Editorial Commentary: Dynamic Anterior Stabilization via Biceps Tenodesis to the Glenoid Is an Option for Anterior Shoulder Instability With Subcritical Glenoid Bone Loss.

A nuanced approach to treatment of anterior shoulder instability is encouraged, particularly in patients with subcritical glenoid bone loss. In patients with bone loss, recurrent instability after isolated arthroscopic Bankart repair has dampened enthusiasm for this procedure. Adjunctive treatment with remplissage or dynamic anterior stabilization via biceps tenodesis to the glenoid is an alternative to bone transfer procedures, which are effective but have higher complication rates. Dynamic anterior stabilization or tenodesis of the long head of the biceps to the 3-o'clock position on the glenoid through a subscapularis split is biomechanically superior to isolated Bankart repair for reducing anterior translation, even in the setting of minor glenoid bone loss due to a sling effect similar to that produced by the Latarjet procedure. A disadvantage is placement of a large implant into the small space of the anterior glenoid and creation of a soft-tissue defect in the capsule.

Patient-Reported Outcome Surveys for Femoroacetabular Impingement Syndrome Demonstrate Strong Correlations, High Minimum Clinically Important Difference Agreement and Large Ceiling Effects.

PURPOSE: To determine the correlation between different patient-reported outcome (PRO) measurements used to assess outcomes after arthroscopic treatment of femoroacetabular impingement syndrome (FAIS) in a single cohort of patients. METHODS: Patients undergoing primary hip arthroscopy for FAIS (without dysplasia, arthritis, or joint hypermobility) were retrospectively analyzed from a prospectively collected cohort. PROs collected before surgery and at 2-year follow-up included the Visual Analog Scale (VAS) for pain, modified Harris Hip Score (mHHS), Hip Disability and Osteoarthritis Outcome Scores (HOOS) with subscales for symptoms, pain, activities of daily living (ADL), sport, and quality of life (QoL), and the physical and mental components of the Short Form-12 (SF-12 PCS and SF-12 MCS). RESULTS: Three hundred patients with 2 years' follow-up (mean age 35.1 ± 11.3, BMI 24.7 ± 3.8, 52.7% female, median Tönnis grade 1) were identified. All patients underwent femoroplasty and labral repair. There was a strong correlation among nearly all the PRO surveys at 2-year follow-up, with the highest correlations identified between mHHS and HOOS-Pain (r = .86, P < .001) and mHHS and HOOS-ADL (r = .85, P < .001). Preoperative scores and the change from preoperative to postoperative scores demonstrated an overall moderate correlation between surveys. There was a consistently weak correlation between the SF-12 MCS and all other PROs. There were strong agreements (67%-77%) in the patients achieving minimal clinically important differences (MCID) for each PRO survey. All surveys except the SF-12 demonstrated a ceiling effect after surgery, with 13% to 43% of patients achieving the maximum score. CONCLUSIONS: PRO surveys used for FAIS demonstrate strong correlations, especially in the evaluation of patients during the postoperative period. MCID for VAS, mHHS, and HOOS demonstrate strong agreement, whereas large ceiling effects were seen with the mHHS and HOOS. The results support a more efficient use of PRO scores while being able to accurately capture patient outcomes. LEVEL OF EVIDENCE: IV, retrospective case series.

To Improve Pain and Function, Platelet-Rich Plasma Injections May Be an Alternative to Surgery for Treating Lateral Epicondylitis: A Systematic Review.

PURPOSE: To determine whether platelet-rich plasma (PRP) injection for lateral epicondylitis offers patients comparable outcomes to lateral epicondylar surgery. METHODS: Embase, Cochrane Library, and MEDLINE databases were searched using the terms lateral epicondylitis, lateral elbow pain, tennis elbow, lateral epicondylalgia, and elbow tendinopathy individually and combined with the terms platelet-rich plasma injections and lateral epicondylar surgery. We compared pain relief, function between the 2 treatment options, and identified whether PRP injection reduced the incidence of lateral epicondylar surgery. Studies must have compared PRP injections with lateral epicondylar surgery for the treatment of lateral epicondylitis; be of Level I, II, or III evidence; and be written in the English language. RESULTS: Three studies (1 Level II and 2 Level III) met inclusion criteria. Two of the studies suggested that PRP injections offer similar relief as surgery in the short and mid-term, one study reported that PRP injections and surgery had similar outcomes in pain improvement and return to work, whereas 1 study reported that surgery may be a better long-term solution. CONCLUSIONS: In comparison with lateral epicondylar surgery, PRP injections offer similar improvements in pain and function for patients suffering from lateral epicondylitis, especially in the short- and mid-term in 2 of the 3 included investigations. Therefore, PRP injections are an appropriate alternative for the treatment of lateral epicondylitis. LEVEL OF EVIDENCE: Level III, Systematic Review of Level III or greater evidence.

The Relationship Between Energy Drink Consumption, Caffeine Content, and Nutritional Knowledge Among College Students.

We sought to determine which demographic characteristics influence energy drink consumption habits and to examine whether caffeine content and knowledge of human nutrition affect college students' decisions to consume these beverages. We used an online survey to ask 265 college students, who did not participate in a varsity sport, to complete a survey consisting of demographic questions, the General Knowledge Questionnaire for adults, and questions about energy drink consumption habits. We found, overall, that 23.1% of our sample used energy drinks. When compared to non-consumers (76.9%), users had a significantly lower GPA, were older, and preferred drinks with a higher caffeine content. Users reported that they consumed these drinks because they wanted to feel more alert and they enjoyed the taste, even though they reported adverse effects such as trouble sleeping, shaking and tremors, and stomachaches. Knowledge of human nutrition did not affect users' choice to consume these drinks. Although the majority of college students do not consume energy drinks, room for improvement remains to curb the use of these caffeinated beverages amongst college students.

Comparative genomics uncovers the prolific and distinctive metabolic potential of the cyanobacterial genus Moorea.

Cyanobacteria are major sources of oxygen, nitrogen, and carbon in nature. In addition to the importance of their primary metabolism, some cyanobacteria are prolific producers of unique and bioactive secondary metabolites. Chemical investigations of the cyanobacterial genus Moorea have resulted in the isolation of over 190 compounds in the last two decades. However, preliminary genomic analysis has suggested that genome-guided approaches can enable the discovery of novel compounds from even well-studied Moorea strains, highlighting the importance of obtaining complete genomes. We report a complete genome of a filamentous tropical marine cyanobacterium, Moorea producens PAL, which reveals that about one-fifth of its genome is devoted to production of secondary metabolites, an impressive four times the cyanobacterial average. Moreover, possession of the complete PAL genome has allowed improvement to the assembly of three other Moorea draft genomes. Comparative genomics revealed that they are remarkably similar to one another, despite their differences in geography, morphology, and secondary metabolite profiles. Gene cluster networking highlights that this genus is distinctive among cyanobacteria, not only in the number of secondary metabolite pathways but also in the content of many pathways, which are potentially distinct from all other bacterial gene clusters to date. These findings portend that future genome-guided secondary metabolite discovery and isolation efforts should be highly productive.

Research Pearls: Checklists and Flowcharts to Improve Research Quality.

To instill quality in published clinical research, reporting guidelines, consisting of checklists and flowcharts, were developed to protect against reporting poorly designed research, and researchers should be aware of the available instruments and their appropriate use. With the popularity of synthetic reviews, meta-analyses, and systematic reviews, there is a greater need to assess risk of bias and study quality. This review highlights the most frequently used guidelines and checklists, risk-of-bias scales, and quality rating scales that can assist researchers with improving their research and its eventual publication.

Periportal Capsulotomy: Technique and Outcomes for a Limited Capsulotomy During Hip Arthroscopy.

PURPOSE: To present the technique and outcomes of a limited periportal capsulotomy without capsular closure for arthroscopic treatment of femoroacetabular impingement (FAI). METHODS: Retrospective review of a prospectively collected database of patients undergoing primary hip arthroscopy for symptomatic FAI was performed to analyze patients who underwent periportal capsulotomy. Periportal capsulotomy was performed through dilation of the midanterior and anterolateral portals without completion of a full interportal capsulotomy, preserving the iliofemoral ligament. Arthroscopic labral treatment and osteochondroplasty were completed as indicated without necessitating capsular closure. Patient demographics, surgical details, and complications were recorded. Pre- and postoperatively, patients completed the modified Harris Hip Score, Hip Disability and Osteoarthritis Outcome Score (HOOS), 12-item Short-Form survey, and visual analog scale. Postoperative outcome data was analyzed at 1- and 2-year follow-up. RESULTS: One hundred and forty-two patients treated with the periportal capsulotomy technique were included (mean age, 35.5 ± 11.7; body mass index, 25.4 ± 4.1; 50.7% men). There were no major postoperative complications including hip instability or reoperation. Significant improvements in mean patient-reported outcomes from preoperative scores were seen at the 1- and 2-year follow-ups (modified Harris Hip Score, 18.4 ± 19.1, 21.1 ±17.7, HOOS symptoms, 20.1 ± 21.2, 22.8 ± 23.5, HOOS pain, 23.4 ± 21.2, 27.6 ± 19.3, HOOS activities of daily life, 21.2 ± 20.8, 24.3 ± 21.6, HOOS sport, 32.5 ± 27.0, 36.5 ± 26.9, HOOS quality of life, 37.9 ± 26.7, 46.0 ± 22.8, and 12-item Short-Form survey physical component score, 16.4 ± 15.3, 20.8 ±13.2, respectively). Only the HOOS quality of life demonstrated further improvement from 1- to 2 years postoperatively (P = .043). CONCLUSIONS: Periportal capsulotomy provides safe and sufficient access to the hip joint for arthroscopic treatment of FAI without necessitating capsular closure. Using this technique, patients showed significant clinical improvement and no postoperative instability at 1 and 2 years after surgery. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Patient-Reported Outcomes After Isolated and Combined Arthroscopic Subscapularis Tendon Repairs.

PURPOSE: To analyze minimum 2-year postoperative patient-reported outcomes of a large group of patients after arthroscopic subscapularis (SSc) repair with respect to surgical findings and concurrent procedures. METHODS: Patients who underwent arthroscopic SSc repair from January 2010 to April 2016 completed the Patient-Reported Outcomes Measurement Information System for Upper Extremity (PROMIS-UE) test and postoperative visual analog scale pain score. Medical records were reviewed for the preoperative visual analog scale pain score and surgical findings. SSc tears were considered partial or complete. Concomitant pathology and treatment of the supraspinatus (SS), infraspinatus (IS), and biceps tendon were recorded. We compared preoperative variables and outcomes between isolated partial SSc repair, partial SSc with SS and/or IS repair, isolated complete SSc repair, and complete SSc with SS and/or IS repair. RESULTS: One hundred forty-five shoulders were included with an average age of 62.0 ± 9.8 years and average follow-up period of 52.2 ± 19.5 months. A significant reduction in the pain score occurred, from 4.8 (95% confidence interval [CI], 4.4-5.2) to 0.9 (95% CI, 0.6-1.1) (P < .001), with a mean postoperative PROMIS-UE score of 50.7 (95% CI, 49.5-52.0). Most SSc tears were partial with SS and/or IS repair (44.1%). Isolated partial SSc tears (29.9%), complete SSc tears with SS and/or IS repair (20.1%), and isolated complete SSc tears (5.9%) were less common. A significant difference in the mean postoperative PROMIS-UE score was not found between groups (P = .609). Biceps tendon pathology was significantly more common in complete SSc tears than partial SSc tears (P < .001), but there was no difference in the rate of biceps intervention (P = .110) or the PROMIS-UE score based on biceps intervention (P = .471). CONCLUSIONS: We observed significant improvements in pain and patient-reported outcomes in line with population means for a large group of patients after SSc tendon repair. Importantly, outcomes were similar despite the size of SSc tear or concurrent SS and/or IS repairs. Biceps pathology was common, and neither its presence nor its treatment influenced postoperative patient outcomes. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Navigating the Research in Rotator Cuff Disease: An Evidence-Based Approach to Improved Patient Outcomes.

Rotator cuff tears are prevalent injuries, yet their management and identifying patients who will benefit from surgical intervention are controversial topics. Population studies demonstrate high rates of asymptomatic tears that, with time, show a general progression of the pathologic state. However, not all tears are or will become symptomatic or require surgical intervention. Surgeons should be aware of the natural history of rotator cuff tears and be able to identify injuries at risk of progression or causing symptoms, be able to determine the cellular level of tear characteristics and healing, understand current management strategies and outcomes, and be familiar with future directions for therapies and research.

The Quality and Accuracy of Online Resources for Total and Reverse Shoulder Replacement.

Recent literature suggests that many online patient resources are poor in quality and lack important clinical information. The purpose of this study was to investigate the value of online resources available to patients considering shoulder arthroplasty. A total of 84 websites were discovered with the terms "total shoulder replacement" (TSR) and "reverse shoulder replacement" (RSR), they were reviewed and graded for quality and accuracy. Overall quality scores were low for TSR and RSR websites, 22.8/45 (95% confidence interval (CI): 19.9-25.6) and 24.2/45 (95% CI: 21.6-26.9), respectively. The authorship of a website significantly influenced the quality for both TSR (p = 0.013) and RSR (p = 0.048). When comparing search rank to quality scores, websites that appeared earlier demonstrated significantly higher quality scores, TSR (p = 0.017) and RSR (p = 0.018). Overall, most websites were accurate but provided incomplete information. Websites authored by professional societies have higher quality scores than websites authored by medical providers or commercial entities. (Journal of Surgical Orthopaedic Advances 28(4):290-294, 2019).

A Maldiisotopic Approach to Discover Natural Products: Cryptomaldamide, a Hybrid Tripeptide from the Marine Cyanobacterium Moorea producens.

Genome sequencing of microorganisms has revealed a greatly increased capacity for natural products biosynthesis than was previously recognized from compound isolation efforts alone. Hence, new methods are needed for the discovery and description of this hidden secondary metabolite potential. Here we show that provision of heavy nitrogen 15N-nitrate to marine cyanobacterial cultures followed by single-filament MALDI analysis over a period of days was highly effective in identifying a new natural product with an exceptionally high nitrogen content. The compound, named cryptomaldamide, was subsequently isolated using MS to guide the purification process, and its structure determined by 2D NMR and other spectroscopic and chromatographic methods. Bioinformatic analysis of the draft genome sequence identified a 28.7 kB gene cluster that putatively encodes for cryptomaldamide biosynthesis. Notably, an amidinotransferase is proposed to initiate the biosynthetic process by transferring an amidino group from arginine to serine to produce the first residue to be incorporated by the hybrid NRPS-PKS pathway. The maldiisotopic approach presented here is thus demonstrated to provide an orthogonal method by which to discover novel chemical diversity from Nature.

The Phormidolide Biosynthetic Gene Cluster: A trans-AT PKS Pathway Encoding a Toxic Macrocyclic Polyketide.

Phormidolide is a polyketide produced by a cultured filamentous marine cyanobacterium and incorporates a 16-membered macrolactone. Its complex structure is recognizably derived from a polyketide synthase pathway, but possesses unique and intriguing structural features that prompted interest in investigating its biosynthetic origin. Stable isotope incorporation experiments confirmed the polyketide nature of this compound. We further characterized the phormidolide gene cluster (phm) through genome sequencing followed by bioinformatic analysis. Two discrete trans-type acyltransferase (trans-AT) ORFs along with KS-AT adaptor regions (ATd) within the polyketide synthase (PKS) megasynthases, suggest that the phormidolide gene cluster is a trans-AT PKS. Insights gained from analysis of the mode of acetate incorporation and ensuing keto reduction prompted our reevaluation of the stereochemistry of phormidolide hydroxy groups located along the linear polyketide chain.

Combining Mass Spectrometric Metabolic Profiling with Genomic Analysis: A Powerful Approach for Discovering Natural Products from Cyanobacteria.

An innovative approach was developed for the discovery of new natural products by combining mass spectrometric metabolic profiling with genomic analysis and resulted in the discovery of the columbamides, a new class of di- and trichlorinated acyl amides with cannabinomimetic activity. Three species of cultured marine cyanobacteria, Moorea producens 3L, Moorea producens JHB, and Moorea bouillonii PNG, were subjected to genome sequencing and analysis for their recognizable biosynthetic pathways, and this information was then compared with their respective metabolomes as detected by MS profiling. By genome analysis, a presumed regulatory domain was identified upstream of several previously described biosynthetic gene clusters in two of these cyanobacteria, M. producens 3L and M. producens JHB. A similar regulatory domain was identified in the M. bouillonii PNG genome, and a corresponding downstream biosynthetic gene cluster was located and carefully analyzed. Subsequently, MS-based molecular networking identified a series of candidate products, and these were isolated and their structures rigorously established. On the basis of their distinctive acyl amide structure, the most prevalent metabolite was evaluated for cannabinomimetic properties and found to be moderate affinity ligands for CB1.

Genomic insights into the physiology and ecology of the marine filamentous cyanobacterium Lyngbya majuscula.

Filamentous cyanobacteria of the genus Lyngbya are important contributors to coral reef ecosystems, occasionally forming dominant cover and impacting the health of many other co-occurring organisms. Moreover, they are extraordinarily rich sources of bioactive secondary metabolites, with 35% of all reported cyanobacterial natural products deriving from this single pantropical genus. However, the true natural product potential and life strategies of Lyngbya strains are poorly understood because of phylogenetic ambiguity, lack of genomic information, and their close associations with heterotrophic bacteria and other cyanobacteria. To gauge the natural product potential of Lyngbya and gain insights into potential microbial interactions, we sequenced the genome of Lyngbya majuscula 3L, a Caribbean strain that produces the tubulin polymerization inhibitor curacin A and the molluscicide barbamide, using a combination of Sanger and 454 sequencing approaches. Whereas ∼ 293,000 nucleotides of the draft genome are putatively dedicated to secondary metabolism, this is far too few to encode a large suite of Lyngbya metabolites, suggesting Lyngbya metabolites are strain specific and may be useful in species delineation. Our analysis revealed a complex gene regulatory network, including a large number of sigma factors and other regulatory proteins, indicating an enhanced ability for environmental adaptation or microbial associations. Although Lyngbya species are reported to fix nitrogen, nitrogenase genes were not found in the genome or by PCR of genomic DNA. Subsequent growth experiments confirmed that L. majuscula 3L is unable to fix atmospheric nitrogen. These unanticipated life history characteristics challenge current views of the genus Lyngbya.

Hippocampal representations of alternative possibilities are flexibly generated to meet cognitive demands.

The cognitive ability to go beyond the present to consider alternative possibilities, including potential futures and counterfactual pasts, can support adaptive decision making. Complex and changing real-world environments, however, have many possible alternatives. Whether and how the brain can select among them to represent alternatives that meet current cognitive needs remains unknown. We therefore examined neural representations of alternative spatial locations in the rat hippocampus during navigation in a complex patch foraging environment with changing reward probabilities. We found representations of multiple alternatives along paths ahead and behind the animal, including in distant alternative patches. Critically, these representations were modulated in distinct patterns across successive trials: alternative paths were represented proportionate to their evolving relative value and predicted subsequent decisions, whereas distant alternatives were prevalent during value updating. These results demonstrate that the brain modulates the generation of alternative possibilities in patterns that meet changing cognitive needs for adaptive behavior.

Spyglass: a framework for reproducible and shareable neuroscience research.

Scientific progress depends on reliable and reproducible results. Progress can also be accelerated when data are shared and re-analyzed to address new questions. Current approaches to storing and analyzing neural data typically involve bespoke formats and software that make replication, as well as the subsequent reuse of data, difficult if not impossible. To address these challenges, we created Spyglass, an open-source software framework that enables reproducible analyses and sharing of data and both intermediate and final results within and across labs. Spyglass uses the Neurodata Without Borders (NWB) standard and includes pipelines for several core analyses in neuroscience, including spectral filtering, spike sorting, pose tracking, and neural decoding. It can be easily extended to apply both existing and newly developed pipelines to datasets from multiple sources. We demonstrate these features in the context of a cross-laboratory replication by applying advanced state space decoding algorithms to publicly available data. New users can try out Spyglass on a Jupyter Hub hosted by HHMI and 2i2c: https://spyglass.hhmi.2i2c.cloud/.

Obesity and Reverse Total Shoulder Arthroplasty.

PURPOSE OF REVIEW: Rates of obesity and reverse total shoulder arthroplasty (rTSA) in the USA have both escalated with time. Obese patients experience arthritis at higher rates than normal weight patients; therefore, these numbers go hand in hand. Obesity has been correlated with health comorbidities such as anxiety, cardiovascular disease, diabetes, and metabolic syndrome as well as poorer outcomes and higher complication rates following lower extremity arthroplasty. The current review investigates these comorbidities as they relate to obese patients undergoing rTSA. RECENT FINDINGS: Functional outcomes are similar to normal weight counterparts. Although longer operative times and a large soft tissue envelope would intuitively predispose these patients to higher risk for infection or other complications, this has not been reliably demonstrated. Technical considerations and awareness of potential risks in the obese patient demographic may aid the surgeon in preoperative planning and counseling of their patient. Obese patients undergoing rTSA have been shown to have higher risks specifically for infection, revision, and medical complications; however, this has not been consistently demonstrated in the single surgeon series where, more often, no difference in these metrics has been found. Outcomes measures and satisfaction are reliably improved, even when considering superobese patients, and majority of studies find their improvements and absolute values to be in line with their normal weight counterparts. Thus, rTSA does not seem to carry the same level of adverse risk associated with lower joint arthroplasty but potential for higher risk still bears consideration when counseling obese patients. Attention to factors that may negatively affect prosthesis positioning may optimize retention rates and limit early failure.

Transcriptomic response of the red tide dinoflagellate, Karenia brevis, to nitrogen and phosphorus depletion and addition.

BACKGROUND: The role of coastal nutrient sources in the persistence of Karenia brevis red tides in coastal waters of Florida is a contentious issue that warrants investigation into the regulation of nutrient responses in this dinoflagellate. In other phytoplankton studied, nutrient status is reflected by the expression levels of N- and P-responsive gene transcripts. In dinoflagellates, however, many processes are regulated post-transcriptionally. All nuclear encoded gene transcripts studied to date possess a 5' trans-spliced leader (SL) sequence suggestive, based on the trypanosome model, of post-transcriptional regulation. The current study therefore sought to determine if the transcriptome of K. brevis is responsive to nitrogen and phosphorus and is informative of nutrient status. RESULTS: Microarray analysis of N-depleted K. brevis cultures revealed an increase in the expression of transcripts involved in N-assimilation (nitrate and ammonium transporters, glutamine synthetases) relative to nutrient replete cells. In contrast, a transcriptional signal of P-starvation was not apparent despite evidence of P-starvation based on their rapid growth response to P-addition. To study transcriptome responses to nutrient addition, the limiting nutrient was added to depleted cells and changes in global gene expression were assessed over the first 48 hours following nutrient addition. Both N- and P-addition resulted in significant changes in approximately 4% of genes on the microarray, using a significance cutoff of 1.7-fold and p ≤ 10-4. By far, the earliest responding genes were dominated in both nutrient treatments by pentatricopeptide repeat (PPR) proteins, which increased in expression up to 3-fold by 1 h following nutrient addition. PPR proteins are nuclear encoded proteins involved in chloroplast and mitochondria RNA processing. Correspondingly, other functions enriched in response to both nutrients were photosystem and ribosomal genes. CONCLUSIONS: Microarray analysis provided transcriptomic evidence for N- but not P-limitation in K. brevis. Transcriptomic responses to the addition of either N or P suggest a concerted program leading to the reactivation of chloroplast functions. Even the earliest responding PPR protein transcripts possess a 5' SL sequence that suggests post-transcriptional control. Given the current state of knowledge of dinoflagellate gene regulation, it is currently unclear how these rapid changes in such transcript levels are achieved.

The unique mechanistic transformations involved in the biosynthesis of modular natural products from marine cyanobacteria.

Cyanobacteria are abundant producers of natural products well recognized for their bioactivity and utility in drug discovery and biotechnology applications. In the last decade, characterization of several modular gene clusters that code for the biosynthesis of these compounds has revealed a number of unusual enzymatic reactions. In this article, we review several mechanistic transformations identified in marine cyanobacterial biosynthetic pathways, with an emphasis on modular polyketide synthase(PKS)/non-ribosomal peptide synthetase (NRPS) gene clusters. In selected instances, we also make comparisons between cyanobacterial gene clusters derived from marine and freshwater strains. We then provide an overview of recent developments in cyanobacterial natural products biosynthesis made available through genome sequencing and new advances in bioinformatics and genetics.