PKCε promotes human Th17 differentiation: Implications in the pathophysiology of psoriasis.

PKCε is implicated in T cell activation and proliferation and is overexpressed in CD4+ -T cells from patients with autoimmune Hashimoto's thyroiditis. Although this might induce the suspicion that PKCε takes part in autoimmunity, its role in the molecular pathophysiology of immune-mediated disorders is still largely unknown. We studied PKCε expression in circulating CD4+ -T cells from patients with psoriasis, a skin disorder characterized by an increased amount of Th17 cells, a CD4+ subset that is critical in the development of autoimmunity. Although the mechanisms that underlie Th17 differentiation in humans are still unclear, we here show that: (i) PKCε is overexpressed in CD4+ -T cells from psoriatic patients, and its expression positively correlates with the severity of the disease, being reduced by effective phototherapy; (ii) PKCε interacts with Stat3 during Th17 differentiation and its overexpression results in an enhanced expression of Stat3 and pStat3(Ser727); iii) conversely, when PKCε is forcibly downregulated, CD4+ -T cells show lower levels of pStat3(Ser727) expression and defective in vitro expansion into the Th17-lineage. These data provide a novel insight into the molecular mechanisms of Th17 cell polarization that is known to play a crucial role in autoimmunity, pinpointing PKCε as a potential target in Th17-mediated diseases.

Sulphurous thermal water inhalation impacts respiratory metabolic parameters in heavy smokers.

Sulphurous thermal water inhalations have been traditionally used in the treatment of airway diseases. In vivo and in vitro studies reported that they ameliorate mucus rheology, mucociliary clearance and reduce inflammation. Cigarette smoking induces an inflammatory damage, with consequent remodeling of respiratory airways, which in turn affect pulmonary functions. Despite the anti-inflammatory effects of H2S are clinically documented in several airway inflammatory diseases, data on the effects of sulphurous thermal water treatment on pulmonary function and biomarkers of airways inflammation in smokers are still scant. Therefore, we investigated whether a conventional cycle of sulphurous thermal water inhalation produced changes in markers of respiratory inflammation and function. A cohort of 504 heavy current and former smokers underwent 10-day cycles of sulphurous thermal water inhalation. Pulmonary function and metabolic analyses on exhaled breath condensate were then performed at day 0 and after the 10-day treatment. Spirometric data did not change after spa therapy, while exhaled breath condensate analysis revealed that a single 10-day cycle of sulphurous water inhalation was sufficient to induce a statistically significant increase of citrulline levels along with a decrease in ornithine levels, thus shifting arginine metabolism towards a reduced nitric oxide production, i.e. an anti-inflammatory profile. Overall, sulphurous thermal water inhalation impacts on arginine catatabolic intermediates of airways cells, shifting their metabolic balance towards a reduction of the inflammatory activity, with potential benefits for smokers.

Safe drugs in drug facilitated crimes and acute intoxications in Northern Italy.

Toxicological analyses are often performed in drug-facilitated sexual assaults (DFSA), when the victim shows or reports impaired consciousness and reduced ability. However, in other crimes or fatalities, especially in cases of concurrent natural disease or when another likely cause of death has been established, the involvement of drugs can be overlooked. The aim of this study is to report a series of cases of (i) victims of drug-facilitated crimes (DFC) other than DFSA and (ii) victims of acute intoxications, in which "licit" psychoactive drugs were found in blood samples, with the aim of understanding in which circumstances and to what extent prescription drugs have been used for non-medical purposes in recent Italian casuistry. Circumstantial, autopsy, and toxicological data were collected through a retrospective analysis performed between 2013 and 2017 in the Forensic Toxicology Unit of the University of Bologna. Cases of "DFC other than DFSA" and "Acute Intoxication" in which "psychoactive drugs" or "prescription drugs" or "licit drugs" were found in the blood samples of the victims were included in the study. Nine cases of DFC other than DFSA, and 11 cases of acute intoxication, were identified. Different categories of "licit" psychoactive drugs (e.g. hypnotics, antipsychotics, antidepressants, anticonvulsants) had been used to facilitate diverse types of crime (homicide, robberies, elder abuse, fatal poisoning) or acute intoxication (suicide, attempted suicide, accidental death). The circumstances of these cases, as well as toxicological findings in blood samples and other relevant forensic elements, are reported, summarized and discussed in this paper. The non-medical use of pharmaceuticals has been identified by recent forensic literature and the present study as a significant and growing phenomenon, and its implication in fatalities should be taken into consideration and accurately investigated through appropriate toxicological analysis. Our study presents an overview of the circumstances of non-medical use of prescription drugs, usually considered "safe drugs", and their involvement in cases of DFC, suicides and accidental intoxication. In order to estimate the real incidence of these medications in DFC and acute intoxication, and thus collect more analytical and contextual data, further studies are needed, along with effective cooperation among police officers, clinicians, forensic pathologists, and toxicologists.

Over 30-year retrospective analyses of moped-motorcycle fatal road accidents in the northern area of the Italian region of Emilia Romagna and review of the literature: Aiming for further preventive measures in the future.

Road traffic injuries are a major cause of morbidity and mortality worldwide, with pedestrians and riders of two-wheeled motor vehicles being the most vulnerable. The present study aims to determine the epidemiological characteristics of fatal motorcycle crashes in a portion of the Italian region of Emilia Romagna, and to compare them with the data available in literature. Data were retrieved from autopsy reports on 350 subjects who died following road accidents involving moped or motorcycle in the cities of Parma, Piacenza, and Reggio Emilia. Two types of data were extrapolated: circumstantial and traumatological. The population was divided into subgroups according to gender, crash time, alcohol positivity, presence or absence of the helmet, and the period elapsed between the accident and death. Most of the considered road accidents occurred during the day and on weekends. 25.5 % of the victims tested positive for alcohol. As far as traumas are concerned, the limbs resulted to be the most affected body segment, followed by the head (87.4 %), the thorax (85.7 %), the abdomen (65.7 %), and lastly the neck (50.3 %). According to similar studies, the sample victim of a moped/ motorcycle accident is a young male subject. The results obtained allow us to demonstrate that the mandatory use of the helmet has reduced skull and brain injury over the years. At present, no law regulates the use of protections for other body parts. Regulatory interventions in this sense would be desirable given the ever more rapid technical evolutions in the field of motorcycles.

Posture and gait in the early course of schizophrenia.

While correlations between postural stability deficits and schizophrenia are well documented, information on dynamic motor alterations in schizophrenia are still scarce, and no data on their onset are available yet. Therefore, the aim of this study was i) to measure gait pattern(s) in patients with schizophrenia; ii) to identify posture and gait alterations which could potentially be used as a predictive clinical tool of the onset of the disorder. Body composition, posture and gait parameters were assessed in a group of 30 patients with schizophrenia and compared to 25 healthy subjects. Sway area was significantly higher in the schizophrenia group compared to controls regardless of whether the participants were in eyes open or eyes closed condition. Gait cadence and speed were significantly lower in patients with schizophrenia, while stride length was similar. We concluded that the combination of an increased sway area (independent from eye closure) and a gait cadence reduction-in the presence of normal gait speed and stride length-might be considered peculiar postural and gait profile characteristic of early schizophrenia.

Clinicopathological Bird's-Eye View of Left Atrial Myocardial Fibrosis in 121 Patients With Persistent Atrial Fibrillation: Developing Architecture and Main Cellular Players.

BACKGROUND: Scientific research on atrial fibrosis in atrial fibrillation (AF) has mainly focused on quantitative or molecular features. The purpose of this study was to perform a clinicoarchitectural/structural investigation of fibrosis to provide one key to understanding the electrophysiological/clinical aspects of AF. METHODS: We characterized the fibrosis (amount, architecture, cellular components, and ultrastructure) in left atrial biopsies from 121 patients with persistent/long-lasting persistent AF (group 1; 59 males; 60±11 years; 91 mitral disease-related AF, 30 nonmitral disease-related AF) and from 39 patients in sinus rhythm with mitral valve regurgitation (group 2; 32 males; 59±12 years). Ten autopsy hearts served as controls. RESULTS: Qualitatively, the fibrosis exhibited the same characteristics in all cases and displayed particular architectural scenarios (which we arbitrarily subdivided into 4 stages) ranging from isolated foci to confluent sclerotic areas. The percentage of fibrosis was larger and at a more advanced stage in group 1 versus group 2 and, within group 1, in patients with rheumatic disease versus nonrheumatic cases. In patients with AF with mitral disease and no rheumatic disease, the percentage of fibrosis and the fibrosis stages correlated with both left atrial volume index and AF duration. The fibrotic areas mainly consisted of type I collagen with only a minor cellular component (especially fibroblasts/myofibroblasts; average value range 69-150 cells/mm2, depending on the areas in AF biopsies). A few fibrocytes-circulating and bone marrow-derived mesenchymal cells-were also detectable. The fibrosis-entrapped cardiomyocytes showed sarcolemmal damage and connexin 43 redistribution/internalization. CONCLUSIONS: Atrial fibrosis is an evolving and inhomogeneous histological/architectural change that progresses through different stages ranging from isolated foci to confluent sclerotic zones which-seemingly-constrain impulse conduction across restricted regions of electrotonically coupled cardiomyocytes. The fibrotic areas mainly consist of type I collagen extracellular matrix and, only to a lesser extent, mesenchymal cells.

A case report positive for synthetic cannabinoids: are cardiovascular effects related to their protracted use?

The use of synthetic cannabinoids is being increasingly recognised worldwide, but the chemical compositions and physiological effects of these drugs are poorly characterised and are continually changing. New substances are constantly being added to the content of synthetic cannabinoids and they are rarely identified on toxicological screening tests. Due to their structures synthetic cannabinoids and their effects have been compared to the psychoactive compound, Δ-9-tetrahydrocannabinol (THC), found in marijuana. On the molecular level, they are potent cannabinoid receptor agonists that also may have affinity for other types of receptors such as those on platelets. Reported symptoms of toxicity include anxiety, agitation, paranoia, hallucinations, tachycardia, hypertension, excessive sweating, nausea, and vomiting. They can also be linked to serious adverse cardiovascular events and can affect the cardiovascular system causing hypotension and bradycardia, myocardial infarction, atrial fibrillation, prolonged QTc, and Mobitz type II atrioventricular block, as well as interfere with the aggregation of platelets. We present a case report of a cardiac tamponade with toxicological findings positive for synthetic cannabinoids. This case highlights the importance of testing routinely for novel psychoactive compounds, and recognising their potential to cause life-threatening conditions.

Planned and unplanned complex suicides: Casuistry of the Institute of Legal Medicine of Parma (Italy).

Complex suicide is performed using more harmful methods, simultaneously or consecutively. In these cases, the distinction between suicide and homicide represents a challenge for forensic pathologists. In literature, complex suicide is divided in two subgroups: "planned complex suicide" or "unplanned complex suicide" depending from forensic features and often related to psychiatric variables. Aim of this study was to show the casuistry of complex suicide in Parma's Forensic service analyzing, for each case, the forensic medical problems (type and site of lesions on the body), and the supplementary data [Police's inspection report, toxicological analysis and psychiatric anamnesis (when available)], trying, through a multidisciplinary approach, to determine a possible correlation between the victim's mood and suicide's method chosen, whether planned or unplanned. Our results showed the importance of all the elements collected on the crime scene to distinguish suicide from homicide, and the correlation between bipolar disorder, borderline personality disorder and schizophrenia with unplanned complex suicide (because of the impulsiveness), and major depression disorder and anxiety disorder with planned complex suicide. Being able to understand the causes behind this extreme gesture may become important not only for forensic pathologists and judicial authority, but also, and above all, for the family as well.

Right posterior diaphragmatic hernia (Bochdalek) with liver involvement and alteration of hepatic outflow in adult: a case report.

INTRODUCTION: Posterior right diaphragmatic hernia is rare in newborn patients but when present, is accompanied by high mortality. Pulmonary hypoplasia seems to be the main cause of death but the presence of liver involvement remains one of the reasons for poor prognosis even when intrauterine surgery is performed. CASE DESCRIPTION: In this article, we will present a rare case that was diagnosed by chance in a 65-year old adult presenting with an adenocarcinoma of the rectosigmoid junction and a right Bochdalek hernia with liver herniation and modification of the hepatic vein outflow with a natural right to left shunt. DISCUSSION: Diaphragmatic repair was performed on the patient with a mash and simultaneous colorectal resection. Intraoperatively, the exceptional natural modification of the hepatic outflow and alteration of the caval system was evident. CONCLUSION: This case report represent an extremely rare anatomic variation and could be useful to give new important information on the evolution that occur in foetal life.