The Curinga–Girifalco Line in the framework of the tectonic evolution of the remnant Alpine chain in Calabria (southern Italy)

AbstractIn the peri-Mediterranean metamorphic belts, the tectonic evolution of the Calabria–Peloritani terrane during the dominant compressive tectonics of the Eocene represents one of the most problematic points in palinspastic restorations. A matter of particular debate is its shortening, which could have occurred during the Alpine or the Apennine subduction. In this regard, a crucial joint is provided by the kinematics of one of the most relevant shear zones such as the Curinga–Girifalco Line, cropping out in central Calabria. This shear zone juxtaposed a nearly complete Hercynian crustal section (i.e. the Sila and Serre Unit) onto the remnants of the Castagna Unit. The data in the available literature on ductile kinematics from the south-eastern branch of the Curinga–Girifalco Line indicate a downward movement of the hanging wall. In the present paper we show new, ductile kinematic data and petrographic evidence from outcrops in the north-western and south-eastern branches of the Curinga–Girifalco Line. Our results highlight the coherent kinematics of the Eocene shortening during the Alpine subduction system, followed by (late Eocene?)Oligocene to early Miocene, dominantly ductile extensional reworking, relating to the Apennines subduction system

MitraClip after heart transplantation: A case report

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The prevalence of peripheral and central hearing impairment and its relation to cognition in older adults.

Age-related hearing loss (ARHL) and dementia are two highly prevalent conditions in the adult population. Recent studies have suggested that hearing loss is independently associated with poorer cognitive functioning. The aim of this study was to evaluate the prevalence of ARHL and cognitive impairment in a large sample of subjects older than 65 years and to correlate hearing function with cognitive function. A total of 488 subjects older than 65 years (mean age 72.8 years) participating in the Great Age Study underwent a complete audiological, neurological and neuropsychological evaluation as part of a multidisciplinary assessment. The prevalence of a hearing loss greater than 25 dB HL was 64.1%, of Central Auditory Processing Disorder (CAPD) was 14.3 and 25.3% of the subjects reported a hearing handicap as reported on the Hearing Handicap Inventory for the Elderly Screening Version questionnaire. Multiple logistic regression analysis corrected for gender, age and education duration showed that mild cognitive impairment (MCI) was significantly associated with hearing impairment (CAPD and hearing threshold; odds ratio 1.6, p = 0.05) and that Alzheimer's disease (AD) was significantly associated with CAPD (odds ratio 4.2, p = 0.05). Given that up to 80% of patients affected by MCI convert to AD, adding auditory tests to a screening cognitive battery might have value in the early diagnosis of cognitive decline

Combination of peripheral neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio is predictive of pathological complete response after neoadjuvant chemotherapy in breast cancer patients

The immune system seems to play a fundamental role in breast cancer responsiveness to chemotherapy. We investigated two peripheral indicators of immunity/inflammation, i.e. neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), in order to reveal a possible relationship with pathological complete response (pCR) in patients with early or locally advanced breast cancer treated with neoadjuvant chemotherapy (NACT). We retrospectively analyzed 373 consecutive patients affected by breast cancer and candidates to NACT. The complete blood cell count before starting NACT was evaluated to calculate NLR and PLR. ROC curve analysis determined threshold values of 2.42 and 104.47 as best cut-off values for NLR and PLR, respectively. The relationships between NLR/PLR and pCR, along with other clinical-pathological characteristics, were evaluated by Pearson's χ 2 or Fisher's exact test as appropriate. Univariate and multivariate analyses were performed using a logistic regression model. NLR and PLR were not significantly associated with pCR if analyzed separately. However, when combining NLR and PLR, patients with a NLRlow/PLRlow profile achieved a significantly higher rate of pCR compared to those with NLRhigh and/or PLRhigh (OR 2.29, 95% CI 1.22-4.27, p 0.009). Importantly, the predictive value of NLRlow/PLRlow was independent from common prognostic factors such as grading, Ki67, and molecular subtypes. The combination of NLR and PLR may reflect patients' immunogenic phenotype. Low levels of both NLR and PLR may thus indicate a status of immune system activation that may predict pCR in breast cancer patients treated with NACT

Tgf-β1 transcriptionally promotes 90K expression: possible implications for cancer progression.

The 90K protein, also known as Mac-2 BP or LGALS3BP, can activate the immune response in part by increasing major histocompatibility (MHC) class I levels. In studies on a non-immune cell model, the rat FRTL-5 cell line, we observed that transforming growth factor (TGF)-β1, like γ-interferon (IFN), increased 90K levels, despite its immunosuppressive functions and the ability to decrease MHC class I. To explain this paradoxical result, we investigated the mechanisms involved in the TGF-β1 regulation of 90K expression with the aim to demonstrate that TGF-β1 utilizes different molecular pathways to regulate the two genes. We found that TGF-β1 was able to increase the binding of Upstream Stimulatory Factors, USF1 and USF2, to an E-box element, CANNTG, at -1926 to -1921 bp, upstream of the interferon response element (IRE) in the 90K promoter. Thyrotropin (TSH) suppressed constitutive and γ-IFN-induced 90K expression by decreasing USF binding to the E-box. TGF-β1 was able to overcome TSH suppression at the transcriptional level by increasing USF binding to the E-box. We suggest that the ability of TGF-β1 to increase 90K did not result in an increase in MHC class I because of a separate suppressive action of TGF-β1 directly on the MHC class I gene. We propose that the increased levels of 90K may play a role, rather than in immune response, in the context of the TGF-β1-induced changing of the cellular microenvironment that predisposes to cell motility and cancer progression. Consistently, analyzing the publicly available cancer patient data sets cBioPortal, we found that 90K expression directly correlated with TGF-β1 and USFs and that high levels of 90K were significantly associated with increased mortality in patients affected by different types of cancer

High familial burden of cancer correlates with improved outcome from immunotherapy in patients with NSCLC independent of somatic DNA damage response gene status

Family history of cancer (FHC) is a hallmark of cancer risk and an independent predictor of outcome, albeit with uncertain biologic foundations. We previously showed that FHC-high patients experienced prolonged overall (OS) and progression-free survival (PFS) following PD-1/PD-L1 checkpoint inhibitors. To validate our findings in patients with NSCLC, we evaluated two multicenter cohorts of patients with metastatic NSCLC receiving either first-line pembrolizumab or chemotherapy. From each cohort, 607 patients were randomly case-control matched accounting for FHC, age, performance status, and disease burden. Compared to FHC-low/negative, FHC-high patients experienced longer OS (HR 0.67 [95% CI 0.46-0.95], p\u2009=\u20090.0281), PFS (HR 0.65 [95% CI 0.48-0.89]; p\u2009=\u20090.0074) and higher disease control rates (DCR, 86.4% vs 67.5%, p\u2009=\u20090.0096), within the pembrolizumab cohort. No significant associations were found between FHC and OS/PFS/DCR within the chemotherapy cohort. We explored the association between FHC and somatic DNA damage response (DDR) gene alterations as underlying mechanism to our findings in a parallel cohort of 118 NSCLC, 16.9% of whom were FHC-high. The prevalence of\u2009 65\u20091 somatic DDR gene mutation was 20% and 24.5% (p\u2009=\u20090.6684) in FHC-high vs. FHC-low/negative, with no differences in tumor mutational burden (6.0 vs. 7.6 Mut/Mb, p\u2009=\u20090.6018) and tumor cell PD-L1 expression. FHC-high status identifies NSCLC patients with improved outcomes from pembrolizumab but not chemotherapy, independent of somatic DDR gene status. Prospective studies evaluating FHC alongside germline genetic testing are warranted

Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients: A case–control matched analysis from a large multicenter study

Background: Improved outcome in tobacco smoking patients with non-small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first-line immunotherapy in patients with high PD-L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts. Methods: We compared clinical outcomes according to the smoking status (never smokers vs. current/former smokers) of two retrospective multicenter cohorts of metastatic NSCLC patients, treated with first-line pembrolizumab and platinum-based chemotherapy. Results: A total of 962 NSCLC patients with PD-L1 expression ≥50% who received first-line pembrolizumab and 462 NSCLC patients who received first-line platinum-based chemotherapy were included in the study. Never smokers were confirmed to have a significantly higher risk of disease progression (hazard ratio [HR] = 1.49 [95% CI: 1.15–1.92], p = 0.0022) and death (HR = 1.38 [95% CI: 1.02–1.87], p = 0.0348) within the pembrolizumab cohort. On the contrary, a nonsignificant trend towards a reduced risk of disease progression (HR = 0.74 [95% CI: 0.52–1.05], p = 0.1003) and death (HR = 0.67 [95% CI: 0.45–1.01], p = 0.0593) were reported for never smokers within the chemotherapy cohort. After a random case–control matching, 424 patients from both cohorts were paired. Within the matched pembrolizumab cohort, never smokers had a significantly shorter progression-free survival (PFS) (HR = 1.68 [95% CI: 1.17–2.40], p = 0.0045) and a nonsignificant trend towards a shortened overall survival (OS) (HR = 1.32 [95% CI: 0.84–2.07], p = 0.2205). On the contrary, never smokers had a significantly longer PFS (HR = 0.68 [95% CI: 0.49–0.95], p = 0.0255) and OS (HR = 0.66 [95% CI: 0.45–0.97], p = 0,0356) compared to current/former smoker patients within the matched chemotherapy cohort. On pooled multivariable analysis, the interaction term between smoking status and treatment modality was concordantly statistically significant with respect to ORR (p = 0.0074), PFS (p = 0.0001) and OS (p = 0.0020), confirming the significantly different impact of smoking status across the two cohorts. Conclusions: Among metastatic NSCLC patients with PD-L1 expression ≥50% receiving first-line pembrolizumab, current/former smokers experienced improved PFS and OS. On the contrary, worse outcomes were reported among current/former smokers receiving first-line chemotherapy

Il collaboratore di giustizia: programma di protezione e analisi in merito alla attendibilità e al valore della collaborazione.

L'elaborato mira ad effettuare una ricostruzione storico-normativa dei soggetti giuridicamente definiti collaboratori di giustizia, partendo dagli anni di piombo sino ad oggi. Viene analizzato così il programma di protezione nei confronti dei suddetti soggetti, iniziando dalla prima normativa fondamentale, il decreto-legge n.81 del 1991, passando dalle varie modifiche del legislatore effettuate con l'emanazione della legge n.45 del 2001. Il terzo capitolo dell'elaborato si divide in due parti: la prima effettua una sintetica analisi del sistema probatorio "differenziato", comunemente conosciuto come "doppio binario probatorio", in particolare, alle deroghe all'acquisizione delle prove previste dall'articolo 190 bis del codice penale nei procedimenti per i reati di mafia; la seconda parte si concentra sul contributo processuale delle dichiarazioni dei chiamati in correità, presentando il caso Adamco c. Slovacchia, il quale ha interessato la Corte europea dei diritti dell'uomo. Inoltre, visti i recenti noti casi di cronaca (pentimento Sandokan), si è analizzata la sentenza n.5817 della Corte di cassazione penale depositata nel gennaio dell'anno corrente. Il quarto ed ultimo capitolo mira ad analizzare il superamento delle preclusioni in materia di ergastolo ostativo. In questo contesto è stata inserita la sentenza n.20 della Corte Costituzionale del 2022 in materia di collaborazione impossibile. Inoltre, è stato analizzato il caso Viola c. Italia n.2) sul quale si è espressa la Corte Sovranazionale. Infine, viene effettuata una sintetica analisi e comparazione del modello dei pentiti francesi con il sistema italiano, vista l'espressa volontà del primo ministro francese di emanare una nuova legge sui pentiti, ispirata proprio alla normativa italiana in materia di collaboratori