The hidden link between late-onset seizures and cerebral amyloid angiopathy: A case-control study.

OBJECTIVE: Epileptic seizures occurring in late adulthood often remain of unknown origin. Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease characterized by intracerebral hemorrhage, microhemorrhage and superficial siderosis, occurring mostly in elderly. This observational case-control study aimed to assess the occurrence of CAA in patients experiencing their first seizure in late adulthood. METHODS: We enrolled consecutive patients aged ≥55 years presenting with late-onset seizures (LOS) to the emergency departments or outpatient clinics of two Italian centers, from April 2021 to October 2022. Two age-matched control subjects with neurological symptoms other than epileptic seizure were recruited for each enrolled case. All participants underwent brain MRI (1.5 Tesla) including blood-sensitive sequences and were assessed for probable CAA diagnosis according to Boston criteria 2.0. Chi-squared test was performed to evaluate group differences. Univariate logistic regression analysis tested the association between clinical variables and CAA. RESULTS: We included 65 patients with LOS (27 females; mean age 72.2 ± 8.9 years) and 130 controls (49 females; mean age 70.3 ± 8.9 years). Diagnosis of probable CAA was achieved in 10.8% (7/65) of LOS patients and 2.3% (3/130) controls, with a statistically significant difference (p = 0.011). The OR for CAA in the LOS group was 5.2 as compared to the control group (95% CI = 1.3-20.6, p = 0.02). SIGNIFICANCE: The frequency of CAA is significatively higher in patients with LOS as compared to other neurological diseases, suggesting that a portion of LOS of unknown or vascular origin are associated with CAA. PLAIN LANGUAGE SUMMARY: Late-onset seizures (LOS) are very frequent in the elderly and often have no clear cause. Cerebral amyloid angiopathy (CAA) is a condition where amyloid proteins build up in the blood vessels of the brain, causing them to become weak and prone to bleeding. In this study, we explored the occurrence of CAA in people with LOS. We found that people with LOS were more likely to have a diagnosis of CAA than controls (i.e., people with other neurological diseases).

A fuzzy-enhanced deep learning approach for early detection of Covid-19 pneumonia from portable chest X-ray images.

The Covid-19 pandemic is the defining global health crisis of our time. Chest X-Rays (CXR) have been an important imaging modality for assisting in the diagnosis and management of hospitalised Covid-19 patients. However, their interpretation is time intensive for radiologists. Accurate computer aided systems can facilitate early diagnosis of Covid-19 and effective triaging. In this paper, we propose a fuzzy logic based deep learning (DL) approach to differentiate between CXR images of patients with Covid-19 pneumonia and with interstitial pneumonias not related to Covid-19. The developed model here, referred to as CovNNet, is used to extract some relevant features from CXR images, combined with fuzzy images generated by a fuzzy edge detection algorithm. Experimental results show that using a combination of CXR and fuzzy features, within a deep learning approach by developing a deep network inputed to a Multilayer Perceptron (MLP), results in a higher classification performance (accuracy rate up to 81%), compared to benchmark deep learning approaches. The approach has been validated through additional datasets which are continously generated due to the spread of the virus and would help triage patients in acute settings. A permutation analysis is carried out, and a simple occlusion methodology for explaining decisions is also proposed. The proposed pipeline can be easily embedded into present clinical decision support systems.

Therapeutic effects of adenosine in high flow 21% oxygen aereosol in patients with Covid19-pneumonia.

BACKGROUND: SARS-Cov2 infection may trigger lung inflammation and acute-respiratory-distress-syndrome (ARDS) that requires active ventilation and may have fatal outcome. Considering the severity of the disease and the lack of active treatments, 14 patients with Covid-19 and severe lung inflammation received inhaled adenosine in the attempt to therapeutically compensate for the oxygen-related loss of the endogenous adenosine→A2A adenosine receptor (A2AR)-mediated mitigation of the lung-destructing inflammatory damage. This off label-treatment was based on preclinical studies in mice with LPS-induced ARDS, where inhaled adenosine/A2AR agonists protected oxygenated lungs from the deadly inflammatory damage. The treatment was allowed, considering that adenosine has several clinical applications. PATIENTS AND TREATMENT: Fourteen consecutively enrolled patients with Covid19-related interstitial pneumonitis and PaO2/FiO2 ratio<300 received off-label-treatment with 9 mg inhaled adenosine every 12 hours in the first 24 hours and subsequently, every 24 days for the next 4 days. Fifty-two patients with analogue features and hospitalized between February and April 2020, who did not receive adenosine, were considered as a historical control group. Patients monitoring also included hemodynamic/hematochemical studies, CTscans, and SARS-CoV2-tests. RESULTS: The treatment was well tolerated with no hemodynamic change and one case of moderate bronchospasm. A significant increase (> 30%) in the PaO2/FiO2-ratio was reported in 13 out of 14 patients treated with adenosine compared with that observed in 7 out of52 patients in the control within 15 days. Additionally, we recorded a mean PaO2/FiO2-ratio increase (215 ± 45 vs. 464 ± 136, P = 0.0002) in patients receiving adenosine and no change in the control group (210±75 vs. 250±85 at 120 hours, P>0.05). A radiological response was demonstrated in 7 patients who received adenosine, while SARS-CoV-2 RNA load rapidly decreased in 13 cases within 7 days while no changes were recorded in the control group within 15 days. There was one Covid-19 related death in the experimental group and 11in the control group. CONCLUSION: Our short-term analysis suggests the overall safety and beneficial therapeutic effect of inhaled adenosine in patients with Covid-19-inflammatory lung disease suggesting further investigation in controlled clinical trials.

Rapid method for the quantification of 13 sulphonamides in milk by conventional high-performance liquid chromatography with diode array ultraviolet detection using a column packed with core-shell particles.

In the present study, a column packed with core-shell particles was used for the separation and the quantification of 13 sulphonamides in milk by conventional high-performance liquid chromatography coupled with diode array ultraviolet detection (HPLC/UV-DAD). Preliminary experiments were carried out to investigate selectivity of different stationary phases. Best results were achieved using a C18 column packed with 2.6µm core-shell particles (diameter 4.6mm, length 75mm). A binary gradient elution based on acetate buffer solution at pH 4.50 and a mixture of methanol acetonitrile 50:50 (v/v) was employed at the flow rate of 1.2mLmin-1 with an injection volume of 6µL. These chromatographic conditions allowed the efficient separation of 13 sulphonamides in about 8min. To evaluate the suitability of the method for official control analysis, the most important validation parameters were investigated according to the European Decision 657/2002/EC as established for analysis of drug residues in food. Sulphonamides were recovered from milk samples by a simple and quick preparation procedure consisting of an extraction step with chloroform/acetone and a purification step with n-hexane. Mean recoveries from raw milk ranged between 55% and 86% at the Maximum Residual Limit of 100µgkg-1, and RSDs% resulted lower than Thompson and Horwitz RSD% reference values for all sulphonamides. The LOQ value (2.7-15µgkg-1) was low enough to satisfy legal limits suggested by European Regulation 37/2010/EC.

Anticoagulant rodenticide poisoning in animals of Apulia and Basilicata, Italy.

This study evaluates the presence of anticoagulant rodenticides in animals with a diagnosis of suspected poisoning and in bait samples. The survey was carried out from 2010 to 2012, in 2 regions of South Italy (Puglia and Basilicata) on 300 organs of animals and 90 suspected bait samples. The qualitative and quantitative analyses were conducted using an analytical method based on high­performance liquid chromatography (HPLC) with fluorimetric detection (FLD) for the simultaneous determination of 8 anticoagulant rodenticides (bromadiolone, brodifacoum, coumachlor, coumafuryl, coumatetralyl, difenacoum, flocoumafen, and warfarin). The presence of anticoagulant rodenticides was detected in 33 organs of animals (11% of the total) and 6 bait samples (7% of the total). The most commonly detected compound was coumachlor (47% of 39 positive samples) followed by bromadiolone (24%), and brodifacoum (11%). The species mostly involved in anticoagulant rodenticide poisoning were dogs and cats. This study emphasizes the relevance of the determinations of anticoagulant rodenticides in cases of suspected poisoning in veterinary practice.

Core-Shell in Liquid Chromatography: Application for Determining Sulphonamides in Feed and Meat Using Conventional Chromatographic Systems.

A C18 column packed with core-shell particles was used for the chromatographic separation of sulphonamides in feed and meat by a conventional high performance liquid chromatography system coupled with a diode array detector. Two analytical methods, already used in our laboratory, have been modified without any changes in the extraction and clean-up steps and in the liquid chromatography instrumentation. Chromatographic conditions applied on a traditional 5-µm column have been optimized on a column packed with 2.6 µm core-shell particles. A binary mobile phase [acetate buffer solution at pH 4.50 and a mixture of methanol acetonitrile 50: 50 (v/v)] was employed in gradient mode at the flow rate of 1.2 mL with an injection volume of 6 µL. These chromatographic conditions allow the separation of 13 sulphonamides with an entire run of 13 minutes. Preliminary studies have been carried out comparing blanks and spiked samples of feed and meat. A good resolution and the absence of interferences were achieved in chromatograms for both matrices. Since no change was made to the sample preparation, the optimized method does not require a complete revalidation and can be used to make routine analysis faster.

Development and validation of an HPLC/DAD method for the determination of 13 sulphonamides in eggs.

A simple, sensitive and selective multiresidue high-performance liquid chromatography with diode array detection method for determination of 13 sulphonamides in eggs was developed and validated. Sample extraction and clean-up conditions were carefully studied and factors as gradient elution and column temperature were found as key parameters to improve separation efficiency. The method was validated following the European Commission Decision 2002/657/EC criteria adopting spiking levels of 20, 40 and 60 µg kg(-1) "As Low As Reasonably Achievable". The necessary requirements for precision (RSDR% below 23%) and trueness (recovery ranging from 45.2% to 87.5%) were fulfilled. Decision limit (CCα) values below 18.5 µg kg(-1), comparable to those reported in LC-MS detection, demonstrated the suitability of the method in residues surveillance plans for the sulphonamides analysis in eggs at the carry-over level without the use of sophisticated and expensive instrumentation.

Validation and application of multi-residue analysis of eight anticoagulant rodenticides by high-performance liquid chromatography with fluorimetric detection.

Poisoning of domestic animals is frequently caused by anticoagulant rodenticides. Validation and applications of a rapid and reliable method for the simultaneous determination of 8 anticoagulant rodenticides (bromadiolone, brodifacoum, coumachlor, coumafuryl, coumatetralyl, difenacoum, flocoumafen, and warfarin) in baits and animal livers using high-performance liquid chromatography with fluorescence detection are reported herein. The methodology was validated by an in-house validation model at 2.5 mg/kg, which is the level commonly found in the tissues of poisoned domestic animals. The 8 anticoagulants can be determined at the concentration range of 1.25-100 mg/kg with determination coefficients higher than 0.992. A recovery value from 70% to 109% was observed for all the studied molecules. The results of the validation process demonstrate suitability for application in official analysis and for monitoring purposes of animal poisoning by anticoagulant rodenticides.

Spectral shifts and structures of phenol...Ar(n) clusters.

A laser spectroscopic investigation of phenol...Ar(n) (n = 1-6) clusters in the first electronically excited state (S(1)) and the cationic ground state (D(0)) is reported. Resonance enhanced two-photon ionisation (R2PI) spectra have been recorded for the investigation of the S(1) state. The origins of S(1)← S(0) (S(1)0(0)) transition of phenol...Ar(n) (n = 1, 2,4-6) are all red shifted compared to the S(1)0(0) state of the monomer by 33 cm(-1), 67 cm(-1), 10 cm(-1), 20 cm(-1), 44 cm(-1), respectively. However, the origin of the phenolAr(3) cluster is blue shifted by 25 cm(-1). For the investigation of the ionic ground state photoionization efficiency (PIE) and mass-analyzed-threshold ionization (MATI) spectroscopy have been applied. The spectra of phenol...Ar(3) and phenol...Ar(4) yield values for the ionization energy (IE) of 68,077 ± 15 cm(-1) and 67,948 ± 15 cm(-1). With the combination of theoretical methods and R2PI, PIE and MATI spectroscopy, the major species present have been positively identified.

Mass analyzed threshold ionization spectra of phenol...Ar2: ionization energy and cation intermolecular vibrational frequencies.

The phenol(+)...Ar(2) complex has been characterized in a supersonic jet by mass analyzed threshold ionization (MATI) spectroscopy via different intermediate intermolecular vibrational states of the first electronically excited state (S(1)). From the spectra recorded via the S(1)0(0) origin and the S(1)ß(x) intermolecular vibrational state, the ionization energy (IE) has been determined as 68,288 ± 5 cm(-1), displaying a red shift of 340 cm(-1) from the IE of the phenol(+) monomer. Well-resolved, nearly harmonic vibrational progressions with a fundamental frequency of 10 cm(-1) have been observed in the ion ground state (D(0)) and assigned to the symmetric van der Waals (vdW) bending mode, ß(x), along the x axis containing the C-O bond. MATI spectra recorded via the S(1) state involving other higher-lying intermolecular vibrational states (σ(s)(1), ß(x)(3), σ(s)(1)ß(x)(1), σ(s)(1)ß(x)(2)) are characterized by unresolved broad structures.

Fragmentation energetics of the phenol(+)···Ar(3) cation cluster.

The various dissociation thresholds of phenol(+)···Ar(3) complexes for the consecutive loss of all three Ar ligands were measured in a molecular beam using resonant photoionization efficiency and mass analyzed threshold ionization spectroscopy via excitation of the first excited singlet state (S(1)). The adiabatic ionization energy is derived as 68077 ± 15 cm(-1). The analysis of the dissociation thresholds demonstrate that all three Ar ligands in the neutral phenol···Ar(3) tetramer are attached to the aromatic ring via π-bonding, denoted phenol···Ar(3)(3π). The value of the dissociation threshold for the loss of one Ar ligand from phenol(+)···Ar(3)(3π), ∼190 cm(-1), is significantly lower than the binding energy measured for the π-bonded Ar ligand in the phenol(+)···Ar(π) dimer, D(0) = 535 ± 3 cm(-1). This difference is rationalized by an ionization-induced π → H isomerization process occurring prior to dissociation, that is, one Ar atom in phenol(+)···Ar(3)(3π) moves to the OH binding site, leading to a structure with one H-bonded and 2 π-bonded ligands, denoted phenol(+)···Ar(3)(H/2π). The dissociation thresholds for the loss of two and three Ar atoms are also reported as 860 and 1730 cm(-1). From these values, the binding energy of the H-bound Ar atom can be estimated as 870 cm(-1).

Dissociation energetics of the phenol(+)⋯Ar(2) cluster ion: The role of π→H isomerization.

The dissociation energetics in the phenol(+)⋯Ar(2)(2π) cluster ion have been investigated using photoionization efficiency and mass analyzed threshold ionization spectroscopy. The appearance energies for the loss of one and two Ar atoms are determined as ∼210 and ∼1115 cm(-1), respectively. The difference between the appearance energy for the first Ar ligand in phenol(+)⋯Ar(2)(2π) and the dissociation energy of the phenol(+)⋯Ar(π) dimer (535cm(-1)) is explained by the isomerization of one π-bound Ar ligand to the OH binding site (H-bond) upon ionization. The energy difference between phenol(+)⋯Ar(2)(2π) and phenol(+)⋯Ar(2)(H/π) could also be estimated to be around 325cm(-1), which corresponds roughly to the difference of the binding energy of a π-bound and H-bound Ar ligands. The binding energy of the H-bound Ar atom in phenol(+)⋯Ar(2)(H/π) is derived to be ∼905cm(-1).

Spinal glioneuronal tumor with neuropil-like islands and meningeal dissemination: histopathological and radiological study of a pediatric case.

Cerebral and spinal location of glioneuronal tumors have been recently described as a novel type of primary CNS neoplasia. A distinctive rare form of glioneuronal tumors with neuropil-like islands (GTNI) have been reported to occur in the adult cerebrum, whereas spinal GTNI localization is extremely rare. In the present report we describe a case of a 15-month-old child with a spinal GTNI of the cervical region and meningeal dissemination. Histologically the tumor was composed of round, small neurocytic-like cells arranged around eosinophilic neuropil cores and embedded in a diffuse fibrillar glial component forming prominent "rosetted" neuropil islands displaying strong immunoreactivity for neuronal markers. Cerebral GTNI shows abundant glial components not rarely exhibiting anaplastic features that justify their inclusion within the group of diffuse astrocytomas. In contrast, including our case, spinal GTNI do not show histological evidence of anaplastic features and exhibits a significant neuronal component that may imply considering these lesions in a separate group. Nevertheless, due to their exceptional rarity, the natural history of these lesions is not yet fully understood, but spinal GTNI seems to have an unfavorable clinical course despite their benign histopathological features, which must be taken into account for appropriate treatment and follow-up of the patient.

PDGFRalpha/FIP1L1-positive chronic eosinophilic leukemia presenting with retro-orbital localization: efficacy of imatinib treatment.

INTRODUCTION: The fusion protein between the platelet-derived growth factor receptor alpha (PDGFRalpha, P) gene and the Fip1-like1 (FIP1L1, F) may be identified in 14 to 60% of HES and it indicates a clonal hypereosinophilic syndrome called F/P-positive CEL. We herein report a case of F/P-positive CEL with retro-orbital localization, who was successfully treated with imatinib. CASE REPORT: A 53-year-old male presented an absolute eosinophil count of 25,000/mm(3), anemia (Hb 10.2 g/dl) and a moderate increase in the platelet count (571,000/mm(3)). A clinical examination revealed left exophthalm, associated with diffuse hypoesthesia and diplopia. A CT scan of orbits showed a lesion located in the lachrymal fossa of the left orbit with intra- and extra-conical extension. Molecular analysis excluded the presence of bcr/abl transcript while a F/P fusion tyrosine kinase signal was documented. Imatinib mesylate (IM) was started and, after 7 days of treatment eosinophil count significantly declined along with a dramatic reduction of the left exophthalm. IM dosage was increased up to 300 mg/day. The drug was well tolerated with an initial modest haematological toxicity. The left exophthalm, as well as hypoesthesia and diplopia, disappeared after IM therapy. MRI showed a clear reduction of the intra- and extra-conical growth process. BM molecular signal of the F/P fusion gene resulted undetectable after 4 weeks of treatment. CONCLUSION: In our case, the diagnosis of FIPIL1-PDGFRA-positive CEL and IM therapy has allowed the patient to experience an excellent clinical therapeutic result, avoiding surgical treatment of the retro-orbital mass.