How do medical and non-medical use of z-drugs relate to psychological distress and the use of other depressant drugs?

BACKGROUND: Z-drugs are hypnotic drugs used for insomnia with considerable potential of abuse. We investigated the relationship of past-year medical and non-medical use of z-drugs with past-year: i) psychological distress; ii) medical use, non-medical use, and DSM-IV use disorder of Benzodiazepine (BZD) tranquilizers; iii) use and DSM-IV alcohol and marijuana use disorders, recreational drugs with a depressant effect on the central nervous system. METHODS: Data came from the 2015-2017 NSDUH (n = 128,740). Participants aged 18+ were asked if they had used any Z-Drug medically or non-medically in the past year. We investigated the associations between the three-level z-drugs variable with psychological distress and BZD, alcohol, and marijuana variables in multinomial logistic regression models. RESULTS: Past-year prevalences of z-drug use were 3.3% for medical and 0.5% for non-medical use. Medical and non-medical users of z-drugs had higher risk of psychological distress, compared to non-users. Medical and non-medical users of z-drugs had higher risk of medical use, non-medical use, and BZD use disorders. Compared to non-users of z-drugs, medical users had higher risk of marijuana and alcohol use and alcohol use disorders, while non-medical users had higher risk of marijuana use and marijuana use disorders and alcohol. CONCLUSION: Z-drug users have elevated risk of use and dependence of BZDs and recreational drugs, possibly due to concurrent prescribing and self-medication.

Does tobacco smoking predispose to apical periodontitis and endodontic treatment need? A systematic review and meta-analysis.

BACKGROUND: Controversial findings exist in the literature regarding the association between tobacco smoking and development of apical periodontitis or need for root canal treatment, with some studies reporting an increase in the prevalence of these outcomes in smokers, whilst others reporting no association. AIM: To evaluate if there is scientific evidence to support an association between tobacco smoking and a greater prevalence of apical periodontitis and/or root canal treatments. DATA SOURCES: A systematic search was performed using MeSH terms and free terms in the PubMed, Scopus, Virtual Health Library (VHL), Cochrane library and Open Gray databases. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Observational studies that evaluated the association between smoking and the development or healing of periapical lesion and/or the prevalence of root canal treatment in humans were included. STUDY APPRAISAL AND SYNTHESIS METHODS: A quality assessment of included studies was performed, and the relevant information and findings were evaluated. A meta-analysis using nine included studies was performed through RevMan software, and the certainty of evidence was evaluated through GRADE. RESULTS: Fifteen studies were included, of which 10 were classified as low risk of bias, 4 were considered as moderate risk of bias and 1 as high risk of bias. Ten studies reported that smoking was associated with a greater prevalence of periapical periodontitis and/or root canal treatment. Five studies reported no association. Nine studies were included in the pooled meta-analysis, comprising two subgroups: apical periodontitis and root canal treatment. From these nine studies, eight studies were included in the apical periodontitis subgroup meta-analysis and demonstrated that this condition was significantly more prevalent in smokers when compared to the nonsmokers (odds ratio = 2.78[CI: 1.60, 4.85], P < 0.001; I2  = 79%; no adjusted odds ratio). Three studies were included in the root canal treatment subgroup meta-analysis and demonstrated an increased prevalence in smokers when compared to the nonsmokers (odds ratio = 2.73 [CI: 1.06, 2.83], P < 0.001; I2  = 72%; no adjusted odds ratio). The pooled meta-analysis demonstrated that smokers had twice the chance of having apical periodontitis and/or root canal treatment when compared to nonsmokers (odds ratio of 2.42 [CI: 1.59, 3.68], P < 0.01; I2  = 85%). The GRADE analysis demonstrated moderate certainty of evidence. LIMITATIONS: Several confounding factors were identified such as misinformation regarding the period of time subjects had smoked, as well as the frequency of smoking and the number of cigarettes consumed. No adjustment in odds ratio data for confounding was performed. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: This systematic review and meta-analysis indicate that tobacco smokers have an increased prevalence of periapical periodontitis and root canal treatments with moderate certainty of evidence.

The effect of ozone therapy in root canal disinfection: a systematic review.

AIM: To answer the following focused question: 'As regards microorganism load reduction for patients undergoing root canal treatment, is the use of ozone therapy comparable to conventional chemomechanical techniques using sodium hypochlorite (NaOCl)?' DATA SOURCES: A systematic review was conducted using controlled vocabulary and free-text key words in the following databases: PubMed, Science Direct, Scopus, Web of Science and Open Grey until 2 November 2018. Additional studies were sought through hand searching of endodontic journals. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: The inclusion criteria comprised studies that compared microbial reduction in root canals after treatments with ozone and NaOCl in extracted mature human teeth or randomized clinical trials. STUDY APPRAISAL AND SYNTHESIS METHODS: The quality assessment of included laboratory studies was performed with the following parameters: (i) sample size calculation, (ii) samples with similar dimensions, (iii) control group, (iv) standardization of procedures, (v) statistical analysis and (vi) other risk of bias. For randomized clinical trials, the qualitative analysis of the studies was performed from the bias risk assessment using the tool 'Bias Risk Assessment of Randomized Controlled Studies' Cochrane Handbook 5.0.2. RESULTS: The search resulted in 180 published studies. After removal of duplicate studies and full-text analysis, eight studies were selected and seven were considered low risk of bias (seven ex vivo studies and one random clinical trial). Overall, the results demonstrated that ozone therapy provides significantly less microbial load reduction than NaOCl. As an adjunct in chemomechanical preparation, ozone was ineffective in increasing the antimicrobial effect of NaOCl. Ozone performance was strongly associated with the application protocol used: it is dose, time and bacterial strain dependent, besides the correlation with the use of complementary disinfection sources. LIMITATIONS: A restricted number of randomized clinical trial was found, and the difference amongst the methodology of the studies did not allow a meta-analysis to be performed. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Although the selected studies had limitations, this review reached a satisfactory methodological and moderate evidence quality contributing to important preliminary information regarding ozone therapy. As regards load reduction of microorganisms for patients undergoing root canal treatment, ozone is not indicated neither to replace nor to complement the antimicrobial action of NaOCl.

Antibacterial properties and compressive strength of new one-step preparation silver nanoparticles in glass ionomer cements (NanoAg-GIC).

OBJECTIVES: This work aimed (1) to develop polyacid formulations by the one-step photoreduction of silver nanoparticles (AgNP) in a polyacrylate solution of conventional glass ionomer cement (GIC), imparting antibacterial activity; and (2) to evaluate handling and mechanical properties of experimental ionomers in comparison to a commercially available conventional GIC. METHODS: Formulations with increasing sub-stoichiometric amounts of AgNO3 were monitored during continuous UV light exposure by UV-vis spectroscopy and analyzed by transmission electron microscopy. The resulted synthesis of formulations containing small and disperse spherical nanoparticles (∼6 nm) were used to design the experimental nano-silver glass ionomer cements (NanoAg-GIC). The cements were characterized as to net setting time and compressive strength according to ISO 9917-1:2007 specifications. The antibacterial activity of these cements was assessed by Ag+ diffusion tests on nutritive agar plates (E. coli) and by MTT assay (S. mutans). RESULTS: The higher concentration of silver (0.50% by mass) in the matrix of NanoAg-GIC allowed viable net setting time and increased in 32% compressive strength of the experimental cement. All groups containing AgNP induced statistically significant E. coli growth inhibition zones (p-value <.05), indicating diffusion of Ag+ ions on the material surroundings. Metabolic activity of S. mutans grown on NanoAg-GIG with higher concentration of silver was significantly affected compared to control (p-value <.01). CONCLUSIONS: Silver nanoparticles one-step preparation in polyacrylate solution allowed the production of highly bioactive water-based cements within suitable parameters for clinical use and with large potential of dental and biomedical application.

A school-based epidemiological field survey: difficulties in collecting psychiatric outcome data in a middle-income country.

BACKGROUND: Low- and middle-income countries (LMICs) face a lack of epidemiological data. The development of high-quality surveys is a key research priority in countries such as Brazil. Our aim is to discuss the difficulties in conducting a longitudinal epidemiological survey in a pilot study of a school-based sample in São Paulo. METHODS: Data came from a cohort of school-attending adolescents in two neighborhoods with different levels of urbanicity in São Paulo. Students born in 2002 and in the 7th grade during 2014 were recruited from nine public schools. Adolescents and caregivers were interviewed separately at baseline and at one year follow-up, using several instruments, including the Schedule for Affective Disorders and Schizophrenia for School-Age Children/Present and Lifetime Version (K-SADS-PL). RESULTS: Achieving unbiased sampling, keeping an updated register of participants' contact information, using a full clinical interview without an algorithm for its scoring, and maintaining a highly-trained research team were among the difficulties faced. CONCLUSION: Working closely with community leaders, organizing group efforts to perform interviews, using a short, easy to understand instrument and providing some reward for participants were identified as alternatives to dealing with these difficulties, useful not only in Brazil, but also in other LMICs.

Bone Density and Clinical Periodontal Attachment in Postmenopausal Women: A Systematic Review and Meta-Analysis.

Osteoporosis is a systemic skeletal disease characterized by low bone mineral density (BMD) and has been considered a risk factor for periodontal disease. The aim of this systematic review and meta-analysis was to verify the scientific evidence for the association of periodontal attachment loss with low BMD in postmenopausal women. A systematic search of the literature was performed in databases until August 2016, in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Eligibility criteria included studies that compared clinical attachment loss (CAL) between postmenopausal women with low and normal BMD. Studies using similar methodology, with lower and higher risk of bias, were pooled into 3 different meta-analyses to compare CAL among women with normal BMD, osteoporosis, and osteopenia. In the first meta-analysis, mean CAL was compared among groups. In the other 2 meta-analyses, the mean percentages of sites with CAL ≥4 mm and ≥6 mm were respectively compared among groups. From 792 unique citations, 26 articles were selected for the qualitative synthesis. Eleven of the studies were appraised as presenting low risk of bias, and the association between low BMD and CAL was observed in 10 of these studies. Thirteen cross-sectional articles were included in the meta-analysis for osteoporosis and 9 in the osteopenia analysis. Women with low BMD presented greater mean CAL than those with normal BMD (osteoporosis = 0.34 mm [95% confidence interval (CI), 0.20-0.49], P < 0.001; osteopenia = 0.07 mm [95% CI, 0.01-0.13], P = 0.02). Only studies with lower risk of bias were available for the analysis of CAL severity. Women with low BMD presented more severe attachment loss, represented as mean percentage of sites with CAL ≥4 mm (osteoporosis = 3.04 [95% CI, 1.23-4.85], P = 0.001; osteopenia = 1.74 [95% CI, 0.36-3.12], P = 0.01) and CAL ≥6 mm (osteoporosis = 5.07 [95% CI, 2.74-7.40], P < 0.001). This systematic review and meta-analysis indicates that postmenopausal women with osteoporosis or osteopenia may exhibit greater CAL compared with women with normal BMD.

Maternal protein restriction during lactation modulated the expression and activity of rat offspring hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2, and CYP2E1 during development.

Early nutrition plays a long-term role in the predisposition to chronic diseases and influences the metabolism of several drugs. This may happen through cytochromes P450 (CYPs) regulation, which are the main enzymes responsible for the metabolism of xenobiotics. Here, we analyzed the effects of maternal protein restriction (MPR) on the expression and activity of hepatic offspring's CYPs during 90 days after birth, using Wistar rats as a mammal model. Hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2 and CYP2E1 mRNA and protein expression, and associated catalytic activities (ECOD, EROD, MROD, BROD, PROD and PNPH) were evaluated in 15-, 30-, 60-, and 90-day-old offspring from dams fed with either a 0% protein (MPR groups) or a standard diet (C groups) during the 10 first days of lactation. Results showed that most CYP genes were induced in 60- and 90-day-old MPR offspring. The inductions detected in MPR60 and MPR90 were of 5.0- and 2.0-fold (CYP1A2), 3.7- and 2.0-fold (CYP2B2) and 9.8- and 5.8- fold (CYP2E1), respectively, and a 3.8-fold increase of CYP2B1 in MPR90. No major alterations were detected in CYP protein expression. The most relevant CYP catalytic activities' alterations were observed in EROD, BROD and PNPH. Nevertheless, they did not follow the same pattern observed for mRNA expression, except for an induction of EROD in MPR90 (3.5-fold) and of PNPH in MPR60 (2.2-fold). Together, these results suggest that MPR during lactation was capable of altering the expression and activity of the hepatic CYP enzymes evaluated in the offspring along development.

Detection of new pathogenic mutations in patients with congenital haemolytic anaemia using next-generation sequencing.

INTRODUCTION: Congenital haemolytic anaemia (CHA) refers to a group of genetically heterogeneous disorders, mainly caused by changes in genes encoding globin chains, cytoskeletal proteins and red cell enzymes, in which accurate diagnosis can be challenging with conventional techniques. METHODS: To set-up a comprehensive assay for detecting mutations that could improve aetiological diagnosis, we designed a custom panel for sequencing coding regions from 40 genes known to be involved in the pathogenesis of CHA, using the Ion Torrent™ (Thermo Fisher Scientific, S.L. Waltham, MA, USA) Personal Genome Machine (PGM) Sequencer. A control group of 16 samples with previously known mutations and a test group of 10 patients with unknown mutations were included for assay validation and application, respectively. RESULTS: In the test group, we identified pathogenic mutations in all cases: four patients had novel mutations in genes related to membrane defects (SPTB, ANK1, SLC4A1 and EPB41), four were homozygous or compound heterozygous for mutations in genes related to enzyme deficiencies (GPI, TPI1 and GSS), one had a mutation in the HBB gene and another presented a homozygous mutation in the ADAMTS13 gene. CONCLUSIONS: Ion PGM sequencing with our custom panel is a highly efficient way to detect mutations causing haemolytic anaemia, including new variations. It is a high-throughput detection method that is ready for application in clinical laboratories.

Analysis of root canal treated primary incisor after trauma: two year outcomes.

BACKGROUND: The low number of clinical studies of traumatized teeth submitted to root canal treatment is completely out of proportion to the seriousness that dental trauma imposes on children in early years. AIM: This study evaluates the outcomes of root canal treatment (RCT) in traumatized primary incisors and identifies the predisposing factors associated with therapy success. METHODS: This is a retrospective study conducted with all dental records of 704 patients who had one or more teeth with traumatic injuries. Patients with irreversible pulp changes in primary teeth leading to RCT with a 24 month follow-up met the inclusion criteria. RESULTS: Twenty-five maxillary incisors of 17 children were evaluated. The children's age at the time of therapy ranged from 24 to 72 months (mean 47.3). Pulp necrosis was the most common disorder (84.0%) and pre-operative periapical lesions were observed in 52.0%. Coronal discoloration was found in 48.0%. The roots were filled with ZOE paste (68.0%) or Guedes-Pinto paste (32.0%). Overall RCT success rate was 68.0%. The absence of pre-operative periapical lesions (p = 0.02) and pathological root resorption (p = 0.02) presented positive association with therapy success. Success was not associated to filling paste (p = 0.49), filling extent (p = 0.44), of discoloration (p = 0.39) nor the patients' age (p = 0.59). CONCLUSIONS: RCT was considered successful in 68.0% of the cases at the 24 month follow-up. Failure of RCT in traumatized primary incisors was associated with pre-operatory periapical lesions and pathological root resorption. The filling paste, the filling extent and the patient's age were unrelated with therapy success.

Molecular diagnosis of haemophilia A at Centro Hospitalar de Coimbra in Portugal: study of 103 families--15 new mutations.

Haemophilia A (HA), the most commonly inherited bleeding disorder, has well known phenotype heterogeneity, influenced by the type of mutation, modulating factors and development of inhibitors. Nowadays, new technologies in association with bioinformatics tools allow a better genotype/phenotype correlation. With the main objective of identifying familial carrier women and to offer prenatal diagnosis, 141 HA patients belonging to 103 families, followed or referred to the Haemophilia Centre of CHC, E.P.E., were studied. Molecular diagnosis strategy was based on HA severity: IVS22 and IVS1 inversions, direct sequencing and MLPA technique. New missense and splicing mutations were further analyzed using molecular modelling. Genotype/phenotype correlation was assessed taking into account the known modulating factors. During this study, mutations were detected in 102/103 families, carrier status was determined in 83 women and 14 prenatal diagnoses were performed. In a total of 46 different mutations identified, 15 have not been reported previously by the HAMSTeRS and HGMD. Genotype/phenotype correlation revealed two cases with a clinical picture less severe than expected by the type of mutation identified. Six patients developed inhibitors: five severe (IVS22, IVS1, large deletion) and one mild (p. Gln2265Lys). The adopted strategy allowed the identification of 99% of the molecular alterations underlying the HA phenotype (98% detection rate for severe and 100% for moderate and mild). Evaluation of genotype-phenotype correlation was complemented with structural protein modelling of newly identified missense mutations, contributing to better understanding of the disease-causing mechanisms and to deepening knowledge on protein structure-function.

Human endothelial cells are activated by interferon-gamma plus tumour necrosis factor-alpha to kill intracellular Pseudomonas aeruginosa.

Proinflammatory cytokines have been shown to activate endothelial cells. To investigate the effect of cytokines on the interaction of human umbilical vein endothelial cells (HUVEC) with Pseudomonas aeruginosa, cells were treated with interferon-gamma (IFN-gamma) plus tumour necrosis factor-alpha (TNF-alpha) for 24 hr and exposed to P. aeruginosa suspension for 1 hr. Light microscopy showed that activated cells internalized significantly more bacteria than control cells. To ascertain the effect of cytokines on the microbicidal activity of HUVEC, the concentrations of viable intracellular (IC) bacteria in control and activated cells were determined, at 1 and 5 hr postinfection, by the gentamicin exclusion assay. In control cells, no significant decrease in the concentration of bacteria was detected 5 hr postinfection. In contrast, in activated cells the concentration of viable bacteria at 5 hr was significantly lower. Concentrations of superoxide and hydrogen peroxide detected in supernatants of activated cells were significantly higher than in control cell supernatants. HUVEC anti-P. aeruginosa activity was insensitive to the antioxidants superoxide dismutase, dimethylthiourea and allopurinol as well as to the L-arginine analogues aminoguanidine and NG-monomethyl-L-arginine (L-NMMA), but was significantly inhibited by catalase. Our results indicate that HUVEC can be activated by IFN-gamma plus TNF-alpha to kill IC P. aeruginosa and suggest a role for reactive oxygen radicals, notably hydrogen peroxide, in HUVEC antibacterial activity.

Exclusion of the first EGF domain of factor VII by a splice site mutation causes lethal factor VII deficiency.

We have studied a family with homozygous lethal, blood coagulation factor VII (FVII) deficiency. To identify the mutation responsible for the deficiency, exons 2 to 8 and the intron-exon junctions of their FVII genes were amplified from peripheral white blood cell DNA by polymerase chain reaction and screened by single-strand conformational polymorphism analysis. The fragment showing aberrant mobility was cloned and sequenced. We detected a single point mutation, a homozygous G to A substitution at nucleotide position 6070, in the invariant GT dinucleotide at the 5' splice site of intron 4. Homozygosity was confirmed by loss of a site for the restriction endonuclease Mlu I. Analysis of the splicing pattern of ectopic transcripts in lymphocytes in the parents revealed that this mutation is associated with skipping of exon 4, which produces an mRNA encoding FVII with an in-frame deletion of the first epidermal growth factor-like domain (EGF 1). Transient transfection of COS-7 cells with an expression vector containing the triangle upEGF 1 FVII cDNA shows that this mutant protein is not expressed. The identification of the molecular basis of the FVII deficiency in this family allowed mutation-specific prenatal diagnosis to be performed in a subsequent pregnancy. In this family complete FVII deficiency is associated with a severe bleeding diathesis but no developmental abnormalities, lending weight to the hypothesis that fetal FVII is not required for the putative angiogenic functions of tissue factor in humans.