Paradoxical activation of oncogenic signaling as a cancer treatment strategy.

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress-response programs that counteract the inherent toxicity of such aberrant signaling. While inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of Protein Phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor suppressive resistance.

Waist circumference is independently associated with liver steatosis and fibrosis in LMNA-related and unrelated Familial Partial Lipodystrophy women.

BACKGROUND: Lipodystrophies are a heterogeneous group of diseases characterized by the selective loss of subcutaneous adipose tissue and ectopic fat deposition in different organs, including the liver. This study aimed to determine the frequencies of liver steatosis (LS) and liver fibrosis (LF) in a sample of individuals with LMNA-related and unrelated Familial Partial Lipodystrophy. METHODS: This cross-sectional study included 17 women with LMNA-related FPLD and 15 women with unrelated FPLD. LS and LF were assessed using transient elastography (TE) with FibroScan®. Anthropometric and biochemical variables were included in a multiple linear regression analysis to identify the variables that were independently related to liver disease. RESULTS: Regarding the presence of LF, 22 (68.2%) women were classified as having non-significant fibrosis, and 10 (31.8%) were classified as having significant or severe fibrosis. Regarding LS, only six women (20.7%) were classified as having an absence of steatosis, and 23 (79.3%) had mild to severe steatosis. After multiple linear regression, waist circumference (but not age, body mass index, or waist-to-hip ratio) was found to be independently related to LS and LF. Among the biochemical variables, only triglyceride levels were independently related to LS but not LF. CONCLUSIONS: In women with FPLD, visceral fat accumulation appears to be the most important determinant of liver disease, including LF, rather than fat scarcity in the lower limbs.

Teeth Damage during General Anesthesia.

INTRODUCTION: Dental injuries during anesthesia, especially when advanced airway management is required, represent a legal problem. Factors such as poor dental condition and excessive pressure during intubation contribute to dental damage. The maxillary central incisors are commonly affected. OBJECTIVE: The objective of this review is to know the incidence of dental injuries in adults undergoing anesthesia that requires airway management. MATERIALS AND METHODS: The search was performed in MEDLINE (through Pubmed), ClinicalTrials.gov, Scopus, LILACS (through the Virtual Health Library Regional Portal), and SciELO for all available literature on the subject up to December 2022. Inclusion criteria involved articles that studied patients aged 18 years or older who underwent general anesthesia requiring airway management with tracheal intubation or insertion of a laryngeal mask airway. RESULTS: Of all the articles, nine report dental injury associated with the type of airway management. Only one article does not have dental injury. DISCUSSION: This study addresses dental injuries related to tracheal intubation during general anesthesia. Although techniques are used to prevent them, these injuries still occur. Laryngoscopy, especially with support on the upper central incisors, can cause damage to the teeth. CONCLUSIONS: It is important that the anesthesiologist is aware of dental trauma and that orotracheal intubation or the placement of the laryngeal mask airway is performed systematically and rigorously, always considering the patient's dentition to choose the best approach in each specific situation.

Neourethra creation using autologous vascularized intestinal graft in cats.

The objective of this study was to assess the application of a urethrostomy technique that utilizes an autologous vascularized intestinal graft as a "neourethra" and to analyze its short- and long-term feasibilities. Six cats with urethral rupture and 8 cats with urethral stricture and a history of urethrostomy were included. The inclusion criteria were the indication for urethroplasty and limited urethral length for perineal urethrostomy. A segment of intestine was prepared as a graft for urethral repair. The diameter of the aboral end was adjusted to facilitate anastomosis with the urethra or neck of the urinary bladder. An ostomy was created in the prepubic region using the oral end. The postoperative follow-up period was at least 1 y. Restoration of urinary flow was successful in all cases immediately after surgery. During postoperative follow-up, minimal complications were observed, with urinary incontinence being one of the most frequent, occurring in 28.5% (4/14) of the cases. Urine culture, carried out at different times during the follow-up period, was positive in 72.7% (8/11) of the cats. The autologous graft from the vascularized intestinal segment was an appropriate urethral substitute and this urethroplasty technique therefore proved to be feasible in cats. The postoperative complications observed were not exclusive to this technique and generally could either be corrected or tolerated. Periodic clinical follow-up examinations are recommended. This procedure allows the reestablishment of urinary flow and should be considered a favorable option, particularly when there is insufficient urethral tissue to allow repair using conventional techniques.

L'objectif de cette étude était d'évaluer l'application d'une technique d'urétrostomie qui utilise une greffe intestinale vascularisée autologue comme « néo-urètre ¼ et d'analyser ses faisabilités à court et à long terme. Six chats avec rupture urétrale et huit chats avec rétrécissement urétral et antécédents d'urétrostomie ont été inclus. Les critères d'inclusion étaient l'indication d'urétroplastie et la longueur urétrale limitée pour l'urétrostomie périnéale. Un segment d'intestin a été préparé comme greffon pour la réparation urétrale. Le diamètre de l'extrémité aborale était ajusté pour faciliter l'anastomose avec l'urètre ou le col de la vessie. Une stomie a été créée dans la région prépubienne en utilisant l'extrémité orale. La période de suivi postopératoire était d'au moins 1 an. La restauration du flux urinaire a réussi dans tous les cas immédiatement après la chirurgie. Au cours du suivi postopératoire, des complications minimes ont été observées, l'incontinence urinaire étant l'une des plus fréquentes, survenant dans 28,5 % (4/14) des cas. La culture urinaire, réalisée à différents moments de la période de suivi, était positive chez 72,7 % (8/11) des chats. La greffe autologue du segment intestinal vascularisé était un substitut urétral approprié et cette technique d'urétroplastie s'est donc avérée réalisable chez le chat. Les complications postopératoires observées n'étaient pas exclusives à cette technique et pouvaient généralement être soit corrigées soit tolérées. Des examens de suivi clinique périodiques sont recommandés. Cette procédure permet le rétablissement du flux urinaire et doit être considérée comme une option favorable, en particulier lorsque le tissu urétral est insuffisant pour permettre une réparation à l'aide de techniques conventionnelles.(Traduit par Docteur Serge Messier).

Drivers of variability in Blue Carbon stocks and burial rates across European estuarine habitats.

The implementation of climate change mitigation strategies based on the conservation and restoration of Blue Carbon ecosystems requires a deep understanding of the magnitude and variability in organic carbon (Corg) storage across and within these ecosystems. This study explored the variability in soil Corg stocks and burial rates across and within intertidal estuarine habitats of the Atlantic European coast and its relation to biotic and abiotic drivers. A total of 136 soil cores were collected across saltmarshes located at different tidal zones (high marsh, N = 45; low marsh, N = 30), seagrass meadows (N = 17) and tidal flats (N = 44), and from the inner to the outer sections of five estuaries characterized by different basin land uses. Soil Corg stocks were higher in high-marsh communities (65 ± 3 Mg ha-1) than in low-marsh communities (38 ± 3 Mg ha-1), seagrass meadows (40 ± 5 Mg ha-1) and unvegetated tidal flats (46 ± 3 Mg ha-1) whereas Corg burial rates also tended to be higher in high marshes (62 ± 13 g m-2 y-1) compared to low marshes (43 ± 15 g m-2 y-1) and tidal flats (35 ± 9 g m-2 y-1). Soil Corg stocks and burial rates decreased from inner to outer estuarine sections in most estuaries reflecting the decrease in the river influence towards the estuary mouth. Higher soil Corg stocks were related to higher content of silt and clay and higher proportion of forest and natural land within the river basin, pointing at new opportunities for protecting coastal natural carbon sinks based on the conservation and restoration of upland ecosystems. Our study contributes to the global inventory of Blue Carbon by adding data from unexplored regions and habitats in Europe, and by identifying drivers of variability across and within estuaries.

Anomalous Nernst Effect in Flexible Co-Based Amorphous Ribbons.

Fe3Co67Cr3Si15B12 ribbons with a high degree of flexibility and excellent corrosion stability were produced by rapid quenching technique. Their structural, magnetic, and thermomagnetic (Anomalous Nernst Effect) properties were studied both in an as-quenched (NR) state and after stress annealing during 1 h at the temperature of 350 °C and a specific load of 230 MPa (AR). X-ray diffraction was used to verify the structural characteristics of our ribbons. Static magnetic properties were explored by inductive technique and vibrating sample magnetometry. The thermomagnetic curves investigated through the Anomalous Nernst Effect are consistent with the obtained magnetization results, presenting a linear response in the thermomagnetic signal, an interesting feature for sensor applications. Additionally, Anomalous Nernst Effect coefficient SANE values of 2.66µV/K and 1.93µV/K were estimated for the as-quenched and annealed ribbons, respectively. The interplay of the low magnetostrictive properties, soft magnetic behavior, linearity of the thermomagnetic response, and flexibility of these ribbons place them as promising systems to probe curved surfaces and propose multifunctional devices, including magnetic field-specialized sensors.

The use of an endoscopic endonasal approach for a secondary intraorbital meningioma: illustrative case.

BACKGROUND: Meningiomas are the most frequent primary tumors in the central nervous system (CNS), but intraorbital location is uncommon and accounts for only 0.2% to 4% of all CNS meningiomas. Lesions in this compartment could be classified as primary, secondary, or ectopic. The close relationship with the optic nerve sheath is a landmark to identify the tumor as primary, whereas secondary tumors commonly come from an extension of an intracranial meningioma, and ectopic meningioma is a concept not yet completely established. OBSERVATIONS: The authors present a rare case of a secondary intraorbital meningioma operated through an endoscopic endonasal approach. Secondary meningiomas at the medial orbit are very uncommon, given their more common superior and lateral location as an extension of sphenoid meningiomas. The endoscopic endonasal route provides direct access to the medial orbit. The authors present an illustrative case of a meningioma located at the medial orbit and resected through an endoscopic endonasal approach that provided excellent visualization and anatomical exposure. Additionally, the authors review the concept and possible similarities between secondary and ectopic intraorbital meningiomas. LESSONS: An endoscopic endonasal approach should be considered as a feasible treatment option for intraorbital meningiomas, especially if they are in the medial orbital wall.

Identifying mutant-specific multi-drug combinations using comparative network reconstruction.

Targeted inhibition of aberrant signaling is an important treatment strategy in cancer, but responses are often short-lived. Multi-drug combinations have the potential to mitigate this, but to avoid toxicity such combinations must be selective and given at low dosages. Here, we present a pipeline to identify promising multi-drug combinations. We perturbed an isogenic PI3K mutant and wild-type cell line pair with a limited set of drugs and recorded their signaling state and cell viability. We then reconstructed their signaling networks and mapped the signaling response to changes in cell viability. The resulting models, which allowed us to predict the effect of unseen combinations, indicated that no combination selectively reduces the viability of the PI3K mutant cells. However, we were able to validate 25 of the 30 combinations that we predicted to be anti-selective. Our pipeline enables efficient prioritization of multi-drug combinations from the enormous search space of possible combinations.

A systematic review on neutrophils interactions with titanium and zirconia surfaces: Evidence from in vitro studies.

OBJECTIVES: This systematic review aimed to assess in vitro studies that evaluated neutrophil interactions with different roughness levels in titanium and zirconia implant surfaces. MATERIAL AND METHODS: An electronic search for literature was conducted on PubMed, Embase, Scopus, and Web of Science and a total of 14 studies were included. Neutrophil responses were assessed based on adhesion, cell number, surface coverage, cell structure, cytokine secretion, reactive oxygen species (ROS) production, neutrophil activation, receptor expression, and neutrophil extracellular traps (NETs) release. The method of assessing the risk of bias was done using the toxicological data reliability assessment tool (TOXRTOOL). RESULTS: Ten studies have identified a significant increase in neutrophil functions, such as surface coverage, cell adhesion, ROS production, and NETs released when interacting with rough titanium surfaces. Moreover, neutrophil interaction with rough-hydrophilic surfaces seems to produce less proinflammatory cytokines and ROS when compared to naive smooth and rough titanium surfaces. Regarding membrane receptor expression, two studies have reported that the FcγIII receptor (CD16) is responsible for initial neutrophil adhesion to hydrophilic titanium surfaces. Only one study compared neutrophil interaction with titanium alloy and zirconia toughened alumina surfaces and reported no significant differences in neutrophil cell count, activation, receptor expression, and death. CONCLUSIONS: There are not enough studies to conclude neutrophil interactions with titanium and zirconia surfaces. However, different topographic modifications such as roughness and hydrophilicity might influence neutrophil interactions with titanium implant surfaces.

Clinicoepidemiological profile and risk factors associated with mortality in traumatized cats admitted to a veterinary teaching hospital in Brazil.

OBJECTIVES: The aim of this study was to evaluate possible risk factors for death in traumatized cats based on the clinicoepidemiological profile, the Animal Trauma Triage (ATT) scale score and the Modified Glasgow Coma Scale (MGCS) score at the time of presentation to the hospital. METHODS: This was a cross-sectional study involving cats admitted to the emergency sector (ES) and the surgical clinic sector (SCS) of a veterinary teaching hospital (VTH) in northeastern Brazil over a 12-month period (2018-2019). Probable risk factors associated with non-survival after trauma were analyzed by calculating the prevalence ratio. The prediction of non-survival was evaluated by analyzing the receiver operating characteristic (ROC) curve employing the ATT scale score, MGCS score and rectal temperature. RESULTS: In 1 year, 89 traumatized cats were admitted to the VTH, of which 90% (n = 80) were young, 54% (n = 48) were male, 79% (n = 70) were intact, 59% (n = 53) were indoor cats and 92% (n = 82) were considered as mixed breed. Blunt trauma was the most prevalent cause of injuries, reported in 76% (n = 68) of the cats. Accidents involving falls (30%; n = 27) that affected the pelvic limbs (50.6%) were the most commonly reported. The prevalence of death among cats admitted to the ES was 9.44 times higher than that of animals treated at the SCS. Trauma as result of being run over and chest trauma were associated with a higher probability of death. Most of the animals that died had a lower rectal temperature than those that survived. The ATT scale score, MGCS score and rectal temperature were predictive of mortality. CONCLUSIONS AND RELEVANCE: Rectal temperature, ATT scale score and MGCS score were effective predictors of an unfavorable prognosis and point to the need for emergency procedures. Hypothermia, being run over and chest trauma were associated with a higher risk of mortality. Our findings highlight the importance of prompt and effective care for these conditions.

Impact of chronic gingivitis management on the cytokine and anti-PPAD expressions in juvenile systemic lupus erythematosus: A six-month follow-up.

OBJECTIVE: To evaluate how chronic gingivitis treatment impacts the oral and circulating cytokine expressions after six-month follow-up in patients with juvenile systemic lupus erythematosus (jSLE) and also to evaluate the circulating expression of anti-Porphyromonas gingivalis peptidylarginine deiminase antibodies (anti-PPAD) before and after treatment. BACKGROUND: Juvenile systemic lupus erythematosus patients present a worse periodontal condition associated with higher gingival crevicular fluid (GCF) levels of interleukin (IL)-1ß, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon-γ and monocyte chemoattractant protein (MCP)-1. MATERIALS AND METHODS: Twenty-one adolescents with jSLE (mean age: 16.2 ± 1.5 years) were recruited. Participants were rheumatologically and periodontally examined. All individuals were clinically diagnosed with gingival inflammation. Chronic gingivitis treatment consisted of supragingival scaling, prophylaxis and oral hygiene instructions. The cytokine levels were determined by bead-based multiplex assays and the anti-PPAD levels by ELISA. Gingival crevicular fluid (GCF) and serum samples were collected at baseline and 6 months after treatment. RESULTS: We observed a reduction in attachment loss, SLE Disease Activity Index (SLEDAI), IL-1ß, IL-10 and MCP-1 GCF levels, and the IL-4 and IL-5 serum levels 6 months after periodontal treatment. On the contrary, a significant increase in GCF expression of IL-4, IL-12, IL-17, IFN-γ and serum levels of anti-PPAD antibody was observed. CONCLUSION: Juvenile systemic lupus erythematosus patients seem to positively benefit from periodontal treatment by a significantly reduced CAL, a GCF reduction of pro-inflammatory cytokines and an increasing of anti-inflammatory ones. However, an increase in the GCF expression of IL-17 and the serum expression of anti-PPAD antibody 6 months after periodontal treatment might negatively affect the treatment outcome of such patients in the long term.

Thinking Differently about Cancer Treatment Regimens.

Most experimental cancer drugs ultimately fail during the course of clinical development, contributing to the high cost of the few that are granted regulatory approval. Moreover, approved drugs often deliver only modest clinical benefit to patients with advanced disease due to the development of resistance. Here, we discuss opportunities we consider promising to overcome drug resistance associated with interactions between signaling pathways and the presence of multiple coexisting cell states within tumors with distinct vulnerabilities. We highlight how understanding drug-resistance mechanisms can enable innovative treatment regimens that deliver longer-lasting benefit to patients.

Invasive Seaweeds in the Iberian Peninsula: A Contribution for Food Supply.

The introduction of exotic organisms in marine ecosystems can lead to economic and ecological losses. Globally, seaweeds represent a significant part of these non-indigenous species (NIS), with 407 introduced algal species. Furthermore, the presence of NIS seaweeds has been reported as a major concern worldwide since the patterns of their potential invasion mechanisms and vectors are not yet fully understood. Currently, in the Iberian Peninsula, around 50 NIS seaweeds have been recorded. Some of these are also considered invasive due to their overgrowth characteristic and competition with other species. However, invasive seaweeds are suitable for industrial applications due to their high feedstock. Hence, seaweeds' historical use in daily food diet, allied to research findings, showed that macroalgae are a source of nutrients and bioactive compounds with nutraceutical properties. The main goal of this review is to evaluate the records of NIS seaweeds in the Iberian Peninsula and critically analyze the potential of invasive seaweeds application in the food industry.

Multiple low dose therapy as an effective strategy to treat EGFR inhibitor-resistant NSCLC tumours.

Resistance to targeted cancer drugs is thought to result from selective pressure exerted by a high drug dose. Partial inhibition of multiple components in the same oncogenic signalling pathway may add up to complete pathway inhibition, while decreasing the selective pressure on each component to acquire a resistance mutation. We report here testing of this Multiple Low Dose (MLD) therapy model in EGFR mutant NSCLC. We show that as little as 20% of the individual effective drug doses is sufficient to completely block MAPK signalling and proliferation when used in 3D (RAF + MEK + ERK) or 4D (EGFR + RAF + MEK + ERK) inhibitor combinations. Importantly, EGFR mutant NSCLC cells treated with MLD therapy do not develop resistance. Using several animal models, we find durable responses to MLD therapy without associated toxicity. Our data support the notion that MLD therapy could deliver clinical benefit, even for those having acquired resistance to third generation EGFR inhibitor therapy.

Effectiveness of technology-enhanced learning to improve periodontics educational outcomes: A systematic review.

OBJECTIVES: Technology-enhanced learning (TEL) has been suggested as a suitable learner-centered pedagogical approach in dental education. However, the results of TEL effectiveness in periodontics education are controversial. Therefore, this systematic review aimed to evaluate the effectiveness of TEL to improve educational outcomes in the periodontics field compared to traditional learning methods. METHODS: The search comprised randomized controlled trials (RCTs) and crossover studies that were related to periodontics education from the following databases: MedLine, PsycINFO, Eric, Scopus, EMBASE, and Web of Science. Two authors independently performed study selection, data extraction, and assessed risk of bias. Kirkpatrick's 4-level evaluation model was used to evaluate educational outcomes. RESULTS: From 1642 studies, after applying inclusion criteria, 7 studies remained for analysis. On level 1 (Reaction), undergraduate dental students reported positive attitudes related to TEL. On level 2 (Learning), 3 studies found that TEL improved knowledge gain compared to traditional learning methods. Three other studies did not show any difference between TEL and conventional learning methods, and one found that traditional learning methods presented superior results. On level 3 (Behavior), 1 study found that TEL application improved students' performance. On level 4 (Results), 5 studies suggested that the implementation of TEL would improve educational outcomes in periodontics education if combined with traditional learning methods. CONCLUSION: The findings showed that the exclusive use of TEL does not significantly improve periodontics educational outcomes when compared to traditional learning methods. However, the combination of TEL and traditional learning methods can be the key to enhancing periodontics education.

Hypoglycaemic activity of Bauhinia holophylla through GSK3-ß inhibition and glycogenesis activation.

CONTEXT: Bauhinia L. species, including Bauhinia holophylla (Bong.) Steud. (Fabaceae), have traditionally been used to treat diabetes. Bauhinia is a complex botanical genus, and the indiscriminate use of the diverse Bauhinia species is reflected in the experimental divergence of their medicinal potential. OBJECTIVE: The hypoglycaemic and hypolipidaemic effects, molecular mechanism of action and phytochemical properties of an authentic extract of B. holophylla leaves were evaluated. MATERIALS AND METHODS: A phytochemical study of a 70% EtOH extract was performed using FIA-ESI-IT-MS/MSn and HPLC-PAD-ESI-IT-MS. The extract (200 or 400 mg/kg b.w.) was administered for 14 days to streptozotocin-induced diabetic Swiss mice. Glucose tolerance and insulin sensitivity, blood parameters, gene and protein expression, and the in vivo and in vitro inhibition of intestinal glucosidases were assessed. RESULTS: HPLC-PAD-ESI-IT-MS analysis identified flavonoid derivatives of quercetin, myricetin, luteolin and kaempferol. Treatment with 400 mg/kg of the extract reduced blood glucose (269.0 ± 32.4 mg/dL vs. 468.0 ± 32.2 mg/dL for diabetic animals), improved glucose tolerance, decreased cholesterol and triglyceride levels, and increased the mRNA expression of proteins involved in glucogenesis in the liver and muscle, such as PI3-K/Akt, GS, GSK3-ß (ser-9), AMPK and Glut4. The activity of intestinal maltase was inhibited in vitro (IC50: 43.0 µg/mL for the extract compared to 516.4 µg/mL for acarbose) and in vivo. DISCUSSION AND CONCLUSIONS: Treatment with B. holophylla was associated with a marked hypoglycaemic effect through the stimulation of glycogenesis and inhibition of gluconeogenesis and intestinal glucose absorption, without increasing basal insulinaemia.

Transient hepatic elastography has the best performance to evaluate liver fibrosis in non-alcoholic fatty liver disease (NAFLD).

INTRODUCTION AND AIM: The gold-standard for fibrosis diagnosis in non-alcoholic fatty liver disease (NAFLD) is liver biopsy, despite its invasive approach, sampling limitations and variability among observers. The objective was to validate the performance of non-invasive methods (Fibroscan™; APRI, FIB4 and NAFLD score) comparing with liver biopsy in the evaluation of liver fibrosis in patients with NAFLD. MATERIAL AND METHODS: NAFLD patients ≥18 years of age who were submitted to liver biopsy were included and evaluated at two reference tertiary hospitals in Brazil with transient hepatic elastography (THE) assessment through Fibroscan™, APRI, FIB4 and NAFLD scores were determined. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values for the diagnosis of advanced fibrosis were calculated to evaluate the performance of these non-invasive methods in NAFLD patients, adopting liver biopsy as the gold standard. RESULTS: A total of 104 patients were studied. At three different cutoff values (7.9, 8.7 and 9.6kPa) THE presented the highest sensitivity values (95%, 90% and 85% respectively), and the highest NPV (98%, 96.4% and 95.1% respectively) for the diagnosis of advanced fibrosis. It also presented the highest AUROC (0.87; CI 95% 0.78-0.97). CONCLUSION: When compared to the gold standard, transient hepatic elastography presented the best performance for the diagnosis and exclusion of advanced fibrosis in patients with NAFLD, overcoming APRI, FIB4 and NAFLD score.

Periodontal disease severity in subjects with dementia: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Despite clinical trials and reviews attempt to assess a possible relationship between dementia and periodontal disease, no meta-analysis has been performed and this issue remains undetermined. The aim of this study is to conduct a systematic review and meta-analysis to assess severity of periodontitis in subjects with dementia. METHODS: The search was conducted in Pubmed, Embase/MEDLINE. Two independent reviewers extracted data and assessed the risk bias (Newcastle-Ottawa scale). Meta-analyses were performed using the means of probing depth (PD) and clinical attachment loss (CAL) in patients with or without dementia. The mean difference were analyzed (P ≤ 0.05). RESULTS: Fourteen studies were included in the systematic review. In the qualitative analysis, most studies reported higher prevalence of periodontal disease in dementia patients. The studies had low risk of bias and two meta-analyses were performed for each parameter, including or not a cross-sectional study. The meta-analyses including the cross-sectional study demonstrated significant association between dementia and periodontal disease (mean difference: PD = 1.41; CAL = 1.40, P < 0.05), however, it wasn't confirmed when the cross-sectional study was removed (1.25 mm, P < 0.22) and CAL (1.20 mm, P < 0.22). CONCLUSION: Although the qualitative analysis have suggested worse periodontal conditions in dementia patients, due to different study types and the high heterogeneity among them, the meta-analysis does not support the association between dementia and severity of periodontal disease.

Occurrence of microplastics in commercial fish from a natural estuarine environment.

Microplastic ingestion has been reported for several marine species, but the level of contamination in transitional systems and associated biota is less known. The aim of this study was to assess the occurrence of microplastic ingestion in three commercial fish species: the sea bass (Dicentrarchus labrax), the seabream (Diplodus vulgaris) and the flounder (Platichthys flesus) from the Mondego estuary (Portugal). Microplastics were extracted from the gastrointestinal tract of 120 individuals by visual inspection and digestion solution. A total of 157 particles were extracted from 38% of total fish (96% fibers), with 1.67 ±â€¯0.27 (SD) microplastics per fish. Significantly higher amount of ingested microplastics was recorded for D. vulgaris (73%). The dominant polymers identified by µ-FTIR were polyester, polypropylene and rayon (semi-synthetic fiber). It is reported for the first time the presence of this pollutant in fish populations from the Mondego estuary raising concerns on their potential negative effects.