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ImportancePreterm birth and socioeconomic status (SES) are associated with brain structure in childhood, but the relative contributions of each during the neonatal period are unknown.ObjectiveTo investigate associations of birth gestational age (GA) and SES with neonatal brain morphology by testing 3 hypotheses: GA and SES are associated with brain morphology; associations between SES and brain morphology vary with GA; and associations between SES and brain structure and morphology depend on how SES is operationalized.Design, Setting, and ParticipantsThis cohort study recruited participants from November 2016 to September 2021 at a single center in the United Kingdom. Participants were 170 extremely and very preterm infants and 91 full-term or near-term infants. Exclusion criteria were major congenital malformation, chromosomal abnormality, congenital infection, cystic periventricular leukomalacia, hemorrhagic parenchymal infarction, and posthemorrhagic ventricular dilatation.ExposuresBirth GA and SES, operationalized at the neighborhood level (using the Scottish Index of Multiple Deprivation), the family level (using parental education and occupation), and subjectively (World Health Organization Quality of Life measure).Main Outcomes and MeasuresBrain volume (85 parcels) and 5 whole-brain cortical morphology measures (gyrification index, thickness, sulcal depth, curvature, surface area) at term-equivalent age (median [range] age, 40 weeks, 5 days [36 weeks, 2 days to 45 weeks, 6 days] and 42 weeks [38 weeks, 2 days to 46 weeks, 1 day] for preterm and full-term infants, respectively).ResultsParticipants were 170 extremely and very preterm infants (95 [55.9%] male; 4 of 166 [2.4%] Asian, 145 of 166 [87.3%] White) and 91 full-term or near-term infants (50 [54.9%] male; 3 of 86 [3.5%] Asian, 78 of 86 [90.7%] White infants) with median (range) birth GAs of 30 weeks, 0 days (22 weeks, 1 day, to 32 weeks, 6 days) and 39 weeks, 4 days (36 weeks, 3 days, to 42 weeks, 1 day), respectively. In fully adjusted models, birth GA was associated with a higher proportion of brain volumes (27 of 85 parcels [31.8%]; β range, −0.20 to 0.24) than neighborhood-level SES (1 of 85 parcels [1.2%]; β = 0.17 [95% CI, −0.16 to 0.50]) or family-level SES (maternal education: 4 of 85 parcels [4.7%]; β range, 0.09 to 0.15; maternal occupation: 1 of 85 parcels [1.2%]; β = 0.06 [95% CI, 0.02 to 0.11] respectively). There were interactions between GA and both family-level and subjective SES measures on regional brain volumes. Birth GA was associated with cortical surface area (β = 0.10 [95% CI, 0.02 to 0.18]) and gyrification index (β = 0.16 [95% CI, 0.07 to 0.25]); no SES measure was associated with cortical measures.Conclusions and RelevanceIn this cohort study of UK infants, birth GA and SES were associated with neonatal brain morphology, but low GA had more widely distributed associations with neonatal brain structure than SES. Further work is warranted to elucidate the mechanisms underlying the association of both GA and SES with early brain development.

Autism is considered to entail a social impairment whereby autistic people experience difficulty interpreting others' mental states. However, recent research has shown that nonautistic people also have difficulty understanding the mental states of autistic people. This mismatch of understanding may explain lower rapport in interactions between autistic and nonautistic people. As mental states can be expressed externally through socially normed signals, it is important to investigate the role of such signals in autistic, nonautistic, and mixed interactions. This study explores variability in two social signals between autistic, nonautistic, and mixed interactions, and how their use may affect rapport within interactions.Videos from a previous study of autistic, nonautistic, and mixed pair interactions in a diffusion chain context in which participants were aware of others' diagnostic status were video coded for mutual gaze and backchanneling as candidate indicators of interactional rapport.Although use of mutual gaze and backchanneling was lower in mixed pairs than in nonautistic pairs, corresponding to lower ratings of interactional rapport, less backchanneling in autistic pairs of both nonverbal and verbal subtypes corresponded to higher ratings of rapport.We observed differences in the use of candidate rapport markers between autistic, mixed, and nonautistic interactions, which did not map onto patterns of rapport scores, suggesting differences in reliance on these cues between autistic and nonautistic people. These results suggest that visible markers of rapport may vary by neurotype or pairing and give clues to inform future investigations of autistic interaction.When someone is autistic, society generally assumes they have difficulty interacting with others. Social difficulties between autistic and nonautistic people are thought to be due to the autistic person not being able to interact using nonautistic social behaviors. This belief can lead to many autistic people feeling alienated. However, recent research supports what autistic people have been saying for a long time: that autistic people are capable of having successful and rewarding interactions with other autistic people. This suggests that social difficulties between autistic and nonautistic people may be due to a mismatch in social norms leading to difficulty for both people, not just the autistic person.In this study, we wanted to investigate whether certain social signals are used differently between autistic and nonautistic people. We also questioned whether using these signals helped or hurt the interaction depending on who was involved.We recorded people passing a story down a chain of people, like the game telephone, to see how they interacted with each other. Afterward, people wrote down scores for how much they enjoyed their interaction. We focused on two parts of the interaction: how much people were looking at each other and when they made short verbal responses such as “mhm” to show they were listening (backchanneling). We watched the recordings back and analyzed how long or how many times these actions were occurring.We found that when one autistic and one nonautistic person were interacting, they looked at each other and backchanneled less than two nonautistic people. This seemed to be linked with a less enjoyable interaction for them. However, backchanneling seemed to matter less in interactions between two autistic people. They backchanneled less while still having enjoyable interactions.Research has previously suggested that different social norms exist between autistic and nonautistic people. This study shows specific examples of this and how they may affect the interaction in a natural setting.This study has some weaknesses. For example, we measured when people looked at each other's faces rather than eye contact specifically, which can only be done with an eye tracker. Also, the people in the study knew whether the person they were talking to was autistic. This can be similar to normal life, as people do sometimes know this, although we would also be interested to see what the effect of not knowing would be.This line of research has important implications for how autistic people can be supported in society. Not only will understanding of social differences between autistic and nonautistic people help the way autistic people are perceived, but it will also help nonautistic people better understand and support the autistic people in their lives.

Structured abstractImportancePreterm birth and socioeconomic status (SES) are associated with brain structure in childhood, but the relative contributions of each during the neonatal period are unknown.ObjectiveTo investigate associations of gestational age (GA) and SES with neonatal brain morphology, by testing 3 hypotheses: GA and SES are associated with brain morphology; associations between SES and brain morphology vary across the GA range, and; associations between SES and brain structure/morphology depend on how SES is operationalized.DesignCohort study, recruited 2016-2021.SettingSingle center, UK.Participants170 preterm infants and 91 term infants with median (range) birth GA 30+0(22+1-32+6) and 39+4(36+3-42+1) weeks, respectively. Exclusion criteria: major congenital malformation, chromosomal abnormality, congenital infection, cystic periventricular leukomalacia, hemorrhagic parenchymal infarction, post-hemorrhagic ventricular dilatation.ExposuresUsing linear ridge regression models, we investigated associations of GA and SES, operationalized at the neighborhood-level (Scottish Index of Multiple Deprivation), family-level (parental education and occupation) and subjectively (WHO Quality of Life), with regional brain volumes and cortical morphology.Main outcomes/measuresBrain volume (85 parcels) and 5 whole-brain cortical morphology measures (gyrification index, thickness, sulcal depth, curvature, surface area) at term-equivalent age.ResultsIn fully adjusted models, GA associated with a higher proportion of brain volumes (22/85 [26%], β range |-0.13| to |0.22|) than neighborhood SES (1/85 [1%], β=0.17). GA associated with cortical surface area (β=0.10 [95% confidence interval (CI) 0.02-0.18]) and gyrification index (β=0.16 [95% CI 0.07-0.25]); neighborhood SES did not. Family-level SES associated with the volumes of more parcels than neighborhood SES, but it did not have as extensive associations with brain structure as GA. There were interactions between GA and both family- and subjective-level SES measures on brain structure.Conclusions/relevanceIn a UK cohort, GA and SES impact neonatal brain morphology, but low GA has more widely distributed effects on neonatal brain structure than neighborhood-level, family-level and subjective measures of SES. Further work is warranted to elucidate the mechanisms embedding GA and level-specific SES in early brain development.Three key pointsQuestionWhat are the impacts of preterm birth and socioeconomic status (SES), operationalized at neighborhood, family, and subjective levels, on neonatal brain structure?FindingAfter mutual adjustment, both low gestational age (GA) and SES associate with brain structure. The nature of SES-brain structure associations varies depending how SES is operationalized; there are interactions between GA and measures of family- and subjective-level SES on brain structure.MeaningLow GA, and to a lesser extent SES, are associated with neonatal brain structure. Further work is required to elucidate the mechanisms that embed preterm birth and level-specific SES in the developing brain.

1AbstractBackgroundPreterm birth is associated with atypical cognitive and socioemotional outcomes in childhood. Secure infant attachment protects against adverse outcomes, but could be modified by alterations in the early caregiving environment inherent to essential neonatal intensive care or co-morbidities of preterm birth. We aimed to test the hypothesis that preterm birth is associated with differences in infant attachment, and to investigate clinical, neurodevelopmental and socioeconomic variables that are associated with infant attachment.Methods82 preterm and 75 term infants with mean (range) gestational age at birth 29.5 (22.1 – 32.9) and 39.6 (36.4 – 42.1) weeks, respectively, completed the Still-Face Paradigm (SFP) at nine months of corrected age. Attachment dimensions and categories were obtained from infant responses to the SFP during the reunion episode using a published coding scheme, and an alternative principal component (PC) and clustering strategy. Neurodevelopment was assessed using the Vineland Adaptive Behavior Scales, and socioeconomic status was operationalized as neighborhood deprivation.ResultsPreterm and term infants significantly differed in fretfulness, attentional PC scores and in their distribution between attachment clusters (p-values ≤ 0.3); with preterm infants exhibiting less fretful and more neutral responses to the SFP. Preterm and term infants did not significantly differ in distress, attentiveness to caregivers, emotional PC scores, or in their distribution between attachment styles (p-values ≥ .13). In the whole sample, fretfulness correlated with socioeconomic deprivation (rs= −0.18, p-value = .02).ConclusionsData reveal subtle attachment differences between preterm and term infants at nine months of age, which may not always be captured by traditional approaches for categorizing attachment. Findings suggests that caregiver-infant attachment relationships may not be fully resilient to the effects of prematurity on the developing infant, but this depends on how attachment is measured. Our results highlight putative links between socioeconomic deprivation and infant attachment that warrant further study.

Shoulder pain is a highly prevalent condition, often resulting in major life limitations, and requiring effective treatments. In this work, we explore the anatomical basis of a proposed approach to the regional anesthesia of the shoulder through a single injection under the subscapularis muscle. Bilateral experimental injections in shoulders from body donors (Radiolar (R) and Methylene-Blue) under the subscapular muscle (n = 11) and cadaveric systematic dissections of other 35 shoulders from body donors were performed. Injectate spread was then qualitatively assessed. Long axis of permeable foramina in the anterior aspect of the shoulder joint capsule was measured in centimeters using a digital caliper. More than 40% of specimens had at least one permeable space (Weitbrech and/or Rouviere foramina) communicating the subscapular bursa and the articular space. We further demonstrate that an ultrasonography-guided injection under the subscapularis muscle allows the spread of the injectate through the anterior, inferior and posterodorsal walls of the articular capsule, the subacromial bursa, and the bicipital groove, as well as into the articular space for some injections. The odds of accidental intraarticular injection decrease when injecting with low volumes. This anatomical study provides a detailed description of foramina between glenohumeral ligaments. Furthermore, the data shown in this work supports, as a proof of concept, a safe alternative for rapid and specific blockade of terminal sensory branches innervating the shoulder joint capsule. (c) 2021 Elsevier GmbH. All rights reserved.

In infancy, stress responses and emotion regulation are often coupled. Both are impacted by prematurity, thoughtheir relationship to one another in the case of infants born preterm is not fully understood. We investigatedemotion regulation behaviours, cortisol reactivity and recovery and coupling between emotion regulation andcortisol reactivity to and recovery from a stressor in preterm infants. 53 preterm and 67 full-term infants withmean (range) gestational age at birth 29+3 (24+0-31+6) and 39+3 (36+2-42+0) weeks respectively were exposedto a socio-emotional stressor, the still-face (SF) paradigm, at 9 months of age (corrected for prematurity). Theduration of negative affect and self-comforting behaviours exhibited in response to the SF, coded from a 10-minutevideo-taped interaction, were compared between groups. Saliva was collected from a subset (20 preterm, 24term infants) at three timepoints: pre-SF and 20- and 30-minutes post SF. Cortisol concentrations at eachtimepoint were compared between groups. Associations between behavioural measures and cortisol concentrationswere explored. There was no significant difference in duration of self-comforting behaviour betweenpreterm and term infants. Preterm infants spent a significantly smaller proportion of time in a negative affectivestate compared to term infants (0.18 vs 0.25 s, p = 0.03). Salivary cortisol concentration was significantly higherin the preterm compared to the term group 30 min post SF (2.85 vs 1.77 nmol/L, p = 0.009), though findingswere no longer significant after adjusting for time of day of sampling and socioeconomic deprivation. Aftercontrolling for time of day, greater negative affect was correlated with higher cortisol concentration 30 min postSF in the full-term (r = 0.58, p = 0.004) but not the preterm group (r = 􀀀 0.01, p > 0.05). Our findings suggestaltered response to an acute stressor in preterm infants, manifesting as a muted emotional response, and a lack ofcoupling between endocrine and behavioural stress response. Replication studies in larger samples would help tofurther understand biological stress repose in preterm infants and its relationship to behaviour, time of day anddeprivation.

Major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BD) have both shared and discrete genetic risk factors, and are associated with peripheral abnormalities. The relationships between such genetic architectures and blood-based markers are, however, unclear. We investigated relationships between polygenic risk scores (PRS) for these disorders and peripheral markers in the UK Biobank cohort. We calculated polygenic risk scores for n = 367,329 (MDD PRS), n = 366,465 (SCZ PRS), and n = 366,383 (BD PRS) UK Biobank cohort subjects. We then examined associations between disorder PRS and 58 inflammatory/immune, hematological, bone, cardiovascular, hormone, liver, renal and diabetes-associated blood markers using two generalized linear regression models: ‘minimally adjusted’ controlling for variables such as age and sex, and ‘fully adjusted’ including additional lifestyle covariates: BMI, alcohol and smoking status, and medication intake. There were 38/58 MDD PRS, 32/58 SCZ PRS, and 20/58 BD PRS-blood marker associations detected for our minimally adjusted model. Of these, 13/38 (MDD PRS), 14/32 (SCZ PRS), and 10/20 (BD PRS) associations remained significant after controlling for lifestyle factors. Many were disorder-specific, with 8/13 unique MDD PRS associations identified. Several disorder-specific associations for MDD and SCZ were immune-related, with mostly positive and negative associations identified for MDD and SCZ PRS respectively. This study suggests that MDD, SCZ and BD have both shared and distinct peripheral markers associated with disorder-specific genetic risk. The results also implicate inflammatory dysfunction in MDD and SCZ, albeit with differences in patterns between the two conditions, and enrich our understanding of potential underlying pathophysiological mechanisms in major psychiatric disorders.

BackgroundMajor depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BD) have both shared and discrete genetic risk factors and abnormalities in blood-based measures of inflammation and blood-brain barrier (BBB) permeability. The relationships between such genetic architectures and blood-based markers are however unclear. We investigated relationships between polygenic risk scores for these disorders and peripheral biomarkers in the UK Biobank cohort.MethodsWe calculated polygenic risk scores (PRS) for samples of n = 367,329 (MDD PRS), n = 366,465 (SCZ PRS), and n = 366,383 (BD PRS) individuals from the UK Biobank cohort. We examined associations between each disorder PRS and 62 blood markers, using two generalized linear regression models: ‘minimally adjusted’ controlling for variables including age and sex, and ‘fully adjusted’ including additional lifestyle covariates such as alcohol and smoking status.Results12/62, 13/62 and 9/62 peripheral markers were significantly associated with MDD, SCZ and BD PRS respectively for both models. Most associations were disorder PRS-specific, including several immune-related markers for MDD and SCZ. We also identified several BBB-permeable marker associations, including vitamin D for all three disorder PRS, IGF-1 and triglycerides for MDD PRS, testosterone for SCZ PRS, and HDL cholesterol for BD PRS.ConclusionsThis study suggests that MDD, SCZ and BD have shared and distinct peripheral markers associated with disorder-specific genetic risk. The results implicate BBB permeability disruptions in all three disorders and inflammatory dysfunction in MDD and SCZ, and enrich our understanding of potential underlying pathophysiological mechanisms in major psychiatric disorders.

Combined ultrasound (US)-guided blockade of the suprascapular and axillary nerves (ANs) has been proposed as an alternative to interscalene blockade for pain control in shoulder joint pathology or postsurgical care. This technique could help avoid respiratory complications and/or almost total upper limb palsy. Nowadays, the AN blockade is mostly performed using an in-plane caudal-to-cephalic approach from the posterior surface of the shoulder, reaching the nerve immediately after it exits the neurovascular quadrangular space (part of the spatium axillare). Despite precluding most respiratory complications, this approach has not made postsurgical pain relief any better than an interscalene blockade, probably because articular branches of the AN are not blocked.Cephalic-to-caudal methylene blue injections were placed in the first segment of the AN of six Thiel-embalmed cadavers using an US-guided anterior approach in order to compare the distribution with that produced by a posterior approach to the contralateral AN in the same cadaver. Another 21 formalin-fixed cadavers were bilaterally dissected to identify the articular branches of the AN.We found a good spread of the dye on the AN and a constant relationship of this nerve with the subscapularis muscle. The dye reached the musculocutaneous nerve, which also contributes to shoulder joint innervation. We describe the anatomical landmarks for an ultrasonography-guided anterior AN blockade and hypothesize that this anterior approach will provide better pain control than the posterior approach owing to complete blocking of the joint nerve. Clin. Anat. 33:488-499, 2020. © 2019 Wiley Periodicals, Inc.

Background Idiopathic pulmonary fibrosis (IPF) is an age-related, progressive and lethal disease, whose pathogenesis is associated with fibroblasts/myofibroblasts foci that produce excessive extracellular matrix accumulation in lung parenchyma. Hypoxia has been described as a determinant factor in its development and progression. However, the role of distinct members of this pathway is not completely described. Methods By western blot, quantitative PCR, Immunohistochemistry and Immunocitochemistry were evaluated, the expression HIF alpha subunit isoforms 1, 2 & 3 as well, as their role in myofibroblast differentiation in lung tissue and fibroblast cell lines derived from IPF patients. Results Hypoxia signaling pathway was found very active in lungs and fibroblasts from IPF patients, as demonstrated by the abundance of alpha subunits 1 and 2, which further correlated with the increased expression of myofibroblast marker αSMA. In contrast, HIF-3α showed reduced expression associated with its promoter hypermethylation. Conclusions This study lends further support to the involvement of hypoxia in the pathogenesis of IPF, and poses HIF-3α expression as a potential negative regulator of these phenomena.

Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration in the substantia nigra and dopamine depletion in the striatum. Non-dopaminergic systems are also affected, including the serotonergic system. Enhanced striatal serotonergic innervation is a proposed compensatory mechanism for the dopaminergic deficit. Meanwhile a serotonergic deficit has been suggested as preceding the nigrostriatal dopaminergic pathology in PD. Our aim was to assess the serotonergic innervation of the striatum in a model of progressive experimental parkinsonism in macaques, from pre-symptomatic to symptomatic stages. The neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) was administered to adult macaque monkeys using a slow intoxication protocol. The intoxicated animals were classified into asymptomatic, recovered, moderate and severe parkinsonian, based on their motor behavior. The serotonergic innervation was studied by immunohistochemistry against serotonin (5-HT). In the striatum, the density of 5-HT-immunoreactive (5-HT+) axons was estimated with stereology. Images of the striatum in the immunostained sections were taken to compare the distribution patterns of the serotonergic innervation between groups. These patterns were apparently similar among the groups. Axonal density estimations showed no differences in striatal 5-HT+ innervation between the intoxicated groups and the control group. Accordingly, this study fails to find significant changes in the striatal serotonergic axonal innervation in MPTP-treated monkeys, coinciding with previous biochemical findings in our model. However, it is possible that alterations in the serotonergic system in PD could be independent of axonal density changes. Consequently, the proposed role for striatal serotonin serving as a compensatory mechanism for dopaminergic denervation merits further study. This article is part of the special issue entitled ‘Serotonin Research: Crossing Scales and Boundaries’.

BackgroundCerebral small vessel disease (SVD) is an important cause of acute ischemic stroke and vascular dementia. Several studies recruiting more males than females have reported sex differences regarding SVD incidence and severity, but it is unclear whether this reflects underlying sex-specific mechanisms or recruitment bias. This work aimed to systematically review and meta-analyze potential sex differences in SVD by assessing the male-to-female ratio (M:F) of recruited participants and incidence of SVD, risk factor presence, distribution and severity of SVD features.MethodsFull text of 228 studies from four databases of recent systematic reviews on SVD and an independent search of MEDLINE were evaluated against inclusion and exclusion criteria (registered protocol: CRD42020193995). Data from participants with clinical or non-clinical presentations of SVD with radiological evidence of SVD were extracted. Sex ratios of total participants or SVD groups were calculated and differences in sex ratios across time, countries, SVD severity and risk factors for SVD were explored.ResultsAmongst 123 relevant studies (n = 36,910 participants) including 53 community-based, 67 hospital-based and 3 mixed studies, more males were recruited in hospital-based than in community-based studies (M:F = 1.16 (0.70) vs M:F = 0.79 (0.35), respectively; p ConclusionsOur results highlight differences in male-to-female ratios in SVD that may reflect sex-specific variability in risk factor exposures, study participation, clinical recognition, genuine SVD severity, or clinical presentation and have important clinical and translational implications.