Mother adversity and co-residence time impact mother-child similarity in genome-wide and gene-specific methylation profiles.

BACKGROUND: The effects of adverse life events on physical and psychological health, with DNA methylation (DNAm) as a critical underlying mechanism, have been extensively studied. However, the epigenetic resemblance between mother and child in the context of neglectful caregiving, and whether it may be shaped by the emotional impact of maternal stressful events and the duration of co-residence (indexed by child age), remains unknown. The present study examined mother-child similarity in methylation profiles, considering the potential effect of mother adversity, mother empathy, neglect-control group, child age (an index of years of mother-child co-residence), and mother age. Using Illumina Epic arrays, we quantified DNAm in 115 mother-child saliva samples. We obtained a methylation similarity index by computing correlation coefficients between methylation profiles within dyads, for the entire epigenome, and five specific genes related to stress and empathy: NR3C1, FKPB5, OXTR, SCL6A4, and BDNF. RESULTS: The methylation profiles of the mother-child familial pairs significantly correlated as compared to mother-child random pairs for the entire epigenome and NR3C1, FKBP5, OXTR and BDNF genes. Next, multiple linear regression models observed associations of mother adversity, child age, and neglect-control group on mother-child methylation similarity, only significant in mother-child familial pairs, after correcting for multiple comparisons. Higher mother adversity was associated with lower mother-child methylation similarity for the epigenome-wide analysis, for the BDNF gene, and in the neglect-control group for the OXTR gene. In turn, being an older child (longer co-residence) was associated with higher mother-child methylation similarity. CONCLUSIONS: Mother adversity and co-residence time are modulating factors in the intergenerational methylation process that offer a window into development-dependent adaptations that can be affected by both hereditary and environmental factors, significantly observed only in biological dyads. A twofold implication for child well-being emerges, one is positive in that children of mothers exposed to life adversity or neglect did not necessarily inherit their methylation patterns. The other is concerning due to the influence of time spent living together, which affects similarity with the mother and potentially increases the risk of inheriting an epigenetic profile associated with future dysfunctional parenting patterns. This underscores the importance of the 'the earlier, the better' recommendation by the Child Protection System, which is not always followed.

Latitude and longitude as drivers of COVID-19 waves' behavior in Europe: A time-space perspective of the pandemic.

BACKGROUND: Social restrictions and vaccination seem to have shaped the pandemic development in Europe, but the influence of geographical position is still debated. This study aims to verify whether the pandemic spread through Europe following a particular direction, during the period between the start of the pandemic and November 2021. The existence of a spatial gradient for epidemic intensity is also hypothesized. METHODS: Daily COVID-19 epidemiological data were extracted from Our World in Data COVID-19 database, which also included vaccination and non-pharmacological interventions data. Latitude and longitude of each country's centroid were used as geographic variables. Epidemic periods were delimited from epidemic surge data. Multivariable linear and Cox's regression models were performed for each epidemic period to test if geographical variables influenced surge dates. Generalized additive models (GAM) were used to test the spatial gradient hypothesis with three epidemic intensity measures. RESULTS: Linear models suggest a possible west-east shift in the first epidemic period and features a significant association of NPIs with epidemic surge delay. Neither latitude nor longitude had significant associations with epidemic surge timing in both second and third periods. Latitude displays strong negative associations with all epidemic intensity measures in GAM models. Vaccination was also negatively associated with intensity. CONCLUSIONS: A longitudinal spread of the pandemic in Europe seems plausible, particularly concerning the first wave. However, a recurrent trend was not observed. Southern Europe countries may have experienced increased transmissibility and incidence, despite climatic conditions apparently unfavourable to the virus.

The shared mother-child epigenetic signature of neglect is related to maternal adverse events.

Studies of DNA methylation have revealed the biological mechanisms by which life adversity confers risk for later physical and mental health problems. What remains unknown is the "biologically embedding" of maternal adverse experiences resulting in maladaptive parenting and whether these epigenetic effects are transmitted to the next generation. This study focuses on neglectful mothering indexed by a severe disregard for the basic and psychological needs of the child. Using the Illumina Human Methylation EPIC BeadChip in saliva samples, we identified genes with differentially methylated regions (DMRs) in those mothers with (n = 51), versus those without (n = 87), neglectful behavior that present similar DMRs patterns in their children being neglected versus non-neglected (n = 40 vs. 75). Mothers reported the emotional intensity of adverse life events. After covariate adjustment and multiple testing corrections, we identified 69 DMRs in the mother epigenome and 42 DMRs in the child epigenome that were simultaneously above the α = 0.01 threshold. The common set of nine DMRs contained genes related to childhood adversity, neonatal and infant diabetes, child neurobehavioral development and other health problems such as obesity, hypertension, cancer, posttraumatic stress, and the Alzheimer's disease; four of the genes were associated with maternal life adversity. Identifying a shared epigenetic signature of neglect linked to maternal life adversity is an essential step in breaking the intergenerational transmission of one of the most common forms of childhood maltreatment.

Regional accents modulate perspective in geographical space.

In this study, participants listened to first-person statements that mentioned a character who was approaching a geographical location close to (Tenerife, Canary Islands) or distant from the participant (Madrid, Spanish peninsula), pronounced with either the participants' local or a distal regional accent. Participants more often judged approaching statements as coherent when they refer to a close place pronounced with local accent or refer to a distant place with distal accent, rather than when they refer to a close place with distal accent or to a distant place with local accent. These results strongly suggest that the local accent induces listeners to keep their own geographical perspective, whereas the distal accent determines shifting to another's perspective. In sum, a subtle paralinguistic cue, the speaker's regional accent, modulates the participants' geographic perspective when they listen to identical first-person sentences with approaching deictic verbs.

Reduction in Epigenetic Age Acceleration Is Related to Empathy in Mothers with Neglectful Caregiving.

DNA methylation clocks are used as molecular estimators of epigenetic age, but with little evidence in mothers and none in neglectful mothering. We investigated differences in epigenetic age acceleration (EAA) and the role of empathy using the PhenoAge clock. We collected saliva samples from mothers with extreme disregard for their child's needs (50 in the neglect group, NG) and mothers with non-neglectful caregiving (87 in the control group, CG). Mothers completed an empathy scale, along with questionnaires of their own childhood maltreatment, adverse life events and psychiatric disorders. Sociodemographic variables potentially affecting EAA were also measured. The ANCOVA solution showed a significant increase in EAA in the NG compared to the CG, after adjustment for maternal age, number of pregnancies, financial assistance, adverse events, childhood maltreatment and psychiatric disorder. The group interaction effects showed a reduction in EAA for greater empathic concern and for a higher education level both as positive factors, and an increment in EAA for mothers living in a two-parent family as a risk factor, all in the NG. Our findings open the search for protective factors of EAA associated with caregiver behavior to reduce health vulnerabilities and poor social functioning, especially for mothers at risk of maladaptive caregiving.

Improving Early Diagnosis of Child Neglect for a Better Response in Healthcare Settings.

Early diagnosis of child neglect is an ongoing challenge with consequences of the child's safety, health, and effective referral for intervention. This study aims to obtain a selected set of family, maternal, and dyadic variables of the immediate caregiving environment for diagnosis, preventive, and intervention responses in healthcare settings. Mothers and their children under five years old: 51 in the neglected group (NG) and 89 in the non-neglected control group (CG), were recruited through pediatric primary care services and social services in Spain. Family demographics, adverse events, childhood maltreatment, maternal psychopathologies, personality variables, and observed mother-child interactions were assessed. Gradient boosting analyses were applied for the contributor's relative importance (RI), followed by logistic regression and discriminant analyses for those with higher RI. Parametric analyses showed high diagnostic accuracy (80-82% of NG and 92% of CG) for risky factors of child neglect: having a physically neglected and depressed mother, living in families in need of financial assistance, and large families; and for protective factors: having an older mother and showing higher mother-child emotional availability. Identifying a select group of features makes early diagnosis and preventive intervention more effective for mitigating the impact of child neglect and building mother-child resilience.

Distinctive Frontal and Occipitotemporal Surface Features in Neglectful Parenting.

Although the brain signatures of adaptive human parenting are well documented, the cortical features associated with maladaptive caregiving are underexplored. We investigated whether cortical thickness and surface area vary in a small group of mothers who had neglected their children (24 in the neglect group, NG) compared to a control group of mothers with non-neglectful caregiving (21 in the control group, CG). We also tested whether the cortical differences were related to dyadic mother-child emotional availability (EA) in a play task with their children and whether alexithymia involving low emotional awareness that characterizes the NG could play a role in the cortical-EA associations. Whole-brain analysis of the cortical mantle identified reduced cortical thickness in the right rostral middle frontal gyrus and an increased surface area in the right lingual and lateral occipital cortices for the NG with respect to the CG. Follow-up path analysis showed direct effects of the right rostral middle frontal gyrus (RMFG) on the emotional availability (EA) and on the difficulty to identify feelings (alexithymia factor), with a marginal indirect RMFG-EA effect through this factor. These preliminary findings extend existing work by implicating differences in cortical features associated with neglectful parenting and relevant to mother-child interactive bonding.

Real-time monitoring shows substantial excess all-cause mortality during second wave of COVID-19 in Europe, October to December 2020.

The European monitoring of excess mortality for public health action (EuroMOMO) network monitors weekly excess all-cause mortality in 27 European countries or subnational areas. During the first wave of the coronavirus disease (COVID-19) pandemic in Europe in spring 2020, several countries experienced extraordinarily high levels of excess mortality. Europe is currently seeing another upsurge in COVID-19 cases, and EuroMOMO is again witnessing a substantial excess all-cause mortality attributable to COVID-19.

Multisession Anodal tDCS on the Right Temporo-Parietal Junction Improves Mentalizing Processes in Adults with Autistic Traits.

Persons with autism spectrum disorder (ASD) have impaired mentalizing skills. In this study, a group of persons with ASD traits (high-AQ scores) initially received sham tDCS before completing a pre-test in two mentalizing tasks: false belief and self-other judgments. Over the next week, on four consecutive days, they received sessions of anodal electrical stimulation (a-tDCS) over the right temporo-parietal junction (rTPJ), a region frequently associated with the theory of mind. On the last day, after the stimulation session, they completed a new set of mentalizing tasks. A control group (with low-AQ scores) matched in age, education and intelligence received just sham stimulation and completed the same pre-test and post-test. The results showed that the high-AQ group improved their performance (faster responses), after a-tDCS, in the false belief and in the self-other judgments of mental features, whereas they did not change performance in the false photographs or the self-other judgments of physical features. These selective improvements cannot be attributed to increased familiarity with the tasks, because the performance of the low-AQ control group remained stable about one week later. Therefore, our study provides initial proof that tDCS could be used to improve mentalizing skills in persons with ASD traits.

Neglectful maternal caregiving involves altered brain volume in empathy-related areas.

The maternal brain undergoes adaptations to sensitive caregiving that are critical for infant well-being. We investigated structural alterations associated with neglectful caregiving and their effects on mother-child interactive behavior. High-resolution 3D volumetric images were obtained on 25 neglectful (NM) and 23 non-neglectful control (CM) mothers. Using voxel-based morphometry, we compared differences in gray and white matter (GM and WM, respectively) volume. Mothers completed an empathy scale and participated with their children in a play task (Emotional Availability Scale, EA). Neglectful mothers showed smaller GM volume in the right insula, anterior/middle cingulate (ACC/MCC), and right inferior frontal gyrus and less WM volume in bilateral frontal regions than did CM. A greater GM volume was observed in the right fusiform and cerebellum in NM than in CM. Regression analyses showed a negative effect of greater fusiform GM volume and a positive effect of greater right frontal WM volume on EA. Mediation analyses showed the role of emotional empathy in the positive effect of the insula and right inferior frontal gyrus and in the negative effect of the cerebellum on EA. Neglectful mothering involves alterations in emotional empathy-related areas and in frontal areas associated with poor mother-child interactive bonding, indicating how critical these areas are for sensitive caregiving.

Limbic-visual attenuation to crying faces underlies neglectful mothering.

Neglectful mothering is one of the most common forms of childhood maltreatment, involving a severe disregard of the child's needs, yet little is known about its neural substrate. A child's needs are usually conveyed by signals of distress revealed by crying faces. We tested whether infant and adult crying faces are processed differently in two sociodemographically similar groups of Neglectful (NM) and non-neglectful Control Mothers (CM). We used functional brain imaging to analyze the BOLD response from 43 mothers (23 neglectful and 20 control) while viewing faces from infants and adults (crying and neutral). In NM as compared to CM, the BOLD responses to both infant and adult crying faces were significantly reduced in the cerebellum, lingual, fusiform, amygdala, hippocampus, parahippocampus, and inferior frontal gyrus. The reduced BOLD was also modulated by comorbid psychiatric symptoms. In the CM, frontal activation to infant versus adult crying faces was enhanced, whereas in the NM activation in the anterior cingulate cortex to infant crying was reduced compared to adult crying. The altered neural response to crying faces in NM, showing generic face and infant-specific face processing deficits, could underlie their characteristic poor social abilities as well as their poor response to infant needs, both affecting the caregiving role.

When syntax meets action: Brain potential evidence of overlapping between language and motor sequencing.

This study aims to extend the embodied cognition approach to syntactic processing. The hypothesis is that the brain resources to plan and perform motor sequences are also involved in syntactic processing. To test this hypothesis, Event-Related brain Potentials (ERPs) were recorded while participants read sentences with embedded relative clauses, judging for their acceptability (half of the sentences contained a subject-verb morphosyntactic disagreement). The sentences, previously divided into three segments, were self-administered segment-by-segment in two different sequential manners: linear or non-linear. Linear self-administration consisted of successively pressing three buttons with three consecutive fingers in the right hand, while non-linear self-administration implied the substitution of the finger in the middle position by the right foot. Our aim was to test whether syntactic processing could be affected by the manner the sentences were self-administered. Main results revealed that the ERPs LAN component vanished whereas the P600 component increased in response to incorrect verbs, for non-linear relative to linear self-administration. The LAN and P600 components reflect early and late syntactic processing, respectively. Our results convey evidence that language syntactic processing and performing non-linguistic motor sequences may share resources in the human brain.

Spread of Ebola virus disease based on the density of roads in West Africa.

On March 23rd 2014 the World Health Organization announced that a new Ebola outbreak had appeared in West Africa involving three countries. The objective of this study was to show how a road density index (RDI) could be constructed and a study of its association with Ebola cases during the outbreak. The study was carried out at the district level across the affected countries. RDI was calculated by km2 of territory as a proxy for the mobility of the population. To calculate this index, the number of km of road constructed in each district was estimated and subsequently divided by the area of each district expressed in km2. The accumulated incidence of Ebola was calculated per district. A generalised linear model with a Poisson distribution was used. The RDI varied from 0.12 to 0.84 between the districts. An RDI increase of 0.01 indicates a 3% increase in Ebola infection risk (RR is 1.03; CI 1.03-1.04). The density of the road network can influence the increased incidence of Ebola cases in the affected zone. An exhaustive mapping of the area could help the relevant organisations to manage another outbreak in the future and it could help the distribution of resources in an emergency situation.

Excess all-cause and influenza-attributable mortality in Europe, December 2016 to February 2017.

Since December 2016, excess all-cause mortality was observed in many European countries, especially among people aged ≥ 65 years. We estimated all-cause and influenza-attributable mortality in 19 European countries/regions. Excess mortality was primarily explained by circulation of influenza virus A(H3N2). Cold weather snaps contributed in some countries. The pattern was similar to the last major influenza A(H3N2) season in 2014/15 in Europe, although starting earlier in line with the early influenza season start.

Mediterranean spotted fever in Spain, 1997-2014: Epidemiological situation based on hospitalization records.

INTRODUCTION: Mediterranean spotted fever (MSF) is a zoonotic disease caused by Rickettsia conorii. In Spain, deficiencies in the official reporting result in misreporting of this disease. This study aims to describe the clinical and temporal-spatial characteristics of MSF hospitalizations between 1997 and 2014. MATERIALS AND METHODS: We performed a retrospective descriptive study using the Hospitalization Minimum Data Set (CMBD). All CMBD's hospital discharges with ICD-9 CM code 082.1 were analyzed. Hospitalization rates were calculated and clinical characteristics were described. Spatial distribution of cases and their temporal behavior were also assessed. RESULTS: A total of 4,735 hospitalizations with MSF diagnosis were recorded during the study period, out of which 62.2% were male, mean age of 48. Diabetes mellitus, alcohol dependence syndrome, and chronic liver disease occurred in 10.8%, 2.4% and 2.8% hospitalizations, respectively. The median annual hospitalization rate showed a decreasing trend from a maximum of 12.9 in 1997 to a minimum rate of 3.1 in 2014. Most admissions occurred during the summer, showing a significant annual seasonal behavior. Important regional differences were found. DISCUSSION: Although MSF hospitalization rates have decreased considerably, it remains a public health problem due to its severity and economic impact. Therefore, it would be desirable to improve its oversight and surveillance.

Inferior fronto-temporo-occipital connectivity: a missing link between maltreated girls and neglectful mothers.

The neurobiological alterations resulting from adverse childhood experiences that subsequently may lead to neglectful mothering are poorly understood. Maternal neglect of an infant's basic needs is the most prevalent type of child maltreatment. We tested white matter alterations in neglectful mothers, the majority of whom had also suffered maltreatment in their childhood, and compared them to a matched control group. The two groups were discriminated by a structural brain connectivity pattern comprising inferior fronto-temporo-occipital connectivity, which constitutes a major portion of the face-processing network and was indexed by fewer streamlines in neglectful mothers. Mediation and regression analyses showed that fewer streamlines in the right inferior longitudinal fasciculus tract (ILF-R) predicted a poorer quality of mother-child emotional availability observed during cooperative play and that effect depended on the respective interactions with left and right inferior fronto-occipital fasciculi (IFO-R/L), with no significant impact of psychopathological and cognitive conditions. Volume alteration in ILF-R but not in IFO-L modulated the impact of having been maltreated on emotional availability. The findings suggest the altered inferior fronto-temporal-occipital connectivity, affecting emotional visual processing, as a possible common neurological substrate linking a history of childhood maltreatment with maternal neglect.

Sentential Negation Might Share Neurophysiological Mechanisms with Action Inhibition. Evidence from Frontal Theta Rhythm.

UNLABELLED: According to the literature, negations such as "not" or "don't" reduce the accessibility in memory of the concepts under their scope. Moreover, negations applied to action contents (e.g., "don't write the letter") impede the activation of motor processes in the brain, inducing "disembodied" representations. These facts provide important information on the behavioral and neural consequences of negations. However, how negations themselves are processed in the brain is still poorly understood. In two electrophysiological experiments, we explored whether sentential negation shares neural mechanisms with action monitoring or inhibition. Human participants read action-related sentences in affirmative or negative form ("now you will cut the bread" vs "now you will not cut the bread") while performing a simultaneous Go/NoGo task. The analysis of the EEG rhythms revealed that theta oscillations were significantly reduced for NoGo trials in the context of negative sentences compared with affirmative sentences. Given the fact that theta oscillations are often considered as neural markers of response inhibition processes, their modulation by negative sentences strongly suggests that negation uses neural resources of response inhibition. We propose a new approach that views the syntactic operator of negation as relying on the neural machinery of high-order action-monitoring processes. SIGNIFICANCE STATEMENT: Previous studies have shown that linguistic negation reduces the accessibility of the negated concepts and suppresses the activation of specific brain regions that operate in affirmative statements. Although these studies focus on the consequences of negation on cognitive and neural processes, the proper neural mechanisms of negation have not yet been explored. In the present EEG study, we tested the hypothesis that negation uses the neural network of action inhibition. Using a Go/NoGo task embedded in a sentence comprehension task, we found that negation in the context of NoGo trials modulates frontal theta rhythm, which is usually considered a signature of action inhibition and control mechanisms.

Readers of narratives take the protagonist's geographical perspective. Evidence from an event-related potential study.

This ERP study explores how the reader's brain is sensitive to the protagonist's perspective in the fictitious environment of narratives. Participants initially received narratives describing a protagonist living in a given geographical place. Later on they were given short paragraphs describing another character as "coming" or "going" to a place either close to or distant from the protagonist. Paragraphs referring to distant places elicited larger negative waves than those with places close to the protagonist. Moreover, narratives with the verb to come incoherent with the protagonist's perspective (e.g., "she came to the distant place") elicited larger negative-going waves in the 320-400ms time window than coherent paragraphs (e.g., "she came to the close place"). These results indicate that readers of narratives were able to take the protagonist's geographical perspective, showing discourse-level coherence effects when they read motion sentences with the marked deictic verb to come.

Brain dynamics in the comprehension of action-related language. A time-frequency analysis of mu rhythms.

EEG mu rhythms (8-13 Hz) recorded at fronto-central electrodes are generally considered as markers of motor cortical activity in humans, because they are modulated when participants perform an action, when they observe another's action or even when they imagine performing an action. In this study, we analyzed the time-frequency (TF) modulation of mu rhythms while participants read action language ("You will cut the strawberry cake"), abstract language ("You will doubt the patient's argument"), and perceptive language ("You will notice the bright day"). The results indicated that mu suppression at fronto-central sites is associated with action language rather than with abstract or perceptive language. Also, the largest difference between conditions occurred quite late in the sentence, while reading the first noun, (contrast Action vs. Abstract), or the second noun following the action verb (contrast Action vs. Perceptive). This suggests that motor activation is associated with the integration of words across the sentence beyond the lexical processing of the action verb. Source reconstruction localized mu suppression associated with action sentences in premotor cortex (BA 6). The present study suggests (1) that the understanding of action language activates motor networks in the human brain, and (2) that this activation occurs online based on semantic integration across multiple words in the sentence.