The rise of new psychoactive substances and psychiatric implications: A wide-ranging,multifaceted challenge that needs far-reaching common legislative strategies

The ever-growing number of novel psychoactive substances (NPS) that have been surfacing globally, as well as related changes in drug abuse trends, undoubtedly constitute a difficult and multifaceted challenge for psychiatry. The intake and abuse of such substances has been linked to a risk of psychopathological disturbances, which stem from imbalances of a range of neurotransmitter pathways and receptors. Through an analysis of relevant research articles and reviews (particularly those outlining NPS neurological and cerebral mechanisms of action and psychopathological consequences arising from NPS abuse; research papers more closely focused on chemical/pharmacological aspects have been ruled out), through a systematic analysis of Pubmed, Medline, PsycLIT and EMBASE literature, as well as data released by health care institutions and drug enforcement agencies (among which the World Health Organization, the United Nations Office on Drugs and Crime, the European Monitoring Centre for Drugs and Drug Addiction, Eurojust, the Novel Psychoactive Treatment UK Network, the Court of Justice of the European Union), the authors aimed to elaborate on the most relevant data relative to NPS-related psychiatric effects, focusing on the conceptual and definition-related complexities inherent to NPS, clinical management and motivations for NPS use; moreover, an effort has been made to highlight the possible measures in order to tackle the unremitting rise of such elusive and potentially harmful substances.     

Effects of tDCS on reward responsiveness and valuation in Parkinson’s patients with impulse control disorders

Journal of Neurology - Parkinson’s disease (PD) patients with impulse control disorders (ICD) frequently report hypersensitivity to rewards. However, a few studies have explored the...     

Prolonged distal motor latency of median nerve does not improve diagnostic accuracy for CIDP

Journal of Neurology - Compression of the median nerve at the carpal tunnel can give demyelinating features and result in distal motor latency (DML) prolongation fulfilling the EFNS/PNS...     

Long-term soluble Abeta1-40 activates CaM kinase II in organotypic hippocampal cultures

Recent findings suggested a role for soluble amyloid-beta (Abeta) peptides in Alzheimer's disease associated cognitive decline. We investigated the action of soluble, monomeric Abeta(1-40) on CaM kinase II, a kinase involved in neuroplasticity and cognition. We treated organotypic hippocampal cultures short-term (up to 4h) and long-term (5 days) with Abeta(1-40) (1nM-5microM). Abeta did not induce cell damage, apoptosis or synaptic loss. Short-term treatment down-regulated enzymatic activity of the kinase, by reducing its Thr(286) phosphorylation. In contrast, long-term treatment (1nM-microM) markedly and significantly up-regulated enzymatic activity, with peak stimulation at 10nM (three-fold). Up-regulation of activity was associated with increased expression of the alpha-isoform of CaM kinase II, increased phosphorylation at Thr(286) (activator residue) and decreased phosphorylation at Thr(305-306) (inhibitory residues). We investigated the effect of glutamate on CaM kinase II following exposure to 1 or 10nM Abeta(1-40). As previously reported, glutamate increased CaM kinase II activity. However, the glutamate effect was not altered by pretreatment of slices with Abeta. Short- and long-term Abeta treatment showed opposite effects on CaM kinase II, suggesting that long-term changes are an adaptation to the kinase early down-regulation. The marked effect of Abeta(1-40) on the kinase suggests that semi-physiological and slowly raising peptide concentrations may have a significant impact on synaptic plasticity in the absence of synaptic loss or neuronal cell death.     

High frequency of the TCRBV20S1 null allele in the Sardinian population

Single nucleotide polymorphisms (SNPs) in the T-cell receptor (TCR) gene segments might play a role in shaping the TCR repertoire. Three polymorphisms have been described for the TCRBV20S1 gene segment, one of which is responsible for a nucleotide substitution at position 524, resulting in the introduction of a stop codon. Individuals homozygous for this inactivating polymorphism ("null allele") are unable to express TCRBV20 gene products. Using DNA restriction digestion analysis, we investigated the frequency of this polymorphism in 111 healthy Sardinian subjects. Inhabitants of the Mediterranean island of Sardinia are considered to represent a genetically isolated population. Our analyses revealed an incidence of 19.8% of homozygosity for the null allele, corresponding to an allele frequency of 0.45. Such an incidence, significantly higher than the one detected in 83 non-Sardinian Caucasians (6%), is the most elevated so far reported in the literature. BV20 is a single member subfamily and the null allele produces a gap in the potential TCR repertoire. Therefore, it is possible that an undetermined selective pressure could have played a role in determining the high frequency of this inactivating polymorphism in Sardinians. Alternatively, this finding could be related to a founder effect in this ancient island population.     

Lower limb immobilization is associated with increased corticospinal excitability

Temporary immobilization of the leg serves as a useful model for the brain’s adaptive responses to casting, long-term confinement to bed rest and possibly to trauma. As part of a larger program using TMS to investigate changes associated with bed rest, we sought to determine whether casting of the leg causes brain excitability changes measurable with TMS, and the time course of resolution of these changes. In this study, eight adults wore a full leg cast for 10 days. TMS measures of motor cortex excitability were gathered before the cast was placed, and then immediately after cast removal, and 24 and 48 h later. A control group did not wear a cast and underwent the same TMS sessions. Significant excitability changes occurred and peaked at 24 h post cast removal in the TMS experimental group but not the non-casted group.     

Influence of circadian rhythm on mortality after myocardial infarction: data from a prospective cohort of emergency calls

Myocardial infarction (MI) occurs more frequently in the morning as a result of the concomitant unfavorable timing of several physiological parameters and/or biochemical conditions. However, little is known about the possible influence of this circadian pattern on prognosis. To evaluate whether the time of symptom onset could potentially influence mortality from acute MI, this prospective study considered all consecutive MIs admitted to the ED of Ferrara, Italy, after a call to the Emergency Coordinating Unit from January 1, 1998, to December 31, 2001. The total sample consisted of 442 MIs (mean age, 68.7 years; males, 72%). Eighty patients (males, 82.5%) died in the ED; the remaining 362 were admitted to the hospital. Of these, 50 (males, 60%) died during their hospital stay. Based on the timing of their symptom onset, cases were categorized both into 24 1-hour intervals and four 6-hour intervals (midnight to 5:59 am, 6:00 am to 11:59 am, noon to 5:59 pm, and 6:00 pm to 11:59 pm), and the circadian distributions of fatal versus nonfatal MIs were compared. The circadian variation of MI peaked between 6:00 am and noon (P < .001), and in this period, there was a trend toward a higher frequency of fatal cases (41.5% vs. 35.2%; chi(2) = 1.911, P = .167). To verify whether this higher frequency of fatal events in the morning hours could be related to possible higher severity of cases observed in that hours, a further separate analysis considering age, infarct site, and peak levels of MB was made. Again, no significant temporal differences among the four 6-hour intervals were found between fatal and nonfatal Mis, although a trend toward older age was observed in morning MIs. Not only the frequency, but also the mortality, of acute MI could be increased in the morning hours. This could be of practical interest for emergency doctors and could have significant implications for acute treatment, because several studies have reported a lowered efficacy of thrombolytic drugs in the morning hours.     

Management of Latent Autoimmune Diabetes in Adults: A Consensus Statement From an International Expert Panel

A substantial proportion of patients with adult-onset diabetes share features of both type 1 diabetes (T1D) and type 2 diabetes (T2D). These individuals, at diagnosis, clinically resemble T2D patients by not requiring insulin treatment, yet they have immunogenetic markers associated with T1D. Such a slowly evolving form of autoimmune diabetes, described as latent autoimmune diabetes of adults (LADA), accounts for 2–12% of all patients with adult-onset diabetes, though they show considerable variability according to their demographics and mode of ascertainment. While therapeutic strategies aim for metabolic control and preservation of residual insulin secretory capacity, endotype heterogeneity within LADA implies a personalized approach to treatment. Faced with a paucity of large-scale clinical trials in LADA, an expert panel reviewed data and delineated one therapeutic approach. Building on the 2020 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus for T2D and heterogeneity within autoimmune diabetes, we propose “deviations” for LADA from those guidelines. Within LADA, C-peptide values, proxy for β-cell function, drive therapeutic decisions. Three broad categories of random C-peptide levels were introduced by the panel: 1) C-peptide levels <0.3 nmol/L: a multiple-insulin regimen recommended as for T1D; 2) C-peptide values ≥0.3 and ≤0.7 nmol/L: defined by the panel as a “gray area” in which a modified ADA/EASD algorithm for T2D is recommended; consider insulin in combination with other therapies to modulate β-cell failure and limit diabetic complications; 3) C-peptide values >0.7 nmol/L: suggests a modified ADA/EASD algorithm as for T2D but allowing for the potentially progressive nature of LADA by monitoring C-peptide to adjust treatment. The panel concluded by advising general screening for LADA in newly diagnosed non–insulin-requiring diabetes and, importantly, that large randomized clinical trials are warranted.