A cross-sectional study of clinical, dermoscopic, histopathological, and molecular patterns of scalp melanoma in patients with or without androgenetic alopecia.

Scalp melanoma (SM) has a worse prognosis than melanoma in other locations likely because of late diagnosis due to hair coverage, difficulties in interpreting dermoscopy findings, and its unique molecular profile. We aimed to describe the clinical, histopathological, molecular, and dermoscopic patterns of SM and its relation to androgenetic alopecia/elastosis at the tumor site. Through a retrospective cross-sectional study, we identified all SM diagnosed at the A.C.Camargo Cancer Center between 2008 and 2018. In all, 48 SM were analyzed: 45.8% of which exhibited moderate/severe androgenetic alopecia and 54.1% exhibited elastosis. Androgenetic alopecia/elastosis at the site of the SM was associated with older age (p < 0.001), chronic sun damage (p < 0.001), lentigo maligna subtype (p = 0.029), and photodamaged dermoscopic pattern (p < 0.001). Additionally, 41 cases were evaluated with a 14-gene panel: 53.7% displayed mutations and 46.3% were wild-type. BRAF mutations were most common (77%), with BRAF V600K being more frequent (50%) than BRAF V600E (31.2%). The NF1 gene was evaluated in 40 samples, of which 20% exhibited mutations. SM presents differently in areas covered by hair compared to in areas with androgenetic alopecia. Patients without alopecia may have higher Breslow thickness due to late diagnosis because of hair concealment. The high frequency of detrimental mutations can also explain the poor prognosis of SM.

Nonparametric Bayesian Regression and Classification on Manifolds, With Applications to 3D Cochlear Shapes.

Advanced shape analysis studies such as regression and classification need to be performed on curved manifolds, where often, there is a lack of standard statistical formulations. To overcome these limitations, we introduce a novel machine-learning method on the shape space of curves that avoids direct inference on infinite-dimensional spaces and instead performs Bayesian inference with spherical Gaussian processes decomposition. As an application, we study the shape of the cochlear spiral-shaped cavity within the petrous part of the temporal bone. This problem is particularly challenging due to the relationship between shape and gender, especially in children. Experimental results for both synthetic and real data show improved performance compared to state-of-the-art methods.

Th17/Regulatory T cells ratio evolution: A prospective study in a group of healthy pregnant women.

During pregnancy, the maternal immune system is challenged to tolerate a semi-allogenic fetus. A shift toward a tolerogenic profile is essential to ensure a healthy fetal and placental development. One of the most important mechanisms involved in the maternal immune tolerance towards the fetal antigens is expressed in the activity of the regulatory T (Treg) and Th17 cells. The behavior and equilibrium of these two T lymphocyte populations were rarely studied in normal healthy pregnancies through the beginning of gestation to the postpartum period. We conducted a prospective longitudinal observational study where peripheral blood lymphocyte subsets were analyzed in each trimester of pregnancy and postpartum period in a group of healthy pregnant women. Our study observed a consistent reduction in peripheric Treg cell count through all pregnancy while the Th17 cell count remained stable. The Th17/Treg ratio increases significantly throughout pregnancy to the postpartum period. These changes could be justified by the migration of the immunotolerant Treg cells to the maternal decidua and lead to the establishment of a systemic pro-inflammatory profile by the end of pregnancy. This data could explain why systemic syndromes like preeclampsia develop in susceptible women during the second half of pregnancy or why many autoimmune disorders flourish in the first weeks postpartum.

Cochlear shape distinguishes southern African early hominin taxa with unique auditory ecologies.

Insights into potential differences among the bony labyrinths of Plio-Pleistocene hominins may inform their evolutionary histories and sensory ecologies. We use four recently-discovered bony labyrinths from the site of Kromdraai to significantly expand the sample for Paranthropus robustus. Diffeomorphometry, which provides detailed information about cochlear shape, reveals size-independent differences in cochlear shape between P. robustus and Australopithecus africanus that exceed those among modern humans and the African apes. The cochlea of P. robustus is distinctive and relatively invariant, whereas cochlear shape in A. africanus is more variable, resembles that of early Homo, and shows a degree of morphological polymorphism comparable to that evinced by modern species. The curvature of the P. robustus cochlea is uniquely derived and is consistent with enhanced sensitivity to low-frequency sounds. Combined with evidence for selection, our findings suggest that sound perception shaped distinct ecological adaptations among southern African early hominins.

Accurate DMBE potential-energy surface for CNO(2A″) and rate coefficients in C(3P)+NO collisions.

A realistic double many-body expansion potential energy surface (PES) is developed for the 2A″ state of the carbon-nitrogen-oxygen (CNO) system based on MRCI-F12/cc-pVQZ-F12 ab initio energies. The new PES reproduces the fitted points with chemical accuracy (root mean square deviation up to 0.043 eV) and explicitly incorporates long range energy terms that can accurately describe the electrostatic and dispersion interactions. Thermal rate coefficients were computed for the C(3P) + NO(2Π) reaction for temperatures ranging from 15 K to 10 000 K, and the values are compared to previously reported results. The differences are rationalized, and the major importance of long range forces in predicting the rate coefficients for barrierless reactions is emphasized.

Reduced space in outdoor feedlot impacts beef cattle welfare.

There is a trend to reduce the space allowance per animal in cattle feedlot, despite its potential negative impact on animal welfare. Aiming to evaluate the effects of space allowance per animal in outdoor feedlots on beef cattle welfare, a total of 1350 Nellore bulls (450 pure and 900 crossbred) were confined for 12 weeks using three space allowances: 6 (SA6), 12 (SA12) and 24 (SA24) m2/animal (n = 450 per treatment). Bulls were housed in three pens per treatment (n = 150 per pen). The first 6 weeks in the feedlot were defined as 'dry' and the last as 'rainy' period, according to the accumulated precipitation. Animal-based (body cleanliness, health indicators and maintenance behaviour) and environmental-based indicators (mud depth and air dust concentration) were assessed weekly during the feedlot period. Most of the health indicators (nasal and ocular discharge, hoof and locomotion alterations, diarrhoea, bloated rumen and breathing difficulty) were assessed in a subset of 15 animals randomly selected from each pen. Coughs and sneezes were counted in each pen. Maintenance behaviours (number of animals lying and attending the feed bunk) were recorded with scan sampling and instantaneous recording at 20-min intervals. Postmortem assessments were carried out in all animals by recording the frequencies of macroscopic signs of bronchitis, pulmonary emphysema, nephritis and urinary cyst and by measuring the weight and cortical and medullar areas of adrenal glands (n = 30 per pen). Compared with SA12 and SA24, SA6 showed a greater number of sneezes per minute during the dry period and a greater percentage of animals with locomotion alterations during the rainy period. Coughing, diarrhoea and nasal discharge affected a larger number of animals in the SA6 relative to the other two groups. During the rainy period, there was a lower percentage of animals with nasal and ocular discharge, and a greater percentage of animals with abnormal hoof and lying. A lower percentage of animals in SA6 and SA12 (but not SA24) attended the feed bunk during the rainy relative to the dry period. A mud depth score of 0 (no mud) was most frequent in SA24 pens, followed by SA12 and then SA6. Adrenal gland weight and cortical area were lower in SA24 animals compared with those in SA6 and SA12. The results show that decreasing the space allowance for beef cattle in outdoor feedlots degrades the feedlot environment and impoverishes animal welfare.

Radial distribution function for liquid gallium from experimental structure factor: a Hopfield neural network approach.

Hopfield neural network was used to retrieve liquid gallium radial distribution function from an experimental structure factor, obtained at 959 K. The inversion framework was carried out under two initial conditions: (a) a constant radial distribution function corresponding to an ideal gas and (b) a step function, simulating a gas with square well potential of interaction. Both situations lead to accurate inverse results if compared with the radial distribution function obtained by Bellisent-Funel et al., using the Fourier transform method and Monte Carlo simulation. The Hopfield neural network has shown to be a powerful strategy to calculate the radial distribution function from experimental data.

Fractional kinetics on thermal analysis: application to lumefantrine thermal decomposition.

The fractional derivative concept to treat non-isothermal solid state thermal decomposition was employed in this work. Simulated data were compared with the exact solutions for the method validation. Calculated fractional kinetics data for four heating rates were initially considered and the Kissinger-Akahira-Sunose (KAS) method demonstrate that, although the activation energy is not retrieved, it can be useful to determine a single or multistep process. Experimental thermal decomposition data of lumefantrine heated at 5, 10 ,15, and 20 oC min- 1 were fitted for a single-step process. The kinetic parameters were retrieved for integer and fractional kinetics, considering some ideal and general models. Application of the KAS method to these data demonstrated an activation energy dependent on the conversion rate, indicating a multistep process. Five data subintervals were fitted separately using the general model with variable derivative order. It was found a process that occours with integer order derivative until α = 0.3 and fractional order for α > 0.3 with combination of simultaneous reactions, since the parameters do not correspond to any ideal model. The determined activation energies showed the same increasing behavior observed in the KAS approach. The results for multistep process presented an error 102 times smaller if compared with the best result, considering a single-step process. Therefore, the fractional kinetic model presents a powerful extension to the usual thermal data analysis.

Autoimmune hepatitis and pregnancy.

Autoimmune hepatitis (AIH) is a rare liver disease of autoimmune aetiology that classically affects women at reproductive age. Diagnosis of AIH is not always straightforward, and other causes of chronic liver disease must be excluded. Pregnancy in patients with AIH is associated with an increased risk of adverse maternal and foetal outcomes. In older studies, the incidence of adverse outcomes was high, with a large number of flare-ups, maternal deaths, and perinatal complications. In the most recent series, improved care based on multidisciplinary surveillance, a larger number of patients treated before and during pregnancy, and reduced incidence of cirrhosis at conception have led to better maternal outcomes and a live-birth rate similar to that in the general population. Nonetheless, AIH is still associated with preterm birth, foetal growth restriction, and unpredictable liver flares, and it represents a group of patients who need close evaluation during pregnancy.

Decidual NK cell-derived conditioned medium from miscarriages affects endometrial stromal cell decidualisation: endocannabinoid anandamide and tumour necrosis factor-α crosstalk.

STUDY QUESTION: What are the effects of endocannabinoid anandamide (AEA) in uterine natural killer (unK) cells from miscarriage decidua, regarding their cytokine profile and endometrial stromal cell (ESC) crosstalk? SUMMARY ANSWER: uNK-conditioned media from miscarriage samples present high TNF-α levels which inhibit ESC decidualisation. WHAT IS KNOWN ALREADY: AEA plasma levels are higher in women who have suffered a miscarriage. Moreover, AEA inhibits ESC proliferation and differentiation, although the levels and impact on the uNK cell cytokine profile at the feto-maternal interface remain elusive. STUDY DESIGN, SIZE, DURATION: This laboratory-based study used human primary uNK cells which were isolated from first-trimester decidua (gestational age, 5-12 weeks) derived from 8 women with elective pregnancy termination and 18 women who suffered a miscarriage. PARTICIPANTS/MATERIALS, SETTING, METHODS: The first-trimester placental tissues were assayed for AEA levels by UPLC-MS/MS and respective enzymatic profile by western blot. The uNK cells were isolated and maintained in culture. The expression of angiogenic markers in uNK cells was examined by quantitative PCR (qPCR). The uNK-conditioned medium was analysed for IFN-γ, TNF-α and IL-10 production by enzyme-linked immunosorbent assay, and the impact on ESC differentiation was assessed by measuring decidual markers Prl, Igfbp-1 and Fox01 mRNA expression using qPCR. MAIN RESULTS AND THE ROLE OF CHANCE: AEA levels were higher in miscarriage decidua compared with decidua from elective terminations. The uNK cell-conditioned medium from the miscarriage samples exhibited high TNF-α levels and interfered with the decidualisation of ESCs. Exacerbated inflammation and elevated TNF-α levels at the feto-maternal interface may trigger AEA signalling pathways that, in turn, may impact decidualisation and the angiogenic ability of uNK cells. LARGE-SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Primary uNK cell responses are based on a simple in vitro model. Thus, in complex microenvironments, such as the feto-maternal interface, the mechanisms may not be exactly the same. Also, the inflammatory events of miscarriage that, in this study, have happened prior to processing of the samples may cause different responses to that observed. In addition, the magnitude of the inflammatory response, required to trigger the AEA pathways that impact decidualisation and the uNK angiogenic ability in vivo, is still unclear. WIDER IMPLICATIONS OF THE FINDINGS: The endocannabinoid AEA is a modulator of reproductive competence. AEA not only may contribute to neuroendocrine homeostasis but also can take part in uterine changes occurring during early pregnancy. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by UID/MULTI/04378/2019 with funding from Fundação para a Ciência e a Tecnologia (FCT)/MCTES through national funds and PORTUGAL 2020 Partnership Agreement, NORTE-01-0145-FEDER-000024. S.C. Cunha acknowledges FCT for the IF/01616/2015 contract. There are no conflicts of interest.

Spatial diffusion of the 2015-2016 Zika, dengue and chikungunya epidemics in Rio de Janeiro Municipality, Brazil.

Different countries, especially Brazil, that have faced recurrent dengue epidemics for decades and chikungunya epidemics since 2014, have had to restructure their health services to combat a triple epidemic of arboviruses - Zika, dengue and Chikungunya - transmitted by the same vector, mainly Aedes aegypti, in 2015-2016. Several efforts have been made to better understand these three arboviruses. Spatial analysis plays an important role in the knowledge of disease dynamics. The knowledge of the patterns of spatial diffusion of these three arboviruses during an epidemic can contribute to the planning of surveillance actions and control of these diseases. This study aimed to identify the spatial diffusion processes of these viruses in the context of the triple epidemic in 2015-2016 in Rio de Janeiro, Brazil. Two study designs were used: cross-sectional and ecological. Sequential Kernel maps, nearest-neighbour ratios calculated cumulatively over time, Moran global autocorrelation correlograms, and local autocorrelation changes over time were used to identify spatial diffusion patterns. The results suggested an expansion diffusion pattern for the three arboviruses during 2015-2016 in Rio de Janeiro. These findings can be considered for more effective control measures and for new studies on the dynamics of these three arboviruses.

Quasiclassical Study of the C(3P) + NO(X2Π) and O(3P) + CN(X2Σ+) Collisional Processes on an Accurate DMBE Potential Energy Surface.

The predicted rate constants for C + NO and O + CN collisions in three potential energy surfaces (PESs) for the 2A' state of the CNO molecule are compared using quasiclassical trajectories. Different temperature dependencies are obtained for the C + NO reaction, which are explained in terms of the long-range properties of the PESs. Recommended values and mechanistic details are also reported. For O + CN collisions, a better agreement between the theoretical results is found, except for temperatures below 100 K.

Cochlear shape reveals that the human organ of hearing is sex-typed from birth.

Sex differences in behavioral and neural characteristics can be caused by cultural influences but also by sex-based differences in neurophysiological and sensorimotor features. Since signal-response systems influence decision-making, cooperative and collaborative behaviors, the anatomical or physiological bases for any sex-based difference in sensory mechanisms are important to explore. Here, we use uniform scaling and nonparametric representations of the human cochlea, the main organ of hearing that imprints its adult-like morphology within the petrosal bone from birth. We observe a sex-differentiated torsion along the 3D cochlear curve in samples of 94 adults and 22 juvenile skeletons from cross-cultural contexts. The cochlear sexual dimorphism measured in our study allows sex assessment from the human skeleton with a mean accuracy ranging from 0.91 to 0.93 throughout life. We conclude that the human cochlea is sex-typed from an early post-natal age. This, for the first time, allows nondestructive sex determination of juveniles' skeletal remains in which the biomolecules are too degraded for study but in which the petrosal is preserved, one of the most common bone within archaeological assemblages. Our observed sex-typed cochlear shape from birth is likely associated with complex evolutionary processes in modern humans for reasons not yet fully understood.

Different outcomes of a cardiac rehabilitation programme in functional parameters among myocardial infarction survivors according to ejection fraction.

INTRODUCTION: Exercise-based cardiac rehabilitation (EBCR) is part of the management of patients who have suffered an acute myocardial infarction (AMI). Patients with a reduced ejection fraction (EF) comprise a higher-risk subgroup and are referred less often for these programmes. This study aimed at assessing the impact of the baseline EF on the functional benefits, as assessed by peak oxygen uptake (pVO2) and exercise duration, of an EBCR programme in AMI survivors. METHODS: Observational, retrospective cohort study including all patients admitted to a tertiary centre due to an AMI who completed a phase II EBCR programme after discharge, between November 2012 and April 2017. Functional parameters were assessed by a symptom-limited cardiopulmonary exercise test. RESULTS: A total of 379 patients were included [40.9% with reduced EF (<50%) at discharge]. After the programme, pVO2 and exercise duration increased significantly (p < 0.001). Patients with a reduced EF had a lower pVO2 and completed a shorter duration of exercise at the beginning and end of the programme. This group presented a higher increase in pVO2 (p = 0.001) and exercise duration (p = 0.007). This was maintained after adjusting for age, gender, history of coronary artery disease, number of sessions, Killip classification, arterial hypertension, dyslipidaemia, diabetes mellitus, smoking status and baseline pVO2. CONCLUSION: A phase II EBCR programme was associated with significant improvements in pVO2 and exercise duration among AMI survivors, irrespective of baseline EF classification. Those with a reduced baseline EF derived an even greater improvement, highlighting the importance of EBCR in this subgroup of patients.

The accuracy of the modified Evan's blue dye test in detecting aspiration in tracheostomised patients.

OBJECTIVES: To evaluate the sensitivity and specificity of the modified Evans blue dye test compared to the fibre-optic endoscopic evaluation of swallowing to detect aspiration in tracheostomised patients. METHODS: This observational accuracy study included 17 patients hospitalised for respiratory complications, subjected to prolonged intubation, and for this reason, tracheostomised. RESULTS: Mean patient age was 60.2 ± 21.0 years. Aspiration was identified in 10 patients when assessed by fibre-optic endoscopic evaluation of swallowing; of these, 1 had aspiration when evaluated by modified Evans blue dye test. The dye test had a sensitivity of 10.0 per cent and specificity of 100.0 per cent for detecting aspiration. Fibre-optic endoscopic evaluation of swallowing revealed no statistically significant associations between aspiration presence and: speech and language therapy duration, intubation time, or tracheostomy plus mechanical ventilation duration. CONCLUSION: The modified Evans blue dye test is simple and inexpensive, and does not require prior knowledge in endoscopy; it may be used as an initial screening test in all tracheostomised patients for evaluating aspiration. However, fibre-optic endoscopic evaluation of swallowing should be used for a more comprehensive diagnosis of tracheostomy patients, especially for those at high risk for aspiration.

Choroid thickness profile in patients with lupus nephritis.

BACKGROUND: Choroidopathy is a rare manifestation of systemic lupus erythematosus (SLE). This entity is associated with active phases of severe SLE and it is frequently accompanied by acute kidney failure, central nervous system involvement and coagulopathy. PURPOSE: To evaluate the choroid thickness of patients with lupus nephritis (LN) without choroidopathy, and to compare this with that of age-matched SLE patients without LN and healthy control subjects. STUDY DESIGN: Cross-sectional case control study. MATERIAL AND METHODS: Fifteen women with LN in remission phase (study group), 15 women with SLE in remission without LN (SLE control group), and 15 healthy women (healthy control group), without ocular diseases or significant refractive error, were recruited. Full ophthalmological examination and a macular optical coherence tomography in enhanced depth imaging mode were performed. The choroid thickness was measured at nine macular points and six lines of mean choroidal thickness were determined. A comparative analysis between the three groups was performed using the one-way ANOVA test and the paired t-test. The choroid thickness of patients under corticotherapy was also compared to that of patients without corticotherapy. Additionally, the correlation between choroid thickness and disease duration was evaluated using the Pearson analysis. RESULTS: The mean macular choroidal thickness was 295.73 ± 67.62 µm in the study group, 233.34 ± 41.01 µm in the SLE control group, and 240.98 ± 37.93 µm in the control group ( p = 0.00006 and p = 0.0003, respectively). Additionally, the choroid thickness was significantly thicker than in the SLE and healthy control groups at the foveal ( p = 0.004 and p < 0.000), nasal ( p < 0.000 and p = 0.001), superior ( p = 0.002 and p < 0.000) and inferior ( p < 0.000 and p = 0.001) mean lines. The choroidal thickness in this group was not associated with the duration of the disease. The subgroup of patients with LN under corticotherapy did not reveal a significantly different choroidal thickness. CONCLUSION: This study suggests a relationship between LN and choroidal changes, which may represent an increased risk for choroidopathy in these patients. Choroid thickening was not related with the duration of the disease. This thickening may be correlated with histopathological changes similar to those occurring in kidney glomeruli.

Effects of cannabis tetrahydrocannabinol on endocannabinoid homeostasis in human placenta.

Cannabis use has become a hot topic in several countries due to the debate about its legalization for medical purposes. However, data are limited regarding adverse events, safety and potential impact on reproductive health. Cannabis consumption during pregnancy has been associated with gestational disorders such as preterm birth, intrauterine growth restriction, low birth weight and increased risk of miscarriage, though the underlying biochemical mechanisms are still unknown. Given that the endocannabinoid system (ECS) is involved in several reproductive processes, we tested the hypothesis that the negative outcomes may result from the impact on the ECS homeostasis caused by the main psychoactive compound of cannabis, Δ9-tetrahydrocannabinol (THC). We demonstrate that THC (10-40 µM) impairs placental endocannabinoid system by disrupting the endocannabinoid anandamide (AEA) levels and the expression of AEA synthetic and degrading enzymes N-arachidonoylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), respectively. Although, no alterations in cannabinoid receptors CB1 and CB2 expression were observed. Thus, long-term local AEA levels are associated with a shift in the enzymatic profile to re-establish ECS homeostasis. In chronic cannabis users, high AEA levels in placenta may disturb the delicate balance of trophoblast cells turnover leading to alterations in normal placental development and foetal growth.

Short communication: Activity of nisin, lipid bilayer fragments and cationic nisin-lipid nanoparticles against multidrug-resistant Staphylococcus spp. isolated from bovine mastitis.

Staphylococci are the main etiological agents of bovine mastitis. Bacteriocins and nanoparticles have emerged as promising alternatives for the future development of antimicrobial agents. This study evaluated the activity of the bacteriocin nisin and bicelles of the synthetic cationic lipid dioctadecyldimethylammonium bromide, alone and in combination, against multidrug-resistant Staphylococcus spp. strains isolated from bovine mastitis. In summary, cationic nisin/dioctadecyldimethylammonium bromide nanoparticles are shown to be a promising alternative for the control of mastitis caused by multidrug-resistant Staphylococcus spp.