Marijuana use, heavy drinking, and cognitive dysfunction in people with Human Immunodeficiency Virus-infection

AIMS: Substance use and dependence is very common among people living with HIV-infection. Since substances like alcohol and marijuana as well as the HIV virus itself are believed to have negative effects on cognition and the brain, our aim was to test the hypothesis that current and lifetime marijuana and heavy alcohol use are associated with cognitive dysfunction in people with HIV-infection. METHODS: Boston ARCH cohort participants consisted of 215 HIV-infected adults with substance dependence or current or past injection drug use. In cross-sectional, regression analyses we tested the association between current marijuana use (number of days marijuana was used in the past 30 days), current heavy alcohol use (number of heavy drinking days in the past 30 days defined as ≥4 drinks for women and ≥ 5 for men in 24 hours), lifetime marijuana use (number of years marijuana was used ≥ 3 times per week), lifetime alcohol use (total Kg), duration of heavy alcohol use (# of years alcohol was use > 84 grams or > 6 drinks per day), and three measures of cognitive dysfunction: i) memory and ii) attention domains of the Montreal Cognitive Assessment (MoCA), and iii) 4-item cognitive function scale (CF4) from the Medical Outcomes Study HIV Health Survey (MOS-HIV, range 0-100). Eight multivariable models were fit comparing: 1. current marijuana use by each cognitive outcome, 2. current heavy alcohol use by each cognitive outcome, 3. lifetime marijuana use by each cognitive outcome, 4. lifetime alcohol use (Kg) by each cognitive outcome, 5. lifetime marijuana use, duration of heavy alcohol use, current heavy alcohol use, and current marijuana use by each cognitive outcome, 6. lifetime marijuana use, lifetime alcohol use (Kg), current heavy alcohol use, and current marijuana use by each cognitive outcome, 7. the interaction between current marijuana and heavy alcohol use by each cognitive outcome, and 8. the interaction between lifetime marijuana and lifetime alcohol use (Kg) by each cognitive outcome. Analyses were adjusted for demographics, primary language, comorbidities, depressive symptoms, anxiety, antiretroviral therapy, HIV-viral load, CD4 count, lifetime cocaine use, cocaine use in the past 30 days, illicit opioid use in the past 30 days, and any prescribed opioids. RESULTS: Participant characteristics were as follows: Mean age 49 yrs., 35% female, 20% white, 66% ≥ 12 years of education, 86% English as primary language, 82% unemployed, mean Charlson comorbidity score 2.9, 28% scored ≥ 3 on the PHQ-2 indicating depressive symptoms, 44% scored ≥ 8 on OASIS indicating symptoms of anxiety, 58% had Hepatitis C infection at some point in their life, 86% were on HAART, 72% had an HIV-viral load < 200 copies/mL, CD4 cell count/mm3 was 10% <200 and 33% 200 - <500, mean HIV duration was 16 years, lifetime cocaine use was 9 years, 30% used cocaine in the past 30 days, 25% used illicit opioids in the past 30 days, and 61% were prescribed opioids. Current marijuana use was significantly associated with a lower MOS-HIV CF4 score in three of the fully adjusted models (1,5, and 6) listed previously with a decrease in 0.30 points for every day of use, but neither MoCA score. Current heavy alcohol use was also associated with a higher MOS-HIV CF4 score in model 5, increasing 0.36 points for every day of use. This finding did not confirm our hypothesis and in fact was opposite our projections. Lifetime marijuana use and lifetime alcohol use were not associated with any measure of cognitive dysfunction, and there was no interaction between lifetime marijuana use and lifetime alcohol use with cognitive dysfunction, and no interaction between current marijuana use and current alcohol use with cognitive dysfunction. CONCLUSION: Current marijuana use may be associated with cognitive dysfunction. We also detected an unexpected association between current heavy alcohol use and better cognitive function, but it is not biologically plausible. However, we did not detect associations between lifetime alcohol or marijuana use and cognitive dysfunction among people with substance dependence and HIV-infection. Further research, particularly on long-term exposure to substances, should include subtler measures of cognitive dysfunction and consider whether or not cognitive dysfunction that may be the consequence of marijuana and alcohol use is detectable among those who have many other factors effecting cognition. These results suggest that marijuana use should not be considered benign for individuals with substance dependence and HIV-infection

Comments on the book "Sticks, stones and broken bones: Neolithic violence in a European perspective"

Wiesław Lorkiewicz and Elżbieta Żądzińsk

The role of the dentist in disaster victim identification – INTERPOL standards and forms

Disaster Victim Identification (DVI) is a series of coordinated and multidisciplinary procedures used to recover and identify all the victims of a mass fatality incident. The identification by dental means is a quick and easy method that requires the comparison of antemortem data obtained from the general dental practitioner with the postmortem data completed at the place of the disaster. The comparative analysis of the dental status is effective enough to be recognised by INTERPOL as one of three primary identification methods (together with fingerprints and DNA analysis). Disaster victim identification at the place of an incident is the responsibility of the forensic odontologists among the DVI team members. However, every single dental practitioner can be asked to help in the identification of victims. The main responsibility of the dental practitioner is then to deliver the most reliable and complete dental records, ideally by means of the Interpol AM form available on its website. The article presents the basic information on how to use the pink and yellow INTERPOL F2 forms

The influence of the secondary electrons induced by energetic electrons impacting the Cassini Langmuir probe at Saturn

The Cassini Langmuir Probe (LP) onboard the Radio and Plasma Wave Science experiment has provided much information about the Saturnian cold plasma environment since the Saturn Orbit Insertion in 2004. A recent analysis revealed that the LP is also sensitive to the energetic electrons (250–450 eV) for negative potentials. These electrons impact the surface of the probe and generate a current of secondary electrons, inducing an energetic contribution to the DC level of the current-voltage (I-V) curve measured by the LP. In this paper, we further investigated this influence of the energetic electrons and (1) showed how the secondary electrons impact not only the DC level but also the slope of the (I-V) curve with unexpected positive values of the slope, (2) explained how the slope of the (I-V) curve can be used to identify where the influence of the energetic electrons is strong, (3) showed that this influence may be interpreted in terms of the critical and anticritical temperatures concept detailed by Lai and Tautz (2008), thus providing the first observational evidence for the existence of the anticritical temperature, (4) derived estimations of the maximum secondary yield value for the LP surface without using laboratory measurements, and (5) showed how to model the energetic contributions to the DC level and slope of the (I-V) curve via several methods (empirically and theoretically). This work will allow, for the whole Cassini mission, to clean the measurements influenced by such electrons. Furthermore, the understanding of this influence may be used for other missions using Langmuir probes, such as the future missions Jupiter Icy Moons Explorer at Jupiter, BepiColombo at Mercury, Rosetta at the comet Churyumov-Gerasimenko, and even the probes onboard spacecrafts in the Earth magnetosphere

A dentist as a member of forensic medical team

In the Polish medico-legal system, the participation of dental practitioner in forensic medical teams is incidental and limited mostly to acting as experts in particular cases. Unlike many other countries, there are no professional forensic odontologists in Poland. Therefore the dentist, usually selected from university staff or an another company cooperating with forensic medicine department or another expert and is not always experienced enough to be involved in activities of medico-legal team. Furthermore, the dentist’s engagement is often the result of non-clinical interests. Among the tasks of a dentist working as a member of forensic medical team are opinions in civil and criminal cases, identification of human remains and victims of disasters by dental means, bite marks analysis, and dental age estimation. As concluded from our previous experience, the dentist is also necessary for reading and interpreting the dental records used in medico-legal practice

Sexual offences – selected cases

Introduction: Expert testimony on violence victims also includes victims of sexual assault. The role of an expert is to classify the injuries by their severity, as defined in art. 157, 156 or 217 of the Criminal Code pertaining to crimes against health and life. Also, the role of an expert opinion is to determine whether the injuries identified during the exam occurred at the time and under the circumstances stated in medical history. The examination of sexual assault victims is conducted by two experts: a gynecologist and a forensic physician. Most examinations are performed at different times and various medical centers. The conclusions are presented in an official report. Regardless of victim age, all sexual crimes are investigated ex officio by the Police Department and the Prosecutor’s Office. Further legal classification of criminal offenses is the task of an appropriate legal body, and the offenses are codified in accordance with the provisions of chapter XXV of the Criminal Code, articles 197 - 205. In controversial cases, i.e. when two different expert opinions appear on the same case, or if, according to the law enforcement, a medical opinion is insufficient for some reason, an appropriate expert or team of experts is appointed to resolve the problem. Objectives: To present selected cases of sexual violence victims treated at the Department of Gynecology and assessed at the Department of Forensic Medicine with reference to the challenges regarding qualification of the sustained injuries and clinical diagnoses. Material and methods: Research material included selected forensic opinions developed for law enforcement offices that involved victims of sexual violence. The expert opinions were prepared either on the basis of submitted evidence, or both, submitted evidence and examination of the victim at the Department of Forensic Medicine. Moreover, the article presents a case of a patient examined and treated at the Department of Gynecology in Poznan. Conclusions: Based on the selected cases, the authors conclude that a medico-legal expert cannot uncritically accept previous diagnoses. Moreover, every expert is given the right and obligation to verify them. The need for complete, rapid and almost simultaneous colaboration between physicians in charge of the case, forensic doctors, police officers and prosecutors was demonstrated. Lack of cooperation may give rise to different opinions, leading to unnecessary elongation of the medico-legal procedures. It was observed that time plays a crucial role if qualification of an injury is required. The obligation of medical staff to inform the law enforcement about all cases of child abuse was also emphasized

Palbociclib Treatment Alters Nucleotide Biosynthesis and Glutamine Dependency in A549 Cells

Background Aberrant activity of cell cycle proteins is one of the key somatic events in non-small cell lung cancer (NSCLC) pathogenesis. In most NSCLC cases, the retinoblastoma protein tumor suppressor (RB) becomes inactivated via constitutive phosphorylation by cyclin dependent kinase (CDK) 4/6, leading to uncontrolled cell proliferation. Palbociclib, a small molecule inhibitor of CDK4/6, has shown anti-tumor activity in vitro and in vivo, with recent studies demonstrating a functional role for palbociclib in reprogramming cellular metabolism. While palbociclib has shown efficacy in preclinical models of NSCLC, the metabolic consequences of CDK4/6 inhibition in this context are largely unknown. Methods In our study, we used a combination of stable isotope resolved metabolomics using [U-13C]-glucose and multiple in vitro metabolic assays, to interrogate the metabolic perturbations induced by palbociclib in A549 lung adenocarcinoma cells. Specifically, we assessed changes in glycolytic activity, the pentose phosphate pathway (PPP), and glutamine utilization. We performed these studies following palbociclib treatment with simultaneous silencing of RB1 to define the pRB-dependent changes in metabolism. Results Our studies revealed palbociclib does not affect glycolytic activity in A549 cells but decreases glucose metabolism through the PPP. This is in part via reducing activity of glucose 6-phosphate dehydrogenase, the rate limiting enzyme in the PPP. Additionally, palbociclib enhances glutaminolysis to maintain mitochondrial respiration and sensitizes A549 cells to the glutaminase inhibitor, CB-839. Notably, the effects of palbociclib on both the PPP and glutamine utilization occur in an RB-dependent manner. Conclusions Together, our data define the metabolic impact of palbociclib treatment in A549 cells and may support the targeting CDK4/6 inhibition in combination with glutaminase inhibitors in NSCLC patients with RB-proficient tumors

Association Between Residential Greenness and Cardiovascular Disease Risk

Background Exposure to green vegetation has been linked to positive health, but the pathophysiological processes affected by exposure to vegetation remain unclear. To study the relationship between greenness and cardiovascular disease, we examined the association between residential greenness and biomarkers of cardiovascular injury and disease risk in susceptible individuals. Methods and Results In this cross-sectional study of 408 individuals recruited from a preventive cardiology clinic, we measured biomarkers of cardiovascular injury and risk in participant blood and urine. We estimated greenness from satellite-derived normalized difference vegetation index ( NDVI ) in zones with radii of 250 m and 1 km surrounding the participants' residences. We used generalized estimating equations to examine associations between greenness and cardiovascular disease biomarkers. We adjusted for residential clustering, demographic, clinical, and environmental variables. In fully adjusted models, contemporaneous NDVI within 250 m of participant residence was inversely associated with urinary levels of epinephrine (-6.9%; 95% confidence interval, -11.5, -2.0/0.1 NDVI ) and F2-isoprostane (-9.0%; 95% confidence interval, -15.1, -2.5/0.1 NDVI ). We found stronger associations between NDVI and urinary epinephrine in women, those not on β-blockers, and those who had not previously experienced a myocardial infarction. Of the 15 subtypes of circulating angiogenic cells examined, 11 were inversely associated (8.0-15.6% decrease/0.1 NDVI ), whereas 2 were positively associated (37.6-45.8% increase/0.1 NDVI ) with contemporaneous NDVI . Conclusions Independent of age, sex, race, smoking status, neighborhood deprivation, statin use, and roadway exposure, residential greenness is associated with lower levels of sympathetic activation, reduced oxidative stress, and higher angiogenic capacity