Exploring Twitter chatter to assess the type and availability of cannabis-related products in Thailand.

Cannabis-related tweets were collected between January and April 2022 to estimate the availability and characteristics of cannabis products advertised on Twitter amid the legalization of recreational cannabis in Thailand. The Twitter API was called using the tweepy Python library to collect cannabis-related tweets in the Thai language. A total of 185,558 unique tweets were collected over the duration of the data collection period based on 83 search terms. Twenty thousand random tweets were manually coded by four Thai native speakers to assess the volume and characteristics of tweets proposing cannabis. 72.6% of collected tweets from the 20,000 random samples were coded as relevant to the study. 54.6% of relevant tweets were advertising cannabis products, 29.8% were personal communications, and 15.6% were related to news or media content. Among the tweets that advertised cannabis products, 94.4% proposed cannabis flower, 2.4% cannabis edibles and 1.8% cannabis concentrates. Consumption of potent forms of cannabis such as cannabis edibles and concentrates increase the risk of harmful side-effects, especially in a population with limited knowledge about these products. Our findings call for additional monitoring efforts and for increasing the public awareness on potent cannabis products emerging in Thailand.

Gut microbiota associations with chronic kidney disease: insights into nutritional and inflammatory parameters.

Introduction: The gut barrier, comprising gut microbiota, plays a pivotal role in chronic kidney disease (CKD) progression and nutritional status. This study aimed to explore gut barrier alterations in hemodialyzed (HD) patients, non-HD (NHD) CKD patients, and healthy volunteers. Methods: Our cross-sectional study enrolled 22 HD patients, 11 NHD patients, and 11 healthy volunteers. We evaluated fecal microbiota composition (assessed via bacterial 16S rRNA gene sequencing), fecal IgA levels, surrogate markers of gut permeability, serum cytokines, appetite mediators, nutritional status, physical activity, and quality of life. Results: HD patients exhibited significant alterations in fecal microbiota composition compared to healthy volunteers, with observed shifts in taxa known to be associated with dietary patterns or producing metabolites acting on human host. In comparison to healthy volunteers, individuals with HD patients exhibited elevated levels of inflammatory markers (CRP, IL-6 and TNF-α), glucagon-like peptide-2, and potential anorexigenic markers (including leptin and peptide YY). NHD patients had increased levels of CRP and peptide YY. Overall fecal microbiota composition was associated with height, soft lean mass, resting energy expenditure, handgrip strength, bone mineral content and plasma albumin and TNF-α. Discussion: Compared to healthy volunteers, HD patients have an altered fecal microbiota composition, a higher systemic inflammation, and a modification in plasma levels of appetite mediators. While some differences align with previous findings, heterogeneity exists likely due to various factors including lifestyle and comorbidities. Despite limitations such as sample size, our study underscores the multifaceted interplay between gut microbiota, physiological markers, and kidney function, warranting further investigation in larger cohorts.

Langerhans cell histiocytosis of the suprasellar region: diagnosis based on thyroid cytology.

Langerhans cell histiocytosis (LCH) may present as unifocal disease of the suprasellar region, with symptoms and signs of hypopituitarism, arginine vasopressin deficiency (AVP-D), and weight gain. Transcranial biopsy is necessary to define diagnosis and guide treatment decisions, but it is associated with significant morbidity. We describe a patient with Hashimoto thyroiditis and a single hypothalamic mass in whom LCH diagnosis was made by thyroid fine-needle aspiration cytology (FNAC) performed despite nonspecific findings in thyroid imaging, on the basis of a slightly elevated [18F]-fluorodeoxyglucose (FDG) avidity on PET/CT and volume increase during follow-up.

[Diabetic gastroparesis and type 1 diabetes]. / Gastroparésie diabétique et diabète de type 1.

Gastroparesis is a rare and late microvascular complication, but a significant one of diabetes. Defined by a slowing of gastric emptying, this condition manifests with nonspecific gastrointestinal symptoms, including nausea, vomiting, abdominal pain, postprandial fullness, and early satiety. Faced with such a clinical presentation, it is often challenging to diagnose gastroparesis. In this article, we discuss the diagnostic procedures, as well as therapeutic approaches and management of the disease.

La gastroparésie est une complication microvasculaire rare et tardive, mais conséquente, du diabète. Définie par un ralentissement de la vidange gastrique, cette pathologie se présente sous la forme de symptômes gastro-intestinaux aspécifiques incluant des nausées, des vomissements, des douleurs abdominales, une sensation de réplétion postprandiale et une satiété précoce. Face à une présentation clinique de ce type, il est souvent difficile de poser le diagnostic de gastroparésie. Dans cet article, nous évoquons donc les examens complémentaires permettant de poser le diagnostic, ainsi que les propositions thérapeutiques et la prise en charge de la maladie.

Wearing a KN95/FFP2 facemask has no measureable effect on functional activity in a challenging working memory n-back task.

Introduction: Wide use of facemasks is one of the many consequences of the COVID-19 pandemic. Methods: We used an established working memory n-back task in functional magnetic resonance imaging (fMRI) to explore whether wearing a KN95/FFP2 facemask affects overall performance and brain activation patterns. We provide here a prospective crossover design 3 T fMRI study with/without wearing a tight FFP2/KN95 facemask, including 24 community-dwelling male healthy control participants (mean age ± SD = 37.6 ± 12.7 years) performing a 2-back task. Data analysis was performed using the FSL toolbox, performing both task-related and functional connectivity independent component analyses. Results: Wearing an FFP2/KN95 facemask did not impact behavioral measures of the 2-back task (response time and number of errors). The 2-back task resulted in typical activations in working-memory related areas in both MASK and NOMASK conditions. There were no statistically significant differences in MASK versus NOMASK while performing the 2-back task in both task-related and functional connectivity fMRI analyses. Conclusion: The effect of wearing a tight FFP2/KN95 facemasks did not significantly affect working memory performance and brain activation patterns of functional connectivity.

Use of GLP1 receptor agonists in early pregnancy and reproductive safety: a multicentre, observational, prospective cohort study based on the databases of six Teratology Information Services.

OBJECTIVES: Glucagon-like peptide 1 receptor agonists (GLP1-RA) are indicated for the treatment of type 2 diabetes and more recently for weight loss. The aim of this study was to assess the risks associated with GLP1-RA exposure during early pregnancy. DESIGN: This multicentre, observational prospective cohort study compared pregnancy outcomes in women exposed to GLP1-RA in early pregnancy either for diabetes or obesity treatment with those in two reference groups: (1) women with diabetes exposed to at least one non-GLP1-RA antidiabetic drug during the first trimester and (2) a reference group of overweight/obese women without diabetes, between 2009 and 2022. SETTING: Data were collected from the databases of six Teratology Information Services. PARTICIPANTS: This study included 168 pregnancies of women exposed to GLP1-RA during the first trimester, alongside a reference group of 156 pregnancies of women with diabetes and 163 pregnancies of overweight/obese women. RESULTS: Exposure to GLP1-RA in the first trimester was not associated with a risk of major birth defects when compared with diabetes (2.6% vs 2.3%; adjusted OR, 0.98 (95% CI, 0.16 to 5.82)) or to overweight/obese (2.6% vs 3.9%; adjusted OR 0.54 (0.11 to 2.75)). For the GLP1-RA group, cumulative incidence for live births, pregnancy losses and pregnancy terminations was 59%, 23% and 18%, respectively. In the diabetes reference group, corresponding estimates were 69%, 26% and 6%, while in the overweight/obese reference group, they were 63%, 29% and 8%, respectively. Cox proportional cause-specific hazard models indicated no increased risk of pregnancy losses in the GLP1-RA versus the diabetes and the overweight/obese reference groups, in both crude and adjusted analyses. CONCLUSIONS: This study offers reassurance in cases of inadvertent exposure to GLP1-RA during the first trimester of pregnancy. Due to the limited sample size, larger studies are required to validate these findings.

Population Pharmacokinetics of Cabotegravir Following Oral Administration and Long-Acting Intramuscular Injection in Real-World People with HIV.

Long-acting cabotegravir has been studied mainly in the stringent framework of clinical trials, which does not necessarily reflect the situation of people with HIV (PWH) in routine clinical settings. The present population pharmacokinetic analysis aims to build real-world reference percentile curves of cabotegravir concentrations, accounting for patient-related factors that may affect cabotegravir exposure. The second objective is to simulate whether dosing interval adjustments of cabotegravir could be considered in specific subpopulations. Overall, 238 PWH contributed to 1,038 cabotegravir levels (186 during the initial oral administration phase and 852 after intramuscular injection). Cabotegravir pharmacokinetics was best described using a one-compartment model with distinct first order-absorption for oral and intramuscular administrations, and identical volume and clearance. Our model showed almost 40% faster absorption and 30% higher clearance than previously reported, resulting in a time to steady-state of 8 months and an elimination half-life of 4.6 weeks for long-acting cabotegravir. Sex and body mass index significantly influenced absorption, and bodyweight affected clearance. Model-based simulations showed that cabotegravir trough concentrations in females were 25% lower 4 weeks after the intramuscular loading dose, but 42% higher during the late maintenance phase. Finally, simulations indicated that in females, despite significantly higher cabotegravir concentrations, longer intervals between injections may not consistently ensure levels above the 4-fold protein-adjusted 90% inhibitory target concentration.

[Obstetrics and Gynecology. Management and screening for gestational diabetes : what's new in 2023]. / Gynécologie-obstétrique. Prise en charge et dépistage du diabète gestationnel : ce qui a changé en 2023.

Gestational diabetes (GDM) is becoming increasingly common as a result of the increase in overweight, obesity and maternal age among pregnant women. As a result, in order to provide early hygienic and dietary management, it is recommended that targeted screening be carried out in the first trimester of pregnancy, based on the identification of risk factors in women. In the absence of risk factors, screening for gestational diabetes should be carried out for all pregnant women between 24 and 28 weeks' gestation. During pregnancy, the safest pharmacological treatment remains insulin, and the term of delivery should take account of additional risk factors, insulin requirements, fœtal growth kinetics and the balance of GDM. In the longer term, gestational diabetes should be regarded as a metabolic and cardiovascular warning sign.

Dû à l'augmentation du surpoids, de l'obésité et de l'âge maternel chez les femmes enceintes, le diabète gestationnel (DG) est de plus en plus fréquent. De ce fait, afin d'offrir une prise en charge hygiénodiététique précoce, il est recommandé d'effectuer un dépistage ciblé au premier trimestre de la grossesse pour identifier les facteurs de risque. En leur absence, le dépistage du DG doit être réalisé chez toutes les femmes enceintes entre 24 et 28 SA. Au cours de la grossesse, le traitement pharmacologique le plus sécuritaire reste l'insuline et le terme d'accouchement doit tenir compte des facteurs de risque surajoutés, des besoins en insuline, de la cinétique de croissance fœtale et de l'équilibre du DG. À plus long terme, le DG doit être considéré comme une alerte métabolique et cardiovasculaire.

Women in acute forensic psychiatric care: comparison of clinical, sociodemographic, and detention-related characteristics in pretrial detention, sentence execution, and court-ordered treatment.

Compared to men inmates, women display decreased prevalence of severe mental disorder but increased occurrence of substance use disorders (SUD) and higher rates of previous contacts with mental health services. The group of women in detention is highly heterogeneous according to the status of incarceration (pre-trial detention (PTD), sentence execution (SE) and court ordered treatments (COT)). Studies focusing on the comparison of sociodemographic patterns, detention-related and clinical variables between these groups are still lacking. We explored these parameters in 136 women admitted for acute psychiatric care in the sole Geneva forensic unit during a nine year period (2014-2023). Sociodemographic and detention-related data included age, nationality, marital status, presence of children, education attainment, most frequently speaking language, social support, employment before conviction and type of offenses. Clinical variables included the main ICD-10 diagnosis, presence of concomitant SUD, type of personality disorders, presence of suicidal thoughts and attempts at admission, as well as number and mean duration of stays. PTD and SE women had at least 9 years of formal education in 38.9% and 30.3% of cases. Most women in PTD (77.7%), SE (56.6%) and COT (56.2%) groups were Swiss or European citizens. The level of French knowledge was excellent in most of the cases. 43.8% of COT women had at least one child and this percentage is even higher for PTD and SE cases. The employment rate before conviction was also quite high, mainly for PTD and SE (61.1% and 60.6%) and, in a lesser degree, for COT (43.8%) women. Significant social support was present in the vast majority of women without any significant group difference. The distribution of type of offenses did not differ between the three types of detention with a predominance of physical violence, and drug trafficking. The number of stays during the period of reference was significantly higher in COT compared to both SE and PTD women. History of previous inpatient care was also significantly more frequent in COT that SE and PTD women. Adjustment and affective disorders were more often found in SE and PTD cases, these diagnoses were absent in the COT group. In contrast, a main diagnosis of psychotic disorders was found in 62.5% of COT cases compared to only 21.2% in SE and 24.1% in PTD cases. The number of stays, history of inpatient care and diagnosis of psychosis were independent predictors of COT status. In conclusion, the present data reveal the good social integration and emotional support of women needing acute psychiatric care in prison independently of the type of detention. Clinically, women in PTD and SE display more often emotional distress whereas those in COT suffer from acute psychotic symptoms with previous history of psychiatric care and multiple inpatient stays.

Guidance for the Interpretation of Long-Acting Cabotegravir and Rilpivirine Concentrations Based on Real-World Therapeutic Drug Monitoring Data and Documented Failures.

The interpretation of long-acting cabotegravir and rilpivirine concentrations is complicated by the lack of consensus on the threshold to consider. Building on real-world therapeutic drug monitoring data and documented virologic failures, this article provides a reappraisal of the existing thresholds and guidance for the interpretation of cabotegravir and rilpivirine concentrations.

[Court-ordered inpatient psychiatric care in Switzerland. Length of stay and treatment outcome]. / Thérapies sous mandat pénal en Suisse. Population clinique, durées de séjour et destinations de sortie.

Mentally disordered offenders may be convicted to court-ordered psychiatric-psychotherapeutic inpatient care. Based on the concept of a forensic therapeutic community, the treatments of 204 inmates of a medium-security hospital, who presented with psychosis, personality disorders or substance-use disorders, have been assessed. After a median stay of 2.5 years, 56% of the offenders had been transferred to a sheltered educational housing or to an open low-security psychiatric ward. Length of stay was independent of psychiatric diagnosis, yet dependent on the nature of the offense. Having a cluster B personality disorder or a conviction for a sexual offense increased the risk of return to prison. Younger age and offenses without interpersonal violence increased the chances to enter sheltered educational housing.

Les auteurs d'infractions atteints d'un trouble mental sévère peuvent être soumis à un traitement psychiatrique-psychothérapeutique par ordonnance pénale. Basés sur le concept de la communauté thérapeutique forensique, les suivis de 204 détenus-patients atteints d'un trouble psychotique ou de la personnalité ou encore d'une dépendance aux substances ont été évalués. Après un séjour médian de 2,5 ans, 56 % ont été transférés dans un foyer socioéducatif ou une unité psychiatrique hors prison. La durée de séjour est indépendante du diagnostic psychiatrique mais dépend du type de délit. Un diagnostic de trouble de la personnalité cluster B ou une infraction sexuelle augmentent la probabilité de retourner en prison. Un jeune âge et un délit sans violence interpersonnelle favorisent une sortie en foyer.

The effect of temporal data aggregation to assess the impact of changing temperatures in Europe: an epidemiological modelling study.

Background: Daily time-series regression models are commonly used to estimate the lagged nonlinear relation between temperature and mortality. A major impediment to this type of analysis is the restricted access to daily health records. The use of weekly and monthly data represents a possible solution unexplored to date. Methods: We temporally aggregated daily temperatures and mortality records from 147 contiguous regions in 16 European countries, representing their entire population of over 400 million people. We estimated temperature-lag-mortality relationships by using standard time-series quasi-Poisson regression models applied to daily data, and compared the results with those obtained with different degrees of temporal aggregation. Findings: We observed progressively larger differences in the epidemiological estimates with the degree of temporal data aggregation. The daily data model estimated an annual cold and heat-related mortality of 290,104 (213,745-359,636) and 39,434 (30,782-47,084) deaths, respectively, and the weekly model underestimated these numbers by 8.56% and 21.56%. Importantly, differences were systematically smaller during extreme cold and heat periods, such as the summer of 2003, with an underestimation of only 4.62% in the weekly data model. We applied this framework to infer that the heat-related mortality burden during the year 2022 in Europe may have exceeded the 70,000 deaths. Interpretation: The present work represents a first reference study validating the use of weekly time series as an approximation to the short-term effects of cold and heat on human mortality. This approach can be adopted to complement access-restricted data networks, and facilitate data access for research, translation and policy-making. Funding: The study was supported by the ERC Consolidator Grant EARLY-ADAPT (https://www.early-adapt.eu/), and the ERC Proof-of-Concept Grants HHS-EWS and FORECAST-AIR.

[Diabetology: what's new in 2023]. / Diabétologie: ce qui a changé en 2023.

Diabetology is a continuously evolving discipline, many molecules are developed and treatment recommendations change often according to the latest published studies. It is therefore often difficult for the primary care physician to be up to date. After lifestyle measures that must always be preferred before any drug, metformin remains the pharmacological basis of treatment. Current recommendations favor the introduction of an SGLT2 inhibitor or a GLP-1 receptor agonist after metformin because these molecules have shown beneficial cardiovascular and renal effects. The purpose of this article is to guide the primary care physician to choose the most suitable pharmacological treatment for each patient, in the light of the 2023 novelties in the field of diabetes.

La diabétologie est une discipline en évolution continue, de nombreuses molécules sont développées et les recommandations de traitement changent fréquemment en fonction des dernières études publiées. Il est donc souvent difficile pour le médecin de premier recours d'être à jour. Après les mesures du style de vie qu'il faut toujours privilégier avant toute approche médicamenteuse, la metformine reste la base pharmacologique du traitement. Les recommandations actuelles préconisent d'instaurer un inhibiteur du SGLT2 ou un agoniste du récepteur du GLP-1 après la metformine car ces molécules ont montré des effets bénéfiques cardiovasculaires et rénaux. Le but de cet article est de fournir une aide au médecin de premier recours dans le choix du traitement pharmacologique le plus adapté à chaque patient, à la lumière des nouveautés 2023 dans le domaine du diabète.

[Pharmacovigilance. Withdrawal and rebound effects: not just with psychotropic drugs]. / Pharmacovigilance. Sevrage et effet rebond: pas seulement avec les psychotropes.

The list of drugs whose abrupt discontinuation is likely to induce withdrawal symptoms or a rebound in the pathology being treated is not limited to psychotropic drugs. It includes a number of somatic drugs (e.g. proton pump inhibitors, opioids, triptans, fingolimod, corticosteroids, antiepileptics, nootropics, antiparkinsonians, denosumab, beta-blockers, laxatives, nasal vasoconstrictors, etc.). This type of unintended effect, often underestimated, generally results from a drug-induced homeostatic imbalance that persists after the drug has been discontinued. Taking this risk into account right from the initial prescription should make it possible to prevent such complications, by encouraging intermittent use of the drug, or by applying a very gradual reduction in dosage when a regular treatment is stopped.

La liste des médicaments dont l'arrêt brusque est susceptible d'entraîner des symptômes de sevrage ou un rebond de la pathologie traitée ne se limite pas aux psychotropes, mais inclut un certain nombre de médicaments somatiques (inhibiteurs de la pompe à protons, opioïdes, triptans, fingolimod, corticostéroïdes, antiépileptiques, nootropes, antiparkinsoniens, dénosumab, bêtabloquants, laxatifs, vasoconstricteurs nasaux, etc.). Ce type d'effet indésirable, souvent méconnu, résulte en général d'un déséquilibre homéostatique causé par le médicament, persistant après son interruption. La prise en compte de ce risque dès la prescription initiale devrait permettre de prévenir ces complications, en privilégiant un recours intermittent au médicament ou en prévoyant une diminution très progressive des posologies au moment de mettre un terme à un traitement continu.

Real-world trough concentrations and effectiveness of long-acting cabotegravir and rilpivirine: a multicenter prospective observational study in Switzerland.

Background: The efficacy and tolerability of long-acting cabotegravir and rilpivirine were demonstrated in Phase III trials. However, low concentrations combined with other risk factors have been associated with an increased risk of virologic failure. This study aims to verify whether drug concentrations measured in a real-world setting are consistent with those previously reported. Methods: SHCS-879 is a nationwide observational study within the Swiss HIV Cohort Study for the monitoring of people with HIV (PWH) on long-acting cabotegravir plus rilpivirine. Samples were collected from March 2022 to March 2023. Findings: Overall, 725 samples were obtained from 186 PWH. Our data show a large inter-individual variability in cabotegravir and rilpivirine concentrations, with some individuals exhibiting repeatedly low concentrations. Rilpivirine trough concentrations were consistent with those from Phase III trials, while cabotegravir concentrations were lower. The first concentrations quartile was only slightly above the target of 664 ng/mL. Exploratory statistical analyses found 35% (p < 0·01) lower cabotegravir trough in males compared to females. Overall, 172 PWH (92%) remained suppressed and three experienced virologic failures (1·6%), of those, two had sub-optimal drug exposure. No association was found between low trough levels and detectable viral load. Interpretation: Real-world cabotegravir concentrations are substantially lower than previously reported. However, these concentrations appear sufficient to ensure sustained virological suppression in almost every PWH. These reassuring data challenge the rather conservative thresholds adopted to date, which may raise unnecessary concerns. Yet, our study reveals that some PWH have repeatedly very low drug levels, for reasons that remain to be elucidated. Funding: This work was funded by the Swiss National Science Foundation, grant number N◦ 324730_192449. This study received no support from pharmaceutical industries. This study was performed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project #879, and by the SHCS research foundation. The SHCS data were gathered by the Five Swiss University Hospitals, two Cantonal Hospitals, 15 affiliated hospitals and 36 private physicians (listed in http://www.shcs.ch/180-health-care-providers).

The paired-pulse TMS paradigm of short intracortical inhibition is mediated by a reduction of repetitive motor neuron discharges.

Transcranial magnetic stimulation (TMS) causes repetitive spinal motoneuron discharges (repMNDs), but the effects of short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) on repMNDs remain unknown. Triple stimulation technique (TST) and the extended TST-protocols that include a fourth and fifth stimulation, the Quadruple (QuadS) and Quintuple (QuintS) stimulation, respectively, offer a precise estimate of cortical and spinal motor neuron discharges, including repMNDs. The objective of our study was to explore the effects of SICI and ICF on repMNDs. We explored conventional paired-pulse TMS protocols of SICI and ICF with the TMS, TST, the QuadS, and the QuintS protocols, in a randomized study design in 20 healthy volunteers. We found significantly less repMNDs in the SICI paradigm compared with a single-pulse TMS (SP-TMS). No significant difference was observed in the ICF paradigm. There was a significant inter- and intrasubject variability in both SICI and ICF. We demonstrate a significant reduction of repMNDs in SICI, which may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no increase in repMNDs in ICF suggesting another mechanism underlying facilitation. This study provides the proof that a reduction of repMNDs mediates the inhibition seen in SICI.NEW & NOTEWORTHY Significant reduction of repetitive motor neuron discharges (repMNDs) in short-interval intracortical inhibition (SICI) may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no change in the number of repMNDs in intracortical facilitation (ICF). There was a significant variability in SICI and ICF in healthy subjects.

S100A9 exerts insulin-independent antidiabetic and anti-inflammatory effects.

Type 1 diabetes mellitus (T1DM) is characterized by insulin deficiency leading to hyperglycemia and several metabolic defects. Insulin therapy remains the cornerstone of T1DM management, yet it increases the risk of life-threatening hypoglycemia and the development of major comorbidities. Here, we report an insulin signaling-independent pathway able to improve glycemic control in T1DM rodents. Co-treatment with recombinant S100 calcium-binding protein A9 (S100A9) enabled increased adherence to glycemic targets with half as much insulin and without causing hypoglycemia. Mechanistically, we demonstrate that the hyperglycemia-suppressing action of S100A9 is due to a Toll-like receptor 4-dependent increase in glucose uptake in specific skeletal muscles (i.e., soleus and diaphragm). In addition, we found that T1DM mice have abnormal systemic inflammation, which is resolved by S100A9 therapy alone (or in combination with low insulin), hence uncovering a potent anti-inflammatory action of S100A9 in T1DM. In summary, our findings reveal the S100A9-TLR4 skeletal muscle axis as a promising therapeutic target for improving T1DM treatment.

"Pressed OXY M30 Pills, Great Press, Potent, Fast Shipping!!!": Availability of Counterfeit and Pharmaceutical Oxycodone Pills on One Major Cryptomarket.

From 2018 to 2021, seizures of counterfeit oxycodone pills containing non-pharmaceutical fentanyl or other novel synthetic opioids increased significantly contributing to continuing increases in overdose mortality in Northern America. Evidence suggests that counterfeit pills are distributed through cryptomarkets. This article presents data regarding the availability and characteristics of oxycodone pills advertised on one major cryptomarket between January and March 2022. Collected data were processed using a dedicated Named Entity Recognition algorithm to identify oxycodone listings and categorized them as either counterfeit or pharmaceutical. Frequency of listings, average number of pills advertised, average prices per milligram, number of sales, and geographic indicators of shipment origin and destination were analyzed. In total, 2,665 listings were identified as oxycodone. 48.2% (1,285/2,665) of these listings were categorized as counterfeit oxycodone, advertising a total of 652,699 pills (93,242.7 pills per datapoint) offered at a lower price than pharmaceutical pills. Our data indicate the presence of a large volume of counterfeit oxycodone pills both in retail- and wholesale-level amounts mostly targeting US and Canadian customers. These exploratory findings call for more research to develop epidemiological surveillance systems to track counterfeit pill and other drug availability on the Dark web environment.

CCR5 deficiency: Decreased neuronal resilience to oxidative stress and increased risk of vascular dementia.

INTRODUCTION: As the chemokine receptor5 (CCR5) may play a role in ischemia, we studied the links between CCR5 deficiency, the sensitivity of neurons to oxidative stress, and the development of dementia. METHODS: Logistic regression models with CCR5/apolipoprotein E (ApoE) polymorphisms were applied on a sample of 205 cognitively normal individuals and 189 dementia patients from Geneva. The impact of oxidative stress on Ccr5 expression and cell death was assessed in mice neurons. RESULTS: CCR5-Δ32 allele synergized with ApoEε4 as risk factor for dementia and specifically for dementia with a vascular component. We confirmed these results in an independent cohort from Italy (157 cognitively normal and 620 dementia). Carriers of the ApoEε4/CCR5-Δ32 genotype aged ≥80 years have an 11-fold greater risk of vascular-and-mixed dementia. Oxidative stress-induced cell death in Ccr5-/- mice neurons. DISCUSSION: We propose the vulnerability of CCR5-deficient neurons in response to oxidative stress as possible mechanisms contributing to dementia.