Re-examining the link between childhood maltreatment and substance use disorder: a prospective, genetically informative study

Childhood maltreatment is considered a risk factor for substance use disorders (SUD), but this is largely based on retrospective self-reports that are subject to recall bias, designs that do not control for familial confounding, or both. The specific contribution of childhood maltreatment to SUD risk thus remains unclear. Here, we evaluated this contribution in a prospective cohort with objectively recorded childhood maltreatment, using a design that allows controlling for familial confounding. We used medical records and registers to study 525 young adults (20-37 years) with prospectively and objectively documented severe maltreatment exposure, 1979 clinical controls (unexposed former child and adolescent psychiatry patients), 1388 matched healthy controls; and their siblings and cousins. We examined the association between maltreatment and SUD using Cox regression models in the population, as well as stratified within siblings in the same family. SUD risk was significantly increased with childhood maltreatment exposure (crude HR: 6.61, 95% CI: 5.81-7.53; HR adjusted for sex, birthyear, externalizing problems, parents SUD and socioeconomic factors: 3.50, 95% CI 2.95, 4.16). An approximately threefold elevated SUD risk remained when comparing exposed individuals with their unexposed siblings (adjusted HR: 3.12, 95% CI 2.21, 4.42). We provide estimates of the association between childhood maltreatment and SUD accounting for possible confounds of both recall bias and familial factors. When familial confounding is controlled for, SUD risk attributable to severe childhood maltreatment is decreased, but nevertheless considerable. These findings establish a specific contribution of childhood maltreatment to SUD, underscoring the need for SUD prevention in young people exposed to maltreatment.Funding Agencies|Swedish Research CouncilSwedish Research CouncilEuropean Commission [2013-2024, 2013-07434]; Medical Training and Research Agreement in ostergotland Region [ALF 2017: LIO-599451, ALF 2018: LIO-692621, ALF 2019: LIO-791581]; Systembolagets alkoholforskningsrad [2016-0018, 2017-0075, 2018-0030]</p

Altered relationship between subjective perception and central representation of touch hedonics in adolescents with autism-spectrum disorder

An impairment of social communication is a core symptom of autism-spectrum disorder (ASD). Affective touch is an important means of social interaction, and C-Tactile (CT) afferents are thought to play a key role in the peripheral detection and encoding of these stimuli. Exploring the neural and behavioral mechanisms for processing CT-optimal touch (similar to 3 cm/s) may therefore provide useful insights into the pathophysiology of ASD. We examined the relationship between touch hedonics (i.e. the subjective pleasantness with which affective touch stimuli are perceived) and neural processing in the posterior superior temporal sulcus (pSTS). This region is less activated to affective touch in individuals with ASD, and, in typically developing individuals (TD), is correlated positively with touch pleasantness. TD and ASD participants received brushing stimuli at CT-optimal, and CT-non-optimal speeds during fMRI. Touch pleasantness and intensity ratings were collected, and affective touch awareness, a measure of general touch hedonics was calculated. As expected, slow touch was perceived as more pleasant and less intense than fast touch in both groups, whereas affective touch awareness was moderately higher in TD compared to ASD. There was a strong, positive correlation between right pSTS activation and affective touch awareness in TD, but not in ASD. Our findings suggest that altered neural coupling between right pSTS and touch hedonics in ASD may be associated with social touch avoidance in ASD.Funding Agencies|Swedish Research CouncilSwedish Research CouncilEuropean Commission [538-2013-7434]; ALF Grants, Region ostergotland [LIO-535931, LIO-520131]</p

The iliac pillar - Definition of an osseous fixation pathway for internal and external fixation.

BACKGROUND: Increasing numbers of unstable pelvic ring fractures, due to the ongoing demographic change and improvements in the rescue of high-energy traumatic events, are challenging trauma and orthopedic surgeons. While initial installation of an external fixation device is often necessary, placement of iliac crest pins can be difficult due to the complex osteology of the ilium. HYPOTHESIS: We aim to analyze (1) the length, localization and angulation of the iliac pillar and (2) to define the dimensions of the surgical corridor for a better understanding of pin entry point and trajectory, thus preventing shortcomings in anterior external fixation of pelvic ring injuries. METHODS: Twenty hemipelvises from 10 fresh-frozen cadaveric torsos (3 female, 7 males; mean age 80.2 years) were harvested. The following measurements were taken with digital calipers: Location of the iliac pillar in relation to the anterior superior iliac spine and to the acetabulum roof, mean length and diameter of the iliac pillar, maximum diameter of the iliac pillar. In addition we measured the width of the different bone layers. RESULTS: The mean length of the hourglass shaped iliac pillar was 107.04mm with a mean width of 17.0mm (min. 15.1; max. 19.2). The mean distance to the anterior superior iliac spine was 69.00mm (min. 64.8; max. 73.4). The mean maximum width of the iliac pillar was 12.16mm (min. 9.4; max. 13.8). Caudally the line describing the iliac pillar intercepts the cranial acetabular rim at 12 o\u27clock. The smallest mean diameter of the cancellous bone was 7.5mm±2.0. CONCLUSION: The iliac pillar is part of the complex osteology of the human pelvis. A cohesive description of its location and dimensions has been lacking. Successful treatment of pelvic fracture depends on an optimal preoperative planning, accurate overall reduction, and stable fixation. We described the origin and angulation to provide a good bone stock for external fixation pin and the width of the different bone layers. This study therefore contributes by facilitating a thorough understanding of pelvic osteology and describing the location and dimensions of an optimal osseous pathway. LEVEL OF EVIDENCE: Anatomical descriptive study

Reference standards for gene fusion molecular assays on cytological samples: an international validation study

Gene fusions assays are key for personalised treatments of advanced human cancers. Their implementation on cytological material requires a preliminary validation that may make use of cell line slides mimicking cytological samples. In this international multi-institutional study, gene fusion reference standards were developed and validated

Reference standards for gene fusion molecular assays on cytological samples: an international validation study

Aims Gene fusions assays are key for personalised treatments of advanced human cancers. Their implementation on cytological material requires a preliminary validation that may make use of cell line slides mimicking cytological samples. In this international multi-institutional study, gene fusion reference standards were developed and validated. Methods Cell lines harbouring EML4(13)-ALK(20) and SLC34A2(4)-ROS1(32) gene fusions were adopted to prepare reference standards. Eight laboratories (five adopting amplicon-based and three hybridisation-based platforms) received, at different dilution points two sets of slides (slide A 50.0%, slide B 25.0%, slide C 12.5% and slide D wild type) stained by Papanicolaou (Pap) and May Grunwald Giemsa (MGG). Analysis was carried out on a total of 64 slides. Results Four (50.0%) out of eight laboratories reported results on all slides and dilution points. While 12 (37.5%) out of 32 MGG slides were inadequate, 27 (84.4%) out of 32 Pap slides produced libraries adequate for variant calling. The laboratories using hybridisation-based platforms showed the highest rate of inadequate results (13/24 slides, 54.2%). Conversely, only 10.0% (4/40 slides) of inadequate results were reported by laboratories adopting amplicon-based platforms. Conclusions Reference standards in cytological format yield better results when Pap staining and processed by amplicon-based assays. Further investigation is required to optimise these standards for MGG stained cells and for hybridisation-based approaches