The FDA “black box” warning on antidepressant suicide risk in young adults: More harm than benefits?

The decision made in the year 2004 by the U.S. Food and Drug Administration (FDA) to require a boxed warning on antidepressants regarding the risk of suicidality in young adults still represents a matter of controversy. The FDA warning was grounded on industry-sponsored trials carried one decade ago or earlier. However, within the past decade, an increasing number of reports have questioned the actual validity of the FDA warning, especially considering a decline in the prescription of the antidepressant drugs associated with an increase in the rate of suicidal events among people with severe depression. The present report provides an overview of the FDA black box warning, also documenting two Major Depressive Disorder patients whose refusal to undergo a pharmacological antidepressant treatment possibly led to an increased risk for suicidal behaviors. The concerns raised by the FDA black box warning need to be considered in real-world clinical practice, stating the associated clinical and public health implications

Extraction and purification of phosphorus from the ashes of incinerated biological sewage sludge

Phosphorus depletion represents a significant problem. Ash of incinerated biological sewage sludge (BSS) contains P, but the presence of heavy metals (e.g., Fe and Al) is the main issue. Based on chemical characterization by SEM-EDS, ED-XRF and ICP-OES techniques, the characteristics and P content of bottom ash (BA) and fly ash (FA) of incinerated BSS were very similar. On BA, P extraction carried out in counter-current with an S:L ratio of 1:10 and H2SO4 0.5 M led to better extraction yields than those of a similar test with H2SO4 1 M and an S:L ratio of 1:5 (93% vs. 86%). Comparing yields with H2SO4 0.5 M (S:L ratio of 1:10), the counter-current method gave better results than those of the crossflow method (93% vs. 83.9%), also improving the performance obtained with HCl in crossflow (93% vs. 89.3%). The results suggest that the purification of the acid extract from heavy metals with pH variation was impractical due to metal precipitation as phosphates. Extraction with H2SO4 and subsequent treatment with isoamyl alcohol represented the best option to extract and purify P, leading to 81% extraction yields of P with low amounts of metals

The Endocannabinoid System: A Putative Role in Neurodegenerative Diseases

BACKGROUND: Following the characterization of the chemical structure of D9-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, researchers have moved on with scientific valuable explorations. OBJECTIVES: The aim of this review is to highlight the role of endocannabinoid system in neurodegenerative diseases. MATERIALS AND METHODS: The article is a critical analysis of the most recent data currently present in scientific literature on the subject; a qualitative synthesis of only the most significant articles has been performed. RESULTS: In central nervous system, endocannabinoids show a neuromodulatory function, often of retrograde type. This way, they play an important role in synaptic plasticity and in cognitive, motor, sensory and affective processes. In addition, in some acute or chronic pathologies of central nervous system, such as neurodegenerative and neuroinflammatory diseases, endocannabinoids can perform a pro-homeostatic and neuroprotective function, through the activation of CB1 and CB2 receptors. Scientific evidence shows that an hypofunction or a dysregulation of the endocannabinoid system may be responsible for some of the symptoms of diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases. CONCLUSIONS: The important role played by endocannabinoid system promises interesting developments, in particular to evaluate the effectiveness of new drugs in both psychiatry and neurology

A comprehensive overview on Kratom

Kratom (Mitragyna speciosa Korth) is a tropical tree, indigenous to South East Asia. Historically, the plant is locally used as a stimulant, a remedy in traditional medicine and in social context. Imported to Western countries, Kratom is classified as a novel psychoactive substance (NPS). A systematic review of the literature on Mitragyna speciosa and its main constituents was carried by our international multidisciplinary group. Results were qualitatively analysed in three main areas of interest: in-vitro and preclinical data on pharmacology and behavioral effects, laboratoristic techniques for identification/characterization, epidemiological/toxicological reports on humans. At present, there is no systematic data on the prevalence of Kratom use in all the native countries, but it seems to be considerable. In South-East Asia, Kratom, even if banned, might be still considered a better option than other illicit drugs, an alternative opioid treatment, a “natural” remedy with no real social stigma attached to its consumption. In parallel, this ethno-drug seems to be popular in Western countries, largely unregulated, easily available on the Internet. Kratom pharmacology appears to be complex, with many alkaloids involved. The subjective effects in humans are very peculiar and seem to be dose-dependent, ranging from psycho-stimulant to sedative-narcotic. Available data on Kratom suggest caution: this psychoactive plant could exhibit a serious harmful potential. Kratom use seems to be associated with drug dependency, development of withdrawal symptoms, craving, serious adverse effects and life-threatening effects in a multidrug-intoxicating scenario. On the other hand, its anxyiolitic, antidepressant and analgesic properties deserve to be further studied

Vis-NIR luminescent lanthanide-doped core-shell nanoparticles for imaging and photodynamic therapy

The preparation of smart Ln:ZrO2@SiO2 nanoplatforms with grafted photosensitizer (Rose Bengal) which couple optical imaging with photo-dynamic therapy (PDT) is presented. A careful control of the lanthanide dopant loading is considered to enhance the photoemission properties of the lanthanide ions (Er, Pr, Yb) inside the ZrO2 crystal structure. The nanosystem with the lowest lanthanide loading maintains the size, phase and morphology of pristine ZrO2 nanoparticles and exhibit the best performances in term of the overall luminescence properties. Upon functionalization with a silica shell to covalently bound Rose Bengal, a theranostic platform is prepared which is very efficient in singlet oxygen generation, as demonstrated by EPR and UV\u2013vis spectroscopy studies. Preliminary cell viability tests show that while both pristine and Ln doped ZrO2 nanoparticles do not exert cytotoxicity, neither upon illumination nor in dark condition, Rose Bengal grafted samples are able to significantly reduce cell viability under light exposure, thus confirming the high potential of these nanoparticles as PDT tools

Pharmacovigilance Signals of the Opioid Epidemic over 10 Years: Data Mining Methods in the Analysis of Pharmacovigilance Datasets Collecting Adverse Drug Reactions (ADRs) Reported to EudraVigilance (EV) and the FDA Adverse Event Reporting System (FAERS)

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).In the past twenty years, the consumption of opioid medications has reached significant proportions, leading to a rise in drug misuse and abuse and increased opioid dependence and related fatalities. Thus, the purpose of this study was to determine whether there are pharmacovigilance signals of abuse, misuse, and dependence and their nature for the following prescription opioids: codeine, dihydrocodeine, fentanyl, oxycodone, pentazocine, and tramadol. Both the pharmacovigilance datasets EudraVigilance (EV) and the FDA Adverse Events Reporting System (FAERS) were analyzed to identify and describe possible misuse-/abuse-/dependence-related issues. A descriptive analysis of the selected Adverse Drug Reactions (ADRs) was performed, and pharmacovigilance signal measures (i.e., reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean) were computed for preferred terms (PTs) of abuse, misuse, dependence, and withdrawal, as well as PTs eventually related to them (e.g., aggression). From 2003 to 2018, there was an increase in ADR reports for the selected opioids in both datasets. Overall, 16,506 and 130,293 individual ADRs for the selected opioids were submitted to EV and FAERS, respectively. Compared with other opioids, abuse concerns were mostly recorded in relation to fentanyl and oxycodone, while tramadol and oxycodone were more strongly associated with drug dependence and withdrawal. Benzodiazepines, antidepressants, other opioids, antihistamines, recreational drugs (e.g., cocaine and alcohol), and several new psychoactive substances, including mitragynine and cathinones, were the most commonly reported concomitant drugs. ADRs reports in pharmacovigilance databases confirmed the availability of data on the abuse and dependence of prescription opioids and should be considered a resource for monitoring and preventing such issues. Psychiatrists and clinicians prescribing opioids should be aware of their misuse and dependence liability and effects that may accompany their use, especially together with concomitant drugs.Peer reviewedFinal Published versio

Extreme rainfall events in karst environments: the case study of September 2014 in the Gargano area (southern Italy)

In the first week of September 2014, the Gargano Promontory (Apulia, SE Italy) was hit by an extreme rainfall event that caused several landslides, floods and sinkholes. As a consequence of the floods, two people lost their lives and severe socio-economic damages were reported. The highest peaks of rainfall were recorded between September 3rd and 6th at the Cagnano Varano and San Marco in Lamis rain gauges with a maximum daily rainfall (over 230 mm) that is about 30% the mean annual rainfall. The Gargano Promontory is characterized by complex orographic conditions, with the highest elevation of about 1000 m a.s.l. The geological setting consists of different types of carbonate deposits affected by intensive development of karst processes. The morphological and climatic settings of the area, associated with frequent extreme rainfall events can cause various types of geohazards (e.g., landslides, floods, sinkholes). A further element enhancing the natural predisposition of the area to the occurrence of landslides, floods and sinkholes is an intense human activity, characterized by an inappropriate land use and management. In order to obtain consistent and reliable data on the effects produced by the storm, a systematic collection of information through field observations, a critical analysis of newspaper articles and web-news, and a co-operation with the Regional Civil Protection and local geologists started immediately after the event. The information collected has been organized in a database including the location, the occurrence time and the type of geohazard documented with photographs. The September 2014 extreme rainfall event in the Gargano Promontory was also analyzed to validate the forecasts issued by the Italian national early-warning system for rainfall-induced landslides (SANF), developed by the Research Institute for Geo-Hydrological Protection (IRPI) for the Italian national Department for Civil Protection (DPC). SANF compares rainfall measurements and forecasts with empirical rainfall thresholds for the prediction of landslide occurrence. SANF forecasts were compared to the documented landslides and discussed