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The outbreak of infectious diseases often exhibits periodicity, and this periodic behavior can be mathematically represented as a limit cycle. However, the periodic behavior has rarely been considered in demonstrating the cluster phenomenon of infection induced by diffusion (the instability modes) in the SIR model. We investigate the emergence of Turing instability from a stable equilibrium and a limit cycle to illustrate the dynamical and biological mechanisms of pattern formation. We identify the Hopf bifurcation to demonstrate the existence of a stable limit cycle using First Lyapunov coefficient in our spatiotemporal diffusion-driven SIR model. The competition between different instability modes induces different types of patterns and eventually spot patterns emerge as stable patterns. We investigate the impact of susceptible, infected, and recovered individuals on the type of patterns. Interestingly, these instability modes play a vital role in selecting the pattern formations, which is directly related to the number of observed spot patterns. Subsequently, we explain the dynamical and biological mechanisms of spot patterns to develop an effective epidemic prevention strategy.
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Enfermedades Transmisibles , Epidemias , Humanos , Simulación por Computador , Periodicidad , Enfermedades Transmisibles/epidemiología , Modelos BiológicosRESUMEN
In recent years, inulin has gained much attention as a promising multifunctional natural biopolymer with numerous applications in drug delivery, prebiotics, and therapeutics. It reveals a multifaceted biopolymer with transformative implications by elucidating the intricate interplay between inulin and the host, microbiome, and therapeutic agents. Their flexible structure, exceptional targetability, biocompatibility, inherent ability to control release behavior, tunable degradation kinetics, and protective ability make them outstanding carriers in healthcare and biomedicine. USFDA has approved Inulin as a nutritional dietary supplement for infants. The possible applications of inulin in biomedicine research inspired by nature are presented. The therapeutic potential of inulin goes beyond its role in prebiotics and drug delivery. Recently, significant research efforts have been made towards inulin's anti-inflammatory, antioxidant, and immunomodulatory properties for their potential applications in treating various chronic diseases. Moreover, its ability to reduce inflammation and modulate immune responses opens new avenues for treating conditions such as autoimmune disorders and gastrointestinal ailments. This review will attempt to illustrate the inulin's numerous and interconnected roles, shedding light on its critical contributions to the advancement of healthcare and biomedicine and its recent advancement in therapeutics, and conclude by taking valuable insights into the prospects and opportunities of inulin.
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Inulina , Prebióticos , Lactante , Humanos , Inulina/química , Suplementos Dietéticos , Tracto Gastrointestinal , Sistemas de Liberación de MedicamentosRESUMEN
Rationale: Trastuzumab (TZM) is a monoclonal antibody that targets the human epidermal growth factor receptor (HER2) and is clinically used for the treatment of HER2-positive breast tumors. However, the tumor microenvironment can limit the access of TZM to the HER2 targets across the whole tumor and thereby compromise TZM's therapeutic efficacy. An imaging methodology that can non-invasively quantify the binding of TZM-HER2, which is required for therapeutic action, and distribution within tumors with varying tumor microenvironments is much needed. Methods: We performed near-infrared (NIR) fluorescence lifetime (FLI) Forster Resonance Energy Transfer (FRET) to measure TZM-HER2 binding, using in vitro microscopy and in vivo widefield macroscopy, in HER2 overexpressing breast and ovarian cancer cells and tumor xenografts, respectively. Immunohistochemistry was used to validate in vivo imaging results. Results: NIR FLI FRET in vitro microscopy data show variations in intracellular distribution of bound TZM in HER2-positive breast AU565 and AU565 tumor-passaged XTM cell lines in comparison to SKOV-3 ovarian cancer cells. Macroscopy FLI (MFLI) FRET in vivo imaging data show that SKOV-3 tumors display reduced TZM binding compared to AU565 and XTM tumors, as validated by ex vivo immunohistochemistry. Moreover, AU565/XTM and SKOV-3 tumor xenografts display different amounts and distributions of TME components, such as collagen and vascularity. Therefore, these results suggest that SKOV-3 tumors are refractory to TZM delivery due to their disrupted vasculature and increased collagen content. Conclusion: Our study demonstrates that FLI is a powerful analytical tool to monitor the delivery of antibody drug tumor both in cell cultures and in vivo live systems. Especially, MFLI FRET is a unique imaging modality that can directly quantify target engagement with potential to elucidate the role of the TME in drug delivery efficacy in intact live tumor xenografts.
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BACKGROUND AND AIMS: The diagnosis of Budd-Chiari syndrome (BCS) is essentially radiologic and is needed to plan appropriate therapy. We therefore conducted this proof of concept study to assess the utility of EUS in assessing the anatomy of BCS. METHODS: This prospective, multicenter, observational study enrolled 50 consecutive patients with a diagnosis of BCS. All patients underwent a detailed EUS examination by 3 independent endosonographers, blinded to the anatomic details of BCS and others' findings. The EUS examination was compared between the endosonographers and with conventional angiography (where available) or magnetic resonance venography (MRV). Outcomes assessed were interobserver agreement, sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy in diagnosing pathologic lesions of BCS. RESULTS: Fifty BCS patients (mean age, 34 years [range, 13-65]) underwent EUS. Results showed good agreement among endosonographers for diagnosing right hepatic vein (κ = .716) and left hepatic vein lesions (κ = .722), moderate agreement for middle hepatic vein lesions (κ = .660), and very good agreement for inferior vena cava (IVC) lesions (κ = .823). EUS demonstrated high sensitivity and positive predictive value, low interobserver variability, and overall diagnostic accuracy for BCS lesions. CONCLUSIONS: EUS is a safe and accurate diagnostic tool for BCS. It can provide accurate mapping of hepatic veins, intrahepatic collaterals, and the IVC.
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Spatio-temporal variation in phytoplankton community dynamics in a temporarily open/closed Swarnamukhi river estuary (SRE), located on the South East coast of India was investigated and correlated to that of the adjacent coastal waters. Understanding the seasonal variability of the phytoplankton community and influencing factors are essential to predicting their impact on fisheries as the river and coastal region serve as the main source of income for the local fishing communities. Downstream before the river meets the sea, an arm of the Buckingham Canal (BC), carrying anthropogenic inputs empties into the Swarnamukhi River (SR1). The impact of anthropogenic effects on the phytoplankton community at BC was compared to other estuarine stations SR2 (upstream), SR1 (downstream), SRM (river mouth) and coastal station (CS). In BC station, harmful algal blooms (HABs) of Chaetoceros decipiens (2940 × 103 cells L-1) and Oscillatoria sp. (1619 × 103 cells L-1) were found during the southwest monsoon and winter monsoon, respectively. These HABs can be linked to the anthropogenic input of increased nutrients and trace metals. The HABs of Oscillatoria sp. were shown to be induced by elevated concentrations of nitrate (10.18 µM) and Ni (3.0 ppm) compared to ambient, while the HABs of C. decipiens were caused by elevated concentrations of silicate (50.35 µM), nitrite (2.1 µM), and phosphate (4.37 µM). Elevated nutrients and metal concentration from the aquaculture farms, and other anthropogenic inputs could be one of the prime reasons for the recorded bloom events at BC station. During this period, observed bloom species density was found low at other estuarine stations and absent at CS. The formation of bloom events during the closure of the river mouth could be a major threat to the coastal ecosystem when it opens. During the Osillatoria sp. bloom, both the Cu and Ni levels were higher at BC. The elevated concentration of nutrients and metals could potentially affect the coastal ecosystem and in turn fisheries sector in the tropical coastal ecosystem.
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Floraciones de Algas Nocivas , Oscillatoria , Fitoplancton , Estuarios , Ecosistema , Monitoreo del Ambiente , RíosRESUMEN
OBJECTIVE: Curcumin has the propensity to inhibit cancer growth, slow cancer development, increase chemotherapy effectiveness, and shield healthy cells from radiation treatment harm. As a result of curcumin's ability to block several signaling pathways, cervical cancer cells can once again proliferate normally. To optimize topically applied curcumin-loaded solid lipid nanoparticles (SLNPs) for the treatment of cervical cancer, this study set out to establish the relationship between design variables and experimental data. It also performed in vitro characterizations to determine the formulation's efficacy and safety. METHODS: Curcumin-loaded SLNPs were constructed and optimized using a systematic design of experiment (DoE) technique. SLNPs that were loaded with curcumin were produced utilizing a cold emulsification ultrasonication process. Using the Box Behnken Design, it was determined how independent variables (factors) like the quantity of lipid (A), the quantity of phospholipid (B), and the concentration of surfactant (C) affected the responses of the dependent variables (responses), such as particle size (Y1), polydispersity index (PDI) (Y2), and entrapment efficiency (EE) (Y3) (BBD). RESULTS: The ideal formulation (SLN9) was chosen using the desirability technique based on 3-D surface response graphs. Using polynomial equations and three-dimensional surface plots, the influence of independent factors on the dependent variables was evaluated. The observed responses were almost equal to the levels that the optimal formulation expected. The improved SLNP gel's shape and other physicochemical characteristics were also assessed, and they were determined to be ideal. The sustained release profile of the produced formulations was validated by in vitro release tests. Studies on hemolysis, immunogenic response, and in vitro cell cytotoxicity demonstrate the efficacy and safety of the formulations. CONCLUSION: To improve the treatment effect, chitosan-coated SLNPs may carry encapsulated curcumin to the desired location and facilitate its localization and deposition in the desired vaginal tissue.
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Curcumina , Nanopartículas , Neoplasias del Cuello Uterino , Femenino , Humanos , Curcumina/farmacología , Curcumina/química , Lípidos/química , Neoplasias del Cuello Uterino/tratamiento farmacológico , Nanopartículas/química , Tensoactivos/química , Tamaño de la Partícula , Portadores de Fármacos/químicaRESUMEN
Background & objectives: The treatment of brain cancer is still challenging for an oncologist due to the presence of the blood-brain barrier (BBB) which inhibits the entry of more than 98 per cent of drugs used during the treatment of brain disease. The cytotoxic drugs used in chemotherapy for brain cancer treatment also affect the normal cells due to lack of targeting. Therefore, the objective of the study was to develop tween 80-coated solid lipid nanoparticles (SLNs) loaded with folic acid-doxorubicin (FAD) conjugate for site-specific drug delivery to brain cancer cells. Methods: The FAD conjugate was synthesized by the conjugation of folic acid with doxorubicin and characterized by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. SLNs loaded with FAD were prepared by the solvent injection method. The SLNs were characterized by the particle size, zeta potential, surface morphology, entrapment efficiency, etc. Results: The average particle size of FAD conjugate-loaded SLNs (SLN-C) was found to be 220.4±2.2 nm, with 36.2±0.6 per cent entrapment efficiency. The cytotoxicity and cellular uptake were determined on U87 MG cell lines. Half maximal inhibitory concentration value of the SLN-C was found to be 2.5 µg/ml, which confirmed the high antitumour activity against brain cancer cells. Interpretation & conclusions: The cell line studies confirmed the cytotoxicity and internalization of SLN-C in U87 MG brain cancer cells. The results confirmed that tween 80-coated SLNs have the potential to deliver the doxorubicin selectively in the brain cancer cells.
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Antineoplásicos , Neoplasias Encefálicas , Nanopartículas , Humanos , Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Doxorrubicina , Ácido Fólico/uso terapéuticoAsunto(s)
COVID-19 , Oncólogos , Humanos , COVID-19/epidemiología , Pandemias , Actitud , Pueblo AsiaticoRESUMEN
Background and aims: Increasing incidence of hepatocellular carcinoma (HCC) in India is a matter of concern and need for adequate profiling and streamlining management strategies cannot be over-emphasized. Methods: This is a prospective multi-centric observational cohort study comprising of an oncology center, one university tertiary hospital with specialized hepatology service, one public hospital with gastroenterology service, and a private liver transplant center located within a 3-km radius. The demographic and clinical parameters were recorded on a prospectively maintained database. The clinical profile, demographics, characteristics of HCC and the allocated treatment were noted and compared among the four centers. Results: In total, 672 patients were enrolled from June 2016 till January 2020. Abdominal pain (64.3%) and weight loss (47.3%) were the most common symptoms. Most common identified etiology was hepatitis B (39%). The cancer center received lesser patients with hepatitis C and those with advanced stage of HCC. The private transplant center reported the highest proportion of NASH, which was also significantly higher in those belonging to higher socioeconomic strata, and lowest proportion of alcoholic cirrhosis. Metastasis was seen in almost one-fifth (19%) cases at diagnosis. Portal vein thrombosis was evident in 40%. Adherence to treatment guidelines was seen in three-fourth cases (76%). Conclusions: Hepatitis B is the most common underlying cause for HCC, whereas other causes like NASH are on the rise. Etiologic profile may vary with selective specialization of centers catering to patients with HCC. Adherence to guideline while allocating treatment was high among all centers with highest non-adherence in BCLC A.
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Autoimmune Hepatitis (AIH) is a chronic liver disease Characterized by interface hepatitis, lymphoplasmacytic infiltrate, and hepatic rosettes. HIV infection is a state of immunosuppression; hence, the possibility of AIH is relatively rare, especially in patients with low CD4 counts. Therefore, we present an interesting case series of four patients with autoimmune liver disease with myriad presentations for the first time from India. We propose that despite the rarity of this presentation with immunosuppression, one should never miss such a treatable cause of liver disease leading to good clinical outcomes.
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OBJECTIVE: Nisin is an antibacterial peptide with anticancer properties, but the main drawback is its rapid enzymatic degradation and limited permeation across the cell membrane. This research aims to overcome these drawbacks by developing nisin-loaded nanoparticles (NPN) with improved cytotoxic effects. SIGNIFICANCE: PLGA nanoparticles are one of the most effective biodegradable and biocompatible drug delivery carriers. In the present study, nisin-loaded nanoparticles showed enhanced anticancer effects. METHODS: NPN was prepared by a double emulsion solvent evaporation method and characterized for different parameters. The cytotoxic investigation of NPN was carried out on various cell lines, including A549, SW-620, HT-29, PC-3, MDA-MB-231, MCF-7, MiaPaca-2, and fR2 by sulforhodamine B (SRB) assay. Mechanistic investigation of cellular cytotoxicity was performed by using bright-field microscopy, DAPI staining, intracellular reactive oxygen species (ROS), changes in mitochondrial membrane potential (ΔΨm), Western blotting and cellular uptake study. A comparative cytotoxicity study of nisin and NPN was performed on normal breast epithelial cells (fR2). RESULTS: NPN showed spherical shape, 289.09 ± 3.63 nm particle size, and 63.37 ± 3.12% entrapment efficiency. NPN was more cytotoxic to the MDA-MB-231 cell line, showing higher nuclear fragmentation, ROS generation, depletion of ΔΨm, and enhanced intracellular uptake with apoptosis signs compared with nisin and with no cytotoxicity on normal cells. CONCLUSIONS: The findings suggest that nisin delivery via PLGA nanoparticles can be used to treat cancer without significant effects on healthy cells.
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Antineoplásicos , Nanopartículas , Nisina , Antibacterianos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Portadores de Fármacos/química , Emulsiones , Humanos , Nanopartículas/química , Nisina/química , Nisina/farmacología , Tamaño de la Partícula , Especies Reactivas de Oxígeno , SolventesRESUMEN
The diffusion of the susceptible and infected is a vital factor in spreading infectious diseases. However, the previous SIR networks cannot explain the dynamical mechanism of periodic behavior and endemic diseases. Here, we incorporate the diffusion and network effect into the SIR model and describes the mechanism of periodic behavior and endemic diseases through wavenumber and saddle-node bifurcation. We also introduce the standard network structured entropy (NSE) and demonstrate diffusion effect could induce the saddle-node bifurcation and Turing instability. Then we reveal the mechanism of the periodic outbreak and endemic diseases by the mean-field method. We provide the Turing instability condition through wavenumber in this network-organized SIR model. In the end, the data from COVID-19 authenticated the theoretical results.
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Purpose: Radiation dermatitis is most common and debilitating side effects of radiotherapy leading to treatment interruption, thereby compromising the local control, and effecting quality of life. With the invent of modern imaging and recent advances in megavoltage radiotherapy, radiation-related side effects have reduced. In this audit, we report the risk factors associated with Grade III dermatitis in modern centers. Materials and Methods: We analyzed 172 patients treated with volume modulated arc therapy (VMAT) and static field intensity-modulated radiotherapy (SFIMRT) at our center. All head and neck, breast, gynecological, GU malignancies, and sarcoma patients treated with a dose of >45 Gy from April 2018 to December 2019 were included in the study. On couch, treatment verification was done with cone-beam computer tomography (CBCT). Slice-by-slice verification of planning target volume (PTV) with CBCT was done in the first three fractions and weekly thereafter. Skin evaluation was done using CTCAE v. 5. Statistical analysis was done using SPSS v. 22. Results: Of the 172 patients treated with VMAT and SFIMRT, 15 patients (8.7%) had Grade III dermatitis. Grade III dermatitis was mostly seen in breast cancer followed by head-and-neck patients. More reactions were observed in patients with advanced stage disease. Treatment verification is important at the later course of treatment, especially in head-and-neck cases where the treatment volume is large and PTV may extend outside skin. Contributing factors of radiation dermatitis at modern radiotherapy center are gene mutation, use of concurrent chemoradiotherapy, and bolus. Conclusion: We hereby conclude that PTV mismatch in weekly treatment verification, genetic mutations, concurrent chemo-radiotherapy, use of thermoplastic mask, and bolus are the contributing factors for Grade III dermatitis in modern radiotherapy centers.
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Oncología por Radiación , Radioterapia de Intensidad Modulada , Humanos , Calidad de Vida , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodosRESUMEN
There is lack of consistent surrogate markers of kidney function to identify established disease, especially in early stages of CKD. Creatinine remains within normal levels until a significant reduction in renal function has occured. Cystatin C appears to be unaffected by muscle mass, diet, or gender. Its clearance is only by glomerular filtration. The plasma concentration is not influenced by inflammation or liver disease. It is not affected by optical interferences. Considering these benefits, it is more useful when trying to detect mild to moderate impairment of kidney function. MATERIAL: An observational, analytical study was conducted over a duration of 18 months. The study participants were divided into 2 groups based on eGFR. OBSERVATION: 67.5% patients had raised Cystatin C as compared to only 12.5% who had raised Creatinine. In our study, we found that Serum Creatinine (r=-0.85, p< 0.001) was better than Cystatin C (r=-0.55, p< 0.001) in all stages of CKD. However, in patients with eGFR ≥ 60 ml/min/m2. Cystatin C (r = -0.68, p<0.001) was a more sensitive marker to detect renal dysfunction at an early stage as compared to Serum Creatinine (r = -0.48, p<0.001). Overall, the AUC (Area Under the Curve) for Serum Creatinine is more than Cystatin C. However, in patients with eGFR≥ 60ml/ min/1.73m2, AUC for cystatin C is more. Thus, Cystatin C is more sensitive than Serum Creatinine to detect early renal dysfunction. CONCLUSION: We found out that both serum creatinine and serum cystatin C were significantly increased across CKD groups but cystatin C is a better predictor of CKD than creatinine in stages with eGFR≥60 ml/min/1.73 m2 as serum cystatin C was found to be raised contrary to serum creatinine which was within normal limits, although in stages with eGFR<60 ml/min/1.73 m2 there was no significant difference between the two. We found out that normal serum creatinine levels during the stage of kidney disease with eGFR≥60 ml/min/1.73 m2 does not necessarily mean normal renal function. Cystatin C should be encouraged as a screening tool for early renal impairment in the patient as the risk of developing CKD, especially in long-standing hypertensive and diabetic patients as an adjunct to creatinine estimation. It should also be included in the management protocol for these patients.
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Cistatina C , Insuficiencia Renal Crónica , Biomarcadores , Creatinina , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Insuficiencia Renal Crónica/diagnósticoRESUMEN
The use of functional information of taxa is a promising approach to uncover the underlying mechanism of ecosystem functioning. We used biological trait analysis (BTA) to assess the functional response of subtidal macrobenthos with multiple stressors. Seventeen environmental variables from 42 stations of five coastal districts were assessed along the southeast coast of India. Dominant fauna was assigned into 20 categories belonging to six functional traits. Additionally, we used five ecological groups (EG) of AMBI as a covariable trait to validate functional traits and EG relationship. The trait composition in the communities showed significant variation between undisturbed and disturbed areas. RLQ/Fourth corner combined approach illustrated the effects of stressors and isolated the corresponding species associated with different stressors. Smaller, short-lived, deposit-feeding, and discretely motile fauna occurred at the disturbed areas, whereas, larger, long-lived, and highly motile at the undisturbed area. Dissolved oxygen, organic enrichment, and metals concentration were the main environmental descriptors influencing the trait composition. The results highlight the importance of the BTA approach to uncover the response of the macrobenthic community to anthropogenic disturbances-driven impacts in multi-stressed near-shore coastal ecosystems.
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Ecosistema , Monitoreo del Ambiente , Animales , Biodiversidad , India , Invertebrados , FenotipoRESUMEN
Video endoscopy is an important modality for the diagnosis and treatment of various gastrointestinal diseases. Most endoscopic procedures are performed as outpatient basis, sometimes requiring sedation and deeper levels of anesthesia. Moreover, advances in endoscopic techniques have allowed invasion into the third space and the performance of technically difficult procedures that require the utmost precision. Hence, formulating strategies for the discharge of patients requiring endoscopy is clinically and legally challenging. In this review, we have discussed the various criteria and scores for the discharge of patients who have undergone endoscopic procedures with and without anesthesia.
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Background: Snakebite is a common occupational hazard in tropical countries such as India. India has the highest number of snakebites and accounts for nearly 50% of global snakebite deaths. Jharkhand is a state with abundant flora and fauna, with a large rural population, prone to snakebite deaths. We aimed to study various clinical and laboratory parameters in snakebite patients and their association with mortality. Material and Methods: This study was an analytical cross-sectional study conducted from October 2019 to April 2021. Snake-bitten individuals admitted in the in-patient department (General Medicine) of a tertiary care centre of Jharkhand state were included in this study. Information regarding gender, species of the snake, site of bite, symptoms (neurological and haematological), signs, reaction to ASVS, procedures performed (haemodialysis), general examinations, systemic examinations, and investigations were collected and analysed to predict mortality. Results: Out of 60 snakebite patients, 39 (65%) were males and 21 (35%) were females. Snakebite in 41.67% patients was because of unknown species, snakebite in 26.67% patients was because of Russell's viper, snakebite in 21.67% was because of krait, and snakebite in 10% was because of cobra. 41.67% of individuals sustained bites over the right leg, 23.33% over the left leg, 18.33% over the right arm, and 15% over the left arm. Mortality was seen in 8 (13.33%) patients. Haemorrhagic manifestations including haematuria and haemoptysis were seen in 10 (16.66%) and 3 (5%) patients, respectively. Neurological symptoms were present in 27 (45%) patients. In laboratory examination, the total leucocyte count, international normalised ratio, d-dimer, urea, creatinine, and amylase were significantly high in the non-survivor group (all P values < 0.05). In this study, mortality was significantly associated with increased requirement of haemodialysis because of renal failure and an increase in duration of hospital stay (P value < 0.05). The duration of hospital stay independently predicts mortality with an odds ratio of 0.514 (95% confidence interval 0.328 to 0.805; P = 0.004). Conclusion: Early evaluation of clinical and laboratory parameters is needed to identify various complications (haematological and neurological) as they may prolong the hospital stay, leading to an increase in mortality.
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Mitochondria fulfill the cell's energy demand and affect the intracellular calcium (Ca2+) dynamics via direct Ca2+ exchange, the redox effect of reactive oxygen species (ROS) on Ca2+ handling proteins, and other signaling pathways. Recent experimental evidence indicates that mitochondrial depolarization promotes arrhythmogenic delayed afterdepolarizations (DADs) in cardiac myocytes. However, the nonlinear interactions among the Ca2+ signaling pathways, ROS, and oxidized Ca2+/calmodulin-dependent protein kinase II (CaMKII) pathways make it difficult to reveal the mechanisms. Here, we use a recently developed spatiotemporal ventricular myocyte computer model, which consists of a 3-dimensional network of Ca2+ release units (CRUs) intertwined with mitochondria and integrates mitochondrial Ca2+ signaling and other complex signaling pathways, to study the mitochondrial regulation of DADs. With a systematic investigation of the synergistic or competing factors that affect the occurrence of Ca2+ waves and DADs during mitochondrial depolarization, we find that the direct redox effect of ROS on ryanodine receptors (RyRs) plays a critical role in promoting Ca2+ waves and DADs under the acute effect of mitochondrial depolarization. Furthermore, the upregulation of mitochondrial Ca2+ uniporter can promote DADs through Ca2+-dependent opening of mitochondrial permeability transition pores (mPTPs). Also, due to much slower dynamics than Ca2+ cycling and ROS, oxidized CaMKII activation and the cytosolic ATP do not appear to significantly impact the genesis of DADs during the acute phase of mitochondrial depolarization. However, under chronic conditions, ATP depletion suppresses and enhanced CaMKII activation promotes Ca2+ waves and DADs.
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The outbreak of novel coronavirus (nCoV) or severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in December 2019 in Wuhan, China, has posed an international public health emergency worldwide and forced people to be confined in their homes. This virus is of high-risk category and is declared a pandemic by the World Health Organization (WHO). The worldwide researchers and various health professionals are working together to determine the best way to stop its spread or halt this virus's spread and circumvent this pandemic condition threatening millions of human lives. The absence of definitive treatment is possible to explore to reduce virus infection and enhance patient recovery. Along with off-label medicines, plasma therapy, vaccines, the researchers exploit the various plants/herbs and their constituents to effectively treat nCoV infection. The present study aimed to present brief and most informative salient features of the numerous facts regarding the SARS-CoV-2, including the structure, genomic sequence, recent mutation, targeting possibility, and various hurdles in research progress, and off-labeled drugs, convalescent plasma therapy, vaccine and plants/herbs for the treatment of coronavirus disease-2019 (COVID-19). Results showed that off-labeled drugs such as hydroxychloroquine, dexamethasone, tocilizumab, antiviral drug (remdesivir, favipiravir), etc., give positive results and approved for use or approved for restricted use in some countries like India. Future research should focus on these possibilities that may allow the development of an effective treatment for COVID-19.