New trends of substance abuse during COVID-19 pandemic: an international perspective

In the late 2019, an epidemic of cases with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has spread from China to the rest of the world, resulting in a global pandemic (COronaVIrus Disease 19, COVID-19 pandemic). Starting from the first months of 2020, several restrictions have been imposed by governments to face the public health threat, impacting the usual patterns of drug abuse throughout the world (1). The temporary border closure affected the usual illicit drug route of shipping from country to country, resulting in scarcity of classic street drugs (2). Moreover, restrictive measures internationally adopted by several countries made necessary to close all the usual recreational settings in which stimulants drugs are commonly abused. On the contrary, since in house drugs abuse became the most feasible option, other private encounters might have caught on, such as chemsex (3). In particular this phenomenon, which originated mainly in the large cities of Northern Europe, has gradually spread across the continent and is now a worrying reality in western European countries. Other rising trends of substance abuse include cognitive enhancers and new psychoactive substances (4, 5). Furthermore, the consequent social isolation and the likely limited access to detoxification centers caused additional psychological distress, pushing drug addicts toward alternative psychotropic drugs, possibly through illegal online marketplaces. An international overview of the new trends of drug abuse during the current COVID-19 pandemic and the related health risks are hereby discussed, taking into consideration different points of view

Commentary- Increasing abuse of anabolic steroids and chemsex drugs as performance and image-enhancing agents

Anabolic Androgenic Steroids (AAS) are a family of synthetic “Appearance and Performance Enhancing Drugs” (APED) derived from natural sex hormones, such as testosterone and its derivatives or precursors (e.g., dihydrotestosterone)1 . Whereas testosterone is the androgen responsible for the development of male secondary sex characteristics and elicits both anabolic and androgenic effects, AAS mostly simulate the anabolic effect of endogenous testosterone, and induce only partial androgenic effects2 . In the 1930s, anabolic steroids were shown to facilitate muscular growthhand consequently became rapidly popular among bodybuilders and other athletes, and were already widespread in the 1960s. AAS have been and still are among the doping agents most frequently misused by athletes, regardless of the type of sport, both in preparations containing natural anabolic drugs [e.g., testosterone and dehydroepiandrosterone (DHEA)] and in those with synthetic substances (e.g., dianazole, nandrolone, stanozolol and tetrahydrogestrinone

Cognitive enhancing drugs: a future challenge for the workplace?

In medical practice, cognitive enhancers (also called nootropics) are defined as therapeutic drugs treating specific cognition impairments in patients with attention deficit hyperactivity disorder, Alzheimer’s disease, stroke schizophrenia or aging. However, the non-medical use of cognitive enhancers with the aim of increasing mental alertness and concentration, improving memory, fighting wakefulness and boosting energy has been spreading worldwide2. In this concern, scarce investigations have been carried out on the possible risks of chronic non-medical use of nootropics, and these risks seem to be largely overlooked, especially among students3. Considering the ever more competitive nature of modern societies, which also reverberates into workplaces, cognitive enhancers are reasonably expected to become even more common over time4. Nonetheless, long-term consequences are as yet unknown. Cognitive enhancers, used by healthy individuals, are widely known as nootropics: they consist of drugs, supplements and other substances that are allegedly known to improve cognitive function, particularly executive functions, and to strengthen memory, creativity or even motivation. Pharmaceutical substances and compounds known as ‘cognitive-enhancers’ allegedly boost mental performance and the ability to focus and keep concentration. In broader terms, such drugs are often claimed to heighten and foster the acquisition of motor capabilities and affective skills (i.e., one’s ability to deal with anxiety stemming from performing certain work tasks or eliciting feelings of trust and affiliation). It is worth noting, however, that no drugs are licensed by medical authorities to be recommended and prescribed as ‘cognitive enhancers’. Thus, the definition of ‘performance-enhancing drug’ is usually linked to the off-label use of drugs prescribed for specific medical conditions. These substances are usually stimulants that preferentially target the catecholamines of the prefrontal cortex of the brain to induce their effects5. Historically, amphetamines have been the first drugs used off-label for the purpose of fostering memory consolidation and increasing concentration6. Since these substances are legally controlled as drugs of abuse, they can only be obtained on illegal markets. This purchase channel is also used to obtain methylphenidate, which is undoubtedly the most misused drug as cognitive enhancer5,7. Mostly prescribed for treating Attention Deficit Hyperactive disorder (ADHD) and narcolepsy, methylphenidate has been scheduled as an illegal drug in many countries for its abuse liability and side effects, resulting in a rapid expansion of methylphenidate legal analogs onto the drug market. Alternative prescription drugs for the treatment of narcolepsy and ADHD, such as modafinil and armodafinil, are also used as cognitive enhancers8. Finally, two last drugs should be mentioned among nootropics: atomoxetine, a selective nor-adrenaline reuptake inhibitor licensed for the treatment of children with methylphenidate-resistant ADHD or undergoing methylphenidate side effects9, and donepezil, a second-generation acetylcholinesterase inhibitor licensed for the treatment of mild to moderately severe symptoms of Alzheimer-related dementia10. At the same time, there has been renewed interest in older prescription drugs (e.g., beta blockers, to decrease performance anxiety) and illicit psychostimulants (e.g., cocaine, amphetamines), sometimes in different forms or doses. Whereas there is still little consensus on the actual effectiveness and nature of the cognitive benefits of the above-mentioned drugs in healthy subjects13, their use to enhance the level of performance in specific workplaces has been reported for decades14. In fact, cognitive enhancement has been a mainstay of military research in the US since the Second World War with the use of amphetamines, modafinil and other cognitive enhancers in the most recent military operations (e.g., Vietnam war, Korean war, operations Desert Shield and Desert Storm in Iraq, later sustained military operations in the Middle East)15,16. Whereas the military use of cognitive enhancers has been known for many years, not only in the US but internationally. More recent studies reported that other occupations present a high prevalence of use: medical doctors and health professionals (e.g., surgeons, surgical technicians’ anesthetists), transportation workers (e.g., truck drivers, car drivers, taxi drivers), financial traders, clinical investigators, research managers and lawyers. Finally, the increase of precarious and part-time home works has been recently associated to psychological discomfort and an increase in prescriptions of psychotropic drugs, and a rise in the misuse of cognitive enhancers can be hypothesized17-19. Another important factor to be taken into account is the role of the internet as a source of information through web forums and as a way of obtaining those substances. Such dynamics also constitute a cultural shift in the way drugs are obtained and consumed: they are anonymously received and safer than street drugs trafficking, although the actual composition and nature of the substances cannot be precisely ascertained. This latter fact creates a gap of information on the diagnosis of misuse in cases of possible intoxications and fatalities, since neither analytical screening nor confirmation methodologies are currently available for documenting exposure to those profuse and chemically diverse substances. In addition, apart from intoxications and fatalities, it has to be reminded that several of these substances present a potential for abuse liability and abstinence symptoms, which, instead of improving work pressure and overload, can worsen the environmental situation. In conclusion, we wish to draw the attention of the whole scientific community and policy makers to the increasing importance of the misuse of cognitive enhancers, and to improve public awareness of the phenomenon and contextual political strategies to stop this incoming threat for the health of current and future worker

Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer. Clinical results and biological observations in taxane-pretreated patients

Background: There is a deep need to improve the care of metastatic breast cancer (MBC) patients, since even today it remains an incurable disease. Taxanes are considered the most effective cytotoxic drugs for the treatment of MBC, both in monotherapy and in combined schedules, but the need for synthetic solvents contributes to the severe toxicities and may have a negative impact on the efficacy. Nanoparticle albumin-bound paclitaxel (Nab-paclitaxel) is a colloidal suspension of paclitaxel and human serum albumin initially developed to avoid the toxicities associated with conventional taxanes. Patients and methods: The aim of this prospective, single-center open-label, noncomparative study was to evaluate the efficacy and safety of nab-paclitaxel in MBC patients pretreated with taxanes. The patients were treated with nab-paclitaxel as a single agent, 260 mg/m2 on day 1 of each 3-week cycle or 125 mg/m2 weekly. The primary endpoint was the overall response rate (ORR). Secondary objectives were duration of response, clinical benefit rate, progression-free survival (PFS), overall survival, and safety. Results: A total of 42 patients (median age 48 years, median Eastern Cooperative Oncology Group performance status 0, triple-negative MBC 19%, all pretreated with a taxane-based therapy, mainly in advanced disease) were enrolled in the study. The ORR was 23.8%, including one complete response (2.4%) and nine partial responses (21.4%); the disease control rate was 50%. The median duration of response was 7.2 months. After a median follow-up of 9 months, the median PFS was 4.6 months. ORR and PFS were similar irrespective of the previous chemotherapy lines, metastatic sites, and biomolecular expression. Nab-paclitaxel was well tolerated, and the most frequent treatment-related toxicities were mild to moderate (grades 1–2). Conclusion: This real-life study shows that nab-paclitaxel has a significant antitumor activity and a manageable safety profile in patients pretreated with taxanes and experiencing a treatment failure after at least one line of chemotherapy

Herbivory promotes dental disparification and macroevolutionary dynamics in grunters (teleostei: Terapontidae), a freshwater adaptive radiation

Trophic shifts into new adaptive zones have played major (although often conflicting) roles in reshaping the evolutionary trajectories of many lineages. We analyze data on diet, tooth, and oral morphology and relate these traits to phenotypic disparification and lineage diversification rates across the ecologically diverse Terapontidae, a family of Australasian fishes. In contrast to carnivores and most omnivores, which have retained relatively simple, ancestral caniniform tooth shapes, herbivorous terapontids appear to have evolved a variety of novel tooth shapes at significantly faster rates to meet the demands of plant-based diets. The evolution of herbivory prompted major disparification, significantly expanding the terapontid adaptive phenotypic continuum into an entirely novel functional morphospace. There was minimal support for our hypothesis of faster overall rates of integrated tooth shape, spacing, and jaw biomechanical evolution in herbivorous terapontids in their entirety, compared with other trophic strategies. There was, however, considerable support for accelerated disparification within a diverse freshwater clade containing a range of specialized freshwater herbivores. While the evolutionary transition to herbivorous diets has played a central role in terapontid phenotypic diversification by pushing herbivores toward novel fitness peaks, there was little support for herbivory driving significantly higher lineage diversification compared with background rates across the family

The ATLAS barrel level-1 Muon Trigger Sector-Logic/RX off-detector trigger and acquisition board

The ATLAS experiment uses a system of three concentric layers of Resistive Plate Chambers (RPC) detector for the Level-1 Muon Trigger in the air-core barrel toroid region. The trigger algorithm looks for hit coincidences within different detector layers inside the programmable geometrical road which defines the transverse momentum cut. The on-detector electronics that provides the trigger and detector readout functionalities collects input signals coming from the RPC front-end. Trigger and readout data are then sent via optical fibres to the off-detector electronics. Six or seven optical fibres from one of the 64 trigger sectors go to one Sector-Logic/RX module, that later elaborates the collected trigger and readout data, and sends data respectively to the Read-Out Driver modules and to the Central Level-1 Trigger. We present the functionality and the implementation of the VME Sector-Logic/RX module, and the configuration of the system for the first cosmic ray data collected using this module