mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis.

BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown. METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141). RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort. CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.

The European Portuguese Version of the Brief Negative Symptom Scale.

Negative symptoms reflect a currently much-untreated loss of normal functioning and are frequently found in psychotic disorders. We present the first translation of the Brief Negative Symptom Scale (BNSS) to European Portuguese and evaluate its validity in a sample of Portuguese male patients with a psychotic spectrum disorder. The Portuguese BNSS showed excellent internal consistency, high convergent validity (i.e., strong correlation with the PANSS negative factor), and high discriminant validity (i.e., a lack of association with the PANSS positive factor). In sum, the present European Portuguese BNSS has shown to be reliable, thus extending this instrument's clinical availability worldwide.

Modeling Lysosomal Storage Disorders in an Innovative Way: Establishment and Characterization of Stem Cell Lines from Human Exfoliated Deciduous Teeth of Mucopolysaccharidosis Type II Patients.

Among the many lysosomal storage disorders (LSDs) that would benefit from the establishment of novel cell models, either patient-derived or genetically engineered, is mucopolysaccharidosis type II (MPS II). Here, we present our results on the establishment and characterization of two MPS II patient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population has been isolated from LSD patient samples obtained from the dental pulp. Taking into account our results on the molecular and biochemical characterization of those cells and the fact that they exhibit visible and measurable disease phenotypes, we consider these cells may qualify as a valuable disease model, which may be useful for both pathophysiological assessments and in vitro screenings. Ultimately, we believe that patient-derived dental pulp stem cells (DPSCs), particularly those isolated from human exfoliated deciduous teeth (SHEDs), may represent a feasible alternative to induced pluripotent stem cells (iPSCs) in many labs with standard cell culture conditions and limited (human and economic) resources.

Myocardial Fibrosis at Cardiac MRI Helps Predict Adverse Clinical Outcome in Patients with Mitral Valve Prolapse.

Background Patients with mitral valve prolapse (MVP) may develop adverse outcomes even in the absence of mitral regurgitation or left ventricular (LV) dysfunction. Purpose To investigate the prognostic value of mitral annulus disjunction (MAD) and myocardial fibrosis at late gadolinium enhancement (LGE) cardiac MRI in patients with MVP without moderate-to-severe mitral regurgitation or LV dysfunction. Materials and Methods In this longitudinal retrospective study, 118 144 cardiac MRI studies were evaluated between October 2007 and June 2020 at 15 European tertiary medical centers. Follow-up was from the date of cardiac MRI examination to June 2020; the minimum and maximum follow-up intervals were 6 months and 156 months, respectively. Patients were excluded if at least one of the following conditions was present: cardiomyopathy, LV ejection fraction less than 40%, ischemic heart disease, congenital heart disease, inflammatory heart disease, moderate or worse mitral regurgitation, participation in competitive sport, or electrocardiogram suggestive of channelopathies. In the remainder, cardiac MRI studies were reanalyzed, and patients were included if they were aged 18 years or older, MVP was diagnosed at cardiac MRI, and clinical information and electrocardiogram monitoring were available within 3 months from cardiac MRI examination. The end point was a composite of adverse outcomes: sustained ventricular tachycardia (VT), sudden cardiac death (SCD), or unexplained syncope. Multivariable Cox regression analysis was performed. Results A total of 474 patients (mean age, 47 years ± 16 [SD]; 244 women) were included. Over a median follow-up of 3.3 years, 18 patients (4%) reached the study end point. LGE presence (hazard ratio, 4.2 [95% CI: 1.5, 11.9]; P = .006) and extent (hazard ratio, 1.2 per 1% increase [95% CI: 1.1, 1.4]; P = .006), but not MAD presence (P = .89), were associated with clinical outcome. LGE presence had incremental prognostic value over MVP severity and sustained VT and aborted SCD at baseline (area under the receiver operating characteristic curve, 0.70 vs 0.62; P = .03). Conclusion In contrast to mitral annulus disjunction, myocardial fibrosis determined according to late gadolinium enhancement at cardiac MRI was associated with adverse outcome in patients with mitral valve prolapse without moderate-to-severe mitral regurgitation or left ventricular dysfunction. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gerber in this issue.

Prevalence and maternal determinants of early and late introduction of complementary foods: results from the Growing Up in New Zealand cohort study.

A nationally generalisable cohort (n 5770) was used to determine the prevalence of non-timely (early/late) introduction of complementary food and core food groups and associations with maternal sociodemographic and health behaviours in New Zealand (NZ). Variables describing maternal characteristics and infant food introduction were sourced, respectively, from interviews completed antenatally and during late infancy. The NZ Infant Feeding Guidelines were used to define early (≤ 4 months) and late (≥ 7 months) introduction. Associations were examined using multivariable multinomial regression, presented as adjusted relative risk ratios and 95 % confidence intervals (RRR; 95% CI). Complementary food introduction was early for 40·2 % and late for 3·2 %. The prevalence of early food group introduction were fruit/vegetables (23·8 %), breads/cereals (36·3 %), iron-rich foods (34·1 %) and of late were meat/meat alternatives (45·9 %), dairy products (46·2 %) and fruits/vegetables (9·9 %). Compared with infants with timely food introduction, risk of early food introduction was increased for infants: breastfed < 6months (2·52; 2·19-2·90), whose mothers were < 30 years old (1·69; 1·46-1·94), had a diploma/trade certificate v. tertiary education (1·39; 1·1-1·70), of Maori v. European ethnicity (1·40; 1·12-1·75) or smoked during pregnancy (1·88; 1·44-2·46). Risk of late food introduction decreased for infants breastfed < 6 months (0·47; 0.27-0·80) and increased for infants whose mothers had secondary v. tertiary education (2·04; 1·16-3·60) were of Asian v. European ethnicity (2·22; 1·35, 3·63) or did not attend childbirth preparation classes (2·23; 1·24-4·01). Non-timely food introduction, specifically early food introduction, is prevalent in NZ. Interventions to improve food introduction timeliness should be ethnic-specific and support longer breast-feeding.

A Comparative Study between Onion Peel Extracts, Free and Complexed with ß-Cyclodextrin, as a Natural UV Filter to Cosmetic Formulations.

The growing concern regarding the adverse effects of synthetic UV filters found in sunscreens has spurred significant attention due to their potential harm to aquatic ecosystems and human health. To address this, the present study aimed to extract and microencapsulate sensitive bioactive compounds derived from by-product onion peel (OP) by molecular inclusion using ß-cyclodextrin as the wall material. Identification and quantification of bioactive compounds within the extract were conducted through high-performance liquid chromatography (HPLC-DAD) analysis, revealing quercetin and resveratrol as the primary constituents. The photoprotection capacity, evaluated by the sun protection factor (SPF), revealed a protection factor comparable to the value for a synthetic UV filter. The produced microparticles presented high antioxidant capacity, significant photoprotection capacity, encapsulation efficiency of 91.8%, mean diameter of 31 µm, and polydispersity of 2.09. Furthermore, to comprehensively evaluate the performance of OP extract and its potential as a natural UV filter, five O/W emulsions were produced. Results demonstrated that microparticles displayed superior ability in maintaining SPF values over a five-week period. Photoprotection evaluation-skin reactivity tests revealed that both extract and microparticles absorb UV radiation in other regions of UV radiation, revealing their potential to be used as a natural UV filter to produce a sustainable and eco-friendly value-added sunscreen.

A Novel Approach in Skin Care: By-Product Extracts as Natural UV Filters and an Alternative to Synthetic Ones.

The cosmetic industry has been focusing on replacing synthetic ingredients with natural ones, taking advantage of their bioactive compounds. This work assessed the biological properties of onion peel (OP) and passion fruit peel (PFP) extracts in topical formulations as an alternative to synthetic antioxidants and UV filters. The extracts were characterized regarding their antioxidant capacity, antibacterial capacity and sun protection factor (SPF) value. Results revealed that the OP extract exhibited better results, which can result from the high concentrations of quercetin, as identified and quantified in HPLC analysis. Afterward, nine formulations of O/W creams were produced with minor changes in the quantity of additives: OP and PFP extract (natural antioxidants and UV filters), BHT (synthetic antioxidant) and oxybenzone (synthetic UV filter). The stability of the formulations was determined for 28 days; it was verified that they remained stable throughout the study period. The assays of the formulations' antioxidant capacity and SPF value revealed that OP and PFP extracts have some photoprotective properties and are excellent sources of antioxidants. As a result, they can be incorporated in daily moisturizers with SPF and sunscreens replacing and/or diminishing the quantities of synthetic ingredients, reducing their negative effects on human health and the environment.

Thermography in complementary assessments of head and neck muscles: A scoping review.

INTRODUCTION: Infrared thermography has the potential to help assess human head and neck muscles, as thermal variation measurements due to muscle imbalance can contribute to the evaluation and therapeutic follow-up of various clinical conditions in the field of health. OBJECTIVE: This study investigated, with a scoping review, the use of infrared thermography in complementary assessments of human head and neck muscles to determine the extent of research on the topic, what methodologies are used in thermal assessment and thermographic analysis, what regions are assessed, and what results are expected in thermography. METHODS: LILACS, MEDLINE, SciELO, and Web of Science were the databases searched to identify articles published on the topic, with no restriction of language or time of publication. Descriptive, analytical, and experimental observational studies on the assessment of the human head and neck muscle surface temperature with infrared thermography were included. Case studies, case series, methodological accuracy, literature review, animal studies, studies that assessed patients with head and neck cancer, and studies that did not assess head and neck muscle temperature with thermography were excluded. The articles were analysed with a protocol developed by the authors, with data on author, year, country, type of study, sample characterisation, muscles assessed, outcomes investigated, thermal assessment methodology, thermographic analysis methodology and thermography measurements. RESULTS: This review identified and analysed 27 articles. The studies assessed thermal distribution in normal individuals and those with pathologies related to hyper- and hypofunctional head and neck muscle conditions for diagnosis or therapeutic follow-up. The masseter, temporal, digastric, anterior cervical region, orbicularis oris, frontalis, buccinator, suprahyoid, trapezius, sternocleidomastoid and levator scapulae muscles were assessed. Quantitative analyses with area selection tool predominated, considering absolute temperatures and temperature differences. The studies investigated temperature and its relationship with myogenic pain, quantitative assessment of muscle parameters and blood flow velocity. The mean temperature ranged from 32.97°C (±2.21) to 34.90°C, and hyper-radiant and/or asymmetric regions were observed in hyperfunctional conditions and normal subjects after muscle activation. CONCLUSION: Thermography is used in complementary assessments of head and neck muscles, identifying hyper-radiant regions and thermal asymmetry related to muscle tension and activation state. Papers are limited to specific clinical conditions and few muscle groups, besides having great methodological variability.

A Potential Valorization Strategy of Wine Industry by-Products and Their Application in Cosmetics-Case Study: Grape Pomace and Grapeseed.

Grape pomace and grapeseed are agro-industrial by-products, whose inadequate treatment generates socioeconomic and environmental concerns. Nevertheless, it is possible to valorize them by extracting their bioactive compounds, such as antioxidants (phenolic compounds), vitamin E and fatty acids. The bioactive compounds were extracted using solid-liquid extraction. The yields for phenolic compounds were 18.4 ± 0.4% for grape pomace, and 17.4 ± 0.4%, for grapeseed. For the oil, the yields were 13.3 ± 0.2% and 14.5 ± 0.3% for grape pomace and grapeseed. Antioxidant capacity was assessed by the assay with 2,2-diphenyl-1-picrylhydrazyl (DPPH), and showed that phenolic extract has higher antioxidant capacity than the oils. Grape pomace and grapeseed extracts exhibit, correspondingly, values of 90.8 ± 0.8 and 87.5 ± 0.5 of DPPH inhibition and IC50 of 48.9 ± 0.5 and 55.9 ± 0.7 µgextract·mLDPPH-1. The antimicrobial capacity was assessed by the disk diffusion test, and revealed that, phenolic extracts inhibit the growth of Staphylococcus aureus and Staphylococcus epidermidis. The obtained extracts were incorporated in 10 face cream formulations, with slight modifications in quantities of formulation stabilizers. Their stability was studied for 35 days, and this revealed the possibility of incorporating extracts and oils obtained from by-products as antioxidants in cosmetics, and replacing synthetic ones. As a future recommendation, microencapsulation of the extracts should be performed, in order to increase their stability.

Sustainability in Skin Care: Incorporation of Avocado Peel Extracts in Topical Formulations.

The avocado peel is an agro-industrial by-product that has exhibited a massive increase in its production in the last few years. The reuse and valorisation of this by-product are essential since its disposal raises environmental concerns. In the present study, ethanolic extracts of avocado peels of the Hass variety were obtained, for three extraction times (1.5 h, 3 h and 4 h) and analysed for their antioxidant and antibacterial properties. Antioxidant evaluations of the extracts revealed that the extraction time of 1.5 h exhibited the best results amongst the three, with a DPPH inhibition percentage of 93.92 ± 1.29 and an IC50 percentage, the necessary concentration of the extract to inhibit 50% of DPPH, of 37.30 ± 1.00. The antibacterial capacity of the extracts was evaluated and it was revealed that they were able to inhibit the growth and development of bacteria of the Staphylococcus family. The obtained extract was incorporated in two types of cosmetic formulations (oil-in-water and water-in-oil) and their stability was evaluated and compared with formulations containing synthetic preservatives (BHT and phenoxyethanol). The results of the stability evaluation suggest that the avocado peel extract has the potential to be incorporated in both types of emulsions, acting as an antioxidant and antibacterial agent, proving it to be a viable option to reduce/replace the use of synthetic preservatives. Furthermore, the avocado peel extract proved to be more effective and stable in oil-in-water emulsions. These results highlight the possibility of obtaining sustainable cosmetics, significantly reducing the negative impacts on the environment by the incorporation of extracts sourced from the avocado peel, an interesting source of phenolic compounds, an abundant and low-cost by-product.

Travel mode preferences among German commuters over the course of COVID-19 pandemic.

The COVID-19 pandemic has changed the way how the people live, work and move, and naturally the transport sector became one of the most affected by this global crisis. Beyond the sudden fall of mobility at the beginning of the pandemic, it is important to understand how people are regaining trust in travelling, even if it is still unpredictable if and when the transport sector will recover to the pre-pandemic levels. This study focuses on the analysis of commuting trips and the changes of travel mode preferences over the first eight months of the pandemic in Germany. A survey with an orthogonal design based on sets of cards containing different transport mode alternatives and attributes was conducted in three waves (April, June, and October 2020). The individual characteristics and the preferences of around 4800 commuters were collected through the survey and modelled using a conditional logit approach. The results show that commuters have regained some trust on public transport since the April-May 2020 lockdown, but this has occurred at a slow pace. The reduction of public transport ticket fares can be the most effective strategy to recover some of the users lost to other modes.

PET imaging reveals early and progressive dopaminergic deficits after intra-striatal injection of preformed alpha-synuclein fibrils in rats.

Alpha-synuclein (a-syn) can aggregate and form toxic oligomers and insoluble fibrils which are the main component of Lewy bodies. Intra-neuronal Lewy bodies are a major pathological characteristic of Parkinson's disease (PD). These fibrillar structures can act as seeds and accelerate the aggregation of monomeric a-syn. Indeed, recent studies show that injection of preformed a-syn fibrils (PFF) into the rodent brain can induce aggregation of the endogenous monomeric a-syn resulting in neuronal dysfunction and eventual cell death. We injected 8 µg of murine a-syn PFF, or soluble monomeric a-syn into the right striatum of rats. The animals were monitored behaviourally using the cylinder test, which measures paw asymmetry, and the corridor task that measures lateralized sensorimotor response to sugar treats. In vivo PET imaging was performed after 6, 13 and 22 weeks using [11C]DTBZ, a marker of the vesicular monoamine 2 transporter (VMAT2), and after 15 and 22 weeks using [11C]UCB-J, a marker of synaptic SV2A protein in nerve terminals. Histology was performed at the three time points using antibodies against dopaminergic markers, aggregated a-syn, and MHCII to evaluate the immune response. While the a-syn PFF injection caused only mild behavioural changes, [11C]DTBZ PET showed a significant and progressive decrease of VMAT2 binding in the ipsilateral striatum. This was accompanied by a small progressive decrease in [11C]UCB-J binding in the same area. In addition, our histological analysis revealed a gradual spread of misfolded a-syn pathology in areas anatomically connected to striatum that became bilateral with time. The striatal a-syn PFF injection resulted in a progressive unilateral degeneration of dopamine terminals, and an early and sustained presence of MHCII positive ramified microglia in the ipsilateral striatum and substantia nigra. Our study shows that striatal injections of a-syn fibrils induce progressive pathological synaptic dysfunction prior to cell death that can be detected in vivo with PET. We confirm that intrastriatal injection of a-syn PFFs provides a model of progressive a-syn pathology with loss of dopaminergic and synaptic function accompanied by neuroinflammation, as found in human PD.

Periphery and brain, innate and adaptive immunity in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder where alpha-synuclein plays a central role in the death and dysfunction of neurons, both, in central, as well as in the peripheral nervous system. Besides the neuronal events observed in patients, PD also includes a significant immune component. It is suggested that the PD-associated immune response will have consequences on neuronal health, thus opening immunomodulation as a potential therapeutic strategy in PD. The immune changes during the disease occur in the brain, involving microglia, but also in the periphery with changes in cells of the innate immune system, particularly monocytes, as well as those of adaptive immunity, such as T-cells. This realization arises from multiple patient studies, but also from data in animal models of the disease, providing strong evidence for innate and adaptive immune system crosstalk in the central nervous system and periphery in PD. Here we review the data showing that alpha-synuclein plays a crucial role in the activation of the innate and adaptive immune system. We will also describe the studies suggesting that inflammation in PD includes early changes in innate and adaptive immune cells that develop dynamically through time during disease, contributing to neuronal degeneration and symptomatology in patients. This novel finding has contributed to the definition of PD as a multisystem disease that should be approached in a more integratory manner rather than a brain-focused classical approach.

Soluble CD163 Changes Indicate Monocyte Association With Cognitive Deficits in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder with a significant immune component, as demonstrated by changes in immune biomarkers in patients' biofluids. However, which specific cells are responsible for those changes is unclear because most immune biomarkers can be produced by various cell types. OBJECTIVES: The aim of this study was to explore monocyte involvement in PD. METHODS: We investigated the monocyte-specific biomarker sCD163, the soluble form of the receptor CD163, in cerebrospinal fluid (CSF) and serum in two experiments, and compared it with other biomarkers and clinical data. Potential connections between CD163 and alpha-synuclein were studied in vitro. RESULTS: CSF-sCD163 increased in late-stage PD and correlated with the PD biomarkers alpha-synuclein, Tau, and phosphorylated Tau, whereas it inversely correlated with the patients' cognitive scores, supporting monocyte involvement in neurodegeneration and cognition in PD. Serum-sCD163 increased only in female patients, suggesting a sex-distinctive monocyte response. CSF-sCD163 also correlated with molecules associated with adaptive and innate immune system activation and with immune cell recruitment to the brain. Serum-sCD163 correlated with proinflammatory cytokines and acute-phase proteins, suggesting a relation to chronic systemic inflammation. Our in vitro study showed that alpha-synuclein activates macrophages and induces shedding of sCD163, which in turn enhances alpha-synuclein uptake by myeloid cells, potentially participating in its clearance. CONCLUSIONS: Our data present sCD163 as a potential cognition-related biomarker in PD and suggest a role for monocytes in both peripheral and brain immune responses. This may be directly related to alpha-synuclein's proinflammatory capacity but could also have consequences for alpha-synuclein processing. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Impairment of adenosinergic system in Rett syndrome: Novel therapeutic target to boost BDNF signalling.

Rett syndrome (RTT; OMIM#312750) is mainly caused by mutations in the X-linked MECP2 gene (methyl-CpG-binding protein 2 gene; OMIM*300005), which leads to impairments in the brain-derived neurotrophic factor (BDNF) signalling. The boost of BDNF mediated effects would be a significant breakthrough but it has been hampered by the difficulty to administer BDNF to the central nervous system. Adenosine, an endogenous neuromodulator, may accomplish that role since through A2AR it potentiates BDNF synaptic actions in healthy animals. We thus characterized several hallmarks of the adenosinergic and BDNF signalling in RTT and explored whether A2AR activation could boost BDNF actions. For this study, the RTT animal model, the Mecp2 knockout (Mecp2-/y) (B6.129P2 (C)-Mecp2tm1.1Bird/J) mouse was used. Whenever possible, parallel data was also obtained from post-mortem brain samples from one RTT patient. Ex vivo extracellular recordings of field excitatory post-synaptic potentials in CA1 hippocampal area were performed to evaluate synaptic transmission and long-term potentiation (LTP). RT-PCR was used to assess mRNA levels and Western Blot or radioligand binding assays were performed to evaluate protein levels. Changes in cortical and hippocampal adenosine content were assessed by liquid chromatography with diode array detection (LC/DAD). Hippocampal ex vivo experiments revealed that the facilitatory actions of BDNF upon LTP is absent in Mecp2-/y mice and that TrkB full-length (TrkB-FL) receptor levels are significantly decreased. Extracts of the hippocampus and cortex of Mecp2-/y mice revealed less adenosine amount as well as less A2AR protein levels when compared to WT littermates, which may partially explain the deficits in adenosinergic tonus in these animals. Remarkably, the lack of BDNF effect on hippocampal LTP in Mecp2-/y mice was overcome by selective activation of A2AR with CGS21680. Overall, in Mecp2-/y mice there is an impairment on adenosinergic system and BDNF signalling. These findings set the stage for adenosine-based pharmacological therapeutic strategies for RTT, highlighting A2AR as a therapeutic target in this devastating pathology.

Exploring Monitoring Systems Data for Driver Distraction and Drowsiness Research.

Driver inattention is a major contributor to road crashes. The emerging of new driver monitoring systems represents an opportunity for researchers to explore new data sources to understand driver inattention, even if the technology was not developed with this purpose in mind. This study is based on retrospective data obtained from two driver monitoring systems to study distraction and drowsiness risk factors. The data includes information about the trips performed by 330 drivers and corresponding distraction and drowsiness alerts emitted by the systems. The drivers' historical travel data allowed defining two groups with different mobility patterns (short-distance and long-distance drivers) through a cluster analysis. Then, the impacts of the driver's profile and trip characteristics (e.g., driving time, average speed, and breaking time and frequency) on inattention were analyzed using ordered probit models. The results show that long-distance drivers, typically associated with professionals, are less prone to distraction and drowsiness than short-distance drivers. The driving time increases the probability of inattention, while the breaking frequency is more important to mitigate inattention than the breaking time. Higher average speeds increase the inattention risk, being associated with road facilities featuring a monotonous driving environment.

The nonsense mutation MSH2 c.2152C>T shows a founder effect in Portuguese Lynch syndrome families.

The mutational spectrum of the MMR genes is highly heterogeneous, but specific mutations are observed at high frequencies in well-defined populations or ethnic groups, due to founder effects. The MSH2 mutation c.2152C>T, p.(Gln718*), has occasionally been described in Lynch families worldwide, including in Portuguese Lynch syndrome families. During genetic testing for Lynch syndrome at the Portuguese Oncology Institutes of Porto and Lisbon, this mutation was identified in 28 seemingly unrelated families. In order to evaluate if this alteration is a founder mutation, haplotype analysis using microsatellite and SNP markers flanking the MSH2 gene was performed in the 28 probands and 87 family members. Additionally, the geographic origin of these families was evaluated and the age of the mutation estimated. Twelve different haplotypes were phased for 13 out of the 28 families and shared a conserved region of ∼3.6 Mb. Based on the mutation and recombination events observed in the microsatellite haplotypes and assuming a generation time of 25 years, the age estimate for the MSH2 mutation was 273 ± 64 years. The geographic origins of these families were mostly from the Northern region of Portugal. Concluding, these results suggest that the MSH2 c.2152C>T alteration is a founder mutation in Portugal with a relatively recent origin. Furthermore, its high proportion indicates that screening for this mutation as a first step, together with the previously reported Portuguese founder mutations, may be cost-effective in genetic testing of Lynch syndrome suspects of Portuguese ancestry.

Saliva NMR metabolomics: Analytical issues in pediatric oral health research.

OBJECTIVES: Saliva metabolome is a promising diagnostic tool concerning oral and systemic diseases. We aimed at establishing a suitable protocol for saliva collection and gauging the relative impacts of gender, dentition stage, and caries on the saliva metabolome of a small children cohort. SUBJECTS AND METHODS: A nuclear magnetic resonance-based metabolomics cross-sectional study of children saliva (n = 38) compared the effects of: (a) stimulation and unstimulation conditions, and (b) collection through passive drool and using an absorbing device. Multivariate and univariate statistical analyses were applied to evaluate such effects and those related to gender, dentition stage and caries. RESULTS: No significant differences were found between unstimulated and stimulated saliva, and the former was used for subsequent studies. Swab collection induced significant changes in sample composition, indicating passive drool as preferential. The impacts of gender and dentition stage were not significant compared to that of caries, which induced variations in the levels of 21 metabolites. These comprised amino acids and monosaccharides observed for the first time to our knowledge regarding children caries, suggesting protein hydrolysis and deglycosylation. CONCLUSIONS: Unstimulated passive drool saliva metabolome may carry a caries signature.

A rare case series of mitral valve clefts diagnosed by 3D echocardiography and mini-review of the literature.

Mitral valve cleft is a rare entity. However, it must be recognized as a differential mechanism for mitral valve regurgitation. 3D transesophageal echocardiography plays an essential role in the evaluation of single and multiple mitral valve clefts, improving morphological and functional assessment of the valve, with potential implications on surgical planning. The authors present four rare cases of mitral valve cleft presenting during adulthood, followed by a mini-review about the role of 3D echocardiography, as well as its pitfalls, in the assessment of this complex congenital mitral valve disease.

Comparison of self-expanding and balloon-expandable transcatheter aortic valves morphology and association with paravalvular regurgitation: Evaluation using multidetector computed tomography.

OBJECTIVES: Compare final morphology of self-expanding and balloon-expandable prosthesis and association with paravalvular regurgitation (PVR). BACKGROUND: PVR after transcatheter aortic valve replacement (TAVR) remains a frequent complication. A better understanding of the prosthesis geometry may be important to improve selection of the best device for each case and possibly reduce the rates of PVR. METHODS: Retrospective study including patients consecutively submitted to transcatheter aortic valve replacement: August/2007-October/2016. Three months after the procedure a multidetector computed tomography (MDCT) was performed to assess prosthesis geometry: dimensions, eccentricity, and expansion. RESULTS: A total of 147 individuals were included (mean age of 78.8 ± 6.7 and 50.3% males), 57% treated with a self-expanding prosthesis. On the postprocedure MDCT, the self-expanding group had higher eccentricity index (15.0 vs. 7.1%, p < .001) and lower expansion (68.3 vs. 82.8%, p < .001). In that group, the volume of calcium of landing zone had a significant correlation with eccentricity index and under-expansion. Patients with ≥mild PVR presented higher eccentricity (12.6 vs. 7.9%, p < .001) and lower expansion (68 vs. 75%, p = .012). Eccentricity index and landing zone calcium volume were independent predictors of PVR. CONCLUSIONS: Self-expanding prosthesis have greater eccentricity and under-expansion. Calcium burden exerts more influence in the final morphology of that type of valve. Calcification and eccentricity are associated with the development of PVR. These factors should be considered in the selection of the most appropriate type of prosthesis for each scenario.