An Environmental Scan of Consumer-Initiated Germline Genetic Testing for Health Risks.

As patient access to laboratory testing outside the clinic grows, health care providers can expect to confront increasing questions about the utility and interpretation of consumer-initiated genetic testing for health risks. We sought to characterize the marketplace diversity of consumer-initiated germline genetic testing options. An environmental scan was conducted to identify germline genetic testing companies that offer testing for at least one diagnosable health condition and are available for purchase by consumers in the US market without a visit to one's health care provider. We limited our scope to tests available between October 1, 2019, and September 30, 2021. We characterized variability in the content and processes used by 21 companies offering 74 distinct test products that met our inclusion and exclusion criteria. A minority (8 of 21 companies) offered tests that assessed the presence of at least 1 US Centers for Disease Control and Prevention Tier 1 condition for which detection can impact an individual's clinical care and for which evidence-based guidelines for detection and management exist.

Incorporation of Whipstitch Suture in Tibial Interference Fixation Improves Pullout in Anterior Cruciate Ligament Soft Tissue Grafts.

INTRODUCTION: Interference screw fixation of soft tissue grafts is commonly used in anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to determine whether including suture material at the graft-screw interface affects ultimate fixation strength of soft tissue grafts using a tibialis anterior tendon allograft model. MATERIALS AND METHODS: Forty fresh-frozen human tibialis anterior tendon allografts were fixed to rigid polyurethane foam simulating the tibial tunnel. Twenty grafts underwent fixation with interference screws and 20 with interference bolts. Within each group, 10 grafts had suture in contact with either the screw or bolt. A load-to-failure test was then performed at a rate of 200 mm/min. RESULTS: The group of allografts with sutures in the tibial tunnel had significantly higher load to failure than the group without sutures. Using interference screw fixation, failure load of the grafts without sutures in the tunnel (535.2 ± 73.40 N) was significantly lower (P = .001) than with sutures in the tunnel (696.3 ± 110.0 N). Using interference bolt fixation, failure load of the grafts without sutures in the tunnel (613.0 ± 83.46 N) was significantly lower (P <.0001) than with sutures in the tunnel (845.8 ± 87.23 N). CONCLUSIONS: In a biomechanical model, suture within the tibial tunnel enhances fixation strength with both interference screw and bolt fixation for soft tissue tibialis anterior allografts. Additionally, there was no difference in load to failure when comparing failure of a screw with suture in the tunnel with an interference bolt without suture. Due to improved biomechanical properties, incorporation of suture in the bone-graft interface should be considered when performing soft tissue ACL allograft reconstructions. Failure at the tibial bone-graft interface is a known complication of ACL reconstruction, and incorporation of suture within the interface should be considered for improved biomechanical properties.

Exposure to ethanol leads to midfacial hypoplasia in a zebrafish model of FASD via indirect interactions with the Shh pathway.

BACKGROUND: Gene-environment interactions are likely to underlie most human birth defects. The most common known environmental contributor to birth defects is prenatal alcohol exposure. Fetal alcohol spectrum disorders (FASD) describe the full range of defects that result from prenatal alcohol exposure. Gene-ethanol interactions underlie susceptibility to FASD, but we lack a mechanistic understanding of these interactions. Here, we leverage the genetic tractability of zebrafish to address this problem. RESULTS: We first show that vangl2, a member of the Wnt/planar cell polarity (Wnt/PCP) pathway that mediates convergent extension movements, strongly interacts with ethanol during late blastula and early gastrula stages. Embryos mutant or heterozygous for vangl2 are sensitized to ethanol-induced midfacial hypoplasia. We performed single-embryo RNA-seq during early embryonic stages to assess individual variation in the transcriptional response to ethanol and determine the mechanism of the vangl2-ethanol interaction. To identify the pathway(s) that are disrupted by ethanol, we used these global changes in gene expression to identify small molecules that mimic the effects of ethanol via the Library of Integrated Network-based Cellular Signatures (LINCS L1000) dataset. Surprisingly, this dataset predicted that the Sonic Hedgehog (Shh) pathway inhibitor, cyclopamine, would mimic the effects of ethanol, despite ethanol not altering the expression levels of direct targets of Shh signaling. Indeed, we found that ethanol and cyclopamine strongly, but indirectly, interact to disrupt midfacial development. Ethanol also interacts with another Wnt/PCP pathway member, gpc4, and a chemical inhibitor of the Wnt/PCP pathway, blebbistatin, phenocopies the effect of ethanol. By characterizing membrane protrusions, we demonstrate that ethanol synergistically interacts with the loss of vangl2 to disrupt cell polarity required for convergent extension movements. CONCLUSIONS: Our results show that the midfacial defects in ethanol-exposed vangl2 mutants are likely due to an indirect interaction between ethanol and the Shh pathway. Vangl2 functions as part of a signaling pathway that regulates coordinated cell movements during midfacial development. Ethanol exposure alters the position of a critical source of Shh signaling that separates the developing eye field into bilateral eyes, allowing the expansion of the midface. Collectively, our results shed light on the mechanism by which the most common teratogen can disrupt development.

Surgical Release of the Pectoralis Minor Tendon for Scapular Dyskinesia and Shoulder Pain.

BACKGROUND: Pectoralis minor (PM) tightness has been linked to pain and dysfunction of the shoulder joint secondary to anterior tilt and internal rotation of the scapula, thus causing secondary impingement of the subacromial space. PURPOSE: To describe outcomes pertaining to nonoperative and operative treatment via surgical release of the PM tendon for pathologic PM tightness in an active population. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Over a 3-year period, a total of 46 patients were enrolled (mean age, 25.5 years; range, 18-33 years). Inclusion criteria consisted of symptomatic shoulder pain, limited range of overhead motion, inability to participate in overhead lifting activities, and examination findings consistent with scapular dysfunction secondary to a tight PM with tenderness to palpation of the PM tendon. All patients underwent a lengthy physical therapy and stretching program (mean, 11.4 months; range, 3-23 months), which was followed by serial examinations for resolution of symptoms and scapular tilt. Of the 46 patients, 6 (13%) were unable to adequately stretch the PM and underwent isolated mini-open PM release. Outcomes were assessed with scapula protraction measurements and pain scales as well as American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), and visual analog scale (VAS) scores. RESULTS: Forty of the 46 patients (87%) resolved the tight PM and scapular-mediated symptoms with a dedicated therapy program (pre- and posttreatment mean outcome scores: 58 and 91 [ASES], 50 and 90 [SANE], 4.9 and 0.8 [VAS]; P < .01 for all), but 6 patients were considered nonresponders (mean score, 48 [ASES], 40 [SANE], 5.9 [VAS]) and elected to have surgical PM release, with improved scores in all domains (mean score, 89 [ASES], 90.4 [SANE], 0.9 [VAS]; P < .01) at final follow-up of 26 months (range, 25-30 months). Additionally, protraction of the scapula improved from 1.2 to 0.3 cm in a mean midline measurement from the chest wall preoperatively to postoperatively ( P < .01), similar to results in nonoperative responders. No surgical complications were reported, and all patients returned to full activities. CONCLUSION: In most patients, PM tightness can be successfully treated with a nonoperative focused PM stretching program. However, in refractory and pathologically tight PM cases, this series demonstrates predictable return to function with notable improvement in shoulder symptoms after surgical release of the PM. Additional research is necessary to evaluate the long-term efficacy of isolated PM treatment.