Influence of age on force and re-lengthening dynamics after tetanic stimulation withdrawal in the tibialis anterior muscle.

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.

Sex-related differences and chronobiology of ST-elevation myocardial infarction: findings from a single hub center in Italy.

OBJECTIVE: Type I acute myocardial infarction (AMI) is a life-threatening condition. Time of event and rescue procedures, and sex-specific differences may play a crucial role. We aimed to investigate chronobiological patterns and sex-specific differences in a cohort of AMI patients referred to a single hub center in Italy. PATIENTS AND METHODS: We considered all patients consecutively admitted for AMI (STEMI) to the Hospital of the Heart, in Massa, Tuscany (a region of Italy), between 2006 to 2018, who underwent interventional procedures. Sex, age, time of hospital admission, outcome (discharged alive/deceased), main comorbidities, and time between symptom onset and emergency medical service (EMS) activation, were analyzed. Chronobiologic analysis was applied according to hour of day, month, and season of the year. RESULTS: Overall 2,522 patients (mean age 64.6±13.1 years, 73% males) were considered. In-hospital death (IHM) occurred in 96 subjects (3.8%). At univariate analysis, deceased subjects were more likely to be female, older, with longer wait for EMS activation and with interventional procedures during night-time. The multivariate analysis identified female sex, age, history of ischemic heart disease, and night-time interventional procedure as independently associated factors to IHM. Chronobiologic analysis showed a pattern with a main morning peak for total sample, males, and females (p=0.00027; p=0.0006); p=0.0121, respectively). Events showed a higher peak in summer, with no differences by sex, but IHM was higher in winter. Females showed a higher delay for EMS activation, compared to males (p<0.001), but with no effects on prognosis. On the contrary, males with a delay showed higher mortality. CONCLUSIONS: Great effort should be spent to reduce patient-related delays in interventional procedures, being this issue crucial in both sexes.

Wastewater analysis and drug consumption: useful assessment tool.

Abstract: 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.

The evolution of European legislation on doping: new challenges in the age of NPS.

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.

Identity and reproductive rights of transgenders: are current legal and ethical frameworks soon to be outdated? Medicolegal implications of potentially life-changing decisions.

Abstract: 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 armed conflict in Ukraine and the risks of inter-country surrogacy: the unsolved dilemma.

Commercial surrogacy in Ukraine has been legal since 2002, and although no official figures are released, estimates point to several thousand births occurring yearly. The country has long been regarded as one of the surrogacy capitals of the world, due to relatively affordable costs and effective targeted legislation making the surrogacy contracts enforceable. Would-be parents come from countries where surrogacy is banned or heavily restricted to start a family despite their infertility, a practice known as inter-country surrogacy. When a child is born through surrogacy, the surrogate mother forfeits her rights over the child, thus allowing the so-called "intended" or "commissioning" parents to be recognized as such on the Ukrainian birth certificate. Inter-country surrogacy has long been a highly controversial practice from an ethical and legal perspective, but the brutally destructive armed conflict erupted in the country over three months ago has laid bare all the pitfalls and deep flaws of such a system. Children born through surrogacy cannot be handed over to their intended parents, and surrogates risk legal issues and see their rights jeopardized by their choices even in a war setting, for instance if they decide to seek refuge abroad. The horrors of war thus risk victimizing the most vulnerable to an irreparable degree. An international effort is now more urgent than ever to seek a tenable balance between the desires of couples to achieve parenthood and the rights and freedom of often vulnerable women who risk exploitation and abuse and their children.

COVID-19 vaccine mandates: what are the current European public perspectives?

The article aims to elaborate on European policy choices for the prevention of SARS­CoV­2 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.

The issue of infertility in times of COVID-19: what do we know about it?

ABSTRACT: Couple infertility constitutes a major source of concern and even distress for those involved, affecting roughly 50-80 million people in the world, according to World Health Organization data. There is no denying that medical and technological advancements in the field of as-sisted reproductive technology (ART) are among the greatest and most beneficial achievements of modern medicine. Countless couples have been able to achieve parenthood who in the past could not have, thanks to ART. Infertility itself used to be deemed insurmountable, especially when arising from uterine conditions (referred to as absolute uterine factor infertility, AUFI), neoplastic conditions or major complications affecting reproductive organs during previous pregnancies. The inability to have children is often considered by couples as a failure severely impacting their relationships, due to the unfulfilled biological potential in regard to parenting. However, in addition to its significance as a social problem, infertility is a medical issue which requires a strict and clearly defined path of diagnosis and treatment, particularly in times of COVID-19, when access to essential care has often been delayed with potentially harmful repercussions for patients seeking to achieve parenthood or to keep their fertility.

Research on supernumerary embryos: the challenge of recon- ciling opposing interests and fast-evolving technologies.

ABSTRACT: 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.

Uterus transplant update: innovative fertility solutions and the widening horizons of bioengineering.

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.

Is there anything left of the Italian law governing medically-assisted procreation?

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.

Normalized maximal rate of torque development during voluntary and stimulated static contraction in human tibialis anterior: Influence of age.

The risk of falling in older adults has been related, among other factors, to the reduction of the rate of torque development (RTD) with age. It is well known that both structural/peripheral and neural factors can influence the RTD. The purpose of this study was to compare the normalized RTD in young and older participants obtained during a) rapid voluntary tension production and b) neuromuscular electrical stimulation. The tibialis anterior of 19 young subjects (10 males and 9 females; age 21-33 years old) and 19 older participants (10 males and 9 females; age 65-80 years old) was studied. The subjects performed a series of maximal isometric explosive dorsiflexions and underwent trains of supra-maximal electrical stimulations (35 Hz) on the tibialis anterior motor point. Muscle shortening was indirectly measured using a laser (surface mechanomyogram, MMG). Both torque and MMG were normalized to their maximum value. Using a 20 ms sliding window on the normalized torque signal, the normalized maximum RTD was calculated for both voluntary and stimulated contractions. Active stiffness of the muscle- tendon unit was calculated as the area of the normalized torque with respect to the normalized MMG. Normalized maximum RTD was found significantly lower in older adults during voluntary activity (young: 751.9 ± 216.3%/s and old: 513.9 ± 173.9%/s; P < .001), and higher during stimulated contractions (young: 753.1 ± 225.9%/s and old: 890.1 ± 221.3%/s; P = .009). Interestingly, active stiffness was also higher in older adults (young: 3524.6 ± 984.6‰ and old 4144.6 ± 816.6‰; P = .041) and significantly correlated to the normalized maximum RTD during stimulated contractions. This dichotomy suggests that modifications in the structural/peripheral muscle properties are not sufficient to counteract the age-related decrease in neural drive to the muscle during voluntary isometric contractions in aged participants.

Advances in Medically-assisted procreation technologies: can malpractice claims and "reproductive damage" be identified.

Medically assisted procreation and assisted reproductive techniques have made giant strides over the past decades, enabling countless couples to achieve parenthood. Still, the ethical and moral concerns that have come to the fore as a result of ART's rise pose a multi-faceted issue that lawmakers have struggled to keep up with; procedures such as heterologous fertilization are strictly regulated, and even banned, in several nations around the globe, among which Italy, where a controversial piece of legislation was passed in 2004; such a reform has been partly nullified by court decisions, among which the Italian Constitutional Court and even the European Court of Human Rights. Relevant scientific articles were identified from Medline, Cochrane Central, Scopus, Web of Science, Science Direct, EMBASE and Google Scholar, through February 2020, by using the following keywords: "assisted reproductive techniques", "heterologous fertilization", "European rulings on ART", "reproductive damages". The rise of ART has laid bare a shortage of adequate legal tools for the purpose of guaranteeing the exercise of reproductive rights for all. Hence, the harmonization of regulations, at least at the European level, is greatly needed in order to ensure equality of parental opportunities for all.

The health threat of new synthetic opioids as adulterants of classic drugs of abuse.

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.

Assisted reproductive technologies and metabolic syndrome complications: medico-legal reappraisal.

In the last 40 years, the number of elderly patients that require Assisted Reproductive Technologies (ART) has risen enormously, especially after heterolougus fertilization techniques have become available. In recent years, the incidence of peripartum cardiomyopathy (PPCM) has substantially grown, as a consequence of the combined effect of increased maternal age, consequent high prevalence of hypertension and metabolic syndrome (MS). That cohort of women may be exposed to a greater number of cardiac, obstetric and anesthesio-logical complications, therefore the incidence of medico-legal issues, litigation, liabilities and claims over the past years has significantly risen. Cardiovascular and hormonal changes during pregnancy can challenge even the healthiest of individuals, and in that pregnant population the risk is even greater. These patients should be monitored before the ART, during pregnancy, delivery and puerperium, to avoid heart failure, thrombotic problems, embolic complications, stroke and death. Management issues regarding pregnancy and delivery are elaborate, including anesthesia considerations. This new population of women needs an accurate cardiac risk stratification with a thorough cardiovascular history and examination, 12 lead ECG, and transthoracic echocardiogram. Therefore, a comprehensive multidisciplinary assessment and management can provide the best opportunity to improve maternal and neonatal outcomes.

Influence of age on motor control accuracy during static ramp contractions.

We investigated the influence of the ageing process on the performance of the motor control system accuracy during a challenging motor task throughout the analysis of force output oscillations. The force signal of the first dorsal interosseous during linearly varying static contraction, 0-100-0% of the maximal volitional abduction in 15 s, was studied in 11 young and older adults. The relative error between the target and the actual force as well as several parameters of the force oscillations (corrections) were estimated. To understand the experimental results, we analyzed the force output generated by a set of computational simulations of a pool of motor units controlled by a proportional-integral-derivative system. Compared to young adults the older subjects presented larger errors and a lower number of corrections with longer duration and larger relative amplitude. The motor control system modelling varied the error update frequency (UF) of the controller (from 1 to 2.5 Hz) as well as the range of contraction time (CT) of the recruited motor unit (30-90 ms and 60-120 ms reflecting young and old ranges, respectively). The simulation generated force profiles with parameters similar to experimental recordings in young (UF = 1.5; CT 30-90 ms) and older (UF = 1; CT 60-120 ms) adults. Interestingly, the results of the simulations suggested that the improvement in the error update frequency of the controller was not able to compensate for the contractile changes in the motor unit twitches. In conclusion, the peripheral contractile changes with age can influence motor unit control strategies and represent a crucial phenomenon in the generation of larger force oscillations in older adults.

Investigation of The Neural Drive During Vibration Exercise by High-density Surface-electromyography.

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.