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1.
J Environ Manage ; 367: 121991, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39094409

ABSTRACT

The Equatorial South Atlantic region, spanning over 1700 km, is currently undergoing extensive exploitation through various activities such as oil extraction, desalination plants, marine mineral explorations, and wind power for green hydrogen production. This undoubtedly also contributes to the exacerbation of pre-existing chronic environmental impacts. This study aims to investigate the concentrations of 60 substances, categorized as Persistent Organic Pollutants (POPs) and Contaminants of Emerging Concern (CECs) from various classes including: polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides (OCPs), as well as Pyrethroids (PPs), Triazines (TPs) and Organophosphates (OPPs) pesticides in consumable fish, shellfish, and crabs. The bivalve (Mytella charruana), crab (Ucides cordatus), and catfish (Sciades herzbergii) samples were collected in areas of ecological, environmental and economic importance. This data was used to estimate concentrations in the organisms, and to calculate cancer and human health risk. The most prevalent pollutant classes in the organisms were OCPs, followed by TPs and PPs. Shellfish and fish samples had more compounds indicating health risks, when compared to crabs. The substances causing cancer risks varied across organisms and study areas. The heightened cancer risks linked to specific compounds in various species highlight the urgent need to address persistent pollutants to prevent long-term health impacts on both humans and wildlife. Compounds such as PPs, TPs, and OPPs pose significant risks of neurotoxicity and endocrine disruption. This study underscores the interconnectedness of environmental and human health in coastal ecosystems, calling for continuous monitoring and adaptive management strategies to protect these fragile environments and the communities that rely on them.

2.
Water Res ; 263: 122149, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39098153

ABSTRACT

Sulfidated nanoscale zerovalent iron (S-nZVI) has demonstrated promising reactivity and longevity for remediating chlorinated volatile compounds (cVOC) contaminants in laboratory tests. However, its effectiveness in field applications remains inadequately evaluated. This study provides the first quantitative evaluation of the long-term effectiveness of carboxymethyl cellulose-stabilized S-nZVI (CMC-S-nZVI) at a cVOC-contaminated field site. A reactive transport model-based numerical approach delineates the change in cVOC concentrations and carbon isotope values (i.e., δ13C from compound-specific stable isotope analysis (CSIA)) caused by dissolution of dense non-aqueous phase liquid, sorption, and pathway-specific degradation and production, respectively. This delineation reveals quantitative insights into remediation effectiveness typically difficult to obtain, including extent of degradation, contributions of different degradation pathways, and degradation rate coefficients. Significantly, even a year after CMC-S-nZVI application, degradation remains an important process effectively removing various cVOC contaminants (i.e., chlorinated ethenes, 1,2-dichloroethanes, and chlorinated methanes) at an extent varying from 5 %-62 %. Although the impacts of CMC-S-nZVI abundance on degradation vary for different cVOC and for different sampling locations at the site, for the primary site contaminants of tetrachloroethene and trichloroethene, their predominance of dichloroelimination pathway (≥ 88 %), high degradation rate coefficient (0.4-1.7 d-1), and occurrence at locations with relatively high CMC-S-nZVI abundance strongly indicate the effectiveness of abiotic remediation. These quantitative assessments support that CMC-S-nZVI supports sustainable ZVI-based remediation. Further, the novel numerical approach presented in this study provides a powerful tool for quantitative cVOC remediation assessments at complex field sites where multiple processes co-occur to control both concentration and CSIA data.

3.
Nat Commun ; 15(1): 6524, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39107278

ABSTRACT

Sequence-based genetic testing identifies causative variants in ~ 50% of individuals with developmental and epileptic encephalopathies (DEEs). Aberrant changes in DNA methylation are implicated in various neurodevelopmental disorders but remain unstudied in DEEs. We interrogate the diagnostic utility of genome-wide DNA methylation array analysis on peripheral blood samples from 582 individuals with genetically unsolved DEEs. We identify rare differentially methylated regions (DMRs) and explanatory episignatures to uncover causative and candidate genetic etiologies in 12 individuals. Using long-read sequencing, we identify DNA variants underlying rare DMRs, including one balanced translocation, three CG-rich repeat expansions, and four copy number variants. We also identify pathogenic variants associated with episignatures. Finally, we refine the CHD2 episignature using an 850 K methylation array and bisulfite sequencing to investigate potential insights into CHD2 pathophysiology. Our study demonstrates the diagnostic yield of genome-wide DNA methylation analysis to identify causal and candidate variants as 2% (12/582) for unsolved DEE cases.


Subject(s)
DNA Copy Number Variations , DNA Methylation , Epilepsy , Humans , DNA Methylation/genetics , Female , Child , Male , Epilepsy/genetics , Epilepsy/diagnosis , DNA Copy Number Variations/genetics , Child, Preschool , DNA-Binding Proteins/genetics , Adolescent , Genetic Testing/methods , Infant
4.
Br J Haematol ; 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030927

ABSTRACT

A young adult African American female presented with normocytic microangiopathic haemolytic anaemia, elevated lactate dehydrogenase and thrombocytopenia. The patient responded to therapeutic plasma exchanges (TPE) for presumed thrombotic microangiopathy caused by thrombotic thrombocytopenic purpura (TTP). After relapsing, the patient was found to have pancytopenia, megaloblastic bone marrow and low vitamin B12 consistent with pernicious anaemia, which improved with intramuscular B12 and discontinuation of TPE. B12-deficient macrocytosis was not seen at presentation due to concomitant alpha-thalassaemia. Initial clinical/laboratory improvement is attributed to B12 present in TPE plasma. B12 deficiency can mimic TTP. Vigilance is needed regarding atypical presentations of pernicious anaemia.

5.
Animals (Basel) ; 14(14)2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39061521

ABSTRACT

Past and ongoing selection shapes the genomes of livestock breeds. Identifying such signatures of selection allows for uncovering the genetic bases of affected phenotypes, including economically important traits and environmental adaptations, for the further improvement of breed genetics to respond to climate and economic challenges. Turano-Mongolian cattle are a group of taurine breeds known for their adaptation to extreme environmental conditions and outstanding production performance. Buryat Turano-Mongolian cattle are among the few breeds adapted to cold climates and poor forage. Wagyu, on the other hand, is famous for high productivity and unique top-quality marbled meat. We used hapFLK, the de-correlated composite of multiple signals (DCMS), PBS, and FST methods to search for signatures of selection in their genomes. The scans revealed signals in genes related to cold adaptation (e.g., STAT3, DOCK5, GSTM3, and CXCL8) and food digestibility (SI) in the Buryat breed, and growth and development traits (e.g., RBFOX2 and SHOX2) and marbling (e.g., DGAT1, IQGAP2, RSRC1, and DIP2B) in Wagyu. Several putatively selected genes associated with reproduction, immunity, and resistance to pathogens were found in both breed genomes. The results of our work could be used for creating new productive adapted breeds or improving the extant breeds.

6.
Blood Adv ; 2024 07 15.
Article in English | MEDLINE | ID: mdl-39008716

ABSTRACT

Central nervous system (CNS) involvement remains a clinical hurdle in treating childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The disease mechanisms of CNS leukemia are primarily investigated using 2D cell culture and mouse models. Given the variations in cellular identity and architecture between the human and murine CNS, it becomes imperative to seek complementary models to study CNS leukemia. Here, we present a first-of-its-kind 3D co-culture model combining human brain organoids and BCP-ALL-cells. We noticed significantly higher engraftment of BCP-ALL cell lines and patient-derived xenograft (PDX) cells in cerebral organoids as compared to non-ALL-cells. To validate translatability between organoid co-culture and in vivo murine models, we confirmed that targeting CNS leukemia relevant pathways like CD79a/Igα or CXCR4-SDF1 reduced the invasion of BCP-ALL-cells into organoids. RNA sequencing and functional validations of organoid-invading leukemia cells compared to the non-invaded fraction revealed significant upregulation of AP-1 transcription factor-complex members in organoid-invading cells. Moreover, we detected a significant enrichment of AP-1 pathway genes in ALL-PDX-cells recovered from the CNS compared to spleen blasts of mice transplanted with TCF3::PBX1+ PDX-cells, substantiating the role of AP-1 signaling in CNS disease. Accordingly, we found significantly higher levels of the AP-1-gene JUN in patients initially diagnosed as CNS-positive compared to CNS-negative cases as well as CNS-relapse vs non-CNS-relapse cases in a cohort of 100 BCP-ALL-patients. Our results suggest CNS-organoids as a novel model to investigate CNS-involvement and identify the AP-1 pathway as a critical driver of CNS-disease in BCP-ALL.

7.
Sensors (Basel) ; 24(11)2024 May 31.
Article in English | MEDLINE | ID: mdl-38894353

ABSTRACT

The paper introduces a computer vision methodology for detecting pitting corrosion in gas pipelines. To achieve this, a dataset comprising 576,000 images of pipelines with and without pitting corrosion was curated. A custom-designed and optimized convolutional neural network (CNN) was employed for binary classification, distinguishing between corroded and non-corroded images. This CNN architecture, despite having relatively few parameters compared to existing CNN classifiers, achieved a notably high classification accuracy of 98.44%. The proposed CNN outperformed many contemporary classifiers in its efficacy. By leveraging deep learning, this approach effectively eliminates the need for manual inspection of pipelines for pitting corrosion, thus streamlining what was previously a time-consuming and cost-ineffective process.

8.
Mar Pollut Bull ; 204: 116561, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38838392

ABSTRACT

In 2015, > 460,000 L of aqueous film-forming foam (AFFF) and fire suppressors containing per- and polyfluoroalkyl substances (PFAS) were used to combat a fire at a petrochemical fuel storage terminal in the Port of Santos (Brazil). Sediments from seven sites were sampled repeatedly from 2 weeks to 1 year after the fire (n = 30). Æ©15PFAS concentrations ranged from 115 to 15,931 pg g-1 dry weight (dw). Perfluorooctane sulfonic acid (PFOS) was the most frequently detected compound with concentrations ranging from 363 to 4517 (average = 1603) pg g-1dw to <47.1 to 642 (average = 401) pg g-1 dw, followed by perfluorohexanoic acid (PFHxA) (from 38.8 to 219 (average = 162) pg g-1 dw after 15 days and from <20.8 to 161 (average = 101) pg g-1 dw one year later). Together, the hydrodynamics and fire events documented in the region were important features explaining the spread of PFAS.


Subject(s)
Alkanesulfonic Acids , Environmental Monitoring , Fluorocarbons , Water Pollutants, Chemical , Fluorocarbons/analysis , Water Pollutants, Chemical/analysis , Alkanesulfonic Acids/analysis , Brazil , Geologic Sediments/chemistry , Caproates/analysis
9.
Biochimie ; 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38857695

ABSTRACT

Uropathogenic strains of E. coli (UPEC) is a leading cause of sepsis, deploying multiple virulence factors to evade host immune responses. Notably, alpha-hemolysin (HlyA) produced by UPEC is implicated in septic symptoms associated with bacteremia, correlating with thrombocytopenia, a critical indicator of organ dysfunction and a predictor of poorer patient prognosis. This study meticulously explores the impact of sublytic concentrations of HlyA on platelets. Findings reveal that HlyA triggers an increase in intracellular calcium, activating calpain and exposing phosphatidylserine to the cell surface, as validated by flow cytometric experiments. Electron microscopy reveals a distinctive balloon-like shape in HlyA-treated platelets, indicative of a procoagulant state. The toxin induces the release of procoagulant extracellular vesicles and the secretion of alpha and dense granules. Overall, the results point to HlyA inducing a necrotic-like procoagulant state in platelets. The effects of sublytic concentrations of HlyA on both erythrocytes and platelets could have a potential impact on capillary microcirculation. Targeting HlyA emerges as a viable therapeutic strategy to mitigate the adverse effects of UPEC infections, especially in South American countries where these infections are endemic, underscoring its significance as a potential therapeutic target.

10.
Rev Mal Respir ; 41(6): 451-454, 2024 Jun.
Article in French | MEDLINE | ID: mdl-38796386

ABSTRACT

Targeted therapies are the standard first-line treatment for metastatic lung adenocarcinoma with certain molecular abnormalities. These abnormalities are particularly common in Southeast Asia and French Polynesia. A 51-year-old Tahitian female non-smoker was diagnosed in 2018 with stage IV lung adenocarcinoma harboring a p.L858R EGFR mutation. She received gefitinib as first-line treatment. Due to locoregional progression and the presence of a resistance mutation (p.T790M of EFGR), she received osimertinib as second-line treatment, after which chemotherapy was proposed as 3rd-line treatment. An additional biopsy detected not only the previously known EGFR mutation, but also a BRAF p.V600E mutation. Following disease progression during chemotherapy, the patient received targeted therapies combining dabrafenib, trametinib and osimertinib. Due to a dissociated response after four months of treatment, a 5th line of paclitaxel bevacizumab was initiated. Subsequent to additional progression and given the ALK rearrangement shown on the re-biopsy, 6th-line treatment with alectinib was proposed. As the response was once again dissociated, a final line was proposed before stopping active treatments due to their toxicity and overall deterioration in the patient's state of health. This exceptional case is characterized by resistance to anti-EGFR through the successive and cumulative acquisition of two new oncogene addictions. The authors underline the importance of re-biopsy at each progression, leading (if at all feasible) to yet around round of targeted therapy.


Subject(s)
Drug Resistance, Neoplasm , ErbB Receptors , Lung Neoplasms , Oncogene Addiction , Female , Humans , Middle Aged , Acrylamides/therapeutic use , Acrylamides/pharmacology , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Anaplastic Lymphoma Kinase/genetics , Anaplastic Lymphoma Kinase/antagonists & inhibitors , Aniline Compounds/therapeutic use , Aniline Compounds/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , ErbB Receptors/genetics , Gefitinib/therapeutic use , Gefitinib/pharmacology , Indoles , Lung Neoplasms/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Mutation , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins B-raf/genetics , Pyrimidines
11.
Water Res ; 258: 121803, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38795548

ABSTRACT

Nano zero-valent metals (nZVMs) have been extensively utilized for decades in the reductive remediation of groundwater contaminated with chlorinated organic compounds, owing to their robust reducing capabilities, simple application, and cost-effectiveness. Nevertheless, there remains a dearth of information regarding the efficient reductive defluorination of linear or branched per- and polyfluoroalkyl substances (PFASs) using nZVMs as reductants, largely due to the absence of appropriate catalysts. In this work, various soluble porphyrin ligands [[meso­tetra(4-carboxyphenyl)porphyrinato]cobalt(III)]Cl·7H2O (CoTCPP), [[meso­tetra(4-sulfonatophenyl) porphyrinato]cobalt(III)]·9H2O (CoTPPS), and [[meso­tetra(4-N-methylpyridyl) porphyrinato]cobalt(II)](I)4·4H2O (CoTMpyP) have been explored for defluorination of PFASs in the presence of the nZn0 as reductant. Among these, the cationic CoTMpyP showed best defluorination efficiencies for br-perfluorooctane sulfonate (PFOS) (94%), br-perfluorooctanoic acid (PFOA) (89%), and 3,7-Perfluorodecanoic acid (PFDA) (60%) after 1 day at 70 °C. The defluorination rate constant of this system (CoTMpyP-nZn0) is 88-164 times higher than the VB12-nZn0 system for the investigated br-PFASs. The CoTMpyP-nZn0 also performed effectively at room temperature (55% for br-PFOS, 55% for br-PFOA and 25% for 3,7-PFDA after 1day), demonstrating the great potential of in-situ application. The effect of various solubilizing substituents, electron transfer flow and corresponding PFASs defluorination pathways in the CoTMpyP-nZn0 system were investigated by both experiments and density functional theory (DFT) calculations. SYNOPSIS: Due to the unavailability of active catalysts, available information on reductive remediation of PFAS by zero-valent metals (ZVMs) is still inadequate. This study explores the effective defluorination of various branched PFASs using soluble porphyrin-ZVM systems and offers a systematic approach for designing the next generation of catalysts for PFAS remediation.


Subject(s)
Zinc , Zinc/chemistry , Porphyrins/chemistry , Fluorocarbons/chemistry , Metalloporphyrins/chemistry , Water Pollutants, Chemical/chemistry , Oxidation-Reduction
12.
Mar Pollut Bull ; 203: 116386, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38703625

ABSTRACT

Ecotoxicological tools, namely biomarkers and bioassays, may provide insights on the ecological quality status of mangroves under restoration. We investigated how 1) physicochemical parameters and water bioassays using Artemia franciscana; and 2) quantification of sublethal (osmoregulatory capacity, biochemical, and oxidative stress) and individual biomarkers (density, length-weight relationship [LWR], parasitic prevalence) in the sentinel fiddler crab Minuca rapax, can improve restoration indicators in mangroves from the Yucatán Peninsula, Southern Gulf of Mexico. We showed that water quality was improved with restoration, but still presented toxicity. Regarding sublethal biomarkers, M rapax from restored areas lower osmotic regulatory capacity, higher oxidative stress, and showed lipid peroxidation. As to the individual biomarkers, the density, LWR, and the prevalence of parasites in M. rapax was higher in restored areas. The use of bioassays/biomarkers were useful as early warning indicators to better assess the health of mangroves under restoration.


Subject(s)
Ecotoxicology , Environmental Monitoring , Wetlands , Animals , Mexico , Environmental Monitoring/methods , Biomarkers , Brachyura , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/analysis , Water Quality , Artemia , Biological Assay , Environmental Restoration and Remediation , Oxidative Stress , Gulf of Mexico
13.
Article in English | MEDLINE | ID: mdl-38734817

ABSTRACT

Considerable research has linked relative reduction in the amplitude of the P3 event-related potential (ERP) during cognitive task performance (i.e., Target-P3) with increased risk of alcohol-related problems. A separate literature indicates that a relative increase in the amplitude of the P3 elicited by cues signaling alcohol availability (i.e., ACR-P3) also is associated with alcohol use and problems. To date, no research has integrated these seemingly discrepant findings. Here, we aimed to demonstrate that P3 amplitudes elicited in different task contexts reflect distinct domains of functioning relevant to problematic alcohol involvement (PAI), and therefore can inform heterogeneity in the etiology of PAI. 156 emerging adults (61% women; 88% White/Non-Hispanic) completed a mental rotation task and a picture-viewing task while ERPs were recorded. Participants also completed questionnaire measures of trait disinhibition, alcohol use, and alcohol-related problems. Findings from regression analyses indicated that (a) Target-P3 was negatively associated and ACR-P3 was positively associated with a PAI latent variable; (b) the two P3s accounted for unique variance in PAI, beyond that accounted for by recent drinking; and (c) the association between Target-P3 and PAI-but not ACR-P3 and PAI-was statistically mediated by trait disinhibition. The present findings highlight the unique contributions of distinct functional domains associated with disinhibition and incentive salience in the etiology of PAI. Moreover, findings are consistent with a nuanced understanding of the P3 ERP, whereby its specific meaning varies according to the task context in which it is elicited.

15.
J Stud Alcohol Drugs ; 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38563280

ABSTRACT

OBJECTIVE: Perception of others' approval of alcohol use (i.e., injunctive drinking norms) is strongly predictive of alcohol use, particularly among young adults (Krieger et al., 2016). While between-person injunctive norms predict alcohol use (Neighbors et al., 2008), there is evidence of within-person fluctuations in the relationship between norms and drinking (Graupensperger et al., 2021). The current study used ecological momentary assessment (EMA) to test within-person, day-level associations between injunctive norms and alcohol use, and to test whether social context moderated this association. METHOD: Participants (n=83, M age=24.0, 50.9% female) completed a two-week EMA protocol using a smartphone application. Injunctive norms, social context (type and gender of companions), and number of drinks consumed were assessed each morning following a drinking event. Multilevel models with repeated measures nested within participants tested main effects and interactions of between- and within-person injunctive norms, type of drinking companions, and gender of drinking companions on number of drinks consumed. RESULTS: Day-level injunctive norms were positively associated with drinking quantity over and above baseline norms. The effect of norms differed by social context such that norms were only positively related to drinking quantity when drinking with a friend or romantic partner (vs. drinking alone). Gender of friends with whom participants drank did not moderate the effect of norms on quantity. CONCLUSIONS: This study provides one of the first examinations of daily fluctuations in injunctive drinking norms. As norms represent a malleable target for intervention (White et al., 2019), results offer new information regarding possible intervention targets.

16.
Glob Chang Biol ; 30(4): e17274, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38605677

ABSTRACT

Climate change and other anthropogenic disturbances are increasing liana abundance and biomass in many tropical and subtropical forests. While the effects of living lianas on species diversity, ecosystem carbon, and nutrient dynamics are receiving increasing attention, the role of dead lianas in forest ecosystems has been little studied and is poorly understood. Trees and lianas coexist as the major woody components of forests worldwide, but they have very different ecological strategies, with lianas relying on trees for mechanical support. Consequently, trees and lianas have evolved highly divergent stem, leaf, and root traits. Here we show that this trait divergence is likely to persist after death, into the afterlives of these organs, leading to divergent effects on forest biogeochemistry. We introduce a conceptual framework combining horizontal, vertical, and time dimensions for the effects of liana proliferation and liana tissue decomposition on ecosystem carbon and nutrient cycling. We propose a series of empirical studies comparing traits between lianas and trees to answer questions concerning the influence of trait afterlives on the decomposability of liana and tree organs. Such studies will increase our understanding of the contribution of lianas to terrestrial biogeochemical cycling, and help predict the effects of their increasing abundance.


Subject(s)
Ecosystem , Tropical Climate , Forests , Trees , Carbon
17.
Blood ; 143(26): 2735-2748, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38518105

ABSTRACT

ABSTRACT: Acute lymphoblastic leukemia (ALL) arises from the uncontrolled proliferation of B-cell precursors (BCP-ALL) or T cells (T-ALL). Current treatment protocols obtain high cure rates in children but are based on toxic polychemotherapy. Novel therapies are urgently needed, especially in relapsed/refractory (R/R) disease, high-risk (HR) leukemias and T-ALL, in which immunotherapy approaches remain scarce. Although the interleukin-7 receptor (IL-7R) plays a pivotal role in ALL development, no IL-7R-targeting immunotherapy has yet reached clinical application in ALL. The IL-7Rα chain (CD127)-targeting IgG4 antibody lusvertikimab (LUSV; formerly OSE-127) is a full antagonist of the IL-7R pathway, showing a good safety profile in healthy volunteers. Here, we show that ∼85% of ALL cases express surface CD127. We demonstrate significant in vivo efficacy of LUSV immunotherapy in a heterogeneous cohort of BCP- and T-ALL patient-derived xenografts (PDX) in minimal residual disease (MRD) and overt leukemia models, including R/R and HR leukemias. Importantly, LUSV was particularly effective when combined with polychemotherapy in a phase 2-like PDX study with CD127high samples leading to MRD-negativity in >50% of mice treated with combination therapy. Mechanistically, LUSV targeted ALL cells via a dual mode of action comprising direct IL-7R antagonistic activity and induction of macrophage-mediated antibody-dependent cellular phagocytosis (ADCP). LUSV-mediated in vitro ADCP levels significantly correlated with CD127 expression levels and the reduction of leukemia burden upon treatment of PDX animals in vivo. Altogether, through its dual mode of action and good safety profile, LUSV may represent a novel immunotherapy option for any CD127+ ALL, particularly in combination with standard-of-care polychemotherapy.


Subject(s)
Xenograft Model Antitumor Assays , Animals , Humans , Mice , Receptors, Interleukin-7/antagonists & inhibitors , Mice, SCID , Phagocytosis/drug effects , Interleukin-7 Receptor alpha Subunit , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Female , Mice, Inbred NOD , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Cell Line, Tumor , Antineoplastic Agents, Immunological/pharmacology , Antineoplastic Agents, Immunological/therapeutic use
18.
J Funct Morphol Kinesiol ; 9(1)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38535420

ABSTRACT

Transcutaneous electrical nerve stimulation (TENS) has proven effective in treating pain in many experimental and clinical studies. In addition to the analgesic effect, direct TENS of peripheral nerves had anti-inflammatory and regenerative effects in the treatment of distal polyneuropathy and spinal cord injury. This work demonstrates the experience of using direct TENS in the treatment of a 52-year-old patient with post-COVID-19 Guillain-Barré (GBS) and acute transverse myelitis (ATM) overlap syndrome. Direct TENS of peripheral nerves showed high efficiency in enhancing the therapeutic effect of combined plasma exchange and pharmacotherapy by 89.5% with a significant reduction in neuropathic pain, motor and sensory deficits, bladder and bowel disorders and regression of neurophysiological changes. We suggest that direct TENS of peripheral nerves can be a promising option for combined therapy of GBS and ATM overlap syndrome and other diseases with the simultaneous development of distal polyneuropathy and spinal cord injury. Further trial studies are required.

19.
Cancer Lett ; 588: 216805, 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38462035

ABSTRACT

Crosstalk between mast cells (MCs) and T lymphocytes (TLs) releases specific signals that create an environment conducive to tumor development. Conversely, they can protect against cancer by targeting tumor cells for destruction. Although their role in immunity and cancer is complex, their potential in anticancer strategies is often underestimated. When peripheral MCs are activated, they can affect cancer development. Tumor-infiltrating TLs may malfunction and contribute to aggressive cancer and poor prognoses. One promising approach for cancer patients is TL-based immunotherapies. Recent reports suggest that MCs modulate TL activity in solid tumors and may be a potential therapeutic layer in multitargeting anticancer strategies. Pharmacologically modulating MC activity can enhance the anticancer cytotoxic TL response in tumors. By identifying tumor-specific targets, it has been possible to genetically alter patients' cells into fully humanized anticancer cellular therapies for autologous transplantation, including the engineering of TLs and MCs to target and kill cancer cells. Hence, recent scientific evidence provides a broader understanding of MC-TL activity in cancer.


Subject(s)
Neoplasms , T-Lymphocytes , Humans , T-Lymphocytes/pathology , Mast Cells/pathology , Neoplasms/pathology , Lymphocytes, Tumor-Infiltrating , Immunotherapy , Tumor Microenvironment
20.
Assessment ; : 10731911241237055, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38515003

ABSTRACT

Given the popularity and ease of single-item craving assessments, we developed a multi-item measure and compared it to common single-item assessments in an ecological momentary assessment (EMA) context. Two weeks of EMA data were collected from 48 emerging adults (56.25% female, 85.42% White) who frequently used cannabis. Eight craving items were administered, and multilevel factor analyses were used to identify the best fitting model. The resulting scale's factors represented purposefulness/general desire and emotionality/negative affect craving. Convergent validity was examined using measures of craving, cannabis use disorder symptoms, frequency of use, cannabis cue reactivity, cannabis use, negative affect, and impulsivity. The scale factors were associated with cue-reactivity craving, negative affect, impulsivity, and subfactors of existing craving measures. For researchers interested in using a single item to capture craving, one item performed particularly well. However, the new scale may provide a more nuanced assessment of mechanisms underlying craving.

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