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Revenues from hydropower generation often depend on the operator's ability to provide firm power in the presence of uncertain inflows. The primary options available for optimizing revenue are negotiation of a firm power contract before operations begin and adjustment of the reservoir release during operations. Contract and release strategy optimization are closely coupled and most appropriately analyzed with stochastic real-time control methods. Here we use an ensemble-based approach to stochastic optimization that provides a convenient way to construct nonparametric revenue probability distributions to explore the implications of uncertainty. The firm power contract is a simplified bilateral fixed price agreement that partially insulates operator and buyer from price fluctuations. The release control laws and firm energy target are jointly optimized to maximize the operator's expected revenue. Revenue probability distributions and related spill performance statistics indicate that predictive operating strategies such as stochastic dynamic programming and model predictive control can give significantly better performance than standard deterministic operating rules. The performance obtained from batch optimization with perfect inflow information establishes a convenient upper bound on potential revenue and provides a baseline for assessing the significance of differences between real-time operating strategies. Sensitivity analysis indicates that the benefits of predictive operational strategies are greatest for reservoirs with medium nondimensional residence times and less important for reservoirs with large residence times. Overall, probabilistic analysis of the coupled hydropower contract-operations problem provides a realistic way to assess revenue and risk for reservoirs that must provide firm power when inflows are uncertain.

In the current study, it was intended to prepare liquisolid tablets of pioglitazone HCl to improve the bioavailability and dissolution time of the drug, as it has low solubility in water. Mathematical formulas were adopted, and the quantities of the carrier (MCC), coating material (colloidal silicon dioxides), and nonvolatile liquid vehicle (Tween 80) were taken. Various ratios of the drug to liquid and carrier to coating had been used in the formulation of liquisolid compacts. The evaluation of the formulated liquisolid compacts was done by performing FTIR, DSC, XRD, and SEM studies. Postcompression parameters, dissolution, stability, and bioavailability were accessed for the optimized formulation. FTIR and DSC studies showed the compatibility of the drugs and excipients. XRD revealed the transition to the amorphous state. It was found that the properties of the newly manufactured liquisolid tablets were within the parameters of what is considered acceptable. The optimized formulation of LST10 showed 99.87 ± 0.19% ( p < 0.05) pioglitazone released within 60 min of dissolution. Dissolution data treatments ( Q 15 , IDR, RDR, %DE, MDT, f 1 , and f 2 ) resulted in better drug release than other drugs studied and marketed tablet formulations. The optimized formulation produced had been proven stable when it was subjected to accelerated stability testing. This suggested that the bioavailability of pioglitazone was enhanced, as indicated by the substantial increase in AUC 0- t (3.06-fold) and C max (4.18-fold). According to the findings, the selected combination and method significantly increased the dissolution time and bioavailability of pioglitazone. Moreover, this developed method can be used for other drugs with low water solubility., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Obesity is a burgeoning global health problem with an escalating prevalence and severe implications for public health. New evidence indicates that long non-coding RNAs (lncRNAs) may play a pivotal role in regulating adipose tissue function and energy homeostasis across various species. However, the molecular mechanisms underlying obesity remain elusive., Scope of Review: This review discusses obesity and fat metabolism in general, highlighting the emerging importance of lncRNAs in modulating adipogenesis. It describes the regulatory networks, latest tools, techniques, and approaches to enhance our understanding of obesity and its lncRNA-mediated epigenetic regulation in humans and Drosophila ., Major Conclusions: This review analyses large datasets of human and Drosophila lncRNAs from published databases and literature with experimental evidence supporting lncRNAs role in fat metabolism. It concludes that lncRNAs play a crucial role in obesity-related metabolism. Cross-species comparisons highlight the relevance of Drosophila findings to human obesity, emphasizing their potential role in adipose tissue biology. Furthermore, it discusses how recent technological advancements and multi-omics data integration enhance our capacity to characterize lncRNAs and their function. Additionally, this review briefly touches upon innovative methodologies like experimental evolution and advanced sequencing technologies for identifying novel genes and lncRNA regulators in Drosophila , which can potentially contribute to obesity research., Competing Interests: There are no financial, professional, or personal affiliations that could be perceived as influencing the research presented in this review manuscript., (© 2024 Published by Elsevier Ltd.)

Background: Delirious mania (DM) is a severe psychiatric condition having rapid onset of delirium, mania, and psychosis. It is an emergency condition as it has acute onset and is characterized by extreme hyperactivity. Catatonic signs may also be present. Very few cases have been reported from India, hence making it imperative to study its clinical characteristics and possible treatment, which can help in providing care to such patients in emergency settings., Clinical Cases Description: This paper describes four cases with a diagnosis of DM - demography, clinical features, investigations, treatment. All the patients had an acute onset and rapid progression of symptoms, with clinical symptoms of talkativeness, increased psychomotor activity, decreased need for sleep, aggressive and violent behavior, increased libido, increased appetite with delusion of grandiosity, disorientation to time/place/person, impaired memory of recent events, impaired attention with fluctuating course, negativism, echolalia, and echopraxia., Conclusion: There is a high likelihood of misdiagnosing DM in the absence of diagnostic guidelines. There should be an active search for the underlying aetiology in all cases of DM. Atypical antipsychotics and mood stabilizers may be used to treat less severe forms of DM. Modified electric convulsive treatment and intravenous benzodiazepines elicit a good response., Competing Interests: Conflict of interest: The authors declare no conflicts of interest., (© Authors, 2024.)

Background  The keystone design perforator island flap (KDPIF) is unique among local flaps because of its high potential for adaptation. We describe our experience with the use of the keystone flap for the reconstruction of a variety of defects in different regions of the body concerning its versatility, surgical outcomes, complications, postoperative pain, operative time, and esthetic outcomes. Methods  A prospective observational study was conducted at our institute from June 2021 to June 2023 where the use of KDPIFs in resurfacing soft tissue defects of different etiopathogenesis was evaluated and the data were analyzed. Results  Forty-four patients were included in the study with soft tissue defects of various etiologies and at different locations. The largest flap raised was 18 × 10 cm and the smallest was 4 × 2 cm. The average intraoperative time for completion of the procedure was 74.86 minutes (range: 45-120 minutes). The success rate of flap survivability was 95.45% with two patients having total flap loss necessitating another reconstructive option. Partial flap dehiscence which healed secondarily was observed in two patients. Postoperative pain showed a significant fall of 83.7% from baseline and 82.9% of cases were extremely satisfied with the esthetic outcome. Conclusion  The keystone flap is a valuable reconstructive tool in the armamentarium of a plastic surgeon. It is technically reproducible, suitable to be done in resource-limited settings, and provides contiguous tissue with good vascularity and fewer complications., Competing Interests: Conflict of Interest None declared., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Resveratrol has demonstrated its ability to regulate BRCA1 gene expression in breast cancer cells, and previous studies have established the binding of MBD proteins to BRCA1 gene promoter regions. However, the molecular mechanism underlying these interactions remains to be elucidated. The aimed to evaluate the impact of MBD proteins on the regulation of BRCA1, BRCA2, and p16 genes and their consequential effects on breast cancer cells., Methods: Efficacy of resveratrol was assessed using the MTT assay. Binding interactions were investigated through EMSA, ChIP, & MeIP assay. Expression analyses of MBD genes and proteins were conducted using qRT-PCR and western blotting, respectively. Functional assays, including clonogenic, migratory, and sphere formation assays were used to assess cancer cells' colony-forming, metastatic, and tumor-forming abilities. The cytotoxicity of resveratrol on cancer cells was also tested using an apoptosis assay., Results: The study determined an IC50 of 30µM for resveratrol. MBD proteins were found to bind to the BRCA1 gene promoter. Resveratrol exhibited regulatory effects on MBD gene expression, subsequently impacting BRCA1 gene expression and protein levels. Higher concentrations of resveratrol resulted in reduced colony and sphere formation, decreases migration of cancer cells, and an increases number of apoptotic cells in breast cancer cells. Impact Identification of MBD2-BRCA1 axis indicates their significant role in the induction of apoptosis and reduction of metastasis and proliferation in breast cancer cells. Further therapy can be designed to target these MBD proteins and resveratrol could be used along with other anticancer drugs to target breast cancer., Conclusions: In conclusion MBD2 protein interact to the BRCA1 gene promoter, and resveratrol modulates MBD2 gene expression, which in turn regulates BRCA1 gene expression, and inhibits cell proliferation, migration, and induces apoptosis in ER+, PR+ & Triple negative breast cancer cells., (© 2024. The Author(s).)

Groundwater resources play an important role for irrigation, particularly in arid and semi-arid regions, where groundwater depletion poses a critical threat to agricultural production and associated local livelihoods. However, the relationship between groundwater use, farming, and poverty, particularly with regards to informal mechanisms of resources management, remains poorly understood. Here, we assess this relationship by developing a behavioural model of groundwater user groups, empirically grounded in the politically fragile context of Tunisia. The model integrates biophysical aquifer dynamics, institutional governance, and farmer decision-making, all of which are co-occurring under conditions of aquifer depletion and illicit groundwater extraction. The paper examines how community-level norms drive distributional outcomes of farmer behaviours and traces pathways of local system collapse - whether hydrogeological or financial. Through this model, we explore how varying levels of trust and leadership, ecological conditions, and agricultural strategies can delay or avoid collapse of the social-ecological system. Results indicate limits to collective action under path-dependent aquifer depletion, which ultimately leads to the hydrogeological collapse of groundwater user groups independent of social and institutional norms. Despite this inevitable hydrogeological collapse of user groups, the most common cause of water user group failure is bankruptcy, which is linked to the erosion of social norms regarding fee payment. Social and institutional norms, however, can serve to delay the financial collapse of user groups. In the politically fragile system of Tunisia, low levels of trust in government result in low social penalties for illicit water withdrawals. In the absence of alternative irrigation sources, this serves as a temporary buffer against income-poverty. These results highlight the need for polycentric coordination at the aquifer-level as well as income diversification beyond agriculture to sustain local livelihoods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

β-carotene is obtained from both plants and animals and has been the subject of intense research because of its provitamin-A, antioxidant, and anticancer effects. Its limited absorption and oxidative degradation significantly reduce its antitumor efficacy when taken orally. In our study, we utilize a central composite design to develop "bio-safe and highly bio-compatible" solid lipid nanoparticles (SLNs) by using only the combination of palmitic acid and poloxamer-407, a block co-polymer as a surfactant. The current research aim to develop and characterize SLNs loaded with β-carotene to improve their bioavailability and therapeutic efficacy. In addition, the improved cytotoxicity of solid lipid nanoparticles loaded with β-carotene was screened in-vitro in human breast cancer cell lines (MCF-7). The nanoparticles exhibits good stability, as indicated by their mean zeta potential of -26.3 ± 1.3 mV. The particles demonstrated high drug loading and entrapment capabilities. The fabricated nanoparticle's prolonged release potential was shown by the in-vitro release kinetics, which showed a first-order release pattern that adhered to the Higuchi model and showed a slow, linear, and steady release over 48 h. Moreover, a diffusion-type release mechanism was used to liberate β-carotene from the nanoparticles. For six months, the nanoparticles also showed a notable degree of physical stability. Lastly, using the MTT assay, the anti-cancer properties of β-carotene-loaded solid lipid nanoparticles were compared with intact β-carotene on MCF-7 cell lines. The cytotoxicity tests have shown that the encapsulation of β-carotene in the lipid bilayers of the optimized formulation does not interfere with the anti-cancer activity of the drug. When compared to standard β-carotene, β-carotene loaded SLNs showed enhanced anticancer efficacy and it is a plausible therapeutic candidate for enhancing the solubility of water-insoluble and degradation-sensitive biotherapeutics like β-carotene., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: We have no conflict of interest If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

The purpose of the current research is to formulate a smart drug delivery system for solubility enhancement and sustained release of hydrophobic drugs. Drug solubility-related challenges constitute a significant concern for formulation scientists. To address this issue, a recent study focused on developing PEG- g -poly(MAA) copolymeric nanogels to enhance the solubility of olmesartan, a poorly soluble drug. The researchers employed a free radical polymerization technique to formulate these nanogels. Nine formulations were formulated. The newly formulated nanogels underwent comprehensive tests, including physicochemical assessments, dissolution studies, solubility evaluations, toxicity investigations, and stability examinations. Fourier transform infrared (FTIR) investigations confirmed the successful encapsulation of olmesartan within the nanogels, while thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) studies verified their thermal stability. Scanning electron microscopy (SEM) images revealed the presence of pores on the surface of the nanogels, facilitating water penetration and promoting rapid drug release. Moreover, powder X-ray diffraction (PXRD) studies indicated that the prepared nanogels exhibited an amorphous structure. The nanogel carrier system led to a significant enhancement in olmesartan's solubility, achieving a remarkable 12.3-fold increase at pH 1.2 and 13.29-fold rise in phosphate buffer of pH 6.8 (NGP3). Significant swelling was observed at pH 6.8 compared to pH 1.2. Moreover, the formulated nexus is nontoxic and biocompatible and depicts considerable potential for delivery of drugs and protein as well as heat-sensitive active moieties., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Four surgical treatment modalities namely cryosurgery, scalpel and blade surgery, diode LASER surgery and CO2 LASER surgery in the management of oral potentially malignant disorders (OPMDs) in terms of healing outcomes post operatively and recurrence is evaluated. The study included sixty outpatients whose biopsies revealed OPMDs (oral lichen planus, homogeneous leukoplakia, non-homogenous leukoplakia and erythroplakia). There is decrease in post-operative pain and oedema in all four treatment categories at one week follow up and two week follow up. It was observed that pain was low in cryosurgery treatment category at day of surgery as well as at one week of follow up as compared to diode LASER and CO2 LASER. Observations from the study highlights that all four surgical modalities used in this study were effective for treatment of OPMDs, and the overall summation of the results of the study showed that cryotherapy seems to offer better clinically significant results than laser therapy., (© 2023 Biomedical Informatics.)

The increasing prevalence of food allergies worldwide and the subsequent life-threatening anaphylactic reactions often have sparse treatment options, providing only symptomatic relief. Great strides have been made in research and in clinics in recent years to offer novel therapies for the treatment of allergic disorders. However, current allergen immunotherapy has its own shortcomings in terms of long-term efficacy and safety, due to the local side effects and the possibility of anaphylaxis. Allergen-specific immunotherapy is an established therapy in treating allergic asthma, allergic rhinitis, and allergic conjunctivitis. It acts through the downregulation of T cell, and IgE-mediated reactions, as well as desensitization, a process of food tolerance without any allergic events. This would result in a protective reaction that lasts for approximately 3 years, even after the withdrawal of therapy. Furthermore, allergen-specific immunotherapy also exploits several routes such as oral, sublingual, and epicutaneous immunotherapy. As the safety and efficacy of allergen immunotherapy are still under research, the exploration of newer routes such as intra-lymphatic immunotherapy would address unfulfilled needs. In addition, the existence of nanoparticles can be exploited immensely in allergen immunotherapy, which would lead to safer and efficacious therapy. This manuscript highlights a novel drug delivery method for allergen-specific immunotherapy that involves the administration of specific allergens to the patients in gradual increasing doses, to induce desensitization and tolerance, as well as emphasizing different routes of administration, mechanism, and the application of nanoparticles in allergen-specific immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Krishna, Farhana, T.P., Hussain, Viswanad, Nasr, Sahu and Khan.)

A highly stereoselective, efficient and facile route was achieved for the synthesis of novel and biochemically potent sugar fused pyrano[3,2- c ]pyranone derivatives starting from inexpensive, naturally occurring d-galactose and d-glucose. First, β- C -glycopyranosyl aldehydes were synthesized from these d-hexose sugars in six steps, with overall yields 41-55%. Next, two different 1- C -formyl glycals were synthesized from these β- C -glycopyranosyl aldehydes by treatment in basic conditions. The optimization of reaction conditions was carried out following reactions between 1- C -formyl galactal and 4-hydroxycoumarin. Next, 1- C -formyl galactal and 1- C -formyl glucal were treated with nine substituted 4-hydroxy coumarins at room temperature (25 °C) in ethyl acetate for ∼1-2 h in the presence of l-proline to obtain exclusively single diastereomers of pyrano[3,2- c ]pyranone derivatives in excellent yields. Four compounds were found to be active for the MCF-7 cancer cell line. The MTT assay, apoptosis assay and migration analysis showed significant death of the cancer cells induced by the synthesized compounds., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

The pathetic malignant mesothelioma (MM) is a extremely uncommon and confrontational tumor that evolves in the mesothelium layer of the pleural cavities (inner lining- visceral pleura and outer lining- parietal pleura), peritoneum, pericardium, and tunica vaginalis and is highly resistant to standard treatments. In mesothelioma, the predominant pattern of lesions is a loss of genes that limit tumour growth. Despite the worldwide ban on the manufacture and supply of asbestos, the prevalence of mesothelioma continues to increase. Mesothelioma presents and behaves in a variety of ways, making diagnosis challenging. Most treatments available today for MM are ineffective, and the median life expectancy is between 10 and 12 months. However, in recent years, considerable progress has already been made in understanding the genetics and molecular pathophysiology of mesothelioma by addressing hippo signaling pathway. The development and progression of MM are related to many important genetic alterations. This is related to NF2 and/or LATS2 mutations that activate the transcriptional coactivator YAP. The X-rays, CT scans, MRIs, and PET scans are used to diagnose the MM. The MM are treated with surgery, chemotherapy, first-line combination chemotherapy, second-line treatment, radiation therapy, adoptive T-cell treatment, targeted therapy, and cancer vaccines. Recent clinical trials investigating the function of surgery have led to the development of innovative approaches to the treatment of associated pleural effusions as well as the introduction of targeted medications. An interdisciplinary collaborative approach is needed for the effective care of persons who have mesothelioma because of the rising intricacy of mesothelioma treatment. This article highlights the key findings in the molecular pathogenesis of mesothelioma, diagnosis with special emphasis on the management of mesothelioma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sahu, Ruhi, Jeppu, Al-Goshae, Syed, Nagdev, Widyowati, Ekasari, Khan, Bhattacharjee, Goyal, Bhattacharya and Jangde.)

Lung cancer is a fatal disease caused by an abnormal proliferation of cells in the lungs. Similarly, chronic kidney disorders affect people worldwide and can lead to renal failure and impaired kidney function. Cyst development, kidney stones, and tumors are frequent diseases impairing kidney function. Since these conditions are generally asymptomatic, early, and accurate identification of lung cancer and renal conditions is necessary to prevent serious complications. Artificial Intelligence plays a vital role in the early detection of lethal diseases. In this paper, we proposed a modified Xception deep neural network-based computer-aided diagnosis model, consisting of transfer learning based image net weights of Xception model and a fine-tuned network for automatic lung and kidney computed tomography multi-class image classification. The proposed model obtained 99.39% accuracy, 99.33% precision, 98% recall, and 98.67% F1-score for lung cancer multi-class classification. Whereas, it attained 100% accuracy, F1 score, recall and precision for kidney disease multi-class classification. Also, the proposed modified Xception model outperformed the original Xception model and the existing methods. Hence, it can serve as a support tool to the radiologists and nephrologists for early detection of lung cancer and chronic kidney disease, respectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bhattacharjee, Rabea, Bhattacharjee, Elkaeed, Murugan, Selim, Sahu, Shazly and Salem Bekhit.)

Head and neck squamous cell carcinoma is a disease that most commonly produce tumours from the lining of the epithelial cells of the lips, larynx, nasopharynx, mouth, or oro-pharynx. It is one of the most deadly forms of cancer. About one to two percent of all neo-plasm-related deaths are attributed to head and neck squamous cell carcinoma, which is responsible for about six percent of all cancers. MicroRNAs play a critical role in cell proliferation, differentiation, tumorigenesis, stress response, triggering apoptosis, and other physiological process. MicroRNAs regulate gene expression and provide new diagnostic, prognostic, and therapeutic options for head and neck squamous cell carcinoma. In this work, the role of molecular signaling pathways related to head and neck squamous cell carcinoma is emphasized. We also provide an overview of MicroRNA downregulation and overexpression and its role as a diagnostic and prognostic marker in head and neck squamous cell carcinoma. In recent years, MicroRNA nano-based therapies for head and neck squamous cell carcinoma have been explored. In addition, nanotechnology-based alternatives have been discussed as a promising strategy in exploring therapeutic paradigms aimed at improving the efficacy of conventional cytotoxic chemotherapeutic agents against head and neck squamous cell carcinoma and attenuating their cytotoxicity. This article also provides information on ongoing and recently completed clinical trials for therapies based on nanotechnology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bhattacharjee, Syeda, Rynjah, Hussain, Chandra Bora, Pegu, Sahu and Khan.)

Purpose: Seroepidemiology and genomic surveillance are valuable tools to investigate infection transmission during a pandemic. North East (NE) India is a strategically important region being the gateway connecting the country with Southeast Asia. Here, we examined the spread of SARS-CoV-2 in NE India during the first and second waves of COVID-19 using serological and whole genome sequencing approaches., Methods: qRT-PCR analysis was performed on a selected population (n ​= ​16,295) from June 2020 to July 2021, and metadata was collected. Immunoassays were studied (n ​= ​2026) at three-time points (August 2020, February 2021, and June 2021) and in a cohort (n ​= ​35) for a year. SARS-CoV-2 whole genomes (n ​= ​914) were sequenced and analyzed with those obtained from the databases., Results: Test positivity rates (TPR) in the first and second waves were 6.34% and 6.64% in Assam, respectively, and a similar pattern was observed in other NE states. Seropositivity in the three time points was 10.63%, 40.3%, and 46.33%, respectively, and neutralizing antibody prevalence was 90.91%, 52.14%, and 69.30%, respectively. Persistence of pan-IgG-N SARS-CoV-2 antibody for over a year was observed among three subjects in the cohort group. Normal variants dominated the first wave, while B.1.617.2 and AY-sublineages dominated the second wave in the region. The prevalence of the variants co-related well with high TPR and seropositivity rate in the region and identified mostly among vaccinated individuals., Conclusion: The COVID-19 first wave in the region witnessed low transmission with the evolution of diverse variants. Seropositivity increased during the study period with over half of the individuals carrying neutralizing antibodies against SARS-CoV-2. High infection and seroprevalence in NE India during the second wave were associated with the dominant emergence of variants of concern., (Copyright © 2022 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

A brain tumor is an uncontrolled cell proliferation, a mass of tissue composed of cells that grow and divide abnormally and appear to be uncontrollable by the processes that normally control normal cells. Approximately 25,690 primary malignant brain tumors are discovered each year, 70% of which originate in glial cells. It has been observed that the blood-brain barrier (BBB) limits the distribution of drugs into the tumour environment, which complicates the oncological therapy of malignant brain tumours. Numerous studies have found that nanocarriers have demonstrated significant therapeutic efficacy in brain diseases. This review, based on a non-systematic search of the existing literature, provides an update on the existing knowledge of the types of dendrimers, synthesis methods, and mechanisms of action in relation to brain tumours. It also discusses the use of dendrimers in the diagnosis and treatment of brain tumours and the future possibilities of dendrimers. Dendrimers are of particular interest in the diagnosis and treatment of brain tumours because they can transport biochemical agents across the BBB to the tumour and into the brain after systemic administration. Dendrimers are being used to develop novel therapeutics such as prolonged release of drugs, immunotherapy, and antineoplastic effects. The use of PAMAM, PPI, PLL and surface engineered dendrimers has proven revolutionary in the effective diagnosis and treatment of brain tumours., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kaurav, Ruhi, Al-Goshae, Jeppu, Ramachandran, Sahu, Sarkar, Khan and Ashif Ikbal.)

Chronic disease can cause tissue and organ damage constituting the largest obstacle to therapy which, in turn, reduces patients' quality-adjusted life-year. Degenerative diseases such as osteoporosis, Alzheimer's disease, Parkinson's disease, and infectious conditions such as hepatitis, cause physical injury to organs. Moreover, damage resulting from chronic conditions such as diabetes can also culminate in the loss of organ function. In these cases, organ transplantation constitutes the therapy of choice, despite the associated problems of immunological rejection, potential disease transmission, and high morbidity rates. Tissue regeneration has the potential to heal or replace tissues and organs damaged by age, disease, or trauma, as well as to treat disabilities. Stem cell use represents an unprecedented strategy for these therapies. However, product availability and mass production remain challenges. A novel therapeutic alternative involving amniotic mesenchymal stem cell metabolite products (AMSC-MP) has been developed using metabolites from stem cells which contain cytokines and growth factors. Its potential role in regenerative therapy has recently been explored, enabling broad pharmacological applications including various gastrointestinal, lung, bladder and renal conditions, as well as the treatment of bone wounds, regeneration and skin aging due to its low immunogenicity and anti-inflammatory effects. The various kinds of growth factors present in AMSC-MP, namely bFGF, VEGF, TGF-β, EGF and KGF, have their respective functions and activities. Each growth factor is formed by different proteins resulting in molecules with various physicochemical properties and levels of stability. This knowledge will assist in the manufacture and application of AMSC-MP as a therapeutic agent., (© 2023. The Author(s).)

Background  The morbidity of donor finger in a cross-finger flap has not received as much importance as the outcomes of the flap itself. The sensory, functional, and aesthetic morbidity of donor fingers, reported by various authors, are often contradictory to each other. In this study, objective parameters for the sensory recovery, stiffness, cold intolerance, cosmetic outcome, and other complications in the donor fingers, reported in the previous studies, are systematically evaluated. Methods  This systematic review is reported using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol and was registered with the International prospective register of systematic reviews (PROSPERO registration no. CRD42020213721). Literature search was done using "cross-finger," "heterodigital," "donor finger," and "transdigital" words. Data regarding demography, patients' number and age, follow-up duration and outcomes of donor finger, including 2-point discrimination, range of motion (ROM), cold intolerance, questionnaires, etc. were extracted from included studies. Meta-analysis was performed using MetaXL and risk of bias was evaluated using Cochrane risk of bias tool. Results  Out of the total 16 included studies, 279 patients were objectively evaluated for donor finger morbidity. Middle finger was most frequently used as donor. Static two-point discrimination seemed to be impaired in donor finger in comparison to contralateral finger. Meta-analysis of ROM suggested that statistically there is no significant difference in ROM of interphalangeal joints in donor and control fingers (pooled weighted mean difference: -12.10; 95% confidence interval: -28.59, 4.39; I2 = 81%, n  = 6 studies). One-third of donor fingers had cold intolerance. Conclusion  There is no significant effect on ROM of donor finger. However, the impairment that seems to be in sensory recovery and aesthetic outcomes needs to be further evaluated objectively., Competing Interests: Conflict of Interest Statement The authors declare that they have no conflict of interest., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Competing Interests: There are no conflicts of interest.

Background  Defining cut-off values of flap glucose levels in diagnosing free flap vascular compromise, without taking patients' glucose levels into account, does not hold good in all circumstances, especially in cases of high fluctuations in patients' capillary blood glucose and in diabetic patients. The aim of our study was to establish the role of capillary blood glucose measurements of the flap in relation to patients' fingertip, as an objective tool for postoperative free flap monitoring. Methods  A total of 76 free flaps underwent postoperative monitoring with reference test (clinical parameters) and simultaneously with our index test (difference between capillary blood glucose of free flap and the patient), in non-diabetic and diabetic patients. Patients' demography and flap characteristics were also recorded. An ROC curve was plotted to determine diagnostic accuracy and cut-offs of the index test in diagnosing free flap vascular compromise. Results  Our Index test has a cut-off value of 24.5 mg/dL with 68.75% sensitivity and 93% specificity, with an accuracy of 91.54%. Conclusion  The difference between capillary blood glucose of free flap and the patient is simple, feasible, and inexpensive, and can be done by any health care professional and does not require any specialized facilities or training. It has an excellent diagnostic accuracy to detect impending free flap vascular compromise, especially in non-diabetics. Although in diabetics, this test becomes less accurate. Being an observer-independent objective test, the difference in capillary blood glucose of patient and flap measurement can be used as a highly reliable tool for postoperative free flap monitoring., Competing Interests: Conflict of Interest None declared., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Context: Effects of coronavirus disease 2019 (COVID-19) pandemic lockdown on road traffic accidents (RTAs) in Chhattisgarh, India., Background: Most neurosurgical emergencies are from brain and spine trauma. RTA is the leading cause of such injuries. While the nationwide lockdown was an extreme measure to control the COVID pandemic, it influenced the overall road traffic dynamics and neurotrauma., Objective: This study aims to assess the impact of the lockdown on neurotrauma., Methods and Materials: This retrospective study included all patients with brain and spine injuries who were admitted between January 17 th and May 31 st , 2020. The study population was divided into prelockdown (PL) and lockdown (L) groups., Results: Of the 668 patients, 436 were placed in the PL and 232 in the L group. The mean ages were 36.34 (SD = 17.96) and 35.98 (SD = 16.93), respectively. Male to female ratios were 82.3:17.7 in the PL group and 79.7:20.3 for the L group. RTA-related injuries were significantly lower during the lockdown period (n = 335 PL vs. 162 L [P = 0.048]). During the lockdown, there were more mild injuries (25.91% PL vs. 36.63% L) and less severe injuries (33.25% PL vs. 18.96% L [P = 0.0002]). Mortality was significantly less (P = 0.029) during the lockdown (n = 48 L vs. 124 PL). The proportion of RTA-related neurotrauma cases increased (33.33% L1, 57.14% L2, 73.13% L3, and 80.39% L4) with each phase of lockdown (L1-L4)., Conclusions: During the lockdown period, the number of trauma cases had decreased, with a significant decrease in RTA-related admissions, along with their severity and mortality. The number of trauma cases and their severity increased gradually with each phase of lockdown., Competing Interests: None

Infantile (fetal and neonatal) megakaryocytes (Mks) have a distinct phenotype consisting of hyperproliferation, limited morphogenesis, and low platelet production capacity. These properties contribute to clinical problems that include thrombocytopenia in neonates, delayed platelet engraftment in recipients of cord blood stem cell transplants, and inefficient ex vivo platelet production from pluripotent stem cell-derived Mks. The infantile phenotype results from deficiency of the actin-regulated coactivator, MKL1, which programs cytoskeletal changes driving morphogenesis. As a strategy to complement this molecular defect, we screened pathways with the potential to affect MKL1 function and found that DYRK1A inhibition dramatically enhanced Mk morphogenesis in vitro and in vivo. Dyrk1 inhibitors rescued enlargement, polyploidization, and thrombopoiesis in human neonatal Mks. Mks derived from induced pluripotent stem cells responded in a similar manner. Progenitors undergoing Dyrk1 inhibition demonstrated filamentous actin assembly, MKL1 nuclear translocation, and modulation of MKL1 target genes. Loss-of-function studies confirmed MKL1 involvement in this morphogenetic pathway. Expression of Ablim2, a stabilizer of filamentous actin, increased with Dyrk1 inhibition, and Ablim2 knockdown abrogated the actin, MKL1, and morphogenetic responses to Dyrk1 inhibition. These results delineate a pharmacologically tractable morphogenetic pathway whose manipulation may alleviate clinical problems associated with the limited thrombopoietic capacity of infantile Mks.

Micromachining of difficult-to-machine materials is of prime focus nowadays. One such material is Titanium, which has numerous applications in aerospace, chemical, and biomedical industries. The micromachining of Titanium has become the need of the day because of its exhilarating properties. This investigation employs a tailor-made electrolyte sonicated micro-electrochemical discharge machining (ES-µ-ECDM) system to generate microholes in a commercially pure titanium plate with a thickness of 1000 µm. The machining chamber is the ultrasonication unit (36 kHz) with process parameters voltage (V), concentration (wt%), and duty factor (DF) chosen at three levels. The FCC-RSM-based DOE is selected for experimentation to study the machining characteristics like material removal rate, overcut, and circularity. Through holes were achieved at parameters of 80 V, 25 wt%, and 60% DF and 80 V, 30 wt%, and 50% DF. The incorporation of ultrasonication into the system enhanced electrolyte replenishment and evacuation of the debris at the machining vicinity. The assistance technique improved the gas film stabilization around the tool enabling uniform machining. The multi-response optimization is performed using the MOJAYA algorithm to obtain Pareto optimal solutions, and the MADM (R-method) is employed to obtain the optimal parameter. The optimal parameter was found to be 69 V, 30 wt%, and 50% DF, at which the machined microhole was found to have a circularity of 0.9615 with minimal surface defects., (© 2022. The Author(s).)

Sauropus androgynus (L.) Merr., in the Indonesian local name known as "Katuk," is a tropical shrub plant of the family Euphorbiaceae. Based on genus and chemotaxonomic approaches, as well as in vitro testing of Plasmodium falciparum , leaves of S. androgynus are presumed to have an active compound content as an antimalarial. The current study aims to investigate the antimalarial activity of 96% ethanol extract and fractions of S. androgynus leaves. The ethanolic extract was fractionated using the vacuum liquid chromatography (VLC) method with three solvents of different polarities (n-hexane, chloroform, and 96% ethanol). The fraction obtained was then evaluated for antimalarial activity against P. falciparum 3D7 strain. The ethanolic extract was evaluated for antimalarial suppressive and prophylactic activity against P. berghei -infected mice, as well as inhibitory activity against the heme detoxification process in vitro. Fractionation of ethanolic extract resulted in seven combined fractions, with the most active fraction being FV (50% inhibitory concentration (IC 50 ) = 2.042  µ g/mL). The ethanolic extract showed good parasitic suppressive (therapeutic) activity with a median effective dose (ED 50 ) value of 15.35 mg/kg body weight. In a prophylactic test, ethanolic extract showed parasite growth inhibitory activity of 67.74 ± 9.21% after the administration of 400 mg/kg body weight for 4 days before infection, and 65.30 ± 10.44% after the administration of 200 mg/kg body weight for 8 consecutive days (4 days before and after infection). The ethanolic extract also showed an effect in inhibiting the formation of β -hematin of about 26.87-79.36% at a concentration of 0.1-4 mg/mL and an IC 50 value of 0.479 mg/mL. The S. androgynus leaves were shown to have antimalarial activity in vitro and in vivo, where ethanolic extract were more active compared with the fraction obtained. The antimalarial properties of the extract showed a higher suppressive activity than prophylactic activity., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Wiwied Ekasari et al.)

Nonvenomous snakebite, far outnumbering venomous bites, is a neglected occupational hazard in the Indian subcontinent. We encountered four cases of traditionally nonvenomous snakebite in pediatric age group with symptoms of limb swelling proximal to the bite site. All cases were found to have extensive fibrinous exudate and fibrinoid necrosis of the deeper layer of fat, deep to the intact skin and superficial layer of fat, extending far from the wound toward the proximal limb in continuity. This obscured presentation of infection and extensive necrosis of only the deeper layer of fat warrants exploratory incisions proximally for thorough debridement, underlying the normal appearing skin., Competing Interests: Conflict of Interest The authors declare that there is no conflict of interest., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

We have previously reported that increased expression and activation of kidney cell complement components play an important role in the pathogenesis of renal scarring. Here, we used floxed green fluorescent protein (GFP)-C5a receptor 1 (C5aR1) knockin mice (GFP- C5ar1 fl/fl ) and the model of folic acid (FA)-induced kidney injury to define the cell types and potential mechanisms by which increased C5aR1 activation leads to fibrosis. Using flow cytometry and confocal microscopy, we identified macrophages as the major interstitial cell type showing increased expression of C5aR1 in FA-treated mice. C5ar1 fl/fl . Lyz2 Cre +/- mice, in which C5aR1 has been specifically deleted in lysozyme M-expressing myeloid cells, experienced reduced fibrosis compared with control C5ar1 fl/fl mice. Examination of C5aR1-expressing macrophage transcriptomes by gene set enrichment analysis demonstrated that these cells were enriched in pathways corresponding to the complement cascade, collagen formation, and the NABA matrisome, strongly pointing to their critical roles in tissue repair/scarring. Since C5aR1 was also detected in a small population of platelet-derived growth factor receptor-β + GFP + cells, we developed C5ar1 fl/fl . Foxd1 Cre +/- mice, in which C5aR1 is deleted specifically in pericytes, and found reduced FA-induced fibrosis. Primary cell cultures of platelet-derived growth factor receptor-β + pericytes isolated from FA-treated C5ar1 fl/fl . Foxd1 Cre +/- mice showed reduced secretion of several cytokines, including IL-6 and macrophage inflammatory protein-2, compared with pericytes isolated from FA-treated control GFP- C5ar1 fl/fl mice. Collectively, these data imply that C5a/C5aR1 axis activation primarily in interstitial cells contributes to the development of renal fibrosis. NEW & NOTEWORTHY This study used novel green fluorescent protein C5a receptor 1 floxed mice and the model of folic acid-mediated kidney fibrosis to demonstrate the pathogenic role of increased expression of this complement receptor on macrophages.

Background: Hearing preservation in vestibular schwannoma resection is a much-discussed topic in these times of functional preservation. Irrespective of the mode of treatment of large tumors, this becomes possible only in a lucky few. The overall burden of such deaf patients is on a rising trend, and therefore, it is high time neurosurgeons look into this often-neglected area of hearing rehabilitation., Objectives: In this review, the authors intend to provide a glimpse of available hearing rehabilitation modalities in the present era., Materials and Methods: : This review deals with both immediate and long-term hearing outcomes following both surgery and stereotactic radiosurgery for sporadic vestibular schwannoma and the need for hearing rehabilitation in these patients. Various databases, including PubMed, Medline/Medscape, Scopus, Cochrane, and Google Scholar were searched to find available literature on hearing rehabilitation after treatment of sporadic vestibular schwannoma. The searched MeSH terms were "Hearing", "Vestibular schwannoma", "Rehabilitation", and "Acoustic Neuroma", alone and in various combinations., Results: : The authors were surprised to find a paucity of literature. Even though neurosurgeons are at the forefront in managing vestibular schwannoma, they are not actively involved in hearing rehabilitation techniques possible for those who are rendered deaf following treatment., Conclusions: : The authors strongly believe that this review will be a wake-up call for neurosurgeons on a relatively untouched topic., Competing Interests: None

Resveratrol enhances the BRCA1 gene expression and the MBD family of proteins bind to the promoter region of the BRCA1 gene. However, the molecular interaction is not yet reported. Here we have analyzed the binding affinity of resveratrol with MBD proteins. Our results suggest that resveratrol binds to the MBD proteins with higher binding affinity toward MeCP2 protein (Δ G = -6.5) by sharing four hydrogen bonds as predicted by molecular docking studies. Further, the molecular dynamics simulations outcomes showed that the backbones of all three protein-ligand complexes are stabilized after the period of 75 ns, constantly fluctuating around the deviations of 0.4 Å, 0.5 Å and 0.7 Å for MBD1, MBD2 and MeCP2, respectively. The inter-molecular hydrogen bonding trajectory analysis for protein-ligand complexes also support the strong binding between MeCP2-resveratrol complex. Further, binding free energy calculations showed binding energy of -94.764 kJ mol -1 , -53.826 kJ mol -1 and -36.735 kJ mol -1 for MeCP2-resveratrol, MBD2-resveratrol and MBD1-resveratrol complexes, respectively, which also supported our docking results. Our study also highlighted that the MBD family of proteins forms a binding interaction with other signaling proteins that are involved in various cancer initiation pathways., Competing Interests: The authors declare that they have no conflicts or financial interests in the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Rheumatoid arthritis (RA) is a systemic, chronic autoimmune disease that causes disability due to progressive inflammation and destruction of the tissues around the joints. Methotrexate is mainly used to prevent the progression of joint destruction and reduce the deformity. The major challenge in treating RA with methotrexate is the systemic side effects that limit dose escalation. Hence, a novel formulation of a methotrexate-loaded nanoemulsion for subcutaneous administration was developed that aims to deliver methotrexate into the system via the lymph. The methotrexate-loaded nanoemulsion was prepared by using the aqueous-titration method. The prepared nanoemulsion was investigated for particle size, surface charge, surface morphology, entrapment efficiency, DSC (differential scanning colorimetry), drug release, hemocompatibility assay, and cytotoxicity, as well as anti-arthritic and stability studies. The vesicle size, zeta potential, PDI (polydispersity index), and entrapment efficiency of the optimized nanoemulsion were 87.89 ± 2.86 nm, 35.9 ± 0.73 mV, 0.27, and 87 ± 0.25%, respectively. The DSC study showed that the crystalline methotrexate was converted to an amorphous form and the drug was fully incorporated into the vesicles. After 72 h, the optimized nanoemulsion showed a drug release of 96.77 ± 0.63%, indicating a sustained-release dosage form. Cytocompatibility testing by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay on macrophage cell lines showed that the nanoemulsion was non-toxic. The formulation showed significant anti-arthritic activity compared to the marketed drug solution. In addition, the nanoemulsion containing methotrexate remained stable for three months when stored at a low temperature. Since the nanoemulsion containing methotrexate has excellent physicochemical properties and lowers systemic side effects by targeted delivery, it is a desirable technology for subcutaneous drug delivery.

Objective: Type II odontoid fractures need surgical stabilization for disabling neck pain and instability. Anterior odontoid screw fixation is a well-known technique. However, certain patients require posterior fixation. We present our surgical results and experiences with nine cases managed by the Goel-Harms technique., Materials and Methods: This is a retrospective review of nine patients operated on between January 2019 and December 2021 for Type II odontoid fractures with posterior fixation technique. Their clinical profile was collected from case files. The radiological data were retrieved from radiology archives. The indications for surgery were instability and refractory neck pain. The surgical decision for posterior fixation was guided by fracture morphology., Results: The mean age of presentation was 37.22 ± 9.85 years. Seven patients had Type II, and two had Type IIa odontoid fracture. All patients presented with unbearable neck pain. One patient had a quadriparesis. The fracture line was anterior-inferior sloping in six, posterior-inferior sloping in two, and transverse in one case. The anterior-posterior displacement of fracture ranged from 0 to 7 mm (mean 2.44 ± 2.18 mm). Partial transverse ligament tear without the Atlanto Axial Dislocation was present in three patients. The C1-C2 joint distraction was required in five cases. C1-C2 joint spacer was required in two cases. Following surgery, neck pain was relieved in all cases. Complete fracture alignment was achieved in eight patients. There were no postoperative complications. At the mean follow-up of 16.22 ± 9.61 months, there was no implant failure., Conclusions: Posterior C1-C2 fixation by the Goel-Harms technique is an excellent alternative to anterior fixation in selected cases., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Craniovertebral Junction and Spine.)

Background: Allergen immunotherapy (AIT) involves the regimen of gradually incrementing doses of the allergen, thereby inducing desensitization and tolerance. Sublingual Immunotherapy tablets (SLIT-tablets) have been formulated for several allergies and had manifested efficacy for allergic rhinitis and allergic asthma. SLIT promises an alternative method to other routes of AIT enabling patients to self-administer AIT., Objective: The study aimed to formulate fast disintegrating SLIT containing crude peanut extract for peanut-induced allergic asthma., Methods: The crude peanut extract was prepared by a simple extraction method and was subjected to quantitative and qualitative analysis. The extract was also characterised for its physical properties. The preformulation study for the extract and excipients of the tablet was performed using FT-IR spectroscopy and Differential scanning calorimetry. The tablet powder blends were characterised for pre-compression properties. The SLIT tablets were developed by direct compression and the post-compression evaluation was performed., Results: The results of the quantitative and qualitative analysis of extract confirmed the presence of peanut proteins in the extract. The preformulation studies using FT-IR spectroscopy and Differential Scanning Calorimetry revealed that there is no significant interaction between the CPE and excipients. The pre-compression characterisation showed that the powder blends had good flowproperties. Three doses of SLIT tablets were formulated with each dose containing four batches and the tablet of each dose was optimized by studying the effect of varying concentrations of super disintegrants on disintegration time and dissolution rate. The post compression characterization of the tablets was performed and the optimized batch of the three doses with the concentration of 5% crospovidone and 2% croscarmellose sodium showed less wetting time and high-water absorption ratio, shorter disintegration time of 14secs and maximum drug release of >90% within 2-3 min., Conclusion: The results indicated the suitability of formulated SLIT tablets for peanut induced allergic asthma., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Hesperidin is a bioflavonoid constituent that among many other biological activities shows significant wound healing properties. However, the bioavailability of hesperidin when applied topically is limited due to its low solubility and systemic absorption, so novel dosage forms are needed to improve its therapeutic efficacy. The objectives of this study were to develop hesperidin-loaded lipid-polymer hybrid nanoparticles (HLPHNs) to enhance the delivery of hesperidin to endogenous sites in the wound bed and promote the efficacy of hesperidin. HLPHNs were optimized by response surface methodology (RSM) using the Box-Behnken design. HLPHNs were prepared using an emulsion-solvent evaporation method based on a double emulsion of water-in-oil-in-water (w/o/w) followed by freeze-drying to obtain nanoparticles. The prepared formulations were characterized using various evaluation parameters. In addition, the antioxidant activity of HLPHN 4 was investigated in vitro using the DPPH model. Seventeen different HLPHNs were prepared and the HLPHN4 exhibited the best mean particle size distribution, zeta potential, drug release and entrapment efficiency. The values are 91.43 nm, +23 mV, 79.97% and 92.8%, respectively. Transmission electron microscope showed similar spherical morphology as HLPHN4. Differential scanning calorimetry verified the physical stability of the loaded drug in a hybrid system. In vitro release studies showed uniform release of the drug over 24 h. HLPHN4 showed potent antioxidant activity in vitro in the DPPH model. The results of this study suggest that HLPHNs can achieve sustained release of the drug at the wound site and exhibit potent in vitro antioxidant activity.

Introduction  The study was carried out to quantify the changes induced by the pandemic in plastic surgery practice and training and to study the impact of the webinars on plastic surgery education from a residents' perspective. Methods  In this multicentric study, the number and type of surgeries, cause of injuries, and their regional variation during the coronavirus disease 2019 (COVID-19) period (February-September 2020) were compared with pre-COVID-19 time. An online survey on the impact of webinars was conducted for plastic surgery trainees across the country. Results  There was a significant reduction in total number of surgeries ( p = 0.003). The procedures for hand ( p = 0.156), faciomaxillary injuries ( p = 0.25), and replantations ( p = 0.46) were comparable; there was a significant reduction in combined orthopedic-plastic-surgical procedures ( p = 0.009) during the pandemic. There was a significant reduction in road accidents ( p = 0.007) and suicidal injuries ( p = 0.002) and increase in assault ( p = 0.03) and domestic accidents ( p = 0.01) during the COVID-19 period. A usefulness score of >8 was given for the webinars by 68.7% residents. There was no significant difference in perception of utility when correlated with the academic program at their institutes ( p = 0.109); 92% opined webinars should continue in post-COVID times. Conclusion  There was a drastic reduction in number of elective and emergency procedures during the COVID-19 time, negatively affecting resident training program. Majority of residents felt that webinars could prove a useful adjunct to training in formal training program in post-COVID-19 scenario., Competing Interests: Conflict of Interest None declared., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Colorectal cancer (CRC) is a serious disease that affects millions of people throughout the world, despite considerable advances in therapy. The formation of colorectal adenomas and invasive adenocarcinomas is the consequence of a succession of genetic and epigenetic changes in the normal colonic epithelium. Genetic and epigenetic processes associated with the onset, development, and metastasis of sporadic CRC have been studied in depth, resulting in identifying biomarkers that might be used to predict behaviour and prognosis beyond staging and influence therapeutic options. A novel biomarker, or a group of biomarkers, must be discovered in order to build an accurate and clinically useful test that may be used as an alternative to conventional methods for the early detection of CRC and to identify prospective new therapeutic intervention targets. To minimise the mortality burden of colorectal cancer, new screening methods with higher accuracy and nano-based diagnostic precision are needed. Cytotoxic medication has negative side effects and is restricted by medication resistance. One of the most promising cancer treatment techniques is the use of nano-based carrier system as a medication delivery mechanism. To deliver cytotoxic medicines, targeted nanoparticles might take advantage of differently expressed molecules on the surface of cancer cells. The use of different compounds as ligands on the surface of nanoparticles to interact with cancer cells, enabling the efficient delivery of antitumor medicines. Formulations based on nanoparticles might aid in early cancer diagnosis and help to overcome the limitations of traditional treatments, including low water solubility, nonspecific biodistribution, and restricted bioavailability. This article addresses about the molecular pathogenesis of CRC and highlights about biomarkers. It also provides conceptual knowledge of nanotechnology-based diagnostic techniques and therapeutic approaches for malignant colorectal cancer.

Background: Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in females worldwide. Schleichera oleosa (kusum tree) belongs to the Sapindaceae family commonly found in many states of India. This plant is traditionally being used in various pathological conditions., Methods: In vitro studies were performed using seed extract of Schleichera oleosa. Different concentrations of seed extracts were treated on MCF-7 breast cancer cell line and its effect on migration and colony formation were observed. BRCA1 and p16 gene expression was analyzed by real-time PCR and Western blotting., Results: We have analyzed anticancer and anti-metastatic effects of seed extract in breast cancer and IC50 was 140µg/ml concentration. Further, its inhibitory role in cell migration and colony formation was at 140µg/ml (P<0.0001) concentration and reduced significantly growth of sphere at 140 µg (P<0.0031) and 150µg (P<0.0010) concentration after 5 days of treatment. The apoptosis study was shown a significant increase at 140 µg (P<0.0001) in apoptotic cells. Expression of BRCA1 and p16 were found to be over-expressed as 1.4 and 1.7 fold, respectively, at 140µg/ml concentration after 24 h of treatment at the transcription level. BRCA1 protein was up-regulated but p16 expression down-regulated at 140 to 150µg/ml (One-Way ANOVA, P<0.0001) concentration., Conclusion: In this study, we found a significant role of S. Oleosa seed extract has an anti-cancer as well as anti-metastatic via up-regulation of BRCA1 and p16 genes in breast cancer cells.

Histone tail residues drive many biological processes by regulating genome-wide transcription. Functions of histone H3 and H4 tail residues in stress-responsive gene transcriptional programs have been extensively studied. The H2A tail residues have been shown to regulate DNA damage repair and oxidative stress response, but the involvement of N-terminal tail of H2A (H2ANtT) in proteostasis regulation is unknown. The unfolded protein response pathway (UPR) is an essential mechanism adopted by cells to prevent protein toxicity in response to ER stress. The disturbance in ER can occur by various factors such as heat stress, redox imbalance, exposure to xenobiotics and metals. Copper is utilized as a cofactor by cellular enzymes, but excessive copper affects ER homeostasis. We found that cells lacking 1-20 residues of H2ANtT are intolerant to copper stress, owing to the accumulation of misfolded proteins in the mutant cells. H2A 1-20 truncation also reduces the physiological UPR, and copper exposure further aggravates this effect. Furthermore, the expression of a spliced version of HAC1 mRNA in H2A∆(1-20) cells, encoding the downstream transcription factor of UPR signalling, rescues their growth under copper stress. Altogether these results provide evidence that H2ANtT reduces copper-induced ER stress by regulating UPR signalling., (© The Author(s) 2021. Published by Oxford University Press on behalf of FEMS.)

The SWI/SNF subfamily remodelers (SWI/SNF and RSC) generally promote gene expression by displacing or evicting nucleosomes at the promoter regions. Their action creates a nucleosome-depleted region where transcription machinery accesses the DNA. Their function has been shown critical for inducing stress-responsive transcription programs. Although the role of SWI/SNF and RSC complexes in transcription regulation of heat shock responsive genes is well studied, their involvement in other pathways such as unfolded protein response (UPR) and protein quality control (PQC) is less known. This study shows that SWI/SNF occupies the promoters of UPR, HSP and PQC genes in response to unfolded protein stress, and its recruitment at UPR promoters depends on Hac1 transcription factor and other epigenetic factors like Ada2 and Ume6. Disruption of SWI/SNF's activity does not affect the remodeling of these promoters or gene expression. However, inactivation of RSC and SWI/SNF together diminishes induction of most of the UPR, HSP and PQC genes tested. Furthermore, RSC and SWI/SNF colocalize at these promoters, suggesting that these two remodelers functionally cooperate to induce stress-responsive genes under proteotoxic conditions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The COVID-19 infection caused by the new SARS-CoV-2 virus has been linked to a broad spectrum of symptoms, from a mild cough to life-threatening pneumonia. As we learn more about this unusual COVID-19 epidemic, new issues are emerging and being reported daily. Mucormycosis, also known as zygomycosis or phycomycosis, causes severe fungal illness to individuals with a weakened immune system. It is a devastating fungal infection, and the most frequent kind is the rhino cerebral type. As a devastating second wave of COVID-19 sweeps India, doctors report several instances involving a strange illness-sometimes known as the "black fungus"-among returning and recovered COVID-19 patients. This paper analyzes the existing statistical data to address the severity of prevalence and further notes the nano-based diagnostic parameters, clinical presentations, its connection with other conditions like diabetes, hypertension, and GI disorders, and the importance of anti-fungal therapy in treating the same. Anti-fungal therapies, as well as surgical interventions, are currently used for the treatment of the disease. Proper and timely diagnosis is necessary, along with the reduction in the spread of COVID-19. From the review, it was found that timely pharmacologic interventions and early diagnosis by using a nano-based diagnostic kit can help control the disease. Additionally, this paper provides novel information about the nanotechnology approaches such as fungal detection biosensors, nucleic acids-based testing, point-of-care tests, and galactomannans detection, in the diagnosis of mucormycosis, and thereby reinforces the need for further research on the topic.

Exploration of an efficient dual-drug based nanocarrier with high drug loading capacity, specific targeting properties, and long-term stability is highly desirable in cancer therapy. Metal-organic frameworks (MOFs) have proven to be a promising class of drug carriers due to their high porosity, crystalline properties with defined structure information, and their potential for further functionalization. To enhance the drug efficacy as well as to overcome the burst effect of drugs, here we synthesized a pH responsive folic acid (FA) and graphene oxide (GO) decorated zeolitical imidazolate frameworks-8 (GO-FA/ZIF-8), for targeted delivery of doxorubicin (DOX) and cyclophosphamide (CP), simultaneously. In this system, DOX molecules were encapsulated in the pores of ZIF-8 during in situ synthesis of ZIF-8 and CP molecules have been captured by the GO surface via hydrogen bonding and π-π interactions as well. Furthermore, the resulting pH-responsive nanocarrier (DOX@ZIF-8/GO-FA/CP) showed in vitro sustained release characteristics (76% of DOX and 80% of CP) by cleavage of chemical bonding and disruption of the MOFs structure under acidic condition (at pH 5.6). Moreover, DOX@ZIF-8/GO-FA/CP has synergistic cytotoxic effects as compared to the combination of both the drugs without ZIF-8/GO-FA when treating MCF-7 and MDA-MB-231 breast cancer cell lines (with a combination index of 0.29 and 0.75 for MCF-7 and MDA-MB-231 cell-lines, respectively). Hence this system can be applied as an effective platform for smart dual drug delivery in breast cancer treatment through its remarkable manageable multidrug release., Competing Interests: Authors declare that they have no conflict of interest., (This journal is © The Royal Society of Chemistry.)