The Augustinian-Bonaventurian approach to the concept of consciousness and its development within the speculative frame of italian critical ontology

Autentična konkretnost misli omogućene prvim Načelom svakog bivstvovanja temeljni je spekulativni argument talijanske kritičke ontologije. U neraskidivosti odnosa misli i bitka, formirao se u Italiji, u prvoj polovici XX. stoljeća i na Kantovim premisama, smjer u filozofiji koji je, u izrazito burnom kontekstu spekulativna promišljanja, a često i u polemici s predominantnim strujama misli, istaknuo temeljnu važnost pitanja Boga kao istinski filozofskog argumenta. Pojam svijesti, kao svijesti o Bogu i od Boga, unutar onoga što u (ἐν) Njemu prebiva, omogućeno od Njega samoga, dokaz je fenomenske nezatvorenosti egzistencije koja je dovela do reforme kritičke ontologije u duhu kršćanskih kategorija misli, a preko implementacije augustinovsko-bonaventurijanskih postavaka franjevačke tradicije. Namjera je, dakle, da se preko priloženog rada predstavi spekulativna konzistentnost te iznimno plodne škole talijanske ontologije, ali i najistaknutiji argument njezina filozofskog promišljanja, drugim riječima, konkretnost svijesti u egzistencijalnom bivstvovanju kao manifestaciji jedinstvenosti bitka.The authentic concreteness of thought made possible by the first principle of every being is the basic speculative argument of Italian critical ontology. In the undividable relation between thought and being a direction of thinking in philosophy has been formed in Italy in the first half of the 20th century. This direction is based on Kant’s premises and, in extremely turbulent context of speculative thinking and often in polemics with dominant currents of though, it has pointed out the fundamental importance of the »God issue« as a true philosophical argument. The concept of consciousness, as consciousness of God and from God, within that that exists in (ἐν) Him, made possible by Him, is the proof of the phenomenal unconfined-ness of what is thought, through implementation of the Augustinian-Bonaventurian principles of the Franciscan tradition. The intention of this article is, therefore, to present speculative consistency of this extremely vital school of Italian ontology, but also the most prominent argument of its philosophical reflection, i.e. the concreteness of consciousness in existential being as a manifestation of uniqueness of being

The Impact of Primary Versus Secondary Muscle-invasive Bladder Cancer at Diagnosis on the Response to Neoadjuvant Chemotherapy.

Background There might be differential sensitivity to neoadjuvant chemotherapy (NAC) in patients with primary muscle-invasive bladder cancer (MIBC) in comparison to patients with secondary MIBC after a history of non–muscle-invasive disease. Objective To investigate pathologic response rates and survival associated with primary versus secondary MIBC among patients treated with cisplatin-based NAC for cT2–4N0M0 MIBC. Design, setting, and participants Oncologic outcomes were compared for 350 patients with primary MIBC and 64 with secondary MIBC treated with NAC and radical cystectomy between 1992 and 2021 at 11 academic centers. Genomic analyses were performed for 476 patients from the Memorial Sloan Kettering/The Cancer Genome Atlas cohort. Outcome measurements and statistical analysis The outcome measures were pathologic objective response (pOR; ≤ypT1 N0), pathologic complete response (pCR; ypT0 N0), overall mortality, and cancer-specific mortality. Results and limitations The primary MIBC group had higher pOR (51% vs 34%; p = 0.02) and pCR (33% vs 17%; p = 0.01) rates in comparison to the secondary MIBC group. On multivariable logistic regression analysis, primary MIBC was independently associated with both pOR (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26–0.87; p = 0.02) and pCR (OR 0.41, 95% CI 0.19–0.82; p = 0.02). However, on multivariable Cox regression analysis, primary MIBC was not associated with overall mortality (hazard ratio 1.70, 95% CI 0.84–3.44; p = 0.14) or cancer-specific mortality (hazard ratio 1.50, 95% CI 0.66–3.40; p = 0.3). Genomic analyses revealed a significantly higher ERCC2 mutation rate in primary MIBC than in secondary MIBC (12.4% vs 1.3%; p < 0.001). Conclusions Patients with primary MIBC have better pathologic response rates to NAC in comparison to patients with secondary MIBC. Chemoresistance might be related to the different genomic profile of primary versus secondary MIBC. Patient summary We investigated the treatment response to neoadjuvant chemotherapy (NAC; chemotherapy received before the primary course of treatment) and survival for patients with a primary diagnosis of muscle-invasive bladder cancer (MIBC) in comparison to patients with a history of non–muscle-invasive bladder cancer that progressed to MIBC. Patients with primary MIBC had a better response to NAC but this did not translate to better survival after accounting for other tumor characteristics.post-print824 K

The Theological character of the concept of being in the Critical ontology of Pantaleo Carabellese (1877 – 1948). From pre-critical intuitions to the mature locution on God as the »pure object of consciousness«

Svrha je ovog rada predstaviti spekulativne pretpostavke talijanske kritičke ontologije, filozofskog pravca započetog djelom Pantalea Carabellesea u prvoj polovici XX. stoljeća i danas još aktivnog ponajprije na talijanskom sveučilištu u Perugii. I sam je Carabelleseov život bio dokaz da autentično filozofsko promišljanje vodi afirmativnom stavu o Bogu kao osnovnom uvjetu i temelju ljudske egzistencije koji kao takav predstavlja, upravo po njegovim riječima, »jedini istinski objekt filozofskog promišljanja«. U prvih trideset godina autorova djelovanja, počevši od obrane diplomskog rada o Rosminiju na Sveučilištu u Napulju 1907. godine do objave Teološkog problema kao filozofije 1931. godine, afirmirala se teorijska relevantnost pojma bitka kao jedinstvenog temelja svijesti, no očito je postalo i da ona misao koja, na osnovi svojih pretpostavaka, ne predviđa nužno teološke ishode vlastite spekulacije, ne može ne promišljati Boga ukoliko na doista autentičan način pristupa argumentu kontemplativne prirode. Istinski je »objekt« filozofska promišljanja, dakle, teološki argument, a filozofija je istinsko koračanje ka metafizičkoj svijesti o Bogu.The purpose of this article is to present speculative presuppositions of Italian critical ontology, a philosophical movement started by the work of Pantaleo Carabellese in the first half of the 20th century, which is still active primarily at the Italian University in Perugia. Carabellese´s life itself was a proof that authentic philosophical reflectionleads to the affi rmative position on God as the fundamental condition and the basis of human existence that, as such, represents, in his words, »the only true object of philosophical reflection«. In the first thirty years of the author´s work, starting with the defence of his diploma thesis on Rosmini at the University of Naples in 1907 until the publication of The Theological Problem as Philosophy in 1931, theoretical relevancy of the concept of being as the unique basis of consciousness has been affirmed. At the same time it has become obvious that a reflection that, on the basis of its own presuppositions, does not necessarily aims for theological outcomes of its own speculation, cannot not reflect on God, if it approaches the argument of contemplative nature in an authentic way. The true »object« of philosophical reflection is, therefore, the theological argument, while philosophy is a true journey towards the metaphysical awareness of God

Iodine carry over in dairy cows: effects of levels of diet fortification and milk yield

Thirty multiparous lactating cows were divided in three groups based on milk yield: high (H), average (A) and low (L). Within each group, cows were randomly allotted to two levels of iodine inclusions into the diet and respectively: level 1 (1): base diet containing 1.55 mg/kg dry matter, level 2 (2): base diet plus 47.2 mg/d. Potassium iodide was used. Feeds, orts, drinking water and individual milk samples were collected and analysed for the iodine content. The iodine concentration and total excretion in milk were affected by the level of iodine supplementation (P<0.05). No effect on milk iodine concentration could be addressed either to the level of milk yield or to the milk yield x treatment interaction. The total amount of iodine excretion and carry over were affected (P<0.05) by the level of milk yield

Effect of allogeneic intraoperative blood transfusion on survival in patients treated with radical cystectomy for nonmetastatic bladder cancer: Results from a single high-volume institution

Transfusion has been related to poor survival after surgery in several cancers. Recently, timing of transfusion has been proposed as crucial in the determination of poor survival expectanies after surgery, in fact, intra- operative but not postoperative transfusion were found to be related. We confirmed these findings in patients who underwent radical cystectomy because of bladder cancer; physicians should avoid use of transfusion intraoperatively. Background: Previous studies have demonstrated that perioperative blood transfusion (BT) is associated with a significantly increased risk of cancer recurrence and mortality after radical cystectomy (RC). Recently, it was shown for the first time that intraoperative transfusion has a detrimental effect on cancer survival. The aim of the current study was to validate this finding in a single European institution. Patients and Methods: The study focused on 1490 consecutive nonmetastatic bladder cancer patients treated with RC at a single tertiary care referral center between January 1990 and August 2013. KaplaneMeier analyses and Cox regression analyses were used to assess the effect of timing of BT administration (no transfusion vs. intraoperative transfusion vs. postoperative transfusion vs. intra- operative and postoperative transfusion) on cancer-specific mortality (CSM), overall mortality (OM), and disease recurrence. Results: Mean age at the time of RC was 67 years. Overall, 322 (21.6%) patients received intraoperative BT and 97 (6.5%) received postoperative BT. At a mean follow-up time of 125 months (median, 110 months), the 5- and 10-year CSM rate was 846 (58%) and 715 (48%), respectively. In multivariable analyses patients who received intraoperative BT had greater risk of disease recurrence (hazard ratio [HR], 1.24; P .2). Conclusion: Our study confirms that intraoperative, but not postoperative BT, are related to a detrimental effect on survival after RC. These results should be take into account by physicians to administer BT using the correct timing

Cysteinyl-glycine in the control of glutathione homeostasis in bovine lenses

PURPOSE: To define a possible metabolic and/or signaling role for Cys-Gly in glutathione homeostasis in bovine eye lenses. METHODS: Bovine lenses were cultured up to 24 h in a medium containing 0.5 mM reduced glutathione (GSH) under different conditions. The intracellular and the extracellular contents of thiol compounds were evaluated using a free zone capillary electrophoresis method. RESULTS: Culture of lenses in the presence of GSH and the gamma-glutamyl transferase inhibitor serine-borate demonstrated a 1.5 fold increase in the level of extra-lenticular glutathione with respect to the initial value. Cys-Gly exogenously added impaired the extra-lenticular accumulation of glutathione. Both cysteine and gamma-Glu-Cys were ineffective in reducing extra-lenticular glutathione accumulation. In all conditions no differences in reduced and total intra-lenticular glutathione levels were observed. CONCLUSIONS: The impairment of Cys-Gly generation correlated with inhibition of gamma-glutamyl transferase by serine/borate, resulting in high extra-lenticular concentration of glutathione effluxed from the bovine lens. The possibility that Cys-Gly may intervene either in the replenishment processes for cysteine in the GSH biosynthetic step or in the function of the efflux GSH-transporters is considered

Modulation of aldose reductase activity by aldose hemiacetals

Glucose is considered as one of the main sources of cell damage related to aldose reductase (AR) action in hyperglycemic conditions and a worldwide effort is posed in searching for specific inhibitors of the enzyme. This AR substrate has often been reported as generating non-hyperbolic kinetics, mimicking a negative cooperative behavior. This feature was explained by the simultaneous action of two enzyme forms acting on the same substrate

Fear avoidance beliefs are associated with reduced lumbar spine flexion during object lifting in pain-free adults

There is a long-held belief that physical activities such as lifting with a flexed spine is generally harmful for the back and can cause low back pain (LBP), potentially reinforcing fear avoidance beliefs underlying pain-related fear. In chronic LBP patients, pain-related fear has been shown to be associated with reduced lumbar range of motion during lifting, suggesting a protective response to pain. However, despite short term beneficial effects for tissue health, recent evidence suggests that maintaining a protective trunk movement strategy may also pose a risk for (persistent) LBP due to possible pro-nociceptive consequences of altered spinal motion, potentially leading to increased loading on lumbar tissues. Yet, it is unknown if similar protective movement strategies already exist in pain-free individuals which would yield potential insights into the role of fear avoidance beliefs in motor behavior in the absence of pain. Therefore, the aim of this study is to test whether fear avoidance beliefs influence spinal motion during lifting in a healthy cohort of pain-free adults without a history of chronic pain. The study subjects (N=57) filled out several pain-related fear questionnaires and were asked to perform a lifting task (5kg-box). High-resolution spinal kinematics were assessed using an optical motion capturing system. Time-sensitive analyses were performed based on statistical parametric mapping. The results demonstrated time-specific and negative relationships between self-report measures of pain-related fear and lumbar spine flexion angles during lifting, indicating potential unfavorable interactions between psychological factors and spinal motion during lifting in pain-free subjects

Catalog of prognostic tissue-based biomarkers in patients treated with neoadjuvant systemic therapy for urothelial carcinoma of the bladder: a systematic review

PURPOSE The present systematic review aimed to identify prognostic values of tissue-based biomarkers in patients treated with neoadjuvant systemic therapy (NAST), including chemotherapy (NAC) and checkpoint inhibitors (NAI) for urothelial carcinoma of the bladder (UCB). MATERIAL AND METHODS The PubMed, Web of Science, and Scopus databases were searched in August 2020 according to the PRISMA statement. Studies were deemed eligible if they compared oncologic or pathologic outcomes in patients treated with NAST for UCB with and without detected pretreatment tissue-based biomarkers. RESULTS Overall, 44 studies met our eligibility criteria. Twenty-three studies used immunohistochemistry (IHC), 19 – gene expression analysis, three - quantitative polymerase chain reaction (QT PCR), and two – next-generation sequencing (NGS). According to the currently available literature, predictive IHC-assessed biomarkers, such as receptor tyrosine kinases and DNA repair pathway alterations, do not seem to convincingly improve our prediction of pathologic response and oncologic outcomes after NAC. Luminal and basal tumor subtypes based on gene expression analysis showed better NAC response, while claudin-low and luminal-infiltrated tumor subtypes did not. In terms of NAI, PD-L1 seems to maintain value as a predictive biomarker, while the utility of both tumor mutational burden and molecular subtypes remains controversial. Specific genomic alterations in DNA repair genes have been shown to provide significant predictive value in patient treated with NAC. QT PCR quantification of specific genes selected through microarray analysis seems to classify cases regarding their NAC response. CONCLUSION We believe that the present systematic review may offer a robust framework that will enable the testing and validation of predictive biomarkers in future prospective clinical trials. NGS has expanded the discovery of molecular markers that are reflective of the mechanisms of the NAST response

Bladder Cancer Tissue-Based Biomarkers

This review aims to provide a practical update regarding the current role of tissue-based biomarkers in bladder cancer. Their prognostic and predictive role both in non-muscle-invasive (NMIBC) and in muscle-invasive disease (MIBC) has been reviewed with particular focus to their use in clinical practice. In summary, the literature on the prediction of disease recurrence in NMIBC is inconclusive, and there is little information on prediction of response to intravesical bacillus Calmette-Guerin (BCG). Concerning disease progression, external prospective validation studies suggest that FGFR3 mutation status and gene signatures may improve models that are based only on clinicopathologic information. In MIBC, tissue-based biomarkers are increasingly important, since they may predict the response to systemic chemotherapy and immunotherapy. In particular, the advent of molecular characterization promises to revolutionize the paradigm of decision-making in the treatment of MIBC. Molecular subtyping has been shown to improve the prediction of pathological stage at RC and to predict the response to systemic chemotherapy and immunotherapy. However, external and prospective validations are warranted to confirm these preliminary findings. Several different tissue-based biomarkers such as PD-1/PD-L1 expression, tumor mutational burden, and the analysis of tumor microenvironment, may in future play a role in selecting patients for systemic immunotherapy. However, to date, no pretreatment recommendations can be definitively made on the basis of any molecular predictors. In conclusion, despite the potential of tissue-based biomarkers, their use in bladder cancer should be limited to experimental settings