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Purpose During alternate movements across a joint, the changeover from one direction of rotation to the opposite may be influenced by the delay and rate of tension reduction and the compliance to re-lengthening of the previously active muscle group. Given the aging process may affect the above-mentioned factors, this work aimed to compare the dynamics of both the ankle torque decline and muscle re-lengthening, mirrored by mechanomyogram (MMG), in the tibialis anterior because of its important role in gait. Methods During the relaxation phase, after a supramaximal 35 Hz stimulation applied at the superficial motor point, in 20 young (Y) and 20 old (O) subjects, the torque (T) and MMG dynamics characteristics were measured. Results The T and MMG analysis provided: (I) the beginning of the decay after cessation of stimulation (T: 22.51 ± 5.92 ms [Y] and 51.35 ± 15.21 ms [O]; MMG: 27.38 ± 6.93 ms [Y] and 61.41 ± 18.42 ms [O]); (II) the maximum rate of reduction (T: − 110.4 ± 45.56 Nm/s [Y] and − 52.72 ± 32.12 Nm/s [O]; MMG: − 24.47 ± 10.95 mm/s [Y] and − 13.76 ± 6.54 mm/s [O]); (III) the muscle compliance, measuring the MMG reduction of every 10% reduction of torque (bin 20–10%: 15.69 ± 7.5[Y] and 10.8 ± 3.3 [O]; bin 10–0%: 22.12 ± 10.3 [Y] and 17.58 ± 5.6 [O]). Conclusion Muscle relaxation results are different in Y and O and can be monitored by a non-invasive method measuring physiological variables of torque and re-lengthening dynamics at the end of the electromechanical coupling previously induced by the neuromuscular stimulation.

Drug use in Europe is now more than ever a multifaceted issue involving a broad and ever-changing range of substances. Alarmingly, recent European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) reports show that roughly 83 million adults aged between 15 and 64 years in the European Union have used illicit substances at least once in their lifetime. Polydrug use is rife, and consumption patterns range from experimental/occasional, habitual use all the way to addiction. Traditional epidemiological methods delineating drug abuse specifics (i.e. number of users, age groups, specific characteristics and patterns of use) are questionnaire-based and therefore present the classic biases linked to the selected sample, thus risking an underesti-mation of the phenomenon. The Mario Negri IRCCS Pharmacological Research Institute has developed a new population screening method based on wastewater-based epidemiology (WBE) which makes it possible to detect drug metabolites in waste water and to estimate which and how many substances are consumed by the entire population belonging to the wastewater treatment plant being monitored. Such a technique has gained great interest at the national and international level, and may be especially valuable as a detection/monitoring tool at a time when novel psychoactive substances have come to trigger a major public health crisis, on account of their elusiveness and potential as substitutes/adulterants of traditional substances of abuse.

Introduction Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor for at least 1 month is the mainstay of therapy after an acute coronary syndrome (ACS). Despite several randomized controlled trials (RCTs) having compared different DAPT regimens after an ACS, the choice of the optimal P2Y12 receptor inhibitor is still debated. Purpose We aimed to compare the efficacy and safety profiles of the new P2Y12 receptor inhibitors (prasugrel and ticagrelor) versus clopidogrel in patients with ACS through a meta-analysis of RCTs. Methods We performed an extensive literature search, from January 1970 to December 2021 using PubMed database. Studies were eligible if they were RCTs directly comparing different oral P2Y12 receptor inhibitors in patients with ACS. Data on study methods, patient characteristics, and outcomes of interest (all-cause and cardiovascular death, recurrent myocardial infarction, stroke, major and non-major bleeding) were extracted from the original publications. We performed a meta-analysis using a random-effects model with the Mantel–Haenszel method. The effect measures of each study included were calculated and reported as odds ratio (OR) with 95% confidence interval (CI), visually presented in forest plots. A two-sided p-value Results A total of 117 studies were available for the analysis; after full reading 11 studies were eligible to be analyzed. The 11 studies reported data on 50,722 patients: 25,424 [50.1%] taking a new oral P2Y12 receptor inhibitor and 25,298 [49.9%] taking clopidogrel. Patients receiving ticagrelor or prasugrel showed a lower risk of all-cause mortality (OR 0.88, 95% confidence interval [CI] 0.80–0.97, I2=8%), cardiovascular mortality (OR 0.88, 95% CI 0.81–0.95, I2=0%), and recurrent myocardial infarction (OR 0.86, 95% CI 0.76–0.97, I2=43%) compared to those receiving clopidogrel. The two groups did not differ significantly concerning the risk of stroke (OR 0.98, 95% CI 0.82–1.17, I2=0%), major bleeding (OR 1.05, 95% CI 0.97–1.15, I2=0%), or non-major bleeding (OR 1.36, 95% CI 0.85–2.20, I2=67%). By restricting the analysis to the studies comparing ticagrelor versus clopidogrel, the ticagrelor group showed a lower risk of all-cause mortality (OR 0.79, 95% CI 0.70–0.90, I2=0%), but a higher risk of non-major bleeding (OR 1.67, 95% CI 1.05–2.66, I2=30%). There was no significant difference between ticagrelor and clopidogrel in terms of cardiovascular death (OR 0.87, 95% CI 0.73–1.05, I2=0%), stroke (OR 1.06, 95% CI 0.85–1.13, I2=0%), or major bleeding (OR 1.02, 95% CI 0.93–1.12, I2=0%). Conclusions In patients with an ACS, a DAPT strategy with aspirin plus either prasugrel or ticagrelor is associated with a reduced risk of all-cause and cardiovascular mortality as well as of recurrent myocardial infarction compared to aspirin plus clopidogrel, without an increased risk of bleeding. Funding Acknowledgement Type of funding sources: None.

The level of recognition that transgender individuals (i.e. those whose gender does not match the sex assigned at birth) enjoy in our societies has certainly made giant strides. Still, there is no denying that the far-reaching ramifications arising from choices about one's gender expression do affect vital aspects of identity in school, workplaces, and the community, and should be clearly defined and addressed by laws and policies. One of the arguments most commonly used by supporters of transgender rights relies on the concept of inalienable human rights, including the rights to live safely, freely, and without fearing discrimination. The authors have set out to succinctly outline and elaborate on the dynamics that have been shaping the legal reco-gnition of transgender individuals in light of the unique legal, social and ethical complexities that such an evolution entails. Moreover, as assisted reproduction technologies make considerable progress and innovations open up new horizons for fertility preservation and restoration, it is worth exploring how such advance can play a role in upholding the reproductive rights of transgender patients who wish to achieve parenthood, and how counseling ought to be implemented taking into account the psychological traits of transgender patients and the implications of every choice they make.

The article aims to elaborate on European policy choices for the prevention of SARS‑CoV‑2 contagion, with a close focus on the rules and regulations enacted in Italy so far. European states have ruled out generalized vaccination mandates but have so far preferred to exert a form of "moral suasion", through the introduction of a digital certificate which can only be granted to those who are vaccinated, cured of COVID-19 or tested negative through an antigen test in the previous 48 hours. Italy has applied this tool, dubbed "Green Pass", very rigorously: many daily activities, including going to work, are only allowed for those who have the certificate. A one-year Green Pass is issued after vaccination, although data show that vaccine protection may subside gradually over about six months; the cost of the antigen tests every 48 hours is to be borne by the patient. Testing the unvaccinated is essential to contain the spread of the infection, but it would have been more logical to mandate that all the unvaccinated undergo regular testing (for example every ten days), instead of imposing a test every 48 hours only to be allowed to engage in some activities. The authors stress that in order to minimize the risk of future possible pandemics, prevention strategies are needed, and poor countries need to be enabled to vaccinate their populations in order to prevent new variants from developing. The pledges made by world leaders in that regard during the recent G20 summit must therefore be honored, for the sake of global health that never in our lifetime has been so threatened.

Surrogacy is an arrangement by which a surrogate mother bears a child for another couple or person, and is often thought of as a form of 'treatment' for couples (or even individuals) with fertility or sterility issues. Still, surrogacy entails ethical issues related to gender, fundamental human rights, exploitation and inequality.Starting from the Italian state of affairs, the authors have set out to briefly expound upon such complexities, taking into account relevant jurisprudence on the subject, with a particular focus on inter-country surrogacy and second-parent adoption, which can themselves engender significant legal dilemmas. When residents of countries where surrogacy is banned travel abroad and hire a surrogate, that may lead to considerable legal hurdles as well.In Italy and elsewhere, the courts have all too often had to fill the vacuum left by the lack of targeted legislation. The Italian Constitutional Court has recently urged lawmakers to enact new legislation to uphold the minor's best interests. In fact, while some countries recognise the surrogate as the legal parent, others ascribe parenthood to the commissioning parents. That discrepancy can lead to a 'clash of laws', resulting in children ending up stateless and unable to maintain an already established family relationship.Just like fundamental protection of human rights and public health, the regulation of revolutionary technologies that change the very notion of reproduction, parenthood, and human identity needs to be governed by uniform standards, shared at least by nations which espouse common core values.

The fight against doping in sport, formally started in 1960 with the constitution of the International Olympic Committee (IOC) and culminated in 1999 with the birth of the World Anti-Doping Agency (WADA), commissioned to chair various activities, including the publication of the annual list of prohibited substances and methods for doping. In Europe, as early as 1967, the Committee of Ministers of the Council of Europe adopted a resolution to stigmatise the intake of substances foreign to the body for the sole purpose of artificially and unfairly influencing sports performance. In 2002, the Council of Europe adopted an Additional Protocol to the 1989 Strasbourg Convention against Doping to ensure mutual recognition of doping controls and to strengthen the enforcement of the Convention. In Italy, the Law of 14 December 2000 n. 376 "Discipline of the health protection of sports activities and the fight against doping", defines doping as "the administration or intake of drugs or biologically or pharmacologically active substances and the adoption or submission to medical practices not justified by pathological conditions and suitable to modify the psychophysical or biological conditions of the organism in order to alter the athletic performance of athletes". The same law regulates the use of drugs or biologically or pharmacologically active substances and update an annual list in agreement with WADA. The article aims to analyse the legislation from a national perspective, offering as complete a view as possible of the current situation.

Uterus transplantation (UTx) aimed at restoring fertility for women suffering from uterine factor infertility has been making significant strides over the past years, leading to the first successful outcome of live birth in 2014. Nonetheless, the ethical issues raised by such a procreative option are uniquely complex and multifaceted. UTx presents unique features, and the most significant risks it entails are the multiple surgeries required and the need for immunosuppressive drugs to prevent organ rejection. Post-transplantation immunosuppressive therapy, rejection monitoring, and immune tolerance are all crucial aspects That affect UTx outcomes and ensuing pregnancy success rates. In time, an alternative tool might become clinically available that could solve all those issues: tissue engineering relying on a combination of cells, biomaterials, and growth factors that harness the body's innate ability to regenerate and repair reproductive organs. Mastering such techniques could lead in the medium-long term to the creation of a bioengineered uterus for the purpose of transplantation, based on scaffolds derived from decellularized organs or tissues that can be recellularized by several types of autologous somatic/stem cells, in particular for uterine tissue engineering.

Diese Empfehlungen wurden in Zusammenarbeit verschiedener Fachgesellschaften und Patientenorganisationen erarbeitet und dienen dazu, ein Nachsorgeprogramm fur erfolgreich behandelte Patientinnen und Patienten zu etablieren.

The paper addresses the issue of the legality and ethical admissi-bility of invasive experiments on embryos and the correlated one of the degree of legal protection and dignity to be recognized for human embryos, particularly in light of the growing importance that scientific research on embryonic stem cells has been gaining from the clinical and biomedical standpoints in the therapeutic treatments of diseases so far considered incurable, in the interest of public health. Furthermore, the issue of experimentation on cryopreserved supernumerary human embryos is still extremely polarizing, which makes it harder to arrive at shared solutions. The author hopes for a broad-ranging debate at the international level, for the ultimate purpose of achieving shared regulatory frameworks.

Medically-assisted-procreation via in vitro fertilization, an integral part of of the so-called "reproductive revolution", is a valuable option for couples with sterility or fertility issues. That has however brought about three relevant results: the rift between procreation and sexual intercourse, the opportunity to use heterologous fertilization through donated gametes, and the ensuing increase in the number of "reproductive contributors" (male and/or female gamete donors, surrogate mothers). In Italy, Law n. 40 has put in place several restrictions, stricter than in most other European countries. Before being declared partly unconstitutional, Law 40 used to impose an array of bans and restrictions other than the ones still currently in force, such as the still unchanged prohibition to use human embryos for experimentation purposes and the ban on surrogacy. For same-sex couples who travel abroad to get around the Italian ban on heterologous fertilization, surrogacy, and MAP for homosexual couples. The authors have attempted to lay out a short analysis of how Italian courts have attempted to uphold the best interests of children born abroad in homosexual families, by taking into account the latest decisions on the subject.

The need to fight a highly aggressive virus such as SARS-CoV-2 has compelled governments to put in place measures, which, in the name of health protection, have constrained many freedoms we all enjoy, including freedom of movement, both nationally and within the European Union. In order to encourage and facilitate the return to free movement, the European Parliament has launched a “COVID-19 digital certificate”. A spirited debate centered around the use of this certificate is still ongoing among scholars, many of whom have pointed out the uncertainties relative to COVID-19 immunity, privacy issues and the risk of discriminatory effects. The authors, while highlighting some critical aspects, argue that the COVID digital certificate in its current approved version can effectively help prevent the spread of the infection and promote free movement, while upholding the right to health as much as possible. However, they also stress the need for a thorough information campaign to illustrate the advantages and limitations of this document in order to avoid creating a false sense of security in the public opinion, who may wrongly assume that the emergency has been overcome for good.

Several factors have been associated with increased risk of maternal and fetal peripartum and postpartum infections, including pre-existing maternal conditions (e g malnutrition, diabetes, obesity, severe anaemia, bacterial vaginosis, and group B streptococcus infections) and unexpected or iatrogenic conditions during labour and childbirth, such as prolonged rupture of membranes (PROM) multiple vaginal examinations, manual removal of the placenta, and cesarean section As such, the strategies to reduce maternal and fetal infections and their short- and long-term complications have been largely directed at preventive measures where such risk factors exist In many cases of maternal and fetal infections, medical negligence may have played a role In fact, a given infection may not have been detected during examinations, or proper treatment may not have been implemented in a timely fashion In fact, some infections may become more severe if they are not properly treated as quickly as possible The Authors have aimed to shed a light on the most common, and feared, childbirth-related infections, by means of a wide-ranging analysis of medical databases (Scopus, Pubmed, Embase, Research Gate, Web of Science), legal archives (Justia, Leagle, Lexis, Casetext) and recommendations issued by medical and scientific institutions (United Nations, World Health Organization, Centers for Disease Control and Prevention, National Health Service, etc…), spanning the 2004-2020 period The inability on the part of physicians to thoroughly document the appropriateness of their interventions and the compliance with guidelines and best practices often results in claims being filed by damaged patients and/or their legal heirs Litigation is typically complex in such cases, and likely to result in substantial compensatory damages being awarded to damaged patients Currently, a higher standard for cautionary rules should be applied by practitioners and medical facilities to minimize the risk of claims being filed, particularly in tort courts As a matter of fact, the current global setting of Covid-19 pandemic crisis has engendered unique conditions Hence, specifically targeted measures are needed in maternity centers in order to stave off the contagion of healthy patients, while at the same time providing the best possible care for Covid-19 positive parturients and their newborns Compliance with directives and regulations issued by health care authorities, aimed at the implementation of adequate diagnostic pathways, isolation protocols and protection requirements, is undoubtedly crucial for preventing malpractice allegations and liability

Extensive scientific evidence shows that there is a broad spectrum of substances used as adulterants, whose effects on the user's health may be extremely harmful. The degree of purity of the drugs most commonly abused is highly variable depending on the region or epidemiological context. Practices of drug adulteration have been substantially evolving over the years: a significant trend has been observed in the last decade indicating a decline in the average purity of most drugs. Although the most frequent adulterants of common street drugs have long been well known, the rise of synthetic opioids has inevitably entailed gaps in knowledge in terms of the substances being used and their composition, which constitutes an even greater threat to public health.

Mechanical vibration applied directly to the muscle belly or tendon has been reported to elicit a specific reflex loop named tonic vibration reflex (TVR), which involves motor unit (MU) activation synchronized and un-synchronized within the vibration cycle. Indirect application of vibration to the muscle by vibration exercise (VE) has also been suggested to evoke TVR, as evidenced by the spectral peaks observed at the vibration frequency in the surface electromyography (sEMG). However, other studies interpreted these spectral peaks as the result of motion artifacts (MAs). The aim of the present study is, therefore, to investigate MU activation patterns during VE in order to clarify the nature of those spectral peaks. To this end, low-intensity isometric contractions were executed with and without VE, and high-density sEMG measurements were performed during the contraction tasks. MU action potential (MUAP) trains were extracted by decomposing the recorded high-density sEMG signals. The spectra of the MUAP trains were then calculated and compared between vibration and no-vibration conditions. Clear MU synchronization was observed during VE, confirming the spectral peaks at the vibration frequency to be mainly due to the reflex loop rather than MAs.

Summary The challenge of this study was to create a 3D geological and structural model of the Kasserine Aquifer System (KAS) in central Tunisia and its natural extension into north-east Algeria. This was achieved using an implicit 3D method, which honors prior geological data for both formation boundaries and faults. A current model is presented which provides defendable predictions for the spatial distribution of geology and water resources in aquifers throughout the model-domain. This work has allowed validation of regional scale geology and fault networks in the KAS, and has facilitated the first-ever estimations of groundwater resources in this region by a 3D method. The model enables a preliminary assessment of the hydraulic significance of the major faults by evaluating their influence and role on groundwater flow within and between four compartments of the multi-layered, KAS hydrogeological system. Thus a representative hydrogeological model of the study area is constructed. The possible dual nature of faults in the KAS is discussed in the context that some faults appear to be acting both as barriers to horizontal groundwater flow, and simultaneously as conduits for vertical flow. Also discussed is the possibility that two flow directions occur within the KAS, at a small syncline area of near Feriana. In summary, this work evaluates the influence of aquifer connectivity and the role of faults and geology in groundwater flow within the KAS aquifer system. The current KAS geological model can now be used to guide groundwater managers on the best placement for drilling to test and further refine the understanding of the groundwater system, including the faults connectivity. As more geological data become available, the current model can be easily edited and re-computed to provide an updated model ready for the next stage of investigation by numerical flow modeling.

ObjectiveThe natural course of chronic hepatitis C varies widely. To improve the profiling of patients at risk of developing advanced liver disease, we assessed the relative contribution of factors for liver fibrosis progression in hepatitis C. Design We analysed 1461 patients with chronic hepatitis C with an estimated date of infection and at least one liver biopsy. Risk factors for accelerated fibrosis progression rate (FPR), defined as ≥0.13 Metavir fibrosis units per year, were identified by logistic regression. Examined factors included age at infection, sex, route of infection, HCV genotype, body mass index (BMI), significant alcohol drinking (≥20 g/day for ≥5 years), HIV coinfection and diabetes. In a subgroup of 575 patients, we assessed the impact of single nucleotide polymorphisms previously associated with fibrosis progression in genome-wide association studies. Results were expressed as attributable fraction (AF) of risk for accelerated FPR.ResultsAge at infection (AF 28.7%), sex (AF 8.2%), route of infection (AF 16.5%) and HCV genotype (AF 7.9%) contributed to accelerated FPR in the Swiss Hepatitis C Cohort Study, whereas significant alcohol drinking, anti-HIV, diabetes and BMI did not. In genotyped patients, variants at rs9380516 (TULP1), rs738409 (PNPLA3), rs4374383 (MERTK) (AF 19.2%) and rs910049 (major histocompatibility complex region) significantly added to the risk of accelerated FPR. Results were replicated in three additional independent cohorts, and a meta-analysis confirmed the role of age at infection, sex, route of infection, HCV genotype, rs738409, rs4374383 and rs910049 in accelerating FPR. ConclusionsMost factors accelerating liver fibrosis progression in chronic hepatitis C are unmodifiable. Refereed/Peer-reviewed

Hepatitis C viral (HCV) kinetics after initiation of interferon-based therapy provide valuable insights for understanding virus pathogenesis, evaluating treatment antiviral effectiveness and predicting treatment outcome. Adverse effects of liver fibrosis and steatosis on sustained virological response have been frequently reported, yet their impacts on the early viral kinetics remain unclear. In this study, associations between histology status and early viral kinetics were assessed in 149 HCV genotype 1-infected patients treated with pegylated interferon alfa-2a and ribavirin (DITTO trial). In multivariate analyses adjusted for critical factors such as IL28B genotype and baseline viral load, presence of significant fibrosis (Ishak stage > 2) was found to independently reduce the odds of achieving an initial reduction (calculated from day 0 to day 4) in HCV RNA of ≥2 logIU/mL (adjusted OR 0.03, P = 0.004) but was not associated with the second-phase slope of viral decline (calculated from day 8 to day 29). On the contrary, presence of liver steatosis was an independent risk factor for not having a rapid second-phase slope, that is, ≥0.3 logIU/mL/week (adjusted OR 0.22, P = 0.012) but was not associated with the first-phase decline. Viral kinetic modelling theory suggests that significant fibrosis primarily impairs the treatment antiviral effectiveness in blocking viral production by infected cells, whereas the presence of steatosis is associated with a lower net loss of infected cells. Further studies will be necessary to identify the biological mechanisms underlain by these findings.

Terra Nova, 23, 35–41, 2011 Abstract To put constraints on the Mesozoic to recent growth of the Anti-Atlas system, we investigated the temperature–time history of rocks by applying extensive low-temperature thermochronological analysis to three Precambrian inliers along the coast and 250 km into the interior. Bedrocks yield old U–Th/He ages on zircon (248–193 Ma) and apatite (150–50 Ma) and also fission-track ages of 173–121 Ma on apatite. These datasets are interpreted as recording passive margin upward movements from central Atlantic rifting until the Early Cretaceous. A phase of sedimentary burial was evidenced for the Cretaceous–Eocene. The extension of this thin (1.5 km) basin is loosely constrained but can be extended to the western regions of northern Africa. Effects of the existing thermal perturbation of lithospheric origin 100 km below the Atlas show that the 120–60 °C isotherms are not much deflected. Large-scale uplift has possibly occurred in the western Anti-Atlas since c. 30 Ma and is associated with a mean denudation rate of 0.08 km Ma−1.

Terra Nova, 22, 354–360, 2010 Abstract The Raman spectrum of carbonaceous material (CM) from advanced diagenesis (∼200 °C) to low-grade metamorphism (∼320 °C) is documented in the Helvetic flysch of the Glarus Alps (Switzerland). The spectrum is complex, with several defect bands at ∼1200 (D4), ∼1350 (D1), ∼1500 (D3) and ∼1620 (D2) cm−1. We document the evolution of these bands relative to the ‘graphite’ G band with increasing metamorphic grade, and we show that this qualitative evolution may be used as a proxy for temperature in the Glarus Alps. We develop a robust peak-fitting method and propose quantitative parameters that may be used as proxies for thermal metamorphism in this region. Further work in other geological contexts is needed to assess whether the spectral evolution observed in the Glarus Alps may be generalized and to critically assess the potential for calibrating a general, empirical and quantitative thermometer based on the Raman spectrum of CM in low-grade rocks.

Clinical progression of chronic hepatitis C depends on several cofactors, which also have a negative affect on the rate of response to interferon-alpha-based therapy. Given the current worldwide prevalence of the metabolic syndrome, the impact of obesity and insulin resistance, and of their histopathological correlate, hepatic steatosis, on the natural history and management of chronic hepatitis C is undoubtedly very important. We will review some of the current knowledge on the clinical consequences of overweight/obesity, steatosis and insulin resistance on chronic hepatitis C, and discuss how this issue may be dealt with in clinical practice.

The objective of this study was to describe the all-cause mortality of participants in the Swiss Hepatitis C Cohort compared to the Swiss general population. Patients with hepatitis C virus (HCV) infection attending secondary and tertiary care centres in Switzerland. One thousand six hundred and forty-five patients with HCV infection were followed up for a mean of over 2 years. We calculated all-cause standardized mortality ratios (SMR) and 95% confidence intervals (CI) using age, sex and calendar year-specific Swiss all-cause mortality rates. Multivariable Poisson regression was used to model the variability of SMR by cirrhotic status, HCV genotype, infection with hepatitis B virus or HIV, injection drug use and alcohol intake. Sixty-one deaths were recorded out of 1645 participants. The crude all-cause SMR was 4.5 (95% CI: 3.5-5.8). Patients co-infected with HIV had a crude SMR of 20 (95% CI: 11.1-36.1). The SMR of 1.1 (95% CI: 0.63-2.03) for patients who were not cirrhotic, not infected with HBV or HIV, did not inject drugs, were not heavy alcohol consumers (

A case of primary liver cancer showing combined hepatocellular and cholangiocellular features and an associated pseudosarcomatous (schwannomatous) component is presented. Histologically, compact microtrabecular and glandular patterns in a dense fibrous stroma were recognized. The latter showed transition towards spindle cell sarcomatous growth in several areas of both the primary and the lymph-node metastasis. Glandular areas expressed acidic mucins and AE1-reactive keratins; albumin mRNA was detected by in situ hybridization in both trabecular and glandular areas. Vimentin and S-100 protein were mostly expressed in the pseudosarcomatous areas. Both the morphological patterns and the phenotypic features indicate that divergent differentiation along both epithelial and mesenchymal lineages took place in this rare primary liver tumor.

30-35 Ma ago a major change occurred in the Mediterranean region, from a regionally compressional subduction coeval with the formation of Alpine mountain belts, to extensional subduction and backarc rifting. Backarc extension was accompanied by gravitational spreading of the mountain belts formed before this Oligocene revolution. Syn-rift basins formed during this process above detachments and low-angle normal faults. Parameters that control the formation and the kinematics of such flat-lying detachments are still poorly understood. From the Aegean Sea to the Tyrrhenian Sea and the Alboran Sea, we have analysed onshore the deformation and P-T-t evolution of the ductile crust exhumed by extension, and the transition from ductile to brittle conditions as well as the relations between deep deformation and basin formation. We show that the sense of shear along crustal-scale detachments is toward the trench when subduction proceeds with little or no convergence (northern Tyrrhenian and Alboran after 20 Ma) and away from the trench in the case of true convergence (Aegean). We tentatively propose a scheme explaining how interactions between the subducting slab and the mantle control the basal shear below the upper plate and the geometry and distribution of detachments and associated sedimentary basins. We propose that ablative subduction below the Aegean is responsible for the observed kinematics on detachments (i.e. away from the trench). The example of the Betic Cordillera and the Rif orogen, where the directions of stretching were different in the lower and the upper crust and changed through time, is also discussed following this hypothesis.

Located at an intermediate position in the External Rif nappe pile, the Temsamane units (northern Morocco) are characterized by an abnormally intense metamorphism and a penetrative ductile deformation. We present new metamorphic data showing that, in spite of their external position in the Rif, part of the Temsamane units underwent medium-pressure low-temperature (MP–LT) metamorphism (at c . 7–9 kbar and 330–430 °C), possibly during the Oligocene. Structural data show that the exhumation of these units, during Middle to Late Miocene times, was characterized by an intense approximately east–west stretching and by top-to-the-west shear senses. We tentatively propose two possible origins for the MP–LT Temsamane units: (1) an internal origin related to the subduction and the HP–LT event recorded in the Internal Rif (Alboran Domain), or (2) an external origin, implying a second subduction system within the External Rif, parallel to and almost contemporaneous with that of the Alboran Domain. This tectonometamorphic evolution of the Temsamane units is set within the context of the External Rif evolution. At a larger scale, we show that the exhumation history of the Temsamane units, which strongly resembles that documented in the core of the internal Betics, is compatible with the westward slab retreat occurring during the Middle to Late Miocene in the Betic–Rif region.

REE mineralogy was characterized at the micrometer scale (using scanning electron microscopy) in the four tectono-metamorphic units of the Beni Mzala window, Sebtide Complex, Internal Rif, Morocco, which sample a HP-LT metamorphic gradient from subgreenschist to blueschist/eclogite facies. These tectonic units are composed of garnet-free metapelites (and associated synmetamorphic veins) from the same homogeneous aluminium-rich and calcium-poor protolith. In that context, mineralogical differences between units are assumed to result from contrasted pressure and temperature histories. Light REE-bearing Al-phosphates of the crandallite group with florencite-rich composition and variable goyazite content are the dominant LREE minerals in the lowest-grade units, Tizgarine (300 °C, 3 kbar as peak conditions) and Boquete de Anjera (350 °C, 10 kbar). In the latter unit, metamorphic florencite is associated with MREE-rich monazite. In the schist of the highest-grade units, Beni Mzala 2 (420–450 °C, 12 kbar) and Beni Mzala 1 (550 °C, 16 kbar), associations of allanite-rich epidote and synchisite (a LREE-fluorocarbonate) are found whereas florencite and monazite are no longer observed. At the wall of the quartz–kyanite veins, retrograde monazite-(Ce) with grain size of 20 to 50 μm is the only LREE-bearing mineral. Th–Pb and U–Pb SIMS data on some of these grains yield ages of 21.3 ± 1.7 Ma and 20.9 ± 2.1 Ma, respectively, consistent with previous K–Ar ages obtained on retrograde clay–mica mixtures in rocks from the same locality. The identification of a stability field for monazite in high-pressure aluminous metapelites with an upper thermal-limit below 450 °C as well as the derivation of meaningful U–Pb and Th–Pb SIMS ages demonstrates the monazite potential for dating HP-LT metapelites. However, since, under these conditions, monazite growth occurs below its admitted closure-temperature, these ages must be interpreted on the basis of monazite textural relationships.

The internal = northern zones of the Maghrebide belt includes allochthonous massifs that define, together with those from the Betics, Sicily and Calabria, a disrupted ‘Alkapeca’ terrane. In the Rif transect, taking advantage of new thermobarometric and geochronologic studies, we recognize a metamorphic complex with a mostly non-Alpine upper plate (Dorsale, Ghomarides–Malaguides), and a lower plate (Sebtides–Alpujarrides) affected by HP–LT, then HT–LP Alpine metamorphism. Some eastern Rif allochthons (Temsamane area) display MP metamorphism and could represent either Sebtide inliers or slivers from the African paleomargin. The Sebtide–Alpujarride late HT event also affects the bottom of the Ghomaride–Malaguide complex and can be related to the onset of the Alboran Sea rifting at ∼ 25 – 22 Ma , whereas their HP event is ascribed to an earlier ( ∼ 30 – 25 Ma ?), north- to northeast-dipping subduction event. A review of the Algerian literature allows us to infer a similar structure and evolution for the Kabylides. The Alkapeca disruption is classically explained by back-arc extension above the retreating subduction of the Ligurian–Maghrebian oceanic lithosphere. The question of whether the latter subduction followed an earlier and opposite Alpine–Betic (Nevado-Filabride) subduction or not, remains open to discussion. To cite this article: A. Michard et al., C. R. Geoscience 338 (2006).

Galectin-3, a marker of well-differentiated thyroid carcinoma, is expressed in thyroid nodules with cytological atypia Aims: The distribution of galectin-3, a widely recognized marker of well-differentiated thyroid carcinoma, was investigated in 95 thyroid lesions including nodules with foci of cytoarchitectural atypia. Methods and results: Twenty-eight papillary carcinomas, five follicular carcinomas, one Hurthle cell carcinoma, three poorly differentiated carcinomas, one anaplastic carcinoma, 25 nodular hyperplasias and 27 follicular adenomas, including nodules with atypical features, three neoplasms of undetermined malignant potential and two thyroiditis cases were examined. By immunohistochemistry, galectin-3 was consistently found in carcinomas; otherwise benign nodules exhibited galectin-3-positive clusters of cells with poorly developed features of differentiated carcinoma (mainly of papillary type) such as nuclear chromatin clearing, nuclear clefting, pseudoinclusions, which, in each case, were not histologically sufficient to warrant a definitive diagnosis of malignancy. In other nodules galectin-3 staining was negative. The latter were either clearly benign or showed constantly a minor degree of chromatin clearing and of other atypical features when compared with galectin-3-positive cases. Conclusions: Galectin-3, a reliable marker of differentiated thyroid carcinoma as confirmed in our series of malignant neoplasms, appears expressed in nodules with an overall benign appearance but with focal areas suspicious for malignancy. The significance of such findings needs to be further investigated.

The hepatic consequences of an infection with the hepatitis C virus (HCV) are well recognised, but extrahepatic manifestations of HCV may be just as severe. Here we have reviewed various extrahepatic manifestations of HCV such as mixed cryoglobulinemia, lymphoma, metabolic features and neurologic consequences and we discuss pathogenesis and management of these clinical problems. We concluded with important aspects of therapy with novel anti-HCV agents and its effects on extrahepatic manifestations.

Regenerative medicine aims to replace a body function or specific cell loss. It includes therapies at the forefront of modem medicine, issuing from translational biomedical research. Transplantation of organs and cells has revolutionized the management of patients for whom medical treatment is a failure. Unfortunately, organ shortage is limiting treatment possibility. As an example, among the 15,000 patients with type I diabetes in Switzerland, only approximately 30 can receive a pancreas or an islet transplant per year. Second example, 500 patients die each year in Switzerland from alcoholic cirrhosis because no treatment is available. Transplantation of islet cells, hepatocytes, mesenchymal stem cells or dopaminergic neurons represents hope fora therapy available for large populations of patients.

30-35 Ma ago a major change occurred in the Mediterranean region, from a regionally compressional sub- duction coeval with the formation of Alpine mountain belts, to extensional subduction and backarc rifting. Backarc ex- tension was accompanied by gravitational spreading of the mountain belts formed before this Oligocene revolution. Syn-rift basins formed during this process above detachments and low-angle normal faults. Parameters that control the formation and the kinematics of such flat-lying detachments are still poorly understood. From the Aegean Sea to the Tyrrhenian Sea and the Alboran Sea, we have analysed onshore the deformation and P-T-t evolution of the ductile crust exhumed by extension, and the transition from ductile to brittle conditions as well as the relations between deep defor- mation and basin formation. We show that the sense of shear along crustal-scale detachments is toward the trench when subduction proceeds with little or no convergence (northern Tyrrhenian and Alboran after 20 Ma) and away from the trench in the case of true convergence (Aegean). We tentatively propose a scheme explaining how interactions between the subducting slab and the mantle control the basal shear below the upper plate and the geometry and distribution of detachments and associated sedimentary basins. We propose that ablative subduction below the Aegean is responsible for the observed kinematics on detachments (i.e. away from the trench). The example of the Betic Cordillera and the Rif orogen, where the directions of stretching were different in the lower and the upper crust and changed through time, is also discussed following this hypothesis.