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Peripheral measures of autonomic nervous system (ANS) activity at rest have been extensively employed as putative biomarkers of autonomic cardiac control. However, a comprehensive characterization of the brain-based central autonomic network (CAN) sustaining cardiovascular oscillations at rest is missing, limiting the interpretability of these ANS measures as biomarkers of cardiac control. We evaluated combined cardiac and fMRI data from 34 healthy subjects from the Human Connectome Project to detect brain areas functionally linked to cardiovagal modulation at rest. Specifically, we combined voxel-wise fMRI analysis with instantaneous heartbeat and spectral estimates obtained from inhomogeneous linear point-process models. We found exclusively negative associations between cardiac parasympathetic activity at rest and a widespread network including bilateral anterior insulae, right dorsal middle and left posterior insula, right parietal operculum, bilateral medial dorsal and ventrolateral posterior thalamic nuclei, anterior and posterior mid-cingulate cortex, medial frontal gyrus/pre-supplementary motor area. Conversely, we found only positive associations between instantaneous heart rate and brain activity in areas including frontopolar cortex, dorsomedial prefrontal cortex, anterior, middle and posterior cingulate cortices, superior frontal gyrus, and precuneus. Taken together, our data suggests a much wider involvement of diverse brain areas in the CAN at rest than previously thought, which could reflect a differential (both spatially and directionally) CAN activation according to the underlying task. Our insight into CAN activity at rest also allows the investigation of its impairment in clinical populations in which task-based fMRI is difficult to obtain (e.g., comatose patients or infants). •We combine fMRI with instantaneous autonomic outflow estimates•The central autonomic network (CAN) sustains cardiovascular oscillations at rest•Cardio-vagal and CAN activities at rest are negatively correlated•CAN activity at rest involves much wider brain networks than previously thought

During 2009–2012, wild animals and their ticks were sampled in two areas within the Amazon biome of Brazil, in the states of Mato Grosso and Pará. Animal tissues, blood, and ticks were molecularly tested for Rickettsia and Coxiella DNA. A total of 182 wild animals were sampled, comprising 28 mammalian, five avian, and three reptilian species. Animal tissues or blood were all negative for Rickettsia or Coxiella DNA. A total of 454 ticks (22 larvae, 226 nymphs, 127 males, 79 females) were collected from 52 (28.6 %) animals, and identified into 15 species: Amblyomma cajennense, A. naponense, A. humerale, A. nodosum, A. goeldii, A. oblongoguttatum, A. longirostre, A. calcaratum, A. coelebs, A. pacae, A. geayii, A. rotundatum, A. auricularium, A. ovale, and Haemaphysalis juxtakochi. While no Coxiella DNA was identified in ticks, six Rickettsia species were detected in the ticks. “Candidatus Rickettsia amblyommii” was the most common agent, detected in four tick species, A. cajennense, A. auricularium, A. longirostre, and A. humerale. The second most common agent, R. bellii, was detected in A. humerale and A. naponense. Rickettsia rhipicephali was detected in H. juxtakochi, and R. felis in A. humerale. Two possible new Rickettsia species were detected in A. naponense ticks, namely, a novel spotted fever group agent close-related to R. africae in Pará, and a novel Canadensis group agent in Mato Grosso. Results of the present study expand our knowledge on the tick fauna, and on the yet infantile knowledge of tick-borne rickettsiae in the Amazon biome.

Until recently, Amblyomma cajennense (Fabricius, 1787) was considered to represent a single tick species in the New World. Recent studies have split this taxon into six species. While the A. cajennense species complex or A. cajennense (sensu lato) (s.l.) is currently represented by two species in Brazil, A. cajennense (sensu stricto) (s.s.) and Amblyomma sculptum Berlese, 1888, their geographical distribution is poorly known. The distribution of the A. cajennense (s.l.) in Brazil was determined by morphological examination of all lots of A. cajennense (s.l.) in two large tick collections of Brazil, and by collecting new material during three field expeditions in the possible transition areas between the distribution ranges of A. cajennense (s.s.) and A. sculptum. Phylogenetic analysis inferred from the ITS2 rRNA gene was used to validate morphological results. Morphological description of the nymphal stage of A. cajennense (s.s.) is provided based on laboratory-reared specimens. From the tick collections, a total 12,512 adult ticks were examined and identified as 312 A. cajennense (s.s.), 6,252 A. sculptum and 5,948 A. cajennense (s.l.). A total of 1,746 ticks from 77 localities were collected during field expeditions, and were identified as 249 A. cajennense (s.s.), 443 A. sculptum, and 1,054 A. cajennense (s.l.) [these A. cajennense (s.l.) ticks were considered to be males of either A. cajennense (s.s.) or A. sculptum]. At least 23 localities contained the presence of both A. cajennense (s.s.) and A. sculptum in sympatry. DNA sequences of the ITS2 gene of 50 ticks from 30 localities confirmed the results of the morphological analyses. The nymph of A. cajennense (s.s.) is morphologically very similar to A. sculptum. Our results confirmed that A. cajennense (s.l.) is currently represented in Brazil by only two species, A. cajennense (s.s.) and A. sculptum. While these species have distinct distribution areas in the country, they are found in sympatry in some transition areas. The current distribution of A. cajennense (s.l.) has important implications to public health, since in Brazil A. sculptum is the most important vector of the bacterium Rickettsia rickettsii, the etiological agent of Brazilian spotted fever.

Rickettsia bacteria are responsible for diseases in humans and animals around the world, however few details are available regarding its ecology and circulation among wild animals and human populations at high transmission risk in Brazil. The aim of this study was to investigate the occurrence of ticks and Rickettsia spp. in wild boars, corresponding hunting dogs and hunters. Serum samples and ticks were collected from 80 free-range wild boars, 170 hunting dogs and 34 hunters from southern and central-western Brazil, from the Atlantic Forest and Cerrado biomes, respectively, between 2016 and 2018. Serum samples were tested by indirect immunofluorescent-antibody assay (IFA) to detect IgG antibodies against Rickettsia rickettsii, Rickettsia parkeri, Rickettsia bellii, Rickettsia rhipicephali and Rickettsia amblyommatis. Tick species were identified by morphological taxonomic keys, as previously described. A total of 164 ticks including A. sculptum, A. brasiliense and A. aureolatum were tested in PCR assays for Spotted Fever Group (SFG) Rickettsia spp. A total of 58/80 (72.5%) wild boars, 24/170 (14.1%) hunting dogs and 5/34 (14.7%) hunters were positive (titers ≥ 64) to at least one Rickettsia species. A total of 669/1,584 (42.2%) ticks from wild boars were identified as Amblyomma sculptum, 910/1,584 (57.4%) as Amblyomma brasiliense, 4/1,584(0.24%) larvae of Amblyomma spp. and 1/1,584 (0.06%) nymph as Amblyolmma dubitatum. All 9 ticks found on hunting dogs were identified as Amblyomma aureolatum and all 22 ticks on hunters as A. sculptum. No tested tick was positive by standard PCR to SFG Rickettsia spp. The present study was the concomitant report of wild boar, hunting dog and hunter exposure to SFG rickettsiae agents, performed in two different Brazilian biomes. Wild boar hunting may increase the risk of human exposure and consequently tick-borne disease Wild boars may be carrying and spreading capybara ticks from their original habitats to other ecosystems. Further studies can be required to explore the ability of wild boars to infecting ticks and be part of transmission cycle of Rickettsia spp.

The life-cycle of Amblyomma calcaratum was evaluated experimentally under laboratory conditions using birds ( Serinus canaria, Gallus gallus ) and rodents ( Calomys callosus ) as hosts for immatures and a rabbit ( Oryctolagus cuniculus ) as host for adults. Developmental periods of the non-parasitic stages were observed in an incubator at 27 °C and 90% RH. The passerine S. canaria was the most suitable host for larvae and nymphs whereas the rodent C. callosus was not suitable to both immatures; only one engorged larva was recovered. The suitability of S. canaria for larvae and nymphs of A. calcaratum supports field data regarding passerine birds as main hosts for A. calcaratum immatures. Among the Amblyomma species which life cycle has been evaluated under laboratory conditions, A. calcaratum is one with the longest off-host developmental periods.

BackgroundFamilial hemiplegic migraine (FHM) is a group of genetic migraine, associated with hemiparesis and aura. Three causative different genes have been identified, all of which are involved in membrane ion transport. Among these, SCN1A encodes the voltage-gated Na+ channel Nav1.1, and FHM caused by mutations of SCN1A is named FHM3. For 7 of the 12 known FHM3-causing SCNA1 mutations functional consequences have been investigated, and even if gain of function effect seems to be a predominant phenotype, for several mutations conflicting results have been obtained and the available data do not reveal a univocal FHM3 pathomechanism.MethodsTo obtain a more complete picture, here, we characterized by patch clamp approach the remaining 5 mutations (Q1489H, I1498M, F1499 L, M1500 V, F1661 L) in heterologous expression systems.ResultsWith the exception of I1498M, all mutants exhibited the same current density as WT and exhibited a shift of the steady state inactivation to more positive voltages, an accelerated recovery from inactivation, and an increase of the persistent current, revealing that most FHM3 mutations induce a gain of function. We also determined the effect of GS967, a late Na+ current blocker, on the above mentioned mutants as well as on previously characterized ones (L1649Q, L1670 W, F1774S). GS967 inhibited persistent currents of all SCNA1 FMH3-related mutants and dramatically slowed the recovery from fast inactivation of WT and mutants, consistent with the hypothesis that GS967 specifically binds to and thereby stabilizes the fast inactivated state.Simulation of neuronal firing showed that enhanced persistent currents cause an increase of ionic fluxes during action potential repolarization and consequent accumulation of K+ and/or exhaustion of neuronal energy resources. In silico application of GS967 largely reduced net ionic currents in neurons without impairing excitability.ConclusionIn conclusion, late Na+ current blockers appear a promising specific pharmacological treatment of FHM3.

Due to the association between dysfunctional maternal autonomic regulation and pregnancy complications, tracking non-invasive features of autonomic regulation derived from wrist-worn photoplethysmography (PPG) measurements may allow for the early detection of deteriorations in maternal health. However, even though a plethora of these features—specifically, features describing heart rate variability (HRV) and the morphology of the PPG waveform (morphological features)—exist in the literature, it is unclear which of these may be valuable for tracking maternal health. As an initial step towards clarity, we compute comprehensive sets of HRV and morphological features from nighttime PPG measurements. From these, using logistic regression and stepwise forward feature elimination, we identify the features that best differentiate healthy pregnant women from non-pregnant women, since these likely capture physiological adaptations necessary for sustaining healthy pregnancy. Overall, morphological features were more valuable for discriminating between pregnant and non-pregnant women than HRV features (area under the receiver operating characteristics curve of 0.825 and 0.74, respectively), with the systolic pulse wave deterioration being the most valuable single feature, followed by mean heart rate (HR). Additionally, we stratified the analysis by sleep stages and found that using features calculated only from periods of deep sleep enhanced the differences between the two groups. In conclusion, we postulate that in addition to HRV features, morphological features may also be useful in tracking maternal health and suggest specific features to be included in future research concerning maternal health.

Background Inflammatory bowel disease (IBD) is a chronic complex disease of the gastrointestinal tract. Patients with IBD can experience a wide range of symptoms, but the pathophysiological mechanisms that cause these individual differences in clinical presentation remain largely unknown. In consequence, IBD is currently classified into subtypes using clinical characteristics. If we are to develop a more targeted treatment approach, molecular subtypes of IBD need to be discovered that can be used as new drug targets. To achieve this, we need multiple layers of molecular data generated from the same IBD patients. Construction and content We initiated the 1000IBD project ( https://1000ibd.org ) to prospectively follow more than 1000 IBD patients from the Northern provinces of the Netherlands. For these patients, we have collected a uniquely large number of phenotypes and generated multi-omics profiles. To date, 1215 participants have been enrolled in the project and enrolment is on-going. Phenotype data collected for these participants includes information on dietary and environmental factors, drug responses and adverse drug events. Genome information has been generated using genotyping ( ImmunoChip , Global Screening Array and HumanExomeChip ) and sequencing (whole exome sequencing and targeted resequencing of IBD susceptibility loci), transcriptome information generated using RNA-sequencing of intestinal biopsies and microbiome information generated using both sequencing of the 16S rRNA gene and whole genome shotgun metagenomic sequencing. Utility and discussion All molecular data generated within the 1000IBD project will be shared on the European Genome-Phenome Archive ( https://ega-archive.org , accession no: EGAS00001002702). The first data release, detailed in this announcement and released simultaneously with this publication, will contain basic phenotypes for 1215 participants, genotypes of 314 participants and gut microbiome data from stool samples (315 participants) and biopsies (107 participants) generated by tag sequencing the 16S gene. Future releases will comprise many more additional phenotypes and -omics data layers. 1000IBD data can be used by other researchers as a replication cohort, a dataset to test new software tools, or a dataset for applying new statistical models. Conclusions We report on the establishment and future development of the 1000IBD project: the first comprehensive multi-omics dataset aimed at discovering IBD biomarker profiles and treatment targets.

The diagnosis of paucibacillary (PB) leprosy cases remains a challenge because of the absence of a confirmatory laboratory method. While quantitative polymerase chain reaction (qPCR) has been shown to provide reliable sensitivity and specificity in PB diagnoses, a thorough investigation of its efficacy in clinical practice has not yet been published. The present study evaluated patients with suspected leprosy skin lesions by using qPCR to identify PB individuals in the Leprosy Outpatient clinic at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. One hundred seventy-two suspected PB cases were included in the study. The patients were evaluated by a dermatologist at three different times. The clinical dermato-neurological examination and collected samples were performed on the first visit. On the second visit, the results of the histopathological analysis and PCR assay (DNA-based Mycobacterium leprae qPCR-targeting 16S gene) results were analyzed, and a decision regarding multi-drug therapy was made. A year later, the patients were re-examined, and the consensus diagnosis was established. In 58% (100/172) of cases, a conclusive diagnosis via histopathological analysis was not possible; however, 30% (30/100) of these cases had a positive PCR. One hundred ten patients (110/172) attended the third visit. The analysis showed that while the sensitivity of the histopathological test was very low (35%), a qPCR alone was more effective for identifying leprosy, with 57% sensitivity. The use of qPCR in suspected PB cases with an inconclusive histology improved the sensitivity of leprosy diagnoses.

The production of railway vehicles determines the handling of a large amount of materials which are transferred from suppliers to production site using industrial packaging. The activity here described is part of the MORIMB project, which dealt with the reduction of waste related to railway sector; wood, plastic, cardboard and metal fasteners are the typical materials which are adopted for such packaging. The study is motivated from the evidence that, due to the peculiarities of the transported components, most of the packaging units were different from standardized formats therefore they were frequently used for a single transport and subsequently scrapped. An applicative methodology for the analysis, redesign, and evaluation of environmental and economic impacts was defined, with particular attention to packaging reusability. An adaptation of the DMAIC approach was used to analyze the various components and find solutions reusability and performance improvement, especially in terms of volume efficiency and component protection. Depending on the item to be transported, specific crates have been designed and structurally verified according to existing technical regulation, and their sustainability has been analyzed considering environmental and economic impact during production, transport and storage phase; appropriate scenarios regarding distance travelled and volume occupancy were defined. The case study presented in detail in this work concerns the concept of special crates for the transport of passenger seats – a key component for train production - for which an increase in packaging density and a reduction of transportation costs was achieved. Other case studies were also considered.