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BackgroundExposure of the developing brain to propofol results in cognitive deficits. Recent data suggest that inhibition of neuronal apoptosis does not prevent cognitive defects, suggesting mechanisms other than neuronal apoptosis play a role in anaesthetic neurotoxicity. Proper neuronal growth during development is dependent upon growth cone morphology and axonal transport. Propofol modulates actin dynamics in developing neurones, causes RhoA-dependent depolymerisation of actin, and reduces dendritic spines and synapses. We hypothesised that RhoA inhibition prevents synaptic loss and subsequent cognitive deficits. The present study tested whether RhoA inhibition with the botulinum toxin C3 (TAT-C3) prevents propofol-induced synapse and neurite loss, and preserves cognitive function.MethodsRhoA activation, growth cone morphology, and axonal transport were measured in neonatal rat neurones (5-7 days in vitro) exposed to propofol. Synapse counts (electron microscopy), dendritic arborisation (Golgi-Cox), and network connectivity were measured in mice (age 28 days) previously exposed to propofol at postnatal day 5-7. Memory was assessed in adult mice (age 3 months) previously exposed to propofol at postnatal day 5-7.ResultsPropofol increased RhoA activation, collapsed growth cones, and impaired retrograde axonal transport of quantum dot-labelled brain-derived neurotrophic factor, all of which were prevented with TAT-C3. Adult mice previously treated with propofol had decreased numbers of total hippocampal synapses and presynaptic vesicles, reduced hippocampal dendritic arborisation, and infrapyramidal mossy fibres. These mice also exhibited decreased hippocampal-dependent contextual fear memory recall. All anatomical and behavioural changes were prevented with TAT-C3 pre-treatment.ConclusionInhibition of RhoA prevents propofol-mediated hippocampal neurotoxicity and associated cognitive deficits.

BackgroundIsoflurane is widely used for anaesthesia in humans. Isoflurane exposure of rodents prior to post-natal day 7 (PND7) leads to widespread neurodegeneration in laboratory animals. Previous data from our laboratory suggest an attenuation of apoptosis with the p75 neurotrophin receptor (p75NTR) inhibitor TAT-Pep5. We hypothesized that isoflurane toxicity leads to behavioural and cognitive abnormalities and can be rescued with pre-anaesthesia administration of TAT-Pep5.MethodsNeonatal mouse pups were pretreated with either TAT-Pep5 (25 μl, 10 μM i.p.) or a scrambled control peptide (TAT-ctrl; 25 μl, 10 μM i.p.) prior to isoflurane exposure (1.4%; 4 h) or control ( n  = 15-26/group). Three to 5 months after exposure, behavioural testing and endpoint assays [brain volume (stereology) and immunoblotting] were performed.ResultsNo significant difference was observed in open field, T-maze, balance beam or wire-hanging testing. The Barnes maze revealed a significant effect of isoflurane ( P  = 0.019) in errors to find the escape tunnel during the day 5 probe trial, a finding indicative of impaired short-term spatial memory. No difference was found for brain volumes or protein expression. TAT-Pep5 treatment did not reverse the effects of isoflurane on neurocognitive behaviour.ConclusionA single isoflurane exposure to early post-natal mice caused a hippocampal-dependent memory deficit that was not prevented by pre-administration of TAT-Pep5, although TAT-Pep5, an inhibitor of p75NTR, has been shown to reduce isoflurane-induced apoptosis. These findings suggest that neuronal apoptosis is not requisite for the development of cognitive deficits in the adults attendant with neonatal anaesthetic exposure.

Mechanical stretch of cardiac muscle modulates action potential propagation velocity, causing potentially arrhythmogenic conduction slowing. The mechanisms by which stretch alters cardiac conduction remain unknown, but previous studies suggest that stretch can affect the conformation of caveolae in myocytes and other cell types. We tested the hypothesis that slowing of action potential conduction due to cardiac myocyte stretch is dependent on caveolae. Cardiac action potential propagation velocities, measured by optical mapping in isolated mouse hearts and in micropatterned mouse cardiomyocyte cultures, decreased reversibly with volume loading or stretch, respectively (by 19±5% and 26±4%). Stretch-dependent conduction slowing was not altered by stretch-activated channel blockade with gadolinium or by GsMTx-4 peptide, but was inhibited when caveolae were disrupted via genetic deletion of caveolin-3 (Cav3 KO) or membrane cholesterol depletion by methyl-β-cyclodextrin. In wild-type mouse hearts, stretch coincided with recruitment of caveolae to the sarcolemma, as observed by electron microscopy. In myocytes from wild-type but not Cav3 KO mice, stretch significantly increased cell membrane capacitance (by 98±64%), electrical time constant (by 285±149%), and lipid recruitment to the bilayer (by 84±39%). Recruitment of caveolae to the sarcolemma during physiologic cardiomyocyte stretch slows ventricular action potential propagation by increasing cell membrane capacitance.

Background: Exposure to anesthetics during synaptogenesis results in apoptosis and subsequent cognitive dysfunction in adulthood. Probrain-derived neurotrophic factor (proBDNF) is involved in synaptogenesis and can induce neuronal apoptosis via p75 neurotrophic receptors (p75). proBDNF is cleaved into mature BDNF (mBDNF) by plasmin, a protease converted from plasminogen by tissue plasminogen activator (tPA) that is released with neuronal activity; mBDNF supports survival and stabilizes synapses through tropomyosin receptor kinase B. The authors hypothesized that anesthetics suppress tPA release from neurons, enhance p75 signaling, and reduce synapses, resulting in apoptosis.Methods: Primary neurons (DIV5) and postnatal day 5-7 (PND5-7) mice were exposed to isoflurane (1.4%, 4 h) in 5% CO2, 95% air. Apoptosis was assessed by cleaved caspase-3 (Cl-Csp3) immunoblot and immunofluorescence microscopy. Dendritic spine changes were evaluated with the neuronal spine marker, drebrin. Changes in synapses in PND5-7 mouse hippocampi were assessed by electron microscopy. Primary neurons were exposed to tPA, plasmin, or pharmacologic inhibitors of p75 (Fc-p75 or TAT-Pep5) 15 min before isoflurane. TAT-Pep5 was administered by intraperitoneal injection to PND5-7 mice 15 min before isoflurane.Results: Exposure of neurons in vitro (DIV5) to isoflurane decreased tPA in the culture medium, reduced drebrin expression (marker of dendritic filopodial spines), and enhanced Cl-Csp3. tPA, plasmin, or TAT-Pep5 stabilized dendritic filopodial spines and decreased Cl-Csp3 in neurons. TAT-Pep5 blocked isoflurane-mediated increase in Cl-Csp3 and reduced synapses in PND5-7 mouse hippocampi.Conclusion: tPA, plasmin, or p75 inhibition blocked isoflurane-mediated reduction in dendritic filopodial spines and neuronal apoptosis in vitro. Isoflurane reduced synapses and enhanced Cl-Csp3 in the hippocampus of PND5-7 mice, the latter effect being mitigated by p75 inhibition in vivo. These data support the hypothesis that isoflurane neurotoxicity in the developing rodent brain is mediated by reduced synaptic tPA release and enhanced proBDNF/p75-mediated apoptosis. [ABSTRACT FROM AUTHOR]

Natural products (NPs) have long been used as a rich source of bioactive compounds for drug development. Recent technological advancements have revitalised natural products research as evidenced by increased publications in this field. In this editorial review, we highlight key points from the 2020 British Journal of Pharmacology (BJP) practical guide, which outlines standards for natural products research reports, and provide papers published in BJP between years 2020 to 2023 that demonstrate adherence to these guidelines. Looking ahead, we discuss the potential of chemical proteomics approaches to elucidate natural products mechanisms of action and identify therapeutic targets for future research. By fostering innovation, we aim to advance natural products research and contribute to the development of novel therapeutics that will have a significant impact on healthcare., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background and Purpose: Traumatic brain injury (TBI) causes lifelong physical and psychological dysfunction in affected individuals. The current study investigated the effects of chronic nicotine exposure via E-cigarettes (E-cig) (vaping) on TBI-associated behavioural and biochemical changes., Experimental Approach: Adult C57/BL6J male mice were subjected to controlled cortical impact (CCI) followed by daily exposure to E-cig vapour for 6 weeks. Sensorimotor functions, locomotion, and sociability were subsequently evaluated by nesting, open field, and social approach tests, respectively. Immunoblots were conducted to examine the expression of mature brain-derived neurotrophic factor (mBDNF) and associated downstream proteins (p-Erk, p-Akt). Histological analyses were performed to evaluate neuronal survival and neuroinflammation., Key Results: Post-injury chronic nicotine exposure significantly improved nesting performance in CCI mice. Histological analysis revealed increased survival of cortical neurons in the perilesion cortex with chronic nicotine exposure. Immunoblots revealed that chronic nicotine exposure significantly up-regulated mBDNF, p-Erk and p-Akt expression in the perilesion cortex of CCI mice. Immunofluorescence microscopy indicated that elevated mBDNF and p-Akt expression were mainly localized within cortical neurons. Immunolabelling of Iba1 demonstrated that chronic nicotine exposure attenuated microglia-mediated neuroinflammation., Conclusions and Implications: Post-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Purpose: To assess the relation between tendon migration, as measured by radiostereometric analysis, and patient-reported outcome measures (PROMs) after biceps tenodesis (BT); to determine the likelihood of achieving clinically significant outcomes (CSOs) after BT; and to identify factors that impact CSO achievement., Methods: Patients undergoing arthroscopic suprapectoral or open subpectoral BT at a single, high-volume academic medical center were prospectively enrolled. A tantalum bead sutured to the tenodesis construct was used as a radiopaque marker. Biceps tendon migration was measured on calibrated radiographs at 12 weeks postoperatively. PROMs (Constant-Murley, Single Assessment Numeric Evaluation [SANE], and Patient-Reported Outcomes Measurement Information System-Upper Extremity [PROMIS-UE] scores) were collected preoperatively and at minimum 2-year follow-up., Results: Of 115 patients enrolled, 94 (82%) were included (median age, 52 years; median body mass index, 31.4). At a mean follow-up of 2.9 years, the median Constant-Murley, SANE, and PROMIS-UE scores were 33 (interquartile range [IQR], 26-35), 90 (IQR, 80-99), and 47 (IQR, 42-58), respectively. Median tantalum bead migration was 6.5 mm (IQR, 1.8-13.8 mm). There were significant correlations between migration and Constant-Murley score (r 2  = 0.222; β = -0.554 [95% confidence interval (CI), -1.027 to -0.081]; P = .022), SANE score (r 2  = 0.238; β = -0.198 [95% CI, -0.337 to -0.058]; P = .006), and PROMIS-UE score (r 2  = 0.233; β = -0.406 [95% CI, -0.707 to -0.104]; P = .009). On univariable analysis, higher body mass index was associated with achievement of substantial clinical benefit (unadjusted odds ratio [OR], 1.078 [95% CI, 1.007 to 1.161]; P = .038). Greater bead migration was negatively associated with achievement of the minimal clinically important difference (unadjusted OR, 0.969 [95% CI, 0.943 to 0.993]; P = .014) and patient acceptable symptomatic state (unadjusted OR, 0.965 [95% CI, 0.937 to 0.989]; P = .008) on all 3 instruments., Conclusions: A 1-cm increase in post-tenodesis biceps tendon migration was associated with a decrease in the Constant-Murley, SANE, and PROMIS-UE scores of 6, 2, and 4 points, respectively, at a mean of 2.9 years after surgery. Most patients achieved CSOs for these PROMs by latest follow-up, and greater biceps tendon construct migration was negatively associated with the likelihood of CSO achievement., Level of Evidence: Level IV, retrospective case series., Competing Interests: Disclosures The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: B.F. reports board membership with American Orthopaedic Society for Sports Medicine and Video Journal of Sports Medicine; receives funding grants from Arthrex, Smith & Nephew, and Stryker Orthopaedics; receives speaking and lecture fees from Elsevier; owns equity or stocks in iBrainTech, Jace Medical, and Sparta Biopharma; and reports a consulting or advisory relationship with Smith & Nephew and Stryker Orthopaedics. E.J.B. owns equity or stocks in Amgen and Pfizer. K.R.O. reports a consulting or advisory relationship with Arthrex and Smith & Nephew. A.B.Y. reports a consulting or advisory relationship with AlloSource and JRF Ortho; receives funding grants from Arthrex; receives funding grants from Organogenesis; reports a consulting or advisory relationship with Patient IQ, Sparta Biopharma, and Stryker Orthopaedics; owns equity or stocks in Patient IQ and Sparta Biopharma; and receives speaking and lecture fees from Stryker Orthopaedics. B.J.C. receives funding grants from Aesculap Implant Systems, Arthrex, and National Institutes of Health; reports board membership with American Journal of Sports Medicine, Arthroscopy Association of North America, and Journal of the American Academy of Orthopaedic Surgeons; reports a consulting or advisory relationship with Arthrex, JRF Ortho, and Operative Techniques in Sports Medicine; owns equity or stocks in Bandgrip and OSSIO; receives speaking and lecture fees from Elsevier and Operative Techniques in Sports Medicine; and is a board member of Arthroscopy Association of North America. N.N.V. reports board membership with American Orthopaedic Society for Sports Medicine, American Shoulder and Elbow Surgeons, Arthroscopy Association of North America, and Slack; receives funding grants from Arthrex, Breg, Ossur, Smith & Nephew, and Stryker Orthopaedics; receives speaking and lecture fees from Smith & Nephew and Stryker Orthopaedics; and reports a consulting or advisory relationship with Stryker Orthopaedics. All other authors (D.K-S., H.H.P., E.M.F., B.T.W.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

In 2023, seventy novel drugs received market authorization for the first time in either Europe (by the EMA and the MHRA) or in the United States (by the FDA). Confirming a steady recent trend, more than half of these drugs target rare diseases or intractable forms of cancer. Thirty drugs are categorized as "first-in-class" (FIC), illustrating the quality of research and innovation that drives new chemical entity discovery and development. We succinctly describe the mechanism of action of most of these FIC drugs and discuss the therapeutic areas covered, as well as the chemical category to which these drugs belong. The 2023 novel drug list also demonstrates an unabated emphasis on polypeptides (recombinant proteins and antibodies), Advanced Therapy Medicinal Products (gene and cell therapies) and RNA therapeutics, including the first-ever approval of a CRISPR-Cas9-based gene-editing cell therapy., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Aggressive periodontitis is a severe form of periodontal disease characterized by rapid tissue destruction and tooth loss. The optimal treatment approach for managing this condition remains a topic of debate., Materials and Methods: A retrospective cohort study was conducted, involving patients diagnosed with aggressive periodontitis who received either surgical or non-surgical treatment between 2010 and 2020. Clinical and radiographic data were collected at baseline and regular intervals over a 5-year follow-up period. Surgical interventions included flap surgery, guided tissue regeneration, and bone grafting, while non-surgical treatments comprised scaling and root planning with or without adjunctive antibiotics. The primary outcomes assessed included changes in probing depth, clinical attachment level, tooth loss, and patient-reported quality of life measures., Results: A total of 120 patients were included in the study, with 60 patients in each treatment group. The surgical group demonstrated significantly greater reductions in probing depth and gains in clinical attachment level compared to the non-surgical group ( P < 0.05). Tooth loss was significantly lower in the surgical group over the 5 years ( P < 0.01). Patient-reported outcomes also favored the surgical group, with improved oral health-related quality of life. However, the surgical group had a higher incidence of postoperative complications., Conclusion: This study suggests that periodontal surgery yields superior long-term outcomes in the management of aggressive periodontitis compared to non-surgical treatment., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Background: While the use of computer-assisted navigation systems in prosthetic implantation is steadily increasing, its utility in reverse shoulder arthroplasty (RSA) remains unclear. The purpose of this study was to evaluate the clinical utility of an intraoperative navigation system in patients undergoing RSA., Materials and Methods: Patients undergoing navigated or standard RSA at a single institution between September 2020 and December 2021 were prospectively enrolled. Exclusion criteria included noncompliance with study procedures or humeral fracture. Outcome measures included postoperative version and inclination, range of motion (ROM), complications, and patient-reported outcome measurements (PROMs: American Shoulder and Elbow Surgeons score [ASES], Disabilities of the Arm, Shoulder, and Hand score [DASH], Simple Shoulder Test [SST], and Visual Analog Scale [VAS]) at final follow-up., Results: The final cohort contained 16 patients with navigation and 17 with standard RSA at a mean follow-up of 16 months (range 12-18 months). Average age was 72 years (range 66-80 years), 8 male (24%) and 25 female (76%). There were no differences in demographics between groups (p > 0.05). At baseline, the navigated group had a greater proportion of Walch B1 and B2 glenoids (p = 0.04). There were no differences between groups regarding baseplate type and native/planned/postoperative glenoid version and inclination. In both groups, planned and postoperative versions were not significantly different (p = 0.76). Patients who did not have navigation demonstrated significant differences between planned and postoperative inclination (p = 0.04), while those with navigation did not (p = 0.09). PROM scores did not differ between groups at final follow-up for SST (p = 0.64), DASH (p = 0.38), ASES (p = 0.77), or VAS (p = 0.1). No difference in final ROM was found between groups (p > 0.05). Over 50% of all screws in both groups were positioned outside the second cortex (p = 0.37), albeit with no complications., Conclusions: There were no statistically significant differences in ROM, PROMs, and satisfaction between patients receiving computer-navigated and standard RSA at a short-term follow-up. Despite more severe preoperative glenoid erosion in the navigated group, all patients were able to achieve an appropriate neutral axis postoperatively. The cost effectiveness and appropriate use of computer-navigated RSA warrant specific investigation in future studies., Level of Evidence: II, prospective cohort study., Trial Registration: 9/1/2020 to 12/31/2021., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The COVID-19 pandemic has disrupted components of traditional education with shifts toward virtual platforms. This report describes the virtual approach to basic surgical skills training during a high school program in the summers of 2020 and 2021., Methods: Two 2-week sessions were held by Zoom (Zoom Video Communications) with 99 students in 2020 and 198 students in 2021. Each student was sent surgical supplies and instruments. Interactive lectures were held each morning, and basic surgical skills instruction was provided each afternoon. After the session, survey links were distributed to students to complete an anonymous 37-item questionnaire regarding surgical skills confidence, simulation kit satisfaction, and technical difficulties., Results: Of the 297 students, 270 (90.9%) completed the questionnaire, including 91 (91.9%) in 2020 and 179 (90.4%) in 2021. On a scale of 1 (fair) to 5 (excellent), students in 2020 and 2021 reported similar confidence in instrument handling (4-5: 90.0% vs 86.3%; P = .38), suturing skin (4-5: 88.9% vs 82.8%; P = .19), and thoracic aorta suturing (4-5: 73.3% vs 73.6%; P = .97). Students reported greater confidence in 2020 in knot tying (4-5: 98.9% vs 87.9%; P = .002), coronary vessel suturing (4-5: 82.2% vs 65.5%; P < .001), and valve model suturing (4-5: 68.5% vs 50.3%; P = .005) than students in 2021. Students had similar satisfaction rates with the program (extremely or somewhat satisfied: 92.3% vs 86.0%; p = .51) between 2020 and 2021., Conclusions: Virtual education carries the potential for basic surgical skills training for a more widespread audience with less access to direct surgical education. Further research is needed to optimize teaching finer surgical skills., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Type 2 diabetes (T2D) has a complex pathophysiology which makes modeling the disease difficult. We aimed to develop a novel model for simulating T2D in vitro, including hyperglycemia, hyperlipidemia, and variably elevated insulin levels targeting muscle cells. We investigated insulin resistance (IR), cellular respiration, mitochondrial morphometry, and the associated function in different T2D-mimicking conditions in rodent skeletal (C2C12) and cardiac (H9C2) myotubes. The physiological controls included 5 mM of glucose with 20 mM of mannitol as osmotic controls. To mimic hyperglycemia, cells were exposed to 25 mM of glucose. Further treatments included insulin, palmitate, or both. After short-term (24 h) or long-term (96 h) exposure, we performed radioactive glucose uptake and mitochondrial function assays. The mitochondrial size and relative frequencies were assessed with morphometric analyses using electron micrographs. C2C12 and H9C2 cells that were treated short- or long-term with insulin and/or palmitate and HG showed IR. C2C12 myotubes exposed to T2D-mimicking conditions showed significantly decreased ATP-linked respiration and spare respiratory capacity and less cytoplasmic area occupied by mitochondria, implying mitochondrial dysfunction. In contrast, the H9C2 myotubes showed elevated ATP-linked and maximal respiration and increased cytoplasmic area occupied by mitochondria, indicating a better adaptation to stress and compensatory lipid oxidation in a T2D environment. Both cell lines displayed elevated fractions of swollen/vacuolated mitochondria after T2D-mimicking treatments. Our stable and reproducible in vitro model of T2D rapidly induced IR, changes in the ATP-linked respiration, shifts in energetic phenotypes, and mitochondrial morphology, which are comparable to the muscles of patients suffering from T2D. Thus, our model should allow for the study of disease mechanisms and potential new targets and allow for the screening of candidate therapeutic compounds.

Purpose : There are many challenges that pharmacist led antimicrobial stewardship programs can encounter including lack of resources, costs, and inaccurate antimicrobial susceptibility testing (AST) results. The COVID-19 pandemic has led to increased resistance especially with gram negative infections. At a small single center community hospital, gram negative infections, particularly Escherichia coli infections, predominately occur. Therefore, this study aims to address gram negative bacteremia burden and its impact on antimicrobial stewardship efforts for combatting Escherichia coli and ESBL organisms with such barriers during the pandemic. Methods : In a retrospective cohort study, patients ≥ 18 years of age from a small community hospital were reviewed. Patients were excluded if their blood cultures were not positive for Escherichia coli and if antibiotics were not initiated during hospital stay. The primary endpoint was to determine the length of hospital stay. Critical secondary endpoints include antibiotic de-escalations, duration of antibiotics, time to definitive antibiotic therapy, serum procalcitonin levels, blood culture availabilities, MIC breakpoints, co-infection of COVID-19, and Clostridioides difficile occurrences. Results : Out of 74 patients with gram negative bacteremia, 41 patients specifically had Escherichia coli bacteremia. The primary endpoint results showed that patients with Escherichia coli bacteremia that stayed in the ICU had a length of stay of 13.6 days. Patients with Escherichia coli bacteremia in the Non-ICU setting has a length of stay of 7.3 days, and patients with ESBL bacteremia in the Non-ICU setting had a length of stay of 6.8 days. Conclusions : Despite the various challenges that antimicrobial stewardship programs (ASP) face in a single center small community hospital, the ASP at this small community hospital utilizes various policies and tools to increase appropriate antibiotic use and decrease hospital length of stay in patients with Escherichia coli bacteremia., (© Individual authors.)

Alzheimer's disease (AD) is the most common cause of dementia worldwide, but the molecular and cellular mechanisms underlying cognitive impairment remain poorly understood. To address this, we generated a single-cell transcriptomic atlas of the aged human prefrontal cortex covering 2.3 million cells from postmortem human brain samples of 427 individuals with varying degrees of AD pathology and cognitive impairment. Our analyses identified AD-pathology-associated alterations shared between excitatory neuron subtypes, revealed a coordinated increase of the cohesin complex and DNA damage response factors in excitatory neurons and in oligodendrocytes, and uncovered genes and pathways associated with high cognitive function, dementia, and resilience to AD pathology. Furthermore, we identified selectively vulnerable somatostatin inhibitory neuron subtypes depleted in AD, discovered two distinct groups of inhibitory neurons that were more abundant in individuals with preserved high cognitive function late in life, and uncovered a link between inhibitory neurons and resilience to AD pathology., Competing Interests: Declaration of interests L.-H.T. is a member of the Scientific Advisory Boards of Cognito Therapeutics, 4M Therapeutics, Cell Signaling Technology, and Souvien Therapeutics, which have no association to the work described in this manuscript., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Skeletal muscle loss and weakness are associated with bad prognosis and poorer quality of life in cancer patients. Tumor-derived factors have been implicated in muscle dysregulation by inducing cachexia and apoptosis. Here, we show that extracellular vesicles secreted by breast cancer cells impair mitochondrial homeostasis and function in skeletal muscle, leading to decreased mitochondrial content and energy production and increased oxidative stress. Mechanistically, miR-122-5p in cancer-cell-secreted EVs is transferred to myocytes, where it targets the tumor suppressor TP53 to decrease the expression of TP53 target genes involved in mitochondrial regulation, including Tfam, Pgc-1α, Sco2, and 16S rRNA. Restoration of Tp53 in muscle abolishes mitochondrial myopathology in mice carrying breast tumors and partially rescues their impaired running capacity without significantly affecting muscle mass. We conclude that extracellular vesicles from breast cancer cells mediate skeletal muscle mitochondrial dysfunction in cancer and may contribute to muscle weakness in some cancer patients., (© 2023 The Authors.)

In obesity, CD11c+ innate immune cells are recruited to adipose tissue and create an inflammatory state that causes both insulin and catecholamine resistance. We found that ablation of Gnas, the gene that encodes Gαs, in CD11c expressing cells protects mice from obesity, glucose intolerance, and insulin resistance. Transplantation studies showed that the lean phenotype was conferred by bone marrow-derived cells and did not require adaptive immunity. Loss of cAMP signaling was associated with increased adipose tissue norepinephrine and cAMP signaling, and prevention of catecholamine resistance. The adipose tissue had reduced expression of catecholamine transport and degradation enzymes, suggesting that the elevated norepinephrine resulted from decreased catabolism. Collectively, our results identified an important role for cAMP signaling in CD11c+ innate immune cells in whole-body metabolism by controlling norepinephrine levels in white adipose tissue, modulating catecholamine-induced lipolysis and increasing thermogenesis, which, together, created a lean phenotype., Article Highlights: We undertook this study to understand how immune cells communicate with adipocytes, specifically, whether cAMP signaling in the immune cell and the adipocyte are connected. We identified a reciprocal interaction between CD11c+ innate immune cells and adipocytes in which high cAMP signaling in the immune cell compartment induces low cAMP signaling in adipocytes and vice versa. This interaction regulates lipolysis in adipocytes and inflammation in immune cells, resulting in either a lean, obesity-resistant, and insulin-sensitive phenotype, or an obese, insulin-resistant phenotype., (© 2023 by the American Diabetes Association.)

Background: Studies suggest that similar clinical results are achieved via arthroscopic and open biceps tenodesis (BT) techniques., Purpose: To quantify the postoperative migration of the BT construct between arthroscopic suprapectoral BT (ASPBT) and open subpectoral BT (OSPBT) techniques via interference screw (IS) or single-suture suture anchor (SSSA) fixation using radiostereometric analysis., Study Design: Cohort study; Level of evidence, 2., Methods: Distal migration of the biceps tendon after OSPBT with a polyetheretherketone IS, OSPBT with 1 SSSA, ASPBT with polyetheretherketone IS, and ASPBT with 2 SSSAs was measured prospectively. Patients with symptomatic biceps tendinopathy and preoperative patient-reported outcome measures (PROMs) including Constant-Murley subjective, Single Assessment Numeric Evaluation, or Patient-Reported Outcomes Measurement Information System-Upper Extremity scores were included. A tantalum bead was sutured on the proximal end of the long head of the biceps tendon before fixation of tendon tissue. Anteroposterior radiographs were performed immediately postoperatively, at 1 week, and at 3 months. Bead migration was measured, and preoperative PROMs were compared with those at latest follow-up., Results: Of 115 patients, 94 (82%) were available for final follow-up. IS fixation yielded the least tendon migration with no difference between the open and arthroscopic approaches (4.31 vs 5.04 mm; P = .70). Fixation with 1 suture anchor demonstrated significantly greater migration than that achieved with an IS at both 1 week (6.47 vs 0.1 mm, 6.47 vs 1.75 mm, P < .001;) and 3 months (14.76 vs 4.31 mm, 14.76 vs 5.04 mm, P < .001) postoperatively. Two-suture anchor fixation yielded significantly greater migration than IS fixation at 1 week (7.02 vs 0.1 mm, P < .001; 7.02 vs 1.75 mm, P = .003) but not 3 months postoperatively (8.06 vs 4.31 mm, P = .10; 8.06 vs 5.04 mm, P = .07). Four patients with suture anchor fixation (3 patients in the OSPBT 1 SSSA group, 9.4%, and 1 patient in the ASPBT 2 SSSAs group, 3.8%) developed a Popeye deformity, whereas no Popeye deformities occurred in the IS groups. Mean 3-month bead migration in patients with and without a Popeye deformity was 60.8 and 11.2 mm, respectively ( P < .0001). PROMs did not differ among groups at final follow-up., Conclusion: Interference screw fixation yielded the least tendon migration whether achieved arthroscopically or open. The available data indicated that fixation with 1 SSSA but not 2 SSSAs resulted in significantly greater migration than that achieved with an IS. Despite variations in tendon migration, PROMs were similar among all groups. When SSSAs are used, tendon migration may be minimized by using ≥2 anchors.

The COVID-19 pandemic has resulted in significant morbidity and mortality worldwide. Management of the pandemic has relied mainly on SARS-CoV-2 vaccines, while alternative approaches such as meditation, shown to improve immunity, have been largely unexplored. Here, we probe the relationship between meditation and COVID-19 disease and directly test the impact of meditation on the induction of a blood environment that modulates viral infection. We found a significant inverse correlation between length of meditation practice and SARS-CoV-2 infection as well as accelerated resolution of symptomology of those infected. A meditation "dosing" effect was also observed. In cultured human lung cells, blood from experienced meditators induced factors that prevented entry of pseudotyped viruses for SARS-CoV-2 spike protein of both the wild-type Wuhan-1 virus and the Delta variant. We identified and validated SERPINA5, a serine protease inhibitor, as one possible protein factor in the blood of meditators that is necessary and sufficient for limiting pseudovirus entry into cells. In summary, we conclude that meditation can enhance resiliency to viral infection and may serve as a possible adjuvant therapy in the management of the COVID-19 pandemic., Competing Interests: Dr. Joe Dispenza's company, Encephalon, runs the meditation retreats. All other authors have no conflicts of interest., (Published by Elsevier Inc.)

Gulf War illness (GWI) is an important exemplar of environmentally-triggered chronic multisymptom illness, and a potential model for accelerated aging. Inflammation is the main hypothesized mechanism for GWI, with mitochondrial impairment also proposed. No study has directly assessed mitochondrial respiratory chain function (MRCF) on muscle biopsy in veterans with GWI (VGWI). We recruited 42 participants, half VGWI, with biopsy material successfully secured in 36. Impaired MRCF indexed by complex I and II oxidative phosphorylation with glucose as a fuel source (CI&CIIOXPHOS) related significantly or borderline significantly in the predicted direction to 17 of 20 symptoms in the combined sample. Lower CI&CIIOXPHOS significantly predicted GWI severity in the combined sample and in VGWI separately, with or without adjustment for hsCRP. Higher-hsCRP (peripheral inflammation) related strongly to lower-MRCF (particularly fatty acid oxidation (FAO) indices) in VGWI, but not in controls. Despite this, whereas greater MRCF-impairment predicted greater GWI symptoms and severity, greater inflammation did not. Surprisingly, adjusted for MRCF, higher hsCRP significantly predicted lesser symptom severity in VGWI selectively. Findings comport with a hypothesis in which the increased inflammation observed in GWI is driven by FAO-defect-induced mitochondrial apoptosis. In conclusion, impaired mitochondrial function-but not peripheral inflammation-predicts greater GWI symptoms and severity., (© 2023. The Author(s).)

Purpose: To determine the relationship between meniscus tear morphologies, stratified by location and pattern, and knee arthroplasty rates in a commercial insurance population., Methods: The PearlDiver database was queried for patients ≥35 years old with a meniscus tear of specified laterality and ≥2 years follow-up between 2015 and 2018. Two analyses were conducted with cohorts matched on age, sex, Charlson Comorbidity Index, obesity, osteoarthritis (OA), and treatment (meniscectomy vs conservative): one with equal-sized subgroups by tear location (medial only, lateral only, or both medial and lateral) and another by tear pattern (bucket-handle, complex, or peripheral). The rate of subsequent total knee arthroplasty (TKA) was compared between matched groups., Results: In total, 129,987 patients (mean age: 57.8 ± 10.5 years) were matched by tear location; 1,734 patients with medial-only tears (4.0%), 1,786 with lateral-only tears (4.1%), and 2,611 with medial plus lateral tears (6.0%) underwent a TKA within 5 years ( P < .001). Patients with both medial and lateral tears were 1.55-fold more likely to undergo TKA. In total, 24,213 patients (mean age: 56.0 ± 10.5 years) were matched by tear pattern; 296 patients with bucket-handle tears (3.7%), 373 with complex tears (4.6%), and 336 with peripheral tears (4.2%) underwent TKA ( P  = .01). Patients with complex tears were 1.29-fold more likely to undergo TKA than patients with bucket-handle tears ( P  = .002)., Conclusions: In matched cohorts of patients with degenerative meniscus tears, having both medial plus lateral tears conferred a 1.5-fold risk of TKA, whereas complex tears conferred a 1.3-fold risk within 5 years. Specific meniscal tear patterns and locations harbor varying risk in progressing to end-stage knee OA, and these data may help counsel patients about their likelihood of progressing to end-stage OA warranting an arthroplasty procedure., Level of Evidence: Level III, retrospective comparative study., (© 2023 The Authors.)

Purpose: Dry eye syndrome (DES) is a global issue occurring due to tear deficiency or excessive tear evaporation. It is associated with a variety of symptoms causing ocular discomfort. The purpose of the study was to evaluate causative factors, treatment modalities, quality of life, and preservatives used in eye drops., Methods: This prospective, follow-up study was conducted in the ophthalmology outpatient department of a tertiary care teaching hospital. Patients older than 18 years of age of either sex diagnosed with DES and willing to give written informed consent were included. The patients were subjected to the Ocular surface disease index Questionnaire (OSDI Questionnaire) twice; at the time of the first visit and at 15 days follow-up., Results: A male preponderance was observed with a 1.86:1 male-to-female ratio. The mean age of the study population was 29.15 ± 10.07 years. The most common presenting complaints were symptoms related to dryness of the eyes followed by refractive error. Exposure to TV/computer screen for more than 6 hours is the most common causative factor. There was a statistically significant improvement in overall quality of life (QoL) in patients of DES on treatment. However, no significant difference was seen in the improvement of quality of life in comparison with different preservatives used in prescribed eye drops for the treatment of DES., Conclusion: DES can adversely affect the quality of life of patients. Prompt treatment of this condition can significantly improve the patient's QoL. Physicians should be encouraged to perform quality of life evaluations for patients with DES to guide them in treatment with more individual-specific treatment options., Competing Interests: None

Background: Proximal humeral fractures are traditionally treated with open reduction and internal fixation (ORIF), but reverse total shoulder arthroplasty (RTSA) has emerged as an increasingly popular treatment option. Although ORIF with angular locking plates is a common treatment for proximal humerus fractures, prior reports suggest high failure and complication rates. Although RTSA has become an increasingly popular option for complex proximal humeral head fractures given its low complication rates, there are concerns it may lead to limited postoperative ROM. Thus, the optimal treatment for patients older than 70 years from a functional and radiographic perspective remains unclear., Questions/purposes: (1) In patients older than 70 years with three-part and four-part proximal humerus fractures, does RTSA result in better functional outcome scores (Constant, American Shoulder and Elbow Surgeons [ASES], and DASH scores) than ORIF with a locking plate? (2) Does RTSA result in greater ROM than ORIF? (3) Does RTSA result in a lower risk of complications than ORIF? (4) In patients with either procedure, what are the rates of negative radiographic outcomes in those treated with ORIF (such as malunion, bone resorption, malalignment, or avascular necrosis) or those with RTSA (such as resorption, notching, and loosening)? (5) At a minimum of 2 years of follow-up, does ORIF result in a greater number of revision procedures than RTSA?, Methods: Between January 1, 2013, and June 30, 2018, we treated 235 patients for a proximal humeral fracture. We considered only patients without previous ipsilateral fracture or surgery, other fractures, or radial nerve injuries; age older than 70 years; and patients without neurologic disease or cognitive dysfunction as potentially eligible. Sixty-nine percent (162 patients) of the patients were eligible; a further 31% (73 patients) were excluded because 18% (13 of 73 patients) did not meet the inclusion criteria, 62% (45 patients) underwent nonoperative treatment, and 21% (15 patients) declined to participate. Patients were nonrandomly allocated to receive RTSA if they had supraspinatus Goutallier/Fuchs Grade 3 or 4 atrophy or ORIF if they had supraspinatus Goutallier/Fuchs Grade 1 or 2 atrophy. This left 81 patients who were treated with RTSA and another 81 patients who were treated with ORIF. Among the 81 patients treated with RTSA, 11% (nine patients) were lost to the minimum study follow-up of 2 years or had incomplete datasets, leaving 89% (72 patients) for analysis. Among the 81 patients treated with ORIF, 19% (15 patients) were lost before the minimal study follow-up of 2 years or had incomplete datasets, leaving 82% (66 patients) for analysis. The median follow-up for both groups was 53 months (range 24 to 72 months). The mean age was 76 ± 2.9 years in the RTSA group and 73 ± 2.9 years in the ORIF group. In the RTSA group, 27 patients had a three-part fracture and 45 patients had a four-part fracture. In the ORIF group, 24 patients had three-part fractures and 42 patients had four-part fractures (p = 0.48). Shoulder function was assessed using functional outcome questionnaires (ASES, DASH, and Constant) and active ROM measurements. A surgical complication was defined as any instance of dislocations, fractures, adhesive capsulitis, nerve injuries, or surgical site infections. Radiographic outcomes after ORIF (malunion, tuberosity resorption, or avascular necrosis) and RTSA (notching and osteolysis) were assessed. In calculating the revision rate, we considered unplanned revision procedures only., Results: Compared with patients treated with ORIF, patients treated with RTSA had superior improvements in Constant (85.0 ± 7.0 versus 53.0 ± 5.0; mean difference 32 [95% CI 30 to 34]; p < 0.01), ASES (46.3 ± 3.7 versus 30.0 ± 3.5; mean difference 16 [95% CI 15 to 18]; p < 0.01), and DASH scores (40.5 ± 4.2 versus 30.5 ± 2.6; mean difference 10 [95% CI 9 to 11]; p < 0.01). The mean elevation was 135° ± 7° for patients with RTSA and 100° ± 6° for patients with ORIF (mean difference 35 o [95% CI 33 to 37]; p < 0.01). The mean abduction was 131° ± 7° for patients with RTSA and 104° ± 6° for those with ORIF (mean difference 27 o [95% CI 25° to 29°]; p < 0.01). The mean external rotation was 85° ± 5° for patients with RTSA and 64° ± 5° for those with ORIF (mean difference 21° [95% CI 19° to 23°]; p < 0.01). The mean internal rotation was 45° ± 6° for patients with RTSA and 40° ± 6° for those with ORIF (mean difference 5° [95% CI 3° to 7°]; p < 0.01). The risk of complications was not different between patients with ORIF and those with RTSA (5% [three of 66] versus 1% [one of 72]; relative risk 3.3 [95% CI 0.3 to 30.7]; p = 0.30). Among patients with ORIF, 8% had varus malunions (five of 66), 6% had resorption of the greater tuberosity (four of 66), and 2% had avascular necrosis of the humeral head (one of 66). In the RTSA group, 24% (17 of 72 patients) demonstrated reabsorption of periprosthetic bone and 79% of patients (57 of 72) exhibited no notching. The risk of revision was not different between the RTSA and ORIF groups (0% [0 of 72] versus 9% [six of 66]; relative risk 0.07 [95% CI 0.0 to 1.2]; p = 0.07)., Conclusion: In patients older than 70 years with three-part and four-part proximal humerus fractures, primary RTSA resulted in better patient-reported outcome scores and better ROM than ORIF with an angular stable locking plate. Our findings might help surgeons decide between internal fixation and arthroplasty to surgically treat these injuries in older patients. Although RTSA seems to be a preferable treatment modality in view of these findings, longer follow-up is required to evaluate its longevity compared with ORIF with an angular locking plate. Dissimilar to ORIF, which is generally stable once healed, arthroplasties are at a continued risk for loosening and infection even after healing is complete., Level of Evidence: Level II, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2022 by the Association of Bone and Joint Surgeons.)

Objectives: To determine in patients with acute respiratory distress syndrome (ARDS) on venovenous extracorporeal membrane oxygenation (VV ECMO) whether reducing driving pressure (ΔP) would decrease plasma biomarkers of inflammation and lung injury (interleukin-6 [IL-6], IL-8, and the soluble receptor for advanced glycation end-products sRAGE)., Design: A single-center prospective physiologic study., Setting: At a single university medical center., Participants: Adult patients with severe COVID-19 ARDS on VV ECMO., Interventions: Participants on VV ECMO had the following biomarkers measured: (1) pre-ECMO with low-tidal-volume ventilation (LTVV), (2) post-ECMO with LTVV, (3) during low-driving-pressure ventilation (LDPV), (4) after 2 hours of very low driving-pressure ventilation (V-LDPV, main intervention ΔP = 1 cmH 2 O), and (5) 2 hours after returning to LDPV., Main Measurements and Results: Twenty-six participants were enrolled; 21 underwent V-LDPV. There was no significant change in IL-6, IL-8, and sRAGE from LDPV to V-LDPV and from V-LDPV to LDPV. Only participants (9 of 21) with nonspontaneous breaths had significant change (p < 0.001) in their tidal volumes (V t ) (mean ± SD), 1.9 ± 0.5, 0.1 ± 0.2, and 2.0 ± 0.7 mL/kg predicted body weight (PBW). Participants with spontaneous breathing, V t were unchanged-4.5 ± 3.1, 4.7 ± 3.1, and 5.6 ± 2.9 mL/kg PBW (p = 0.481 and p = 0.065, respectively). There was no relationship found when accounting for V t changes and biomarkers., Conclusions: Biomarkers did not significantly change with decreased ΔPs or V t changes during the first 24 hours post-ECMO. Despite deep sedation, reductions in V t during V-LDPV were not reliably achieved due to spontaneous breaths. Thus, patients on VV ECMO for ARDS may have higher V t (ie, transpulmonary pressure) than desired despite low ΔPs or V t ., (Published by Elsevier Inc.)

Role of blood-based factors in development and progression of heart failure (HF) is poorly characterized. Blood contains factors released during pathophysiological states that may impact cellular function and provide mechanistic insights to HF management. We tested effects of blood from two distinct HF models on cardiac metabolism and identified possible cellular targets of the effects. Blood plasma was obtained from daunorubicin- and myocardial infarction-induced HF rabbits (Dauno-HF and MI-HF) and their controls (Dauno-Control and MI-Control). Effects of plasma on bioenergetics of myocardial tissue from healthy mice and cellular cardiac components were assessed using high-resolution respirometry and Seahorse flux analyzer. Since endothelial cell respiration was profoundly affected by HF plasma, effects of plasma on endothelial cell barrier function and death were further evaluated. Western-blotting and electron microscopy were performed to evaluate mitochondrial proteins and morphology. Brief exposure to HF plasma decreased cardiac tissue respiration. Endothelial cell respiration was most impacted by exposure to HF plasma. Endothelial cell monolayer integrity was decreased by incubation with Dauno-HF plasma. Apoptosis and necrosis were increased in cells incubated with Dauno-HF plasma for 24 h. Down-regulation of voltage-dependent anion-selective channel (VDAC)-1, translocase of outer membrane 20 (Tom20), and mitochondrial fission factor (MFF) in cells exposed to Dauno-HF plasma and mitochondrial signal transducer and activator of transcription 3 (Stat3) and MFF in cells exposed to MI-HF plasma were observed. Mitochondrial structure was disrupted in cells exposed to HF plasma. These findings indicate that endothelial cells and mitochondrial structure and function may be primary target where HF pathology manifests and accelerates. High-throughput blood-based screening of HF may provide innovative ways to advance disease diagnosis and management., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The popularity of platelet-rich plasma (PRP) injections for the treatment of orthopaedic conditions has grown markedly. We sought to better define the trends in the usage of orthopaedic PRP injections across an insured US population over the past decade., Methods: The PearlDiver M91Ortho commercial administrative claims database was queried for all patients receiving PRP injections for orthopaedic conditions from 2010 through the first quarter of 2020 (Q1.2020). Trends in PRP use, reimbursement charges, demographics, joints injected, and administering physicians were assessed over time and reported as year-over-year (YOY) changes., Results: Over the study period, 14,096 unique patients had 17,759 orthopaedic PRP injections. The number of PRP injections administered had a YOY increase of 7.1% (144 injections/year, 95% confidence interval [CI] = 89 to 199, Ptrend = 0.0009). A YOY increase of 895% was observed in total nonsurgical charges ($683,974/yr, 95% CI 441,504 to 926,444, Ptrend = 0.0009). The median age of PRP recipients increased (YOY change = +0.6 years, 95% CI 0.4 to 0.8, Ptrend = 0.0005). Injections to the elbow (YOY change = -0.8%, 95% CI -0.10% to [-0.06%], Ptrend = 0.005) and foot/ankle (YOY change = -1.0%, 95% CI -1.4% to [-0.06%], Ptrend = 0.002) decreased, whereas hip (YOY change = +0.4%, 95% CI 0.2% to 0.6%, Ptrend = 0.019), knee (YOY change = +0.9%, 95% CI 0.3% to 1.2%, Ptrend = 0.016), and spine (YOY change = +0.2%, 95% CI 0.0% to 0.4%, Ptrend = 0.033) injections increased. PRP injections given by sports medicine orthopaedic surgeons (YOY change = +0.8%, 95% CI 0.6% to 1.2%, Ptrend <0.0001) increased over time, whereas those by general orthopaedic surgeons decreased (YOY change = -0.9, 95% CI -1.2 to [-0.6%], Ptrend = 0.001)., Conclusion: PRP injections quadrupled in prevalence from 2010 to Q1.2020, with a projected increase in annual usage in this data set of 66% by 2030. As greater evidence-based indications for PRP use are identified, more specialists and insurance providers may consider expanding their involvement in this growing field., Level of Evidence: III, retrospective cohort study., (Copyright © 2022 by the American Academy of Orthopaedic Surgeons.)

The "oxygen paradox" can be explained as two opposing biological processes with oxygen (O 2 ) as a reactant. On the one hand, oxygen is essential to aerobic metabolism, powering oxidative phosphorylation in mitochondria. On the other hand, an excess supply of oxygen will generate reactive species which are harmful for the cell. In healthy tissues, the first process must be maximized relative to the second one. We have hypothesized that curved and cholesterol-enriched membrane invaginations called caveolae help maintain the proper oxygen level by taking up oxygen and attenuating its release to the mitochondria. The mechanism by which caveolae may help to buffer the oxygen level in cells is still unclear. Here, we aim to assess how structural aspects of caveolae, the curvature of the membrane, influence the local oxygen abundance and the membrane partitioning. We have modelled a flat bilayer and a liposome composed of dipalmitoylphosphatidylcholine (DPPC), using molecular dynamics simulation. Associated changes in the membrane-level oxygen partition coefficient and free energy profiles will be presented., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Persistent quadriceps weakness is a problematic sequela of anterior cruciate ligament reconstruction (ACLR). The purposes of this review are to summarize neuroplastic changes after ACL reconstruction; provide an overview of a promising interventions, motor imagery (MI), and its utility in muscle activation; and propose a framework using a brain-computer interface (BCI) to augment quadriceps activation. A literature review of neuroplastic changes, MI training, and BCI-MI technology in postoperative neuromuscular rehabilitation was conducted in PubMed, Embase, and Scopus. Combinations of the following search terms were used to identify articles: "quadriceps muscle," "neurofeedback," "biofeedback," "muscle activation," "motor learning," "anterior cruciate ligament," and "cortical plasticity." We found that ACLR disrupts sensory input from the quadriceps, which results in reduced sensitivity to electrochemical neuronal signals, an increase in central inhibition of neurons regulating quadriceps control and dampening of reflexive motor activity. MI training consists of visualizing an action, without physically engaging in muscle activity. Imagined motor output during MI training increases the sensitivity and conductivity of corticospinal tracts emerging from the primary motor cortex, which helps "exercise" the connections between the brain and target muscle tissues. Motor rehabilitation studies using BCI-MI technology have demonstrated increased excitability of the motor cortex, corticospinal tract, spinal motor neurons, and disinhibition of inhibitory interneurons. This technology has been validated and successfully applied in the recovery of atrophied neuromuscular pathways in stroke patients but has yet to be investigated in peripheral neuromuscular insults, such as ACL injury and reconstruction. Well-designed clinical studies may assess the impact of BCI on clinical outcomes and recovery time. Quadriceps weakness is associated with neuroplastic changes within specific corticospinal pathways and brain areas. BCI-MI shows strong potential for facilitating recovery of atrophied neuromuscular pathways after ACLR and may offer an innovative, multidisciplinary approach to orthopaedic care., Level of Evidence: V, expert opinion., (© 2022 The Authors.)

Purpose: Consensus guidelines recommend administering a corticosteroid injection (CSI) for patients with a symptomatic degenerative meniscus lesion prior to arthroscopic partial meniscectomy (APM). A recent study found that CSI administered within 1 month prior to meniscectomy is associated with an increased risk of postoperative infection. However, infections may range in severity from superficial infections to serious infections requiring surgical interventions. The aim of this analysis was to define the rate of infections requiring surgery after APM and determine its relationship to preoperative CSI., Methods: The PearlDiver Mariner administrative claims database was queried for patients > 35 years old who had a CSI in the year prior to isolated APM. Rates of deep infection and infection requiring surgery within 6 months were reported between matched patients with a CSI and no injection., Results: After matching, there were 16,009 patients per group with a mean age of 59.4 years (SD = 9.6), 53.5% obesity, and 40% male. Forty-four of 113 patients who developed a postoperative deep infection went on to have a reoperation for irrigation and/or debridement (0.1% of all APM). Of these 44 patients, 30 had a preoperative CSI and 14 were controls unadjusted odds ratio (unadj-OR) if given CSI = 1.95, 95% CI 1.03-3.68, P = 0.04). Having a CSI within the month before surgery conferred a 4.56-fold increase in odds of an infection warranting surgery (95% CI 1.96-10.21, P < 0.01), whilst having a CSI 4-8 weeks before surgery conferred a 2.42-fold increase in odds (95% CI 1.04-5.42, P = 0.03). Receiving multiple CSI in the year prior to APM was associated with 5.27-fold increased odds of an infection requiring surgery (95% CI 1.19-23.27, P = 0.03), compared to having a single CSI., Conclusions: Serious infections requiring a surgical intervention are rare after a meniscectomy, occurring in 0.1% of APMs in a matched cohort of patients over 35. Patients were five times more likely to return to the operating room for infection after APM if they had a CSI in the month before or had multiple CSIs in the year before surgery. The risk of infection was no longer significant if there was at least a 2-month interval between preoperative CSI and APM., Level of Evidence: Level III., (© 2022. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

➢: Posterior humeral avulsions of the inferior glenohumeral ligament represent an increasingly recognized but likely underdiagnosed source of posterior shoulder instability and pain., ➢: Injuries are commonly reported in athletic individuals who have sustained injury by either traumatic or atraumatic mechanisms; the ligament is most susceptible to injury with the shoulder in flexion, adduction, and internal rotation., ➢: Posterior humeral avulsions of the glenohumeral ligament often occur in the setting of concurrent injuries to the posterior or inferior labrum., ➢: Diagnosis is often challenging due to nonspecific symptoms and physical examination findings; a magnetic resonance arthrogram generally is utilized to identify avulsion from the humeral attachment; however, a definitive diagnosis is often made at the time of arthroscopic evaluation., ➢: In patients with persistent discomfort and limitations following nonoperative management, operative fixation, primarily utilizing arthroscopic techniques, can be performed to restore motion and glenohumeral stability., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/A853)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Purpose: To characterize how severe acute respiratory syndrome coronavirus 2 infection in the perioperative period affects the medical adverse event (MAE) rates in arthroscopic sports medicine procedures., Methods: The Mariner coronavirus disease 2019 (COVID-19) database was queried for all shoulder, hip, or knee arthroscopies, 2010 to 2020. Patients with COVID-19 in the 3 months before to 3 months after their surgery were matched by age, sex, and Charlson Comorbidity Index to patients with an arthroscopy but no perioperative COVID-19 infection, or a COVID-19 infection but no arthroscopic procedure. MAEs in the 3 months after surgery or illness were compared between groups., Results: The final cohort consisted of 1,299 matched patients in 3 groups: COVID-19 alone, arthroscopy and perioperative COVID-19, and arthroscopy alone. There were 265 MAEs if a patient had COVID-19 alone (20.4%), 200 MAEs if a patient had arthroscopy with COVID-19 (15.4%), and 71 (5.5%) MAEs if a patient had arthroscopy alone ( P < .01). If a patient had an arthroscopy, having COVID-19 was associated with 3.1-fold elevated odds (95% confidence interval [CI] 2.9-3.4, P < .01) of MAE. Among patients with an arthroscopy, MAEs were more common if a patient acquired COVID-19 in the 3 months after their surgery (pooled odds ratio 7.39, 95% CI 5.49-9.95, P < .01) but not if a patient had preoperative COVID-19 (pooled odds ratio 0.66, 95% CI 0.42-1.03, P  = .07)., Conclusions: Having COVID-19 during the postoperative period appears to confer a 7-fold elevated risk of MAEs after shoulder, hip, and knee arthroscopy compared with matched patients with arthroscopy and no perioperative COVID-19 but equivalent to that of patients with COVID-19 and no arthroscopy. However, there was no increase in postoperative MAEs if a patient had COVID-19 during the 3 months preceding surgery. Therefore, it appears safe to conduct an arthroscopic procedure shortly after recovery from COVID-19 without an increase in acute medical complication rates., Level of Evidence: Level III, retrospective cohort study., (© 2022 Published by Elsevier Inc. on behalf of the Arthroscopy Association of North America.)