Pathogenic SCN2A variants cause early-stage dysfunction in patient-derived neurons.

Pathogenic heterozygous variants in SCN2A, which encodes the neuronal sodium channel NaV1.2, cause different types of epilepsy or intellectual disability (ID)/autism without seizures. Previous studies using mouse models or heterologous systems suggest that NaV1.2 channel gain-of-function typically causes epilepsy, whereas loss-of-function leads to ID/autism. How altered channel biophysics translate into patient neurons remains unknown. Here, we investigated iPSC-derived early-stage cortical neurons from ID patients harboring diverse pathogenic SCN2A variants [p.(Leu611Valfs*35); p.(Arg937Cys); p.(Trp1716*)] and compared them with neurons from an epileptic encephalopathy (EE) patient [p.(Glu1803Gly)] and controls. ID neurons consistently expressed lower NaV1.2 protein levels. In neurons with the frameshift variant, NaV1.2 mRNA and protein levels were reduced by ~ 50%, suggesting nonsense-mediated decay and haploinsufficiency. In other ID neurons, only protein levels were reduced implying NaV1.2 instability. Electrophysiological analysis revealed decreased sodium current density and impaired action potential (AP) firing in ID neurons, consistent with reduced NaV1.2 levels. In contrast, epilepsy neurons displayed no change in NaV1.2 levels or sodium current density, but impaired sodium channel inactivation. Single-cell transcriptomics identified dysregulation of distinct molecular pathways including inhibition of oxidative phosphorylation in neurons with SCN2A haploinsufficiency and activation of calcium signaling and neurotransmission in epilepsy neurons. Together, our patient iPSC-derived neurons reveal characteristic sodium channel dysfunction consistent with biophysical changes previously observed in heterologous systems. Additionally, our model links the channel dysfunction in ID to reduced NaV1.2 levels and uncovers impaired AP firing in early-stage neurons. The altered molecular pathways may reflect a homeostatic response to NaV1.2 dysfunction and can guide further investigations.

Zirconia Implants Produced by Additive Manufacturing - A Scoping Review.

INTRODUCTION: Additive manufacturing is a tool with potential use in medicine and dentistry. The manufacture of metals and composites is already advanced, however, concerns about titanium hypersensitivity, tissue staining, and corrosion caused by gradual material degradation encourage research into more biocompatible alternatives. OBJECTIVE: This systematic scoping review aimed to gather studies that evaluated zirconia implants produced by additive manufacturing to describe the current stage of the printing technique and the final product. METHODS: Searches in Embase, PubMed, SCOPUS, Web of Science, and Google Scholar databases were enriched with manual searches between February and March 2021 and updated in June 2022 using keywords: zirconium implants, zirconium oxide, additive manufacturing, rapid prototyping, 3D printing, selective laser melting, and electron beam melting. The criteria included studies that evaluated or described zirconia implants obtained by 3D printing, with a direct relationship to dentistry or orthopedics. RESULTS: The database search resulted in 671 articles. Eight articles were selected for full reading and remained in this systematic review. CONCLUSION: The printing technique for zirconia implants is promising. However, further studies are required before implants produced by the printing technique can be tested clinically. The literature with results regarding the impression product is still limited.

Does the Incorporation of Graphene Oxide into PMMA Influence its Antimicrobial Activity?

INTRODUCTION: The increase in infectious diseases mediated by oral bacteria has been one of the most potent threats to human health, specifically to the elderly. Researchers seek to incorporate antimicrobial nanomaterials into PMMA to control the colonization of microorganisms and reduce deadly diseases. OBJECTIVE: To conduct a systematic review to answer the question: "Does graphene oxide incorporated into polymethylmethacrylate influence its antimicrobial activity?" METHODS: The electronic search was performed in PubMed, Embase, Web of Science, Scopus, and Google Scholar databases, and articles published until October 2021 were selected. The search terms were: ("acrylic resin" OR PMMA) AND (graphene OR "oxide graphene") AND (antimicrobial OR antibacterial OR "anti-infective agent"). The risk of bias analysis of the articles was performed using the quasi-experimental study assessment tool adapted from the JBI. RESULTS: Two hundred and fifty-nine articles were found in the databases. After removing the duplicates, 245 were analyzed by title and abstract. Of these, 06 were selected for full reading, of which 03 met the eligibility criteria and were included in this systematic review. CONCLUSION: This systematic review's findings can infer that the incorporation of graphene in the form of graphene-based coatings to PMMA showed antimicrobial effectiveness.

ConectAR: Collaborative network of patients with asthma and carers actively involved in health research: a protocol for patient and public involvement.

Summary: Background. Patients and Public Involvement in every stage of the patient-centered health research cycle is the key to the development of innovative solutions with an impact on patients' care. Methods. This protocol describes the development of ConectAR, a network to promote the involvement of patients with asthma and their carers in the health research cycle. Results. This protocol comprehends 4 tasks: 1) define the mission, vision, governance and activities of the network through focus groups; 2) establish the communication strategy and tools; 3) test the feasibility of the network in a Delphi study on the research priorities for asthma in Portugal; 4) coordination and dissemination activities. Conclusions. This network will improve research by ensuring that patients and carers have an active role in the co-creation of impactful solutions for asthma.

Surface Characteristics and Microbial Adhesion in Polymethylmethacrylate for Denture Base Submitted to Antimicrobial Agents and Cleaning Agents: A Systematic Review.

This review aimed to identify the influence of antimicrobial and cleaning agents on surface characteristics such as surface free energy (SFE) and wettability, and microbial adhesion in polymethylmethacrylate (PMMA) for denture base. The review question, based on PICO, was: "Does intervention with antimicrobial and cleaning agents in PMMA influence the surface free energy, wettability, and consequently the microbial adhesion?" and the protocol was registered in Open Science Framework (osf. io/v3xgn). The search was performed in PubMed, Lilacs, Embase, Scopus, and Science Direct databases, using the terms: ("acrylic resin" OR PMMA) AND (antimicrobial OR antibacterial) AND ("electrostatic interaction" OR surface free energy) AND (biofilm OR "bacteria adhesion"), and resulted in 462 articles, of which 7 were included. The antimicrobials polypara-xylylene, carboxybetaine methacrylate, ethylene glycol methacrylate phosphate, and deposition of F and Ag ions in PMMA influenced the SFE and wettability. Denture cleaners reduced microbial adhesion. Five of the included studies evaluated the microbial adhesion, however, only two observed a direct relationship between SFE, wettability, and microbial adhesion. It was concluded that the intervention with antimicrobial and cleaning agents in PMMA can interfere in SFE and surface wettability, but no correlation was observed between microbial adhesion and these surface characteristics in PMMA.

Factors that Affect the Shear Bond Strength of Pit and Fissure Sealants to Tooth Structure: A Systematic Review.

INTRODUCTION: Pit and fissure sealants are effective in preventing caries disease, however, they may present flaws that damage the physical barrier leading to treatment failure. OBJECTIVE: To answer the question ''Do pit and fissure sealants present good adhering to the dental structure when analyzed by their resistance to shear/microshear?". METHODS: This systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) and was recorded in Open Science Framework. Embase, PubMed, SCOPUS, and Web of Science databases were used for the search strategy. The articles were selected according to the eligibility criteria. The risk of bias was performed with the adaptation of the quasi-experimental studies tool by Joanna Briggs Institute (JBI). RESULTS: 1245 studies were found in the databases when applying the search strategy, after removal of duplicates 881 were evaluated and 44 were selected. After applying the JBI tool, 30 studies presented low risk and 15 moderate risk of bias. Meta-analysis was not possible to performed due to the heterogeneity of the studies. CONCLUSION: The adhesion is dependent on the application protocol, and among the protocols evaluated, conditioning with 37% phosphoric acid for 60 seconds and contamination of the substrate, as these can affect sealant adhesion.

Prevention of Caries in Cancer Patients: A Systematic Review on the Effectiveness of Dental Materials.

This study aims to identify dental materials and their effectiveness in preventing caries in patients after chemotherapy and radiotherapy for the head and neck. The electronic search was performed in PubMed, Science Direct, Embase and Scopus. All 653 articles found passed through a double-blinded screening process. The exclusion of articles by reading titles and abstracts selected 16 articles for full reading, of which 4 were included into the study. A risk of bias analysis for non-randomized and randomized articles was performed using respectively the ROBINS I and ROB II tools. The data extraction suggested that the casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), in association with fluorine, is able to form harder surfaces compared to the control group, the intraoral fluoride-releasing system (IFRS) effectiveness is similar to the fluorine in gel and a mouthwash composed of natural enzymes (Oral7) did not demonstrate effectiveness in the prevention dental caries. New randomized controlled clinical trials are necessary to evaluate the effectiveness of prevention when applying dental materials in patients after treatment of head and neck cancer.

Pythium and Phytopythium species associated with weeds collected in vegetable production fields in Brazil.

This study aimed to identify Pythium and Phytopythium species from weeds collected in vegetable fields and test their pathogenicity. Weeds with symptoms of damping-off, root rot or wilt were sampled in the Brazilian states of Ceará, Goiás and Pernambuco, as well as in the Distrito Federal, for isolation and identification of the causal agents. Once isolated, colonies with typical Pythium and Phytopythium characteristics grew in selective V8 medium. Procedures for species identification included morphology and amplification of the ITS and Cox II regions, which were compared with other accessions available at GenBank. The phylogenetic relationships among the isolates and pathogenicity to their original hosts were evaluated. Six Pythium species were identified: P. aphanidermatum, P. oopapillum, P. orthogonon, P. ultimum var. ultimum, P. myriotylum and P. sylvaticum, and two species of Phytopythium, Phy. chamaehyphon and Phy. oedochilum. In the pathogenicity tests, the 10 weed hosts showed symptoms of damping-off or root rot after inoculation, with exception of Portulaca oleraceae in which none of the isolates was pathogenic. Therefore, common weeds in vegetable fields areas can host different Pythium and Phytopythium species and play an important role in the epidemiology of vegetable diseases, in particular on pathogen survival and population increase.

De novo variants in MED12 cause X-linked syndromic neurodevelopmental disorders in 18 females.

PURPOSE: MED12 is a subunit of the Mediator multiprotein complex with a central role in RNA polymerase II transcription and regulation of cell growth, development, and differentiation. This might underlie the variable phenotypes in males carrying missense variants in MED12, including X-linked recessive Ohdo, Lujan, and FG syndromes. METHODS: By international matchmaking we assembled variant and clinical data on 18 females presenting with variable neurodevelopmental disorders (NDDs) and harboring de novo variants in MED12. RESULTS: Five nonsense variants clustered in the C-terminal region, two splice variants were found in the same exon 8 splice acceptor site, and 11 missense variants were distributed over the gene/protein. Protein truncating variants were associated with a severe, syndromic phenotype consisting of intellectual disability (ID), facial dysmorphism, short stature, skeletal abnormalities, feeding difficulties, and variable other abnormalities. De novo missense variants were associated with a less specific, but homogeneous phenotype including severe ID, autistic features, limited speech and variable other anomalies, overlapping both with females with truncating variants as well as males with missense variants. CONCLUSION: We establish de novo truncating variants in MED12 as causative for a distinct NDD and de novo missense variants as causative for a severe, less specific NDD in females.

Species diversity, novel interactions and absence of well-supported host-guided phylogenetic groupings of Neotropical Alternaria isolates causing foliar lesions in Solanaceae.

AIM: To report the characterization of 120 Alternaria isolates inducing early blight-like foliar lesions in nine species of five Solanaceae genera collected across all macrogeographical Brazilian regions. MATERIAL AND RESULTS: Phylogenetic relationships were assessed via analyses of the Alternaria alternata allergenic protein-coding, glyceraldehyde-3-phosphate dehydrogenase and the calmodulin gene sequences. Most of the tomato isolates were placed into the Alternaria linariae cluster, whereas most of the potato isolates were grouped with Alternaria grandis. Novel host-pathogen interactions were also reported. Seventeen isolates were selected for morphometrical characterization, and a subsample of 13 isolates was employed in pathogenicity assays on tomato, potato, eggplant, scarlet eggplant, Capsicum annuum, Datura stramonium, Physalis angulata and Nicotiana tabacum. Eleven isolates were able to induce foliar lesions in tomatoes but none in C. annuum. Potato was susceptible to a subgroup of isolates but displayed a subset of isolate-specific interactions. Morphological traits were in overall agreement with molecular and host range data. CONCLUSION: Alternaria linariae and A. grandis were confirmed as the major causal agents of tomato and potato early blight, respectively. However other Alternaria species are also involved with early blight in solanaceous hosts in Brazil. SIGNIFICANCE AND IMPACT OF THE STUDY: The diversity and host-specific patterns of the Alternaria isolates from Solanaceae may have practical implications in establishing effective early blight genetic resistance and cultural management strategies especially for tomato and potato crops.

A three-decade survey of Brazilian Fusarium oxysporum f. sp. lycopersici races assessed by pathogenicity tests on differential tomato accessions and by molecular markers.

AIM: Physiological race determination of 143 Fusarium oxysporum f. sp. lycopersici (FOL) isolates collected along 30 years in major tomato-producing regions of Brazil. MATERIALS AND RESULTS: Physiological races were determined via root-dipping inoculation of differential tomato accessions and by the PCR-based marker system of Hirano and Arie (2006). According to pathogenicity/virulence assays, five race 1, 23 race 2 and 115 race 3 isolates were identified. FOL race 1 and 2 isolates prevailed up to early 2000s. Afterwards, the large majority of the isolates was classified as the invasive race 3. Novel reports of race 3 were done in five states, thus expanding its geographical distribution. Using this PCR-based marker system, a precise discrimination was observed for all race 3 isolates. However, all race 1 and 2 isolates displayed only the cosmopolitan race 1-specific amplicon pattern. CONCLUSION: The development and/or validation of novel race-specific marker systems are necessary to allow a precise discrimination of the potentially endemic Brazilian FOL race 2. SIGNIFICANCE AND IMPACT OF THE STUDY: The present characterization of isolates indicates that distinct evolutionary mechanisms are acting to select new FOL races and/or genetic variants across agroecosystems around the globe.

Topical application of a desensitizing agent containing potassium nitrate before dental bleaching: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to evaluate the risk and intensity of tooth sensitivity (TS) after topical application of desensitizers containing potassium nitrate before dental bleaching. METHODS: We searched PubMed, Scopus, Web of Science, LILACS, BBO, Cochrane Library, and SIGLE. We also surveyed gray literature without restrictions. We meta-analyzed the data using the random-effects model to compare potassium nitrate and placebo in terms of risk and intensity of TS and color change (∆SGU or ∆E). The quality of the evidence was rated using the GRADE approach. The risk of bias (RoB) of the included studies was analyzed using the Cochrane RoB tool. RESULTS: After the database screening, 24 articles remained. A significant 12% lower risk for the groups where desensitizing agents were applied (p = 0.02), with a risk ratio of 0.88 (95% CI 0.78 to 0.98). About the intensity of TS, a significant average mean difference of - 0.77 units of VAS units (95%CI - 1.34 to - 0.19; p = 0.01) in favor of the desensitizer group. In the NRS scale, a significant average mean difference of - 0.36 (95% CI - 0.61 to - 0.12; p value = 0.004) in favor of the desensitizer group. No significant difference was observed in color change (p > 0.28) in ∆SGU and ∆E. CONCLUSIONS: Although a significant reduction in the risk and intensity of TS was observed in groups treated with a potassium nitrate at some point during the bleaching, the clinical significance of this reduction is subtle and clinically questionable. Color change is not affected by the use of agents. CLINICAL RELEVANCE: The reduction in the risk and intensity of TS with the topical application of potassium nitrate-based desensitizing agents in dental bleaching is subtle and maybe clinically questionable.

A subpopulation of human Adark spermatogonia behaves as the reserve stem cell.

Human spermatogonial stem cells (SSCs) are an essential source to maintain spermatogenesis as an efficient process for daily sperm production with high self-renewal capacity along adulthood. However, the phenotype and the subpopulation that represent the real reserve SSC for the human testis remain unknown. Moreover, although SSC markers have been described for undifferentiated spermatogonia (Adark and Apale), the existence of a specific subtype that could be identified as the actual/true SSC has not yet been fully determined. Herein we evaluated spermatogonial morphology, kinetics, positioning regarding blood vasculature in relation to protein expression (UTF1, GFRA1, and KIT) as well as proliferative activity (MCM7) and identified a small subpopulation of Adark with nuclear rarefaction zone (AdVac) that behaves as the human reserve SSC. We show that AdVac is the smallest human spermatogonial population (10%), staying quiescent (89%) and positioned close to blood vessels throughout most of the stages of the seminiferous epithelium cycle (SEC) and divides only at stages I and II. Within this AdVac population, we found a smaller pool (2% of A undifferentiated spermatogonia) of entirely quiescent cells exhibiting a high expression of UTF1 and lacking GFRA1. This finding suggests them as the real human reserve SSC (AdVac UTF1+/GFRA1-/MCM7-). Additionally, Adark without nuclear vacuole (AdNoVac) and Apale have similar kinetic and high proliferative capacity throughout the SEC (47%), indicating that they are actively dividing undifferentiated spermatogonia. Identification of human stem cells with evident reserve SSC functionality may help further studies intending to sort SSCs to treat male diseases and infertility.

The smokeless tobacco habit and DNA damage: A systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review was to evaluate the frequency of micronuclei or other DNA damage in the oral mucosa of adults that have smokeless tobacco habits compared to adults that not have these habits. MATERIAL AND METHODS: We searched PubMed, Scopus, Web of Science, LILACS, BBO and Cochrane Library and SIGLE. We also surveyed gray literature. We included only clinical trials that compare the frequency of micronuclei or other DNA damage in the oral mucosa of adults that have smokeless tobacco habits compared to adults that not have these habits. Quality assessments of the selected trials were evaluated by two independent reviewers, using the Effective Public Health Practice Project - (EPHPP) with modifications. RESULTS: After the database screening and removal of duplicates, 2574 studies were identified. After title screening, 172 studies remained, and this number was reduced to 25 after careful examination of the abstracts. The standardized mean difference of the frequency of micronuclei between groups was 1.88, with a 95% confidence interval of 1.40 to 2.36 (p < 0.00001). In all analyses heterogeneity was detected. CONCLUSIONS: Despite the heterogeneity of studies, the frequency of micronuclei was significant bigger in adults who have the smokeless tobacco habit when compared to those not have this habit. The same occurred with the frequency of binucleated cells, karyolisis and karyorrhexis.

Analgesic efficacy of ketorolac associated with a tramadol/acetaminophen combination after third molar surgery - a randomized, triple-blind clinical trial.

BACKGROUND: This study compared the efficacy of ketorolac alone versus its combination with tramadol/acetaminophen for pain control after mandibular third molar surgery. MATERIAL AND METHODS: A randomized, triple-blind clinical trial was carried out with 52 patients divided into 2 groups: Group K+T+A (1 tablet of Ketorolac 10 mg plus and 1 capsule of Tramadol 37.5 mg/acetaminophen 325 mg) and Group K (1 tablet of Ketorolac 10 mg plus and 1 placebo capsule). The treatments were given 1 h before the surgery and was repeated 4 times per day, for 48 h. The difference in postoperative pain was assessed by 4 primary end-points: pain intensity (VAS 100mm, for 48 h), rescue medication, overall assessment and adverse effects. RESULTS: Significant differences in pain intensity were observed in the different times (p < 0.05). The comparison of groups in each time showed significant differences only of 9 h, with lower level of pain intensity for group K+T+A (p = 0.005). The need of analgesics was higher in Group K (p < 0.001), the need of antiemetic were greater in Group K+T+A (p < 0.0001). No significant difference between groups were observed in overall assessment. The adverse effects was higher in Group K+T+A. CONCLUSIONS: The current study showed that both ketorolac and the combination of ketorolac plus tramadol/acetaminophen showed good control of pain after the extraction of the lower third molars. Although the combination group showed lower pain at 9 h, the difference is small and not clinically relevant.

Preparation and quantitative characterization of polydimethylsiloxane optical phantoms with zinc-phthalocyanine dye absorbers.

We described a method for the preparation of polydimethylsiloxane (PDMS) phantoms to mimic the optical properties of biologic tissues at distinct wavelengths ranging from the visible to the near-infrared spectra. The present method for fabricating solid optical tissue phantoms using zinc-phthalocyanine chromophores has demonstrated high photostability with optical absorption coefficients up to 1.0 mm-1, making this phantom proper with absorption bands ranging from 600 to 850 nm. It also happens that the chromophore absorption coefficient is linear as a function of its concentration inside the previous optical window. The optical scattering properties were quantitatively selected by adding TiO2 particle concentrations to the PDMS phantom. Thus, the quantitative optical properties of absorption and scattering for a large-batch fabrication were demonstrated, making the zinc-phthalocyanine phantoms suitable for use as a reference standard.

Evidence for genetic overlap between adult onset Still's disease and hereditary periodic fever syndromes.

OBJECTIVE: Adult onset Still's disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD. METHODS: We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD. RESULTS: We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (p c = 2.34E- 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (p c = 2.40E- 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment. CONCLUSION: Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients.

Cytokine expression in response to root repair agents.

AIM: To evaluate the expression of TNF-α, IL-6, IFN-γ, TGF-ß, IL-4, IL-10, RANKL, RANK and OPG on mouse calvarial bone treated with MTA, Geristore® and Emdogain® . METHODOLOGY: Bone wounds were made on the heads of C57BL/6 mice, breaking the periosteum and the cortical surface of the calvaria. Each repair agent was inserted into sectioned Eppendorf microtubes and placed on the bone wound, and soft tissues were sutured. At 14 and 21 days, animals were sacrificed and the treated region was dissected. The calvaria bone was removed, and RNA was extracted. mRNA expression of the aforementioned cytokines was assessed using real-time PCR. Data were analysed by nonparametric methods, including the Mann-Whitney and Kruskal-Wallis tests (P < 0.05). RESULTS: Following treatment with Emdogain® and MTA, mRNA expression of RANKL, RANK and OPG increased significantly (P < 0.05) between days 14 to 21. Geristore® did not alter the basal expression of these mediators during the same period of evaluation. Whilst treatment with Emdogain® did cause a significant increase in TNF-α mRNA expression between days 14 and 21 (P < 0.05), treatment with MTA did not alter the basal expression of this cytokine at either experimental time point. However, TNF-α mRNA expression was down-regulated significantly at day 21 (P < 0.05) when Geristore® was applied. A significant increase in the mRNA expression of IL-6, TGF-ß, IL-10, IL-4 and IFN-γ was observed with Emdogain® and MTA treatment between days 14 to 21, whereas Geristore® reduced significantly the expression of IL-6, TGF-ß and IL-4 (P < 0.05). CONCLUSION: The clinical indication of these repair agents depends on the root resorption diagnosis. Whilst MTA and Emdogain® induce a pro- and anti-inflammatory response early and late, respectively, Geristore® was not associated with an inflammatory reaction when compared with both repair agents.

Killing two birds with one stone? Association between tobacco and alcohol consumption.

OBJECTIVES: Tobacco and excessive alcohol consumption are addictive behaviours, listed among the 10 leading risk factors that cause death and disability in the world, and health consequences are greater if their consumption is combined. There is sparse empirical evidence on the variables that influence the simultaneous consumption of tobacco and alcohol. This study aims to identify the variables that influence the joint decision to consume alcohol and tobacco, and that encourage drinkers to smoke. STUDY DESIGN: The sample includes Portuguese adults, mainly aged 50 years and over, extracted from the Survey of Health, Ageing and Retirement in Europe, covering the year 2011. METHODS: We propose a bivariate probit model, which allows us to model simultaneously the two goods, accounting for potential correlation between smoking and drinking decisions. RESULTS: We identified the variables that influence joint consumption, and tobacco consumption among drinkers, which could be used as policy instruments to develop concerted policies. Prevention policies should focus on males, younger and more educated individuals, as well as on individuals with unhealthy eating habits, because these variables were statistically significant and increased joint consumption. In addition, these characteristics also should be regarded if we want to control tobacco consumption among alcohol consumers. CONCLUSIONS: The analysis of the interdependence between alcohol and tobacco use presented in this article may allow reducing their consumption with a common intervention, enabling policymakers to 'kill two birds with one stone' and to achieve extended health and economic gains.

Human predisposition to cognitive impairment and its relation with environmental exposure to potentially toxic elements.

New lines of evidence suggest that less than 10% of neurodegenerative diseases have a strict genetic aetiology and other factors may be prevalent. Environmental exposures to potentially toxic elements appear to be a risk factor for Parkinson's, Alzheimer's and sclerosis diseases. This study proposes a multidisciplinary approach combining neurosciences, psychology and environmental sciences while integrating socio-economic, neuropsychological, environmental and health data. We present the preliminary results of a neuropsychological assessment carried out in elderly residents of the industrial city of Estarreja. A battery of cognitive tests and a personal questionnaire were administered to the participants. Multivariate analysis and multiple linear regression analysis were used to identify potential relationships between the cognitive status of the participants and environmental exposure to potentially toxic elements. The results suggest a relationship between urinary PTEs levels and the incidence of cognitive disorders. They also point towards water consumption habits and profession as relevant factors of exposure. Linear regression models show that aluminium (R 2 = 38%), cadmium (R 2 = 11%) and zinc (R 2 = 6%) are good predictors of the scores of the Mini-Mental State Examination cognitive test. Median contents (µg/l) in groundwater are above admissible levels for drinking water for aluminium (371), iron (860), manganese (250), and zinc (305). While the World Health Organization does not provide health-based reference values for aluminium, results obtained from this study suggest that it may have an important role in the cognitive status of the elderly. Urine proved to be a suitable biomarker of exposure both to elements with low and high excretion rates.