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Medicina (Kaunas, Lithuania) May 2024Amyotrophic lateral sclerosis (ALS) is an incurable rare neurodegenerative condition, with 45% of cases showing the symptom of dysphagia; its clinical signs are atrophy,...
Amyotrophic lateral sclerosis (ALS) is an incurable rare neurodegenerative condition, with 45% of cases showing the symptom of dysphagia; its clinical signs are atrophy, weakness, and fasciculations of the facial muscles, tongue, and pharynx. Furthermore, dysphagia is the main cause of aspiration pneumonia. The traditional treatment for dysphagia varies based on the patient's difficulty of swallowing. The initial phase consists of dietary consistency adjustments, progressing to alternatives like nasogastric tubes or percutaneous endoscopic gastrostomy (PEG) in advanced stages. Osteopathic manipulative treatment (OMT) is a complementary 'hands-on' approach that has already shown positive results as an add-on therapy in various health conditions. This study is a case report of a man diagnosed with ALS with initial dysphagia, managed with a protocol that extraordinarily included OMT. The patient showed somatic dysfunctions in the mediastinal region, upper cervical region, and occipital area which are all anatomically related to the nervous system, especially the glossopharyngeal reflex. At the end of the rehabilitation protocol, there was a reduction in the swallowing problems measured with Strand Scale and swallowing tests, and the patient reported an improved psycho-physical well-being assessed with the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40). Instead, the neurological function measured with ALSFRS-S remained stable. Although the nature of this study design prevents any causal assumption, the positive results should lead to future randomized controlled trials to assess the effectiveness of OMT as an adjunctive therapeutic proposal to improve the health of ALS patients.
Topics: Humans; Amyotrophic Lateral Sclerosis; Male; Deglutition Disorders; Middle Aged; Manipulation, Osteopathic; Treatment Outcome
PubMed: 38929462
DOI: 10.3390/medicina60060845 -
International Journal of Molecular... Jun 2024At present, the magnetic selection of genetically modified cells is mainly performed with surface markers naturally expressed by cells such as CD4, LNGFR (low affinity...
At present, the magnetic selection of genetically modified cells is mainly performed with surface markers naturally expressed by cells such as CD4, LNGFR (low affinity nerve growth factor receptor), and MHC class I molecule H-2Kk. The disadvantage of such markers is the possibility of their undesired and poorly predictable expression by unmodified cells before or after cell manipulation, which makes it essential to develop new surface markers that would not have such a drawback. Earlier, modified CD52 surface protein variants with embedded HA and FLAG epitope tags (CD52/FLAG and CD52/HA) were developed by the group of Dr. Mazurov for the fluorescent cell sorting of CRISPR-modified cells. In the current study, we tested whether these markers can be used for the magnetic selection of transduced cells. For this purpose, appropriate constructs were created in MigR1-based bicistronic retroviral vectors containing EGFP and DsRedExpress2 as fluorescent reporters. Cytometric analysis of the transduced NIH 3T3 cell populations after magnetic selection evaluated the efficiency of isolation and purity of the obtained populations, as well as the change in the median fluorescence intensity (MFI). The results of this study demonstrate that the surface markers CD52/FLAG and CD52/HA can be effectively used for magnetic cell selection, and their efficiencies are comparable to that of the commonly used LNGFR marker. At the same time, the significant advantage of these markers is the absence of HA and FLAG epitope sequences in cellular proteins, which rules out the spurious co-isolation of negative cells.
Topics: Animals; Mice; NIH 3T3 Cells; CD52 Antigen; Recombinant Fusion Proteins; Humans; Flow Cytometry; Cell Separation; Biomarkers
PubMed: 38928060
DOI: 10.3390/ijms25126353 -
Biomolecules May 2024Duckweed () rises as a crucial model system due to its unique characteristics and wide-ranging utility. The significance of physiological research and phytoremediation... (Review)
Review
Duckweed () rises as a crucial model system due to its unique characteristics and wide-ranging utility. The significance of physiological research and phytoremediation highlights the intricate potential of duckweed in the current era of plant biology. Special attention to duckweed has been brought due to its distinctive features of nutrient uptake, ion transport dynamics, detoxification, intricate signaling, and stress tolerance. In addition, duckweed can alleviate environmental pollutants and enhance sustainability by participating in bioremediation processes and wastewater treatment. Furthermore, insights into the genomic complexity of species and the flourishing field of transgenic development highlight the opportunities for genetic manipulation and biotechnological innovations. Novel methods for the germplasm conservation of duckweed can be adopted to preserve genetic diversity for future research endeavors and breeding programs. This review centers around prospects in duckweed research promoting interdisciplinary collaborations and technological advancements to drive its full potential as a model organism.
Topics: Araceae; Biodegradation, Environmental; Models, Biological
PubMed: 38927032
DOI: 10.3390/biom14060628 -
BMC Sports Science, Medicine &... Jun 2024Vagally-mediated heart rate variability (vm-HRV) shows promise as a biomarker of internal training load (ITL) during exergame-based training or motor-cognitive training...
Test-retest reliability and validity of vagally-mediated heart rate variability to monitor internal training load in older adults: a within-subjects (repeated-measures) randomized study.
BACKGROUND
Vagally-mediated heart rate variability (vm-HRV) shows promise as a biomarker of internal training load (ITL) during exergame-based training or motor-cognitive training in general. This study evaluated the test-retest reliability of vm-HRV during exergaming in healthy older adults (HOA) and its validity to monitor ITL.
METHODS
A within-subjects (repeated-measures) randomized study was conducted that included baseline assessments and 4 measurement sessions. Participants played 5 exergames at 3 standardized levels of external task demands (i.e., "easy", "challenging", and "excessive") in random order for 90 s. Test-retest reliability was assessed on the basis of repeated-measures analyses of variance (ANOVA), intraclass correlation coefficients (ICC), standard errors of measurement (SEM), and smallest detectable differences (SDD). Validity was determined by examining the effect of game level on vm-HRV in the ANOVA.
RESULTS
Fourty-three HOA (67.0 ± 7.0 years; 58.1% females (25 females, 18 males); body mass index = 23.7 ± 3.0 kg·m) were included. Mean R-R time intervals (mRR) and parasympathetic nervous system tone index (PNS-Index) exhibited mostly good to excellent relative test-retest reliability with no systematic error. Mean SEM% and SDD% were 36.4% and 100.7% for mRR, and 44.6% and 123.7% for PNS-Index, respectively. Significant differences in mRR and PNS-Index were observed between standardized levels of external task demands, with mostly large effect sizes (mean r = 0.847). These results persisted irrespective of the type of neurocognitive domain trained and when only motoric and cognitive demands were manipulated while physical intensity was kept constant. The remaining vm-HRV parameters showed inconsistent or poor reliability and validity.
CONCLUSION
Only mRR and PNS-Index demonstrated reliable measurement and served as valid biomarkers for ITL during exergaming at a group level. Nonetheless, the presence of large SEMs hampers the detection of individual changes over time and suggests insufficient precision of these measurements at the individual level. Future research should further investigate the reliability and validity of vm-HRV with a specific focus on comparing different measurement methodologies and exercise conditions, particularly focusing on ultra-short-term HRV measurements, and investigate the potential implications (i.e., superiority to other markers of ITL or monitoring strategies?) of using vm-HRV as a biomarker of ITL.
PubMed: 38926777
DOI: 10.1186/s13102-024-00929-y -
Cell Reports Jun 2024Alcohol is the most widely used addictive substance, potentially leading to brain damage and genetic abnormalities. Despite its prevalence and associated risks, current...
Alcohol is the most widely used addictive substance, potentially leading to brain damage and genetic abnormalities. Despite its prevalence and associated risks, current treatments have yet to identify effective methods for reducing cravings and preventing relapse. In this study, we find that 4-Hz alternating bilateral sensory stimulation (ABS) effectively reduces ethanol-induced conditioned place preference (CPP) in male mice, while 4-Hz flash light does not exhibit therapeutic effects. Whole-brain c-Fos mapping demonstrates that 4-Hz ABS triggers notable activation in superior colliculus GABAergic neurons (SC). SC forms monosynaptic connections with ventral tegmental area dopaminergic neurons (VTA), which is implicated in ethanol-induced CPP. Bidirectional chemogenetic manipulation of SC-VTA circuit either replicates or blocks the therapeutic effects of 4-Hz ABS on ethanol-induced CPP. These findings elucidate the role of SC-VTA circuit for alleviating ethanol-related CPP by 4-Hz ABS and point to a non-drug and non-invasive approach that might have potential for treating alcohol use disorder.
PubMed: 38923461
DOI: 10.1016/j.celrep.2024.114383 -
Pathogens (Basel, Switzerland) Jun 2024The emergence of multidrug-resistant bacteria is undoubtedly one of the most serious global health threats. One response to this threat that has been gaining momentum... (Review)
Review
The emergence of multidrug-resistant bacteria is undoubtedly one of the most serious global health threats. One response to this threat that has been gaining momentum over the past decade is 'phage therapy'. According to this, lytic bacteriophages are used for the treatment of bacterial infections, either alone or in combination with antimicrobial agents. However, to ensure the efficacy and broad applicability of phage therapy, several challenges must be overcome. These challenges encompass the development of methods and strategies for the host range manipulation and bypass of the resistance mechanisms developed by pathogenic bacteria, as has been the case since the advent of antibiotics. As our knowledge and understanding of the interactions between phages and their hosts evolves, the key issue is to define the host range for each application. In this article, we discuss the factors that affect host range and how this determines the classification of phages into different categories of action. For each host range group, recent representative examples are provided, together with suggestions on how the different groups can be used to combat certain types of bacterial infections. The available methodologies for host range expansion, either through sequential adaptation to a new pathogen or through genetic engineering techniques, are also reviewed.
PubMed: 38921819
DOI: 10.3390/pathogens13060522 -
Marine Drugs Jun 2024Overwhelming evidence points to an aberrant Wnt/β-catenin signaling as a critical factor in hepatocellular carcinoma (HCC) and cervical cancer (CC) pathogenesis....
Overwhelming evidence points to an aberrant Wnt/β-catenin signaling as a critical factor in hepatocellular carcinoma (HCC) and cervical cancer (CC) pathogenesis. Dicerandrol C (DD-9), a dimeric tetrahydroxanthenone isolated from the endophytic fungus DHS-48 obtained from mangrove plant via chemical epigenetic manipulation of the culture, has demonstrated effective anti-tumor properties, with an obscure action mechanism. The objective of the current study was to explore the efficacy of DD-9 on HepG2 and HeLa cancer cells and its functional mechanism amid the Wnt/β catenin signaling cascade. Isolation of DD-9 was carried out using various column chromatographic methods, and its structure was elucidated with 1D NMR. The cytotoxicity of DD-9 on HepG2 and HeLa cells was observed with respect to the proliferation, clonality, migration, invasion, apoptosis, cell cycle, and Wnt/β-catenin signaling cascade. We found that DD-9 treatment significantly reduced tumor cell proliferation in dose- and time-dependent manners in HepG2 and HeLa cells. The subsequent experiments in vitro implied that DD-63 could significantly suppress the tumor clonality, metastases, and induced apoptosis, and that it arrested the cell cycle at the G/G phase of HepG2 and HeLa cells. Dual luciferase assay, Western blot, and immunofluorescence assay showed that DD-9 could dose-dependently attenuate the Wnt/β-catenin signaling by inhibiting β-catenin transcriptional activity and abrogating β-catenin translocated to the nucleus; down-regulating the transcription level of β-catenin-stimulated Wnt target gene and the expression of related proteins including -GSK3-β, β-catenin, LEF1, Axin1, -Myc, and CyclinD1; and up-regulating GSK3-β expression, which indicates that DD-9 stabilized the β-catenin degradation complex, thereby inducing β-catenin degradation and inactivation of the Wnt/β-catenin pathway. The possible interaction between DD-9 and β-catenin and GSK3-β protein was further confirmed by molecular docking studies. Collectively, DD-9 may suppress proliferation and induce apoptosis of liver and cervical cancer cells, possibly at least in part via GSK3-β-mediated crosstalk with the Wnt/β-catenin signaling axis, providing insights into the mechanism for the potency of DD-9 on hepatocellular and cervical cancer.
Topics: Humans; HeLa Cells; Apoptosis; Wnt Signaling Pathway; Cell Proliferation; Hep G2 Cells; beta Catenin; Antineoplastic Agents; Liver Neoplasms; Xanthones; Carcinoma, Hepatocellular; Cell Movement; Uterine Cervical Neoplasms
PubMed: 38921589
DOI: 10.3390/md22060278 -
Biosensors May 2024The µTAS/LOC, a highly integrated microsystem, consolidates multiple bioanalytical functions within a single chip, enhancing efficiency and precision in bioanalysis and...
The µTAS/LOC, a highly integrated microsystem, consolidates multiple bioanalytical functions within a single chip, enhancing efficiency and precision in bioanalysis and biomedical operations. Microfluidic centrifugation, a key component of LOC devices, enables rapid capture and enrichment of tiny objects in samples, improving sensitivity and accuracy of detection and diagnosis. However, microfluidic systems face challenges due to viscosity dominance and difficulty in vortex formation. Acoustic-based centrifugation, particularly those using surface acoustic waves (SAWs), have shown promise in applications such as particle concentration, separation, and droplet mixing. However, challenges include accurate droplet placement, energy loss from off-axis positioning, and limited energy transfer from low-frequency SAW resonators, restricting centrifugal speed and sample volume. In this work, we introduce a novel ring array composed of eight Lamb wave resonators (LWRs), forming an Ultra-Fast Centrifuge Tunnel (UFCT) in a microfluidic system. The UFCT eliminates secondary vortices, concentrating energy in the main vortex and maximizing acoustic-to-streaming energy conversion. It enables ultra-fast centrifugation with a larger liquid capacity (50 μL), reduced power usage (50 mW) that is one order of magnitude smaller than existing devices, and greater linear speed (62 mm/s), surpassing the limitations of prior methods. We demonstrate successful high-fold enrichment of 2 μm and 10 μm particles and explore the UFCT's potential in tissue engineering by encapsulating cells in a hydrogel-based micro-organ with a ring structure, which is of great significance for building more complex manipulation platforms for particles and cells in a bio-compatible and contactless manner.
Topics: Centrifugation; Humans; Lab-On-A-Chip Devices; Microfluidic Analytical Techniques; Acoustics
PubMed: 38920584
DOI: 10.3390/bios14060280 -
Journal of Anaesthesiology, Clinical... 2024Intra-cuff pressure of Air-Q self-pressurized laryngeal airways (Air-Q SP) balances airway pressure and adapts to patient's pharyngeal and periglottic structures, thus...
BACKGROUND AND AIMS
Intra-cuff pressure of Air-Q self-pressurized laryngeal airways (Air-Q SP) balances airway pressure and adapts to patient's pharyngeal and periglottic structures, thus improves oropharyngeal leak pressure (OLP).This study was performed to compare efficacy of Air-Q SP with Proseal laryngeal mask airway (PLMA) in patients undergoing elective surgery.
MATERIAL AND METHODS
The study design was prospective, randomized and controlled. Ninety patients were randomly assigned to Air-Q SP or PLMA group. All patients were premedicated and shifted to operation theatre. Monitoring was instituted. After securing IV-line, induction with inj. Morphine + Propofol, relaxation with inj. Vecuronium was done. Supraglottic was inserted according to group allocation. Outcome measures were OLP, fibreoptic view of larynx, success rate, device insertion parameters, haemodynamic and respiratory parameters and post-operative laryngopharyngeal complications. Neostigmine + glycopyrrolate were given, device was extubated.
RESULTS
All supraglottic airway devices (SADs) were successfully placed in two attempts. The mean initial OLP, OLP at 10 minutes, and device insertion time were significantly lower in Air-Q SP group. Fiber-optic laryngeal view grading was significantly better with Air-Q SP. No significant difference was observed with respect to rate of successful insertion in first attempt, ease of insertion, and manipulations required. The hemodynamic/respiratory parameters and post-operative sore throat in the two both groups were similar.
CONCLUSIONS
Proseal LMA has a higher OLP than Air-Q SP but average insertion time was better, and fiber-optic grading of laryngeal view was shorter with Air-Q SP. However, Air-Q SP and Proseal LMA were both effective for lung ventilation.
PubMed: 38919429
DOI: 10.4103/joacp.joacp_248_22 -
Frontiers in Neuroergonomics 2024Measuring an operator's physiological state and using that data to predict future performance decrements has been an ongoing goal in many areas of transportation....
INTRODUCTION
Measuring an operator's physiological state and using that data to predict future performance decrements has been an ongoing goal in many areas of transportation. Regarding Army aviation, the realization of such an endeavor could lead to the development of an adaptive automation system which adapts to the needs of the operator. However, reaching this end state requires the use of experimental scenarios similar to real-life settings in order to induce the state of interest that are able to account for individual differences in experience, exposure, and perception to workload manipulations. In the present study, we used an individualized approach to manipulating workload in order to account for individual differences in response to workload manipulations, while still providing an operationally relevant flight experience.
METHODS
Eight Army aviators participated in the study, where they completed two visits to the laboratory. The first visit served the purpose of identifying individual workload thresholds, with the second visit resulting in flights with individualized workload manipulations. EEG data was collected throughout both flights, along with subjective ratings of workload and flight performance.
RESULTS
Both EEG data and workload ratings suggested a high workload. Subjective ratings were higher during the high workload flight compared to the low workload flight ( < 0.001). Regarding EEG, frontal alpha ( = 0.04) and theta ( = 0.01) values were lower and a ratio of beta/(alpha+theta) ( = 0.02) were higher in the baseline flight scenario compared to the high workload scenario. Furthermore, the data were compared to that collected in previous studies which used a group-based approach to manipulating workload.
DISCUSSION
The individualized method demonstrated higher effect sizes in both EEG and subjective ratings, suggesting the use of this method may provide a more reliable way of producing high workload in aviators.
PubMed: 38919336
DOI: 10.3389/fnrgo.2024.1397586