Sternohyoid or sternocleidomastoid muscle flap for tracheoesophageal puncture closure in irradiated patients: A CARE case series.

INTRODUCTION: A novel technique for tracheoesophageal puncture (TEP) closure is described in which the sternohyoid muscles are rotated and interposed between the tracheal and esophageal walls. The results of this technique are reported, following CARE guidelines, and compared with those obtained using the sternocleidomastoid flap. A literature review on the techniques previously described for TEP closure in irradiated patients is presented. CASE SERIES: The novel technique was performed in six patients in whom the infrahyoid muscles were preserved during total laryngectomy. All received adjuvant radiotherapy. Successful closure was achieved in three cases; in one case a small leak was noted after initial closure and was successfully managed with simple sutures; and the other two failures occurred in patients with diabetes. The sternocleidomastoid flap was performed in five patients (only one with previous radiation) and success was achieved in two patients. In another patient a micro-fistular orifice appeared six months after the operation. DISCUSSION: The sternohyoid muscles pose a low morbidity alternative to be considered in surgical TEP closure. Patient selection is a key factor to surgical success, and this technique should be reserved for small to moderate size fistulas and in the absence of multiple impaired wound healing conditions.

Tumour microenvironment and pituitary tumour behaviour.

The pituitary tumour microenvironment encompasses a spectrum of non-tumoural cells, such as immune, stromal or endothelial cells, as well as enzymes and signalling peptides like cytokines, chemokines and growth factors, which surround the tumour cells and may influence pituitary tumour behaviour and tumourigenic mechanisms. Recently, there has been intensive research activity in this field describing various pituitary tumour-infiltrating immune and stromal cell subpopulations, and immune- and microenvironment-related pathways. Key changes in oncological therapeutic avenues resulted in the recognition of pituitary as a target of adverse events for patients treated with immune checkpoint regulators. However, these phenomena can be turned into therapeutic advantage in severe cases of pituitary tumours. Therefore, unravelling the pituitary tumour microenvironment will allow a better understanding of the biology and behaviour of pituitary tumours and may provide further developments in terms of diagnosis and management of patients with aggressively growing or recurrent pituitary tumours.

Features of lumbar spine texture extracted from routine MRI correlate with bone mineral density and can potentially differentiate patients with and without fragility fractures in the spine.

The use of routine magnetic resonance imaging (MRI) to potentially assess skeletal fragility has been widely studied in osteoporosis. The aim of this study was to evaluate bone texture attributes (TA) from routine lumbar spine (LS) MRI and their correlation with vertebral fragility fractures (VFF) and bone mineral density (BMD). Sixty-four post-menopausal women were submitted to LS densitometry, total spine radiographs, and routine T2-weighted LS MRI. Twenty-two TA were extracted with the platform IBEX from L3 vertebra. The statistical difference was evaluated using ANOVA and Duncan's post-test. Correlation analyses were performed using Spearman's coefficient. Statistical significance was considered when P<0.05. The results did not show a significant difference in BMD between the women with and without fractures. Two bone TA (cluster tendency and variance) were significantly lower in the fracture group. Cluster tendency with VFF in osteopenia was 1.54±1.37 and in osteoporosis was 1.11±58. Cluster tendency without VFF in osteopenia was 2.23±1.38 and in osteoporosis was 1.88±1.14). Variance with VFF in osteopenia was 1.44±1.37 and in osteoporosis was 1.13±59. Variance without VFF in osteopenia was 2.34±1.38 and in osteoporosis was 1.89±1.14. There was a significant correlation between BMD and cluster prominence (r=0.409), cluster tendency (r=0.345), correlation (r=0.570), entropy (r=0.364), information measure corr1 (r=0.378), inverse variance (r=0.449), sum entropy (r=0.320), variance (r=0.338), sum average (r=-0.274), and sum variance (r=-0.266). Our results demonstrated the potential use of TA extracted from routine MRI as a biomarker to assess osteoporosis and identify the tendency of skeletal fragility vertebral fractures.

Associations between self-reported sleep quality and cerebrospinal fluid biomarkers in mild cognitive impairment and Alzheimer's disease.

Sleep disorders are very common in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Several parameters of polysomnography seem to correlate with cognitive scores and amyloid biomarkers in the different stages of AD. However, there is limited evidence for the relationship between self-reported sleep impairment and disease biomarkers. In this study, we assessed the relationship between self-reported sleep complaints, with the Pittsburgh Sleep Quality Index, and both cognitive function and cerebrospinal fluid biomarkers in 70 patients with MCI and 78 patients with AD. Sleep duration and daytime dysfunction were higher in AD. Daytime dysfunction had a negative correlation with cognitive scores (Mini-Mental-State Examination and Montreal Cognitive Assessment) and with amyloid-beta1-42 protein, and a positive correlation with total tau protein. However, daytime dysfunction was an independent predictor only of t-tau values (F=57.162; 95% CI: [18.118; 96.207], P=0.004). These findings support a relationship between daytime dysfunction, cognitive scores and neurodegeneration, further expanding recent findings that it may signal a risk of dementia.

Features of lumbar spine texture extracted from routine MRI correlate with bone mineral density and can potentially differentiate patients with and without fragility fractures in the spine

The use of routine magnetic resonance imaging (MRI) to potentially assess skeletal fragility has been widely studied in osteoporosis. The aim of this study was to evaluate bone texture attributes (TA) from routine lumbar spine (LS) MRI and their correlation with vertebral fragility fractures (VFF) and bone mineral density (BMD). Sixty-four post-menopausal women were submitted to LS densitometry, total spine radiographs, and routine T2-weighted LS MRI. Twenty-two TA were extracted with the platform IBEX from L3 vertebra. The statistical difference was evaluated using ANOVA and Duncan's post-test. Correlation analyses were performed using Spearman's coefficient. Statistical significance was considered when P<0.05. The results did not show a significant difference in BMD between the women with and without fractures. Two bone TA (cluster tendency and variance) were significantly lower in the fracture group. Cluster tendency with VFF in osteopenia was 1.54±1.37 and in osteoporosis was 1.11±58. Cluster tendency without VFF in osteopenia was 2.23±1.38 and in osteoporosis was 1.88±1.14). Variance with VFF in osteopenia was 1.44±1.37 and in osteoporosis was 1.13±59. Variance without VFF in osteopenia was 2.34±1.38 and in osteoporosis was 1.89±1.14. There was a significant correlation between BMD and cluster prominence (r=0.409), cluster tendency (r=0.345), correlation (r=0.570), entropy (r=0.364), information measure corr1 (r=0.378), inverse variance (r=0.449), sum entropy (r=0.320), variance (r=0.338), sum average (r=-0.274), and sum variance (r=-0.266). Our results demonstrated the potential use of TA extracted from routine MRI as a biomarker to assess osteoporosis and identify the tendency of skeletal fragility vertebral fractures.

SCREENER, an educational game for teaching the Drug Discovery and Development process.

Although the use of games as an educational strategy is an important current trend, there is practically no option available for training people on the Drug Discovery and Development (DDD) process. To fill this gap, we designed "SCREENER", a science game that is intended to be educational, but also challenging and interesting enough to ensure player engagement. Our main target audience is students of postgraduate programs in pharmacology, medicinal chemistry, pharmacy, and medicine. This game could also be of interest to the pharmaceutical industry and regulatory and patent agencies for training new employees. We discuss the creation of SCREENER, a hybrid of board and card games, and present its components with some examples of cards and resources, as well as the dynamics of the game. SCREENER mimics the process of drug discovery and development from validating a target to registering the new drug with the regulatory agency, and can be played individually (self-learning) or with the help of a monitor who assists up to six players/teams. Briefly, 29 task cards categorized in four major areas (efficacy, safety, pharmacokinetics, and pharmaceutical development) must be purchased sequentially. Classic characteristics of games such as decision making and challenge have been incorporated. More in-depth information on the tasks and technical terms is available through QR codes. The vagaries of the DDD process are mimicked by the bonus/setback cards. The evaluation of our first test with students is presented and supports the usefulness of this new tool.

Anabolic steroids and their effects of on neuronal density in cortical areas and hippocampus of mice / Esteroides anabolizantes e seus efeitos na densidade neuronal em áreas corticais e no hipocampo de camundongos

Abstract Anabolic substances have been increasingly used by bodybuilders and athletes with the goal of improving performance and aesthetics. However, this practice has caused some concern to physicians and researchers because of unknowledge of consequences that the indiscriminate and illicit use of these substances can cause. Thus, this study analyzed the effects of two commercially available anabolic steroids (AS), Winstrol Depot® (Stanozolol) and Deposteron® (Testosterone Cypionate), in the neuronal density of limbic, motor and sensory regions on the cerebral cortex and in CA1, CA2, CA3 regions of the hippocampus. A total of 60 Swiss mice were used (30 males and 30 females), separated into three groups: control and two experimental groups, which received the AAS. From each brain, homotypic and semi-serial samples were taken in frontal sections from areas established for the study. The results showed that females treated with testosterone cypionate presented a reduction in all regions tested and the ones treated with Stanozolol showed a decrease in some hippocampal areas. Regarding male animals, stanozolol led to a decrease in neuron number in one hippocampal region. These data allow us to conclude that supra-physiological doses of steroids used in this study, can cause considerable damage to nervous tissue with ultrastructural and consequently behavioral impairment. These changes could interfere with the loss of physical yield and performance of athletes and non-athletes and may cause irreparable damage to individuals making irresponsible use of anabolic steroids.

Resumo As substancias anabólicas tem sido cada vez mais utilizadas por fisiculturistas e atletas com o objetivo de melhorar o desempenho e a estética. No entanto, essa prática tem causado algumas preocupações aos médicos e pesquisadores, devido ao desconhecimento das consequencias que o uso indiscriminado e ilícito dessas substâncias podem causar. Diante disso, este estudo analisou os efeitos de dois esteroides anabolizantes (EA) comercialmente disponíveis, Winstrol Depot® (Stanozolol) e Deposteron® (cipionato de testosterona), na densidade neuronal das regiões corticais límbica, motora e sensitive bem como das áreas CA1, CA2, CA3 do hipocampo. Foram utilizados 60 camundongos Swiss (30 machos e 30 fêmeas), separados em três grupos: controle e dois grupos experimentais, que receberam o EA. De cada cérebro, foram coletadas amostras homotípicas e semi-seriadas em cortes frontais das áreas estabelecidas para o estudo. Os resultados mostraram que as fêmeas tratadas com cipionato de testosterona apresentaram uma redução em todas as regiões analisadas já as fêmeas tratadas com Stanozolol mostraram uma diminuição em algumas áreas do hipocampo. Em relação aos animais machos, o stanozolol levou a uma diminuição na densidade neuronal em uma região do hipocampo. Estes dados nos permitem concluir que doses supra fisiológicas de esteroides utilizadas neste estudo podem causar danos consideráveis ao tecido nervoso com comprometimento ultraestrutural e consequentemente comportamental. Essas alterações podem interferir na perda de rendimento físico e no desempenho de atletas e não atletas e podem causar danos irreparáveis a indivíduos que fazem uso irresponsável destes EA.

Femtosecond laser micromachining of an optofluidics-based monolithic whispering-gallery mode resonator coupled to a suspended waveguide.

A monolithic lab-on-a-chip fabricated by femtosecond laser micromachining capable of label-free biosensing is reported. The device is entirely made of fused silica, and consists of a microdisk resonator integrated inside a microfluidic channel. Whispering gallery modes are excited by the evanescent field of a circular suspended waveguide, also incorporated within the channel. Thermal annealing is performed to decrease the surface roughness of the microstructures to a nanometric scale, thereby reducing intrinsic losses and maximizing the Q-factor. Further, thermally-induced morphing is used to position, with submicrometric precision, the suspended waveguide tangent to the microresonator to enhance the spatial overlap between the evanescent field of both optical modes. With this fabrication method and geometry, the alignment between the waveguide and the resonator is robust and guaranteed at all instances. A maximum sensitivity of 121.5 nm/RIU was obtained at a refractive index of 1.363, whereas near the refractive index range of water-based solutions the sensitivity is 40 nm/RIU. A high Q-factor of 105 is kept throughout the entire measurement range.

Human amylin aggregates release within exosomes as a protective mechanism in pancreatic ß cells: Pancreatic ß-hippocampal cell communication.

Pancreatic ß cells are essential in the maintenance of glucose homeostasis during the progression to type 2 Diabetes Mellitus (T2DM), generating compensatory hyperinsulinemia to counteract insulin resistance. It is well known, that throughout the process there is an increased mTORC1 signaling pathway, with an impairment in different quality control systems including ubiquitin-proteasome system and autophagy. In addition, under this situation, pancreatic ß cells start to accumulate amylin protein (IAPP) in aggregates, and this accumulation contributes to the failure of autophagy, damaging different organelles such as plasma membrane, endoplasmic reticulum, mitochondria, and others. Here, we report that IAPP can be incorporated to multivesicular bodies (MVB) and secreted into exosomes, a mechanism responsible for the exportation of these toxic aggregates as vehicles of cell to cell communication. On this regard, we have demonstrated that the exosomes bearing toxic hIAPP released from pancreatic ß cells are capable to induce hyperactivation of mTORC1 signaling, a failure in the autophagic cellular quality control, and favor pro-fission status of the mitochondrial dynamics in hippocampal cells. In summary, our results show that harmful accumulation of hIAPP in pancreatic ß cells may be detoxified by the release of exosomes, which may be captured by endocytosis mechanism damaging neuronal hippocampal cells, which suggest an underlying molecular mechanism to the link between type 2 diabetes and neurodegenerative diseases.

Anabolic steroids and their effects of on neuronal density in cortical areas and hippocampus of mice.

Anabolic substances have been increasingly used by bodybuilders and athletes with the goal of improving performance and aesthetics. However, this practice has caused some concern to physicians and researchers because of unknowledge of consequences that the indiscriminate and illicit use of these substances can cause. Thus, this study analyzed the effects of two commercially available anabolic steroids (AS), Winstrol Depot® (Stanozolol) and Deposteron® (Testosterone Cypionate), in the neuronal density of limbic, motor and sensory regions on the cerebral cortex and in CA1, CA2, CA3 regions of the hippocampus. A total of 60 Swiss mice were used (30 males and 30 females), separated into three groups: control and two experimental groups, which received the AAS. From each brain, homotypic and semi-serial samples were taken in frontal sections from areas established for the study. The results showed that females treated with testosterone cypionate presented a reduction in all regions tested and the ones treated with Stanozolol showed a decrease in some hippocampal areas. Regarding male animals, stanozolol led to a decrease in neuron number in one hippocampal region. These data allow us to conclude that supra-physiological doses of steroids used in this study, can cause considerable damage to nervous tissue with ultrastructural and consequently behavioral impairment. These changes could interfere with the loss of physical yield and performance of athletes and non-athletes and may cause irreparable damage to individuals making irresponsible use of anabolic steroids.

SCREENER, an educational game for teaching the Drug Discovery and Development process

Although the use of games as an educational strategy is an important current trend, there is practically no option available for training people on the Drug Discovery and Development (DDD) process. To fill this gap, we designed "SCREENER", a science game that is intended to be educational, but also challenging and interesting enough to ensure player engagement. Our main target audience is students of postgraduate programs in pharmacology, medicinal chemistry, pharmacy, and medicine. This game could also be of interest to the pharmaceutical industry and regulatory and patent agencies for training new employees. We discuss the creation of SCREENER, a hybrid of board and card games, and present its components with some examples of cards and resources, as well as the dynamics of the game. SCREENER mimics the process of drug discovery and development from validating a target to registering the new drug with the regulatory agency, and can be played individually (self-learning) or with the help of a monitor who assists up to six players/teams. Briefly, 29 task cards categorized in four major areas (efficacy, safety, pharmacokinetics, and pharmaceutical development) must be purchased sequentially. Classic characteristics of games such as decision making and challenge have been incorporated. More in-depth information on the tasks and technical terms is available through QR codes. The vagaries of the DDD process are mimicked by the bonus/setback cards. The evaluation of our first test with students is presented and supports the usefulness of this new tool.

Electives in the medical curriculum - an opportunity to achieve students' satisfaction?

BACKGROUND: Electives are perceived by medical students as a valuable, highly regarded experience, allowing them to customize learning experiences and enabling them to early differentiate during medical training. The present work aims to uncover students' major determinants of satisfaction and how they interfere with their future elective choices in order to identify the best approach to implement electives in medical curricula. METHODS: A cross-sectional study was conducted through a written evaluation survey concerning the electives available in the academic year 2015-2016. Our institution provides 106 electives to students from the 2nd to the 5th year. Students' satisfaction was assessed through a validated questionnaire with eight sentences expressing opinions related to electives global satisfaction. Data from 538 inquiries from 229 students were analyzed quantitatively using regression and correlation models, and qualitatively through phenomenography. RESULTS: Quantitative analysis of the questionnaires allowed to establish both: 1) The determinants of students' satisfaction with electives, which were Agreement with teaching and learning methodologies, followed by Agreement with assessment methodologies employed, Perception of the workload demanded and Requirement for continuous work and 2) The predictors of students preferences in the following years, namely, Agreement with assessment methodologies employed, Classes attendance and Ranking of the allocated elective established in the previous year. Qualitative analysis of questionnaires revealed that students consider electives as being innovative and interesting, claiming that some, for their relevant content, could be integrated into the medical core curriculum. CONCLUSIONS: Our work raises awareness on the best practices when it comes to electives' organization to meet students' satisfaction. We can conclude that medical schools should measure students satisfaction as a tool to organize and predict future needs of electives and placements when designing and implementing this alternative student-centred curriculum or even to improve the existing practices regarding electives in medical courses.

Cognitive changes in patient living with HIV-AIDS and apolipoprotein-E polymorphism: is there an association?

Patients with HIV-AIDS treated with antiretroviral drugs still have high prevalence of cognitive disorders and many factors are likely to contribute for ongoing neurologic decline such as chronic low-level infection, coinfections with hepatitis B and C and genetic influences, both the virus and the host. Some evidences suggest that the genetic APOE polymorphism may be an associated risk factor. This study aimed to evaluate the association between APOE polymorphisms and cognitive disorders in patients with HIV-AIDS. This was a cross-sectional study comprising 133 patients aged 19-59 years old, with HIV-AIDS and were assisted at the infectious disease outpatient clinics at Hospital Universitário Oswaldo Cruz, in Recife, Brazil. For cognitive evaluation, Mini-Mental State Examination test (MMSE) and Montreal Cognitive Assessment test (MoCA) were used. The determination of APOE gene polymorphism was performed by using the PCR-RFLP technique. Sociodemographic and clinical characteristics were not significantly associated to APOE ε4 polymorphism, except for the high results of CD4 rate (p < 0.015). There was an absence associated between APOE ε4 polymorphism and neurocognitive tests. This study found no association between cognitive alterations and APOE polymorphism in patients with HIV-AIDS in the Northeast of Brazil. The imbalance of APOE allelic frequency distribution, according to Hardy-Weinberg law, there could be an adjustment phase of its equilibrium suffered by the HIV virus, however, the mechanism is still unknown.

Manual and semiautomatic segmentation of bone sarcomas on MRI have high similarity.

The aims of this study were to evaluate the intra- and interobserver reproducibility of manual segmentation of bone sarcomas in magnetic resonance imaging (MRI) studies and to compare manual and semiautomatic segmentation methods. This retrospective study included twelve osteosarcoma and eight Ewing sarcoma MRI studies performed prior to any therapeutic intervention. All cases were histopathologically confirmed. Three radiologists used 3D-Slicer software to perform manual segmentation of bone sarcomas in a blinded and independent manner. One radiologist segmented manually and also performed semiautomatic segmentation with the GrowCut tool. Segmentation exercises were timed for comparison. The dice similarity coefficient (DSC) and Hausdorff distance (HD) were used to evaluate similarity between the segmentation results and further statistical analyses were performed to compare DSC, HD, and volumetric results. Manual segmentation was reproducible with intraobserver DSC varying from 0.83 to 0.97 and HD from 3.37 to 28.73 mm. Interobserver DSC of manual segmentation showed variation from 0.73 to 0.97 and HD from 3.93 to 33.40 mm. Semiautomatic segmentation compared to manual segmentation resulted in DSCs of 0.71-0.96 and HDs of 5.38-31.54 mm. Semiautomatic segmentation required significantly less time compared to manual segmentation (P value ≤0.05). Among all situations compared, tumor volumetry did not show significant statistical differences (P value >0.05). We found excellent intra- and interobserver agreement for manual segmentation of osteosarcoma and Ewing sarcoma. There was high similarity between manual and semiautomatic segmentation, with a significant reduction of segmentation time using the semiautomatic method.

Manual and semiautomatic segmentation of bone sarcomas on MRI have high similarity

The aims of this study were to evaluate the intra- and interobserver reproducibility of manual segmentation of bone sarcomas in magnetic resonance imaging (MRI) studies and to compare manual and semiautomatic segmentation methods. This retrospective study included twelve osteosarcoma and eight Ewing sarcoma MRI studies performed prior to any therapeutic intervention. All cases were histopathologically confirmed. Three radiologists used 3D-Slicer software to perform manual segmentation of bone sarcomas in a blinded and independent manner. One radiologist segmented manually and also performed semiautomatic segmentation with the GrowCut tool. Segmentation exercises were timed for comparison. The dice similarity coefficient (DSC) and Hausdorff distance (HD) were used to evaluate similarity between the segmentation results and further statistical analyses were performed to compare DSC, HD, and volumetric results. Manual segmentation was reproducible with intraobserver DSC varying from 0.83 to 0.97 and HD from 3.37 to 28.73 mm. Interobserver DSC of manual segmentation showed variation from 0.73 to 0.97 and HD from 3.93 to 33.40 mm. Semiautomatic segmentation compared to manual segmentation resulted in DSCs of 0.71−0.96 and HDs of 5.38−31.54 mm. Semiautomatic segmentation required significantly less time compared to manual segmentation (P value ≤0.05). Among all situations compared, tumor volumetry did not show significant statistical differences (P value >0.05). We found excellent intra- and interobserver agreement for manual segmentation of osteosarcoma and Ewing sarcoma. There was high similarity between manual and semiautomatic segmentation, with a significant reduction of segmentation time using the semiautomatic method.

The SIGMA rat brain templates and atlases for multimodal MRI data analysis and visualization.

Preclinical imaging studies offer a unique access to the rat brain, allowing investigations that go beyond what is possible in human studies. Unfortunately, these techniques still suffer from a lack of dedicated and standardized neuroimaging tools, namely brain templates and descriptive atlases. Here, we present two rat brain MRI templates and their associated gray matter, white matter and cerebrospinal fluid probability maps, generated from ex vivo [Formula: see text]-weighted images (90 µm isotropic resolution) and in vivo T2-weighted images (150 µm isotropic resolution). In association with these templates, we also provide both anatomical and functional 3D brain atlases, respectively derived from the merging of the Waxholm and Tohoku atlases, and analysis of resting-state functional MRI data. Finally, we propose a complete set of preclinical MRI reference resources, compatible with common neuroimaging software, for the investigation of rat brain structures and functions.