Stem End Blockage in Cut Grevillea 'Crimson Yul-lo' Inflorescences

Grevillea Crimson Yul-lo inflorescences have cut flower potential, but their vase life is short. End of vase life is characterised by early wilting. The possibility of physiologically mediated stem end blockage was investigated. Hydraulic conductance of 2 cm long stem end segments declined rapidly and remained lower throughout vase life than that of 2 cm long stem segments from immediately above. Re-cutting daily to remove basal 2 cm stem ends increased solution uptake, delayed declines in inflorescence water potential and water content, and improved inflorescence vase life. S-Carvone is a potential inhibitor of wound related suberin formation, via inhibition of phenylalanine ammonia-lyase, and vase solution treatments with S-carvone (0.318 and 0.636 mM) delayed the decline in hydraulic conductance of basal 2 cm long stem end segments and decreases in vase solution uptake and relative fresh weight of cut stems, and extended vase life. Treatments with the catechol oxidase inhibitor 4-hexylresorcinol (2.5-10 mM) also delayed stem end blockage. These findings suggest that stem end blockage in cut G. Crimson Yul-lo stems is physiologically mediated

Kidney Function in Patients With Neuromuscular Disease:Creatinine Versus Cystatin C

Background: Accurate measurement of kidney function in patients with neuromuscular disorders is challenging. Cystatin C, a marker not influenced by skeletal muscle degradation, might be of clinical value in these patients.Methods: We consecutively enrolled 39 patients with neuromuscular disorders. We investigated the association of the eGFR, based on plasma creatinine and Cystatin C, with clinical and biochemical variables associated with kidney function, namely age and galectin-3.Results: Creatinine-based eGFR was 242 (±80) and Cystatin C-based eGFR was 110 (±23) mL/min/1.73 m2. Cystatin C-based eGFR was associated with age (β −0.63 p < 0.0001) and galectin-3 levels (β −0.43 p < 0.01), while creatinine-based eGFR was not (β −0.22 p = 0.20; β −0.28 p = 0.10). Sensitivity analyses in Duchenne and Becker patients revealed the same results: Cystatin C-based eGFR was associated with age (β −0.61 p < 0.01) and galectin-3 levels (β −0.43 p = 0.05), while creatinine-based eGFR was not (β −0.32 p = 0.13; β −0.34 p = 0.14).Conclusions: These data indicate that estimation of renal function in patients with neuromuscular disorders cannot reliably be achieved with creatinine, while Cystatin C appears a reasonable alternative. Since a large proportion of patients with neuromuscular disorders develops heart failure, and requires heart failure medication, adequate monitoring of renal function is warranted

Antigenic characterization of highly pathogenic avian influenza A(H5N1) viruses with chicken and ferret antisera reveals clade-dependent variation in hemagglutination inhibition profiles.

Highly pathogenic avian influenza (HPAI) A(H5N1) viruses pose a significant economic burden to the poultry industry worldwide and have pandemic potential. Poultry vaccination against HPAI A(H5N1) viruses has been an important component of HPAI control measures and has been performed in Vietnam since 2005. To systematically assess antigenic matching of current vaccines to circulating field variants, we produced a panel of chicken and ferret antisera raised against historical and contemporary Vietnamese reference viruses representing clade variants that were detected between 2001 and 2014. The antisera were used for hemagglutination inhibition (HI) assays to generate data sets for analysis by antigenic cartography, allowing for a direct comparison of results from chicken or ferret antisera. HI antigenic maps, developed with antisera from both hosts, revealed varying patterns of antigenic relationships and clustering of viruses that were dependent on the clade of viruses analyzed. Antigenic relationships between existing poultry vaccines and circulating field viruses were also aligned with in vivo protection profiles determined by previously reported vaccine challenge studies. Our results establish the feasibility and utility of HPAI A(H5N1) antigenic characterization using chicken antisera and support further experimental and modeling studies to investigate quantitative relationships between genetic variation, antigenic drift and correlates of poultry vaccine protection in vivo

Introduction of Heated Cow's Milk Protein in Challenge-Proven Cow's Milk Allergic Children:The iAGE Study

The introduction of baked milk products in cow's milk (CM) allergic children has previously been shown to accelerate induction tolerance in a selected group of children. However, there is no standardized baked milk product on the market. Recently, a new standardized, heated and glycated cow's milk protein (HP) product was developed. The aim of this study was to measure safety and tolerability of a new, well characterized heated CM protein (HP) product in cow's milk allergic (CMA) children between the age of 3 and 36 months. The children were recruited from seven clinics throughout The Netherlands. The HP product was introduced in six incremental doses under clinical supervision. Symptoms were registered after introduction of the HP product. Several questionnaires were filled out by parents of the children. Skin prick tests were performed with CM and HP product, sIgE to CM and α-lactalbumin (Bos d4), β-lactoglobulin (Bos d5), serum albumin (Bos d 6), lactoferrin (Bos d7) and casein (Bos d8). Whereas 72% percent (18 out of 25) of the children tolerated the HP product, seven children experienced adverse events. Risk factors for intolerance to the HP product were higher skin prick test (SPT) histamine equivalent index (HEP) results with CM and the HP product, higher specific IgE levels against Bos d4 and Bos d8 levels and Bos d5 levels. In conclusion, the HP product was tolerated by 72% of the CM allergic children. Outcomes of SPT with CM and the HP product, as well as values of sIgE against caseins, α-lactalbumin, and β-lactoglobulin may predict the tolerability of the HP product. Larger studies are needed to confirm these conclusions.</p

Ventral tegmental area disconnection contributes two years early to correctly classify patients converted to Alzheimer's Disease: implications for treatment

Background: Recent cross-sectional studies highlighted the loss of dopaminergic neurons in the ventral tegmental area (VTA) as an early pathophysiological event in Alzheimer’s disease (AD). Objective: In this study, we longitudinally investigated by resting-state fMRI (RS-fMRI) a cohort of patients with mild cognitive impairment (MCI) due to AD to evaluate the impact of VTA disconnection in predicting the conversion to AD. Methods: a cohort of 35 patients with MCI due to AD were recruited and followed-up for 24 months. They underwent cognitive evaluation and RS-fMRI to assess VTA connectivity at baseline and at follow-up. Results: At 24-month follow-up, 16 out of 35 patients converted to AD. Although converters and non-converters to AD did not differ in demographic and behavioral characteristics at baseline, the first group showed a significant reduction of VTA-driven connectivity in the posterior cingulate and precentral cortex. This pattern of additional disconnection in MCI-converters compared to non-converters remained substantially unchanged at 24-month follow-up. Discussion: This study reinforces the hypothesis of an early contribution of dopaminergic dysfunction to AD evolution by targeting the default-mode network. These results have potential implications for AD staging and prognosis and support new opportunities for therapeutic interventions to slow down disease progressio

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Training human mesenchymal stromal cells for bone tissue engineering applications

Human mesenchymal stromal cells (hMSCs) are an interesting source for cell therapies and tissue engineering applications, because these cells are able to differentiate into various target tissues, such as bone, cartilage, fat and endothelial cells. In addition, they secrete a wide array of growth factors and cytokines that exert immunomodulatory and trophic effects on surrounding cells. A large number of clinical trials is currently employed to investigate the use of MSCs and these trophic/immunomodulatory effects. The differentiation of hMSCs towards the osteogenic lineage is controlled by several signal transduction pathways, amongst which the cAMP/PKA pathway, but its exact role is still incompletely understood. In this thesis we show that activation of this pathway in hMSCs with the small molecules dibutyryl-cAMP (db-cAMP) and forskolin result in osteogenic differentiation, whereas treatment of these cells with a second cAMP analogue (8-br-cAMP) resulted in adipogenic differentiation. We observed differences in the PKA activation patterns as well as in genetic profiles, but the precise mechanism underlying these different effects on differentiation remain to be elucidated. For bone tissue engineering applications, the differentiation of MSCs towards the osteogenic lineage prior to implantation, is generally believed to account for enhanced bone formation. Here, we demonstrated that the differentiation of hMSCs induced by db-cAMP not only resulted in enhanced in vitro osteogenic differentiation and in vivo bone formation, but also resulted in enhanced secretion of bone specific growth factors, such as insulin-like growth factor 1 and bone morphogenetic protein 2. Furthermore, conditioned medium derived from these db-cAMP-treated cells induced proliferation and differentiation of fresh cells, demonstrating a trophic effect of these factors. To investigate how the secretome of hMSCs can be modulated further, a high throughput screen based on the hypoxia responsive element (HRE) was developed and by using this assay, we identified phenanthroline as a novel hypoxia mimic that is able to shift the hMSC secretome towards a trophic angiogenic profile. These data demonstrate that, besides their direct differentiation, hMSCs can be ‘trained’ to secrete specific growth factors for specific applications that can be induced by treatment with small molecules, but also by i.e. scaffold modifications

Therapeutic Applications of Mesenchymal Stromal Cells: Paracrine Effects and Potential Improvements

Among the various types of cell-to-cell signaling, paracrine signaling comprises those signals that are trans- mitted over short distances between different cell types. In the human body, secreted growth factors and cytokines instruct, among others, proliferation, differentiation, and migration. In the hematopoietic stem cell (HSC) niche, stromal cells provide instructive cues to stem cells via paracrine signaling and one of these cell types, known to secrete a broad panel of growth factors and cytokines, is mesenchymal stromal cells (MSCs). The factors secreted by MSCs have trophic, immunomodulatory, antiapoptotic, and proangiogenic properties, and their paracrine profile varies according to their initial activation by various stimuli. MSCs are currently studied as treatment for inflammatory diseases such as graft-versus-host disease and Crohn’s disease, but also as treatment for myocardial infarct and solid organ transplantation. In addition, MSCs are investigated for their use in tissue engineering applications, in which their differentiation plays an important role, but as we have recently demonstrated, their trophic factors may also be involved. Furthermore, a functional improvement of MSCs might be obtained after preconditioning or tailoring the cells themselves. Also, the way the cells are clinically administered may be specialized for specific therapeutic scenarios. In this review we will first discuss the HSC niche, in which MSCs were recently identified and are thought to play an instructive and supportive role. We will then evaluate therapeutic applications that currently try to utilize the trophic and/or immunomodulatory properties of MSCs, and we will also discuss new options to enhance their therapeutic effects