The emergence of socioeconomic inequalities in smoking during adolescence and early adulthood.

BACKGROUND: While it is known that educational inequalities in smoking start during early and middle adolescence, it is unknown how they further develop until adulthood. The aim of this article is to map, in the Portuguese context, how educational inequalities in smoking emerge from pre-adolescence until young adulthood. METHODS: This study used longitudinal data from the EPITeen Cohort, which recruited adolescents enrolled in schools in Porto, Portugal. We included the 1,038 participants followed at ages 13 (2003/2004), 17, 21, and 24 years. We computed the odds ratio (OR) for the prevalence of smoking states (never smoking, experimenter, less-than-daily, daily and former smoker) and the incidence of transitions between these states, as function of age and education, stratified by sex. We also added interaction terms between age and education. RESULTS: Educational inequalities in daily smoking prevalence, with higher prevalence among those with lower educational level, emerged at 17 years old and persisted until higher ages. They were formed in a cumulative way by the increased risk of experimenting between 13 and 17 years, and increased risk of becoming daily smoker between 17 and 21 years. The incidence of smoking cessation was higher among the higher educated. Inequalities were formed similarly for women and men, but with lower level and showed no significance among women. CONCLUSIONS: These results highlight that actions to prevent smoking should also take in account the potential impact in smoking inequalities, and should focus not only on middle adolescence but also on late adolescence and early adulthood.

Nanoscaled Discovery of a Shunt Rifamycin from Salinispora arenicola Using a Three-Color GFP-Tagged Staphylococcus aureus Macrophage Infection Assay.

Antimicrobial resistance has emerged as a global public health threat, and development of novel therapeutics for treating infections caused by multi-drug resistant bacteria is urgent. Staphylococcus aureus is a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival of S. aureus in macrophages contributes to immune evasion, dissemination, and resilience to antibiotic treatment. Here, we present a confocal fluorescence imaging assay for monitoring macrophage infection by green fluorescent protein (GFP)-tagged S. aureus as a front-line tool to identify antibiotic leads. The assay was employed in combination with nanoscaled chemical analyses to facilitate the discovery of a new, active rifamycin analogue. Our findings indicate a promising new approach for the identification of antimicrobial compounds with macrophage intracellular activity. The antibiotic identified here may represent a useful addition to our armory in tackling the silent pandemic of antimicrobial resistance.

Oral carcinogenesis triggers a nociceptive behavior and c-Fos expression in rats' trigeminal pathway.

OBJECTIVE: To recognize changes that occur along the trigeminal pathway in oral cancer in order to establish an effective approach to pain control. METHODS: Wistar rats were divided into control and 4-NQO groups for 8, 12, 16, or 20 weeks. 4-NQO suspension was administered on the animals' tongues. Mechanical hyperalgesia, assessment of facial expressions, and an open-field test were performed. After euthanasia, the animals' tongues were removed for macro- and microscopic analysis. c-Fos expression was analyzed in the trigeminal pathway structures. RESULTS: 4-NQO induced time-dependent macroscopic lesions that were compatible with neoplastic tumors. Histopathological analysis confirmed oral squamous cell carcinoma in 50% of the animals on the 20th week. There was a significant nociceptive threshold reduction during the first two weeks, followed by a threshold return to the baseline levels, decreasing again from the 12th week. Facial nociceptive expression scores were observed on the 20th week, while increased grooming and exploratory activity were observed on the 8th week. Trigeminal ganglion showed an increased c-Fos immunoexpression on the 20th week, and in the trigeminal subnucleus caudalis, it occurred on the 16th and 20th. The long-term carcinogenic exposure caused changes in the nociceptive behavior and c-Fos expression in the rats' trigeminal pathway.

Multidisciplinary management of idiopathic intracranial hypertension in pregnancy: case series and narrative review

Abstract Idiopathic intracranial hypertension (IIH) is a neurological condition characterized by raised intracranial pressure of unknown etiology with normal cerebrospinal fluid (CSF) composition and no brain lesions. It occurs in pregnant patients at approximately the same frequency as in general population, but obstetric and anesthetic management of the pregnancy and labor remains controversial. In this article we provide a multidisciplinary review of the main aspects of IIH in pregnancy including treatment options, mode of delivery and anesthetic techniques. Additionally, we report three cases of pregnant women diagnosed with IIH between 2012 and 2019 in our institution.

Metronidazole for Treatment of Clostridioides difficile Infections in Brazil: A Single-Center Experience and Risk Factors for Mortality.

We describe the epidemiology of C. difficile infections (CDIs) focused on treatment and analyze the risk factors for mortality. This is a retrospective cohort study of CDI cases with a positive A/B toxin in the stool in 2017-2018. We analyzed the demographic data, comorbidities, previous use of antimicrobials, severity, and treatment, and we performed multivariate analysis to predict the 30-days mortality. We analyzed 84 patients, 37 (44%) of which were male, where the mean age was 68.1 years and 83 (99%) had comorbidities. The percentage of positivity of the A/B toxin was 11.6%, and the overall incidence density was 1.78/10,000 patient days. Among the patients, 65.4% had previous use of antimicrobials, with third-generation cephalosporins being the class most prescribed, and 22.6% of cases were severe. Treatment was prescribed for 70 (83.3%) patients, and there was no statistically significant difference between the initial treatment with metronidazole and vancomycin even in severe cases. The 30-day mortality was 7/84 (8.3%), and the risk factors associated with mortality was a severity score ≥2 (OR: 6.0; CI: 1.15-31.1; p = 0.03). In this cohort of CDI-affected patients with comorbidities and cancer, metronidazole was shown to be a good option for treating CDIs, and the severity score was the only independent risk factor for death.

Hydrolysates containing xylooligosaccharides produced by different strategies: Structural characterization, antioxidant and prebiotic activities.

This study explores the structural characterization, antioxidant and prebiotic activities of hydrolysates containing xylooligosaccharides (XOS) produced by different strategies: direct fermentation of beechwood xylan (FermBX) and enzymatic treatment of beechwood (EnzBX) and rice husk (EnzRH) xylans. EnzBX and EnzRH showed XOS with a backbone of (1 â†’ 4)-linked-xylopyranosyl residues and branches of arabinose, galactose, and uronic acids. FermBX presented the highest content of total phenolic compounds (14 mg GAE/g) and flavonoids (0.6 mg QE/g), which may contribute to its antioxidant capacity -39.1 µmol TE/g (DPPH), 45.7 µmol TE/g (ABTS), and 79.9 µmol Fe II/g (FRAP). The fermentation of hydrolysates decreased the abundance of microorganisms associated with intestinal diseases from Eubacteriales, Desulfovibrionales and Methanobacteriales orders, while stimulating the growth of organisms belonging to Bacteroides, Megamonas and Limosilactobacillus genera. The production of short-chain fatty acids, ammonia, and CO2 suggested the prebiotic potential. In conclusion, hydrolysates without previous purification and obtained from non-chemical approaches demonstrated promising biological activities for further food applications.

Multidisciplinary management of idiopathic intracranial hypertension in pregnancy: case series and narrative review.

Idiopathic intracranial hypertension (IIH) is a neurological condition characterized by raised intracranial pressure of unknown etiology with normal cerebrospinal fluid (CSF) composition and no brain lesions. It occurs in pregnant patients at approximately the same frequency as in general population, but obstetric and anesthetic management of the pregnancy and labor remains controversial. In this article we provide a multidisciplinary review of the main aspects of IIH in pregnancy including treatment options, mode of delivery and anesthetic techniques. Additionally, we report three cases of pregnant women diagnosed with IIH between 2012 and 2019 in our institution.

Unravelling the Anti-Inflammatory and Antioxidant Potential of the Marine Sponge Cliona celata from the Portuguese Coastline.

Inflammation is a double-edged sword, as it can have both protective effects and harmful consequences, which, combined with oxidative stress (OS), can lead to the development of deathly chronic inflammatory conditions. Over the years, research has evidenced the potential of marine sponges as a source of effective anti-inflammatory therapeutic agents. Within this framework, the purpose of this study was to evaluate the antioxidant and the anti-inflammatory potential of the marine sponge Cliona celata. For this purpose, their organic extracts (C1-C5) and fractions were evaluated concerning their radical scavenging activity through 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and anti-inflammatory activity through a (lipopolysaccharides (LPS)-induced inflammation on RAW 264.7 cells) model. Compounds present in the two most active fractions (F5 and F13) of C4 were tentatively identified by gas chromatography coupled to mass spectrometry (GC-MS). Even though samples displayed low antioxidant activity, they presented a high anti-inflammatory capacity in the studied cellular inflammatory model when compared to the anti-inflammatory standard, dexamethasone. GC-MS analysis led to the identification of n-hexadecanoic acid, cis-9-hexadecenal, and 13-octadecenal in fraction F5, while two major compounds, octadecanoic acid and cholesterol, were identified in fraction F13. The developed studies demonstrated the high anti-inflammatory activity of the marine sponge C. celata extracts and fractions, highlighting its potential for further therapeutic applications.

Smoking cessation among adolescents in Europe: The role of school policy and programmes.

INTRODUCTION: European estimates of adolescent smoking cessation are lacking and studies on the role of schools in quit behaviour are scarce. We aimed to describe smoking cessation attempts and success among adolescents in Europe and explored the association with school policy and programmes. METHODS: We used cross-sectional data from the 2013 and 2016-2017 surveys of the European SILNE and SILNE-R projects. We included 4,509 12-19-year-old current or ex-smokers in 67 secondary schools in seven countries (Belgium, Germany, Finland, Ireland, Italy, the Netherlands, and Portugal). School staff reported strength of smoke-free school policies (SFSPs), proportion of grades in which anti-tobacco education was offered, and whether the school offered any form of cessation support programme. Multilevel logistic regression analysis determined school-level variation and the association of school-level and individual-level variables with self-reported and self-defined quit attempts and quit success. RESULTS: Over three quarters (77.3%) of students reported a quit attempt and half of them (50.1%) reported quit success. Prevalence rates of quit success and quit attempts, showed relatively small variations between schools within countries. Associations of smoke-free school policy, tobacco educational programmes and cessation programmes with quit attempts and quit success could not be demonstrated with statistical significance. Quit attempts and quit success were inversely associated with alcohol use, parental smoking, and friend smoking. CONCLUSION: This study demonstrates that adolescence is an important time to encourage quitting and to support quit attempts. We did not find evidence for a contribution of school policies and programmes to quit behaviour of adolescent smokers.

Language assessment in awake brain surgery: the Portuguese adaptation of the Dutch linguistic intraoperative protocol (DuLIP).

Awake brain surgery, combined with neurophysiological evaluation and intraoperative mapping, is one of the preferential lines of treatment when approaching low-grade gliomas. Speech and language assessment is used while applying Direct Electrical Stimulation (DES) and during the resection of a lesion/tumour, as it allows to establish related eloquent areas and optimise the extent of the resection and avoid impairments. Patients need to be assessed pre, intra and post-surgery, but in under resourced countries such as Portugal, there are still no standardised and validated tools to conduct this type of evaluation. To address this need, the tasks of the Dutch Linguistic Intraoperative Protocol (DuLIP) were adapted to European Portuguese, and the resulting materials were standardised for a group of 144 Portuguese participants. For each task, the impact of age, gender and schooling were measured. The resulting Portuguese version of the DuLIP (DuLIP-EP) consists of 17 tasks, including phonological, syntactic, semantic, naming and articulatory tests. No significant differences were found between male and female participants. However, schooling influenced phonological and syntactic fluency, object naming and verb generation. Schooling and age had a significant impact on semantic fluency and reading with semantic odd word out tasks. This is the first contribution to the standardisation of a tool that can be used during an awake brain surgery in Portugal, which includes a new phonological odd word out task that is not currently available in the Dutch version.

Electronic cigarette use among 14- to 17-year-olds in Europe.

BACKGROUND: Studies comparing adolescent e-cigarette use in different countries are scarce. We study students' e-cigarette and conventional cigarette ever-use, their social correlates and e-liquid use in seven EU countries. METHODS: SILNE-R data (N=12 167, response rate 79.4%) of 14-17-year-olds from Amersfoort (NL), Coimbra (PT), Dublin (IR), Hanover (GE), Latina (IT), Namur (BE) and Tampere (FI) were used. E-cigarette and conventional cigarette ever-use, dual-use, type of e-liquid and social correlates were measured with a school survey and analyzed with cross-tabulations and multinomial logistic regression. RESULTS: About 34% had tried e-cigarettes, but the variation was large between the cities (Latina 50%; Hanover 23%). Of e-cigarette ever-users, 37% had used nicotine e-liquid, 43% exclusively non-nicotine liquid and 20% did not know the content. Nicotine e-liquid was more prevalent among monthly e-cigarette users and weekly smoking e-cigarette users. The social correlates were mainly the same for exclusive e-cigarette ever-use, exclusive conventional cigarette ever-use and dual-use. Boys had greater odds for exclusive e-cigarette and dual-use compared to girls. Of social correlates, low academic achievement and parental smoking were positively associated with all categories of use, but parental education and immigrant background were not. The strongest association was found between peer smoking (most/all best friends smoke) and dual-use (OR 34.29). CONCLUSIONS: Students' e-cigarette ever-use varies greatly between EU countries. E-cigarettes seem not to be a substitute for conventional cigarettes but more a complementary product. Tobacco control policies might also prevent e-cigarette use but specific regulations on e-cigarettes are needed to prevent nicotine addiction originating from them.

Change in the Prevalence and Social Patterning of First-and Second-Hand Smoking in PORTUGAL: A Repeated Cross-Sectional Study (2005 and 2014).

Between 2005 and 2007, important reinforcements of the tobacco legislation have been implemented in Portugal, which may have affected smoking patterns. The aim of this study was to measure the change in prevalence of first- and second-hand smoking (SHS) among adults, and its socio-demographic patterning in Portugal from 2005 to 2014. Data from the last two Portuguese National Health Interview Surveys (2005 and 2014) were used. The changes in daily smoking and SHS were measured using Poisson regressions, stratifying by sex and survey year. The inequalities were measured using relative inequality indexes (RII). From 2005 to 2014, there was a reduction in SHS (75%-54% among men, and 52%-38% among women), and a reduction in smoking among men (27%-26%), and an increase among women (9%-12%). SHS reduction was more marked among less privileged people. Among Portuguese men, inequalities in daily smoking have increased slightly, while among women the gap favoring low-educated reduced. Between 2005 and 2014, SHS decreased, but not daily smoking, particularly among women. Additionally, socioeconomic inequalities in smoking increased. Future policies should simultaneously tackle smoking and SHS prevalence, and their socioeconomic patterning. More comprehensive policies such as comprehensive national (non-partial) bans, combined with price increases could be more effective.

Smoking beliefs across genders, a comparative analysis of seven European countries.

BACKGROUND: Most European countries have seen a decrease in the prevalence of adolescent smoking. This decrease has, however, been patterned by gender. Girls' smoking rates have now overtaken boys' in many European countries. The two genders may not, however, share the same smoking beliefs and this could explain differences between the genders in smoking prevalence. We describe gender differences in smoking beliefs and investigate variations between countries, along with their gender context. METHODS: In 2016, we conducted the SILNE R study (Smoking Inequalities Learning from Natural Experiments - Renew) in 55 schools located in seven European countries: Belgium, Italy, The Netherlands, Portugal, Finland, Ireland, and Germany. We surveyed 12,979 students aged 14-16 years (50% were girls). We classified smoking beliefs into four categories: positive individual, positive social, negative individual, and negative social beliefs. We expected girls to score higher on the last three of those categories and we hypothesized that countries with a more gender-equal culture would have less gender difference in beliefs about smoking. RESULTS: One out of two smoking beliefs differed significantly between genders. Negative social beliefs were more common in girls, while beliefs about the dating-related aspects of smoking were more common in boys. We identified Germany and Belgium as the only countries with no gender differences in any of the belief scales. No correlation was found, however, between these scales and the Gender Inequality Index. CONCLUSIONS: In some countries, gender-specific interventions might be implemented; however, two opposing strategies might be used, depending on whether such programs are aimed at boys or girls.

Where do teens smoke? Smoking locations of adolescents in Europe in relation to smoking bans in bars, schools and homes.

This study aimed to assess where European adolescents smoke. Data of 2,140 13-19-year-olds from 55 secondary schools in seven European cities was analysed using multilevel logistic regression analyses. Adolescents most often reported regularly smoking in 'other public locations (e.g., streets and parks)' (69%) and friends' homes (50%). Adolescents were less likely to smoke in bars, at school or at home when exposed to strong smoking bans at these locations. Bans on smoking in bars or at home were associated with regular smoking in other public locations, suggesting that smoking may have displaced towards these locations.

Lingual Incision Subperiosteal Tunnel Access: Proof of Concept 18-Month Follow-Up.

INTRODUCTION: Gingival recession is a common manifestation in most populations. The mechanism by which gingival recession occurs is not well understood but it seems to be complex and multifactorial. The main etiological factors are the accumulation of dental plaque biofilm with the resulting inflammatory periodontal diseases and mechanical trauma due to faulty oral hygiene technique, especially in thin biotypes. CASE PRESENTATION: This case report describes the treatment of lingual recessions associated with bone loss, with a lingual incision subperiosteal tunnel access (LISTA) technique associated with a connective tissue graft. Nine months after the surgery, clinically significant root coverage and increased thickness of keratinized tissue were achieved; the patient was observed at 9, 12, and 18 months. CONCLUSION: The clinical results, although without 100% root coverage, satisfied the patient entirely. LISTA technique associated with a connective tissue graft is a promising alternative for minimally invasive treatment of multiple lingual gingival recessions.

Immunoexpression of canonical Wnt and NF-κB signaling pathways in the temporomandibular joint of arthritic rats.

OBJECTIVE: To investigate the participation of canonical Wnt and NF-κB signaling pathways in an experimental model of chronic arthritis induced by methylated bovine serum albumin (mBSA) in rat temporomandibular joint (TMJ). MATERIALS AND METHODS: Wistar rats were sensitized by mBSA+Complete Freund Adjuvant (CFA)/Incomplete Freund Adjuvant (IFA) on the first 14 days (1 ×/week). Subsequently, they received 1, 2 or 3 mBSA or saline solution injections into the TMJ (1 ×/week). Hypernociceptive threshold was assessed during the whole experimental period. 24 h after the mBSA injections, the TMJs were removed for histopathological and immunohistochemical analyses for TNF-α, IL-1ß, NF-κB, RANKL, Wnt-10b, ß-catenin and DKK1. RESULTS: The nociceptive threshold was significantly reduced after mBSA injections. An inflammatory infiltrate and thickening of the synovial membrane were observed only after mBSA booster injections. Immunolabeling of TNF-α, IL-1ß and Wnt-10b was increased in the synovial membrane in arthritic groups. The immunoexpression of nuclear ß-catenin was significantly higher only in the group that received 2 booster TMJ injections. However, NF-κB, RANKL and DKK1 immunoexpression were increased only in animals with 3 mBSA intra-articular injections. CONCLUSION: Our results suggest that canonical Wnt and NF-κB signaling pathways participate in the hypernociception and inflammatory response in TMJ synovial membrane during the development of rheumatoid arthritis in rats.

Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations.

The proliferation, differentiation and survival of mononuclear phagocytes depend on signals from the receptor for macrophage colony-stimulating factor, CSF1R. The mammalian Csf1r locus contains a highly conserved super-enhancer, the fms-intronic regulatory element (FIRE). Here we show that genomic deletion of FIRE in mice selectively impacts CSF1R expression and tissue macrophage development in specific tissues. Deletion of FIRE ablates macrophage development from murine embryonic stem cells. Csf1rΔFIRE/ΔFIRE mice lack macrophages in the embryo, brain microglia and resident macrophages in the skin, kidney, heart and peritoneum. The homeostasis of other macrophage populations and monocytes is unaffected, but monocytes and their progenitors in bone marrow lack surface CSF1R. Finally, Csf1rΔFIRE/ΔFIRE mice are healthy and fertile without the growth, neurological or developmental abnormalities reported in Csf1r-/- rodents. Csf1rΔFIRE/ΔFIRE mice thus provide a model to explore the homeostatic, physiological and immunological functions of tissue-specific macrophage populations in adult animals.

Inequalities in adolescent self-rated health and smoking in Europe: comparing different indicators of socioeconomic status.

BACKGROUND: Although there is evidence for socioeconomic inequalities in health and health behaviour in adolescents, different indicators of socioeconomic status (SES) have rarely been compared within one data sample. We examined associations of five SES indicators with self-rated health (SRH) and smoking (ie, a leading cause of health inequalities) in Europe. METHODS: Data of adolescents aged 14-17 years old were obtained from the 2013 SILNE survey (smoking inequalities: learning from natural experiments), carried out in 50 schools in 6 European cities (N=10 900). Capturing subjective perceptions of relative SES and objective measures of education and wealth, we measured adolescents' own SES (academic performance, pocket money), parental SES (parental educational level) and family SES (Family Affluence Scale, subjective social status (SSS)). Logistic regression models with SRH and smoking as dependent variables included all SES indicators, age and gender. RESULTS: Correlations between SES indicators were weak to moderate. Low academic performance (OR=1.96, 95% CI 1.53 to 2.51) and low SSS (OR=2.75, 95% CI 2.12 to 3.55) were the strongest indicators of poor SRH after adjusting for other SES-indicators. Results for SSS were consistent across countries, while associations with academic performance varied. Low academic performance (OR=5.71, 95% CI 4.63 to 7.06) and more pocket money (OR=0.21, 95% CI 0.18 to 0.26) were most strongly associated with smoking in all countries. CONCLUSIONS: Socioeconomic inequalities in adolescent health were largest according to SES indicators more closely related to the adolescent's education as well as the adolescent's perception of relative family SES, rather than objective indicators of parental education and material family affluence. For future studies on adolescent health inequalities, consideration of adolescent-related SES indicators was recommended.

Everolimus in combination with Imatinib overcomes resistance in Chronic myeloid leukaemia.

Although Imatinib and other tyrosine kinase inhibitors (TKIs) have excellent results, the appearance of resistance is a problem in chronic myeloid leukaemia (CML). PI3K/AKT/mTOR pathway is activated by BCR-ABL playing a crucial rule in CML. This study aimed to evaluate the therapeutic potential of Everolimus, in CML models sensitive and resistant to Imatinib. We used one CML cell line sensitive to Imatinib (K562) and two resistant (K562-RC and K56-RD). Cell lines were treated with Everolimus alone and in combination with Imatinib. Cell viability was analysed by resazurin assay. Cell death and cell cycle were analysed by flow cytometry. Additionally, we also studied peripheral blood samples obtained from 52 patients under TKI treatment. Everolimus reduced cell line viability in sensitive (IC50 = 20 µM) and resistant models (K562-RC, IC50 = 25 µM; K562-RD, IC50 = 30 µM). This drug induced cell death by apoptosis and cell cycle arrest in G0/G1 phase. Everolimus also reduced cell viability by increasing apoptosis of haematopoietic stem cells (CD34+ cells) with low cytotoxicity to lymphocytes. Everolimus at 25 µM increased apoptotic cells 18.7% in CD34+ cells and only 8% in lymphocytes. The response to Everolimus was influenced by TKI treatment, with a better response in samples from patients under 2nd and 3rd generation TKI and with less toxicity to lymphocytes. Our results reveal that Everolimus induce cell death in CML cells sensitive and resistant to Imatinib, with low cytotoxicity to normal cells, suggesting that Everolimus could be an alternative targeted therapeutic approach in CML patients, even in cases of Imatinib resistance.