Effective ropivacaine delivery using lipid nanoparticles enables simultaneous cancer therapy and pain control.

Incorporating Individual Early Response in the Dose-Effect Relationship of Complete Pathological Response Following Neoadjuvant Radiochemotherapy for Rectal Cancer.

Collagen II hydrogel-mediated sustained delivery of lacosamide attenuates cartilage degeneration and pain in osteoarthritis.

Performic acid disinfection in wastewater effluent and combined sewer overflows: A review.

Semen parameters in unirradiated, alkylating agent-exposed childhood cancer survivors in the St. Jude Lifetime Cohort Study.

The sRNA-encoded peptide TimP rewires the Escherichia coli envelope via LamB to sensitize bacteria to polymyxins.

Single-session, virtual, pain relief skills class for adults with chronic pain on long-term opioids: A randomized controlled trial.

Quantitative evaluation of patient-emitted radiation in dual-injection Tc-99m MIBI myocardial perfusion scintigraphy: A multiregional, multi-distance, and scenario-based safety analysis.

A germinal matrix hemorrhage (GMH) model that recapitulates both GMH-like tissue injury and intraventricular hemorrhage via injection of clostridial collagenase into the ganglionic eminence (GE; germinal matrix) has been well established in rats. A dose-response injection study was performed using weight-based collagenase doses extrapolated from established rat models. Reproducible targeting of the right GE in neonatal mice was achieved by the following stereotactic injection protocol: needle entry 1.1 mm lateral and 1.5 mm anterior to lambda, insertion to a depth of 1.3 mm prior to collagenase injection. High rates of ventriculomegaly were observed across collagenase injection groups compared with controls, with a significant dose-dependent effect. The weight-based equivalent dose of collagenase (0.024 collagenase digestion units [CDU] /μL) was identified as the optimal dose for this neonatal mouse model compared to lower or higher CDUs. Positive GFAP and CD68 labeling suggested accurate GE targeting. Intraventricular blood injection was used as a positive control. A neonatal mouse model that recapitulates GMH-like tissue injury using stereotactic injection method and weight-based dosing extrapolated from prior reported rat models, while achieving high rates of hydrocephalus with minimal complications and mortality, has not yet been well established. Our group developed a GMH/posthemorrhagic hydrocephalus (PHH) mouse model with reproducible stereotactic injection coordinates. This model provides a foundation for future studies using genetically modified mouse strains aimed to advance understanding of the inflammation-related molecular mechanisms underlying acquired hydrocephalus and to support the preclinical evaluation of potential therapeutic interventions.

Antipsychotic polypharmacy (APP), defined as the concurrent use of two or more antipsychotic agents, remains common in clinical practice despite antipsychotic monotherapy being the recommended standard for schizophrenia treatment. This nationwide cross-sectional survey examined the prevalence and determinants of APP among outpatients with schizophrenia in Japan. Data were collected from 3657 patients across 36 medical institutions between 21 and 25 October 2024. Patients were categorized into antipsychotic monotherapy and APP groups, and demographic and clinical characteristics, including age, sex, medication administration frequency, use of long-acting injectables, clozapine, and concomitant psychotropic medications, were compared. Antipsychotic doses were standardized to chlorpromazine equivalents and analyzed by sex and age group. APP was observed in 40.8% of patients. Multivariable analyses showed that APP was significantly associated with male sex, older age, long-acting injectable use, and concomitant use of antiparkinsonian agents, anxiolytics/hypnotics, and mood stabilizers, whereas clozapine use was inversely associated with APP. Chlorpromazine equivalent doses increased with the number of antipsychotics prescribed, peaking in patients aged 40-59 years and declining thereafter. Second-generation antipsychotics predominated overall, although first-generation antipsychotic use increased with polypharmacy. These findings underscore the importance of careful management of APP, taking sex- and age-related prescribing patterns into consideration.

Effect of non-consecutive treatment during hypofractionated stereotactic radiosurgery (HF-SRS) for brain metastases.

The attitude towards using glucocorticosteroids (GCs) for the management of patients with systemic lupus erythematosus (SLE) has undergone drastic changes over the last decades. While the role of GCs for the rapid control of inflammation is uncontested, the former 'dogma' that GCs must never be withdrawn due to fear of severe flares was proven wrong and replaced by a strategy that invites both tapering GCs to 0 and questioning whether they even need to be initiated at all in individual patients. Moreover, the daily prednisone equivalent dose acceptable for long-term use is limited to ≤ 5 mg in current recommendations. These changes are a consequence of a substantial body of evidence that links higher GC doses to infections, cardiovascular events and other damage, and an increasing number of studies showing that GC withdrawal is feasible in many SLE patients who are in remission. Despite methodological concerns, with observational data inherently prone to confounding by indication, the worldwide experience of the last decades suggests that the limit of 5 mg daily is justified. Moreover, current strategies and novel medications have made it a reality for many SLE patients, to actually maintain the goal of remission or low disease activity on not >5 mg of prednisone per day.

To evaluate the effects of a plant-based milk with fermented brown rice on constipation symptoms in patients with functional constipation and to identify post-intervention gut microbial alterations that may underlie potential mechanisms. This is a randomized controlled trial among 100 participants with functional constipation. Participants were randomly assigned to the intervention group (plant-based milk with fermented brown rice, 2 bottles/day, 500ml in total), or the control group (an isocaloric plant protein milk, equivalent dose) for 3 weeks. The primary outcome is complete spontaneous bowel movement (CSBM) rate, while secondary outcomes include score of individual symptoms assessment of constipation, bowel movement frequency (BMF), and gut microbial changes (metagenomics). A total of 99 participants completed the intervention. CSBM and BMF increased, and GSRS scores decreased over time in both groups, with no significant between-group differences. The plant-based milk with fermented brown rice relieved constipation symptoms more than the control group did, with significant between-group differences in straining, bloating and abdominal pain (all P < 0.05). The intervention group showed increases in 8 species, including three beneficial species in the genus Blautia, associated with relief of abdominal pain after the intervention. Meanwhile, machine learning models identified gut microbiota features predicting intervention responders. Our study did not find between-group difference in CSBM, while the plant-based milk with fermented brown rice showed greater effectiveness in relieving constipation symptoms and optimizing gut microbiota. Functional species benefiting intestinal health in response to the intervention were also identified. This study has been registered in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/, ChiCTR2400088688).

In this study, soil cores (0-20cm) were collected at 45 sites located within a 30-km radius zone around the Belarusian nuclear power plant (BelNPP) in 2019 before its commissioning. Activity of gamma-emitting radionuclides was measured in the samples using HPGe detectors. The study revealed low levels of 137Cs in the soil: the weighted average dry weight (d.w.) activity concentration (ACw) varied from 1.13 to 8.71Bq/kg (d.w.). The ACw of natural radionuclides ranged: for 226Ra from 7.8 to 30.8Bq/kg (d.w.), for 232Th from 10.9 to 33.0Bq/kg (d.w.), and for 40K from 376 to 789Bq/kg (d.w.). A good agreement between the ambient dose equivalent rate (ADER) values calculated with the soil samples and the ADER values previously measured in situ at the same sites is observed. The sites characterized here now have established pre-operational levels of 137Cs, 226Ra, 232Th, and 40K in soil thus can be surveyed again in future environmental studies.

We assessed the risk of perfluorooctanoic acid (PFOA) to ovarian function by integrating in vivo mouse data with physiologically based toxicokinetic (PBTK) modeling and population-level analysis. Adult mice received PFOA (0.06, 1.15, 22 mg/kg bw/day; 14 days), followed by analysis of ovarian histology and whole-ovary transcriptomics. Effect doses were converted to human equivalent doses (HEDs) and propagated through a PBTK model to estimate ovarian bioactive concentrations (OBCs) in human ovaries. Median histology HEDs were 41 and 501 mg/week, whereas transcriptomic HED was 322 mg/week values above PFOA levels inferred from follicular fluid (FF) (∼0.002-0.0069 μg/mL). Lowest histology OBC was 25.6 μg/mL, and the fifth percentile transcriptomic OBC was 21.3 μg/mL, both exceeding PFOA FF levels. A subset of 21 ovarian genes had OBCs within 100-fold of PFOA FF levels. Clinical conditions such as cirrhosis Child-Pugh (CP) class C (CP-C), end-stage renal disease (ESRD), and morbid obesity double the risk for PFOA-induced ovarian dysfunction. Weibull distributions to gene-level OBCs across clinical populations and extrapolation to low percentiles (p = 0.05-10-4) showed that cirrhosis CP-C, ESRD, and morbid obesity demonstrated progressively smaller OBC percentiles compared with healthy as p decreased. Other populations showed modest changes or slight increases at the lowest percentiles. Overall, predicted PFOA OBCs remain above currently reported human PFOA FF levels, supporting a population-level margin of safety under current exposure. The gene-level and vulnerable population analyses identify sensitive molecular targets and subgroups in which this margin is reduced, warranting prioritization in future biomonitoring and reproductive risk assessment.

This article describes aregional study performed in patients with bone metastases from prostate cancer hypothesizing that intensified radiotherapy (metastases directed and prostate directed) may result in longer overall survival. Aretrospective study of 246 consecutive male patients who received 347 courses of radiotherapy in the time period 2011-2025 was performed. Patients were stratified into three cohorts spanning 5‑year intervals (2011-2015, 2016-2020, 2021-2025). Survival was analyzed in allcomers and separately in patients without visceral metastases treated within the first year after diagnosis (n = 119). Median overall survival was shortest in the earliest phase of the study (2011-15). The two recent cohorts had similar survival. Outpatients with high performance status irradiated early after diagnosis and to all known sites of disease experienced superior survival. In the subgroup of 119 patients, simultaneous prostate radiotherapy prolonged survival (numerically better than no prostate RT, median 40vs.26months, 5‑year rate 47vs.18%, p = 0.11). The impact of bone radiotherapy dose (dichotomized < 3 Gy × 13 or its biological equivalent vs. higher doses) was significant (if synchronous metastases, 5‑year rate 64vs.17%, p = 0.026; if metachronous metastases, 5‑year rate 48vs.8%, p < 0.001). Bone dose remained significant in multivariate analyses, together with clinical baseline parameters. In our healthcare region, outcomes largely resemble those of prospective trials. Comprehensive radiotherapy to the prostate and bone oligometastases plus guideline-based systemic therapy resulted in favorable 5‑year survival.

Pancreatic cancer carries a disproportionate burden of mortality and highlights a need to identify therapies that improve local control and survival outcomes. Radiotherapy is an option for the large proportion of patients who are surgically unresectable but has previously been restricted by surrounding dose-limiting organs. The use of stereotactic body radiotherapy (SBRT) can overcome these limitations and deliver a higher biologically equivalent dose to improve local control. Eighty-seven patients with locally advanced, unresectable and histologically confirmed pancreatic adenocarcinoma treated with SBRT were enrolled. Patients underwent SBRT with endoscopic fiducial seed guidance, with either concurrent chemotherapy or dose-escalated radiotherapy alone. Fractionation regimens ranged from 3 to 5 fractions. With a median follow up of 8 months (range 8-51), the median overall survival was 8 months. The local control in those alive at 1 year was 75%. Five patients had Grade 3 toxicity and 5 had moderate (Grade 2) toxicity, with the remaining patients having mild or no toxicity. There were no Grade 4 or greater toxicities. SBRT potentially bypasses the dose limitations of adjacent organs compared with conventional radiotherapy, allowing for improved local control and shorter treatment times. The additional benefit of manageable toxicities makes this an appealing therapy for patients with unresectable pancreatic cancer.

Objective.Secondary neutrons are an unavoidable by-product of ion beam therapy and contribute to out-of-field doses. Quantifying these doses is crucial for ensuring the safety of the patients, particularly for paediatric patients.Approach.Out-of-field neutron measurements were performed for protons, helium ions and carbon ions, treating a 10-year-old paediatric phantom with a virtual brain tumour. Neutron spectrometry was performed using a Bonner sphere spectrometer, and ambient dose equivalents,H∗(10), were additionally measured with an extended-range rem counter (WENDI II). Both measurements were carried out at two locations in the treatment room, positioned upstream and downstream of the primary beam. Monte Carlo (MC) simulations were used to obtaina priorispectra for the unfolding and to complement the measurements.Main results.The measured neutron energy spectra showed the characteristic features of secondary neutrons in ion beam therapy, consistent with the MC simulations. For all three ions, both the fast neutron and high-energy neutron peaks were observed at the downstream position, along with thermal and epithermal neutron contributions, while no high-energy neutron peak was observed upstream. The highest ambient dose equivalentH∗(10)measured with WENDI II was 11.8μSv per 4 Gy relative biological effectiveness (RBE) for helium ions at the downstream position, and the lowest value of 1.1μSv per 4 Gy(RBE) was obtained by the MC simulations for carbon ions upstream.Significance.The energy distribution of the secondary neutrons during ion beam treatment of a paediatric phantom was successfully measured and used to estimate the ambient dose equivalent.

West Qasr El-Farafra area is particularly important for establishing new integrated urban communities. It is characterized by its flat area covered with slopes of limestone and sandstone limestone and sandstone rocks. Airborne gamma ray spectrometry and magnetic data were used for environmental radiation monitoring and mapping the basement surface in the west Farafra area. This study investigates the concentrations and distribution patterns of three radionuclides-238U, 232Th, and 40K-in sedimentary rocks. Analysis reveals that 238U has a mean concentration of 37Bq kg-1 with high variability and a positively skewed distribution, suggesting localized enrichment processes. 232Th shows a mean concentration of 32Bq kg-1 and exhibits moderate skewness and a flatter kurtosis, likely due to the presence of thorium-bearing minerals. In contrast, 40K has a mean concentration of 665Bq kg-1 with the least variability and a near-normal distribution, attributed to the widespread presence of potassium-bearing minerals. Radiological parameters, including the radium equivalent activity (Raeq), dose rate (Dair), and annual effective dose (AED), generally indicate lower radiological hazards compared to global averages, though some samples exhibit elevated levels. Pearson correlation analysis demonstrates strong associations among the radionuclides and radiological risk indicators, with 232Th showing the highest correlation. Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) further reveal that 40K and 232Th are more closely related, while 238U behaves distinctly, indicating different geological or environmental influences. Consequently, as a result of the above findings, the location of interest is generally radiologically acceptable for redevelopment purposes pending verification of a site specific nature within those areas where anomalous levels can be found.

This work establishes a representative ambient dose equivalent rate constant (ΓH(*10)) for I-131 as a first step toward patient body-attenuation studies. Monte Carlo simulations with the EGSnrc code were used to evaluate ΓH(*10) for point sources and the ICRU sphere, employing two photon-spectra datasets (RADAR and ICRP 107) and two scoring methods (fluence and air-kerma scoring). Simulations considered only photons above 20 keV, omitted electron transport, and achieved statistical uncertainties ≤3%. Our results were consistent across spectra and geometries, yielding a representative mean ΓH(*10) value of 63.6 ± 0.2% µSv.m².GBq⁻¹.h⁻¹. Comparison with published ΓH(*10) values for I-131 showed differences ranging from -17% to +22% and close agreement with recent values and the literature average value. An adult male voxel phantom with biodistributed I-131 was then simulated to obtain the body ambient dose equivalent rate constant (ΓH*(10),body) and a corresponding body attenuation factor (BAF) of 0.729 ± 0.002 at 1 m was estimated. As complementary validation, F-18 (511 keV photons) with FDG biodistribution produced a BAF of 0.628 ± 0.002 in the model used in this work. This value agrees with the literature. The proposed representative ΓH(*10) reduces uncertainty in BAF estimates and can improve shielding calculations and dose assessments for caregivers and family members of patients undergoing I-131 therapy.