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.

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.

Large heterogeneities in comet 67P as revealed by active pits from sinkhole collapse.

Pits have been observed on many cometary nuclei mapped by spacecraft. It has been argued that cometary pits are a signature of endogenic activity, rather than impact craters such as those on planetary and asteroid surfaces. Impact experiments and models cannot reproduce the shapes of most of the observed cometary pits, and the predicted collision rates imply that few of the pits are related to impacts. Alternative mechanisms like explosive activity have been suggested, but the driving process remains unknown. Here we report that pits on comet 67P/Churyumov-Gerasimenko are active, and probably created by a sinkhole process, possibly accompanied by outbursts. We argue that after formation, pits expand slowly in diameter, owing to sublimation-driven retreat of the walls. Therefore, pits characterize how eroded the surface is: a fresh cometary surface will have a ragged structure with many pits, while an evolved surface will look smoother. The size and spatial distribution of pits imply that large heterogeneities exist in the physical, structural or compositional properties of the first few hundred metres below the current nucleus surface.

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.

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.

The dynamics of stress: a longitudinal MRI study of rat brain structure and connectome.

Stress is a well-established trigger for a number of neuropsychiatric disorders, as it alters both structure and function of several brain regions and its networks. Herein, we conduct a longitudinal neuroimaging study to assess how a chronic unpredictable stress protocol impacts the structure of the rat brain and its functional connectome in both high and low responders to stress. Our results reveal the changes that stress triggers in the brain, with structural atrophy affecting key regions such as the prelimbic, cingulate, insular and retrosplenial, somatosensory, motor, auditory and perirhinal/entorhinal cortices, the hippocampus, the dorsomedial striatum, nucleus accumbens, the septum, the bed nucleus of the stria terminalis, the thalamus and several brain stem nuclei. These structural changes are associated with increasing functional connectivity within a network composed by these regions. Moreover, using a clustering based on endocrine and behavioural outcomes, animals were classified as high and low responders to stress. We reveal that susceptible animals (high responders) develop local atrophy of the ventral tegmental area and an increase in functional connectivity between this area and the thalamus, further spreading to other areas that link the cognitive system with the fight-or-flight system. Through a longitudinal approach we were able to establish two distinct patterns, with functional changes occurring during the exposure to stress, but with an inflection point after the first week of stress when more prominent changes were seen. Finally, our study revealed differences in functional connectivity in a brainstem-limbic network that distinguishes resistant and susceptible responders before any exposure to stress, providing the first potential imaging-based predictive biomarkers of an individual's resilience/vulnerability to stressful conditions.

Structural laterality is associated with cognitive and mood outcomes: An assessment of 105 healthy aged volunteers.

The human brain presents multiple asymmetries that dynamically change throughout life. These phenomena have been associated with cognitive impairments and psychiatric disorders although possible associations with specific patterns of cognitive aging are yet to be determined. We have therefore mapped and quantified morphological asymmetries in a heterogeneous and aged population (65.2±8.0 years old, 52 male and 53 female) to explore potential associations between the asymmetries in specific brain regions and cognitive performance. The sample was characterized in a battery of neuropsychological tests and in terms of brain structural asymmetries using a ROI-based approach. A substantial number of brain areas presented some degree of asymmetry. Such biases survived a stringent statistical correction and were largely confirmed in a voxel-based analysis. In specific brain areas, like the thalamus and insula, asymmetry was correlated with cognition and mood descriptors as the Stroop words/colors test or depressive mood scale, respectively. Curiously in the latter, the association was independent of its left/right direction. Altogether, results reveal that asymmetry is widespread in the aged brain and that area-specific biases (degree and direction) associate with the functional profile of the individual.

Do different tendons exhibit the same response following chronic exposure to statins?

Over the past few years, a number of cases of tendon injuries associated with statin therapy have been reported. In this study, we assessed whether statins can affect the extracellular matrix (ECM) of the deep digital flexor tendon (DDFT) and patellar tendon (PT). Wistar rats were assigned to groups treated with atorvastatin (A20, A80), treated with simvastatin (S20, S80), and control. Zymography, Western blotting for collagen I, non-collagenous proteins (NCP), glycosaminoglycans (GAGs), and hydroxyproline quantifications were performed. DDFT findings: NCP were increased in A20 and A80; higher concentration of hydroxyproline was found in S80; levels of GAGs was increased in all statin-treated groups; collagen I was increased in S80 and pro-MMP-2 activity was reduced in A80, S20, and S80. PT findings: NCP were reduced in A20, A80, and S80; GAGs was reduced in A80 and S20; collagen I was increased in A20 and pro-MMP-2 activity was reduced in the S20. Both the statins provoked marked changes in both tendons. All these changes may make the tendons more prone to microdamage and ruptures. Therefore, a better understanding of the behavior of the tendon ECM components under statin therapy may provide important insights into the mechanisms behind statin-induced tendon injuries.

Regular and moderate aerobic training before allergic asthma induction reduces lung inflammation and remodeling.

Experimental studies have reported that aerobic exercise after asthma induction reduces lung inflammation and remodeling. Nevertheless, no experimental study has analyzed whether regular/moderate aerobic training before the induction of allergic asthma may prevent these inflammatory and remodeling processes. For this purpose, BALB/c mice (n = 96) were assigned into non-trained and trained groups. Trained animals ran on a motorized treadmill at moderate intensity, 30 min/day, 3 times/week, for 8 weeks, and were further randomized into subgroups to undergo ovalbumin sensitization and challenge or receive saline using the same protocol. Aerobic training continued until the last challenge. Twenty-four hours after challenge, compared to non-trained animals, trained mice exhibited: (a) increased systolic output and left ventricular mass on echocardiography; (b) improved lung mechanics; (c) decreased smooth muscle actin expression and collagen fiber content in airways and lung parenchyma; (d) decreased transforming growth factor (TGF)-ß levels in bronchoalveolar lavage fluid (BALF) and blood; (e) increased interferon (IFN)-γ in BALF and interleukin (IL)-10 in blood; and (f) decreased IL-4 and IL-13 in BALF. In conclusion, regular/moderate aerobic training prior to allergic asthma induction reduced inflammation and remodeling, perhaps through increased IL-10 and IFN-γ in tandem with decreased Th2 cytokines.

Cytotoxic activity of Secondary Metabolites from Marine-derived Fungus Neosartorya siamensis in Human Cancer Cells.

Compounds isolated from the marine sea fan-derived fungus Neosartorya siamensis (KUFA 0017), namely, 2,4-dihydroxy-3-methylacetophenon (1), chevalone C (2), nortryptoquivaline (4), tryptoquivaline H (6), tryptoquivaline F (7), fiscalin A (8), epi-fiscalin A (9), epi-neofiscalin A (11) and epi-fiscalin C (13) were tested for anti-proliferative activity by MTT assay, DNA damage induction by comet assay, and induction of cell death by nuclear condensation assay on colon HCT116, liver HepG2 and melanoma A375 cancer cell lines. Compounds 2, 4, 8, 9, 11 and 13 presented IC50 values ranging from 24 to 153 µM in the selected cell lines. Cell death was induced in HCT116 by compounds 2, 4 and 8. In HepG2, compounds 4, 8, 9 and 11 were able to induce significant cell death. This induction of cell death is possibly not related to genotoxicity because none of the compounds induced significant DNA damage. These results suggest that selected compounds present an interesting anti-proliferative activity and cell death induction, consequently showing potential (specifically epi-fiscalin C) as future leads for chemotherapeutic agents. Further studies on mechanisms of action should ensue. Copyright © 2016 John Wiley & Sons, Ltd.

Clinico-biochemical characteristics of 229 Portuguese infertile women with polycystic ovary syndrome: clinical relevance and relationship with fertility treatment results.

PURPOSE: Polycystic ovary syndrome (PCOS) affects 6-20% of reproductive-age women. The authors aimed to evaluate the characteristics of PCOS women and its relationship with fertility treatment outcomes. MATERIALS AND METHODS: The authors reviewed records of PCOS women assisted at Hospital Santa Maria. Fertility treatment results were assessed as pregnancy rate, number of cycles, and miscarriage rate. RESULTS: They identified 229 PCOS women, 179 (78.2%) had waist circumference > 80 cm, 72 (31.4%) had type 2 diabetes mellitus (T2DM) familial history and glucose abnormalities, hypertriglyceridemia and low cholesterol-HDL were detected in 23(10.1%), 15 (6.6%) and 103 (45.0%), respectively. Pregnancy was achieved in 164 women. The mean number of cycles to achieve pregnancy was 2.7 (±2.2). Statistical analysis identified factors associated with longer/higher number of treatments: primary infertility, T2DM familial history, hypertriglyceridemia, and low cholesterol-HDL. Waist circumference > 80 cm, older age, and increased LH level were associated with miscarriage. CONCLUSIONS: Primary infertility, T2DM familial history, hypertriglyceridemia, low cholesterol-HDL, older age, waist circumference > 80 cm, and high LH may confer poorer fertility treatment results.

Diagnosis of the strongyloid nematode Strongyloides venezuelensis in experimentally infected rats.

Strongyloides venezuelensis is an intestinal nematode of rats, frequently used as a model for studying human and animal strongyloidiasis. In the present study, we evaluated parasitological, serological and molecular methods for the diagnosis of experimental S. venezuelensis in rats, Rattus norvegicus. Blood and faecal samples were collected and analysed up to 60 days post infection (pi) with adult worm recovery occurring from 5 to 45 days pi. Using an enzyme-linked immunosorbent assay (ELISA), serum levels of IgG antibodies increased up to 28 days pi, thereafter decreasing by day 60 pi. Polymerase chain reaction (PCR) assays detected S. venezuelensis DNA in faecal samples of rats from 5 to 21 days pi. The present study therefore represents the first step towards improving the diagnosis of experimental strongyloidiasis.

Odours stimulate neuronal activity in the dorsolateral area of the hippocampal formation during path integration.

The dorsolateral area of the hippocampal formation of birds is commonly assumed to play a central role in processing information needed for geographical positioning and homing. Previous work has interpreted odour-induced activity in this region as evidence for an 'olfactory map'. Here, we show, using c-Fos expression as a marker, that neuronal activation in the dorsolateral area of the hippocampal formation of pigeons is primarily a response to odour novelty, not to the spatial distribution of odour sources that would be necessary for an olfactory map. Pigeons exposed to odours had significantly more neurons activated in this area of the brain than pigeons exposed to filtered air with odours removed. This increased activity was observed only in response to unfamiliar odours. No change in activity was observed when pigeons were exposed to home odours. These findings are consistent with non-home odours activating non-olfactory components of the pigeon's navigation system. The pattern of neuronal activation in the triangular and dorsomedial areas of the hippocampal formation was, by contrast, consistent with the possibility that odours play a role in providing spatial information.

Triggering cell death by nanographene oxide mediated hyperthermia.

Graphene oxide (GO) has been proposed as an hyperthermia agent for anticancer therapies due to its near-infrared (NIR) optical absorption ability which, with its small two-dimensional size, could have a unique performance when compared to that of any other nanoparticle. Nevertheless, attention should be given to the hyperthermia route and the kind of GO-cell interactions induced in the process. The hyperthermia laser irradiation parameters, such as exposure time and laser power, were investigated to control the temperature rise and consequent damage in the GOs containing cell culture medium. The type of cell damage produced was evaluated as a function of these parameters. The results showed that cell culture temperature (after irradiating cells with internalized GO) increases preferentially with laser power rather than with exposure time. Moreover, when laser power is increased, necrosis is the preferential cell death leading to an increase of cytokine release to the medium.

Grazing behaviour of a non-herbivorous characin: revisiting plasticity.

Feeding behaviour and diet of Bryconamericus microcephalus differed between canopy conditions. At the open canopy site, a behavioural modification, grazing on algae, was observed. This was also reflected in gut content analysis and suggests behavioural plasticity in response to resource availability.

Wiki as a tool for microbiology teaching, learning and assessment.

INTRODUCTION: Evidence suggests that cooperative learning and peer-assessment fosters students' ability to work with others and may lead to better cognitive outcomes and higher achievement. This work aimed to assess the use of an online collaborative tool for the teaching/learning and assessment of Microbiology. MATERIALS AND METHODS: A total of 144 students were grouped and assigned to create wiki entries as well as to peer review wikis created by colleagues (peer-assessment process) using the Wiki module from Moodle Virtual Learning Environment (MVLE). MVLE actions log was used for tracking students' activity. RESULTS: The number of student's actions within wiki did not present a strong correlation with wiki scores, so it should not be used as a heavy evaluation parameter. The amount of work developed between members of the same group differed significantly, suggesting that final scores should be attributed individually. When peer-assessment process was implemented, the number of editing actions increased, suggesting that the peer-assessment strategy encourages the development of a better work. The vast majority of students execute the work in the last 10% of the period assigned for task development, which can be counter-productive for a truly collaborative work. CONCLUSIONS: Wiki revealed to be a useful tool for Microbiology teaching/learning and assessment, promoting collaborative work, promoting virtual mobility and facilitating the real-time monitoring of the students' work. This pedagogical project promoted also the involvement of students in their assessment process, encouraging their critical sense and quest for Excellency.

Periodontal inflammation in renal transplant recipients receiving everolimus or tacrolimus - preliminary results.

OBJECTIVE: To compare oral health status between renal transplant recipients (RTRs) receiving tacrolimus (Tac) or everolimus (ERL) as immunosuppressive therapy. DESIGN: This study is a cross-sectional study. METHODS: Thirty-six RTRs receiving Tac and 22 RTRs receiving ERL were included in the study. Age, gender, time since transplant and pharmacological data were recorded for both groups. Oral health status was assessed through the evaluation of teeth, periodontal parameters as well as saliva flow rate and pH. RESULTS: RTRs receiving ERL were older than those receiving Tac. No differences were found between groups concerning oral hygiene habits, oral symptoms, smoking habits, unstimulated and stimulated saliva flow rate and pH, clinical attachment level or the number of decayed, missing and filled teeth. However, RTRs receiving ERL presented lower visible plaque index and lower values for bleeding on probing when compared to RTRs receiving Tac. In addition, RTRs receiving ERL presented a gingival index varying from normal to moderate inflammation whereas RTRs receiving Tac presented a gingival index varying from mild to severe inflammation. CONCLUSIONS: RTRs receiving ERL have lower periodontal inflammation when compared to RTRs receiving Tac.

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.