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

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

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

Verbal Learning Abilities in ALS Patients (P01.109)

Objective: to study the neurocognitive dysfunctions spectrum in ALS. Background neurocognitive impairment involves mainly executive dysfunction (1). On the other hand, is not clear if memory is involved primary (2). Design/Methods: fifty-five consecutive ALS patients referred to Motor NeuronCenter, Department of Neurology, University of Bari. The diagnosis was based on El Escorial criteria (Brooks, 1994). Seventy healthy age-matched control were recruited. We examined the memory abilities through the Rey's Auditory Verbal Learning Test (RAVLT): free recall in five trials, immediate and delayed recall, verbal learning, verbal forgetting, primary and recency effect score. All subjects completed also the following neuropsychological battery: Mini Mental State Examination (MMSE), Frontal Assessment Battery (FAB): Digit span forward (DSF); Digit span backward (DSB); Attentional Matrices (AM); Verbal Fluency Test (VFT); Stroop Test (ST); Raven's Colored Matrices (RCM). Results: we enrolled 33 men and 22 women in ALS group (age 59.7±9.7; educational level 9.6±4.1 yrs; disease duration at baseline 30.9±32.1 months; ALSFRS-r 37.8±6.2; FVC 92.5±22.7; MMT 8.1±1.3). Compared with controls, ALS patients performed worse on the recall immediate (p=.007). The recency and primary effect was less evident in ALS than control group (p=.018; p=.004). Moreover, the ALS group performed worse on short-term memory (DSF, p=.005), working memory (DSB, p=.000), verbal fluency (VFT, p=.000), flexibility (RCM, p=.025) and general cognitive abilities (MMSE, p=.001; FAB, p=.009). The different indices of RAVLT showed a significant correlation with all executive measures in ALS group. Conclusions: ALS patients present impairment of both executive and memory dysfunctions. The executive dysfunctions are primary involved with failure of elaborative encoding and strategic retrieval processing, as a consequence of verbal learning identified by free recall, recency and primary effect scores. On the other hand, storage processes, a main component of memory, are intact

Frontal assessment battery for detecting executive dysfunction in amyotrophic lateral sclerosis without dementia: a retrospective observational study

The frontal assessment battery (FAB) is a quick and reliable method of screening to evaluate frontal lobe dysfunction in amyotrophic lateral sclerosis (ALS). However, previous studies were generally conducted on small samples representing different stages of disease and severity. We assessed the diagnostic accuracy of the FAB in detecting executive functions and its association with demographic and clinical features in ALS without dementia

Cortical thinning and clinical heterogeneity in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) has heterogeneous clinical features that could be translated into specific patterns of brain atrophy. In the current study we have evaluated the relationship between different clinical expressions of classical ALS and measurements of brain cortical thickness. Cortical thickness analysis was conducted from 3D-MRI using FreeSurfer software in 29 ALS patients and 20 healthy controls. We explored three clinical traits of the disease, subdividing the patients into two groups for each of them: the bulbar or spinal onset, the higher or lower upper motor neuron burden, the faster or slower disease progression. We used both a whole brain vertex-wise analysis and a ROI analysis on primary motor areas. ALS patients showed cortical thinning in bilateral precentral gyrus, bilateral middle frontal gyrus, right superior temporal gyrus and right occipital cortex. ALS patients with higher upper motor neuron burden showed a significant cortical thinning in the right precentral gyrus and in other frontal extra-motor areas, compared to healthy controls. ALS patients with spinal onset showed a significant cortical thinning in the right precentral gyrus and paracentral lobule, compared to healthy controls. ALS patients with faster progressive disease showed a significant cortical thinning in widespread bilateral frontal and temporal areas, including the bilateral precentral gyrus, compared to healthy controls. Focusing on the primary motor areas, the ROI analysis revealed that the mean cortical thickness values were significantly reduced in ALS patients with higher upper motor neuron burden, spinal onset and faster disease progression related to healthy controls. In conclusion, the thickness of primary motor cortex could be a useful surrogate marker of upper motor neuron involvement in ALS; also our results suggest that cortical thinning in motor and non motor areas seem to reflect the clinical heterogeneity of the disease

Pseudobulbar affect (PBA) in an incident ALS cohort: results from the Apulia registry (SLAP).

International audienceThe aim of this study is to investigate the frequency and the clinical correlations of pseudobulbar affect (PBA) in a population-based incident cohort of ALS patients. Incident ALS cases, diagnosed in 2011 and 2012, according to El Escorial criteria were enrolled from a prospective population-based registry in Apulia, Southern Italy. Neurological status was assessed using a standard neurological examination and the revised ALS Functional Rating Scale (ALSFRSr). The Center for Neurologic Study-Lability Scale (CNS-LS), a self-administered questionnaire, was used to evaluate the presence and severity of PBA. Total scores range from 7 to 35. A score ≥13 was used to identify the presence of PBA. One-hundred thirty-two sporadic incident ALS cases were enrolled. Median disease duration was 20 months (range 2-143), median onset-diagnosis interval (ODI) 12 months (range 2-131), median ALSFRSr at baseline 36/48 (range 2-47) and median ALSFRSr bulbar sub-score 10/12 (range 0-12). Neurological examination revealed presence of PBA in 34/132 patients (26%). Pathological CNS-LS score was found in 45/132 patients (34%). Median total CNS-LS score was 9/35 (range 7-29). The subgroup with pathological CNS-LS was characterized by a short disease duration from symptom onset, ODI, time to diffusion to a second region, time to generalization and ALSFRSr bulbar sub-score, bulbar onset, "definite" diagnostic category, bulbar upper motor-neuron involvement and presence of PBA at neurological examination. In population-based setting, one-third of ALS patients present PBA at diagnosis. The presence of PBA is associated with bulbar UMN involvement and markers of a more severe phenotype

Midlife Metabolic Profile and the Risk of Late-Life Cognitive Decline

Among metabolic syndrome components, the effects of higher plasma glucose levels on cognitive decline (CD) have been considered in few studies. We evaluated the associations among midlife glycemia, total cholesterol, high-density lipoprotein cholesterol, triglycerides, midlife insulin resistance [homeostasis model assessment for insulin resistance (HOMA-index)], and CD in the older subjects of the population-based MICOL Study (Castellana Grotte, Italy) at baseline (M1) and at follow-ups seven (M2) and twenty years later (M3). At M1, a dementia risk score and a composite cardiovascular risk score for dementia were calculated. For 797 subjects out of 833, we obtained a Mini-Mental State Examination (MMSE) score at M3, subdividing these subjects in three cognitive functioning subgroups: normal cognition, mild CD, and moderate-severe CD. Mean fasting glycemia at baseline was significantly higher in moderate-severe CD subgroup (114.6±71.4mg/dl) than in the normal cognition subgroup (101.2±20.6). Adjusting for gender, age, and other metabolic components, higher fasting glycemia values both at M1 [odds ratio (OR)=1.31; 95% confidence interval (CI): 1.08-1.59] and M2 (OR=1.26; 95% CI: 1.01-1.57) were associated with an increased risk of moderate-severe CD. Mean HOMA index value was significantly higher in the moderate-severe CD subgroup (5.7±9.4) compared to the normal cognition subgroup (2.9±1.4) at M1. The dementia risk probability (MMSE<24) increased moving through higher categories of the dementia risk score and decreased as long as the cardiovascular score increased. The present findings highlighted the indication to control blood glucose levels, regardless of a diagnosis of diabetes mellitus, as early as midlife for prevention of late-life dementia