Dog and human neural sensitivity to voicelikeness: A comparative fMRI study.

Voice-sensitivity in the auditory cortex of a range of mammals has been proposed to be determined primarily by tuning to conspecific auditory stimuli, but recent human findings indicate a role for a more general tuning to voicelikeness. Vocal emotional valence, a central characteristic of vocalisations, has been linked to the same basic acoustic parameters across species. Comparative neuroimaging revealed that during voice perception, such acoustic parameters modulate emotional valence-sensitivity in auditory cortical regions in both family dogs and humans. To explore the role of voicelikeness in auditory emotional valence-sensitivity across species, here we constructed artificial emotional sounds in two sound categories: voice-like vs. sine-wave sounds, parametrically modulating two main acoustic parameters, f0 and call length. We hypothesised that if mammalian auditory systems are characterised by a general tuning to voicelikeness, voice-like sounds will be processed preferentially, and acoustic parameters for voice-like sounds will be processed differently than for sine-wave sounds - both in dogs and humans. We found cortical areas in both species that responded stronger to voice-like than to sine-wave stimuli, while there were no regions responding stronger to sine-wave sounds in either species. Additionally, we found that in bilateral primary and emotional valence-sensitive auditory regions of both species, the processing of voice-like and sine-wave sounds are modulated by f0 in opposite ways. These results reveal functional similarities between evolutionarily distant mammals for processing voicelikeness and its effect on processing basic acoustic cues of vocal emotions.

Heritability of Subcortical Grey Matter Structures.

Background and Objectives: Subcortical grey matter structures play essential roles in cognitive, affective, social, and motoric functions in humans. Their volume changes with age, and decreased volumes have been linked with many neuropsychiatric disorders. The aim of our study was to examine the heritability of six subcortical brain volumes (the amygdala, caudate nucleus, pallidum, putamen, thalamus, and nucleus accumbens) and four general brain volumes (the total intra-cranial volume and the grey matter, white matter, and cerebrospinal fluid (CSF) volume) in twins. Materials and Methods: A total of 118 healthy adult twins from the Hungarian Twin Registry (86 monozygotic and 32 dizygotic; median age 50 ± 27 years) underwent brain magnetic resonance imaging. Two automated volumetry pipelines, Computational Anatomy Toolbox 12 (CAT12) and volBrain, were used to calculate the subcortical and general brain volumes from three-dimensional T1-weighted images. Age- and sex-adjusted monozygotic and dizygotic intra-pair correlations were calculated, and the univariate ACE model was applied. Pearson's correlation test was used to compare the results obtained by the two pipelines. Results: The age- and sex-adjusted heritability estimates, using CAT12 for the amygdala, caudate nucleus, pallidum, putamen, and nucleus accumbens, were between 0.75 and 0.95. The thalamus volume was more strongly influenced by common environmental factors (C = 0.45-0.73). The heritability estimates, using volBrain, were between 0.69 and 0.92 for the nucleus accumbens, pallidum, putamen, right amygdala, and caudate nucleus. The left amygdala and thalamus were more strongly influenced by common environmental factors (C = 0.72-0.85). A strong correlation between CAT12 and volBrain (r = 0.74-0.94) was obtained for all volumes. Conclusions: The majority of examined subcortical volumes appeared to be strongly heritable. The thalamus was more strongly influenced by common environmental factors when investigated with both segmentation methods. Our results underline the importance of identifying the relevant genes responsible for variations in the subcortical structure volume and associated diseases.

Genetic and Environmental Effects on the Development of White Matter Hyperintensities in a Middle Age Twin Population.

Introduction: White matter hyperintensities (WMH) indicate white matter brain lesions in magnetic resonance imaging (MRI), which can be used as a marker for brain aging and cerebrovascular and neurodegenerative disorders. Twin studies revealed substantial but not uniform WMH heritability in elderly twins. The objective of our study was to investigate the genetic and environmental components of WMH, as well as their importance in a healthy twin population, utilizing 3T MRI scanners in a middle-aged twin population. Methods: Brain MRI was performed on 120 healthy adult twins from the Hungarian Twin Registry on a 3T scanner (86 monozygotic, MZ and 34 dizygotic, DZ twins; median age 50 ± 26.5 years, 72.5% female and 27.5% male). The count of WMH on FLAIR images was calculated using an automated volumetry pipeline (volBrain) and human processing. The age- and sex-adjusted MZ and DZ intra-pair correlations were determined and the total variance was decomposed into genetic, shared and unique environmental components using structural equation modeling. Results: Age and sex-adjusted MZ intrapair correlations were higher than DZ correlations, indicating moderate genetic influence in each lesion (rMZ = 0.466, rDZ = -0.025 for total count; rMZ = 0.482, rDZ = 0.093 for deep white matter count; rMZ = 0.739, rDZ = 0.39 for infratentorial count; rMZ = 0.573, rDZ = 0.372 for cerebellar count and rMZ = 0.473, rDZ = 0.19 for periventricular count), indicating a moderate heritability (A = 40.3%, A = 45%, A = 72.7% and A = 55.5%and 47.2%, respectively). The rest of the variance was influenced by unique environmental effects (E between 27.3% and 59.7%, respectively). Conclusions: The number of WMH lesions is moderately influenced by genetic effects, particularly in the infratentorial region in middle-aged twins. These results suggest that the distribution of WMH in various brain regions is heterogeneous.

Comparative Brain Imaging Reveals Analogous and Divergent Patterns of Species and Face Sensitivity in Humans and Dogs.

Conspecific-preference in social perception is evident for multiple sensory modalities and in many species. There is also a dedicated neural network for face processing in primates. However, the evolutionary origin and the relative role of neural species sensitivity and face sensitivity in visuo-social processing are largely unknown. In this comparative study, species sensitivity and face sensitivity to identical visual stimuli (videos of human and dog faces and occiputs) were examined using functional magnetic resonance imaging in dogs (n = 20; 45% female) and humans (n = 30; 50% female). In dogs, the bilateral mid suprasylvian gyrus showed conspecific-preference, no regions exhibited face-preference, and the majority of the visually-responsive cortex showed greater conspecific-preference than face-preference. In humans, conspecific-preferring regions (the right amygdala/hippocampus and the posterior superior temporal sulcus) also showed face-preference, and much of the visually-responsive cortex showed greater face-preference than conspecific-preference. Multivariate pattern analyses (MVPAs) identified species-sensitive regions in both species, but face-sensitive regions only in humans. Across-species representational similarity analyses (RSAs) revealed stronger correspondence between dog and human response patterns for distinguishing conspecific from heterospecific faces than other contrasts. Results unveil functional analogies in dog and human visuo-social processing of conspecificity but suggest that cortical specialization for face perception may not be ubiquitous across mammals.SIGNIFICANCE STATEMENT To explore the evolutionary origins of human face-preference and its relationship to conspecific-preference, we conducted the first comparative and noninvasive visual neuroimaging study of a non-primate and a primate species, dogs and humans. Conspecific-preferring brain regions were observed in both species, but face-preferring brain regions were observed only in humans. In dogs, an overwhelming majority of visually-responsive cortex exhibited greater conspecific-preference than face-preference, whereas in humans, much of the visually-responsive cortex showed greater face-preference than conspecific-preference. Together, these findings unveil functional analogies and differences in the organizing principles of visuo-social processing across two phylogenetically distant mammal species.

Fronto-thalamic structural and effective connectivity and delusions in schizophrenia: a combined DTI/DCM study.

BACKGROUND: Schizophrenia (SZ) is a complex disorder characterized by a range of behavioral and cognitive symptoms as well as structural and functional alterations in multiple cortical and subcortical structures. SZ is associated with reduced functional network connectivity involving core regions such as the anterior cingulate cortex (ACC) and the thalamus. However, little is known whether effective coupling, the directed influence of one structure over the other, is altered during rest in the ACC-thalamus network. METHODS: We collected resting-state fMRI and diffusion-weighted MRI data from 18 patients and 20 healthy controls. We analyzed fronto-thalamic effective connectivity using dynamic causal modeling for cross-spectral densities in a network consisting of the ACC and the left and right medio-dorsal thalamic regions. We studied structural connectivity using fractional anisotropy (FA). RESULTS: We found decreased coupling strength from the right thalamus to the ACC and from the right thalamus to the left thalamus, as well as increased inhibitory intrinsic connectivity in the right thalamus in patients relative to controls. ACC-to-left thalamus coupling strength correlated with the Positive and Negative Syndrome Scale (PANSS) total positive syndrome score and with delusion score. Whole-brain structural analysis revealed several tracts with reduced FA in patients, with a maximum decrease in white matter tracts containing fronto-thalamic and cingulo-thalamic fibers. CONCLUSIONS: We found altered effective and structural connectivity within the ACC-thalamus network in SZ. Our results indicate that ACC-thalamus network activity at rest is characterized by reduced thalamus-to-ACC coupling. We suggest that positive symptoms may arise as a consequence of compensatory measures to imbalanced fronto-thalamic coupling.

Groundwater, soil and compost, as possible sources of virulent and antibiotic-resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a major public health concern all around the world. In the frame of this work, a set of diverse environmental P. aeruginosa isolates with various antibiotic resistance profiles were examined in a Galleria mellonella virulence model. Motility, serotypes, virulence factors and biofilm-forming ability were also examined. Molecular types were determined by pulsed-field gel electrophoresis (PFGE). Based on our results, the majority of environmental isolates were virulent in the G. mellonella test and twitching showed a positive correlation with mortality. Resistance against several antibiotic agents such as Imipenem correlated with a lower virulence in the applied G. mellonella model. PFGE revealed that five examined environmental isolates were closely related to clinically detected pulsed-field types. Our study demonstrated that industrial wastewater effluents, composts, and hydrocarbon-contaminated sites should be considered as hot spots of high-risk clones of P. aeruginosa.

Increased activation of the pregenual anterior cingulate cortex to citalopram challenge in migraine: an fMRI study.

BACKGROUND: The anterior cingulate cortex (ACC) is a key structure of the pain processing network. Several structural and functional alterations of this brain area have been found in migraine. In addition, altered serotonergic neurotransmission has been repeatedly implicated in the pathophysiology of migraine, although the exact mechanism is not known. Thus, our aim was to investigate the relationship between acute increase of brain serotonin (5-HT) level and the activation changes of the ACC using pharmacological challenge MRI (phMRI) in migraine patients and healthy controls. METHODS: Twenty-seven pain-free healthy controls and six migraine without aura patients participated in the study. All participant attended to two phMRI sessions during which intravenous citalopram, a selective serotonin reuptake inhibitor (SSRI), or placebo (normal saline) was administered. We used region of interest analysis of ACC to compere the citalopram evoked activation changes of this area between patients and healthy participants. RESULTS: Significant difference in ACC activation was found between control and patient groups in the right pregenual ACC (pgACC) during and after citalopram infusion compared to placebo. The extracted time-series showed that pgACC activation increased in migraine patients compared to controls, especially in the first 8-10 min of citalopram infusion. CONCLUSIONS: Our results demonstrate that a small increase in 5-HT levels can lead to increased phMRI signal in the pregenual part of the ACC that is involved in processing emotional aspects of pain. This increased sensitivity of the pgACC to increased 5-HT in migraine may contribute to recurring headache attacks and increased stress-sensitivity in migraine.

Are the Variants of the Circle of Willis Determined by Genetic or Environmental Factors? Results of a Twin Study and Review of the Literature.

BACKGROUND: Anatomic variants of the circle of Willis (CW) are commonly observed in healthy subjects. Genetic and environmental factors influencing these variants remain unclear. Our aim was to assess the genetic and environmental background affecting variant CW phenotypes. METHODS: A total of 122 adult healthy twins from the Hungarian Twin Registry (39 monozygotic (MZ) and 22 dizygotic (DZ) pairs, average age 49.7 ± 13.4 years) underwent Time-of-Flight magnetic resonance angiography and transcranial Doppler sonography. We investigated the anterior and posterior CW according to morphological categories. Prevalence and concordance rates of CW variants were calculated. MZ twins discordant for CW variants were analyzed for cardiovascular risk factors and altered blood flow. RESULTS: Complete CW (45.0%) and bilaterally absent posterior communicating artery (PCoA) (22.5%) were the most prevalent variants in the anterior and posterior CW, respectively. There was no significant difference regarding the prevalence of variants across zygosity except for bilaterally hypoplastic PCoA (p = .02). DZ concordance was higher compared to MZ twins regarding morphological categories of the CW. Cardiovascular risk factors were not significantly associated with variant CW in MZ twins discordant to CW morphology. Flow parameters did not differ significantly among MZ twins discordant to CW variants. CONCLUSION: CW variants may not be determined by substantial genetic effects and are not influenced by altered blood flow in healthy individuals. Further investigations are needed to identify potential environmental factors affecting these variants.

ICN_Atlas: Automated description and quantification of functional MRI activation patterns in the framework of intrinsic connectivity networks.

Generally, the interpretation of functional MRI (fMRI) activation maps continues to rely on assessing their relationship to anatomical structures, mostly in a qualitative and often subjective way. Recently, the existence of persistent and stable brain networks of functional nature has been revealed; in particular these so-called intrinsic connectivity networks (ICNs) appear to link patterns of resting state and task-related state connectivity. These networks provide an opportunity of functionally-derived description and interpretation of fMRI maps, that may be especially important in cases where the maps are predominantly task-unrelated, such as studies of spontaneous brain activity e.g. in the case of seizure-related fMRI maps in epilepsy patients or sleep states. Here we present a new toolbox (ICN_Atlas) aimed at facilitating the interpretation of fMRI data in the context of ICN. More specifically, the new methodology was designed to describe fMRI maps in function-oriented, objective and quantitative way using a set of 15 metrics conceived to quantify the degree of 'engagement' of ICNs for any given fMRI-derived statistical map of interest. We demonstrate that the proposed framework provides a highly reliable quantification of fMRI activation maps using a publicly available longitudinal (test-retest) resting-state fMRI dataset. The utility of the ICN_Atlas is also illustrated on a parametric task-modulation fMRI dataset, and on a dataset of a patient who had repeated seizures during resting-state fMRI, confirmed on simultaneously recorded EEG. The proposed ICN_Atlas toolbox is freely available for download at http://icnatlas.com and at http://www.nitrc.org for researchers to use in their fMRI investigations.

Impaired mixed emotion processing in the right ventrolateral prefrontal cortex in schizophrenia: an fMRI study.

BACKGROUND: Schizophrenia has a negative effect on the activity of the temporal and prefrontal cortices in the processing of emotional facial expressions. However no previous research focused on the evaluation of mixed emotions in schizophrenia, albeit they are frequently expressed in everyday situations and negative emotions are frequently expressed by mixed facial expressions. METHODS: Altogether 37 subjects, 19 patients with schizophrenia and 18 healthy control subjects were enrolled in the study. The two study groups did not differ in age and education. The stimulus set consisted of 10 fearful (100%), 10 happy (100%), 10 mixed fear (70% fear and 30% happy) and 10 mixed happy facial expressions. During the fMRI acquisition pictures were presented in a randomized order and subjects had to categorize expressions by button press. RESULTS: A decreased activation was found in the patient group during fear, mixed fear and mixed happy processing in the right ventrolateral prefrontal cortex (VLPFC) and the right anterior insula (RAI) at voxel and cluster level after familywise error correction. No difference was found between study groups in activations to happy facial condition. Patients with schizophrenia did not show a differential activation between mixed happy and happy facial expression similar to controls in the right dorsolateral prefrontal cortex (DLPFC). CONCLUSIONS: Patients with schizophrenia showed decreased functioning in right prefrontal regions responsible for salience signaling and valence evaluation during emotion recognition. Our results indicate that fear and mixed happy/fear processing are impaired in schizophrenia, while happy facial expression processing is relatively intact.

[Pharmacological and other options in preventing dementia: a literature review]. / Demenciák megelozésének gyógyszeres és egyéb lehetoségei: irodalmi összefoglaló

BACKGROUND: At present 34 million people live with Alzheimer's disease around the world. This figure is expected to triple in the next 40 years. The major cause of this increase is the well-known aging of the society in Europe and in the US as well. AIMS AND METHODS: In this paper we review the results of the last 10 years, and discuss those pharmaceutical and other methods, which can be effective in the prevention of dementias. RESULTS: The most important pharmaceutical agents are beta secretase inhibitors, and active and passive immunizations. Several drugs in these groups are in phase III at the moment. The results from studies with intranasal insulin are also encouraging. As a non-drug option Mediterranean diet can be effective. However at present cognitive trainings seem to be the most effective in the prevention of dementias. These remediation therapies are based on the lifelong plasticity of the human brain. CONCLUSIONS: In summary we can conclude that there are promising drug developments in progess for the prevention of dementias, but the breakthrough has not been achieved yet. At present the best option is decreasing risk factors, that is treatment of hypertension, prevention of obesity and diabetes, and cognitive trainings are recommended for prevention.

The antipsychotic agent sulpiride microinjected into the ventral pallidum restores positive symptom-like habituation disturbance in MAM-E17 schizophrenia model rats.

Dysfunction of subcortical D2-like dopamine receptors (D2Rs) can lead to positive symptoms of schizophrenia, and their analog, the increased locomotor activity in schizophrenia model MAM-E17 rats. The ventral pallidum (VP) is a limbic structure containing D2Rs. The D2R antagonist sulpiride is a widespread antipsychotic drug, which can alleviate positive symptoms in human patients. However, it is still not known how sulpiride can influence positive symptoms via VP D2Rs. We hypothesize that the microinjection of sulpiride into the VP can normalize hyperactivity in MAM-E17 rats. In addition, recently, we showed that the microinjection of sulpirid into the VP induces place preference in neurotypical rats. Thus, we aimed to test whether intra-VP sulpiride can also have a rewarding effect in MAM-E17 rats. Therefore, open field-based conditioned place preference (CPP) test was applied in neurotypical (SAL-E17) and MAM-E17 schizophrenia model rats to test locomotor activity and the potential locomotor-reducing and rewarding effects of sulpiride. Sulpiride was microinjected bilaterally in three different doses into the VP, and the controls received only vehicle. The results of the present study demonstrated that the increased locomotor activity of the MAM-E17 rats was caused by habituation disturbance. Accordingly, larger doses of sulpiride in the VP reduce the positive symptom-analog habituation disturbance of the MAM-E17 animals. Furthermore, we showed that the largest dose of sulpiride administered into the VP induced CPP in the SAL-E17 animals but not in the MAM-E17 animals. These findings revealed that VP D2Rs play an important role in the formation of positive symptom-like habituation disturbances in MAM-E17 rats.

[Differentiation between mild cognitive impairment and healthy elderly population using neuropsychological tests]. / Az enyhe kognitív deficitben szenvedok differenciálása az egészséges idos populációtól neuropszichológiai tesztek segítségével.

OBJECTIVE: Paired Associates Learning (PAL) test assesses brain functions in those brain regions affected earliest by Alzheimer's dementia. The aim of the present study was to assess the usability of our implementation of the PAL test for screening mild cognitive impairment. METHODOLOGY: Based on Petersen criteria, 14 out of the 63 subjects were diagnosed with mild cognitive impairment. Visuospatial learning was assessed by our implementation of PAL test. The ability of the PAL test to differentiate between study groups was compared to the Addenbrook Cognitive Examination (ACE) and to the Mini Mental State Examination (MMSE). Linear logistic regression was used for statistical analysis, and the results are presented as Receiver Operating Characteristics (ROC) curves. All analyses were performed by SAS 9.2. RESULTS: All the results of neuropsychological tests differed significantly between the study groups. However, considerable difference could be detected between the tests regarding specificity and sensitivity. The PAL test reached the sensitivity of the ACE, while its specificity was slightly under the ACE. DISCUSSION: The PAL test developed in the framework of the present study is found to be able to differentiate between MCI and healthy controls. It outperformed the MMSE in terms of sensitivity and specificity, while it needs comparable time to perform. Its sensitivity, the important parameter for screening, is comparable to ACE, while it needs significantly shorter time and less assistance.

Diet of wolves Canis lupus returning to Hungary.

At the end of the nineteenth century, the wolf Canis lupus was extinct in Hungary and in recent decades has returned to the northern highland area of the country. The diet of wolves living in groups in Aggteleki National Park was investigated using scat analysis (n = 81 scats) and prey remains (n = 31 carcasses). Throughout the year wolves (average, minimum two wolves per year) consumed mostly wild-living ungulates (mean percent of biomass consumed, B% 97.2%; relative frequency of occurrence, %O 74.0%). The wild boar Sus scrofa was the most common prey item found in wolf scat (%B 35.6%) and is also the most commonly occurring ungulate in the study areas. The second most commonly occurring prey item in wolf scat was red deer Cervus elaphus (B% 32.8%). Conversely, prey remain analyses revealed wild boar as the second most commonly utilised prey species (%O 16.1%) after red deer (%O 67.7%). The roe deer Capreolus capreolus that occurs at lower population densities was the third most commonly utilised prey species. The importance of low population density mouflon Ovis aries, livestock and other food types was low. The results are similar to those found in the northern part of the Carpathian Mountains.

The antipsychotic drug sulpiride in the ventral pallidum paradoxically impairs learning and induces place preference.

Sulpiride, as a D2-like dopamine (DA) receptor (D2R) antagonist, is an important antipsychotic drug in the treatment of schizophrenia. Recently, we have shown that the activation of D2Rs in the ventral pallidum (VP) modulates the activity of the ventral tegmental area (VTA) DAergic neurons. According to our hypothesis, intra-VP sulpiride can influence the motivational and learning processes, pervasively modifying the behavior of examined animals. In the present study, sulpiride was microinjected into the VP of male Wistar rats in three different doses. Morris water maze (MWM) test was applied to investigate the effects of sulpiride on spatial learning, while conditioned place preference (CPP) test was used to examine the potential rewarding effect of the drug. In order to show, whether the animals can associate the rewarding effect with an area which can be recognized only on its spatial location, we introduced a modified version of the CPP paradigm, the spatial CPP test. Our results show that the intra-VP sulpiride dose-dependently impairs learning processes. However, the largest dose of sulpiride induces place preference. Results of the spatial CPP paradigm demonstrate that the animals cannot associate the rewarding effect of the drug with the conditioning area based on its spatial location. In the CPP paradigm, locomotor activity decrease could be observed in the sulpiride-treated rats, likely because of a faster habituation with the conditioning environment. In summary, we can conclude that intra-VP sulpiride has a dual effect: it diminishes the hippocampus-dependent spatial learning processes, in addition, it has a dose-dependent rewarding effect.

Effect of D1- and D2-like Dopamine Receptor Antagonists on the Rewarding and Anxiolytic Effects of Neurotensin in the Ventral Pallidum.

BACKGROUND: Neurotensin (NT) acts as a neurotransmitter and neuromodulator in the central nervous system. It was shown previously that NT in the ventral pallidum (VP) has rewarding and anxiolytic effects. NT exerts its effect in interaction with dopamine (DA) receptors in numerous brain areas; however, this has not yet been investigated in the VP. The aim of this study was to examine whether the inhibition of D1-like and D2-like DA receptors of the VP can modify the above mentioned effects of NT. METHODS: Microinjection cannulas were implanted by means of stereotaxic operations into the VP of male Wistar rats. The rewarding effect of NT was examined by means of a conditioned place preference test. Anxiety was investigated with an elevated plus maze test. To investigate the possible interaction, D1-like DA receptor antagonist SCH23390 or D2-like DA receptor antagonist sulpiride were microinjected prior to NT. All of the drugs were also injected independently to analyze their effects alone. RESULTS: In the present experiments, both the rewarding and anxiolytic effects of NT in the VP were prevented by both D1-like and D2-like DA receptor antagonists. Administered on their own, the antagonists did not influence reward and anxiety. CONCLUSION: Our present results show that the activity of the D1-like and D2-like DA receptors of the VP is a necessary requirement for both the rewarding and anxiolytic effects of NT.

Countrywide population movement monitoring using mobile devices generated (big) data during the COVID-19 crisis.

Mobile phones have been used to monitor mobility changes during the COVID-19 pandemic but surprisingly few studies addressed in detail the implementation of practical applications involving whole populations. We report a method of generating a "mobility-index" and a "stay-at-home/resting-index" based on aggregated anonymous Call Detail Records of almost all subscribers in Hungary, which tracks all phones, examining their strengths and weaknesses, comparing it with Community Mobility Reports from Google, limited to smartphone data. The impact of policy changes, such as school closures, could be identified with sufficient granularity to capture a rush to shops prior to imposition of restrictions. Anecdotal reports of large scale movement of Hungarians to holiday homes were confirmed. At the national level, our results correlated well with Google mobility data, but there were some differences at weekends and national holidays, which can be explained by methodological differences. Mobile phones offer a means to analyse population movement but there are several technical and privacy issues. Overcoming these, our method is a practical and inexpensive way forward, achieving high levels of accuracy and resolution, especially where uptake of smartphones is modest, although it is not an alternative to smartphone-based solutions used for contact tracing and quarantine monitoring.

Distance measurement for pulse wave velocity estimation in pediatric age: Comparison with intra-arterial path length.

BACKGROUND AND AIMS: Central pulse wave velocity (PWV) is a marker of arterial stiffness and is calculated by dividing the pulse wave travel distance by the transit time. However, there is no consensus as to the ideal distance measurement in children. The aim of our study was to identify the more reliable method to assess the distance measurement in the pediatric age. METHODS: Carotid-femoral PWV was measured by applanation tonometry in 988 healthy children aged 6.5-19.9 years. Two different surface distances were assessed: the subtraction method, representing the distance from the suprasternal notch to the femoral artery minus the distance from the carotid artery to the suprasternal notch, and the direct method, consisting of 80% of the distance from the carotid artery to the femoral artery. Both these methods were compared with the actual path length determined by magnetic resonance imaging (MRI) in 31 children. RESULTS: Subtraction and direct methods were significantly correlated in patients aged <14 years and the corresponding PWV values showed a good agreement. In children aged ≥14 years, a significant difference between the two methods was found: subtraction - direct distance = -45 ± 28 mm, with a significant difference in the resulting PWV values = -0.57 ± 0.35 m/s (p < 0.0001). This result was confirmed by MRI, showing a 10% overestimation in distance measurement by the direct method in subjects aged ≥14 years, resulting in a significantly higher PWV. CONCLUSIONS: These data suggest a greater reliability of the subtractive method of distance measurement compared to the direct method in children.

HER2-Targeted Tyrosine Kinase Inhibitors Cause Therapy-Induced-Senescence in Breast Cancer Cells.

Prolonged treatment of HER2 positive breast cancer cells with tyrosine kinase inhibitors (TKIs) leads to the emergence of acquired resistance. However, the effects of continuous TKI exposure on cell fate, and the steps leading to the acquisition of a resistant phenotype are poorly understood. To explore this, we exposed five HER2 positive cells lines to HER2 targeted therapies for periods of up to 4 weeks and examined senescence associated ß-galactosidase (SA-ß-gal) activity together with additional markers of senescence. We found that lapatinib treatment resulted in phenotypic alterations consistent with a senescent phenotype and strong SA-ß-gal activity in HER2-positive cell lines. Lapatinib-induced senescence was associated with elevated levels of p15 and p27 but was not dependent on the expression of p16 or p21. Restoring wild type p53 activity either by transfection or by treatment with APR-246, a molecule which reactivates mutant p53, blocked lapatinib-induced senescence and caused increased cell death. In contrast to lapatinib, SA-ß-gal activity was not induced by exposing the cells to trastuzumab as a single agent but co-administration of lapatinib and trastuzumab induced senescence, as did treatment of the cells with the irreversible HER2 TKIs neratinib and afatinib. Neratinib- and afatinib-induced senescence was not reversed by removing the drug whereas lapatinib-induced senescence was reversible. In summary, therapy-induced senescence represents a novel mechanism of action of HER2 targeting agents and may be a potential pathway for the emergence of resistance.

Flying into the Sun.

After 60 years of technological and materials development, in August this year the Parker Solar Probe set off on its journey to skim the atmosphere of the Sun. Mission Scientist Adam Szabo summarizes this ambitious adventure.