Correction: IL-22 produced by type 3 innate lymphoid cells (ILC3s) reduces the mortality of type 2 diabetes mellitus (T2DM) mice infected with Mycobacterium tuberculosis.

[This corrects the article DOI: 10.1371/journal.ppat.1008140.].

Cannibalistic enemy-pest model: effect of additional food and harvesting.

Biological control using natural enemies with additional food resources is one of the most adopted and ecofriendly pest control techniques. Moreover, additional food is also provided to natural enemies to divert them from cannibalism. In the present work, using the theory of dynamical system, we discuss the dynamics of a cannibalistic predator prey model in the presence of different harvesting schemes in prey (pest) population and provision of additional food to predators (natural enemies). A detailed mathematical analysis and numerical evaluations have been presented to discuss the pest free state, coexistence of species, stability, occurrence of different bifurcations (saddle-node, transcritical, Hopf, Bogdanov-Takens) and the impact of additional food and harvesting schemes on the dynamics of the system. It has been obtained that the multiple coexisting equilibria and their stability depend on the additional food (quality and quantity) and harvesting rates. Interestingly, we also observe that the pest population density decreases immediately even when small amount of harvesting is implemented. Also the eradication of pest population (stable pest free state) could be achieved via variation in the additional food and implemented harvesting schemes. The individual effects of harvesting parameters on the pest density suggest that the linear harvesting scheme is more effective to control the pest population rather than constant and nonlinear harvesting schemes. In the context of biological control programs, the present theoretical work suggests different threshold values of implemented harvesting and appropriate choices of additional food to be supplied for pest eradication.

HIV-Differentiated Metabolite N-Acetyl-L-Alanine Dysregulates Human Natural Killer Cell Responses to Mycobacterium tuberculosis Infection.

Mycobacterium tuberculosis (Mtb) has latently infected over two billion people worldwide (LTBI) and caused ~1.6 million deaths in 2021. Human immunodeficiency virus (HIV) co-infection with Mtb will affect the Mtb progression and increase the risk of developing active tuberculosis by 10-20 times compared with HIV- LTBI+ patients. It is crucial to understand how HIV can dysregulate immune responses in LTBI+ individuals. Plasma samples collected from healthy and HIV-infected individuals were investigated using liquid chromatography-mass spectrometry (LC-MS), and the metabolic data were analyzed using the online platform Metabo-Analyst. ELISA, surface and intracellular staining, flow cytometry, and quantitative reverse-transcription PCR (qRT-PCR) were performed using standard procedures to determine the surface markers, cytokines, and other signaling molecule expressions. Seahorse extra-cellular flux assays were used to measure mitochondrial oxidative phosphorylation and glycolysis. Six metabolites were significantly less abundant, and two were significantly higher in abundance in HIV+ individuals compared with healthy donors. One of the HIV-upregulated metabolites, N-acetyl-L-alanine (ALA), inhibits pro-inflammatory cytokine IFN-γ production by the NK cells of LTBI+ individuals. ALA inhibits the glycolysis of LTBI+ individuals' NK cells in response to Mtb. Our findings demonstrate that HIV infection enhances plasma ALA levels to inhibit NK-cell-mediated immune responses to Mtb infection, offering a new understanding of the HIV-Mtb interaction and providing insights into the implication of nutrition intervention and therapy for HIV-Mtb co-infected patients.

IL-22 produced by type 3 innate lymphoid cells (ILC3s) reduces the mortality of type 2 diabetes mellitus (T2DM) mice infected with Mycobacterium tuberculosis.

Previously, we found that pathological immune responses enhance the mortality rate of Mycobacterium tuberculosis (Mtb)-infected mice with type 2 diabetes mellitus (T2DM). In the current study, we evaluated the role of the cytokine IL-22 (known to play a protective role in bacterial infections) and type 3 innate lymphoid cells (ILC3s) in regulating inflammation and mortality in Mtb-infected T2DM mice. IL-22 levels were significantly lower in Mtb-infected T2DM mice than in nondiabetic Mtb-infected mice. Similarly, serum IL-22 levels were significantly lower in tuberculosis (TB) patients with T2DM than in TB patients without T2DM. ILC3s were an important source of IL-22 in mice infected with Mtb, and recombinant IL-22 treatment or adoptive transfer of ILC3s prolonged the survival of Mtb-infected T2DM mice. Recombinant IL-22 treatment reduced serum insulin levels and improved lipid metabolism. Recombinant IL-22 treatment or ILC3 transfer prevented neutrophil accumulation near alveoli, inhibited neutrophil elastase 2 (ELA2) production and prevented epithelial cell damage, identifying a novel mechanism for IL-22 and ILC3-mediated inhibition of inflammation in T2DM mice infected with an intracellular pathogen. Our findings suggest that the IL-22 pathway may be a novel target for therapeutic intervention in T2DM patients with active TB disease.

Effect of contrast medium on treatment modalities planned with different photon beam energies: a planning study.

BACKGROUND: Routinely, patient's planning scans are acquired after administration of iodinized contrast media but they will be treated in the absence of that. Similarly, high energy photons have a better penetrating power, while low energy photons will result in tighter dose distribution and negligible neutron contamination. The aim of the study was to investigate a suitable photon beam energy in the presence of intravenous contrast medium. MATERIALS AND METHODS: An indigenously made original-contrast (OC) phantom was mentioned as virtual-contrast (VC) and virtual-without-contrast (VWC) phantom were generated by assigning the Hounsfield Units (HU) to different structures. Intensity-modulated (IMRT) and volumetric-modulated-arc (VMAT) plans were generated as per criteria of the TG-119 protocol. RESULTS: It was observed that the maximum dose to the spinal cord was better with 6 mega-voltage (MV) in IMRT. The coverage of Prostate PTV (PR PTV) was similar with all the photon energies and was comparable with TG-119, except for original-contrast (OC) phantom using the VMAT technique. Homogeneity-index (HI) was comparatively better for VMAT plans. CONCLUSION: The contrast CT images lower the dose to targets. IMRT or VMAT plans, generated on such CT images will be delivered with higher doses than evaluated. However, the overdose remains non-significant.

Alcohol enhances type 1 interferon-α production and mortality in young mice infected with Mycobacterium tuberculosis.

In the current study, we used a mouse model and human blood samples to determine the effects of chronic alcohol consumption on immune responses during Mycobacterium tuberculosis (Mtb) infection. Alcohol increased the mortality of young mice but not old mice with Mtb infection. CD11b+Ly6G+ cells are the major source of IFN-α in the lungs of Mtb-infected alcohol-fed young mice, and IFN-α enhances macrophage necroptosis in the lungs. Treatment with an anti-IFNAR-1 antibody enhanced the survival of Mtb-infected alcohol-fed young mice. In response to Mtb, peripheral blood mononuclear cells (PBMCs) from alcoholic young healthy individuals with latent tuberculosis infection (LTBI) produced significantly higher amounts of IFN-α than those from non-alcoholic young healthy LTBI+ individuals and alcoholic and non-alcoholic old healthy LTBI+ individuals. Our study demonstrates that alcohol enhances IFN-α production by CD11b+Ly6G+ cells in the lungs of young Mtb-infected mice, which leads to macrophage necroptosis and increased mortality. Our findings also suggest that young alcoholic LTBI+ individuals have a higher risk of developing active TB infection.

IL-21 Receptor Signaling Is Essential for Optimal CD4+ T Cell Function and Control of Mycobacterium tuberculosis Infection in Mice.

In this study, we determined the role of IL-21R signaling in Mycobacterium tuberculosis infection, using IL-21R knockout (KO) mice. A total of 50% of M. tuberculosis H37Rv-infected IL-21R KO mice died in 6 mo compared with no deaths in infected wild type (WT) mice. M. tuberculosis-infected IL-21R KO mice had enhanced bacterial burden and reduced infiltration of Ag-specific T cells in lungs compared with M. tuberculosis-infected WT mice. Ag-specific T cells from the lungs of M. tuberculosis-infected IL-21R KO mice had increased expression of T cell inhibitory receptors, reduced expression of chemokine receptors, proliferated less, and produced less IFN- γ, compared with Ag-specific T cells from the lungs of M. tuberculosis-infected WT mice. T cells from M. tuberculosis-infected IL-21R KO mice were unable to induce optimal macrophage responses to M. tuberculosis. This may be due to a decrease in the Ag-specific T cell population. We also found that IL-21R signaling is associated with reduced expression of a transcriptional factor Eomesodermin and enhanced functional capacity of Ag-specific T cells of M. tuberculosis-infected mice. The sum of our findings suggests that IL-21R signaling is essential for the optimal control of M. tuberculosis infection.

Interleukin-21 Regulates Natural Killer Cell Responses During Mycobacterium tuberculosis Infection.

Background: In the current study, we determined the effects of interleukin (IL)-21 on human natural killer (NK) cells and monocyte responses during Mycobacterium tuberculosis (Mtb) infection. Methods: We found that Mtb stimulated CD4+ and NK T cells from healthy individuals with latent tuberculosis infection (LTBI+) are major sources of IL-21. CD4+ cells from tuberculosis patients secreted less IL-21 than did CD4+ cells from healthy LTBI+ individuals. Interleukin-21 had no direct effect on Mtb-stimulated monocytes. Results: Interleukin-21-activated NK cells produced interferon (IFN)-γ, perforin, granzyme B, and granulysin; lysed Mtb-infected monocytes; and reduced Mtb growth. Interleukin-21-activated NK cells also enhanced IL-1ß, IL-18, and CCL4/macrophage-inflammatory protein (MIP)-1ß production and reduced IL-10 production by Mtb-stimulated monocytes. Recombinant IL-21 (1) inhibited Mtb growth, (2) enhanced IFN-γ, IL-1ß, IL-18, and MIP-1ß, and (3) reduced IL-10 expression in the lungs of Mtb-infected Rag2 knockout mice. Conclusions: These findings suggest that activated T cells enhance NK cell responses to lyse Mtb-infected human monocytes and restrict Mtb growth in monocytes through IL-21 production. Interleukin-21-activated NK cells also enhance the immune response by augmenting IL-1ß, IL-18, and MIP-1ß production and reducing IL-10 production by monocytes in response to an intracellular pathogen.

NK-CD11c+ Cell Crosstalk in Diabetes Enhances IL-6-Mediated Inflammation during Mycobacterium tuberculosis Infection.

In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice. Levels of IL-6 also increased. Anti-IL-6 monoclonal antibody treatment of Mtb-infected acute- and chronic-T2DM mice increased survival (to 100%) and reduced pro- and anti-inflammatory cytokine expression. CD11c+ cells were the major source of IL-6 in Mtb-infected T2DM mice. Pulmonary natural killer (NK) cells in Mtb-infected T2DM mice further increased IL-6 production by autologous CD11c+ cells through their activating receptors. Anti-NK1.1 antibody treatment of Mtb-infected acute-T2DM mice increased survival and reduced pro- and anti-inflammatory cytokine expression. Furthermore, IL-6 increased inflammatory cytokine production by T lymphocytes in pulmonary tuberculosis patients with T2DM. Overall, the results suggest that NK-CD11c+ cell interactions increase IL-6 production, which in turn drives the pathological immune response and mortality associated with Mtb infection in diabetic mice.

Tissue factor expression by myeloid cells contributes to protective immune response against Mycobacterium tuberculosis infection.

Tissue factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium tuberculosis (M. tb) infection by using mice lacking the TF gene in myeloid cells (TF(Δ) ) and human monocyte derived macrophages (MDMs). We found that during M. tb infection, a deficiency of TF in myeloid cells was associated with reduced inducible nitric oxide synthase (iNOS) expression, enhanced arginase 1 (Arg1) expression, enhanced IL-10 production and reduced apoptosis in infected macrophages, which augmented M. tb growth. Our results demonstrate that a deficiency of TF in myeloid cells promotes M2-like phenotype in M .tb infected macrophages. A deficiency in TF expression by myeloid cells was also associated with reduced fibrin deposition and increased matrix metalloproteases (MMP)-2 and MMP-9 mediated inflammation in M. tb infected lungs. Our studies demonstrate that TF expressed by myeloid cells has newly recognized abilities to polarize macrophages and to regulate M. tb growth.

A rho GDP dissociation inhibitor produced by apoptotic T-cells inhibits growth of Mycobacterium tuberculosis.

In this study, we found that a subpopulation of CD4(+)CD25(+) (85% Foxp3(+)) cells from persons with latent tuberculosis infection (LTBI) inhibits growth of M. tuberculosis (M. tb) in human monocyte-derived macrophages (MDMs). A soluble factor, Rho GDP dissociation inhibitor (D4GDI), produced by apoptotic CD4(+)CD25(+) (85% Foxp3(+)) cells is responsible for this inhibition of M. tb growth in human macrophages and in mice. M. tb-expanded CD4(+C)D25(+)Foxp3(+)D4GDI(+) cells do not produce IL-10, TGF-ß and IFN-γ. D4GDI inhibited growth of M. tb in MDMs by enhancing production of IL-1ß, TNF-α and ROS, and by increasing apoptosis of M. tb-infected MDMs. D4GDI was concentrated at the site of disease in tuberculosis patients, with higher levels detected in pleural fluid than in serum. However, in response to M. tb, PBMC from tuberculosis patients produced less D4GDI than PBMC from persons with LTBI. M. tb-expanded CD4+CD25+ (85% Foxp3(+)) cells and D4GDI induced intracellular M. tb to express the dormancy survival regulator DosR and DosR-dependent genes, suggesting that D4GDI induces a non-replicating state in the pathogen. Our study provides the first evidence that a subpopulation of CD4(+)CD25(+) (85% Foxp3+) cells enhances immunity to M. tb, and that production of D4GDI by this subpopulation inhibits M. tb growth.

Molecular insight into the structural and functional aspects of arene Ru(II) complexes bearing bulky thiourea ligands.

Herein we report four new arene ruthenium(II) complexes [RuII(η6-p-cymene)(L1)к1(S)Cl2] (C1), [RuII(η6-benzene)(L1)к1(S)Cl2] (C2) where L1 is N-((2,6-dimethylphenyl)carbamothioyl)benzamide (L1), and [RuII(η6-p-cymene)(L2)к1(S)Cl2] (C3), [RuII(η6-benzene)(L2)к1(S)Cl2] (C4) where L2 is N-((2,6-diisopropylphenyl)carbamothioyl)benzamide (L2) which were synthesized and evaluated for biological activity. The monodentate coordination of thione sulphur (S) to ruthenium ion along with two terminal chloride was confirmed by X-Ray diffraction analysis thus revealing a typical "piano-stool" pseudo tetrahedral geometry. DPPH radical scavenging activity showed that ligands were less efficient however on complex formation it showed significant efficacy with C4 showing the highest activity. The ligands and ruthenium complexes exhibited minimal to no cytotoxic effects on HEK cells within the concentration range of 10-300 µM. Evaluating the cytotoxicity against prostate cancer cells (DU145) L1, L2 and C1 displayed more pronounced cytotoxic activity with C1 showing high cytotoxicity against the cancer cells, in comparison to cisplatin indicating its potential for further investigation and analysis. Considering this, compound C1 was used to further study its interaction with BSA using fluorescence spectroscopy and it was found to be 2.64 × 106 M-1. Findings from CD spectroscopy indicate the binding in the helix region which was further confirmed with the molecular docking studies.

Targeting chemokine-receptor mediated molecular signaling by ethnopharmacological approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Infection and inflammation are critical to global human health status and the goal of current pharmacological interventions intends formulating medications/preventives as a measure to deal with this situation. Chemokines and their cognate receptors are major regulatory molecules in many of these ailments. Natural products have been a keen source to the drug development industry, every year contributing significantly to the growing list of FDA approved drugs. A multiverse of natural resource is employed as a part of curative regimen in folk/traditional/ethnomedicine which can be employed to discover, repurpose, and design potent medications for the diseases of clinical concern. AIM OF THE STUDY: This review aims to systematically document the ethnopharmacologically active agents targeting the infectious-inflammatory diseases through the chemokine-receptor nexus. MATERIALS AND METHODS: Articles related to chemokine/receptor modulating ethnopharmacological anti-inflammatory, anti-infectious natural sources, bioactive compounds, and formulations have been examined with special emphasis on women related diseases. The available literature has been thoroughly scrutinized for the application of traditional medicines in chemokine associated experimental methods, their regulatory outcomes, and pertinence to women's health wherever applicable. Moreover, the potential traditional regimens under clinical trials have been critically assessed. RESULTS: A systematic and comprehensive review on the chemokine-receptor targeting ethnopharmaceutics from the available literature has been provided. The article discusses the implication of traditional medicine in the chemokine system dynamics in diverse infectious-inflammatory disorders such as cardiovascular diseases, allergic diseases, inflammatory diseases, neuroinflammation, and cancer. On this note, critical evaluation of the available data surfaced multiple diseases prevalent in women such as osteoporosis, rheumatoid arthritis, breast cancer, cervical cancer and urinary tract infection. Currently there is no available literature highlighting chemokine-receptor targeting using traditional medicinal approach from women's health perspective. Moreover, despite being potent in vitro and in vivo setups there remains a gap in clinical translation of these formulations, which needs to be strategically and scientifically addressed to pave the way for their successful industrial translation. CONCLUSIONS: The review provides an optimistic global perspective towards the applicability of ethnopharmacology in chemokine-receptor regulated infectious and inflammatory diseases with special emphasis on ailments prevalent in women, consecutively addressing their current status of clinical translation and future directions.

Baicalin functionalized PEI-heparin carbon dots as cancer theranostic agent.

The worldwide prevalence of cancer and its significantly rising risks with age have garnered the attention of nanotechnology for prompt detection and effective therapy with minimal or no adverse effects. In the current study, heparin (HP) polymer derived heteroatom (N, S-) co-doped CDs were synthesized using hydrothermal synthesis method to efficiently deliver natural anticancer compound baicalin (BA). Heparin carbon dots (HCDs) were passivated with polyethylenimine (PEI) to improve its fluorescence quantum yield. The surface passivation of CDs by polycationic PEI polymer not only facilitated loading of BA, but also played a crucial role in the pH-responsive drug delivery. The sustained release of BA (up to 80 %) in mildly acidic pH (5.5 and 6.5) conditions endorsed its drug delivery potential for cancer-specific microenvironments. BA-loaded PHCDs exhibited enhanced anticancer activity as compared to BA/PHCDs indicating the effectiveness of the nanoformulation, Furthermore, the flow cytometry analysis confirmed that BA-PHCDs treated cells were arrested in the G2/M phase of cell cycle and had a higher potential for apoptosis. Bioimaging study demonstrated the excellent cell penetration efficiency of PHCDs with complete cytoplasmic localization. All this evidence comprehensively demonstrates the potency of BA-loaded PHCDs as a nanotheranostic agent for cancer.

Gallate Moiety of Catechin Is Essential for Inhibiting CCL2 Chemokine-Mediated Monocyte Recruitment.

Leukocyte recruitment witnesses an orchestrated complex formation between the chemokines and their molecular partners. CCL2 chemokine that regulates monocyte trafficking is a worthwhile system from the pharmaceutical perspective. In the current study, four major catechins (EC/EGC/ECG/EGCG) were assessed for their inhibitory potential against CCL2-regulated monocyte/macrophage recruitment. Interestingly, catechins with the gallate moiety (ECG/EGCG) could only attenuate the CCL2-induced macrophage migration. These molecules specifically bound to CCL2 on a pocket comprising the N-terminal, ß0-sheets, and ß3-sheets, and the binding affinity of ECGC (Kd = 22 ± 4 µM) is ∼4 times higher than that of the ECG complex (Kd = 85 ± 6 µM). MD simulation analysis evidenced that the molecular specificity/stability of CCL2-catechin complexes is regulated by multiple factors, including stereospecificity, number of hydroxyl groups on the annular ring-B, the positioning of the carbonyl group, and the methylation of the galloyl ring. Further, a significant overlap on the binding surface of CCL2 for EGCG/ECG and receptor interactions as evidenced from NMR data provided the rationale for the observed inhibition of macrophage migration in response to EGCG/ECG binding. In summary, these galloylated epicatechins can be considered as potent protein-protein interaction (PPI) inhibitors that regulate CCL2-directed leukocyte recruitment for resolving inflammatory/immunomodulatory disorders.

HIV-differentiated metabolite N-Acetyl-L-Alanine dysregulates human natural killer cell responses to Mycobacterium tuberculosis infection.

Background: Mycobacterium tuberculosis ( Mtb ) has latently infected over two billion people worldwide (LTBI) and causes 1.8 million deaths each year. Human immunodeficiency virus (HIV) co-infection with Mtb will affect the Mtb progression and increase the risk of developing active tuberculosis by 10-20 times compared to the HIV-LTBI+ patients. It is crucial to understand how HIV can dysregulate immune responses in LTBI+ individuals. Methods: Plasma samples collected from healthy and HIV-infected individuals were investigated by liquid chromatography-mass spectrometry (LC-MS), and the metabolic data were analyzed using an online platform Metabo-Analyst. ELISA, surface and intracellular staining, flow cytometry, quantitative reverse transcription PCR (qRT-PCR) were performed by standard procedure to determine the surface markers, cytokines and other signaling molecule expression. Seahorse extra cellular flux assays were used to measure the mitochondrial oxidative phosphorylation and glycolysis. Results: Six metabolites were significantly less abundant, and two were significantly higher in abundance in HIV+ individuals compared to healthy donors. One of the HIV-upregulated metabolites, N-Acetyl-L-Alanine (ALA), inhibits pro-inflammatory cytokine IFN-□ production by NK cells of LTBI+ individuals. ALA inhibits glycolysis of LTBI+ individuals' NK cells in response to Mtb . Conclusions: Our findings demonstrate that HIV infection enhances plasma ALA levels to inhibit NK cell-mediated immune responses to Mtb infection, offering a new understanding of the HIV- Mtb interaction and providing the implication of nutrition intervention and therapy for HIV- Mtb co-infected patients.

Characterization, Antioxidant, and Antimicrobial Properties of Mulberry Lattices.

In order to find the most advantageous bioactive compounds from mulberry latex for drug development in the near future, this study was conducted to characterize and evaluate antioxidant and antimicrobial properties from four different mulberry lattices (BR-2, S-1, AR-14, and S-146). The characterization of the lattices was performed by scanning electron microscopy with energy-dispersive X-ray spectroscopy, gas chromatography coupled to mass spectroscopy, and Fourier transform infrared spectroscopy. Further, screenings of the antioxidant and antimicrobial potential of selected lattices were performed in vitro using 2,2-diphenyl-1-picrylhydrazyl assay and agar well diffusion methods, respectively. Interestingly, the outcome of the current study revealed that tested mulberry lattices contain a considerable amount of bioactive phytoconstituents, particularly antimicrobial and antioxidant compounds, as revealed by chromatographic analysis. BR-2 latex was found to have significant antioxidant activity (75%) followed by S-146 (64.6%) and AR-14 (52.9%). The maximum antimicrobial activity was found in BR-2 latex compared to other tested latex varieties. The results of this investigation showed that mulberry latex from the BR-2 type may successfully control both bacterial and fungal infections, with the added benefit of having enhanced antioxidant capabilities.

Magnetic-nanoparticle-doped carbogenic nanocomposite: an effective magnetic resonance/fluorescence multimodal imaging probe.

A novel and facile approach is developed to synthesize a magnetic nanoparticle (iron oxide)-doped carbogenic nanocomposite (IO-CNC) for magnetic resonance (MR)/fluorescence imaging applications. IO-CNC is synthesized by thermal decomposition of organic precursors in the presence of Fe(3) O(4) nanoparticles with an average size of 6 nm. IO-CNC shows wavelength-tunable fluorescence properties with high quantum yield. Magnetic studies confirm the superparamagnetic nature of IO-CNC at room temperature. IO-CNC shows MR contrast behavior by affecting the proton relaxation phenomena. The measured longitudinal (r(1) ) and transverse (r(2) ) relaxivity values are 4.52 and 34.75 mM(-1) s(-1) , respectively. No apparent cytotoxicity is observed and the nanocomposite shows a biocompatible nature. In vivo MR studies show both T(1) and T(2) * contrast behavior of the nanocomposite. Fluorescence imaging indicates selective uptake of IO-CNC by macrophages in spleen.

Dosimetric analysis of intensity-modulated radiation therapy and volumetric-modulated arc therapy in comparison with conventional box technique in the treatment of carcinoma cervix: An impact of prosthetic implant.

Introduction: The number of patients for carcinoma cervix with implanted hip prostheses has been increasing worldwide during the past several decades. Technological advancements are useful for delivering higher doses, i.e., dose escalation to the target, but the presence of high-density implanted hip prosthesis creates challenges for the planner. Materials and Methods: A population of 25 patients was selected for the study. Plans were generated using the MONACO treatment planning system keeping the isocenter same. The parameters evaluated for planning target volume (PTV) were D98%, D50%, D2%, Dmax, Dmean, V107%, and V110%. Similarly, the parameters Dmax, Dmean, and D2cc were evaluated for the delineated critical organs. Average monitor units (TMUmean) were also assessed. Results: D98% of PTV was 44.51 (standard deviation [SD]: 0.13) Gy, 44.41 (SD: 0.38) Gy, 44.58 (SD: 0.14) Gy, 44.08 (SD: 0.41) Gy and 44.46 (SD: 0.32) Gy for 4F, intensity-modulated radiation therapy (IMRT), IMRT_WP, volumetric-modulated arc therapy (VMAT), and VMAT_WP techniques, respectively, where WP stands for "without prosthesis". Volume of bowel receiving 45 Gy was 86.82 (SD: 66.38) cm3, 6.97 (SD: 5.77) cm3, 14.11 (SD: 14.29) cm3, 13.31 (SD: 6.57) cm3, and 10.31 (SD: 10.94) cm3 for 4F, IMRT, IMRT_WP, VMAT and VMAT_WP techniques, respectively. Discussion: Radiotherapy is standard care of practice for known cases of cervical malignancies. As per our investigations, VMAT has generated comparable plans in terms of target coverage (D98%) as compared to IMRT and 4F techniques (P = 0.015 and P = 0.002) and with prosthesis also (P = 0.024). The mean dose to the bladder was significantly lesser with IMRT and VMAT. Our results highlight that VMAT has reduced the mean dose to the rectum (P = 0.001) in presence of high-density implant. The mean dose to femoral heads was also reduced when compared with the 4-field technique. Conclusion: VMAT has an edge over other techniques in terms of target coverage and sparing of critical organs in the presence of metallic prosthesis. Information about the geometry and density of prosthesis will be beneficial for treatment planning.

Diffusion Tensor and Dynamic Contrast-Enhanced Magnetic Resonance Imaging Correlate with Molecular Markers of Inflammation in the Synovium.

Objectives: It is difficult to capture the severity of synovial inflammation on imaging. Herein we hypothesize that diffusion tensor imaging (DTI) derived metrics may delineate the aggregation of the inflammatory cells and expression of inflammatory cytokines and dynamic contrast-enhanced (DCE) imaging may provide information regarding vascularity in the inflamed synovium. Patients and methods: Patients with knee arthritis (>3-months duration) underwent conventional (T2-weighted fast spin echo and spin echo T1-weighted images) as well as DTI and DCE MRI and thereafter arthroscopic guided synovial biopsy. DCE and DTI metrics were extracted from the masks of the segments of the inflamed synovium which enhanced on post-contrast T1-weighted MRI. These metrics were correlated with immunohistochemistry (IHC) parameters of inflammation on synovium. Statistical analysis: Pearson's correlation was performed to study the relationship between DTI- and DCE-derived metrics, IHC parameters, and post-contrast signal intensity. Linear regression model was used to predict the values of IHC parameters using various DTI and DCE derived metrics as predictors. Results: There were 80 patients (52 male) with mean age 39.78 years and mean disease duration 19.82 months. Nineteen patients had tuberculosis and the rest had chronic undifferentiated monoarthritis (n = 31), undifferentiated spondyloarthropathy (n = 14), rheumatoid arthritis (n = 6), osteoarthritis (n = 4), reactive arthritis (n = 3), ankylosing spondylitis (n = 2), and juvenile idiopathic arthritis (n = 1). Fractional anisotropy (FA), a metric of DTI, had significant correlation with number of immune cells (r = 0.87, p < 0.01) infiltrating into the synovium and cytokines (IL-1ß, r = 0.55, p < 0.01; TNF-α, r = 0.42, p < 0.01) in all patients and also in each group of patients and adhesion molecule expressed on these cells in all patients (CD54, r = 0.51, p < 0.01). DCE parameters significantly correlated with CD34 (blood flow, r = 0.78, p < 0.01; blood volume, r = 0.76, p < 0.01) in each group of patients, a marker of neo-angiogenesis. FA was the best predictor of infiltrating inflammatory cells, adhesion molecule and proinflammatory cytokines. Amongst the DCE parameters, blood volume, was best predictor of CD34. Conclusion: DTI and DCE metrics capture cellular and molecular markers of synovial inflammation in patients with chronic inflammatory arthritis.