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2.
Eur Stroke J ; 9(2): 391-397, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38183279

ABSTRACT

INTRODUCTION: Most intracerebral hemorrhage (ICH) trials assessed outcome at 3 months but the recovery trajectory of ICH survivors may continue up to 1 year after the index event. We aimed to describe the predictors of functional outcome improvement from 3 to 12 months after ICH. MATERIALS AND METHODS: Retrospective analysis of patients admitted to six European Stroke Centers for supratentorial ICH. Functional outcome was measured with the modified Rankin Scale (mRS) at 3 and 12 months. Predictors of functional outcome improvement were explored with binary logistic regression. RESULTS: We included 703 patients, of whom 245 (34.9%) died within 3 months. Among survivors, 131 (28.6%) had an mRS improvement, 78 (17.0%) had a worse mRS and 249 (54.4%) had a stable functional status at 12 months. Older age and the presence of baseline disability (defined as pre-stroke mRS > 1), were associated with lower odds of functional outcome improvement (Odds Ratio (OR) 0.98 per year increase, 95% Confidence Interval (CI) 0.96-1.00, p = 0.017 and OR 0.45, 95% CI 0.25-0.81, p = 0.008 respectively). Conversely, deep ICH location increased the probability of long term mRS improvement (OR 1.67, 95% CI, 1.07-2.61, p = 0.023). Patients with mild-moderate disability at 3 months (mRS 2-3) had the highest odds of improvement at 12 months (OR 8.76, 95% CI 3.68-20.86, p < 0.001). DISCUSSION AND CONCLUSION: Long term recovery is common after ICH and associated with age, baseline functional status, mRS at 3 months and hematoma location. Our findings might inform future trials and improve long-term prognostication in clinical practice.


Subject(s)
Cerebral Hemorrhage , Recovery of Function , Humans , Male , Female , Cerebral Hemorrhage/mortality , Cerebral Hemorrhage/therapy , Aged , Middle Aged , Retrospective Studies , Treatment Outcome , Aged, 80 and over , Time Factors
3.
J Neurol Neurosurg Psychiatry ; 95(5): 471-476, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38041670

ABSTRACT

BACKGROUND: Non-convulsive status epilepticus (NCSE) is a time-dependent neurological disorder often misdiagnosed in the emergency setting. Electroencephalography (EEG) is often not available on a 24/7 basis, and Salzburg criteria may at times miss the diagnosis. Here, we tested the accuracy of hyperperfusion on CT perfusion imaging (CTP) in the identification of NCSE against Salzburg criteria, to define its potential role in a pragmatic diagnostic workflow. METHODS: We enrolled consecutive patients with suspected acute seizure or seizure disorder undergoing brain imaging with CTP and EEG from January 2021 to March 2023. EEG recordings, Salzburg criteria and CTP hyperperfusion were rated and adjudicated by two independent experts blinded to patient status. A reference standard including all clinical, lab, imaging, EEG and therapeutic data was used to adjudicate NCSE diagnosis. Sensitivity, specificity, diagnostic accuracy, positive and negative predictive values (NPV) were calculated for CTP hyperperfusion and Salzburg criteria versus NCSE adjudicated according to reference standard. RESULTS: Seventy-seven patients were enrolled. Among 21 NCSE cases, 17 were adjudicated according to Salzburg criteria (81%) and 4 received NCSE diagnosis according to reference standard. Agreement between EEG and CTP emerged in 16/21 NCSE cases, reaching sublobar level in 37.5% of cases. Receiver operator curve analysis suggested good accuracy for CTP hyperperfusion for the diagnosis of NCSE (AUROC 0.79, 95% CI 0.69 to 0.89). CTP hyperperfusion had a high NPV for NCSE (NPV 0.97, 95% CI 0.86 to 1). CONCLUSION: CTP hyperperfusion may be implemented in the emergency fast-track to rule out NCSE, given very high NPV. Further validation studies are needed to evaluate CTP application in real-world setting for NCSE codes.


Subject(s)
Status Epilepticus , Humans , Brain , Electroencephalography/methods , Perfusion , Status Epilepticus/diagnostic imaging , Prospective Studies
4.
Methods Mol Biol ; 2713: 183-197, 2024.
Article in English | MEDLINE | ID: mdl-37639124

ABSTRACT

The intestinal macrophage pool represents the largest population of macrophages present within the body. Nevertheless, flow cytometry analysis of intestinal macrophages remains challenging due to historical lack of consensus on surface markers, variations in sample preparation, and a certain capriciousness of the isolation procedure itself. Furthermore, recent studies have uncovered a hitherto unknown heterogeneity of intestinal macrophages, accompanied by a vast increase of subset-identifying surface markers. Here, the isolation procedure for intestinal tissue for flow cytometry analysis is laid out, with particular attention toward the procedures for isolated intestinal layers, and a trouble-shooting section with strategies to avoid common pitfalls and mistakes.


Subject(s)
Intestines , Macrophages , Flow Cytometry , Consensus , Specimen Handling
5.
Heliyon ; 9(11): e21287, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38074879

ABSTRACT

Homeopathy is the subject of frequent debates, especially in public media. This systematic review aims to give an overview of conceptual criticisms of homeopathy in the scientific literature. The literature search was conducted in four databases (EMBASE, PubMed, Web of Science, PhilPapers) on August 25, 2020. Included were peer reviewed articles in English or German criticising the basic concepts of homeopathy as main topic; excluded were articles criticising homeopathy primarily based on analysis of empirical clinical and/or preclinical data. The formal structure of publications included was evaluated regarding the recommended structure for scientific publications (IMRaD, acronym for 'Introduction', 'Methods', 'Results' and 'Discussion'). Arguments criticising the concepts of homeopathy were extracted and classified into groups. The literature search revealed 5139 articles, of which 15 articles (published between 1959 and 2020) met the inclusion criteria. These articles complied only partly with the IMRaD structure; just four articles considered with 8 or 9 IMRaD criteria the majority of the defined 11 IMRaD criteria. Extracted arguments against the concepts of homeopathy were classified into five groups: 'Conflict with current scientific principles and the foundations of modern medicine', 'Lack of a scientific basis', 'Arguments based on scientific theories', 'Ethical considerations and social consequences', 'Lack of empirical clinical evidence'. This classification is intended to provide a basis for future in-depth scientific analyses and discussions. Based on the number of articles found in the peer reviewed literature, it can be concluded that the on-going discussion about homeopathy in the public media is not reflected in a corresponding academic debate.

6.
Rev Argent Microbiol ; 2023 Nov 07.
Article in Spanish | MEDLINE | ID: mdl-37945434

ABSTRACT

Bovine genital campylobacteriosis (BGC) and bovine trichomonosis (BT) are sexually transmitted diseases (STDs) that affect bovine breeding herds, decreasing their reproductive efficiency. The objective of this work was to estimate the prevalence of these diseases and their temporal-spatial distribution in the province of Formosa, Argentina. The cross-sectional study conducted between 2018 and 2021 included a total of 15,571 bulls, inter-herd prevalence being 29.62% and 17.23% for BGC and BT, respectively. The prevalence of positive animals was 2.05% for BGC and 0.43% for BT. The temporal-spatial analysis of BGC showed two distinct spatial groupings, one group had a low risk of contracting the disease (RR = 0.13; p < 0.001; 2018-2021) while the other group had a high risk (RR = 2.84; p < 0.001; 2020-2021). BT had a high-risk group for the disease (RR = 35.24; p < 0.001; 2019). This study shows that STDs are endemic in the region, providing updated and valuable information as a tool for the health management of these diseases.

7.
Nature ; 618(7966): 818-826, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37316669

ABSTRACT

Correct development and maturation of the enteric nervous system (ENS) is critical for survival1. At birth, the ENS is immature and requires considerable refinement to exert its functions in adulthood2. Here we demonstrate that resident macrophages of the muscularis externa (MMϕ) refine the ENS early in life by pruning synapses and phagocytosing enteric neurons. Depletion of MMϕ before weaning disrupts this process and results in abnormal intestinal transit. After weaning, MMϕ continue to interact closely with the ENS and acquire a neurosupportive phenotype. The latter is instructed by transforming growth factor-ß produced by the ENS; depletion of the ENS and disruption of transforming growth factor-ß signalling result in a decrease in neuron-associated MMϕ associated with loss of enteric neurons and altered intestinal transit. These findings introduce a new reciprocal cell-cell communication responsible for maintenance of the ENS and indicate that the ENS, similarly to the brain, is shaped and maintained by a dedicated population of resident macrophages that adapts its phenotype and transcriptome to the timely needs of the ENS niche.


Subject(s)
Enteric Nervous System , Intestines , Macrophages , Enteric Nervous System/cytology , Enteric Nervous System/growth & development , Enteric Nervous System/physiology , Intestines/innervation , Lymphotoxin-alpha/metabolism , Macrophages/metabolism , Macrophages/physiology , Neurons/physiology , Weaning , Cell Communication , Transcriptome , Phenotype , Phagocytosis , Synapses , Neuronal Plasticity , Gastrointestinal Transit
8.
Klin Monbl Augenheilkd ; 240(9): 1046-1051, 2023 Sep.
Article in English, German | MEDLINE | ID: mdl-37353213

ABSTRACT

There have been marked increases in the numbers of patients with retinal detachments at individual centres in recent years and this is supported by the subjective impression of many experts. We therefore surveyed the literature on changes in the incidence of retinal detachments worldwide. This revealed quite significant methodological differences between the studies, so that it was difficult to achieve a conclusive comparison of the development of the incidence of retinal detachment. Despite these limitations, all data from recent studies suggest an increase in the number of retinal detachments. The incidence of retinal detachment in the western world currently seems to be more than 20 cases per 100,000 person-years, which is significantly higher than described in earlier decades. It can be assumed that an increase in the number of individuals with myopia, a demographic increase in patients of the typical age group for retinal detachment and an increasing number of cataract surgeries, especially in younger patients, are responsible for the rising incidence of retinal detachment.


Subject(s)
Global Health , Retinal Detachment , Humans , Germany/epidemiology , Global Health/statistics & numerical data , Hospitals, University , Incidence , Outpatient Clinics, Hospital , Retinal Detachment/epidemiology , Male , Female , Middle Aged , Aged
9.
Neurogastroenterol Motil ; 35(2): e14490, 2023 02.
Article in English | MEDLINE | ID: mdl-36371706

ABSTRACT

BACKGROUND: Methods to study gastric emptying in rodents are time consuming or terminal, preventing repetitive assessment in the same animal. Magnetic resonance imaging (MRI) is a non-invasive technique increasingly used to investigate gastrointestinal function devoid of these shortcomings. Here, we evaluated MRI to measure gastric emptying in control animals and in two different models of gastroparesis. METHODS: Mice were scanned using a 9.4 Tesla MR scanner. Gastric volume was measured by delineating the stomach lumen area. Control mice were scanned every 30 min after ingestion of a 0.2 g meal and stomach volume was quantified. The ability of MRI to detect delayed gastric emptying was evaluated in models of morphine-induced gastroparesis and streptozotocin-induced diabetes. KEY RESULTS: Magnetic resonance imaging reproducibly detected increased gastric volume following ingestion of a standard meal and progressively decreased with a half emptying time of 59 ± 5 min. Morphine significantly increased gastric volume measured at t = 120 min (saline: 20 ± 2 vs morphine: 34 ± 5 mm3 ; n = 8-10; p < 0.001) and increased half emptying time using the breath test (saline: 85 ± 22 vs morphine: 161 ± 46 min; n = 10; p < 0.001). In diabetic mice, gastric volume assessed by MRI at t = 60 min (control: 23 ± 2 mm3 ; n = 14 vs diabetic: 26 ± 5 mm3 ; n = 18; p = 0.014) but not at t = 120 min (control: 21 ± 3 mm3 ; n = 13 vs diabetic: 18 ± 5 mm3 ; n = 18; p = 0.115) was significantly increased compared to nondiabetic mice. CONCLUSIONS AND INFERENCES: Our data indicate that MRI is a reliable and reproducible tool to assess gastric emptying in mice and represents a useful technique to study gastroparesis in disease models or for evaluation of pharmacological compounds.


Subject(s)
Diabetes Mellitus, Experimental , Gastroparesis , Mice , Animals , Gastroparesis/chemically induced , Gastroparesis/diagnostic imaging , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/diagnostic imaging , Gastric Emptying , Magnetic Resonance Imaging/methods , Morphine Derivatives
10.
Immunity ; 55(9): 1530-1548, 2022 09 13.
Article in English | MEDLINE | ID: mdl-36103851

ABSTRACT

The gastrointestinal tract has the important task of absorbing nutrients, a complex process that requires an intact barrier allowing the passage of nutrients but that simultaneously protects the host against invading microorganisms. To maintain and regulate intestinal homeostasis, the gut is equipped with one of the largest populations of macrophages in the body. Here, we will discuss our current understanding of intestinal macrophage heterogeneity and describe their main functions in the different anatomical niches of the gut during steady state. In addition, their role in inflammatory conditions such as infection, inflammatory bowel disease, and postoperative ileus are discussed, highlighting the roles of macrophages in immune defense. To conclude, we describe the interaction between macrophages and the enteric nervous system during development and adulthood and highlight their contribution to neurodegeneration in the context of aging and diabetes.


Subject(s)
Enteric Nervous System , Inflammatory Bowel Diseases , Adult , Homeostasis , Humans , Macrophages
11.
Medicina (Kaunas) ; 58(3)2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35334535

ABSTRACT

Introduction: Minimally invasive surgical techniques for hallux valgus have gained popularity, showing good results characterized by smaller postoperative scars, less pain, lower infection risk, and fewer wound complications. Given the lack of evidence available in our country regarding this subject, especially about this type of surgical technique, our paper aims to compare open and MIS approaches for chevron osteotomy. We evaluated the outcome and complications after 12 months. Materials and Methods: We undertook a prospective, randomized, controlled, single-center study between October 2017 and December 2020. The patients were randomized into two groups: one group that received percutaneous chevron osteotomy (MIS), and the other, open chevron osteotomy (OC). For clinical assessment, we determined the function and the level of pain using the Visual Analogue Scale (VAS) and The American Orthopaedic Foot and Ankle Surgery score (AOFAS). The VAS scale was measured before the surgical procedure, at discharge, and at 3 weeks, 6 weeks, 6 months, and 12 months after surgery. The AOFAS score was calculated preoperatively and after 6 months. The hallux angle (HVA) and intramedullary angle (IMA) were measured preoperatively, and at 6 weeks, 6 months and 12 months. Results: We included 26 cases in the open chevron osteotomy group (24 female, 2 male) and 24 in the MIS group (24 female, 0 male). Both groups demonstrated improvements regarding the IMA and HVA at the last follow-up without any significant differences between the groups at the final assessment. The VAS showed significantly better post-operative results for the MIS group at discharge (p < 0.001) and 3 weeks (p < 0.001), 6 weeks (p < 0.001), and 6 months (p = 0.004) post-surgery. The AOFAS showed no significant differences either before or after surgery. Four cases with screw prominence were reported, three of which belonged to the MIS group. Only one case with metatarsalgia was found in the OC group. Conclusions: This paper demonstrates that minimally invasive chevron osteotomy has comparable results with open chevron osteotomy, even though surgical time and radiological exposure are significantly longer. More studies are required to evaluate the complications and the risk of recurrences.


Subject(s)
Hallux Valgus , Female , Hallux Valgus/diagnostic imaging , Hallux Valgus/surgery , Humans , Male , Osteotomy/adverse effects , Osteotomy/methods , Prospective Studies , Radiography , Treatment Outcome
12.
Cureus ; 14(2): e22217, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35186608

ABSTRACT

Concomitant diagnosis of non-Hodgkin lymphoma (NHL) and acute myeloid leukemia secondary to chronic myeloproliferative neoplasms (MPNs) is rarely reported. Patients with MPNs may have a second neoplasm, and the risk of lymphoid line neoplasms is 2.5-3.5 times for lymphoid line neoplasms. The explanation for this association is the genetic instability of hematopoietic progenitors in MPNs. An 80-year-old Caucasian man, with many comorbidities, presents for physical asthenia, sweating. The right inguinal adenopathy was known one month before the examination. The patient was diagnosed concomitantly with diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) secondary to primary myelofibrosis (PMF) and presented trisomy 8, trisomy 13, and triple-negative PMF status. The patient initially received two well-tolerated R mini CHOP series. This type of treatment was selected to treat DLBCL for one unfit patient for intensive chemotherapy due to his age and comorbidities. R mini CHOP administration was followed by severe aplasia that lasted approximately two weeks followed by severe thrombocytosis that reached 4000 x109/L, and Thromboreductin recommendation was mandatory. The result of the treatment was a partial response but with severe adverse events like neutropenia G4, due to the delay of the treatment the patient lost the response. It was mandatory to select another treatment line and the chosen was venetoclax; it was selected for the simultaneous treatment of DLBCL and the underlying AML. It was obtained a significant reduction in the size of the inguinal lymph node block in two weeks of treatment. Severe neutropenia was diagnosed and complicated with sepsis. The evolution is unfavorable with the installation of multiple organ dysfunction. The presence of a complex karyotype (trisomy 8, trisomy 13) in a patient with myeloid metaplasia with triple-negative PMF was associated with blast transformation and severe thrombocytosis. The patient was diagnosed concomitantly with DLBCL, making the therapeutic decision difficult. Venetoclax has been shown to be useful in the treatment of DLBCL but has been associated with severe neutropenia, which has led to infectious complications.

13.
Cell Res ; 32(3): 229-230, 2022 03.
Article in English | MEDLINE | ID: mdl-34903855

Subject(s)
Macrophages , Neurons
14.
Klin Monbl Augenheilkd ; 238(12): 1299-1304, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34587630

ABSTRACT

INTRODUCTION: Polypoidal choroidal vasculopathy (PCV) is a vascular disease of the choroid. Diagnosis is mainly based on polypoidal aneurysm-like lesions seen in indocyanine green (ICG) angiography. Various therapeutic options have been proposed. METHODS: Outcomes of 10 cases with extrafoveal PCV and consecutive macular edema treated with thermal laser are reported. Diagnosis of PCV was confirmed by ICG angiography. RESULTS: Upon successful occlusion of the polyps in 10 eyes after thermal laser treatment demonstrated in ICG angiography, a regression of central foveal edema was seen in optical coherence tomography and color fundus photography. Visual acuity improved from logMAR 0.8 to logMAR 0.3. Follow-up ranged from 4 months to 15 years, with a median of 1 year. Two eyes had a recurrence of exudative maculopathy 5 and 7 years after laser treatment, respectively. CONCLUSION: A careful differentiation between various subforms of exudative maculopathy using fluorescein and ICG angiography can identify certain selected patients with extrafoveal PCV, for whom thermal laser monotherapy can be a therapeutic option.


Subject(s)
Choroid Diseases , Choroidal Neovascularization , Polyps , Vascular Diseases , Choroid/diagnostic imaging , Fluorescein Angiography , Humans , Indocyanine Green , Lasers , Polyps/surgery , Retrospective Studies , Tomography, Optical Coherence
15.
Genes (Basel) ; 12(6)2021 05 30.
Article in English | MEDLINE | ID: mdl-34070898

ABSTRACT

Acute myeloid leukemia (AML) is a heterogeneous disorder characterized by a wide range of genetic defects. Cytogenetics, molecular and genomic technologies have proved to be helpful for deciphering the mutational landscape of AML and impacted clinical practice. Forty-eight new AML patients were investigated with an integrated approach, including classical and molecular cytogenetics, array-based comparative genomic hybridization and targeted next generation sequencing (NGS). Various genetic defects were identified in all the patients using our strategy. Targeted NGS revealed known pathogenic mutations as well as rare or unreported variants with deleterious predictions. The mutational screening of the normal karyotype (NK) group identified clinically relevant variants in 86.2% of the patients; in the abnormal cytogenetics group, the mutation detection rate was 87.5%. Overall, the highest mutation prevalence was observed for the NPM1 gene, followed by DNMT3A, FLT3 and NRAS. An unexpected co-occurrence of KMT2A translocation and DNMT3A-R882 was identified; alterations of these genes, which are involved in epigenetic regulation, are considered to be mutually exclusive. A microarray analysis detected CNVs in 25% of the NK AML patients. In patients with complex karyotypes, the microarray analysis made a significant contribution toward the accurate characterization of chromosomal defects. In summary, our results show that the integration of multiple investigative strategies increases the detection yield of genetic defects with potential clinical relevance.


Subject(s)
Leukemia, Myeloid, Acute/genetics , Mutation Rate , DNA Copy Number Variations , DNA Methyltransferase 3A/genetics , GTP Phosphohydrolases/genetics , Genetic Testing/statistics & numerical data , High-Throughput Nucleotide Sequencing , Histone-Lysine N-Methyltransferase/genetics , Humans , Leukemia, Myeloid, Acute/pathology , Membrane Proteins/genetics , Myeloid-Lymphoid Leukemia Protein/genetics , Nucleophosmin/genetics , fms-Like Tyrosine Kinase 3/genetics
16.
Parasitol Res ; 120(6): 2157-2164, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33855619

ABSTRACT

Equine piroplasmosis (EP) is a disease of equids caused by Theileria equi and Babesia caballi, members of the order Piroplasmida, transmitted by several species of ticks. As the disease is endemic in many countries, a clinical examination or a serological test are required prior to movement of horses to prove freedom from infection and to avoid the introduction of EP with its sanitary and economic impact, especially in areas where it is absent. Currently, numerous diagnostic PCR protocols are available, some of which are recommended by the World Organisation for Animal Health (OIE). In order to adopt this diagnostic method, the Italian National Reference Centre for Equine Diseases (NRC-ED) conducted a preliminary comparison between an end-point PCR, nested PCR, real-time PCR, and commercial real-time PCR, for the detection of T. equi and B. caballi, respectively. One hundred and three field samples, collected during spring-summer 2013 in Latium and Tuscany regions, were employed for the study, and results discordant between detection assays were confirmed by sequencing. The reference assay was defined as that showing the highest sensitivity, and the relative sensitivity (rSe) and specificity (rSp) of the other methods were estimated referring to this assay. Agreement between methods was estimated by calculating the concordance between each pair of methods. Although no statistical differences were detected among PCR-based methods, the non-commercial real-time PCR assays seemed to be the most suitable for detection of T. equi and B. caballi, respectively. An important advantage of direct PCR detection of the pathogen, in comparison to indirect detection using serological methods, is that it allows specific treatment against the causative pathogen species responsible of the infection as well as for the definition of the infectious status of an animal for international movement.


Subject(s)
Babesia/isolation & purification , Babesiosis/parasitology , Horse Diseases/parasitology , Polymerase Chain Reaction/veterinary , Theileria/isolation & purification , Theileriasis/parasitology , Animals , Babesia/genetics , Babesiosis/epidemiology , Horse Diseases/epidemiology , Horses , Italy/epidemiology , Molecular Diagnostic Techniques/veterinary , Polymerase Chain Reaction/methods , Real-Time Polymerase Chain Reaction/veterinary , Retrospective Studies , Theileria/genetics , Theileriasis/epidemiology
17.
Nature ; 590(7844): 151-156, 2021 02.
Article in English | MEDLINE | ID: mdl-33442055

ABSTRACT

Up to 20% of people worldwide develop gastrointestinal symptoms following a meal1, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H1-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders.


Subject(s)
Abdominal Pain/immunology , Abdominal Pain/pathology , Allergens/immunology , Food Hypersensitivity/immunology , Food/adverse effects , Intestines/immunology , Irritable Bowel Syndrome/immunology , Abdominal Pain/etiology , Abdominal Pain/microbiology , Adult , Animals , Citrobacter rodentium/immunology , Diarrhea/immunology , Diarrhea/microbiology , Diarrhea/pathology , Enterobacteriaceae Infections/complications , Enterobacteriaceae Infections/immunology , Enterobacteriaceae Infections/microbiology , Female , Food Hypersensitivity/complications , Food Hypersensitivity/microbiology , Food Hypersensitivity/pathology , Glutens/immunology , Humans , Immunoglobulin E/immunology , Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Intestines/microbiology , Intestines/pathology , Irritable Bowel Syndrome/etiology , Irritable Bowel Syndrome/microbiology , Irritable Bowel Syndrome/pathology , Male , Mast Cells/immunology , Mice , Mice, Inbred BALB C , Middle Aged , Milk/immunology , Ovalbumin/immunology , Quality of Life , Receptors, Histamine H1/metabolism , Soybean Proteins/immunology , Triticum/immunology
18.
Gut ; 70(7): 1383-1395, 2021 07.
Article in English | MEDLINE | ID: mdl-33384336

ABSTRACT

Intestinal resident macrophages are at the front line of host defence at the mucosal barrier within the gastrointestinal tract and have long been known to play a crucial role in the response to food antigens and bacteria that are able to penetrate the mucosal barrier. However, recent advances in single-cell RNA sequencing technology have revealed that resident macrophages throughout the gut are functionally specialised to carry out specific roles in the niche they occupy, leading to an unprecedented understanding of the heterogeneity and potential biological functions of these cells. This review aims to integrate these novel findings with long-standing knowledge, to provide an updated overview on our understanding of macrophage function in the gastrointestinal tract and to speculate on the role of specialised subsets in the context of homoeostasis and disease.


Subject(s)
Cellular Microenvironment , Intestines/cytology , Intestines/physiology , Macrophages/cytology , Macrophages/physiology , Blood Vessels/cytology , Humans , Intestinal Mucosa/cytology , Intestinal Mucosa/immunology , Intestines/blood supply , Muscle, Smooth/cytology , Neurons , Peyer's Patches/cytology , Phagocytosis , Submucous Plexus/cytology
19.
J Clin Med ; 11(1)2021 Dec 26.
Article in English | MEDLINE | ID: mdl-35011859

ABSTRACT

BACKGROUND AND OBJECTIVES: In acute myeloid leukemia (AML), extensive bleeding is one of the most frequent causes of death. Impaired activation and aggregation processes were identified in previous studies on platelet behaviour associated with this disease. This study's aim was to examine platelet function in correlation with other haemorrhage risk factors (fever, sepsis, recent bleeding, uraemia, leucocytosis, haematocrit value, treatment). DESIGN AND METHODS: The analysis of platelet surface proteins (Glycoprotein Ib-IX (CD42b, CD42a), Glycoprotein IIb-IIIa (CD41, CD61), p-selectin (CD62P), granulophysin (CD63)) was conducted by flowcytometry from samples of whole blood in patients with acute myeloid leukaemia in different stages of diagnosis and therapy (n = 22) in comparison with healthy human controls (n = 10). RESULTS AND INTERPRETATIONS: Our results show a significant decrease in fluorescence level associated with platelet activation markers (CD63 (14.11% vs. 40.78 % p < 0.05); CD62P (15.26% vs. 28.23% p < 0.05)); adhesion markers (CD42b (69.08% vs. 84.41% p < 0.05)) and aggregation markers (CD61 (83.79% vs. 98.62% p < 0.001)) in patients compared to controls. The levels of CD41 (80.62% vs. 86.31%, p = 0.290) and CD42a (77.98% vs. 94.15%, p = 0.99) demonstrate no significant differences in the two groups. CONCLUSION: The AML patients present changes in adhesion receptors and activation markers, suggesting a functional defect or denatured intracellular signalling in platelets. The exposed data indicate that flow cytometry can effectively identify multiple functional platelet impairments in AML pathogenesis.

20.
J Cell Mol Med ; 24(13): 7675-7679, 2020 07.
Article in English | MEDLINE | ID: mdl-32460405

ABSTRACT

INTRODUCTION: FLT3 internal tandem duplication (ITD) mutations are found in around 25% of all acute myeloid leukaemia (AML) cases and is associated with shorter disease-free and overall survival. Previous reports have shown that FLT3-ITD induces a specific phenotype in leukemic blasts, which is characterized by high levels of CD33 and CD123, and that expression of CD33 and CD123 is directly influenced by the DNA FLT3-ITD/wild-type FLT3 allelic ratio (AR). METHODS: A total of 42 FLT3-ITD and 104 FLT3-ITD-negative AML patients were analysed. Immunophenotyping data were used to calculate antigen expression levels as the ratio between the geometric mean fluorescence intensities (MFIs) of leukemic blasts and MFIs of negative lymphocyte populations. FLT3-ITD-DNA and RNA analysis was performed, under the same conditions, by capillary electrophoresis. RESULTS: Compared with the control group, the FLT3-ITD cohort presented significantly higher CD7, CD33 and CD123 levels. In order to assess the impact of FLT3-ITD abundance on antigen expression, the patients were grouped for each parameter into two cohorts using the following threshold values: (a) 0.5 for the AR, according to current AML guidelines; (b) 0.7 for the FLT3-ITD/FLT3-WT mRNA ratio (RR); and (c) 1.3 for the FLT3-ITD RR/AR ratio. We found higher values of CD33 for RR/AR ≥1.3, and no other statistical differences between CD7, CD33 and CD123 levels of the other FLT3-ITD groups. In terms of correlations between MFI values and FLT3-ITD parameters, we only observed a moderate interdependence between CD33 MFI and the RR/AR ratio, and a weak negative correlation between CD123 MFI and AR. CONCLUSION: FLT3-ITD mutations induce a specific antigen profile in AML blasts, and our data do not onfirm previous reports of FLT3-ITD AR influencing both CD33 and CD123 expression.


Subject(s)
Antigens, CD7/metabolism , DNA/genetics , Gene Duplication , Gene Expression Regulation, Leukemic , Interleukin-3 Receptor alpha Subunit/metabolism , Leukemia, Myeloid, Acute/genetics , Sialic Acid Binding Ig-like Lectin 3/metabolism , fms-Like Tyrosine Kinase 3/genetics , Antigens, Neoplasm/metabolism , Fluorescence , Humans , RNA, Messenger/genetics , RNA, Messenger/metabolism , fms-Like Tyrosine Kinase 3/metabolism
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