3D-printed portable device for illicit drug identification based on smartphone-imaging and artificial neural networks.

In this manuscript, a 3D-printed analytical device has been successfully developed to classify illicit drugs using smartphone-based colorimetry. Representative compounds of different families, including cocaine, 3,4-methylenedioxy-methamphetamine (MDMA), amphetamine and cathinone derivatives, pyrrolidine cathinones, and 3,4-methylenedioxy cathinones, have been analyzed and classified after appropriate reaction with Marquis, gallic acid, sulfuric acid, Simon and Scott reagents. A picture of the colored products was acquired using a smartphone, and the corrected RGB values were used as input data in the chemometric treatment. ANN using two active layers of nodes (6 nodes in layer 1 and 2 nodes in layer 2) with a sigmoidal transfer function and a minimum strict threshold of 0.50 identified illicit drug samples with a sensitivity higher than 83.4 % and a specificity of 100 % with limits of detection in the microgram range. The 3D printed device can operate connected to a rechargeable lithium-ion cell portable battery, is inexpensive, and requires minimal training. The analytical device has been able to discriminate the analyzed psychoactive substances from cutting and mixing agents, being a useful tool for law enforcement agents to use as a screening method.

Incidence of HIV type 1 infection, antiretroviral drug resistance, and molecular characterization in newly diagnosed individuals in Argentina: A Global Fund Project.

An HIV incidence estimation was performed among men who have sex with men (MSM), drug users (DUs), sex workers (SWs), and pregnant women (PW) from Argentina. Volunteers older than 18 years old without a previous HIV-positive diagnosis were included. HIV-positive samples were analyzed by the Serological Testing Algorithm for Recent HIV Seroconversion (STARHS) to estimate incidence. By partial RT-PCR and sequencing of the HIV pol gene, an HIV subtype and resistance profile were determined. A total of 12,192 volunteers were recruited from October 2006 to September 2008. A higher HIV prevalence was detected among trans SWs (33.9%, 38/112), male SWs (10.8%, 12/111), and MSM 10.4% (161/1549). HIV incidence estimates by STARHS was also higher on trans SWs (11.31 per 100 person-years), male SWs (6.06 per 100 person-years), and MSM (6.36 per 100 person-years). Antiretroviral primary resistant mutations were detected in 8.4% of the study group, with a higher frequency in female DUs (33.3%). Phylogenetic analysis showed that 124 (57.9%) samples were subtype B, 84 (39.3%) intersubtype BF recombinants, 5 (2.3%) subtype C, and 1 (0.5%) subtype F in the pol region. Subtype B was most commonly found in MSM and male SWs whereas the intersubtype BF recombinant was more prevalent in female DUs, female SWs, and PW. Given the high HIV prevalence and incidence found in most of these groups, monitoring the continuing spread of the HIV epidemic is essential for determining public health priorities, assessing the impact of interventions, and estimating current and future health care needs.

[A potential neuroprotective and synaptic plasticity mechanism induced by estradiol through PI3K/GSK3beta in cerebral ischaemia]. / Mecanismo potencial de neuroprotección y plasticidadsináptica inducidas por el estradiol a través dePI3K/GSK3beta en la isquemia cerebra.

AIM: To review the basic molecular mechanisms that are triggered by neuroactive steroids related to protection and plasticity, and their possible therapeutic application in cases of cerebral ischaemia. DEVELOPMENT: The term 'neuroprotection' embraces a series of strategies and effects that are aimed at preventing, impeding or delaying anomalies in the functioning of the central nervous system. The neuroactive steroids, and particularly estradiol, have been widely reported owing to their neuroprotective action because they give rise to a wide range of cell signals and generate effects in genes by means of canonical pathways or through non-conventional mechanisms that are involved in neuronal survival, dendritogenesis and synapse remodelling. Thus, neuroactive steroids become an important long-term protective therapeutic alternative due to the fact that such effects converge on neuronal plasticity. CONCLUSIONS: Further work needs to be carried out to study the mechanisms of action of neuroactive steroids, especially the non-conventional ones, which involve proteins such as GSK-3beta and beta-catenin. These proteins are involved in the functions of synaptic plasticity and survival, and play a crucial role in maintaining and recovering the functional integrity of the brain after the appearance of the lesions caused by cerebral ischaemia.

Mecanismo potencial de neuroprotección y plasticidad sináptica inducidas por el estradiol a través de PI3K/GSK3beta en la isquemia cerebral / A potential neuroprotective and synaptic plasticity mechanism induced by estradioll through PI3K/GSK3beta in cerebral ischaemia

Revisar los mecanismos moleculares básicos desencadenados por esteroides neuroactivos relacionadoscon la protección y la plasticidad, y su posible aplicación terapéutica en la isquemia cerebral. Desarrollo. El término ‘neuroprotección’abarca una serie de estrategias y efectos encaminados a prevenir, impedir o retrasar anomalías en el funcionamiento del sistema nervioso central. Los esteroides neuroactivos, en particular el estradiol, se han referenciado ampliamente por su acción neuroprotectora porque originan una gran diversidad de señales celulares y producen efectos génicos por mediode rutas canónicas o a través de mecanismos no convencionales, involucrados en la supervivencia neuronal, la dendritogénesis y la remodelación sináptica, lo que convierte a los esteroides neuroactivos en una importante alternativa terapéuticade protección a largo plazo por su convergencia con dichos efectos en plasticidad neuronal. Conclusión. Es necesario profundizar en el estudio de los mecanismos de acción de los esteroides neuroactivos, en especial sobre los no convencionales, que involucran proteínas tales como la GSK-3beta y la beta-catenina, en las cuales convergen funciones de supervivencia y plasticidadsináptica y que pueden desempeñar un papel crucial en el mantenimiento y la recuperación de la integridad funcional del cerebro frente a las lesiones propias de la isquemia cerebral

To review the basic molecular mechanisms that are triggered by neuroactive steroids related to protection and plasticity, and their possible therapeutic application in cases of cerebral ischaemia. Development. The term ‘neuroprotection’ embraces a series of strategies and effects that are aimed at preventing, impeding or delaying anomalies in the functioning ofthe central nervous system. The neuroactive steroids, and particularly estradiol, have been widely reported owing to their neuroprotective action because they give rise to a wide range of cell signals and generate effects in genes by means ofcanonical pathways or through non-conventional mechanisms that are involved in neuronal survival, dendritogenesis and synapse remodelling. Thus, neuroactive steroids become an important long-term protective therapeutic alternative due to thefact that such effects converge on neuronal plasticity. Conclusions. Further work needs to be carried out to study the mechanisms of action of neuroactive steroids, especially the non-conventional ones, which involve proteins such as GSK-3beta and beta-catenin. These proteins are involved in the functions of synaptic plasticity and survival, and play a crucial role inmaintaining and recovering the functional integrity of the brain after the appearance of the lesions caused by cerebral ischaemia

Discrepant results in the interpretation of HIV-1 drug-resistance genotypic data among widely used algorithms.

OBJECTIVES: The aim of this study was to assess the concordance on the interpretation of HIV-1 drug-resistance genotypic data by three widely used algorithms: Stanford University Database (SU), TruGene (Visible Genetics, Canada) (VG) and VirtualPhenotype (Virco, Belgium) (VP). METHODS: Genotypic data from 293 HIV-1-infected individuals with treatment failure was interpreted for 14 antiretroviral drugs by the three algorithms. RESULTS: Complete concordant results among the three systems for all the drugs studied were found in 40/293 (13.7%) samples. Low concordance in the interpretation was observed for most nucleoside reverse transcriptase inhibitors (NRTIs), while results agreed highly for all nonnucleoside reverse transcriptase inhibitors (NNRTIs) and most protease inhibitors (PIs). In pair-wise comparisons, discordant interpretations between SU and VP were found in over 50% of the samples for didanosine, zalcitabine, stavudine and abacavir, and the level of disagreement between VG and VP exceeded 40% for the same drugs. Major discrepancies (high-level resistance interpretation by one algorithm with sensitive interpretation by another) were observed between VG and VP in over 10% of the cases for didanosine, zalcitabine, stavudine and abacavir. On the other hand, the three algorithms had concordant results for lamivudine in over 90% of the cases. CONCLUSIONS: This work demonstrates the great level of discordance in the interpretation of genotyping results among algorithms, clearly showing the necessity for clinical validation. Moreover, these results suggest that a joint effort from the scientific community as well as national and international HIV societies is needed to achieve a consensus for the interpretation of genotypic data.

HIV type 1 genetic diversity is a major obstacle for antiretroviral drug resistance hybridization-based assays.

Human immunodeficiency virus type 1 (HIV-1) is characterized by high genetic diversity. Current antiretroviral (ARV) drug resistance genotyping assays have been designed on the basis of the most prevalent sequence patterns circulating in the United States and Europe, which belong to the B subtype. However, little is known about their performance on non-B subtype samples. In Argentina, circulating forms have been characterized as subtypes B, C, F, and B/F recombinant forms. Our aim was to analyze the association between the genetic diversity of HIV-1 forms circulating in Argentina and the lack of reactivity at codon 74 in an ARV drug resistance hybridization-based assay. Samples taken from 93 HIV-1-infected individuals of Buenos Aires, Argentina were studied. The reverse transcriptase (RT) region of HIV-1 was genotypically assessed by a line probe assay (INNO-LiPA HIV-1 RT; Innogenetics, Ghent, Belgium) and automatic sequencing (TruGene and OpenGene; Visible Genetics, Toronto, Canada). Phylogenetic and intersubtype recombination analyses were carried out, showing that 52 of 93 (55.9%) samples belonged to subtype B, whereas 41 of 93 (44.1%) showed a (5') F1/B (3') subtype recombinant genomic structure. For codon 74 in the LiPA test, 4 of 52 (7.7%) B-subtype samples were nonreactive, whereas 27 of 41 (65.9 %) F1/B recombinant samples showed a nonreacting result, indicating a significant difference in the subtype distribution of the nonreacting samples. The presence of a synonymous polymorphism at codon 72 of RT (AGA --> AGG) associated with the lack of reaction at codon 74 in LiPA, was more prevalent in F1/B subtype recombinant samples (p < 0.001). The present data indicate that HIV-1 genetic diversity is a major obstacle for ARV drug resistance hybridization-based assays.