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We established two iPSC lines starting from skin fibroblasts of two healthy individuals using Sendai-virus-based technique. The obtained iPSCs were characterized showing same STR profile as starting fibroblasts, normal karyotype, loss of stemness vectors, expression of stemness markers, both through real-time PCR and immunofluorescence, (OCT4, SOX2, TRA-1-60, NANOG and SSEA4) and in vitro differentiation into three germ layers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Despite extensive research, a clear understanding of the role of the interaction between lifestyle and socioeconomic status (SES) on cognitive health is still lacking. We investigated the joint association of socioeconomic factors in early to midlife and lifestyle in later life and Mild Cognitive Impairment (MCI)., Design: Observational cross-sectional study., Setting: NutBrain study in northern Italy., Participants: 773 community-dwelling adults aged 65 years and older (73.2 ± 6.0 SD, 58.6% females) participating in the NutBrain study (2019-2023)., Measurements: Three SES indicators (home ownership, educational level, occupation) and five lifestyle factors (adherence to Mediterranean diet, physical activity, smoking habits, social network, leisure activities) were selected. Each factor was scored and summed to calculate SES and healthy lifestyle scores; their joint effect was also examined. The association with MCI was assessed by logistic regression controlling for potential confounders. Sex-stratified analysis was performed., Results: In total, 24% of the subjects had MCI. The multivariable logistic model showed that a high SES and a high lifestyle score were associated with 81.8% (OR0.182; 95%CI 0.095-0.351), and 44.1% (OR0.559; 95%CI 0.323-0.968) lower odds of having MCI, respectively. When examining the joint effect of SES and lifestyle factors, the cognitive benefits of a healthy lifestyle were most pronounced in participants with low SES. A healthier lifestyle score was found to be significantly associated with lower odds of MCI, only in females., Conclusions: According to our findings, SES was positively associated with preserved cognitive function, highlighting the importance of active lifestyles in reducing socioeconomic health inequalities, particularly among those with a relatively low SES., Trial Registration: Trial registration number NCT04461951, date of registration July 7, 2020 (retrospectively registered, ClinicalTrials.gov)., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The introduction of computerized medical records in hospitals has reduced burdensome activities like manual writing and information fetching. However, the data contained in medical records are still far underutilized, primarily because extracting data from unstructured textual medical records takes time and effort. Information Extraction, a subfield of Natural Language Processing, can help clinical practitioners overcome this limitation by using automated text-mining pipelines. In this work, we created the first Italian neuropsychiatric Named Entity Recognition dataset, PsyNIT, and used it to develop a Transformers-based model. Moreover, we collected and leveraged three external independent datasets to implement an effective multicenter model, with overall F1-score 84.77 %, Precision 83.16 %, Recall 86.44 %. The lessons learned are: (i) the crucial role of a consistent annotation process and (ii) a fine-tuning strategy that combines classical methods with a "low-resource" approach. This allowed us to establish methodological guidelines that pave the way for Natural Language Processing studies in less-resourced languages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The present study aimed to identify clusters of cognitive profiles as well as to explore the effects of these clusters on demographic/individual characteristics and on improvements after a computer-based cognitive training (CCT) in early cognitive impairment. Fifty-seven subjects underwent to an adaptive CCT for 3 weeks (4 individual face-to-face sessions/week of 45 min) and were evaluated at baseline (T0), post-intervention (T1), and after 6 (T2) and 12 (T3) months. Clusters of cognitive profiles were explored with k-means analysis. The analysis revealed two clusters, which were composed by 27 and 30 patients characterized by lower (Cluster 1) and higher (Cluster 2) cognitive functioning. At T1, cognitive performance improved in both groups, but Cluster 1 gained more benefits in global cognitive functioning than Cluster 2. However, at T3, Cluster 2 remained stable in its clinical condition, whereas Cluster 1 showed a pronounced worsening. In conclusion, Cluster 1 profile was associated with a more marked but also short-lasting responsiveness to CCT, whereas patients fitting with Cluster 2 characteristics seemed to obtain more CCT benefits in terms of stability or even delay of cognitive/functional decline. These findings may have relevant implications in informing the timing and modality of delivery of CCT., (© 2023. The Author(s).)

Background: Intracerebral hemorrhage and cognitive decline are typical clinical presentations of cerebral amyloid angiopathy (CAA)., Objective: To determine whether magnetic resonance imaging (MRI) features differ between CAA with hemorrhagic versus cognitive onset., Methods: In this retrospective study, sixty-one patients with CAA were classified by onset presentation of the disease: hemorrhage (n = 31) or cognitive decline (n = 30). The two groups were compared for MRI markers of small vessel disease, namely cerebral microbleeds (CMBs), cortical superficial siderosis, white matter hyperintensities (WMHs), enlarged perivascular spaces, cortical microinfarcts, and visual rating scales for cortical atrophy. In the patients with cognitive onset, further exploratory analyses investigated MRI markers according to cerebrospinal fluid (CSF) and neuropsychological profiles., Results: Patients with cognitive onset showed a higher prevalence of CMBs ( p < 0.001), particularly in temporal ( p = 0.015) and insular ( p = 0.002) lobes, and a higher prevalence of WMHs ( p = 0.012). Within the cognitive onset group, 12 out of 16 (75%) patients had an Alzheimer's disease (AD) CSF profile but did not differ in MRI markers from those without AD pathology. Patients with cognitive onset displayed a multidomain profile in 16 out of 23 (70%) cases; patients with this profile showed increased WMHs and CMBs in parietal lobes compared with the amnestic group ( p = 0.002) and dysexecutive group ( p = 0.032), respectively., Conclusion: Higher burdens of WMHs and CMBs, especially in temporal and insular lobes, are associated with the cognitive onset of CAA. MRI markers could help to shed light on the clinical heterogeneity of the CAA spectrum and its underlying mechanisms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: To investigate the potential contributions of diastolic and systolic blood pressure (BP) and the circadian rhythm of BP to chronic migraine evolution., Methods: This cross-sectional study included four groups of patients selected based on migraine frequency (high frequency ≥ 10 days per month and low frequency < 10) and on the presence of hypertension. Among-group and pairwise comparisons were carried out to investigate potential neurophysiologic differences in the cerebral vessel reactivity to a nitroglycerin test, in autonomic balance (tilting test), and BP circadian rhythm., Results: A more marked decrease in cerebral blood flow velocity was observed in hypertensive high-frequency migraineurs compared to all other groups (P = .037). Moreover, a smaller decrease in vagal tone was recorded in the orthostatic position in hypertensive subjects, whether they were high- (P = .032) or low-frequency migraineurs (P = .014), with a consistently higher vagal to sympathetic tone ratio (P = .033). Finally, in nonhypertensive subjects, a higher but not significant prevalence of systolic nondippers was detected in high-frequency migraineurs (67%) compared to low-frequency subjects (25%; P = .099)., Conclusion: These findings suggest that hypertension may contribute to the chronic evolution of headache with mechanisms shared with migraine; ie, vascular tone alteration and autonomic dysregulation.

Objectives: There is a lack of effective biomarkers for neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia. Extracellular vesicle (EV) RNA cargo can have an interesting potential as a non-invasive biomarker for NDs. However, the knowledge about the abundance of EV-mRNAs and their contribution to neurodegeneration is not clear., Methods: Large and small EVs (LEVs and SEVs) were isolated from plasma of patients and healthy volunteers (control, CTR) by differential centrifugation and filtration, and RNA was extracted. Whole transcriptome was carried out using next generation sequencing (NGS)., Results: Coding RNA (i.e., mRNA) but not long non-coding RNAs (lncRNAs) in SEVs and LEVs of patients with ALS could be distinguished from healthy CTRs and from other NDs using the principal component analysis (PCA). Some mRNAs were found in commonly deregulated between SEVs of patients with ALS and frontotemporal dementia (FTD), and they were classified in mRNA processing and splicing pathways. In LEVs, instead, one mRNA and one antisense RNA (i.e., MAP3K7CL and AP003068.3) were found to be in common among ALS, FTD, and PD. No deregulated mRNAs were found in EVs of patients with AD., Conclusion: Different RNA regulation occurs in LEVs and SEVs of NDs. mRNAs and lncRNAs are present in plasma-derived EVs of NDs, and there are common and specific transcripts that characterize LEVs and SEVs from the NDs considered in this study., Competing Interests: SZ was employed by EnGenome SRL. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sproviero, Gagliardi, Zucca, Arigoni, Giannini, Garofalo, Fantini, Pansarasa, Avenali, Ramusino, Diamanti, Minafra, Perini, Zangaglia, Costa, Ceroni, Calogero and Cereda.)

Background: Vascular lesions may be a common finding also in Alzheimer's dementia, but their role on cognitive status is uncertain., Objective: The study aims to investigate their distribution in patients with Alzheimer's, vascular or mixed dementia and detect any distinctive neuroradiological profiles., Methods: Seventy-six subjects received a diagnosis of Alzheimer's (AD=32), vascular (VD=26) and mixed (MD=18) dementia. Three independent raters assessed the brain images acquired with an optimized 3T MRI protocol (including (3D FLAIR, T1, SWI, and 2D coronal T2 sequences) using semiquantitative scales for vascular lesions (periventricular lesions (PVL), deep white matter lesions (DWML), deep grey matter lesions (DGML), enlarged perivascular spaces (PVS), and microbleeds (MB)) and brain atrophy (medial temporal atrophy (MTA), posterior atrophy (PA), global cortical atrophy- frontal (GCA-F) and Evans' index)., Results: Raters reached a good-to-excellent agreement for all scales (ICC ranging from 0.78-0.96). A greater number of PVL (p<0.001), DWML (p<0.001), DGML (p=0.010), and PVS (p=0.001) was observed in VD compared to AD, while MD showed a significant greater number of PVL (p=0.001), DWML (p=0.002), DGML (p=0.018), and deep and juxtacortical MB (p=0.006 and p<0.001, respectively). Comparing VD and MD, VD showed a higher number of PVS in basal ganglia and centrum semiovale (p=0.040), while MD showed more deep and juxtacortical MB (p=0.042 and p=0.022, respectively). No significant difference was observed in scores of cortical atrophy scales and Evans' index among the three groups., Conclusion: The proposed MRI protocol represents a useful advancement in the diagnostic assessment of patients with cognitive impairment by more accurately detecting vascular lesions, mainly microbleeds, without a significant increase in time and resource expenditure. Our findings confirm that white and grey matter lesions predominate in vascular and mixed dementia, whereas deep and juxtacortical microbleeds predominate in mixed dementia, suggesting that cerebral amyloid angiopathy could be the main underlying pathology., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Previous studies have suggested that evening intake of benzodiazepine affects blood pressure (BP) and/or heart rate (HR) in healthy and hypertensive subjects. The aim of this study was to compare the effect of chronic oral administration of alprazolam and lorazepam as hypnotics on ambulatory BP and HR in patients with mild hypertension., Methods: Consecutive outpatients of both sexes with newly diagnosed, never-treated mild hypertension were randomized, after a 4-week placebo run-in period, to receive alprazolam 0.5 mg plus placebo, lorazepam 1 mg plus placebo, or placebo plus placebo for 2 weeks in 3 crossover periods, each separated by a 1-week placebo wash-out period. At the end of the initial placebo run-in and of each treatment period, 24-hour ambulatory BP and HR monitoring was performed using a noninvasive device., Results: In the 32 patients, no treatment had any effect on 24-hour and daytime systolic BP (SBP), diastolic BP (DBP), and HR, which remained unchanged. During the nighttime, SBP and DBP values were unaffected by alprazolam, as compared with placebo, whereas DBP was significantly higher after treatment with lorazepam (+3.7%, P < 0.05 vs placebo). Nocturnal HR mean values were significantly increased by lorazepam (+10.1%, P < 0.01 vs placebo), whereas they did not change after alprazolam., Conclusions: In patients with mild hypertension, oral intake of alprazolam or lorazepam as hypnotics did not affect ambulatory BP or HR values. A slight increase in nighttime DBP was observed with lorazepam, whereas alprazolam showed no effect on nocturnal BP and HR, probably reflecting a stimulating effect of the drug on central α2-receptors., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: With the shift of research focus to personalized medicine in Alzheimer's Dementia (AD), there is an urgent need for tools that are capable of quantifying a patient's risk using diagnostic biomarkers. The Medical Informatics Platform (MIP) is a distributed e-infrastructure federating large amounts of data coupled with machine-learning (ML) algorithms and statistical models to define the biological signature of the disease. The present study assessed (i) the accuracy of two ML algorithms, i.e., supervised Gradient Boosting (GB) and semi-unsupervised 3C strategy (Categorize, Cluster, Classify-CCC) implemented in the MIP and (ii) their contribution over the standard diagnostic workup. Methods: We examined individuals coming from the MIP installed across 3 Italian memory clinics, including subjects with Normal Cognition (CN, n = 432), Mild Cognitive Impairment (MCI, n = 456), and AD ( n = 451). The GB classifier was applied to best discriminate the three diagnostic classes in 1,339 subjects, and the CCC strategy was used to refine the classical disease categories. Four dementia experts provided their diagnostic confidence (DC) of MCI conversion on an independent cohort of 38 patients. DC was based on clinical, neuropsychological, CSF, and structural MRI information and again with addition of the outcome from the MIP tools. Results: The GB algorithm provided a classification accuracy of 85% in a nested 10-fold cross-validation for CN vs. MCI vs. AD discrimination. Accuracy increased to 95% in the holdout validation, with the omission of each Italian clinical cohort out in turn. CCC identified five homogeneous clusters of subjects and 36 biomarkers that represented the disease fingerprint. In the DC assessment, CCC defined six clusters in the MCI population used to train the algorithm and 29 biomarkers to improve patients staging. GB and CCC showed a significant impact, evaluated as +5.99% of increment on physicians' DC. The influence of MIP on DC was rated from "slight" to "significant" in 80% of the cases. Discussion: GB provided fair results in classification of CN, MCI, and AD. CCC identified homogeneous and promising classes of subjects via its semi-unsupervised approach. We measured the effect of the MIP on the physician's DC. Our results pave the way for the establishment of a new paradigm for ML discrimination of patients who will or will not convert to AD, a clinical priority for neurology., (Copyright © 2020 Redolfi, De Francesco, Palesi, Galluzzi, Muscio, Castellazzi, Tiraboschi, Savini, Nigri, Bottini, Bruzzone, Ramusino, Ferraro, Gandini Wheeler-Kingshott, Tagliavini, Frisoni, Ryvlin, Demonet, Kherif, Cappa and D'Angelo.)

Background: Trigeminal neuralgia (TN) is a severe, disabling form of painful cranial neuropathy. Even though TN has a typical clinical picture, diagnosis it is often missed or delayed in clinical practice. In order to investigate the occurrence of diagnostic and therapeutic errors in TN, we studied 102 patients suffering from TN recruited through a multicentric survey., Methods: We performed a Pubmed database search on errors and pittfalls in TN diagnosis and management. Then, patients with TN were consecutively enrolled in the period from February 2017 to October 2019, by several European Headache Centers participating in the study, following a call of the Headache and Pain Scientific Panels of the European Academy of Neurology (EAN). Diagnosis of Classical Trigeminal Neuralgia (CTN) was made according to the International Headache Society (IHS) criteria (Tölle et al., Pain Pract 6:153-160, 2006). All the patients were evaluated using telephone/frontal interviews conducted by headache/pain specialists using an ad hoc questionnaire., Results: A number of 102 patients were recruited, mostly females (F:M ratio 2.64:1). Eighty-six percent of the patients consulted a physician at the time they experienced the first pain attacks. Specialists consulted before TN diagnosis were: primary care physicians (PCP) (43.1%), dentists (in 30.4%), otorhinolaryngologists (3.9%), neurosurgeons (3.9%), neurologists or headache specialists (14.7%), others (8%). The final diagnosis was made mainly by a neurologist or headache specialist (85.3%), and the mean interval between the disease onset and the diagnosis made by a specialist was 10.8 ± 21.2 months. The "diagnostic delay" was 7.2 ± 12.5 months, and misdiagnoses at first consultation were found in 42.1% of cases. Instrumental and laboratory investigations were carried out in 93.1% of the patients before the final diagnosis of TN., Conclusion: While TN has typical features and it is well defined by the available international diagnostic criteria, it is still frequently misdiagnosed and mistreated. There is a need to improve the neurological knowledge in order to promptly recognize the clinical picture of TN and properly adhere to the specific guidelines. This may result in a favorable outcome for patients, whose quality of life is usually severely impaired.

Purpose: To compare the incremental diagnostic value of amyloid-PET and CSF (Aβ42, tau, and phospho-tau) in AD diagnosis in patients with mild cognitive impairment (MCI) or mild dementia, in order to improve the definition of diagnostic algorithm., Methods: Two independent dementia experts provided etiological diagnosis and relative diagnostic confidence in 71 patients on 3 rounds, based on (1) clinical, neuropsychological, and structural MRI information alone; (2) adding one biomarker (CSF amyloid and tau levels or amyloid-PET with a balanced randomized design); and (3) adding the other biomarker., Results: Among patients with a pre-biomarker diagnosis of AD, negative PET induced significantly more diagnostic changes than amyloid-negative CSF at both rounds 2 (CSF 67%, PET 100%, P = 0.028) and 3 (CSF 0%; PET 78%, P < 0.001); PET induced a diagnostic confidence increase significantly higher than CSF on both rounds 2 and 3., Conclusions: Amyloid-PET should be prioritized over CSF biomarkers in the diagnostic workup of patients investigated for suspected AD, as it provides greater changes in diagnosis and diagnostic confidence., Trial Registration: EudraCT no.: 2014-005389-31.

Trigeminal autonomic cephalalgias (TACs) are primary headaches that include cluster headache (CH), paroxysmal hemicrania (PH), and short-lasting unilateral neuralgiform headache attacks (SUNHAs) with conjunctival injection and tearing (SUNCT) or cranial autonomic features (SUNA). Hemicrania continua (HC) is another form that has been ascribed to TACs for clinical and pathophysiologic reasons. Cluster headache is the most common of these syndromes, even if comparatively rare, with a lifetime prevalence of around 1 in 1,000. TACs share many aspects from a pathophysiologic standpoint (a hypothalamic activation may be involved in all forms initiating the attacks), but differences in attack duration and frequency and in extent of treatment response distinguish one from the other. This review focuses on the treatments currently available for these headaches according to the most recent guidelines. Due to the low frequency of most TACs, there are little data from randomized controlled trials; therefore, evidence from simple open studies in small case series or single-case observations are reported. Promising results have been recently obtained with novel modes of drug administration, invasive pericranial interventions, and different strategies such as neurostimulation. There are also some future treatments being studied at present.

Purpose: The present study was carried out in order to assess the effects of chronic administration of flunitrazepam (as an oral hypnotic) on 24-h blood pressure (BP) and heart rate (HR) in healthy young adults., Materials and Methods: Following a 2-week placebo run-in period, 28 healthy volunteers (13 males and 15 females) between 21 and 30 years were randomized to receive either flunitrazepam 1 mg or placebo (both administered once a day in the evening) for 4 weeks in two cross-over periods; each separated by a 2-week placebo period. At the end of each study period, non-invasive 24-h BP and HR ambulatory monitoring was performed., Results: Flunitrazepam produced a significant decrease in nighttime systolic blood pressure (SBP) (- 6.4 mmHg) and diastolic blood pressure (DBP) (- 4.1 mmHg) (both P < 0.05 vs placebo) without affecting nocturnal HR. During the morning hours, significantly higher values of SBP (+ 7.4 mmHg, P < 0.01), DBP (+ 3.4 mmHg, P < 0.05) and HR (+ 3.9 beats/min, P < 0.05) were observed in the flunitrazepam group compared to the placebo-treated group. No significant differences were noted between the two groups during afternoon and evening hours., Conclusions: These results suggest that chronic oral administration of 1 mg flunitrazepam as a hypnotic agent causes a significant nocturnal fall in BP and a transient rebound increase of both BP and HR at awakening in the morning. Mechanisms underlying these cardiovascular effects remain unclear, although the direct vasodilatory effect, which is typical of flunitrazepam (with consequent reflex counter-regulatory responses), and the attenuation of baroreflex sensitivity are likely to play a major role.

Alzheimer disease (AD) and vascular dementia (VaD) together represent the majority of dementia cases. Since their neuropsychological profiles often overlap and white matter lesions are observed in elderly subjects including AD, differentiating between VaD and AD can be difficult. Characterization of these different forms of dementia would benefit by identification of quantitative imaging biomarkers specifically sensitive to AD or VaD. Parameters of microstructural abnormalities derived from diffusion tensor imaging (DTI) have been reported to be helpful in differentiating between dementias, but only few studies have used them to compare AD and VaD with a voxelwise approach. Therefore, in this study a whole brain statistical analysis was performed on DTI data of 93 subjects (31 AD, 27 VaD, and 35 healthy controls-HC) to identify specific white matter patterns of alteration in patients affected by VaD and AD with respect to HC. Parahippocampal tracts were found to be mainly affected in AD, while VaD showed more spread white matter damages associated with thalamic radiations involvement. The genu of the corpus callosum was predominantly affected in VaD, while the splenium was predominantly affected in AD revealing the existence of specific patterns of alteration useful in distinguishing between VaD and AD. Therefore, DTI parameters of these regions could be informative to understand the pathogenesis and support the etiological diagnosis of dementia. Further studies on larger cohorts of subjects, characterized for brain amyloidosis, will allow to confirm and to integrate the present findings and, furthermore, to elucidate the mechanisms of mixed dementia. These steps will be essential to translate these advances to clinical practice.

The aim of the study was to evaluate the usefulness of Holter monitoring for the detection of silent myocardial ischemia (SMI) in elderly type 2 diabetic patients with hypertension and the possible relationship between SMI and cardiovascular autonomic neuropathy (CAN). Two hundred and forty-three asymptomatic outpatients, aged 65-75 years, with type 2 diabetes and essential hypertension underwent 24-h ECG monitoring and 5 tests for the evaluation of both parasympathetic (heart rate variability, response to breath deeping, and Valsalva manoeuvre) and sympathetic (cold pressor test and orthostatic hypotension test) autonomic function. A total of 518 asymptomatic episodes of ST depression during Holter monitoring indicative of SMI were detected in 51 of the 243 studied patients (20.9 %). None of the patients with ST depression episodes exhibited a normal response to at least one of the evaluated autonomic function tests, whereas 22 of the 192 patients without ST changes (11.4 %) exhibited a normal response to all tests. Abnormality in both parasympathetic and sympathetic function test responses was found in 94.1 % of patients with ST depression episodes vs 26.1 % of those without ST changes (P < 0.001). Statistical evaluation of the relationship between the abnormal response to single autonomic function test and episodes of ST depression was highly significant for all the 5 tests (P < 0.001). These results indicate that: (a) Holter monitoring enables to detect ST segment changes indicative of SMI in 20.9 % of elderly diabetic patients with hypertension; (b) the presence of autonomic cardiac dysfunction in these patients suggests a role of diabetic neuropathy in the pathogenesis of SMI; and, ((c) findings of severe autonomic dysfunction in more than 25 % of patients without ST depression episodes suggest that these patients might be at risk of myocardial ischemia and should possibly be addressed to closer specialistic evaluation, since Holter monitoring might have not detected SMI in these patients due to its low sensitivity and relatively short duration of recordings.)

Introduction: The aim of this study was to compare the effect of ramipril/canrenone versus ramipril/hydrochlorothiazide (HCTZ) combination on atrial fibrillation (AF) recurrence in type 2 diabetic hypertensives with and without cardiac autonomic neuropathy (CAN)., Material and Methods: A total of 289 hypertensive type 2 diabetic patients, 95 with CAN, in sinus rhythm but with at least two episodes of AF in the previous 6 months were randomized to ramipril 5 mg plus canrenone 50 mg (titrated to 10/100 mg) or to ramipril 5 mg plus HCTZ 12.5 mg (titrated to 10/25 mg) or to amlodipine 5 mg (titrated to 10 mg) for 1 year. Clinic blood pressure (BP) and a 24-h ECG were evaluated monthly. Patients were asked to report any episode of symptomatic AF and to perform an ECG as early as possible. Serum procollagen type I carboxy-terminal peptide (PIP) and carboxy-terminal telopeptide of collagen type I (CITP) were evaluated before and after each treatment period., Results: Blood pressure was similarly and significantly reduced by all treatments. A total of 51% of patients with amlodipine had a recurrence of AF, as did 31% of patients with ramipril/HCTZ ( p < 0.05 vs. amlodipine) and 13% of patients with ramipril/canrenone ( p < 0.01 vs. amlodipine and p < 0.05 vs. ramipril/HCTZ). A similar trend was found in diabetic patients with CAN. Both combinations reduced PIP and increased CITP, but the effects of ramipril/canrenone were significantly more marked., Conclusions: These findings suggest that in type 2 diabetic hypertensives, ramipril/canrenone treatment was more effective than ramipril/HCTZ in reducing AF recurrence. This could be related to the greater improvement in cardiac fibrosis., Competing Interests: The authors declare no conflict of interest.

Background and Aims: Neurogenic dysphagia linked to failed relaxation of the upper esophageal sphincter (UES) can be treated by injecting botulinum toxin (BTX) into the cricopharyngeal (CP) muscle. We compared the effects of this treatment in different neurological disorders with dysphagia, to evaluate its efficacy over time including the response to a second injection. Materials and Methods: Sixty-seven patients with neurogenic dysphagia associated with incomplete or absent opening of the UES (24 with brainstem or hemispheric stroke, 21 with parkinsonian syndromes, 12 with multiple sclerosis, and 10 with spastic-dystonic syndromes secondary to post-traumatic encephalopathy) were treated with the injection of IncobotulinumtoxinA (dose 15-20 U) into the CP muscle under electromyographic guidance. The patients were assessed at baseline and after the first and second treatment through clinical evaluation and fiberoptic endoscopy of swallowing, while their dysphagia was quantified using the Dysphagia Outcome and Severity Scale (DOSS). An electrokinesiographic/electromyographic study of swallowing was performed at baseline. Results : Most patients responded to the first BTX treatment: 35 patients (52.2%) were classified as high responders (DOSS score increase >2 levels), while other 19 patients (28.4%) were low responders (DOSS score increase of ≤2 levels). The effect of the first treatment usually lasted longer than 4 months (67%), and in some cases up to a year. The treatment efficacy remained high also after the second injection: 31 patients (46.3%) qualified as high responders and other 22 patients (32.8%) showed a low response. Only in the parkinsonian syndromes group we observed a reduction in the percentage of high responders as compared with the first treatment. Side effects were mostly mild and reported in non-responders following the first injection. A severe side effect, consisting of ingestion pneumonia, was observed following the second BTX injection in two patients who had both been non-responders to the first. Non-responders were characterized electromyographically by higher values of the oropharyngeal interval. Conclusion: These findings confirm the effectiveness of IncobotulinumtoxinA injection in the treatment of neurogenic dysphagia due to hyperactivity and relaxation failure of the UES. Caution should be used as regards, the re-injection in non-responders to the first treatment.

Purpose: The aim of this study was to evaluate the relationship between orthostatic hypotension (OH), defined as a decrease in systolic blood pressure (SBP) ≥20 mmHg and/or a decrease in diastolic blood pressure (DBP) ≥10 mmHg, and 24-h ambulatory BP profile in elderly hypertensive type 2 diabetic patients., Methods: After a 2-week antihypertensive wash-out period, 200 hypertensive well-controlled diabetic outpatients, aged 65-75 years, underwent a clinical examination, including BP measurements, ECG, 24-h ABP monitoring (ABPM), an orthostatic test, and three tests for cardiovascular autonomic function assessment [deep breathing, heart rate (HR) variability, resting HR]., Results: According to their nighttime BP profile, patients were divided into three groups: dippers (n = 86) (BP fall during nighttime ≥10 %), non-dippers (n = 80) (BP fall during nighttime 0-10 %), and reverse dippers (n = 34) (nighttime BP > daytime BP). Orthostatic test produced a significantly greater orthostatic SBP fall in dippers and even more in reverse dippers. In these latter, a significant fall was observed also in DBP. Prevalence of OH was 9.3 % in dippers, 30 % in non-dippers, and 79.4 % in reverse dippers., Conclusions: In elderly hypertensive type 2 diabetics, a blunted nocturnal BP fall is associated with OH and autonomic dysfunction. These data suggest that ABPM should be performed in the assessment of hypertensive diabetic patients in whom the cardiovascular dysautonomia is suspected or the signs of it are present (such as OH).

Trigeminal autonomic cephalalgias (TACs) are a group of primary headaches including cluster headache (CH), paroxysmal hemicrania (PH) and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). Another form, hemicrania continua (HC), is also included this group due to its clinical and pathophysiological similarities. CH is the most common of these syndromes, the others being infrequent in the general population. The pathophysiology of the TACs has been partly elucidated by a number of recent neuroimaging studies, which implicate brain regions associated with nociception (pain matrix). In addition, the hypothalamic activation observed in the course of TAC attacks and the observed efficacy of hypothalamic neurostimulation in CH patients suggest that the hypothalamus is another key structure. Hypothalamic activation may indeed be involved in attack initiation, but it may also lead to a condition of central facilitation underlying the recurrence of pain episodes. The TACs share many pathophysiological features, but are characterised by differences in attack duration and frequency, and to some extent treatment response. Although alternative strategies for the TACs, especially CH, are now emerging (such as neurostimulation techniques), this review focuses on the available pharmacological treatments complying with the most recent guidelines. We discuss the clinical efficacy and tolerability of the currently used drugs. Due to the low frequency of most TACs, few randomised controlled trials have been conducted. The therapies of choice in CH continue to be the triptans and oxygen for acute treatment, and verapamil and lithium for prevention, but promising results have recently been obtained with novel modes of administration of the triptans and other agents, and several other treatments are currently under study. Indomethacin is extremely effective in PH and HC, while antiepileptic drugs (especially lamotrigine) appear to be increasingly useful in SUNCT. We highlight the need for appropriate studies investigating treatments for these rare, but lifelong and disabling conditions.

Several dietary habits and lifestyles can be associated with different headache types or with their progression to chronic forms. Different population-based studies have tried to investigate this relationship with poor or contradictory results. We shortly reported the current knowledges available in literature in this regard, paying particular attention to the role that certain factors play in modifying frequency and intensity of headache in adults and in adolescents. Future studies are necessary to clarify the real weight which the different factors have in natural history and in clinic evolution of headache, especially in adolescence, but the already known data suggest an important modulating action. If they will be confirmed, these results will be likely to influence clinical practice as well to address educational programs in preadolescents and adolescents.

The crystallisation conditions and the physicochemical properties of the modifications I and II of (R,S) propranolol hydrochloride were investigated. Detailed methods of preparation of the two forms were described. Data from FTIR spectroscopy, X-ray powder diffraction, thermal analysis, solubility and dissolution studies were used for the identification and the characterisation of the two forms. The forms I and II were easily differentiated by their IR spectra, X-ray patterns and thermal behaviour. The two polymorphs were found to be enantiotropically related to each other. Their stability was followed at room temperature over a period of 1 year and under different conditions of temperature, grinding and compression to verify the tendency to solid solid transition and to study the existence range of the two forms. The equilibrium solubilities of the two polymorphs in n-octanol were determined as well as their dissolution profiles as pellets in aqueous medium. These studies showed that form I, the less thermodynamically stable, was more soluble (by more than 34%) and dissolved faster than form II in agreement with the thermodynamic rules (A. Burger, R. Ramberger, Mikrochim. Acta II (1979) 259-271).

Three crystalline modifications of fluocinolone acetonide, A, B and C, were characterized by means of FTIR, DSC, TG-FTIR, MICRO-FTIR and X-ray diffractometry. They were easily differentiated by their IR absorption bands in the 3600-3400 cm-1 range. The thermal behavior was also elucidated using combined techniques; thermomicroscopy and thermogravimetry coupled with Fourier transform infrared spectroscopy were found to be very useful tools for a better understanding of thermal events. On heating, form A and C were fully converted into form B. Polymorph A was found to be enantiotropically related to B, while form C was monotropically related to B. The existence of three polymorphs was confirmed by means of their different X-ray diffraction patterns. Detailed methods of preparation of the three modifications are also described.