Chemical composition, cytotoxicity, antimicrobial, antibiofilm, and anti-quorum sensing potential of Mentha Piperita essential oil against the oral pathogen Streptococcus mutans.

Dental caries is a highly prevalent oral disease affecting billions of individuals globally. The disease occurs chemically as a result of breakdown of the tooth surface attributed to metabolic activity in colonizing biofilm. Biofilms, composed of exopolysaccharides and proteins, protect bacteria like Streptococcus mutans, which is notable for its role in tooth decay due to its acid-producing abilities. While various antimicrobial agents may prevent biofilm formation, these drugs often produce side effects including enamel erosion and taste disturbances. This study aimed to examine utilization of the Mentha piperita essential oil as a potential antibiofilm activity agent against S. mutans. M. piperita oil significantly (1) reduced bacterial biofilm, (2) exhibited a synergistic effect when combined with chlorhexidine, and (3) did not induce cell toxicity. Chemical analysis identified the essential oil with 99.99% certainty, revealing menthol and menthone as the primary components, constituting approximately 42% and 26%, respectively. Further, M. piperita oil eradicated preformed biofilms and inhibited biofilm formation at sub-inhibitory concentrations. M. piperita oil also interfered with bacterial quorum sensing communication and did not produce any apparent cell toxicity in immortalized human keratinocytes (HaCaT). M. piperita represented an alternative substance for combating S. mutans and biofilm formation and a potential combination option with chlorhexidine to minimize side effects. An in-situ performance assessment requires further studies.

The addition of curcumin to the diet of post-weaning dairy calves: effects on ruminal fermentation, immunological, and oxidative responses.

Incorporating Curcumin into animal diets holds significant promise for enhancing both animal health and productivity, with demonstrated positive impacts on antioxidant activity, anti-microbial responses. Therefore, this study aimed to determine whether adding Curcumin to the diet of dairy calves would influence ruminal fermentation, hematologic, immunological, oxidative, and metabolism variables. Fourteen Jersey calves were divided into a control group (GCON) and a treatment group (GTRA). The animals in the GTRA received a diet containing 65.1 mg/kg of dry matter (DM) Curcumin (74% purity) for an experimental period of 90 days. Blood samples were collected on days 0, 15, 45, and 90. Serum levels of total protein and globulins were higher in the GTRA group (P < 0.05) than the GCON group. In the GTRA group, there was a reduction in pro-inflammatory cytokines (IL-1ß and IL-6) (P < 0.05) and an increase in IL-10 (which acts on anti-inflammatory responses) (P < 0.05) when compared to the GCON. There was a significantly higher (P < 0.05) concentration of immunoglobulin A (IgA) in the serum of the GTRA than the GCON. A Treatment × Day interaction was observed for haptoglobin levels, which were higher on day 90 in animals that consumed Curcumin than the GCON (P < 0.05). The catalase and superoxide dismutase activities were significantly higher (P < 0.05) in GTRA, reducing lipid peroxidation when compared to the GCONT. Hematologic variables did not differ significantly between groups. Among the metabolic variables, only urea was higher in the GTRA group when compared to the GCON. Body weight and feed efficiency did not differ between groups (meaning the percentage of apparent digestibility of dry matter, crude protein, and acid detergent fiber (ADF) and neutral detergent fiber (NDF). There was a tendency (P = 0.09) for treatment effect and a treatment x day interaction (P = 0.05) for levels of short-chain fatty acids in rumen fluid, being lower in animals that consumed curcumin. There was a treatment vs. day interaction (P < 0.05) for the concentration of acetate in the rumen fluid (i.e., on day 45, had a reduction in acetate; on day 90, values were higher in the GTRA group when compared to the GCON). We conclude that there was no evidence in the results from this preliminary trial that Curcumin in the diet of dairy calves interfered with feed digestibility. Curcumin may have potential antioxidant, anti-inflammatory, and immune effects that may be desirable for the production system of dairy calves.

Linseed oil supplementation alters milk fatty acid profile, mitigates heat stress, and improves summer milk yield in grazing dairy cows.

Dietary supplementation of fat can be an important source of energy to compensate for the reduction in dry matter intake in dairy cows during heat stress periods. Studies have reported that supplementing dairy cow diets with linseed oil (LO) can increase milk yield and enhance the levels of beneficial fatty acids, such as omega-3 fatty acids, in the milk. The objective of this research was to evaluate the effect of LO supplementation on milk fatty acids profile, milk yield and composition, and physiological parameters of grazing cows. The study was conducted in two seasons, one in spring and one in summer. A 2 × 2 Latin square design was used in each experiment. Twelve Holstein and crossbred Holstein x Jersey cows were involved in each season. Cows were divided into two groups: control (TC) with no supplementation and treatment (TL) supplemented with 400 g/day of LO. The results showed that LO supplementation altered the milk fatty acid profile: decreased concentrations of short and medium-chain fatty acids (C10:0 - C17:1) except for C13:0 and increased concentrations of long-chain fatty acids (C18, C18:1 (both trans and cis isomers), C18:2 (specific conjugated linoleic acid - CLA isomers), and C18:3 n3 (omega-3)). Additionally, milk yield increased by 1.5 l per day during summer in LO-supplemented cows, while milk fat, protein, and casein content decreased. Milk stability increased by 2.2% in the LO-supplemented group. LO-supplemented cows reduced internal body temperature and heart frequency in the afternoon and increased daily rumination time by 20 min. In conclusion, LO supplementation can be an effective strategy to improve the nutritional profile of milk by altering fatty acid composition towards potentially healthier fats, mitigate the negative effects of heat stress on grazing cows during summer, as evidenced by reduced body temperature and heart frequency and increase milk yield.

Grape seed oil in the diet of primiparous Jersey cows before and after parturition: effects on performance, health, rumen environment, and milk quality.

The objective of the study was to determine whether adding grape seed oil (GSO) to the diet of primiparous Jersey breeds during the transition period would improve animal health by measuring effects on the rumen environment, serum biochemistry, oxidative response, and the composition and quality of milk. We used 14 Jersey heifers, weighing an average of 430 kg and 240 days of gestation. The animals were divided into two groups and offered a basal diet, including GSO in the concentrate for the GSO group (dose of 25 mL per animal day) and the same dose of soybean oil (SO) for the control group. The animals were allocated and maintained in a compost barn system, receiving an anionic diet (pre-partum) and a diet for postpartum lactating animals. Dry matter intake (DMI), milk production, serum biochemistry, serum and milk oxidative stability, ruminal fluid and milk fatty acid profile, milk qualitative aspects, and ruminal parameters such as pH, bacterial activity, and protozoan count were evaluated. The addition of GSO had a positive effect on the health of the cows, especially on the oxidative stability of the cows, by increasing total thiols (P = 0.03), higher plasma ferric reducing capacity (FRAP) (P = 0.01), and total antioxidant capacity (TAC) (P = 0.01). In the oxidative stability of the milk produced by the treated animals, there was also an increase in TAC (P = 0.05) and FRAP (P = 0.03). Discreet changes were observed in the ruminal environment with a decreasing trend in pH (P = 0.04) but an increase in bacterial activity (P = 0.05) and protozoa counts (P = 0.07) in cows that consumed the additive. GSO consumption affected the fatty acid profile in milk, increasing saturated fatty acids (SFA) (P = 0.05) and reducing unsaturated fatty acids (UFA) (P = 0.03). The oil did not affect milk production or efficiency in the postpartum period. Based on this information, it is concluded that the addition of GSO positively affects the cow's antioxidant system.

A Systematic Review on Alcohol Consumption among Non-Religious and Religious Adults.

Background: Research has suggested that religiosity is a protective factor in alcohol use, but this is an area that could be further explored. Objective: To undertake a systematic review of the literature on drinking patterns and their relationship with religiosity and non-religiosity in adult populations. Methods: We searched for relevant studies using the PubMed, LILACS, Web of Science, Scopus, and Psych-INFO databases. This review included only studies of people aged 18 and over which had a non-religious group as a comparison measure. Results: Fifty-one studies met the inclusion criteria. The present review showed that religious people tend to have lower alcohol consumption compared to those with no religion. However, this difference appears only when religions are analyzed together without differentiating between religious affiliations (Catholicism, Buddhism, Evangelicalism, etc.). Some religious affiliations, such as Buddhism, Catholicism and Lutheranism, appear to be risk factors for alcohol consumption. Definitions of risk consumption showed high heterogeneity, ranging from eight to 21 or more doses per week, a difference of 13 doses of alcohol between studies. Conclusions: The present review showed that religious people tend to have lower alcohol consumption compared to non-religious people. However, the results are contradictory when religious affiliations are analyzed separately and compared with non-religious participants. Adequately understanding which dimensions of religiosity and non-religiosity (e.g., group processes, engagement, meaning, rules of behavior) are protective in adulthood is fundamental to the construction of more effective interventions in this age group.

Regional Frequency Analysis applied to extreme rainfall events: Evaluating its conceptual assumptions and constructing null distributions.

Besides increasing the amount of data that can be used in a fitting process, the Regional Frequency Analysis (RFA) also assesses the quality of weather station networks. This technique assumes that it is possible to form homogeneous groups of meteorological series presenting independent and identically distributed data. Based on the hypothesis that such homogeneous groups can be formed under tropical-subtropical conditions, this study applied the RFA to assess the probability of one-day annual maximum rainfall in the State of São Paulo, Brazil. Critical limits used in previous studies to declare a region/group as 'acceptable homogeneous' (H≤1.00) or to select a distribution (|Z|≤1.64) were evaluated through Monte Carlo simulations. While the limit H≤1 is appropriate, the limit |Z|≤1.64 may lead to unacceptably high rates of rejecting a true null hypothesis. This statement is particularly true for the general logistic distribution. A computational algorithm allowing the selection of critical limits corresponding to pre-specified probabilities of rejecting a true null hypothesis is provided. Considering the new critical limits, data from one of the largest weather station networks of the State have been pooled into four homogeneous groups. Both generalized logistic and extreme value distributions are recommended for the probabilistic assessment of such groups.

Impact of mining activities on areas of environmental protection in the southwest of the Amazon: A GIS- and remote sensing-based assessment.

The southwest Brazilian Amazon state of Rondônia has a relatively recent non-indigenous occupation, which subsequently develops a variety of human pressures and conflicts of interest presently identified in the region. Given such framework, it is worthwhile to note that there are 57 Conservation Units that must guarantee the biodiversity protection of Amazonia biome. However, due to the need for electricity and the international high demand for minerals, the highlighted scenario has dramatically changed in recent years. Official data from mining processes in the studied area demonstrated the existence of high interest for minerals, especially cassiterite and gold. Mining is indeed an essential activity for the nation mainly due to the generation of jobs and income. On the other hand, it produces several environmental and social impacts that vary accordingly to the peculiarities of the mining and with respect to the type of ore. Therefore, this research work investigated the concentration of mining projects in the state of Rondônia and complementarily evaluated the impact of such activities on areas of environmental protection. Landsat 8 OLI imageries were employed to map the diversity of land covers across the study area and also to evaluate the corresponding impact of mining activities. More than 500 processes have been identified within the Conservation Units. A significant part of the mining areas, covering about 26 km2, was observed inside one of the three types of evaluated areas (Integral Protection Sustainable Use Conservation Units and Damping Zone), clearly showing the development of the illegal activity, as defined in terms of the National System of Conservation Units. If deforestation is considered in this analysis, the area increases to about 6110 km2, representing more than 5.2% of the Conservation Units. In addition, we proposed the creation of the Mining Pressure Index (MPI), which allows classifying a Conservation Unit by the degree of pressure from mining activities. The proposed index revealed to be very efficient since it predicted high values over Conservation Units where it was expected a greater vulnerability. The index is a promising tool for public policy formulation and management of protected areas, as well as for enforcement action. The results provide a new horizon in terms of the perspective of importance and applicability of geotechnologies in the evaluation of environmental impacts, not restricted to mining activity.

Distal 22q11.2 microduplication combined with typical 22q11.2 proximal deletion: a case report.

The 22q11 chromosomal region contains low copy repeats (LCRs) sequences that mediate non-allelic homologous recombination, which predisposes to copy number variations (CNVs) at this locus. Hemizygous deletions of the proximal 22q11.2 region result in the 22q11.2 deletion syndrome (22q11.2 DS). In addition, 22q11.2 duplications involving the distal LCR22s have been reported. This article describes a patient presenting a 2.5-Mb de novo deletion at proximal 22q11.21 region (between LCRs A-D), combined with a 1.3-Mb maternally inherited duplication at distal 22q11.23 region (between LCRs F-H). The presence of concomitant chromosomal imbalances found in this patient has not been reported previously. Clinical and molecular data were compared with literature, in order to contribute to genotype-phenotype correlation. These findings exemplify the complexity and genetic heterogeneity observed in 22q11.2 deletion syndrome and highlights the difficulty to make genetic counseling and predict phenotypic consequences in these situations.

Use of Cracker Residue in the Diet of Dairy Heifers: Impacts on Animal Health, Ruminal Fatty Acids Profile, Digestibility, Weight Gain, and Economic Viability.

This study determined whether the isomeric or isoenergetic/isoproteic substitution of corn in the diet of Jersey heifers in the rearing phase with cracker residue would impair growth and health, as well as reducing production costs. Fourteen Jersey females in the growth phase were used, separated into two treatments with seven animals in each lot in collective pens. The experiment used 7-month-old animals (169.8 ± 2.89 kg) and lasted for four months. In Experiment I, the animals were divided into two groups: treatment, with the partial replacement of 40% corn with cracker residue, and control, in which the animals consumed the same diet with 100% corn (isometric diet kg for kg). In Experiment II, the animals with a body weight of 200.2 ± 3.85 kg were divided into two groups: Treatment, replacing 100% of the corn with cracker residue, and control, in which the animals consumed an isoprotein and isoenergetic diet but with 100% of the corn in the formulation. The diet consisted of concentrate, Tifton 85 hay, and corn silage, supplied twice a day individually, with animals contained in their feeders by kennels. There was water ad libitum in the bay. Biweekly weighing and monthly blood analysis were performed, totaling four collections per part for hematologic evaluation, carbohydrate, lipid, and protein metabolism variables. At the end of each experiment, ruminal fluid was collected to measure the volatile fatty acid profile, and feces were collected to determine the apparent digestibility coefficient (ADC). Experiments I and II showed no effect of treatment on body weight, weight gain, average daily weight gain, feed intake, and feed efficiency. There was no effect of treatment on leukocyte, erythrocyte, lymphocyte, neutrophil, monocyte, and eosinophil counts, hematocrit, and hemoglobin concentration (p > 0.05). Experiment I showed a difference between groups for the variables albumin, globulin, total proteins, cholesterol, glucose, and urea, which did not happen in Experiment II. In both experiments, a higher ADC of nutrients was found in the treatment group which had cracker residue (p > 0.05). The concentration of volatile fatty acids in Experiment I was higher in the control group, unlike in Experiment II, where the highest concentration was in the treatment group (p > 0.05). Because experiment I had an isometric substitution, the diets had different bromatological composition, which is the probable cause of the difference between groups; this did not happen in experiment II, in which the diets consumed by the animals was isoproteic and isoenergetic. Based on these data we conclude that the substitution of cracker residue in an isomeric or isoenergetic/isoproteic form does not negatively affect weight gain and animal health, as well as reduces the cost of the concentrate, consequently reducing the cost of production of these animals.

Access to genetic evaluation of 1463 individuals with orofacial cleft in Brazil.

OBJECTIVE: The current study delves into the accessibility of genetic evaluations for individuals with orofacial clefts (OC), comparing data between genetics and treatment centers across Brazil. METHODS: This cross-sectional retrospective study analyzed primary data from 1463 OC individuals registered in the Brazilian Database of Craniofacial Anomalies (BDCA) between 2008 and 2018 without age or sex selection. Diagnostic exam results stemming from research projects until 2023 were considered. RESULTS: Of the 1463 individuals with typical OC, 987 were non-syndromic, 462 were syndromic (SOC), 10 presented atypical forms, and three were not specified OC cases. The average age for accessing laboratory diagnosis was 8.5 years among SOC individuals. Notably, more SOC cases were registered in genetics centers than treatment and rehabilitation centers (37.1 % vs. 29 %, p = 0.0015). Those originating from genetics centers accessed diagnosis at an average age of 7.3 years, while those from treatment and rehabilitation centers experienced delays with an average age of 10.7 years (p = 0.0581). CONCLUSIONS: Irrespective of the center of origin, the data highlight delayed diagnosis and challenges in accessing genetic tests for the syndromic group. Given the widespread reliance on the public health system by most of the Brazilian population, disseminating this data can significantly contribute to shaping an informed perspective on healthcare access. These insights can improve public policies tailored to the unique needs of individuals with OC.

22q11.2 Deletion Syndrome: Influence of Parental Origin on Clinical Heterogeneity.

22q11.2 deletion syndrome (22q11.2DS) shows significant clinical heterogeneity. This study aimed to explore the association between clinical heterogeneity in 22q11.2DS and the parental origin of the deletion. The parental origin of the deletion was determined for 61 individuals with 22q11.2DS by genotyping DNA microsatellite markers and single-nucleotide polymorphisms (SNPs). Among the 61 individuals, 29 (47.5%) had a maternal origin of the deletion, and 32 (52.5%) a paternal origin. Comparison of the frequency of the main clinical features between individuals with deletions of maternal or paternal origin showed no statistically significant difference. However, Truncus arteriosus, pulmonary atresia, seizures, and scoliosis were only found in patients with deletions of maternal origin. Also, a slight difference in the frequency of other clinical features between groups of maternal or paternal origin was noted, including congenital heart disease, endocrinological alterations, and genitourinary abnormalities, all of them more common in patients with deletions of maternal origin. Although parental origin of the deletion does not seem to contribute to the phenotypic variability of most clinical signs observed in 22q11.2DS, these findings suggest that patients with deletions of maternal origin could have a more severe phenotype. Further studies with larger samples focusing on these specific features could corroborate these findings.

Percutaneous ablation of functioning adrenal adenoma: a report on 11 cases and a review of the literature.

PURPOSE: Percutaneous ablation of functioning adrenal adenomas has been an alternative to videolaparoscopic treatment. This study aimed to evaluate the feasibility, safety and efficacy of radiofrequency ablation (RFA) in the treatment of functioning adrenal tumors using a computed tomography (CT)-guided percutaneous technique as demonstrated by our experience and the literature. METHODS: Eleven adult patients (mean age 46 years) with a diagnosis of functioning adrenal adenoma underwent CT-guided RFA between October 2011 and August 2012. All RFA procedures were performed using a needle electrode with a single lateral filament and the RITA(®) 1500X radiofrequency generator. The RFA protocol consisted of two cycles of 5 min each with 1-min interval, with no additional ablation cycles. Contrast-enhanced CT scans were obtained and analyzed for immediate treatment success and possible complications. RESULTS: Maximum tumor dimension ranged from 1.2 to 3.4 cm. The mean procedure time was 74 min, and length of hospital stay ranged from 0.9 to 3.2 days (mean 1.8 days). One patient had residual pneumothorax and one patient had neuritis involving the T10 dermatome. Of 11 patients, 10 recovered from their condition. Only one patient remained with hyperaldosteronism, but with reduced anti-hypertensive medication. CONCLUSIONS: CT-guided percutaneous RFA was a safe and effective treatment for functioning adrenal adenomas, with short hospital length of stay and low complication rate.

Feeding Infants With Cleft Lip and/or Palate in Brazil: Suggestions to Improve Health Policy and Research.

Objective : To verify feeding resources used prior to corrective surgery among cleft babies from Brazil and to discuss suggestions to improve common feeding problems around the world. Design : Cross-sectional descriptive study conducted at eight medical centers. Participants : A total of 215 parents or guardians of cleft children. Methods : Interview based upon a prevalidated questionnaire. The chi-square test and comparison of means by analysis of variance were used; significance level adopted was 5% (P < .05). Results : Feeding guidelines were provided in the maternity unit to 53% of the families. Breast-feeding was encouraged among 80% of mothers, predominantly in the South (P = .016). However, follow-up after maternity discharge was not appropriately carried out and failure to breast-feed occurred in 78% of families. The feeding tube was used in 21%. According to families, for those who used the ordinary nipple, it was considered the best option by the majority (29%). Conclusion : Neonatal feeding in cleft babies is a global challenge. Reports about the difficulties encountered and successful experiences would be helpful to disseminate strategies and stimulate research directed at the large-scale applicability of neonatal feeding for cleft babies on public health. This study detected the need to increase professional training and emphasizes the need for public policies addressing neonatal referral to specialized care wherever possible. It also stimulates research into using an ordinary nipple as another resource for feeding cleft babies and suggests an international discussion about specific recommendations for humanized primary health care.

Performance of preschool and schoolchildren on the ProNOH protocol: macrostructure aspects. / Desempenho de pré-escolares e escolares no protocolo ProNOH: aspectos macroestruturais.

PURPOSE: To investigate if the narrative score of the ProNOH protocol allows for discriminating age groups, as well as its relation with the global coherence level of the story. The performance of preschool and schoolchildren on the macrostructure aspects. METHODS: Participants were 97 preschoolers and schoolchildren with typical language development, aged between five and 12 years old, and both sexes who attended public schools. The "Protocolo de Avaliação da Narrativa Oral de História (ProNOH)" (Protocol for the Evaluation of Oral Storytelling) was applied and the narrative score in the macrostructure dimension was calculated with story grammar elements. These same story elements were used to obtain the global coherence level of the story, as proposed by Spinillo and Martins (1997). RESULTS: A statistically significant difference was found between age groups, mainly between the borderline ages of 5-6 years, 7-8 years, 9-10 years, and 11-12 years. Positive and statistically significant correlations were found between the narrative score and global coherence and age, as well as between the narrative score and global coherence. CONCLUSION: The protocol proved to be useful for identifying the repertoire of typical story grammar elements as an objective measure that differs in oral narrative across age groups. The results also indicate that the narrative score can provide an idea about the global coherence of the story, although this value does not replace a specific analysis.

OBJETIVO: Investigar se o escore narrativo obtido por meio da aplicação do "Protocolo de Avaliação da Narrativa Oral de História (ProNOH)" permite discriminar os grupos etários estudados, bem como sua relação com o nível de coerência global da história. MÉTODO: Participaram 97 pré-escolares e escolares com desenvolvimento típico de linguagem, entre 5 e 12 anos, ambos os sexos que frequentavam escola pública. Foi aplicado o "Protocolo de Avaliação da Narrativa Oral de História (ProNOH)" e calculado o escore narrativo na dimensão macroestrutural a partir dos elementos estruturais previstos no modelo da gramática de história. Esses mesmos elementos foram usados para obter o nível de coerência global da história, segundo proposta de análise de Spinillo e Martins (1997). RESULTADOS: Diferença estatisticamente significante foi encontrada entre os grupos etários, principalmente entre as idades fronteiriças de 5-6 anos, 7-8 anos, 9-10 anos e 11-12 anos. Correlação positiva e estatisticamente significante foi encontrada com a idade e o escore narrativo e a coerência global, bem como entre o escore narrativo e o nível de coerência global. CONCLUSÃO: O protocolo mostrou ser útil para identificar o repertório de elementos típicos da gramática de história na narrativa oral como uma medida objetiva que diferenciou a narrativa oral de grupos etários. Os resultados indicaram ainda que o escore narrativo pode ser uma medida norteadora do nível de coerência da história, apesar deste valor não substituir uma análise específica.

Textural properties of microglial activation in Alzheimer's disease as measured by (R)-[11C]PK11195 PET.

Alzheimer's disease is the most common form of dementia worldwide, accounting for 60-70% of diagnosed cases. According to the current understanding of molecular pathogenesis, the main hallmarks of this disease are the abnormal accumulation of amyloid plaques and neurofibrillary tangles. Therefore, biomarkers reflecting these underlying biological mechanisms are recognized as valid tools for an early diagnosis of Alzheimer's disease. Inflammatory mechanisms, such as microglial activation, are known to be involved in Alzheimer's disease onset and progression. This activated state of the microglia is associated with increased expression of the translocator protein 18 kDa. On that account, PET tracers capable of measuring this signature, such as (R)-[11C]PK11195, might be instrumental in assessing the state and evolution of Alzheimer's disease. This study aims to investigate the potential of Gray Level Co-occurrence Matrix-based textural parameters as an alternative to conventional quantification using kinetic models in (R)-[11C]PK11195 PET images. To achieve this goal, kinetic and textural parameters were computed on (R)-[11C]PK11195 PET images of 19 patients with an early diagnosis of Alzheimer's disease and 21 healthy controls and submitted separately to classification using a linear support vector machine. The classifier built using the textural parameters showed no inferior performance compared to the classical kinetic approach, yielding a slightly larger classification accuracy (accuracy of 0.7000, sensitivity of 0.6957, specificity of 0.7059 and balanced accuracy of 0.6967). In conclusion, our results support the notion that textural parameters may be an alternative to conventional quantification using kinetic models in (R)-[11C]PK11195 PET images. The proposed quantification method makes it possible to use simpler scanning procedures, which increase patient comfort and convenience. We further speculate that textural parameters may also provide an alternative to kinetic analysis in (R)-[11C]PK11195 PET neuroimaging studies involving other neurodegenerative disorders. Finally, we recognize that the potential role of this tracer is not in diagnosis but rather in the assessment and progression of the diffuse and dynamic distribution of inflammatory cell density in this disorder as a promising therapeutic target.

Craniofacial microsomia: Reflections on diagnosis and severity assessment based on a series of cases.

This study aims to discuss diagnostic criteria and severity assessment for craniofacial microsomia (CFM). A series of 61 patients with diverse CFM phenotypes had their clinical data collected by experienced dysmorphologists using a single protocol. Genetic abnormalities were searched through karyotype and chromosomal microarray analysis. Sex ratio, prenatal risk factors, and recurrence rate corroborated the literature. Despite the wide variability of clinical findings, ear disruption was universal. Eight patients were assigned as syndromic, four of whom had demonstrable genetic alterations. The majority of patients (67.2%) fulfilled four known diagnostic criteria, while 9.8% fulfilled one of them. Data strengthened disruptions of the ear and deafness as a semiotically valuable sign in CFM. Facial impairment should consider asymmetry as a mild expression of microsomia. Spinal and cardiac anomalies, microcephaly, and developmental delay were prevalent among extra craniofacial features and should be screened before planning treatment and follow up. The severity index was able to recognize the less and the most affected patients. However, it was not useful to support therapeutic decisions and prognosis in the clinical scenario due to syndromic and non-syndromic phenotypes overlapping. These issues make contemporary the debate on diagnostic methods and disease severity assessment for CFM. They also impact care and etiopathogenetic studies.

Desempenho de pré-escolares e escolares no protocolo ProNOH: aspectos macroestruturais / Performance of preschool and schoolchildren on the ProNOH protocol: macrostructure aspects

RESUMO Objetivo Investigar se o escore narrativo obtido por meio da aplicação do "Protocolo de Avaliação da Narrativa Oral de História (ProNOH)" permite discriminar os grupos etários estudados, bem como sua relação com o nível de coerência global da história. Método Participaram 97 pré-escolares e escolares com desenvolvimento típico de linguagem, entre 5 e 12 anos, ambos os sexos que frequentavam escola pública. Foi aplicado o "Protocolo de Avaliação da Narrativa Oral de História (ProNOH)" e calculado o escore narrativo na dimensão macroestrutural a partir dos elementos estruturais previstos no modelo da gramática de história. Esses mesmos elementos foram usados para obter o nível de coerência global da história, segundo proposta de análise de Spinillo e Martins (1997). Resultados Diferença estatisticamente significante foi encontrada entre os grupos etários, principalmente entre as idades fronteiriças de 5-6 anos, 7-8 anos, 9-10 anos e 11-12 anos. Correlação positiva e estatisticamente significante foi encontrada com a idade e o escore narrativo e a coerência global, bem como entre o escore narrativo e o nível de coerência global. Conclusão O protocolo mostrou ser útil para identificar o repertório de elementos típicos da gramática de história na narrativa oral como uma medida objetiva que diferenciou a narrativa oral de grupos etários. Os resultados indicaram ainda que o escore narrativo pode ser uma medida norteadora do nível de coerência da história, apesar deste valor não substituir uma análise específica.

ABSTRACT Purpose To investigate if the narrative score of the ProNOH protocol allows for discriminating age groups, as well as its relation with the global coherence level of the story. The performance of preschool and schoolchildren on the macrostructure aspects. Methods Participants were 97 preschoolers and schoolchildren with typical language development, aged between five and 12 years old, and both sexes who attended public schools. The "Protocolo de Avaliação da Narrativa Oral de História (ProNOH)" (Protocol for the Evaluation of Oral Storytelling) was applied and the narrative score in the macrostructure dimension was calculated with story grammar elements. These same story elements were used to obtain the global coherence level of the story, as proposed by Spinillo and Martins (1997). Results A statistically significant difference was found between age groups, mainly between the borderline ages of 5-6 years, 7-8 years, 9-10 years, and 11-12 years. Positive and statistically significant correlations were found between the narrative score and global coherence and age, as well as between the narrative score and global coherence. Conclusion The protocol proved to be useful for identifying the repertoire of typical story grammar elements as an objective measure that differs in oral narrative across age groups. The results also indicate that the narrative score can provide an idea about the global coherence of the story, although this value does not replace a specific analysis.

Clinico-pathological discrepancies in the diagnoses of solid malignancies.

Autopsy is a valuable tool in evaluating diagnostic accuracy. Solid malignancies may have a protracted presentation, and diagnosis frequently requires imaging and deep-sited biopsies; clinical and postmortem diagnosis discrepancies may occur in a high rate in these diseases. Here, we analyzed the occurrence of clinico-pathological discrepancies in the diagnoses of solid malignancies in a Brazilian academic hospital. We reviewed charts and autopsy reports of the patients that died from 2001 to 2003 with at least one solid neoplasm. Patients were classified in concordant and discordant cases regarding cancer diagnosis. Discordant cases were categorized in undiagnosed cases (no suspicion of cancer) and in misdiagnosed cases (clinical suspicion of cancer but incompletely diagnosed). Among the 264 patients with a single non-incidental solid neoplasm, the clinico-pathological discrepancy rate was 37.1%. Liver (22.5%), lung (19.4%), and pancreatic cancer (15.3%) were the most frequent malignancies in the discordant group. Misdiagnosis category comprised 68% of the discordant cases, i.e., there was no correct knowledge about the tumor primary site and/or the histological type during life. Our data show that a high rate of discrepancies occurs in solid malignancies. Autopsies may provide the basis for a better understanding of diagnostic deficiencies in different circumstances.

Increased epidermal growth factor receptor gene copy number detected by fluorescence in situ hybridization associates with increased sensitivity to gefitinib in patients with bronchioloalveolar carcinoma subtypes: a Southwest Oncology Group Study.

PURPOSE: Bronchioloalveolar carcinoma (BAC) and adenocarcinomas with BAC features seem to be increasing in incidence, particularly in younger, never-smoking women. Epidermal growth factor receptor (EGFR) inhibitors demonstrated response rates of 20% to 30% in patients with advanced BAC subtypes, but selection methods for patient therapy are not established. PATIENTS AND METHODS: EGFR and HER2 gene copy numbers were assessed by fluorescence in situ hybridization (FISH) in 81 patients treated with gefitinib 500 mg/d (Southwest Oncology Group protocol S0126) and were correlated to treatment outcome. Tumors were classified into two main strata: FISH-positive (high polysomy/gene amplification) and FISH-negative (disomy/low polysomy). RESULTS: In 81 patients, the median survival time for EGFR/FISH-negative patients was 8 months and not yet reached for FISH-positive patients (but approaching 18 months; hazard ratio [HR] = 2.02; P = .042). Median progression-free survival time for EGFR/FISH-positive patients was 9 months versus 4 months for the FISH-negative patients (HR = 1.67; P = .072). In multivariate analysis, EGFR copy number by FISH remained a significant predictive factor for survival after accounting for smoking status, sex, histology, and performance status. Fifty-five patients were evaluated for response using Response Evaluation Criteria in Solid Tumors Group, and 12 of 19 EGFR/FISH-positive patients (63%) demonstrated disease control versus 14 (39%) of 36 patients in the FISH-negative group (P = .087). No association was found between HER2 gene copy number and response (n = 39 patients) or survival (n = 56 patients; P > .10). CONCLUSION: Increased EGFR gene copy number detected by FISH is associated with improved survival after gefitinib therapy in patients with advanced BAC, suggesting FISH methodology can be used to assess survival potential in patients treated with EGFR tyrosine kinase inhibitors.

Age-Related Changes in the Synaptic Density of Amyloid-ß Protein Precursor and Secretases in the Human Cerebral Cortex.

Amyloid-ß protein precursor (AßPP) is involved in synaptic formation and function. In the human cingulate cortex, AßPP was preferentially located in the presynaptic active zone as in rodents, indicating a preserved subsynaptic AßPP distribution across species and brain regions. Synaptic AßPP immunoreactivity was decreased with aging in cortical samples collected from autopsies of males (20-80 years), whereas the synaptic levels of α-secretase (ADAM10) and ß-secretase (BACE1) did not significantly change. Decreased AßPP levels may be related to lower allostasis of synapses in the aged brain and their greater susceptibility to dysfunction characteristic of the onset of neurodegenerative disorders.