Evaluation of PD-L1 expression on vortex-isolated circulating tumor cells in metastatic lung cancer.

Metastatic non-small cell lung cancer (NSCLC) is a highly fatal and immunogenic malignancy. Although the immune system is known to recognize these tumor cells, one mechanism by which NSCLC can evade the immune system is via overexpression of programmed cell death ligand 1 (PD-L1). Recent clinical trials of PD-1 and PD-L1 inhibitors have returned promising clinical responses. Important for personalizing therapy, patients with higher intensity staining for PD-L1 on tumor biopsies responded better. Thus, there has been interest in using PD-L1 tumor expression as a criterion for patient selection. Currently available methods of screening involve invasive tumor biopsy, followed by histological grading of PD-L1 levels. Biopsies have a high risk of complications, and only allow sampling from limited tumor sections, which may not reflect overall tumor heterogeneity. Circulating tumor cell (CTC) PD-L1 levels could aid in screening patients, and could supplement tissue PD-L1 biopsy results by testing PD-L1 expression from disseminated tumor sites. Towards establishing CTCs as a screening tool, we developed a protocol to isolate CTCs at high purity and immunostain for PD-L1. Monitoring of PD-L1 expression on CTCs could be an additional biomarker for precision medicine that may help in determining response to immunotherapies

Air Toxics Under The Big Sky – A High School Science Teaching Tool

A project has been developed between Big Sky High School and The University of Montana (UM) which has brought together high school students and teachers, university scientists, and county environmental health officials in a multilayered research experience focusing on the collection and analysis of specific air toxics, and investigating their relationship to respiratory diseases. The Air Toxics Under the Big Sky project allows students to benefit from an independent experience linking science, research, and local environmental issues. We see this as a long term project which will be built upon and expanded by future students during each new school year and as new schools are added. This project will foster a long-term scientific collaboration between UM and Montana high schools, and establishes high school students as valuable contributors to the scientific community while educating them about environmental issues

Air Toxics under the Big Sky: A Real-World Investigation To Engage High School Science Students

This paper describes a problem-based chemistry education model in which students perform scientific research on a local environmentally relevant problem. The project is a collaboration among The University of Montana and local high schools centered around Missoula, Montana. Air Toxics under the Big Sky involves high school students in collecting air samples inside and outside their homes within and near Missoula. As part of this program, teachers, students, and university researchers investigate the relationship between air pollutants and their harmful respiratory effects. Students experience scientific research, use scientific equipment, gain an insight into the relationship between the environment and public health, and develop scientific hypotheses. UM benefits by having a pipeline of high school students, several of whom participated in the program while in high school and now attend UM. The local community benefits from the work students and university researchers have done producing high-quality data that are being used in a tracking database for respiratory disease in western Montana. Student research efforts have culminated in three annual symposia that allowed students to present their results at a public forum

Recurrence of Stachybotrys chartarum during mycological and toxicological study of bioaerosols collected in a dairy cattle shed

International audienceAgricultural occupations associated with animal breeding and the processing of animal materials in confinement systems could potentially lead to bioaerosol exposures. Moulds and mycotoxins could be constituents of bioaerosols and should be studied because of their possible involvement in respiratory diseases and cancers. In order to characterize the fungal contamination of the indoor air in a dairy barn, bioaerosols were collected during 20 days in a cattle farm located in Normandy (France). Mycobiota, mycotoxins and the mutagenicity of bioaerosols were studied. The toxigenic ability of Aspergillus flavus group and Aspergillus fumigatus isolates was also evaluated in vitro. The prevalent airborne moulds were from the following potentially toxigenic species: Aspergillus flavus group, Aspergillus fumigatus, Penicillium chrysogenum, Stachybotrys chartarum, and the allergenic species Ulocladium chartarum, Cladosporium cladosporioides. In comparison with harvesting, grain handling or broiler breeding, the concentrations of viable moulds were lower in the cattle shed. Seasonal variations in levels of several species were also observed. This study revealed that aflatoxins were detected in bioaerosols and, for the first time, showed that farmers are possibly exposed to Stachybotrys chartarum during routine barn work. Moreover, the finding of mutagenicity from bioaerosols needs further investigations on bioaerosol composition

A systematic practice review: providing palliative care for people with Parkinson's disease and their caregivers

Background: People with Parkinson’s disease has significant and increasing physical, psychosocial and spiritual needs, as well as problems with coordination and continuity of care. Despite the benefits that palliative care could offer, there is no consensus on how it should be delivered. Aim: The aim of this study is to provide a pragmatic overview of the evidence to make clinical recommendations to improve palliative care for people with Parkinson’s disease and their caregivers. Design:A systematic review method was adopted to determine the strength of evidence, supported by feedback from an expert panel, to generate the ‘do’, ‘do not do’ and ‘do not know’ recommendations for palliative care. Data sources: Searches were conducted via OVID to access CINAHL, MEDLINE, EMBASE and the Cochrane Library from 01/01/2006 to 31/05/2021. An additional search was conducted in December 2022. The search was limited to articles that included empirical studies of approaches to enabling palliative care. Results: A total of 62 studies met inclusion criteria. There is evidence that education about palliative care and movement disorders is essential. palliative care should be multi-disciplinary, individualised and coordinated. Proactive involvement and support of caregivers throughout the illness is recommended. Limited data provide referral indicators for palliative care integration. Discussions about advance care planning should be held early.Conclusions: Consideration of palliative care integration based on symptom burden and personal preferences, coordination and continuity of care are needed to maintain the quality of life of people with Parkinson’s disease and their caregivers.info:eu-repo/semantics/publishedVersio

Multisession transcranial direct current stimulation facilitates verbal learning and memory consolidation in young and older adults

This study investigated effects of multisession transcranial direct-current stimulation on learning and maintenance of novel memory content and scrutinised effects of baseline cognitive status and the role of multi-session tDCS on overnight memory consolidation. In a prospective, randomized, double-blind, parallel-group, sham-tDCS controlled design, 101 healthy young and older adults completed a five-day verbal associative learning paradigm while receiving multisession tDCS to the task-relevant left prefrontal cortex. In older adults, active multisession tDCS enhanced recall performance after each daily training session. Effects were maintained the next morning and during follow-up assessments (one week; three months). In young adults, multisession tDCS significantly increased long-term recall. Unlike previous findings in the motor domain, beneficial effects of multisession tDCS on cognitive learning and memory were not exclusively due to enhanced memory consolidation. Positive stimulation effects were primarily found in participants with lower baseline learning ability, suggesting that multisession tDCS may counteract memory impairment in health and disease

Phase 2 Study of Pemetrexed Plus Carboplatin, or Pemetrexed Plus Cisplatin with Concurrent Radiation Therapy Followed by Pemetrexed Consolidation in Patients with Favorable-Prognosis Inoperable Stage IIIA/B Non–Small-Cell Lung Cancer

IntroductionThere is no consensus chemotherapy regimen with concurrent radiotherapy (RT) for inoperable stage IIIA/B non–small-cell lung cancer. This trial evaluated pemetrexed with carboplatin (PCb) or cisplatin (PC) with concurrent RT followed by consolidation pemetrexed.MethodsIn this open-label, noncomparative phase II trial, patients with inoperable stage IIIA/B non–small-cell lung cancer (initially all histologies, later restricted to nonsquamous) were randomized (1:1) to PCb or PC with concurrent RT (64–68 Gy over days 1–45). Consolidation pemetrexed monotherapy was administered every 21 days for three cycles. Primary endpoint was 2-year overall survival (OS) rate.ResultsFrom June 2007 to November 2009, 98 patients were enrolled (PCb: 46; PC: 52). The 2-year OS rate was PCb: 45.4% (95% confidence interval [CI], 29.5–60.0%); PC: 58.4% (95% CI, 42.6–71.3%), and in nonsquamous patients was PCb: 48.0% (95% CI, 29.0–64.8%); PC: 55.8% (95% CI, 38.0–70.3%). Median time to disease progression was PCb: 8.8 months (95% CI, 6.0–12.6 months); PC: 13.1 months (95% CI, 8.3–not evaluable [NE]). Median OS (months) was PCb: 18.7 (95% CI, 12.9–NE); PC: 27.0 (95% CI, 23.2–NE). The objective response rates (ORRs) were PCb: 52.2%; PC: 46.2%. Grade 4 treatment-related toxicities (% PCb/% PC) were: anemia, 0/1.9; neutropenia, 6.5/3.8; thrombocytopenia, 4.3/1.9; and esophagitis, 0/1.9. Most patients completed scheduled chemotherapy and RT during induction and consolidation phases. No drug-related deaths were reported during chemoradiotherapy.ConclusionsBecause of study design, efficacy comparisons cannot be made. However, both combinations with concurrent RT were active and well tolerated

ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer:ANSELMA

BACKGROUND: Now that immunotherapy plus chemotherapy (CT) is one standard option in first-line treatment of advanced non-small cell lung cancer (NSCLC), there exists a medical need to assess the efficacy of second-line treatments (2LT) with antiangiogenics (AA). We performed an individual patient data meta-analysis to validate the efficacy of these combinations as 2LT. METHODS: Randomised trials of AA plus standard 2LT compared to 2LT alone that ended accrual before 2015 were eligible. Fixed-effect models were used to compute pooled hazard ratios (HRs) for overall survival (OS, main end-point), progression-free survival (PFS) and subgroup analyses. RESULTS: Sixteen trials were available (8,629 patients, 64% adenocarcinoma). AA significantly prolonged OS (HR = 0.93 [95% confidence interval {CI}: 0.89; 0.98], p = 0.005) and PFS (0.80 [0.77; 0.84], p < 0.0001) compared with 2LT alone. Absolute 1-year OS and PFS benefit for AA were +1.8% [-0.4; +4.0] and +3.5% [+1.9; +5.1], respectively. The OS benefit of AA was higher in younger patients (HR = 0.87 [95% CI: 0.76; 1.00], 0.89 [0.81; 0.97], 0.94 [0.87; 1.02] and 1,04 [0.93; 1.17] for patients <50, 50-59, 60-69 and ≥ 70 years old, respectively; trend test: p = 0.02) and in patients who started AA within 9 months after starting the first-line therapy (0.88 [0.82; 0.99]) than in patients who started AA later (0.99 [0.91; 1.08]) (interaction: p = 0.03). Results were similar for PFS. AA increased the risk of hypertension (p < 0.0001), but not the risk of pulmonary thromboembolic events (p = 0.21). CONCLUSIONS: In the 2LT of advanced NSCLC, adding AA significantly prolongs OS and PFS, but the benefit is clinically limited, mainly observed in younger patients and after shorter time since the start of first-line therapy