Inhibiting SIRT-2 by AK-7 restrains airway inflammation and oxidative damage promoting lung resurgence through NF-kB and MAP kinase signaling pathway.

Introduction: Chronic obstructive pulmonary disease (COPD) is a major global cause of mortality with limited effective treatments. Sirtuins (SIRT) are histone deacetylases that are involved in the regulation of redox and inflammatory homeostasis. Hence, the present study aims to investigate the role of SIRT-2 in modulating inflammation in a murine model of COPD. Methods: COPD in mice was established by cigarette smoke (CS) exposure for 60 days, and AK-7 was used as the specific SIRT-2 inhibitor. AK-7 (100 µg/kg and 200 µg/kg body weight) was administered intranasally 1 h before CS exposure. Molecular docking was performed to analyze the binding affinity of different inflammatory proteins with AK-7. Results: Immune cell analysis showed a significantly increased number of macrophages (F4/80), neutrophils (Gr-1), and lymphocytes (CD4+, CD8+, and CD19+) in the COPD, group and their population was declined by AK-7 administration. Total reactive oxygen species, total inducible nitric oxide synthase, inflammatory mediators such as neutrophil elastase, C-reactive protein, histamine, and cytokines as IL4, IL-6, IL-17, and TNF-α were elevated in COPD and declined in the AK-7 group. However, IL-10 showed reverse results representing anti-inflammatory potency. AK-7 administration by inhibiting SIRT-2 decreased the expression of p-NF-κB, p-P38, p-Erk, and p-JNK and increased the expression of Nrf-2. Furthermore, AK-7 also declined the lung injury by inhibiting inflammation, parenchymal destruction, emphysema, collagen, club cells, and Kohn pores. AK-7 also showed good binding affinity with inflammatory proteins. Discussion: The current study reveals that SIRT-2 inhibition mitigates COPD severity and enhances pulmonary therapeutic interventions, suggesting AK-7 as a potential therapeutic molecule for COPD medication development.

Comparing color match by conventional trial and error method with maxillofacial spectrophotometer method for the skin of Indian participants: A subjective and objective assessment.

STATEMENT OF PROBLEM: The comparative accuracy of different color-matching methods for maxillofacial prostheses is lacking. PURPOSE: This clinical study aimed to compare prosthesis color matching using the conventional trial and error method with that using the maxillofacial spectrophotometer method. MATERIAL AND METHODS: Fifty-four Indian participants were enrolled based on skin color and divided into Light, Medium, and Dark groups (n=18). Silicone specimens of different thicknesses were fabricated using both the conventional trial and error and maxillofacial spectrophotometer coloration methods for all participants. The color match of the specimens with natural skin was assessed subjectively and objectively using expert consensus and fiber optic spectroscopy with the CIELab color difference formula, respectively. Statistical analyzes included the Shapiro-Wilk and independent sample t tests (α=.05). RESULTS: The mean ΔL* (white-black axis) value for the Skin-Conventional color match difference was significantly lower and positive compared with the Skin-Spectrophotometer match (P=.090) for the sample. The mean Δb* (yellow-blue axis) value for the Skin-Conventional color difference was significantly positive compared with the Skin-Spectrophotometer match (P=.020). The mean ΔE* (color difference) for the Skin-Conventional color match was significantly lower than the Skin-Spectrophotometer value (P=.034). Expert opinion as assessed with a visual analog scale found color matching using the conventional method (7.12) to be significantly better than with the spectrophotometer (6.30). A qualitative analysis of expert opinion revealed that conventional color matching should have been less red (34.3%) and that spectrophotometer matching should have been less yellow (30.1%). CONCLUSIONS: Across different thicknesses of silicone and Indian skin shades, color matching was significantly better for the conventional versus the maxillofacial spectrophotometer method, both objectively and subjectively. The spectrophotometer match was significantly yellower and lighter than natural skin.

Local incomplete combustion emissions define the PM2.5 oxidative potential in Northern India.

The oxidative potential (OP) of particulate matter (PM) is a major driver of PM-associated health effects. In India, the emission sources defining PM-OP, and their local/regional nature, are yet to be established. Here, to address this gap we determine the geographical origin, sources of PM, and its OP at five Indo-Gangetic Plain sites inside and outside Delhi. Our findings reveal that although uniformly high PM concentrations are recorded across the entire region, local emission sources and formation processes dominate PM pollution. Specifically, ammonium chloride, and organic aerosols (OA) from traffic exhaust, residential heating, and oxidation of unsaturated vapors from fossil fuels are the dominant PM sources inside Delhi. Ammonium sulfate and nitrate, and secondary OA from biomass burning vapors, are produced outside Delhi. Nevertheless, PM-OP is overwhelmingly driven by OA from incomplete combustion of biomass and fossil fuels, including traffic. These findings suggest that addressing local inefficient combustion processes can effectively mitigate PM health exposure in northern India.

Optical thickness measurement of occluded samples by lens-less Fourier transform digital holography, thermal loading, and machine learning.

Thickness measurements of objects, especially transparent and semi-transparent objects, are essential for their characterization and identification. However, in the case of occluded objects, the optical thickness determination becomes difficult, and an indirect way must be devised. Thermal loading of the objects changes their opto-thermal properties, which will be reflected as a change in their optical thickness. The key to quantifying such occluded objects lies in collecting these opto-thermal signatures. This could be achieved by imaging the changes occurring to a probe wavefront passing through the object while it is being thermally loaded. Digital holographic interferometry is an ideal tool for observing phase changes, as it can be used to compare wavefronts recorded at different instances of time. Lens-less Fourier transform digital holographic imaging provides the phase information from a single Fourier transform of the recorded hologram and can be used to quantify occluded phase objects. Here we describe a technique for the measurement of change in optical thickness of thermally loaded occluded phase samples using lens-less Fourier transform digital holography and machine learning. The advantage of the proposed technique is that it is a single shot, lens-less imaging modality for quasi-real-time quantification of phase samples behind thin occlusions.

Blocking µ-opioid receptor by naltrexone exaggerates oxidative stress and airway inflammation via the MAPkinase pathway in a murine model of asthma.

Opioids regulate various physiological and pathophysiological functions, including cell proliferation, immune function, obesity, and neurodegenerative disorders. They have been used for centuries as a treatment for severe pain, binding to opioid receptors a specific G protein-coupled receptor. Common opioids, like ß-endorphin, [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO), and dynorphins, have analgesic effects. The use of a potent antagonist, like naltrexone hydrochloride, to block the effects of mu Opioid Receptor (µOR) may result in the withdrawal of physiological effects and could potentially impact immune responses in many diseases including respiratory disease. Asthma is a respiratory disease characterized by airway hyperresponsiveness, inflammation, bronchoconstriction, chest tightness, stress generation and release of various cytokines. Airway inflammation leads recruitment and activation of immune cells releasing mediators, including opioids, which may modulate inflammatory response by binding to their respective receptors. The study aims to explore the role of µOR antagonist (naltrexone) in regulating asthma pathophysiology, as the regulation of immune and inflammatory responses in asthma remains unclear. Balb/c mice were sensitized intranasally by 1% TDI and challenged with 2.5% TDI. Naltrexone hydrochloride (1 mg/kg body weight) was administered through intraperitoneal route 1 h before TDI induction. Blocking µOR by naltrexone exacerbates airway inflammation by recruiting inflammatory cells (lymphocytes and neutrophils), enhancing intracellular Reactive oxygen species in bronchoalveolar lavage fluid (BALF), and inflammatory mediator (histamine, Eosinophil peroxidase and neutrophil elastase) in lungs. Naltrexone administration modulated inflammatory cytokines (TNF-α, IL-4, IL-5, IL-6, IL-10, and IL-17A), and enhanced IgE and CRP levels. Naltrexone administration also increased the expression of NF-κB, and phosphorylated p-P38, p-Erk, p-JNK and NF-κB by inhibiting the µOR. Docking study revealed good binding affinity of naltrexone with µOR compared to δ and κ receptors. In future it might elucidate potential therapeutic against many respiratory pathological disorders. In conclusion, µOR blocking by naltrexone regulates and implicates inflammation, bronchoconstriction, and lung physiology.

Pharmacological inhibition of SIRT-2 by AK-7 modulates redox status and apoptosis via regulating Nrf2 in an experimental model of chronic obstructive pulmonary disease: an invivo and insilico study.

Chronic obstructive pulmonary disease (COPD) is defined by inflammation and emphysema. Sirtuins (SIRT) are NAD+-dependent histone deacetylases that regulate oxidative stress and inflammation. The present work investigates the modulatory role of SIRT-2 in experimental COPD model. Insilico comparative assessment of SIRT-2 inhibitors (AK-7 and AGK-2) by ADMET and molecular docking revealed AK-7 as suitable candidate for invivo application. COPD in mice was established by cigarette smoke (CS) exposure for 2 months. AK-7 (100 µg/kg and 200 µg/kg body weight) was administered intranasally one hour before CS exposure. The present investigation demonstrates that CS exposure increases total cell count, and free radical production (total reactive oxygen species, total oxidant status, myeloperoxidase, and nitric oxide), which were decreased by AK-7. It also altered antioxidant enzymatic activity (total antioxidant status, catalase, superoxide dismutase, glutathione peroxidase, glutathione-s-transferase, glutathione reductase, and reduced glutathione), hence preserving the redox balance. AK-7 significantly decreases apoptosis, protein carbonylation, lipid peroxidation, TNF-α and IFN-ï»» levels represent COPD generation in mice and were dramatically decreased by AK-7. Histopathological studies shows that CS exposure damages alveoli and produces peribronchiolar inflammation; both of these events were reduced by AK-7. The antioxidative potency of AK-7 was confirmed by observing Nrf2 and Keap1 proteins. Keap-dependent Nrf2 regulation was observed, with cytosolic Nrf2 and Keap1 expression elevated in COPD and reduced in the AK-7 group while nuclear Nrf2 was reduced in COPD and increased in the AK-7 group. The present study concludes that inhibition of SIRT-2 minimizes COPD severity and mediates therapeutic effects in the lungs.

Clinical profile and microbiological spectrum of patients with continuous ambulatory peritoneal dialysis-associated peritonitis at a tertiary care center.

Background: We present risk factors, clinical profile, and microbiological spectrum of patients with continuous ambulatory peritoneal dialysis (CAPD)-associated peritonitis who were managed at our center. Methods: All consecutive patients with CAPD-associated peritonitis who presented to our center between July 2018 and December 2019 were included in the study. Risk factors, microbiological spectrum, clinical profile, and outcome of patients were studied. Results: Eighty-five patients with CAPD-associated peritonitis and 50 patients who never had peritonitis during the study period were included. Diabetes Mellitus (OR 0.058, 95% CI0.007-0.493, p < 0.05), residence in rural area (OR 3.376, 95% CI 1.084-10.516, p < 0.05), duration of peritoneal dialysis (OR 0.935, 95% CI 0.886-0.987, p < 0.05), mean serum hemoglobin (OR 1.674, 95% CI 1.119-2.502, p < 0.05) and serum albumin (OR 0.148, 95% CI 0.066-0.333, p < 0.05) were associated with higher risk of peritonitis in CAPD patients. Eight-three patients (98.8%) had turbid CAPD fluid and 52 (61.2%) had fever at the time of presentation to the hospital. The mean CAPD fluid TLC on day 1, 3, and 5 were 2034.3 ± 3330.1 cells/cumm, 1049.0 ± 1210.9 cells/cumm, and 605.2 ± 950.5 cells/cumm, respectively. The organisms isolated were two Escherichia coli (2.4%), one Staphylococcus aureus (1.2%), one Klebsiella (1.2%), two Acinetobacter (2.4%), 10 Fungal organisms (11.7%), and in two (2.4%) cases, Mycobacterium tuberculosis (MTB) was detected by polymerase chain reaction (PCR) of CAPD fluid. Thirty-seven (43.5%) patients had a complete cure and 48 (56.5%) patients were refractory to treatment; hence catheter was removed in them (catheter loss). Six (7.0%) patients died during the study period. Conclusion: CAPD-associated peritonitis is an important risk factor for technique failure. The majority of episodes are culture-negative, and PCR can help in detecting fungal and tubercular peritonitis early in the course.

Introduction to Osteoporosis, Osteomalacia, and Fragility Fractures.

Background: Osteoporosis is a disease of the bones leading to decreased bone mineral density, leading to fragility fractures. This article is an overview of osteoporosis, osteomalacia and fragility fractures and serves as an introductory article for this special issue on osteoporosis. Methods: This is a short, comprehensive account of the given conditions with concepts and a review from the recent literature. The authors provide relevant references from the literature in the bibliography. The sections herein have also been deliberated in the meetings of experts of osteoporosis. Results: An overview of osteoporosis, osteomalacia and fragility fractures is provided, including definitions and summaries of aetiology, pathophysiology, diagnosis, prevention, and management. A detailed account of some of these topics will be provided in subsequent chapters. Conclusion: Osteoporosis is a silent disease with the potential to cause significant morbidity and mortality if not detected early. It is important to differentiate from and diagnose associated osteomalacia to provide accurate therapy. It is also important to identify the type of fragility fractures and initiate treatment for bone strengthening to prevent subsequent fractures.

ß-Endorphin (an endogenous opioid) inhibits inflammation, oxidative stress and apoptosis via Nrf-2 in asthmatic murine model.

Asthma, a chronic respiratory disease is characterized by airway inflammation, remodelling, airflow limitation and hyperresponsiveness. At present, it is considered as an umbrella diagnosis consisting several variable clinical presentations (phenotypes) and distinct pathophysiological mechanisms (endotypes). Recent evidence suggests that oxidative stress participates in airway inflammation and remodelling in chronic asthma. Opioids resembled by group of regulatory peptides have proven to act as an immunomodulator. ß-Endorphin a natural and potent endogenous morphine produced in the anterior pituitary gland play role in pain modulation. Therapeutic strategy of many opioids including ß-Endorphin as an anti­inflammatory and antioxidative agent has not been yet explored despite its promising analgesic effects. This is the first study to reveal the role of ß-Endorphin in regulating airway inflammation, cellular apoptosis, and oxidative stress via Nrf-2 in an experimental asthmatic model. Asthma was generated in balb/c mice by sensitizing with 1% Toulene Diisocyanate on day 0, 7, 14 and 21 and challenging with 2.5% Toulene Diisocyanate from day 22 to 51 (on every alternate day) through intranasal route. ß-Endorphin (5 µg/kg) was administered through the nasal route 1 h prior to sensitization and challenge. The effect of ß-Endorphin on pulmonary inflammation and redox status along with parameters of oxidative stress were evaluated. We found that pre-treatment of ß-Endorphin significantly reduced inflammatory infiltration in lung tissue and cell counts in bronchoalveolar lavage fluid. Also, pre-treatment of ß-Endorphin reduced reactive oxygen species, Myeloperoxidase, Nitric Oxide, Protein and protein carbonylation, Glutathione Reductase, Malondialdehyde, IFN-γ, and TNF-α. Reversely, ß-Endorphin significantly increased Superoxide dismutase, Catalase, glutathione, Glutathione-S-Transferase, and activation of NF-E2-related factor 2 (Nrf-2) via Kelch-like ECH-associated protein 1 (Keap1), independent pathway in the lung restoring architectural alveolar and bronchial changes. The present findings reveal the therapeutic potency of ß-END in regulating asthma by Keap-1 independent regulation of Nrf-2 activity. The present findings reveal the therapeutic potency of ß-Endorphin in regulating asthma.

A multi-model forecasting approach for solid waste generation by integrating demographic and socioeconomic factors: a case study of Prayagraj, India.

Projecting municipal solid waste generation and identifying socioeconomic factors affecting waste generation is crucial for integrated waste management strategies. The present research work focuses on the projection of municipal solid waste (MSW) generation in Prayagraj, India, based on demographics and socioeconomic factors, using long short-term memory (LSTM), autoregressive integrated moving average (ARIMA), and incremental increase models (IIM). The model was integrated with nine socioeconomic variables to improve accuracy. The influence of socioeconomic variables on MSW generation was evaluated using correlation and fuzzy logic approaches. Waste generation data collected from the Central Pollution Control Board (CPCB) from 1997 to 2015 were used to train the models. The results of the correlation study indicate that population growth, employment, and households have a substantial impact on waste generation rates. Root mean squared error (RMSE), mean absolute percent error (MAPE), and coefficient of determination (R2) suggest that LSTM is the best model to forecast MSW generation in Prayagraj, India. The R2 value indicates that the LSTM is more accurate (0.92) than ARIMA (0.72) and IIM (0.70). LSTM projection indicates that the city will have a population of 1.6 million by 2031, and waste generation will increase by 70.6% in 2031.

Design, synthesis, and evaluation of benzofuran-based chromenochalcones for antihyperglycemic and antidyslipidemic activities.

A series of benzofuran-based chromenochalcones (16-35) were synthesized and evaluated for in vitro and in vivo antidiabetic activities in L-6 skeletal muscle cells and streptozotocin (STZ)-induced diabetic rat models, respectively, and further in vivo dyslipidemia activity of the compounds was evaluated in a Triton-induced hyperlipidemic hamster model. Among them, compounds 16, 18, 21, 22, 24, 31, and 35 showed significant glucose uptake stimulatory effects in skeletal muscle cells and were further evaluated for in vivo efficacy. Compounds 21, 22, and 24 showed a significant reduction in blood glucose levels in STZ-induced diabetic rats. Compounds 16, 20, 21, 24, 28, 29, 34, 35, and 36 were found active in antidyslipidemic studies. Furthermore, compound 24 effectively improved the postprandial and fasting blood glucose levels, oral glucose tolerance, serum lipid profile, serum insulin level, and the HOMA-index of db/db mice, following 15 days of successive treatment.

Potential of hydroethanolic leaf extract of Ocimum sanctum in ameliorating redox status and lung injury in COPD: an in vivo and in silico study.

Oxidative stress and inflammation are hypothesised as the main contributor for Chronic Obstructive Pulmonary Disease (COPD). Cigarette smoke (CS), a major cause of COPD leads to inflammation resulting in recruitment of neutrophils and macrophages which are rich sources of oxidants. Activation of these cells produces excess oxidants and depletes antioxidants resulting in stress. Presently, effective drug for COPD is limited; therefore, novel compounds from natural sources, including plants are under exploration. The present study aims to investigate the protective effect of Ocimum sanctum leaf extract (OLE) in CS - induced model of COPD. Exposure to CS was performed thrice a week for 8 weeks and OLE (200 mg/kg and 400 mg/kg) was administered an hour before CS exposure. Control group (negative control) were exposed to ambient air while COPD group was exposed to CS (positive control). Administration of OLE doses reduced inflammation, decreased oxidant concentration and increased antioxidant concentration (p < 0.01). Molecular docking studies between the major phytocompounds of OLE (Eugenol, Cyclohexane and Caryophyllene) and antioxidant enzymes Superoxide dismutase (SOD), Catalase, Glutathione peroxidase (GPx), Glutathione reductase (GR) and Glutathione S Transferase (GST) showed strong binding interaction in terms of binding energy. In vivo and in silico findings for the first time indicates that OLE extract significantly alleviates oxidative stress by its potent free radical scavenging property and strong interaction with antioxidant enzymes. OLE extract may prove to be a therapeutic option for COPD prevention and treatment.

Nucleic Acid Nanotechnology: Trends, Opportunities and Challenges.

Nucleic acids (DNA and RNA) hold great potential for the advancement of future medicine but suffer from unsatisfactory clinical success due to the challenges accompanied with their delivery. Nucleic acid-mediated nanomaterials have riveted the researchers from the past two decades and exhilarating tasks have prevailed. Nucleic acid nanotechnology offers unique control over the shape, size, time, mechanics and anisotropy. It can transfect numerous types of tissues and cells without any toxic effect, minimize the induced immune response, and penetrate most of the biological barriers and hence it reveals itself as a versatile tool for multidisciplinary research field and for various therapeutic purposes. Nucleic acid combines with other nanoscale objects also by altering the chemical functional groups and reproducing the varied array of nanomaterials. Interestingly, nucleic acidderived nanomaterials are characterized easily at atomic level accuracy. However, this advent of nanoscience has vital issues which must be addressed, such as the high cost of nucleic acids, their self-assembly nature, etc. Hence, the aim of this review is to highlight the systematic advances and methodology of nucleic acid-mediated synthesis of nanomaterials and their therapeutic applications.

On the Coupled Thermal and Hydrodynamic Interaction of Adjacently Located Vapor Bubbles on Highly Wetting Surfaces.

Spatio-temporally resolved IR measurements coupled with high-speed videography have been made to propose the regime map of the interaction between two adjacently located vapor bubbles on high-wettability surfaces. The modes of interaction (thermal and/or hydrodynamic) have been studied as a function of distance between the two nucleation sites under saturated nucleate pool boiling conditions with water as the working fluid, and their effects on the wall heat-transfer rates have been quantified. Based on the comprehensive observations and analyses of the simultaneously mapped vapor bubble dynamics, substrate surface temperature, and the associated wall heat flux distributions, the possible regimes of bubble interactions have been identified. Experiments revealed three dominant mechanisms of bubble interactions: hydrodynamic interaction (HI), thermal interaction (TI), and horizontal coalescence (C). Depending on the relative spacing of the two nucleation sites, a regime map has been prepared wherein various possible bubble interactions (and/or their combinations) have been classified as HI + TI + C, HI + C, and HI. The IR thermography-based measurements revealed a strong dependence of bubble base evaporation-driven heat transfer on the possible bubble interaction mechanism(s) encountered in each regime. The dependence of microlayer formation beneath the growing vapor bubble(s) and its evaporation on HI is further corroborated through thin-film interferometric measurements. Plausible explanation(s) for mechanisms through which bubble interactions influence heat transfer have been discussed. A trend of variation of wall heat-transfer performance with bubble interaction regimes has been deduced and discussed.

Serine 408 phosphorylation is a molecular switch that regulates structure and function of the occludin α-helical bundle.

Occludin is a tetramembrane-spanning tight junction protein. The long C-terminal cytoplasmic domain, which represents nearly half of occludin sequence, includes a distal bundle of three α-helices that mediates interactions with other tight junction components. A short unstructured region just proximal to the α-helical bundle is a phosphorylation hotspot within which S408 phosphorylation acts as molecular switch that modifies tight junction protein interactions and barrier function. Here, we used NMR to define the effects of S408 phosphorylation on intramolecular interactions between the unstructured region and the α-helical bundle. S408 pseudophosphorylation affected conformation at hinge sites between the three α-helices. Further studies using paramagnetic relaxation enhancement and microscale thermophoresis indicated that the unstructured region interacts with the α-helical bundle. These interactions between the unstructured domain are enhanced by S408 phosphorylation and allow the unstructured region to obstruct the binding site, thereby reducing affinity of the occludin tail for zonula occludens-1 (ZO-1). Conversely, S408 dephosphorylation attenuates intramolecular interactions, exposes the binding site, and increases the affinity of occludin binding to ZO-1. Consistent with an increase in binding to ZO-1, intravital imaging and fluorescence recovery after photobleaching (FRAP) analyses of transgenic mice demonstrated increased tight junction anchoring of enhanced green fluorescent protein (EGFP)-tagged nonphosphorylatable occludin relative to wild-type EGFP-occludin. Overall, these data define the mechanisms by which S408 phosphorylation modifies occludin tail conformation to regulate tight junction protein interactions and paracellular permeability.

Evolving Long Short-Term Memory Network-Based Text Classification.

Recently, long short-term memory (LSTM) networks are extensively utilized for text classification. Compared to feed-forward neural networks, it has feedback connections, and thus, it has the ability to learn long-term dependencies. However, the LSTM networks suffer from the parameter tuning problem. Generally, initial and control parameters of LSTM are selected on a trial and error basis. Therefore, in this paper, an evolving LSTM (ELSTM) network is proposed. A multiobjective genetic algorithm (MOGA) is used to optimize the architecture and weights of LSTM. The proposed model is tested on a well-known factory reports dataset. Extensive analyses are performed to evaluate the performance of the proposed ELSTM network. From the comparative analysis, it is found that the LSTM network outperforms the competitive models.

Assessment of Risk Factors and Outcome of Early Versus Late Cytomegalovirus Infection Infection in Living-related D+/R + Renal Allograft Recipients.

Introduction: Cytomegalovirus infection (CMV) in a kidney transplant recipient (KTR) is a serious complication resulting in increased morbidity, mortality and reduced graft survival. There is limited data on early (within 3 months posttransplant) CMV infection (ECMVI) vs. late CMV infection (LCMVI) in patients not receiving CMV prophylaxis. In India, majority of kidney transplants are D + R + combination. This study aimed to compare the risk factors and outcome of ECMVI vs. LCMVI in living related post-KTR. Methods: This was a single-center ambispective study of adult KTR from living donor between January 2001 and December 2015 who had CMV infection. This study had two cohorts: retrospective and prospective. Retrospective cohort included all KTR from January 2001 to September 2014. Prospective cohort included KTR who received transplants from October 2014 to December 2015. Of both cohorts, patients with early and late CMV infection were included. All patients received triple-drug immunosuppression. CMV infection was diagnosed when KTR had detectable CMV copies > 500/mL. In the prospective cohort, CMV PCR was done at 45 days, 3, 6, 9 and 12 months in all patients. Patients with CMV were treated on conventional lines. All patients were followed up till June 2016. Results: Of 2175 retrospective cohort, 97 and of the 155 prospective cohorts 75 had CMV infection, total being 172 CMV infections. Of these, 90 patients had ECNVI and 82 LCMVI. Induction was used in 48.8% in ECMVI group vs. 35.3% in LCMVI group (p = 0.02). CNI toxicity was present prior to CMV infection in 15 (17.4%) in ECMVI as compared to 14 (17.9%) in LCMVI (P = 0.93). In the ECMVI, 6 (6.6%) had acute rejection as compared to 13 (15.8%) in the LCMVI (P = 0.05). While asymptomatic CMV infection was more common in early (63.3% vs 37.8%, P = 0.001), symptomatic CMV without tissue diagnosis was more common in late (54.8% vs. 31.1%, P = 0.002). Total duration of post-transplant follow-up was 22.8 ± 22.1 months in ECMVI as compared to 49.7 + 40.9 months in the LCMVI (P < 0.001). The serum creatinine at last follow-up was 1.9 ± 1.6 mg/dL in ECMVI group and 2.4 ± 2.0 mg/dL in LCMVI (P = 0.02). Conclusion: In D+/R + living renal transplant recipients, without routine CMV prophylaxis, late CMV infection had more tissue invasive disease and is associated with inferior graft function on long-term follow-up.

Extraction and characterization of microalgae-derived phenolics for pharmaceutical applications: A systematic review.

Microalgae are regarded as a rich trove of diverse secondary metabolites that exert remarkable biological activities. In particular, microalgae-derived bioactive phenolic compounds (MBPCs) are a boon to biopharmaceutical and nutraceutical industries due to their diverse bioactivities, including antimicrobial, anticancer, antiviral, and immunomodulatory activities. The state-of-the-art green technologies for extraction and purification of MBPCs, along with the modern progress in the identification and characterization of MBPCs, have accelerated the discovery of novel active pharmaceutical compounds. However, several factors regulate the production of these bioactive phenolic compounds in microalgae. Furthermore, some microalgae species produce toxic phenolic compounds that negatively impact the aquatic ecosystem, animal, and human life. Therefore, the focus of this review paper is to bring into light the current innovations in bioprospection, extraction, purification, and characterization of MBPCs. This review is also aimed at a better understanding of the physicochemical factors regulating the production of MBPCs at an industrial scale. Finally, the present review covers the recent advances in toxicological evaluation, diverse applications, and future prospects of MBPCs in biopharmaceutical industries.

Microbial Brazil nut effect.

The Brazil nut effect (BNE) is a counter-intuitive process of segregation of a large object inside a vibrated granular medium (GM), which has been studied widely by subjecting GMs to various kinds of shears and vibrations. In this article, we report a new kind of BNE which occurs as a consequence of granular fluctuations induced by microbe-generated gas bubbles. We call it the 'microbial Brazil nut effect'. The paper demonstrates microbial BNE for a bidisperse granular mixture as well as for intruder segregation. Furthermore, using X-ray µCT and a simple scaling argument for segregation velocity, the paper clarifies the transport mechanics of an intruder inside a bubbly granular bed. We think the reported phenomenon should be ubiquitous in the microbe-populated wet sandy floors of waterbodies and may have some implication on the distribution of material near the floors.

Non-biodegradable objects may boost microbial growth in water bodies by harnessing bubbles.

Given the ubiquity of bubbles and non-biodegradable wastes in aqueous environments, their transport through bubbles should be widely extant in water bodies. In this study, we investigate the effect of bubble-induced waste transport on microbial growth by using yeasts as model microbes and a silicone rubber object as model waste. Noteworthily, this object repeatedly rises and sinks in fluid through fluctuations in bubble-acquired buoyant forces produced by cyclic nucleation, growth and release of bubbles from object's surface. The rise-sink movement of the object gives rise to a strong bulk mixing and an enhanced resuspension of cells from the floor. Such spatially dynamic contaminant inside a nutrient-rich medium also leads to an increment in the total microbe concentration in the fluid. The enhanced concentration is caused by strong nutrient mixing generated by the object's movement which increases the nutrient supply to growing microbes and thereby, prolonging their growth phases. We confirm these findings through a theoretical model for cell concentration and nutrient distribution in fluid medium. The model is based on the continuum hypothesis and it uses the general conservation law which takes an advection-diffusion growth form. We conclude the study with the demonstration of bubble-induced digging of objects from model sand.