Impact of age, comorbidities and relevant changes on surveillance strategy of intraductal papillary mucinous neoplasms: a competing risk analysis.

OBJECTIVE: Cost-effectiveness of surveillance for branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) is debated. We combined different categories of risks of IPMN progression and of IPMN-unrelated mortality to improve surveillance strategies. DESIGN: Retrospective analysis of 926 presumed BD-IPMNs lacking worrisome features (WFs)/high-risk stigmata (HRS) under surveillance. Charlson Comorbidity Index (CACI) defined the severity of comorbidities. IPMN relevant changes included development of WF/HRS, pancreatectomy or death for IPMN or pancreatic cancer. Pancreatic malignancy-unrelated death was recorded. Cumulative incidence of IPMN relevant changes were estimated using the competing risk approach. RESULTS: 5-year cumulative incidence of relevant changes was 17.83% and 1.6% developed pancreatic malignancy. 5-year cumulative incidences for IPMN relevant changes were 13.73%, 19.93% and 25.04% in low-risk, intermediate-risk and high-risk groups, respectively. Age ≥75 (HR: 4.15) and CACI >3 (HR: 3.61) were independent predictors of pancreatic malignancy-unrelated death. 5-year cumulative incidence for death for other causes was 15.93% for age ≥75+CACI >3 group and 1.49% for age <75+CACI ≤3. 5-year cumulative incidence of IPMN relevant changes were 13.94% in patients with age <75+CACI ≤3 compared with 29.60% in those with age ≥75+CACI >3. In this group 5-year rate of malignancy-free patients was 95.56% with a 5-year survival of 79.51%. CONCLUSION: Although it is not uncommon the occurrence of changes considered by current guidelines as relevant during surveillance of low risk BD-IPMNs, malignancy rate is low and survival is significantly affected by competing patients' age and comorbidities. IPMN surveillance strategy should be tailored based on these features and modulated over time.

Probiotics as an Alternative to Antibiotics: Genomic and Physiological Characterization of Aerobic Spore Formers from the Human Intestine.

A total of thirty-two aerobic spore former strains were isolated from intestinal samples of healthy children and analyzed for their hemolytic and antibiotic-resistant activities. Four strains selected as non-hemolytic and sensitive to all antibiotics recommended as relevant by regulatory agencies were short-listed and evaluated for their in silico and in vitro probiotic potentials. The four selected strains were assigned to the Bacillus velezensis (MV4 and MV11), B. subtilis (MV24), and Priestia megaterium (formerly Bacillus megaterium) (MV30) species. A genomic analysis indicated that MV4, MV11, and MV24 contained a homolog of the gene coding for the fibrinolytic enzyme nattokinase while only MV30 encoded a glutamic acid decarboxylase essential to synthesize the neurotransmitter GABA. All four strains contained gene clusters potentially coding for new antimicrobials, showed strong antioxidant activity, formed biofilm, and produced/secreted quorum-sensing peptides able to induce a cytoprotective stress response in a model of human intestinal (HT-29) cells. Altogether, genomic and physiological data indicate that the analyzed strains do not pose safety concerns and have in vitro probiotic potentials allowing us to propose their use as an alternative to antibiotics.

Exploring the potential of contrast agents in breast cancer echography: current state and future directions.

Breast cancer stands as the most frequent malignancy and leading cause of death among women. Early and accurate detection of this pathology represents a crucial factor in enhancing both incidence and mortality rates. Ultrasound (US) examination has been extensively adopted in clinical practice due to its non-invasiveness, affordability, ease of implementation, and wide accessibility, thus representing a valuable first-line diagnostic tool for the study of the mammary gland. In this scenario, recent developments in nanomedicine are paving the way for new interpretations and applications of US diagnostics, which are becoming increasingly personalized based on the molecular phenotype of each tumor, allowing for more precise and accurate evaluations. This review highlights the current state-of-the-art of US diagnosis of breast cancer, as well as the recent advancements related to the application of US contrast agents to the field of molecular diagnostics, still under preclinical study.

Sporulation efficiency and spore quality in a human intestinal isolate of Bacillus cereus.

Bacteria classified as Bacillus cereus sensu stricto cause two different type of gastrointestinal diseases associated with food poisoning. Outbreaks of this opportunistic pathogen are generally due to the resistance of its spores to heat, pH and desiccation that makes hard their complete inactivation from food products. B. cereus is commonly isolated from a variety of environments, including intestinal samples of infected and healthy people. We report the genomic and physiological characterization of MV19, a human intestinal strain closely related (ANI value of 98.81%) to the reference strain B. cereus ATCC 14579. MV19 cells were able to grow in a range of temperatures between 20 and 44 °C. At the optimal temperature the sporulation process was rapidly induced and mature spores efficiently released, however these appeared structurally and morphologically defective. At the sub-optimal growth temperature of 25 °C sporulation was slow and less efficient but a high total number of fully functional spores was produced. These results indicate that the reduced rapidity and efficiency of sporulation at 25 °C are compensated by a high quality and quantity of released spores, suggesting the relevance of different performances at different growth conditions for the adaptation of this bacterium to diverse environmental niches.

Utilização de banco de dados policiais como perspectiva para redução do sub-registro da violência contra mulheres / Using police databases as a prospect to reduce under-recording of violence against women / Utilizar las bases de datos policiales como perspectiva para reducir el subregistro de la violencia contra las mujeres

Objetivo: buscou-se avaliar a concordância entre o Sistema de Informação de Agravo de Notificação (SINAN) e dados policiais para casos de violência física e sexual contra mulheres, bem como o perfil das mulheres agredidas, das agressões e dos agressores. Método: foi realizado estudo transversal com casos ocorridos em uma cidade de Minas Gerais, notificados no SINAN e/ou identificados na base policial, entre os anos de 2015 e 2016. Criou-se uma base consolidada, composta pelos casos elegíveis das duas fontes, tendo sido realizadas análises descritivas. Em uma base pareada contendo casos comuns aos dois bancos, foi realizada análise de concordância pelo teste Fleiss'Kappa. Resultados: 1.185 casos compuseram a base consolidada e 56 constituíram a base pareada. Houve sub-registro de 83,54% nos dados do SINAN, além de incompletude importante de informações. A base policial apresentou cerca de oito vezes maior captação. A concordância de informações foi elevada/moderada para sete de 11 características avaliadas para os casos comuns. Na base consolidada, as vítimas foram predominantemente negras, solteiras ou viúvas, com idade entre 18 e 39 anos. Os homens, especialmente (ex)parceiros e familiares, foram os principais agressores. Conclusão: o sub-registro e a incompletude de informações sobre violência contra mulher no SINAN é uma realidade que precisa ser tratada. O cruzamento com fontes de dados policiais é uma alternativa para melhorar a qualidade das informações, reduzindo o sub-registro. Apesar dos dados subestimados, percebeu-se que a violência física e doméstica, cometida por (ex)parceiro contra mulheres jovens e negras continua sendo prevalente, atentando para o fato que se deve manter foco de políticas públicas.(AU)

Objective: this study sought to evaluate the agreement between the Information System for Notifiable Health Problems (Sistema de Informação de Agravo de Notificação, SINAN) and Police data for cases of physical and sexual violence against women, as well as the profile of the assaulted women, the aggressions and the aggressors. Method: a cross-sectional study was conducted with cases in a city from Minas Gerais, notified to the SINAN and/or identified in the Police database between 2015 and 2016. A consolidated database was created, comprised by the eligible cases from both sources, with performance of descriptive analyses. An agreement analysis by means of the Fleiss Kappa test was performed in a paired database containing cases common to both databases. Results: a total of 1,185 cases comprised the consolidated database, whereas 56 were included in the paired one. There was 83.54% under-recording in the SINAN data, in addition to important information incompleteness. The Police database presented nearly eight times more recording of cases. Agreement of all the information was high/moderate for seven out of 11 characteristics evaluated for the common cases. In the consolidated databases, the victims were predominantly black-skinned, single or widowed, and aged between 18 and 39 years old. The main aggressors were men, mainly (former) partners and family members. Conclusion: under-recording and incompleteness of diverse information about violence against women in the SINAN is a reality that needs to be dealt with. Cross-referencing with Police data sources represent an alternative to improve quality of the information, reducing under-recording. Despite the underestimated data, it was noticed that physical and domestic violence, perpetrated by (former) partners against young and black-skinned women, continues to be prevalent, pointing to the fact that it should remain as the focus of public policies.(AU)

Objetivo: se buscó evaluar la concordancia entre el Sistema de Informação de Agravo de Notificação (SINAN) y los datos policiales para los casos de violencia física y sexual contra las mujeres, así como el perfil de las mujeres maltratadas, de las agresiones y agresores. Método...(AU)

CotG Mediates Spore Surface Permeability in Bacillus subtilis.

Proteins and glycoproteins that form the surface layers of the Bacillus spore assemble into semipermeable arrays that surround and protect the spore cytoplasm. Such layers, acting like molecular sieves, exclude large molecules but allow small nutrients (germinants) to penetrate. We report that CotG, a modular and abundant component of the Bacillus subtilis spore coat, controls spore permeability through its central region, formed by positively charged tandem repeats. These repeats act as spacers between the N and C termini of the protein, which are responsible for the interaction of CotG with at least one other coat protein. The deletion but not the replacement of the central repeats with differently charged repeats affects the spore resistance to lysozyme and the efficiency of germination-probably by reducing the coat permeability to external molecules. The presence of central repeats is a common feature of the CotG-like proteins present in most Bacillus species, and such a wide distribution of this protein family is suggestive of a relevant role for the structure and function of the Bacillus spore. IMPORTANCE Bacterial spores are quiescent cells extremely resistant to a variety of unphysiological conditions, including the presence of lytic enzymes. Such resistance is also due to the limited permeability of the spore surface, which does not allow lytic enzymes to reach the spore interior. This article proposes that the spore permeability in B. subtilis is mediated by CotG, a modular protein formed by a central region of repeats of positively charged amino acid acting as a "spacer" between the N and C termini. These, in turn, interact with other coat proteins, generating a protein layer whose permeability to external molecules is controlled by the distance between the N and C termini of CotG. This working model is most likely expandable to most sporeformers of the Bacillus genus, since they all have CotG-like proteins, not homologous to CotG of B. subtilis but similarly characterized by central repeats.

CotG controls spore surface formation in response to the temperature of growth in Bacillus subtilis.

Bacterial spores of the Bacillus genus are ubiquitous in nature and are commonly isolated from a variety of diverse environments. Such wide distribution mainly reflects the spore resistance properties but some Bacillus species can grow/sporulate in at least some of the environments where they have been originally isolated. Growing and sporulating at different conditions is known to affect the structure and the resistance properties of the produced spore. In B. subtilis the temperature of growth and sporulation has been shown to influence the structure of the spore surface throughout the action of a sporulation-specific and heat-labile kinase CotH. Here we report that CotG, an abundant component of the B. subtilis spore surface and a substrate of the CotH kinase, assembles around the forming spore but also accumulates in the mother cell cytoplasm where it forms aggregates with at least two other coat components. Our data suggest that the thermo-regulator CotH contributes to the switch between the coat of 25°C and that of 42°C spores by controlling the phosphorylation levels of CotG that, in turn, regulates the assembly of at least two other coat components.

The Psychophysiological Effects of Different Tempo Music on Endurance Versus High-Intensity Performances.

The use of music during training represents a special paradigm for trainers to stimulate people undertaking different types of exercise. However, the relationship between the tempo of music and perception of effort during different metabolic demands is still unclear. Therefore, the aim of this research was to determine whether high intensity exercise is more sensitive to the beneficial effects of music than endurance exercise. This study assessed 19 active women (age 26.4 ± 2.6 years) during endurance (walking for 10' at 6.5 km/h on a treadmill) and high intensity (80% on 1-RM) exercise under four different randomly assigned conditions: no music (NM), with music at 90-110 bpm (LOW), with music at 130-150 bpm (MED), and with music at 170-190 bpm (HIGH). During each trial, heart rate (HR) and the rating of perceived exertion (RPE) were assessed. Repeated analysis of variance measures was used to detect any differences between the four conditions during high intensity and low intensity exercise. RPE showed more substantial changes during the endurance exercises (11%), than during high intensity exercise (6.5%), between HIGH and NM conditions. The metabolic demand during the walking exercise increased between NM and HIGH bpm conditions. This study indicates the benefits of music under stress conditions as well as during endurance and high intensity training. The results demonstrate that the beneficial effects of music are more likely to be seen in endurance exercise. Consequently, music may be considered an important tool to stimulate people engaging in low intensity physical exercise.

MMP-9 microsatellite polymorphism: association with the progression of intima-media thickening and constrictive remodeling of carotid atherosclerotic plaques.

Intima-media thickening (IMT) of carotid arteries and constrictive remodeling (CR) of atherosclerotic plaques are vascular pathologic characteristics that precede the onset of vascular events. SMC migration and proliferation are linked both to IMT and CR and are matrix metalloproteinase 9 (MMP-9) dependent. A genetic polymorphism (PM) of MMP-9, a CA (13-27) microsatellite in the promoter region, which accounts for differential expression of MMP-9, could be linked to progression of IMT and CR. Progression of IMT and CR of plaques in carotid arteries were studied in 55 consecutive patients with a 12-18 months follow-up. All patients were genotyped for MMP-9 PM. A positive linear relationship between the number of repeats and the progression of IMT (P=0.028) as well as of CR (P=0.018) was found. The analogous relationship was obtained when only the allele with longer microsatellite was considered. Carriers of more than 20 repeats in one allele showed faster both IMT growth (P=0.045) and stenosis progressions of plaques (P=0.019). In multivariate analysis, age, dyslipidemia, and MMP-9 PM were determinants of IMT progression, while MMP-9 PM was the only one of CR. In conclusion, the high number of CA repeats in MMP-9 promoter is positively correlated with faster IMT and CR progression.