Perfusion imaging metrics after acute traumatic spinal cord injury are associated with injury severity in rats and humans.

Traumatic spinal cord injury (tSCI) causes an immediate loss of neurological function, and the prediction of recovery is difficult in the acute phase. In this study, we used contrast-enhanced ultrasound imaging to quantify intraspinal vascular disruption acutely after tSCI. In a rodent thoracic tSCI model, contrast-enhanced ultrasound revealed a perfusion area deficit that was positively correlated with injury severity and negatively correlated with hindlimb locomotor function at 8 weeks after injury. The spinal perfusion index was calculated by normalizing the contrast inflow at the injury center to the contrast inflow in the injury periphery. The spinal perfusion index decreased with increasing injury severity and positively correlated with hindlimb locomotor function at 8 weeks after injury. The feasibility of intraoperative contrast-enhanced ultrasound imaging was further tested in a cohort of 27 patients with acute tSCI of varying severity and including both motor-complete and motor-incomplete tSCIs. Both the perfusion area deficit and spinal perfusion index were different between motor-complete and motor-incomplete patients. Moreover, the perfusion area deficit and spinal perfusion index correlated with the injury severity at intake and exhibited a correlation with extent of functional recovery at 6 months. Our data suggest that intraoperative contrast-enhanced, ultrasound-derived metrics are correlated with injury severity and chronic functional outcome after tSCI. Larger clinical studies are required to better assess the reliability of the proposed contrast-enhanced ultrasound biomarkers and their prognostic capacity.

Contrast-enhanced ultrasound imaging detects anatomical and functional changes in rat cervical spine microvasculature with normal aging.

Normal aging is associated with significant deleterious cerebrovascular changes; these have been implicated in disease pathogenesis and increased susceptibility to ischemic injury. While these changes are well documented in the brain, few studies have been conducted in the spinal cord. Here, we utilize specialized contrast-enhanced ultrasound (CEUS) imaging to investigate age-related changes in cervical spinal vascular anatomy and hemodynamics in male Fisher 344 rats, a common strain in aging research. Aged rats (24-26 mo., N=6) exhibited significant tortuosity in the anterior spinal artery and elevated vascular resistance compared to adults (4-6 mo., N=6; tortuosity index 2.20±0.15 vs 4.74±0.45, p<0.05). Baseline blood volume was lower in both larger vessels and the microcirculation in the aged cohort, specifically in white matter (4.44e14±1.37e13 vs 3.66e14±2.64e13 CEUS bolus AUC, p<0.05). To elucidate functional differences, animals were exposed to a hypoxia challenge; whereas adult rats exhibited significant functional hyperemia in both gray and white matter (GM: 1.13±0.10-fold change from normoxia, p<0.05; WM: 1.16±0.13, p<0.05), aged rats showed no response. Immunohistochemistry revealed reduced pericyte coverage and activated microglia behavior in aged rats, which may partially explain the lack of vascular response. This study provides the first in vivo description of age-related hemodynamic differences in the cervical spinal cord.

Contrast-enhanced ultrasound imaging detects anatomical and functional changes in rat cervical spine microvasculature with normal aging.

Normal aging is associated with significant deleterious cerebrovascular changes; these have been implicated in disease pathogenesis and increased susceptibility to ischemic injury. While these changes are well documented in the brain, few studies have been conducted in the spinal cord. Here, we utilize specialized contrast-enhanced ultrasound (CEUS) imaging to investigate age-related changes in cervical spinal vascular anatomy and hemodynamics in male Fisher 344 rats, a common strain in aging research. Aged rats (24-26 mo., N=6) exhibited significant tortuosity in the anterior spinal artery and elevated vascular resistance compared to adults (4-6 mo., N=6; tortuosity index 2.20±0.15 vs 4.74±0.45, p<0.05). Baseline blood volume was lower in both larger vessels and the microcirculation in the aged cohort, specifically in white matter (4.44e14±1.37e13 vs 3.66e14±2.64e13 CEUS bolus AUC, p<0.05). To elucidate functional differences, animals were exposed to a hypoxia challenge; whereas adult rats exhibited significant functional hyperemia in both gray and white matter (GM: 1.13±0.10-fold change from normoxia, p<0.05; WM: 1.16±0.13, p<0.05), aged rats showed no response. Immunohistochemistry revealed reduced pericyte coverage and activated microglia behavior in aged rats, which may partially explain the lack of vascular response. This study provides the first in vivo description of age-related hemodynamic differences in the cervical spinal cord.

Adulterants present in the San Diego county fentanyl supply: a laboratory analysis of seized law enforcement samples.

BACKGROUND: The opioid overdose crisis is one of the worst public health crises ever to face the US and emerging evidence suggests its effects are compounded by the presence of drug adulterants. Here we report our efforts to characterize the adulterants present within the local fentanyl supply of San Diego County, obtained from undifferentiated drug samples seized by local law enforcement over the calendar year 2021. METHODS: Thirty-two participating local law enforcement agencies across San Diego submitted 4838 unknown individual illicit drug samples (total of 312 kg) to the San Diego County Sheriff's Department Regional Crime Laboratory for identification. RESULTS: Qualitative analysis of these samples via FTIR and GC-MS identified methamphetamine (38.7%), fentanyl (20.8%), diacetylmorphine (heroin) (10.2%), codeine (5.8%) and alprazolam (4.3%) as the most common illicit substances and the presence of 52 unique adulterants. The most common adulterants included 4-methylaminoantipyrine (4-MAAP) (10.9%), mannitol (9%), acetaminophen (8.5%), methamphetamine (4.2%), diacetylmorphine (heroin) (3.6%), tramadol (1.9%), and xylazine (1.7%). Several additional pharmacologically active adulterants and contaminants of interest were also identified. CONCLUSION: This analysis is vital for public health use and harm reduction efforts at the level of the individual consumer. Continued direct surveillance of the drug supply is necessary for the detection of potentially harmful adulterants that may pose serious threats to the public.

Quantifying injury expansion in the cervical spinal cord with intravital ultrafast contrast-enhanced ultrasound imaging.

Spinal cord injury is characterized by hemodynamic disruption at the injury epicenter and hypoperfusion in the penumbra, resulting in progressive ischemia and cell death. This degenerative secondary injury process has been well-described, though mostly using ex vivo or depth-limited optical imaging techniques. Intravital contrast-enhanced ultrasound enables longitudinal, quantitative evaluation of anatomical and hemodynamic changes in vivo through the entire spinal parenchyma. Here, we used ultrasound imaging to visualize and quantify subacute injury expansion (through 72 h post-injury) in a rodent cervical contusion model. Significant intraparenchymal hematoma expansion was observed through 72 h post-injury (1.86 ± 0.17-fold change from acute, p < 0.05), while the volume of the ischemic deficit largely increased within 24 h post-injury (2.24 ± 0.27-fold, p < 0.05). Histology corroborated these findings; increased apoptosis, tissue and vessel loss, and sustained tissue hypoxia were observed at 72 h post-injury. Vascular resistance was significantly elevated in the remaining perfused tissue, likely due in part to deformation of the central sulcal artery nearest to the lesion site. In conjunction, substantial hyperemia was observed in all perilesional areas examined except the ipsilesional gray matter. This study demonstrates the utility of longitudinal ultrasound imaging as a quantitative tool for tracking injury progression in vivo.

Case report: Two unexpected cases of DGUOK-related mitochondrial DNA depletion syndrome presenting with hyperinsulinemic hypoglycemia.

Timely diagnosis of persistent neonatal hypoglycemia is critical to prevent neurological sequelae, but diagnosis is complicated by the heterogenicity of the causes. We discuss two cases at separate institutions in which clinical management was fundamentally altered by the results of molecular genetic testing. In both patients, critical samples demonstrated hypoketotic hypoglycemia and a partial glycemic response to glucagon stimulation, thereby suggesting hyperinsulinism (HI). However, due to rapid genetic testing, both patients were found to have deoxyguanosine kinase (DGUOK)-related mitochondrial DNA depletion syndrome, an unexpected diagnosis. Patients with this disease typically present with either hepatocerebral disease in the neonatal period or isolated hepatic failure in infancy. The characteristic features involved in the hepatocerebral form of the disease include lactic acidosis, hypoglycemia, cholestasis, progressive liver failure, and increasing neurologic dysfunction. Those with isolated liver involvement experience hepatomegaly, cholestasis, and liver failure. Although liver transplantation is considered, research has demonstrated that for patients with DGUOK-related mitochondrial DNA depletion syndrome and neurologic symptoms, early demise occurs. Our report advocates for the prompt initiation of genetic testing in patients presenting with persistent neonatal hypoglycemia and for the incorporation of mitochondrial DNA depletion syndromes in the differential diagnosis of HI.

Examination of Participant Characteristics and Utilization Trends of a Web-Based Public Health Practice Training Curriculum.

CONTEXT: Public health workforce development has been an ongoing challenge. Understanding the needs, interests, and demographics of public health practice communities is essential for advancing the field of public health workforce development. PROGRAM: The North Dakota Public Health Training Network (NDPHTN) is addressing the needs of public health practice communities through virtual training curricula. The NDPHTN curriculum is based upon 7 domains of public health practice workforce development training, identified via reports, a job task analysis, and workforce competency and skill needs surveys. The curricula also align with the Council on Education for Public Health competencies, and courses offer registrants the opportunity to earn Certified Public Health Continuing Education credit. IMPLEMENTATION: The NDPHTN curriculum launched on August 1, 2019, is offered on the Public Health Foundation's TRAIN platform. The educational trainings are available as 6 "courses," a group of related sessions on a public health workforce topic, or 72 Continuing Education Unit credits ("CEUs"), stand-alone sessions that are not part of a course. The courses were created to meet specialized certificate requirements, while CEUs present both overlapping materials with courses and unique "Special Topics," such as education and training related to the COVID-19 pandemic. CEUs on "Special Topics" are regularly revised to provide up-to-date information on evolving topics. This research study period was August 1, 2019, to January 5, 2021. EVALUATION: Using posttraining evaluations on quality and usefulness of NDPHTN sessions through the TRAIN platform, 96.71% of respondents reported that the sessions would be useful to their work. DISCUSSION: The TRAIN platform is an excellent channel to provide public health practice workforce development training to a diverse workforce. This examination of learner characteristics and utilization trends provides indications of topics deemed valuable by members of the public health workforce who engage in continuing education and training opportunities.

A qualitative exploration of positive body image experiences among nonbinary individuals.

One group whose positive body image experiences remain under-explored is individuals who identify as nonbinary, gender fluid, and/or genderqueer (including other nonbinary identities). Thus, we sought to answer the questions: What does it look like to have a positive body image for a nonbinary person? and How do nonbinary persons form and maintain a positive body image? To answer these questions, we conducted in-depth, semi-structured interviews with 15 nonbinary individuals who were assessed as having positive body image using the Body Appreciation Scale-2 (Tylka & Wood-Barcalow, 2015a). Data were analyzed using reflexive thematic analysis. Four themes were identified as characterizing the core features of positive body image among nonbinary persons: body appreciation, body- and self-acceptance, bodily appearance embodied their authentic self, and holding flexible ideals for ways of being. Six themes were identified as related to on-going processes that explain how body image is formed and maintained among nonbinary persons: reframing negative body image information, staging resistance, experiencing representation, receiving and giving social support, practicing self-compassion and self-care, and using dress to create a satisfying presentation of self. In keeping with the tenets of queer theory, findings reflected how gender identity set a context for participants' positive body image experiences.

Quantitative tissue perfusion imaging using nonlinear ultrasound localization microscopy.

Ultrasound localization microscopy (ULM) is a recent advancement in ultrasound imaging that uses microbubble contrast agents to yield vascular images that break the classical diffraction limit on spatial resolution. Current approaches cannot image blood flow at the tissue perfusion level since they rely solely on differences in velocity to separate tissue and microbubble signals; lower velocity microbubble echoes are removed during high pass wall filtering. To visualize blood flow in the entire vascular tree, we have developed nonlinear ULM, which combines nonlinear pulsing sequences with plane-wave imaging to segment microbubble signals independent of their velocity. Bubble localization and inter-frame tracking produces super-resolved images and, with parameters derived from the bubble tracks, a rich quantitative feature set that can describe the relative quality of microcirculatory flow. Using the rat spinal cord as a model system, we showed that nonlinear ULM better resolves some smaller branching vasculature compared to conventional ULM. Following contusion injury, both gold-standard histological techniques and nonlinear ULM depicted reduced in-plane vessel length between the penumbra and contralateral gray matter (-16.7% vs. -20.5%, respectively). Here, we demonstrate that nonlinear ULM uniquely enables investigation and potential quantification of tissue perfusion, arguably the most important component of blood flow.

Assessing students' mental health in two American dental hygiene programs.

OBJECTIVES: Dental hygiene students adapt to new environments while learning technical skills and providing clinical care during their education. Understanding how stress affects students in their professional healthcare program warrants exploration. This study assessed stress among dental hygiene students in two educational settings in the Southeastern United States. METHODS: First and second-year dental hygiene students (N = 136) from a community college setting (n = 67) and a university setting (n = 69) were invited to complete an anonymous online survey on mental health in fall 2019. Validated surveys on depression, anxiety, social support, and burnout were included. Data analysis included chi-squared and Mantel-Haenszel statistics, depending on the scale of measurement, with the level of significance set at 0.05 for all analyses. RESULTS: Participants included 54 dental hygiene students from a community college (Response rate = 80.6%) and 69 dental hygiene students from a university (RR = 100%). There was a statistically significant difference in the proportion of students reporting moderately severe or severe anxiety (p = 0.007), with 56% (n = 30) of the community college respondents and 36% (n = 24) of the university reporting these anxiety levels. Students attending a community college were also more likely to express feelings of worry (n = 34) compared to students in a university setting (p = 0.005). There was no statistically significant difference in depression (p = 0.07) or suicidal thoughts (p = 0.41). CONCLUSION: Dental hygiene students enrolled in these two programs reported high levels of self-reported stress, mental and emotional concerns that may increase suicidal tendencies.

Gaps in Neurogenetics Education During Child Neurology Residency: Results of a National Survey.

The practice of child neurology has changed significantly in the past two decades as we have integrated genetic testing into our standard of care to achieve precise diagnoses and to guide management of many childhood neurological conditions. Despite this paradigm shift, there appears to be a gap in both clinical exposure to neurogenetic disorders and education provided to residents in ordering and interpreting genetic testing. We therefore conducted a national survey for child neurology trainees in all programs across the United States to delineate their perception of the adequacy of current training and didactics in genetic/neurogenetic disorders. The results revealed knowledge gaps related to ordering and interpreting genetic testing, managing acute metabolic emergencies, and identifying resources for referral of patients to clinical trials. Responders considered their current curriculum in neurogenetics to be insufficient and voted favorably for an educational platform using recorded lectures and interactive sessions.

Blood Flow Changes Associated with Spinal Cord Injury Assessed by Non-linear Doppler Contrast-Enhanced Ultrasound.

Contrast-enhanced ultrasound (CEUS) is clinically used to image the microcirculation at lower imaging frequencies (<2 MHz). Recently, plane-wave acquisitions and Doppler processing have revealed improved microbubble sensitivity, enabling CEUS use at higher frequencies (15 MHz) and the ability to image simultaneously blood flow in the micro- and macrocirculations. We used this approach to assess acute and chronic blood flow changes within contused spinal cord in a rodent spinal cord injury model. Immediately after spinal cord injury, we found significant differences in perfusion deficit between moderate and severe injuries (1.73 ± 0.1 mm2 vs. 3.2 ± 0.3 mm2, respectively), as well as a delay in microbubble arrival time in tissue adjacent to the injury site (0.97 ± 0.1 s vs. 1.54 ± 0.1 s, respectively). Acutely, morphological changes to central sulcal arteries were observed where vessels rostral to the contusion were displaced 4.8 ± 2.2° and 8.2 ± 3.1° anteriorly, and vessels caudal to the contusion 17.8 ± 3.9° and 24.2 ± 4.1° posteriorly, respectively, for moderate and severe injuries. Significant correlation of the acute perfusion deficit and arrival time were found with the chronic assessment of locomotive function and histological estimate of spared spinal cord tissue.

Select Ethical Aspects of Next-Generation Sequencing Tests for Newborn Screening and Diagnostic Evaluation of Critically Ill Newborns.

In this review, we analyze medical and select ethical aspects of the increasing use of next-generation sequencing (NGS) based tests in newborn medicine. In the last five years, there have been several studies exploring the role of rapid exome sequencing (ES) and genome sequencing (GS) in critically ill newborns. While the advantages include a high diagnostic yield with potential changes in interventions, there have been ethical dilemmas surrounding consent, information about adult-onset diseases and resolution of variants of uncertain significance. Another active area of research includes a cohort of studies funded under Newborn Sequencing in Genomic Medicine and Public Health pertaining to the use of ES and GS in newborn screening (NBS). While these techniques may allow for screening for several genetic disorders that do not have a detectable biochemical marker, the high costs and long turnaround times of these tests are barriers in their utilization as public health screening tests. Discordant results between conventional NBS and ES-based NBS, as well as challenges with consent, are other potential pitfalls of this approach. Please see the Bush, Al-Hertani and Bodamer article in this Special Issue for the broader scope and further discussion.

Transition to a Competency-informed Dental Hygiene Clinical Evaluation System.

Purpose: Competency-informed clinical education includes rigorous and specific performance outcomes with an emphasis on demonstrated outcomes. The purpose of this study was to assess faculty and dental hygiene (DH) student perceptions and elicit feedback regarding the transition to a competency-informed clinical evaluation model in the DH program at the University of North Carolina Adams School of Dentistry for the purpose of continuous quality improvement.Methods: A mixed-methods approach was utilized to survey senior DH student (n = 36) and clinical DH faculty (n = 15) during the 2018 -19 academic year. Cohort-specific surveys included demographics, Likert-scale questions, and open-ended questions to gauge perceptions of the new system. Two debriefing sessions were held, one for faculty and one for students, to provide open feedback and expand discussions. Survey responses were compared using descriptive statistics. Open-ended responses and debriefing comments were reviewed to identify common themes.Results: All senior DH students (n=36) and two-thirds of the faculty (67%, n=10) completed the survey. Findings revealed an overall preference to the new evaluation system and indicated that it was a more accurate reflection of clinical performance. Open-ended and debriefing comments revealed an increased quantity and quality of faculty feedback with an emphasis on patient-centered care, rather than a grade-based focus. Students reported decreased stress levels regarding asking clinical care questions and grade outcomes. While improvement in faculty calibration was reported, students also noted a need for continued calibration.Conclusion: Surveys and debriefing sessions revealed areas of strengths and challenges in a competency-informed clinical evaluation system. Transitioning to a competency-based system provided an environment that is conducive to learning and patient-centered care rather than focused on grades.

Adolescent Posttraumatic Growth: A Review.

Existing literature on posttraumatic growth following adverse experiences has questioned adolescent capacity to experience such growth given immature cognitive and affective development. The aim of this review was to conduct the first review of the literature regarding post-traumatic growth among adolescents (ages 12-18) to determine whether there is empirical evidence of adolescent post-traumatic growth. Results of the review, conducted according to PRISMA guidelines, are reported to (1) summarize existing support for adolescent post-traumatic growth within available empirical literature, (2) discuss potential moderators of adolescent post-traumatic growth occurrence, and (3) review existing measures of post-traumatic growth. Evidence of adolescent post-traumatic growth was found within three studies with correlational designs and two studies with longitudinal designs. The majority of the literature regarding adolescent post-traumatic growth provides initial support in the form of correlational evidence; however, such support is difficult to empirically establish given the lack of longitudinal studies in this area. Critiques of the extant research and areas for future research are discussed.

Teaching methodologies for improving dental students' implementation of ergonomic operator and patient positioning.

OBJECTIVES: Musculoskeletal disorders (MSDs) related to operator and patient positioning are prevalent among dentists. Knowledge of correct operator and patient positioning promotes safe working postures that can prevent the development of MSDs. The aim of this study was to assess the impact of inter-professional teaching on the application of those skills associated with correct operator and patient positioning in dental settings. METHODS: A randomized case-control study was conducted with 83 first-year dental students at the UNC-Chapel Hill Adams School of Dentistry in 2019. Forty-one (n = 41) of the students solicited for the project participated. All 83 students in the cohort participated in a didactic lecture on ergonomics and correct operator and patient positioning, along with a pre-clinical practice session with peer patients. During the clinical practice session, students in the case group received an additional 10 minutes of 1-on-1 instruction by a trained physical therapy student or dental faculty member. Two weeks later, the final cohort (n = 41) was assessed by 2 faculty members using a scored rubric on operator and patient positioning for restorative work on an anterior tooth, posterior mandibular tooth, and posterior maxillary tooth. RESULTS: There was a statistically significant difference between the 2 groups with respect to the composite ergonomic positioning score (P = 0.006), operator shoulder abduction position (P = 0.03), and lateral flexion of the spinal column (P = 0.02). CONCLUSIONS: Hands on instruction with physical therapists and trained dental faculty positively affects ergonomic compliance and provides students with tailored feedback that can be applied to clinical practice.

Routine Screening in a California Jail : Effect of Local Policy on Identification of Syphilis in a High-Incidence Area, 2016-2017.

OBJECTIVES: California is experiencing a syphilis and congenital syphilis epidemic, and many persons diagnosed with syphilis report a history of recent incarceration or sexual contact with a person who has recently been incarcerated. Fresno County's local health department and jail collaborated to implement a routine syphilis screening policy for male adults aged 18-30 and female adults aged 18-35 booked into the facility. We evaluated syphilis screening, case finding, and treatment rates after implementation of the new policy. METHODS: We linked jail census and laboratory data to syphilis surveillance data to assess screening coverage, positivity, and treatment rates for age-eligible persons who were booked into Fresno County Jail from April 1, 2016, through December 31, 2017. RESULTS: Of 24 045 age-eligible persons who were booked into the jail during the study period, 5897 (24.5%) were female and 18 148 (75.5%) were male. Of 7144 (29.7%) persons who were screened for syphilis, 611 (8.6%) had a reactive rapid plasma reagin blood test result (16.4% [253 of 1546] of female adults; 6.4% [358 of 5598] of male adults) and 238 (3.3%) were newly diagnosed with syphilis, as confirmed by matching to the surveillance system (6.9% [106 of 1546] of female adults; 2.4% [132 of 5598] of male adults). Of persons identified with syphilis, 51.7% (n = 123 of 238) received adequate recommended treatment (59.4% [63 of 106] of female adults; 45.5% [60 of 132] of male adults). CONCLUSIONS: The age-based syphilis screening policy adopted in this jail yielded high positivity, including newly identified syphilis infections among female adults of childbearing age. The targeted screening policy was formalized in the county-negotiated contract with the jail's private correctional health care company in 2018-a strategy that can be replicated.

Minimally invasive gas embolization using acoustic droplet vaporization in a rodent model of hepatocellular carcinoma.

Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. Many patients are not eligible for curative therapies, such as surgical resection of the tumor or a liver transplant. Transarterial embolization is one therapy clinically used in these cases; however, this requires a long procedure and careful placement of an intraarterial catheter. Gas embolization has been proposed as a fast, easily administered, more spatially selective, and less invasive alternative. Here, we demonstrate the feasibility and efficacy of using acoustic droplet vaporization to noninvasively generate gas emboli within vasculature. Intravital microscopy experiments were performed using the rat cremaster muscle to visually observe the formation of occlusions. Large gas emboli were produced within the vasculature in the rat cremaster, effectively occluding blood flow. Following these experiments, the therapeutic efficacy of gas embolization was investigated in an ectopic xenograft model of hepatocellular carcinoma in mice. The treatment group exhibited a significantly lower final tumor volume (ANOVA, p = 0.008) and growth rate than control groups - tumor growth was completely halted. Additionally, treated tumors exhibited significant necrosis as determined by histological analysis. To our knowledge, this study is the first to demonstrate the therapeutic efficacy of gas embolotherapy in a tumor model.

Pilot data supporting an attachment-based theory of adolescent social media use.

BACKGROUND: Adolescents have virtually universal access to social media. Despite ample research linking attachment to social functioning in youth, neither this empirical research nor related theory has been extended to the virtual social context. The broad aim of this study was to test an attachment-based model of social media use in adolescents in order to address a gap in the literature during this developmental stage and examine attachment and the related process of mentalizing as correlates of online behavior. METHOD: Online social comparison/feedback-seeking was selected as an outcome variable due to its known negative effects on adolescents. Analyses were conducted in a sample of 68 adolescents ranging in age from 15 to 18. RESULTS: No evidence of a main effect of parent-child attachment on social comparison/feedback-seeking was found, but a significant mediational effect indicated that more insecure parent-child attachment is linked with hypermentalizing errors (i.e., overinterpretation of others' mental states) and that such errors explain increased social comparison/feedback-seeking. CONCLUSIONS: The current study confirmed previously documented relations between parent-child attachment and hypermentalization as well as research demonstrating that parent-child attachment acts on an adolescent's social world - in this case their virtual social world - through anomalous mentalization.

Spatiotemporally-controlled transgene expression in hydroxyapatite-fibrin composite scaffolds using high intensity focused ultrasound.

Conventional tissue engineering approaches rely on scaffold-based delivery of exogenous proteins, genes, and/or cells to stimulate regeneration via growth factor signaling. However, scaffold-based approaches do not allow active control of dose, timing, or spatial localization of a delivered growth factor once the scaffold is implanted, yet these are all crucial parameters in promoting tissue regeneration. To address this limitation, we developed a stable cell line containing a heat-activated and rapamycin-dependent gene expression system. In this study, we investigate how high intensity focused ultrasound (HIFU) can spatiotemporally control firefly luciferase (fLuc) transgene activity both in vitro and in vivo by the tightly controlled generation of hyperthermia. Cells were incorporated into composite scaffolds containing fibrin and hydroxyapatite particles, which yielded significant increases in acoustic attenuation and heating in response to HIFU compared to fibrin alone. Using 2.5 MHz HIFU, transgene activation was observed at acoustic intensities of 201 W/cm2 and higher. Transgene activation was spatially patterned in the scaffolds by rastering HIFU at speeds up to 0.15 mm/s. In an in vivo study, a 67-fold increase in fLuc activity was observed in scaffolds exposed to HIFU and rapamycin versus rapamycin only at 2 days post implantation. Repeated activation of transgene expression was also demonstrated 8 days after implantation. No differences in in vivo scaffold degradation or compaction were observed between +HIFU and -HIFU groups. These results highlight the potential utility of using this heat-activated and rapamycin-dependent gene expression system in combination with HIFU for the controlled stimulation of tissue regeneration.