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1.
Plast Reconstr Surg ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38967643

ABSTRACT

BACKGROUND: Enophthalmos is a surgical indication for orbital fracture repair. However, guidelines to predict enophthalmos in orbital fractures are ambiguous. We systematically reviewed the existing literature on utilizing CT findings to establish objective metrics to predict enophthalmos in asymptomatic patients during initial trauma work-up. METHODS: PRISMA guidelines were followed. PubMed and Embase were used to identify studies of interest. The Quality in Prognosis Studies (QUIPS) tool was used for risk of bias assessment. Random effects model meta-analyses of orbital volume change and fracture area values were completed. Regression analyses were performed to determine thresholds that predicted 2 mm enophthalmos. RESULTS: Of the initial 2236 abstracts, 36 met inclusion criteria. Thirty retrospective studies evaluated a total of 2851 patients and 6 prospective studies evaluated 211 patients. All 36 studies had predominantly low risk of bias. Predictors of enophthalmos assessed were orbital volume change (21 papers), fracture surface area (13 papers), inferior rectus muscle (IRM) displacements (7 papers), and fracture location (4 papers). Studies reporting on orbital volume change offered values ranging from 0.69 to 4.26 cm3. Fracture area predictor values ranged from 1.50 to 3.38 cm2. Meta-analyses confirmed the validity of both predictors. Pooled regression analyses demonstrated that 3.33 cm3 of orbital volume increase or fracture area of 3.12 cm2 were predictors of 2 mm enophthalmos. CONCLUSIONS: Both orbital volume change and fracture area measured on CT scan are good predictors of late post-traumatic enophthalmos. Pooled data indicates 3.12 cm2 of fracture area or 3.33 cm3 of orbital volume increase are predictive of enophthalmos.

2.
Pharmaceutics ; 16(7)2024 Jun 25.
Article in English | MEDLINE | ID: mdl-39065554

ABSTRACT

The steady rise of drug-resistant tuberculosis (TB), which renders standard therapy regimens ineffective, necessitates the development of innovative treatment approaches. Immunotherapeutic vaccines have the potential to effectively regulate the anti-TB immune response and enhance the efficacy of anti-TB treatment. In the present study, we aimed to evaluate the potency of the mucosal vector vaccine TB/FLU-06E as part of a complex treatment regimen for drug-susceptible (DS) or drug-resistant (DR) tuberculosis in C57BL/6 mice. Incorporating TB/FLU-06E into the treatment protocol significantly increased the effectiveness of therapy for both forms of tuberculosis. It was evidenced by higher survival rates and reduced pulmonary bacterial load (1.83 lg CFU for DS tuberculosis and 0.93 lg CFU for DR tuberculosis). Furthermore, the treatment reduced pathomorphological lesions in the lungs and stimulated the local and systemic T-helper 1 (Th1) and cytotoxic T-lymphocyte (CTL) anti-TB immune responses. Thus, therapeutic immunization with the TB/FLU-06E vaccine significantly enhances the efficacy of tuberculosis treatment, which is particularly important in DR tuberculosis.

3.
Cancer Cell ; 42(7): 1217-1238.e19, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38981438

ABSTRACT

Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas.


Subject(s)
Brain Neoplasms , Glioma , Protein Tyrosine Phosphatase, Non-Receptor Type 11 , Signal Transduction , Humans , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism , Glioma/genetics , Glioma/pathology , Glioma/metabolism , Mutation , Proteomics/methods , Protein Processing, Post-Translational , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Glioblastoma/pathology , Glioblastoma/metabolism , Phosphorylation , Neoplasm Grading , Isocitrate Dehydrogenase/genetics , Isocitrate Dehydrogenase/metabolism
4.
Cereb Cortex ; 34(7)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38990517

ABSTRACT

Aberrations in non-verbal social cognition have been reported to coincide with major depressive disorder. Yet little is known about the role of the eyes. To fill this gap, the present study explores whether and, if so, how reading language of the eyes is altered in depression. For this purpose, patients and person-by-person matched typically developing individuals were administered the Emotions in Masked Faces task and Reading the Mind in the Eyes Test, modified, both of which contained a comparable amount of visual information available. For achieving group homogeneity, we set a focus on females as major depressive disorder displays a gender-specific profile. The findings show that facial masks selectively affect inferring emotions: recognition of sadness and anger are more heavily compromised in major depressive disorder as compared with typically developing controls, whereas the recognition of fear, happiness, and neutral expressions remains unhindered. Disgust, the forgotten emotion of psychiatry, is the least recognizable emotion in both groups. On the Reading the Mind in the Eyes Test patients exhibit lower accuracy on positive expressions than their typically developing peers, but do not differ on negative items. In both depressive and typically developing individuals, the ability to recognize emotions behind a mask and performance on the Reading the Mind in the Eyes Test are linked to each other in processing speed, but not recognition accuracy. The outcome provides a blueprint for understanding the complexities of reading language of the eyes within and beyond the COVID-19 pandemic.


Subject(s)
Depressive Disorder, Major , Emotions , Facial Expression , Humans , Female , Adult , Emotions/physiology , Depressive Disorder, Major/psychology , Depressive Disorder, Major/physiopathology , Young Adult , Facial Recognition/physiology , Middle Aged , COVID-19/psychology , Reading
5.
World J Gastrointest Oncol ; 16(6): 2304-2317, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38994146

ABSTRACT

After reading the review by An et al "Biological factors driving colorectal cancer metastasis", which covers the problem of the metastasis of colorectal cancer (CRC), I had a desire to discuss with readers one of the exciting problems associated with dormant metastases. Most deaths from CRCs are caused by metastases, which can be detected both at diagnosis of the primary tumor and several years or even decades after treatment. This is because tumor cells that enter the bloodstream can be destroyed by the immune system, cause metastatic growth, or remain dormant for a long time. Dormant tumor cells may not manifest themselves throughout a person's life or, after some time and under appropriate conditions, may give rise to the growth of metastases. In this editorial, we will discuss the most important features of dormant metastases and the mechanisms of premetastatic niche formation, as well as factors that contribute to the activation of dormant metastases in CRCs. We will pay special attention to the possible mechanisms involved in the formation of circulating tumor cell complexes and the choice of therapeutic strategies that promote the dormancy or destruction of tumor cells in CRCs.

6.
Molecules ; 29(13)2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38999177

ABSTRACT

A short 19 bp dsRNA with 3'-trinucleotide overhangs acting as immunostimulating RNA (isRNA) demonstrated strong antiproliferative action against cancer cells, immunostimulatory activity through activation of cytokines and Type-I IFN secretion, as well as anti-tumor and anti-metastatic effects in vivo. The aim of this study was to determine the tolerance of chemical modifications (2'-F, 2'-OMe, PS, cholesterol, and amino acids) located at different positions within this isRNA to its ability to activate the innate immune system. The obtained duplexes were tested in vivo for their ability to activate the synthesis of interferon-α in mice, and in tumor cell cultures for their ability to inhibit their proliferation. The obtained data show that chemical modifications in the composition of isRNA have different effects on its individual functions, including interferon-inducing and antiproliferative effects. The effect of modifications depends not only on the type of modification but also on its location and the surrounding context of the modifications. This study made it possible to identify leader patterns of modifications that enhance the properties of isRNA: F2/F2 and F2_S/F2 for interferon-inducing activity, as well as F2_S5/F2_S5, F2-NH2/F2-NH2, and Ch-F2/Ch-F2 for antiproliferative action. These modifications can improve the pharmacokinetic and pharmacodynamic properties, as well as increase the specificity of isRNA action to obtain the desired effect.


Subject(s)
Cell Proliferation , RNA, Double-Stranded , RNA, Double-Stranded/pharmacology , RNA, Double-Stranded/chemistry , Animals , Cell Proliferation/drug effects , Mice , Humans , Cell Line, Tumor , Interferon-alpha/metabolism , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/chemistry , Interferons/metabolism
7.
J Neurophysiol ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38988288

ABSTRACT

Growing evidence suggests that neuropeptide signaling shapes auditory computations. We previously showed that neuropeptide Y (NPY) is expressed in the inferior colliculus (IC) by a population of GABAergic stellate neurons and that NPY regulates the strength of local excitatory circuits in the IC. NPY neurons were initially characterized using the NPY-hrGFP mouse, in which humanized renilla Green Fluorescent Protein (hrGFP) expression indicates NPY expression at the time of assay, i.e., an expression-tracking approach. However, studies in other brain regions have shown that NPY expression can vary based on several factors, suggesting that the NPY-hrGFP mouse might miss NPY neurons not expressing NPY on the experiment date. Here, we hypothesized that neurons with the ability to express NPY represent a larger population of IC GABAergic neurons than previously reported. To test this hypothesis, we used a lineage-tracing approach to irreversibly tag neurons that expressed NPY at any point prior to the experiment date. We then compared the physiological and anatomical features of neurons labeled with this lineage-tracing approach to our prior data set, revealing a larger population of NPY neurons than previously found. In addition, we used optogenetics to test the local connectivity of NPY neurons and found that NPY neurons routinely provide inhibitory synaptic input to other neurons in the ipsilateral IC. Together, our data expand the definition of NPY neurons in the IC, suggest that NPY expression might be dynamically regulated in the IC, and provide functional evidence that NPY neurons form local inhibitory circuits in the IC.

8.
J Org Chem ; 89(14): 10283-10292, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-38981920

ABSTRACT

A photoinduced one-pot method for the synthesis of azepines by the reaction of aryl azides with 1,3-dicarbonyl compounds under weakly basic conditions is described. This method offers a simple route for the synthesis of 1,3-dicarbonyl-substituted azepines in good to excellent yields and high regioselectivity and was tested on 1,3-dicarbonyl compounds with different acidity levels. The resulting azepines have electrophilic and nucleophilic centers of varying degrees of activity, which facilitate reactions leading to further structural transformations.

9.
Methods Mol Biol ; 2823: 173-191, 2024.
Article in English | MEDLINE | ID: mdl-39052221

ABSTRACT

Immunoprecipitation is one of the most effective methods for enrichment of lysine-acetylated peptides for comprehensive acetylome analysis using mass spectrometry. Manual acetyl peptide enrichment method using non-conjugated antibodies and agarose beads has been developed and applied in various studies. However, it is time-consuming and can introduce contaminants and variability that leads to potential sample loss and decreased sensitivity and robustness of the analysis. Here we describe a fast, automated enrichment protocol that enables reproducible and comprehensive acetylome analysis using a magnetic bead-based immunoprecipitation reagent.


Subject(s)
Immunoprecipitation , Workflow , Immunoprecipitation/methods , Acetylation , Humans , Proteomics/methods , Lysine/metabolism , Peptides/chemistry , Mass Spectrometry/methods , Protein Processing, Post-Translational , Proteome/analysis
10.
J Control Release ; 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39038544

ABSTRACT

Nano-mupirocin is a PEGylated nano-liposomal formulation of the antibiotic mupirocin, undergoing evaluation for treating infectious diseases and intratumor bacteria. Intratumoral microbiota play an important role in the regulation of tumor progression and therapeutic efficacy. However, antibiotic use to target intratumoral bacteria should be performed in a way that will not affect the gut microbiota, found to enable the efficacy of cancer treatments. Nano-mupirocin may offer such a selective treatment. Herein, we demonstrate the ability of Nano-mupirocin to successfully target tumor-residing Fusobacterium nucleatum without an immediate effect on the gut microbiome. In-depth characterization of this novel formulation was performed, and the main findings include: (i). the pharmacokinetic analysis of mupirocin administered as Nano-mupirocin vs mupirocin lithium (free drug) demonstrated that most of the Nano-mupirocin in plasma is liposome associated; (ii). microbiome analysis of rat feces showed no significant short-term difference between Nano-mupirocin, mupirocin lithium and controls; (iii). Nano-mupirocin was active against intratumoral F. nucleatum, a tumor promoting bacteria that accumulates in tumors of the AT3 mice model of breast cancer. These data suggest the ability of Nano-mupirocin to target tumor residing and promoting bacteria.

11.
HGG Adv ; 5(3): 100324, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-38956874

ABSTRACT

Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed, essential enzymes that complete the first step of protein translation: ligation of amino acids to cognate tRNAs. Genes encoding ARSs have been implicated in myriad dominant and recessive phenotypes, the latter often affecting multiple tissues but with frequent involvement of the central and peripheral nervous systems, liver, and lungs. Threonyl-tRNA synthetase (TARS1) encodes the enzyme that ligates threonine to tRNATHR in the cytoplasm. To date, TARS1 variants have been implicated in a recessive brittle hair phenotype. To better understand TARS1-related recessive phenotypes, we engineered three TARS1 missense variants at conserved residues and studied these variants in Saccharomyces cerevisiae and Caenorhabditis elegans models. This revealed two loss-of-function variants, including one hypomorphic allele (R433H). We next used R433H to study the effects of partial loss of TARS1 function in a compound heterozygous mouse model (R432H/null). This model presents with phenotypes reminiscent of patients with TARS1 variants and with distinct lung and skin defects. This study expands the potential clinical heterogeneity of TARS1-related recessive disease, which should guide future clinical and genetic evaluations of patient populations.


Subject(s)
Caenorhabditis elegans , Saccharomyces cerevisiae , Threonine-tRNA Ligase , Animals , Mice , Caenorhabditis elegans/genetics , Saccharomyces cerevisiae/genetics , Threonine-tRNA Ligase/genetics , Threonine-tRNA Ligase/metabolism , Humans , Phenotype , Loss of Function Mutation , Disease Models, Animal , Mutation, Missense
12.
Heliyon ; 10(13): e33801, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39027545

ABSTRACT

Co-precipitation of biopolymers into calcium carbonate crystals changes their physicochemical and biological properties. This work studies hybrid microcrystals of vaterite obtained in the presence of natural polysaccharides, as carriers for the delivery of proteins and enzymes. Hybrid microcrystals with dextran sulfate, chondroitin sulfate, heparin, fucoidan, and pectin were obtained and compared. The impact of polysaccharides on the morphology (particle diameter, surface area, nanocrystallite and pore size), polysaccharide content and surface charge of hybrid microcrystals was studied. Only microcrystals with fucoidan and heparin exhibited antioxidant activity against •ОН radical. The surface charge and pore size of the hybrid microcrystals affected the sorption of albumin, catalase, chymotrypsin, mucin. A decrease in the catalytic constant and Michaelis constant was observed for catalase sorbed on the hybrid crystals. The biocompatibility of microcrystals depended on the nature of the included polysaccharide: crystals with sulfated polysaccharides increased blood plasma coagulation but not platelet aggregation, and crystals with dextran sulfate had the greatest cytotoxicity against HT-29 cells but not erythrocytes. Hybrid microcrystals with all polysaccharides except chondroitin sulfate reduced erythrocyte lysis in vitro compared with vaterite crystals. The obtained results enable to create novel carriers based on hybrid vaterite crystals with polysaccharides, beneficial for the delivery of protein drugs.

13.
World J Clin Oncol ; 15(5): 614-634, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38835849

ABSTRACT

BACKGROUND: Lung cancer (LC) is the leading cause of morbidity and mortality among malignant neoplasms. Improving the diagnosis and treatment of LC remains an urgent task of modern oncology. Previously, we established that in gastric, breast and cervical cancer, tumor microvessels (MVs) differ in morphology and have different prognostic significance. The connection between different types of tumor MVs and the progression of LC is not well understood. AIM: To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma (LUSC). METHODS: A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts, respectively. All patients underwent radical surgery (R0) at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021. Tumor sections were routinely processed, and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34 (CD34), podoplanin, Snail and hypoxia-inducible factor-1 alpha were performed. The morphological features of different types of tumor MVs, tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis. Statistical analysis was performed using Statistica 10.0 software. Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes (RLNs) and disease recurrence. Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence. The effectiveness of the predictive models was assessed by the area under the curve. Survival was analyzed using the Kaplan-Meier method. The log-rank test was used to compare survival curves between patient subgroups. A value of P < 0.05 was considered to indicate statistical significance. RESULTS: Depending on the morphology, we classified tumor vessels into the following types: normal MVs, dilated capillaries (DCs), atypical DCs, DCs with weak expression of CD34, "contact-type" DCs, structures with partial endothelial linings, capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates. We also evaluated the presence of loose, fine fibrous connective tissue (LFFCT) and retraction clefts in the tumor stroma, tumor spread into the alveolar air spaces (AASs) and fragmentation of the tumor solid component. According to multivariate analysis, the independent predictors of LUSC metastasis in RLNs were central tumor location (P < 0.00001), the presence of retraction clefts (P = 0.003), capillaries in the tumor solid component (P = 0.023) and fragmentation in the tumor solid component (P = 0.009), whereas the independent predictors of LUSC recurrence were tumor grade 3 (G3) (P = 0.001), stage N2 (P = 0.016), the presence of LFFCT in the tumor stroma (P < 0.00001), fragmentation of the tumor solid component (P = 0.0001), and the absence of tumor spread through the AASs (P = 0.0083). CONCLUSION: The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.

14.
J Dairy Sci ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38851578

ABSTRACT

Few studies have examined the N kinetics of individual feeds with stable isotope tracing. We hypothesized that N partitioning to milk and excreta pools as well as the rates of the processes that drive this partitioning would differ for alfalfa silage, corn silage, corn grain, and soybean meal. Feed ingredients were endogenously labeled with 15N and included in 4 diets to create treatments with the same dietary composition and different labeled feed. Diets were fed to 12 late-lactation dairy cows for 4 d (96 h) and feces, urine, and milk collection proceeded during the 4 d of 15N enrichment and for 3 d (80 h) after cessation of label feeding. Nonlinear models of 15N enrichment and decay were fit to milk (MN), urine (UN), and fecal N (FN) in R with the nlme package and feed-specific parameter estimates were compared. The estimated proportions of feed N that were excreted in feces supported our understanding that N from soybean meal and corn grain is more digestible than N from alfalfa and corn silage. Estimates for the N partitioning between milk (MN) and urine (UN) from the 2 concentrate feeds (soybean meal and corn grain) indicated that UN:MN ratios were less than or equal to 1:1 indicating either more or equal nitrogen partitioning to milk compared with urine. It is important to maintain factual accuracy in representing the results rather than implying a desired outcome unsupported by the data. In contrast, UN:MN ratios for forage feeds (corn and alfalfa silage) were > 1:1, indicating more N partitioning to urine than milk. The modeled proportion of total FN that originated from feed N was 82.2% which is in line with previous research using a similar 15N measurement timeframe. However, the proportion of urinary and MN originating from feed N was much lower (60.5% for urine, 57.9% for milk), suggesting that approximately 40% of urinary and MN directly originate from body N sources related to protein turnover.

15.
J Surg Oncol ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935857

ABSTRACT

BACKGROUND AND OBJECTIVES: Gastric cancer (GC) prognosis is influenced by the extent of the tumor, lymph node involvement (LNM), and metastasis. Endoscopic resection (ER) or gastrectomy with lymphadenectomy are standard treatments for early GC (EGC). This study evaluated LNM frequency according to eCura categories, clinicopathological characteristics, disease-free (DFS), and overall (OS) survival rates. METHODS: We included EGC patients who underwent curative gastrectomy between 2009 and 2020 from our single-center database. Anatomopathological and clinical reports were reviewed to analyze eCura categories. RESULTS: We included 160 EGC patients who underwent gastrectomy with eCura categories A, B, and C, comprising 26.3%, 13.8%, and 60%, respectively. Baseline clinical characteristics showed no intergroup disparities. LNM incidence for A, B, and C was 4.8%, 18.2%, and 19.8%. When evaluating the criteria for ER and its association with eCura categories, we found that 95.2% of eCura A and 100% of eCura B patients had classic or expanded criteria for ER. On the other hand, 97.9% of eCura C patients were referred to surgical resection. Multivariate analysis demonstrated that lymphatic (OR = 5.57, CI95% = 1.45-21.29, p = 0.012) and perineural (OR = 15.8, CI95% = 1.39-179.88, p = 0.026) invasions were associated with a higher risk of LNM. No significant differences in DFS or OS were found among eCura categories. CONCLUSION: The eCura categories were associated with the occurrence of LNM. In most patients, those with classic and expanded indication criteria for ER were classified as eCura A and B.

16.
PLoS One ; 19(6): e0305671, 2024.
Article in English | MEDLINE | ID: mdl-38917231

ABSTRACT

Access to brushes allows for natural scratching behaviors in cattle, especially in confined indoor settings. Cattle are motivated to use brushes, but brush use varies with multiple factors including social hierarchy and health. Brush use might serve an indicator of cow health or welfare, but practical application of these measures requires accurate and automated monitoring tools. This study describes a machine learning approach to monitor brush use by dairy cattle. We aimed to capture the daily brush use by integrating data on the rotation of a mechanical brush with data on cow identify derived from either 1) low-frequency radio frequency identification or 2) a computer vision system using fiducial markers. We found that the computer vision system outperformed the RFID system in accuracy, and that the machine learning algorithms enhanced the precision of the brush use estimates. This study presents the first description of a fiducial marker-based computer vision system for monitoring individual cattle behavior in a group setting; this approach could be applied to develop automated measures of other behaviors with the potential to better assess welfare and improve the care for farm animals.


Subject(s)
Behavior, Animal , Machine Learning , Animals , Cattle , Dairying/methods , Dairying/instrumentation , Radio Frequency Identification Device/methods , Female , Algorithms , Animal Welfare
17.
Article in English | MEDLINE | ID: mdl-38881692

ABSTRACT

Background: Essential tremor (ET) is the most common movement disorder in adults and is considered to be highly heritable. A reduction of the tremor amplitude after alcohol consumption is reported in approximately half of the patients. In this study, we describe the alcohol response in our familial ET cohort by employing an alcohol responsivity test designed by Knudsen et al. outside its original research group for the first time. Methods: We recruited families with at least three trembling family members and confirmed ET diagnoses. During the in-hospital alcohol responsivity test, tremor was measured using Archimedes spirals before alcohol consumption (T0), one hour after alcohol intake (T1), and the next morning (T2). The spirals were rated by two independent raters using the Bain Findley scale. The average of these two scores was calculated as the Archimedes Spiral Rating (ASR) for each time point. Results: Twenty-four confirmed ET patients were included for analysis. The median ASR at T0 (5.0) and T2 (4.75) were significantly higher than the median ASR at T1 (3.25) (both p < 0.001). In 67% of patients, a difference in ASR between T0 and T1 (dASR) ≥ 2 pointed towards an improvement of tremor after consuming alcohol. Discussion: We confirmed that the alcohol responsiveness test of Knudsen et al. is useful in determining objective alcohol responsivity. We established a significantly reduced ASR after alcohol consumption in 67% of familial ET patients in our cohort. In the future, a larger population is needed to establish whether familial aggregation of alcohol responsivity occurs in essential tremor patients. Highlights: The test designed by Knudsen et al. effectively established objective alcohol responsiveness outside its original research group.We found an objective alcohol response in 67% of our familial ET cohort.Subjective VAS scores were significantly lower after alcohol consumption.There was no correlation between the objective and subjective alcohol responsiveness.Familial aggregation of alcohol responsiveness in ET should be studied in a larger cohort.


Subject(s)
Alcohol Drinking , Essential Tremor , Humans , Essential Tremor/genetics , Essential Tremor/physiopathology , Male , Female , Middle Aged , Aged , Adult , Cohort Studies
18.
J Dairy Sci ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38825128

ABSTRACT

Dominance hierarchies are known for mitigating conflicts and guiding priority of access to limited resources in gregarious animals. The dominance hierarchy of dairy cows is typically investigated using agonistic interactions, often monitored at the feed bunk right after fresh feed delivery when competition is high resulting in frequent interactions. Yet, the outcome of agonistic interactions during times of high competition may be more influenced by cows' high valuation of fresh feed than their intrinsic attributes, such that the dominance hierarchy constructed using agonistic interactions under high versus low competition times might differ. We tested how the structure of the dominance hierarchy changes in relation to different levels of competition in a dynamic group of 48 lactating dairy cows over 10 mo, with 6 cows exchanged every 16 d for a total of 159 cows. Using a validated algorithm we continuously detected the actor and reactor of replacement behaviors in 30 feed bins as cows competed for feed. We also calculated the percentage of occupied feed bins to characterize competition at the moment of each replacement. These data were combined to create hierarchies using Elo ratings, separately for 25 occupancy levels ranging from 13% to 100%. For each 1% rise in feeder occupancy, hierarchy steepness fell by 2.41 × 10-3 ± 9.71 × 10-5 (SE), and the percentage of dyads where both cows replaced each other rose by 0.13% ± 0.01%. At the highest feeder occupancy level in comparison to the lowest one, we observed 7.57% more dyads in which the dominant individual (those won more interactions at the lowest feeder occupancy) started to lose proportionally more. The magnitude of decrease in the winning rate of the dominant individual in those dyads also got amplified by 1.06 × 10-3% ± 1.37 × 10-4% (SE) for each 1% increase in feeder occupancy. These findings illustrate how inferred hierarchies vary with competition, with high competition flattening the hierarchy due to increased success of subordinate animals. We suggest that during heightened competition, increased valuation of resources can affect competitive success more than the individual's intrinsic dominance attributes. We recommend against calculating dominance hierarchies based on agonistic interactions during periods of high competition alone, and more generally urge researchers to differentiate agonistic interactions based on context when constructing dominance hierarchies.

19.
Nanomaterials (Basel) ; 14(11)2024 May 22.
Article in English | MEDLINE | ID: mdl-38869529

ABSTRACT

Currently, one of the most important problems of environmental protection is the deep and complex processing of mineral raw materials. This problem is especially relevant when processing substandard ores and production waste, one of which is phosphogypsum. This study examines the process of CaSO4/CaS composite material formation during the reduction of phosphogypsum with citric acid. The composite structure formation mechanism is proposed. The resulting materials are characterized using various methods, including X-ray diffraction (XRD), transmission electron microscopy, the Scherrer method, thermogravimetric analysis (TGA), and FT-IR spectroscopy. The reduced sample emits orange radiation in the range of 500-750 nm with a quantum yield of 0.17. Experimental results showed that the sample decomposition process in the solid state consisted of two components with a predominant contribution from the long-lived component (~46 ns). The optimal conditions for producing luminescent materials by reducing phosphogypsum with citric acid were determined: a heat treatment temperature of 1073 K, a holding time of 60 min, and a reducing agent mole fraction of 37%. It was found that an increase in temperature with a simultaneous decrease in heat treatment time, as well as a decrease in temperature with a simultaneous increase in heat treatment time, led to a decrease in the luminescent properties of the synthesized material compared to optimal values. The results can be used to develop technology for recycling large-tonnage waste from the chemical industry into luminescent materials.

20.
Neurobiol Dis ; 199: 106555, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38844245

ABSTRACT

Progressive myoclonus ataxia (PMA) is a rare clinical syndrome characterized by the presence of progressive myoclonus and ataxia, and can be accompanied by mild cognitive impairment and infrequent epileptic seizures. This is the first study to describe the natural history of PMA and identify clinical, electrophysiological, and genetic features explaining the variability in disease progression. A Dutch cohort of consecutive patients meeting the criteria of the refined definition of PMA was included. The current phenotype was assessed during in-person consultation by movement disorders experts, and retrospective data was collected to describe disease presentation and progression, including brain imaging and therapy efficacy. Extensive genetic and electrophysiological tests were performed. The presence of cortical hyperexcitability was determined, by either the identification of a cortical correlate of myoclonic jerks with simultaneous electromyography-electroencephalography or a giant somatosensory evoked potential. We included 34 patients with PMA with a median disease duration of 15 years and a clear progressive course in most patients (76%). A molecular etiology was identified in 82% patients: ATM, CAMTA1, DHDDS, EBF3, GOSR2, ITPR1, KCNC3, NUS1, POLR1A, PRKCG, SEMA6B, SPTBN2, TPP1, ZMYND11, and a 12p13.32 deletion. The natural history is a rather homogenous onset of ataxia in the first two years of life followed by myoclonus in the first 5 years of life. Main accompanying neurological dysfunctions included cognitive impairment (62%), epilepsy (38%), autism spectrum disorder (27%), and behavioral problems (18%). Disease progression showed large variability ranging from an epilepsy free PMA phenotype (62%) to evolution towards a progressive myoclonus epilepsy (PME) phenotype (18%): the existence of a PMA-PME spectrum. Cortical hyperexcitability could be tested in 17 patients, and was present in 11 patients and supported cortical myoclonus. Interestingly, post-hoc analysis showed that an absence of cortical hyperexcitability, suggesting non-cortical myoclonus, was associated with the PMA-end of the spectrum with no epilepsy and milder myoclonus, independent of disease duration. An association between the underlying genetic defects and progression on the PMA-PME spectrum was observed. By describing the natural history of the largest cohort of published patients with PMA so far, we see a homogeneous onset with variable disease progression, in which phenotypic evolution to PME occurs in the minority. Genetic and electrophysiological features may be of prognostic value, especially the determination of cortical hyperexcitability. Furthermore, the identification of cortical and non-cortical myoclonus in PMA helps us gain insight in the underlying pathophysiology of myoclonus.


Subject(s)
Disease Progression , Humans , Female , Male , Adult , Middle Aged , Young Adult , Retrospective Studies , Electroencephalography/methods , Aged , Electromyography , Ataxia/genetics , Ataxia/physiopathology , Adolescent , Myoclonus/physiopathology , Myoclonus/genetics
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