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Clinical Nutrition ESPEN Jun 2024The present systematic review and meta-analysis aims to determine the difference in the interdialytic weight gain (IDWG) between low salt intake diet and normal/high...
OBJECTIVE
The present systematic review and meta-analysis aims to determine the difference in the interdialytic weight gain (IDWG) between low salt intake diet and normal/high salt intake diet or between nutritional counseling aimed at reducing diet salt intake and no nutritional counseling in patients on chronic hemodialysis.
METHODS
Medline, PubMed, Web of Science, and the Cochrane Library were searched. Randomized, crossover or parallel studies and observational studies were considered for inclusion and: 1) included adult patients on chronic hemodialysis since at least 6 months; 2) compared normal salt intake diet with low salt intake diet on IDWG; 3) compared nutritional counseling aimed at reducing diet salt intake with no intervention on IDWG; 4) reported on IDWG.
RESULTS
Eight articles (783 patients) were fully assessed for eligibility and included in the investigation. Meta-analysis showed frequencies of patients that increased their weight after dialysis more than 2.5 Kg (events) over total enrolled subjects for each group (control and experimental). As no significant heterogeneity was observed (I = 8%; p = 0.36), the pooled analysis was performed using a fixed-effect model. Funnel plot was generated and no obvious asymmetry was observed. The Overall Odds Ratio to get an event in the experimental group, in respect to controls, is 0.57 (0.33-0.97) (p = 0.04] with single studies OR ranging between 0.11 and 1.08.
CONCLUSION
The present systematic review and meta-analysis suggest that the use of a low salt diet sodium or a nutritional counseling aimed at reducing diet salt intake is associated with a statistically significant reduction of the IDWG in patients on chronic hemodialysis.
PubMed: 38941185
DOI: 10.1016/j.clnesp.2024.06.022 -
GigaScience Jan 2024Colletotrichum fungi infect a wide diversity of monocot and dicot hosts, causing diseases on almost all economically important plants worldwide. Colletotrichum is also a...
BACKGROUND
Colletotrichum fungi infect a wide diversity of monocot and dicot hosts, causing diseases on almost all economically important plants worldwide. Colletotrichum is also a suitable model for studying gene family evolution on a fine scale to uncover events in the genome associated with biological changes.
RESULTS
Here we present the genome sequences of 30 Colletotrichum species covering the diversity within the genus. Evolutionary analyses revealed that the Colletotrichum ancestor diverged in the late Cretaceous in parallel with the diversification of flowering plants. We provide evidence of independent host jumps from dicots to monocots during the evolution of Colletotrichum, coinciding with a progressive shrinking of the plant cell wall degradative arsenal and expansions in lineage-specific gene families. Comparative transcriptomics of 4 species adapted to different hosts revealed similarity in gene content but high diversity in the modulation of their transcription profiles on different plant substrates. Combining genomics and transcriptomics, we identified a set of core genes such as specific transcription factors, putatively involved in plant cell wall degradation.
CONCLUSIONS
These results indicate that the ancestral Colletotrichum were associated with dicot plants and certain branches progressively adapted to different monocot hosts, reshaping the gene content and its regulation.
Topics: Colletotrichum; Transcriptome; Genome, Fungal; Evolution, Molecular; Phylogeny; Adaptation, Physiological; Gene Expression Profiling; Plant Diseases
PubMed: 38940768
DOI: 10.1093/gigascience/giae036 -
Health Technology Assessment... Jun 2024Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a non-acute anterior cruciate ligament injury can be non-surgical (rehabilitation) or surgical (reconstruction). However, insufficient evidence exists to guide treatment.
OBJECTIVE(S)
To determine in patients with non-acute anterior cruciate ligament injury and symptoms of instability whether a strategy of surgical management (reconstruction) without prior rehabilitation was more clinically and cost-effective than non-surgical management (rehabilitation).
DESIGN
A pragmatic, multicentre, superiority, randomised controlled trial with two-arm parallel groups and 1:1 allocation. Due to the nature of the interventions, no blinding could be carried out.
SETTING
Twenty-nine NHS orthopaedic units in the United Kingdom.
PARTICIPANTS
Participants with a symptomatic (instability) non-acute anterior cruciate ligament-injured knee.
INTERVENTIONS
Patients in the surgical management arm underwent surgical anterior cruciate ligament reconstruction as soon as possible and without any further rehabilitation. Patients in the rehabilitation arm attended physiotherapy sessions and only were listed for reconstructive surgery on continued instability following rehabilitation. Surgery following initial rehabilitation was an expected outcome for many patients and within protocol.
MAIN OUTCOME MEASURES
The primary outcome was the Knee Injury and Osteoarthritis Outcome Score 4 at 18 months post randomisation. Secondary outcomes included return to sport/activity, intervention-related complications, patient satisfaction, expectations of activity, generic health quality of life, knee-specific quality of life and resource usage.
RESULTS
Three hundred and sixteen participants were recruited between February 2017 and April 2020 with 156 randomised to surgical management and 160 to rehabilitation. Forty-one per cent ( = 65) of those allocated to rehabilitation underwent subsequent reconstruction within 18 months with 38% ( = 61) completing rehabilitation and not undergoing surgery. Seventy-two per cent ( = 113) of those allocated to surgery underwent reconstruction within 18 months. Follow-up at the primary outcome time point was 78% ( = 248; surgical, = 128; rehabilitation, = 120). Both groups improved over time. Adjusted mean Knee Injury and Osteoarthritis Outcome Score 4 scores at 18 months had increased to 73.0 in the surgical arm and to 64.6 in the rehabilitation arm. The adjusted mean difference was 7.9 (95% confidence interval 2.5 to 13.2; = 0.005) in favour of surgical management. The per-protocol analyses supported the intention-to-treat results, with all treatment effects favouring surgical management at a level reaching statistical significance. There was a significant difference in Tegner Activity Score at 18 months. Sixty-eight per cent ( = 65) of surgery patients did not reach their expected activity level compared to 73% ( = 63) in the rehabilitation arm. There were no differences between groups in surgical complications ( = 1 surgery, = 2 rehab) or clinical events ( = 11 surgery, = 12 rehab). Of surgery patients, 82.9% were satisfied compared to 68.1% of rehabilitation patients. Health economic analysis found that surgical management led to improved health-related quality of life compared to non-surgical management (0.052 quality-adjusted life-years, = 0.177), but with higher NHS healthcare costs (£1107, < 0.001). The incremental cost-effectiveness ratio for the surgical management programme versus rehabilitation was £19,346 per quality-adjusted life-year gained. Using £20,000-30,000 per quality-adjusted life-year thresholds, surgical management is cost-effective in the UK setting with a probability of being the most cost-effective option at 51% and 72%, respectively.
LIMITATIONS
Not all surgical patients underwent reconstruction, but this did not affect trial interpretation. The adherence to physiotherapy was patchy, but the trial was designed as pragmatic.
CONCLUSIONS
Surgical management (reconstruction) for non-acute anterior cruciate ligament-injured patients was superior to non-surgical management (rehabilitation). Although physiotherapy can still provide benefit, later-presenting non-acute anterior cruciate ligament-injured patients benefit more from surgical reconstruction without delaying for a prior period of rehabilitation.
FUTURE WORK
Confirmatory studies and those to explore the influence of fidelity and compliance will be useful.
TRIAL REGISTRATION
This trial is registered as Current Controlled Trials ISRCTN10110685; ClinicalTrials.gov Identifier: NCT02980367.
FUNDING
This award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/140/63) and is published in full in ; Vol. 28, No. 27. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Male; Female; Anterior Cruciate Ligament Injuries; Adult; United Kingdom; Cost-Benefit Analysis; Anterior Cruciate Ligament Reconstruction; Quality of Life; Quality-Adjusted Life Years; Middle Aged; Young Adult; State Medicine; Joint Instability; Adolescent; Technology Assessment, Biomedical
PubMed: 38940695
DOI: 10.3310/VDKB6009 -
Journal of Agricultural and Food... Jun 2024Hydroxytyrosol, a naturally occurring compound with antioxidant and antiviral activity, is widely applied in the cosmetic, food, and nutraceutical industries. The...
Hydroxytyrosol, a naturally occurring compound with antioxidant and antiviral activity, is widely applied in the cosmetic, food, and nutraceutical industries. The development of a biocatalytic approach for producing hydroxytyrosol from simple and readily accessible substrates remains a challenge. Here, we designed and implemented an effective biocatalytic cascade to obtain hydroxytyrosol from 3,4-dihydroxybenzaldehyde and l-threonine via a four-step enzymatic cascade composed of seven enzymes. To prevent cross-reactions and protein expression burden caused by multiple enzymes expressed in a single cell, the designed enzymatic cascade was divided into two modules and catalyzed in a stepwise manner. The first module (FM) assisted the assembly of 3,4-dihydroxybenzaldehyde and l-threonine into (2,3)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid, and the second module (SM) entailed converting (2,3)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid into hydroxytyrosol. Each module was cloned into BL21 (DE3) and engineered in parallel by fine-tuning enzyme expression, resulting in two engineered whole-cell catalyst modules, BL21(FM01) and BL21(SM13), capable of converting 30 mM 3,4-dihydroxybenzaldehyde to 28.7 mM hydroxytyrosol with a high space-time yield (0.88 g/L/h). To summarize, the current study proposes a simple and effective approach for biosynthesizing hydroxytyrosol from low-cost substrates and thus has great potential for industrial applications.
PubMed: 38940657
DOI: 10.1021/acs.jafc.4c04228 -
Chembiochem : a European Journal of... Jun 2024Water-soluble phthalocyanine (Pc) derivatives have been regarded as potential G-quadruplex (G4) nucleic acid-targeting ligands for anticancer therapy and have been...
Water-soluble phthalocyanine (Pc) derivatives have been regarded as potential G-quadruplex (G4) nucleic acid-targeting ligands for anticancer therapy and have been extensively studied as effective photosensitizers for photodynamic therapy (PDT). Understanding how photosensitizers interact with nucleic acids and the subsequent photolytic reactions is essential for deciphering the initial steps of PDT, thereby aiding in the development of new photosensitizing agents. In this study, we found that red-light irradiation of a mixture of a Zn(II) Pc derivative and an all-parallel G4 DNA leads to catalytic and selective photodegradation of the DNA by reactive oxygen species (ROS) generated from the Zn(II) Pc derivative bound to DNA through a reaction mechanism similar to that of an enzyme reaction. This finding provides a novel insight into the molecular design of a photosensitizer to enhance its PDT efficacy.
PubMed: 38940417
DOI: 10.1002/cbic.202400197 -
ACS Applied Bio Materials Jun 2024In order to treat most vascular diseases, arterial grafts are commonly employed for replacing small-diameter vessels, yet they often cause thrombosis. The growth of...
In order to treat most vascular diseases, arterial grafts are commonly employed for replacing small-diameter vessels, yet they often cause thrombosis. The growth of endothelial cells along the interior surfaces of these grafts (substrates) is critical to mitigate thrombosis. Typically, endothelial cells are cultured inside these grafts under laminar flow conditions to emulate the native environment of blood vessels and produce an endothelium. Alternatively, the substrate structure could have a similar influence on endothelial cell behavior as laminar flow conditions. In this study, we investigated whether substrates with aligned fiber structures could induce responses in human umbilical vein endothelial cells (HUVECs) akin to those elicited by laminar flow. Our observations revealed that HUVECs on aligned substrates displayed significant morphological changes, aligning parallel to the fibers, similar to effects reported under laminar flow conditions. Conversely, HUVECs on random substrates maintained their characteristic cobblestone appearance. Notably, cell migration was more significant on aligned substrates. Also, we observed that while vWF expression was similar between both substrates, the HUVECs on aligned substrates showed more expression of platelet/endothelial cell adhesion molecule-1 (PECAM-1/CD31), laminin, and collagen IV. Additionally, these cells exhibited increased gene expression related to critical functions such as proliferation, extracellular matrix production, cytoskeletal reorganization, autophagy, and antithrombotic activity. These findings indicated that aligned substrates enhanced endothelial growth and behavior compared to random substrates. These improvements are similar to the beneficial effects of laminar flow on endothelial cells, which are well-documented compared to static or turbulent flow conditions.
PubMed: 38939951
DOI: 10.1021/acsabm.4c00504 -
Neurology. Clinical Practice Oct 2024Endovascular therapy (EVT) for stroke has emerged as an important therapy for selected stroke patients, and shorter times to clot removal improve functional outcomes....
BACKGROUND AND OBJECTIVES
Endovascular therapy (EVT) for stroke has emerged as an important therapy for selected stroke patients, and shorter times to clot removal improve functional outcomes. EVT requires the close coordination of multiple departments and poses unique challenges to care coordination in large hospitals. We present the results of our quality improvement project that aimed to improve our door-to-groin puncture (DTP) times for patients who undergo EVT after direct presentation to our emergency department.
METHODS
We conducted time-motion studies to understand the full process of an EVT activation and conducted Gemba walks in multiple hospitals. We also reviewed the literature and interviewed stakeholders to create interventions that were implemented over 4 Plan-Do-Study-Act (PDSA) cycles. We retrospectively collected data starting from baseline and during every PDSA cycle. During each cycle, we studied the impact of the interventions, adjusted the interventions, and generated further interventions. A variety of interventions were introduced targeting all aspects of the EVT process. This included parallel processing to reduce waiting time, standardization of protocols and training of staff, behavioral prompts in the form of a stroke clock, and push systems to empower staff to facilitate the forward movement of the patient. A novel role-based communication app to facilitate group communications was also used.
RESULTS
Eighty-eight patients spanning across 22 months were analyzed. After the final PDSA cycle, the median DTP time was reduced by 36.5% compared with baseline (130 minutes (interquartile range [IQR] 111-140) to 82.5 minutes (IQR 74.8-100)). There were improvements in all phases of the EVT process with the largest time savings occurring in EVT decision to patient arrival at the angiosuite. Interventions that were most impactful are described.
DISCUSSION
EVT is a complex process involving multiple processes and local factors. Analysis of the process from all angles and intervening on multiple small aspects can add up to significant improvements in DTP times.
PubMed: 38939047
DOI: 10.1212/CPJ.0000000000200325 -
Journal of Extracellular Biology Apr 2024Isolation of extracellular vesicles (EV) has been developing rapidly in parallel with the interest in EVs. However, commonly utilized protocols may not suit more...
Isolation of extracellular vesicles (EV) has been developing rapidly in parallel with the interest in EVs. However, commonly utilized protocols may not suit more challenging sample matrixes and could potentially yield suboptimal results. Knowing and assessing the pitfalls of isolation procedure to be used, should be involved to some extent for EV analytics. EVs in cow milk are of great interest due to their abundancy and large-scale availability as well as their cross-species bioavailability and possible use as drug carriers. However, the characteristics of milk EVs overlap with those of other milk components. This makes it difficult to isolate and study EVs individually. There exists also a lack of consensus for isolation methods. In this study, we demonstrated the differences between various differential centrifugation-based approaches for isolation of large quantities of EVs from cow milk. Samples were further purified with gradient centrifugation and size exclusion chromatography (SEC) and differences were analyzed. Quality measurements were conducted on multiple independent platforms. Particle analysis, electron microscopy and RNA analysis were used, to comprehensively characterize the isolated samples and to identify the limitations and possible sources of contamination in the EV isolation protocols. Vesicle concentration to protein ratio and RNA to protein ratios were observed to increase as samples were purified, suggesting co-isolation with major milk proteins in direct differential centrifugation protocols. We demonstrated a novel size assessment of vesicles using a particle mobility analyzer that matched the sizing using electron microscopy in contrast to commonly utilized nanoparticle tracking analysis. Based on the standards of the International Society for Extracellular Vesicles and the quick checklist of EV-Track.org for EV isolation, we emphasize the need for complete characterization and validation of the isolation protocol with all EV-related work to ensure the accuracy of results and allow further analytics and experiments.
PubMed: 38938848
DOI: 10.1002/jex2.149 -
JACS Au Jun 2024Reductive catalytic fractionation (RCF) is a promising method to extract and depolymerize lignin from biomass, and bench-scale studies have enabled considerable progress...
Reductive catalytic fractionation (RCF) is a promising method to extract and depolymerize lignin from biomass, and bench-scale studies have enabled considerable progress in the past decade. RCF experiments are typically conducted in pressurized batch reactors with volumes ranging between 50 and 1000 mL, limiting the throughput of these experiments to one to six reactions per day for an individual researcher. Here, we report a high-throughput RCF (HTP-RCF) method in which batch RCF reactions are conducted in 1 mL wells machined directly into Hastelloy reactor plates. The plate reactors can seal high pressures produced by organic solvents by vertically stacking multiple reactor plates, leading to a compact and modular system capable of performing 240 reactions per experiment. Using this setup, we screened solvent mixtures and catalyst loadings for hydrogen-free RCF using 50 mg poplar and 0.5 mL reaction solvent. The system of 1:1 isopropanol/methanol showed optimal monomer yields and selectivity to 4-propyl substituted monomers, and validation reactions using 75 mL batch reactors produced identical monomer yields. To accommodate the low material loadings, we then developed a workup procedure for parallel filtration, washing, and drying of samples and a H nuclear magnetic resonance spectroscopy method to measure the RCF oil yield without performing liquid-liquid extraction. As a demonstration of this experimental pipeline, 50 unique switchgrass samples were screened in RCF reactions in the HTP-RCF system, revealing a wide range of monomer yields (21-36%), S/G ratios (0.41-0.93), and oil yields (40-75%). These results were successfully validated by repeating RCF reactions in 75 mL batch reactors for a subset of samples. We anticipate that this approach can be used to rapidly screen substrates, catalysts, and reaction conditions in high-pressure batch reactions with higher throughput than standard batch reactors.
PubMed: 38938803
DOI: 10.1021/jacsau.4c00126 -
Aging & Mental Health Jun 2024Loneliness has been associated with psychotic-like experiences (PLEs) in the general population, but the mechanisms underlying this association are poorly understood....
OBJECTIVES
Loneliness has been associated with psychotic-like experiences (PLEs) in the general population, but the mechanisms underlying this association are poorly understood. Theoretical models, corroborated by empirical findings, signify the key role of biased cognition in both loneliness and psychosis. This study tested whether two cognitive biases - Selective Attention to Threat (ATB) and External Attribution Bias (EAB) - account for the association between loneliness and PLEs.
METHOD
A convenience sample ( = 357) of middle-aged and older adults (aged 40+) was recruited online from the UK population. The parallel mediation model with two the aforementioned cognitive biases as mediators was tested.
RESULTS
A mediation effect between loneliness and PLEs ATB ( = 0.441, 95% CI = [0.264, 0.646]) and EAB ( = 0.354, 95% CI [0.124, 0.627] was established. This model remained significant after controlling for the current symptoms of anxiety and depression.
CONCLUSION
Greater loneliness was associated with a higher rate of PLEs in the sample of middle-aged and older adults. This association was fully explained by ATB and EAB, independent of the current symptoms of anxiety and depression.
PubMed: 38938159
DOI: 10.1080/13607863.2024.2372072