Outcomes of initial nonoperative treatment of traumatic full-thickness rotator cuff tears.

BACKGROUND: Nonsurgical management of chronic, degenerative rotator cuff tears (RCTs) can be an effective treatment strategy, but there is limited evidence to support conservative treatment of acute, traumatic RCTs. The objective of this study was to assess clinical outcomes and predictors of treatment success in patients with traumatic RCTs who elected for initial nonoperative treatment. METHODS: Patients from a single institution were retrospectively identified using diagnostic codes for traumatic RCTs followed by confirmed initial treatment with ≥2 months of physical therapy. The exclusion criteria included surgery within 2 months of injury and greater than grade I fatty infiltration on magnetic resonance imaging. At minimum 2-year follow-up, patients were contacted by telephone to collect interval surgical history and standardized patient-reported outcomes. Physical therapy was considered to have failed in all those who underwent surgical treatment and those with satisfaction ratings of "moderately dissatisfied" or "very dissatisfied." RESULTS: Follow-up outcomes were obtained in 40 of 49 patients (82%), with an average follow-up time of 4.2 years. Of the RCTs, 9 (22%) were small (<1 cm), 22 (54%) were medium (>1 cm to <3 cm), and 9 (22%) were large (>3 cm to <5 cm). Grade I fatty infiltration was seen on 25% of magnetic resonance imaging scans (n = 10). Rotator cuff repair was performed in 18 patients (45%) following an average of 6 months of nonoperative treatment (range, 3-12 months). Nonoperative treatment was determined to have failed in 23 of 40 patients (58%) in total. Conservative management was more likely to fail in patients with multiple tendons torn (P = .014). Tear size and retraction were not significantly different between patients who underwent surgery and those who did not. Patients who underwent surgical management had an 83% satisfaction rate at final follow-up compared with a 55% satisfaction rate for patients who did not undergo surgery (P = .054). There was no statistically significant difference in the American Shoulder and Elbow Surgeons score or visual analog scale score between these groups. Although patients who underwent surgery had a higher mean Single Alpha Numeric Evaluation score (86.3 vs. 75.1, P = .041), this difference was below the previously established minimal clinically important difference. CONCLUSION: Nonoperative treatment remains a viable option for certain patients with traumatic RCTs; however, the results of our study demonstrate a considerable early failure rate. This study further supports historical literature demonstrating reliably successful outcomes with surgical treatment of acute, traumatic RCTs.

Impact of Sharing Dance Older Adults on Physical and Psychosocial Outcomes.

Dance for older adults is increasingly being used to support health and well-being. While dance may be enjoyable for many, understanding its benefits for those with limited physical and cognitive abilities may provide further support for how dance may be used in these contexts. This was a study of Sharing Dance Older Adults, a dance program with remotely streamed sessions. Data were collected from 48 older adults who took part in the On Your Feet version of the program, and from 38 who took part in the In Your Seat version. Measures included interviews, physical fitness tests and surveys on mood, quality of life, and program satisfaction. Physical fitness significantly improved for both groups, unlike for mood, social well-being, or quality of life. This contrasts with qualitative findings, with participants reporting how the program enhanced their mood, social interactions, and quality of life.

Lymphatic disorders caused by mosaic, activating KRAS variants respond to MEK inhibition.

Central conducting lymphatic anomaly (CCLA) due to congenital maldevelopment of the lymphatics can result in debilitating and life-threatening disease with limited treatment options. We identified 4 individuals with CCLA, lymphedema, and microcystic lymphatic malformation due to pathogenic, mosaic variants in KRAS. To determine the functional impact of these variants and identify a targeted therapy for these individuals, we used primary human dermal lymphatic endothelial cells (HDLECs) and zebrafish larvae to model the lymphatic dysplasia. Expression of the p.Gly12Asp and p.Gly13Asp variants in HDLECs in a 2­dimensional (2D) model and 3D organoid model led to increased ERK phosphorylation, demonstrating these variants activate the RAS/MAPK pathway. Expression of activating KRAS variants in the venous and lymphatic endothelium in zebrafish resulted in lymphatic dysplasia and edema similar to the individuals in the study. Treatment with MEK inhibition significantly reduced the phenotypes in both the organoid and the zebrafish model systems. In conclusion, we present the molecular characterization of the observed lymphatic anomalies due to pathogenic, somatic, activating KRAS variants in humans. Our preclinical studies suggest that MEK inhibition should be studied in future clinical trials for CCLA due to activating KRAS pathogenic variants.

What are the effects of colorectal cancer screening interventions among Asian Americans? A meta-analysis.

Objective: Great strides have been made to conduct intervention studies aimed at increasing colorectal cancer (CRC) screening rates that are informed by sound theoretical frameworks and conducted using rigorous methodologies; however, efforts are still gaining wave to understand the efficacy of theory-based interventions among Asian American (AA) population. The purpose of this study was to report the results of a meta-analysis conducted on the effects of CRC screening interventions.Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to evaluate the CRC screening interventions. Literature search was performed on October 2018, and studies published in English and conducted in the United States were eligible for inclusion if they (1) conducted interventions with aims to increase CRC screening rates among AA and (2) utilized a randomized control trial or quasi-experimental study design, (3) reported quantitative screening rates following the intervention, and (4) included a comparison or control group for comparison. No publication year restriction was applied.Result: In total, 14 Odds Ratio (OR) from 16 studies were included in the meta-analysis. Overall, results indicated that AA participants who received the screening interventions aimed at improving screening were 1.78 times more likely to obtain a CRC screening at post-intervention compared to those in the control or comparison group, OR = 1.78 (1.44, 2.11).Conclusion: Understanding the efficacy of interventions designed to promote CRC screening among AA population is imperative to decrease CRC burden and mortality. Although research in this area is limited, this review sheds light on important socio-cultural strategies to developing a CRC screening intervention aimed at increasing screening rates among AA. Findings in this review demonstrate that improvement in screening can be achieved through a variety of ways, but the common feature across all the studies was the culturally responsive foundation of their respective interventions.

CCR2 contributes to host defense against Staphylococcus aureus orthopedic implant-associated infections in mice.

C-C motif chemokine receptor 2 (CCR2) is an important mediator of myeloid cell chemotaxis during inflammation and infection. Myeloid cells such as monocytes, macrophages, and neutrophils contribute to host defense during orthopedic implant-associated infections (OIAI), but whether CCR2-mediated chemotaxis is involved remains unclear. Therefore, a Staphylococcus aureus OIAI model was performed by surgically placing an orthopedic-grade titanium implant and inoculating a bioluminescent S. aureus strain in knee joints of wildtype (wt) and CCR2-deficient mice. In vivo bioluminescent signals significantly increased in CCR2-deficient mice compared with wt mice at later time points (Days 14-28), which was confirmed with ex vivo colony-forming unit enumeration. S. aureus γ-hemolysin utilizes CCR2 to induce host cell lysis. However, there were no differences in bacterial burden when the OIAI model was performed with a parental versus a mutant γ-hemolysin-deficient S. aureus strain, indicating that the protection was mediated by the host cell function of CCR2 rather than γ-hemolysin virulence. Although CCR2-deficient and wt mice had similar cellular infiltrates in the infected joint tissue, CCR2-deficient mice had reduced myeloid cells and γδ T cells in the draining lymph nodes. Taken together, CCR2 contributed to host defense at later time points during an OIAI by increasing immune cell infiltrates in the draining lymph nodes, which likely contained the infection and prevented invasive spread.

A novel MBTPS2 variant associated with BRESHECK syndrome impairs sterol-regulated transcription and the endoplasmic reticulum stress response.

Ichthyosis follicularis, atrichia, and photophobia syndrome (IFAP syndrome) is a rare, X-linked disorder caused by pathogenic variants in membrane-bound transcription factor protease, site 2 (MBTPS2). Pathogenic MBTPS2 variants also cause BRESHECK syndrome, characterized by the IFAP triad plus intellectual disability and multiple congenital anomalies. Here we present a patient with ichthyosis, sparse hair, pulmonic stenosis, kidney dysplasia, hypospadias, growth failure, thrombocytopenia, anemia, bone marrow fibrosis, and chronic diarrhea found by research-based exome sequencing to harbor a novel, maternally inherited MBTPS2 missense variant (c.766 G>A; (p.Val256Leu)). In vitro modeling supports variant pathogenicity, with impaired cell growth in cholesterol-depleted media, attenuated activation of the sterol regulatory element-binding protein pathway, and failure to activate the endoplasmic reticulum stress response pathway. Our case expands both the genetic and phenotypic spectrum of BRESHECK syndrome to include a novel MBTPS2 variant and cytopenias, bone marrow fibrosis, and chronic diarrhea.

Factors Associated with Mental Health Help-Seeking Among Asian Americans: a Systematic Review.

OBJECTIVE: Asian Americans are underutilizing mental health services. The aim of the current systematic review was to identify protective and risk factors of mental health help-seeking patterns among the disaggregated Asian Americans and to classify types of help. METHODS: A systematic literature review was conducted using the PRISMA guidelines. The Health Belief Model served as the theoretical framework for this review. Thirty-four articles were reviewed, and the studies investigated one of the following Asian ethnic subgroups: Chinese, Filipino, Asian Indian, Korean, or Vietnamese. Data were extracted based on the study characteristics, sample characteristics, and protective and risk factors to mental health help-seeking patterns. RESULTS: Predisposing factors like female gender, higher levels of English proficiency, and history of mental illness increased the likelihood for help-seeking across several ethnic groups. Interestingly, cues to action and structural factors were under-examined. However, cues to action like having a positive social network did increase the likelihood of using formal support services among Chinese and Filipinx participants. Structural factors like lacking ethnic concordant providers and access to healthcare served as barriers for Korean and Vietnamese participants. DISCUSSION: The findings showed a need for ethnic tailored approaches when supporting mental health help-seeking patterns. Asian ethnic group's immigration status, acculturation level, and psychological barriers to help-seeking should continue to be emphasized. Psychoeducational groups can be beneficial to expand the knowledge base surrounding mental illness and to link group members to culturally responsive resources.

Strengths-based inquiry of resiliency factors among refugees in Metro Vancouver: A comparison of newly-arrived and settled refugees.

STRENGTHS-BASED INQUIRY OF RESILIENCY FACTORS AMONG REFUGEES IN METRO VANCOUVER: A comparison of newly-arrived and settled refugees. OBJECTIVE: To identify the resiliency factors among refugees in the Metro Vancouver area, and compare these factors between newly-arrived and settled refugees. DESIGN: Semi-structured individual interviews. SETTING: Vancouver, British Columbia, and surrounding suburban communities. PARTICIPANTS: 13 key informants from resettlement, healthcare, and public education sectors who work closely with refugees, 13 refugees who have resided less than five years in Canada (LTFYRs), and 8 refugees who have resided greater than five years in Canada (GTFYRs). Refugee source countries were Syria, Iraq, Afghanistan, Iran, Kenya, Vietnam, Somalia, and Mexico. MAIN FINDINGS: Key informants stated that knowledge from this study would help create and improve current supports for refugees, inform policy, increase understanding of refugee perspectives, and promote strengths-based resettlement strategies. Resiliency factors were grouped into themes, which were categorized as internal or external resiliency factors. Internal resiliency factors included fixed characteristics (age at arrival, female gender, and past education/skills), positive coping strategies (acceptance and positivity), proactivity, and integration (personal identity and adaptation). External resiliency factors identified were support systems, employment and finances, living environment, and societal encouragement of refugees. Comparison of responses between LTFYRs and GTFYRs revealed overall consistency in resiliency factors, but with LTFYRs identifying characteristics that assisted with acute integration, such as age at arrival, more often than GTFYRs. Comparison of responses between refugees and key informants revealed that key informants less frequently identified internal resiliency factors. CONCLUSION: This study qualitatively describes several internal and external resiliency factors of refugees in Vancouver. Awareness and promotion of these resiliency factors in refugee populations, in collaboration with healthcare providers, settlement organizations and education systems, may improve refugee resettlement. These findings will also help generate the groundwork for local interventions that can support refugee resiliency in the population studied.

Liking of food textures and its relationship with oral physiological parameters and mouth-behavior groups.

Researchers have categorized people into four "mouth-behavior" groups based on their oral processing preferences, and claimed that members of those mouth-behavior groups differ in their food texture preferences. If people could be classified into groups based on their liking of different textures, food products could be targeted to specific subgroups, potentially enhancing consumer acceptability. In the first part of our study, we grouped people based on their liking ratings of a wide variety of food textures by asking 288 participants to rate their liking of 106 food texture attributes in an online survey. In the second part of our study, we further examined relationships among individuals' food texture liking ratings, mouth-behavior group membership, and measurements of four oral physiological parameters (saliva flow rate, chewing efficiency, biting force, and particle size sensitivity). One-hundred participants completed the online survey on food texture liking, classified themselves into one of four mouth-behavior groups (Chewers, Crunchers, Smooshers, and Suckers), and were measured for four oral physiological parameters. We refuted the idea that large texture-liking subgroups exist. Although our participants self-categorized themselves into the four mouth-behavior groups similarly to previous researchers, our texture liking measurements did not support the presumed preferences of those mouth-behavior groups. Clustering of participants on their oral physiological measurements produced a "low particle-size sensitivity" cluster, a "high biting force" cluster, a "high saliva flow rate" cluster, and a "low saliva flow and low chewing efficiency" cluster. Neither our texture liking nor our oral physiological measurements predicted membership in the four mouth-behavior groups.

Efficacy of a Multimechanistic Monoclonal Antibody Combination against Staphylococcus aureus Surgical Site Infections in Mice.

Surgical site infections (SSIs) are commonly caused by Staphylococcus aureus We report that a combination of three monoclonal antibodies (MEDI6389) that neutralize S. aureus alpha-toxin, clumping factor A, and four leukocidins (LukSF, LukED, HlgAB, and HlgCB) plus vancomycin had enhanced efficacy compared with control antibody plus vancomycin in two mouse models of S. aureus SSI. Therefore, monoclonal antibody-based neutralization of multiple S. aureus virulence factors may provide an adjunctive perioperative approach to combat S. aureus SSIs.

Selective Enzymatic Digestion of Proteoglycans and Collagens Alters Cartilage T1rho and T2 Relaxation Times.

Our objective was to determine the relationship of T1rho and T2 relaxation mapping to the biochemical and biomechanical properties of articular cartilage through selective digestion of proteoglycans and collagens. Femoral condyles were harvested from porcine knee joints and treated with either chondroitinase ABC (cABC) followed by collagenase, or collagenase followed by cABC. Magnetic resonance images were acquired and cartilage explants were harvested for biochemical, biomechanical, and histological analyses before and after each digestion. Targeted enzymatic digestion of proteoglycans with cABC resulted in elevated T1rho relaxation times and decreased sulfated glycosaminoglycan content without affecting T2 relaxation times. In contrast, extractable collagen and T2 relaxation times were increased by collagenase digestion; however, neither was altered by cABC digestion. Aggregate modulus decreased with digestion of both components. Overall, we found that targeted digestion of proteoglycans and collagens had varying effects on biochemical, biomechanical, and imaging properties. T2 relaxation times were altered with changes in extractable collagen, but not changes in proteoglycan. However, T1rho relaxation times were altered with proteoglycan loss, which may also coincide with collagen disruption. Since it is unclear which matrix components are disrupted first in osteoarthritis, both markers may be important for tracking disease progression.

Activities of daily living influence tibial cartilage T1rho relaxation times.

Quantitative T1rho magnetic resonance imaging (MRI) can potentially help identify early-stage osteoarthritis (OA) by non-invasively assessing proteoglycan concentration in articular cartilage. T1rho relaxation times are negatively correlated with proteoglycan concentration. Cartilage compresses in response to load, resulting in water exudation, a relative increase in proteoglycan concentration, and a decrease in the corresponding T1rho relaxation times. To date, there is limited information on changes in cartilage composition resulting from daily activity. Therefore, the objective of this study was to quantify changes in tibial cartilage T1rho relaxation times in healthy human subjects following activities of daily living. It was hypothesized that water exudation throughout the day would lead to decreased T1rho relaxation times. Subjects underwent MR imaging in the morning and afternoon on the same day and were free to go about their normal activities between scans. Our findings confirmed the hypothesis that tibial cartilage T1rho relaxation times significantly decreased (by 7%) over the course of the day with loading, which is indicative of a relative increase in proteoglycan concentration. Additionally, baseline T1rho values varied with position within the cartilage, supporting a need for site-specific measurements of T1rho relaxation times. Understanding how loading alters the proteoglycan concentration in healthy cartilage may hold clinical significance pertaining to cartilage homeostasis and potentially help to elucidate a mechanism for OA development. These results also indicate that future studies using T1rho relaxation times as an indicator of cartilage health should control the loading history prior to image acquisition to ensure the appropriate interpretation of the data.

Determination of the Position of the Knee at the Time of an Anterior Cruciate Ligament Rupture for Male Versus Female Patients by an Analysis of Bone Bruises.

BACKGROUND: The incidence of anterior cruciate ligament (ACL) ruptures is 2 to 4 times higher in female athletes as compared with their male counterparts. As a result, a number of recent studies have addressed the hypothesis that female and male patients sustain ACL injuries via different mechanisms. The efficacy of prevention programs may be improved by a better understanding of whether there are differences in the injury mechanism between sexes. Hypothesis/Purpose: To compare knee positions at the time of a noncontact ACL injury between sexes. It was hypothesized that there would be no differences in the position of injury. STUDY DESIGN: Controlled laboratory study. METHODS: Clinical T2-weighted magnetic resonance imaging (MRI) scans from 30 participants (15 male and 15 female) with a noncontact ACL rupture were reviewed retrospectively. MRI scans were obtained within 1 month of injury. Participants had contusions associated with an ACL injury on both the medial and lateral articular surfaces of the femur and tibia. Three-dimensional models of the femur, tibia, and associated bone bruises were created via segmentation on MRI. The femur was positioned relative to the tibia to maximize bone bruise overlap, thereby predicting the bone positions near the time of the injury. Flexion, valgus, internal tibial rotation, and anterior tibial translation were measured in the predicted position of injury. RESULTS: No statistically significant differences between male and female patients were detected in the position of injury with regard to knee flexion ( P = .66), valgus ( P = .87), internal tibial rotation ( P = .26), or anterior tibial translation ( P = .18). CONCLUSION: These findings suggest that a similar mechanism results in an ACL rupture in both male and female athletes with this pattern of bone bruising. CLINICAL RELEVANCE: This study provides a novel comparison of male and female knee positions at the time of an ACL injury that may offer information to improve injury prevention strategies.

Unraveling the Determinants to Colorectal Cancer Screening Among Asian Americans: a Systematic Literature Review.

Colorectal cancer (CRC) is one of the top three cancers experienced among Asian American (AA) men and women. One effective way to decrease incidence and mortality from CRC is the adherence of regular CRC screening; however, AA continue to receive the lowest screening rates compared to other racial/ethnic groups. When disaggregating this heterogeneous population, further disparities exist between subgroups. Examination of facilitators and barriers to cancer screening among AA subgroups is fairly recent and the synthesis of this information is limited. As such, a systematic review was conducted examining the facilitators and the barriers among Chinese, Filipino, Korean, and Japanese Americans using a systematic literature review method. The Health Belief Model served as the primary theoretical framework for this study and used to organize and synthesize the facilitators and barriers to CRC screening. In total, 22 articles yielded 29 examinations of each of the AA subgroups. Different facilitators and barriers to screening uptake for each subgroup were revealed; however, consistent across all the subgroups was physician recommendation as a facilitator and participants' unawareness of screening tests and those stating having no problems/symptoms of CRC as a barrier across screening modalities. Tailored approach in outreach and intervention efforts are suggested when achieving to improve CRC screening in AA ethnic subgroups.

Relationship between T1rho magnetic resonance imaging, synovial fluid biomarkers, and the biochemical and biomechanical properties of cartilage.

Non-invasive techniques for quantifying early biochemical and biomechanical changes in articular cartilage may provide a means of more precisely assessing osteoarthritis (OA) progression. The goals of this study were to determine the relationship between T1rho magnetic resonance (MR) imaging relaxation times and changes in cartilage composition, cartilage mechanical properties, and synovial fluid biomarker levels and to demonstrate the application of T1rho imaging to evaluate cartilage composition in human subjects in vivo. Femoral condyles and synovial fluid were harvested from healthy and OA porcine knee joints. Sagittal T1rho relaxation MR images of the condyles were acquired. OA regions of OA joints exhibited an increase in T1rho relaxation times as compared to non-OA regions. Furthermore in these regions, cartilage sGAG content and aggregate modulus decreased, while percent degraded collagen and water content increased. In OA joints, synovial fluid concentrations of sGAG decreased and C2C concentrations increased compared to healthy joints. T1rho relaxation times were negatively correlated with cartilage and synovial fluid sGAG concentrations and aggregate modulus and positively correlated with water content and permeability. Additionally, we demonstrated the application of these in vitro findings to the study of human subjects. Specifically, we demonstrated that walking results in decreased T1rho relaxation times, consistent with water exudation and an increase in proteoglycan concentration with in vivo loading. Together, these findings demonstrate that cartilage MR imaging and synovial fluid biomarkers provide powerful non-invasive tools for characterizing changes in the biochemical and biomechanical environments of the joint.

Mechanism of Histone H3K4me3 Recognition by the Plant Homeodomain of Inhibitor of Growth 3.

Aberrant access to genetic information disrupts cellular homeostasis and can lead to cancer development. One molecular mechanism that regulates access to genetic information includes recognition of histone modifications, which is carried out by protein modules that interact with chromatin and serve as landing pads for enzymatic activities that regulate gene expression. The ING3 tumor suppressor protein contains a plant homeodomain (PHD) that reads the epigenetic code via recognition of histone H3 tri-methylated at lysine 4 (H3K4me3), and this domain is lost or mutated in various human cancers. However, the molecular mechanisms targeting ING3 to histones and the role of this interaction in the cell remain elusive. Thus, we employed biochemical and structural biology approaches to investigate the interaction of the ING3 PHD finger (ING3PHD) with the active transcription mark H3K4me3. Our results demonstrate that association of the ING3PHD with H3K4me3 is in the sub-micromolar range (KD ranging between 0.63 and 0.93 µm) and is about 200-fold stronger than with the unmodified histone H3. NMR and computational studies revealed an aromatic cage composed of Tyr-362, Ser-369, and Trp-385 that accommodate the tri-methylated side chain of H3K4. Mutational analysis confirmed the critical importance of Tyr-362 and Trp-385 in mediating the ING3PHD-H3K4me3 interaction. Finally, the biological relevance of ING3PHD-H3K4me3 binding was demonstrated by the failure of ING3PHD mutant proteins to enhance ING3-mediated DNA damage-dependent cell death. Together, our results reveal the molecular mechanism of H3K4me3 selection by the ING3PHD and suggest that this interaction is important for mediating ING3 tumor suppressive activities.