Primary Repair of Complete Quadriceps Tendon Rupture with Extensor Mechanism Deficit.

Background: Whereas partial quadriceps tendon ruptures may be treated nonoperatively if the extensor mechanism remains functional, complete ruptures require primary operative repair to achieve optimal functional results1,2. The 2 most common techniques are the use of transosseous tunnels and the use of suture anchors. The goal of these procedures is to reconstruct and restore mobility of the extensor mechanism of the leg. Description: The patient is positioned supine with the injured leg exposed. A midline incision to the knee is made over the quadriceps tendon defect, exposing the distal quadriceps and proximal patella. Irrigation is utilized to evacuate the residual hematoma, and the distal quadriceps and proximal patella are debrided of degenerative tissue. When utilizing transosseous tunnels, a nonabsorbable suture is passed full-thickness through the medial or lateral half of the quadriceps tendon in a locked, running pattern (i.e., Krackow). A second nonabsorbable suture is passed full-thickness through the other half of the tendon. There should then be 4 loose strands at the distal quadriceps. The anatomic insertion of the quadriceps tendon is roughened with a sharp curet to expose fresh cancellous bone. Three parallel bone tunnels are created along the longitudinal axis of the patella. The knee is placed in full extension, with a bump under the heel in order to provide slight recurvatum at the knee and to allow for a properly tensioned repair. In pairs, the free ends of the sutures are passed through the tunnels. The sutures are tensioned and tied together in pairs at the distal aspect of the patella. Alternatively, when utilizing suture anchors, Arthrex FiberTape is passed full-thickness through the medial or lateral half of the quadriceps tendon in a Krackow pattern. A second FiberTape is passed full-thickness through the other half of the tendon. There should then be 4 loose tails at the distal quadriceps. The 2 tails of the medial FiberTape are placed into a knotless Arthrex SwiveLock anchor; this step is repeated for the 2 lateral tails. The anatomic insertion of the quadriceps tendon is roughened to expose fresh cancellous bone. With use of a 3.5-mm drill, create 2 parallel drill holes along the longitudinal axis of the patella, with sufficient depth to bury the SwiveLock anchor. Unlike in the transosseous tunnel technique, these drill holes do not run the length of the patella. The holes are then tapped. Following irrigation, the anchors are tensioned into the bone tunnels, and extra tape is cut flush to the bone. For both techniques, additional tears in the medial and lateral retinacula are repaired if present. Alternatives: Alternatives include nonoperative treatment with use of a hinged knee brace; operative treatment with use of simple sutures; and augmentation with use of wire reinforcement, cancellous screws, the Scuderi technique, the Codivilla technique, tensor fasciae latae reinforcement, and/or MERSILENE tape (Ethicon). Rationale: Primary operative repair of quadriceps tendon ruptures is a well-documented, successful procedure with biomechanical, clinical, and patient-reported data to support its use3-7. However, literature comparing the 2 most common surgical techniques remains controversial. Transosseous tunnel repair is the most common technique utilized to repair quadriceps tendon ruptures, but suture anchors have become increasingly popular in the past several years1,4. Most studies have reported no significant difference in biomechanical, clinical, and patient-reported outcome measures between these 2 techniques3,4,8-10. Decreased operative time and a smaller incision have been suggested as advantages of suture anchors4,9. However, this method incurs a higher average cost of surgery and risks a more complex revision in the event of deep infection9,10. Simple suture repair is a less commonly utilized technique and is now reserved for midsubstance tendon repairs. Nonoperative treatment of complete quadriceps tendon rupture is exceedingly rare and not recommended because of the profound functional consequences. Relative indications for nonoperative treatment include a patient who is unfit for surgery, is not ambulatory at baseline, or retains full extensor mechanism function. Nonoperative treatment is typically reserved for partial quadriceps ruptures and typically involves early immobilization with a hinged knee brace. Expected Outcomes: Primary repair of quadriceps tendon ruptures, utilizing either the transosseous tunnel or suture anchor technique, yields excellent outcomes. Following surgical treatment, patients have near-full recovery in range of motion, with studies reporting a <5° deficit compared with the contralateral, uninjured limb3,4,10,11. The vast majority of patients (>90%) return to pre-injury levels of function and work3,4,7,11. The majority of patients also report satisfactory results, as assessed with use of patient-reported outcome measures3,4,10. The most commonly reported complications are knee stiffness and quadriceps muscle atrophy, which can both be treated with proper rehabilitation. Even in the event of these complications, however, patients can maintain adequate knee function2,3. More severe complications are rare (<3%) and include deep venous thrombosis and/or pulmonary embolism, superficial and/or deep infection, and tendon rerupture2-4,10-12. Delayed operative treatment is associated with worse outcomes and increased complication rates1,3,4,10,11. Important Tips: When performing the Krackow stitch, be sure to tension and remove all slack before performing another tissue pass.Surgical repair should be performed as soon as possible from the time of injury in order to minimize risks and to achieve optimal surgical outcomes.If there is concern that the primary construct would be unstable, it can be augmented with wire reinforcement, cancellous screws, the Scuderi technique, the Codivilla technique, tensor fasciae latae reinforcement, and/or MERSILENE tape.Identify and repair patellar retinaculum tears, which are common concomitant injuries in the setting of complete quadriceps rupture. Acronyms and Abbreviations: MRI = magnetic resonance imaging.

Musical training does not enhance neural sound encoding at early stages of the auditory system: A large-scale multisite investigation.

Musical training has been associated with enhanced neural processing of sounds, as measured via the frequency following response (FFR), implying the potential for human subcortical neural plasticity. We conducted a large-scale multi-site preregistered study (n > 260) to replicate and extend the findings underpinning this important relationship. We failed to replicate any of the major findings published previously in smaller studies. Musical training was related neither to enhanced spectral encoding strength of a speech stimulus (/da/) in babble nor to a stronger neural-stimulus correlation. Similarly, the strength of neural tracking of a speech sound with a time-varying pitch was not related to either years of musical training or age of onset of musical training. Our findings provide no evidence for plasticity of early auditory responses based on musical training and exposure.

Operative treatment of clavicle fractures results in more opioids prescribed as compared to non-operative management.

PURPOSE: The operative treatment of mid-shaft clavicle fractures shows benefit in union rates, return to work, and lower pain scores relative to non-operative treatment. We sought to determine if the surgical treatment of isolated mid-shaft clavicle fractures would result in fewer opioids prescribed as compared to those managed non-operatively. METHODS: All mid-shaft clavicle fractures treated at a Level 1 trauma center were identified from 2012 to 2016. Demographics, fracture characteristics, surgical complications/outcomes, non-operative outcomes, and all narcotics prescribed for 6 months post-injury were collected. Narcotic prescriptions, in morphine equivalents (ME), were obtained through the state prescription drug monitoring program (PDMP). RESULTS: One hundred and ten operative and 48 non-operative patients were included. Age, gender, previous alcohol, tobacco or drug use, and final range of motion were similar between groups. Pre-treatment fracture shortening (1.8 cm vs. 0.7 cm, p < 0.001) and displacement (150% vs. 70%, p < 0.001) were greater in the operative group. Total ME's (604 vs. 187, p < 0.001) and post-operative ME's (420 vs. 187, p < 0.001) were greater for the operative group. In either group, no other variable influenced ME's prescribed. CONCLUSION: Clavicles treated operatively receive substantially more opiates than those treated non-operatively, despite data suggesting that operative treatment makes clavicle fractures less painful. The total amount of narcotic analgesics obtained by operatively treated patients was over three times that obtained by non-operatively managed patients, which equates to 55 5 mg oxycodone pills or 85 5 mg hydrocodone pills per patient. While there may certainly be advantages to the operative treatment of clavicle fractures, they must be weighed against the risks of a significant increase in opiate prescribing and potential consumption.

Local mRNA Delivery from Nanocomposites Made of Gelatin and Hydroxyapatite Nanoparticles.

Local delivery of messenger ribonucleic acid (mRNA) is increasingly being advocated as a promising new strategy to enhance the performance of biomaterials. While extensive research has been dedicated to the complexation of these oligonucleotides into nanoparticles to facilitate systemic delivery, research on developing suitable biomaterial carriers for the local delivery of mRNA is still scarce. So far, mRNA-nanoparticles (mRNA-NPs) are mainly loaded into traditional polymeric hydrogels. Here, we show that calcium phosphate nanoparticles can be used for both reinforcement of nanoparticle-based hydrogels and the complexation of mRNA. mRNA was incorporated into lipid-coated calcium phosphate nanoparticles (LCPs) formulated with a fusogenic ionizable lipid in the outer layer of the lipid coat. Nanocomposites of gelatin and hydroxyapatite nanoparticles were prepared at various ratios. Higher hydroxyapatite nanoparticle content increased the viscoelastic properties of the nanocomposite but did not affect its self-healing ability. Combination of these nanocomposites with peptide, lipid, and the LCP mRNA formulations achieved local mRNA release as demonstrated by protein expression in cells in contact with the biomaterials. The LCP-based formulation was superior to the other formulations by showing less sensitivity to hydroxyapatite and the highest cytocompatibility.

Association between papillary thyroid cancer and primary aldosteronism in individuals with hypertension.

BACKGROUND: Aldosterone excess chronically induces oxidative stress and cell proliferation. Previously, a single study investigated primary aldosteronism (PA) in patients with papillary thyroid cancer (PTC), albeit without a matched control group. METHODS: We conducted a propensity score matched case-control study to investigate the association between PA and PTC in individuals with arterial hypertension (HT). PA was investigated in 137 patients with PTC and HT. The control group included 137 (1:1) age, sex-, and body mass index (BMI)-matched individuals with HT. We conducted a secondary analysis in which the controls were also matched according to HT stage. RESULTS: The prevalence of PA was 29.20% (95% confidence interval [CI], 21.91%-37.68%) in the PTC group and 20.44% (95% CI, 14.22%-28.35%) in the controls not matched for HT stage (p = 0.093). Although the PA prevalence was similar in both groups, the frequency of severe HT (stage III or resistant) was significantly lower in the PTC group (23%) compared to the hypertensive controls (73%, p < 0.001). After matching the controls by HT stage, the prevalence of PA in the PTC group was significantly higher compared to the hypertensive controls (9.56%; 95% CI, 5.39%-16.1%, p < 0.0001). In the multivariable analysis, PTC was independently associated with PA in both unmatched hypertensive individuals (odds ratio [OR] 4.74; 95% CI, 2.26-10.55; p< 0.001) and in those matched for HT stage (OR 5.88, 95% CI, 2.79-13.37; p< 0.001). CONCLUSION: PTC was an independent variable associated with a diagnosis of PA in hypertensive individuals. Therefore, we propose the association between PTC and HT as a new recommendation for PA screening regardless of HT severity.

Oligomerization-driven avidity correlates with SARS-CoV-2 cellular binding and inhibition.

Cellular processes are controlled by the thermodynamics of the underlying biomolecular interactions. Frequently, structural investigations use one monomeric binding partner, while ensemble measurements of binding affinities generally yield one affinity representative of a 1:1 interaction, despite the majority of the proteome consisting of oligomeric proteins. For example, viral entry and inhibition in SARS-CoV-2 involve a trimeric spike surface protein, a dimeric angiotensin-converting enzyme 2 (ACE2) cell-surface receptor and dimeric antibodies. Here, we reveal that cooperativity correlates with infectivity and inhibition as opposed to 1:1 binding strength. We show that ACE2 oligomerizes spike more strongly for more infectious variants, while exhibiting weaker 1:1 affinity. Furthermore, we find that antibodies use induced oligomerization both as a primary inhibition mechanism and to enhance the effects of receptor-site blocking. Our results suggest that naive affinity measurements are poor predictors of potency, and introduce an antibody-based inhibition mechanism for oligomeric targets. More generally, they point toward a much broader role of induced oligomerization in controlling biomolecular interactions.

The Escherichia coli TolC efflux pump protein is immunogenic and elicits protective antibodies.

Antimicrobial resistance is an increasing worldwide public health burden that threatens to make existent antimicrobials obsolete. An important mechanism of antimicrobial resistance is the overexpression of efflux pumps, which reduce the intracellular concentration of antimicrobials. TolC is the outer membrane protein of an efflux pump that has gained attention as a therapeutic target. Little is known about the immune response against TolC. Here we evaluated the immune response against TolC from Escherichia coli. TolC in silico epitope prediction showed several residues that could bind to human antibodies, and we showed that human plasma presented higher titers of anti-TolC IgG and IgA, than IgM. E. coli recombinant TolC protein stimulated macrophages in vitro to produce nitric oxide, as well as IL-6 and TNF-α, assessed by Griess assay and ELISA, respectively. Immunization of mice with TolC intraperitoneally and an in vitro re-stimulation led to increased T cell proliferation and IFNγ production, evaluated by flow cytometry and ELISA, respectively. TolC mouse immunization stimulated anti-TolC IgM and IgG production, with higher levels of IgG1 and IgG2, amongst the IgG subclasses. Anti-TolC murine antibodies could bind to live E. coli and increase bacterial uptake and elimination by macrophages in vitro. Intraperitoneal or intranasal, but not oral, immunizations with inactivated E. coli also led to anti-TolC antibody production. Finally, TolC immunization increased mouse survival rates to antimicrobial-sensitive or resistant E. coli infection. Our results showed that TolC is immunogenic, leading to the production of protective antibodies against E. coli, reinforcing its value as a therapeutic target.

Copper(II)-Catalyzed Amination of Aryl Chlorides in Aqueous Ammonia.

Anilines are ubiquitous in bio-active compounds and their synthesis can be achieved via metal-catalyzed cross-coupling reactions involving aryl halides. We describe an unusual, yet simple, CuII-catalyzed system for the amination of aryl chlorides in pure aqueous ammonia with 2.5 mol% catalyst loading under non-inert conditions. Different from previous systems, the reaction proceeds even without an additional organic solvent. Copper(II) sulfate in combination with 4,7-dimethoxy-1,10-phenanthroline enabled the amination of several aryl chlorides containing electron-neutral, -donating and -withdrawing groups to the corresponding anilines with good to excellent yields. The upscaling potential of the procedure has been shown by the synthesis at 50 mmol scale. The reaction proceeds as one of the rare cases of a CuII-assisted coupling, in contrast to the typical CuI-CuIII intermediates postulated for most Ullmann-type coupling reactions. The copper(II) center allows for a nucleophilic substitution pathway, enabled by the deprotonation of coordinated ammonia.

Ca2+-dependent lipid preferences shape synaptotagmin-1 C2A and C2B dynamics: Insights from experiments and simulations.

Signal transmission between neurons requires exocytosis of neurotransmitters from the lumen of synaptic vesicles into the synaptic cleft. Following an influx of Ca2+, this process is facilitated by the Ca2+ sensor synaptotagmin-1. The underlying mechanisms involve electrostatic and hydrophobic interactions tuning the lipid preferences of the two C2 domains of synaptotagmin-1; however, the details are still controversially discussed. We, therefore, follow a multidisciplinary approach and characterize lipid and membrane binding of the isolated C2A and C2B domains. We first target interactions with individual lipid species, and then study interactions with model membranes of liposomes. Finally, we perform molecular dynamics simulations to unravel differences in membrane binding. We found that both C2 domains, as a response to Ca2+, insert into the lipid membrane; however, C2A adopts a more perpendicular orientation while C2B remains parallel. These findings allow us to propose a mechanism for synaptotagmin-1 during membrane fusion.

Post-Traumatic Arthritis of the Knee and Ankle.

Post-traumatic osteoarthritis (PTOA) occurs following injury to joints. It accounts for approximately 12% of osteoarthritis and has far-reaching effects on individual patients and social/health care systems. Present work focuses on evaluating the role of the post-traumatic inflammatory response in the development and progression of the disease. As there is minimal evidence to suggest the capacity of cartilage to undergo self-healing, most of this work focuses strictly on the avoidance or prevention of PTOA as opposed to treatment solutions following its onset. Ongoing and future investigations may reveal therapeutic targets for possible intervention and ultimately the prophylaxis of PTOA development.

The combined talus and sustentaculum fracture: A case series.

BACKGROUND: The sustentaculum tali is a biomechanically important stabilizer of the hindfoot and contributes to articular congruency of the subtalar joint. Sustentaculum injury associated with a talus fracture has been described infrequently and treatment of this combined injury varies. The purpose of this study was to describe and evaluate the outcomes of the combined talus and sustentaculum fracture. METHODS: Retrospective chart and radiographic review was performed on all talus fractures (n = 436) requiring operative fixation over a 21-year period at a single Level-1 trauma center. All talus fractures with sustentaculum fractures were included. Statistical analysis was performed using Chi-squared and Fishers exact tests where appropriate. RESULTS: Sustentaculum fractures occurred in 6.2 % (n = 27) of patients with talus fractures. Average follow-up was 14 months; 18.5 % were open fractures, 88.8 % were from high-energy mechanisms, and 44.4 % were polytraumas. Diagnosis of the sustentaculum fracture was missed on presenting radiographs in 69.2 % (n = 18). The most common associated talus fracture was a talar neck fracture (40.7 %) and the majority (73.7 %) were Hawkins II. Overall, 40.7 % (n = 11) of the sustentaculum fractures were treated with independent fixation and 7.4 % (n = 2) were treated with acute subtalar arthrodesis. Subtalar post-traumatic osteoarthritis (PTOA) at final follow-up was seen in 23.1 % of combined injuries. Independent sustentaculum fixation did not influence the rate of PTOA or re-operation (p = 0.92, p = 0.91, respectively). CONCLUSION: Talar fractures have an associated sustentaculum fracture in approximately 6 % of cases, especially with Hawkins II fracture-dislocations. Over two-thirds of the associated sustentaculum fractures were missed on presenting radiographs, reiterating the need for heightened awareness and consideration of advanced imaging for all talus fractures. The rate of PTOA following these combined injuries at mean follow-up of 24 months does not exceed established rates after isolated talus fractures. Further research is required to determine the optimal management of the sustentaculum in these combined injuries. LEVEL OF EVIDENCE: IV.

An outcome-driven threshold for pulse pressure amplification.

Pulse pressure amplification (PPA) is the brachial-to-aortic pulse pressure ratio and decreases with age and cardiovascular risk factors. This individual-participant meta-analysis of population studies aimed to define an outcome-driven threshold for PPA. Incidence rates and standardized multivariable-adjusted hazard ratios (HRs) of cardiovascular and coronary endpoints associated with PPA, as assessed by the SphygmoCor software, were evaluated in the International Database of Central Arterial Properties for Risk Stratification (n = 5608). Model refinement was assessed by the integrated discrimination (IDI) and net reclassification (NRI) improvement. Age ranged from 30 to 96 years (median 53.6). Over 4.1 years (median), 255 and 109 participants experienced a cardiovascular or coronary endpoint. In a randomly defined discovery subset of 3945 individuals, the rounded risk-carrying PPA thresholds converged at 1.3. The HRs for cardiovascular and coronary endpoints contrasting PPA < 1.3 vs ≥1.3 were 1.54 (95% confidence interval [CI]: 1.00-2.36) and 2.45 (CI: 1.20-5.01), respectively. Models were well calibrated, findings were replicated in the remaining 1663 individuals analyzed as test dataset, and NRI was significant for both endpoints. The HRs associating cardiovascular and coronary endpoints per PPA threshold in individuals <60 vs ≥60 years were 3.86 vs 1.19 and 6.21 vs 1.77, respectively. The proportion of high-risk women (PPA < 1.3) was higher at younger age (<60 vs ≥60 years: 67.7% vs 61.5%; P < 0.001). In conclusion, over and beyond common risk factors, a brachial-to-central PP ratio of <1.3 is a forerunner of cardiovascular coronary complications and is an underestimated risk factor in women aged 30-60 years. Our study supports pulse wave analysis for risk stratification.

Platelet transcription factors license the pro-inflammatory cytokine response of human monocytes.

In humans, blood Classical CD14+ monocytes contribute to host defense by secreting large amounts of pro-inflammatory cytokines. Their aberrant activity causes hyper-inflammation and life-threatening cytokine storms, while dysfunctional monocytes are associated with 'immunoparalysis', a state of immune hypo responsiveness and reduced pro-inflammatory gene expression, predisposing individuals to opportunistic infections. Understanding how monocyte functions are regulated is critical to prevent these harmful outcomes. We reveal platelets' vital role in the pro-inflammatory cytokine responses of human monocytes. Naturally low platelet counts in patients with immune thrombocytopenia or removal of platelets from healthy monocytes result in monocyte immunoparalysis, marked by impaired cytokine response to immune challenge and weakened host defense transcriptional programs. Remarkably, supplementing monocytes with fresh platelets reverses these conditions. We discovered that platelets serve as reservoirs of key cytokine transcription regulators, such as NF-κB and MAPK p38, and pinpointed the enrichment of platelet NF-κB2 in human monocytes by proteomics. Platelets proportionally restore impaired cytokine production in human monocytes lacking MAPK p38α, NF-κB p65, and NF-κB2. We uncovered a vesicle-mediated platelet-monocyte-propagation of inflammatory transcription regulators, positioning platelets as central checkpoints in monocyte inflammation.

Early development of the glucocorticoid stress response in poison frog tadpoles.

In vertebrates, the glucocorticoid response through the hypothalamic-pituitary-adrenal (HPA) axis controls many essential functions, including behavior, metabolism, and ontogenetic transitions. However, there are tradeoffs associated with high levels of glucocorticoids, including reduced growth rate and lowered immunity. These tradeoffs drive variation in the timing of the development of the HPA axis across taxa. In anurans (frogs and toads), corticosterone has critical roles in development and behavior, and concentrations can fluctuate in response to environmental stressors. Given the role of corticosterone in ontogenetic changes and behaviors, we hypothesized that species with immediate habitat transitions and challenges would develop an HPA axis early in development. To test this hypothesis, we studied tadpoles of the dyeing poison frog ( Dendrobates tinctorius ), a species in which tadpoles hatch terrestrially and are transported to pools of water by their parent. We measured the excretion rate and whole-body concentration of corticosterone and the corticosterone response to adrenocorticotropic hormone (ACTH). We found no significant differences in excretion rates and whole-body concentration of corticosterone, nor physiological response to ACTH injection across tadpole development. These findings indicate that the glucocorticoid response is developed early in ontogeny. These findings generally differ from those found in other species of tadpoles, which may suggest the unique ecological pressures of D. tinctorius has shaped the development of its HPA axis. More broadly, this study illustrates how life history strategies and tradeoffs of glucocorticoids impact the timing of the development of the HPA axis. Highlights: The timing of HPA axis development differs across species. We studied the HPA axis across tadpole development in Dendrobates tinctorius . No difference in corticosterone concentration across development.No difference in corticosterone response to ACTH across development.Results suggest an early developed HPA axis is essential for their life history.

Dual Plating of Distal Femoral Fractures.

Background: Dual plating of the distal femur is indicated for the treatment of complex intra-articular fractures, supracondylar femoral fractures, low periprosthetic fractures, and nonunions. The aim of this procedure is anatomical alignment of the articular surface, restoration of the articular block, and prevention of varus collapse. Description: Following preoperative planning, the patient is positioned supine with the knee flexed at 30°. The lateral incision is made first, with a mid-lateral incision that is in line with the femoral shaft. If intra-articular work is needed this incision can be extended by curving anteriorly over the lateral femoral condyle. Next, the iliotibial band is transected in line with its fibers. The vastus lateralis fascia is incised and elevated off the septum, working distal to proximal. Care should be taken to maintain hemostasis when encountering femoral artery perforating vessels. Once there is adequate exposure, several reduction aids can be utilized, including a bump under the knee, Schanz pins, Kirschner wires, and reduction clamps. A lateral precontoured plate is placed submuscularly, and the most proximal holes are filled percutaneously. The medial incision begins distally at the adductor tubercle and is a straight incision made proximally in line with the femoral shaft. The underlying fascia is transected in line with the skin incision, and the vastus medialis is elevated. Care should be taken to avoid the descending geniculate artery, as well as its articular branch and the muscular branch to the vastus medialis. A lateral tibial plateau plate is contoured and placed. Alternatives: Nonoperative treatment of distal femoral fractures is rare, but relative indications for nonoperative treatment include frailty of the patient, lack of ambulatory status, a non-reconstructible fracture, or a stable fracture. These patients are placed in a long-leg cast followed by a hinged knee brace1. There are several other surgical fixation options, including lateral plating, retrograde intramedullary nailing, distal femoral replacement, and augmentation of a retrograde nail with a plate. Rationale: Dual plating has several benefits, depending on the clinical scenario. Biomechanical studies have found that dual plating results in increased stiffness and construct strength2,3. Additional construct stability can be offered through the use of locking plates, particularly in osteoporotic bone. Taken together, this increased stability and construct strength can allow for earlier weight-bearing, which is particularly important for fractures in the geriatric population. Furthermore, the increased stiffness and construct strength make this procedure a favorable treatment option for nonunion, and it has been shown to result in lower rates of postoperative nonunion compared with lateral plating alone4-7. Adjunctive use of a medial plate also has been suggested to prevent varus collapse, particularly with metaphyseal comminution and poor bone quality2,3,8. Finally, in the periprosthetic fracture population, dual plating also removes the concern of incompatibility with a retrograde nail. Expected Outcomes: The outcomes of dual plating are promising, given the severity of the injury. When comparing operative to nonoperative treatment outcomes, nonoperatively managed patients had worse functional outcomes and higher rates of complications related to immobility1. Dual plating of supracondylar fractures and intra-articular distal femoral fractures yields nonunion rates ranging from 0% to 12.5%, lower than the 18% to 20% reported with lateral locking plates4-7,9-12. This reduction in nonunions has been shown to lead to fewer revisions when compared with single-plating techniques7. In prior studies, 95% of nonunions treated with the dual-plating technique achieved union postoperatively11. One concern when utilizing the medial approach is critical damage to medial vascularity; however, this result has not been reported in the literature, and there is a safe operating window13. Despite the benefits of dual plating, there are relatively high rates of infection following dual plating (0% to 16.7%) compared with lateral plating alone (3.6% to 8.5%)5,14-17. However, many of these studies are small case series, highlighting that a surgeon's comfort and skill with these procedures is paramount to patient outcomes. Important Tips: Meticulous placement and contouring of lateral and medial plates are required to prevent malreduction of the articular block that creates a "golf-club deformity."18,19During the medial approach, be aware of descending geniculate artery-particularly its muscular branch, which is ∼5 cm from the adductor tubercle/medial epicondyle, and its root, which enters the compartment at the adductor hiatus at ∼16 cm13.

An Optimal, Power Efficient, Internet of Medical Things Framework for Monitoring of Physiological Data Using Regression Models.

The sensors used in the Internet of Medical Things (IoMT) network run on batteries and need to be replaced, replenished or should use energy harvesting for continuous power needs. Additionally, there are mechanisms for better utilization of battery power for network longevity. IoMT networks pose a unique challenge with respect to sensor power replenishment as the sensors could be embedded inside the subject. A possible solution could be to reduce the amount of sensor data transmission and recreate the signal at the receiving end. This article builds upon previous physiological monitoring studies by applying new decision tree-based regression models to calculate the accuracy of reproducing data from two sets of physiological signals transmitted over cellular networks. These regression analyses are then executed over three different iteration varieties to assess the effect that the number of decision trees has on the efficiency of the regression model in question. The results indicate much lower errors as compared to other approaches indicating significant saving on the battery power and improvement in network longevity.

Abietane Diterpenes from Medusantha martiusii and Their Anti-Neuroinflammatory Activity.

Seven new abietane diterpenoids, comprising medusanthol A-G (1-3, 5, 7-9) and two previously identified analogs (4 and 6), were isolated from the hexane extract of the aerial parts of Medusantha martiusii. The structures of the compounds were elucidated by HRESIMS, 1D/2D NMR spectroscopic data, IR spectroscopy, NMR calculations with DP4+ probability analysis, and ECD calculations. The anti-neuroinflammatory potential of compounds 1-7 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and the proinflammatory cytokine TNF-α in BV2 microglia stimulated with LPS and IFN-γ. Compounds 1-4 and 7 exhibited decreased NO levels at a concentration of 12.5 µM. Compound 1 demonstrated strong activity with an IC50 of 3.12 µM, and compound 2 had an IC50 of 15.53 µM; both compounds effectively reduced NO levels compared to the positive control quercetin (IC50 11.8 µM). Additionally, both compounds significantly decreased TNF-α levels, indicating their potential as promising anti-neuroinflammatory agents.

A Multiomics Perspective on Plant Cell Wall-Degrading Enzyme Production: Insights from the Unexploited Fungus Trichoderma erinaceum.

Trichoderma erinaceum is a filamentous fungus that was isolated from decaying sugarcane straw at a Brazilian ethanol biorefinery. This fungus shows potential as a source of plant cell wall-degrading enzymes (PCWDEs). In this study, we conducted a comprehensive multiomics investigation of T. erinaceum to gain insights into its enzymatic capabilities and genetic makeup. Firstly, we performed genome sequencing and assembly, which resulted in the identification of 10,942 genes in the T. erinaceum genome. We then conducted transcriptomics and secretome analyses to map the gene expression patterns and identify the enzymes produced by T. erinaceum in the presence of different substrates such as glucose, microcrystalline cellulose, pretreated sugarcane straw, and pretreated energy cane bagasse. Our analyses revealed that T. erinaceum highly expresses genes directly related to lignocellulose degradation when grown on pretreated energy cane and sugarcane substrates. Furthermore, our secretome analysis identified 35 carbohydrate-active enzymes, primarily PCWDEs. To further explore the enzymatic capabilities of T. erinaceum, we selected a ß-glucosidase from the secretome data for recombinant production in a fungal strain. The recombinant enzyme demonstrated superior performance in degrading cellobiose and laminaribiose compared to a well-known enzyme derived from Trichoderma reesei. Overall, this comprehensive study provides valuable insights into both the genetic patterns of T. erinaceum and its potential for lignocellulose degradation and enzyme production. The obtained genomic data can serve as an important resource for future genetic engineering efforts aimed at optimizing enzyme production from this fungus.

A Comprehensive Investigation of Methanol Electrooxidation on Copper Anodes: Spectroelectrochemical Insights and Energy Conversion in Microfluidic Fuel Cells.

Here, we comprehensively investigated methanol electrooxidation on Cu-based catalysts, allowing us to build the first microfluidic fuel cell (µFC) equipped with a Cu anode and a metal-free cathode that converts energy from methanol. We applied a simple, fast, small-scale, and surfactant-free strategy for synthesizing Cu-based nanoparticles at room temperature in steady state (ST), under mechanical stirring (MS), or under ultrasonication (US). The morphology evaluation of the Cu-based samples reveals that they have the same nanoparticle (NP) needle-like form. The elemental mapping composition spectra revealed that pure Cu or Cu oxides were obtained for all synthesized materials. In addition to having more Cu2O on the surface, sample US had more Cu(OH)2 than the others, according to X-ray diffractograms and X-ray photoelectron spectroscopy. The sample US is less carbon-contaminated because of the local heating of the sonic bath, which also enhances the cleanliness of the Cu surface. The activity of the Cu NPs was investigated for methanol electrooxidation in an alkaline medium through electrochemical and spectroelectrochemical measurements. The potentiodynamic and potentiostatic experiments showed higher current densities for the NPs synthesized in the US. In situ FTIR experiments revealed that the three synthesized NP materials eletcrooxidize methanol completely to carbonate through formate. Most importantly, all pathways were led without detectable CO, a poisoning molecule not found at high overpotentials. The reaction path using the US electrode experienced an additional round of formate formation and conversion into carbonate (or CO2 in the thin layer) after 1.0 V (vs. Ag/Ag/Cl), suggesting improved catalysis. The high activity of NPs synthesized in the US is attributed to effective dissociative adsorption of the fuel due to the site's availability and the presence of hydroxyl groups that may fasten the oxidation of adsorbates from the surface. After understanding the surface reaction, we built a mixed-media µFC fed by methanol in alkaline medium and sodium persulfate in acidic medium. The µFC was equipped with Cu NPs synthesized in ultrasonic-bath-modified carbon paper as the anode and metal-free carbon paper as the cathode. Since the onset potential for methanol electrooxidation was 0.45 V and the reduction reaction revealed 0.90 V, the theoretical OCV is 0.45 V, which provides a spontaneous coupled redox reaction to produce power. The µFC displayed 0.56 mA cm-2 of maximum current density and 26 µW cm-2 of peak power density at 100 µL min-1. This membraneless system optimizes each half-cell individually, making it possible to build fuel cells with noble metal-free anodes and metal-free cathodes.

Age and Sex Differences in the Contribution of Mean Arterial Pressure to Pulse Pressure Before Middle Age.

INTRODUCTION: A lower ability to buffer pulse pressure (PP) in the face of increasing mean arterial pressure (MAP) may underlie the disproportionate increase in systolic blood pressure (SBP) in women from young adulthood through middle-aged relative to men. AIM: To evaluate the contribution of MAP to the change in PP and pressure wave contour in men and women from young adulthood to middle age. METHODS: Central pressure waveform was obtained from radial artery applanation tonometry in 312 hypertensive patients between 16 to 49 years (134 women, mean age 35 ± 9 years), 185 of whom were on antihypertensive treatment. RESULTS: Higher MAP levels (≥ 100 mmHg) were significantly associated with higher brachial and central SBP (P < 0.001), PP (P < 0.001), incident wave (P = 0.005), AP (P < 0.001), and PWV (P < 0.001) compared to lower MAP levels. The relationship between MAP and brachial PP (P < 0.001), central PP (P < 0.001), incident wave (P < 0.001), and AP (P < 0.01), but not PWV, strengthens with age. The age-related increase in the contribution of MAP to brachial PP (P < 0.001), central PP (P < 0.001), and incident wave (P < 0.001) was more prominent in women than in men beginning in the fourth decade. In multiple regression analyses, MAP remained a significantly stronger predictor of central PP and incident wave in women than in men, independent of age, heart rate, and antihypertensive treatment. In turn, age remained a significantly stronger predictor of central PP and incident wave in women than in men, independent of MAP, heart rate, and antihypertensive treatment. CONCLUSIONS: Women of reproductive age showed a steeper increase in PP with increasing MAP, despite comparable increases in arterial stiffness in both sexes. The difference was driven by a greater contribution of MAP to the forward component of the pressure wave in women.