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Frontiers in Public Health 2024Treatments that currently exist in the strategic national stockpile for acute radiation syndrome (ARS) focus on the hematopoietic subsyndrome, with no treatments on...
INTRODUCTION
Treatments that currently exist in the strategic national stockpile for acute radiation syndrome (ARS) focus on the hematopoietic subsyndrome, with no treatments on gastrointestinal (GI)-ARS. While the gut microbiota helps maintain host homeostasis by mediating GI epithelial and mucosal integrity, radiation exposure can alter gut commensal microbiota which may leave the host susceptible to opportunistic pathogens and serious sequelae such as sepsis. To mitigate the effects of hematopoietic ARS irradiation, currently approved treatments exist in the form of colony stimulating factors and antibiotics: however, there are few studies examining how these therapeutics affect GI-ARS and the gut microbiota. The aim of our study was to examine the longitudinal effects of Neulasta and/or ciprofloxacin treatment on the gut microbiota after exposure to 9.5 Gy Co gamma-radiation in mice.
METHODS
The gut microbiota of vehicle and drug-treated mice exposed to sham or gamma-radiation was characterized by shotgun sequencing with alpha diversity, beta diversity, and taxonomy analyzed on days 2, 4, 9, and 15 post-irradiation.
RESULTS
No significant alpha diversity differences were observed following radiation, while beta diversity shifts and taxonomic profiles revealed significant alterations in , , and . Ciprofloxacin generally led to lower Shannon diversity and prevalence with increases in and compared to vehicle treated and irradiated mice. While Neulasta increased Shannon diversity and by day 9 had more similar taxonomic profiles to sham than ciprofloxacin-or vehicle-treated irradiated animals. Combined therapy of Neulasta and ciprofloxacin induced a decrease in Shannon diversity and resulted in unique taxonomic profiles early post-irradiation, returning closer to vehicle-treated levels over time, but persistent increases in and compared to Neulasta alone.
DISCUSSION
This study provides a framework for the identification of microbial elements that may influence radiosensitivity, biodosimetry and the efficacy of potential therapeutics. Moreover, increased survival from H-ARS using these therapeutics may affect the symptoms and appearance of what may have been subclinical GI-ARS.
Topics: Animals; Ciprofloxacin; Gastrointestinal Microbiome; Mice; Anti-Bacterial Agents; Acute Radiation Syndrome; Gamma Rays; Male; Female
PubMed: 38807988
DOI: 10.3389/fpubh.2024.1365161 -
Dental Research Journal 2024The presence of treatment-resistant microorganisms is known as the main cause of pulpectomy failure in the endodontic treatment of deciduous teeth. The usage of lasers...
BACKGROUND
The presence of treatment-resistant microorganisms is known as the main cause of pulpectomy failure in the endodontic treatment of deciduous teeth. The usage of lasers can contribute to reducing these microorganisms. This study aimed to compare the effect of three disinfection methods for deciduous teeth canals using laser diode 810 nm, photodynamic therapy with laser 660 nm and methylene blue, and sodium hypochlorite.
MATERIALS AND METHODS
In this experimental study, 58 single-root deciduous teeth with no root resorption were investigated in four groups, including one control group of 10 and three intervention groups of 16. Preparation of the samples was done using manual files up to three numbers after the initial file. After sterilizing the samples in an autoclave, bacteria were cultured in the canals. In the first group, irrigating with hypochlorite 2.5% was done; in the second group, photodynamic therapy was performed using a laser diode and 0.1 mg/mL methylene solution; and in the third group, high-intensity laser 810 nm direct radiation was done into the canal. Next, samples were taken from all canals. The colony formation unit (CFU) of the bacteria was counted in the blood agar culture medium. The data were analyzed using Kruskal-Wallis and negative binomial regression test (α =0.05).
RESULTS
The mean CFU differed significantly between the four groups. The rate of incidence of colonies showed a reduction in all three intervention groups compared to the negative control. In the high-intensity laser 810 nm group, there was 68.4%; in the photodynamic therapy with diode 660 nm and methylene blue, there was 88%; and in the hypochlorite group, 98.3% reduction was observed compared to the negative control group.
CONCLUSION
Based on the results of this study, to compare three disinfection methods of the deciduous teeth canals without preparation of canals, sodium hypochlorite had greater efficiency. All three groups of laser, photodynamic therapy, and sodium hypochlorite showed reductions of bacterial colony compared to the control group. The reductive effects of CFU were greater in the hypochlorite sodium group, followed by photodynamic and direct laser radiation groups.
PubMed: 38807661
DOI: No ID Found -
Journal of Environmental Radioactivity Jul 2024In recent years, there has been a significant surge in interest in measuring low radon levels in the environment. These measurements are valuable, particularly for...
In recent years, there has been a significant surge in interest in measuring low radon levels in the environment. These measurements are valuable, particularly for identifying radon priority areas as required by the European Council Directive 2013/59/EURATOM and for research related to climate change. Due to the limited sensitivity of existing radon detectors/monitors in addressing these challenges, substantial efforts have been devoted to developing new designs. This report compares the sensitivity of several innovative designs with that of existing passive radon monitors. These novel designs incorporate alpha track detectors, including large area low background detectors, with activated carbon fabric used as an efficient radon adsorber/radiator. Recent innovative solutions to mitigate the impact of temperature and humidity on detectors using adsorbers are also discussed. The background signal of detectors intended for use in these novel designs is examined, and their sensitivity is evaluated. The findings demonstrate that these novel designs have the potential to significantly enhance the sensitivity of long-term radon measurements, surpassing the detectors currently in widespread use by more than an order of magnitude.
Topics: Radon; Radiation Monitoring; Air Pollutants, Radioactive; Air Pollution, Indoor
PubMed: 38805778
DOI: 10.1016/j.jenvrad.2024.107461 -
Lasers in Medical Science May 2024Conventional approaches for enhancing wound healing may not always yield satisfactory results. Instead, we test the effectiveness of a newly developed photodynamic...
PURPOSE
Conventional approaches for enhancing wound healing may not always yield satisfactory results. Instead, we test the effectiveness of a newly developed photodynamic therapy (PDT) that uses methylene blue (MB) loaded with polyethylene glycol (PEG) (MB-PEG) hydrogel to accelerate wound healing process in mice.
METHODS
A dorsal skin incision with 6 mm punch which topically subjected to MB-PEG hydrogel and a low-level laser light of red light to assess the regeneration process of wounded skin. A total of 63 adult male CD1 mice divided into normal group (no treatment) and other wound groups received different treatments of laser (650 ± 5 nm and power intensity of 180 mW/cm), MB-PEG, or PDT (MB-PEG followed by laser). The wound healing parameters were investigated by histological examination of the skin and measuring of proinflammatory cytokines at the early stage (48 h) and a late one on day 21.
RESULTS
at 48 h, the score of tissue granulation, inflammation, and angiogenesis process were markedly improved in wounded groups that received MB + PEG combined with laser compared to the group treated with laser alone. On day 21, a significant improvement of the inflammation was detected in the group treated with MB + PEG plus laser compared to the other groups. At 48 h, the upregulated serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the wound group were significantly (P < 0.001) reduced in the group treated with MB + PEG combined with laser.
CONCLUSION
MB-PEG based hydrogel improves and accelerates wound closure in the context of laser compared to either single treatment.
Topics: Animals; Wound Healing; Mice; Photochemotherapy; Polyethylene Glycols; Methylene Blue; Male; Skin; Hydrogels; Photosensitizing Agents; Cytokines
PubMed: 38801600
DOI: 10.1007/s10103-024-04084-1 -
Neuro-oncology Advances 2024Standard treatment for newly diagnosed high-grade gliomas remains suboptimal. Preclinical data indicate that mesenchymal transition and radiation resistance in...
BACKGROUND
Standard treatment for newly diagnosed high-grade gliomas remains suboptimal. Preclinical data indicate that mesenchymal transition and radiation resistance in glioblastoma are driven by NF-κB and microglia activation, which can be inhibited by minocycline. We assessed the safety and efficacy of minocycline combined with standard radiation and temozolomide in newly diagnosed high-grade gliomas.
METHODS
Adults with newly diagnosed high-grade glioma were eligible. Minocycline was given with concurrent and adjuvant temozolomide. Minocycline doses were escalated using a 3 + 3 design and expanded to identify the maximum tolerated dose (MTD) and adverse event profile. Individual progression-free survival (PFS) was compared to predicted PFS based on RTOG RPA class using a binomial test. The relationships between mesenchymal and microglial biomarkers were analyzed with immunohistochemistry.
RESULTS
The MTD of minocycline was 150 mg twice per day ( = 20); 1 patient (5%) experienced CTCAE grade 3 + nausea and dizziness, and 2 patients (10%) demonstrated thrombocytopenia requiring temozolomide interruptions. Twelve patients exceeded their predicted PFS (60%), which did not meet the predefined efficacy endpoint of 70%. Symptoms increased during post-radiation treatment but remained mild. No significant correlation was seen between biomarkers and PFS. Expression levels of P-p65, a marker of NF-κB activation, were correlated with the microglia marker IBA-1.
CONCLUSIONS
Minocycline at 150 mg twice per day is well tolerated with standard chemoradiation in patients with newly diagnosed high-grade gliomas. PFS was not significantly increased with the addition of minocycline when compared to historical controls. NF-κB activation correlates with microglia levels in high-grade glioma.
PubMed: 38800698
DOI: 10.1093/noajnl/vdae063 -
Journal of Hepatocellular Carcinoma 2024The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti-PD1) showed preliminary efficacy in hepatocellular carcinoma (HCC). This...
PURPOSE
The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti-PD1) showed preliminary efficacy in hepatocellular carcinoma (HCC). This study aimed to identify the prognostic factors and construct a nomogram to predict the overall survival (OS) of patients with advanced HCC after treatment with intensity-modulated radiotherapy (IMRT) plus anti-PD1.
PATIENTS AND METHODS
The OS and progression-free survival (PFS) of 102 patients with BCLC stage C HCC was analyzed using the Kaplan-Meier method. Potential independent prognostic factors were determined using univariate and multivariate Cox regression analyses. A nomogram was established to predict prognosis whose accuracy and reliability was verified by a calibration curve and area under the receiver operating characteristic curve (AUROC).
RESULTS
The median PFS and OS rates of the 102 patients with advanced HCC were 9.9 months and 14.3 months, respectively. Ninety-three patients were evaluated for efficacy, including five (5.38%) with complete response and 48 (51.61%) with partial response, with an overall response rate of 56.99%. Grade 3 and 4 adverse reactions (AEs) were observed in 32.35% of patients; no grade 5 AEs occurred. Multivariate Cox analysis revealed albumin and alpha-fetoprotein levels, neutrophil counts 3-4 weeks after IMRT initiation, and platelet-to-lymphocyte ratio 3-4 weeks after IMRT initiation to be independent prognostic factors. The nomogram model constructed using these factors had good consistency and accuracy with 1-3 years AUROC of 78.7, 78.6, and 93.5, respectively.
CONCLUSION
IMRT plus anti-PD1 showed promising efficacy and controllable adverse reactions in treating advanced HCC. The nomogram model demonstrated good reliability and clinical applicability.
PubMed: 38799002
DOI: 10.2147/JHC.S459683 -
Scientific Reports May 2024Numerous heat transfer applications, such as heat exchangers, solar trough collectors, and fields including food processing, material research, and aerospace...
Numerous heat transfer applications, such as heat exchangers, solar trough collectors, and fields including food processing, material research, and aerospace engineering, utilize hybrid nanofluids. Compared to conventional fluids, hybrid nanofluids exhibit significantly enhanced thermal conductivity. The aim of this work is to explore flow and heat transmission features under of magneto-hydrodynamic bioconvective flow of carbon nanotubes over the stretched surface with Dufour and Soret effects. Additionally, comparative dynamics of the carbon nanotubes (SWCMT - MWCNT/CHO with SWCMT - MWCNT/CHO - HO) flow using the Prandtl fluid model in the presence of thermal radiation and motile microorganisms has been investigated. Novel feature Additionally, the focus is also to examine the presence of microorganisms in mixture base hybrid nanofluid. To examine heat transfer features of Prandtl hybrid nanofluid over the stretched surface convective heating is taken into consideration while modeling the boundary conditions. Suitable similarity transform has been employed to convert dimensional flow governing equations into dimensionless equations and solution of the problem has been obtained using effective, accurate and time saving bvp-4c technique in MATLAB. Velocity, temperature, concentration and microorganisms profiles have been demonstrated graphically under varying impact of various dimensionless parameters such as inclined magnetization, mixed convection, Dufour effect, Soret effect, thermal radiation effect, and bioconvection lewis number. It has been observed that raising values of magnetization (0.5 ≤ M ≤ 4), mixed convection (0.01 ≤ λ ≤ 0.05) and inclination angle (0° ≤ α ≤ 180°) enhance fluid motion rapidly in Ethylene glycol based Prandtl hybrid nanofluid (SWCMT - MWCNT/CHO) when compared with mixture base working fluid of carbon nanotubes SWCMT - MWCNT/CHO - HO). Raising thermal radiation (0.1 ≤ Rd ≤ 1.7) and Dufour number (0.1 ≤ Du ≤ 0.19) values improves temperature profile. Moreover, a good agreement has been found between the current outcome and existing literature for skin friction outcomes.
PubMed: 38796613
DOI: 10.1038/s41598-024-62647-2 -
BMC Cancer May 2024The proposed trial is to examine the feasibility of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided...
Protocol for CHAMPION study: a prospective study of maximal-cytoreductive therapies for patients with de novo metastatic hormone-sensitive prostate cancer who achieve oligopersistent metastases during systemic treatment with apalutamide plus androgen deprivation therapy.
BACKGROUND
The proposed trial is to examine the feasibility of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided cytoreduction plus apalutamide and androgen deprivation therapy (ADT) for newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) at oligometastatic state.
METHODS
CHAMPION (NCT05717582) is an open-label, single-arm, phase II trial, planning to enroll newly diagnosed mHSPC cases with oligometastases (≤ 10 distant metastatic sites in conventional imaging). Patients will receive 6 cycles of apalutamide plus ADT. Patients with oligometastatic disease at PSMA PET/CT after 3 treatment cycles will receive cytoreductive radical prostatectomy. PSMA PET/CT-guided metastasis-directed external radiation therapy will be determined by the investigators. Apalutamide plus ADT will be continued for 2 weeks postoperatively. The primary endpoint is the proportion of patients with undetectable prostate-specific antigen (PSA), no disease progression, and no symptom deterioration after 6 cycles of apalutamide plus ADT. Secondary endpoints include the percentage of patients with PSA ≤ 0.2 ng/mL and oligometastases by the end of 3 treatment cycles, PSA response rate, and safety. Fleming's two-stage group sequential design will be adopted in the study, where the null hypothesis is that the rate of patients with an undetectable PSA is ≤ 40% after 6 cycles of treatment, while the alternate hypothesis is an undetectable PSA of > 60%; with one-sided α = 0.05, power = 0.80, and an assumed dropout rate of 10%, the required number of patients for an effective analysis is 47. Enrolment in the study commenced in May 2023.
DISCUSSION
The multi-modal therapy based on treatment response may improve the prognosis of newly diagnosed mHSPC patients with oligometastases.
TRIAL REGISTRATION
The study is registered with Clinical Trials.Gov (NCT05717582). Registered on 8th February 2023.
Topics: Humans; Male; Thiohydantoins; Androgen Antagonists; Prostatic Neoplasms; Prospective Studies; Neoplasm Metastasis; Positron Emission Tomography Computed Tomography; Antineoplastic Combined Chemotherapy Protocols; Aged; Prostate-Specific Antigen; Middle Aged; Clinical Trials, Phase II as Topic; Prostatectomy
PubMed: 38796422
DOI: 10.1186/s12885-024-12395-3 -
Materials (Basel, Switzerland) May 2024In this study, the rolling process of the warm-rolled duplex-phase Mg-8.3Li-3.1Al-1.09Si alloy and the strengthening mechanism of as-rolled Mg-Li alloy were...
In this study, the rolling process of the warm-rolled duplex-phase Mg-8.3Li-3.1Al-1.09Si alloy and the strengthening mechanism of as-rolled Mg-Li alloy were investigated. The highest ultimate tensile strength (UTS, 323.66 ± 19.89 MPa) could be obtained using a three-pass rolling process with a 30% thickness reduction for each pass at 553 K. The strength of the as-rolled LAS831 alloy is determined by a combination of second-phase strengthening, grain refinement strengthening, dislocation strengthening, and load-transfer reinforcement. Of these factors, dislocation strengthening, which is caused by strain hardening of the α-Mg phase, can produce a good strengthening effect but also cause a decrease in plasticity. The MgSi phase is broken up into particles or strips during the rolling process. After three passes, the AlLi particles were transformed into an AlLi phase, and the MgSi particles and nanosized AlLi particles strengthened the second phase to form a hard phase. The average size of the DRXed β-Li grains decreased with each successive rolling pass, and the average size of recrystallized grains in the three-pass-rolled LAS831 alloy became as low as 0.27 μm. The interface between the strip-like MgSi phase and the α-Mg phase is characterized by semicoherent bonding, which can promote the transfer of tensile and shear forces from the matrix to the strip-like MgSi phase, thereby improving the strength of the matrix and thus strengthening the LAS831 alloy.
PubMed: 38793388
DOI: 10.3390/ma17102321 -
Microorganisms May 2024Along with the standard therapies for glioblastoma, patients are commonly prescribed trimethoprim-sulfamethoxazole (TMP-SMX) and dexamethasone for preventing infections...
Along with the standard therapies for glioblastoma, patients are commonly prescribed trimethoprim-sulfamethoxazole (TMP-SMX) and dexamethasone for preventing infections and reducing cerebral edema, respectively. Because the gut microbiota impacts the efficacy of cancer therapies, it is important to understand how these medications impact the gut microbiota of patients. Using mice that have been colonized with human microbiota, this study sought to examine how TMP-SMX and dexamethasone affect the gut microbiome. Two lines of humanized microbiota (HuM) Rag1 mice, HuM1Rag and HuM2Rag, were treated with either TMP-SMX or dexamethasone via oral gavage once a day for a week. Fecal samples were collected pre-treatment (pre-txt), one week after treatment initiation (1 wk post txt), and three weeks post-treatment (3 wk post txt), and bacterial DNA was analyzed using 16S rRNA-sequencing. The HuM1Rag mice treated with TMP-SMX had significant shifts in alpha diversity, beta diversity, and functional pathways at all time points, whereas in the HuM2Rag mice, it resulted in minimal changes in the microbiome. Likewise, dexamethasone treatment resulted in significant changes in the microbiome of the HuM1Rag mice, whereas the microbiome of the HuM2Rag mice was mostly unaffected. The results of our study show that routine medications used during glioblastoma treatment can perturb gut microbiota, with some microbiome compositions being more sensitive than others, and these treatments could potentially affect the overall efficacy of standard-of-care therapy.
PubMed: 38792844
DOI: 10.3390/microorganisms12051015