Many details of oxidative folding of proteins remain obscure, in particular, the role of oxidized glutathione (GSSG). This study reveals some unknown aspects. When a reduced ribonuclease A refolds in ...the presence of GSSG, most of its eight cysteines accomplish a very fast glutathionylation. In particular, one single cysteine, identified as Cys95 by mass spectrometry, displays 3600 times higher reactivity when compared with an unperturbed protein cysteine. Furthermore, the other five cysteines show 40-50 times higher reactivity toward GSSG. This phenomenon is partially due to a low p
value of most of these cysteines (average p
= 7.9), but the occurrence of a reversible GSSG-ribonuclease complex (
= 0.12 mM) is reasonably responsible for the extraordinary hyper-reactivity of Cys95. Neither hyper-reactivity nor some protein-disulfide complexes have been found by reacting a reduced ribonuclease with other natural disulfides i.e., cystine, cystamine, and homocystine. Hyper-reactivity of all cysteines was observed toward 5,5'-dithiobis-(2-nitrobenzoic acid). Given that GSSG is present in high concentrations in the endoplasmic reticulum, this property may shed light on the early step of its oxidative folding. The ultra-rapid glutathionylation of cysteines, only devoted to form disulfides, is a novel property of the molten globule status of the ribonuclease.
The purpose of this study was to describe and compare the spectral response of common beans desiccated with diquat and glufosinate-ammonium (GLA) using a hyperspectral terrestrial sensor and report ...how the desiccants influence dry bean visual appearance. Bean plants were desiccated with two different types of diquat and GLA desiccants. After the measurements of the spectral curves were carried out, from these values the indices of vegetation and derivatives were calculated, the chlorophyll content of the leaves on the days of the campaign was also measured. After harvesting the grains, some qualitative variables of the grains, such as cooking time and color, were evaluated Vegetation indices (VIs) in the near-infrared and mid-infrared regions of the spectrum (wavelength locations of 705, 750, 860, and 1240 nm) were significantly different between desiccant treatments (p<=0.05) two days after application (DAA). Desiccant application caused chlorophyll degradation as detected at the wavelength of 650 and 800 nm at DAA 1. The red edge and first derivatives showed that crop injury was higher in the diquat treatment because peak magnitude for this treatment became smaller over time. The desiccant application negatively affected seed quality, resulting in smaller Hue values and longer cooking time (CT). Hue angle correlated negatively with plant water content variation and CT Our results suggest that hyperespectral terrestrial sensing can differentiate the effects caused by the desiccants, showing that ammonium glufosinate causes less damage to seed quality and the water loss is like the control group.
Breast-conserving surgery (BCS) and whole breast radiation therapy (WBRT) are the standard of care for early-stage breast cancer (BC). Based on the observation that most local recurrences occurred ...near the tumor bed, accelerated partial breast irradiation (APBI), consisting of a higher dose per fraction to the tumor bed over a reduced treatment time, has been gaining ground as an attractive alternative in selected patients with low-risk BC. Although more widely delivered in postoperative setting, preoperative APBI has also been investigated in a limited, though increasing, and number of studies. The aim of this study is to test the feasibility, safety and efficacy of preoperative radiotherapy (RT) in a single fraction for selected BC patients.
This is a phase I/II, single-arm and open-label single-center clinical trial using CyberKnife. The clinical investigation is supported by a preplanning section which addresses technical and dosimetric issues. The primary endpoint for the phase I study, covering the 1st and 2nd year of the research project, is the identification of the maximum tolerated dose (MTD) which meets a specific target toxicity level (no grade 3-4 toxicity). The primary endpoint for the phase II study (3rd to 5th year) is the evaluation of treatment efficacy measured in terms of pathological complete response rate.
The study will investigate the response of BC to the preoperative APBI from different perspectives. While preoperative APBI represents a form of anticipated boost, followed by WBRT, different are the implications for the scientific community. The study may help to identify good responders for whom surgery could be omitted. It is especially appealing for patients unfit for surgery due to advanced age or severe co-morbidities, in addition to or instead of systemic therapies, to ensure long-term local control. Moreover, patients with oligometastatic disease synchronous with primary BC may benefit from APBI on the intact tumor in terms of tumor progression free survival. The study of response to RT can provide useful information about BC radiobiology, immunologic reactions, genomic expression, and radiomics features, to be tested on a larger scale.
The study was prospectively registered at clinicaltrials.gov ( NCT04679454 ).
We evaluated the presence of Porphyromonas gingivalis (Pg) DNA in the synovial tissue through synovial biopsy and in other compartments of rheumatoid arthritis (RA) patients in comparison with ...patients affected by other arthritides. Possible links with clinical, immunologic and genetic features were assessed.
Peripheral blood (PB), sub-gingival dental plaque, synovial fluid (SF) and synovial tissue samples were collected from 69 patients with active knee arthritis (32 with RA and 37 with other arthritides, of which 14 had undifferentiated peripheral inflammatory arthritis - UPIA). Demographic, clinical, laboratory and immunological data were recorded. The presence of Pg DNA was evaluated through PCR. The HLA-DR haplotype was assessed for 45 patients with RA and UPIA.
No differences arose in the positivity for Pg DNA in the sub-gingival plaque, PB and SF samples between RA and the cohort of other arthritides. Full PB samples showed a higher positivity for Pg DNA than plasma samples (11.8% vs. 1.5%, P = 0.04). Patients with RA showed a higher positivity for Pg DNA in the synovial tissue compared to controls (33.3% vs. 5.9%, P <0.01). UPIA and RA patients carrying the HLA DRB1*04 allele showed a higher positivity for Pg DNA in the synovial tissue compared to patients negative for the allele (57.1% vs. 16.7%, P = 0.04). RA patients positive for Pg DNA in the sub-gingival plaque had a lower disease duration and a higher peripheral blood leucocyte and neutrophil count. The presence of Pg DNA did not influence disease activity, disease disability or positivity for autoantibodies.
The presence of Pg DNA in the synovial tissue of RA patients suggests a pathogenic role of the bacterium. The higher positivity of Pg DNA in full peripheral blood and synovial tissue samples compared to plasma and synovial fluid suggests a possible intracellular localization of Pg, in particular in patients positive for HLA-DR4.
Paracelso y la medicina del Renacimiento en el cine D’Ottavio-Callegari, María Silvia; D’Ottavio-Cattani, Alberto Enrique; D’Ottavio-Callegari, María Eugenia
Revista de medicina y cine,
2023, Letnik:
19, Številka:
4
Journal Article
Recenzirano
Odprti dostop
La breve, azarosa y fructífera vida de Paracelso, médico del siglo XVI, motivó en 1943, aproximadamente 400 años después de su muerte, a un film homenaje alemán que rescató un fragmento de su ...existencia. El rodaje y estreno se realizó en plena segunda guerra mundial y fue controlado rigurosamente por el nazismo. Esto produjo determinadas polémicas, aún vigentes, relacionadas con su director. Este trabajo intenta dar cuenta de ambos hechos.
Purpose
This work explores the potential benefits of aligning the strategic planning process with a BPM program in a clinical research center (CRC). The purpose of this paper is to define a process ...for executing strategic planning oriented towards the promotion of a BPM program.
Design/methodology/approach
The method applied is action research. This allowed the solution of a practical problem and at the same time the proposition of a new approach to promote BPM in alignment with strategy, which was synthesized in the model presented.
Findings
The analysis and structuring of the strategic planning process, with the assessment of the as-is situation, were adequate as a preparation step for the first cycle of a BPM program in the CRC. Based on lessons learned along the research project, a model was proposed for the strategic planning process oriented towards promoting BPM.
Research limitations/implications
The model was conceived from a single application at a CRC, through a cycle of action research. This is one of the limitations of this work. The model was not yet sufficiently tested in other contexts. This represents opportunities for future research.
Practical implications
The evaluation step in the action research cycle revealed that the organization in focus was satisfied with the results. New management practices in the organizations in focus were implemented as a result of this work.
Originality/value
Process improvement initiatives are a novelty in the CRC context, and this work may serve as a reference for CRC managers seeking to improve overall performance. The proposed model in this work indicates that a BPM program should start with strategic planning. An initial assessment of the as-is situation of the organization in focus was performed based on the analysis of the undesirable effects in the organization’s management practices, using a technique of the Theory of Constraints. The use of this technique facilitated the identification of solutions to the root causes identified in the assessment. The level of the assessment was deeper in comparison to results obtained with traditional tools used in strategic planning processes. The assessment supports the definition of actions oriented to solving the majority of the management dysfunctions of the organization in focus.
Introduction
Central line‐associated bloodstream infection (CLABSI) is a public health problem that harms patients' outcomes and healthcare costs, especially in susceptible populations such as ...patients with cancer. Overall, systematic queries about etiology, risks, and epidemiology are explained by data from observational studies, which better underline the relationship between factors and incidence of disease. However, no recent systematic reviews of observational studies on adult patients with cancer have been conducted on this topic, considering the wide range of all potential factors which can contribute to the increase in infection rate in the hospitalized adults with cancer. This study systematically reviewed observational studies investigating the occurrence rate of CLABSI and its risk factors for long‐term inserted central catheter‐related infections in hospitalized adult cancer patients.
Methods
A systematic review was performed on four databases from the earliest available date until December 2020. Retrospective and prospective cohort studies focused on the occurrence rate of CLABSI and its risk factors in hospitalized adult cancer patients. The pooled occurrence rate of CLABSI (95% CI) was calculated by applying a random‐effects model.
Results
Of 1712 studies, 8 were eligible, and the data of device‐related infection rate were meta‐analyzed. The pooled occurrence rate of CLABSI was roughly 8% (95% CI 4%, 14%). The device characteristics, device's management aspects, therapies administration, and select patients' clinical conditions represent the main risk factors for long‐term catheter‐related infection in cancer patients.
Linking Evidence to Action
Considering the substantial infection rate among cancer patients, identifying risk rate factors is pivotal to support evidence‐grounded preventive strategies and maximize cancer patient safety. This study's results could guide policymakers and healthcare leaders and future research studies to disseminate appropriate risk‐reducing management culture and implement standardized research and clinical approach to the investigated phenomenon as an infection surveillance strategy.
Treatment of chronically infected wounds is a challenge, and bacterial environmental contamination is a growing issue in infection control. Ozone may have a role in these situations. The objective of ...this study was to determine whether a low dose of gaseous ozone/oxygen mixture eliminates pathogenic bacteria cultivated in Petri dishes.
A pilot study with 6 bacterial strains was made using different concentrations of ozone in an ozone-oxygen mixture to determine a minimally effective dose that completely eliminated bacterial growth. The small and apparently bactericidal gaseous dose of 20 μg/mL ozone/oxygen (1:99) mixture, applied for 5 min under atmospheric pressure was selected. In the 2nd phase, eight bacterial strains with well characterized resistance patterns were evaluated in vitro using agar-blood in adapted Petri dishes (105 bacteria/dish). The cultures were divided into 3 groups: 1--ozone-oxygen gaseous mixture containing 20 μg of O(3)/mL for 5 min; 2--100% oxygen for 5 min; 3--baseline: no gas was used.
The selected ozone dose was applied to the following eight strains: Escherichia coli, oxacillin-resistant Staphylococcus aureus, oxacillin-susceptible Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, extended-spectrum beta-lactamase-producing Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii, Acinetobacter baumannii susceptible only to carbapenems, and Pseudomonas aeruginosa susceptible to imipenem and meropenem. All isolates were completely inhibited by the ozone-oxygen mixture while growth occurred in the other 2 groups.
A single topical application by nebulization of a low ozone dose completely inhibited the growth of all potentially pathogenic bacterial strains with known resistance to antimicrobial agents.
Rectum and bladder volumes play an important role in the dose distribution reproducibility in prostate cancer adenocarcinoma (PCa) radiotherapy, especially for particle therapy, where density ...variation can strongly affect the dose distribution. We investigated the reliability and reproducibility of our image-guided radiotherapy (IGRT) and treatment planning protocol for carbon ion radiotherapy (CIRT) within the phase II mixed beam study (AIRC IG 14300) for the treatment of high-risk PCa. In order to calculate the daily dose distribution, a set of synthetic computed tomography (sCT) images was generated from the cone beam computed tomography (CBCT) images acquired in each treatment session. Planning target volume (PTV) together with rectum and bladder volume variation was evaluated with sCT dose-volume histogram (DVH) metric deviations from the planning values. The correlations between the bladder and rectum volumes, and the corresponding DVH metrics, were also assessed. No significant difference in the bladder, rectum, and PTV median volumes between the planning computed tomography (pCT) and the sCT was found. In addition, no significant difference was assessed when comparing the average DVHs and median DVH metrics between pCT and sCT. Dose deviations determined by bladder and rectum filling variations demonstrated that dose distributions were reproducible in terms of both target coverage and organs at risk (OARs) sparing.
•Boost dose is beneficial for young patients affected by breast cancer.•Intraoperative electrons (IOERT) boost and hypofractionated whole breast irradiation (HWBI) represent a suitable ...modality.•Local control with IOERT/HWBI was excellent, even in very young patients.•High tumor bed fibrosis was observed due to high cumulative EQD2 boost dose.
To evaluate outcome of intraoperative electron boost (IOERT) and hypofractionated whole breast irradiation (HWBI) for breast cancer (BC) in young women.
Women aged ≤ 48 with pT1-2 N0-1 BC received 12 Gy IOERT boost during conservative surgery followed by 3-dimensional conformal HWBI in 13 fractions (2.85 Gy/die). Local relapses (LR) and survival (disease-free, DFS; specific, BCSS; overall, OS) were analyzed.
481 consecutive BC patients, mostly node negative, with median age of 42 were treated between 2004 and 2014. Median tumor size was 1.48 cm and median IOERT collimator was 4 cm. After 25-day mean interval, HWBI was delivered. At a median follow-up of 9.6 years, there were 23 LRs (4.8 %, 9 of which were in the boost region). Ten-year LR cumulative incidence was 4.1 % (95 %CI, 2.5–6.3). Over time, local control rate decreased for Luminal A and HER2 positive with negative hormonal receptors, while remained steady for triple negative. At multivariate analysis, LR predictors included age < 40, extensive intraductal component and the use of 4-cm IOERT collimator size. Ten-year survival outcomes were as follows: DFS 80.0 % (95 % CI, 75.8–83.5), BCSS 97.5 % (95 % CI, 95.5–98.6 %), OS 96.5 % (95 % CI, 94.3–97.9). Luminal B HER2 negative had the worse survival outcomes. Perioperative complications were uncommon (16.4 %), acute toxicity was mild (<2% Grade 3), but moderate/severe fibrosis was described in 40.8 % of the cases. Cosmesis was scored as excellent/good in 86 % of the cases.
ELIOT boost and HWBI achieved an excellent local control at the cost of tumor bed fibrosis. IOERT boost dose lower than 12 Gy is advisable.
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