ABSTRACT
Periodontitis (PDS) is a chronic inflammatory disease initiated by a dysbiosis of oral pathogenic bacterial species, such as Porphyromonas gingivalis (Pg). These bacteria can penetrate the bloodstream, releasing various endo and exotoxins that fuel the infection, and stimulate toxic inflammation in different compartments, including the brain. However, the specific mechanisms by which PDS/Pg contribute to brain disorders, such as Alzheimer's disease (AD), remain unclear. This study assessed the effects of Pg's virulence factors - lipopolysaccharide (LPS-Pg) and gingipains (gps) K (Kgp) and Rgp - on SH-SY5Y cells. Our results demonstrated that LPS-Pg activated signaling through the Toll-like receptor (TLR)-2/4 induced a significant downregulation of G protein-coupled receptor kinase 5 (GRK5). Additionally, LPS-Pg stimulation resulted in a robust increase in Tau phosphorylation (pTau) and p53 levels, while causing a marked reduction in Bcl2 and increased cell death compared to unstimulated cells (Ns). LPS-Pg also elevated inducible nitric oxide synthase (iNOS) expression, leading to oxidative damage. In cells overexpressing GRK5 via Adenovirus, LPS-Pg failed to increase iNOS and pTau levels compared to GFP control cells. High GRK5 levels also prevented the nuclear accumulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Furthermore, the overexpression of a GRK5 mutant form lacking the nuclear localization signal (ΔNLS) nearly abolished LPS-Pg induced p53 and iNOS upregulation. Finally, we tested whether Kgp and Rgp mediated similar effects and our data showed that both gps caused a marked downregulation of GRK5 leading to increased p53 and pTau levels. In conclusion, this study provides further insight into the toxic effects elicited by Pg in cells and suggests that preventing GRK5 deficiency may be a valid strategy to mitigate Pg-induced toxic effects (i.e. cell death, oxidative damage, and Tau hyperphosphorylation) in SH-SY5Y cells, which are typical molecular hallmarks of neurodegenerative disorders.
ABSTRACT
Colistin is a polymyxin antibiotic currently experiencing renewed clinical interest due to its efficacy in the treatment of multidrug resistant (MDR) bacterial infections. The frequent onset of acute dose-dependent kidney injury, with the potential of leading to long-term renal damage, has limited its use and hampered adequate dosing regimens, increasing the risk of suboptimal plasma concentrations during treatment. The mechanism of colistin-induced renal toxicity has been postulated to stem from mitochondrial damage, yet there is no direct evidence of colistin acting as a mitochondrial toxin. The aim of this study was to evaluate whether colistin can directly induce mitochondrial toxicity and, if so, uncover the underlying molecular mechanism. We found that colistin leads to a rapid permeability transition of mitochondria isolated from mouse kidney that was fully prevented by co-incubation of the mitochondria with desensitizers of the mitochondrial transition pore cyclosporin A or L-carnitine. The protective effect of L-carnitine was confirmed in experiments in primary cultured mouse tubular cells. Consistently, the relative risk of colistin-induced kidney damage, calculated based on histological analysis as well as by the early marker of tubular kidney injury, Kim-1, was halved under co-administration with L-carnitine in vivo. Notably, L-carnitine neither affected the pharmacokinetics of colistin nor its antimicrobial activity against relevant bacterial strains. In conclusion, colistin targets the mitochondria and induces permeability transition thereof. L-carnitine prevents colistin-induced permeability transition in vitro. Moreover, L-carnitine co-administration confers partial nephroprotection in mice treated with colistin, without interfering with its pharmacokinetics and antibacterial activity.
Subject(s)
Acute Kidney Injury , Anti-Bacterial Agents , Carnitine , Colistin , Mitochondria , Animals , Colistin/adverse effects , Colistin/administration & dosage , Acute Kidney Injury/prevention & control , Acute Kidney Injury/chemically induced , Acute Kidney Injury/metabolism , Carnitine/pharmacology , Carnitine/administration & dosage , Mice , Mitochondria/drug effects , Mitochondria/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Male , Mitochondrial Permeability Transition Pore/metabolism , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Mice, Inbred C57BL , CyclosporineABSTRACT
Objective: MRI is an emerging imaging modality to assess skeletal maturity. This study aimed to chart the learning curves of paediatric radiologists when using an unfamiliar MRI grading system of skeletal maturity and to assess the clinical feasibility of implementing said system. Methods: 958 healthy paediatric volunteers were prospectively included in a dual-facility study. Each subject underwent a conventional MRI scan at 1.5 T. To perform the image reading, the participants were grouped into five subsets (subsets 1-5) of equal size (nâ¼192) in chronological order for scan acquisition. Two paediatric radiologists (R1-2) with different levels of MRI experience, both of whom were previously unfamiliar with the study's MRI grading system, independently evaluated the subsets to assess skeletal maturity in five different growth plate locations. Congruent cases at blinded reading established the consensus reading. For discrepant cases, the consensus reading was obtained through an unblinded reading by a third paediatric radiologist (R3), also unfamiliar with the MRI grading system. Further, R1 performed a second blinded image reading for all included subjects with a memory wash-out of 180 days. Weighted Cohen kappa was used to assess interreader reliability (R1 vs consensus; R2 vs consensus) at non-cumulative and cumulative time points, as well as interreader (R1 vs R2) and intrareader (R1 vs R1) reliability at non-cumulative time points. Results: Mean weighted Cohen kappa values for each pair of blinded readers compared to consensus reading (interreader reliability, R1-2 vs consensus) were ≥0.85, showing a strong to almost perfect interreader agreement at both non-cumulative and cumulative time points and in all growth plate locations. Weighted Cohen kappa values for interreader (R1 vs R2) and intrareader reliability (R1 vs R1) were ≥0.72 at non-cumulative time points, with values ≥0.82 at subset 5. Conclusions: Paediatric radiologists' clinical confidence when introduced to a new MRI grading system for skeletal maturity was high from the outset of their learning curve, despite the radiologists' varying levels of work experience with MRI assessment. The MRI grading system for skeletal maturity investigated in this study is a robust clinical method when used by paediatric radiologists and can be used in clinical practice. Advances in knowledge: Radiologists with fellowship training in paediatric radiology experienced no learning curve progress when introduced to a new MRI grading system for skeletal maturity and achieved desirable agreement from the first time point of the learning curve. The robustness of the investigated MRI grading system was not affected by the earlier different levels of MRI experience among the readers.
ABSTRACT
"How tall will I be?" Every paediatrician has been asked this during their career. The growth plate is the main site of longitudinal growth of the long bones. The chondrocytes in the growth plate have a columnar pattern detectable by diffusion tensor imaging (DTI). DTI shows the diffusion of water in a tissue and whether it is iso- or anisotropic. By detecting direction and magnitude of diffusion, DTI gives information about the microstructure of the tissue. DTI metrics include tract volume, length, and number, fractional anisotropy (FA), and mean diffusivity. DTI metrics, particularly tract volume, provide quantitative data regarding skeletal growth and, in conjunction with the fractional anisotropy, be used to determine whether a growth plate is normal. Tractography is a visual display of the diffusion, depicting its direction and amplitude. Tractography gives a more qualitative visualization of cellular orientation in a tissue and reflects the activity in the growth plate. These two components of DTI can be used to assess the growth plate without ionizing radiation or pain. Further refinements in DTI will improve prediction of post-imaging growth and growth plate closure, and assessment of the positive and negative effect of treatments like cis-retinoic acid and growth hormone administration.
ABSTRACT
PURPOSE: To assess the performance of a 2.5-minute multi-contrast brain MRI sequence (NeuroMix) in diagnosing acute cerebral infarctions. METHODS: Adult patients with a clinical suspicion of acute ischemic stroke were retrospectively included. Brain MRI at 3 T included NeuroMix and routine clinical MRI (cMRI) sequences, with DWI/ADC, T2-FLAIR, T2-weighted, T2*, SWI-EPI, and T1-weighted contrasts. Three radiologists (R1-3) independently assessed NeuroMix and cMRI for the presence of acute infarcts (DWI ↑, ADC = or ↓) and infarct-associated abnormalities on other image contrasts. Sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) were calculated and compared using DeLong's test. Inter- and intra-rater agreements were studied with kappa statistics. Relative DWI (rDWI) and T2-FLAIR (rT2-FLAIR) signal intensity for infarctions were semi-automatically rendered, and the correlation between methods was evaluated. RESULTS: According to the reference standard, acute infarction was present in 34 out of 44 (77%) patients (63 ± 17 years, 31 men). Other infarct-associated signal abnormalities were reported in similar frequencies on NeuroMix and cMRI (p > .08). Sensitivity for infarction detection was 94%, 100%, and 94% evaluated by R1, R2, R3, for NeuroMix and 94%, 100%, and 100% for cMRI. Specificity was 100%, 90%, and 100% for NeuroMix and 100%, 100%, and 100% for cMRI. AUC for NeuroMix was .97, .95, and .97 and .97, 1, and 1 for cMRI (DeLong p = 1, .32, .15), respectively. Inter- and intra-rater agreement was κ = .88-1. The correlation between NeuroMix and cMRI was R = .73 for rDWI and R = .83 for rT2-FLAIR. CONCLUSION: Fast multi-contrast MRI NeuroMix has high diagnostic performance for detecting acute cerebral infarctions.
Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Adult , Male , Humans , Retrospective Studies , Magnetic Resonance Imaging/methods , Brain Ischemia/diagnostic imaging , Diffusion Magnetic Resonance Imaging/methods , Acute Disease , Brain/diagnostic imaging , Cerebral Infarction , Infarction , Stroke/diagnostic imagingABSTRACT
PURPOSE: To identify prognostic circulating biomarkers to cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), we performed a mutational analysis on circulating tumor DNA (ctDNA) samples from patients included in the TREnd trial, which randomly assigned patients to receive the CDK4/6i palbociclib alone or with the endocrine treatment (ET) to which they had progressed. METHODS: Forty-six patients were enrolled in this substudy. Plasma was collected before treatment (T0), after the first cycle of therapy (T1), and at the time of progression (T2). ctDNA hybridization and capture were performed using the Illumina TruSight Tumor 170 Kit. Acquired mutations were confirmed by digital polymerase chain reaction. Progression-free survival analysis was estimated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: The most frequently mutated genes at T0 were ESR1 (23%), PIK3CA (17%), AR, FGFR2, and TP53 (10%). Mutations in ESR1 at T0 conferred higher risk of progression in the entire population (P = .02) and in patients treated with palbociclib + ET (P = .04). ESR1 mutation effect remained significant after correction for clinical variables (P = .03). PIK3CA mutations at T0 were not prognostic, but higher risk of progression was observed when a broader analysis of PI3K pathway was performed (P = .04). At T2, we observed the emergence of nine new mutations in seven genes. CONCLUSION: Mutations in ESR1 and in PI3K pathway genes at T0 were associated with worse prognosis in palbociclib-treated patients. We describe the emergence of newly acquired mutations in palbociclib-treated patients, which might potentially affect subsequent treatment.
Subject(s)
Breast Neoplasms , Circulating Tumor DNA , Piperazines , Pyridines , Receptor, ErbB-2 , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Circulating Tumor DNA/genetics , Phosphatidylinositol 3-Kinases , Receptors, Estrogen/geneticsABSTRACT
BACKGROUND: Brain CT can be used to evaluate pediatric patients with suspicion of cerebral pathology when anesthetic and MRI resources are scarce. This study aimed to assess if pediatric patients referred for an elective brain CT could endure a diagnostic fast brain MRI without general anesthesia using a one-minute multi-contrast EPI-based sequence (EPIMix) with comparable diagnostic performance. METHODS: Pediatric patients referred for an elective brain CT between March 2019 and March 2020 were prospectively included and underwent EPIMix without general anesthesia in addition to CT. Three readers (R1-3) independently evaluated EPIMix and CT images on two separate occasions. The two main study outcomes were the tolerance to undergo an EPIMix scan without general anesthesia and its performance to classify a scan as normal or abnormal. Secondary outcomes were assessment of disease category, incidental findings, diagnostic image quality, diagnostic confidence, and image artifacts. Further, a side-by-side evaluation of EPIMix and CT was performed. The signal-to-noise ratio (SNR) was calculated for EPIMix on T1-weighted, T2-weighted, and ADC images. Descriptive statistics, Fisher's exact test, and Chi-squared test were used to compare the two imaging modalities. RESULTS: EPIMix was well tolerated by all included patients (n = 15) aged 5-16 (mean 11, SD 3) years old. Thirteen cases on EPIMix and twelve cases on CT were classified as normal by all readers (R1-3), while two cases on EPIMix and three cases on CT were classified as abnormal by one reader (R1), (R1-3, p = 1.00). There was no evidence of a difference in diagnostic confidence, image quality, or the presence of motion artifacts between EPIMix and CT (R1-3, p ≥ 0.10). Side-by-side evaluation (R2 + R4 + R5) reviewed all scans as lacking significant pathological findings on EPIMix and CT images. CONCLUSIONS: Full brain MRI-based EPIMix sequence was well tolerated without general anesthesia with a diagnostic performance comparable to CT in elective pediatric patients. TRIAL REGISTRATION: This study was approved by the Swedish Ethical Review Authority (ethical approval number/ID Ethical approval 2017/2424-31/1). This study was a clinical trial study, with study protocol published at ClinicalTrials.gov with Trial registration number NCT03847051, date of registration 18/02/2019.
Subject(s)
Brain , Magnetic Resonance Imaging , Child , Child, Preschool , Humans , Brain/diagnostic imaging , Feasibility Studies , Prospective Studies , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: The Asian elephant (Elephas maximus), which is an endangered species, harbors several parasites. Among the ectoparasites that it harbors, ear mites of the genus Loxanoetus have the potential to cause external otitis, an inflammation that may also be associated with the presence of other microorganisms. We assessed the relationships between ear mites, nematodes, yeast, bacterial rods, and cocci sampled from the ears of captive Asian elephants in Thailand. In addition, we discuss the possibility that dust-bathing behavior may be triggered by ear mite infestation, and that this in turn may lead to contamination of the ears with soil microorganisms. METHODS: Legally owned captive Asian elephants (n = 64) were sampled. Ear swabs were individually collected from both ears and microscopically examined for the presence of mites, nematodes, yeast, bacterial rods, cocci, and host cells. Mites and nematodes were identified to species level using morphological and molecular methods. RESULTS: Loxanoetus lenae mites were present in 43.8% (n = 28/64) of the animals (19 animals with mites in one ear and nine animals with mites in both ears). Nematodes of the genus Panagrolaimus were detected in 23.4% (n = 15/64) of the animals (10 with nematodes in one ear and five with nematodes in both ears). In adult elephants (Fisher's exact test, P = 0.0278) and female elephants (Fisher's exact test, P = 0.0107), the presence of nematodes in both ears was significantly associated with the presence of mites. In addition, higher categorical burdens of nematodes were also significantly associated with the presence of mites (Fisher's exact test, P = 0.0234) and epithelial cells (Fisher's exact test, P = 0.0108), and marginally significantly associated with bacterial cocci (Fisher's exact test, P = 0.0499). CONCLUSIONS: The presence of L. lenae mites in the ear canals of the Asian elephants was significantly associated with the occurrence of other microorganisms, such as soil nematodes, bacteria and yeasts. The presence of mites in their ears may increase the dust-bathing behavior of elephants which, if confirmed, represents a further paradigmatic example of a parasitic infestation affecting animal behavior.
Subject(s)
Bacillus , Elephants , Mites , Nematoda , Otitis Externa , Female , Animals , Saccharomyces cerevisiae , Bacteria/genetics , DustABSTRACT
DNA-methylation alterations are common in cancer and display unique characteristics that make them ideal markers for tumor quantification and classification. Here we present MIMESIS, a computational framework exploiting minimal DNA-methylation signatures composed by a few dozen informative DNA-methylation sites to quantify and classify tumor signals in tissue and cell-free DNA samples. Extensive analyses of multiple independent and heterogenous datasets including >7200 samples demonstrate the capability of MIMESIS to provide precise estimations of tumor content and to enable accurate classification of tumor type and molecular subtype. To assess our framework for clinical applications, we designed a MIMESIS-informed assay incorporating the minimal signatures for breast cancer. Using both artificial samples and clinical serial cell-free DNA samples from patients with metastatic breast cancer, we show that our approach provides accurate estimations of tumor content, sensitive detection of tumor signal and the ability to capture clinically relevant molecular subtype in patients' circulation. This study provides evidence that our extremely parsimonious approach can be used to develop cost-effective and highly scalable DNA-methylation assays that could support and facilitate the implementation of precision oncology in clinical practice.
Subject(s)
Breast Neoplasms , Cell-Free Nucleic Acids , Humans , Female , Cell-Free Nucleic Acids/genetics , Precision Medicine , DNA Methylation , Breast Neoplasms/genetics , Biomarkers, Tumor/genetics , DNA, Neoplasm/geneticsABSTRACT
BACKGROUND: Attenuation correction (AC) is an important topic in PET/MRI and particularly challenging after brain tumor surgery, near metal implants, adjacent bone and burr holes. In this study, we evaluated the performance of two MR-driven AC methods, zero-echo-time AC (ZTE-AC) and atlas-AC, in comparison to reference standard CT-AC in patients with surgically treated brain tumors at 11C-methionine PET/MRI. METHODS: This retrospective study investigated seven postoperative patients with neuropathologically confirmed brain tumor at 11C-methionine PET/MRI. Three AC maps - ZTE-AC, atlas-AC and reference standard CT-AC - were generated for each patient. Standardized uptake values (SUV) were obtained at the metal implant, adjacent bone and burr hole. Standard uptake ratio (SUR) SURmetal/mirror, SURbone/mirror and SURburrhole/mirror were then calculated and analyzed with Bland-Altman, Pearson correlation and intraclass correlation reliability. RESULTS: Smaller mean percent bias range (Bland-Altman) was found for ZTE-AC than atlas-AC in all analyses (metal ZTE -0.46 to -0.02, metal atlas -3.57 to -3.26; bone ZTE -4.60 to -2.16, bone atlas -5.25 to -3.81; burr hole ZTE -0.95 to -0.52, burr hole atlas 7.86 to 8.87). Percent SD range (Bland-Altman) was large for both methods in all analyses, with lower absolute values for ZTE-AC (ZTE 7.02-8.49; atlas 11.47-14.83). A very strong correlation (Pearson correlation) was demonstrated for both methods compared to CT-AC (ZTE ρ 0.97-0.99, P<0.001; atlas ρ 0.88-0.91, P≤0.009) with higher absolute values for ZTE. An excellent intraclass correlation coefficient was found across all analyses for ZTE, atlas and CT maps (ICC ≥0.88). CONCLUSIONS: ZTE for MR-driven PET attenuation correction presented a more comparable performance to reference standard CT-AC at the postoperative site. ZTE-AC may serve as a useful diagnostic tool for MR-driven AC in patients with surgically treated brain tumors.
Subject(s)
Brain Neoplasms , Multimodal Imaging , Humans , Carbon Radioisotopes , Multimodal Imaging/methods , Retrospective Studies , Reproducibility of Results , Brain/diagnostic imaging , Fluorodeoxyglucose F18 , Positron-Emission Tomography/methods , Magnetic Resonance Imaging/methods , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Brain Neoplasms/pathology , Methionine , Craniotomy , Racemethionine , Tomography, X-Ray Computed/methods , Image Processing, Computer-Assisted/methodsABSTRACT
The term "microbial control" has been used to describe the use of microbial pathogens (bacteria, viruses, or fungi) or entomopathogenic nematodes (EPNs) to control various insect pest populations. EPNs are among the best biocontrol agents, and major developments in their use have occurred in recent decades, with many surveys having been conducted all over the world to identify EPNs that may have potential in the management of insect pests. For nematodes, the term "entomopathogenic" means "causing disease to insects" and is mainly used in reference to the bacterial symbionts of Steinernema and Heterorhabditis (Xenorhabdus and Photorhabdus, respectively), which cause EPN infectivity. A compendium of our multiannual experiences on EPN surveys and on their collection, identification, characterization, and use in agro-forestry ecosystems is presented here to testify and demonstrate once again that biological control with EPNs is possible and offers many advantages over chemicals, such as end-user safety, minimal damage to natural enemies, and lack of environmental pollution, which are essential conditions for an advanced IPM strategy.
ABSTRACT
During a nematological survey in Iraq, in the Bashika area, Ninevah province, an anguinid nematode population was isolated from galls of infected barley plants. The morphological characteristics indicated that the recovered species is identical to Anguina tritici. The barley population of A. tritici was molecularly characterized by sequencing two ribosomal regions (ITS and 18S rRNA genes), and their phylogenetic analyses revealed the newly generated sequences are in sister relation to corresponding sequences of A. tritici from wheat in the Bayesian tree, providing further evidence that the host plant can contribute to the separation of new isolates of plant parasitic nematodes.
ABSTRACT
Since the first detection of Meloidogyne graminicola in Piedmont, North Italy, in 2016, further inspections for the presence of the rice root-knot nematode were carried out in rice fields of neighboring regions, in accordance with the Italian NPPO (National Plant Protection Organization) to support the official phytosanitary measures, to enable the early detection of the rice pest, and to prevent its spread within the national territory. In 2018, surveys of rice fields in Lombardy region revealed a new occurrence of M. graminicola. In the present study, we confirmed the identification of the rice nematode in Lombardy using the ribosomal ITS region and the mitochondrial COI and COII genes. The sequences and phylogenetic analyses revealed that Lombardy M. graminicola population grouped in all trees in the main cluster containing Meloidogyne species belonging to graminis group, but always in a different subgroup compared to the Piedmont population of M. graminicola. These results clearly suggest that the two Italian populations have been recently and independently introduced and confirm that the geographic origin is not the main factor leading to M. graminicola population variability.
ABSTRACT
BACKGROUND: Coronavirus pandemic has influenced our society with social distancing and management of chronic disease such as cystic fibrosis (CF). During the Italian lockdown from March to May 2020, CF patients reduced the number of outpatient visits, limited social interactions and spent more time at home. The aim of this study is to evaluate the impact of the lockdown on body mass index (BMI) and lung function tests on CF patients. METHODS: We retrospectively reviewed clinical data about 111 CF patients followed in our Regional Cystic Fibrosis Reference Centre (Policlinico Umberto I, Rome) according to two periods: pre-lockdown (from October 2019-March 2020) and post-lockdown (from May 2020-October 2020). We collected data on nutritional (BMI and body weight) and lung function status; we chose the best values of the 'pre-lockdown' and 'post-lockdown' period for each patient. Patients were divided into 3 groups according to FEV1 value (Forced Expiratory Volume in the 1st second): group 1 (FEV1 <40%), group 2 (FEV1 40-70%), group 3 (FEV1 >70%). All patients received a telephone interview asking for the number of hours per week devoted to physical activity, number of pulmonary acute exacerbations and subjective evaluation of adherence to medical therapy, respiratory physiotherapy and diet, during the two periods. RESULTS: Comparing weight, BMI and respiratory function between pre and post lockdown periods, we noticed an increase in weight during among overall patients. Male patients improved weight, BMI, FEF 25-75% (Forced Expiratory flow between 25% and 75% of vital capacity) and Tiffenau index more than female patients. The most severely compromised patients (group 1), showed a significant loss of both weight and BMI. Instead, patients with moderate respiratory function (group 2) showed a significant increase of both weight and BMI and a slightly reduced CVF (Forced Vital capacity). We found no differences among patients with good respiratory function (group 3). Comparing each clinical sub-groups, we noticed a significative improvement of weight (p = 0.018) and BMI (p = 0.030) among patients with moderate respiratory function compared to patients with compromised respiratory function. During lockdown, patients reported less physical activity, no variation in food amount and composition, more adherence to therapy (43%) and more consistent daily respiratory physiotherapy (47.6%). CONCLUSIONS: Lockdown period had benefit among CF patients in terms of weight in particular in male patient. The greatest benefit on nutritional state was observed in patients with moderate reduction of respiratory function. In addition, we noted a stabilization and sometimes a slight improvement of lung function, instead of a continuous and steady decline that is normally observed in CF patients. These beneficial effects are slight but significative, bearing in mind the general worsening that CF patients experience annually.
Subject(s)
COVID-19 , Cystic Fibrosis , COVID-19/epidemiology , Communicable Disease Control , Cystic Fibrosis/epidemiology , Cystic Fibrosis/therapy , Cystic Fibrosis Transmembrane Conductance Regulator , Female , Humans , Male , Retrospective StudiesABSTRACT
Microscopic observations and transcriptomic RNA-Seq analyses were applied to investigate the effect of water stress during the formation of tomato galls formation 1 and 2 weeks after inoculation with the root-knot nematode Meloidogyne incognita. Water stress affected root growth and the nematode ability to mount an efficient parasitism. The effects of water stress on the feeding site development were already observed at 1 week after nematode inoculation, with smaller giant cells, delayed development, and thinner cell walls. These features suggested changes in the expression levels of genes involved in the feeding site formation and maintenance. Gene Ontology (GO) enrichment and expression patterns were used to characterize differentially expressed genes. Water stress modified the expression profile of genes involved in the synthesis, degradation, and remodeling of the cell wall during the development of nematode feeding site. A comparison of gene expression with unstressed galls revealed that water stress intensified the up or downregulation of most genes. However, it particularly influenced the expression pattern of expansin A11 (Solyc04g081870.4.1), expansin-like B1(Solyc08g077910.3.1), a pectin acetylesterase (Solyc08g005800.4.1), and the pectin methylesterase pmeu1 (Solyc03g123630.4.1) which were upregulated in unstressed galls and repressed by water stress, at both sampling times. The expression of most members of the genes involved in cell wall metabolism, i.e., those coding for Csl, fasciclin, and COBRA proteins, were negatively influenced. Interestingly, alteration in the expression profiles of most dirigent protein genes (DIRs) and upregulation of five gene coding for Casparian strip domain protein (CASP)-like proteins were found. Gene expression analysis of galls from water stressed plants allowed us to better understand the molecular basis of M. incognita parasitism in tomato. Specific genes, including those involved in regulation of cellulose synthesis and lignification process, require further study to develop defense strategies against root-knot nematodes.
ABSTRACT
BACKGROUND: Fast 78-second multicontrast echo-planar MRI (EPIMix) has shown good diagnostic performance for detecting infarctions at a comprehensive stroke center, but its diagnostic performance has not been evaluated in a prospective study at a primary stroke center. PURPOSE: To prospectively determine whether EPIMix was noninferior in detecting ischemic lesions compared to routine clinical MRI. STUDY TYPE: Prospective cohort study. POPULATION: A total of 118 patients with acute MRI and symptoms of ischemic stroke. FIELD STRENGTH AND SEQUENCE: A 3 T. EPIMix (echo-planar based: T1-FLAIR, T2-weighted, T2-FLAIR, T2*, DWI) and routine clinical MRI sequences (T1-weighted fast spin echo, T2-weighted PROPELLER, T2-weighted-FLAIR fast spin echo, T2* gradient echo echo-planar, and DWI spin echo echo-planar). ASSESSMENT: Three radiologists, blinded for clinical information, assessed signs of ischemic lesions (DWI↑, ADC↓, and T2/T2-FLAIR↑) on EPIMix and routine clinical MRI, with disagreements solved in consensus with a fourth reader to establish the reference standard. STATISTICAL TESTS: Diagnostic performance including sensitivity and specificity against the reference standard was evaluated. EPIMix sensitivity was tested for noninferiority compared to the reference standard using Nam's restricted maximum likelihood estimation (RMLE) Score. A P-value < 0.05 was considered statistically significant. RESULTS: Of 118 patients (mean age 62 ± 16 years, 58% males), 25% (n = 30) had MRI signs of acute infarcts. EPIMix was noninferior with 97% (95% CI 83-100) sensitivity for reader 1, 100% (95% CI 88-100) sensitivity for reader 2, and 90% (95% CI 88-98) sensitivity for reader 3 vs. 93% (95% CI 78-99) sensitivity for readers 1 and 2 and 90% (95% CI 74-98) for reader 3 on routine clinical MRI. Specificity was 99% (95% CI 94-100) for reader 1, 100% (95% CI 96-100) for reader 2, and 98% (95% CI 92-100) for reader 3 on EPIMix vs. 100% (95% CI 96-100) for all readers on routine clinical MRI. CONCLUSION: EPIMix was noninferior to routine clinical MRI for the diagnosis of acute ischemic stroke. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.
Subject(s)
Ischemic Stroke , Aged , Brain/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuroimaging , Prospective Studies , Sensitivity and SpecificityABSTRACT
In the last few decades, many studies have reported an increasing global incidence of type 1 diabetes. Studies on migrant populations have underlined the importance of both environmental and genetic factors. AIMS: Evaluate the incidence of type 1 diabetes in North African vs Italian children aged 0-14 years from 1 January 2015, to 31st December 2018, in Emilia-Romagna region, Italy. METHODS: Clinical and epidemiological data about childhood onset type 1 diabetes in Emilia Romagna region were retrospectively collected by the regional centers of pediatric diabetology and matched using 3 different data sources. RESULTS: 365 new cases were diagnosed. Total cumulative incidence was 15.4/100,000/year. North African cases showed a cumulative incidence of 53.8/100,000/year, statistically significant compared to cumulative incidence of the Italian cases alone 13.1/100,000/year (p value < 0.001). The annual incidence did not differ in the 4 years for both groups. Conclusion: The incidence of type 1 diabetes in the pediatric age (0 14 years) was significantly higher in the North African population than in the Italian one, suggesting that a mix of genetic and environmental factors may have caused the increase in newly diagnosed cases. WHAT IS KNOWN: ⢠The incidence of type 1 diabetes largely varies worldwide. ⢠Study on immigrants helped to better understand the interplay role between genetics and environment. WHAT IS NEW: ⢠This is the first study focused on the incidence of children and adolescents of North African migrants in Italy. ⢠The incidence of children and adolescents of North African migrants in Emilia Romagna region, Italy, seems to be higher than that reported in the host countries, and, above all, than that reported in highest-incidence countries in Europe and in the world.
Subject(s)
Diabetes Mellitus, Type 1 , Emigrants and Immigrants , Transients and Migrants , Adolescent , Child , Child, Preschool , Diabetes Mellitus, Type 1/epidemiology , Humans , Incidence , Infant , Infant, Newborn , Italy/epidemiology , Retrospective StudiesABSTRACT
Healthy ageing has been associated with a bias toward positive information and greater psychological well-being. However, to what extent this positivity bias also applies to prioritizing positive information under emotional competition is unclear. Old and young adults performed a word-face interference task, in which they responded to the valence of positive and negative target-words while ignoring happy or angry distractor-faces that could be affectively congruent or incongruent. A control condition with scrambled neutral distractor-faces was also used. Findings showed small facilitation effects with faster responses when targets and distractors were affectively congruent and large interference effects with slower responses when targets and distractors were affectively incongruent compared to the control condition. Importantly, whereas for younger adults there was a similar pattern of interference from happy and angry distractor-faces, for older adults there was greater interference from angry distractor-faces. The present findings are discussed in the context of emotional bias literature.
Subject(s)
Emotions , Facial Expression , Aged , Anger , Bias , Happiness , Healthy Aging , Humans , Young AdultABSTRACT
Importance: Although several studies have provided information on short-term clinical outcomes in children with perinatal exposure to SARS-CoV-2, data on the immune response in the first months of life among newborns exposed to the virus in utero are lacking. Objective: To characterize systemic and mucosal antibody production during the first 2 months of life among infants who were born to mothers infected with SARS-CoV-2. Design, Setting, and Participants: This prospective cohort study enrolled 28 pregnant women who tested positive for SARS-CoV-2 infection and who gave birth at Policlinico Umberto I in Rome, Italy, from November 2020 to May 2021, and their newborns. Maternal and neonatal systemic immune responses were investigated by detecting spike-specific antibodies in serum, and the mucosal immune response was assessed by measuring specific antibodies in maternal breastmilk and infant saliva 48 hours after delivery and 2 months later. Exposures: Maternal infection with SARS-CoV-2 in late pregnancy. Main Outcomes and Measures: The systemic immune response was evaluated by the detection of SARS-CoV-2 IgG and IgA antibodies and receptor binding domain-specific IgM antibodies in maternal and neonatal serum. The mucosal immune response was assessed by measuring spike-specific antibodies in breastmilk and in infant saliva, and the presence of antigen-antibody spike IgA immune complexes was investigated in breastmilk samples. All antibodies were detected using an enzyme-linked immunosorbent assay. Results: In total, 28 mother-infant dyads (mean [SD] maternal age, 31.8 [6.4] years; mean [SD] gestational age, 38.1 [2.3] weeks; 18 [60%] male infants) were enrolled at delivery, and 21 dyads completed the study at 2 months' follow-up. Because maternal infection was recent in all cases, transplacental transfer of virus spike-specific IgG antibodies occurred in only 1 infant. One case of potential vertical transmission and 1 case of horizontal infection were observed. Virus spike protein-specific salivary IgA antibodies were significantly increased (P = .01) in infants fed breastmilk (0.99 arbitrary units [AU]; IQR, 0.39-1.68 AU) vs infants fed an exclusive formula diet (0.16 AU; IQR, 0.02-0.83 AU). Maternal milk contained IgA spike immune complexes at 48 hours (0.53 AU; IQR, 0.25-0.39 AU) and at 2 months (0.09 AU; IQR, 0.03-0.17 AU) and may have functioned as specific stimuli for the infant mucosal immune response. Conclusions and Relevance: In this cohort study, SARS-CoV-2 spike-specific IgA antibodies were detected in infant saliva, which may partly explain why newborns are resistant to SARS-CoV-2 infection. Mothers infected in the peripartum period appear to not only passively protect the newborn via breastmilk secretory IgA but also actively stimulate and train the neonatal immune system via breastmilk immune complexes.