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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., Competing Interests: Conflict of interest No potential conflict of interest related to this article was reported., (© 2021 Greater Poland Cancer Centre.)

Background: The number of people with implanted hip prosthesis has grown worldwide. For radiotherapy planning of patients with hip implants, few main challenges are encountered. The aim of the present study was to evaluate the feasibility of different planning algorithms in the presence of high-density metallic implant in the treatment of patients with carcinoma cervix., Results: It was found that D 98% were 44.49 ± 0.11, 44.51 ± 0.13, 44.39 ± 0.22, and 44.45 ± 0.16 Gy for 4FMC6MV (4-field technique calculated with Monte-Carlo algorithm and 6 MV photon energy), 4FMC6MV_WP (4-field technique calculated with Monte-Carlo algorithm and 6 MV photon energy without prosthesis), 4FCC6MV (4-field technique calculated with collapse-cone-convolution algorithm and 6 MV photon energy), and 4FCC6MV_WP (4-field technique calculated with collapse-cone-convolution algorithm and 6 MV photon energy without prosthesis) respectively. Similarly, D 2% were 49.40 ± 0.84, 49.05 ± 0.76, 48.97 ± 0.91, and 48.57 ± 0.85 Gray (Gy) for 4FMC6MV, 4FMC6MV_WP, 4FCC6MV, and 4FCC6MV_WP respectively. The present study has not suggested any major difference between the Monte-Carlo (MC) and collapse-cone-convolution (CCC) calculation algorithm in the presence of high-Z metallic implants. Volume of bowel receiving 15 Gy dose has shown a significant difference with prosthesis cases. This study investigates that hip prosthesis creates considerable changes in the treatment planning of cervical malignancies., Conclusion: CCC algorithm is in good agreement with MC calculation algorithm in the presence of high-density metallic implants in terms of target coverage and avoidance organ sparing except few parameters.

Macrophages are professional phagocytes known to play a vital role in controlling Mycobacterium tuberculosis (Mtb) infection and disease progression. Here we compare Mtb growth in mouse alveolar (AMs), peritoneal (PMs), and liver (Kupffer cells; KCs) macrophages and in bone marrow-derived monocytes (BDMs). KCs restrict Mtb growth more efficiently than all other macrophages and monocytes despite equivalent infections through enhanced autophagy. A metabolomics comparison of Mtb-infected macrophages indicates that ornithine and imidazole are two top-scoring metabolites in Mtb-infected KCs and that acetylcholine is the top-scoring in Mtb-infected AMs. Ornithine, imidazole and atropine (acetylcholine inhibitor) inhibit Mtb growth in AMs. Ornithine enhances AMPK mediated autophagy whereas imidazole directly kills Mtb by reducing cytochrome P450 activity. Intranasal delivery of ornithine or imidazole or the two together restricts Mtb growth. Our study demonstrates that the metabolic differences between Mtb-infected AMs and KCs lead to differences in the restriction of Mtb growth.

Chemokines are small regulatory proteins that play a crucial role in the coordinated migration of cell populations to the site of infection/inflammation by binding to their cognate receptors. In principle, chemokine receptors, which are serpentine G protein-coupled receptors (GPCRs), mediate the series of downstream intracellular signaling events that occur inside the cells to resolve the pathogenicity. Intracellular signaling pathways regulated by the kinase protein sub-families are the center of attention for chemokine derived functional responses. Kinases potentially influence cell migration, cell growth, transcriptional activation, and other essential molecular events. The regulation and flow of the signals by the kinases are different for each physiological and pathological event and are tightly regulated by the nature and pairing of chemokine(s) with its receptor(s). For example, phosphoinositide 3-kinase (PI3K) is activated during the initial steps of the chemokine induced signaling cascade to regulate chemotaxis, transcription, and cell survival. G protein-coupled receptor kinase (GRKs) plays a crucial role in the desensitization and internalization of the chemokine receptors. The regulation of chemokine receptor is also governed by kinases like protein kinase A (PKA), protein kinase C (PKC), mitogen-activated protein kinases / extracellular signal-regulated kinases (MAPK/ERK), etc . It was also established that tyrosine-protein kinases (TECs) such as ITK and RLK play a significant role in chemokine signaling in T lymphocytes. On a similar note, many others like janus kinases (JAKs), Protein kinase B (PKB), PKC, etc. are also studied in chemokine mediated disease models. The present review elucidates the role of different kinases involved in the chemokine/chemokine receptor mediated signaling cascade during various pathophysiological processes.

Purpose: To evaluate the feasibility of flattening filter free beam (FFFB) for the treatment of gastric tumors and to review their benefits over 6MV flatten beam (6MV&#95;FFB)., Methods: Fifteen patients with histologically proven gastric carcinoma were selected. CT scans with slice thickness of 0.3 cm were acquired and planning target volume (PTV) and organ at risk (OAR) were delineated. Plans were made retrospectively for each patient for the prescription dose of 45 Gy/25 fractions to the PTV. Four isocentric plans were compared in the present study on Varian TrueBeam linear accelerator (Varian Medical Systems, Palo Alto, CA, USA)., Results: PTV D98% was 44.41 ± 0.12, 44.38 ± 0.13, 44.59 ± 0.14, and 44.49 ± 0.19 Gy for IMRT 6MV&#95;FFB, IMRT 6MV&#95;FFFB, VMAT 6MV&#95;FFB, and VMAT 6MV&#95;FFFB respectively. 6MV&#95;FFFB beam minimizes the mean heart dose D mean (P = 0.001). VMAT dominates over IMRT when it came to kidney doses V 12Gy (P = 0.02), V 23Gy (P = 0.015), V 28Gy (P = 0.011), and D max (P < 0.01). VMAT has significantly reduced the doses to kidneys. It was analyzed that 6MV&#95;FFFB significantly reduces the dose to normal tissues (P = 0.006 and P = 0.018). VMAT significantly reduces the TMU, which is required to deliver the similar dose by IMRT (P < 0.01)., Conclusions: Unflattened beam spares the organs at risk significantly to avoid the chances of secondary malignancies and reduces the intra-fraction motion during treatment due to provision of higher dose rate. Hence, we conclude that 6MV unflattened beam can be used to treat gastric carcinoma.

Aim: This study validated the RapidArc (RA) delivery using a volumetric ArcCHECK phantom as per the guidelines proposed in Task Group Report 119 from the American Association of Physicists in Medicine Task group 119 (AAPM TG 119). This study also investigated the impact of the Acuros XB (AXB) algorithm in comparison to analytical anisotropic algorithm (AAA) on the RA dose calculations in the homogeneous medium of the ArcCHECK phantom., Materials and Methods: A volumetric ArcCHECK phantom along with AAPM TG 119 tests was used to evaluate the RA plans and verify the dose delivery for photon beam of 6 MV energy., Results: The RA planning results were comparable and satisfied the planning criteria stated in the TG 119 report for all test cases. The average percentage gamma passing rates for the AAA-calculated plans were 98.5 (standard deviation [SD]: 0.6), 98.5 (SD: 1.3), and 98.1 (SD: 2.0) and for the AXB-calculated plans were 95.1 (SD: 1.8), 96.1 (SD: 1.3), and 94.0 (SD: 0.9) for the Clinac-iX (6 MV) and TrueBeam (TB)-STx (6 MV&#95;filtered beam [FB] and 6 MV&#95;flattening filter-free beam [FFFB]), respectively. For ion chamber measurements, the average percentage dose differences for the AAA-calculated plans were 1.5 (SD: 2.5), 2.7 (SD: 1.4), and 1.4(SD: 2.7) and for AXB-calculated plans were 2.3 (SD: 1.6), 3.2 (SD: 1.5), and 2.3 (SD: 2.0) for Clinac-iX (6 MV) and TB-STx (6 MV&#95;FB and 6 MV&#95;FFFB), respectively., Conclusion: Thus, the ArcCHECK can successfully be utilized for the validation of the RA delivery. The AXB has potential to perform dose calculations comparable to those of the AAA for RA plans in the homogeneous medium of the ArcCHECK phantom., Competing Interests: There are no conflicts of interest.

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-1β, IL-18, and CCL4/macrophage-inflammatory protein (MIP)-1β production and reduced IL-10 production by Mtb-stimulated monocytes. Recombinant IL-21 (1) inhibited Mtb growth, (2) enhanced IFN-γ, IL-1β, IL-18, and MIP-1β, 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-1β, IL-18, and MIP-1β production and reducing IL-10 production by monocytes in response to an intracellular pathogen.

Corticosteroids (CS) are the mainstay of treatment in systemic lupus erythematosus (SLE) patients. However, some patients have poor response to CS treatment. Among the multiple mechanisms of CS resistance, overexpression of P-glycoprotein (P-gp) on peripheral blood lymphocytes (PBL) may be one of them as this result in efflux of CS from lymphocytes. Thus, we evaluated the role of P-gp protein on PBLs in patients with SLE in its response to CS therapy. SLE patients (n = 42) (fulfilling ACR revised criteria) who were naïve to CS and immunosuppressive drugs were enrolled. Disease activity was assessed using SLE disease activity index (SLEDAI) and expression, and function of P-gp was evaluated by flow cytometry at baseline and after 3 months of therapy with CS. At 3 months, patients with SLEDAI >4 and SLEDAI ≤4 were grouped as nonresponders and responders, respectively. P-gp expression was significantly increased on PBLs of SLE patients as compared to healthy controls (p < 0.001). P-gp expression and function correlated with SLEDAI (r = 0.49, p = 0.005; and r = 0.49, p = 0.001, respectively). P-gp expression and function were not different in responders and nonresponders at baseline. However, at 3 months of CS therapy, P-gp expression and function decreased in responders (p < 0.001 and p < 0.005, respectively), whereas in nonresponders, it remained unchanged. Persistent overexpression and activity of P-gp are associated with poor response to CS in CS naïve patients of SLE.