Investigation of microglial diversity in a LRRK2 G2019S mouse model of Parkinson's disease.

Microglia contribute to the outcomes of various pathological conditions including Parkinson's disease (PD). Microglia are heterogenous, with a variety of states recently identified in aging and neurodegenerative disease models. Here, we delved into the diversity of microglia in a preclinical PD model featuring the G2019S mutation in LRRK2, a known pathological mutation associated with PD. Specifically, we investigated the 'dark microglia' (DM) and the 'disease-associated microglia' (DAM) which present a selective enrichment of CLEC7A expression. In the dorsal striatum - a region affected by PD pathology - extensive ultrastructural features of cellular stress as well as reduced direct cellular contacts, were observed for microglia from old LRRK2 G2019S mice versus controls. In addition, DM were more prevalent while CLEC7A-positive microglia had extensive phagocytic ultrastructural characteristics in the LRRK2 G2019S mice. Furthermore, our findings revealed a higher proportion of DM in LRRK2 G2019S mice, and an increased number of CLEC7A-positive cells with age, exacerbated by the pathological mutation. These CLEC7A-positive cells exhibited a selective enrichment of ameboid morphology and tended to cluster in the affected animals. In summary, we provide novel insights into the occurrence and features of recently defined microglial states, CLEC7A-positive cells and DM, in the context of LRRK2 G2019S PD pathology.

Estimates of genetic parameters for rumination time, feed efficiency, and methane production traits in first-lactation Holstein cows.

The large-scale recording of traits such as feed efficiency (FE) and methane emissions (ME) for use in genetic improvement programs is complex, costly, and time-consuming. Therefore, heritable traits that can be continuously recorded in dairy herds and are correlated with FE and ME traits could provide useful information for genetic evaluation. Rumination time has been suggested to be associated with FE, methane production (MeP; ME in g/d), and production traits at the phenotypic level. Therefore, the objective of this study was to investigate the genetic relationships among rumination time (RT), FE, methane and production traits using 7,358 records from 656 first-lactation Holstein cows. The estimated heritabilities were moderate for RT (0.45 ± 0.14), MeP (0.36 ± 0.12), milk yield (0.40 ± 0.08), fat yield (0.29 ± 0.06), protein yield (0.32 ± 0.07), and energy-corrected milk (0.28 ± 0.07), but were low and nonsignificant for FE (0.15 ± 0.07), which was defined as the residual of the multiple linear regression of DMI on energy-corrected milk and metabolic body weight. A favorable negative genetic correlation was estimated between RT and MeP (-0.53 ± 0.24), whereas a positive favorable correlation was estimated between RT and energy-corrected milk (0.49 ± 0.11). The estimated genetic correlation of RT with FE (-0.01 ± 0.17) was not significantly different from zero but showed a trend of a low correlation with dry matter intake (0.21 ± 0.13). These results indicate that RT is genetically associated with MeP and milk production traits, but high standard errors indicate that further analyses should be conducted to verify these findings when more data for RT, MeP, and FE become available.

Photoanthropometric craniofacial parameters in individuals with osteogenesis imperfecta.

BACKGROUND: This study aimed to evaluate facial photoanthropometric parameters in patients with OI. MATERIAL AND METHODS: We selected 20 Brazilian patients diagnosed with OI treated at the Extension Service for Minors in Need of Specialized Treatment of the Dentistry Course at the Federal University of Ceará (Fortaleza, Brazil), of both sexes, without age restriction, and able to understand and sign the informed consent form (ICF). As a control group, 38 non-syndromic Brazilian individuals, categorized as ASA I, able to understand and sign the ICF, matched by sex, age, and Legan and Burstone facial profile were selected. The exclusion criteria were: previous orthodontic treatment, craniofacial trauma and/or surgery, and the presence of any other systemic diseases. Photoanthropometric analysis of the 18 facial parameters proposed by Stengel-Rutkowski et al. (1984), previously established in the literature for craniofacial syndromes, were conducted. A single examiner digitally performed all effective and angular measurements with the CorelDRAWX7® software. RESULTS: Horizontally shortened ears (p<0.001) but larger in height in relation to the face (p=0.012) were shown to be alterations belonging to individuals with OI. CONCLUSIONS: OI patients present distinct photoanthropometric parameters inherent in this condition.

Incidence of the tensor of the vastus intermedius: A cadaveric study.

INTRODUCTION: The quadriceps femoris muscle is present in the anterior region of the thigh and is classically described as a muscle with four heads: rectus femoris, vastus lateralis, vastus medialis, and vastus intermedius. A few years ago, a "fifth head" was described and named the tensor of the vastus intermedius (TVI). The TVI belly is in line with the belly of the vastus lateralis, and its aponeurosis imposes considerable tension on the vastus intermedius, medializing its action, to play a significant role in knee extension. OBJECTIVE: To perform a study of the TVI incidence in a Brazilian population and describe its variations. MATERIAL AND METHODS: We dissected lower limbs from cadavers previously fixed in 10% formaldehyde, belonging to the Laboratory of Anatomy of the Department of Morphology of the Biosciences Center of the Federal University of Rio Grande do Norte. RESULTS: Eighty-one lower limbs were analyzed with only 33 (40.74%) of them presenting TVI. All four types of TVI described by the literature were present in our sample with the following distribution: type 1 with 15.15%; type 2 with 9.1%; type 3 with 33.33%; type 4 with 42.42%. DISCUSSION: Although the literature points to the TVI as a normal belly of the quadriceps, making it a "quinticeps", our analysis points to the TVI as a variation and probably a matter of regionality. However, the presence of TVI is not a rare case and cannot be disregarded, which makes this study important for anatomists, physiotherapists, physicians, and surgeons.

Infection and disruption of placental multidrug resistance (MDR) transporters: Implications for fetal drug exposure.

P-glycoprotein (P-gp, encoded by the ABCB1 gene) and breast cancer resistance protein (BCRP/ABCG2) are efflux multidrug resistance (MDR) transporters localized at the syncytiotrophoblast barrier of the placenta and protect the conceptus from drug and toxin exposure throughout pregnancy. Infection is an important modulator of MDR expression and function. This review comprehensively examines the effect of infection on the MDR transporters, P-gp and BCRP in the placenta. Infection PAMPs such as bacterial lipopolysaccharide (LPS) and viral polyinosinic-polycytidylic acid (poly I:C) and single-stranded (ss)RNA, as well as infection with Zika virus (ZIKV), Plasmodium berghei ANKA (modeling malaria in pregnancy - MiP) and polymicrobial infection of intrauterine tissues (chorioamnionitis) all modulate placental P-gp and BCRP at the levels of mRNA, protein and or function; with specific responses varying according to gestational age, trophoblast type and species (human vs. mice). Furthermore, we describe the expression and localization profile of Toll-like receptor (TLR) proteins of the innate immune system at the maternal-fetal interface, aiming to better understand how infective agents modulate placental MDR. We also highlight important gaps in the field and propose future research directions. We conclude that alterations in placental MDR expression and function induced by infective agents may not only alter the intrauterine biodistribution of important MDR substrates such as drugs, toxins, hormones, cytokines, chemokines and waste metabolites, but also impact normal placentation and adversely affect pregnancy outcome and maternal/neonatal health.

The skin redoxome.

Redoxome is the network of redox reactions and redox active species (ReAS) that affect the homeostasis of cells and tissues. Due to the intense and constant interaction with external agents, the human skin has a robust redox signalling framework with specific pathways and magnitudes. The establishment of the skin redoxome concept is key to expanding knowledge of skin disorders and establishing better strategies for their prevention and treatment. This review starts with its definition and progress to propose how the master redox regulators are maintained and activated in the different conditions experienced by the skin and how the lack of redox regulation is involved in the accumulation of several oxidation end products that are correlated with various skin disorders.

Is there a role in the central nervous system development for using corticosteroids to treat meningomyelocele and hydrocephalus?

INTRODUCTION: Myelomeningocele (MMC) is the most frequent neural tube defect and is frequently associated (around 80% of cases) with hydrocephalus (HC). Both diseases can have severe clinical consequences, insomuch as they require surgical treatment whose complications are not negligible, either when performed in utero or after birth. Therefore, clinical therapies that could have an impact on the incidence and progression of MMC and HC would be certainly valuable; however, this is not the current picture, and there are no effective pharmacological treatments for such patients to this day. AIM AND METHODS: Therefore, knowing that an inflammatory process comes associated with these disorders, mostly due to nervous tissue distension, the present article aimed at reviewing the role of corticosteroids in reducing inflammation and thus improving the outcome of patients with HC and MMC, considering the well-established anti-inflammatory effects of CS. RESULTS: The systematic review performed herein has found varying results regarding the role of steroids (even though a positive trend was observed) on the treatment and prevention of hydrocephalus, whereas for MMC. CONCLUSION: There are many reports demonstrating beneficial effects of CS therapy, from a clinical and histopathological point of view.

Microbial dynamics associated with the decomposition of coconut and maize residues in a microcosm experiment with tropical soils under two nitrogen fertilization levels.

AIMS: The microbial dynamics associated with the decomposition of maize (Zea mays) and coconut (Cocos nucifera) residues were investigated to assess the feasibility of using them as mulch in tropical soils. METHODS AND RESULTS: Phospholipid fatty-acid (PLFA) profiling, microbial biomass (MB-C), basal respiration, C-cycle enzyme activities and inorganic N dynamics were monitored in a microcosm experiment incubating soil samples with plant residues for 425 days. Maize stover (MS) showed a higher decomposition, respiration rate, MB-C, enzymes activities and shift in microbial community structure than coconut husk (CH), which was barely changed. In MS, the lower N level increased C losses and decreased N mineralization compared to the higher N level. CONCLUSIONS: Maize stover is suitable for mulching and has a high potential of increasing soil quality if the proper N fertilization level is used, avoiding excessive C mineralization and N immobilization. Coconut husk decomposition was mostly impaired, indicating that a pre-processing is necessary to improve the benefits of this residue. SIGNIFICANCE AND IMPACT OF THE STUDY: Tropical soils are prone to degradation. Mulching can promote soil conservation, but depends on residue type and soil chemistry. Our study showed that MS managed under the recommended N fertilization level is suitable for mulching while CH is highly inaccessible for microbial degradation.

Probiotic properties of yeasts isolated from Brazilian fermented table olives.

AIMS: To investigate the probiotic potential of yeasts isolated from naturally fermented Brazilian table olives. METHODS AND RESULTS: Eighteen yeast strains were tested in terms of: safety; survival of gastrointestinal and digestion conditions; antimicrobial activity; cellular hydrophobicity; autoaggregation ability and adhesion to epithelial cells; coaggregation and inhibition of pathogenic bacteria adhesion. Six yeasts showed favourable results for all probiotic attributes: Saccharomyces cerevisiae CCMA 1746, Pichia guilliermondii CCMA 1753, Candida orthopsilosis CCMA 1748, Candida tropicalis CCMA 1751, Meyerozyma caribbica CCMA 1758 and Debaryomyces hansenii CCMA 1761. These yeasts demonstrated resistance to 37°C, pH 2·0 and bile salts, and survived in vitro digestion (≥106  CFU per ml). Furthermore, the yeasts exhibited a hydrophobic cell surface (42·5-92·2%), autoaggregation capacity (41·0-91·0%) and adhesion to Caco-2 (62·0-82·8%) and HT-29 (57·6-87·3%) epithelial cell lines. Also, the strains showed antimicrobial activity against Salmonella Enteritidis as well as the ability to coaggregate and reduce the adhesion of this pathogen to intestinal cells. CONCLUSIONS: Autochthonous yeasts from naturally fermented Brazilian table olives have probiotic properties, with potential for development of new probiotic food products. SIGNIFICANCE AND IMPACT OF STUDY: These data are important and contribute to the knowledge of new potential probiotic yeasts capable of surviving gastrointestinal tract conditions and inhibiting pathogenic bacteria.

Management of type 2 diabetes using non-insulin glucose-lowering therapies: a critical appraisal of clinical practice guidelines with the AGREE II instrument.

AIM: Type 2 diabetes is a major global epidemic affecting over 400 million people worldwide. The objective of this systematic review was to provide an overview of recommendations from clinical practice guidelines (guidelines) addressing non-insulin based pharmacological management of among non-pregnant adults in an outpatient setting, and critically appraise their methodological development. METHODS: We systematically searched MEDLINE and Embase databases, for relevant guidelines using the Ovid interface. We scanned the bibliographies of all eligible guidelines for additional relevant citations. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility and appraised the reporting quality of guidelines using the Advancing Guideline Development, Reporting and Evaluation in Health Care instrument II (AGREE II) instrument. RESULTS: Our search yielded 11264 unique citations, of which 124 were retrieved for full-text review; 17 guidelines proved eligible. The highest scoring AGREE domain was 'clarity of presentation' (66%; range 7-92%), followed by 'scope and purpose' (58%; range 25-92%), 'editorial independence' (55%; range 0-91%), 'stakeholder involvement' (45%; range 11-90%) and 'rigour of development' (43%; range 4-92%). The poorest domain was 'applicability' (37%; range 6-84%). The guidelines authored by the World Health Organization group achieved the highest AGREE overall score. CONCLUSIONS: Most of the guidelines provided recommendations with a local jurisdictional focus and showed significant variation in the quality. Nevertheless, only a small number of those scored well overall.

Energy-dependent effect trial of photobiomodulation on blood pressure in hypertensive rats.

The main purpose of this work was to construct an energy-dependent response curve of photobiomodulation on arterial pressure in hypertension animal model. To reach this objective, we have used a two-kidney one clip (2K-1C) rat model. Animals received acute laser light irradiation (660 nm) on abdominal region using different energy (0.6, 1.8, 3.6, 7.2, 13.8, 28.2, 55.8, and 111.6 J), the direct arterial pressure was measured by femoral cannulation, and systolic arterial pressure (SAP), diastolic arterial pressure (DAP), heart rate (HR), and time of effect were obtained. Our results indicated that 660 nm laser light presents an energy-dependent hypotensive effect, and 28.2 J energy irradiation reached the maximum hypotensive effect, inducing a decreased SAP, DAP, and HR (decrease in SAP: - 19.23 ± 1.82 mmHg, n = 11; DAP: - 9.57 ± 2.23 mmHg, n = 11; HR: - 39.15 ± 5.10 bpm, n = 11; and time of hypotensive effect: 3068.00 ± 719.00 s, n = 11). The higher energy irradiation evaluated (111.6 J) did not induce a hypotensive effect and induced an increase in HR (21.69 ± 7.89 bpm, n = 7). Taken together, our results indicate that red laser energy irradiation from 7.2 to 55.8 J is the effective therapeutic window to reduce SAP, DAP, MAP, and HR and induce a long-lasting hypotensive effect in rats, with effect loss at higher energy irradiation (111.6 J).

Associations between anthropometric indicators in early life and low-grade inflammation, insulin resistance and lipid profile in adolescence.

BACKGROUND AND AIMS: The long-term relations between excessive adiposity in early childhood and unfavourable cardiometabolic profiles in later ages are not yet completely understood. We aimed to assess the associations between birth weight (BW) and BMI from 6 months to 6 years of age, with biomarkers indicative of low-grade inflammation, insulin resistance and lipid profiles in adolescence. METHODS AND RESULTS: Retrospective school-based study with 415 Portuguese adolescents (220 girls), mean age of 14.08 ± 1.6 years old. Anthropometric data from birth to 6 years old was extracted from individual child health book records. Actual weight and height were measured and BMI calculated. Participants were classified at each time point as normal weight or overweight according to WHO reference values. Biomarkers were obtained from venous blood samples. Linear regressions were used to explore the associations between the biomarkers and early life anthropometric indicators. From 2 years onwards, BMI associated positively with the inflammatory score and HOMA-IR in adolescence. Children who were overweight/obese from 2 to 6 years of age presented significantly higher inflammatory score and HOMA-IR later in adolescence. TC/HDL ratio was also positively associated with BMI from the age of 5 years onwards. The associations between BMI and cardiometabolic outcomes remained positive in adolescence, with overweight adolescents presenting a higher inflammatory score, HOMA-IR and TC/HDL than normal weight adolescents. CONCLUSION: A high BMI from an early age was consistently associated with worse inflammatory and lipid profiles and insulin resistance in adolescence. No associations were found between BW and the same studied outcomes.

Biofilm contamination of high-touched surfaces in intensive care units: epidemiology and potential impacts.

The aim of this study was to determine the epidemiology (location, microbial load, microbiome, presence/absence of biofilm and pathogens, including ESKAPE-Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species, and antimicrobial susceptibility profiles) of the bacterial contamination on intensive care units (ICUs) surfaces. Fifty-seven high-touched surfaces were collected from adult, paediatric and neonatal ICUs from two large public Brazilian hospitals from central and north regions. Samples (c. 4 cm2 ) were subjected to culture (qualitative), qPCR targeting 16s rRNA gene (microbial load-bacteria per cm2 ), 16s rRNA amplicon sequencing (microbiome analysis) and scanning electron (SEM) or confocal laser scanning microscopy (CLSM) (biofilm presence). Multidrug resistant organisms (MROs) were detected using specific chromogenic agar. The average bacterial load was 1·32 × 104 bacteria per cm2 , container for newborn feeding bottles, stretcher mattress, humidicrib mattress filling and computer keyboards presented the higher bioburden. However, only 45·6% (26/57) were culture-positive, including 4/26 with MROs. ESKAPE organisms were detected in 51·8% of the samples subjected to next-generation sequencing. Viability staining and CLSM demonstrated live bacteria on 76·7% of culture-negative samples. Biofilm was present on all surfaces subjected to microscopy (n = 56), demonstrating that current cleaning practices are suboptimal and reinforcing that MROs are incorporated into hospital surfaces biofilm. SIGNIFICANCE AND IMPACT OF THE STUDY: Contamination of healthcare facilities surfaces has been shown to play a major role in transmission of pathogens. The findings of this study show that dry surface biofilms are widespread and can incorporate pathogens and multidrug-resistant organisms (MROs). Biofilms on highly touched surfaces pose a risk to patients, as dry surface biofilms persist for long period and micro-organisms within biofilm have been shown to be transmitted. This study also provides a better understanding of microbial populations in hospital environments, reinforcing that pathogens and MROs are found incorporated into biofilm, which impacts the difficulty in cleaning/disinfection.

Evaluation of the effects of quercetin on brain lesions secondary to experimental hydrocephalus in rats.

INTRODUCTION: Hydrocephaly is a disease that affects not only the dynamics of the cerebrospinal fluid, but also other structures of the central nervous system. Although shunt is effective in reducing ventriculomegaly, many neurological damages are not reversed with surgery. Several studies demonstrate that oxidative stress is involved in the genesis of hydrocephalus lesions. OBJECTIVE: Evaluate the neuroprotective response of quercetin in hydrocephalus. MATERIALS AND METHODS: Male newborns rats were used, which received the 15% kaolin injection in the cisterna magna for induction of hydrocephalus. They were divided into control group (C), untreated hydrocephalic (HN), shunted hydrocephalic (HD), hydrocephalic treated with distilled water (HA), hydrocephalic treated with distilled water and shunt (HDA), hydrocephalic treated with quercetin peritoneal (HQp), hydrocephalic treated with quercetin peritoneal and shunt (HDQp), hydrocephalic treated with quercetin by gavage (HQg), and hydrocephalus treated with quercetin by gavage and shunt (HDQg). RESULTS: Quercetin significantly improved the immunohistochemical markers, mainly caspase and GFAP. There were no significant changes in clinical/behavioral assessment. The use of isolated quercetin does not alter the volume and ventricular size, and the realization of ventriculo-subcutaneous shunt in newborn rats with hydrocephalus presents a high morbi-mortality. CONCLUSION: The use of quercetin shows laboratory improvement of the effects of glial lesion and corpus callosum fibers and is therefore not justified by the use of the routine substance as neuroprotective.

Fruit, vegetable consumption and blood pressure in healthy adolescents: A longitudinal analysis from the LabMed study.

BACKGROUND AND AIMS: The associations between fruit and vegetable consumption and high blood pressure among adults are well studied. Nonetheless, data on the influence of a low consumption of fruit and vegetables on cardiovascular disease risk, particularly blood pressure, among healthy adolescents are scarce. Therefore, we aim to analyse the associations between fruit and/or vegetable intake and blood pressure over a two-year period in healthy adolescents. METHODS AND RESULTS: As part of a cohort, 606 adolescents from the LabMed Physical Activity study were evaluated in 2011 (baseline) and 2013 (follow-up). Blood pressure was measured according to standardized procedures and fruit and vegetable consumption was assessed with a food frequency questionnaire. Anthropometric variables, socioeconomic status, pubertal stage and lifestyle determinants were gathered and used as confounders. Prospective associations between fruit and/or vegetable intake and blood pressure were examined using generalized linear models. Girls who consumed more fruit at baseline had a significant decrease in diastolic blood pressure at follow-up [unstandardized beta: -0.005 mmHg (95%CI: -0.01; -0.0002) (p = 0.038)]. CONCLUSION: In apparently healthy adolescents, fruit intake may already start to have an effect in blood pressure. Girls who consumed more fruit exhibited lower levels of diastolic blood pressure.

Longitudinal association between ideal cardiovascular health status and muscular fitness in adolescents: The LabMed Physical Activity Study.

BACKGROUND AND AIMS: Muscular fitness is an emerging predictor for cardiovascular disease mortality. The ideal cardiovascular health metrics has been inversely related to a subsequent cardiometabolic health in adulthood. However, evidence regarding muscular fitness and ideal cardiovascular health in adolescents is scarce. This study aimed to examine the longitudinal association between ideal cardiovascular health index and muscular fitness. METHODS AND RESULTS: This study cohort consisted of 331 adolescents (183 girls) from the LabMed Physical Activity Study who were followed from 2011 to 2013. Ideal cardiovascular health, as defined by the American Heart Association, was determined as meeting ideal health factors (total cholesterol, blood pressure, and glucose) and behaviors (smoking status, body mass index, physical activity, and diet). Handgrip strength and standing long jump tests assessed muscular fitness and were transformed into standardized values according to age and sex. ANCOVA showed a significant association between the accumulation of ideal cardiovascular health metrics at baseline and muscular fitness indices at follow-up (F(4, 322) = 2.280, p = 0.04). In addition, the higher the number of ideal cardiovascular health metrics accumulated, the higher the likelihood of having a high muscular fitness over a two-year period (p for trend = 0.01), after adjustments for age, sex, pubertal stage and socioeconomic status and muscular fitness at baseline. CONCLUSION: The ideal cardiovascular health status during adolescence was associated with high muscular fitness levels over a two-year period.

Analysis of a Minimally Invasive Intracranial Pressure Signals During Infusion at the Subarachnoid Spinal Space of Pigs.

OBJECTIVE: We developed a new minimally invasive method for intracranial pressure monitoring (ICPMI). The objective of this project is to verify the similarities between the ICPMI and the invasive method (ICPInv), for different components of the intracranial pressure signal-namely, the mean value (trend) as well as its pulsatile component. MATERIALS AND METHODS: A 9 kg anesthetized pig was used for simultaneous ICP monitoring with both methods. ICP was increased by performing ten infusions of 6 ml 0.9% saline into the spinal subarachnoid space, using a catheter implanted in the lumbar region. For correlation analysis, the signals were decomposed into two components-trend and pulsatile signals. Pearson correlation coefficient was calculated between ICPInv and ICPMI. RESULTS: During the infusions, the correlation between the pulsatile components of the signals was above 0.5 for most of the time. The signal trends showed a good agreement (correlation above 0.5) for most of the time during infusions. CONCLUSIONS: The ICPMI signal trends showed a good linear agreement with the signal obtained invasively. Based on the waveform analysis of the pulsatile component of ICP, our results indicate the possibility of using the minimally invasive method for assessing the neuroclinical state of the patient.

Effect of Zirconia Pigmentation on Translucency.

PURPOSE: the aim of this study was to investigate the effect of shading on translucency and mean grain size of three Zirconia systems (Lava Frame, Ice Zirkon Translucent and Prettau Zirkon). MATERIALS AND METHODS: specimens pigmented in A1, A4 and a non-pigmented specimen was evaluated with Scanning Electron Microscopy and spectrophotometery. RESULTS: the transmittance ranged between 0.18 and 0.52, in Ice Zirkon Translucent A4 and Prettau Zircon non-pigmented, respectively. The pigmentation A1 and A4 significantly reduced the light transmission in all the systems evaluated (p⟨0.05), with the exception of Lava A1. The light transmittance of each ceramic system is different from each other in the three pigmentations, except for the Prettau Zirkon A1, which did not show a significant difference compared with Lava A1 (p⟩0.05). The mean grain size increased with pigmentation. The mean grain size ranged between 0.43 µm, for Prettau Zirkon non-pigmented, and 0.82 µm for Prettau Zirkon A4. CONCLUSION: Light transmission and mean grain size was affected by pigmentation of dental zirconia ceramics.

Melaleuca alternifolia nanoparticles against Candida species biofilms.

Candida infection is an important cause of morbidity and mortality on immunosuppressed patients. This growing trend has been associated with resistance to the antimicrobial therapy and the ability of microorganism to form biofilms. TTO oil is used as antimicrobial which shows antibiofilm activity against Candida species. However, it presents problems due to its poor solubility and high volatility. The present study aimed to evaluate in vitro antibiofilm activity of TTO nanoparticles against many Candida species. It was performed the characterization of the oil and nanoparticles. The levels of exopolysaccharides, proteins, and the biomass of biofilms were measured. The chromatographic profile demonstrated that the TTO oil is in accordance with ISO 4730 with major constituents of 41.9% Terpinen-4-ol, 20.1% of γ-Terpinene, 9,8% of α-Terpinene, and 6,0% of 1,8-Cineole. The TTO nanoparticles showed pH of 6.3, mean diameter of 158.2 ± 2 nm, polydispersion index of 0.213 ± 0.017, and zeta potential of -8.69 ± 0.80 mV. The addition of TTO and its nanoparticles represented a significant reduction of biofilm formed by all Candida species, as well as a reduction of proteins and exopolysaccharides levels. It was possible to visualize the reduction of biofilm in presence of TTO nanoparticles by Calcofluor White method.

A2A adenosine receptor deletion is protective in a mouse model of Tauopathy.

Consumption of caffeine, a non-selective adenosine A2A receptor (A2AR) antagonist, reduces the risk of developing Alzheimer's disease (AD) in humans and mitigates both amyloid and Tau burden in transgenic mouse models. However, the impact of selective A2AR blockade on the progressive development of AD-related lesions and associated memory impairments has not been investigated. In the present study, we removed the gene encoding A2AR from THY-Tau22 mice and analysed the subsequent effects on both pathological (Tau phosphorylation and aggregation, neuro-inflammation) and functional impairments (spatial learning and memory, hippocampal plasticity, neurotransmitter profile). We found that deleting A2ARs protect from Tau pathology-induced deficits in terms of spatial memory and hippocampal long-term depression. These effects were concomitant with a normalization of the hippocampal glutamate/gamma-amino butyric acid ratio, together with a global reduction in neuro-inflammatory markers and a decrease in Tau hyperphosphorylation. Additionally, oral therapy using a specific A2AR antagonist (MSX-3) significantly improved memory and reduced Tau hyperphosphorylation in THY-Tau22 mice. By showing that A2AR genetic or pharmacological blockade improves the pathological phenotype in a Tau transgenic mouse model, the present data highlight A2A receptors as important molecular targets to consider against AD and Tauopathies.