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Stroke produces a limited process of neural repair. Axonal sprouting in cortex adjacent to the infarct is part of this recovery process, but the signal that initiates axonal sprouting is not known. Growth and differentiation factor 10 (GDF10) is induced in peri-infarct neurons in mice, non-human primates and humans. GDF10 promotes axonal outgrowth in vitro in mouse, rat and human neurons through TGFβRI and TGFβRII signaling. Using pharmacogenetic gain- and loss-of-function studies, we found that GDF10 produced axonal sprouting and enhanced functional recovery after stroke; knocking down GDF10 blocked axonal sprouting and reduced recovery. RNA sequencing from peri-infarct cortical neurons revealed that GDF10 downregulated PTEN, upregulated PI3 kinase signaling and induced specific axonal guidance molecules. Using unsupervised genome-wide association analysis of the GDF10 transcriptome, we found that it was not related to neurodevelopment, but may partially overlap with other CNS injury patterns. Thus, GDF10 is a stroke-induced signal for axonal sprouting and functional recovery.

Understanding how habitat attributes (e.g., patch area and sizes, connectivity) control recruitment and how this is modified by processes operating at larger spatial scales is fundamental to understanding population sustainability and developing successful long‐term restoration strategies for marine foundation species—including for globally threatened reef‐forming oysters. In two experiments, we assessed the recruitment and energy reserves of oyster recruits onto remnant reefs of the oyster Saccostrea glomerata in estuaries spanning 550 km of coastline in southeastern Australia. In the first experiment, we determined whether recruitment of oysters to settlement plates in three estuaries was correlated with reef attributes within patches (distances to patch edges and surface elevation), whole‐patch attributes (shape and size of patches), and landscape attributes (connectivity). We also determined whether environmental factors (e.g., sedimentation and water temperature) explained the differences among recruitment plates. We also tested whether differences in energy reserves of recruits could explain the differences between two of the estuaries (one high‐ and one low‐sedimentation estuary). In the second experiment, across six estuaries (three with nominally high and three with nominally low sedimentation rates), we tested the hypothesis that, at the estuary scale, recruitment and survival were negatively correlated to sedimentation. Overall, total oyster recruitment varied mostly at the scale of estuaries rather than with reef attributes and was negatively correlated with sedimentation. Percentage recruit survival was, however, similar among estuaries, although energy reserves and condition of recruits were lower at a high‐ compared to a low‐sediment estuary. Within each estuary, total oyster recruitment increased with patch area and decreased with increasing tidal height. Our results showed that differences among estuaries have the largest influence on oyster recruitment and recruit health and this may be explained by environmental processes operating at the same scale. While survival was high across all estuaries, growth and reproduction of oysters on remnant reefs may be affected by sublethal effects on the health of recruits in high‐sediment estuaries. Thus, restoration programs should consider lethal and sublethal effects of whole‐estuary environmental processes when selecting sites and include environmental mitigation actions to maximize recruitment success. [ABSTRACT FROM AUTHOR]

The human reward system is sensitive to both social (e.g., validation) and non-social rewards (e.g., money) and is likely integral for relationship development and reputation building. However, data is sparse on the question of whether implicit social reward processing meaningfully contributes to explicit social representations such as trust and attachment security in pre-existing relationships. This event-related fMRI experiment examined reward system prediction-error activity in response to a potent social reward-social validation-and this activity's relation to both attachment security and trust in the context of real romantic relationships. During the experiment, participants' expectations for their romantic partners' positive regard of them were confirmed (validated) or violated, in either positive or negative directions. Primary analyses were conducted using predefined regions of interest, the locations of which were taken from previously published research. Results indicate that activity for mid-brain and striatal reward system regions of interest was modulated by social reward expectation violation in ways consistent with prior research on reward prediction-error. Additionally, activity in the striatum during viewing of disconfirmatory information was associated with both increases in post-scan reports of attachment anxiety and decreases in post-scan trust, a finding that follows directly from representational models of attachment and trust.

Corticotropin-releasing factor (CRF) signaling pathways are involved in the stress response, and there is growing evidence supporting hair growth inhibition of murine hair follicle in vivo upon stress exposure. We investigated whether the blockade of CRF receptors influences the development of hair loss in CRF over-expressing (OE)-mice that display phenotypes of Cushing's syndrome and chronic stress, including alopecia. The non-selective CRF receptors antagonist, astressin-B (5 µg/mouse) injected peripherally once a day for 5 days in 4-9 months old CRF-OE alopecic mice induced pigmentation and hair re-growth that was largely retained for over 4 months. In young CRF-OE mice, astressin-B prevented the development of alopecia that occurred in saline-treated mice. Histological examination indicated that alopecic CRF-OE mice had hair follicle atrophy and that astressin-B revived the hair follicle from the telogen to anagen phase. However, astressin-B did not show any effect on the elevated plasma corticosterone levels and the increased weights of adrenal glands and visceral fat in CRF-OE mice. The selective CRF₂ receptor antagonist, astressin₂-B had moderate effect on pigmentation, but not on hair re-growth. The commercial drug for alopecia, minoxidil only showed partial effect on hair re-growth. These data support the existence of a key molecular switching mechanism triggered by blocking peripheral CRF receptors with an antagonist to reset hair growth in a mouse model of alopecia associated with chronic stress.

Adult acquired buried penis (AABP) is a morbid condition often necessitating surgical intervention. Accurate assessment of pre- and postoperative symptoms is crucial to understand how AABP impacts a patients' quality of life, verify surgical effectiveness, and practice patient-centered care. There is no validated patient-reported outcome instrument specific for AABP evaluation. We undertook a comprehensive review of existing literature on patient-reported outcome instruments post-AABP surgery to highlight the importance of developing a specific tool. Following the preferred reporting items for systematic reviews and meta-analysis 2020 guidelines, we queried three databases using relevant keywords (e.g., "buried penis repair"). Inclusion criteria were studies that discussed surgical management of AABP with patient-reported outcomes. Pediatric and congenital cases were excluded. Information collected included study design, level of evidence, number of participants included in the study, etiology of buried penis, surgical technique, preoperative or postoperative patient-reported outcomes, and patient-reported outcome instrument used. Initial query identified 998 records. After abstract screening and applying the inclusion or exclusion criteria, a total of 19 articles with 440 patients were included. Eight studies implemented patient-reported outcome instruments. The international index of erectile dysfunction-5 and Likert satisfaction scales were used most frequently. Although all instruments were validated, none were validated in the specific context of AABP surgical intervention. There is considerable heterogeneity within the AABP literature regarding patient symptomatology, postoperative complications, patient-reported outcomes, and instruments used. The results of this study emphasize the need for a patient-reported outcome measure to examine the influence of AABP repair on patient satisfaction and health-related quality of life. [ABSTRACT FROM AUTHOR]

Given that patients with morbid obesity are predisposed to frailty, we sought to determine whether the 5-Factor Modified Frailty Index (mFI-5) predicts postoperative complications following surgery for adult-acquired buried penis, and secondarily, to compare the mFI-5 to body mass index (BMI) and American Society of Anesthesiologists (ASA) status as preoperative risk stratification measures. We included all patients who underwent surgical management for adult-acquired buried penis at an academic Level I trauma center between 2015 and 2023. A manual chart review was performed to collect data on patient demographics, modified frailty index variables, intraoperative data, postoperative outcomes, and complications. A total of 55 patients underwent surgical repair of adult-acquired buried penis, with 26 experiencing postoperative complications (47.3%). Univariable regression analyses revealed that the mFI-5 was a significant predictor of postoperative complications (odds ratio [OR] 3.40, 95% confidence interval [CI]: 1.56–7.42, p =.002), ongoing postoperative urinary problems (OR 2.03, 95% CI: 1.02–4.05, p =.045), patient dissatisfaction with outcomes (OR 3.29, 95% CI: 1.35–8.02, p =.009), and persistent postoperative symptoms (OR 2.42, 95% CI: 1.10–5.35, p =.029). There was no significant association between ASA classification and postoperative complications (OR 1.59, 95% CI:.544–4.63, p =.398). Multivariable analysis demonstrated that the mFI-5 was an independent predictor of postoperative complications (OR 5.34, 95% CI: 1.80–15.9, p =.003) when controlling for BMI and age. The mFI-5 is an independent predictor of postoperative complications in patients undergoing surgical repair of adult-acquired buried penis. The simplicity of the index permits efficient preoperative risk stratification of adult-acquired buried penis patients and provides important counseling information that may not be reflected by age or BMI alone. [ABSTRACT FROM AUTHOR]

The hypothesis of this study was that trigeminal nerve stimulation (TNS) or peripheral nerve stimulation (PNS) could improve functional outcomes of peripheral nerve injury in a rat forelimb model when compared to control rats not receiving electrical stimulation (ES). While PNS is known to improve outcomes after nerve surgery, the role of TNS has not been explored. Lewis rats were trained to perform a reach and grasp task before receiving a 2 mm gap repair of the ulnar and median nerves and randomized into four treatment groups: (1) sham injury, (2) nerve injury with sham ES, (3) nerve injury with PNS, and (4) nerve injury with TNS. Functional motor (median pull force and percent success in motor task) and sensory metrics (forelimb paw withdrawal thresholds) were collected both pre-injury and throughout rehabilitation. Nerves stained using Gomori's trichrome were assessed quantitatively and qualitatively. The sham ES group did not recover their pre-injury baseline functional outcomes. In contrast, the TNS and PNS groups fully recovered following injury, with no difference in functional outcomes between the pre-injury baseline and the final week of rehabilitation (P > 0.05, all). Histomorphology results demonstrated no quantitative difference, but qualitative differences in architecture were evident. Electrical stimulation of the trigeminal nerve or the injured nerve improved the functional outcomes of nerve regeneration in rodents. Histomorphology results of nerves from the TNS group support the proposed central mechanisms. This is an important step in translating this therapy as an adjunct, non-invasive treatment for high, mixed nerve injuries in humans. [ABSTRACT FROM AUTHOR]

What might Web 3.0 mean for education--that is, education seen as an intellectual and philosophical endeavour where we seek to critique the world and understand our place in it with others? In this paper, I argue that current emphases on the semantic functionality of Web 3.0 have the potential to concomitantly challenge and extend the humanist educational enterprise, both as practice and intellectual endeavour. I present a brief history and description of Web 3.0, before providing an analysis of the two dominant scenarios in the Web 3.0 educational literature: the administrative scenario and the pedagogical scenario. My main point is that the role of the teacher in the Web 3.0 landscape must be understood as one of discernment--that is, the ability to judge and judge well on the part of both teacher and learner--for it is discernment that underlies the uniquely human ability to create meaning and thus make sense of the world.