Targeting the Sweet Spot: A Systematic Review With Meta-Analysis of Anterior Versus Posterior Glenohumeral Joint Injections for Adhesive Capsulitis.

OBJECTIVE: To compare clinical outcomes following steroid injections using the anterior and posterior approaches. DESIGN: Systematic review with meta-analysis. SETTING: Embase, Web of Science, and Cochrane Center Register of Controlled Trials were searched for randomized control trials (RCTs) and prospective comparative studies. PATIENTS: Patients with adhesive capsulitis. INTERVENTIONS: Glenohumeral steroid injections using either anterior or posterior approach. MAIN OUTCOME MEASURES: Pain visual analog scale (VAS) and shoulder range of motion (ROM) at 12 weeks, accuracy, and adverse events. Standardized mean difference (SMD) for VAS and weighted mean difference (WMD) for ROMs. RESULTS: We identified 6 RCTs and one prospective comparative study with a total of 468 patients. While there was no difference in pain VAS at 12 weeks between the 2 approaches (SMD, -0.86; 95% CI, -1.76 to 0.04), the anterior approach resulted in greater improvements in external rotation (WMD, 8.08; 95% CI, 0.79-15.38) and abduction (WMD, 6.76; 95% CI, 3.05-10.48) compared with the posterior approach. Subgroup analysis with RCTs that utilized steroid injection with hydrodilatation for both approaches demonstrated greater reduction in pain VAS at 12 weeks with the anterior approach (SMD, -0.52; 95% CI, -0.98 to -0.07). Overall, procedures were well tolerated without major complications. CONCLUSIONS: While pain reduction is similar, the anterior approach may be more beneficial in restoring shoulder external rotation and abduction compared with the posterior approach at 12 weeks. Steroid injection combined with hydrodilatation may further improve pain control when performed with the anterior approach at 12 weeks.

Team USA injury and illness incidence at the 2022 Beijing Winter Olympic and Paralympic Games.

OBJECTIVE: The purpose of this study was to determine the injury and illness incidence from Team USA athletes from the 2022 Beijing Winter Olympic and Paralympic Games and assess any sex-based differences or differences between Olympic and Paralympic athletes. METHODS: Team USA Olympic (n=231, 48.5% female) and Team USA Paralympic (n=63, 22.2% female) athletes had medical encounters documented during the Games. Injuries and illnesses were defined according to the 2020 International Olympic Committee Consensus Statement and reviewed for accuracy by a physician. Incidence rates were calculated per 1000 athlete-days and further analysed by sex, sport, anatomical location, type of illness, injury event and injury mechanism, with incident rate ratios (IRRs) used for group comparisons. RESULTS: There were no differences in illness (Olympic illness, IRR=0.99 (95% CI 0.48 to 2.07), p=0.998; Paralympic illness, IRR=1.43 (95% CI 0.41 to 4.97), p=0.572) or injury rates (Olympic injury, IRR=0.63 (95% CI 0.39 to 1.03), p=0.062; Paralympic injury, IRR=1.01 (95% CI 0.43 to 2.35), p=0.988) between male and female (reference group) athletes. However, Olympic athletes had significantly lower illness (IRR=0.41 (95% CI 0.22 to 0.76), p=0.003) and injury (IRR=0.56 (95% CI 0.37 to 0.87), p=0.009) risks compared with Paralympic athletes. CONCLUSION: No significant sex-related differences in injury or illness were detected in Team USA Olympic or Paralympic participating in the 2022 Beijing Winter Games. However, Paralympic athletes exhibited higher rates of injury and illness compared with their Olympic counterparts. This study highlights delegation-specific epidemiological data which may facilitate more focused approaches for injury and illness prevention.

Acute Thumb Metacarpophalangeal Joint Ulnar Collateral Ligament Injury: Diagnosis, Management, and Return to Sports Considerations.

ABSTRACT: Thumb metacarpophalangeal joint ulnar collateral ligament injuries are common in athletes and range from mild sprains to complete retracted tears. The typical injury mechanism of a valgus force directed onto an abducted or extended thumb is frequently seen in certain sporting activities, such as skiing, football, and baseball. Ultrasound and magnetic resonance imaging are excellent imaging supplements to the clinical evaluation for diagnosis confirmation. Positive treatment outcomes have been demonstrated when these injuries are appropriately managed both nonoperatively and surgically. When deciding on a treatment plan, it is paramount to take the athlete's injury severity and sport-specific factors into account. The aim of this review is to summarize the sport epidemiology, diagnosis, treatment options, and return to play considerations for athletes who sustain an acute thumb metacarpophalangeal joint ulnar collateral ligament injury.

Functional Gains Using Radial and Combined Shockwave Therapy in the Management of Achilles Tendinopathy.

Achilles tendinopathy is a common condition and many patients have functional limitations after initial conservative treatment. Shockwave therapy has been shown to improve function within patients; however, comparative outcomes for different forms of shockwave are poorly described. In this retrospective cohort study, we describe findings from a quality improvement initiative evaluating safety and functional outcomes after treatment with radial shockwave therapy (n = 58) or combined radial and focused shockwave therapy (n = 29) for patients with Achilles tendinopathy refractory to exercise therapy. All patients were prescribed an eccentric exercise program. We hypothesized both groups would see improvements in function quantified using the Victorian Institute of Sports Assessment-Achilles with similar safety outcomes. Overall, the minimal clinically important difference (defined at 7 for insertional and 12 for noninsertional Achilles tendinopathy) was met in a greater proportion of patients treated with combined shockwave compared to radial shockwave (26 [89.7%] vs 37 [63.8%], p = .022). The change in Victorian Institute of Sports Assessment-Achilles from baseline to final treatment was not different between combined and radial-only groups (23.3 ± 12.6 vs 19.9 ± 18.7, p = .2). Within group differences from baseline to final follow-up measures (mean duration 17.9 ± 14.8 weeks) demonstrated overall functional improvement for both groups (both p < .0001). No serious adverse effects were observed. Our findings suggest combined radial and focused shockwave therapy may provide more predictable functional gains for treatment of Achilles tendinopathy compared to radial shockwave therapy.

Similar Functional Gains Using Radial Versus Combined Shockwave Therapy in Management of Plantar Fasciitis.

Plantar fasciitis is a common condition that causes foot pain. While shockwave therapy has been shown to provide successful results, comparative outcomes from different forms of shockwave therapy have yet to be described for this condition. In this retrospective cohort study, we describe findings from a quality improvement initiative assessing safety and functional outcomes for patients with plantar fasciitis treated with radial shockwave therapy (n = 20) or radial and focused shockwave therapy (combined shockwave, n = 18). Most were runners (n = 31, 81.6%), mean age was 43.3 ± 12.9 years, and average symptom duration 12.1 ± 11.1 months. All patients were prescribed an exercise program focusing on foot intrinsic strengthening. We hypothesized both groups would have improvement in function using the foot and Ankle Ability Measure, with a similar safety profile. Both radial and combined groups received similar number of total treatments (4.9 ± 2.5 and 4.1 ± 2.4, respectively; p = .33). Within group score changes for the Activities of Daily Living and Sports subscales were observed for both the radial (16.5 ± 16.3, p < .001; 31.7 ± 23.1, p < .001) and combined groups (19.8 ± 10.8, p = .001; 26.0 ± 21.5, p = .003). There was no difference in proportion of patients meeting the minimal clinically important difference between radial and combined groups regarding the Activities of Daily Living (14 (70%) vs 14 (77.8%), p = .58) and Sports subscales (17 (85%) vs 12 (75%), p = .45). Collectively, these findings suggest that a majority of patients with chronic plantar fasciitis may achieve functional gains using either form of shockwave therapy.

Alkynyl Benzoxazines and Dihydroquinazolines as Cysteine Targeting Covalent Warheads and Their Application in Identification of Selective Irreversible Kinase Inhibitors.

With a resurgence in interest in covalent drugs, there is a need to identify new moieties capable of cysteine bond formation that are differentiated from commonly employed systems such as acrylamide. Herein, we report on the discovery of new alkynyl benzoxazine and dihydroquinazoline moieties capable of covalent reaction with cysteine. Their utility as alternative electrophilic warheads for chemical biological probes and drug molecules is demonstrated through site-selective protein modification and incorporation into kinase drug scaffolds. A potent covalent inhibitor of JAK3 kinase was identified with superior selectivity across the kinome and improvements in in vitro pharmacokinetic profile relative to the related acrylamide-based inhibitor. In addition, the use of a novel heterocycle as a cysteine reactive warhead is employed to target Cys788 in c-KIT, where acrylamide has previously failed to form covalent interactions. These new reactive and selective heterocyclic warheads supplement the current repertoire for cysteine covalent modification while avoiding some of the limitations generally associated with established moieties.

Regenerative Medicine for Axial and Radicular Spine-Related Pain: A Narrative Review.

INTRODUCTION: Regenerative injection-based therapy has established itself as a therapeutic option for the management of a variety of painful musculoskeletal conditions. The aim of this work was to review the current literature regarding regenerative injection therapy for axial/radicular spine pain. METHODS: A comprehensive literature review was conducted on the use of regenerative medicine for axial/radicular spine pain. Eligible articles analyzed the therapeutic injection effects of platelet-rich plasma (PRP), prolotherapy, or mesenchymal signaling cells (MSCs) via intradiscal, facet joint, epidural, or sacroiliac joint delivery. RESULTS: Regarding intradiscal PRP, there are level I/IV studies supporting its use. Regarding intradiscal prolotherapy, there are level III to IV studies supporting its use. Regarding intradiscal MSCs, there are level I/IV studies supporting its use with the exception of one level IV study that found no significant improvement at 12 months. Regarding facet joint injections with PRP, there are level I/IV studies supporting its use. Regarding facet joint injections with prolotherapy, there are level IV studies supporting its use, though the one level I study did not demonstrate any statistical significance supporting its use. Regarding epidural injections with PRP, there are level I/IV studies supporting its use. Regarding epidural injections with prolotherapy, there are level IV studies supporting its use, though the one level I study did not demonstrate statistical significance beyond 48 hours. Regarding sacroiliac joint injections with PRP, there are level I/IV studies supporting its use. Regarding sacroiliac joint injections with prolotherapy, there are level I/III studies supporting its use. CONCLUSIONS: Currently, there are level I studies to support the use of PRP and MSC injections for discogenic pain; facet joint injections with PRP; epidural injections of autologous conditioned serum and epidural prolotherapy; and PRP and prolotherapy for sacroiliac joint pain. One level I study showed that facet joint prolotherapy has no significant benefit. Notably, no intervention has multiple published level I studies.

What determines catalyst functionality in molecular water oxidation? Dependence on ligands and metal nuclearity in cobalt clusters.

The metal-oxo M4O4 "cubane" topology is of special significance to the field of water oxidation as it represents the merging of bioinspired structural principles derived from natural photosynthesis with successful artificial catalysts known to date. Herein, we directly compare the rates of water oxidation/O2 evolution catalyzed by six cobalt-oxo clusters including the Co4O4 cubanes, Co4O4(OAc)4(py)4 and [Co4O4(OAc)2(bpy)4](2+), using the common Ru(bpy)3(2+)/S2O8(2-) photo-oxidant assay. At pH 8, the first-order rate constants for these cubanes differ by 2-fold, 0.030 and 0.015 s(-1), respectively, reflecting the number of labile carboxylate sites that allow substrate water binding in a pre-equilibrium step before O2 release. Kinetic results reveal a deprotonation step occurs on this pathway and that two electrons are removed before O2 evolution occurs. The Co4O4 cubane core is shown to be the smallest catalytic unit for the intramolecular water oxidation pathway, as neither "incomplete cubane" trimers [Co3O(OH)3(OAc)2(bpy)3](2+) and [Co3O(OH)2(OAc)3(py)5](2+) nor "half cubane" dimers [Co2(OH)2(OAc)3(bpy)2](+) and [Co2(OH)2(OAc)3(py)4](+) were found capable of evolving O2, despite having the same ligand sets as their cubane counterparts. Electrochemical studies reveal that oxidation of both cubanes to formally Co4(3III,IV) (0.7 V vs Ag/AgCl) occurs readily, while neither dimers nor trimers are oxidized below 1.5 V, pointing to appreciably greater charge delocalization in the [Co4O4](5+) core. The origin of catalytic activity by Co4O4 cubanes illustrates three key features for water oxidation: (1) four one-electron redox metals, (2) efficient charge delocalization of the first oxidation step across the Co4O4 cluster, allowing for stabilization of higher oxidizing equivalents, and (3) terminal coordination site for substrate aquo/oxo formation.

Patient-reported outcomes during telehealth versus in-person follow-up visits for patients treated with extracorporeal shockwave therapy.

BACKGROUND: The limited research describing clinical outcomes using telehealth for management of musculoskeletal conditions is primarily within orthopedic surgery care. OBJECTIVE: To characterize differences in patient reported outcomes using telehealth compared with in-person follow-up visits in patients with Achilles tendinopathy (AT) or plantar fasciitis (PF) treated using extracorporeal shockwave therapy (ESWT). DESIGN: Retrospective chart review. SETTING: Outpatient sports medicine clinic. PATIENTS: 82 patients with AT and 46 patients with PF. INTERVENTIONS: In-person (n = 76) and telehealth (n = 52) follow-up visits. MAIN OUTCOME MEASUREMENTS: Victorian Institute of Sports Assessment-Achilles (VISA-A) for AT and Foot and Ankle Ability Measure (FAAM) for PF as well as billing level. RESULTS: There was significant improvement from baseline to final VISA-A (p < .01) and FAAM (p < .01) following ESWT. No significant difference existed in the proportion of patients who met the minimal clinically important difference based on in-person (71.1%) versus telehealth (71.2%) follow-up (p = .99). The in-person group demonstrated higher billing levels compared to the telehealth group (Level: 3.5 ± 0.6 vs. 2.8 ± 0.7, p < .01). CONCLUSIONS: Given no significant differences in outcomes between two modes of follow-ups, telehealth may serve as an alternative method to guide management of musculoskeletal injuries with ESWT and other procedures.

Nonsteroidal Anti-Inflammatory Drug Injections versus Steroid Injections in the Management of Upper and Lower Extremity Orthopedic Conditions: A Systematic Review with Meta-Analysis.

BACKGROUND: Although corticosteroid injections are an effective treatment for musculoskeletal pathologies, they may not be suitable for all patients. The purpose of this systematic review was to compare clinical outcomes between patients who received NSAID and corticosteroid injections for various orthopedic conditions. METHODS: Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were searched, and meta-analyses were performed using a random-effects model for outcomes presented in three or more studies. Other studies were qualitatively analyzed. RESULTS: A total of 28 articles with 2113 patients were included. A meta-analysis of five studies in patients with shoulder impingement syndrome demonstrated that there was no significant difference in the pain visual analogue scale (VAS) between subacromial NSAID injections and corticosteroid injections at 1 month [weighted mean difference (WMD) -0.244; 95% CI, -1.232 to 0.745; I2, 94.5%]. For patients with knee osteoarthritis, a meta-analysis of three studies demonstrated that there was no significant difference between intraarticular NSAID injections and corticosteroid injections in pain VAS at 1 month (WMD 0.754; 95% CI, -0.413 to 1.921; I2, 90.2%) and 3 months (WMD-0.089; 95% CI, -0.345 to 0.166; I2, 0%). A review of the studies assessing pain outcomes for hip osteoarthritis, adhesive capsulitis, and plantar fasciitis showed no significant differences between the NSAID and corticosteroid groups. CONCLUSION: NSAID injections may be safe and effective alternatives to steroid injections, especially in shoulder impingement syndrome and knee osteoarthritis.

Incidence of staff injury and illness at the Tokyo 2020 and Beijing 2022 Olympic and Paralympic Games.

Objective: To report epidemiological data regarding injury and illness among the Team USA staff during the Tokyo 2020 Summer Olympic and Paralympic Games and Beijing 2022 Winter Olympic and Paralympic Games. Methods: A retrospective review of all Team USA staff (total staff, N=1703 (62.5% female); total staff days (SD)=34 489) medical encounters during the Tokyo 2020 Games and Beijing 2022 Games was conducted. Details related to injury and illness were evaluated. Incidence with 95% CI per 1000 staff days were calculated. Results: A total of 32 illnesses (incidence [95% CI] 0.9 [0.6, 1.2]) and 23 injuries (incidence 0.7 [0.4, 0.9]) were sustained by the Team USA delegation staff members during the Tokyo 2020 Games and Beijing 2022 Games. Female staff reported more illnesses (illnesses proportion (IP) 2.9%; incidence 1.4 [0.8, 2.0]), while male staff incurred more injuries (IP 1.8%; incidence 0.9 [0.5, 1.3]). When stratified by physiological system, dermatological and infectious were the most common systems involved with illness (IP 0.5%; incidence 0.2 [0.1, 0.4]). Injuries to the upper limb were most common (IP 0.3%; incidence 0.3 [0.1, 0.5]). Conclusion: Injury and illness rates among the Team USA staff during the Tokyo 2020 Games and Beijing 2022 Games were low, but notable. Knowledge of injury and illness risks contributes to staffing decisions and prevention strategies for staff supporting athletes during competition.

Photochemical water oxidation by crystalline polymorphs of manganese oxides: structural requirements for catalysis.

Manganese oxides occur naturally as minerals in at least 30 different crystal structures, providing a rigorous test system to explore the significance of atomic positions on the catalytic efficiency of water oxidation. In this study, we chose to systematically compare eight synthetic oxide structures containing Mn(III) and Mn(IV) only, with particular emphasis on the five known structural polymorphs of MnO2. We have adapted literature synthesis methods to obtain pure polymorphs and validated their homogeneity and crystallinity by powder X-ray diffraction and both transmission and scanning electron microscopies. Measurement of water oxidation rate by oxygen evolution in aqueous solution was conducted with dispersed nanoparticulate manganese oxides and a standard ruthenium dye photo-oxidant system. No Ru was absorbed on the catalyst surface as observed by XPS and EDX. The post reaction atomic structure was completely preserved with no amorphization, as observed by HRTEM. Catalytic activities, normalized to surface area (BET), decrease in the series Mn2O3 > Mn3O4 ≫ λ-MnO2, where the latter is derived from spinel LiMn2O4 following partial Li(+) removal. No catalytic activity is observed from LiMn2O4 and four of the MnO2 polymorphs, in contrast to some literature reports with polydispersed manganese oxides and electro-deposited films. Catalytic activity within the eight examined Mn oxides was found exclusively for (distorted) cubic phases, Mn2O3 (bixbyite), Mn3O4 (hausmannite), and λ-MnO2 (spinel), all containing Mn(III) possessing longer Mn-O bonds between edge-sharing MnO6 octahedra. Electronically degenerate Mn(III) has antibonding electronic configuration e(g)(1) which imparts lattice distortions due to the Jahn-Teller effect that are hypothesized to contribute to structural flexibility important for catalytic turnover in water oxidation at the surface.

Ultrasound-guided percutaneous carpal tunnel release: A systematic review.

OBJECTIVE: Carpal tunnel syndrome (CTS) is the most common peripheral entrapment mononeuropathy. The purpose of this systematic review is to evaluate the reported clinical effectiveness and safety of ultrasound-guided percutaneous carpal tunnel release (USCTR) for the treatment of CTS. LITERATURE SURVEY: PubMed, EMBASE, and ScienceDirect databases were queried from database inception to February 20, 2021, to identify clinical studies on USCTR. METHODOLOGY: Two reviewers independently completed title, abstract, and full-text screening, and they extracted data in duplicate for analysis. Procedure techniques, outcome measures, and complications were descriptively analyzed. SYNTHESIS: Eighty-seven studies were eligible for screening. Twenty studies (three randomized controlled trials, three prospective cohort studies, and 14 case series) met inclusion criteria, with a total of 1772 USCTR cases. The overall level of evidence was very low, with seven studies with at least moderate risk of bias. Thirteen studies exceeded the minimal clinically important difference (MCID) for the Boston Carpal Tunnel Questionnaire Symptom Severity Scale (BCTQ-SS) and Boston Carpal Tunnel Questionnaire Functional Status Scale (BCTQ-FS), and six studies exceeded the MCID for the Quick Disabilities of Arm, Shoulder & Hand (QDASH). Five studies reported statistically significant improvement in these functional outcome measures as early as the first week post-procedure. A major complication occurred in one patient who developed suspected compartment syndrome, and minor complications were reported in 24 patients. CONCLUSIONS: Based on very low level of evidence, early studies suggest that USCTR may be an effective treatment for CTS, with potential for short post-procedure recovery times.

Economic and environmental assessment of U.S. broiler production: opportunities to improve sustainability.

The United States is the largest broiler producer in the world, and Americans consume about 45 kg of chicken per capita per year, which generates substantial economic and environmental footprints. We conduct techno-economic analysis and life cycle assessment (TEA/LCA) to evaluate the sustainability performance of the U.S. broiler industry and quantify the cost, greenhouse gas (GHG) emissions, energy, water, land, fertilizer, and respiratory impacts of 7 broiler production scenarios for a contract Grower, Integrator, and Combined control volume. The assessment is a farm-gate to farm-gate analysis that includes capital cost of chicken houses, labor, chicks brought into the farm, feeds, on-site fuels, and on-site emissions. We found that economics for the Integrator are profitable and dominated by the cost of corn and soybean meal feeds, payments to the Grower, and revenue from live broilers. Additionally, we found that economics for the Grower generate modest return on investment (ROI) largely based on the cost of houses and labor when compared to contract revenue from the Integrator. Environmental impacts for GHG, energy, and respiratory effects are primarily associated with upstream feed production (roughly 65%-80% of total impacts) and on-site fuel consumption (∼20%-35% of total impacts), while those for water, land, and eutrophication are almost entirely attributable to upstream feed production (litter spreading has a low economic allocation factor). Tradeoffs among sustainability metrics are further explored with a sensitivity analysis and by evaluating cost/environmental benefit scenarios.

Incidence of injury and illness among paediatric Team USA athletes competing in the 2020 Tokyo and 2022 Beijing Olympic and Paralympic Games.

Objective: To describe the incidence of injuries and illnesses among paediatric Team USA athletes competing in the Tokyo 2020 Olympic and Paralympic Games, and the 2022 Beijing Olympic and Paralympic Games. Methods: An electronic medical record system documented all injuries and illnesses that occurred while competing in the four Games periods. Incidence (IR) with 95% CI per 1000 athlete days were calculated for both injuries and illnesses. Incidence rate ratios (IRR) were calculated to compare injury and illness rates based on age (paediatric vs non-paediatric) sex, Games period and sport type. Results: Two hundred paediatric athletes (age range, 15-21 years) competed across the four Games periods, representing 16.1% of all Team USA athletes. The overall injury IR (95% CI) was 13.4 (9.8 to 18.1), and the overall illness IR was 5.5 (3.3 to 8.7). There were no differences in incidence between paediatric and non-paediatric athletes for either injury (IRR (95% CI): 0.9 (0.6 to 1.2)) or illness (IRR (95% CI): 0.9 (0.5 to 1.5)). Female paediatric athletes were more likely to sustain an injury compared with male paediatric athletes (IRR (95% CI): 2.4 (1.1 to 5.3)). The most common mechanism of injury was gradual onset (IR, 4.3 (2.3 to 7.2)), and injuries most commonly occurred during practices (IR, 7.0 (4.5 to 10.5)). Conclusion: Paediatric athletes account for a substantial proportion of Team USA athletes. It is essential that paediatric sports medicine experts are included in the medical team given that paediatric Team USA athletes are just as likely as their adult teammates to sustain an injury or illness.

Clinical evaluation and management of calcific tendinopathy: an evidence-based review.

Calcific tendinopathy (CT) is an important musculoskeletal condition most commonly seen in the shoulder girdle, accounting for 10-42% of all shoulder pain. Despite the high prevalence within the shoulder region, CT has been demonstrated in many tendons throughout the axial and appendicular skeleton. Unlike degenerative tendinopathies, CT appears to be a self-limiting condition that affects otherwise-healthy tendon with deposition of calcium hydroxyapatite crystals between healthy tenocytes. In patients with functionally limiting symptoms or pain, the clinical course may be accelerated through a multitude of treatments including physical therapy and pain management, extracorporeal shock wave therapy, ultrasound-guided percutaneous lavage (UGPL), and operative debridement. Currently, the most efficacious and frequently utilized treatment for shoulder CT is UGPL due to its ability to effectively reduce calcium burden and pain while limiting soft-tissue damage. However, more evidence regarding the treatment and course of CT is needed before determining the most appropriate treatment at all potential sites of CT.

Musculoskeletal Ultrasound as a Motivator for Selecting a Physical Medicine and Rehabilitation Residency Program in the United States: A Multicenter Survey Study.

ABSTRACT: This study aimed to determine the influence of musculoskeletal ultrasound (MSKUS) curriculum on applicants during the residency-selection process. A survey of 666 applicants for the Johns Hopkins University, Mayo Clinic, and Harvard/Spaulding Rehabilitation Physical Medicine and Rehabilitation programs was conducted in June 2020. A total of 180 respondents scored the influence of a MSKUS curriculum on their decision making for residency selection. In addition, applicants were asked to rank specific areas of physical medicine and rehabilitation that influenced their decision making. Participants most commonly included MSKUS in their top three areas of interest when constructing their rank order list. When asked whether MSKUS presence within a program had an effect during the interview-selection process, 71% responded with "very important" or "absolutely essential" (P < 0.001). For 74% of applicants, exposure to MSKUS in residency was an important factor when creating their rank order list (P < 0.001). More than 92% of applicants stated that they are "likely" or "very likely" to use MSKUS in their future practice and 83% would recommend a program with MSKUS to future candidates (P < 0.001). Based on these results, a large percentage of physical medicine and rehabilitation applicants intend on using MSKUS in their future practice. Therefore, MSKUS may be an important factor for residency selection.

Discovery of AZD4625, a Covalent Allosteric Inhibitor of the Mutant GTPase KRASG12C.

KRAS is an archetypal high-value intractable oncology drug target. The glycine to cysteine mutation at codon 12 represents an Achilles heel that has now rendered this important GTPase druggable. Herein, we report our structure-based drug design approach that led to the identification of 21, AZD4625, a clinical development candidate for the treatment of KRASG12C positive tumors. Highlights include a quinazoline tethering strategy to lock out a bio-relevant binding conformation and an optimization strategy focused on the reduction of extrahepatic clearance mechanisms seen in preclinical species. Crystallographic analysis was also key in helping to rationalize unusual structure-activity relationship in terms of ring size and enantio-preference. AZD4625 is a highly potent and selective inhibitor of KRASG12C with an anticipated low clearance and high oral bioavailability profile in humans.

A Co4O4 "cubane" water oxidation catalyst inspired by photosynthesis.

Herein we describe the molecular Co(4)O(4) cubane complex Co(4)O(4)(OAc)(4)(py)(4) (1), which catalyzes efficient water oxidizing activity when powered by a standard photochemical oxidation source or electrochemical oxidation. The pH dependence of catalysis, the turnover frequency, and in situ monitoring of catalytic species have revealed the intrinsic capabilities of this core type. The catalytic activity of complex 1 and analogous Mn(4)O(4) cubane complexes is attributed to the cubical core topology, which is analogous to that of nature's water oxidation catalyst, a cubical CaMn(4)O(5) cluster.

Non-operative orthobiologic use for rotator cuff disorders and glenohumeral osteoarthritis: A systematic review.

BACKGROUND: Shoulder pain from rotator cuff pathology and glenohumeral osteoarthritis is a common entity encountered in musculoskeletal practices. Orthobiologic agents are being increasingly used as a treatment option and understanding their safety and efficacy is necessary. OBJECTIVE: To systematically evaluate the available evidence for orthobiologic use in rotator cuff and glenohumeral pathology. METHODS: A systematic review was undertaken following PRISMA guidelines. Randomized clinical trials (RCTs) and prospective cohort studies evaluating non-operative treatment with prolotherapy, platelet-rich plasma (PRP), or medicinal signaling cells (MSCs) for rotator cuff pathology and glenohumeral osteoarthritis were included. Bias risk assessments used were the Cochrane tool and Newcastle-Ottawa score. RESULTS: The search yielded 852 potential articles, of which 20 met the inclusion criteria with a breakdown of 5 prolotherapy, 13 PRP, and 2 MSC. Sixteen studies were RCTs and 4 were cohort studies. Six studies were deemed "low risk of bias or good quality". Efficacy results were mixed, and no serious adverse events were reported from orthobiologic treatment. CONCLUSIONS: Orthobiologics offer a relatively safe management option with inconclusive evidence for or against its use for rotator cuff pathology. No studies on glenohumeral osteoarthritis met the inclusion criteria. Adoption of standardized preparation reporting and consistent use of functional outcome measures is imperative for future studies to consider.