Neither All-Inside, nor Inside-Out, nor Outside-In Repair Demonstrates Superior Biomechanical Properties for Vertical Meniscal Tears: A Systematic Review of Human Cadaveric Studies.

PURPOSE: To systematically review the literature regarding the biomechanical properties of different repair techniques and fixation methods for vertically oriented meniscal tears. METHODS: Human cadaveric studies evaluating the biomechanical properties of different repair techniques for vertically oriented meniscal tears were identified using the PubMed, EMBASE, and Cumulative Index to Nursing & Allied Health databases. Primary outcomes included load to failure, displacement, stiffness, peak contact pressure, and contact area of repaired menisci. Repair techniques from included studies were reclassified into a total of 19 distinct all-inside (AI), inside-out (IO), or outside-in (OI) techniques. RESULTS: Sixteen studies were included (420 total menisci). Contact pressure and area were restored to intact-state values across all 5 compressive load studies at low knee flexion angles but not at greater knee flexion angles (i.e., >60°). There were no significant differences in contact pressure or area between AI, IO, and OI techniques across all studies. Some studies demonstrated statistically significant advantages in tensile properties with IO techniques when compared with AI techniques, whereas others found AI techniques to be superior. No studies directly compared tensile properties of OI techniques with those of AI or IO techniques. Vertical mattress suture configurations resulted in significantly greater load to failure and decreased displacement compared with horizontal mattress configurations in 67% of studies comparing the 2 techniques. There was no difference in the rate of tissue failure in AI (66.97%), IO (60.38%), or OI (66.67%, χ2 = 0.83, P = .66) techniques. CONCLUSIONS: Contact mechanics are reliably restored after repair of vertical meniscal tears at low flexion angles but inconsistently restored at greater flexion angles, regardless of technique. Vertical mattress configurations outperformed horizontal mattress configurations under tensile load. There are conflicting data regarding the comparison of tensile properties between AI and IO techniques. Ultimately, neither AI, IO, nor OI repair demonstrated superior biomechanical properties in the present literature. CLINICAL RELEVANCE: Several repair techniques demonstrate favorable biomechanical properties for vertical meniscal tears under tensile and compressive loads. Neither AI, IO, nor OI repair techniques demonstrate superior biomechanical properties at this time.

Cocaine addiction is associated with abnormal prefrontal function, increased striatal connectivity and sensitivity to monetary incentives, and decreased connectivity outside the human reward circuit.

Cocaine addiction has been associated with increased sensitivity of the human reward circuit to drug-related stimuli. However, the capacity of non-drug incentives to engage this network is poorly understood. Here, we characterized the functional sensitivity to monetary incentives and the structural integrity of the human reward circuit in abstinent cocaine-dependent (CD) patients and their matched controls. We assessed the BOLD response to monetary gains and losses in 30 CD patients and 30 healthy controls performing a lottery task in a magnetic resonance imaging scanner. We measured brain gray matter volume (GMV) using voxel-based morphometry and white matter microstructure using voxel-based fractional anisotropy (FA). Functional data showed that, after monetary incentives, CD patients exhibited higher activation in the ventral striatum than controls. Furthermore, we observed an inverted BOLD response pattern in the prefrontal cortex, with activity being highest after unexpected high gains and lowest after losses. Patients showed increased GMV in the caudate and the orbitofrontal cortex, increased white matter FA in the orbito-striatal pathway but decreased FA in antero-posterior association bundles. Abnormal activation in the prefrontal cortex correlated with GMV and FA increases in the orbitofrontal cortex. While functional abnormalities in the ventral striatum were inversely correlated with abstinence duration, structural alterations were not. In conclusion, results suggest abnormal incentive processing in CD patients with high salience for rewards and punishments in subcortical structures but diminished prefrontal control after adverse outcomes. They further suggest that hypertrophy and hyper-connectivity within the reward circuit, to the expense of connectivity outside this network, characterize cocaine addiction.

Muscle magnetic resonance imaging abnormalities in X-linked myopathy with excessive autophagy.

INTRODUCTION: X-linked myopathy with excessive autophagy (XMEA) is an X-linked recessive myopathy due to recently reported mutations in the VMA21 gene. METHODS: Four men from 2 separate families were studied. The clinical presentation, genetic data, muscle biopsy, and muscle MRI were analyzed. RESULTS: A known VMA21 mutation, c.163+4A>G, and a new mutation, c.163+3A>G, respectively, were found in the 2 families. The clinical course was characterized by onset in childhood and progressive muscle weakness with a limb-girdle pattern. Muscle biopsy revealed a mild myopathy with an increased number of giant autophagic vacuoles. Whole-body muscle MRI showed that pelvic girdle and proximal thighs were the most and earliest affected territories, with sparing of rectus femoris muscles. Muscle changes essentially consisted of degenerative fatty replacement. CONCLUSIONS: This study highlights a distinctive MRI pattern of muscle involvement, which can be helpful for diagnosis of XMEA, even before muscle biopsy or genetic analysis.

Mutations in dynamin 2 cause dominant centronuclear myopathy.

Autosomal dominant centronuclear myopathy is a rare congenital myopathy characterized by delayed motor milestones and muscular weakness. In 11 families affected by centronuclear myopathy, we identified recurrent and de novo missense mutations in the gene dynamin 2 (DNM2, 19p13.2), which encodes a protein involved in endocytosis and membrane trafficking, actin assembly and centrosome cohesion. The transfected mutants showed reduced labeling in the centrosome, suggesting that DNM2 mutations might cause centronuclear myopathy by interfering with centrosome function.

RPM: An open-source Rotation Platform for open- and closed-loop vestibular stimulation in head-fixed Mice.

Head fixation allows the recording and presentation of controlled stimuli and is used to study neural processes underlying spatial navigation. However, it disrupts the head direction system because of the lack of vestibular stimulation. To overcome this limitation, we developed a novel rotation platform which can be driven by the experimenter (open-loop) or by animal movement (closed-loop). The platform is modular, affordable, easy to build and open source. Additional modules presented here include cameras for monitoring eye movements, visual virtual reality, and a micro-manipulator for positioning various probes for recording or optical interference. We demonstrate the utility of the platform by recording eye movements and showing the robust activation of head-direction cells. This novel experimental apparatus combines the advantages of head fixation and intact vestibular activity in the horizontal plane. The open-loop mode can be used to study e.g., vestibular sensory representation and processing, while the closed-loop mode allows animals to navigate in rotational space, providing a better substrate for 2-D navigation in virtual environments. The full build documentation is maintained at https://ranczlab.github.io/RPM/.

The subacromial bursa modulates tendon healing after rotator cuff injury in rats.

Rotator cuff injuries result in more than 500,000 surgeries annually in the United States, many of which fail. These surgeries typically involve repair of the injured tendon and removal of the subacromial bursa, a synovial-like tissue that sits between the rotator cuff and the acromion. The subacromial bursa has been implicated in rotator cuff pathogenesis and healing. Using proteomic profiling of bursa samples from nine patients with rotator cuff injury, we show that the bursa responds to injury in the underlying tendon. In a rat model of supraspinatus tenotomy, we evaluated the bursa's effect on the injured supraspinatus tendon, the uninjured infraspinatus tendon, and the underlying humeral head. The bursa protected the intact infraspinatus tendon adjacent to the injured supraspinatus tendon by maintaining its mechanical properties and protected the underlying humeral head by maintaining bone morphometry. The bursa promoted an inflammatory response in injured rat tendon, initiating expression of genes associated with wound healing, including Cox2 and Il6. These results were confirmed in rat bursa organ cultures. To evaluate the potential of the bursa as a therapeutic target, polymer microspheres loaded with dexamethasone were delivered to the intact bursae of rats after tenotomy. Dexamethasone released from the bursa reduced Il1b expression in injured rat supraspinatus tendon, suggesting that the bursa could be used for drug delivery to reduce inflammation in the healing tendon. Our findings indicate that the subacromial bursa contributes to healing in underlying tissues of the shoulder joint, suggesting that its removal during rotator cuff surgery should be reconsidered.

Severe Charcot-Marie-Tooth disease type 1E caused by a novel p.Phe84Leufs*24 PMP22 point mutation.

We report a severe phenotype of Charcot-Marie-Tooth (CMT) disease type 1E caused by a novel p.Phe84Leufs*24 PMP22 point mutation. Ultrastructural examination of a nerve biopsy showed non- or partly myelinated axons which were surrounded by "onion bulb" formations mainly composed of concentric basement membranes and characterized by the presence of prominent concentric or longitudinal collagen fibrils interspersed with basement membranes. PMP22 point mutations are rare and responsible for polyneuropathies often demyelinating with onion bulb formations composed of concentric and redundant basement membranes. Entrapment of prominent collagen fibrils within onion bulb formations is unusual, even in the large spectrum of CMT disease with long duration and severe damage.

Spastic paraplegia gene 7 in patients with spasticity and/or optic neuropathy.

Mutations in the spastic paraplegia 7 (SPG7) gene encoding paraplegin are responsible for autosomal recessive hereditary spasticity. We screened 135 unrelated index cases, selected in five different settings: SPG7-positive patients detected during SPG31 analysis using SPG31/SPG7 multiplex ligation-dependent probe amplification (n = 7); previously reported ambiguous SPG7 cases (n = 5); patients carefully selected on the basis of their phenotype (spasticity of the lower limbs with cerebellar signs and/or cerebellar atrophy on magnetic resonance imaging/computer tomography scan and/or optic neuropathy and without other signs) (n = 24); patients with hereditary spastic paraparesis referred consecutively from attending neurologists and the national reference centre in a diagnostic setting (n = 98); and the index case of a four-generation family with autosomal dominant optic neuropathy but no spasticity linked to the SPG7 locus. We identified two SPG7 mutations in 23/134 spastic patients, 21% of the patients selected according to phenotype but only 8% of those referred directly. Our results confirm the pathogenicity of Ala510Val, which was the most frequent mutation in our series (65%) and segregated at the homozygous state with spastic paraparesis in a large family with autosomal recessive inheritance. All SPG7-positive patients tested had optic neuropathy or abnormalities revealed by optical coherence tomography, indicating that abnormalities in optical coherence tomography could be a clinical biomarker for SPG7 testing. In addition, the presence of late-onset very slowly progressive spastic gait (median age 39 years, range 18-52 years) associated with cerebellar ataxia (39%) or cerebellar atrophy (47%) constitute, with abnormal optical coherence tomography, key features pointing towards SPG7-testing. Interestingly, three relatives of patients with heterozygote SPG7 mutations had cerebellar signs and atrophy, or peripheral neuropathy, but no spasticity of the lower limbs, suggesting that SPG7 mutations at the heterozygous state might predispose to late-onset neurodegenerative disorders, mimicking autosomal dominant inheritance. Finally, a novel missense SPG7 mutation at the heterozygous state (Asp411Ala) was identified as the cause of autosomal dominant optic neuropathy in a large family, indicating that some SPG7 mutations can occasionally be dominantly inherited and be an uncommon cause of isolated optic neuropathy. Altogether, these results emphasize the clinical variability associated with SPG7 mutations, ranging from optic neuropathy to spastic paraplegia, and support the view that SPG7 screening should be carried out in both conditions.

Rerupture and wound complications following Achilles tendon repair: A systematic review.

Despite the relatively high frequency of Achilles ruptures, there is no general consensus on the optimal treatment method. A general trend toward more patients being treated nonoperatively has emerged recently with the advent of functional rehabilitation. However, much of the recent data on this subject has been highly variable. This systematic review focused on Achilles tendon rupture (ATR) treatment outcomes, with a focus on rerupture and complication rates. This systematic review specifically focused on articles regarding ATR treatment that also included rerupture and complication rates. Treatments were divided into three categories: open minimally invasive, open standard, and nonoperative. Bivariate analyses were performed to compare complication and rerupture rates among pairs of treatment options, as well as between early weight bearing versus immobilization. There was significantly higher complications for minimally invasive compared to nonoperative treatment (risk ratio [RR] = 4.4154; p < 0.05), lower complication rates for minimally invasive compared to open treatment (RR = 0.3231; p < 0.05), and higher complications for open standard compared to nonoperative treatment (RR = 5.6350; p < 0.001). There were significantly lower rerupture rates in minimally invasive compared to nonoperative treatment (RR = 0.4085; p < 0.001), a significantly lower rerupture rate in nonoperative treatment compared to open treatment (RR = 0.2282; p < 0.001), and no significant difference in rerupture rates when comparing minimally invasive to open standard treatment. We found that operative treatment is associated with fewer reruptures and more complications than a nonoperative approach. Minimally invasive surgery appears to be associated with a lower rate of complications than open operative treatment.

The subacromial bursa is a key regulator of the rotator cuff and a new therapeutic target for improving repair.

Rotator cuff injuries result in over 500,000 surgeries performed annually, an alarmingly high number of which fail. These procedures typically involve repair of the injured tendon and removal of the subacromial bursa. However, recent identification of a resident population of mesenchymal stem cells and inflammatory responsiveness of the bursa to tendinopathy indicate an unexplored biological role of the bursa in the context of rotator cuff disease. Therefore, we aimed to understand the clinical relevance of bursa-tendon crosstalk, characterize the biologic role of the bursa within the shoulder, and test the therapeutic potential for targeting the bursa. Proteomic profiling of patient bursa and tendon samples demonstrated that the bursa is activated by tendon injury. Using a rat to model rotator cuff injury and repair, tenotomy-activated bursa protected the intact tendon adjacent to the injured tendon and maintained the morphology of the underlying bone. The bursa also promoted an early inflammatory response in the injured tendon, initiating key players in wound healing. In vivo results were supported by targeted organ culture studies of the bursa. To examine the potential to therapeutically target the bursa, dexamethasone was delivered to the bursa, prompting a shift in cellular signaling towards resolution of inflammation in the healing tendon. In conclusion, contrary to current clinical practice, the bursa should be retained to the greatest extent possible and provides a new therapeutically target for improving tendon healing outcomes. One Sentence Summary: The subacromial bursa is activated by rotator cuff injury and regulates the paracrine environment of the shoulder to maintain the properties of the underlying tendon and bone.

Hedgehog Activation for Enhanced Rotator Cuff Tendon-to-Bone Healing.

BACKGROUND: Rotator cuff repair is a common orthopaedic procedure, yet the rate of failure to heal after surgery is high. Repair site rupture is due to poor tendon-to-bone healing and lack of regeneration of the native fibrocartilaginous enthesis. During development, the enthesis is formed and mineralized by a pool of progenitors activated by hedgehog signaling. Furthermore, hedgehog signaling drives regenerative enthesis healing in young animals, in contrast to older animals, in which enthesis injuries heal via fibrovascular scar and without participation of hedgehog signaling. HYPOTHESIS: Hedgehog activation improves tendon-to-bone healing in an animal model of rotator cuff repair. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 78 adult Sprague-Dawley rats were used. Supraspinatus tendon injury and repair were completed bilaterally, with microsphere-encapsulated hedgehog agonist administered to right shoulders and control microspheres administered to left shoulders. Animals were sacrificed after 3, 14, 28, or 56 days. Gene expression and histological, biomechanical, and bone morphometric analyses were conducted. RESULTS: At 3 days, hedgehog signaling pathway genes Gli1 (1.70; P = .029) and Smo (2.06; P = .0173), as well as Runx2 (1.69; P = .0386), a transcription factor of osteogenesis, were upregulated in treated relative to control repairs. At 14 days, transcription factors of tenogenesis, Scx (4.00; P = .041), and chondrogenesis, Sox9 (2.95; P = .010), and mineralized fibrocartilage genes Col2 (3.18; P = .031) and Colx (1.85; P = .006), were upregulated in treated relative to control repairs. Treatment promoted fibrocartilage formation at the healing interface by 28 days, with improvements in tendon-bone maturity, organization, and continuity. Treatment led to improved biomechanical properties. The material property strength (2.43 vs 1.89 N/m2; P = .046) and the structural property work to failure (29.01 vs 18.09 mJ; P = .030) were increased in treated relative to control repairs at 28 days and 56 days, respectively. Treatment had a marginal effect on bone morphometry underlying the repair. Trabecular thickness (0.08 vs 0.07 mm; P = .035) was increased at 28 days. CONCLUSION: Hedgehog agonist treatment activated hedgehog signaling at the tendon-to-bone repair site and prompted increased mineralized fibrocartilage production. This extracellular matrix production and mineralization resulted in improved biomechanical properties, demonstrating the therapeutic potential of hedgehog agonism for improving tendon-to-bone healing after rotator cuff repair. CLINICAL RELEVANCE: This study demonstrates the therapeutic potential of hedgehog agonist treatment for improving tendon-to-bone healing after rotator cuff injury and repair.

A low-cost device for cryoanesthesia of neonatal rodents.

Studying the development of neural circuits in rodent models requires surgical access to the neonatal brain. Since commercially available stereotaxic and anesthetic equipment is designed for use in adults, reliable targeting of brain structures in such young animals can be challenging. Hypothermic cooling (cryoanesthesia) has been used as a preferred anesthesia approach in neonates. This commonly involves submerging neonates in ice, an approach that is poorly controllable. We have developed an affordable, simple to construct device - CryoPup - that allows for fast and robust cryoanesthesia of rodent pups. CryoPup consists of a microcontroller controlling a Peltier element and a heat exchanger. It is capable of both cooling and heating, thereby also functioning as a heating pad during recovery. Importantly, it has been designed for size compatibility with common stereotaxic frames. We validate CryoPup in neonatal mice, demonstrating that it allows for rapid, reliable and safe cryoanesthesia and subsequent recovery. This open-source device will facilitate future studies into the development of neural circuits in the postnatal brain.

The Posterior Cranial Vertical Line: A Novel Radiographic Marker for Classifying Global Sagittal Alignment.

OBJECTIVE: To define a novel radiographic measurement, the posterior cranial vertical line (PCVL), in an asymptomatic adult population to better understand global sagittal alignment. METHODS: We performed a multicenter retrospective review of prospectively collected radiographic data on asymptomatic volunteers aged 20-79. The PCVL is a vertical plumb line drawn from the posterior-most aspect of the occiput. The horizontal distances of the PCVL to the thoracic apex (TA), posterior sagittal vertical line (PSVL, posterosuperior endplate of S1), femoral head center, and tibial plafond were measured. Classification was either grade 1 (PCVL posterior to TA and PSVL), grade 2 (PCVL anterior to TA and posterior to PSVL), or grade 3 (PCVL anterior to TA and PSVL). RESULTS: Three hundred thirty-four asymptomatic patients were evaluated with a mean age of 41 years. Eighty-three percent of subjects were PCVL grade 1, 15% were grade 2, and 3% were grade 3. Increasing PCVL grade was associated with increased age (p < 0.001), C7-S1 sagittal vertical axis (SVA) (p < 0.001), C2-7 SVA (p < 0.001). Additionally, it was associated with decreased SS (p = 0.045), increased PT (p < 0.001), and increased knee flexion (p < 0.001). CONCLUSION: The PCVL is a radiographic marker of global sagittal alignment that is simple to implement and interpret. Increasing PCVL grade was significantly associated with expected changes and compensatory mechanisms in the aging population. Most importantly, it incorporates cervical alignment parameters such as C2-7 SVA. The PCVL defines global sagittal alignment in adult volunteers and naturally distributes into 3 grades, with only 3% being grade 3 where the PCVL lies anterior to the TA and PSVL.

OptoPi: An open source flexible platform for the analysis of small animal behaviour.

Behaviour is the ultimate output of neural circuit computations, and therefore its analysis is a cornerstone of neuroscience research. However, every animal and experimental paradigm requires different illumination conditions to capture and, in some cases, manipulate specific behavioural features. This means that researchers often develop, from scratch, their own solutions and experimental set-ups. Here, we present OptoPi, an open source, affordable (∼ £600), behavioural arena with accompanying multi-animal tracking software. The system features highly customisable and reproducible visible and infrared illumination and allows for optogenetic stimulation. OptoPi acquires images using a Raspberry Pi camera, features motorised LED-based illumination, Arduino control, as well as irradiance monitoring to fine-tune illumination conditions with real time feedback. Our open-source software (BioImageProcessing) can be used to simultaneously track multiple unmarked animals both in on-line and off-line modes. We demonstrate the functionality of OptoPi by recording and tracking under different illumination conditions the spontaneous behaviour of larval zebrafish as well as adult Drosophila flies and their first instar larvae, an experimental animal that due to its small size and transparency has classically been hard to track. Further, we showcase OptoPi's optogenetic capabilities through a series of experiments using transgenic Drosophila larvae.

Mutational spectrum in the Ca(2+)--activated cation channel gene TRPM4 in patients with cardiac conductance disturbances.

Very recently, mutations in the TRPM4 gene have been identified in four pedigrees as the cause of an autosomal dominant form of cardiac conduction disease. To determine the role of TRPM4 gene variations, the relative frequency of TRPM4 mutations and associated phenotypes was assessed in a cohort of 160 unrelated patients with various types of inherited cardiac arrhythmic syndromes. In eight probands with atrioventricular block or right bundle branch block--five familial cases and three sporadic cases--a total of six novel and two published TRPM4 mutations were identified. In patients with sinus node dysfunction, Brugada syndrome, or long-QT syndrome, no mutations were found. The novel mutations include six amino acid substitutions and appeared randomly distributed through predicted TRPM4 protein. In addition, eight polymorphic sites including two in-frame deletions were found. Mutations separated from polymorphisms by absence in control individuals and familial cosegregation in some families. In summary, TRPM4 gene mutations appear to play a major role in cardiac conduction disease but not for other related syndromes so far. The phenotypes are variable and clearly suggestive of additional factors modulating the disease phenotype in some patients.

Hedgehog signaling underlying tendon and enthesis development and pathology.

Hedgehog (Hh) signaling has been widely acknowledged to play essential roles in many developmental processes, including endochondral ossification and growth plate maintenance. Furthermore, a rising number of studies have shown that Hh signaling is necessary for tendon enthesis development. Specifically, the well-tuned regulation of Hh signaling during development drives the formation of a mineral gradient across the tendon enthesis fibrocartilage. However, aberrant Hh signaling can also lead to pathologic heterotopic ossification in tendon or osteophyte formation at the enthesis. Therefore, the therapeutic potential of Hh signaling modulation for treating tendon and enthesis diseases remains uncertain. For example, increased Hh signaling may enhance tendon-to-bone healing by promoting the formation of mineralized fibrocartilage at the healing interface, but pathologic heterotopic ossification may also be triggered in the adjacent tendon. Further work is needed to elucidate the distinct functions of Hh signaling in the tendon and enthesis to support the development of therapies that target the pathway.

Risk of distal junctional kyphosis in scheuermann's kyphosis is decreased by selecting the LIV as two vertebrae distal to the first lordotic disc.

PURPOSE: To determine whether (1) distal junctional kyphosis (DJK) is decreased by selecting the stable sagittal vertebra (SSV), versus the vertebra below the 1st lordotic disc (1stLD), as the lowest instrumented level (LIV); (2) DJK is decreased if the LIV is two versus one vertebrae distal to the 1stLD. METHODS: A multi-institution prospective database was queried for SK patients who underwent posterior-only instrumentation and fusion with > 2 year follow-up. DJK was defined as > 10° change in the distal junctional angle postoperative from the preoperative junctional angle. Statistical analysis was performed using t test, chi-square test and logistic regression. RESULTS: Of 94 patients included, 38 (40%) developed radiographic DJK. 31 (39%) patients in whom the LIV was at or distal to the SSV developed DJK, whereas 7 (47%) in whom the LIV was proximal to the SSV developed DJK. 20 (59%) patients in whom the LIV was one vertebra below and 10 (22%) in whom the LIV was two vertebrae below the 1stLD developed DJK. Logistic regression demonstrated a significant increase in DJK development if the LIV was one vertebra below the 1stLD (OR = 3.2 (1.28-8.18)). There was not a significant relationship between DJK development and LIV position relative to the SSV. CONCLUSION: In SK surgery, LIV selection/fusion to two vertebrae below the 1stLD decreased the development of DJK. A significant relationship was not found between DJK development and location of distal fusion level in regards to the SSV, possibly due to the small number of patients who had LIV proximal to SSV.

Intraoperative Scrub Nurse Handoffs Are Associated with Increased Operative Times for Lower Extremity Orthopaedic Sports Procedures.

PURPOSE: The purpose of this study was to evaluate the effect of intraoperative scrub nurse handoffs on surgical times for arthroscopically-assisted anterior cruciate ligament (ACL) reconstructions and hip arthroscopies. METHODS: A retrospective chart review was done at a major, urban academic medical center for all patients who underwent arthroscopically-assisted ACL reconstructions and hip arthroscopies for femoroacetabular impingement syndrome between May 2014 and May 2020. All ACL reconstructions were performed by 1 of 6 sports medicine fellowship-trained surgeons, and all hip arthroscopies were performed by a single surgeon. Operative times, number of scrub nurse handoffs, surgeon, patient demographics, and procedure-specific information were recorded. The association between patient characteristics and the number of handoffs, as well as the association between patient characteristics and operative times, stratified by scrub nurse handoffs, were calculated. A multivariable linear regression was performed to assess the association between intra-operative handoffs and operative times. RESULTS: Eight hundred twenty ACL reconstructions and 269 hip arthroscopies were identified. Multivariable linear regression demonstrated increasing intraoperative scrub nurse handoffs were associated with increased operative times for all patients. For ACL reconstructions, when including all possible covariates, 1 scrub nurse handoff increased operative times by 21.1 minutes (95% confidence interval [CI]: 15.36 to 26.89; P < .001), and 2+ handoffs increased operative times by 34.2 minutes (95% CI: 26.28 to 42.15; P < .001). For hip arthroscopies, 1 scrub nurse handoff increased operative times by 7.0 minutes (95% CI: 0.31 to 13.74; P = .04). CONCLUSION: Although a causal link cannot be made, intraoperative scrub nurse handoffs were associated with statistically significant increase in operative times for both ACL reconstructions and hip arthroscopies. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Metalloradical activation of carbonyl azides for enantioselective radical aziridination.

Organic azides have been increasingly employed as nitrogen sources for catalytic olefine aziridination due to their ease of preparation and generation of benign N2 as the only byproduct. Among common organic azides, carbonyl azides have not been previously demonstrated as effective nitrogen sources for intermolecular olefin aziridination despite the synthetic utilities of N-carbonyl aziridines. As a new application of metalloradical catalysis, we have developed a catalytic system that can effectively employ the carbonyl azide TrocN3 for highly asymmetric aziridination of alkenes at room temperature. The resulting enantioenriched N-Trocaziridines have been shown as valuable chiral synthons for stereoselective synthesis of other chiral aziridines and various chiral amines. The Co(II)-based metalloradical system, which proceeds with distinctive stepwise radical mechanism, may provide a general method for asymmetric synthesis of chiral aziridines from alkenes with organic azides.

Roles and Regulation of Voltage-gated Calcium Channels in Arrhythmias.

Calcium flowing through voltage-dependent calcium channels into cardiomyocytes mediates excitation-contraction coupling, controls action-potential duration and automaticity in nodal cells, and regulates gene expression. Proper surface targeting and basal and hormonal regulation of calcium channels are vital for normal cardiac physiology. In this review, we discuss the roles of voltage-gated calcium channels in the heart and the mechanisms by which these channels are regulated by physiological signaling pathways in health and disease.