A non-transitive relevant implication corresponding to classical logic consequence

In this paper we first develop a logic independent account of relevant implication. We propose a stipulative denition of what it means for a multiset of premises to relevantly L-imply a multiset of conclusions, where L is a Tarskian consequence relation: the premises relevantly imply the conclusions iff there is an abstraction of the pair <premises, conclusions> such that the abstracted premises L-imply the abstracted conclusions and none of the abstracted premises or the abstracted conclusions can be omitted while still maintaining valid L-consequence.          Subsequently we apply this denition to the classical logic (CL) consequence relation to obtain NTR-consequence, i.e. the relevant CL-consequence relation in our sense, and develop a sequent calculus that is sound and complete with regard to relevant CL-consequence. We present a sound and complete sequent calculus for NTR. In a next step we add rules for an object language relevant implication to thesequent calculus. The object language implication reflects exactly the NTR-consequence relation. One can see the resulting logic NTR-> as a relevant logic in the traditional sense of the word.       By means of a translation to the relevant logic R, we show that the presented logic NTR is very close to relevance logics in the Anderson-Belnap-Dunn-Routley-Meyer tradition. However, unlike usual relevant logics, NTR is decidable for the full language, Disjunctive Syllogism (A and ~AvB relevantly imply B) and Adjunction (A and B relevantly imply A&B) are valid, and neither Modus Ponens nor the Cut rule are admissible

The importance of atrial fibrillation and selected echocardiographic parameters for the effectiveness and safety of thrombolytic therapy in patients with stroke

Background The efficacy and safety of thrombolytic therapy in stroke depend on multiple factors. The aim of this study was to evaluate the significance of atrial fibrillation the prognosis in terms of the functional status in patients with stroke treated with intravenous thrombolysis. An additional aim was also to assess the potential significance of reduced ejection fraction (EF) and enlarged left atrium (LA) of the heart for the prognosis in patients with stroke who underwent thrombolytic therapy. Methodology A prospective study involved enrollment of 222 patients, mean age of 72 years with first-in-life ischemic stroke. In all participants there were realized procedures as follows: neurological status before administering rt-PA (NIHSS), selected echocardiographic parameters, functional status on the 14th day from the onset (mRankin scale) and analysis the bleeding events. Results Atrial fibrillation was significantly more frequent in women than men; females had higher CHA2DS2VASc scores and heavier neurological conditions on day 1 of stroke. Two independent factors for poor prognosis (3–5 points by mRankin) were found: the NIHSS score and the CHA2DS2VASc score ≥3. We identified 2 independent factors for death within 14 days from the onset: the result by NIHSS and the EF. The NIHSS score turned out to be the only independent predictor of hemorrhage during hospitalization: RR 1.19; CI [1.06–1.33]; p=0.003; p for model=0.0025. Conclusions The presence of atrial fibrillation worsens the patient's prognosis in terms of the functional status and survival during the acute period of stroke in patients treated with intravenous thrombolysis. Higher NIHSS and CHA2DS2VASc scores and reduced EF in patients with stroke treated with thrombolysis are the predictors of unfavorable short-term prognosis

Treatment of 5 dogs with immune-mediated thrombocytopenia using Romiplostim

Background Immune thrombocytopenia (ITP) in dogs is analogous to that in humans. Romiplostim, a novel thrombopoietin receptor (TPO-R) agonist, is currently used for the treatment of refractory ITP in humans, but not in dogs. Here, we describe the response to romiplostim in five dogs with refractory ITP. Five dogs with severe and refractory ITP (three primary and two secondary) received romiplostim subcutaneously. Four dogs were administered 3–5 μg/kg and one dog received 10–13 μg/kg body weight once weekly. Results Romiplostim was well-tolerated and administration was associated with an increase in platelet counts in all five dogs. Four of the five dogs entered remission and relapses were not observed over a follow-up period of 3–10 months. Conclusions Romiplostim is effective in the treatment of ITP in dogs at least as well as in humans. This finding may help to develop and use new therapeutics for ITP in dogs and humans

The Reactions of H2_{2}O2_{2} and GSNO with the Zinc Finger Motif of XPA. Not A Regulatory Mechanism, but No Synergy with Cadmium Toxicity

Tetrathiolate zinc fingers are potential targets of oxidative assault under cellular stress conditions. We used the synthetic 37-residue peptide representing the tetrathiolate zinc finger domain of the DNA repair protein XPA, acetyl-DYVICEECGKEFMSYLMNHFDLPTCDNCRDADDKHK-amide (XPAzf) as a working model to study the reaction of its Zn(II) complex (ZnXPAzf) with hydrogen peroxide and S-nitrosoglutathione (GSNO), as oxidative and nitrosative stress agents, respectively. We also used the Cd(II) substituted XPAzf (CdXPAzf) to assess the situation of cadmium assault, which is accompanied by oxidative stress. Using electrospray mass spectrometry (ESI-MS), HPLC, and UV-vis and circular dichroism spectroscopies we demonstrated that even very low levels of H$_{2}$O$_{2}$ and GSNO invariably cause irreversible thiol oxidation and concomitant Zn(II) release from ZnXPAzf. In contrast, CdXPAzf was more resistant to oxidation, demonstrating the absence of synergy between cadmium and oxidative stresses. Our results indicate that GSNO cannot act as a reversible modifier of XPA, and rather has a deleterious effect on DNA repair

Overexpression of phytochelatin synthase in tobacco: distinctive effects of AtPCS1 and CePCS genes on plant response to cadmium

Phytochelatins, heavy-metal-binding polypeptides, are synthesized by phytochelatin synthase (PCS) (EC 2.3.2.15). Previous studies on plants overexpressing PCS genes yielded contrasting phenotypes, ranging from enhanced cadmium tolerance and accumulation to cadmium hypersensitivity. This paper compares the effects of overexpression of AtPCS1 and CePCS in tobacco (Nicotiana tabacum var. Xanthi), and demonstrates how the introduction of single homologous genes affects to a different extent cellular metabolic pathways leading to the opposite of the desired effect. In contrast to WT and CePCS transformants, plants overexpressing AtPCS1 were Cd-hypersensitive although there was no substantial difference in cadmium accumulation between studied lines. Plants exposed to cadmium (5 and 25 μM CdCl2) differed, however, in the concentration of non-protein thiols (NPT). In addition, PCS activity in AtPCS1 transformants was around 5-fold higher than in CePCS and WT plants. AtPCS1 expressing plants displayed a dramatic accumulation of γ-glutamylcysteine and concomitant strong depletion of glutathione. By contrast, in CePCS transformants, a smaller reduction of the level of glutathione was noticed, and a less pronounced change in γ-glutamylcysteine concentration. There was only a moderate and temporary increase in phytochelatin levels due to AtPCS1 and CePCS expression. Marked changes in NPT composition due to AtPCS1 expression led to moderately decreased Cd-detoxification capacity reflected by lower SH:Cd ratios, and to higher oxidative stress (assessed by DAB staining), which possibly explains the increase in Cd-sensitivity. The results indicate that contrasting responses to cadmium of plants overexpressing PCS genes might result from species-dependent differences in the activity of phytochelatin synthase produced by the transgenes

Relevance of admission hyperglycaemia and diabetes mellitus to efficacy and safety of mechanical thrombectomy in stroke patients

Introduction. The relevance of diabetes mellitus (DM) to the efficacy of mechanical thrombectomy (MT) has been the subject of few studies and with only inconclusive results. Objectives. This study aimed to evaluate the effect of DM and admission hyperglycaemia on the efficacy and safety of MT in stroke patients. Material and methods. This retrospective study analysis focused on the relevance of admission hyperglyacemia and DM to the functional status of patients treated with MT at the Upper Silesian Medical Centre of the Silesian Medical University in Katowice, Poland. Results. 417 stroke patients (median age 70 years) were qualified for the study. There were 103 patients (24.70%) with DM. Admission hyperglycaemia ≥ 140 mg% was found in 91 patients (21.82%), of whom 69 were diagnosed with DM before or during hospitalisation. The parameters with the strongest effect on the functional status on days 7, 90 and 365 were: age, and neurological status according to the National Institutes of Health Stroke Scale (NIHSS) on the first day of ischaemic stroke before MT. The angiographic effect indirect after MT and patient functional status on days 7, 90 and 365 were comparable between the groups, regardless of the DM burden. The frequency of symptomatic intracranial bleeding 24 hours after MT was comparable between patients with and patients without DM (p = 0.092). Model based on parameters were age, NIHSS on the first day of ischaemic stroke, an when score in Thrombolysis In Cerebral Infarct (TICI) showed good predictive attributes for the functional status of patients in the acute period (day 7). Age, a lack of admission hyperglycaemia, and the neurological state on day 1 of ischaemic stroke (before MT) were the key parameters for a favourable outcome (≤ 2 points on the modified Rankin Scale, mRS) on day 90. Admission hyperglycaemia ≥ 140 mg/dL, regardless of the presence or absence of DM, had a negative effect on achieving a good functional status one week after stroke onset. Conclusions. Diabetes mellitus has a neutral effect on the angiographic and clinical outcomes of mechanical thrombectomy in stroke patients. It does not increase the risk of intracranial haemorrhage after instrumental therapy. It is admission hyperglycaemia, rather than diabetes mellitus, that is a predictor of poor functional status in patients treated with thrombectomy. According to our results, the patient’s neurological status, age, and the outcome of thrombectomy are relevant to the functional status in the acute ischaemic stroke period

Aβ5−xPeptides: N‑Terminal Truncation Yields Tunable Cu(II)Complexes

The Aβ5−x peptides (x = 38, 40, 42) are minor Aβ species in normal brains but elevated upon the application of inhibitors of Aβ processing enzymes. They are interesting from the point of view of coordination chemistry for the presence of an Arg-His metal binding sequence at their N-terminus capable of forming a 3-nitrogen (3N) three-coordinate chelate system. Similar sequences in other bioactive peptides were shown to bind Cu(II) ions in biological systems. Therefore, we investigated Cu(II) complex formation and reactivity of a series of truncated Aβ5−x peptide models comprising the metal binding site: Aβ5−9, Aβ5−12, Aβ5−12Y10F, and Aβ5−16. Using CD and UV−vis spectroscopies and potentiometry, we found that all peptides coordinated the Cu(II) ion with substantial affinities higher than 3 × 1012 M−1 at pH 7.4 for Aβ5−9 and Aβ5−12. This affinity was elevated 3-fold in Aβ5−16 by the formation of the internal macrochelate with the fourth coordination site occupied by the imidazole nitrogen of the His13 or His14 residue. A much higher boost of affinity could be achieved in Aβ5−9 and Aβ5−12 by adding appropriate amounts of the external imidazole ligand. The 3N Cu-Aβ5−x complexes could be irreversibly reduced to Cu(I) at about −0.6 V vs Ag/AgCl and oxidized to Cu(III) at about 1.2 V vs Ag/AgCl. The internal or external imidazole coordination to the 3N core resulted in a slight destabilization of the Cu(I) state and stabilization of the Cu(III) state. Taken together these results indicate that Aβ5−x peptides, which bind Cu(II) ions much more strongly than Aβ1−x peptides and only slightly weaker than Aβ4−x peptides could interfere with Cu(II) handling by these peptides, adding to copper dyshomeostasis in Alzheimer brains

Recanalisation of cerebral artery aneurysms treated endovascularly — a midterm follow-up

Endovascular methods of aneurysm treatment, as an alternative to neurosurgical clipping, have proved a welcome opportunity to treat patients with unruptured aneurysms or those disqualified from neurosurgical intervention. This paper presents our own experience of endovascular treatment of cerebral aneurysms in 107 patients. It includes clinical and technical data from the perioperative period and a 12-month radiological follow-up of 78 patients. Method. Our retrospective evaluation covered patients with intracranial aneurysms treated endovascularly. The following were analysed: age, sex, neurological symptoms, and familial burden of intracranial aneurysm. Multivariate analysis was performed to determine independent factors of recanalisation of the cerebral aneurysm 12 months after embolisation. Results. The data of 107 patients at a mean age of 61 years [57.09 ± 14.27] treated with embolisation was analysed. The indication for intervention in 16 patients was subarachnoid haemorrhage; in the remaining 91 cases, aneurysms were revealed during diagnostic procedures for different symptoms or during imaging examinations. The intracranial segment of the internal carotid artery and the anterior communicating artery were the most common locations for aneurysms. After embolisation, subarachnoid haemorrhage occurred in one patient, ischaemic stroke in two patients, and one patient died because of acute circulatory insufficiency. The functional status of 94 patients on the day of discharge from the department (on days 4-21) was very good. 78 patients completed a 12-month follow-up period. In 11 of those, a follow-up MR angiography revealed recanalisation 12 months after the intervention. Except for one patient reporting vertigo, aneurysm recanalisation procedures were asymptomatic. The only independent risk factor for recanalisation was the size of aneurysm > 10 mm; OR 3.0; CI [1.15–7.83] p = 0.0255. Conclusions. Embolisation of cerebral aneurysms is a safe method with few perioperative complications, and most of these are mild and transient.The size of the aneurysm during qualification for embolisation is a risk factor for recanalisation in the subsequent 12 months. Recanalisation of embolised cerebral aneurysms concerns less than 20% of patients in a one-year follow-up and is most often asymptomatic

Mechanical thrombectomy in acute stroke – Five years of experience in Poland

Objectives Mechanical thrombectomy (MT) is not reimbursed by the Polish public health system. We present a description of 5 years of experience with MT in acute stroke in Comprehensive Stroke Centers (CSCs) in Poland. Methods and results We retrospectively analyzed the results of a structured questionnaire from 23 out of 25 identified CSCs and 22 data sets that include 61 clinical, radiological and outcome measures. Results Most of the CSCs (74%) were founded at University Hospitals and most (65.2%) work round the clock. In 78.3% of them, the working teams are composed of neurologists and neuro-radiologists. All CSCs perform CT and angio-CT before MT. In total 586 patients were subjected to MT and data from 531 of them were analyzed. Mean time laps from stroke onset to groin puncture was 250±99min. 90.3% of the studied patients had MT within 6h from stroke onset; 59.3% of them were treated with IV rt-PA prior to MT; 15.1% had IA rt-PA during MT and 4.7% – emergent stenting of a large vessel. M1 of MCA was occluded in 47.8% of cases. The Solitaire device was used in 53% of cases. Successful recanalization (TICI2b–TICI3) was achieved in 64.6% of cases and 53.4% of patients did not experience hemorrhagic transformation. Clinical improvement on discharge was noticed in 53.7% of cases, futile recanalization – in 30.7%, mRS of 0–2 – in 31.4% and mRS of 6 in 22% of cases. Conclusion Our results can help harmonize standards for MT in Poland according to international guidelines