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Purpose: The metal present in the implant creates artifacts during the treatment simulation, which impacts the treatment planning and delivery of the prescribed dose to the target and sparing normal tissues. This retrospective study evaluated the uncertainties in the planning and delivery of doses for prosthesis cases with dedicated phantom. Materials and Methods: In this retrospective study, 11 patients with a hip prosthesis having cervix carcinoma were selected. Two treatment plans were generated on treatment planning system (TPS) for each case. Plan_No_Res was without any beam restriction, and Plan_exit_only was the plan with restricted beam entry through the metallic implant. An indigenous phantom was utilized to verify the accuracy of the treatment. In the phantom, some groves were present, which could be filled by implants that mimic the patient’s geometries, like left, right and bilateral femur implants. The delivered doses were recorded using optically stimulated luminescence dosimeters (OSLDs), which were placed at different positions in the phantom. The plans were further calculated using megavoltage computed tomography (MVCT) scans acquired during treatment. Results: The patient data showed no significant dose changes between the two planning methods. The treatment time increases from 412.18 ± 86.65 to 427.36 ± 104.80 with P = 0.03 for Plan_No_Res and Plan_exit_only, respectively. The difference between planned and delivered doses of various points across phantom geometries was within ± 9.5% in each case as left, right, and bilateral implant. The variations between OSLDs and MVCT calculated doses were also within ± 10.8%. Conclusion: The study showed the competency of tomotherapy planning for hip prosthesis cases. The phantom measurements demonstrate the errors in dosimetry near the implant material, suggesting the need for precise methods to deal with artifact-related issues.

The secondary consequences of predator species on prey species have substantial implications for population dynamics. A deeper comprehension of the dynamics between prey and predator can be achieved through the examination of indirect consequences. This work examines the dynamic behavior of a modified Holling-Tanner model. The interactions between the species are characterized by a functional response of the Beddington–DeAngelis type. Factors such as prey refuge, fear factor, disturbance intensity, and cross diffusion have been taken into account. The boundedness, feasibility of equilibrium points, their stability and restrictions for Hopf bifurcation of non-spatial model system are derived. The study explores the combined effects of prey refuge presence and fear factors on population dynamics. Furthermore, the investigation focuses on the stability of spatial self-diffusion and cross-diffusion model systems, as well as the specific conditions that lead to Turing instability. Ultimately, it has been shown that in the context of self-diffusion, a moderate level of fear promotes the survival of prey, whereas an excessive level of dread hinders the survival of prey. Concurrently, the mean density of prey exhibited a gradual decline as the refuge parameters increased. The spatial patterns of the population have also been investigated. As the mutual interference between prey populations intensifies, the spatial distribution of the prey population transitions from a clustered pattern to a combination of striped and clustered patterns, ultimately settling into a striped pattern. With the gradual growth of the half saturation constant, the prey population reached a state of uniform distribution. In the scenario of cross diffusion, when the prey is heavily impacted by the pursuit of predators, the fear effect, when appropriately used, did not have a significant impact on the survival of the prey. This work adds to the existing body of knowledge by revealing novel insights into the influence of indirect factors on the behavior of predator and prey populations.

Introduction: Considering the unwanted exposure to organs in the path of the beam, 4-field (4F) and subsequently, Intensity-modulated-radiation-therapy (IMRT), is known as the standard mode of treatment of carcinoma cervix. It is routine practice to inject intravenous contrast during simulation scan which elopes after that from the patient body. Therefore, the impact of contrast media should be investigated for radiation dose calculations. Material and Methods: An indigenously made phantom, named as ‘original contrast (OC)’, was used with dimensions 15 x 15 x 30 cm3. A sleeve was given to place the ionization chamber at the isocentre of the planning target volume (PTV) inside the cylindrical vial of iodinized contrast. Similarly, a virtual phantom was created with similar dimensions in the presence and absence of contrast media, called as ‘virtual contrast (VC)’ and ‘virtual without contrast (VWC)’ phantom. Plans were generated with photon energies (6MV/10MV/15MV/6FFF/10FFF) using 4F and IMRT technique. Plans were evaluated for PTV (D99%, D10%, Dmean) and Bladder & Rectum (V30Gy, V10Gy). Normal-tissue-integral-dose (NTID) and total-monitor-units (TMU) were also evaluated. Results: D99% of the PTV was comparable in VC and VWC phantoms but was decreased for OC phantom. Similarly, D10% was reportedly higher as 54.03 Gy (4F, 6 MV), 54.71 Gy (4F, 15 MV), 55.78 Gy (4F, 6 FFF) and 57.64 Gy (4F, 10 FFF) for OC phantom. D30% of the bladder and also the NTID was lesser for IMRT cases in all the selected phantoms. Additionally, 4F has shown lesser spillage with 6MV/15 MV photon beam energies in OC phantom. The ‘total monitor units (TMU)’ required for IMRT plans were significantly higher. Conclusion: The contrast material under-estimates the planned dose yet has an insignificant influence on the dose calculation. Therefore, unnecessary exposure of dual scans should be avoided the use of 6MV and IMRT technique should be continued in the clinics.

Purpose: To study the impact of different optimization methods in dealing with metallic hip implant using intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques. Materials and Methods: A cohort of 16 patients having metallic implants was selected for the study. Three sets of IMRT and VMAT plans were generated. Set 1 IMRT (IM_Base), VMAT (VM_Base) without any restrictions on beam entry and exit, set 2 (IM_ENT and VM_ENT) optimizer restricts the beam entry and set 3 (IM_EXT+ENT), neither entry nor exit doses were allowed toward the metallic implant. Results: There was no significant difference in target (D95%) and organ-at-risk doses between IM_Base and IM_ENT. There were significant (P = 0.002) improvements in planning target volume (PTV) V95% and homogeneity from IM_EXT+ENT to IM_ENT. There was no significant difference in plan quality between VM_Base and VM_ENT. There were significant (P = 0.005) improvements in PTV, V95%, homogeneity from VM_EXT+ENT to VM_ENT. V40Gy, V30Gy for bladder, rectum, bowel, and bowel maximum dose decreases significantly (P < 0.005) in IM_ENT compared to IM_EXT+ENT, but not significant for VMAT plans. Similarly, there was a significant decrease in dose spill outside target (P < 0.05) comparing 40%, 50%, 60%, and 70% dose spills for IM_ENT compared to IM_EXT+ENT, but variations among VMAT plans are insignificant. VMAT plans were always superior to IMRT plans for the same optimization methods. Conclusion: The best approach is to plan hip prosthesis cases with blocked entry of radiation beam for IMRT and VMAT. The VMAT plans had more volumetric coverage, fewer hotspots, and lesser heterogeneity.

ABSTRACT Nontuberculous mycobacteria (NTM) cause pulmonary disease in individuals without obvious immunodeficiency. This study was initiated to gain insight into the immunological factors that predispose persons to NTM pulmonary disease (NTMPD). Blood was obtained from 15 pairs of NTMPD patients and their healthy household contacts. Peripheral blood mononuclear cells (PBMCs) were stimulated with the Mycobacterium avium complex (MAC). A total of 34 cytokines and chemokines were evaluated in plasma and PBMC culture supernatants using multiplex immunoassays, and gene expression in the PBMCs was determined using real-time PCR. PBMCs from NTMPD patients produced significantly less interleukin-1β (IL-1β), IL-18, IL-1α, and IL-10 than PBMCs from their healthy household contacts in response to MAC. Although plasma RANTES levels were high in NTMPD patients, they had no effect on IL-1β production by macrophages infected with MAC. Toll-like receptor 2 (TLR2) and TWIK2 (a two-pore domain K+ channel) were impaired in response to MAC in PBMCs of NTMPD patients. A TLR2 inhibitor decreased all four cytokines, whereas a two-pore domain K+ channel inhibitor decreased the production of IL-1β, IL-18, and IL-1α, but not IL-10, by MAC-stimulated PBMCs and monocytes. The ratio of monocytes was reduced in whole blood of NTMPD patients compared with that of healthy household contacts. A reduced monocyte ratio might contribute to the attenuated production of IL-1 family cytokines by PBMCs of NTMPD patients in response to MAC stimulations. Collectively, our findings suggest that the attenuated IL-1 response may increase susceptibility to NTM pulmonary infection through multiple factors, including impaired expression of the TLR2 and TWIK2 and reduced monocyte ratio. IMPORTANCE Upon MAC stimulation, the production of IL-1 family cytokines and IL-10 by PBMCs of NTMPD patients was attenuated compared with that of healthy household contacts. Upon MAC stimulation, the expression of TLR2 and TWIK2 (one of the two-pore domain K+ channels) was attenuated in PBMCs of NTMPD patients compared with that of healthy household contacts. The production of IL-1 family cytokines by MAC-stimulated PBMCs and MAC-infected monocytes of healthy donors was reduced by a TLR2 inhibitor and two-pore domain K+ channel inhibitor. The ratio of monocytes was reduced in whole blood of NTMPD patients compared with that of healthy household contacts. Collectively, our data suggest that defects in the expression of TLR2 and TWIK2 in human PBMCs or monocytes and reduced monocyte ratio are involved in the reduced production of IL-1 family cytokines, and it may increase susceptibility to NTM pulmonary infection.

To determine the mechanisms that mediate resistance to Mycobacterium tuberculosis (M. tuberculosis) infection in household contacts (HHCs) of patients with tuberculosis (TB), we followed 452 latent TB infection–negative (LTBI–) HHCs for 2 years. Those who remained LTBI– throughout the study were identified as nonconverters. At baseline, nonconverters had a higher percentage of CD14+ and CD3–CD56+CD27+CCR7+ memory-like natural killer (NK) cells. Using a whole-transcriptome and metabolomic approach, we identified deoxycorticosterone acetate as a metabolite with elevated concentrations in the plasma of nonconverters, and further studies showed that this metabolite enhanced glycolytic ATP flux in macrophages and restricted M. tuberculosis growth by enhancing antimicrobial peptide production through the expression of the surface receptor sialic acid binding Ig-like lectin–14. Another metabolite, 4-hydroxypyridine, from the plasma of nonconverters significantly enhanced the expansion of memory-like NK cells. Our findings demonstrate that increased levels of specific metabolites can regulate innate resistance against M. tuberculosis infection in HHCs of patients with TB who never develop LTBI or active TB.

Background: Management of deep burn requires aggressive debridement of non-viable burnt tissue and closure with skin grafts or flaps but challenge is to manage wound exudates and patient discomfort and to avoid shear force and pain cause by frequent dressing changes. This observational case series assessed outcomes of negative pressure wound therapy (NPWT) use as a bolster in pilot surgery (primary surgery) over skin grafts in patients with severe burns in a burn center in Indore, India in term of wound healing, pain, caregivers and nurses workload. Methods: Patients with extensive burns (≥30% total body surface area [TBSA]) were admitted to the burn unit between January and December 2020. Acute burn victims (burns present

Longevity in life span of city dwellers depends upon the quality of ambient air, which is often compromised due to urbanization. In this context, since independence, Bengaluru has rampantly grown with elevated air and automobile pollution levels. Ambient Carbon Monoxide [CO], which is considered to be the most dangerous criteria air pollutant, however has insufficient research/literature for the city of Bengaluru. To plug this gap, the pre-sent study engages a detailed examination for Temporal and Spatial Map-ping variation of Ambient ‘CO’ concentration in different wards of Bengaluru using calibrated Digital ‘CO’ sensor. The methodology involved primarily an intensive literature review followed by reconnaissance survey for fixation of monitoring stations about each ‘ward’. Further at these observatories, extensive primary data collection was ensued at periodic and regular intervals. The objective serves to delineate the most critical and non-critical places in Bengaluru to incorporate remedial measures. Startling 400+ violations with potential of triggering congestive heart failure, impaired performance in time discrimination, shortened time to angina response and vigilance decrement were observed. Sustainability measures conclude the study.

Abstract 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.

Kupffer cells are more resistant to M. tuberculosis when compared with alveolar macrophages. Here the authors show that this distinction is caused by the presence of ornithine and imidazole in Kupffer cells and that these metabolites can drive autophagy and M. tuberculosis killing in alveolar macrophages when given intranasally to infected mice.

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-1β, 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.

In the current study, we followed 839 household contacts (HHCs) of tuberculosis (TB) patients for 2 years and identified the factors that enhanced the development of TB. Fourteen of the 17 HHCs who progressed to TB were in the 15- to 30-year-old age group. At baseline (the “0“ time point, when all the individuals were healthy), the concentration of the thyroid hormone thyroxine (T4) was lower, and there were increased numbers of Tregs in PBMCs of TB progressors. At baseline, PBMCs from TB progressors stimulated with early secretory antigenic target 6 (ESAT-6) and 10 kDa culture filtrate antigen (CFP-10) produced less IL-1α. Thyroid hormones inhibited Mycobacterium tuberculosis (Mtb) growth in macrophages in an IL-1α–dependent manner. Mtb-infected Thra1PV/+ (mutant thyroid hormone receptor) mice had increased mortality and reduced IL-1α production. Our findings suggest that young HHCs who exhibit decreased production of thyroid hormones are at high risk of developing active TB disease.

Introduction To evaluate the dosimetric effect of photon energies on fixed field intensity-modulated radiotherapy (IMRT) and dual arc (DA) planning and to compare the dosimetric differences between conventional IMRT and DA radiotherapy planning. Materials and Methods IMRT and DA plans were generated for 15 patients having cervical cancer using different photon energies. IMRT and DA plans were generated using seven fields and double arcs, respectively. Dosimetric comparison was done in terms of planning target volume (PTV) coverage, sparing of organ at risk (OAR), homogeneity index (HI), conformity index (CI), and monitor units (MUs). Photo-neutron (energy ≤10MV) contribution was not considered for this study. Near region (NR) and far region (FR) were contoured to evaluate the dose deposited in nontarget area. Results No significant difference was observed (p > 0.05) in PTV coverage for conventional IMRT and DA; however, 6 MV yielded significantly better coverage over 15 MV (p < 0.05) for both the treatment modalities. Mean bladder dose was significantly more for conventional IMRT compared with DA. For rectal mean dose, p-value was nonsignificant for IMRT in comparison to DA, while significant difference was observed for change in photon energies for both treatment modalities respectively, except for 10 MV versus 15 MV DA plans. Significant improvements in HI (except 6 MV vs. 10 MV DA), CI (except 6 MV vs. 10 MV IMRT and DA), MUs, NR, and FR were noted. Conclusion DA generates more conformal, homogenous plans, requires less numbers of MUs, and deposits fewer doses to NR and FR regions of nontarget tissues in comparison to conventional IMRT. Although increase in photon energy for IMRT and DA plans reduces numbers of MUs and dose deposited to NR and FR regions, yet the choice for treatment of carcinoma cervix remains 6 MV due to production of photo-neutrons at higher energies.

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_filtered beam [FB] and 6 MV_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_FB and 6 MV_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.

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

Electrostatic modes present in laser produced plasma are capable of generating strong harmonic radiation. Electrostatic waves provide phase matching and contribute to non-linear coupling. In this paper, lower hybrid waves assist in k-matching to produce the third harmonic of the laser. As the frequency of the lower hybrid wave is very small, the harmonic produced is close to exact. At normalized parameters (amplitude, density, and plasma length), the normalized amplitude of the third harmonic is quite high at a particular value of ω0/ωp and ωc/ωp. This occurs in the proximity of upper hybrid resonance as the process becomes resonant for this value. The magnitude of the normalized amplitude increases as ω02 is close to ωUH2.

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.

Tolerance is required to prevent rejection of intrahepatic islet allografts as a potential treatment for type 1 diabetes. Here the authors show that IL-22 produced by NK1.1+cells in the liver of streptozotocin T1D model mice can drive tolerance to allografted islets.