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Efficient telmisartan delivery for hypertension management requires the incorporation of meglumine and/or sodium hydroxide as an alkalizer in the formulation. Long-term use of powerful alkalis with formulation as part of chronic therapy can cause metabolic alkalosis, ulcers, diarrhea, and body pain. Here, we aimed to design a telmisartan formulation without alkalizers. Telmisartan properties were tailor-made by microfluidizer-based physical modification. After microfluidization, telmisartan nanosuspension was lyophilized to obtain telmisartan premix powder. The optimized telmisartan nanosuspension had an average particle size of 579.85⯱â¯32.14â¯nm. The lyophilized premix was characterized by FT-IR, DSC, and PXRD analysis to ensure its physicochemical characteristics. The solubility analysis of premix showed 2.2 times, 2.3 times, and 6 times solubility improvement in 0.1â¯N HCl, phosphate buffer pH 7.5, and pH 6.8 compared to pure telmisartan. A 3D in-vitro Caco-2 model was developed to compare apparent permeability of API and powder premix. It showed that the powder premix was more permeable than pure API. The tablet formulation prepared from the telmisartan premix showed a dissolution profile comparable to that of the marketed formulation. The technique present herein can be used as a platform technology for solubility and permeability improvement of similar classes of molecules.
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Breast cancer (BC) is the second deadliest cancer after lung cancer. Similar to all cancers, it is also driven by a 3D microenvironment. The extracellular matrix (ECM) is an essential component of the 3D tumor micro-environment, wherein it functions as a scaffold for cells and provides metabolic support. BC is characterized by alterations in the ECM. Various studies have attempted to mimic BC-specific ECMs using artificial materials, such as Matrigel. Nevertheless, research has proven that naturally derived decellularized extracellular matrices (dECMs) are superior in providing the essential in vivo-like cues needed to mimic a cancer-like environment. Developing in vitro 3-D BC models is not straightforward and requires extensive analysis of the data established by researchers. For the benefit of researchers, in this review, we have tried to highlight all developmental studies that have been conducted by various scientists so far. The analysis of the conclusions drawn from these studies is also discussed. The advantages and drawbacks of the decellularization methods employed for generating BC scaffolds will be covered, and the review will shed light on how dECM scaffolds help develop a BC environment. The later stages of the article will also focus on immunogenicity issues arising from decellularization and the origin of the tissue. Finally, this review will also discuss the biofabrication of matrices, which is the core part of the bioengineering process.
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Knowledge regarding the lesser common breast tumours, including malignant papillary neoplasms and glycogen-rich clear cell carcinoma, is limited. Overall, cases of papillary carcinoma of the breast fare better than invasive breast carcinoma, from the data available in literature. Glycogen-rich clear cell carcinoma is characterized by the presence of clear cells, having mostly a poorer prognosis. We hereby present three such cases which would add to the existing available information. Case 1 is a 79-year-old female who presented with a left breast lump and bloody nipple discharge. Mammography suggested malignant lesion, with FNAC suspicious of malignancy. Surgery was done and histopathological examination showed irregular islands of tumour cells having papillary fronds with absence of myoepithelial layer. Immunohistochemically, the tumour was GATA3, CK7, ER, PR positive, HER2 negative, with Ki67 index 10%. The case was diagnosed as Solid papillary carcinoma. Case 2 is a 57-year-old female presenting with a left breast lump along with bloody nipple discharge. Mammography and FNAC were in favour of malignancy. Trucut biopsy was done, microscopy revealing a tumour having >90% papillary architecture with infiltrative pattern. Features were suggestive of Invasive breast carcinoma with papillaroid features. The tumour was GATA3, CK7, ER, PR positive, HER2 negative, with Ki67 index 15%. Case 3 is a 70-year-old female presenting with a right breast lump with nipple retraction. Mammography and FNAC were suggestive of malignancy. Trucut biopsy followed by microscopy revealed polygonal tumour cells with clear cytoplasm in nested pattern, showing positive staining for Periodic Acid Schiff. Immunostaining showed GATA3 positive, PAX8 negative, ER and PR positive, HER2 negative, and Ki67 index 20%. A diagnosis of Invasive breast carcinoma with Glycogen-rich clear cell pattern was made. Identifying these rare entities is important along with assessing hormone status for avoiding overtreatment and undertreatment and applying appropriate targeted therapies.
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In developing countries, informal sector is the primary job provider for a significant portion of the workforce. This study aims to analyze how jobs in the informal sector affect the unemployment dynamics of developing nations. To achieve this goal, we formulate a nonlinear mathematical model by categorizing the considered workforce into three distinct classes: unemployed, employed, and self-employed, and include a separate dynamic variable to represent vacancies within the informal sector. The proposed model is analyzed using the qualitative theory of dynamical systems. A threshold quantity known as the reproduction number is derived and using this, one can compute the job generation rate necessary to stabilize the system. It is observed that variations in the reproduction number lead to qualitative changes, such as transcritical (forward or backward) and saddle-node bifurcations in the formulated system. Moreover, we propose an optimal control problem to determine an optimal strategy for government policy implementation in enhancing the employment rate of unemployed individuals and promoting the self-employment of informal employees inside the informal sector. Further, the analytical findings are validated numerically. The obtained results suggest that promoting the self-employment of informal employees for job generation effectively reduces unemployment.
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BACKGROUND: Urothelial carcinoma (UC) is a common malignancy, predominantly affecting males. Many tumor cells use the interaction between programmed death-ligand 1 (PD-L1) and programmed death receptor (PD-1) to inactivate T-cells in the microenvironment and evade host immune response. Our study aims to evaluate the expression of PD-L1 in UC and correlate its expression with histomorphological parameters. MATERIALS AND METHODS: After obtaining approval from the Institute Ethics Committee, we conducted a prospective observational study on transurethral resection of urinary bladder tumor (TURBT) and cystectomy specimens histopathologically diagnosed as UC between 2022 and 2023, comprising 50 cases. All standard protocol was followed and immunohistochemistry (IHC) was done using PD-L1 with rabbit anti-human PD-L1 monoclonal antibody (Clone: IHC411; Biogenics Inc., San Francisco, CA, USA). Results: Among the 50 cases of UC, the majority were papillary type (35 cases), high grade (28 cases), and non-muscle invasive (30 cases). Among the cases studied, 15 of them showed PD-L1 positivity; 55% of the cases of muscle-invasive bladder cancer were found to be positive for PD-L1 out of which the results were statistically significant. CONCLUSION: PD-L1 expression by IHC staining can differentiate between muscle-invasive and non-muscle-invasive UC cases. This observation allows for further exploring the potential role of immune checkpoint inhibitors in adjuvant and neoadjuvant therapy, especially in muscle-invasive cases of UC.
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OBJECTIVES: To explore the magnitude of sex bias and determinants of treatment abandonment (TA) in childhood cancer in India. METHODS: Individual data of children (0-19 y) registered between January 1, 2017 and July 31, 2022, was compiled. TA was defined as defaulting curative intent treatment ≥4 wk. Defaulting treatment irrespective of intent ≥4 wk was defined as Treatment Default (TD). The primary outcome was the proportion of male-to-female children with TA. Secondary outcomes included the proportion of male-to-female children with upfront TA, TA at relapse, TD, TD-p (TD only in the palliative setting). The impact of clinico-demographic factors on TA was analysed using multivariable regression and propensity score matching (PSM). RESULTS: Three thousand two hundred eighty four patients were analysed. The overall male-to-female ratio (MFR) was 2.08 (95% CI 1.94-2.24). Of 2906 patients treated with curative intent, 415 (14·3%) abandoned treatment. TA was higher in females than males (16·4% vs. 13·3%; p = 0·022) with adjusted MFR of 0·81 (0·66-0·98). The adjusted MFR of TA for treatment-naïve and relapsed patients and TD were 0·73 (0·59-0·91), 1·13 (0·65-1·96) and 0·84 (0·71-1·00) respectively. Sex independently predicted TA on multivariable analysis. However, on PSM analysis including socio-economic variables, lower maternal education predicted higher TA in children with cancer (10·1% vs. 6%, p = 0·015). CONCLUSIONS: Child sex predicted TA in childhood cancer in India with more females abandoning treatment. Maternal education is a more crucial factor predicting TA over child sex, when socio-economic factors were considered. Hence, policies promoting female education and gender equality may mitigate sex-based gaps in childhood cancer care.
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Gene therapy is a revolutionary approach aimed at treating various diseases by manipulating the expression of specific genes. The composition and formulation of ultra-deformable vesicles play a crucial role in determining their properties and performance as siRNA delivery vectors. In the development of ultra-deformable vesicles for siRNA delivery, careful lipid selection and optimization are crucial for achieving desirable vesicle characteristics and efficient siRNA encapsulation and delivery. The stratum corneum acts as a protective barrier, limiting the penetration of molecules, including siRNA, into the deeper layers of the skin. Ultradeformable vesicles offer a promising solution to overcome this barrier and facilitate efficient siRNA delivery to target cells in the skin. The stratum corneum, the outermost layer of the skin, acts as a significant barrier to the penetration of siRNA.These engineering approaches enable the production of uniform and well-defined vesicles with enhanced deformability and improved siRNA encapsulation efficiency. Looking ahead, advancements in ultra-deformable vesicle design and optimization, along with continued exploration of combination strategies and regulatory frameworks, will further drive the field of ultra-deformable vesicle-based siRNA delivery.
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Background Mucormycosis, attributed to a group of molds known as mucormycosis, is a rare yet life-threatening fungal infection often colloquially referred to as black fungus. While its incidence notably surged during the second wave of COVID-19 infections in India, it's essential to recognize that mucormycosis was a significant concern even before the advent of the pandemic. Understanding the prevalence and characteristics of this infection in the pre-COVID era provides a crucial context for evaluating its impact and dynamics during the pandemic. Multiple diagnostic methods, such as potassium hydroxide (KOH) mount, culture, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and histopathological examination (HPE), are available for identifying this lethal infection. The primary objective of this study is to ascertain the sensitivity of various diagnostic methods for mucormycosis and to analyze the comparative effectiveness of microbiological versus histopathological diagnoses. Methods We conducted a retrospective observational study spanning six months, from May 2021 to October 2021, encompassing all mucormycosis cases meeting the inclusion criteria and diagnosed via histopathological examination (HPE) in the departments of pathology and microbiology. Microbiological tests were performed prior to the histopathological examinations. Sensitivity was assessed through statistical analysis, and the relationship between microbiological and histopathological diagnoses was evaluated using the chi-square test. Results Biopsy samples of 77 patients were collected, comprising 56 male and 21 female patients. Regarding age distribution, most patients fell within the 41-60 age bracket, while the smallest proportion was over 60 years old. The sensitivity and specificity of histopathological diagnosis, confirmed with periodic acid-Schiff (PAS) and Grocott-Gomori's methenamine silver (GMS) staining, both recorded a flawless 100%. KOH mount sensitivity stood at 88.3%, while fungal culture and MALDI-TOF exhibited sensitivities of 75.3%. Histopathological analysis revealed that 17% of cases displayed minimal fungal hyphae alongside necrotic tissue, whereas 58% exhibited abundant fungal hyphae accompanied by inflammatory cells. Additionally, absolute neutrophilia was observed in 55% of cases. Conclusions In our study, histopathology and KOH mount emerged as not only compassionate but also cost-effective diagnostic tools for identifying mucormycosis. The economic aspect of these diagnostic methods is highlighted in the results section to provide a comprehensive understanding of their cost-effectiveness. Additionally, we utilized MALDI-TOF MS as a straightforward, economically viable, and expeditious method specifically for confirming the fungal subtype in mucormycosis cases. The rationale behind choosing either MALDI-TOF MS or KOH for the diagnosis is elucidated, contributing to a clearer interpretation of our diagnostic approach. Furthermore, our findings indicate that absolute neutrophilia consistently manifests in 55% of mucormycosis cases.
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The present study hypothesises that the selective brain ß2 receptor activation through ß2-adrenoreceptor agonist (ß2ARA), Formoterol (FMT), suppresses SNCA gene expression, a pathological hallmark of Parkinson's disease (PD) in brain. Further, it is also hypothesized that brain targeted delivery of Formoterol via polysorbate-80 surface modified solid lipid nanoparticles of Formoterol (FMT-SLNs-PS80) can improve its stability, therapeutic efficacy and avoid/reduce peripheral off-target side effects. FMT-SLNs-PS80 was prepared by solvent injection method, the formulation was optimized by using Box-Behnken design and characterized by measuring drug content, entrapment efficacy, particle size, zeta potentials and poly dispersibility. The FMT-SLNs-PS80, significantly decreases the SNCA expression, mitochondrial membrane damage and rotenone induced changes in oxidative (SOD, CAT, GSH and ROS) stress markers in SH-SY5Y cell lines. The ex vivo permeation study of the formulation using everted chicken ileum exhibited a steady state flux. The pharmacokinetic and tissue distribution studies of the formulation in rats showed a significant improvement in the kinetic parameters when compared to naïve FMT, further the formulation also improved the brain bioavailability of FMT. The anti-Parkinson's efficacy studies of the formulation in mice showed a significant neuroprotection against rotenone-induced changes in behavioural and biochemical parameters. Further, the histopathological analysis of mice brain confirms a significant neuroprotective benefit. The present study successfully establishes the brain targeted delivery and anti-Parkinson's therapeutic efficacy of FMT-SLNs-PS80.
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Nanopartículas , Neuroblastoma , Doença de Parkinson , Ratos , Camundongos , Humanos , Animais , Polissorbatos/farmacologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Rotenona/farmacologia , Lipídeos/química , alfa-Sinucleína/farmacologia , Nanopartículas/química , Estresse Oxidativo , Expressão Gênica , Tamanho da Partícula , Portadores de Fármacos/químicaRESUMO
Nanotechnology provides effective methods for precisely delivering chemotherapeutics to cancer cells, thereby improving efficacy and reducing off-target side effects. The targeted delivery of nanoscale chemotherapeutics is accomplished by two different approaches, namely the exploitation of leaky tumor vasculature (EPR effect) and the surface modification of nanoparticles (NPs) with various tumor-homing peptides, aptamers, oligonucleotides, and monoclonal antibodies (mAbs). Because of higher binding affinity and specificity, mAbs have received a lot of attention for the detection of selective cancer biomarkers and also for the treatment of various types of cancer. Antibody-conjugated nanoparticles (ACNPs) are an effective targeted therapy for the efficient delivery of chemotherapeutics specifically to the targeted cancer cells. ACNPs combine the benefits of NPs and mAbs to provide high drug loads at the tumor site with better selectivity and delivery efficiency. The mAbs on the NP surfaces recognize their specific receptors expressed on the target cells and release the chemotherapeutic agent in a controlled manner. Appropriately designed and synthesized ACNPs are essential to fully realize their therapeutic benefits. In blood stream, ACNPs instantly interact with biological molecules, and a protein corona is formed. Protein corona formation triggers an immune response and affects the targeting ability of the nanoformulation. In this review, we provide recent findings to highlight several antibody conjugation methods such as adsorption, covalent conjugation, and biotin-avidin interaction. This review also provides an overview of the many effects of the protein corona and the theranostic applications of ACNPs for the treatment of cancer.
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Early-season agricultural drought is frequent over South Asian region due to delayed or deficient monsoon rainfall. These drought events often cause delay in sowing and can even result in crop failure. The present study focuses on monitoring early-season agricultural drought in a semi-arid region of India over 5-year period (2016-2020). It utilizes hydro-climatic and biophysical variables to develop a combined drought index (CDI), which integrates anomalies in soil moisture conditions, rainfall, and crop-sown area progression. Synthetic aperture radar (SAR)-based soil moisture index (SMI) represents in situ measured soil moisture with reasonable accuracy (r=0.68). Based on the highest F1-score, SAR backscatter in VH (vertical transmit-horizontal receive) polarization with specific values for parameter threshold (-18.63 dB) and slope threshold (-0.072) is selected to determine the start of season (SoS) with a validation accuracy of 73.53%. The CDI approach is used to monitor early-season agricultural drought and identified drought conditions during June-July in 2019 and during July in 2018. Conversely, 2020 experienced consistently wet conditions, while 2016 and 2017 had near-normal conditions. Overall, the study highlights the use of SAR data for early-season agricultural drought monitoring, which is mainly governed by soil moisture-driven crop-sowing progression. The proposed methodology holds potential for effective monitoring, management, and decision-making in early-season agricultural drought scenarios.
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Secas , Radar , Estações do Ano , Monitoramento Ambiental/métodos , SoloRESUMO
CIM-Saumya is an improved, methyl chavicol rich variety of Ocimum basilicum (Family-Lamiaceae), developed by Council of Scientific and Industrial Research-Central Institute of Medicinal and Aromatic Plants. This plant possesses analgesic, anti-ulcerogenic, anti-inflammatory, anti-oxidant, cardiac stimulant, Central Nervous System depressant, hepatoprotective and immunomodulator activities due to the presence of various phytoconstituents. Among them rosmarinic acid, caffeic acid and ferulic acid are the three major phenolic compounds responsible for its therapeutic utility. These compounds are produced in very low amounts in the in vivo plants. Therefore, the present study has been conducted for establishment of cell suspensions, optimization of inoculums size, growth kinetics and screening of elicitor and precursors for the accumulation of cell biomass and the production of the three important phenolic compounds in cell suspension of O. basilicum (CIM-Saumya). Leaf derived friable callus was used for establishing the cell suspension in liquid Murashige and Skoog's medium fortified with 1 g/L casein hydrolysate + 2.26 µM 2,4-dichlorophenoxyacetic acid + 0.465 µM kinetin + 2.68 µM naphthalene acetic acid. The growth kinetic analysis pattern of cell suspension revealed the maximum biomass increments (% BI = 486.7) and production of RA 8.086 mg/g dry weight was found in 30th day harvested cells. Whereas, the other two phenolic compounds i.e. ferulic acid (0.0125 mg/g dry weight) and caffeic acid (0.38 mg/g dry weight) was recorded highest on 25th day of growth cycle. In the present study, one biotic elicitor i.e. yeast extract and three precursors [peptone, tryptone and lactalbumin hydrolysate] were tested, among them, lactalbumin hydrolysate (100 mg/L; added at 16th day) treated cells recorded highest estimated phenolic compounds yield (251.5 mg/L; 6.81 fold compared to the control) and biomass increments i.e. % BI = 1207 with 1.85 fold compared to the control. The highest rosmarinic acid content i.e. 25.47 mg/g DW (4.4 fold compared to the control) and 24.42 mg/g dry weight (4.1 folds compared to the control) was noticed in 30th day harvested cells treated with yeast extract (1 g/L on 0 day) and lactalbumin hydrolysate (100 mg/L added on 16th day), respectively. While caffeic acid content (0.91 mg/g dry weight) showed 2.9 folds higher compared to the control in cells treated with peptone 200 mg/L added on 16th day of culture cycle. All the treated cells showed enhanced phenylalanine ammonia-lyase enzyme activity with highest specific activity in lactalbumin hydrolysate followed by tryptone, peptone, and yeast extract. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01316-6.
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Escherichia coli infection is the major bacterial disease affecting the poultry industry and the continuous use of antibiotics in poultry farming has resulted in antibiotic resistance. So this study was planned to evaluate the use of an ecologically safe alternative to fight against infections. The leaf gel of the Aloe vera plant was selected based on its antibacterial activity assessed in in-vitro tests. The objective of the present study was to evaluate the effect of A. vera leaf extract supplementation on the severity of clinical signs and pathological lesions, mortality rate, levels of antioxidant enzymes, and immune response in experimentally E. coli-infected broiler chicks. Broiler chicks were supplemented with aqueous Aloe vera Leaf (AVL) extract @ 20 ml per liter of water from day one of age. After seven days of age, they were experimentally infected with E. coli O78 @ 107 CFU/0.5 ml intraperitoneally. Blood was collected at weekly intervals up to 28 days and assayed for antioxidant enzyme assays, and humoral and cellular immune response. The birds were observed daily for clinical signs and mortality. Dead birds were examined for gross lesions and representative tissues were processed for histopathology. The activities of antioxidants, Glutathione reductase (GR), and Glutathione-S-Transferase (GST) were significantly higher than the control infected group. The E. coli-specific antibody titer and Lymphocyte stimulation Index were comparatively higher in the AVL extract-supplemented infected group as compared to the control infected group. No considerable change was noted in the severity of clinical signs and pathological lesions, and mortality. Thus, Aloe vera Leaf gel extract enhanced the antioxidant activities and cellular immune responses of infected broiler chicks to combat this infection.
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Aloe , Escherichia coli , Animais , Antioxidantes , Galinhas , Extratos Vegetais/farmacologiaRESUMO
India generates 126.6 and 42 million tons of Rice straw (RS) and Rice husk (RH) annually, respectively. These agro-processing wastes feedstock are dumped in landfills or burnt, releasing toxic gases and particulate matter into the environment. This paper explores the valorization of these wastes feedstock into sustainable, economic products. We compare these wastes as matrices for lipase immobilization. These matrices were characterized, different parameters (pH, temperature, ionic strength, and metal ion cofactors) were checked, and the selected matrix was analyzed for reusability and hydrolysis of vegetable oils. Lipase immobilized Rice straw (LIRS) showed the highest activity with 72.84% protein loading. Field emission scanning electron microscopy (FESEM) demonstrated morphological changes after enzyme immobilization. FTIR showed no new bond formation, and immobilization data was fitted to Freundlich adsorption isotherm (with K = 12.18 mg/g, nF = 4.5). The highest activity with protein loading, 91.05%, was observed at pH 8, 37 °C temperature, 50 mM ionic strength, and lipase activity doubled in the presence of Mg2+ ions. The LIRS retained 75% of its initial activity up to five cycles and efficiently hydrolyzed different oils. The results reflected that the LIRS system performs better and can be used to degrade oily waste.
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Lipase , Oryza , Lipase/química , Oryza/metabolismo , Hidrólise , Enzimas Imobilizadas/química , Óleos de Plantas , Adsorção , Concentração de Íons de HidrogênioRESUMO
One of the most significant threats in Parkinson's disease (PD) is neurodegeneration. Neurodegeneration at both nigral as well as non-nigral regions of the brain is considered responsible for disease progression in PD. The key factors that initiate neurodegeneration are oxidative stress, neuroinflammation, mitochondrial complex-1 inhibition, and abnormal α-synuclein (SNCA) protein aggregations. Nigral neurodegeneration results in motor symptoms (tremor, bradykinesia, rigidity, shuffling gait, and postural instability) whereas; non-nigral neurodegeneration is responsible for non-motor symptoms (depression, cognitive dysfunctions, sleep disorders, hallucination, and psychosis). The available therapies for PD aim at increasing dopamine levels. The medications such as Monoamine oxidase B (MAO-B) inhibitors, catechol o-methyltransferase (COMT) inhibitors, Dopamine precursor (Levodopa), dopamine agonists, and dopamine reuptake inhibitors drastically improve the motor symptoms and quality of life only in the early stages of the disease. However, dopa resistant motor symptoms (abnormality in posture, speech impediment, gait, and balance problems), dopa resistant non-motor signs (sleep problems, autonomic dysfunction, mood, and cognitive impairment, pain), and drug-related side effects (motor fluctuations, psychosis, and dyskinesias) are considered responsible for the failure of these therapies. Further, none of the treatments, alone or in combination, are capable of halting the disease progression in the long run. Therefore, there is a need to develop safe and efficient neuroprotective agents, which can slow or stop the disease progression for the better management of PD. In this review, an effort has been made to discuss the various mechanisms responsible for progressive neurodegeneration (disease progression) in PD and also multiple strategies available for halting disease progression.
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Antiparkinsonianos , Doença de Parkinson , Antiparkinsonianos/uso terapêutico , Progressão da Doença , Dopamina , Dopaminérgicos/uso terapêutico , Humanos , Levodopa/uso terapêutico , Inibidores da Monoaminoxidase , Doença de Parkinson/metabolismo , Qualidade de VidaRESUMO
Background: Surge of SARS CoV-2 infections ascribed to omicron variant began in December 2021 in New Delhi. We determined the infection and reinfection density in a cohort of health care workers (HCWs) along with vaccine effectiveness (VE) against symptomatic infection within omicron transmission period (considered from December 01, 2021 to February 25, 2022. Methods: This is an observational study from the All India Institute of Medical Sciences, New Delhi. Data were collected telephonically. Person-time at risk was counted from November 30, 2021 till date of infection/ reinfection, or date of interview. Comparison of clinical features and severity was done with previous pandemic periods. VE was estimated using test-negative case-control design [matched pairs (for age and sex)]. Vaccination status was compared and adjusted odds ratios (OR) were computed by conditional logistic regression. VE was estimated as (1-adjusted OR)X100-. Findings: 11474 HCWs participated in this study. The mean age was 36â 2 (±10â 7) years. Complete vaccination with two doses were reported by 9522 (83%) HCWs [8394 (88%) Covaxin and 1072 Covishield (11%)]. The incidence density of all infections and reinfection during the omicron transmission period was 34â 8 [95% Confidence Interval (CI): 33â 5-36â 2] and 45â 6 [95% CI: 42â 9-48â 5] per 10000 person days respectively. The infection was milder as compared to previous periods. VE was 52â 5% (95% CI: 3â 9-76â 5, p = 0â 036) for those who were tested within 14-60 days of receiving second dose and beyond this period (61-180 days), modest effect was observed. Interpretation: Almost one-fifth of HCWs were infected with SARS CoV-2 during omicron transmission period, with predominant mild spectrum of COVID-19 disease. Waning effects of vaccine protection were noted with increase in time intervals since vaccination. Funding: None.
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Triple-negative breast cancer (TNBC) is the most aggressive and heterogeneous cancer subtypes. High rates of metastasis, poor prognosis, and drug resistance are the major problems associated with TNBC. The current chemotherapeutics eliminate only the bulk tumor cells (non-BCSCs) and do not affect breast cancer stem cells (BCSCs). The BCSCs which are left behind after chemotherapy is reported to promote recurrence and metastasis of TNBC. Death receptor-5 (DR-5) is exclusively expressed in TNBCs and mediates the extrinsic pathway of apoptosis. DR-5, therefore, can be exploited for targeted drug delivery and to induce apoptosis. Gamma-secretase mediated Notch signaling in BCSCs regulates its proliferation, differentiation, and metastasis. The endogenous ligand, Delta-like ligand 4 (DLL4), is reported to activate this Notch signaling in TNBC. Blocking this signaling pathway using both gamma-secretase inhibitors (GSIs) and DLL4 monoclonal antibody (mAb) may produce synergistic benefits. Further, the GSIs (DAPT, LY-411575, RO4929097, MK0752, etc.) suffer from poor bioavailability and off-target side effects such as diarrhea, suppression of lymphopoiesis, headache, hypertension, fatigue, and ventricular dysfunctions. In this hypothesis, we discuss Solid lipid nanoparticles (SLNs) based drug delivery systems containing GSIs and surface modified with DR-5 and DLL4 monoclonal antibodies (mAb) to effectivity target and treat TNBC. The delivery system is designed to deliver the drug cargo precisely to TNBCs through its DR-5 receptors and hence expected to reduce the off-target side effects of GSIs. Further, DLL4 mAb and GSIs are expected to act synergistically to block the Notch signal mediated BCSCs proliferation, differentiation, and metastasis.
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In this work, Ru x Pd y alloy nanoparticles were uniformly decorated on a two-dimensional reduced graphene oxide (rGO) sheet by an in situ chemical co-reduction process. The resulting products were characterized by various physiochemical techniques such as X-ray diffraction, Raman spectroscopy, energy-dispersive X-ray spectroscopy, inductively coupled plasma atomic absorption spectroscopy, X-ray photoelectron spectroscopy, and transmission electron microscopy. Further, the synthesized Ru x Pd y @rGO nanocomposites have been employed as a heterogeneous catalyst for three different catalytic reactions: (1) dehydrogenation of aqueous ammonia borane (AB); (2) hydrogenation of aromatic nitro compounds using ammonia borane as the hydrogen source, and (3) for the synthesis of aromatic azo derivatives. The present work illustrates the sustainable anchoring of metal nanoparticles over the surface of rGO nanosheets, which could be used for multifarious catalytic reactions.
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Cranial vault defects are either congenital or acquired in origin. Cranioplasty is most commonly done in patients after trauma, decompressive craniectomies, tumor resections, infections or because of congenital malformations. The purpose of a Cranioplast is to protect the underlying brain tissues, reduce pain, and to improve the calvarial contour, symmetry, and esthetics. Rehabilitation of these defects possesses a challenge to the surgical team and prosthodontist. With advancement in three-dimensional (3D) engineering technology, the use of rapid prototyping technology (RPT) can be used in the fabrication of 3D skull eliminating conventional impression for recording defect region. Custom-made cranial prosthesis now can be fabricated using the conventional method of wax-up and lost-wax method. Case 1 had a history of road traffic accident followed by decompressive craniectomy, which led to frontoparietotemporal defect of the right side. The 3D model was fabricated using RPT technology. The wax pattern fabricated on 3D prototyped skull was contoured using digital photographic superimposition method. Case 2 had a history of trauma on the head causing intracerebral hemorrhage followed by decompressive craniectomy which led to frontoparietotemporal defect of the right side. The 3D model was fabricated using RPT. The wax pattern fabricated on 3D prototyped skull was contoured using the compass method. The use of these methods with the added advantage of RPT resulted in prosthesis with good esthetics and better fit. The contour of the prosthesis was replicated in the same manner as compared to the contralateral side. These techniques are easy to use and are less time consuming and had few chances of errors.
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The ß-diketo-modified isoxazole derivative of curcumin (IOC) is well renowned for its anticancer, antioxidant, antimalarial, antiproliferative, and many other biological activities. With the aim of obtaining fundamental knowledge on the photophysics of IOC, the present work was directed toward delineating those at different pH environments and studying the degradation profiles of IOC at five different pH values. Because one of the primary drawbacks of curcumin is its rapid degradation at physiological conditions, the studies showed that the problem could be resolved, as the IOC molecule was extremely stable even in a highly alkaline medium. Further, in order to encounter the problems associated with the low solubility of IOC in aqueous media, ß-CD (ß-cyclodextrin) was used and calculations of the thermodynamic parameters revealed that the process of development of the host-guest inclusion complex was highly spontaneous in nature. The synthesis of the IOC:ß-CD inclusion complex has also been accomplished in the solid state, and the solid formed has been characterized using various physicochemical techniques. Finally, while variations in the pH as well as addition of foreign metal ions in +1 and +2 oxidation states showed minimal effect on the photophysics of the IOC:ß-CD inclusion complex, antiproliferative studies performed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays revealed their nontoxic nature on fibroblast L929 normal cell lines and extremely toxic activity on human lung cancer A549 cell lines.