Integra® Dermal Regeneration Template in Complex Scalp Reconstruction.

Background/Objectives: The need for surgical reconstruction of scalp defects following the excision of cutaneous skin cancers is an increasingly common procedure. Particular challenges arise when considering options for reconstruction of large defects not amenable to local skin flap coverage. The use of skin grafts poses the risk of donor site morbidity. This paper investigates the emerging use of Integra®, a synthetic acellular dermal regeneration template, as an alternative or adjunct to skin grafting in scalp reconstruction. Methods: The study presents a retrospective analysis of 101 patients who underwent Integra®-based reconstruction of scalp defects. Demographics, procedure details, complications, need for further surgery, and time to healing were evaluated. Results: The overall success rate of the one-stage Integra®-only procedure was 95%, with a minor complication rate of 30.7%. Anticoagulation medication was identified as an independent risk factor for post-operative infection, while previous head and neck radiotherapy and increased defect depth were associated with the requirement for a second-stage skin graft. Conclusions: These findings support the consideration of Integra® as a safe and viable alternative for both partial and full thickness scalp defects in a select cohort of complex highly co-morbid patients, reducing complications and the need for additional procedures.

Surviving the serenade: how conflicting selection pressures shape the early stages of sexual signal diversification.

Understanding how the early stages of sexual signal diversification proceed is critically important because these microevolutionary dynamics directly shape species trajectories and impact macroevolutionary patterns. Unfortunately, studying this is challenging because signals involve complex interactions between behavior, morphology, and physiology, much of which can only be measured in real-time. In Hawaii, male Pacific field cricket song attracts both females and a deadly parasitoid fly. Over the past two decades, there has been a marked increase in signal variation in Hawaiian populations of these crickets, including novel male morphs with distinct mating songs. We capitalize on this rare opportunity to track changes in morph composition over time in a population with three novel morphs, investigating how mate and parasitoid attraction (components of sexual and natural selection) may shape signal evolution. We find dramatic fluctuation in morph proportions over the three years of the study, including the arrival and rapid increase of one novel morph. Natural and sexual selection pressures act differently among morphs, with some more attractive to mates and others more protected from parasitism. Collectively, our results suggest that differential protection from parasitism among morphs, rather than mate attraction, aligns with recent patterns of phenotypic change in the wild.

Alkaptonuria.

Alkaptonuria is a rare inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase activity. The consequent homogentisic acid (HGA) accumulation in body fluids and tissues leads to a multisystemic and highly debilitating disease whose main features are dark urine, ochronosis (HGA-derived pigment in collagen-rich connective tissues), and a painful and severe form of osteoarthropathy. Other clinical manifestations are extremely variable and include kidney and prostate stones, aortic stenosis, bone fractures, and tendon, ligament and/or muscle ruptures. As an autosomal recessive disorder, alkaptonuria affects men and women equally. Debilitating symptoms appear around the third decade of life, but a proper and timely diagnosis is often delayed due to their non-specific nature and a lack of knowledge among physicians. In later stages, patients' quality of life might be seriously compromised and further complicated by comorbidities. Thus, appropriate management of alkaptonuria requires a multidisciplinary approach, and periodic clinical evaluation is advised to monitor disease progression, complications and/or comorbidities, and to enable prompt intervention. Treatment options are patient-tailored and include a combination of medications, physical therapy and surgery. Current basic and clinical research focuses on improving patient management and developing innovative therapies and implementing precision medicine strategies.

Detecting defects that reduce breakdown voltage using machine learning and optical profilometry.

Semiconductor wafer manufacturing relies on the precise control of various performance metrics to ensure the quality and reliability of integrated circuits. In particular, GaN has properties that are advantageous for high voltage and high frequency power devices; however, defects in the substrate growth and manufacturing are preventing vertical devices from performing optimally. This paper explores the application of machine learning techniques utilizing data obtained from optical profilometry as input variables to predict the probability of a wafer meeting performance metrics, specifically the breakdown voltage (Vbk). By incorporating machine learning techniques, it is possible to reliably predict performance metrics that cause devices to fail at low voltage. For diodes that fail at a higher (but still below theoretical) breakdown voltage, alternative inspection methods or a combination of several experimental techniques may be necessary.

Nanoscale Infrared Spectroscopic Characterization of Extended Defects in 4H-Silicon Carbide.

Extended defects in wide-bandgap semiconductors have been widely investigated using techniques providing either spectroscopic or microscopic information. Nano-Fourier transform infrared spectroscopy (nano-FTIR) is a nondestructive characterization method combining FTIR with nanoscale spatial resolution (∼20 nm) and topographic information. Here, we demonstrate the capability of nano-FTIR for the characterization of extended defects in semiconductors by investigating an in-grown stacking fault (IGSF) present in a 4H-SiC epitaxial layer. We observe a local spectral shift of the mid-infrared near-field response, consistent with the identification of the defect stacking order as 3C-SiC (cubic) from comparative simulations based on the finite dipole model (FDM). This 3C-SiC IGSF contrasts with the more typical 8H-SiC IGSFs reported previously and is exemplary in showing that nanoscale spectroscopy with nano-FTIR can provide new insights into the properties of extended defects, the understanding of which is crucial for mitigating deleterious effects of such defects in alternative semiconductor materials and devices.

Ratcheting synthesis.

Synthetic chemistry has traditionally relied on reactions between reactants of high chemical potential and transformations that proceed energetically downhill to either a global or local minimum (thermodynamic or kinetic control). Catalysts can be used to manipulate kinetic control, lowering activation energies to influence reaction outcomes. However, such chemistry is still constrained by the shape of one-dimensional reaction coordinates. Coupling synthesis to an orthogonal energy input can allow ratcheting of chemical reaction outcomes, reminiscent of the ways that molecular machines ratchet random thermal motion to bias conformational dynamics. This fundamentally distinct approach to synthesis allows multi-dimensional potential energy surfaces to be navigated, enabling reaction outcomes that cannot be achieved under conventional kinetic or thermodynamic control. In this Review, we discuss how ratcheted synthesis is ubiquitous throughout biology and consider how chemists might harness ratchet mechanisms to accelerate catalysis, drive chemical reactions uphill and programme complex reaction sequences.

Rectus Sheath Block Improves Patient Recovery Following Open Aortic Surgery.

BACKGROUND: Postoperative pain management remains a barrier to recovery following aortic surgery. Although epidural catheters help in adjunctive pain management, less is known about the use of rectus sheath blocks. We compared patient recovery following open abdominal aortic surgery (OAS) with and without adjunctive rectus block. METHODS: Adult patients undergoing open abdominal aortic aneurysm repair and aortobifemoral or aortoiliac bypass for occlusive disease were identified and stratified by use of general anesthesia alone (GA) versus adjunctive use of a rectus sheath block (GA + RB). A small number of patients with GA and concomitant epidural analgesia, along with patients that had retroperitoneal repairs, were not included in further analysis. Outcomes included time to extubation, intraoperative and postoperative morphine milligram equivalents (MME) utilization, length of stay, discharge MME, and postoperative complications. Categorial data were compared with Person Chi-Square tests or Fisher's exact tests. Continuous data were tested with independent t-tests or Mann-Whitney U-tests. RESULTS: From January 2017 to April 2022, there were 106 patients who underwent open aortic surgery, 55 patients with GA alone, 39 with GA + RB, and 12 patients who had a GA with concomitant epidural analgesia. Between GA and GA + RB, patients were comparable in both groups in terms of age, BMI (body mass index), smoking history, hypertension, diabetes, CAD (coronary artery disease), COPD (chronic obstructive pulmonary disease), and ASA (American Society of Anesthesiologists) class and prior opioid use. Patients with GA + RB were more likely to have scheduled elective procedures (80% GA cohort vs. 94.9% RB, P = 0.040), and a lower incidence of retroperitoneal exposure (14.5% GA cohort vs. 0% RB, P = 0.019). Patients with GA + RB had shorter time to extubation than GA (84.6% < 12 hr vs. 44.4%, P < 0.001), greater rate of procedural ketamine usage (GA + RB: 61.5% vs. GA: 40.0%, P = 0.049), lower MME at first postoperative day (median MME GA + RB: 25.0 vs. GA: 67.5, P = 0.002), lower discharge MME (median MME GA + RB: 142.5 vs. GA: 225.0, P = 0.036), and overall shorter length of stay (median stay GA + RB: 5 vs. GA: 6 days, P = 0.006). Postoperative complications were similar between groups. Similar findings were found in the comparison between elective-only GA and GA + RB patients and after exclusion of patients who only had a single shot of regional anesthesia. CONCLUSIONS: Patients that receive adjunctive rectus sheath blocks for pain control following OAS utilize fewer opioid medications during hospital stay and at discharge. Rectus sheath blocks represent an alternative option to other periprocedural analgesia following open aortic surgery.

A novel cricket morph has diverged in song and wing morphology across island populations.

Divergence of sexual signals between populations can lead to speciation, yet opportunities to study the immediate aftermath of novel signal evolution are rare. The recent emergence and spread of a new mating song, purring, in Hawaiian populations of the Pacific field cricket (Teleogryllus oceanicus) allows us to investigate population divergence soon after the origin of a new signal. Male crickets produce songs with specialized wing structures to attract mates from afar (calling) and entice them to mate when found (courtship). However, in Hawaii, these songs also attract an eavesdropping parasitoid fly (Ormia ochracea) that kills singing males. The novel purring song, produced with heavily modified wing morphology, attracts female crickets but not the parasitoid fly, acting as a solution to this conflict between natural and sexual selection. We've recently observed increasing numbers of purring males across Hawaii. In this integrative field study, we investigated the distribution of purring and the proportion of purring males relative to other morphs in six populations on four islands and compared a suite of phenotypic traits (wing morphology, calling song and courtship song) that make up this novel signal across populations of purring males. We show that purring is found in varying proportions across five, and is locally dominant in four, Hawaiian populations. We also show that calling songs, courtship songs and wing morphology of purring males differ geographically. Our findings demonstrate the rapid pace of evolution in island populations and provide insights into the emergence and divergence of new sexual signals over time.

Nitisinone Treatment Affects Biomarkers of Bone and Cartilage Remodelling in Alkaptonuria Patients.

Nitisinone has been approved for treatment of alkaptonuria (AKU). Non-invasive biomarkers of joint tissue remodelling could aid in understanding the molecular changes in AKU pathogenesis and how these can be affected by treatment. Serological and urinary biomarkers of type I collagen and II collagen in AKU were investigated in patients enrolled in the randomized SONIA 2 (NCT01916382) clinical study at baseline and yearly until the end of the study (Year 4). The trajectories of the biomarkers over time were observed. After treatment with nitisinone, the biomarkers of type I collagen remodelling increased at Year 1 (19% and 40% increase in CTX-I and PRO-C1, respectively), which was potentially reflected in the higher degree of mobility seen following treatment. The biomarkers of type II collagen remodelling decreased over time in the nitisinone group: C2M showed a 9.7% decline at Year 1, and levels then remained stable over the following visits; CTX-II showed a 26% decline at Year 3 and 4 in the nitisinone-treated patients. Nitisinone treatment induced changes in biomarkers of bone and cartilage remodelling. These biomarkers can aid patient management and deepen our knowledge of the molecular mechanisms of this rare disease.

Increased prevalence of Parkinson's disease in alkaptonuria.

Amongst a cohort of 88 alkaptonuria (AKU) patients attending the United Kingdom National Alkaptonuria Centre (NAC), four unrelated patients had co-existing Parkinson's disease (PD). Two of the NAC patients developed PD before receiving nitisinone (NIT) while the other two developed overt PD during NIT therapy. NIT lowers redox-active homogentisic acid (HGA) and profoundly increases tyrosine (TYR). A further unpublished case of a Dutch patient with AKU and PD on deep brain stimulation is included in this report. A Pubmed search revealed a further five AKU patients with PD, all without NIT usage. The prevalence of PD in AKU in the NAC appears to be nearly 20-times higher than in the non-AKU population (p < 0.001) even when adjusted for age. We propose that life-long exposure to redox-active HGA may account for the higher prevalence of PD in AKU. Furthermore, the appearance of PD in AKU patients during NIT therapy may be due to unmasking dopamine deficiency in susceptible individuals, as a result of the tyrosinaemia during NIT therapy inhibiting the rate-limiting brain tyrosine hydroxylase.

Evaluation of Homogentisic Acid, a Prospective Antibacterial Agent Highlighted by the Suitability of Nitisinone in Alkaptonuria 2 (SONIA 2) Clinical Trial.

Despite urgent warnings about the spread of multidrug-resistant bacteria, the antibiotic development pipeline has remained sparsely populated. Naturally occurring antibacterial compounds may provide novel chemical starting points for antibiotic development programs and should be actively sought out. Evaluation of homogentisic acid (HGA), an intermediate in the tyrosine degradation pathway, showed that the compound had innate activity against Gram-positive and Gram-negative bacteria, which was lost following conversion into the degradation product benzoquinone acetic acid (BQA). Anti-staphylococcal activity of HGA can be attributed to effects on bacterial membranes. Despite an absence of haemolytic activity, the compound was cytotoxic to human HepG2 cells. We conclude that the antibacterial activity and in vitro safety profile of HGA render it more suitable for use as a topical agent or for inclusion in a small-molecule medicinal chemistry program.

Dorsal Cheilectomy Using Great Toe Metatarsophalangeal Joint Arthroscopy for the Treatment of Hallux Rigidus.

Great toe metatarsophalangeal joint (MTPJ) arthroscopy has been described in the literature for more than 50 years for treatment of a multitude of first MTPJ pathologies, including hallux rigidus, hallux valgus, and osteochondritis dissecans, among others. Despite this, the use of great toe MTPJ arthroscopy has not become widely used for treatment of these conditions as the result of reported difficulties with adequate visualization of the joint surface and manipulation of surrounding soft-tissue structures with the instruments available. We propose a simple technique with illustrations of the operating room setup and procedural steps to perform a dorsal cheilectomy in those with early-stage hallux rigidus using great toe MTPJ arthroscopy and a minimally invasive surgical burr in a way that is reproducible by foot and ankle surgeons.

Assessing thermal imagery integration into object detection methods on air-based collection platforms.

Object detection models commonly focus on utilizing the visible spectrum via Red-Green-Blue (RGB) imagery. Due to various limitations with this approach in low visibility settings, there is growing interest in fusing RGB with thermal Long Wave Infrared (LWIR) (7.5-13.5 µm) images to increase object detection performance. However, we still lack baseline performance metrics evaluating RGB, LWIR and RGB-LWIR fused object detection machine learning models, especially from air-based platforms. This study undertakes such an evaluation, finding that a blended RGB-LWIR model generally exhibits superior performance compared to independent RGB or LWIR approaches. For example, an RGB-LWIR blend only performs 1-5% behind the RGB approach in predictive power across various altitudes and periods of clear visibility. Yet, RGB fusion with a thermal signature overlay provides edge redundancy and edge emphasis, both which are vital in supporting edge detection machine learning algorithms (especially in low visibility environments). This approach has the ability to improve object detection performance for a range of use cases in industrial, consumer, government, and military applications. This research greatly contributes to the study of multispectral object detection by quantifying key factors affecting model performance from drone platforms (including distance, time-of-day and sensor type). Finally, this research additionally contributes a novel open labeled training dataset of 6300 images for RGB, LWIR, and RGB-LWIR fused imagery, collected from air-based platforms, enabling further multispectral machine-driven object detection research.

Hereditary Tyrosinemia Type 1 Mice under Continuous Nitisinone Treatment Display Remnants of an Uncorrected Liver Disease Phenotype.

Hereditary tyrosinemia type 1 (HT1) is a genetic disorder of the tyrosine degradation pathway (TIMD) with unmet therapeutic needs. HT1 patients are unable to fully break down the amino acid tyrosine due to a deficient fumarylacetoacetate hydrolase (FAH) enzyme and, therefore, accumulate toxic tyrosine intermediates. If left untreated, they experience hepatic failure with comorbidities involving the renal and neurological system and the development of hepatocellular carcinoma (HCC). Nitisinone (NTBC), a potent inhibitor of the 4-hydroxyphenylpyruvate dioxygenase (HPD) enzyme, rescues HT1 patients from severe illness and death. However, despite its demonstrated benefits, HT1 patients under continuous NTBC therapy are at risk to develop HCC and adverse reactions in the eye, blood and lymphatic system, the mechanism of which is poorly understood. Moreover, NTBC does not restore the enzymatic defects inflicted by the disease nor does it cure HT1. Here, the changes in molecular pathways associated to the development and progression of HT1-driven liver disease that remains uncorrected under NTBC therapy were investigated using whole transcriptome analyses on the livers of Fah- and Hgd-deficient mice under continuous NTBC therapy and after seven days of NTBC therapy discontinuation. Alkaptonuria (AKU) was used as a tyrosine-inherited metabolic disorder reference disease with non-hepatic manifestations. The differentially expressed genes were enriched in toxicological gene classes related to liver disease, liver damage, liver regeneration and liver cancer, in particular HCC. Most importantly, a set of 25 genes related to liver disease and HCC development was identified that was differentially regulated in HT1 vs. AKU mouse livers under NTBC therapy. Some of those were further modulated upon NTBC therapy discontinuation in HT1 but not in AKU livers. Altogether, our data indicate that NTBC therapy does not completely resolves HT1-driven liver disease and supports the sustained risk to develop HCC over time as different HCC markers, including Moxd1, Saa, Mt, Dbp and Cxcl1, were significantly increased under NTBC.

A delayed benign anastomotic stricture after anterior resection for sigmoid adenocarcinoma with concomitant collagenous colitis.

Benign anastomotic strictures most commonly occur within 3-12 months after anterior resection (AR) with chronic symptoms amenable to endoscopic treatment. This case describes an acute large bowel obstruction secondary to a severe delayed benign anastomotic stricture in a 74-year-old female who had previously underwent a laparoscopic AR for sigmoid adenocarcinoma 3 years prior. The pathophysiology of benign anastomotic strictures remains poorly understood. This case was likely multifactorial. Potential contributing factors include anastomotic ischaemia and concomitant collagenous colitis, with inflammation leading to fibrosis and stricture development. Surgical techniques to optimize anastomotic vascularity are important to consider, particularly in older patients with multiple co-morbidities.

Using machine learning with optical profilometry for GaN wafer screening.

To improve the manufacturing process of GaN wafers, inexpensive wafer screening techniques are required to both provide feedback to the manufacturing process and prevent fabrication on low quality or defective wafers, thus reducing costs resulting from wasted processing effort. Many of the wafer scale characterization techniques-including optical profilometry-produce difficult to interpret results, while models using classical programming techniques require laborious translation of the human-generated data interpretation methodology. Alternatively, machine learning techniques are effective at producing such models if sufficient data is available. For this research project, we fabricated over 6000 vertical PiN GaN diodes across 10 wafers. Using low resolution wafer scale optical profilometry data taken before fabrication, we successfully trained four different machine learning models. All models predict device pass and fail with 70-75% accuracy, and the wafer yield can be predicted within 15% error on the majority of wafers.

Talar Arthroscopic Reduction and Internal Fixation (TARIF): A Novel All-Inside Soft-Tissue-Preserving Technique.

Background: Talar arthroscopic reduction and internal fixation (TARIF) is an alternative approach for the operative fixation of talar fractures that may be utilized instead of more traditional open approaches such as medial, lateral, or even dual anterolateral. The TARIF approach allows for nearly anatomic fracture reduction and fixation of talar neck, body, and posterior dome fractures while minimizing the soft-tissue stripping and vascular injury associated with the standard anterolateral approach. Description: Following initial closed fracture reduction and any associated procedures, we recommend obtaining computed tomography scans of the injured ankle in order to evaluate the fracture pattern and allow for preoperative planning. Most patients can be positioned prone for this procedure, except for those with fractures associated with anterior loose bodies and those with neck fractures requiring reduction, which are both amenable to lateral positioning1. The feet are positioned off the end of the bed in a neutral position with room to plantar flex and dorsiflex the ankle freely for reduction maneuvers. Following induction of anesthesia and positioning of the patient, the fluoroscopic screen and arthroscopy equipment are positioned on the side opposite the surgeon. A mini C-arm is utilized for the fluoroscopy. The team may then proceed with preparing and draping the surgical field. The surgeon proceeds with creating posteromedial and posterolateral portals to view the fracture site. For talar neck fractures, we utilize standard posterolateral and posteromedial portals directly adjacent to the Achilles tendon at the level of the tip of the medial malleolus, which have previously been established as safe with respect to neurovascular structures4. Of note, for talar body fractures these portals are placed slightly more distal at the level of the distal fibula, allowing the screws to be placed perpendicular to the fracture site. An accessory sinus tarsi portal can be established if further reduction to correct varus is needed. The flexor hallucis longus tendon serves as a landmark throughout the case to maintain orientation. We prefer to utilize a 1.9-mm malleable arthroscopic NanoScope (Arthrex), which maximizes our view in the small subtalar space and allows for visualization over the talar dome. A shaver is then utilized to clear out the deep joint capsule and remove fracture hematoma. In our experience, after the initial primary reduction attempt by the orthopaedic trauma provider, the fracture is relatively stable and often held by an external fixator. The remaining reduction is performed with use of manipulation of the ankle in combination with an accessory sinus tarsi portal, utilizing an elevator or a small reduction tool in 1 of the posterior portals. We have also utilized percutaneous Kirschner wires to "joystick" the fragments prior to the placement of the guidewires. We then place multiple 1.1-mm guidewires under direct arthroscopic and fluoroscopic visualization, utilizing the flexor hallucis longus tendon as our safe margin to ensure that we are lateral on the posterior talar dome. This approach in turn allows us to ensure the integrity of the neurovascular structures, such as the tibial artery and nerve medially as well as the sural nerve laterally. Finally, cannulated headless compression screws are passed over the guidewire to achieve fixation. The senior author (K.D.M.) prefers fully threaded, cannulated 3.5-mm titanium headless compression screws because the cannulation allows the guidewires to be placed through the posterolateral and posteromedial portals, while the headless design allows the screws to be placed under the articular cartilage. Additionally, the use of titanium allows for improved postoperative magnetic resonance imaging quality as well as favorable biomechanics as titanium has a modulus of elasticity similar to bone. After drilling is complete, we sequentially tighten the screws by hand to prevent varus or valgus angulation. Although we have not experienced failure or a poor bite when utilizing the 3.5-mm fully threaded compression screw, we have found that the partially threaded screw can at times have a poorer bite. Additionally, we select a 3.5-mm screw rather than a larger screw-say 5.5 mm-as we have found that the larger screws do not easily pass through our portals, which are minimal in size when utilizing this approach. Throughout this process, fluoroscopy, in tandem with arthroscopy, is obtained in multiple views to ensure that fixation and orientation are appropriate and the screws are in the optimal position, off of the articular surface. If large osseous defects or collapse are encountered, an accessory anteromedial portal is utilized to add grafting material. Following confirmation of adequate fracture fixation, final arthroscopic images of the talar dome continuity, subtalar continuity, and ankle joint during range of motion are obtained. The portal sites are closed with use of 3-0 nonabsorbable sutures, and a well-padded L and U splint is applied postoperatively. Alternatives: Alternatives include the standard anterolateral approach to fixation or dual anterior approach, a medial or lateral approach, and external fixation with interval operative fixation. Rationale: TARIF is indicated for reduction of a wide variety of talar fractures, including neck, body, and posterior facet fractures, and offers the added advantage of minimizing the soft-tissue stripping and vascular injury associated with the standard anterolateral approach. Additionally, TARIF is well suited for patients with a compromised soft-tissue envelope or associated vascular injury, such as those with open-fracture pathology, because the approach avoids further disruption of these tissues. The overall aim of the procedure is to obtain adequate fracture reduction while avoiding the neurovasculature and soft-tissue envelope that would commonly be encountered anteriorly. The procedure is completed through 2 incisions, a posteromedial portal and a posterolateral portal, through which the fracture is visualized, reduced, and fixated using cannulated screws. The fixated talus is tested through its range of motion while under arthroscopy and fluoroscopy to ensure adequate fixation while preserving range of motion. Expected Outcomes: The TARIF procedure has been shown to successfully treat many complex talar fractures2. We theorize that this procedure produces equivalent outcomes when compared with the standard approaches to fracture fixation, with the added benefit of avoiding excessive soft-tissue disruption and neurovascular compromise. Our arthroscopic approach allows for direct visualization of articular injuries and reduction, with the ability to evacuate loose bodies and fracture hematoma, reducing matrix metalloproteinases (MMPs) known to cause posttraumatic ankle arthritis1,3. Multiple case series have assessed the use of this technique, showing preserved range of motion and minimal residual pain or disability, as measured with use of multiple scoring systems such as the American Orthopaedic Foot & Ankle Society Ankle-Hindfoot scale1,2. Important Tips: Immediately after accessing the ankle via the operative portals, identify the flexor hallucis longus tendon to prevent iatrogenic injury to the neurovascular bundle.Plantar flexion of the ankle while applying anterior force to the talar body often aids in reduction.Place the medial guidewire directly adjacent to the flexor hallucis tendon in order to ensure that it is medial enough.Utilize anterior-to-posterior fluoroscopic images of the foot and ankle to ensure screw placement.Directly visualize the fracture site as the screws are sequentially tightened in order to prevent malalignment.Countersink all screw heads and directly verify with arthroscopic visualization. Acronyms & Abbreviations: MVC = motor vehicle collisionXR = x-ray (radiograph)CT = computed tomographyEx-fix = external fixatorMRI = magnetic resonance imagingFT = fully threadedFHL = flexor hallucis longusAP = anteroposteriorROM = range of motionDVT = deep vein thrombosisBID = bis in die (twice daily dosing).

Low-Flow Ankle Arthroscopy for Gunshot Wounds With Retained Intra-Articular Ballistic.

Gunshot injuries to the foot and ankle can cause unique and challenging situations for orthopaedic surgeons. The foot and ankle have limited soft-tissue coverage and highly congruent joint spaces, leading to injuries that are often intra-articular with substantial tissue loss. These injuries are often confounded by feet shod in footwear that is pulled into the path of the missile and corresponding tissue. Thus, we report our experience of using low-flow arthroscopy for extraction of retained ballistics, while irrigating and debriding the path of the missile.

Decoupling of sexual signals and their underlying morphology facilitates rapid phenotypic diversification.

How novel phenotypes evolve is challenging to imagine because traits are often underlain by numerous integrated phenotypic components, and changes to any one form can disrupt the function of the entire module. Yet novel phenotypes do emerge, and research on adaptive phenotypic evolution suggests that complex traits can diverge while either maintaining existing form-function relationships or through innovations that alter form-function relationships. How these alternate routes contribute to sexual signal evolution is poorly understood, despite the role of sexual signals in generating biodiversity. In Hawaiian populations of the Pacific field cricket, male song attracts both female crickets and a deadly acoustically orienting parasitoid fly. In response to this conflict between natural and sexual selection, male crickets have evolved altered wing morphologies multiple times, resulting in loss and dramatic alteration of sexual signals. More recently, we and others have observed a radical increase in sexual signal variation and the underlying morphological structures that produce song. We conducted the first combined analysis of form (wing morphology), function (emergent signal), and receiver responses to characterize novel variation, test alternative hypotheses about form-function relationships (Form-Function Continuity vs. Form-Function Decoupling), and investigate underlying mechanistic changes and fitness consequences of novel signals. We identified three sound-producing male morphs (one previously undescribed, named "rattling") and found that relationships between morphology and signals have been rewired (Form-Function Decoupling), rapidly and repeatedly, through the gain, loss, and alteration of morphological structures, facilitating the production of signals that exist in novel phenotypic space. By integrating across a hierarchy of phenotypes, we uncovered divergent morphs with unique solutions to the challenge of attracting mates while evading fatal parasitism.

Effects of Nitisinone on Oxidative and Inflammatory Markers in Alkaptonuria: Results from SONIA1 and SONIA2 Studies.

Nitisinone (NTBC) was recently approved to treat alkaptonuria (AKU), but there is no information on its impact on oxidative stress and inflammation, which are observed in AKU. Therefore, serum samples collected during the clinical studies SONIA1 (40 AKU patients) and SONIA2 (138 AKU patients) were tested for Serum Amyloid A (SAA), CRP and IL-8 by ELISA; Advanced Oxidation Protein Products (AOPP) by spectrophotometry; and protein carbonyls by Western blot. Our results show that NTBC had no significant effects on the tested markers except for a slight but statistically significant effect for NTBC, but not for the combination of time and NTBC, on SAA levels in SONIA2 patients. Notably, the majority of SONIA2 patients presented with SAA > 10 mg/L, and 30 patients in the control group (43.5%) and 40 patients (58.0%) in the NTBC-treated group showed persistently elevated SAA > 10 mg/L at each visit during SONIA2. Higher serum SAA correlated with lower quality of life and higher morbidity. Despite no quantitative differences in AOPP, the preliminary analysis of protein carbonyls highlighted patterns that deserve further investigation. Overall, our results suggest that NTBC cannot control the sub-clinical inflammation due to increased SAA observed in AKU, which is also a risk factor for developing secondary amyloidosis.