Conserved 5-methyluridine tRNA modification modulates ribosome translocation.

While the centrality of post-transcriptional modifications to RNA biology has long been acknowledged, the function of the vast majority of modified sites remains to be discovered. Illustrative of this, there is not yet a discrete biological role assigned for one the most highly conserved modifications, 5-methyluridine at position 54 in tRNAs (m 5 U54). Here, we uncover contributions of m 5 U54 to both tRNA maturation and protein synthesis. Our mass spectrometry analyses demonstrate that cells lacking the enzyme that installs m 5 U in the T-loop (TrmA in E. coli , Trm2 in S. cerevisiae ) exhibit altered tRNA modifications patterns. Furthermore, m 5 U54 deficient tRNAs are desensitized to small molecules that prevent translocation in vitro. This finding is consistent with our observations that, relative to wild-type cells, trm2 Δ cell growth and transcriptome-wide gene expression are less perturbed by translocation inhibitors. Together our data suggest a model in which m 5 U54 acts as an important modulator of tRNA maturation and translocation of the ribosome during protein synthesis.

Mitigating a TDP-43 proteinopathy by targeting ataxin-2 using RNA-targeting CRISPR effector proteins.

The TDP-43 proteinopathies, which include amyotrophic lateral sclerosis and frontotemporal dementia, are a devastating group of neurodegenerative disorders that are characterized by the mislocalization and aggregation of TDP-43. Here we demonstrate that RNA-targeting CRISPR effector proteins, a programmable class of gene silencing agents that includes the Cas13 family of enzymes and Cas7-11, can be used to mitigate TDP-43 pathology when programmed to target ataxin-2, a modifier of TDP-43-associated toxicity. In addition to inhibiting the aggregation and transit of TDP-43 to stress granules, we find that the in vivo delivery of an ataxin-2-targeting Cas13 system to a mouse model of TDP-43 proteinopathy improved functional deficits, extended survival, and reduced the severity of neuropathological hallmarks. Further, we benchmark RNA-targeting CRISPR platforms against ataxin-2 and find that high-fidelity forms of Cas13 possess improved transcriptome-wide specificity compared to Cas7-11 and a first-generation effector. Our results demonstrate the potential of CRISPR technology for TDP-43 proteinopathies.

Anthropometric measures and arsenic methylation among pregnant women in rural northern Bangladesh.

INTRODUCTION: Arsenic methylation converts inorganic arsenic (iAs) to monomethyl (MMA) and dimethyl (DMA) arsenic compounds. Body mass index (BMI) has been positively associated with arsenic methylation efficiency (higher DMA%) in adults, but evidence in pregnancy is inconsistent. We estimated associations between anthropometric measures and arsenic methylation among pregnant women in rural northern Bangladesh. METHODS: We enrolled pregnant women (n = 784) (median [IQR] gestational week: 14 [13, 15]) in Gaibandha District, Bangladesh from 2018 to 2019. Anthropometric measures were BMI, subscapular and triceps skinfold thicknesses, and mid-upper arm circumference (MUAC), fat area (MUAFA), and muscle area (MUAMA). Arsenic methylation measures were urinary iAs, MMA, and DMA divided by their sum and multiplied by 100 (iAs%, MMA%, and DMA%), primary methylation index (MMA/iAs; PMI), and secondary methylation index (DMA/MMA; SMI). In complete cases (n = 765 [97.6%]), we fitted linear, beta, and Dirichlet regression models to estimate cross-sectional differences in iAs%, MMA%, DMA%, PMI, and SMI per IQR-unit difference in each anthropometric measure, adjusting for drinking water arsenic, age, gestational age, education, living standards index, and plasma folate, vitamin B12, and homocysteine. RESULTS: Median (IQR) BMI, subscapular skinfold thickness, triceps skinfold thickness, MUAC, MUAFA, and MUAMA were 21.5 (19.4, 23.8) kg/m2, 17.9 (13.2, 24.2) mm, 14.2 (10.2, 18.7) mm, 25.9 (23.8, 28.0) cm, 15.3 (10.5, 20.3) cm2, and 29.9 (25.6, 34.2) cm2, respectively. Median (IQR) iAs%, MMA%, DMA%, PMI, and SMI were 12.0 (9.3, 15.2)%, 6.6 (5.3, 8.3)%, 81.0 (77.1, 84.6)%, 0.6 (0.4, 0.7), and 12.2 (9.3, 15.7), respectively. In both unadjusted and adjusted linear models, all anthropometric measures were negatively associated with iAs%, MMA%, and PMI and positively associated with DMA% and SMI. For example, fully adjusted mean differences (95% CI) in DMA% per IQR-unit difference in BMI, subscapular skinfolds thickness, triceps skinfold thickness, MUAC, MUAFA, and MUAMA were 1.72 (1.16, 2.28), 1.58 (0.95, 2.21), 1.74 (1.11, 2.37), 1.45 (0.85, 2.06), 1.70 (1.08, 2.31), and 0.70 (0.13, 1.27) pp, respectively. CONCLUSIONS: Anthropometric measures were positively associated with arsenic methylation efficiency among pregnant women in the early second trimester.

Methylated guanosine and uridine modifications in S. cerevisiae mRNAs modulate translation elongation.

Chemical modifications to protein encoding messenger RNAs (mRNAs) influence their localization, translation, and stability within cells. Over 15 different types of mRNA modifications have been observed by sequencing and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) approaches. While LC-MS/MS is arguably the most essential tool available for studying analogous protein post-translational modifications, the high-throughput discovery and quantitative characterization of mRNA modifications by LC-MS/MS has been hampered by the difficulty of obtaining sufficient quantities of pure mRNA and limited sensitivities for modified nucleosides. We have overcome these challenges by improving the mRNA purification and LC-MS/MS pipelines. The methodologies we developed result in no detectable non-coding RNA modifications signals in our purified mRNA samples, quantify 50 ribonucleosides in a single analysis, and provide the lowest limit of detection reported for ribonucleoside modification LC-MS/MS analyses. These advancements enabled the detection and quantification of 13 S. cerevisiae mRNA ribonucleoside modifications and reveal the presence of four new S. cerevisiae mRNA modifications at low to moderate levels (1-methyguanosine, N2-methylguanosine, N2,N2-dimethylguanosine, and 5-methyluridine). We identified four enzymes that incorporate these modifications into S. cerevisiae mRNAs (Trm10, Trm11, Trm1, and Trm2, respectively), though our results suggest that guanosine and uridine nucleobases are also non-enzymatically methylated at low levels. Regardless of whether they are incorporated in a programmed manner or as the result of RNA damage, we reasoned that the ribosome will encounter the modifications that we detect in cells. To evaluate this possibility, we used a reconstituted translation system to investigate the consequences of modifications on translation elongation. Our findings demonstrate that the introduction of 1-methyguanosine, N2-methylguanosine and 5-methyluridine into mRNA codons impedes amino acid addition in a position dependent manner. This work expands the repertoire of nucleoside modifications that the ribosome must decode in S. cerevisiae. Additionally, it highlights the challenge of predicting the effect of discrete modified mRNA sites on translation de novo because individual modifications influence translation differently depending on mRNA sequence context.

Mitigating a TDP-43 proteinopathy by targeting ataxin-2 using RNA-targeting CRISPR effector proteins.

The TDP-43 proteinopathies, which include amyotrophic lateral sclerosis and frontotemporal dementia, are a devastating group of neurodegenerative disorders that are characterized by the mislocalization and aggregation of TDP-43. Here we demonstrate that RNA-targeting CRISPR effector proteins, a programmable class of gene silencing agents that includes the Cas13 family of enzymes and Cas7-11, can be used to mitigate TDP-43 pathology when programmed to target ataxin-2, a modifier of TDP-43-associated toxicity. In addition to inhibiting the aggregation and transit of TDP-43 to stress granules, we find that the in vivo delivery of an ataxin-2-targeting Cas13 system to a mouse model of TDP-43 proteinopathy improved functional deficits, extended survival, and reduced the severity of neuropathological hallmarks. Further, we benchmark RNA-targeting CRISPR platforms against ataxin-2 and find that high-fidelity forms of Cas13 possess improved transcriptome-wide specificity compared to Cas7-11 and a first-generation effector. Our results demonstrate the potential of CRISPR technology for TDP-43 proteinopathies.

A humanized yeast model reveals dominant-negative properties of neuropathy-associated alanyl-tRNA synthetase mutations.

Aminoacyl-tRNA synthetases (ARSs) are essential enzymes that ligate tRNA molecules to cognate amino acids. Heterozygosity for missense variants or small in-frame deletions in six ARS genes causes dominant axonal peripheral neuropathy. These pathogenic variants reduce enzyme activity without significantly decreasing protein levels and reside in genes encoding homo-dimeric enzymes. These observations raise the possibility that neuropathy-associated ARS variants exert a dominant-negative effect, reducing overall ARS activity below a threshold required for peripheral nerve function. To test such variants for dominant-negative properties, we developed a humanized yeast assay to co-express pathogenic human alanyl-tRNA synthetase (AARS1) mutations with wild-type human AARS1. We show that multiple loss-of-function AARS1 mutations impair yeast growth through an interaction with wild-type AARS1, but that reducing this interaction rescues yeast growth. This suggests that neuropathy-associated AARS1 variants exert a dominant-negative effect, which supports a common, loss-of-function mechanism for ARS-mediated dominant peripheral neuropathy.

The Pregnancy, Arsenic, and Immune Response (PAIR) Study in rural northern Bangladesh.

BACKGROUND: Arsenic exposure and micronutrient deficiencies may alter immune reactivity to influenza vaccination in pregnant women, transplacental transfer of maternal antibodies to the foetus, and maternal and infant acute morbidity. OBJECTIVES: The Pregnancy, Arsenic, and Immune Response (PAIR) Study was designed to assess whether arsenic exposure and micronutrient deficiencies alter maternal and newborn immunity and acute morbidity following maternal seasonal influenza vaccination during pregnancy. POPULATION: The PAIR Study recruited pregnant women across a large rural study area in Gaibandha District, northern Bangladesh, 2018-2019. DESIGN: Prospective, longitudinal pregnancy and birth cohort. METHODS: We conducted home visits to enrol pregnant women in the late first or early second trimester (11-17 weeks of gestational age). Women received a quadrivalent seasonal inactivated influenza vaccine at enrolment. Follow-up included up to 13 visits between enrolment and 3 months postpartum. Arsenic was measured in drinking water and maternal urine. Micronutrient deficiencies were assessed using plasma biomarkers. Vaccine-specific antibody titres were measured in maternal and infant serum. Weekly telephone surveillance ascertained acute morbidity symptoms in women and infants. PRELIMINARY RESULTS: We enrolled 784 pregnant women between October 2018 and March 2019. Of 784 women who enrolled, 736 (93.9%) delivered live births and 551 (70.3%) completed follow-up visits to 3 months postpartum. Arsenic was detected (≥0.02 µg/L) in 99.7% of water specimens collected from participants at enrolment. The medians (interquartile ranges) of water and urinary arsenic at enrolment were 5.1 (0.5, 25.1) µg/L and 33.1 (19.6, 56.5) µg/L, respectively. Water and urinary arsenic were strongly correlated (Spearman's ⍴ = 0.72) among women with water arsenic ≥ median but weakly correlated (⍴ = 0.17) among women with water arsenic < median. CONCLUSIONS: The PAIR Study is well positioned to examine the effects of low-moderate arsenic exposure and micronutrient deficiencies on immune outcomes in women and infants. REGISTRATION: NCT03930017.

Estimating Causal Effects of Interventions on Early-life Environmental Exposures Using Observational Data.

PURPOSE OF REVIEW: We discuss how epidemiologic studies have used observational data to estimate the effects of potential interventions on early-life environmental exposures. We summarize the value of posing questions about interventions, how a group of techniques known as "g-methods" can provide advantages for estimating intervention effects, and how investigators have grappled with the strong assumptions required for causal inference. RECENT FINDINGS: We identified nine studies that estimated health effects of hypothetical interventions on early-life environmental exposures. Of these, six examined air pollution. Interventions evaluated by these studies included setting exposure levels at a specific value, shifting exposure distributions, and limiting exposure levels to less than a threshold value. Only one study linked exposure contrasts to a specific intervention on an exposure source, however. There is growing interest in estimating intervention effects of early-life environmental exposures, in part because intervention effects are directly related to possible public health actions. Future studies can build on existing work by linking research questions to specific hypothetical interventions that could reduce exposure levels. We discuss how framing questions around interventions can help overcome some of the barriers to causal inference and how advances related to machine learning may strengthen studies by sidestepping the overly restrictive assumptions of parametric regression models. By leveraging advancements in causal inference and exposure science, an intervention framework for environmental epidemiology can guide actionable solutions to improve children's environmental health.

mRNA and tRNA modification states influence ribosome speed and frame maintenance during poly(lysine) peptide synthesis.

Ribosome speed is dictated by multiple factors including substrate availability, cellular conditions, and product (peptide) formation. Translation slows during the synthesis of cationic peptide sequences, potentially influencing the expression of thousands of proteins. Available evidence suggests that ionic interactions between positively charged nascent peptides and the negatively charged ribosome exit tunnel impede translation. However, this hypothesis was difficult to test directly because of inability to decouple the contributions of amino acid charge from mRNA sequence and tRNA identity/abundance in cells. Furthermore, it is unclear if other components of the translation system central to ribosome function (e.g., RNA modification) influence the speed and accuracy of positively charged peptide synthesis. In this study, we used a fully reconstituted Escherichia coli translation system to evaluate the effects of peptide charge, mRNA sequence, and RNA modification status on the translation of lysine-rich peptides. Comparison of translation reactions on poly(lysine)-encoding mRNAs conducted with either Lys-tRNALys or Val-tRNALys reveals that that amino acid charge, while important, only partially accounts for slowed translation on these transcripts. We further find that in addition to peptide charge, mRNA sequence and both tRNA and mRNA modification status influence the rates of amino acid addition and the ribosome's ability to maintain frame (instead of entering the -2, -1, and +1 frames) during poly(lysine) peptide synthesis. Our observations lead us to expand the model for explaining how the ribosome slows during poly(lysine) peptide synthesis and suggest that posttranscriptional RNA modifications can provide cells a mechanism to precisely control ribosome movements along an mRNA.

Investigating the consequences of mRNA modifications on protein synthesis using in vitro translation assays.

The ribosome translates the information stored in the genetic code into functional proteins. In this process messenger RNAs (mRNAs) serve as templates for the ribosome, ensuring that amino acids are linked together in the correct order. Chemical modifications to mRNA nucleosides have the potential to influence the rate and accuracy of protein synthesis. Here, we present an in vitro Escherichia coli translation system utilizing highly purified components to directly investigate the impact of mRNA modifications on the speed and accuracy of the ribosome. This system can be used to gain insights into how individual chemical modifications influence translation on the molecular level. While the fully reconstituted system described in this chapter requires a lengthy time investment to prepare experimental materials, it is highly verstaile and enables the systematic assessment of how single variables influence protein synthesis by the ribosome.

The modern use of the extended humeral head (cuff tear arthropathy) hemiarthroplasty.

Today, the treatment of osteoarthritis in the rotator cuff-deficient population is largely dominated by reverse shoulder arthroplasty (RSA). Despite the popularity of and increased familiarity with this procedure, the complication rate of RSA remains significant. An extended humeral head hemiarthroplasty may provide a less invasive alternative for select patients with cuff tear arthropathy (CTA) and preserved glenohumeral active elevation. With the indications for reverse arthroplasty expanding to younger patients, there are concerns about the longevity of this implant, as well as the associated revision burden. In the setting of failed RSA, the bone stock available for glenosphere baseplate fixation can be inadequate for reimplantation. The treatment strategies for complex shoulder deformities and failed RSA are limited by patient-specific issues, such as anatomy and risk factors. In this review, we discuss the potential role of extended humeral head hemiarthroplasty (CTA hemiarthroplasty) as a primary surgical option in select patients (1) who have preserved elevation > 90°, (2) who have maintained stability (intact coracoacromial ligament), and (3) who desire to circumvent the complications associated with RSA. Furthermore, CTA hemiarthroplasty may be used for severe glenoid erosion, for a fragmented acromion, and in the revision setting for failed RSA aimed at a reliable salvage procedure.

Clinical Outcomes of Superior Capsular Reconstruction for Massive, Irreparable Rotator Cuff Tears: A Systematic Review Comparing Acellular Dermal Allograft and Autograft Fascia Lata.

PURPOSE: To investigate clinical outcomes after superior capsular reconstruction (SCR) for the treatment of massive and/or irreparable rotator cuff tears treated with either allograft or autograft. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines, in April 2020 a systematic review was performed using PubMed, MEDLINE, EMBASE, and Cochrane databases. Clinical studies were assessed for patient-reported outcomes and range of motion, comparing dermal allografts to fascia lata autografts, with a minimum follow-up of 12 months. RESULTS: A total of 16 clinical studies involving 598 patients (606 shoulders) were included for data analysis, with a weighted mean follow-up of 36.9 months (range 12 to 60). Visual analogue scale (VAS) pain scores decreased from 4.0 to 6.9 mm preoperatively to 0 to 2.5 mm postoperatively. American Shoulder & Elbow Surgeons score increased from 20.3 to 54.5 preoperatively to 73.7 to 97.0 postoperatively. Forward flexion increased from 27.0° to 142.7° preoperatively to 134.5° to 167.0° postoperatively. External rotation increased from 13.2° to 41.0° preoperatively to 30.0° to 59.0° postoperatively. Acromiohumeral distance increased from 3.4 to 7.1 mm preoperatively to 6.0 to 9.7 mm postoperatively. The total rates of complications, graft failure, and revision surgery were 5.6%, 13.9%, and 6.9%, respectively. CONCLUSIONS: Irrespective of tissue source, SCR serves as a reasonable joint-preserving option for massive, irreparable rotator cuff tears, with favorable short- to midterm improvements in patient-reported outcomes and range of motion. LEVEL OF EVIDENCE: IV, systematic review of level III and IV studies.

Periprosthetic Fractures Through Tracking Pin Sites Following Computer Navigated and Robotic Total and Unicompartmental Knee Arthroplasty: A Systematic Review.

BACKGROUND: Use of computer-assisted navigation (CAN) and robotic-assisted (RA) surgery in total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA) both necessitate the use of tracking pins rigidly fixed to the femur and tibia. Although periprosthetic fractures through tracking pin sites are rare, there is a paucity of literature on this potential complication. Therefore, the purpose of this study was to perform a systematic review of the current literature to assess the incidence and clinical outcomes of periprosthetic fractures through tracking pin sites following CAN and RA TKA and UKA. METHODS: A systematic review was performed following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines using the PubMed, MEDLINE, and Cochrane databases in April 2020. Studies were assessed for the presence of pin site fractures, fracture characteristics, and clinical outcomes. RESULTS: Seventeen clinical studies (5 case series, 1 cohort study, and 11 case reports) involving 29 pin-related fractures were included for review. The overall incidence ranged from 0.06% to 4.8%. The mean time from index arthroplasty to fracture was 9.5 weeks (range, 0 to 40 weeks). The majority of fractures occurred in the femoral diaphysis (59%). Nineteen fractures (66%) were displaced and 10 (34%) were nondisplaced or occult. The majority of cases were atraumatic in nature or involved minor trauma and were typically preceded by persistent leg pain. A transcortical pin trajectory, large pin diameter (>4 mm), diaphyseal fixation, multiple placement attempts, and the use of non-self-drilling, non-self-tapping pins were the most commonly reported risk factors for pin-related periprosthetic fractures following CAN or RA TKA. CONCLUSIONS: Surgeons should maintain a high index of suspicion for pin-related fractures in patients with ongoing leg or thigh pain after CAN or RA TKA in order to avoid fracture displacement and additional morbidity. As CAN and RA TKA have unique complication risks, the debate regarding the value of technology-assisted TKA and its cost-effectiveness continues. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Superior Capsular Reconstruction Provides Sufficient Biomechanical Outcomes for Massive, Irreparable Rotator Cuff Tears: A Systematic Review.

PURPOSE: To critically review the literature reporting biomechanical outcomes of superior capsular reconstruction (SCR) for the treatment of massive and/or irreparable rotator cuff tears. METHODS: A systematic review was performed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines using the PubMed, MEDLINE, and Cochrane Library databases in August 2020. Cadaveric studies were assessed for glenohumeral translation, subacromial contact pressure, and superior humeral translation comparing SCR with an intact cuff with reference to a torn control state. RESULTS: A total of 15 studies (142 shoulders) were included in our data analysis. SCR showed improvements in superior humeral translation, subacromial contact force, and glenohumeral contact force when biomechanically compared with the massive and/or irreparably torn rotator cuff. No statistically significant differences were found between SCR and the intact rotator cuff regarding superior humeral translation (standard mean difference [SMD], 2.09 mm vs 2.50 mm; P = .54) or subacromial contact force (SMD, 2.85 mPa vs 2.83 mPa; P = .99). Significant differences were observed between SCR and the intact cuff for glenohumeral contact force only, in favor of the intact cuff (SMD, 1.73 N vs 5.45 N; P = .03). CONCLUSIONS: SCR may largely restore static restraints to superior humeral translation in irreparable rotator cuff tears, although active glenohumeral compression is diminished relative to the intact rotator cuff. CLINICAL RELEVANCE: Investigating the biomechanical outcomes of SCR will help surgeons better understand the effectiveness of this treatment option.

The Vacuum Phenomenon in the Elbow: A Case Report.

CASE: A 33-year-old man presented with a closed distal humerus fracture after a fall from scaffolding. Computed tomography demonstrated intra-articular gas, despite the lack of arthrotomy, open fracture, or skin defects. The "vacuum phenomenon" (VP), or the presence of intra-articular gas in closed injuries, has primarily been described in the axial skeleton. To our knowledge, there are no reports in fractures of the elbow. CONCLUSION: The incidence of the VP is under-reported and represents a lack of physician awareness. The VP should remain a diagnosis of exclusion; however, physicians should be aware of this phenomenon to prevent unnecessary patient harm.

Is a Partial Anterior Cruciate Ligament Tear Truly Partial? A Clinical, Arthroscopic, and Histologic Investigation.

PURPOSE: (1) To determine whether examination under anesthesia (EUA) and/or magnetic resonance imaging (MRI) is an accurate means for determining patient selection for a selective-bundle reconstruction, (2) to determine whether the preoperative clinical assessment correlates with the arthroscopic examination, and (3) to examine histologically whether a partial anterior cruciate ligament (ACL) tear is truly partial in terms of vascular insult. METHODS: This prospective, nonrandomized cohort study included 95 patients who underwent primary ACL reconstruction from January 2013 through May 2014. All patients underwent an EUA, MRI, and arthroscopic evaluation. In patients with partial ACL tears, the intact bundle was resected and underwent histologic examination. The χ2 test was used to compare EUA and MRI in the detection of partial tears. RESULTS: Of the 95 patients included, 40 (42%) had EUA findings consistent with a partial ACL tear whereas 22 (23%) had MRI findings interpreted as showing a partial ACL tear. Arthroscopic examination confirmed a partial ACL tear in only 11 patients (12%). The sensitivity of EUA and MRI in the detection of partial ACL tears was 100% and 90.9%, and the specificity was 65% and 85.7%, respectively. The χ2 test suggested statistically significant associations between the method of evaluation and diagnostic outcome [χ2(1) = 7.83, P = .005]. MRI was 1.24 times more likely to correctly identify a partial tear (95% confidence interval, 1.06-1.45). EUA was 2.23 times as likely to incorrectly identify a partial tear (95% confidence interval, 1.24-4.02). The histologic analysis showed increased numbers of lymphocytes, absent polymorphonuclear leukocytes, predominant fibroblasts, neovascularization, and variable collagen orientation. CONCLUSIONS: There is a disparity between EUA, MRI, and arthroscopic findings in the evaluation of partial ACL tears. Arthroscopy remains the gold standard for diagnosing the macroscopic integrity of the intact bundle. Microscopic analysis reveals that the integrity of the remaining intact ligament material is altered and may show a histologic response similar to a complete ACL rupture. LEVEL OF EVIDENCE: Level III, prospective, nonrandomized cohort study.

The Push-Through Sign-Making the Decision for Selective-Bundle Anterior Cruciate Ligament Surgery.

Partial anterior cruciate ligament (ACL) tears are often difficult to diagnose and treat. Recent interest in the literature has focused on performing selective-bundle ACL reconstruction in patients with symptomatic partial ACL tears when one of the ACL bundles is intact. However, the clinical examination, magnetic resonance imaging, and arthroscopic evaluation of partial ACL tears may not correlate, and proper assessment of the integrity of the intact portion of the ACL continues to be a challenge. If a selective-bundle ACL reconstruction is performed in a patient with an apparently intact but structurally damaged individual bundle, the outcome would be compromised by leaving the damaged bundle in place. This technical note provides a description of a simple and reliable arthroscopic method to aid in the diagnosis of a partial ACL tear. The use of this method to assess remaining ligamentous tissue will assist surgeons in deciding for or against selective-bundle ACL reconstruction.

Predictors of Intrusive Sexual Behaviors in Preschool-Aged Children.

Intrusive sexual behaviors (ISBs) are a specific type of problematic sexual behavior characterized by the invasive nature of the acts (e.g., touching others' private parts, attempting intercourse; Friedrich, 1997). The limited amount of research on ISBs has focused on sexual abuse history as the primary predictor. However, Friedrich, Davies, Feher, and Wright (2003) found that ISBs in children up to age 12 were related to four broad conceptual factors: (a) exposure to sexual content, (b) exposure to violent behavior, (c) family adversity, and (d) child vulnerabilities. The current study sought to replicate Friedrich's study using a clinical sample of 217 preschool-aged children (ages two to six). Results supported variables from within the child vulnerabilities construct (externalizing behaviors, ßEXT = 0.032, p = 0.001), post-traumatic stress disorder (PTSD) criteria met (ßPTSD = 0.177, p = 0.02), and an inverse relationship with age (ßAGE = -0.206, p = 0.024). These results highlight the importance of considering childhood behavioral patterns and reactivity to traumatic events as correlates of ISBs in young children.

A Qualitative Evaluation of Engagement and Attrition in a Nurse Home Visiting Program: From the Participant and Provider Perspective.

Beginning parenting programs in the prenatal and early postnatal periods have a large potential for impact on later child and maternal outcomes. Home-based parenting programs, such as the Nurse Family Partnership (NFP), have been established to help address this need. Program reach and impact is dependent on successful engagement of expecting mothers with significant risks; however, NFP attrition rates remain high. The current study qualitatively examined engagement and attrition from the perspectives of NFP nurses and mothers in order to identify mechanisms that enhance service engagement. Semi-structured interviews were conducted in focus groups composed of either engaged (27 total mothers) or unengaged (15 total mothers) mothers from the NFP program. NFP nurses (25 total nurses) were recruited for individual semi-structured interviews. Results suggest that understanding engagement in the NFP program requires addressing both initial and sustained engagement. Themes associated with enhanced initial engagement include nurse characteristics (e.g., flexible, supportive, caring) and establishment of a solid nurse-family relationship founded on these characteristics. Factors impacting sustained engagement include nurse characteristics, provision of educational materials on child development, individualized services for families, and available family support. Identified barriers to completing services include competing demands and lack of support. Findings of this study have direct relevance for workforce planning, including hiring and training through integrating results regarding effective nurse characteristics. Additional program supports to enhance parent engagement may be implemented across home-based parenting programs in light of the current study's findings.