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Background. Dupuytren's disease (DD) is a chronic and progressive fibroproliferative disease consisting of the progressive pathological fibrosis of the palmar fascia leading to permanent flexion and deficit of extension, with marked deformity and severe disability. Among treatment options, conservative and infiltrative therapies, physiotherapy, or surgery, with less invasive surgical options, are reported. The therapeutic planning, shared with the patient, must consider the severity of the disease, surgical risks, the functional, aesthetic, and occupational consequences, and the risk of recurrence. Case report. We describe a complicated clinical case that led her to a claim for compensation under presumed medical professional liability profiles. A female patient, 32-years-old, suffering from early symptomatic DD in the left non-dominant hand, underwent to palmar fasciotomy complicated by severe paraesthesia. In the re-surgery, vascular and nerve injury was found, leading to permanent disabling sequelae. Discussion. The early stage of DD, although symptomatic, without previous medical or infiltrative therapy, in a young subject with insulindependent diabetes and a high risk of recurrence contraindicated the surgical approach, especially palmar fasciotomy, according to the best evidence. The vascular-nervous lesion in the hand palm indicated a censurable surgical execution technique. The technical consultation ascertained the causal relationship between impairments and surgical malpractice, followed by compensation. Conclusion. The analysis of this case highlights the value of informed clinical practice to provide optimal care and mitigate the risks associated with the management of DD. The choice of possible treatment options must be tailored to the patient in accordance with the best evidence. Clin Ter 2024; 175 (5):333-336 doi: 10.7417/ CT.2024.5138 [ABSTRACT FROM AUTHOR]

Primary synovial chondromatosis of the hip is a rare joint condition characterized by the abnormal proliferation of cartilaginous tissue within the synovial membrane, which leads to the formation of clusters of chondrocytes floating in the joint space. This commentary provides a comprehensive overview of the pathology, including symptoms, diagnosis, treatment options and long-term management. Patients with primary synovial chondromatosis complaint pain and functional impairment, together with a peculiar joint popping sensation during movement, so determining early disability. The early treatment can lead to better clinical outcomes, with increased preservation of joint function and reduced risk of long-term disability, but strictly depend on symptoms acknowledgement and proper imaging interpretation. As a chronic pathology, surgical approach must necessarily be part of a larger medical and rehabilitative care planning, with long period follow-up. Multidisciplinary team management, with the active involvement of the patient is pivotal in improving the clinical outcomes and quality of life. [ABSTRACT FROM AUTHOR]

This writing aims to convey the essential nature and features of a cultural tool based on a set of skills and capabilities generally referred to as "life skills", which allow for the proper management (in the medical and medical-forensic professional realms) of daily situations in an effective and rewarding fashion. Such a process is based on individual tools such as communication, problem solving, stress management, self-control, the ability to make timely decisions, empathy, creativity and the opportunity to work in a multidisciplinary setting. Life skills include everything the professional should rely on in order to minimize the risks of a professional error, through the acquisition of knowledge and behavioral traits which constitute the fundamental, experiencebased starting point. The chief objective of this commentary is to outline the scope of a straightforward discussion by specifically defining such skills; that in turn will make it possible to identify all the technical issues to address during the medical-diagnostic assessment, also from a medico-legal perspective, in order to frame the residual life skills and evaluate the possibilities of recovery and any disabilities, based on observation and interactions with each patient aimed at weighing their psychophysical performance. [ABSTRACT FROM AUTHOR]

Background: Dupuytren's disease (DD) is a chronic and progressive fibroproliferative disease consisting of the progressive pathological fibrosis of the palmar fascia leading to permanent flexion and deficit of extension, with marked deformity and severe disability. Among treatment options, conservative and infiltrative therapies, physiotherapy, or surgery, with less invasive surgical options, are reported. The therapeutic planning, shared with the patient, must consider the severity of the disease, surgical risks, the functional, aesthetic, and occupational consequences, and the risk of recurrence., Case Report: We describe a complicated clinical case that led her to a claim for compensation under presumed medical professional liability profiles. A female patient, 32-years-old, suffering from early symptomatic DD in the left non-dominant hand, underwent to palmar fasciotomy complicated by severe paraesthesia. In the re-surgery, vascular and nerve injury was found, leading to permanent disabling sequelae., Discussion: The early stage of DD, although symptomatic, without previous medical or infiltrative therapy, in a young subject with insulin-dependent diabetes and a high risk of recurrence contraindicated the surgical approach, especially palmar fasciotomy, according to the best evidence. The vascular-nervous lesion in the hand palm indicated a censurable surgical execution technique. The technical consultation ascertained the causal relationship between impairments and surgical malpractice, followed by compensation., Conclusion: The analysis of this case highlights the value of informed clinical practice to provide optimal care and mitigate the risks associated with the management of DD. The choice of possible treatment options must be tailored to the patient in accordance with the best evidence.

Abstract: Primary synovial chondromatosis of the hip is a rare joint condition characterized by the abnormal proliferation of cartilaginous tissue within the synovial membrane, which leads to the formation of clusters of chondrocytes floating in the joint space. This commentary provides a comprehensive overview of the pathology, including symptoms, diagnosis, treatment options and long-term management. Patients with primary synovial chondromatosis complaint pain and functional impairment, together with a peculiar joint popping sensation during movement, so determining early disability. The early treatment can lead to better clinical outcomes, with increased preservation of joint function and reduced risk of long-term disability, but strictly depend on symptoms acknowledgement and proper imaging interpretation. As a chronic pathology, surgical approach must necessarily be part of a larger medical and rehabilitative care planning, with long period follow-up. Multidisciplinary team management, with the active involvement of the patient is pivotal in improving the clinical outcomes and quality of life.

Abstract: This writing aims to convey the essential nature and features of a cultural tool based on a set of skills and capabilities generally referred to as "life skills", which allow for the proper management (in the medical and medical-forensic professional realms) of daily situations in an effective and rewarding fashion. Such a process is based on individual tools such as communication, problem solving, stress management, self-control, the ability to make timely decisions, empathy, creativity and the opportunity to work in a multidisciplinary setting. Life skills include everything the professional should rely on in order to minimize the risks of a professional error, through the acquisition of knowledge and behavioral traits which constitute the fundamental, experience-based starting point. The chief objective of this commentary is to outline the scope of a straightforward discussion by specifically defining such skills; that in turn will make it possible to identify all the technical issues to address during the medical-diagnostic assessment, also from a medico-legal perspective, in order to frame the residual life skills and evaluate the possibilities of recovery and any disabilities, based on observation and interactions with each patient aimed at weighing their psychophysical performance.

Background: Comorbid conditions are common in people with multiple sclerosis (pwMS). They can delay diagnosis and negatively impact the disease course, progression of disability, therapeutic management, and adherence to treatment., Objective: To quantify the economic impact of comorbidity in multiple sclerosis (MS), based on cost-of-illness estimates made using a bottom-up approach., Methods: A retrospective study was carried out in two northern Italian areas. The socio-demographic and clinical information, including comorbidities data, were collected through ad hoc anonymous self-assessment questionnaire while disease costs (direct and indirect costs of disease and loss of productivity) were estimated using a bottom-up approach. Costs were compared between pwMS with and without comorbidity. Adjusted incremental costs associated with comorbidity were reported using generalized linear models with log-link and gamma distributions or two-part models., Results: 51.0% of pwMS had at least one comorbid condition. Hypertension (21.0%), depression (15.7%), and anxiety (11.7%) were the most prevalent. PwMS with comorbidity were more likely to use healthcare resources, such as hospitalizations (OR = 1.21, p < 0.001), tests (OR = 1.59, p < 0.001), and symptomatic drugs and supplements (OR = 1.89, p = 0.012), and to incur non-healthcare costs related to investment (OR = 1.32, p < 0.001), transportation (OR = 1.33, p < 0.001), services (OR = 1.33, p < 0.001), and informal care (OR = 1.43, p = 0.16). Finally, they experienced greater productivity losses (OR = 1.34, p < 0.001) than pwMS without comorbidity. The adjusted incremental annual cost per patient due to comorbidity was €3,106.9 (13% of the overall costs) with MS disability found to exponentially affect annual costs., Conclusion: Comorbidity has health, social, and economic consequences for pwMS., (© 2022. The Author(s).)

Here, we aim to describe COVID-19 pathology across different tissues to clarify the disease's pathophysiology. Lungs, kidneys, hearts, and brains from nine COVID-19 autopsies were compared by using antibodies against SARS-CoV-2, macrophages-microglia, T-lymphocytes, B-lymphocytes, and activated platelets. Alzheimer's Disease pathology was also assessed. PCR techniques were used to verify the presence of viral RNA. COVID-19 cases had a short clinical course (0-32 days) and their mean age was 77.4 y/o. Hypoxic changes and inflammatory infiltrates were present across all tissues. The lymphocytic component in the lungs and kidneys was predominant over that of other tissues ( p < 0.001), with a significantly greater presence of T-lymphocytes in the lungs ( p = 0.020), which showed the greatest presence of viral antigens. The heart showed scant SARS-CoV-2 traces in the endothelium-endocardium, foci of activated macrophages, and rare lymphocytes. The brain showed scarce SARS-CoV-2 traces, prominent microglial activation, and rare lymphocytes. The pons exhibited the highest microglial activation ( p = 0.017). Microthrombosis was significantly higher in COVID-19 lungs ( p = 0.023) compared with controls. The most characteristic pathological features of COVID-19 were an abundance of T-lymphocytes and microthrombosis in the lung and relevant microglial hyperactivation in the brainstem. This study suggests that the long-term sequelae of COVID-19 derive from persistent inflammation, rather than persistent viral replication.

Alzheimer's disease (AD) and Lewy body dementia (LBD) are two different forms of dementia, but their pathology may involve the same cortical areas with overlapping cognitive manifestations. Nonetheless, the clinical phenotype is different due to the topography of the lesions driven by the different underlying molecular processes that arise apart from genetics, causing diverse neurodegeneration. Here, we define the commonalities and differences in the pathological processes of dementia in two kindred cases, a mother and a son, who developed classical AD and an aggressive form of AD/LBD, respectively, through a neuropathological, genetic (next-generation sequencing), and transcriptomic (RNA-seq) comparison of four different brain areas. A genetic analysis did not reveal any pathogenic variants in the principal AD/LBD-causative genes. RNA sequencing highlighted high transcriptional dysregulation within the substantia nigra in the AD/LBD case, while the AD case showed lower transcriptional dysregulation, with the parietal lobe being the most involved brain area. The hippocampus (the most degenerated area) and basal ganglia (lacking specific lesions) expressed the lowest level of dysregulation. Our data suggest that there is a link between transcriptional dysregulation and the amount of tissue damage accumulated across time, assessed through neuropathology. Moreover, we highlight that the molecular bases of AD and LBD follow very different pathways, which underlie their neuropathological signatures. Indeed, the transcriptome profiling through RNA sequencing may be an important tool in flanking the neuropathological analysis for a deeper understanding of AD and LBD pathogenesis.

Objective: Few studies have examined lockdown effects on the way of living and well-being of older adults stratified by cognitive state. Since cognitive deficits are common in this population, we investigated how cognition influenced their understanding of the pandemic, socio-behavioral responses and lifestyle adaptations during lockdown, and how these factors affected their mood or memory., Method: Telephone-based survey involving 204 older adults ≥65 y/o (median: 82) with previous assessments of cognitive state: 164 normal-old (NOLD), 24 mild-neurocognitive disorder (mild-NCD), 18 mild-moderate dementia. A structured questionnaire was developed to assess psychological and socio-behavioral variables. Logistic regression was used to ascertain their effects on mood and memory., Results: With increasing cognitive deficits, understanding of the pandemic and the ability to follow lockdown policies, adapt to lifestyle changes, and maintain remote interactions decreased. Participants with dementia were more depressed; NOLDs remained physically and mentally active but were more bored and anxious. Sleeping and health problems independently increased the likelihood of depression (OR: 2.29; CI: 1.06-4.93; p  = 0.034 and OR: 2.45; CI: 1.16-5.16; p  = 0.018, respectively); Regular exercise was protective (OR: 0.30; CI: 0.12-0.72; p  = 0.007). Worsening subjective memory complaints were associated with dementia ( p  = 0.006) and depression ( p  = 0.004); New-onset sleeping problems raised their odds (OR: 10.26; CI: 1.13-93.41; p  = 0.039). Finally, >40% with health problems avoided healthcare mainly due to fear of contagion., Discussion: NOLD and mild-NCD groups showed similar mood-behavioral profiles suggesting better tolerance of lockdown. Those with dementia were unable to adapt and suffered from depression and cognitive complaints. To counteract lockdown effects, physical and mental activities and digital literacy should be encouraged.

In people with multiple sclerosis (PwMS), strict follow-up is essential. Telemedicine has the potential to overcome many of the difficulties in routine management. Herein, we present a structured protocol that can be used to remotely manage patients with MS, describing in detail the steps to be taken and exams needed at each stage. A working group was established which developed a tailored protocol that can be adapted to a variety of settings. The overall protocol consisted of 5 phases: enrolment, document sharing phase, pre-evaluation, virtual visit, and post-visit phase, which was divided into 14 individual steps. As of October 2020, 25 virtual visits have been carried out, all via Skype. The patient's caregiver was present during visits and had an active role. The average duration of the virtual visit was 24 min, and that of the pre-visit and post-visit were around 15 min each. Overall satisfaction as rated by physicians was considered high (8.0 ± 0.5). Using the system usability scale (SUS), patients also favorably rated the virtual visit (96.6 ± 6.1). In 20% of cases, the virtual visit was not sufficient to provide adequate information and an in-person clinical visit was recommended. The described protocol has the potential to provide benefits for the healthcare system as well as patients and their caregivers both during and beyond COVID-19 pandemic., (© 2021. The Author(s).)

Since the association of SARS-Cov-2 infection with Nervous System (NS) manifestations, we performed RNA-sequencing analysis in Frontal Cortex of COVID-19 positive or negative individuals and affected or not by Dementia individuals. We examined gene expression differences in individuals with COVID-19 and Dementia compared to Dementia only patients by collecting transcript counts in each sample and performing Differential Expression analysis. We found eleven genes satisfying our significance criteria, all of them being protein coding genes. These data are suitable for integration with supplemental samples and for analysis according to different individuals' classification. Also, differential expression evaluation may be implemented with other scientific purposes, such as research of unannotated genes, mRNA splicing and genes isoforms. The analysis of Differential Expressed genes in COVID-19 positive patients compared to non-COVID-19 patients is published in: S. Gagliardi, E.T. Poloni, C. Pandini, M. Garofalo, F. Dragoni, V. Medici, A. Davin, S.D. Visonà, M. Moretti, D. Sproviero, O. Pansarasa, A. Guaita, M. Ceroni, L. Tronconi, C. Cereda, Detection of SARS-CoV-2 genome and whole transcriptome sequencing in frontal cortex of COVID-19 patients., Brain. Behav. Immun. (2021). https://doi.org/10.1016/j.bbi.2021.05.012., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2021 Published by Elsevier Inc.)

SARS-Cov-2 infection is frequently associated with Nervous System manifestations. However, it is not clear how SARS-CoV-2 can cause neurological dysfunctions and which molecular processes are affected in the brain. In this work, we examined the frontal cortex tissue of patients who died of COVID-19 for the presence of SARS-CoV-2, comparing qRT-PCR with ddPCR. We also investigated the transcriptomic profile of frontal cortex from COVID-19 patients and matched controls by RNA-seq analysis to characterize the transcriptional signature. Our data showed that SARS-CoV-2 could be detected by ddPCR in 8 (88%) of 9 examined samples while by qRT-PCR in one case only (11%). Transcriptomic analysis revealed that 11 genes (10 mRNAs and 1 lncRNA) were differential expressed when frontal cortex of COVID-19 patients were compared to controls. These genes fall into categories including hypoxia, hemoglobin-stabilizing protein, hydrogen peroxide processes. This work demonstrated that the quantity of viral RNA in frontal cortex is minimal and it can be detected only with a very sensitive method (ddPCR). Thus, it is likely that SARS-CoV-2 does not actively infect and replicate in the brain; its topography within encephalic structures remains uncertain. Moreover, COVID-19 may have a role on brain gene expression, since we observed an important downregulation of genes associated to hypoxia inducting factor system (HIF) that may inhibit the capacity of defense system during infection and oxigen deprivation, showing that hypoxia, well known multi organ condition associated to COVID-19, also marked the brain., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The actual role of SARS-CoV-2 in brain damage remains controversial due to lack of matched controls. We aim to highlight to what extent is neuropathology determined by SARS-CoV-2 or by pre-existing conditions. Findings of 9 Coronavirus disease 2019 (COVID-19) cases and 6 matched non-COVID controls (mean age 79 y/o) were compared. Brains were analyzed through immunohistochemistry to detect SARS-CoV-2, lymphocytes, astrocytes, endothelium, and microglia. A semi-quantitative scoring was applied to grade microglial activation. Thal-Braak stages and the presence of small vessel disease were determined in all cases. COVID-19 cases had a relatively short clinical course (0-32 days; mean: 10 days), and did not undergo mechanical ventilation. Five patients with neurocognitive disorder had delirium. All COVID-19 cases showed non-SARS-CoV-2-specific changes including hypoxic-agonal alterations, and a variable degree of neurodegeneration and/or pre-existent SVD. The neuroinflammatory picture was dominated by ameboid CD68 positive microglia, while only scant lymphocytic presence and very few traces of SARS-CoV-2 were detected. Microglial activation in the brainstem was significantly greater in COVID-19 cases (p = 0.046). Instead, microglial hyperactivation in the frontal cortex and hippocampus was clearly associated to AD pathology (p = 0.001), regardless of the SARS-CoV-2 infection. In COVID-19 cases complicated by delirium (all with neurocognitive disorders), there was a significant enhancement of microglia in the hippocampus (p = 0.048). Although higher in cases with both Alzheimer's pathology and COVID-19, cortical neuroinflammation is not related to COVID-19 per se but mostly to pre-existing neurodegeneration. COVID-19 brains seem to manifest a boosting of innate immunity with microglial reinforcement, and adaptive immunity suppression with low number of brain lymphocytes probably related to systemic lymphopenia. Thus, no neuropathological evidence of SARS-CoV-2-specific encephalitis is detectable. The microglial hyperactivation in the brainstem, and in the hippocampus of COVID-19 patients with delirium, appears as a specific topographical phenomenon, and probably represents the neuropathological basis of the "COVID-19 encephalopathic syndrome" in the elderly., (© 2021 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

The new Italian Law no. 10 of 2020, titled 'Rules relating to the directives of one's body and tissues post-mortem for study, training, and scientific research purposes' (10 February, 2020), has opened the doors to a new and clearer regimentation on body donation to science, according to the procedure already introduced by Law no. 219/2017 on the 'Rules relating to informed consent and advance directives of treatment'. The authors exposed some concerning regarding the application of the law, such as donation mistrust, also linked to our cultural heritage; the incomplete protection of minor and incompetent people; the complexity of an adequate information, which could undermine the informed consent; and finally, the fees overload for research institutes, with already exiguous budgets. Next, the authors analysed some positive aspects of the law and in primis the central role of corpses in scientifical knowledge and medical training. Moreover, a simple mechanism based on a conscious and pre-stated consent, registered in a database that follows European data protection Regulation, is discussed. Further, the procedure of the restitution of the bodies to their families, which represents a way to guarantee the relatives' commemoration, is also elucidated. In conclusion, the authors proposed a format of informed consent, to try a direct application of the law, thereby fastening the process of standardisation and centralisation of all the living wills. The authors optimistically investigated the opportunities offered by the law and encouraged a conscientious participation by citizens., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Purpose: Whatman™ 903 cards represent a valid type of support for collection, storage, and analysis of dried blood spots (DBS). Whatman™ FTA (Flinders Technology Associates) are a type of cards soaked in chemicals that cause denaturation of proteins, while preserving DNA and ensuring the safe handling of DBS; to date, these cards are still rarely employed in forensic toxicology. The aim of this study was to analyze several psychoactive substances on not-dried blood on the two different cards and to compare the qualitative and quantitative results., Methods: Twenty cardiac postmortem blood samples were collected and deposed on Whatman™ 903 and Whatman™ FTA cards. Spots and not-dried blood were analyzed following our validated and previously published liquid chromatography-mass spectrometry methods., Results: We were able to identify: eight drugs of abuse and their metabolites (15 cases), five benzodiazepines and their metabolites (3 cases), six antidepressants (6 cases) and two antipsychotics (3 cases). We observed a perfect qualitative correspondence and a general good quantitative correlation between data obtained from not-dried blood and the two different DBS cards, except for alprazolam, diazepam, desmethyldiazepam, fluoxetine and sertraline, that showed a lower concentration on FTA. Additional experiments suggest that the chemicals, adsorbed on FTA, are not the cause of the loss of signal observed for the substances previously mentioned and that methanol should be preferred as extraction solvent., Conclusions: This study proved that FTA cards are a good and a hazard-free alternative sample storage method for analysis of several psychoactive substances in postmortem blood., Supplementary Information: The online version contains supplementary material available at 10.1007/s11419-020-00567-2., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2021.)

Nowadays fentanyl and its analogs represent the most numerous group among synthetic opioid and, due to their higher potency in comparison to traditionl opioids, the main cause of the critical increase of fatal intoxications opioids-intake related in the USA. We developed an LC-MS/MS method for the detection and quantification of fentanyl and its analogs in hair, then applied to 117 real samples, 97 collected from drugs users and 20 from postmortem cases of drugs addicts. The ionization and MRM parameters have been optimized for 27 molecules: 20 reached the acceptance criteria for identification and quantification. LODs and LOQs of 0.2 and 0.5 pg/mg, respectively, were reached for most of the substances, except for five compounds for which were set at 0.5 and 1.0 pg/mg. 2 out of the 97 samples collected from drug users tested positive; one for carfentanil, butyryl fentanyl, THFF and ocfentanil; the other one for 3-methyl norfentanyl. 2 out of the 20 postmortem samples show positive results: one only for fentanyl, the other for furanyl fentanyl, acetyl fentanyl, methoxyacetyl fentanyl, methoxyacetyl norfentanyl, ocfentanil and 4-ANPP. Despite the relatively small number of samples, the results suggest that the method should be included in routine hair analyses for monitoring the new synthetic opioids potential intake by drug users., Competing Interests: Declaration of Competing Interest All authors have participated in (a) conception and design, or analysis and interpretation of the data; (b) drafting the article or revising it critically for important intellectual content; and (c) approval of the final version. This manuscript has not been submitted to, nor is under review at, another journal or other publishing venue. The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Delirium may be one of the presenting symptoms of COVID-19, complicating diagnosis and care of elderly patients with dementia. We aim to identify the prevalence and prognostic significance of delirium as the sole onset manifestation of COVID-19., Methods: This is a retrospective single-centre study based on review of medical charts, conducted during the outbreak peak (March 27-April 18, 2020) in a Lombard dementia facility, including 59 elderly subjects with dementia and laboratory-confirmed COVID-19., Findings: Of the 59 residents, 57 (96⋅6%) tested positive (mean age: 82⋅8; women: 66⋅7%). Comorbidities were present in all participants, with 18/57 (31⋅6%) having three or more concomitant diseases. Delirium -Onset COVID-19 (DOC) was observed in 21/57 (36⋅8%) subjects who were chiefly older (mean age: 85⋅4 y/o) and with multiple comorbidities. Eleven/21 DOC patients (52⋅4%) had hypoactive delirium , while hyperactive delirium occurred in ten/21 (47⋅6%). Lymphopenia was present in almost all subjects (median: 1⋅3 × 10 9 /L). Overall mortality rate was 24⋅6% (14/57) and dementia severity per se had no impact on short-term mortality due to COVID-19. DOC was strongly associated with higher mortality ( p <0⋅001). Also, DOC and male gender were independently associated with increased risk of mortality (OR: 17⋅0, 95% CI: 2⋅8-102⋅7, p  = 0⋅002 and 13⋅6, 95% CI: 2⋅3-79⋅2, p  = 0⋅001 respectively)., Interpretation: Delirium occurrence in the elderly with dementia may represent a prodromal phase of COVID-19, and thus deserves special attention, especially in the presence of lymphopenia. Hypoxia and a severe inflammatory state may develop subsequently. DOC cases have higher short-term mortality rate., Funding: None., Competing Interests: None, (© 2020 The Author(s).)

Migraine is a highly prevalent and disabling disorder accounted among the primary headaches. It is the expression of a complex, and not yet fully understood, pathophysiology involving the sensitization of peripheral and central nociceptive pathways. In this review we succinctly illustrate the molecular, anatomical, and functional abnormalities underlying the migraine attack that are relevant for understanding in more depth the neurobiology behind the therapeutic effect of Botulinum Toxin Type A (BoNT-A). BoNT-A has proved effective in several neurological conditions and, more recently, also in chronic migraine. Its antimigraine mechanism of action was initially thought to be limited to the periphery and interpreted as an inhibitory activity on the processes associated to the local release of neuropeptides, with subsequent induction of peripheral sensitization. Increasing experimental evidence has become available to suggest that additional mechanisms are possibly involved, including the direct/indirect inhibition of sensitization processes in central nociceptive pathways., Competing Interests: Declaration of competing interest In the last 3 years CT has participated in advisory boards for Allergan, ElectroCore, Eli Lilly, Novartis and Teva; she has lectured at symposia sponsored by Allergan, Eli Lilly, Novartis and TEVA; she is PI or collaborator in clinical trials sponsored by Alder, Eli-Lilly and Teva. She has received grants from the European Commission, the Italian Ministry of Health and the Italian Ministry of University. DM, AS, LV have no o conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The interest in antimicrobial compounds as feed additives is currently increasing. Among different options, tannins seem to have several beneficial effects when employed in animals diet. The present study aimed at investigating the influence on caecal microbial communities of the supplementation of a chestnut and quebracho tannins mix in meat rabbit's diet, also considering animals live performances. Four groups of rabbits were fed with a different diet: a control diet (C); a control diet with coccidiostat (CC), and two experimental diets with 0.3% (T0.3) and 0.6% (T0.6) chestnut and quebracho tannins mix. For microbial analysis, culture-dependent and culture-independent methods were employed. Live performances were not significantly affected by tannins mix supplementations, as well as culturable microbial loads of E. coli, Enterobacteriaceae, Bacteroides spp. and Bifidobacterium spp. C. perfringens was always under the detection limit. A consistent result was obtained by qPCR. As for PCR-DGGE analysis, the Richness and evenness (Shannon-Weiner index) of bacterial communities in caecum resulted significantly higher in control samples (C and CC) than in those from rabbit fed with tannin-containing diets. Sequencing analysis revealed that the phylum Firmicutes was less represented in samples from control groups. As for the methanogen archaeal DGGE, no significant differences were found in richness and diversity among different groups, all dominated by Methanobrevibacter spp.. This work highlights the potential antimicrobial effect of chestnut and quebracho tannins mix in an in vivo system revealed by molecular analysis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

There are few literature evidences about the intellectual profile of adolescents with headache and no study has used the fourth edition of the Wechsler Intelligence Scale for Children (WISC-IV) in patients with a diagnosis of headache according to the ICHD-III-beta. We recruited 30 patients (age 11-14 years; male:female = 1:2) seen for headache in a tertiary center in Northern Italy and 30 healthy controls matched for age and sex, recruited in a public school from the same geographic area. The diagnosis of headache was done according to the ICHD-III criteria (beta version): the case group was composed of 16 patients with migraine and 14 with tension-type headache. Cognitive functioning was assessed using the WISC-IV. Recruited patients with idiopathic headache diagnosis had on average a cognitive function within the normal range. We found no statistically significant differences in the total Intellective Quotient comparing patients with headache and controls; the Working Memory Index was, however, lower in patients with headache ( p  = 0.012), and in particular, we found a lower Digit Span ( p  < 0.001). We also found a borderline statistical difference ( p  = 0.051) between case and controls Verbal Comprehension Index (CVI), which was due to a lower score in the Similarities subtest ( p  < 0.001). Our results suggest that, although within normal limits, cognitive functioning of adolescents with headache differs from that of healthy peers regarding memory and verbal skills. The Working Memory Index is related to the subject's ability to store new information and keep them in short-term memory, to maintain focused attention and to manipulate them to find solutions. The difference in Similarities is also important because it provides a measure of the level of verbal reasoning and concept formation; it is also a measure of verbal abstract thinking skills relevant for language development, lexical knowledge, auditory comprehension, memory, and ability to discriminate between essential and non-essential characteristics. Our data, in keep with previous findings, suggest the need for further researches to better understand the pathogenesis of these difficulties and obtain ideas for an adequate rehabilitative treatment.

According to/After the conferences taken place on 30th October and on 18th December 2008, the company doctor functions have been enlarged: at present they include the duty of effectuating toxicological tests in order to find psychotropic and drug substances in some specific working classes, mainly in workers employed in public transports. Company doctors have the duty to report any possible positive matching in these workers'tests. From there, regulations in force are analyzed focusing to critical situations described in the complex and well articulated frame of reference.

Congestive heart failure represents the most common medical hospital discharge diagnosis, and can occur in patients with preserved indexes of left ventricular systolic function, even in absence of patent coronary or valvular heart disease. The present review examines the role of imaging techniques in the diagnosis and follow-up of these patients. Imaging of the heart has undergone dramatic advances with the development and refinement of new imaging modalities such as echocardiography, computed tomography, magnetic resonance and radionuclide emission tomography. The role of "low-tech" modalities such as chest roentgenogram is discussed. The possibilities offered by ultrasounds or magnetic resonance in tissue characterization are then compared with the actual capability of cardiac imaging in detecting myocardial tissue alterations (oedema, ischemia, myocarditis, etc.) and/or degeneration (fatty degeneration, fibrosis, amyloidosis, etc.). Finally, the potential use in modern clinical medicine of magnetic resonance spectroscopy and positron emission tomography to study myocardial metabolism and cellular function are discussed.

The continuity equation, applied to the flow convergence region (FCR), fournishes a simple alternative to calculate stenotic valve area. The flow rate in the FCR can be calculated by multiplying the hemispheric isovelocity surface area by the velocity of the isovelocity surface. Since according to the continuity principle the flow rate through any isovelocity surface equals the flow rate through the stenotic orifice, the stenotic orifice area can be calculated as: 2 pi r2Vr/Vm, where 2 pi r2 is the hemispheric isovelocity area, Vr is the velocity at the radial distance r from the orifice and Vm is the peak jet velocity. This study was designed to analyze the validity of application of the continuity equation to the FCR for estimating mitral orifice area by Dopler ultrasound. We studied 35 consecutive patients with rheumatic mitral stenosis. Three patients were excluded; the final study population consisted of 32 patients (8 men and 24 women; mean age 56 years). Nine patients were in normal sinus rhythm and 23 in atrial fibrillation. Doppler examination was performed from the apical approach within 24 hours of cardiac catheterization. On color Doppler image Vr was defined as the first aliasing limit (lowered to 38 cm/s to increase FCR r); r represented the maximal early diastolic distance between the first alias and the stenotic orifice in a direction parallel to that of the transducer; Vm was the early diastolic peak jet velocity by continuous wave Doppler.(ABSTRACT TRUNCATED AT 250 WORDS)

In prosthetic or paravalvular prosthetic mitral regurgitation, transthoracic color Doppler flow mapping can sometimes fail to detect the regurgitant jet within the left atrium because of the shadowing by the prosthetic valve. To overcome this limitation, we assessed the utility of color Doppler visualization of the flow convergence region (FCR) proximal to the regurgitant orifice in 20 consecutive patients with mechanical prosthetic mitral regurgitation documented by surgery and cardiac catheterization (13 of 20 patients). In addition, we studied 33 patients with normally functioning mitral prostheses. Doppler studies were performed in the apical, subcostal, and parasternal long-axis views. An FCR was detected in 95% (19 of 20) of patients with prosthetic mitral regurgitation. A jet area in the left atrium was detected in 60% (12 of 20) of patients. In 18 of 19 patients with Doppler-detected FCR, the site of the leak was correctly identified by observing the location of the FCR. A trivial jet area was detected in eight patients with a normally functioning mitral prosthesis; in none was an FCR identified. Thus color Doppler visualization of the FCR proximal to the regurgitant orifice is superior to the jet area in the diagnosis of mechanical prosthetic mitral regurgitation. Moreover, FCR permits localization of the site of the leak with good accuracy.

Congenital absence of the left pericardium, partial or complete, is an uncommon cardiac defect. Most patients affected by this abnormality are asymptomatic. Usually it is suspected on the basis of a chest X-ray showing a normal sized cardiac shadow projecting entirely to the left of the spine. Computed axial tomography confirmed the absence of the left pericardium detecting the interposition of the left lung between the ascending aorta and main pulmonary artery. The M-mode, two-dimensional, and Doppler-cardiographic findings of complete congenital absence of the left pericardium are described in two cases. Imaging seems to be not specific for this abnormality; however in both cases pulsed Doppler detected mild tricuspid and pulmonic valve regurgitation.