Before their disappearance from the fossil record approximately 40,000 years ago, Neanderthals, the ancient hominin lineage most closely related to modern humans, interbred with ancestors of ...present-day humans. The legacy of this gene flow persists through Neanderthal-derived variants that survive in modern human DNA; however, the neural implications of this inheritance are uncertain. Here, using MRI in a large cohort of healthy individuals of European-descent, we show that the amount of Neanderthal-originating polymorphism carried in living humans is related to cranial and brain morphology. First, as a validation of our approach, we demonstrate that a greater load of Neanderthal-derived genetic variants (higher "NeanderScore") is associated with skull shapes resembling those of known Neanderthal cranial remains, particularly in occipital and parietal bones. Next, we demonstrate convergent NeanderScore-related findings in the brain (measured by gray- and white-matter volume, sulcal depth, and gyrification index) that localize to the visual cortex and intraparietal sulcus. This work provides insights into ancestral human neurobiology and suggests that Neanderthal-derived genetic variation is neurologically functional in the contemporary population.
Purpose To identify the accuracy of measuring the alpha angle on the false-profile, anteroposterior (AP), and 90° Dunn lateral views of the hip as compared with computed tomography (CT) scan ...findings. Methods Forty patients were needed to have power greater than 80%. Forty-five consecutive patients undergoing hip arthroscopy were retrospectively reviewed with preoperative radial oblique CT reformatted scans and plain radiographs. Alpha angles were measured on plain radiographs (AP, 90° Dunn lateral, and false profile) and CT reformatted views. Abnormal alpha angles were considered greater than 50.5°. Two orthopaedic surgeons independently measured the images, and the results were compared between imaging modalities. Results The false-profile view was 60% sensitive and 89.0% specific for diagnosing cam deformities of the hip. All radiographs combined were 86% sensitive and 75% specific for diagnosing cam deformities. The false-profile view most strongly correlated with the 2-o'clock ( R = 0.746, P = .001) and 3-o'clock ( R = 0.698, P < .0001) positions. An intraclass correlation coefficient of 0.81 was found for measurement of the alpha angle on the false-profile view. Conclusions This study has proved that the false-profile view effectively characterizes cam deformity, especially anterior deformity at the 3-o'clock position. Measuring the alpha angle on the false-profile view appears to be reproducible. The false-profile view along with standing AP pelvis and 90° Dunn lateral views of the hip comprises a good screening radiographic series for patients presenting with symptoms of femoroacetabular impingement. Level of Evidence Level III, diagnostic study.
To determine the impact of gender-affirming mastectomy on depression, anxiety, and body image.
There are many cross-sectional and ad-hoc studies demonstrating the benefits of gender-affirming ...surgery. There are few prospective investigations of patient-reported outcomes in gender-affirming surgery using validated instruments.
In this prospective study, patients presenting to the University of Michigan for gender-affirming Mastectomy were surveyed preoperatively and 6-months postoperatively. Primary outcomes were patient-reported measurements of anxiety measured by General Anxiety Disorder-7, depression measured by Patient Health Questionnaire-9, body image measured by BODY-Q and Body Image Quality of Life Index, psychosocial and sexual functioning measured by BREAST-Q, and satisfaction with decision measured by BREAST-Q. Linear regression analysis was used to control for presence of complication and existing history of mental health conditions.
A total of 70 patients completed the study. The average age of participants was 26.7. The mean Patient Health Questionnaire-9 score pre-operatively was 7.8 and postoperatively was 5.4 ( P =0.001). The mean preoperative and postoperative General Anxiety Disorder-7 scores were 7.6 and 4.6, respectively ( P <0.001). There were significant improvements in both psychosocial (35 to 79.2, P <0.001) and sexual (33.9 to 67.2, P< 0.001) functioning related to chest appearance as measured by the BREAST-Q and global psychosocial functioning (-15.6 to +32, P <0.001) as measured by the Body Image Quality of Life Index. Satisfaction with chest contour (14.3 to 93.8, P <0.001) and nipple appearance (29.3 to 85.9, P <0.001) measured by the BODY-Q significantly improved. Patients had a mean satisfaction with outcome score of 93.1.
Patients undergoing gender-affirming mastectomy in this single-center prospective study reported significant improvements in anxiety, depression, body image, psychosocial, and sexual functioning after this procedure. Patients were extremely satisfied with the decision to undergo this operation.
Stress exposure can cause lasting changes in cognition, but certain individual traits, such as cognitive flexibility, have been shown to reduce the degree, duration, or severity of cognitive changes ...following stress. Both stress and cognitive flexibility training affect decision making by modulating monoamine signaling. Here, we test the role cognitive flexibility training, and high vs. low cognitive flexibility at the individual level, in attenuating stress-induced changes in memory and monoamine levels using the single prolonged stress (SPS) rodent model of traumatic stress in male Sprague-Dawley rats. Exposure to SPS can heighten fear responses to conditioned cues (i.e., freezing) after a fear association has been extinguished, referred to as a deficit in extinction retention. This deficit is thought to reflect an impairment in context processing that is characteristic of posttraumatic stress disorder (PTSD). During a cognitive flexibility training we assessed individual variability in cognitive skills and conditioned rats to discriminately use cues in their environment. We found that cognitive flexibility training, alone or followed by SPS exposure, accelerated extinction learning and decreased fear responses over time during extinction retention testing, compared with rats not given cognitive flexibility training. These findings suggest that cognitive flexibility training may improve context processing in individuals with and without traumatic stress exposure. Individual performance during the reversal phase of the cognitive flexibility training predicted subsequent context processing; individuals with high reversal performance exhibited a faster decrease in freezing responses during extinction retention testing. Thus, high reversal performance predicted enhanced retention of extinction learning over time and suggests that cognitive flexibility training may be a strategy to promote context processing. In a brain region vital for maintaining cognitive flexibility and fear suppression, the prelimbic cortex (PLC), cognitive flexibility training also lastingly enhanced dopamine (DA) and norepinephrine (NE) levels, in animals with and without traumatic stress exposure. In contrast, cognitive flexibility training prior to traumatic stress exposure decreased levels of DA and its metabolites in the striatum, a region mediating reflexive decision making. Overall, our results suggest that cognitive flexibility training can provide lasting benefits by enhancing extinction retention, a hallmark cognitive effect of trauma, and prelimbic DA, which can maintain flexibility across changing contexts.
Triclosan is an anti-microbial chemical incorporated into products that are applied to the skin of healthcare workers. Exposure to triclosan has previously been shown to be associated with allergic ...disease in humans and impact the immune responses in animal models. Additionally, studies have shown that exposure to triclosan dermally activates the NLRP3 inflammasome and disrupts the skin barrier integrity in mice. The skin is the largest organ of the body and plays an important role as a physical barrier and regulator of the immune system. Alterations in the barrier and immune regulatory functions of the skin have been demonstrated to increase the risk of sensitization and development of allergic disease. In this study, the impact of triclosan exposure on the skin barrier and keratinocyte function was investigated using a model of reconstructed human epidermis. The apical surface of reconstructed human epidermis was exposed to triclosan (0.05-0.2%) once for 6, 24, or 48 h or daily for 5 consecutive days. Exposure to triclosan increased epidermal permeability and altered the expression of genes involved in formation of the skin barrier. Additionally, exposure to triclosan altered the expression patterns of several cytokines and growth factors. Together, these results suggest that exposure to triclosan impacts skin barrier integrity and function of human keratinocytes and suggests that these alterations may impact immune regulation.
Water ice in the Martian mid‐latitudes has advanced and retreated in response to variations in the planet's orbit, obliquity, and climate. A 150 m‐diameter new impact crater near 35°N provides the ...lowest‐latitude impact exposure of subsurface ice on Mars. This is the largest known ice‐exposing crater and provides key constraints on Martian climate history. This crater indicates a regional, relatively pure ice deposit that is unstable and has nearly vanished. In the past, this deposit may have been tens of meters thick and extended equatorward of 35°N. We infer that it is overlain by pore ice emplaced during temporary stable intervals, due to recent climate variability. The marginal survival of ice here suggests that it is near the edge of shallow ice that regularly exchanges with the atmosphere.
Plain Language Summary
A 150 m‐diameter new impact crater on Mars exposes water ice, constraining the nature of past and present ice sheets and paleoclimate. The past climate has varied, gradually removing a massive ice deposit that has nearly been lost at 35°N but survives at higher latitude.
Key Points
Water ice is exposed in a 150 m‐diameter new impact crater near 35°N on Mars
The ice includes both massive ice and a covering layer of pore ice
This ice marks the southern margin of remaining ice deposits from high‐obliquity periods
Abstract Background Severely injured pediatric trauma patients often present to hospital with early coagulopathy and metabolic acidosis. These derangements are associated with poor outcomes, but it ...is unclear to what degree they predict transfusion of packed red blood cells (pRBC). Methods We retrospectively identified pediatric trauma patients from a level 1 trauma center from 2006 to 2013. Inclusion criteria were age less than 18 years, Injury Severity Score greater than 12, and pRBC transfusion within 24 h of admission. Results We identified 96 pediatric trauma patients who underwent pRBC transfusion within 24 h of presentation to hospital. On admission, 43% of these patients had one or more signs of coagulopathy, and 81% had metabolic acidosis. Size of pRBC transfusion in the first 24 h ranged from 3 to 177 mL/kg (mean 29 mL/kg), and nineteen patients (20%) underwent massive transfusion (> 40 ml/kg in 24 h). Univariate analysis indicated that size of pRBC transfusion was associated with initial base excess (r = 0.46), international normalized ratio (r = 0.35), partial thromboplastin time (r = 0.41), fibrinogen (r = 0.46), and BIG score (Base deficit, INR, Glasgow Coma Scale (GCS), r = 0.36). Platelet count, age, GCS, and direct versus referred presentation were not predictive. Multivariable linear regression confirmed that coagulopathy and metabolic acidosis remained predictive after adjusting for direct versus referred presentation (R2 = 0.30). Conclusions Early coagulopathy and metabolic acidosis predict size of pRBC transfusion among pediatric trauma patients. Further research is needed to develop massive transfusion protocols and guidelines for activation.
The involvement of oxidative stress in the mechanism of antibiotics-meditated cell death is unclear and subject to debate. The kinetic profile and a quantitative relationship between the release of ...reactive oxygen species (ROS), bacteria and antibiotic type remain elusive. Here we report direct measurements and analytical quantification of the release of superoxide radicals (O2·−), a major contributor to ROS, in antibiotics-treated bacterial cultures using a cytochrome c electrochemical biosensor. The specificity of electrochemical measurements was established by the addition of superoxide dismutase (SOD) which decreased the O2·− signal. Measurements using a general ROS-specific fluorescence dye and colony forming units (CFU) assays were performed side-by-side to determine the total ROS and establish the relationship between ROS and the degree of lethality. Exposure of Escherichia coli and Listeria monocytogenes cultures to antibiotics increased the release of O2·− radicals in a dose-dependent manner, suggesting that the transmembrane generation of ROS may occur as part of the antibiotic action. The study provides a quantitative methodology and fundamental knowledge to further explore the role of oxidative stress in antibiotics-meditated bacterial death and to assess physiological changes associated with the complex metabolic events related to oxidative stress and bacterial resistance.
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•Real-time measurement of antibiotics-induced superoxide release is demonstrated.•Performance of a cytochrome c-based electrochemical biosensor in bacterial cultures is established.•Specificity of superoxide measurements was demonstrated via addition of superoxide dismutase.•Quantitative assessment of the dynamics of antibiotics-induced ROS release in bacteria is provided.
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