Treatment Intensity Research Articles

Phenolic Acids and Their Relationship to Nutritional and Technological Grain Parameters of Durum Wheat Under Variable Treatment Intensity in Central European Conditions

The objective of this two-year study was primarily the evaluation of the free and the bound forms of phenolic acids and phenolic aldehydes (PAAs) in grains of four selected cultivars of spring durum wheat subjected to three treatment intensities (GD—Green Deal, BT—Basic and IT—Intensive). All treatments included a common basic level and different spring production levels of nitrogen fertilisation (0 kg N in the case of GD; 30 kg N in the case of BT; and 60 kg N in the case of IT). Pesticide applications included herbicides and insecticides in both the BT and IT treatments, which were supplemented by combinations of fungicide and morphoregulator in the IT treatment. The GD treatment included only basic nitrogen, herbicide protection, and the application of a biostimulator (ExelGrow). The spring durum wheat cultivars subjected to testing were cultivated under Central European conditions, specifically in the Czech Republic’s central Bohemian region. UHPLC-ESI-MS/MS was used for the detection and accurate quantification of PAAs. In parallel, 12 other nutritional and basic technological parameters of the cereal were evaluated. Nine bound and seven free forms of PAAs were quantified in the analysed cereal samples. Bound forms of PAAs were dominant, accounting for 99.4% of total PAAs. Considering single PAAs, ferulic acid was the most abundant, accounting for 87% of the total bound PAAs. Interestingly, year and treatment intensity were the key factors in the variability of both free and bound PAAs, but these factors had different effects on bound PAAs. Under low nitrogen conditions, plants responded with an increase in free PAAs in particular, as well as in three bound PAAs. Unfavourable weather conditions, combined with the presence of biotic factors (e.g., Fusarium infections), significantly influenced the increase in both PAA groups, with the exception of free p-coumaric acid. PCA analysis confirmed close relationships between PAAs within both categories (free and bound). Subsequent correlation analysis further revealed that the immunoreactive gluten component (G12) exhibited a high negative correlation with the dominant ferulic acid (r = −0.70) and sinapic acid (r = −0.68). Additionally, moderate negative correlations were observed between four bound phenolic acids and grain hardness (r = −0.48–−0.60).

Impact of thermal seed treatment on spermosphere microbiome, metabolome and viability of winter wheat

Thermal seed treatment can be used as an alternative method to prevent infection by seed-borne diseases, but exposure duration and temperature during thermal treatment are important to maintain high seed viability and emergence whilst decreasing infection rate. A method for predicting suitable treatment parameters to maintain viability and eliminate seed-borne pathogens is therefore needed. Seeds of winter wheat were subjected to thermal treatment at four levels of intensity and pre-treatments with or without imbibition. Treatment impact was measured by metabolome analysis using LC-MS and GC-MS, analysis of spermosphere bacterial and fungal metagenomes using Illumina MiSeq, and detection of presence of Fusarium spp. and Microdochium spp. using ddPCR. The results showed that moderate treatment intensity reduced signs of infection and increased seedling emergence. In imbibed samples, myo-inositol concentration and myo-inositol: glucose ratio were positively correlated with treatment intensity, whereas concentrations of glucose and citric acid were negatively correlated. No correlations were found for non-imbibed samples. Imbibition had a large significant impact on microbial community composition of the wheat spermosphere. Imbibition of wheat seeds prior to thermal treatment altered wheat spermosphere microbiota. The concentration of myo-inositol, potentially in combination with glucose, could be a candidate predictor for suitable thermal treatment intensity of wheat seeds.

Clinicopathological Analysis of a European Cohort of MYOD1 Mutant Rhabdomyosarcomas in Children and Young Adults

ABSTRACTBackgroundPatients with PAX3/7‐FOXO1 fusion‐negative rhabdomyosarcomas (fnRMS) harbouring the rare L122R MYOD1 mutation have significantly poorer prognosis than other fnRMS. We undertook a detailed clinicopathological evaluation of a cohort of patients with MYOD1 mutated fnRMS in order to improve risk stratification and treatment options.ProcedureHistological, mutational and clinical data from a cohort of patients with MYOD1 mutant RMS treated in Europe were analysed.ResultsThirty‐two cases with mutant MYOD1 RMS were identified from patients enrolled in sequential European rhabdomyosarcoma clinical trials from 1992 to 2022 (n = 22) and non‐trial cohorts (n = 10). Thirty cases had the recurrent L122R missense mutation, one case harboured a K124E mutation and one case had a truncating mutation (S63X). Increased MyoD1 and reduced MYF4 immunostaining were consistent features of MYOD1L122R‐mutated RMS. Applying the risk stratification of the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 trial, among 20 localised RMS cases that could be assigned a risk category, one was Very High Risk, 13 were High Risk and six were Standard Risk. Eight patients had distant metastases at diagnosis. Of the 25 patients with adequate clinical follow‐up data, 15/25 (60%) patients had an event at a median time of 9 months (12/15 included failure of local control) and 13/25 (52%) died of disease.ConclusionThis MYOD1 mutant cohort demonstrates increased MYOD and reduced MYF4 immunostaining, high risk of local failure and poor survival in agreement with other studies. Increased treatment intensity and improved local control should be considered for these patients.

COVID-19 infection in children with blood cancer: A systematic review.

Blood cancer is the most common type of cancer and the leading cause of death by disease past infancy among children. Children with blood cancer are vulnerable population to viral infections such as coronavirus disease 2019 (COVID-19). To estimate the incidence of COVID-19 in children with blood cancer and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with blood cancer with COVID-19 illness. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature for studies on the development of COVID-19 in children with blood cancer, published from December 1, 2019 to April 30, 2023, with English language restriction. Of the 3077 papers that were identified, 155 articles were included in the systematic review (83 case report, 54 cohort and 18 case-series studies). Studies involving 1289 children with blood cancer with confirmed COVID-19 were analysed. Leukaemias (1141 cases) were the most frequent types of blood cancer observed in children who developed COVID-19, followed by non-Hodgkin's lymphomas (59 cases), Hodgkin's lymphomas (36 cases), Langerhans cell histiocytosis (7 cases), myelodysplastic syndrome (7 cases) and myeloid neoplasm (1 case). Among all 1289 blood cancer paediatric cases who transmitted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some children were documented to be admitted to the intensive care unit (ICU) (n = 175, 13.6%), intubated and placed on mechanical ventilation (MV) (n = 111, 8.6%), suffered acute respiratory distress syndrome (ARDS) (n = 144, 11.2%) or died (n = 111, 8.6%). Overall, COVID-19 in children with different types of blood cancer resulted in no or low severity of disease in 78.6% of all included cases (COVID-19 severity: asymptomatic = 238, mild = 601, or moderate = 171). Treatment for COVID-19 was not necessary in a small number of children with blood cancer (n = 94, 7.3%). Fatality in children with blood cancer with COVID-19 was reported in any of the included blood cancer categories for leukaemias (n = 99/1141, 8.7%), non-Hodgkin's lymphomas (n = 7/59, 11.9%), Hodgkin's lymphomas (n = 2/36, 5.5%), myelodysplastic syndrome (n = 1/7, 14.3%) or myeloid neoplasm (n = 1/1, 100%). Fatality rate in children with blood cancer infected with SARS-CoV-2 was the highest in patients with Hispanic ethnicity (n = 44/111, 39.6%) and COVID-19-related fatality was highest in male patients (76.5% of deceased patients). Most studies reported to alter the intensity and regimen of anticancer treatment in children with blood cancer during course of SARS-CoV-2 infection, however, many studies have reported to successfully treat COVID-19 without any changes to the anticancer treatment. Globally, leukaemias were the most prevalent and myeloid neoplasms were the least prevalent blood cancer types in children who developed SARS-CoV-2 infection. Children with blood cancer infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the healthy pediatric populations. Mortality in children with blood cancer and infected with SARS-CoV-2 was highest in cases belonging to male gender and Hispanic ethnicity. However, children with blood cancer tend to have milder COVID-19 symptoms and are less likely to be hospitalized and have better prognosis when compared to adults. Continuation of anticancer treatment in individual paediatric blood cancer patients with COVID-19 seems to be possible.

Phase II Trial of Pathology-based Tripartite Treatment Stratification for Patients with CNS Germ Cell Tumors: A Long-term Follow-up Study.

A previous Phase II clinical trial, conducted from 1995 to 2003, evaluated CNS germ cell tumors (GCTs) using a three-group treatment stratification based on histopathology. The primary objective of the study was to assess the long-term efficacy of standardized treatment regimens, while the secondary objective focused on identifying associated long-term complications. Total 228 patients were classified into three groups for treatment: germinoma (n=161), intermediate prognosis (n=38), and poor prognosis (n=28), excluding one mature teratoma case. Treatment involved stratified chemotherapy regimens and varied radiation doses/coverage. Clinical data was retrospectively analyzed at a median follow-up of 18.5 years. The treatment outcomes for germinoma, with or without syncytiotrophoblastic giant cell, were similar. The 10- and 20-year event-free survival rates for the germinoma, intermediate, and poor prognosis groups were 82/76/49% and 73/66/49%, respectively. Overall survival (OS) rates were 97/87/61% at 10 years and 92/70/53% at 20 years. Germinomas in the basal ganglia, treated without whole-brain radiation therapy (WBRT), frequently relapsed but were effectively managed with subsequent WBRT. Deaths in germinoma cases had varied causes, whereas deaths in the poor prognosis group were predominantly disease-related. Nineteen treatment-related complications were identified in 16 patients, with cumulative event rates of 1.9% at 10 years and 11.3% at 20 years. OS rates at 1 and 2 years post-relapse for tumors initially classified as germinoma, intermediate, and poor prognosis were 94/88/18% and 91/50/9%, respectively. Initial treatment intensity is crucial for managing non-germinomatous GCTs, while long-term follow-up for relapse and complications is imperative in germinomas. Irradiation extending beyond the immediate tumor site is essential for basal ganglia germinomas. Addressing relapse in non-germinomatous GCT remains a significant challenge.

Three decades of lipid-lowering therapy in type 2 diabetic patients with angiographically proven stable coronary artery disease

Abstract Lipid-lowering therapy (LLT) is key to reducing the burden of macrovascular diabetes complications. Here, we aim to assess long-term trends in LLT and LDL-C levels among patients with type 2 diabetes (T2DM) with angiographically proven coronary artery disease (CAD). We investigated T2DM patients (n=590), who were referred to elective coronary angiography and were diagnosed with CAD in one of three observational cohort studies (OS) spanning 25 years: OS1: 1999-2000 (n=190); OS2: 2005-2008 (n=241); OS3: 2022-2023 (n=159). These studies were conducted at the same cardiology unit of a tertiary care hospital in Central Europe. The proportion of patients receiving statin therapy (C10AA and C10AB) increased significantly from 57.9% in OS1 to 64.3% in OS2 and 78.6% in OS3 (ptrend<0.001). Further, there was an increase in patients receiving high-intensity statin therapy, rising from none in OS1 to 8.5% in OS2 and 73.4% in OS3 (ptrend<0.001). The proportion of patients receiving more than one LLT compound also increased (OS1: 2.1%; OS2: 2.1%; OS3: 35.2%; ptrend<0.001). Use of ezetimibe (C10AX09) increased (OS1: 0.0%; OS2: 1.2%; OS3: 39.0%; ptrend<0.001) and fibrate use (C10AB) decreased (OS1: 5.3%; OS2: 3.3%; OS3: 0.6%; ptrend=0.015). Newly approved compounds (C10AX13 - C10AX16) were prescribed for 3.8% of patients in OS3. Among statin combination therapies, ezetimibe was predominantly used (93.5%). Mean LDL-C levels declined significantly from 123±38 mg/dL (OS1) to 115±39 mg/dL (OS2) and 77±38 mg/dL (OS3; ptrend<0.001). However, only 2.2% of patients in OS1, 2.5% in OS2 and 32.1% in OS3 reached an LDL-C target of <55 mg/dL (ptrend<0.001). This analysis suggests an upward trend in treatment intensity and a substantial improvement in LDL-C levels among T2DM patients with CAD. However, the majority of these patients still does not reach their LDL-C target.

Dis-continuity in Continuity-of-Care: a pathway for more equal access to mental health care services?

Abstract Background Access to healthcare is core to achieving universal health coverage. Reaching and obtaining appropriate health care services requires engagement by health care organizations and users. For people with mental illness, access emerges as a continuous process, reflecting oscillating health conditions. This challenges aspirations of continuity of care (COC), but we know little about the experiences of users. Methods We carried out observations of interactions between professionals and users (n = 18) and semi-structured interviews with users, professionals, and managers (n = 33) in the specialised mental health services in Central Denmark Region and FACT-inspired teams in three municipalities. We also conducted 3 focus groups with regional and municipal professionals from these teams. Data was analysed through a qualitative thematic analysis. Results From the perspective of users, COC builds on the acknowledgment of their entire life situation. For users, this is about making connections between their past, present and future lives. Past experience affect their present abilities to follow treatment and influence future hopes and expectations. The acknowledgment of these connections often translates into spaces of discontinuity in continuity, where users need occasional breaks from treatment but worry about being excluded from treatment. Crucially, the organization of the FACT-inspired teams allows for flexibility in the intensity of visits and treatment. The norms of professionals also support users’ perspectives on COC, as the norms focus on building trust in the relations between users and professionals. Conclusions One important step to achieve more equal access is to integrate the social world of users. This requires organizational and professional approaches that allow for user needs for dis-continuity in COC. Key messages • For mental health service users, continuity-of-care includes breaks from treatment (discontinuity). • More equal health access requires adapting continuity-of-care to needs as perceived by users.

Modeling a biofluid-derived extracellular vesicle surface signature to differentiate pediatric idiopathic nephrotic syndrome clinical subgroups

Idiopathic Nephrotic Syndrome (INS) is a common childhood glomerular disease requiring intense immunosuppressive drug treatments. Prediction of treatment response and the occurrence of relapses remains challenging. Biofluid-derived extracellular vesicles (EVs) may serve as novel liquid biopsies for INS classification and monitoring. Our cohort was composed of 105 INS children at different clinical time points (onset, relapse, and persistent proteinuria, remission, respectively), and 19 healthy controls. The expression of 37 surface EV surface markers was evaluated by flow cytometry in serum (n = 83) and urine (n = 74) from INS children (mean age = 10.1, 58% males) at different time points. Urine EVs (n = 7) and serum EVs (n = 11) from age-matched healthy children (mean age = 7.8, 94% males) were also analyzed. Tetraspanin expression in urine EVs was enhanced during active disease phase in respect to the remission group and positively correlates with proteinuria levels. Unsupervised clustering analysis identified an INS signature of 8 markers related to immunity and angiogenesis/adhesion processes. The CD41b, CD29, and CD105 showed the best diagnostic scores separating the INS active phase from the healthy condition. Interestingly, combining urinary and serum EV markers from the same patient improved the precision of clinical staging separation. Three urinary biomarkers (CD19, CD44, and CD8) were able to classify INS based on steroid sensitivity. Biofluid EVs offer a non-invasive tool for INS clinical subclassification and “personalized” interventions.

Circulating Amyloid beta 1-40 is independently associated with statin treatment and LDL cholesterol reduction: a prospective cohort study

Abstract Background Accumulating evidence suggests that circulating amyloid beta 1-40 (Aβ40), a pro-inflammatory and pro-atherogenic peptide, is associated with atherosclerotic cardiovascular disease (ASCVD), providing incremental prognostic value and risk stratification refinement in primary and secondary prevention settings. Existing evidence supports conflicting off-target effects of statins on plasma Aβ40. We aim to explore the impact of cardiovascular risk reduction through statin therapy on Aβ40 plasma levels in subjects with dyslipidemia and with/without ASCVD. Methods In this prospective study, patients with dyslipidemia who visited for the first time our lipid clinic for risk stratification and treatment plan assessment (n=146) were consecutively recruited. Αβ40 was measured in plasma samples by enzyme-linked immunosorbent assay at baseline and after a mean follow-up of 5.2 and 15 months. Patients in whom statin treatment was initiated or intensified in terms of dose or regimen (n= 68) were compared against patients not treated with statins or with unchanged statin intensity (n = 78). Statin intensity treatment was defined based on the European Society of Cardiology (ESC) guidelines. Results Increased Aβ40 plasma levels at baseline were associated with ASCVD presence, decreased glomerular filtration rate (GFR), and history of heart failure (p<0.05 for all). An increase in Aβ40 circulating levels between baseline and follow-up 1 was observed in patients in whom statin treatment was initiated or intensified (p=0.041). However, in patients not treated with statins or treated with unchanged statin intensity, an increase in Aβ40 circulating levels was observed between follow-up 1 and follow-up 2 (p=0.05, Figure 1A). These changes in Aβ40 were significantly different between the two groups during the short follow-up period (β=0.226, p for interaction =0.025) independently from age and changes in GFR, systolic blood pressure, and LDL-C. Additionally, patients who achieved a reduction in low-density lipoprotein cholesterol (LDL-C) ≥ 50% in follow-up 2 have unchanged Aβ40 levels during the long follow-up period, while an increase in Aβ40 was observed in the rest population (p=0.012, Figure 1B). These changes were significantly different between the two LDL-C groups independently of statin treatment and changes in high sensitive C-reactive protein (hs-CRP) (β= -0.231, p for interaction=0.035). Conclusion In a dyslipidemic population, statin initiation or intensification and LDL-C decrease showed a short-term increase and a long-term return to initial levels, respectively, in circulating Aβ40 levels. From a mechanistic point of view, our findings suggest that statins have an impact on Aβ40, possibly through an LDL-C-dependent and a non-LDL-C-dependent pathway. Further studies are needed to evaluate the utility of circulating Aβ40 as a novel biomarker in ASCVD risk reduction assessment.

Comparative insights into type non-A non-B vs type B acute aortic syndromes and their blood pressure management: a monocentric, retrospective, 11-year study

Abstract Background Acute aortic syndromes (AAS) are classified either as type A, if the ascending aorta is involved, or as type B, if only the descending aorta is; AAS affecting the aortic arch, alone or in combination with the descending aorta, have recently been classified as type non-A-non-B (NANB). Few and discordant data are available about the differences between type B and type NANB AAS, especially in terms of presentation, management and prognosis. Little evidence also exists about the effects of blood pressure (BP) management, peaks and variability on in-hospital outcomes in such context. In particular, the largest international AAS registry suggests a comparable course and prognosis, while a recent meta-analysis indicates a poorer clinical outcome with higher rate of complications, need of invasive treatment and mortality in the case of type NANB AAS. Methods We conducted a monocentric, observational, analytical, retrospective registry study including all patients ≥ 18 years old admitted to our tertiary referral hospital with a diagnosis of type B or type NANB AAS from January 2011 to December 2021. Epidemiological, clinical, operative and outcome data were analyzed by comparing type B and type NANB AAS patients. We also focused on systolic and diastolic BP, in terms of both peak values as well as BP variability (BPV); BPV was defined as the difference between the peak and the through value on a certain day. Blood pressure variables were analyzed in relationship with mortality and the failure of an initial conservative management. Results 274 type B and 44 type NANB AAS patients were enrolled. The only significant differences between the two groups were a higher rate of pre-operative complications in type NANB patients (p=0.002) resulting in a higher rate of invasive management (p=0.005), particularly as failure of an initial conservative strategy (p=0.018). However, comparable rates of post-operative complications and in-hospital mortality (overall 7%) were observed. In the overall population, lower limb ischemia, ST segment depression, and post-operative visceral ischemia were associated with higher in-hospital mortality. Peri-aortic effusion was independently associated with failure of conservative management, whereas diagnosis of intramural hematoma (as opposed to other subtypes of AAS) appeared to be protective. Among all BP variables (including anti-hypertensive treatment intensity and daily systolic or diastolic BP peaks and variability), only peak systolic BP on day 5 was found to be non-independently associated with a higher risk of in-hospital mortality and failure of an initially conservative strategy. Conclusions In our study type NANB AAS were more often complicated and treated invasively than type B AAS, while having the same rates of post-operative complications and overall mortality. BP peaks had only a minor effect on outcomes, while BPV and BP management intensity did not have any significant impact.OutcomesBlood Pressure

Outcomes of post-acute coronary syndrome patients enrolled in a phase 2 cardiac rehabilitation program

Abstract Introduction Cardiac rehabilitation (CR) is a class I recommendation in the management of patients with acute coronary syndrome (ACS), namely ST-elevation myocardial infarction (STEMI) and non-ST acute coronary syndrome (NST-ACS). Reported mortality and recurrent cardiovascular (CV) events are still unacceptably high in these patients. Purpose To assess CV outcomes of patients enrolled in a CR program and its association with ACS presentation. Methods Single-center, retrospective observational study that included all consecutive post-ACS patients enrolled in a phase 2 CR program in 2017, with a follow-up of 24 months. Group 1 were patients with STEMI; group 2 were patients with NST-ACS. Major adverse cardiovascular events (MACE) were defined as a composite of death, non-fatal ACS, non-fatal stroke, and unplanned revascularization. Results Of the 202 ACS patients who attended the CR program in 2017, 4 were excluded due to missing data. Of the 198 patients analyzed (age 60.3±10.7 years, 82% male), 101 patients had a STEMI and 97 NST-ACS. STEMI patients were significantly younger (57±9.5 vs. 63±10, p<0.001), with fewer CV risk factors (diabetes 16% vs. 32%, p=0.008; hypertension 51% vs. 72%, p=0.002; obesity 17% vs. 31%, p=0.020; dyslipidemia 54% vs. 77%, p<0.001), except for active smoking (53% vs. 29%, p=0.001), and were less likely to have previous history of coronary artery disease (9% vs. 31%, p<0.001). During the 3-month CR program, both groups achieved significant reduction in body mass index, LDL-Cholesterol, functional capacity, and smoking cessation rates. At 3-, 12-, and 24-months evaluation, both groups showed no differences in risk factor management, nor differences in lipid-lowering therapy, namely percentage of high-intensity statin and ezetimibe use. STEMI patients were treated more frequently with ticagrelor (86% vs. 67%, p=0.001) at baseline. MACE occurrence was significantly lower in STEMI patients (11% vs. 28%, p=0.003), driven mainly by recurrent ACS (4% vs. 15%, p=0.006). Conclusions In our study, NST-ACS patients had significantly higher CV disease burden and worse outcomes at 24-month follow-up. Despite the heightened CV risk in this group, secondary prevention treatment intensity was similar in both groups.

Does the distribution of light intensity within the barn impact broiler production and welfare?

ABSTRACT 1. The objective of this study was to determine if rearing broilers under variable light intensity (VLI) impacted their welfare or productivity. 2. Ross 308 broilers (n = 7,256) were reared until 35 d of age and exposed to a uniform intensity of 10 lux (CON) or VLI with low intensity areas of 2–5 lux proximal to the walls and high intensity areas of 84–133 lux proximal to feeders. 3. The data were analysed as a complete randomised design using an analysis of variance. Significance was declared when p ≤ 0.05. 4. Applying VLI resulted in increased feed intake early in life but had no impact on body weight. Overall efficiency was improved in the CON treatment. Mortality diagnoses of skeletal problems were reduced under VLI. Treatment had no impact on footpad, hock or gait score, heterophil to lymphocyte ratio or melatonin concentration. Birds performed certain behaviours in specific locations within the room, independent of light intensity treatment. 5. In conclusion, raising broilers under VLI had little impact on production or most welfare parameters assessed in this study. However, satisfying the bird’s preference for different light intensities may improve welfare.

Effect of Different Intensities of Leaf Removal on Tomato Development and Yield

Defoliation (leaf removal or pruning) is a common practice in tomato production that makes crops more manageable, prevents conditions conducive to fungal attack and increases the exposure of the fruit to light, especially in winter conditions. The intensity and frequency of leaf removal on commercial farms often vary according to workforce availability criteria, which makes it difficult to determine their effect on tomato crop yields. It would be reasonable to think that a reduction in leaf area influences radiation interception and, therefore, the production of assimilates and biomass. However, in intensive production systems with a high leaf area index (LAI), leaf pruning can increase radiation interception, either by reducing competition between productive and vegetative organs or by increasing radiation use efficiency. This study was therefore designed to assess the effect of different intensities and frequencies of basal leaf removal on dry matter production and partitioning between the different organs of the plant, and thus on tomato crop productivity. A series of trials were conducted over three consecutive seasons, with a trial conducted per season: (a) Trial 1: leaf removal control—LRC (with leaves removed from the base to two leaves below the truss close to harvest, T0) was compared with LR1 (leaf removal from the base to two leaves below the truss above T0, i.e., T1) and LR2 (two trusses above T0 (T2)); (b) Trial 2: LRC compared with LR2 and LR4 (four trusses above T0 (T4)), carried out at two frequencies; and (c) Trial 3: LRC compared with an intense leaf removal treatment (LRI) whereby between 10 and 12 leaves were left on each stem. LAI saturation values under our conditions were found to be around 2.0. No significant differences in yield were found between the control and treatments LR1, LR2 and LR4, with a reduction in the number of leaves of up to 35% and LAI values during harvest above 2.0. The intense leaf removal treatment (LRI), which reduced the number of leaves by 47% and the LAI value from 2.8 to 1.5 compared to the control, resulted in a 15% reduction in dry biomass and a 17% decrease in fruit yield.

Feasibility and Acceptability of a Palliative Care Intervention Among Older or Adults with Advanced CKD and their Caregivers.

In non-nephrology settings, specialty Palliative Care (PC) improves decision-making, patient's quality of life (QoL), advance care planning (ACP), and certain indicators of the quality of end-of-life (EoL) care. This pilot RCT explored the feasibility and acceptability of a PC intervention, CKD-EDU, for older adults ≥75 years with eGFR ≤25 ml/min and their caregivers. Participants randomized to the control group received standard nephrology care and routine kidney therapy (KT) education, while those randomized to CKD-EDU received a decision aid and met with a PC clinician up to three times to discuss KT decisions and EoL planning. Patients were assessed at baseline, 4-6, 12-14, and 24-26 weeks. Main outcomes included intervention feasibility and acceptability, decision-conflict, and patient QoL. The mediating effects of reduced decision conflict on improved QOL were explored, as were the effects of CKD-EDU on ACP, EoL treatment intensity and 6-month-hospitalization. Statistical analyses encompassed descriptive analyses, adjusted repeated-measure-models, mediation analyses and logistic-regression models. Among the 127 eligible patients screened, 58 (44%) consented: 30 were randomized to CKD-EUD and 28 to the control arm. All patients completed baseline assessments, and 89% completed at least one intervention session (n=26/29), underscoring intervention adherence and feasibility. Similarly, assessments completion rates at 4 (83%, n=45/54) ), 12 (93%, n=42/45), and 24 (95%, n=40/42) weeks were high. The intervention received over 85% acceptability ratings for all questions. Patients exposed to CKD-EDU exhibited significant improvement in decisional conflict scale scores (P = 0.003) at 4-6 weeks and improvements in QoL at 24-26 weeks (P=0.02). Exploratory analyses were not statistically significant in this pilot, but all effect sizes were in the predicted direction. This study demonstrates the feasibility and acceptability of CKD-EDU. A larger scale trial is warranted to assess its effectiveness in improving key outcomes important to patients and families.

Predicting non-responders to lifestyle intervention in prediabetes: a machine learning approach.

The clinical care process for people with prediabetes starts with lifestyle intervention, often escalating to more intense treatment due to the low success rate of the first-line intervention. Clinicians lack clear guidelines on which patients would benefit from early treatment with more intensive therapeutic options, so we aimed to develop an algorithm to early identify non-responders to lifestyle intervention for prediabetes. Several statistical and machine learning algorithms were screened with internal cross-validation on the basis of accuracy and discrimination ability to correctly classify patients that would fail to normalize fasting glycemia within one year of being prescribed a lifestyle intervention, solely based on the first examination measurements. Of the many screened algorithm, only a random forest model performed with sufficient accuracy to exceed the historical failure rate of patients within our center, with an accuracy of 0.689 (CI 0.669, 0.710) and an AUROC of 0.687 (CI 0.673, 0.701). This study showcases the ability of machine learning models to provide useful insight in clinical practice leveraging knowledge contained in routinely collected data.

Prioritising Patients and Planet: Advocating for Change in Respiratory Care

The global burden of respiratory diseases, particularly asthma and chronic obstructive pulmonary disease (COPD), continues unabated. Suboptimal management places a significant strain on both patients and urgent or emergency care services. With an ageing population in many countries, the demand for these services is set to increase further. At the same time, healthcare systems are striving to reduce their carbon footprint and achieve net zero emissions, as the healthcare sector is a significant contributor to carbon emissions worldwide. Although these two goals may appear contradictory, they need not be in conflict. This article reviews an industry-sponsored symposium held at the European Respiratory Society (ERS) Congress 2024 in Vienna, Austria, in September 2024. The session addressed the urgent need to change the delivery model for respiratory healthcare in response to the increasing prevalence of respiratory diseases and the challenges posed by climate change. Co-chair John Hurst, Professor of Respiratory Medicine at University College London (UCL), UK, underscored the importance of innovative solutions for managing respiratory diseases and highlighted the challenges faced by healthcare decision-makers. This was further elaborated on by Omar Usmani, Professor of Respiratory Medicine at Imperial College London, UK, who emphasised the importance of clinical choice. He stated that inhaled medicines, which form the cornerstone of treatment, should not be considered interchangeable. He also discussed ongoing efforts to maintain access to essential medicines by developing novel next-generation propellants (NGP) for pressurised metered-dose inhaler (pMDI) devices, which will reduce their carbon footprint to levels comparable with dry powder inhalers (DPI). Additionally, he described the European Chemicals Agency (ECHA) proposal to restrict a broad range of chemicals classed as per- and polyfluoroalkyl substances (PFAS). This precautionary measure would affect both current propellants in pMDIs and the transition to NGPs, with global implications for inhaled medicines. Erika Penz, Associate Professor of Respirology, Critical Care, and Sleep Medicine at the University of Saskatchewan, Canada, noted that suboptimal management of respiratory disease is associated with a disproportionately high burden on both patients and the environment. The forthcoming availability of pMDI medicines with NGPs alone will not resolve this larger issue. As every healthcare interaction carries a carbon footprint, which increases with the intensity of treatment, the implementation of guidelines into clinical practice would improve patient outcomes and reduce the demand on healthcare services and the associated carbon emissions. Co-chair Helen Reddel, Clinical Professor and Research Leader at the Woolcock Institute of Medical Research, Australia, concluded by re-emphasising the urgent need to implement guidelines immediately for the benefit of both patients and the environment.

New South Wales alcohol and other drug service providers' perceptions of the relative importance of client variables for determining treatment need.

This study examines alcohol and other drug (AOD) service providers' perceptions of the most important variables (client complexity and demographic) for determining treatment need and intensity of intervention. Online cross-sectional survey of N = 188 clinicians/service managers working in AOD services across metropolitan and regional/rural New South Wales, Australia. Participants ranked the importance of demographic and family factors, substance use, physical health, mental health, functioning and activities of daily living and youth-specific variables in identifying treatment need (five-point Likert scales). More than 90% of participants ranked 43 out 56 potential variables as 'very important'/'essential' in identifying treatment need. The 10 variables most ranked as 'very important'/'essential' were 'pregnant or breastfeeding' (95.2%), 'suicide/self-harm' (95.2%), 'overdose risk' (94.7%), 'abuse/neglect' (among youth/adolescent populations; 94.1%), 'mental health severity' (93.6%), 'dependent children' (93.1%), 'co-existing mental health concerns' (93.0%), 'hospitalisations due to mental health' (92.5%), 'child protection concerns' (among youth/adolescent populations; 92.2%) and 'disability' (91.5%). The 10 variables most commonly ranked as 'slightly important'/'not at all important' included 'citizenship' (63.3%), 'sex' (59.6%), 'country of birth' (54.8%), 'highest education' (50.0%), 'sexual orientation' (44.1%), 'relationship status' (33.5%), 'gender' (31.4%), 'transport' (28.2%), 'employment' (23.9%) and 'refugee status' (24.0%). Some ratings differed by geographic location (metropolitan vs. regional/rural) and job role (allied health worker, nurse, doctor or manager). This study provides insight into service providers' perceptions of treatment need and intensity associated with a range of client factors. It is a first step towards improvements in routine data collections that are used to inform treatment planning.

Advances in Research on the Improvement of Low-Salt Meat Product Through Ultrasound Technology: Quality, Myofibrillar Proteins, and Gelation Properties.

The high sodium content in meat products poses health risks to consumers and does not align with modern green and healthy living standards. Current strategies for directly reducing the sodium content in meat products are limited by their negative impact on the sensory or quality attributes of the products. In recent years, there has been great interest in applying ultrasound technology to reduce sodium content. This paper discusses the advantages and disadvantages of current mainstream strategies for reducing the sodium content in meat products, as well as the potential mechanisms by which ultrasound-assisted marination improves the quality of low-salt meat products. The main findings indicate that ultrasound, through its cavitation and mechanical effects, facilitates the transition of proteins from stable insoluble aggregates to stable soluble complexes, exposing more hydrophilic groups and, thus, enhancing protein solubility. At the same time, ultrasound promotes a greater number of proteins to participate in the formation of interfacial layers, thereby increasing emulsifying activity. Furthermore, ultrasound treatment promotes the interaction between proteins and water, leading to partial unfolding of protein chains, which allows polar residues to more readily capture water in the gel, thereby improving the water-holding capacity of the gel. These effects will contribute to the formation of high-quality low-salt meat products. However, variations in the frequency, intensity, and duration of ultrasound treatment can lead to differing effects on the quality improvement of low-salt meat products.

Fibrin-Associated Large B-Cell Lymphoma in a Young Patient in the Setting of Pleural Effusion

Abstract Introduction/Objective Fibrin-associated large B-cell lymphoma (FA-LBCL) is a proliferation of EBV-positive large B- cells in association with fibrinous debris, typically in the context of prostheses, hematomas, pseudocysts and myxomas. It is a newly described entity and is extremely rare, with no deaths reported as a direct result. It is indolent and not visible on imaging, instead being found incidentally on microscopy. It is mainly a diagnosis of exclusion and is characterized by sheets of neoplastic lymphocytes contained within a fibrin background. The median age of presentation is 55, with 75% of cases being reported among elderly patients. The prognosis is excellent and surgery is considered curative. It needs to be distinguished from malignant lymphomas, mainly diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI), which is also EBV-positive but occurs in elderly patients with a longstanding history of inflammation. The two have identical immunohistochemical profiles but vastly different clinical presentations and outcomes. Methods/Case Report A 35-year-old male with end-stage renal disease and a history of recurrent pleural effusions presented with dyspnea. CT showed a large loculated right-sided pleural effusion with no lymphadenopathy. Pleural fluid cytology was negative for any malignant cells. He underwent decortication to relieve pleural rind constriction. Microscopy revealed small layers of fibrin with an infiltrate of atypical, EBV-positive B-cells with a Ki-67 index of 60%. As the morphological findings and clinical presentation did not fit other known lymphomas, the case was signed out as FA-LBCL. The patient has followed up with oncology and PET scans have been negative for any malignancy. He is currently on the waiting list for a renal transplant. Results (if a Case Study enter NA) NA Conclusion FA-LBCL is a rare benign neoplasm, identified incidentally and cured by surgical resection. It is mainly diagnosed in the elderly, but the number of cases is limited and the age distribution may be skewed. This case involved a much younger patient and is the first known diagnosis in the pleural setting. It is important to differentiate this entity from DLBCL-CI, which is aggressive and requires intense oncological treatment. In addition, patients with FA-LBCL can undergo immediate solid organ transplantation, whereas those with DLBCL-CI need to be in remission for at least three years before receiving a transplant.

Sublethal Damage Caused by Cold Plasma on Bacillus cereus Cells: Impact on Cell Viability and Biofilm-Forming Capacity.

The Bacillus cereus group represents a serious risk in powdered and amylaceous foodstuffs. Cold plasma (the fourth state of matter) is emerging as an alternative effective nonthermal technology for pasteurizing a wide range of matrices in solid, liquid, and powder form. The present study aims to evaluate the mechanisms involved in Bacillus cereus inactivation via cold plasma, focusing on (i) the technology's ability to generate damage in cells (at the morphological and molecular levels) and (ii) studying the effectiveness of cold plasma in biofilm mitigation through the direct effect and inhibition of the biofilm-forming capacity of sublethally damaged cells post-treatment. Dielectric barrier discharge cold plasma (DBD-CP) technology was used to inactivate B. cereus, B. thuringiensis, and B. mycoides under plasma power settings of 100, 200, and 300 W and treatment times ranging from 1 to 10 min. Inactivation levels were achieved in 2-7 log10 cycles under the studied conditions. Percentages of sublethally damaged cells were observed in a range of 45-98%, specifically at treatment times below 7 min. The sublethally damaged cells showed poration, erosion, and loss of integrity at the superficial level. At the molecular level, proteins and DNA leakage were also observed for B. cereus but were minimal for B. mycoides. Biofilms formed by B. cereus were progressively disintegrated under the DBD-CP treatment. The greater the CP treatment intensity, the greater the tearing of the bacteria's biofilm network. Additionally, cells sublethally damaged by DBD-CP were evaluated in terms of their biofilm-forming capacity. Significant losses in the damaged cells' biofilm network density and aggregation capacity were observed when B. cereus was recovered after inactivation at 300 W for 7.5 min, compared with the untreated cells. These results provide new insights into the future of tailored DBD-CP design conditions for both the inactivation and biofilm reduction capacity of B. cereus sensu lato species, demonstrating the effectiveness of cold plasma and the risks associated with sublethal damage generation.