Patient-Perceived Outcomes of Recovery After Trigger Digit Release.

PURPOSE: Trigger finger release (TFR) is one of the most commonly performed hand surgeries; nevertheless, the time until patients subjectively feel recovered has not been well documented. The limited literature on patient perceptions of recovery after any type of surgery has described that patients and surgeons may have differing views on the time until full recovery. Our primary study question was to determine how long it takes for patients to subjectively feel fully recovered after TFR. METHODS: In this prospective study, patients who underwent isolated TFR completed questionnaires before surgery and at multiple time points following surgery until they reported full recovery. Patients completed visual analog scale (VAS) pain scores and QuickDASH (Disabilities of the Arm, Shoulder, and Hand) and were asked if they felt fully recovered at 4 weeks, 6 weeks, and 3, 6, 9, and 12 months. RESULTS: The average time to self-reported full recovery was 6.2 months (SD 2.6), and the median time to self-reported full recovery was 6 months (IQR 4 months). At 12 months, four out of 50 patients (8%) did not feel fully recovered. QuickDASH and VAS pain scores improved significantly from preoperative assessment to final follow-up. All patients reported improvement in both VAS pain scores and QuickDASH scores greater than the minimal clinically important difference between 6 weeks and 3 months after surgery. Higher preoperative VAS and QuickDASH scores were associated with failure to fully recover by 12 months after surgery. CONCLUSIONS: The length of time after surgery until patients felt fully recovered after isolated TFR is longer than the senior authors' expectations. This suggests that patients and surgeons may consider distinctly different parameters when discussing recovery. Surgeons should be aware of this discrepancy when discussing recovery after surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Functional Characterization of the m6A-Dependent Translational Modulator PfYTH.2 in the Human Malaria Parasite.

Posttranscriptional regulation of gene expression is central to the development and replication of the malaria parasite, Plasmodium falciparum, within its human host. The timely coordination of RNA maturation, homeostasis, and protein synthesis relies on the recruitment of specific RNA-binding proteins to their cognate target mRNAs. One possible mediator of such mRNA-protein interactions is the N6-methylation of adenosines (m6A), a prevalent mRNA modification of parasite mRNA transcripts. Here, we used RNA protein pulldowns, RNA modification mass spectrometry, and quantitative proteomics to identify two P. falciparum YTH domain proteins (PfYTH.1 and PfYTH.2) as m6A-binding proteins during parasite blood-stage development. Interaction proteomics revealed that PfYTH.2 associates with the translation machinery, including multiple subunits of the eukaryotic initiation factor 3 (eIF3) and poly(A)-binding proteins. Furthermore, knock sideways of PfYTH.2 coupled with ribosome profiling showed that this m6A reader is essential for parasite survival and is a repressor of mRNA translation. Together, these data reveal an important missing link in the m6A-mediated mechanism controlling mRNA translation in a unicellular eukaryotic pathogen.IMPORTANCE Infection with the unicellular eukaryotic pathogen Plasmodium falciparum causes malaria, a mosquito-borne disease affecting more than 200 million and killing 400,000 people each year. Underlying the asexual replication within human red blood cells is a tight regulatory network of gene expression and protein synthesis. A widespread mechanism of posttranscriptional gene regulation is the chemical modification of adenosines (m6A), through which the fate of individual mRNA transcripts can be changed. Here, we report on the protein machinery that "reads" this modification and "translates" it into a functional outcome. We provide mechanistic insight into one m6A reader protein and show that it interacts with the translational machinery and acts as a repressor of mRNA translation. This m6A-mediated phenotype has not been described in other eukaryotes as yet, and the functional characterization of the m6A interactome will ultimately open new avenues to combat the disease.

Outcomes of Arthroscopic Surgical Treatment of Osteochondral Lesions of the Elbow in Pediatric and Adolescent Athletes.

BACKGROUND: Osteochondral injuries of the elbow are limiting and affect the ability of pediatric and adolescent athletes to participate in sports. PURPOSE: To report short- and midterm outcomes on athletes undergoing microfracture or fragment fixation of osteochondral elbow lesions and evaluate the effects thereof on sporting activity. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This was a retrospective study analyzing patients who underwent surgical treatment via microfracture or fragment fixation for osteochondral elbow lesions. Patients were treated at a single institution by a single surgeon between 2012 and 2019. Diagnosis was confirmed with magnetic resonance imaging, and patients were indicated for surgery after having persistent symptoms despite trialing rest, immobilization, and/or activity restriction for at least 3 months. Demographic data including sports of choice were collected preoperatively. Imaging and intraoperative findings were documented, and any complications were noted. Range of motion (ROM) was compared pre- to postoperatively. Return-to-sport evaluation included the ability to play the preoperative sport of choice. RESULTS: In total, 23 patients (25 elbows) were included with a mean follow-up of 23.5 months (range, 6-60.3 months) and a mean age of 13.8 years. Of 25 lesions, 20 (80%) were on the athlete's dominant side. There was significant improvement from pre- to postoperative ROM, including extension (mean ± SD, 6.4° ± 5.3° to 0.04° ± 0.2°; P < .00001), flexion (129.2° ± 10.6° to 138.6° ± 4.4°; P = .00013), and arc of ROM (122.6° ± 13.2° to 138.6° ± 4.4°; P < .00001). Mean lesion size was 81.9 ± 59.3 mm2 (range, 15-225 mm2). All elbows demonstrated radiographic healing postoperatively. Mean time to release to sport was 4.48 ± 1.38 months (range, 2.5-8 months). Six (26.1%) patients changed or stopped their preoperative sporting activity, including 2 of 4 gymnasts and 4 of 11 baseball players. CONCLUSION: Arthroscopic technique with lesion debridement and microfracture or fixation appears safe and results in radiographic healing; however, with these techniques, there remains a high rate of inability to return to sport in patients involved in higher-demand upper extremity activity, such as baseball and gymnastics. Further treatment strategies, including cartilage restoration procedures, may be warranted in this population.

Exploring the virulence gene interactome with CRISPR/dCas9 in the human malaria parasite.

Mutually exclusive expression of the var multigene family is key to immune evasion and pathogenesis in Plasmodium falciparum, but few factors have been shown to play a direct role. We adapted a CRISPR-based proteomics approach to identify novel factors associated with var genes in their natural chromatin context. Catalytically inactive Cas9 ("dCas9") was targeted to var gene regulatory elements, immunoprecipitated, and analyzed with mass spectrometry. Known and novel factors were enriched including structural proteins, DNA helicases, and chromatin remodelers. Functional characterization of PfISWI, an evolutionarily divergent putative chromatin remodeler enriched at the var gene promoter, revealed a role in transcriptional activation. Proteomics of PfISWI identified several proteins enriched at the var gene promoter such as acetyl-CoA synthetase, a putative MORC protein, and an ApiAP2 transcription factor. These findings validate the CRISPR/dCas9 proteomics method and define a new var gene-associated chromatin complex. This study establishes a tool for targeted chromatin purification of unaltered genomic loci and identifies novel chromatin-associated factors potentially involved in transcriptional control and/or chromatin organization of virulence genes in the human malaria parasite.

Transcriptome-wide dynamics of extensive m6A mRNA methylation during Plasmodium falciparum blood-stage development.

Malaria pathogenesis results from the asexual replication of Plasmodium falciparum within human red blood cells, which relies on a precisely timed cascade of gene expression over a 48-h life cycle. Although substantial post-transcriptional regulation of this hardwired program has been observed, it remains unclear how these processes are mediated on a transcriptome-wide level. To this end, we identified mRNA modifications in the P. falciparum transcriptome and performed a comprehensive characterization of N6-methyladenosine (m6A) over the course of blood-stage development. Using mass spectrometry and m6A RNA sequencing, we demonstrate that m6A is highly developmentally regulated, exceeding m6A levels known in any other eukaryote. We characterize a distinct m6A writer complex and show that knockdown of the putative m6A methyltransferase, PfMT-A70, by CRISPR interference leads to increased levels of transcripts that normally contain m6A. In accordance, we find an inverse correlation between m6A methylation and mRNA stability or translational efficiency. We further identify two putative m6A-binding YTH proteins that are likely to be involved in the regulation of these processes across the parasite's life cycle. Our data demonstrate unique features of an extensive m6A mRNA methylation programme in malaria parasites and reveal its crucial role in dynamically fine-tuning the transcriptional cascade of a unicellular eukaryote.

Concurrent and Overlapping Surgery: Perspectives From Parents of Adolescents Undergoing Spinal Posterior Instrumented Fusion for Idiopathic Scoliosis.

STUDY DESIGN: Prospective cross-sectional survey. OBJECTIVE: To determine the perspectives of parents of patients undergoing posterior instrumented fusion for adolescent idiopathic scoliosis (AIS) regarding simultaneous surgery and trainee participation. SUMMARY OF BACKGROUND DATA: Simultaneous ("at the same time") surgery is under scrutiny by the public, government, payers, and the medical community. The objective of this study is to determine the perspectives of parents of patients undergoing posterior instrumented fusion for adolescent idiopathic scoliosis. Our goal is to inform the national conversation on this subject with real patient and family voices. METHODS: A survey was prospectively administered to 31 consecutive parents of patients undergoing posterior instrumented fusion for adolescent idiopathic scoliosis at a large academic medical center. "Overlapping" was defined as simultaneity during "noncritical" parts of an operation. "Concurrent" was defined as simultaneity that includes "critical" part(s) of an operation. Participants were asked to provide levels of agreement with overlapping and concurrent surgery and anesthesia, as well as with trainee involvement. RESULTS: On average, respondents "strongly agree" with the need to be informed about overlapping or concurrent surgery. They "disagree" with both overlapping and concurrent scheduling, and "disagree" with trainees operating without direct supervision, even for "noncritical" parts. Informing parents about the presence of a back-up surgeon or research demonstrating safety of simultaneous surgery did not make them agreeable to simultaneous scheduling. CONCLUSION: Parents have a strong desire to be informed of simultaneous spinal surgery and anesthesia as part of consent on behalf of their children. Their disagreement with simultaneous surgery, as well as with trainees operating without direct supervision, suggests discordance with current guidelines and practice and should inform the national conversation moving forward. LEVEL OF EVIDENCE: N/A.

Medial patellofemoral ligament repair restores stability in pediatric patients when compared to reconstruction.

BACKGROUND: Pediatric patellar instability has a high recurrence rate with non-operative care, and medial patellofemoral ligament (MPFL) reconstruction has known complications. MPFL repair offers an alternative method to restore patellar stability. This study's purpose was to assess the outcomes of MPFL repair in a pediatric cohort, and to compare these outcomes to a cohort of pediatric patients who underwent MPFL reconstruction. METHODS: One surgeon performed 16 MPFL repairs on pediatric patients for traumatic patellar instability, with an average follow-up of 1.5 years. Age, sex, skeletal maturity, trochlear dysplasia, additional procedures, final range of motion, and complications were recorded. A sub-cohort with >1 dislocation (10 patients) was compared to a historical group (22 patients) with >1 dislocation who underwent allograft MPFL reconstructions by the same surgeon. RESULTS: Ten out of 16 (63%) patients had >1 dislocation event at time of presentation. Thirteen out of 16 (81%) patients had trochlear dysplasia. There were no complications and no recurrent instability in the repair group at last follow-up. Patients in the reconstruction group were older than the repair group (15.6 years vs. 13.0 years, p < 0.05), had lower Caton-Deschamps ratio (1.2 vs. 1.4, p < 0.05), and had lower percentage of additional procedures (59% vs. 100%, p < 0.05). There were three complications in the reconstruction group: two patients with recurrent instability and one patient with patella fracture requiring revision surgery. CONCLUSIONS: MPFL repair in pediatric patients resulted in a low risk of recurrent instability with rates comparable or better than that of allograft reconstruction.

Minimally Invasive Spine Surgery: Analyzing Internet-based Education Material.

STUDY DESIGN: This is a cross-sectional study. OBJECTIVE: The purpose of this study is to evaluate the content of information available on the Internet regarding minimally invasive spine surgery (MISS). SUMMARY OF BACKGROUND DATA: Patients look to the Internet for quick and accessible information on orthopedic procedures to help guide their personal decision making process regarding the care they receive. However, the quality of internet-based orthopedic education material varies significantly with respect to accuracy and readability. MATERIALS AND METHODS: The top 50 results were generated from each of 3 search engines (Google, Yahoo!, and Bing) using the search term "minimally invasive spine surgery." Results were categorized by authorship type and evaluated for their description of key factors such as procedural benefits, risks, and techniques. Comparisons between search engines and between authorship types were done using the Freeman-Halton extension for the Fisher exact test. The content of websites certified by Health on the Net Foundation (HONcode) was compared with those not HONcode certified. RESULTS: Of the 150 websites and videos, only 26% were authored by a hospital or university, whereas 50% were by a private physician or clinic. Most resources presented some benefits of MISS (84%, 126/150), but only 17% presented risks of the procedure (26/150). Almost half of all resources described the technique of MISS, but only 27% had thorough descriptions that included visual representations while 26% failed to describe the procedure. Only 12 results were HONcode certified, and 10 (83%) of these were authored by a medical industry company. CONCLUSIONS: Internet-based resources on MISS provide inconsistent content and tend to emphasize benefits of MISS over risks.

Potential Sex Bias Exists in Orthopaedic Basic Science and Translational Research.

BACKGROUND: Potential sex bias has been shown in general surgery basic science and translational research, with unequal representation of male and female specimens. Because basic science research forms the foundation for clinical studies on which patient care is based, it is important that this research equally consider both sexes. The purpose of this study was to determine if potential sex bias exists in the basic science and translational orthopaedic literature. METHODS: A systematic review was conducted of all articles published in 2014 in The Journal of Bone & Joint Surgery, Clinical Orthopaedics and Related Research, The Bone & Joint Journal, and the Journal of Orthopaedic Research (JOR). All original research articles utilizing animals, cells, or cadavers were included. The data abstracted included study type, sex of specimen studied, and presence of sex-based reporting of data. A second review was performed of all basic science articles published in JOR in 1994, 2004, and 2014 to compare sex bias trends across 3 decades. Distributions of variables were compared using the Fisher exact test, with significance defined as p < 0.05. RESULTS: Of 1,693 articles reviewed, 250 (15%) were included: 122 animal-based studies (49%), 71 cell-based studies (28%), and 57 human cadaver-based studies (23%). Overall, authors in 88 studies (35%) did not report the sex of animals, cells, or cadavers used. Of 162 studies in which the authors did report sex, 69 (43%) utilized male only, 40 (25%) utilized female only, and 53 (33%) utilized both sexes. Of those studies that used both sexes, authors in only 7 studies (13%) reported sex-based results. A subanalysis of JOR articles across 3 decades revealed a significant increase in studies specifying sex (p = 0.01) from 2004 to 2014. CONCLUSIONS: Potential sex bias exists in orthopaedic surgery basic science and translational research, with an overrepresentation of male specimens. CLINICAL RELEVANCE: Inequality in sex representation must be addressed as basic science and translational research creates the foundation for subsequent clinical research, which ultimately informs clinical care.

Electronic Cigarettes in Mississippi: Issues Facing Healthcare Providers and Policy Makers.

BACKGROUND: Electronic cigarettes (e-cigarettes) are currently unregulated nicotine delivery products, and use is increasing among youth and young adults in the U.S. Little is known about use in Mississippi. DESIGN/METHODS: Surveys assessed e-cigarette use among Mississippi adolescents and adults. UMMC provided data on reported cases of e-cigarette poisonings. RESULTS: From 2010 to 2014, current e-cigarette use increased from 0.6% to 6.7% among middle school students, from 1.2% to 10.1% among high school students, and from 0.2% to 6.8% among adults. There were no reported cases of e-cigarette poisonings in 2010, 2011, or 2013. There was one case in 2012. Cases increased to 26 in 2014, and 17 cases were reported in 2015. CONCLUSION: E-cigarette use has increased substantially. E-cigarettes expose users and bystanders to harmful chemicals and cancer-causing compounds. Regulation of e-cigarettes at the local, state, and federal levels is needed to address the clear harms to non-smokers.

Weight management during and after pregnancy: A multi-disciplinary approach.

The Specialist Weight Management Service (SWMS) Maternity Pathway was launched in January 2012 as a result of growing public health issues surrounding obesity and the production of NICE Guidelines for weight management before, during and after pregnancy (PH27). Our unique NHS service is aimed at pregnant women with a BMI>35 and supports them with introducing healthy lifestyle changes during pregnancy and safely minimising weight gain in this period. We also actively encourage service users to re-engage with the integrated SWMS pathway for up to 18months post-partum. The majority of referrals are received directly from midwives, and women can also self-refer. Pregnant women who come to our service are seen in multi-disciplinary clinics by a Dietitian, Physiotherapist and Health-Improvement Midwife. The service-users can also access Occupational Therapists, Medical Consultants and Health Trainers if required. Our staff use a patient-centred behavior change approach, often adopting motivational interviewing techniques to help engage patients with implementing positive lifestyle changes. The pathway also helps expectant mothers and their wider families access other services including smoking cessation, breastfeeding networks and healthy-start services to name a few. Plans are in place to launch an outreach service to the more deprived areas of the Borough, where drop-in sessions will be held at accessible locations to improve engagement of pregnant women in these areas. We believe that this multi-disciplinary approach to weight management is unique, and early statistics indicate that the support we offer pregnant women during the ante and post natal period are a success in terms of key outcome measures.

Gender differences in mesenteric vasoconstrictor reactivity following chronic hypoxia.

Male rats demonstrate persistent endothelium-dependent attenuation of vasoconstrictor reactivity following chronic hypoxia (CH). Since estrogen may interfere with hypoxia-induced gene expression, we hypothesized that gender differences exist in this response to CH. However, in conscious, instrumented rats, we found that CH resulted in a similar persistent reduction of pressor/total peripheral resistance responses to phenylephrine (PE) in rats of both genders. In contrast, although previous studies show mesenteric vascular responses to PE are reduced in CH males, we found that mesenteric reactivity was maintained in CH females. Since normoxic females demonstrate greater nitric oxide (NO) production, we hypothesized that the failure of CH to further diminish mesenteric reactivity in females was due to the inhibition of NO-dependent vasodilation. To test this hypothesis, constrictor reactivity of mesenteric arteries from male and female rats was examined. NO synthase (NOS) inhibition augmented constrictor responses to PE in arteries from both normoxic and CH males and normoxic females. In contrast, NOS inhibition had no effect in CH female vessels. Endothelial NOS (eNOS) levels were not different in arteries from control and CH females. Endothelial [Ca2+]i was greater in arterioles from CH females. Thus, CH reduces NO-dependent mesenteric dilation in females; this effect is not due to altered eNOS levels or diminished endothelial [Ca2+]i.

Katanin regulates dynamics of microtubules and biogenesis of motile cilia.

The in vivo significance of microtubule severing and the mechanisms governing its spatial regulation are not well understood. In Tetrahymena, a cell type with elaborate microtubule arrays, we engineered null mutations in subunits of the microtubule-severing complex, katanin. We show that katanin activity is essential. The net effect of katanin on the polymer mass depends on the microtubule type and location. Although katanin reduces the polymer mass and destabilizes the internal network of microtubules, its activity increases the mass of ciliary microtubules. We also show that katanin reduces the levels of several types of post-translational modifications on tubulin of internal and cortical microtubules. Furthermore, katanin deficiencies phenocopy a mutation of beta-tubulin that prevents deposition of polymodifications (glutamylation and glycylation) on microtubules. We propose that katanin preferentially severs older, post-translationally modified segments of microtubules.

Detection and measurement of alternative splicing using splicing-sensitive microarrays.

Splicing and alternative splicing are major processes in the interpretation and expression of genetic information for metazoan organisms. The study of splicing is moving from focused attention on the regulatory mechanisms of a selected set of paradigmatic alternative splicing events to questions of global integration of splicing regulation with genome and cell function. For this reason, parallel methods for detecting and measuring alternative splicing are necessary. We have adapted the splicing-sensitive oligonucleotide microarrays used to estimate splicing efficiency in yeast to the study of alternative splicing in vertebrate cells and tissues. We use gene models incorporating knowledge about splicing to design oligonucleotides specific for discriminating alternatively spliced mRNAs from each other. Here we present the main strategies for design, application, and analysis of spotted oligonucleotide arrays for detection and measurement of alternative splicing. We demonstrate these strategies using a two-intron yeast gene that has been altered to produce different amounts of alternatively spliced RNAs, as well as by profiling alternative splicing in NCI 60 cancer cell lines.