Carbodiimide-Mediated Beckmann Rearrangement of Oxyma-B as a Side Reaction in Peptide Synthesis.

The suppression of side reactions is one of the most important objectives in peptide synthesis, where highly reactive compounds are involved. Recently, the violuric acid derivative Oxyma-B was introduced into peptide synthesis protocols as a promising additive to efficiently control the optical purity of the amino acids prone to racemization. However, we discovered a side reaction involving the Beckmann rearrangement of Oxyma-B during the coupling reaction, which compromises the yield and purity of the target peptides. Here, we present the investigation of the mechanism of this rearrangement and the optimization of the coupling reaction conditions to control it. These results can be taken into account for the design of novel efficient oxime-based coupling reagents.

The Double Effect of COVID-19 Confinement Measures and Economic Recession on High-Risk Drug Users and Drug Services.

The ongoing COVID-19 pandemic is likely to have a profound impact on the lives of high-risk drug users and on the services responding to their needs in at least two important ways: first, through the restrictive measures introduced to mitigate the spread of the virus and, second, as a result of extensive economic downturn. Currently there is great uncertainty as to the future intensity and duration of the pandemic. In addition, the lessons we have been able to learn from previous economic downturns may be of limited applicability to the current situation, which differs in a number of significant respects. Experience nevertheless suggests that the potential consequences for drug users' health and well-being may be severe. The ongoing uncertainty serves to underline the importance of close monitoring of the drug situation and preparing flexible and innovative solutions to be able to meet new challenges which may arise.

Mental health outcomes in times of economic recession: a systematic literature review.

BACKGROUND: Countries in recession experience high unemployment rates and a decline in living conditions, which, it has been suggested, negatively influences their populations' health. The present review examines the recent evidence of the possible association between economic recessions and mental health outcomes. METHODS: Literature review of records identified through Medline, PsycINFO, SciELO, and EBSCO Host. Only original research papers, published between 2004 and 2014, peer-reviewed, non-qualitative research, and reporting on associations between economic factors and proxies of mental health were considered. RESULTS: One-hundred-one papers met the inclusion criteria. The evidence was consistent that economic recessions and mediators such as unemployment, income decline, and unmanageable debts are significantly associated with poor mental wellbeing, increased rates of common mental disorders, substance-related disorders, and suicidal behaviours. CONCLUSION: On the basis of a thorough analysis of the selected investigations, we conclude that periods of economic recession are possibly associated with a higher prevalence of mental health problems, including common mental disorders, substance disorders, and ultimately suicidal behaviour. Most of the research is based on cross-sectional studies, which seriously limits causality inferences. Conclusions are summarised, taking into account international policy recommendations concerning the cost-effective measures that can possibly reduce the occurrence of negative mental health outcomes in populations during periods of economic recession.

Fluorescence Anisotropy and Polarization in the Characterization of Biomolecular Association Processes and Their Application to Study SH2 Domain Binding Affinity.

Fluorescence anisotropy (or polarization) is a powerful technique to study biomolecular association processes, by following the rotational motions of one of the two partners in the interaction, labeled with a fluorophore. It can be used to determine dissociation constants in solution, down to nM values, and unlabeled ligands can be characterized, too, by using competition experiments. In this chapter, we introduce the basic principles of the technique, compare it with other experimental approaches, and discuss the experimental details with specific examples regarding SH2 domain/phosphopeptide association processes. The experimental protocols to be used in binding experiments and displacement studies are described, as well as the caveats to be considered in performing accurate measurements.

Identifying the impact of the business cycle on drug-related harms in European countries.

BACKGROUND: The evidence resulting from the analysis of the association between economic fluctuations and their impact on the substance use is mixed and inconclusive. Effects can be pro-cyclical (drug-related harms are predicted to rise when economic conditions improve), counter-cyclical (drug-related harms are predicted to rise in bad economic times) or unrelated to business cycle conditions as different transmission mechanisms could operate simultaneously. METHODS: The main aim of this study is to assess, from a macroeconomic perspective, the impact of economic cycles on illegal drug-related harms in European countries over the 2000-2020 period. To this end, the regime-dependent relationship between drug-related harm, proxied by unemployment, and the business cycle, proxied by overdose deaths will be identified. Applying a time dynamic linear analysis, within the framework of threshold panel data models, structural-breaks will also be tested. RESULTS: The relationship between economic cycles (proxied by unemployment) and drug-related harms (proxied by overdose deaths) is negative, and therefore found to be pro-cyclical. One percentage point in the country unemployment rate is predicted to reduce the overdose death rate by a statistically significant percentage of 2.42. A counter-cyclical component was identified during the 2008 economic recession. The threshold model captures two effects: when unemployment rates are lower than the estimated thresholds, ranging from 3.92% to 4.12%, drug-related harms and unemployment have a pro-cyclical relationship. However, when unemployment rates are higher than this threshold, this relationship becomes counter-cyclical. CONCLUSIONS: The relationship between economic cycles and drug-related harms is pro-cyclical. However, in situations of economic downturns, a counter-cyclical effect is detected, as identified during the 2008 economic recession.

Expenditure on the treatment of drug and alcohol disorders in hospitals: How much and what explain it?

BACKGROUND: The role of hospitals in providing treatment for drug and alcohol abuse varies markedly across countries. Knowing public expenditure on drug treatment in hospitals is an essential input for any cost-effectiveness and policy analysis. However, information on the level and trend in spending is often unavailable. This study aims firstly to estimate the expenditure on hospital treatment for illicit drug and alcohol use as primary diagnoses across Europe for the 2013-2015 period, secondly to explain recent expenditure trends and lastly to analyse their impact on policy. METHODS: The study uses annual health expenditure data from Eurostat which complies with the 'System of Health Accounts' framework and covers the countries of the European Union as well as Norway. Data on hospital activities exist for 'Mental and Behavioural Disorders', which includes a breakdown into disorders caused by the use of alcohol and other psychoactive substances. The study uses 'attributable fractions' to estimate the proportion of hospital expenditure allocated to drug and alcohol treatments, based on data about this activity. Last, but not least, a panel data approach for the 2006-2015 period is used to explain expenditure determinants. RESULTS: In 2015, it is estimated that EUR 5.8 thousand million and EUR 2.9 thousand million were spent on the treatment of alcohol and drug disorders in hospitals as primary diagnoses, respectively, for a set of 24 European countries with available data. Cross-country differences can be explained by the level of income, the burden of disease and the structures of health systems - for instance, the proportion of public spending and the level (or share) of resources allocated for outpatient care. CONCLUSION: These estimates allow a better evaluation of treatment provision and, therefore, a better allocation of scarce resources. This information can support service providers, health policymakers and taxpayers. In this sense, it is a first step in developing policy evaluation and cost-effectiveness analysis.

National income inequality and declining GDP growth rates are associated with increases in HIV diagnoses among people who inject drugs in Europe: a panel data analysis.

BACKGROUND: There is sparse evidence that demonstrates the association between macro-environmental processes and drug-related HIV epidemics. The present study explores the relationship between economic, socio-economic, policy and structural indicators, and increases in reported HIV infections among people who inject drugs (PWID) in the European Economic Area (EEA). METHODS: We used panel data (2003-2012) for 30 EEA countries. Statistical analyses included logistic regression models. The dependent variable was taking value 1 if there was an outbreak (significant increase in the national rate of HIV diagnoses in PWID) and 0 otherwise. Explanatory variables included the growth rate of Gross Domestic Product (GDP), the share of the population that is at risk for poverty, the unemployment rate, the Eurostat S80/S20 ratio, the Gini coefficient, the per capita government expenditure on health and social protection, and variables on drug control policy and drug-using population sizes. Lags of one to three years were investigated. FINDINGS: In multivariable analyses, using two-year lagged values, we found that a 1% increase of GDP was associated with approximately 30% reduction in the odds of an HIV outbreak. In GDP-adjusted analyses with three-year lagged values, the effect of the national income inequality on the likelihood of an HIV outbreak was significant [S80/S20 Odds Ratio (OR) = 3.89; 95% Confidence Interval (CI): 1.15 to 13.13]. Generally, the multivariable analyses produced similar results across three time lags tested. INTERPRETATION: Given the limitations of ecological research, we found that declining economic growth and increasing national income inequality were associated with an elevated probability of a large increase in the number of HIV diagnoses among PWID in EEA countries during the last decade. HIV prevention may be more effective if developed within national and European-level policy contexts that promote income equality, especially among vulnerable groups.

Unemployment and drug treatment.

BACKGROUND: Since 2007 the economic recession has hit most industrial countries and this raises the question of how economic hardship affects illicit drug users' decisions to enter drug treatment. METHODS: We test the hypothesis that an improvement in the employment prospects, as measured by a decline in unemployment, strengthens the intrinsic motivation of an unemployed drug user to enter treatment. Our hypothesis is that the "payoff" of entering treatment increases when the unemployed drug user has a greater probability of finding a job. We reviewed the literature and found considerable evidence to substantiate this effect. We tested the hypothesis econometrically using two different data sets, one EU-wide and one German data set. RESULTS: Our main findings were that unemployment has a significant negative effect on the number of drug users entering treatment, i.e. when unemployment declines (increases) the number of drug treatment clients increases (declines). We also found that unemployed drug users entering treatment are most sensitive to variations in the economy-wide unemployment rate. Employed drug users, in contrast, are not influenced by these variations when deciding to enter treatment. CONCLUSION: Our empirical results confirm that the creation of job prospects adds significantly to the willingness of unemployed drug users to enter treatment. This lends support to the idea that drug treatment should be embedded in programmes to improve the job prospects of drug users.

Globalization and the price decline of illicit drugs.

BACKGROUND: This study aims at understanding the mechanisms underlying the dramatic decline of the retail prices of major drugs like cocaine and heroin during the past two decades. It also aims at analysing the implications of this decline for drug policies. METHODS: We use a theoretical model to identify the possible causes of this price decline. This allows us to formulate the hypothesis that the major driving force behind the price decline is a reduction of the intermediation margin (the difference between the retail and producer prices). We also develop the hypothesis that globalization has been an important factor behind the decline of the intermediation margin. We then analyse the statistical information to test these hypotheses. RESULTS: We find that the decline in the retail prices of drugs is related to the strong decline in the intermediation margin in the drug business, and that globalization is the main driving force behind this phenomenon. Globalization has done so by increasing the efficiency of the distribution of drugs, by reducing the risk premium involved in dealing with drugs, and by increasing the degree of competition in the drug markets. CONCLUSION: We conclude that the cocaine and heroin price declines were due to a sharp fall in the intermediation margin, which was probably influenced by globalization. This phenomenon might have a strong impact on the effectiveness of drug policies, increasing the relative effectiveness of policies aiming at reducing the demand of drugs.

The cocaine and heroin markets in the era of globalisation and drug reduction policies.

BACKGROUND: Despite the large volume of public effort devoted to restrain drug supply and the growing attention given to drug demand reduction policies, the use of cocaine and heroin remains steady. Furthermore, retail drug prices have fallen significantly in Europe and the US. This puzzling evidence leads us to develop a model aiming at systematically analysing illicit drug markets. METHODS: We model the markets of cocaine and heroin from production to the final retail markets. One novelty of the analysis consists in characterising the retail market as a monopolistic competitive one. Then, upper level dealers have some market power in the retail market. This allows them to charge a markup and to earn extra profits. These extra profits attract newcomers so that profits tend to fall over time. RESULTS: Theoretical model was used to analyse the effect of supply containment policies on the retail market, the producer market and the export-import business. This introduces the discussion of the impact of demand reduction policies on the high level traffickers' profit. Finally, globalisation enters in the model. CONCLUSIONS: Law enforcement measures increase the risk premia received by the lower and higher level traffickers. Consequently, trafficking intermediation margins tend to increase. However, globalisation has the opposite effect. It lowers intermediation margins and, then, pushes retail prices down, thereby stimulating consumption. In doing so, globalisation offsets the effects of supply containment policies. Finally, we discuss how the effectiveness of supply containment policies can be enhanced by combining them with demand reduction policies.