Modulated Arc Therapy for hippocampal-avoidance whole brain radiation therapy: planning comparison with intensity modulated Radiation Therapy.

This study aimed to evaluate the modulated arc therapy (mARC) technique as a planning and treatment option for hippocampal sparing whole brain radiotherapy (HS-WBRT) following the Radiation Therapy Oncology Group (RTOG) 0933 dosimetric criteria. Computed tomography (CT) and magnetic resonance imaging (MRI) were selected retrospectively for 15 patients. Two types of plans were created for each patient, namely an intensity-modulated radiation therapy (IMRT) and a mARC plan. IMRT and mARC plans were compared in terms of plan quality indices, absorbed dose to organs at risk (OARs), number of monitor units (MUs), and treatment time. All plans in both techniques were considered clinically acceptable for treatment. However, IMRT plans presented a higher conformity (p = 0.01) as well as a higher homogeneity as compared to mARC plans, but this difference was not statistically significant (p > 0.05). In terms of the preservation of the hippocampus, it was observed that the IMRT plans achieved significantly lower doses for both 100% of its volume and for its maximum dose (p < 0.001). The evaluation of the remaining OARs showed that the IMRT technique resulted in lower doses, and significant differences were observed for the following organs: left cochlea (p < 0.001), left eye (p < 0.001), right eye (p = 0.03), both lenses of the eye (p < 0.001), and right optic nerve (p = 0.02). Despite these differences, the absolute differences in all dosimetric parameters were low enough to bear any clinical relevance. A drastic (close to 65%) and significant (p < 0.001) decrease was observed in the number of MUs for the mARC plans. This resulted in a substantial decrease in treatment time (60.45%, p < 0.001). It is concluded that the mARC technique is a feasible planning and treatment solution for HS-WBRT that meets the RTOG 0933 criteria. The main advantage of using mARC over IMRT for HS-WBRT is the considerable reduction in MUs and treatment time.

Unmasking seasonal cycles in a high-input dairy herd in a hot environment: How climate shapes dynamics of milk yield, reproduction, and productive status.

This study aimed to predict the annual herd milk yield, lactation, and reproductive cycle stages in a high-input dairy herd in a zone with prolonged thermal stress. Also, the impact of climatic conditions on milk yield and productive and reproductive status was assessed. An autoregressive integrated moving average (ARIMA) model was used in data fitting to predict future monthly herd milk yield and reproductive status using data from 2014 to 2020. Based on the annual total milk output, the highest predicted percentage of milk yield based on the yearly milk production was in February (9.1%; 95% CI = 8.3-9.9) and the lowest in August (6.9%; 95% CI = 6.0-7.9). The predicted highest percentage of pregnant cows for 2021 was in May (61.8; 95% CI = 53.0-70.5) and the lowest for November (33.2%; 95% CI = 19.9-46.5). The monthly percentage of dry cows in this study showed a steady trend across years; the predicted highest percentage was in September (20.1%; CI = 16.4-23.7) and the lowest in March (7.5%; 4.0-11.0). The predicted days in milk (DIM) were lower in September (158; CI = 103-213) and highest in May (220; 95% CI = 181-259). Percentage of calvings was seasonal, with the predicted maximum percentage of calvings occurring in September (10.3%; CI = 8.0-12.5) and the minimum in April (3.2%; CI = 1.0-5.5). The highest predicted culling rate for the year ensuing the present data occurred in November (4.3%; 95% CI = 3.2-5.4) and the lowest in April (2.5%; 95% CI = 1.4-3.5). It was concluded that meteorological factors strongly influenced rhythms of monthly milk yield and reproductive status. Also, ARIMA models robustly estimated and forecasted productive and reproductive events in a dairy herd in a hot environment.

Design and fabrication of a lightweight 3D first surface mirror aluminized by DC magnetron sputtering.

Aluminum thin films were deposited on a 3D prototype employing the direct current magnetron sputtering technique to fabricate a lightweight 3D first surface mirror. Before the aluminizing, the surface of the prototypes was evaluated with interferometry and atomic force microscope (AFM). The thin films were characterized using profilometry, UV-Vis spectroscopy, x-ray diffraction, AFM, x-ray photoelectron spectroscopy (XPS), and scanning electron microscopy. High adherence and homogeneous deposition of the aluminum's thin films were achieved. In addition, the purity of the material was confirmed by XPS analysis.

Association between the cardiac contact distance and the maximum dose at the left anterior descending coronary artery in post mastectomized patients.

The clinical information on the relationship between the cardiac contact distance (CCD), the maximum dose (Dmax) delivered to the left anterior descending (LAD) coronary artery and the mean heart dose has mostly focused on patients with breast-conserving surgery (BCS), being scarce in postmastectomy patients. The aim of this study is to determine the association between the CCD and the Dmax delivered to the LAD. The secondary objective was to evaluate the dosimetric results of comparing three-dimensional conformal radiotherapy (3D-CRT) to intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques for post mastectomized breast cancer patients with irradiation to the left chest wall. 53 cases of women who received adjuvant standard fractionated postmastectomy radiotherapy (PMRT) were used. Three types of plans were created for each patient: 3D-CRT, seven equidistant IMRT fields, and four partial VMAT arcs. Correlations were evaluated using Pearson's correlation coefficient. Plans made with IMRT and VMAT showed improved homogeneity and conformity. Associations between CCD and Dmax to LAD were positive for all three plan types. Compared to 3D-CRT, the modulated intensity plans obtained better dose homogeneity and conformity to the target volume. The LAD and heart doses were significantly lower for IMRT and VMAT plans. The CCD can be used as a predictor of the maximum and mean doses of the LAD. Modulated intensity techniques allow for better dose distribution and dose reduction to the heart and LAD.

SAFETY AND EFFICACY OF THYMIC PEPTIDES IN THE TREATMENT OF HOSPITALIZED COVID-19 PATIENTS IN HONDURAS.

Coronavirus disease 2019 (Covid-19) active cases continue to demand the development of safe and effective treatments. This is the first clinical trial to evaluate the safety and efficacy of oral thymic peptides. ; We conducted a nonrandomized phase 2 trial with a historic control group to evaluate the safety and efficacy of a daily 250-mg oral dose of thymic peptides in the treatment of hospitalized Covid-19 patients. Comparisons based on standard care from registry data were performed after propensity score matching. The primary outcomes were survival, time to recovery, and number of participants with treatment-related adverse events or side effects by day 20. ; A total of 44 patients were analyzed in this study: 22 in the thymic peptide group and 22 in the standard care group. There were no deaths in the intervention group compared to 24% mortality in standard care by day 20 (log-rank P=0.02). Kaplan-Meier analysis showed a significantly shorter time to recovery by day 20 in the thymic peptide group than in the standard care group (median, 6 days vs. 12 days; hazard ratio for recovery, 2.75 [95% confidence interval, 1.34 to 5.62]; log-rank P=0.002). No side effects or adverse events were reported. ; In patients hospitalized with Covid-19, the use of thymic peptides resulted in no side effects, adverse events, or deaths by day 20. Compared with the registry data, a significantly shorter time to recovery and mortality reduction were measured.

Immune checkpoint expression on peripheral cytotoxic lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis.

Immune checkpoint therapy to reverse natural killer (NK) and T cell exhaustion has emerged as a promising treatment in various cancers. While anti-programmed cell death 1 (PD-1) pembrolizumab has recently gained Food and Drug Administration (FDA) approval for use in recurrent or metastatic cervical cancer, other checkpoint molecules, such as T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) and T cell immunoglobulin and mucin-domain containing-3 (Tim-3), have yet to be fully explored in this disease. We report expression of TIGIT, Tim-3 and PD-1 on subsets of peripheral blood NK (CD56dim/neg CD16bright/dim/neg and CD56bright CD16dim/neg ) and T cells. The percentages of these cells were increased in women with cervical cancer and pre-malignant lesions. PD-1+ NK and T cells were likely to co-express TIGIT and/or Tim-3. These cells, with an apparently 'exhausted' phenotype, were augmented in patients. A subset of cells were also natural killer group 2 member D (NKG2D)- and DNAX accessory molecule 1 (DNAM-1)-positive. PD-1int and PD-1high T cells were notably increased in cervical cancer. Soluble programmed cell death ligand 1 (PD-L1) was higher in cancer patient blood versus healthy donors and we observed a positive correlation between sPD-L1 and PD-1+ T cells in women with low-grade lesions. Within the cancer group, there were no significant correlations between sPD-L1 levels and cervical cancer stage. However, when comparing cancer versus healthy donors, we observed an inverse association between sPD-L1 and total T cells and a correlation between sPD-L1 and CD56dim NK cells. Our results may show an overview of the immune response towards pre-cancerous lesions and cervical cancer, perhaps giving an early clue as to whom to administer blocking therapies. The increase of multiple checkpoint markers may aid in identifying patients uniquely responsive to combined antibody therapies.

Clinical effectiveness of Lactobacillus reuteri in the treatment of peri-implant diseases: a systematic review and meta-analysis.

In the last decades, the presence of peri-implant diseases (PD) has increased. One of the therapies currently used is probiotics with Lactobacillus reuteri (LR). The aim of this article is to determinate, through a systematic review and meta-analysis, the clinical effectiveness of LR in the treatment of PD. We searched the literature until January 2021, in the biomedical databases: Pubmed, Embase, Scielo, Science Direct, Scopus, SIGLE, LILACS, Google Scholar and Cochrane Central Registry of Clinical Trials. The selection criteria of the studies were: randomized controlled clinical trials, without language and time restriction, reporting the clinical effects (depth to probing, plaque index and bleeding index) of the LR in the PD treatment. The risk of study bias was analyzed through the Cochrane tool for randomized studies using Review Manager software. The search strategy resulted in 6 articles of which four investigated peri-implantitis and three peri-implant mucositis. All studies reported that there was a difference in the depth of the probing in the treatment of PD, in favor of the group using LR, though not always achieving significance. The use of LR can be clinically effective in terms of pocket depth reduction in the treatment of PD.

Dosimetric study of a hybrid plan technique for external beam radiotherapy in patients with cervical cancer.

The aim of this study was to investigate the effect of a hybrid technique which results from combining intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) for the treatment of cervical cancer patients. Plans made with the hybrid technique and pure IMRT and VMAT were retrospectively compared in 20 patients with cervical cancer at different stages. All plans were made using the same contours based on the original computed tomography (CT) scans. Conformity (CI) and homogeneity (HI) indices of the planning target volumes (PTVs) were calculated for each technique in order to evaluate plan quality. All techniques were compared in terms of dose to organs at risk (OARs), number of monitor units (MUs) and treatment time. It turned out that plans made with the hybrid technique had improved dose conformity and homogeneity compared to plans made only with IMRT and VMAT (p < 0.001). Regarding the OARs, the maximum dose (Dmax) delivered to the bladder, rectum and femoral heads was lower for the hybrid plans compared to the IMRT and VMAT plans (p < 0.001). The volumes irradiated to doses of 50 Gy (V50Gy) for rectum, bladder and bowel were lower for the hybrid plans (p < 0.001, p = 0.002). Furthermore, the treatment time and MU values for the hybrid plans were found to be between of the values for the IMRT and VMAT plans. It is concluded that, as compared to IMRT and VMAT plans, the hybrid plan technique allowed a better conformity and homogeneity for the dose distribution in the PTV and a dose reduction to the OARs.

Expression of Toll-like receptors 2 and 4 and its association with matrix metalloproteinases in symptomatic and asymptomatic apical periodontitis.

To determine Toll-like receptors (TLR)2 and TLR4 expression levels and associate them with matrix metalloproteinases (MMPs) in asymptomatic apical periodontitis (AAP), symptomatic apical periodontitis (SAP), and healthy controls. Apical tissue/lesion samples were obtained from chronic AAP (n = 35) and SAP (n = 29), and healthy periodontal ligament (HPL, n = 10) with indication of tooth extraction, respectively. mRNA expression levels of TLR2, TLR4, MMP-1, MMP-2, MMP-8, and MMP-13 were determined by real-time reverse-transcription polymerase chain reaction. The data were analyzed with Kruskal-Wallis and Dunn's pot hoc test (p < 0.05). The correlation coefficient was obtained using the Spearman correlation (p < 0.05). TLR2, MMP-1, MMP-2, and MMP-13 mRNA levels were the highest in SAP followed by AAP and controls (p < 0.05). TLR4 and MMP-8 were over expressed in AAP and SAP compared to HPL (p < 0.05). TLR2 positively correlated with TLR4, MMP-1, MMP-8, and MMP-13 in SAP (p < 0.05). TLR2 and TLR4 are overexpressed in apical lesions versus healthy periodontal ligament and correlate with collagenolytic MMPs. Particularly, TLR2 is overexpressed in SAP in association with MMP-1, MMP-8, and MMP-13. Our results suggest that the activation of TLR2 along with MMP overexpression might contribute to SAP clinical presentation and progression. TLRs, MMPs, and their interaction can explain the clinical presentations and evolution of apical periodontitis and might represent key targets for new diagnostic and treatment approaches.

The interleukin-6-hepcidin-hemoglobin circuit in systemic lupus erythematosus flares.

Objective Hepcidin regulates iron availability and may be responsible for the anemia of chronic disease because it is induced by interleukin-6. This study investigated the IL-6-hepcidin-hemoglobin axis in patients with lupus. Methods IL-6 and hepcidin were measured in serial serum samples collected before, during and after lupus flares by specific ELISAs. Results During renal and non-renal SLE flare cycles IL-6 did not predict hepcidin and hepcidin did not predict hemoglobin. When lupus nephritis patients were in remission, IL-6 and hepcidin were correlated, but hepcidin and hemoglobin were not. Conclusion Hepcidin does not contribute significantly to anemia during active lupus.