Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet

Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GR βgeo/+ mice were generated from embryonic stem (ES) cells with a gene trap integration of a β-galactosidase-neomycin phosphotransferase (βgeo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GRβgeo/+ mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin- aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GRβgeo/+ mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GRβgeo/+ mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet

Diet quality, overweight and daily monetary allowance of Greek adolescents.

Objective: To investigate cross-correlates of pocket-money on diet quality and weight status of Greek adolescents. Methods: A total of 172 adolescents (55.2% boys), aged between 10 and 15 years old were recruited. Body weight and height were measured, body mass index (BMI) was computed. Weight status was assessed according to the International Obesity Task Force criteria and diet quality was evaluated via the Healthy Eating Index (HEI) - 2010. Results: Adolescents were allowed a mean allowance of €4.63 ± 3.66 daily. Among boys participants, BMI correlated with pocket money (r = 0.311, p ≤ 0.002) and normoweight boys received statistically less money than their overweight peers (p ≤ 0.019). In both sexes, normoweight was more prevalent in the lowest monetary quartiles. Pocket money was not associated with HEI. Among boys, moderate HEI was more prevalent in the third quartile of pocket money, significantly higher compared to all others (p ≤ 0.01 for all). For girls, the prevalence of moderate HEI declined by each ascending pocket money quartile (p ≤ 0.05 for all). Conclusion: In our sample, adolescents exhibited high rates of pooled overweight including obesity. The majority of the participants followed a diet of moderate quality. Pocket money was associated with BMI only among boys. As pocket money was not associated with diet quality, it is highly possible that adolescents might choose to spend their money on items other than foods. Our study shows that pocket money should be controlled during adolescence and teenagers should be educated on spending their money on healthier food choices

Exciting new advances in oral cancer diagnosis: avenues to early detection

The prognosis for patients with oral squamous cell carcinoma remains poor in spite of advances in therapy of many other malignancies. Early diagnosis and treatment remains the key to improved patient survival. Because the scalpel biopsy for diagnosis is invasive and has potential morbidity, it is reserved for evaluating highly suspicious lesions and not for the majority of oral lesions which are clinically not suspicious. Furthermore, scalpel biopsy has significant interobserver and intraobserver variability in the histologic diagnosis of dysplasia. There is an urgent need to devise critical diagnostic tools for early detection of oral dysplasia and malignancy that are practical, noninvasive and can be easily performed in an out-patient set-up. Diagnostic tests for early detection include brush biopsy, toluidine blue staining, autofluorescence, salivary proteomics, DNA analysis, biomarkers and spectroscopy. This state of the art review critically examines these tests and assesses their value in identifying oral squamous cell carcinoma and its precursor lesions

Evaluation of dentists’ knowledge of the use of oral exfoliative cytology in clinical practice

Oral exfoliative cytology (EC) is a rapid and practical complementary test that can be used in the diagnosis of various diseases. The objectives of this study were to assess dentists'knowledge of EC and to disseminate information on the technique. The study included 240 dentists from the city of Anapolis (Goias, Brazil) who answered a questionnaire regarding demographic data and data relating to EC and who then received information on the technique. The data revealed that 26.92% of the dentists did not know about EC. Among those who reported knowledge of EC, 33.91% did not know the procedures for performing the technique, and 85.38% had no experience with EC. In addition, 54.09% of the answers regarding the instrument used to collect the material and 56.82% of the answers concerning suitable fixatives were inappropriate. Although 73.02% of the dentists adequately identified the pathologies for which EC is recommended, it was concluded that the respondents had poor knowledge of EC. There is a need to increase dentists'awareness of this subject and of EC's use in diagnostic practices.Universidade de Taubaté, Departamento de OdontologiaUniversidade Estadual Paulista, Departamento de Biociências e Diagnóstico Bucal, Instituto de Ciência e Tecnologia de São José dos Campo

Duration of Treatment for Pseudomonas aeruginosa Bacteremia : a Retrospective Study

Introduction: There is no consensus regarding optimal duration of antibiotic therapy for Pseudomonas aeruginosa bacteremia. We aimed to evaluate the impact of short antibiotic course. Methods: We present a retrospective multicenter study including patients with P. aeruginosa bacteremia during 2009-2015. We evaluated outcomes of patients treated with short (6-10 days) versus long (11-15 days) antibiotic courses. The primary outcome was a composite of 30-day mortality or bacteremia recurrence and/or persistence. Univariate and inverse probability treatment-weighted (IPTW) adjusted multivariate analysis for the primary outcome was performed. To avoid immortal time bias, the landmark method was used. Results: We included 657 patients; 273 received a short antibiotic course and 384 a long course. There was no significant difference in baseline characteristics of patients. The composite primary outcome occurred in 61/384 patients in the long-treatment group (16%) versus 32/273 in the short-treatment group (12%) (p = 0.131). Mortality accounted for 41/384 (11%) versus 25/273 (9%) of cases, respectively. Length of hospital stay was significantly shorter in the short group [median 13 days, interquartile range (IQR) 9-21 days, versus median 15 days, IQR 11-26 days, p = 0.002]. Ten patients in the long group discontinued antibiotic therapy owing to adverse events, compared with none in the short group. On univariate and multivariate analyses, duration of therapy was not associated with the primary outcome. Conclusions: In this retrospective study, 6-10 days of antibiotic course for P. aeruginosa bacteremia were as effective as longer courses in terms of survival and recurrence. Shorter therapy was associated with reduced length of stay and less drug discontinuation

A cost-utility analysis of cervical cancer vaccination in preadolescent Canadian females

<p>Abstract</p> <p>Background</p> <p>Despite the fact that approximately 70% of Canadian women undergo cervical cancer screening at least once every 3 years, approximately 1,300 women were diagnosed with cervical cancer and approximately 380 died from it in 2008. This study estimates the effectiveness and cost-effectiveness of vaccinating 12-year old Canadian females with an AS04-adjuvanted cervical cancer vaccine. The indirect effect of vaccination, via herd immunity, is also estimated.</p> <p>Methods</p> <p>A 12-health-state 1-year-cycle Markov model was developed to estimate lifetime HPV related events for a cohort of 12-year old females. Annual transition probabilities between health-states were derived from published literature and Canadian population statistics. The model was calibrated using Canadian cancer statistics. From a healthcare perspective, the cost-effectiveness of introducing a vaccine with efficacy against HPV-16/18 and evidence of cross-protection against other oncogenic HPV types was evaluated in a population undergoing current screening practices. The base-case analysis included 70% screening coverage, 75% vaccination coverage, $135/dose for vaccine, and 3$18,672-$31,687 per QALY-gained, the lower range representing inclusion of cross-protective efficacy and herd immunity. The cost per QALY-gained was most sensitive to duration of vaccine protection, discount rate, and the correlation between probability of screening and probability of vaccination.</p> <p>Conclusion</p> <p>In the context of current screening patterns, vaccination of 12-year old Canadian females with an ASO4-ajuvanted cervical cancer vaccine is estimated to significantly reduce cervical cancer and mortality, and is a cost-effective option. However, the economic attractiveness of vaccination is impacted by the vaccine's duration of protection and the discount rate used in the analysis.</p

Diagnostic and epidemiological landscape of anaerobic bacteria in Europe, 2020-2023 (ANAEuROBE).

Despite being implicated in a wide spectrum of community- and healthcare-acquired infections, anaerobes have not yet been incorporated into systematic surveillance programs in Europe. We conducted a multicentre retrospective observational study analysing all anaerobic strains isolated from blood cultures in 44 European Hospital Centres over a 4-y period (2020-2023). Diagnostic approach, epidemiology, and antimicrobial susceptibility according to EUCAST v. 15.0 were investigated. Our study included 14,527 anaerobes, most of which were Gram-positive (45%) or Gram-negative (40%) bacilli. MALDI-TOF coupled to mass spectrometry was the most widely used tool for species identification (98%). Antimicrobial susceptibility testing was performed in the vast majority of centres, using mostly gradient diffusion strip (77%) and disk diffusion (45%) methods according to EUCAST guidelines. The most prevalent species were Cutibacterium acnes (18.7%), Bacteroides fragilis (16.3%), Clostridium perfringens (5.3%), Bacteroides thetaiotaomicron (4.2%), Fusobacterium nucleatum (3.5%), and Parvimonas micra (3.4%). C. acnes showed high resistance to benzylpenicillin (18%), clindamycin (39%), and imipenem (19% and 13% by MIC methods and disk diffusion, respectively). B. fragilis showed high resistance to amoxicillin/clavulanate (24%), piperacillin/tazobactam (22% and 14% by MIC methods and disk diffusion, respectively), clindamycin (22% by both MIC methods and disk diffusion), meropenem (13%), and metronidazole (10%, only by disk diffusion). A similar resistance pattern was observed in B. thetaiotaomicron, Bacteroides ovatus, and Parabacteroides distasonis. C. perfringens showed high resistance to clindamycin (69% and 45% by MIC methods and disk diffusion, respectively), while benzylpenicillin and metronidazole maintained over 90% activity. F. nucleatum showed high resistance to benzylpenicillin (11%), while Fusobacterium necrophorum showed alarming rates of resistance to clindamycin (12%), meropenem (16%) and metronidazole (11%). This study presented an up-to-date analysis of the diagnostics and epidemiology of anaerobic bacteria in Europe, providing insights for future comparative analyses and the development of antimicrobial diagnostic and management strategies, as well as the optimization of current antibiotic treatments

Oral squamous cell cancer: early detection and the role of alcohol and smoking

Objective: Oral squamous cell carcinoma has a remarkable incidence worldwide and a fairly onerous prognosis, encouraging further research on factors that might modify disease outcome. Data sources: A web-based search for all types of articles published was initiated using Medline/Pub Med, with the key words such as oral cancer, alcohol consumption, genetic polymorphisms, tobacco smoking and prevention. The search was restricted to articles published in English, with no publication date restriction (last update 2010). Review Methods: In this review article, we approach the factors for a cytologic diagnosis during OSCC development and the markers used in modern diagnostic technologies as well. We also reviewed available studies of the combined effects of alcohol drinking and genetic polymorphisms on alcohol-related cancer risk. Results: The interaction of smoking and alcohol significantly increases the risk for aero-digestive cancers. The interaction between smoking and alcohol consumption seems to be responsible for a significant amount of disease. Conclusion: Published scientific data show promising pathways for the future development of more effective prognosis. There is a clear need for new prognostic indicators, which could be used in diagnostics and, therefore a better selection of the most effective treatment can be achieved

Efeitos agudos de diferentes intensidades de exercício sobre a ingestão alimentar pós-exercício

O objetivo do presente estudo foi verificar os efeitos agudos de diferentes intensidades de exercício aerróbio (40 e 80% do VO2pico) sobre a ingestão alimentar pós-exercício. Participaram do estudo 18 adultos jovens, eutróficos (22,20 ± 1,72 kg/m²) e fisicamente ativos. Todos os sujeitos foram submetidos aleatoriamente a três condições experimentais: controle (sem exercício); EBI, exercício de baixa intensidade (40% doVO2pico) e EAI, exercício de alta intensidade (80% do VO2pico). As sessões de exercício foram isocalróricas (350 kcal). Após 120 minutos de recuperação passiva, os voluntários tinham livre acesso a um "buffet" variado de alimentos, a ingestão alimentar foi determinada atravéz da pesagem dos alimentos ingeridos. Os dados alimentares obtidos foram então tabulados e analisados por meio do "software" Nutwin 6.0 (UNIFESP, 2002), para estimativa do consumo energético total (kcal) e ingestão dos macronutrientes (carboidratos, proteínas e lipídeos) em gramas. Os resultados não demonstram nenhuma diferença na ingesto alimentar entre as condições experimentais analisadas. Dessa forma, podemos concluir que a ingestão alimentar pós-exercício não se mostrou dependente da intensidade do esforóo em curto prazo em indivíduos adultos jovens fisicamente ativos.The aim of this study was to investigate the acute effects of different aerobic exercise intensities (40 and 80% do VO2peak) on post-exercise food intake. The sample was composed of eighteen healthy, physically active young men, of normal weight (22.20 ± 1.72 kg/m²). Subjects were randomly submitted to three experimental conditions: control (no exercise); low-intensity exercise (LIE -40% of VO2peak) and high-intensity exercise (HIE- 80% of VO2peak). Exercise trials were iso-caloric (350 Kcal). After 120 minutes of passive recovery, the volunteers had free access to a variety food buffet, and food intake was determined thru food weight. Data was analyzed by the software Nutwin 6.0 (UNIFESP, 2002) to estimate total energy intake (kcal) and consumption of the macronutrients (carbohydrates, proteins and lipids). The results suggest that food intake after exercise showed no significant differences between the experimental conditions. In conclusion, food intake after exercise is not dependent on exercise intensity in healthy young men