Weeks Of Levels Research Articles

Jumbo quail responses to diets containing incremental levels of apple (Malus domestica Borkh) pomace

The utilization of nutraceutical sources such as apple (Malus domestica Borkh) pomace powder (APP) could be a strategy to reduce the excessive disposal of this agro-waste in landfills and promote sustainable Jumbo quail (Coturnix sp.) production. However, the amount of the APP that can be included in Jumbo quail diets to achieve optimum production is unknown. This study evaluated the impact of including incremental levels of APP on performance metrics, haemato-biochemical parameters, and meat quality responses in Jumbo quail. A total of 350 Jumbo quail (7-day-old; 28.0 ± 0.817 g live weight) were weighed and randomly allotted to five dietary treatments, where each treatment had seven replicates with 10 birds each. The diets were formulated to contain 0, 25, 50, 75, and 100 g/kg APP. Dietary APP induced negative quadratic effects (p < 0.05) on feed intake in weeks 2 and 3. Body weight gain and gain-to-feed ratio decreased linearly in weeks 2, 3, and 4, but quadratically responded to APP levels in week 5. Platelets, heterophils, lymphocytes, and serum phosphorus and calcium showed linear or quadratic responses (p < 0.05) as APP levels increased. Increasing levels of APP linearly (p < 0.05) reduced carcass performance and 24-hour breast meat redness and chroma values but increased 1-hour yellowness and 24-hour lightness. The inclusion of APP compromised growth and carcass performance in young growing Jumbo quail. However, feed efficiency and final body weight were maximized between 50 and 75 g APP levels/kg diet in five-week-old Jumbo quail without compromising blood and meat quality parameters.

Dietary incorporation of brown seaweed spent oyster mushroom substrate alters growth performance, physiological responses and meat quality parameters in Boschveld roosters

Use of brown seaweed (Ecklonia maxima) as a nutraceutical source in indigenous chicken diets is limited by high dietary fibre levels. Inoculating seaweeds with oyster mushroom (Pleurotus ostreatus) spawn (OMS) could enhance the utility of the spent mushroom substrate (SMS). This study investigated the effect of feeding incremental levels of brown seaweed SMS on growth performance, physiological responses, and meat quality parameters in Boschveld roosters. A total of 324, 4-week-old Boschveld roosters were weighed and randomly allotted to 36 pens (9 birds per pen) to produce six replicates per dietary treatment. The diets were formulated as follows: a standard grower diet (CON); and CON containing 150 g/kg of brown seaweed inoculated with OMS at 0 (SMS0), 20 (SMS20), 30 (SMS30), 40 (SMS40) and 50% (SMS50). Birds fed diet CON had the least feed intake (p < 0.05) than all the other SMS treatment levels in weeks 7, 8, 12, 14 and 15. Diet SMS40 promoted higher (p < 0.05) body weight gain (BWG) than CON in weeks 6, 7, 9 and 14. Gain-to-feed ratio linearly increased in weeks 7 [R2 = 0.288; p = 0.010], 11 [R2 = 0.581, p = 0.0001] and 14 [R2 = 0.389, p = 0.004], respectively. Quadratic responses (p < 0.05) were observed for BWG in week 5, white blood cells, heterophils, platelets, lymphocytes, monocytes, and relative spleen and large intestine weights as OMS levels increased. Linear increases were recorded for slaughter [R2 = 0.197, p = 0.017] and breast weights [R2 = 0.197, p = 0.020] as OMS levels increased. Diet SMS0 promoted higher (p < 0.05) relative caeca weights than the CON and SMS treatment groups. Neither quadratic nor linear responses (p > 0.05) were observed for breast meat quality parameters. In conclusion, feeding brown seaweed SMS improved growth performance and slaughter weight, altered some blood parameters and internal organs, without affecting breast meat quality of Boschveld roosters. Based on the quadratic response for BWG, the optimum OMS level was deduced at 20% in a brown seaweed-based Boschveld rooster diet.

Effects of Transition from Remote to In-Person Learning in University Students: A Longitudinal Study.

Previous studies have shown that the transition from the University environment to remote learning impacted student mental health. Our study aimed to investigate the effects of university environment on anxiety and depressive symptoms in health sciences students. Students at the Technical University of Manabí, Ecuador, with 6-10 in-person semesters, who shifted to remote learning and then returned to face-to-face learning were selected. Students responded to the General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). In addition, questions regarding social interaction, physical exercise, mood and sleep habits were also asked. This longitudinal study tracked 323 students during the return to in-person classes and term end. The results showed similar rates of anxiety (GAD-7, p = 0.011-p = 0.002) and depression (PHQ-9 p = 0.001-p = 0.032) among students at week 1 and week 15. Previous diagnosis of depression (OR, 0.171; CI 0.050-0.579, p < 0.005) was shown to correlate with depression levels in week 1, with no changes seen at follow-up. Anxiety levels were shown to be associated with a previous diagnosis of the disorder at week 1, but not at follow-up (OR 0.233; CI 0.085-0.643, p < 0.005). The return to in-person learning among university students maintained levels of anxiety and depressive symptoms, underscoring ongoing vulnerabilities to mental health disorders in this group.

Exploring the prognostic significance of β-HCG levels in cervicovaginal secretions and maternal risk factors for early birth.

Preterm birth is one of the leading causes of death in the perinatal period, this study was conducted to investigate the predictive value of β-HCG Levels in cervicovaginal secretions and maternal risk factors in preterm delivery. This cross-sectional study was conducted over a six-month period from January 1 to June 30, 2021, in Baghdad hospitals. The data were collected and used from the mothers who went to the hospital for delivery. Demographic information of patients and some risk factors were investigated. Vaginal secretions were sampled with a cotton swab. β-HCG level in weeks 29, 31, 33, and 35 was measured by ELISA method. Data were analyzed with SPSS Ver 25 software and a significance level of less than 0.05 was considered. The mean age of the study participants was 28.29 ± 5.68 years. There was a significant difference in the level of β-HCG between women with full-term delivery and pre-term women in weeks 29, 31, 33, and 35 of pregnancy (P ≤ 0.001). Maternal factors such as age older than 35 years, BMI, history of thyroid disease, blood pressure, premature rupture of the amniotic sac, parity, twin and multiple births, and decreased amniotic fluid volume have been identified as factors affecting preterm delivery. The β-HCG level can also be a helpful marker for preterm birth.

Suppression of pathogens in properly refrigerated raw milk

Conflicting claims exist regarding pathogen growth in raw milk. A small pilot study was designed to provide definitive data on trends for pathogen growth and decline in raw bovine milk hygienically produced for direct human consumption. An independent laboratory conducted the study, monitoring growth and decline of pathogens inoculated into raw milk. Raw milk samples were inoculated with foodborne pathogens (Campylobacter, E. coli O157:H7, Listeria monocytogenes, or Salmonella) at lower (&lt;162 colony forming units (CFU) per mL) and higher levels (&lt;8,300 CFU/mL). Samples were stored at 4.4°C and quantified over time after inoculation (days 0, 3, 6, 9, 12, and 14) by standard culture-based methods. Statistical analysis of trends using the Mann-Kendall Trend Test and Analysis of Variance were conducted for 48 time series observations. Evidence of pathogen growth was documented for L. monocytogenes in 8 of 12 replicates (P = 0.001 to P = 0.028). Analysis of variance confirmed significant increases for L. monocytogenes at both initial levels in week 2. No evidence of growth was documented over 14 days for the three pathogens predominantly associated with raw milk outbreaks in the US (Campylobacter, E. coli O157:H7, and Salmonella). Further research is needed to characterize parameters for pathogen growth and decline to support re-assessment of risks that were based on incorrect assumptions about interactions of pathogens with the raw milk microbiota.

The Use of Wearable Activity Monitors to Measure Upper Limb Physical Activity After Axillary Lymph Node Dissection and Sentinel Lymph Node Biopsy

BackgroundWe suspect that morbidity from both sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) has been inadequately evaluated to date. Current methodologies are subjective and susceptible to bias. Objective assessment using wearable activity monitors (WAMs) would allow quantitative analysis of recovery by measuring physical activity (PA) and could provide evidence for axillary de-escalation.Patients and MethodsA prospective, single center, observational study was conducted from February 2020 to May 2022. Consecutive patients undergoing breast and/or reconstructive surgery and axillary surgeries were identified from the operating schedules. Patients wore WAMs for an average of 3 days prior to surgery and up to 2 weeks following surgery. In total, 56 patients with breast cancer were recruited, of whom 35 underwent SLNB and 21 ALND.ResultsPatients who underwent ALND experienced significantly worse PA compared with those who underwent SLNB in week 2 (median 66.4% versus 72.7%, p = 0.015). Subgroup analysis revealed significantly lower PA in simple mastectomy (Mx)-ALND versus Mx-SLNB (median 90.3% versus 70.5%, p = 0.015) in week 2. The PA for SLNB did not return to baseline at 2 weeks after surgery.ConclusionsCompared with SLNB, ALND results in a lower PA level in week 2. The findings also indicate that SLNB has a protracted effect on PA levels, which extend to 2 weeks postoperatively. Monitoring recovery objectively following breast cancer surgery provides patients and surgeons with more information regarding the predicted outcomes of their surgery, which can drive the development of a personalized rehabilitation program.

#5864 EFFECT OF IV FERRIC CARBOXYMALTOSE ON PHYSICAL PERFORMANCE AND QOL IN PATIENTS WITH CKD NOT ON DIALYSIS, MILD ANEMIA AND IRON DEFICIENCY

Abstract Background and Aims Iron deficiency (ID) in patients with chronic kidney disease (CKD) is highly prevalent and contributes to a poorer quality of life. According to current guidelines, treatment with intravenous (IV) iron is limited to CKD patients with ID and anemia to avoid/delay the use of erythropoiesis-stimulating agents (ESAs) or the reduce the doses of ESA in patients treated with these drugs. Considering the effects of the correction of ID in other settings, we hypothetized that treatment with IV iron in patients with ID and borderline anemia can improve physical performance and their quality of life, independent of the effects on hemoglobin. Method Prospective, unicentric, single-arm study in CKD patients with ID, mild anemia and with-out heart failure. The inclusion criteria were: age ≥ 18 years, CKD patients stages 3–5 not on dialysis, iron deficiency (ferritin &amp;lt;100 ng/ml or ferritin &amp;lt;200 ng/ml if TSAT &amp;lt;20%), mild anaemia (Hb 10.5-11.5 g/dL). At the baseline visit, after all the studies were performed, iv ferric carboxymaltose was administered in a single dose, according to the degree of ID calculated by the Ganzoni´s formula. The co-primary outcome was the change in physical performance, evaluated through the 6 minute-walk test (6MWT) at one week and at four weeks. Secondary end-points: Patient's global assessment (PGA) and quality of life (EQ-5D), Piper's fatigue test, serum phosphorous at four week. Laboratory data, PGA, EQ-5D and Piper test questionnaires were evaluated at baseline, and at weeks 1 and 4 after receiving IV ferric carboximaltose. Results 41 patients completed the study. Primary end-point: the 6MWT increased significantly from 296 ± 101 m to 314 ± 106 m at week 1 (p&amp;lt;0.01), and to 325 ±111 meters at week 4 (p&amp;lt;0.01). at week 4 (p = 0.083). A significant improvement in the PGA test values was detected when compared baseline vs 4 weeks (adjusted p value = 0.031). No significant differences were found between the baseline and week 1 (adjusted p value = 0.083), and week 1 and week 4 visits (adjusted p value = 0.086). No significant differences were found between the initial, 1-week, and 4-week visits in the EQ-5D quality of life questionnaire nor Piper's fatigue test. Phosphorus levels decreased significantly at week 1 from baseline (3.16 ± 0.7 vs 3.72 ± 0.6) (adjusted p&amp;lt;0.001), with a partial recovery of serum levels in week 4 (3.57 ± 0.7 mg/dL). There were no significant increases in hemoglobin concentration between the different time periods. Conclusion IV ferric carboximaltose administration significantly improved the functional capacity of CKD patients with ID in short term. PGA also improved slightly but significantly. Effects that were independent of hemoglobin changes, suggesting a role of ID for a lower physical performance in CKD patients without heart failure, independent of the presence of anemia.

Abstract 3273: Guadecitabine plus ipilimumab in unresectable melanoma: Five-year follow-up and correlation with integrated, multi-omic analysis in the NIBIT-M4 trial

Abstract DNA hypomethylating agents (DHA) combined with immune-checkpoint inhibitors (ICI) is a promising strategy to improve the effect of immunotherapy. Providing initial support to this notion, the phase Ib NIBIT-M4 study, a dose-escalation trial of the DHA guadecitabine plus ipilimumab, has shown this regimen to be safe, tolerable and with promising immunomodulatory and anti-tumor activity in advanced melanoma. Here we report the 5-year clinical outcome of NIBIT-M4 patients and its correlation with an integrated multi-omic analysis. The NIBIT-M4 enrolled unresectable Stage III or IV cutaneous melanoma patients. Median Overall Survival (OS), Progression Free Survival (PFS), 5-year OS and PFS rate, and median Duration of Response (DoR) were assessed. Tumor biopsies were performed at baseline and at week 4 and 12 on-treatment. RNA-seq, whole exome sequencing (WES), RRBS methylation profiling, and tumor immune contexture data generated by immunohistochemistry (IHC), were integratively analyzed and correlated with clinical outcome. Patients were classified as responder (R) or non-responder (NR) based on Disease Control. Nineteen patients were enrolled in the NIBIT-M4 study between October 2015, and August 2018. As of July 1, 2022, median OS was 25.6 months (mo) (95% CI, 0.0-52.9), median PFS was 5.2 mo (95% CI, 4.0-6.4); 5-year OS rate was 28.9% and 5-year PFS rate was 5.3 %; median DoR was 20.6 mo (95% CI, 12.4-28.8). Tumor biopsies for correlative analyses were available from 14 patients. Compared to NR, R patients showed higher mutation frequency in NRAS, while NR patients harbored more frequent somatic alterations in genes involved in Epithelial to Mesenchymal Transition (EMT) and chromatin organization pathways. By tumor transcriptome analysis, NR patients showed enrichment for proliferation/differentiation/EMT pathways associated with suppression of INF-ɣ/HLA-II/immune-related transcriptional modules. R patients displayed a dynamic pattern of activated immune signatures related to CD8+ Tex cells, B cells, tertiary lymphoid structures, TFH cells and IFN-ɣ, reaching highest expression levels in week 12 biopsies. Deconvolution of transcriptomic data showed higher CD8+ and NK cell content and higher correlation of TCRB clonality with CD8+ content in R patients. By integration of a genetic immunoediting index (GIE) with an adaptive immunity signature (ICR) lesions were stratified into four distinct subsets. Interestingly, the ICR/GIE classification discriminated 5-year OS and PFS while the classification based on response groups did not. Moreover, patients with a “high ICR/non-GIE” (i.e., without immunoediting) showed lower expression of antigen presentation and processing-related genes associated with defective HLA-class I expression in the lesions, in spite of high CD8+ content. Citation Format: Teresa Noviello, Anna Maria Di Giacomo, Francesca Pia Caruso, Alessia Covre, Giovanni Scala, Luigi Ferraro, Sandra Coral, Wolf H. Fridman, Catherine Sautes-Fridman, Roberta Mortarini, Elena Simonetti, Maria Fortunata Lofiego, Davide Bedognetti, Andrea Anichini, Michele Ceccarelli, Michele Maio. Guadecitabine plus ipilimumab in unresectable melanoma: Five-year follow-up and correlation with integrated, multi-omic analysis in the NIBIT-M4 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3273.

Chemical composition and biological activities of Jamaican Cannabis sativa essential oils as the plant matures

AbstractCannabis sativa is a flowering plant belonging to the Cannabinaceae family. There have been numerous ongoing studies globally on C. sativa which include investigating the yield and quality of essential oils. However, this study is the first to assess the chemical composition and biological activities of Jamaican C. sativa essential oils (EOs) extracted via hydrodistillation as the plants mature from week 8 through to week 12. EOs from fresh landrace female plants were analysed by gas chromatography–mass spectrometry (GC–MS) and GC coupled to a flame ionization detector (GC‐FID). Cannabis sativa essential oils were screened for their in vitro antimicrobial activity using the disc diffusion method and further with tube dilution method. The antioxidant properties were investigated using the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging assay. In total, 36 constituents were identified in the C. sativa EOs by comparison of the Kováts retention indices (RI), the mass spectra data with those in the Natural Institute of Standards and Technology (NIST) library and by co‐elution with authentic samples where available. The major constituents were β‐caryophyllene (25.34%) and α‐humulene (α‐caryophyllene) (10.94%) both at the highest levels in week nine and were the most abundant constituents present at all stages of maturity. All extracted C. sativa essential oils did not exhibit antioxidant properties. However, the C. sativa essential oils exhibit significant to moderate antimicrobial property against the test gram‐positive microorganisms, Enterococcus faecalis, Streptococcus Group A and Streptococcus Group B with MIC values ranging from 16 to 125 μg/mL.

THE MASON CARES RANDOMIZED STUDY: ASSESSING CAREGIVER BURDEN FOLLOWING A STRESS MANAGEMENT PROGRAM

Abstract OBJECTIVE The Mason CARES study examines the impact of a virtual stress management program and personalized music intervention on the stress of family caregivers of older adults with dementia. This study presents early findings on 31 participants (Cohort 1) who enrolled in January 2022. METHODS Using primary data, we analyzed caregiver stress levels among 31 participants in Weeks 1 and 5 of a stress management program. Caregiver stress was measured using the Zarit Burden Interview (ZBI) score with a range from 0 to 48 (Bédard, 2001). Higher values (ZBI &amp;gt;=17.0) are associated with higher levels of stress. RESULTS Among the 31 caregivers, 51.6% were spouses and 48.4% were non-spouses (e.g., adult children, nephew, etc.). While mean ZBI scores in Week 1 were similar for spouses and non-spouses (24.2 vs. 24.9), caregiver stress was higher when older adults had advanced versus moderate dementia (26.2 vs. 23.2). Between Weeks 1 and 5, spouses reported a greater decrease in stress (-2.6 vs. -2.2) compared to non-spouses. However, caregivers of older adults with advanced dementia experienced less of an improvement (-1.5 vs. -3.0). CONCLUSION Findings show that all caregivers had high stress levels in Week 1 (ZBI score of 17 or more) with no difference between spouses and non-spouses. Between Week 1 and 5, spouses reported greater stress improvement than non-spouses. However, caregivers of older adults with advanced dementia had less improvement in stress. Future research will examine caregiver stress levels after random assignment to a Phase 2 music intervention group and control group.

Analysis of the first surface nitrogen dioxide concentration observations over the South African Highveld derived from the Pandora-2s instrument

Anthropogenic emissions from industry, biomass burning and traffic are significant contributors to the atmospheric loading of nitrogen dioxide on the South African Highveld. These sources are dispersed across the region and emit nitrogen oxides (NO and NO2)into the atmosphere at different elevations above the earth's surface. Additionally, atmospheric stability in the form of surface andelevated inversions decreases the dispersion of air pollutants and stratifies pollutants into distinctive layers above the surface. Thisstudy explores the Highveld near-surface nitrogen dioxide concentrations obtained using the ground-based Pandora-2s monitoringsystem. The Pandora-2s instrument retrieves surface NO2 levels from clear sky measurements using a fully parameterised algorithm.We present the first near-surface concentration measurements of atmospheric NO2 at Wakkerstroom, a site between Volksrust andAmersfoort, downstream of major source conglomerates, the Majuba power station and other industries. These data are exploredin the presence and context of potential background NO2 concentrations in the area derived from other ground-based sensors. Thequasicontinuous data show elevated surface NO2 levels in week 37 (September) of 2020 (7.3 ± 5.7 ppb), while the lowest levels wereobserved in week 15 (April) of 2020 (0.2 ± 0.04 ppb). The elevated surface NO2 levels are driven by dominant emission sources andtransport trajectories, while the accuracy in the measurements is based on the high temporal resolution of the ground-based Pandora2s instrument.

The value of plasma hypoxia markers for predicting imaging-based hypoxia in patients with head-and-neck cancers undergoing definitive chemoradiation

BackgroundTumor hypoxia worsens the prognosis of head-and-neck squamous cell carcinoma (HNSCC) patients, and plasma hypoxia markers may be used as biomarkers for radiotherapy personalization. We therefore investigated the role of the hypoxia-associated plasma proteins osteopontin, galectin-3, vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) as surrogate markers for imaging-based tumor hypoxia. MethodsSerial blood samples of HNSCC patients receiving chemoradiation within a prospective trial were analyzed for osteopontin, galectin-3, VEGF and CTGF concentrations. Tumor hypoxia was quantified in treatment weeks 0, 2 and 5 using [18F]FMISO PET/CT. The association between PET-defined hypoxia and the plasma markers was determined using Pearson’s correlation analyses. Receiver-operating characteristic analyses were conducted to reveal the diagnostic value of the hypoxia markers. ResultsBaseline osteopontin (r = 0.579, p < 0.01) and galectin-3 (r = 0.429, p < 0.05) correlated with the hypoxic subvolume (HSV) prior to radiotherapy, whereas VEGF (r = 0.196, p = 0.36) and CTGF (r = 0.314, p = 0.12) showed no association. Patients with an HSV > 1 mL in week 2 exhibited increased VEGF (p < 0.05) and CTGF (p < 0.05) levels in week 5. Pretherapeutic osteopontin levels were higher in patients exhibiting residual hypoxia at the end of treatment (104.7 vs. 60.8 ng/mL, p < 0.05) and could therefore predict residual hypoxia (AUC = 0.821, 95% CI 0.604–1.000, p < 0.05). ConclusionIn this exploratory analysis, osteopontin correlated with the initial HSV and with residual tumor hypoxia; therefore, there may be a rationale to study hypoxic modification based on osteopontin levels. However, as plasma hypoxia markers do not correspond to any spatial information of tumor hypoxia, they have limitations regarding the replacement of [18F]FMISO PET-based focal treatments. The results need to be validated in larger patient cohorts to draw definitive conclusions.

Interleukin-6 as surrogate marker for imaging-based hypoxia dynamics in patients with head-and-neck cancers undergoing definitive chemoradiation—results from a prospective pilot trial

PurposeIntratumoral hypoxia increases resistance of head-and-neck squamous cell carcinoma (HNSCC) to radiotherapy. [18F]FMISO PET imaging enables noninvasive hypoxia monitoring, though requiring complex logistical efforts. We investigated the role of plasma interleukin-6 (IL-6) as potential surrogate parameter for intratumoral hypoxia in HNSCC using [18F]FMISO PET/CT as reference.MethodsWithin a prospective trial, serial blood samples of 27 HNSCC patients undergoing definitive chemoradiation were collected to analyze plasma IL-6 levels. Intratumoral hypoxia was assessed in treatment weeks 0, 2, and 5 using [18F]FMISO PET/CT imaging. The association between PET-based hypoxia and IL-6 was examined using Pearson’s correlation and multiple regression analyses, and the diagnostic power of IL-6 for tumor hypoxia response prediction was determined with receiver-operating characteristic analyses.ResultsMean IL-6 concentrations were 15.1, 19.6, and 31.0 pg/mL at baseline, week 2 and week 5, respectively. Smoking (p=0.050) and reduced performance status (p=0.011) resulted in higher IL-6 levels, whereas tumor (p=0.427) and nodal stages (p=0.334), tumor localization (p=0.439), and HPV status (p=0.294) had no influence. IL-6 levels strongly correlated with the intratumoral hypoxic subvolume during treatment (baseline: r=0.775, p<0.001; week 2: r=0.553, p=0.007; week 5: r=0.734, p<0.001). IL-6 levels in week 2 were higher in patients with absent early tumor hypoxia response (p=0.016) and predicted early hypoxia response (AUC=0.822, p=0.031). Increased IL-6 levels at week 5 resulted in a trend towards reduced progression-free survival (p=0.078) and overall survival (p=0.013).ConclusionPlasma IL-6 is a promising surrogate marker for tumor hypoxia dynamics in HNSCC patients and may facilitate hypoxia-directed personalized radiotherapy concepts.Trial registrationThe prospective trial was registered in the German Clinical Trial Register (DRKS00003830). Registered 20 August 2015

Phase I study of single agent NIZ985, a recombinant heterodimeric IL-15 agonist, in adult patients with metastatic or unresectable solid tumors

BackgroundNIZ985 is a recombinant heterodimer of physiologically active interleukin (IL-)15 and IL-15 receptor alpha. In preclinical models, NIZ985 promotes cytotoxic lymphocyte proliferation, killing function, and organ/tumor infiltration, with resultant anticancer...

Novel RNA Viral Vectors for Chemically Regulated Gene Expression in Embryonic Stem Cells.

RNA viral vectors that replicate without DNA intermediates are attractive platforms for manipulation of cells for biomedical and veterinary applications because they have minimal risk of chromosomal integration. Vesicular stomatitis virus (VSV) vectors are among the most well-studied RNA viral vectors due to their low pathogenicity to humans and ability to express transgenes at high levels for weeks to months. However, their applications have been mostly limited to oncolytic and vaccine vectors due to their cytopathogenicity. We discovered two mutations in the VSV vector that synergistically confer improved stability in mouse embryonic stem cells (ESCs) with markedly lower cytopathic effects. We also demonstrated chemical regulation of transgene expression through embedded riboswitches. The ESCs infected with the mutant vector were shown to maintain pluripotency. This new vector sets the stage for precise regulation of gene expression in ESCs to produce a variety of differentiated cells without chromosomal alteration.

Plasma fibulin-1 levels during pregnancy and delivery: a longitudinal observational study

BackgroundFibulin-1 is an extracellular matrix protein expressed at high levels in the placenta. Elevated circulating fibulin-1 have been observed in women with severe pre-eclampsia, whereas low levels have been found in the fetal membranes, prior to membrane rupture. The aim of the study was primarily to evaluate plasma fibulin-1 during expected normal pregnancy and delivery, and secondarily to explore fibulin-1 levels in women developing pre-eclampsia or preterm premature rupture of fetal membranes (PPROM).MethodsFrom the historical longitudinal cohort originally consisting of 801 healthy Danish women with a singleton pregnancy, 128 women (632 samples) were selected. Of these, 107 women had normal pregnancies, nine experienced PPROM, and 12 pre-eclampsia. All samples were analyzed for fibulin-1, and levels were compared with blood donors. Differences in mean fibulin-1 between groups were estimated using a linear mixed model.ResultsThe mean concentration of fibulin-1 in 120 blood donors was 15.7 µg/mL, (25th-75th-percentiles, 12.3–18.2), with no significant difference in groups stratified by gender or age. Compared to baseline levels in week 12–20, fibulin-1 levels increased significantly from week 29–34 (estimated difference, 5.6 µg/mL; standard error, 1.7; p < 0.001) and 35–42 (12.5 µg/mL; 1.6; p < 0.001) and normalized after birth. The decrease at delivery tended to be more pronounced after elective (-7.0 µg/mL; 2.3; p = 0.002) and emergency (-5.6 µg/mL; 2.9; p = 0.05) cesarean section than after vaginal delivery (reference group). Women who developed PPROM had lower fibulin-1 levels throughout their pregnancies (-11.6 µg/mL; 4.2; p = 0.006). We did not observe a correlate between late pre-eclampsia and fibulin-1 (-0.2 µg/mL; 3.0; p = 0.9).ConclusionsFibulin-1 was above non-pregnant levels at week 12 and increased significantly throughout pregnancy. We observed an association between low levels of fibulin-1 and PPROM. Further studies are needed to examine if fibulin-1 could serve as biomarker for the risk of PPROM. However, its role in late preeclampsia is doubtful.Trial registrationThe study was conducted in accordance with the Declaration of Helsinki. The participants provided written informed consent, including storage for future use. The study was approved on July 18, 2005 by The Danish National Committee on Bioethics (No. KA 05065 and S-20,090,061) and the Danish Data Protection Agency.

Kinematic Comparison on Lower Limb Kicking Action of Fetuses in Different Gestational Weeks: A Pilot Study.

The fetal movements during different gestational weeks are essential for normal musculoskeletal development. The kinematic characteristics of fetuses with small differences in gestational weeks may be different and important. Ultrasonographic videos of fetal kicking action and plantarflexion action were collected from three healthy pregnant women (24, 27, and 30 gestational weeks) with normal fetal development. The kinematic characteristics, including angular range and angular velocity, were analyzed. These kinematic parameters were measured using simi motion. The final knee angle was found to decrease with progressive gestational weeks. Compared with 24 w, the knee joint angle at 27 w and 30 w was significantly reduced at the end of a kick-type movement (p < 0.01). Except for the mean angular velocity of the knee joint, there were no significant differences in the other conditions. The value at 30 w for mean angular velocity was significantly higher than that at 24 w (p = 0.02). In the ankle joint, no significant differences were observed between different conditions. Therefore, we can conclude that there was no significant difference in the kinematic characteristics of the ankle joint for small gestational age gaps, but there was a significant difference in the knee joint. As the gestation weeks increase, the range of kicking motion tends to decrease. The reason may be that with the increase of gestational weeks, fetal lower limb musculoskeletal development is gradually enhanced; the slower growth rate indicates that development reaches a peak level in weeks 24 to 30.

The effect of nurse-led telephone support on adherence to blood pressure control and drug treatment in individuals with primary hypertension: A randomized controlled study.

The aim of this study was to evaluate the effect of telephone monitoring, in combination with texts, on medication adherence and blood pressure (BP) control in primary hypertension. Data were collected from August to December 2016. Seventy-seven adults were randomized to the intervention and control groups. A 12-week intervention consisted of regular text messages and phone calls. The control group received usual hypertension care. The outcomes were evaluated with blood pressure measurement and medication adherence self-efficacy scale short form. Medication adherence in Week 12 was found to be significantly higher in the intervention group than in the control group. Mean systolic and diastolic BP levels in Weeks 4, 8 and 12 were statistically significantly lower in the intervention group than in the control group (p < 0.05). Using text messaging and nurse-led telephone monitoring improved adherence and BP control in adults with hypertensive in primary care.

Switch z originálního na bio­similární adalimumab SB-5 u nemocných s Crohnovou chorobou – dlouhodobé výsledky

Background and aims: Originator-adalimumab, an established treatment for patients with Crohn‘s disease (CD) showed no difference in efficacy or adverse events vs the adalimumab biosimilar SB5 (SB5-adalimumab) over 10 weeks of treatment. To understand the long-term efficacy of SB5-adalimumab in CD, patients who switched from originator-adalimumab to SB5-adalimumab were compared to a cohort who remained on originator-adalimumab over a follow up of 104 weeks. Methods: In this analysis, data on patients ≥18 years and diagnosed with CD treated at the IBD ISCARE centre were collected prospectively between July 2018 and January 2021. Clinical disease activity as measured by Harvey-Bradshaw index (HBI) at Week 52 was the primary outcome, while C-reactive protein (CRP), faecal calprotectin (FC), adalimumab trough levels in Weeks 10, 26, 52, 78, and 104, adverse events leading to therapy withdrawal, and persistence on treatment were secondary outcomes. To ensure comparable treatment cohorts, patients were propensity score matched (PSM) for age, gender, diagnosis, and disease activity. Results: A total of 54 patients were matched according to the given criteria in each group. At Week 52, the mean [SD] HBI score was 3.2 (2.5) in the originator-adalimumab group and 4.0 (3.6) in SB5-adalimumab patients (difference [95% CI] –0.78 [–2.8, 1.3]). Similarly, no clinically significant differences in CRP, FC, or trough levels were noted between originator-adalimumab and SB5-adalimumab cohorts through Week 52. The Kaplan-Meier estimates (95% CI) of patients remaining on treatment for the originator-adalimumab vs SB5-adalimumab cohorts were 0.870 (0.785–0.965) vs 0.648 (0.533–0.789) at Week 52. Conclusions: These long-term study results in CD patients after a non-medical switch from originator-adalimumab to SB5-adalimumab showed that the biosimilar SB5 had similar therapeutic effects as originator-adalimumab in terms of clinical disease activity, biological parameters, and pharmacokinetics profile at the primary endpoint of 52 weeks, as well as 104 weeks. Differences in persistence were not clinically driven. Persistence on treatment was lower in patients treated with biosimilar adalimumab SB-5.

Impact of COVID-19 and Nationwide Lockdowns on Vegetable Prices: Evidence from Wholesale Markets in China.

In this paper, we employ a combination of time regression discontinuity design method (T‐RD) and the difference‐in‐difference method (DID) to identify and quantify the causal effects of the strict lockdown policy on vegetable prices using multiple‐year daily price data from 151 wholesale markets of Chinese cabbage. We find that the lockdown policy caused a large and immediate surge in price and price dispersion of Chinese cabbage, though they fluctuated smoothly for the same period in normal years. The DID results further show that the price surge peaked in the fourth week of lockdown but gradually came down to the level of a normal year by week 11. However, the price rose again (though to a much smaller extent) in response to the resurgence of COVID‐19 in a few provinces in early‐mid April but quickly returned to the normal level in week 15 when the lockdown measures were largely removed. We also find that the supply chain disruption is the driving factor for the price hike. Policy implications are drawn.