Spatial regulation of gene expression during growth of articular cartilage in juvenile mice.

BACKGROUND: In juvenile mammals, the epiphyses of long bones grow by chondrogenesis within the articular cartilage. A better understanding of the molecular mechanisms that regulate the growth of articular cartilage may give insight into the antecedents of joint disease, such as osteoarthritis. METHODS: We used laser capture microdissection to isolate chondrocytes from the superficial, middle, and deep zones of growing tibial articular cartilage in the 1-wk-old mouse and then investigated expression patterns by microarray. To identify molecular markers for each zone of the growing articular cartilage, we found genes showing zone-specific expression and confirmed by real-time PCR and in situ hybridization. RESULTS: Bioinformatic analyses implicated ephrin receptor signaling, Wnt signaling, and bone morphogenetic protein signaling in the spatial regulation of chondrocyte differentiation during growth. Molecular markers were identified for superficial (e.g., Cilp, Prg4), middle (Cxcl14, Tnn), and deep zones (Sfrp5, Frzb). Comparison between juvenile articular and growth plate cartilage revealed that the superficial-to-deep zone transition showed similarity with the hypertrophic-to-resting zone transition. CONCLUSION: Laser capture microdissection combined with microarray analysis identified novel signaling pathways that are spatially regulated in growing mouse articular cartilage and revealed similarities between the molecular architecture of the growing articular cartilage and that of growth plate cartilage.

Effect of arm position and foot placement on the five times sit-to-stand test completion times of female adults older than 50 years of age.

The five times-sit-to stand test (FTSTS) is a clinical test which is commonly used to assessed the functional muscle strength of the lower limbs of older adults. The aim of this study was to examine the effect of different arm positions and foot placements on the FTSTS completion times of older female adults. [Subjects and Methods] Twenty-nine healthy female subjects, aged 63.1±5.3 years participated in this cross-sectional study. The times required to complete the FTSTS with 3 different arm positions (hands on thighs, arms crossed over chest, and an augmented arm position with the arms extended forward) and 2 foot placements (neutral and posterior) were recorded. The interaction effect and main effect of arm positions and foot placements were examined using a 3 (arm position) × 2 (foot placement) two-way repeated measures analysis of variance (ANOVA). [Results] There was no interaction effect among the 3 arm positions in the 2 foot placements. A significant main effect was identified for foot placement, but not arm position. Posterior foot placement led to a shorter FTSTS time compared to that of normal foot placement. [Conclusion] With the same arm position, FTSTS completion times with posterior foot placement tended to be shorter. Therefore, the standard foot placement should be used for FTSTS administration.

Contributions of the Abductor Muscles to Rotational and Distractive Stability of the Hip in a Biomechanical Cadaveric Model.

Background: The gluteus minimus (GMin) and gluteus medius (GMed) are important dynamic stabilizers of the hip, but quantitative data on their biomechanical roles in stabilizing the hip are currently lacking. Purpose: To (1) establish a reproducible biomechanical cadaveric model of the hip abductor complex and (2) characterize the effects of loading the GMin and GMed on extraneous femoral rotation and distraction. Study Design: Controlled laboratory study. Methods: A total of 10 hemipelvises were tested in 4 muscle loading states: (1) unloaded, (2) the GMin loaded, (3) the GMed loaded, and (4) both the GMin and GMed loaded. Muscle loads were applied via cables, pulleys, and weights attached to the tendons to replicate the anatomic lines of action. Specimens were tested under internal rotation; external rotation; and axial traction forces at 0°, 15°, 30°, 60°, and 90° of hip flexion. Results: When loaded together, the GMin and GMed reduced internal rotation motion at all hip flexion angles (P < .05) except 60° and reduced external rotation motion at all hip flexion angles (P < .05) except 0°. Likewise, when both the GMin and GMed were loaded, femoral distraction was decreased at all angles of hip flexion (P < .05). Conclusion: The results of this study demonstrated that the GMin and GMed provide stability against rotational torques and distractive forces and that the amount of contribution depends on the degree of hip flexion. Clinical Relevance: Improved understanding of the roles of the GMin and GMed in preventing rotational and distractive instability of the hip will better guide treatment of hip pathologies and optimize nonoperative and operative therapies.

Evaluation of a Web-based social network electronic game in enhancing mental health literacy for young people.

BACKGROUND: Internet-based learning programs provide people with massive health care information and self-help guidelines on improving their health. The advent of Web 2.0 and social networks renders significant flexibility to embedding highly interactive components, such as games, to foster learning processes. The effectiveness of game-based learning on social networks has not yet been fully evaluated. OBJECTIVES: The aim of this study was to assess the effectiveness of a fully automated, Web-based, social network electronic game on enhancing mental health knowledge and problem-solving skills of young people. We investigated potential motivational constructs directly affecting the learning outcome. Gender differences in learning outcome and motivation were also examined. METHODS: A pre/posttest design was used to evaluate the fully automated Web-based intervention. Participants, recruited from a closed online user group, self-assessed their mental health literacy and motivational constructs before and after completing the game within a 3-week period. The electronic game was designed according to cognitive-behavioral approaches. Completers and intent-to-treat analyses, using multiple imputation for missing data, were performed. Regression analysis with backward selection was employed when examining the relationship between knowledge enhancement and motivational constructs. RESULTS: The sample included 73 undergraduates (42 females) for completers analysis. The gaming approach was effective in enhancing young people's mental health literacy (d=0.65). The finding was also consistent with the intent-to-treat analysis, which included 127 undergraduates (75 females). No gender differences were found in learning outcome (P=.97). Intrinsic goal orientation was the primary factor in learning motivation, whereas test anxiety was successfully alleviated in the game setting. No gender differences were found on any learning motivation subscales (P>.10). We also found that participants' self-efficacy for learning and performance, as well as test anxiety, significantly affected their learning outcomes, whereas other motivational subscales were statistically nonsignificant. CONCLUSIONS: Electronic games implemented through social networking sites appear to effectively enhance users' mental health literacy.

Arthroscopic In Situ Biceps Tenodesis Using a Double Loop-and-Tack Knotless Suture Anchor.

The long head biceps tendon is a common culprit of anterior shoulder pain and dysfunction that can be surgically treated with tenotomy or tenodesis. Many techniques exist for tenodesis. This article submits an arthroscopic technique using two loop-and-tack sutures and a knotless suture anchor to tenodese the long head biceps tendon in the proximal bicipital groove in situ. The advantage of this technique is that it maintains the biceps in its native position by performing tenodesis before tenotomy. Most other techniques attempt to restore native position of the biceps through approximation. The transverse humeral ligament is also released to decompress the bicipital groove. This technique can be used to treat isolated biceps pathology or combined with rotator cuff and labral procedures.

Interobserver reliability of biplanar radiography is unaffected by clinical factors relevant to individuals at risk of pathological lower limb torsion.

BACKGROUND: Assessments of lower limb torsion are ubiquitous in clinical gait analysis practice as pathologic lower limb rotational deformity may contribute to gait abnormalities, anterior knee pain, as well as other debilitating conditions. Understandably, the overall utility of any torsional assessment is dependent on the measurement method's intrinsic accuracy, precision, and robustness to clinical interference factors. Recently, biplanar radiography (BPR) measurements of torsion have been shown to be both accurate and precise, but the robustness of BPR to potential interference factors is unknown. RESEARCH QUESTION: How robust are BPR lower limb torsional assessments to six potential interference factors: amount of torsion, skeletal maturity, radiograph quality, prior osteotomy, presence of implants, and observer training background and experience? METHODS: In this retrospective cohort study, four observers of diverse backgrounds and experience generated digital 3D reconstructions of 44 lower limbs using BPR images obtained during standard of care visits (age range 7-35 years). From each reconstruction, four lower limb torsional parameters were computed: femoral torsion, femorotibial rotation, tibial torsion, and transmalleolar axis equivalent. The mean absolute deviation (MAD) of each torsional parameter - calculated across the four observers - was used as the measure of reliability and tested against all interference factors. RESULTS: Results demonstrated that the average MAD was 2.1 degrees for femoral torsion, 3.0 degrees for transmalleolar axis equivalent, 3.8 degrees for femorotibial rotation, and 4.7 degrees for tibial torsion. None of the six potential interference factors were found to systematically influence BPR reliability across all four torsional parameters. Of the factors found to statistically influence one or more torsional parameter, none affected MAD values to a clinically meaningful extent. SIGNIFICANCE: In addition to being accurate and precise, BPR appears to be robust to several clinical factors relevant to children and young adults with or at risk for pathological lower limb torsion.

Osteochondritis Dissecans of the Knee in Young Athletes.

Osteochondritis dissecans of the knee is a relatively rare disorder in young athletes that can lead to premature osteoarthritis. It may be caused by multiple factors, including repetitive stress, local ischemia, aberrant endochondral ossification of the subarticular physis, and hereditary disposition. Nonoperative treatment is typically attempted for patients with open physes, stable lesions, and minimal symptoms. Operative treatment is offered to patients with closed physes, unstable lesions, mechanical symptoms, and failure of nonoperative treatment. Customized rehabilitation and return to sport programs are important for successful outcomes regardless of treatment type.

Rotational Osteotomy for Femoral Version/Tibial Torsion.

PURPOSE OF REVIEW: The purpose of this review is to discuss the current state of knowledge regarding axial plane deformities in patellofemoral instability, indications and techniques for treatment of those deformities, and outcomes following treatment. RECENT FINDINGS: There is opportunity for more information in the literature on all aspects of axial plane deformities in patellofemoral instability. This includes how to assess axial plane deformities on imaging, what is normal and what is an appropriate goal for correction, what techniques are best used depending on the deformity or concomitant pathology, and larger and more discriminating studies on outcomes. Rotational deformity of both the tibia and femur is an important risk factor to consider as a cause of patellar instability. Recent research has shown that surgical correction of these deformities on either the femoral or tibial side can have a positive effect on outcome in terms of patellar instability and knee pain. Further research, however, is warranted to determine what are normal values for femoral version and tibial torsion, and at what values surgical intervention is warranted.

Rotational Deformity-When and How to Address Femoral Anteversion and Tibial Torsion.

Rotational deformity is a less common cause of patellar instability than trochlear dysplasia and patella alta. In some cases, rotational deformity is the primary bony factor producing the instability and should be corrected surgically. More research is needed on what are normal values for femoral version and tibial torsion, as well as when the axial plane alignment needs to be corrected. Many tools can be used to evaluate the axial plane and surgeons should be familiar with each of them. Understanding the advantages and disadvantages of each site for osteotomy will help the surgeon choose the most appropriate osteotomy.

The synovial microenvironment suppresses chondrocyte hypertrophy and promotes articular chondrocyte differentiation.

During the development of the appendicular skeleton, the cartilaginous templates undergo hypertrophic differentiation and remodels into bone, except for the cartilage most adjacent to joint cavities where hypertrophic differentiation and endochondral bone formation are prevented, and chondrocytes instead form articular cartilage. The mechanisms that prevent hypertrophic differentiation and endochondral bone formation of the articular cartilage have not been elucidated. To explore the role of the synovial microenvironment in chondrocyte differentiation, osteochondral allografts consisting of articular cartilage, epiphyseal bone, and growth plate cartilage from distal femoral epiphyses of inbred Lewis rats expressing enhanced green fluorescent protein from a ubiquitous promoter were transplanted either in inverted or original (control) orientation to matching sites in wildtype littermates, thereby allowing for tracing of transplanted cells and their progenies. We found that no hypertrophic differentiation occurred in the growth plate cartilage ectopically placed at the joint surface. Instead, the transplanted growth plate cartilage, with time, remodeled into articular cartilage. This finding suggests that the microenvironment at the articular surface inhibits hypertrophic differentiation and supports articular cartilage formation. To explore this hypothesis, rat chondrocyte pellets were cultured with and without synoviocyte-conditioned media. Consistent with the hypothesis, hypertrophic differentiation was inhibited and expression of the articular surface marker lubricin (Prg4) was dramatically induced when chondrocyte pellets were exposed to synovium- or synoviocyte-conditioned media, but not to chondrocyte- or osteoblast-conditioned media. Taken together, we present evidence for a novel mechanism by which synoviocytes, through the secretion of a factor or factors, act directly on chondrocytes to inhibit hypertrophic differentiation and endochondral bone formation and promote articular cartilage formation. This mechanism may have important implications for articular cartilage development, maintenance, and regeneration.

Optimized protocols for in situ hybridization, immunohistochemistry, and immunofluorescence on skeletal tissue.

Assessment of gene and protein expression in tissue sections is instrumental in medical research. However, this is often challenging to perform on skeletal tissues that require prolonged decalcification and have poor adhesion to slides. In this study, we optimized selected steps of in situ hybridization (ISH), immunohistochemistry (IHC), and immunofluorescence (IF) for formalin fixed and decalcified skeletal tissues. Sections from distal femur of 6-, 8- and 14- week-old rats injected with BrdU with or without a hemizygous eGFP transgene expressed under the control of a ubiquitous promotor were used. We report that proteinase K digestion is critical for the sensitivity of ISH, as concentrations that were too strong and too mild both resulted in loss of signal. In addition, intensified RNase A digestion removed nonspecific riboprobe-mRNA hybrids. Furthermore, enzymatic antigen retrieval using proteinase K provided more consistent results in IHC and can therefore be a useful alternative to heat induced epitope retrieval (HIER) for skeletal tissues where such treatment often damages the morphology. A mild proteinase K digestion also improved IF detection of GFP and worked well for double labeling IF of GFP and osteocalcin on frozen sections of formalin fixed and decalcified rat bones while maintaining morphology. In summary, this study provides strategies to improve protocols for enzymatic digestion in ISH, IHC, and IF for skeletal tissues and also demonstrates the importance of careful optimization and validation with the use of these techniques.

Open Supracondylar Humerus Fractures in Children.

PURPOSE: Supracondylar humerus (SCH) fractures are the most common elbow fracture in children; however, they rarely occur as open injuries. Open fractures are associated with higher rates of infection, neurovascular injury, compartment syndrome, and nonunion. The purpose of this study was to evaluate the treatment and outcomes of open SCH fractures in children. METHODS: Between 2008 and 2015, four children (1%) had open injuries among 420 treated for SCH fractures at a single center. The mean patient age was six years (range, four to eight years). Two patients had Gustilo-Anderson grade 1 open fractures and two had grade 2 fractures. Tetanus immunization was up-to-date in all. First dose of intravenous antibiotics was given on average 3hr 7min after onset of injury (range, 1hr 38min to 8hr 15min). Time from injury to irrigation and debridement (I&D) and closed reduction and percutaneous pinning (CRPP) was on average 8hr 16min (range, 4hr 19min to 13hr 15min). All patients received 24-hour intravenous antibiotics. Pins were removed at four weeks and bony union occurred by six weeks. RESULTS: After an average follow-up period of 12 months (range, 6 to 22 months), there were no infections, neurovascular deficits, compartment syndromes, cubitus varus deformities, or range of motion losses. All outcomes were excellent according to the Flynn criteria. Due to the unstable nature of open SCH fractures, a medial pin was used in all four cases. No loss of reduction or ulnar nerve injury occurred. CONCLUSION:  Open injuries occur in approximately 1% of all SCH fractures in children. The authors recommend urgent intravenous antibiotics, I&D, and CRPP involving a medial pin to treat open SCH fractures. Excellent outcomes based on the Flynn criteria were obtained in four cases.

Osteochondritis Dissecans: Current Understanding of Epidemiology, Etiology, Management, and Outcomes.

➤: Osteochondritis dissecans occurs most frequently in the active pediatric and young adult populations, commonly affecting the knee, elbow, or ankle, and may lead to premature osteoarthritis. ➤: While generally considered an idiopathic phenomenon, various etiopathogenetic theories are being investigated, including local ischemia, aberrant endochondral ossification of the secondary subarticular physis, repetitive microtrauma, and genetic predisposition. ➤: Diagnosis is based on the history, physical examination, radiography, and advanced imaging, with elbow ultrasonography and novel magnetic resonance imaging protocols potentially enabling early detection and in-depth staging. ➤: Treatment largely depends on skeletal maturity and lesion stability, defined by the presence or absence of articular cartilage fracture and subchondral bone separation, as determined by imaging and arthroscopy, and is typically nonoperative for stable lesions in skeletally immature patients and operative for those who have had failure of conservative management or have unstable lesions. ➤: Clinical practice guidelines have been limited by a paucity of high-level evidence, but a multicenter effort is ongoing to develop accurate and reliable classification systems and multimodal decision-making algorithms with prognostic value.

The Vacuum-Assisted Closure Device Increases Value in the Treatment of Gustilo Grade IIIb Open Tibia Fractures in Children.

Background Wound management associated with Gustilo grade IIIb open tibia fractures in children often requires muscle flaps, skin grafts, and amputations. The purpose of this study is to report the outcomes and complications of vacuum-assisted closure (VAC) treatment, as well as discuss its role in optimizing value when treating these injuries. Methods A retrospective review of medical records and imaging studies was performed from 2008-2015. Six pediatric patients with Gustilo grade IIIb fractures managed with the VAC were identified. The time to treatment, frequency of VAC changes, VAC size, and closure attempts, including muscle flaps and skin grafts, were documented. Fracture fixation methods, the incidence of delayed union or nonunion, as well as the occurrence of deep tissue infection and compartment syndrome were detailed. Results Five patients were male and one was female with an average age of 12 years (range 8-15 years). All patients sustained a Gustilo IIIb open tibia fracture and were treated with irrigation, debridement, intravenous (IV) antibiotics, fixation, and a VAC as a wound care adjunct. Three patients required both a muscle flap and a skin graft. One patient required a skin graft. There was one case of deep tissue infection. Three patients were treated successfully with the VAC alone and did not require any flap procedures. Conclusions Wound care for Gustilo grade IIIb open tibia fractures in children traditionally involved potentially painful twice-daily dressing changes with solutions such as dilute bleach or iodine. The implementation of VAC markedly reduced the frequency of dressing changes every three days. In the current study, the open wound gradually closed with only a VAC in 50% of Gustilo grade IIIb open pediatric tibia fractures. In summary, the VAC is an adjunct that increases value in the care of pediatric patients with Gustilo grade IIIb open tibia fractures (Value = Outcomes/Cost). Level of evidence Therapeutic level IV.

Traumatic Glenosphere Dissociation Following Reverse Total Shoulder Endoprosthetic Reconstruction for Proximal Humerus Periosteal Chondrosarcoma: A Case Report.

INTRODUCTION: Reverse total shoulder endoprosthetic reconstruction after margin-negative tumor resection of the proximal humerus is becoming more conventional in orthopeadic oncology practices. Mid-term survival and functional outcomes have been satisfactory. This case report corroborates with current literature and further describes a rare traumatic complication. CASE PRESENTATION: We report a case of a 70-year-old male with periosteal chondrosarcoma of the proximal humerus who underwent margin-negative resection and reverse total shoulder endoprosthetic reconstruction that was complicated by glenosphere dissociation sustained from falling onto a hyperflexed arm. Successful revision arthroplasty was performed. CONCLUSION: Enhancing glenohumeral joint stability after wide resection of the proximal humerus is important to address rotator cuff insufficiency. The greater levering effect of a longer humeral prosthesis used to increase soft tissue tension may also increase the risk of glenosphere dissociation secondary to trauma. Proper soft-tissue tensioning and surgical technique are critical.

Evidence That Rat Chondrocytes Can Differentiate Into Perichondrial Cells.

During early bone formation, mesenchymal cells condense and then differentiate into collagen type II-expressing chondrocytes that make up the cartilaginous bone anlagen. This anlage then becomes enclosed by the perichondrium. The mechanisms by which the perichondrium forms are not known. The purpose of this study was to determine whether epiphyseal chondrocytes can differentiate into perichondrial cells. Novel perichondrium markers were identified by expression microarray of microdissected rat perichondrium and growth plate cartilage. A dissection method that allowed for removal of contaminating perichondrium was developed and the absence was confirmed by histological examination and by expression of perichondrium markers. Perichondrium formation surrounding chondrocyte pellets was studied using histology, real-time PCR, and in situ hybridization for chondrocyte and perichondrium markers. Cultured chondrocyte pellets developed an exterior perichondrium-like layer. This surrounding tissue did not express chondrocyte markers, collagen-type II and type X, as assessed by in situ hybridization. Instead, perichondrium markers, periostin, Dickkopf 3 (Dkk3), roundabout 2, cadherin 2, L-galectin 1 (Lgals1), and thrombospondin 2 (Thbs2) were upregulated following formation of the perichondrium-like layer as assessed by real-time PCR. Interestingly, markers specific for the cambium layer, Dkk3, Thbs2, and Lgals1, but not for the fibrous layer, collagen-type XIV and decorin, were upregulated. The findings suggest that epiphyseal chondrocytes of postnatal animals retain the potential to differentiate into perichondrial cells, supporting the hypothesis that the perichondrium originates from collagen type II-expressing chondrocytes at the periphery of the cartilaginous bone template. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Functional Outcomes of Symptomatic Implant Removal Following Ankle Fracture Open Reduction and Internal Fixation.

BACKGROUND: Orthopedic implant removal following open reduction internal fixation of a fracture is a common procedure, especially in the foot and ankle. The purpose of this study was to evaluate functional change after the removal of symptomatic implants following ankle fracture open reduction internal fixation (ORIF) using the Short Musculoskeletal Function Assessment (SMFA) outcome score. We hypothesized that implant removal after ankle fracture would result in improved functional outcomes. METHODS: Retrospective review of prospectively collected data on patients with a closed ankle fracture between 2013 and 2016 was performed. Inclusion criteria were skeletal maturity, symptomatic ankle implants and completion of the SMFA questionnaire prior to and 6 months after removal. Exclusion criteria were development of a nonunion, prior or current infection, peripheral neuropathy or ongoing litigation surrounding the surgery. The primary outcome was change in SMFA score from baseline to follow-up using Wilcoxon signed-rank test. Additional logistic regression models evaluated the effects of age, sex, body mass index, smoking status, and patient American Society of Anesthesiologists scores. RESULTS: The study population consisted of 43 patients. There was a statistically significant improvement in function, represented by a decrease in SMFA scores from baseline to the 6-month follow-up period (∆ = -4.1 [95% confidence interval, -7.0, -1.3]; P = .003). Secondary outcome measures of the bother index and daily activities domain also demonstrated significant improvements ( P = .005 and P = .002, respectively). Additional logistical regression models identified no significant effects by assessed covariates for change in SMFA scores. CONCLUSION: Patients with symptomatic implants following ankle fracture ORIF had a statistically significant improvement in function following implant removal. There appears to be value in removing implants from the ankle in patients who report discomfort during daily activities. Further investigation into the specific indications for implant removal and the impact of injury and fracture pattern on outcomes is warranted. LEVEL OF EVIDENCE: Level IV, case series.

Gradients in bone morphogenetic protein-related gene expression across the growth plate.

In the growth plate, stem-like cells in the resting zone differentiate into rapidly dividing chondrocytes of the proliferative zone and then terminally differentiate into the non-dividing chondrocytes of the hypertrophic zone. To explore the molecular switches responsible for this two-step differentiation program, we developed a microdissection method to isolate RNA from the resting (RZ), proliferative (PZ), and hypertrophic zones (HZ) of 7-day-old male rats. Expression of approximately 29,000 genes was analyzed by microarray and selected genes verified by real-time PCR. The analysis identified genes whose expression changed dramatically during the differentiation program, including multiple genes functionally related to bone morphogenetic proteins (BMPs). BMP-2 and BMP-6 were upregulated in HZ compared with RZ and PZ (30-fold each, P < 0.01 and 0.001 respectively). In contrast, BMP signaling inhibitors were expressed early in the differentiation pathway; BMP-3 and gremlin were differentially expressed in RZ (100- and 80-fold, compared with PZ, P < 0.001 and 0.005 respectively) and growth differentiation factor (GDF)-10 in PZ (160-fold compared with HZ, P < 0.001). Our findings suggest a BMP signaling gradient across the growth plate, which is established by differential expression of multiple BMPs and BMP inhibitors in specific zones. Since BMPs can stimulate both proliferation and hypertrophic differentiation of growth plate chondrocytes, these findings suggest that low levels of BMP signaling in the resting zone may help maintain these cells in a quiescent state. In the lower RZ, greater BMP signaling may help induce differentiation to proliferative chondrocytes. Farther down the growth plate, even greater BMP signaling may help induce hypertrophic differentiation. Thus, BMP signaling gradients may be a key mechanism responsible for spatial regulation of chondrocyte proliferation and differentiation in growth plate cartilage.

Engagement of vulnerable youths using internet platforms.

AIM: The aim of this study was to explore the online distress and help-seeking behavior of youths in Hong Kong. METHODS: A cross-sectional telephone-based survey was conducted among 1,010 young people in Hong Kong. Logistic regression analysis was then performed to identify the factors associated with those who reported expressing emotional distress online and the differences in help-seeking behavior among four groups of youths: (1) the non-distressed (reference) group; (2) "Did not seek help" group; (3) "Seek informal help" group; and (4) "Seek formal help" group. RESULTS: The seeking of help and expression of distress online were found to be associated with a higher lifetime prevalence of suicidal ideation. The "Seek formal help" and "Did not seek help" groups had a similar risk profile, including a higher prevalence of suicidal ideation, non-suicidal self-injury, unsafe sex, and being bullied. The "Seek informal help" group was more likely to express distress online, which indicates that this population of youths may be accessible to professional identification. Approximately 20% of the distressed youths surveyed had not sought help despite expressing their distress online. IMPLICATION: The study's results indicate that helping professionals have opportunities to develop strategic engagement methods that make use of social media to help distressed youths.