[Inhaled marijuana and the lung, a toxic cocktail?] / Cannabis inhalé et poumon, une liaison dangereuse ?

Unlike the well-documented effects of tobacco smoke on the lung, the effects of cannabis smoke remain controversial, the main bias consisting in co-consumption of tobacco. That said, the composition of joint smoke is close to that of cigarettes, containing many compounds that are carcinogenic and/or alter the respiratory epithelium. Confirmed respiratory effects in chronic cannabis smokers include aggravated chronic bronchitis symptoms, a cumulative effect with tobacco on COPD and emphysema occurrence, an increased risk of bullous emphysema, and pneumothorax with heightened risk of recurrence after pleural symphysis. Recent prospective studies have shown a negative impact on lung function, with not only damage to the airways, but also DLCO alteration and an accelerated drop in FEV1. Finally, cannabis smoking is very common among young patients with lung cancer. Its consumption could lead to a different lung cancer profile, potentially more undifferentiated and less accessible to targeted therapy. Questioning about cannabis consumption must be systematic and targeted medical care should be offered.

Transdermal nicotine in non-smokers: A systematic review to design COVID-19 clinical trials.

Recent data show an interaction between COVID-19 and nicotine and indicate the need for an assessment of transdermal nicotine use in non-smokers. Assessments have been conducted into the short-term cognitive effects of nicotine and into diseases such as Parkinson's, Tourette syndrome, ADHD or ulcerative colitis. METHODS: Analyses of nicotine administration protocols and safety were conducted after reviewing Medline and Science Direct databases performing a search using the words [transdermal nicotine] AND [non-smoker] AND selected diseases. RESULTS: Among 298 articles identified, there were 35 reviewed publications reporting on 33 studies of non-smokers receiving transdermal nicotine for >48hours. In the 16 randomized trials, 7 crossover, 1 case/control and 9 open studies patients received an initial nicotine dose of between 2.5mg and 15mg/day. In 22 studies, daily doses increased by 2 to 7 steps in 3 to 96 days until the dose was between 5mg and 105mg/day. The target nicotine dose was 19.06±20.89mg/day. The 987 non-smokers (534 never-smokers, 326 ex-smokers and 127 classified as "non-smokers") received or did not receive nicotine. The most common side-effects were nausea and skin itching. Forty-three (7.1%) non-smokers stopped treatment because of an adverse event of nicotine. No hospitalization related to nicotine side-effects were reported. CONCLUSION: Despite a relatively safe tolerance profile, transdermal nicotine therapy in non-smokers can only be used in clinical trials. There is a lack of formal assessment of the potential risk of developing a tobacco addiction. This review offers baseline data to set a transdermal nicotine protocol for non-smokers with a new purpose.

Draft Genome Sequence of a Listeria monocytogenes Isolate of Core Genome Multilocus Sequence Typing Complex Type 2521 from Ready-to-Eat Meat Sausage Related to an Outbreak (Sigma1) in Germany.

We report here the draft genome sequence of a Listeria monocytogenes strain, core genome multilocus sequence typing (cgMLST) complex type 2521 (CT2521), isolated from ready-to-eat meat sausage related to a protracted and supraregional listeriosis outbreak (Sigma1) in Germany from 2014 to 2019.

[Improved patient safety through a clinical decision support system in laboratory medicine]. / Verbesserte Patientensicherheit durch "clinical decision support systems" in der Labormedizin.

BACKGROUND: Laboratory diagnostics are essential for diagnosis, initiation of therapy, and monitoring of patients. Laboratory results that are overlooked or incorrectly interpreted lead to adverse events and endanger patient safety. Clinical decision support systems (CDSSs) may facilitate appropriate interpretation of results and subsequent medical response. OBJECTIVES: The research project on digital laboratory medicine (AMPEL) aims at developing a CDSS based on laboratory diagnostics, which supports practitioners in ensuring the necessary medical consequences. MATERIALS AND METHODS: A literature review of CDSSs describes the current state of research. The research project AMPEL is presented with its objectives, challenges, and first results. Furthermore, the development of a framework and reporting system is illustrated through the clinical example of severe hypokalemia. RESULTS AND CONCLUSION: Through interdisciplinary development and constant optimization, a specific CDSS with high acceptance among clinicians was developed. Initial results in the case of severe hypokalemia show a positive effect on patient care. Thereby, more complex frameworks such as sepsis diagnostics or acute coronary syndrome are implemented. The limited availability of standardized and digital clinical data is challenging. In addition to the application of classic decision trees in CDSS, the use of machine learning offers a promising perspective for future developments.

First Bosnian Study of the Relationship between APOE rs7412 and rs429358 Variants and Pregnancy Loss.

Due to inconsistent results of APOE variants in the survival of pregnancy we investigated the potential relationship of APOE rs7412 and rs429358 with pregnancy loss (PL) in Bosnian women. We enrolled 154 women with PL. The minimum week of miscarriage was 6, while the maximum was 28. As a control group, an equal number of mothers with at least one live-born child was included. All women were recruited from the Institution of Health Protection of Women and Motherhood in Sarajevo, Bosnia and Herzegovina. Genotyping was performed by real- time PCR at the Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University. The prevalence of genotypes E2/E3, E2/E4, E3/E3, E3/E4, E4/E4 in the group with and without PL were: 14.3 %, 1.3 %, 70.8 %, 12.3 %, 1.3 %, and 13.6 %, 1.3 %, 70.1 %, 14.3 %, 0.7 %, respectively. The frequency of the E4/E4 genotype in women with 1-2 and 3-4 PL compared to women without PL did not differ significantly between those three groups (P value = 0.0712). The frequencies of alleles ԑ2, ԑ3, ԑ4 in the group with and without PL were: 6.8 %, 85.1 %, 8.1 % and 7.5 %, 84.1 %, 8.4 %, respectively, and did not differ significantly. We conclude that our study does not confirm rs7412 and rs429358 as a potential risk factor for PL in the studied group. To elucidate the relationship between PL and variants of the APOE gene, studies with a larger sample size and placental histomorphology and genetic diagnosis are required.

Maternal mood disorders and lithium exposure in utero were not associated with poor cognitive development during childhood.

AIM: This study evaluated whether maternal mood disorders (MMD), particularly bipolar disorder, and lithium treatment during pregnancy influenced the neonatal health and cognition of children born from 2006 to 2010. METHODS: Our study at Karolinska University Hospital, Stockholm, Sweden, focused on women with and without mood disorders and their children. Information on pharmacotherapy, mental health, delivery and neonatal complications was retrospectively collected from electronic patient records. Children were tested in a blinded manner at four to five years of age with the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition. Maternal health, child health and social situations were evaluated. RESULTS: Of the 39 children, 20 were exposed to lithium and MMD during pregnancy, eight were exposed to MMD but not lithium and 11 were not exposed to MMD or lithium. The children's full scale intelligence quotient (IQ), performance IQ and verbal IQ results did not differ significantly between the groups. The processing speed quotient was significantly lower in children exposed to mood disorders, but there was a high level of missing data for this subtest. CONCLUSION: This small, clinical cohort showed no significant association between mothers' prenatal exposure to lithium or mood disorders and their offspring's IQ.

Practical guidelines on e-cigarettes for practitioners and others health professionals. A French 2016 expert's statement.

A group of 11 French medical experts has developed guidelines through a Delphi progressive consensus about smoking management at the e-cigarette era. The lack of scientific data about e-cigarettes led the experts to set out recommendations, mainly based on clinical practice while waiting for scientific validations. The validated smoking cessation treatments keep the first place in the prevention and the treatment of tobacco-induced damages. The e-cigarette, experimented by a large proportion of smokers, is a safer product than tobacco. The health professional must answer the patients about the e-cigarettes: (1) A smoker who questions about e-cigarettes should receive information. Even if there is a lack of data, e-cigarettes offer much lower risks than tobacco. (2) A dual user is at high risk of returning to exclusive tobacco use; he should also optimize other nicotine intakes by combining nicotine replacement therapy and/or optimizing the nicotine intake through the e-cigarette. (3) A smoker who wish to use the e-cigarette in order to quit with or without associated pharmacological treatment should be accompanied and not discouraged. (4) A vaper who is tired to continuing to vape should be accompanied to quit. Specific guidelines are also provided for adolescents, pregnant women, patients during perioperative periods and also for pulmonary, cardiac and schizophrenic patients.

Phenotypes optimized for early-life reproduction exhibit faster somatic deterioration with age, revealing a latent cost of high condition.

High condition enables individuals to express a phenotype with greater reproductive potential. However, life-history theory predicts that reproduction will trade off with somatic maintenance and viability, and several studies have reported faster age-related decline in performance in high-condition individuals, suggesting that high condition in early life is associated with accelerated somatic deterioration. This trade-off may be especially pronounced in males, which often express condition-dependent secondary sexual traits that can impose viability costs during development and through damage-inflicting adult sexual behaviours. To test this prediction, we reared larvae of the neriid fly Telostylinus angusticollis on diets of varying nutrient content and quantified somatic deterioration in solitary males, males housed in all-male or mixed-sex groups and immobilized males subjected to mechanical stress. We found that males reared on a nutrient-rich larval diet (high-condition males) suffered a higher rate of somatic deterioration with age, particularly when housed in groups. Perhaps as a result of accelerated somatic deterioration, high-condition males did not outlive low-condition males. In addition, high-condition males housed in all-male groups experienced a greater reduction in escape response with age than males housed in mixed-sex groups, suggesting that male-male combat promotes somatic deterioration. However, even when immobilized, high-condition males were still found to be more susceptible to somatic damage than low-condition males. Our findings suggest that a high-condition male phenotype is more prone to somatic damage, both as a result of associated behaviours such as combat, and because of the inherent fragility of the high-condition body.

Pulmonary function testing in infants with tetralogy of Fallot and absent pulmonary valve syndrome.

AIM: Absent pulmonary valve syndrome (APVS) is found in 3-6% of patients with Tetralogy of Fallot (TOF). Along with findings of TOF, absence of pulmonary valve tissue results in aneurysmal dilatation of the main and branch pulmonary arteries compressing the trachea, main-stem, and intrapulmonary bronchi leading to obstructive airways disease. Our objective was to review pulmonary function tests (PFT) in TOF-APVS patients. MATERIALS AND METHODS: Eight PFT were performed on five mechanically ventilated TOF-APVS patients in the intensive care unit. Tidal volume, forced vital capacity (FVC), maximal expiratory flow 25%, resistance and compliance of the respiratory system were measured. RESULTS: Pre-operative PFTs showed markedly elevated airways resistance (RRS) (median 0.45 cmH2O/mL/sec, range 0.17-0.66) and marked variability of the static compliance of the respiratory system (CRS) (median 0.6 mL/cmH2O/kg, range 0.25-2.6). Flow-volume loops measured by forced deflation showed flow limitation within the medium to small airways. Post-operative FVC was reduced in four of the five patients (median 46 mL/kg, IQR 42.9 - 48.8 mL/kg). Patients studied with various levels of positive end expiratory pressure (PEEP) showed improvement in tidal volume and reduced obstruction with PEEP greater than 10 cmH2O. For three patients with pre-operative data available, surgical correction resulted in near-normal post-operative CRS and improved, but still elevated RRS (median 0.14 cmH2O/mL/sec, interquartile range [IQR] 0.11-0.31). CONCLUSION: For our patients with TOF-APVS, airway resistance was elevated. Flow limitation was seen in the medium to small airways with a mild reduction of FVC. PFTs may help guide management of mechanical ventilation for TOF-APVS patients.

'Carriers of variant luteinizing hormone (V-LH) among 1593 Baltic men have significantly higher serum LH'.

Luteinizing hormone (LH) is a pituitary heterodimeric glycoprotein essential in male and female reproduction. Its functional polymorphic variant (V-LH) is determined by two missense mutations (rs1800447, A/G, Trp8Arg; rs34349826, A/G, Ile15Thr) in the LH ß-subunit encoding gene (LHB; 19q13.3; 1111 bp; 3 exons). Among women, V-LH has been associated with higher circulating LH and reduced fertility, but the knowledge of its effect on male reproductive parameters has been inconclusive. The objective of this study was to assess the effect of V-LH on hormonal, seminal and testicular parameters in the Baltic young men cohort (n = 986; age: 20.1 ± 2.1 years) and Estonian idiopathic infertility patients (n = 607; 35.1 ± 5.9 years). V-LH was detected by genotyping of the underlying DNA polymorphisms using PCR-RFLP combined with resequencing of a random subset of subjects. Genetic associations were tested using linear regression under additive model and results were combined in meta-analysis. No significant difference was detected between young men and infertility patients for the V-LH allele frequency (11.0 vs. 9.3%, respectively). V-LH was associated with higher serum LH in both, the young men cohort (p = 0.022, allelic effect = 0.26 IU/L) and the idiopathic infertility group (p = 0.008, effect = 0.59 IU/L). In meta-analysis, the statistical significance was enhanced (p = 0.0007, resistant to Bonferroni correction for multiple testing; effect = 0.33 IU/L). The detected significant association of V-LH with increased serum LH remained unchanged after additional adjustment for the SNPs previously demonstrated to affect LH levels (FSHB -211G/T, FSHR Asn680Ser, FSHR -29A/G). Additionally, a suggestive trend for association with reduced testicular volume was observed among young men, and with lower serum FSH among infertility patients. The V-LH carrier status did not affect sperm parameters and other circulating reproductive hormones. For the first time, we show a conclusive contribution of V-LH to the natural variance in male serum LH levels. Its downstream clinical consequences are still to be learned.

[Biocompatibility of composites--literature review].

Composites are a large family of materials composed of polymer matrices imbedded with different types of fillers. The specific properties achievable with diverse chemical combinations provide for a wide range of implications in many industrial fields. Materials designed for medical use must not only efficiently serve the purpose of their use, but also be biocompatible to the tissues they contact and the body as a whole. Dental composites and their components have been studied intensely to assess their potential local and systemic side effects, to establish biocompatibility, in order to receive the proper conformation allowing their safe clinical use. The purpose of the following paper is to summarize several aspects of research focused on determining cytotoxicity, genotoxicity, carcinogenicity, hypersensitivity, and microbial effects of composite components, in order to ascertain in fact how biocompatible dental composite materials are. Research shows that several chemical components may be released from different types of composites, and are able to cause toxic, allergic, mutagenic and other biological effects. However, because of the small amounts applied and the unique conditions in the oral cavity, the clinical relevance of these findings is questionable. Nevertheless, caution should be taken when using these materials, to avoid possible negative outcomes. Future studies should focus on targeting most toxic components and finding biocompatible alternatives and development of materials with high polymerization efficiency in order to reduce the amount of leachable components.

Effect of carbetocin, oxytocin and prostaglandin E2 and F2α on intrauterine pressure in cows in dioestrus and oestrus.

OBJECTIVE: To describe the physiological activity of the myometrium in oestrus and dioestrus and the induced activity after medication in cows with particular reference to segmental differences. MATERIAL AND METHODS: Six cows were given the pharmaceuticals carbetocin, oxytocin and prostaglandin (PG) F2α (dinoprost) intramuscularly and PGE2 intravenously. The physiological myometrial activity was recorded for 15 minutes and the induced activity for 105 minutes by using a transcervically attached pressure probe containing six pressure microtransducers. RESULTS: Lower pressures were measured in dioestrus compared to oestrus before (dioestrus 3.2±8.88 mmHg, oestrus 12.4±13.23 mmHg, p<0.0001) and after the drug administration. Carbetocin provoked the longest lasting effect (60 minutes in dioestrus, 75 minutes in oestrus) followed by PGE2 (45 minutes in dioestrus, 60 minutes in oestrus), PGF2α (30 minutes each) and oxytocin (15 minutes in oestrus only). In contrast to the other drugs carbetocin did not cause any pressure decrease beneath the base level after the primary pressure increase in dioestrus. In dioestrus the pressure before drug administration was significantly higher in the cervix (3.6±19.40 mmHg) and the uterine body (7.1±36.10 mmHg) than in the uterine horn (1.1±7.21 mmHg). Conversely, in oestrus the pressure in the uterine horn (16.6±17.73 mmHg) was significantly higher than in the uterine body (6.2±16.59 mmHg) and the cervix (10.4±17.91 mmHg). Drug administration in dioestrus caused a cornual pressure increase and the pressure in the uterine body decreased, whereas in oestrus the pressure increased in all uterine segments. The physiological frequency of the pressure waves in dioestrus was 5.2±3.02 in 15 minutes compared to 7.5±2.89 in 15 minutes in oestrus. No traceable changes of the contraction frequency were found after medication. CONCLUSION AND CLINICAL RELEVANCE: Carbetocin caused the most enduring increase in intrauterine pressure in dioestrus and oestrus and may therefore be indicated best for therapeutic use. The tested drugs had the same effects on the various uterine segments and no effect on the contraction frequency.

Application of RNA interference to improve mechanistic understanding of omics responses to a hepatotoxic drug in primary rat hepatocytes.

Inhibition of the glucagon receptor (GCGR) has been identified as a potential therapeutic approach for the treatment of type 2 diabetes. However, a small molecule drug candidate antagonizing GCGR (BAY16) failed during preclinical drug development, in part due to drug induced hepatotoxicity in animals. Since there is evidence to suggest that endogenous GCGR signaling might be important for hepatocyte survival, we hypothesized that on-target effects, i.e., modulation of GCGR activity by BAY16, may contribute to BAY16 hepatotoxicity and associated gene expression changes in rats. To understand the role of GCGR inhibition in BAY16 toxicity, we analyzed cell viability and gene expression profiles in non-silenced and GCGR-targeting siRNA transfected primary rat hepatocytes with and without exposure to BAY16 to discriminate between on- and off-target effects of BAY16. siRNA-mediated silencing of the GCGR did not affect cell viability in primary rat hepatocytes, indicating that cytotoxicity of BAY16 occurs independent of its pharmacological effects. In support of this, gene expression analysis of GCGR silenced hepatocytes revealed no transcriptional alterations relevant to toxicity. In contrast, BAY16 caused a concentration-dependent decrease in cell viability, along with changes in the expression of genes associated with altered xenobiotic metabolism, oxidative stress, increased fatty acid synthesis, and alterations in cholesterol and bile acid metabolic processes. Based on gene expression data, it appears that hepatocytes inhibit cholesterol synthesis and increase detoxifying and eliminating processes in order to protect themselves from accumulation of bile acids, cholesterol or drug intermediates. Importantly, comparison of transcriptional changes in the absence and presence of GCGR revealed that the same pathways were affected in both silenced and non-silenced hepatocytes, indicating that BAY16 toxicity occurs independent of the GCGR receptor.

[A tooth or an implant--literature based decision making].

The common use of dental implants in the daily practice led to a profound change in the available treatment strategies. The option of replacing a diagnosed doubtful tooth with an implant has become widely accepted and often used. The prognosis systems in use today are based on the three major disciplines: endodontics, periodontics and prosthodontics. Combining these three may impair and bias the decision making process and increase the tendency to base it on subjective clinical experience and personal preference. Reading and reviewing the relevant literature gives no clear tool for use. Root canal treatment is considered a highly predictable treatment procedure and a treated tooth is affected mainly by the quality and type of the fabricated restoration and the risk of caries. Periodontal treatment followed by a suitable maintenance regimen will likely allow long term tooth survival. When comparing the success rates of natural teeth rehabilitation versus implant supported restorations, it appears that with implants an additional treatment is demanded along the years. This coincides with the fact that to date there is no consensus regarding the extent of perimplantitis and perimucositis that is to be expected around a restored implant. In addition, a peri implant tissue problem or a failure of a dental implant may prove to be more challenging than a failure of a tooth. It is important to remember that a dental implant is made to substitute a missing tooth and it is a treatment modality with known and clear indications for rehabilitation of an edentulous space. The aim of this paper is to review and discuss the various aspects of whether to maintain a compromised or a doubtful tooth or to prefer a treatment modality using dental implants. In conclusion it is advised here, to incorporate the discussed issues in the decision making process towards the most suitable treatment plan.

Microgravity studies of aqueous wet foams.

Foams and foaming pose important questions and problems for both fundamental research and practical applications. Despite the fact that foams have been extensively studied, many aspects of foam physics and chemistry still remain unclear. Experiments on foams performed under microgravity can be extended far beyond their counterpart where gravity is fully present (i.e. most experiments on Earth). They allow, in particular, observation of the wet foams obtained during the foaming process; on Earth, foams at this stage evolve too quickly due to gravity drainage and cannot be studied. This paper reviews the existing studies of foams under microgravity, which include studies in parabolic flights, in sounding rockets and in the International Space Station.

A non-interventional phase IV Belgian survey to assess the antiviral effectiveness of pegylated interferon-alpha-2b and ribavirin treatment according to the stage of liver fibrosis in previously untreated patients with genotype 1/4/5/6 chronic hepatitis C (PRACTICE).

BACKGROUND AND STUDY AIMS: This was an observational, non-interventional, multicenter, phase IV study, in patients with genotype 1/4/5/6 chronic hepatitis C (CHC). The primary objectives were to evaluate SVR in patients with no or minimal fibrosis (METAVIR F0-F1) versus well established fibrosis (F2-F4), and to estimate response on Weeks 12, 24 and 48 on treatment in previously untreated patients with genotypes 1/4/5/6 CHC. PATIENTS AND METHODS: 538 patients treated with pegylated interferon alfa 2b 1.5 mcg/kg in combination with ribavirin 800-1200 mg/day were enrolled in 55 sites in Belgium and Luxembourg, 505 being considered for the analysis. 40% of the patients were female and 60% male, the average age was 47.5 years, 10.5% were 65 or older. RESULTS: SVR was observed in 35% of the patients, EVR in 68%, of which pEVR in 33% and cEVR in 35%. SVR was observed in 43% of the low fibrosis group (F0, F1) and 30% of the high fibrosis group (F2, F3, F4) (p = 0.005). SVR rates were 34% for genotype 1, 37% for genotype 4, and 47% for genotype 5 (NS). Multivariate analysis showed that EVR and baseline METAVIR score are independent prognostic factors for SVR. CONCLUSIONS: This trial confirms that fibrosis stage and early viral response are the most important key-factors to predict sustained response, suggesting that the earlier patients are treated, the better the outcome. Non-invasive techniques enable us to closely monitor progression of fibrosis, allowing a better selection of patients for antiviral treatment in the DAA-era.

Response of Black African patients with hepatitis C virus genotype 4 to treatment with peg-interferon and ribavirin.

AIM: To compare responses to therapy of Black African (BA) and non-Black African (non- BA) patients with hepatitis C virus genotype 4 (HCV-4) residing in Belgium. METHODS: In this retrospective multicenter study, 473 patients with HCV-4 were selected from databases at 7 Belgian centers; 209 treatment-naive patients (154 BA) had received treatment with peg-interferon (peg-IFN) plus ribavirin (RBV) and were included in the study. RESULTS: There was a greater percentage of female patients in the BA group than in the non- BA group; BA patients were also older, had a greater body mass index, and more frequently had abnormal glucose metabolism. The route of contamination was more frequently unknown in BA than in non-BA patients and BA patients had more HCV-4 subtypes. There were no differences in other demographic factors between the groups. Sustained viral response (SVR) and complete early viral response rates were significantly lower and relapse rates significantly higher in BA than in non-BA patients. There were no differences between groups in rates of dose modification or in drug tolerance. CONCLUSION: In our cohort, treatment-naive BA patients with HCV-4 who were treated with peg-IFN and ribavirin had a much lower SVR rate than treatment-naive non-BA patients with HCV-4 who were treated with peg-IFN and ribavirin, and a higher relapse rate, possibly related to a weaker response to interferon-based therapy. Treatment may need to be adapted in this population.