Long-term organic carbon preservation enhanced by iron and manganese.

The balance between degradation and preservation of sedimentary organic carbon (OC) is important for global carbon and oxygen cycles1. The relative importance of different mechanisms and environmental conditions contributing to marine sedimentary OC preservation, however, remains unclear2-8. Simple organic molecules can be geopolymerized into recalcitrant forms by means of the Maillard reaction5, although reaction kinetics at marine sedimentary temperatures are thought to be slow9,10. More recent work in terrestrial systems suggests that the reaction can be catalysed by manganese minerals11-13, but the potential for the promotion of geopolymerized OC formation at marine sedimentary temperatures is uncertain. Here we present incubation experiments and find that iron and manganese ions and minerals abiotically catalyse the Maillard reaction by up to two orders of magnitude at temperatures relevant to continental margins where most preservation occurs4. Furthermore, the chemical signature of the reaction products closely resembles dissolved and total OC found in continental margin sediments globally. With the aid of a pore-water model14, we estimate that iron- and manganese-catalysed transformation of simple organic molecules into complex macromolecules might generate on the order of approximately 4.1 Tg C yr-1 for preservation in marine sediments. In the context of perhaps only about 63 Tg C yr-1 variation in sedimentary organic preservation over the past 300 million years6, we propose that variable iron and manganese inputs to the ocean could exert a substantial but hitherto unexplored impact on global OC preservation over geological time.

Principal role of fungi in soil carbon stabilization during early pedogenesis in the high Arctic.

Climate warming is causing widespread deglaciation and pioneer soil formation over glacial deposits. Melting glaciers expose rocky terrain and glacial till sediment that is relatively low in biomass, oligotrophic, and depleted in nutrients. Following initial colonization by microorganisms, glacial till sediments accumulate organic carbon and nutrients over time. However, the mechanisms driving soil nutrient stabilization during early pedogenesis after glacial retreat remain unclear. Here, we traced amino acid uptake by microorganisms in recently deglaciated high-Arctic soils and show that fungi play a critical role in the initial stabilization of the assimilated carbon. Pioneer basidiomycete yeasts were among the predominant taxa responsible for carbon assimilation, which were associated with overall high amino acid use efficiency and reduced respiration. In intermediate- and late-stage soils, lichenized ascomycete fungi were prevalent, but bacteria increasingly dominated amino acid assimilation, with substantially decreased fungal:bacterial amino acid assimilation ratios and increased respiration. Together, these findings demonstrate that fungi are important drivers of pedogenesis in high-Arctic ecosystems that are currently subject to widespread deglaciation from global warming.

Comparative secretome analysis of Striga and Cuscuta species identifies candidate virulence factors for two evolutionarily independent parasitic plant lineages.

BACKGROUND: Many parasitic plants of the genera Striga and Cuscuta inflict huge agricultural damage worldwide. To form and maintain a connection with a host plant, parasitic plants deploy virulence factors (VFs) that interact with host biology. They possess a secretome that represents the complement of proteins secreted from cells and like other plant parasites such as fungi, bacteria or nematodes, some secreted proteins represent VFs crucial to successful host colonisation. Understanding the genome-wide complement of putative secreted proteins from parasitic plants, and their expression during host invasion, will advance understanding of virulence mechanisms used by parasitic plants to suppress/evade host immune responses and to establish and maintain a parasite-host interaction. RESULTS: We conducted a comparative analysis of the secretomes of root (Striga spp.) and shoot (Cuscuta spp.) parasitic plants, to enable prediction of candidate VFs. Using orthogroup clustering and protein domain analyses we identified gene families/functional annotations common to both Striga and Cuscuta species that were not present in their closest non-parasitic relatives (e.g. strictosidine synthase like enzymes), or specific to either the Striga or Cuscuta secretomes. For example, Striga secretomes were strongly associated with 'PAR1' protein domains. These were rare in the Cuscuta secretomes but an abundance of 'GMC oxidoreductase' domains were found, that were not present in the Striga secretomes. We then conducted transcriptional profiling of genes encoding putatively secreted proteins for the most agriculturally damaging root parasitic weed of cereals, S. hermonthica. A significant portion of the Striga-specific secretome set was differentially expressed during parasitism, which we probed further to identify genes following a 'wave-like' expression pattern peaking in the early penetration stage of infection. We identified 39 genes encoding putative VFs with functions such as cell wall modification, immune suppression, protease, kinase, or peroxidase activities, that are excellent candidates for future functional studies. CONCLUSIONS: Our study represents a comprehensive secretome analysis among parasitic plants and revealed both similarities and differences in candidate VFs between Striga and Cuscuta species. This knowledge is crucial for the development of new management strategies and delaying the evolution of virulence in parasitic weeds.

Arctic plasmidome analysis reveals distinct relationships among associated antimicrobial resistance genes and virulence genes along anthropogenic gradients.

Polar regions are relatively isolated from human activity and thus could offer insight into anthropogenic and ecological drivers of the spread of antibiotic resistance. Plasmids are of particular interest in this context given the central role that they are thought to play in the dissemination of antibiotic resistance genes (ARGs). However, plasmidomes are challenging to profile in environmental samples. The objective of this study was to compare various aspects of the plasmidome associated with glacial ice and adjacent aquatic environments across the high Arctic archipelago of Svalbard, representing a gradient of anthropogenic inputs and specific treated and untreated wastewater outflows to the sea. We accessed plasmidomes by applying enrichment cultures, plasmid isolation and shotgun Illumina sequencing of environmental samples. We examined the abundance and diversity of ARGs and other stress-response genes that might be co/cross-selected or co-transported in these environments, including biocide resistance genes (BRGs), metal resistance genes (MRGs), virulence genes (VGs) and integrons. We found striking differences between glacial ice and aquatic environments in terms of the ARGs carried by plasmids. We found a strong correlation between MRGs and ARGs in plasmids in the wastewaters and fjords. Alternatively, in glacial ice, VGs and BRGs genes were dominant, suggesting that glacial ice may be a repository of pathogenic strains. Moreover, ARGs were not found within the cassettes of integrons carried by the plasmids, which is suggestive of unique adaptive features of the microbial communities to their extreme environment. This study provides insight into the role of plasmids in facilitating bacterial adaptation to Arctic ecosystems as well as in shaping corresponding resistomes. Increasing human activity, warming of Arctic regions and associated increases in the meltwater run-off from glaciers could contribute to the release and spread of plasmid-related genes from Svalbard to the broader pool of ARGs in the Arctic Ocean.

Three mutations repurpose a plant karrikin receptor to a strigolactone receptor.

Uncovering the basis of small-molecule hormone receptors' evolution is paramount to a complete understanding of how protein structure drives function. In plants, hormone receptors for strigolactones are well suited to evolutionary inquiries because closely related homologs have different ligand preferences. More importantly, because of facile plant transgenic systems, receptors can be swapped and quickly assessed functionally in vivo. Here, we show that only three mutations are required to turn the nonstrigolactone receptor, KAI2, into a receptor that recognizes the plant hormone strigolactone. This modified receptor still retains its native function to perceive KAI2 ligands. Our directed evolution studies indicate that only a few keystone mutations are required to increase receptor promiscuity of KAI2, which may have implications for strigolactone receptor evolution in parasitic plants.

Management of Patellar Tendinopathy.

Patellar tendinopathy is a common pathology typically seen in athletes involved in repetitive explosive jumping and running activities. Also known as jumpers' knee, it is commonly seen in high-level basketball players. Typically, athletes continue to play with symptoms, which can be aggravated and progress to partial patellar tendon tears. When partial patellar tendon tears occur, prolonged recovery and decreased performance is commonly seen. The pathology and treatment can be frustrating for both the athlete and medical provider. Patellar tendinopathy typically does not involve inflammation but rather microinjury to the tendon fibers, which leads to mucoid degeneration, necrosis, and loss of transitional fibrocartilage. When partial tendon tears do occur, the typical location is posteromedially adjacent to the patella. Treatment involves a stepwise approach starting with nonoperative means, including activity modification, nonsteroidal anti-inflammatories, and physical therapy focused on eccentrics. Extracorporeal shock wave treatments and injections with platelet-rich plasma or bone marrow aspirate concentrate should be considered, with evolving literature to support their use. Ultrasound percutaneous tendon scrapping with a needle supplemented with the aforementioned injections is an emerging treatment option that the authors have found to be helpful, although further studies are required. Surgical intervention is considered after failure of nonoperative treatments, and typically occurs in tears greater than 50% of the tendon thickness and in tendons with increased thickness (>8.8 mm). Open or arthroscopic debridement can be considered, with no studies showing superior outcomes with either technique; however, no high-quality comparison studies exist. The authors prefer an open technique where, much like a bone-patellar tendon-bone harvest, the unhealthy proximal tendon and bone are excised with then closure of the healthy tendon with absorbable sutures. Suture anchor repair may also be used when necessary. In a recent systematic review, surgical management of patellar tendinopathy has been shown to result in improved patient-reported outcomes with return to sport at high levels.1 Treatment for the difficult and sometimes frustrating pathology of patellar tendinopathy continues to evolve, with biologic and less-invasive ultrasound-based treatments showing promise, and surgical intervention providing reliable outcomes.

Granulomatosis With Polyangiitis (Wegener's) Nasal Reconstruction: Improved Outcomes With No Surgical Delay.

BACKGROUND: Granulomatosis with polyangiitis (Wegener's) causes progressive nasal collapse, nasal obstruction, and central face deformity. It is not known whether cartilaginous nasal reconstruction should be performed immediately or delayed (after disease 'burn-out'). OBJECTIVES: For Wegener's nasal collapse to: (1) Assess the functional and aesthetic outcomes following immediate versus delayed nasal reconstruction; (2) Measure the impact of psychosocial well-being (anxiety, depression, social isolation) in immediate versus delayed nasal reconstruction. METHODS: Wegener's patients were compared with either 1) immediate or 2) delayed nasal surgery (n = 61). Functional and aesthetic severity were compared with the validated Standard Cosmesis and Health Nasal Outcome Survey (SCHNOS) score (student's t-test). In addition, Patient-Reported Outcomes Measurement Information System (PROMIS) perioperative/1-year follow-up surveys were analyzed. RESULTS: At initial consultation, SCHNOS score severity types were similar for each group (Immediate vs Delayed): Mild (15% vs. 15%), Moderate (59% vs. 60%), and Severe (26% vs. 25%). Over a 30 ± 4 month wait, Delayed Surgery patients' conditions deteriorated with a shift from mild to more severe SCHNOS scores: Initial consultation vs. Prior to surgery (25 to 85). PROMIS scores at presentation were high compared to the general public; by the time of Delayed Surgery, patients significantly worsened: Anxiety (28 to 73), Depression (18 to 62), and Social Isolation (20 to 80). Although both immediate and delayed groups improved after surgery in functional and psychosocial scores, the immediate group was superior. CONCLUSIONS: Data showed superior functional/aesthetic scores, and superior psychosocial indicators with immediate cartilaginous nasal reconstruction compared to waiting until disease 'burn-out'.

Ethical Issues Surrounding Facial Feminization Surgery: Five Major Considerations.

Facial feminization surgery (FFS) is a form of gender-affirming care for the transgender population that is currently a highly debated topic both inside and outside of the medical community. Currently, a paucity of information is available in plastic surgery literature on ethical issues surrounding FFS. In this paper, we discuss 5 major ethical considerations for plastic surgeons with regard to FFS: (1) how society's changing view of gender has impacted the importance of FFS; (2) whether FFS is medically necessary and should be covered by insurance; (3) to what extent resources should be invested in removing barriers to access FFS; (4) how patient selection criteria should address the irreversibility of the procedure and age of consent; and (5) how femininity and beauty standards contribute to each other and whether they can be disentangled. This paper aims to analyze the arguments made for and against each of these 5 nuanced issues and to expand these debates from the theoretical to the practical by suggesting approaches for reconciliation.

Redefining a discovery: Charles Bell, the respiratory nervous system and the birth of the emotions.

Charles Bell was famous for the discovery of the separate motor and sensory roots of the spinal and facial nerves, although in recent years his right to priority has been challenged by historians and scientists. But Charles Bell did discover something even if has not been accorded the status of a scientific fact. Between 1821 and 1823 he unveiled the 'respiratory nervous system', a distinct system of nerves that acted as the 'organ of the passions', which he then elaborated upon in his 1824 Essays on the Anatomy and Philosophy of Expression. As Bell and his allies attempted to claim priority in the spinal and facial nerves, the respiratory nerves were pushed to the background, subordinated to the motor and sensory nerves. This essay, therefore, redefines Charles Bell's major discovery as the 'respiratory nerves', providing a detailed description of their anatomy and physiology and the way in which they underwrote Bell's theory of the emotions. It also demonstrates how his aesthetics were intertwined with his research programme. It then connects the respiratory nerves to Thomas Dixon's assertion that Bell was one of the founders of the modern psychological category of the emotions, providing a deeper and more nuanced genealogy of the emotions, including the impact that Bell had upon William James's seminal article 'What is an Emotion?'

Severity of Illness Scores and Biomarkers for Prognosis of Patients with Coronavirus Disease 2019.

The spectrum of disease severity and the insidiousness of clinical presentation make it difficult to recognize patients with coronavirus disease 2019 (COVID-19) at higher risk of worse outcomes or death when they are seen in the early phases of the disease. There are now well-established risk factors for worse outcomes in patients with COVID-19. These should be factored in when assessing the prognosis of these patients. However, a more precise prognostic assessment in an individual patient may warrant the use of predictive tools. In this manuscript, we conduct a literature review on the severity of illness scores and biomarkers for the prognosis of patients with COVID-19. Several COVID-19-specific scores have been developed since the onset of the pandemic. Some of them are promising and can be integrated into the assessment of these patients. We also found that the well-known pneumonia severity index (PSI) and CURB-65 (confusion, uremia, respiratory rate, BP, age ≥ 65 years) are good predictors of mortality in hospitalized patients with COVID-19. While neither the PSI nor the CURB-65 should be used for the triage of outpatient versus inpatient treatment, they can be integrated by a clinician into the assessment of disease severity and can be used in epidemiological studies to determine the severity of illness in patient populations. Biomarkers also provide valuable prognostic information and, importantly, may depict the main physiological derangements in severe disease. We, however, do not advocate the isolated use of severity of illness scores or biomarkers for decision-making in an individual patient. Instead, we suggest the use of these tools on a case-by-case basis with the goal of enhancing clinician judgment.

Inferiorly Directed Posterior Cranial Vault Distraction for Treatment of Chiari Malformations.

OBJECTIVE: The authors present a case series of patients with Chiari I malformations treated with distraction osteogenesis of the posterior cranial vault, utilizing a vertical distraction vector for appropriate cranial vault expansion while mitigating the risks of scaphocephaly and cerebellar ptosis. PATIENTS AND METHODS: Patients with syndromic and nonsyndromic Chiari I malformations treated with vertical-vector distraction osteogenesis of the posterior cranial vault were identified from 2008 to 2014. Demographics, preoperative and postoperative clinical symptoms, and perioperative details were assessed. Long-term esthetic outcomes, complications, and symptomatic improvement were evaluated in conjunction with neurosurgery. RESULTS: Nine patients were identified. Five had known syndromes, 2 likely had unidentified syndromes, and 2 were nonsyndromic. Seven had prior Chiari-related surgeries. Most presented with hydrocephalus, motor symptoms, and developmental delay. Operatively, 2 to 3 internal distraction fixators were applied such that the vector of distraction was along a cephalad-caudad axis. Devices were activated on postoperative day 5 and distracted 1 mm per day. Three postoperative complications were found within the first 3 months which included a dislodged distraction arm, a device extrusion, and a local cellulitis. No complications affected the clinical outcome. Radiographic follow-up showed good bone formation, decompression of the posterior fossa, improved cerebrospinal fluid flow, and no cerebellar ptosis. Neurological surveillance showed improvement in intracranial pressure, hydrocephalus, motor symptoms, and behavioral problems. CONCLUSION: The authors have presented 9 patients with Chiari I malformations treated with distraction osteogenesis, along with a novel technique to safely and effectively expand the posterior fossa while minimizing the risk of cerebellar ptosis. LEVEL OF EVIDENCE: Level II (prognostic/risk studies).

Facial Feminization Surgery: Anatomical Differences, Preoperative Planning, Techniques, and Ethical Considerations.

Facial Feminization Surgery (FFS) is a transformative surgical approach aimed at aligning the facial features of transgender women with their gender identity. Through a systematic analysis, this paper explores the clinical differences between male and female facial skeletons along with the craniofacial techniques employed in FFS for each region. The preoperative planning stage is highlighted, emphasizing the importance of virtual planning and AI morphing as valuable tools to be used to achieve surgical precision. Consideration is given to special circumstances, such as procedure sequencing for older patients and silicone removal. Clinical outcomes, through patient-reported outcome measures and AI-based gender-typing assessments, showcase the efficacy of FFS in achieving proper gender recognition and alleviating gender dysphoria. This comprehensive review not only offers valuable insights into the current state of knowledge regarding FFS but also emphasizes the potential of artificial intelligence in outcome evaluation and surgical planning to further advance patient care and satisfaction with FFS.

On the outside looking in: roles of endogenous and exogenous strigolactones.

A collection of small molecules called strigolactones (SLs) act as both endogenous hormones to control plant development and as ecological communication cues between organisms. SL signalling overlaps with that of a class of smoke-derived compounds, karrikins (KARs), which have distinct yet overlapping developmental effects on plants. Although the roles of SLs in shoot and root development, in the promotion of arbuscular mycorrhizal (AM) fungal branching and in parasitic plant germination have been well characterized, recent data have illustrated broader roles for these compounds in the rhizosphere. Here, we review the known roles of SLs in development, growth of AM fungi and germination of parasitic plants to develop a framework for understanding the use of SLs as molecules of communication in the rhizosphere. It appears, for example, that there are many connections between SLs and phosphate utilization. Low phosphate levels regulate SL metabolism and, in turn, SLs sculpt root and shoot architecture to coordinate growth and optimize phosphate uptake from the environment. Plant-exuded SLs attract fungal symbionts to deliver inorganic phosphate (Pi) to the host. These and other examples suggest the boundary between exogenous and endogenous SL functions can be easily blurred and a more holistic view of these small molecules is likely to be required to fully understand SL biology. Related to this, we summarize and discuss evidence for a primitive role of SLs in moss as a quorum sensing-like molecule, providing a unifying concept of SLs as endogenous and exogenous signalling molecules.

Genome-enabled discovery of candidate virulence loci in Striga hermonthica, a devastating parasite of African cereal crops.

Parasites have evolved proteins, virulence factors (VFs), that facilitate plant colonisation, however VFs mediating parasitic plant-host interactions are poorly understood. Striga hermonthica is an obligate, root-parasitic plant of cereal hosts in sub-Saharan Africa, causing devastating yield losses. Understanding the molecular nature and allelic variation of VFs in S. hermonthica is essential for breeding resistance and delaying the evolution of parasite virulence. We assembled the S. hermonthica genome and identified secreted proteins using in silico prediction. Pooled sequencing of parasites growing on a susceptible and a strongly resistant rice host allowed us to scan for loci where selection imposed by the resistant host had elevated the frequency of alleles contributing to successful colonisation. Thirty-eight putatively secreted VFs had very different allele frequencies with functions including host cell wall modification, protease or protease inhibitor and kinase activities. These candidate loci had significantly higher Tajima's D than the genomic background, consistent with balancing selection. Our results reveal diverse strategies used by S. hermonthica to overcome different layers of host resistance. Understanding the maintenance of variation at virulence loci by balancing selection will be critical to managing the evolution of virulence as part of a sustainable control strategy.

Management of Complex and Revision Anterior Shoulder Instability.

Treatment of recurrent anterior shoulder instability has gained significant interest in recent years and involves evaluation of both glenoid and humeral sided bone loss. Decision making is more complex in patients with significant humeral or glenoid bone defects or in those who underwent previous instability surgery. Appropriate assessment of the glenoid track is necessary as "off track" lesions typically require treatments beyond arthroscopic labral repair alone. In those with significant humeral or glenoid sided bone loss, the authors recommend three-dimensional computed tomography in addition to magnetic resonance imaging for accurate evaluation. The Glenoid Track Instability Management Score is a useful guide to help direct treatment by using the glenoid track as well as other known risk factors for recurrence. In circumstances with significant glenoid bone loss, typically over 20%, a coracoid transfer such as the Latarjet is recommended. In patients that previously failed a coracoid transfer, the authors recommend a distal tibia allograft; however, distal clavicle and iliac crest autograft have also been reported to have high success rates. In those with large Hill-Sachs lesions, remplissage or bone grafting are recommended. An estimation of the postoperative glenoid track after glenoid bone augmentation is required for appropriate Hill-Sachs lesion treatment. The authors typically recommend against revision instability surgical treatment with arthroscopic repair alone.

Disabled Throwing Shoulder: 2021 Update: Part 2-Pathomechanics and Treatment.

The purpose of this paper is to provide updated information for sports healthcare specialists regarding the disabled throwing shoulder (DTS). A panel of experts, recognized for their experience and expertise in this field, was assembled to address and provide updated information on several topics that have been identified as key areas in creating the DTS spectrum. Each panel member submitted a concise presentation on one of the topics within these areas, each of which were then edited and sent back to the group for their comments and consensus agreement in each area. Part two presents the following consensus conclusions and summary findings regarding pathomechanics and treatment, including (1) internal impingement results from a combination of scapular protraction and humeral head translation; (2) the clinically significant labral injury that represents pathoanatomy can occur at any position around the glenoid, with posterior injuries most common; (3) meticulous history and physical examination, with a thorough kinetic chain assessment, is necessary to comprehensively identify all the factors in the DTS and clinically significant labral injury; (4) surgical treatment should be carefully performed, with specific indications and techniques incorporating low profile implants posterior to the biceps that avoid capsular constraint; (5) rehabilitation should correct all kinetic chain deficits while also developing high-functioning, throwing-specific motor patterns and proper distribution of loads and forces across all joints during throwing; and (6) injury risk modification must focus on individualized athlete workload to avoid overuse. LEVEL OF EVIDENCE: V, expert opinion.

Disabled Throwing Shoulder 2021 Update: Part 1-Anatomy and Mechanics.

The purpose of this article is to provide updated information for sports health care specialists regarding the Disabled Throwing Shoulder (DTS). A panel of experts, recognized for their experience and expertise in this field, was assembled to address and provide updated information on several topics that have been identified as key areas in creating the DTS spectrum. Each panel member submitted a concise presentation on one of the topics within these areas, each of which were then edited and sent back to the group for their comments and consensus agreement in each area. Part 1 presents the following consensus conclusions and summary findings regarding anatomy and mechanics, including: 1) The current understanding of the DTS identifies internal impingement, resulting from a combination of causative factors, as the final common pathway for the great majority of the labral pathoanatomy; 2) intact labral anatomy is pivotal for glenohumeral stability, but its structure does not control or adapt well to shear or translational loads; 3) the biceps plays an active role in dynamic glenohumeral stability by potentiating "concavity compression" of the glenohumeral joint; 4) the ultimate function of the kinetic chain is to optimize the launch window, the precise biomechanical time, and position for ball release to most effectively allow the ball to be thrown with maximum speed and accuracy, and kinetic chain function is most efficient when stride length is optimized; 5) overhead throwing athletes demonstrate adaptive bony, capsular, and muscular changes in the shoulder with repetitive throwing, and precise measurement of shoulder range of motion in internal rotation, external rotation, and external rotation with forearm pronation is essential to identify harmful and/or progressive deficits. LEVEL OF EVIDENCE: Level V, expert opinion.

Cardiac PANK1 deletion exacerbates ventricular dysfunction during pressure overload.

Coenzyme A (CoA) is an essential cofactor required for intermediary metabolism. Perturbations in homeostasis of CoA have been implicated in various pathologies; however, whether CoA homeostasis is changed and the extent to which CoA levels contribute to ventricular function and remodeling during pressure overload has not been explored. In this study, we sought to assess changes in CoA biosynthetic pathway during pressure overload and determine the impact of limiting CoA on cardiac function. We limited cardiac CoA levels by deleting the rate-limiting enzyme in CoA biosynthesis, pantothenate kinase 1 (Pank1). We found that constitutive, cardiomyocyte-specific Pank1 deletion (cmPank1-/-) significantly reduced PANK1 mRNA, PANK1 protein, and CoA levels compared with Pank1-sufficient littermates (cmPank1+/+) but exerted no obvious deleterious impact on the mice at baseline. We then subjected both groups of mice to pressure overload-induced heart failure. Interestingly, there was more ventricular dilation in cmPank1-/- during the pressure overload. To explore potential mechanisms contributing to this phenotype, we performed transcriptomic profiling, which suggested a role for Pank1 in regulating fibrotic and metabolic processes during the pressure overload. Indeed, Pank1 deletion exacerbated cardiac fibrosis following pressure overload. Because we were interested in the possibility of early metabolic impacts in response to pressure overload, we performed untargeted metabolomics, which indicated significant changes to metabolites involved in fatty acid and ketone metabolism, among other pathways. Collectively, our study underscores the role of elevated CoA levels in supporting fatty acid and ketone body oxidation, which may be more important than CoA-driven, enzyme-independent acetylation in the failing heart.NEW & NOTEWORTHY Changes in CoA homeostasis have been implicated in a variety of metabolic diseases; however, the extent to which changes in CoA homeostasis impacts remodeling has not been explored. We show that limiting cardiac CoA levels via PANK deletion exacerbated ventricular remodeling during pressure overload. Our results suggest that metabolic alterations, rather than structural alterations, associated with Pank1 deletion may underlie the exacerbated cardiac phenotype during pressure overload.

Proximal Hamstring Tendon Injuries: Diagnosis and Management.

Proximal hamstring tendon injuries are common among active and athletic populations and exist on a spectrum ranging from proximal tendinopathy to partial tears to complete avulsions. Imaging should include plain radiography as bony avulsions have been observed in skeletally immature patients. Magnetic resonance imaging is diagnostic in the setting of both partial tears and complete tears. A high-intensity (on T2-weighted images), crescent-shaped signal at the tendon-bone interface ("sickle sign") is indicative of a partial-thickness tear of the proximal hamstring tendons. In the setting of complete avulsions, magnetic resonance imaging is also useful in demonstrating the extent of tendon avulsion and quantifying the number of tendons torn. Nonoperative treatment for proximal tendinopathy, acute partial tears, and complete tears with minimal tendon retraction includes activity modification, eccentric stretching and strengthening, and potentially platelet rich plasma injections. Surgical repair should be considered for partial tears refractory to nonoperative management, acute tears with greater than 2 cm of distal retraction, and/or chronic retracted tears. The surgical approach is generally made through a transverse incision within the gluteal crease, which can be extended distally in a "T" configuration in the setting of chronic retracted tears. In the setting of chronic retracted tears, a sciatic nerve neurolysis may be required owing to scarring. Following the surgical procedure, a graduated rehabilitation protocol is commenced with the expectation for a return to full, unrestricted activities by 6 months postoperative, and excellent outcomes can be anticipated. Compared with repair of chronic tears, acute repairs have improved functional outcomes and lower re-tear rates.

Platelet-Rich Plasma: Fundamentals and Clinical Applications.

Platelet-rich plasma (PRP) is perhaps the most widely studied of the biologic therapies, with an ever-growing body of evidence supporting its safety and efficacy in decreasing inflammation and pain and promoting healing in the setting of both nonoperative and operative treatments. PRP is produced by the centrifugation of whole blood, isolating its constituent parts based on their unique densities. These density gradients can be selectively harvested so as to obtain different concentrations of various blood product components, such as platelets and leukocytes. A precise and consistent method for describing the essential characteristics of different PRP formulations is critical for both practical and research purposes. The concentration of platelets, method of activation, and the total number of red blood cells (RBCs), white blood cells (WBCs), and neutrophils relative to baseline values are all of particular importance in accurately describing a PRP formulation. The biologic activity of PRP is manifold: platelet α granules promote the release of various growth factors, including vascular endothelial growth factor and tissue growth factor ß, while inflammation is modulated through inhibition of the nuclear factor-κB pathway. PRP has been convincingly shown to be efficacious in the setting of patellar tendinopathies, knee osteoarthritis, and lateral epicondylitis. In fact, several recent randomized controlled trials have demonstrated the superiority of PRP over both corticosteroids and hyaluronic acid in treating knee OA-related symptoms. There is also substantial promise for the utility of PRP in treating partial hamstring tears and as an adjunct to rotator cuff (RC) repair, especially in the setting of small- to medium-sized tears, where it appears to exert substantial analgesic effects and promote enhanced rates of RC repair healing.