to be efficacious and safe to overcome the failures of the drug resulting from lack of efficacy, poor bioavailability, and toxicity. In this view, we aimed to evaluate the pharmacokinetic functionalities and safety margin of an optimized CS-SS nanoformulation (F40) by in vitro/in vivo methods. The everted sac technique was used to evaluate the improved absorption of a simvastatin formulation. In vitro protein binding in bovine serum and mice plasma was performed. The formulation's liver and intestinal CYP3A4 activity and metabolic pathways were investigated by the qRT-PCR technique. The excretion of cholesterol and bile acids was measured to demonstrate the formulation's cholesterol depletion effect. Safety margins were determined by histopathology as well as fiber typing studies. In vitro protein binding results revealed the existence of a high percentage of free drugs (22.31 ± 3.1%, 18.20 ± 1.9%, and 16.9 ± 2.2%, respectively) compared to the standard formulation. The controlled metabolism in the liver was demonstrated from CYP3A4 activity. The formulation showed enhanced PK parameters in rabbits such as a lower Cmax, clearance, and a higher Tmax, AUC, Vd, and t1/2. qRT-PCR screening further proved the different metabolic pathways followed by simvastatin (SREBP-2) and chitosan (PPAR-γ pathway) in the formulation. The results from qRT-PCR and histopathology confirmed the toxicity level. Hence, this pharmacokinetic profile of the nanoformulation proved it has a unique synergistic hypolipidemic modality. [ABSTRACT FROM AUTHOR]

A simple, sensitive, accurate and inexpensive UV-reversed-phase high-performance liquid chromatographic method was developed for the determination of ascorbic acid in tablet formulations. The method was based on the separation of ascorbic acid using a mobile phase of an acetonitrile-NaH2PO4-H3PO4 buffer solution (pH = 3) (5:95 v/v) with a UV detection wavelength of 245 nm and a flow rate of 0.8 mL min−1 at ambient column temperature. The variables of the proposed method, such as acetonitrile fraction (%), flow rate (mL min−1) and column temperature (°C), were optimized on the peak area by response surface methodology via the Box–Behnken design. The mobile phase was passed isocratically, and the separation of ascorbic acid was performed at the retention time of 4.1 min. A calibration graph was obtained and found to be linear in the concentration range of 10–180 µg mL−1. The method suitability was assessed and an asymmetry factor of 1.15 was obtained. The proposed method was successfully applied for the determination of ascorbic acid in tablet formulations and statistically compared with the results of the reference method. The performance of the proposed method was excellent and in agreement with the reference method. The recovery percentage of the proposed and reference methods was in the range of 99.98–100.04% and showed compliance (100 ± 2%) with regulatory guidelines. [ABSTRACT FROM AUTHOR]

The article presents an obituary for Ignacio Vives Ponseti, a physician who developed the Ponseti Method of treating clubfoot.

In Pakistan and other developing countries, the available data on the association of T2DM and HCV is limited. We therefore made an attempt to report the association of HCV and diabetes in Pakistani population through this meta-analysis. HCV and diabetes related studies were identified using various key words, from a number of databases including CINAHL, PubMed, Web of Science and Embase. Using RevMan5, the main outcome was regarded as type 2 diabetes associations with hepatitis c virus infection in Pakistan. Independent analyses were made for "HCV in diabetic patients" and "diabetes cases in hepatitis C virus patients". Using random effect model, odds ratios were calculated with 95% CIs (dichotomous data). I2 statistics were used to calculate heterogeneity. From a total of 53 studies, we finally selected 6 studies for the meta-analysis. Using random effects model, hepatitis c virus patients in 3 studies (n = 1,902) demonstrated that HCV is a risk factor in developing diabetes, contrary to patients with no HCV infection (OR 0.01, 95% CI: 0.00-0.06, I2 = 0%; RR 0.01, 95% CI: 0.00-0.07, I2 = 0%). The remaining 3 studies (n = 13,710) had reported HCV infections in type 2 diabetic patients and patients with no diabetes. Similarly, our meta-analysis revealed higher prevalence of HCV infections in patients with type 2 diabetes (OR 0.7, 95% CI: 0.17-0.42, I2 = 32%; RR 0.30, 95% CI: 0.20-0.46, I2 = 32%) as compared to patients with no type 2 diabetes mellitus. Our meta-analysis demonstrates a significant link between HCV and T2DM. Further studies are recommended with adequate sample sizes [ABSTRACT FROM AUTHOR]

Peach flat-headed borer, Sphenoptera dadkhani (Oben.) is the major insect-pest of stone fruit orchards. Survey of three districts of Khyber Pakhtunkhwa revealed the highest mean infestation in plum orchards of district Peshawar (89.60%), followed by Nowshera (75.79%) and Swat (45.42%). In peach orchards, highest mean infestation was recorded in Peshawar (88.33%), followed by Nowshera (72.77%) and Swat (53.72%). The mean infestation of 70.86% was recorded in apricot orchards in Peshawar, followed by Nowshera (62.40%) and Swat (40.73%). Bordeaux mixture treatment applied to tree trunks was very effective in reducing the borer infestation during dormant season. After pruning orchards, Nurelle-D 505EC and Triazofos 40EC @ 75ml of each proved to be the best toxicants, which showed synergistic effect in Bordeaux mixture (Copper oxychloride 75g + Lime 3kg + water 10L) in reducing borer infestation (exit holes/ gum points) in the month of January. [ABSTRACT FROM AUTHOR]

Background: Aspergillosis is a rare cause of osteomyelitis and septic arthritis. Aspergillus osteomyelitis is a debilitating infection affecting both immunocompromised and immunocompetent patients. It is associated with a high incidence of morbidity and mortality. Infection with Aspergillus flavus species in the knee has been very rarely seen in the past. Case presentation: We present a case of septic arthritis of the knee in an Indian patient secondary to infection with Aspergillus flavus, which was earlier managed as a case of tuberculosis based on the endemicity of the condition, later leading to disseminated aspergillosis. There was no clinical feature or investigation suggesting immunocompromised state. Following knee arthrotomy, Aspergillus flavus was isolated and patient was subsequently managed with antifungals leading to recovery after three months. Conclusions: Disseminated aspergillosis can mimic tuberculosis both clinically and radiologically. Though fungal infections affect joints rarely but they must always be ruled out to avoid later complications. [ABSTRACT FROM AUTHOR]

Surface osteosarcomas are a rare form of osteosarcomas accounting for around 3-6% of all osteosarcomas. Three major groups of surface osteosarcomas are parosteal, periosteal and the high grade surface osteosarcomas. Of these, the parosteal osteosarcoma is the most common. Parosteal and periosteal osteosarcomas are distinct clinical entities and it is important to identify the clinicoradiological differences between the two types. Surface osteosarcomas occur at a later age as compared to conventional osteosarcomas. The classical site is the lower end of the femur followed by the upper end of the tibia and upper end of humerus, in that order. The periosteal variant affects the tibia more commonly than the parosteal variety. Neo‑adjuvant chemotherapy is the standard of care for high grade surface osteosarcomas. Parosteal osteosarcomas, being low grade lesions, can be treated by upfront wide excision without adjuvant systemic therapy. Controversy prevails over the need for chemotherapy in periosteal osteosarcomas, which are intermediate grade lesions. [ABSTRACT FROM AUTHOR]

Several generations of antiepileptic drugs (AEDs) are available in the market for the treatment of seizures, but these are amalgamated with acute to chronic side effects. The most common side effects of AEDs are dose-related, but some are idiosyncratic adverse drug reactions (ADRs) that transpire due to the formation of reactive metabolite (RM) after the bioactivation process. Because of the adverse reactions patients usually discontinue the medication in between the treatment. The AEDs such as valproic acid, lamotrigine, phenytoin etc., can be categorized under such types because they form the RM which may prevail with life-threatening adverse effects or immune-mediated reactions. Hepatotoxicity, teratogenicity, cutaneous hypersensitivity, dizziness, addiction, serum sickness reaction, renal calculi, metabolic acidosis are associated with the metabolites of drugs such as arene oxide, N -desmethyldiazepam, 2-(1-hydroxyethyl)-2-methylsuccinimide, 2-(sulphamoy1acetyl)-phenol, E−2-en-VPA and 4-en-VPA and carbamazepine-10,11-epoxide, etc. The major toxicities are associated with the moieties that are either capable of forming RM or the functional groups may itself be too reactive prior to the metabolism. These functional groups or fragment structures are typically known as structural alerts or toxicophores. Therefore, minimizing the bioactivation potential of lead structures in the early phases of drug discovery by a modification to low-risk drug molecules is a priority for the pharmaceutical companies. Additionally, excellent potency and pharmacokinetic (PK) behaviour help in ensuring that appropriate (low dose) candidate drugs progress into the development phase. The current review discusses about RMs in the anticonvulsant drugs along with their mechanism vis -a- vis research efforts that have been taken to minimize the toxic effects of AEDs therapy. [Display omitted] • Reactive metabolites of established antiepileptic drugs (AEDs) with their acute/chronic side-effects are reported. • Various synthetic strategies to minimize the toxicity under each category of AEDs are discussed. • Preclinical data for the synthesized derivatives is represented as compared to standard AEDs. • Structural activity relationship has been discussed for various synthesized derivatives. [ABSTRACT FROM AUTHOR]

In the present study, a novel series of new furanone-based benzothiazole derivatives (4a-j) were synthesized from 4-(benzo[d]thiazol-2-yl)-4-oxobutanoic acid (3) as potential anticancer agents. In vitro cytotoxicity against three human cancer cell lines (A549, MCF7, and DUI45) revealed substantial activity. Di-substituted compound, 4i emerged as a promising anticancer compound which showed IC50 values of 7.2 ± 0.5, 6.6 ± 1.4, and 7.3 ± 0.1 µM against A549, MCF7, and DUI45 cell lines, respectively. Four compounds 4c, 4e, 4f, and 4i evaluated for their acute toxicity were found to be non-toxic on the two vital organs (liver and heart). Further, these compounds were found to be more efficient and less hepatotoxic in comparison to standard drug doxorubicin. Molecular docking studies carried out with VEGFR-2 revealed compounds 4a and 4i as potential VEGFR-2 kinase inhibitors. In silico ADME evaluation was carried out to estimate and predict drug-likeness. Compound 4i demonstrated the best ADME parameters. Based on the results of docking analyses, ADME, and in vitro cytotoxicity, compound 4i is identified as the lead compound for further development of anticancer agents. [ABSTRACT FROM AUTHOR]

Minimally invasive approaches such as sclerotherapy have been introduced to treat aneurysmal bone cysts. Sclerotherapy has been associated with reasonable healing rates during the past two decades. However, it is unclear whether sclerotherapy compares with the more traditional extended curettage and bone grafting. We therefore compared the healing rates and functional scores in patients having percutaneous repetitive sclerotherapy using polidocanol (Group 1) with those with intralesional excision (extended curettage with a high-speed burr) and bone grafting (Group 2) for treatment of aneurysmal bone cyst. We randomly divided 94 patients into two treatment groups. We assessed healing rates (primary outcome measure), pain relief, time to healing and recurrence, hospital stay, and the Enneking functional score. Forty-five patients from Group 1 and 46 from Group 2 were available for study. The minimum followup was 3.2 years (mean, 4.4 years; range, 3.2–6.1 years). At last followup, 93.3% in Group 1 and 84.8% in Group 2 had achieved healing. Complications in Group 1 were minor and resolved. In Group 2, three patients had deep infections and five had superficial infections, and two had growth disturbances. Although the healing rates were similar, we found higher rates of clinically important complications, worse functional outcomes, and higher hospital burden associated with intralesional excision. Repetitive sclerotherapy using polidocanol is a minimally invasive, safer method of treatment for aneurysmal bone cysts compared with intralesional excision and bone grafting. In this preliminary study, we found similar recurrence rates for the two treatment methods, however, this will require confirmation in larger studies. Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

• Recent developments of nitrogen-containing heterocyclic compounds as antidepressant have been discussed. • The antidepressant profile of the potent derivatives along with structural insights is presented. • The SAR studies of recently developed compounds are discussed in details for providing key structural features. • The lead compounds for further development are identified and discussed in the perspective part of this review. According to the World Health Organization (WHO), depression is a common mental disorder and includes complex interaction between social and psychological behaviour affecting 264 million people worldwide. The review aims to highlight the role and importance of nitrogen-based heterocyclics in the development of antidepressant compounds. Many research groups have attempted to design drug candidates capable of binding within the receptors. The commonest drug design strategy includes the incorporation of different structural features widely recognized as an antidepressant in the synthesized derivatives to enhance their CNS antidepressant effects. In this review, we have shed light on nitrogenous heterocyclic moieties such as quinazoline, pyridine, pyrimidine, pyrrolidine, imidazole, pyrazole, piperidine, oxadiazole, benzimidazole, benzothiazole, piperazine, triazine, purine, benzoxazole, and isoxazole as core nucleus and/or in combination as an antidepressant compound. These molecules with different structural features were noted to exert their antidepressant effects by multiple mechanisms viz., selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase (MAO) inhibitors, and Catechol- O -methyltransferase (COMT) inhibitors. The review focuses on the selection of these heterocyclic moieties for the further design and development of promising antidepressants by taking a clue from the earlier reported potent antidepressant compounds or from the marketed products. The results have been correlated with their structural activity relationship (SAR) to identify the substituents for the potency and selectivity within the receptors. This review might help the researchers working in the antidepressant field to develop more novel molecules that could fill the gap by improving potency and reducing toxicity. [Display omitted] [ABSTRACT FROM AUTHOR]

Protein kinase inhibitors (PKIs) are important therapeutic agents. As of 31 May 2021, the United States Food and Drug Administration (USFDA) has approved 70 PKIs. Most of the PKIs are employed to treat cancer and inflammatory diseases. Imatinib was the first PKI approved by USFDA in 2001. This review summarizes the compound patents and the essential polymorph patents of the PKIs approved by the USFDA from 2001 to 31 May 2021. The dates on the generic drug availability of the PKIs in the USA market have also been forecasted. It is expected that 19 and 48 PKIs will be genericized by 2025 and 2030, respectively, due to their compound patent expiry. This may reduce the financial toxicity associated with the existing PKIs. There are nearly 535 reported PKs. However, the USFDA approved PKIs target only about 10–15% of the total said PKs. As a result, there are still a large number of unexplored PKs. As the field advances during the next 20 years, one can anticipate that PKIs with many scaffolds, chemotypes, and pharmacophores will be developed. [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]

Background: Skeletal metastases of bone sarcomas are indicators of poor prognosis. Various imaging modalities are available for their identification, which include bone scan, positron emission tomography/CT scan, MRI, and bone marrow aspiration/biopsy. However, there is considerable ambiguity regarding the best imaging modality to detect skeletal metastases. To date, we are not sure which of these investigations is best for screening of skeletal metastasis.Question/purpose: Which staging investigation-18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT), whole-body MRI, or 99mTc-MDP skeletal scintigraphy-is best in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in detecting skeletal metastases in patients with osteosarcoma and those with Ewing sarcoma?Methods: A prospective diagnostic study was performed among 54 of a total 66 consecutive osteosarcoma and Ewing sarcoma patients who presented between March 2018 and June 2019. The institutional review board approved the use of all three imaging modalities on each patient recruited for the study. Informed consent was obtained after thoroughly explaining the study to the patient or the patient's parent/guardian. The patients were aged between 4 and 37 years, and their diagnoses were proven by histopathology. All patients underwent 99mTc-MDP skeletal scintigraphy, 18F-FDG PET/CT, and whole-body MRI for the initial staging of skeletal metastases. The number and location of bone and bone marrow lesions diagnosed with each imaging modality were determined and compared with each other. Multidisciplinary team meetings were held to reach a consensus about the total number of metastases present in each patient, and this was considered the gold standard. The sensitivity, specificity, PPV, and NPV of each imaging modality, along with their 95% confidence intervals, were generated by the software Stata SE v 15.1. Six of 24 patients in the osteosarcoma group had skeletal metastases, as did 8 of 30 patients in the Ewing sarcoma group. The median (range) follow-up for the study was 17 months (12 to 27 months). Although seven patients died before completing the minimum follow-up, no patients who survived were lost to follow-up.Results: With the number of patients available, we found no differences in terms of sensitivity, specificity, PPV, and NPV among the three staging investigations in patients with osteosarcoma and in patients with Ewing sarcoma. Sensitivities to detect bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (6 of 6 [95% CI 54% to 100%]), 83% (5 of 6 [95% CI 36% to 100%]), and 67% (4 of 6 [95% CI 22% to 96%]) and specificities were 100% (18 of 18 [95% CI 82% to 100%]), 94% (17 of 18 [95% CI 73% to 100%]), and 78% (14 of 18 [95% CI 52% to 94%]), respectively, in patients with osteosarcoma. In patients with Ewing sarcoma, sensitivities to detect bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 88% (7 of 8 [95% CI 47% to 100%]), 88% (7 of 8 [95% CI 47% to 100%]), and 50% (4 of 8 [95% CI 16% to 84%]) and specificities were 100% (22 of 22 [95% CI 85% to 100%]), 95% (21 of 22 [95% CI 77% to 100%]), and 95% (21 of 22 [95% CI 77% to 100%]), respectively. Further, the PPVs for detecting bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (6 of 6 [95% CI 54% to 100%]), 83% (5 of 6 [95% CI 36% to 100%]), and 50% (4 of 8 [95% CI 16% to 84%]) and the NPVs were 100% (18 of 18 [95% CI 82% to 100%]), 94% (17 of 18 [95% CI 73% to 100%]), and 88% (14 of 16 [95% CI 62% to 98%]), respectively, in patients with osteosarcoma. Similarly, the PPVs for detecting bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (7 of 7 [95% CI 59% to 100%]), 88% (7 of 8 [95% CI 50% to 98%]), and 80% (4 of 5 [95% CI 28% to 100%]), and the NPVs were 96% (22 of 23 [95% CI 78% to 100%]), 95% (21 of 22 [95% CI 77% to 99%]), and 84% (21 of 25 [95% CI 64% to 96%]), respectively, in patients with Ewing sarcoma. The confidence intervals around these values overlapped with each other, thus indicating no difference between them.Conclusion: Based on these results, we could not demonstrate a difference in the sensitivity, specificity, PPV, and NPV between 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy for detecting skeletal metastases in patients with osteosarcoma and Ewing sarcoma. For proper prognostication, a thorough metastatic workup is essential, which should include a highly sensitive investigation tool to detect skeletal metastases. However, our study findings suggest that there is no difference between these three imaging tools. Since this is a small group of patients in whom it is difficult to make broad recommendations, these findings may be confirmed by larger studies in the future.Level Of Evidence: Level II, diagnostic study. [ABSTRACT FROM AUTHOR]

A series of benzimidazole‐derived–furanones (4a–l) were synthesized, characterized, and explored for their in vitro anticancer activities. The pharmacokinetic parameters assessed revealed that all the compounds followed the Lipinski's rule of five, making them potential drug candidates. Further, the results of anticancer activity revealed that (E)‐5‐(1H‐benzo[d]imidazol‐2‐yl)‐3‐(3,4,5‐trimethoxybenzylidene)furan‐2(3H)‐one (4a), was active against A549, MCF7, and DU145 with an IC50 values of 10.4 ± 0.39, 11.1 ± 0.43, and 10.7 ± 0.19 μM, respectively. While another compound (E)‐5‐(1H‐benzo[d]imidazol‐2‐yl)‐3‐([5‐phenyl]furan‐2‐yl)furan‐2(3H)‐one (4k) also exhibited good activity against A549, MCF7, and DU145 with IC50 values of 11.4 ± 0.39, 9.1 ± 0.43, and 12.7 ± 0.19 μM, respectively. Doxorubicin was used as the standard drug. Further, molecular docking studies were carried out to provide binding mode into the binding sites of vascular endothelial growth factor receptor (VEGFR). Docking scores and binding energies corroborated well with the results of experimental anticancer activity. Pharmacokinetic (ADME) parameters of the potent derivatives were also found to be in an acceptable range. The benzimidazole‐furanonone conjugates seem to be a potential source for the further development of potent cytotoxic agents. [ABSTRACT FROM AUTHOR]

Abstract: Low grade central osteosarcoma is a rare primary bone tumor. This fibro-osseous lesion shares some radiological and histopathological resemblance with fibrous dysplasia, which is a more common entity. Thus it may be mistaken as fibrous dysplasia and may receive inadequate treatment resulting in a more malignant recurrent bone tumor. We present a case of low grade central osteosarcoma of the right tibia, which was initially treated as fibrous dysplasia with curettage and bone grafting. Three years later the tumor recurred with greater soft tissue and bony involvement but without metastasis. The patient was treated with above knee amputation and has been asymptomatic for the last two years. [Copyright &y& Elsevier]

Résumé: L’ostéosarcome central de faible malignité est une tumeur osseuse primitive rare. En raison de certaines caractéristiques radiographiques et histologiques communes, cette tumeur fibro-osseuse peut être confondue avec la dysplasie fibreuse (lésion osseuse bénigne plus fréquente) et entraîner un traitement inadapté, à l’origine d’une récidive tumorale osseuse de malignité plus élevée. Nous présentons le cas d’un ostéosarcome central de faible malignité du tibia droit, initialement traité comme une dysplasie fibreuse par curetage et greffe osseuse. Trois ans plus tard, la tumeur a récidivé avec un envahissement plus important des parties molles et de l’os, mais sans dissémination métastatique. Le patient a été traité par une amputation au-dessus du genou. Il est resté asymptomatique au cours des deux dernières années. [Copyright &y& Elsevier]

Abstract: Kimura''s disease is a rare, chronic inflammatory disorder, presenting usually as head and neck swellings and regional cervical lymphadenopathy. The disease is more often described from oriental literature but the osseous manifestations and involvement of extremity are rare and unidentified in literature. We present an unusual case of long bone periosteal reaction in a patient of Kimura''s disease of extremity. This potentially innocuous disorder must be kept in mind as a radiological differential of periosteal reaction. [Copyright &y& Elsevier]

Résumé: La maladie de Kimura est une affection chronique inflammatoire rare qui se traduit habituellement par des masses sous-cutanées à la tête et au cou, accompagnées d’adénopathies cervicales. La plupart des cas décrits à ce jour ont été observés en Asie. L’atteinte des membres et les lésions osseuses sont rares. Nous décrivons une observation inhabituelle de maladie de Kimura responsable d’une réaction périostée le long du fémur gauche. Cette maladie bénigne doit faire partie des diagnostics évoqués devant une réaction périostée radiologique. [Copyright &y& Elsevier]