Profiles of Early Childhood Adversity in an Urban Pediatric Clinic: Implications for Pediatric Primary Care.

Pediatricians are well-positioned to screen for early childhood adversities, but effective responses to positive screens require an understanding of which adversities typically co-occur, and to what extent they are associated with other risk or protective factors. Among children seen at an urban academic pediatric practice, this study aimed to (1) examine the prevalence of different types of early adversity and protective experiences reported by primary caregivers, and (2) define latent classes of co-occurring adversities. Of 1434 children whose parents completed the Safe Environment for Every Kid (SEEK) at well-child visits during November 2019-January 2021, three classes of adverse experiences emerged, including those reporting low adversity (L; 73%), caregiver stress (CS; 17%), and both caregiver stress and depression (CSD; 10%). Among those who also completed the Adverse Childhood Experiences Questionnaire (ACE-Q, n = 1373) and the Protective and Compensatory Experiences Scale (PACES, n = 1377), belonging to the L class was associated with lower ACE-Q and higher PACES scores. For parent-respondents only, ACE-Q scores were significantly greater for the CSD class compared to the CS and L classes. Pediatricians should attend to the needs of caregivers reporting both stress and depression, as these families may face especially high levels of adversity and low levels of protective factors.

Establishing Trauma-Informed Primary Care: Qualitative Guidance from Patients and Staff in an Urban Healthcare Clinic.

Patients present to primary care clinics with a variety of experiences, including exposure to adverse childhood experiences (ACEs) and other social determinants of health. The pervasive impact of early adversity on later healthcare outcomes has resulted in the development of trauma-informed care principles that can be applied to healthcare settings. The primary aim of this study is to improve understanding of patient and staff experiences within a trauma-informed urban healthcare setting to guide considerations and recommendations when implementing such a model. A phenomenologic approach was taken using an interpretivist paradigm to collect qualitative data by conducting patient and staff focus groups. The following themes were identified: the communal experience of significant trauma, lack of continuity of care and time for each appointment, the importance of a sense of community and standardization and normalization of asking about trauma, development of social support networks, and creating a safe and non-judgmental healthcare space. Based on findings, considerations for implementing a trauma-informed healthcare model are provided.

Pediatric Integrated Care Models: A Systematic Review.

Psychiatric disorders are becoming more frequently diagnosed within the pediatric primary care setting. Despite increased diagnosis within primary care, only a minority of patients receive further psychiatric or specialty care. The integrated/collaborative care treatment model was designed to improve access within primary care. The purpose of this review is to identify randomized controlled trials and quasi-experimental studies that have investigated whether increased access improves treatment engagement, satisfaction, and improved mental health outcomes. Six studies met inclusion criteria. Studies reviewed indicated increased access to behavioral health treatment through use of the integrated/collaborative care model and improved mental health outcomes. Recommendations for screening and treatment are provided. Limitations of the reviewed studies include lack of generalizability to urban populations, minority youth, and youth younger than 4 years of age. Practice recommendations to address these limitations are identified.

SLAMF1 is required for TLR4-mediated TRAM-TRIF-dependent signaling in human macrophages.

Signaling lymphocytic activation molecule family 1 (SLAMF1) is an Ig-like receptor and a costimulatory molecule that initiates signal transduction networks in a variety of immune cells. In this study, we report that SLAMF1 is required for Toll-like receptor 4 (TLR4)-mediated induction of interferon ß (IFNß) and for killing of Gram-negative bacteria by human macrophages. We found that SLAMF1 controls trafficking of the Toll receptor-associated molecule (TRAM) from the endocytic recycling compartment (ERC) to Escherichia coli phagosomes. In resting macrophages, SLAMF1 is localized to ERC, but upon addition of E. coli, it is trafficked together with TRAM from ERC to E. coli phagosomes in a Rab11-dependent manner. We found that endogenous SLAMF1 protein interacted with TRAM and defined key interaction domains as amino acids 68 to 95 of TRAM as well as 15 C-terminal amino acids of SLAMF1. Interestingly, the SLAMF1-TRAM interaction was observed for human but not mouse proteins. Overall, our observations suggest that SLAMF1 is a new target for modulation of TLR4-TRAM-TRIF inflammatory signaling in human cells.

Hepatitis C virus triggers Golgi fragmentation and autophagy through the immunity-related GTPase M.

Positive-stranded RNA viruses, such as hepatitis C virus (HCV), assemble their viral replication complexes by remodeling host intracellular membranes to a membranous web. The precise composition of these replication complexes and the detailed mechanisms by which they are formed are incompletely understood. Here we show that the human immunity-related GTPase M (IRGM), known to contribute to autophagy, plays a previously unrecognized role in this process. We show that IRGM is localized at the Golgi apparatus and regulates the fragmentation of Golgi membranes in response to HCV infection, leading to colocalization of Golgi vesicles with replicating HCV. Our results show that IRGM controls phosphorylation of GBF1, a guanine nucleotide exchange factor for Arf-GTPases, which normally operates in Golgi membrane dynamics and vesicle coating in resting cells. We also find that HCV triggers IRGM-mediated phosphorylation of the early autophagy initiator ULK1, thereby providing mechanistic insight into the role of IRGM in HCV-mediated autophagy. Collectively, our results identify IRGM as a key Golgi-situated regulator that links intracellular membrane remodeling by autophagy and Golgi fragmentation with viral replication.

Pediatric Community Mental Health.

The emotional health and wellbeing of children and adolescents and their families is of utmost importance. Pediatricians are at the front line in identifying mental illness in children and adolescents and either linking them to resources in the community or providing treatment options themselves. Collaboration and integrative health care models is the cornerstone of effective strategies to provide access and quality mental health care to children and families in communities across the country.

The effects of refreezing on the viscoelastic and tensile properties of ligaments.

Biomechanical testing protocols for ligaments can be extensive and span two or more days. During this time, a specimen may have to undergo more than one cycle of freezing and thawing. Thus, the objective of this study was to evaluate the effects of refreezing on the viscoelastic and tensile properties of ligaments. The femur-medial collateral ligament-tibia complexes (FMTC) from six pairs of rabbit knees were used for this study. Following sacrifice, one leg in each pair was assigned to the fresh group and the FMTC was immediately dissected and prepared for testing. The contralateral knees were fresh-frozen at -20 degrees C for 3 weeks, thawed, dissected and then refrozen for one additional week before being tested as the refrozen group. The cross-sectional area and shape of the medial collateral ligament (MCL) was measured using a laser micrometer system. Stress relaxation and cyclic stress-relaxation tests in uniaxial tension were performed followed by a load to failure test. When the viscoelastic behavior of the MCL was described by the quasi-linear viscoelastic (QLV) theory, no statistically significant differences could be detected for the five constants (A, B, C, tau1, and tau2) between the fresh and refrozen groups (p > or = 0.07) based on our sample size. In addition, the structural properties of the FMTCs and the mechanical properties of the MCLs were also found to be similar between the two groups (p > or = 0.68). These results suggest that careful refreezing of the specimens had little or no effect on the biomechanical properties measured.

A novel methodology to reproduce previously recorded six-degree of freedom kinematics on the same diarthrodial joint.

The objective of this study was to develop a novel method to more accurately reproduce previously recorded 6-DOF kinematics of the tibia with respect to the femur using robotic technology. Furthermore, the effect of performing only a single or multiple registrations and the effect of robot joint configuration were investigated. A single registration consisted of registering the tibia and femur with respect to the robot at full extension and reproducing all kinematics while multiple registrations consisted of registering the bones at each flexion angle and reproducing only the kinematics of the corresponding flexion angle. Kinematics of the knee in response to an anterior (134 N) and combined internal/external (+/-10 N m) and varus/valgus (+/-5 N m) loads were collected at 0 degrees , 15 degrees , 30 degrees , 60 degrees , and 90 degrees of flexion. A six axes, serial-articulated robotic manipulator (PUMA Model 762) was calibrated and the working volume was reduced to improve the robot's accuracy. The effect of the robot joint configuration was determined by performing single and multiple registrations for three selected configurations. For each robot joint configuration, the accuracy in position of the reproduced kinematics improved after multiple registrations (0.7+/-0.3, 1.2+/-0.5, and 0.9+/-0.2 mm, respectively) when compared to only a single registration (1.3+/-0.9, 2.0+/-1.0, and 1.5+/-0.7 mm, respectively) (p<0.05). The accuracy in position of each robot joint configuration was unique as significant differences were detected between each of the configurations. These data demonstrate that the number of registrations and the robot joint configuration both affect the accuracy of the reproduced kinematics. Therefore, when using robotic technology to reproduce previously recorded kinematics, it may be necessary to perform these analyses for each individual robotic system and for each diarthrodial joint, as different joints will require the robot to be placed in different robot joint configurations.

Functional tissue engineering for ligament healing: potential of antisense gene therapy.

Traumatic knee injuries frequently involve the disruption of multiple ligaments, such as a complete tear of the medial collateral ligament (MCL) together with a rupture of the anterior cruciate ligament (ACL) (Miyasaka, K., D. M. Daniel, M. L. Stone, and P. Hirshman. Am. J. Knee Surg. 4:3-8, 1991). Despite the high incidence, clinical management of this type of injury is still debated. Laboratory studies have shown that the ACL and MCL share the responsibility of stabilizing the knee, especially in response to valgus and other rotatory torques as well as anterior tibial loads (Inoue, M., E. McGurk-Burleson, J. M. Hollis, and S. L-Y. Woo. Am. J. Sports Med. 15:15-21, 1987; Kanamori, A., M. Sakane, J. Zeminski, T. W. Rudy, and S. L-Y. Woo. J. Ortho. Sci. 5:567-571, 2000; Ma, C. B., C. D. Papageogiou, R. E. Debski, and S. L. Woo. Acta Orthop. Scand. 71:387-393, 2000; Sakane, M., G. A. Livesay, R. J. Fox, T. W. Rudy, T. J. Runco, and S. L-Y. Woo. Knee Surg. Sports Traumatol. Arthrosc. 7:93-97, 1999). When one structure is deficient, the force in the other increases significantly to compensate. The injured ACL does not heal and requires surgical replacement by tissue grafts. On the other hand, after an isolated MCL tear or in a combined MCL and ACL injury, the MCL can heal spontaneously without surgical intervention and can function well in most cases. Nevertheless, the biomechanical and biochemical properties as well as the histomorphological appearance of the healing MCL are substantially different to those of normal tissue (Bray, R. C., D. J. Butterwick, M. R. Daschak, and J. V. Tyberg. J. Orthop. Res. 14:618-625, 1996; Loitz-Ramage, B. J., C. B. Frank, and N. G. Shrive. Clin. Orthop.:272-280, 1997; Weiss, J. A., S. L-Y. Woo, K. J. Ohland, S. Horibe, and P. O. Newton. J. Orthop. Res. 9:516-528, 1991). In an effort to improve the outcome of injuries to these and other ligaments, therapeutic strategies associated with improving biomechanical, biochemical, and histomorphological properties of ligaments have been investigated in recent years. These therapeutic strategies include growth factor stimulation (Conti, N. A., and L. E. Dahners. Presented at Orthopaedic Research Society, San Francisco, CA; Deie, M., T. Marui, C. R. Allen, K. A. Hildebrand, H. I. Georgescu, et al. Mech. Ageing Dev. 97:121-130, 1997), cell therapy (Menetrey, J., C. Kasemkijwattana, C. S. Day, P. Bosch, F. H. Fu, et al. Tissue Eng. 5:435-442, 1999; Watanabe, N., S. L-Y. Woo, C. Papageorgiou, C. Celechovsky, and S. Takai. Microsc. Res. Tech. 58:39-44, 2002), as well as gene stherapy (Nakamura N., D. A. Hart, R. S. Boorman, Y. Kaneda, N. G. Shrive, et al. J. Orthop. Res. 18:517-523, 2000; Shimomura, T., F. Jia, C. Niyibizi, and S. L-Y. Woo. Connect. Tissue Res.:2003). The knowledge gained by studying these therapeutic strategies could potentially be applied to other ligaments and tendons. In this article, antisense gene therapy to alter gene expression by using antisense oligonucleotides will be examined as a possible solution.

Passive strain distribution in the interosseous ligament of the forearm: implications for injury reconstruction.

PURPOSE: For severe forearm injuries such as an Essex-Lopresti fracture-dislocation, functional reconstruction necessitates repair of the interosseous ligament (IOL) to restore normal load sharing between the radius and ulna. Locating or tensioning such a reconstruction improperly can lead to abnormal load sharing and/or restriction of forearm rotation. The normal IOL strains should indicate the proper location of reconstruction grafts and the proper forearm rotation for tensioning the grafts. The objective of this study was to quantify the passive strain distribution of the IOL of the forearm with passive rotation of the forearm throughout the range of motion. METHODS: The 3-dimensional motions of the radius with respect to the ulna were measured throughout forearm rotation in 10 cadaveric forearms by using an instrumented spatial linkage. From the bone motions and ligament insertion site geometry from dissection and computed tomographic scanning, insertion site motions were determined and used to calculate changes in ligament fiber lengths. RESULTS: The measured strain distribution in the IOL was nonuniform and varied with forearm rotation. The overall magnitude of IOL strain was found to be greatest in supination and smallest in pronation. In supination the strains varied across fibers with strains being greatest in the distal fibers and lowest in the proximal fibers. Strains in neutral rotation were uniform across fibers. Although fibers were generally slack in pronation proximal fibers were less slack than distal fibers. CONCLUSIONS: The results of this study indicate that fiber strains in the IOL vary from proximal to distal and depend on forearm rotation. Our data suggest that to prevent restriction of forearm rotation all grafts should be tensioned in supination, where measured strains were generally highest. Our data also suggest that a 2-bundle IOL reconstruction may be necessary for proper load transfer between the radius and ulna in both supination and pronation.

Distribution of in situ forces in the anterior cruciate ligament in response to rotatory loads.

The anterior cruciate ligament (ACL) can be anatomically divided into anteromedial (AM) and posterolateral (PL) bundles. Current ACL reconstruction techniques focus primarily on reproducing the AM bundle, but are insufficient in response to rotatory loads. The objective of this study was to determine the distribution of in situ force between the two bundles when the knee is subjected to anterior tibial and rotatory loads. Ten cadaveric knees (50+/-10 years) were tested using a robotic/universal force-moment sensor (UFS) testing system. Two external loading conditions were applied: a 134 N anterior tibial load at full knee extension and 15 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion and a combined rotatory load of 10 Nm valgus and 5 Nm internal tibial torque at 15 degrees and 30 degrees of flexion. The resulting 6 degrees of freedom kinematics of the knee and the in situ forces in the ACL and its two bundles were determined. Under an anterior tibial load, the in situ force in the PL bundle was the highest at full extension (67+/-30 N) and decreased with increasing flexion. The in situ force in the AM bundle was lower than in the PL bundle at full extension, but increased with increasing flexion, reaching a maximum (90+/-17 N) at 60 degrees of flexion and then decreasing at 90 degrees. Under a combined rotatory load, the in situ force of the PL bundle was higher at 15 degrees (21+/-11 N) and lower at 30 degrees of flexion (14+/-6 N). The in situ force in the AM bundle was similar at 15 degrees and 30 degrees of knee flexion (30+/-15 vs. 35+/-16 N, respectively). Comparing these two external loading conditions demonstrated the importance of the PL bundle, especially when the knee is near full extension. These findings provide a better understanding of the function of the two bundles of the ACL and could serve as a basis for future considerations of surgical reconstruction in the replacement of the ACL.

Tensile properties of an anterior cruciate ligament graft after bone-patellar tendon-bone press-fit fixation.

Hardware used for fixation of ACL autografts in bone tunnels frequently complicates revision surgery, requiring two-stage procedures when a bone-patellar tendon-bone (B-PT-B) autograft is used for ACL reconstruction. Therefore alternative procedures that eliminate hardware have been advocated. This study compared the mechanical behavior of two fixation procedures: a widely used interference screw (IFS) fixation and a press-fit fixation that is hardware free. Twenty hind limbs from skeletally mature Saanen breed goats were used in this study, ten each in IFS and press-fit groups. After ACL reconstruction the specimens were dissected, leaving a femur-ACL graft-tibia complex (FATC) for uniaxial tensile testing. The tests included a series of three cyclic creep tests (C1-C3) for the evaluation of residual elongation followed by a tensile load to failure test to obtain linear stiffness and ultimate load of the FATCs. Four of ten specimens failed during the cyclic creep test for the press-fit group, compared to one for the IFS group. For the remaining specimens residual elongation following three cyclic creep tests (C1-C3) was 1.7+/-0.5 mm in the press-fit group compared to 1.3+/-0.6 mm in the IFS group, and there was no statistical significant difference between the two fixations. In the load to failure test there was also no statistical significant difference in linear stiffness between the two fixations. However, the ultimate load for the press-fit group (215+/-75 N) was significantly lower than that for the IFS group (328+/-103 N). These results provide the basis for future studies involving the time course of healing of these two procedures using the goat model.