Quite a Pickle: A 10-Year Increase in Pickleball-Related Hand Injuries.

BACKGROUND: Pickleball popularity has significantly increased in the United States. Wrist, hand, and finger injuries are commonly seen among pickleball players and are on the rise. METHODS: The National Electronic Injury Surveillance System database was queried from 2013 to 2022 tennis- and pickleball-related injuries in the United States. Data were filtered to include wrist, hand, and finger injuries only. RESULTS: There were a total of 12 021 estimated pickleball injuries between 2013 and 2022, most commonly in white women greater than 55 years old. The most common mechanism of injury (90.5%) was a fall. The number of injuries increased by 765.6% between 2013 and 2022. The growth in the number of pickleball-related injuries was found to be statistically significant (P < .05), whereas the growth for tennis-related injuries was found to be not statistically different from 0. There was a statistical difference between the growth of the number of pickleball injuries per year and the number of tennis injuries. The wrist was the most common location of injury (70.0%) compared with the hand (10.5%) and fingers (19.5%). The most common injury diagnosis was fracture (60.3%). Overall, the most common injury was wrist fracture (50.0%). CONCLUSIONS: Hand surgeons should be aware of the increasing prevalence of pickleball-related injuries as an alternative mechanism of injury, particularly among the elderly.

From the fat body to the hemolymph: Profiling tick immune and storage proteins through transcriptomics and proteomics.

Ticks are blood-feeding arachnids that are known to transmit various pathogenic microorganisms to their hosts. During blood feeding, ticks activate their metabolism and immune system to efficiently utilise nutrients from the host's blood and complete the feeding process. In contrast to insects, in which the fat body is known to be a central organ that controls essential metabolic processes and immune defense mechanisms, the function of the fat body in tick physiology is still relatively unexplored. To fill this gap, we sought to uncover the repertoire of genes expressed in the fat body associated with trachea (FB/Tr) by analyzing the transcriptome of individual, partially fed (previtellogenic) Ixodes ricinus females. The resulting catalog of individual mRNA sequences reveals a broad repertoire of transcripts encoding proteins involved in nutrient storage and distribution, as well as components of the tick immune system. To gain a detailed insight into the secretory products of FB/Tr specifically involved in inter-tissue transport and humoral immunity, the transcriptomic data were complemented with the proteome of soluble proteins in the hemolymph of partially fed female ticks. Among these proteins, the hemolipoglyco-carrier proteins were predominant. When comparing immune peptides and proteins from the fat body with those produced by hemocytes, we found that the fat body serves as a unique producer of certain immune components. Finally, time-resolved transcriptional regulation of selected immune transcripts from the FB/Tr was examined in response to experimental challenges with model microbes and analyzed by RT-qPCR. Overall, our data show that the fat body of ticks, similar to insects, is an important metabolic tissue that also plays a remarkable role in immune defense against invading microbes. These findings improve our understanding of tick biology and its impact on the transmission of tick-borne pathogens.

Changes in saliva protein profile throughout Rhipicephalus microplus blood feeding.

BACKGROUND: When feeding on a vertebrate host, ticks secrete saliva, which is a complex mixture of proteins, lipids, and other molecules. Tick saliva assists the vector in modulating host hemostasis, immunity, and tissue repair mechanisms. While helping the vector to feed, its saliva modifies the site where pathogens are inoculated and often facilitates the infection process. The objective of this study is to uncover the variation in protein composition of Rhipicephalus microplus saliva during blood feeding. METHODS: Ticks were fed on calves, and adult females were collected, weighed, and divided in nine weight groups, representing the slow and rapid feeding phases of blood feeding. Tick saliva was collected, and mass spectrometry analyses were used to identify differentially secreted proteins. Bioinformatic tools were employed to predict the structural and functional features of the salivary proteins. Reciprocal best hit analyses were used to identify conserved families of salivary proteins secreted by other tick species. RESULTS: Changes in the protein secretion profiles of R. microplus adult female saliva during the blood feeding were observed, characterizing the phenomenon known as "sialome switching." This observation validates the idea that the switch in protein expression may serve as a mechanism for evading host responses against tick feeding. Cattle tick saliva is predominantly rich in heme-binding proteins, secreted conserved proteins, lipocalins, and protease inhibitors, many of which are conserved and present in the saliva of other tick species. Additionally, another remarkable observation was the identification of host-derived proteins as a component of tick saliva. CONCLUSIONS: Overall, this study brings new insights to understanding the dynamics of the proteomic profile of tick saliva, which is an important component of tick feeding biology. The results presented here, along with the disclosed sequences, contribute to our understanding of tick feeding biology and might aid in the identification of new targets for the development of novel anti-tick methods.

In-depth transcriptomic analysis of Anopheles gambiae hemocytes uncovers novel genes and the oenocytoid developmental lineage.

BACKGROUND: Hemocytes are immune cells that patrol the mosquito hemocoel and mediate critical cellular defense responses against pathogens. However, despite their importance, a comprehensive transcriptome of these cells was lacking because they constitute a very small fraction of the total cells in the insect, limiting the study of hemocyte differentiation and immune function. RESULTS: In this study, an in-depth hemocyte transcriptome was built by extensive bulk RNA sequencing and assembly of hemocyte RNAs from adult A. gambiae female mosquitoes, based on approximately 2.4 billion short Illumina and about 9.4 million long PacBio high-quality reads that mapped to the A. gambiae PEST genome (P4.14 version). A total of 34,939 transcripts were annotated including 4,020 transcripts from novel genes and 20,008 novel isoforms that result from extensive differential splicing of transcripts from previously annotated genes. Most hemocyte transcripts identified (89.8%) are protein-coding while 10.2% are non-coding RNAs. The number of transcripts identified in the novel hemocyte transcriptome is twice the number in the current annotation of the A. gambiae genome (P4.14 version). Furthermore, we were able to refine the analysis of a previously published single-cell transcriptome (scRNAseq) data set by using the novel hemocyte transcriptome as a reference to re-define the hemocyte clusters and determine the path of hemocyte differentiation. Unsupervised pseudo-temporal ordering using the Tools for Single Cell Analysis software uncovered a novel putative prohemocyte precursor cell type that gives rise to prohemocytes. Pseudo-temporal ordering with the Monocle 3 software, which analyses changes in gene expression during dynamic biological processes, determined that oenocytoids derive from prohemocytes, a cell population that also gives rise to the granulocyte lineage. CONCLUSION: A high number of mRNA splice variants are expressed in hemocytes, and they may account for the plasticity required to mount efficient responses to many different pathogens. This study highlights the importance of a comprehensive set of reference transcripts to perform robust single-cell transcriptomic data analysis of cells present in low abundance. The detailed annotation of the hemocyte transcriptome will uncover new facets of hemocyte development and function in adult dipterans and is a valuable community resource for future studies on mosquito cellular immunity.

A longitudinal transcriptomic analysis of Rhipicephalus microplus midgut upon feeding.

Rhipicephalus microplus, a highly host-specific tick that primarily feeds on cattle, posing a significant threat to livestock production. The investigation of tick physiology is crucial for identifying potential targets in tick control. Of particular interest adult female ticks undergo a significant expansion of the midgut during feeding, leading to an over 100-fold increase in body weight. Beyond the functions of storing and digesting blood meals, the tick midgut plays a crucial role in acquiring and transmitting pathogens. However, our understanding of tick midgut physiology remains limited. In this study we conducted a comprehensive longitudinal transcriptome analysis of the midgut from adult female R. microplus ticks collected at various feeding stages, providing an overview of the transcriptional modulation in this organ as feeding progress. By employing a de novo assembly approach followed by coding-sequences (CDS) extraction, 60,599 potential CDS were identified. In preparation for functional annotation and differential expression analysis, transcripts that showed an average transcript per million (TPM) ≥ 3 in at least one of the biological conditions were extracted. This selection process resulted in a total of 10,994 CDS, which were categorized into 24 functional classes. Notably, our differential expression analysis revealed three main transcriptional profiles. In the first one, representing the slow-feeding stage, the most abundant functional classes were the "protein synthesis" and "secreted" groups, reflecting the highly active state of the tick midgut. The second profile partially accounts for the rapid-feeding stage, in which a high number of differentially expressed transcripts was observed. Lastly, the third transcriptional profile represents post-detached ticks. Notably the highest number of modulated transcripts was observed up to 48 h post-detachment (hpd), however no major differences was observed up to 168 hpd. Overall, the data presented here offers a temporal insight into tick midgut physiology, contributing to the identification of potential targets for the development of anti-tick control strategies.

Acid phosphatase-like proteins, a biogenic amine and leukotriene-binding salivary protein family from the flea Xenopsylla cheopis.

The salivary glands of hematophagous arthropods contain pharmacologically active molecules that interfere with host hemostasis and immune responses, favoring blood acquisition and pathogen transmission. Exploration of the salivary gland composition of the rat flea, Xenopsylla cheopis, revealed several abundant acid phosphatase-like proteins whose sequences lacked one or two of their presumed catalytic residues. In this study, we undertook a comprehensive characterization of the tree most abundant X. cheopis salivary acid phosphatase-like proteins. Our findings indicate that the three recombinant proteins lacked the anticipated catalytic activity and instead, displayed the ability to bind different biogenic amines and leukotrienes with high affinity. Moreover, X-ray crystallography data from the XcAP-1 complexed with serotonin revealed insights into their binding mechanisms.

Insight Into the Dynamics of the Ixodes ricinus Nymphal Midgut Proteome.

Ticks are ectoparasites that feed on blood and have an impressive ability to consume and process enormous amounts of host blood, allowing extremely long periods of starvation between blood meals. The central role in the parasitic lifestyle of ticks is played by the midgut. This organ efficiently stores and digests ingested blood and serves as the primary interface for the transmission of tick-borne pathogens. In this study, we used a label-free quantitative approach to perform a novel dynamic proteomic analysis of the midgut of Ixodesricinus nymphs, covering their development from unfed to pre-molt stages. We identified 1534 I. ricinus-specific proteins with a relatively low proportion of host proteins. This proteome dataset, which was carefully examined by manual scrutiny, allowed precise annotation of proteins important for blood meal processing and their dynamic changes during nymphal ontogeny. We focused on midgut molecules related to lipid hydrolysis, storage, and transport, opening a yet unexplored avenue for studying lipid metabolism in ticks. Further dynamic profiling of the tick's multi-enzyme digestive network, protease inhibitors, enzymes involved in redox homeostasis and detoxification, antimicrobial peptides, and proteins responsible for midgut colonization by Borrelia spirochetes promises to uncover new targets for targeting tick nymphs, the most critical life stage for transmission the pathogens that cause tick-borne diseases.

A longitudinal transcriptomic analysis from unfed to post-engorgement midguts of adult female Ixodes scapularis.

The hematophagy behavior has evolved independently several times within the Arthropoda phylum. Interestingly, the process of acquiring a blood meal in ticks is considerably distinct from that observed in other blood-feeding arthropods. Instead of taking seconds to minutes to complete a blood meal, an adult female Ixodes scapularis tick can remain attached to its host for numerous days. During this extended feeding period, the tick undergoes drastic morphological changes. It is well established that the tick midgut plays a pivotal role not only in blood meal digestion but also in pathogen acquisition and transmission. However, our understanding of the underlying molecular mechanisms involved in these events remains limited. To expedite tick research, we conducted a comprehensive longitudinal RNA-sequencing of the tick midgut before, during, and after feeding. By collecting ticks in different feeding stages (unfed, slow feeding, rapid feeding, and early post-detached), we obtained a comprehensive overview of the transcripts present in each stage and the dynamic transcriptional changes that occur between them. This provides valuable insights into tick physiology. Additionally, through unsupervised clustering, we identified transcripts with similar patterns and stage-specific sequences. These findings serve as a foundation for selecting targets in the development of anti-tick control strategies and facilitate a better understanding of how blood feeding and pathogen infection impact tick physiology.

Plastic Surgery Roles in Wound Centers in the Northeastern United States.

INTRODUCTION: Wound care is a substantial industry costing nearly $19 billion USD, and dedicated wound care centers play a critical role via a multidisciplinary team-based approach. At the same time, plastic surgeons are often considered experts in evaluation and management of wounds, particularly chronic and complex wounds. However, the extent of direct involvement of plastic surgeons in wound care centers is unclear. In this study, we sought to evaluate the presence of plastic surgeons and other specialties in wound care centers across all Northeastern states Connecticut, Delaware, District of Columbia, Maine, Maryland, Massachusetts, New Jersey, New York, New Hampshire, Pennsylvania, Rhode Island, Virginia, West Virginia, and Vermont. METHODS: A comprehensive list of wound care clinics in northeastern United States was obtained from the Healogics website. For each site, information was gathered via website listings, including number of providers and the professional certification/specialization for each provider. Providers were those with qualifications including Doctor of Medicine (MD), Doctor of Osteopathic Medicine (DO), Doctor of Physical Therapy (DPT), Doctor of Podiatric Medicine (DPM), Certified Registered Nurse Anesthetist (CRNA), Certified Registered Nurse Practitioner (CRNP), Physician Associate (PA), and Physical Therapist (PT). RESULTS: A total of 118 Healogics wound care clinics and 492 providers were located across 14 northeastern states including District of Columbia. After researching each location, updated in November 2022, plastic surgeons were only 3.7% (18 of 492) providers employed. Specialties such as internal medicine (90 of 492 [18%]), general surgery (76 of 492 [15%]), podiatry (68 of 292 [13.8% ]), and other midlevel providers such as nurse practitioners (35 of 492 [7.1%]) were more frequently employed over plastic surgery. All plastic surgeons were board certified the American Board of Plastic Surgery. CONCLUSIONS: Wound care requires collaboration between specialties, with significant repercussions on health care costs and patient outcomes. Plastic surgery provides unique surgical services for the healing of wounds, and the natural expectation would be that plastic surgery should be heavily involved at wound care centers. However, the data do not reflect significant involvement at an official level. Further studies will investigate causes and the societal, financial, and patient impacts of this lack of direct engagement. Although many plastic surgeons may not desire the majority of their practice to be wound care management, it stands to reason that some affiliation, at least for patient awareness and referral, may be warranted.

A deeper insight into the sialome of male and female Culex quinquefasciatus mosquitoes.

INTRODUCTION: During evolution, blood-feeding arthropods developed a complex salivary mixture that can interfere with host haemostatic and immune response, favoring blood acquisition and pathogen transmission. Therefore, a survey of the salivary gland contents can lead to the identification of molecules with potent pharmacological activity in addition to increase our understanding of the molecular mechanisms underlying the hematophagic behaviour of arthropods. The southern house mosquito, Culex quinquefasciatus, is a vector of several pathogenic agents, including viruses and filarial parasites that can affect humans and wild animals. RESULTS: Previously, a Sanger-based transcriptome of the salivary glands (sialome) of adult C. quinquefasciatus females was published based on the sequencing of 503 clones organized into 281 clusters. Here, we revisited the southern mosquito sialome using an Illumina-based RNA-sequencing approach of both male and female salivary glands. Our analysis resulted in the identification of 7,539 coding DNA sequences (CDS) that were functionally annotated into 25 classes, in addition to 159 long non-coding RNA (LncRNA). Additionally, comparison of male and female libraries allowed the identification of female-enriched transcripts that are potentially related to blood acquisition and/or pathogen transmission. CONCLUSION: Together, these findings represent an extended reference for the identification and characterization of the proteins containing relevant pharmacological activity in the salivary glands of C. quinquefasciatus mosquitoes.

Revisiting the sialome of the cat flea Ctenocephalides felis.

The hematophagous behaviour emerged independently in several instances during arthropod evolution. Survey of salivary gland and saliva composition and its pharmacological activity led to the conclusion that blood-feeding arthropods evolved a distinct salivary mixture that can interfere with host defensive response, thus facilitating blood acquisition and pathogen transmission. The cat flea, Ctenocephalides felis, is the major vector of several pathogens, including Rickettsia typhi, Rickettsia felis and Bartonella spp. and therefore, represents an important insect species from the medical and veterinary perspectives. Previously, a Sanger-based sialome of adult C. felis female salivary glands was published and reported 1,840 expressing sequence tags (ESTs) which were assembled into 896 contigs. Here, we provide a deeper insight into C. felis salivary gland composition using an Illumina-based sequencing approach. In the current dataset, we report 8,892 coding sequences (CDS) classified into 27 functional classes, which were assembled from 42,754,615 reads. Moreover, we paired our RNAseq data with a mass spectrometry analysis using the translated transcripts as a reference, confirming the presence of several putative secreted protein families in the cat flea salivary gland homogenates. Both transcriptomic and proteomic approaches confirmed that FS-H-like proteins and acid phosphatases lacking their putative catalytic residues are the two most abundant salivary proteins families of C. felis and are potentially related to blood acquisition. We also report several novel sequences similar to apyrases, odorant binding proteins, antigen 5, cholinesterases, proteases, and proteases inhibitors, in addition to putative novel sequences that presented low or no sequence identity to previously deposited sequences. Together, the data represents an extended reference for the identification and characterization of the pharmacological activity present in C. felis salivary glands.

Inferiorly Directed Posterior Cranial Vault Distraction for Treatment of Chiari Malformations.

OBJECTIVE: The authors present a case series of patients with Chiari I malformations treated with distraction osteogenesis of the posterior cranial vault, utilizing a vertical distraction vector for appropriate cranial vault expansion while mitigating the risks of scaphocephaly and cerebellar ptosis. PATIENTS AND METHODS: Patients with syndromic and nonsyndromic Chiari I malformations treated with vertical-vector distraction osteogenesis of the posterior cranial vault were identified from 2008 to 2014. Demographics, preoperative and postoperative clinical symptoms, and perioperative details were assessed. Long-term esthetic outcomes, complications, and symptomatic improvement were evaluated in conjunction with neurosurgery. RESULTS: Nine patients were identified. Five had known syndromes, 2 likely had unidentified syndromes, and 2 were nonsyndromic. Seven had prior Chiari-related surgeries. Most presented with hydrocephalus, motor symptoms, and developmental delay. Operatively, 2 to 3 internal distraction fixators were applied such that the vector of distraction was along a cephalad-caudad axis. Devices were activated on postoperative day 5 and distracted 1 mm per day. Three postoperative complications were found within the first 3 months which included a dislodged distraction arm, a device extrusion, and a local cellulitis. No complications affected the clinical outcome. Radiographic follow-up showed good bone formation, decompression of the posterior fossa, improved cerebrospinal fluid flow, and no cerebellar ptosis. Neurological surveillance showed improvement in intracranial pressure, hydrocephalus, motor symptoms, and behavioral problems. CONCLUSION: The authors have presented 9 patients with Chiari I malformations treated with distraction osteogenesis, along with a novel technique to safely and effectively expand the posterior fossa while minimizing the risk of cerebellar ptosis. LEVEL OF EVIDENCE: Level II (prognostic/risk studies).

Comprehensive Treatment and Reconstructive Algorithm for Functional Restoration after Ballistic Facial Injury.

Background: Ballistic facial injuries are rare, with most trauma centers reporting 1-20 cases annually. These patients present significant management challenges to reconstructive surgeons, not only due to their rarity but also due to the complex decision-making process that is involved. The aim of this study was to review our experience with the application of craniofacial microsurgery in management of facial gunshot wounds. Methods: A retrospective review of a single-surgeon experience at a level I trauma center from 2011 to 2020 for patients sustaining self-inflicted gunshot wounds to the face requiring microsurgical reconstruction was performed. Outcomes included reconstructive techniques, free flap type and indication, airway evolution, feeding modality, respective timing of interventions, and complications. Results: Between 2012 and 2021, 13 patients presented for microsurgical reconstruction at our institution for gunshot wounds to the face. The majority (90%) of patients were men, and the average age at time of injury was 26. The median from the time of injury to first free flap was 93 days. Thirteen patients represented 23 free flaps. On average, patients underwent a total of two free flaps. The most common microsurgical flap was the fibula flap (14) followed by the radial forearm flap (6). Conclusions: Based on our findings, we describe a novel algorithm for function restoration and aesthetic revisions based on injury location. Underlying principles include avoiding early use of reconstruction plates, establishing occlusion early, and aligning bony segments using external fixation. An algorithmic approach to these injuries can improve outcomes.

A deeper insight into the sialome of male and female Ochlerotatus triseriatus mosquitoes.

Over the last 20 years, advancements in sequencing technologies have highlighted the unique composition of the salivary glands of blood-feeding arthropods. Further biochemical and structural data demonstrated that salivary proteins can disrupt host hemostasis, inflammation and immunity, which favors pathogen transmission. Previously, a Sanger-based sialome of adult Ochlerotatus triseriatus female salivary glands was published based on 731 expressed sequence tag (ESTs). Here, we revisited O. triseriatus salivary gland contents using an Illumina-based sequencing approach of both male and female tissues. In the current data set, we report 10,317 DNA coding sequences classified into several functional classes. The translated transcripts also served as a reference database for proteomic analysis of O. triseriatus female saliva, in which unique peptides from 101 proteins were found. Finally, comparison of male and female libraries allowed for the identification of female-enriched transcripts that are potentially related to blood acquisition and virus transmission.

Integrated analysis of the sialotranscriptome and sialoproteome of the rat flea Xenopsylla cheopis.

Over the last 20 years, advances in sequencing technologies paired with biochemical and structural studies have shed light on the unique pharmacological arsenal produced by the salivary glands of hematophagous arthropods that can target host hemostasis and immune response, favoring blood acquisition and, in several cases, enhancing pathogen transmission. Here we provide a deeper insight into Xenopsylla cheopis salivary gland contents pairing transcriptomic and proteomic approaches. Sequencing of 99 pairs of salivary glands from adult female X. cheopis yielded a total of 7432 coding sequences functionally classified into 25 classes, of which the secreted protein class was the largest. The translated transcripts also served as a reference database for the proteomic study, which identified peptides from 610 different proteins. Both approaches revealed that the acid phosphatase family is the most abundant salivary protein group from X. cheopis. Additionally, we report here novel sequences similar to the FS-H family, apyrases, odorant and hormone-binding proteins, antigen 5-like proteins, adenosine deaminases, peptidase inhibitors from different subfamilies, proteins rich in Glu, Gly, and Pro residues, and several potential secreted proteins with unknown function. SIGNIFICANCE: The rat flea X. cheopis is the main vector of Yersinia pestis, the etiological agent of the bubonic plague responsible for three major pandemics that marked human history and remains a burden to human health. In addition to Y. pestis fleas can also transmit other medically relevant pathogens including Rickettsia spp. and Bartonella spp. The studies of salivary proteins from other hematophagous vectors highlighted the importance of such molecules for blood acquisition and pathogen transmission. However, despite the historical and clinical importance of X. cheopis little is known regarding their salivary gland contents and potential activities. Here we provide a comprehensive analysis of X. cheopis salivary composition using next generation sequencing methods paired with LC-MS/MS analysis, revealing its unique composition compared to the sialomes of other blood-feeding arthropods, and highlighting the different pathways taken during the evolution of salivary gland concoctions. In the absence of the X. cheopis genome sequence, this work serves as an extended reference for the identification of potential pharmacological proteins and peptides present in flea saliva.

An Unoperated Crouzon Family Treated with Monobloc Distraction: Challenges and Lessons.

Crouzon syndrome (CS) is a rare form of craniosynostosis characterized by bicoronal craniosynostosis and facial features including severe midface hypoplasia, exophthalmos, and hypertelorism. Most patients are diagnosed and treated in early childhood; however, there are a few reports of Crouzon patients treated as adults with monobloc facial advancement. To our knowledge, this is the first report of a family affected by CS treated sequentially with monobloc facial advancement using combined internal and external distraction osteogenesis (rigid external distraction). METHODS: We present a family from Jamaica (mother 47 years old, older daughter 17, and younger daughter 9) who were brought to our craniofacial clinic with stigmata of CS and no previous surgical intervention. Patients had bicoronal craniosynostosis and exorbitism, with varying severity, sequelae, and comorbidities. Here, we delineate our technique of monobloc distraction osteogenesis with advancement osteotomies using dual "push-pull" method, elevation of a split anteriorly based tunneled pericranial flap to seal off nasal cavity, and internal and external distraction. RESULTS: Our patients had favorable outcomes after reconstruction to reduce ocular symptoms and improve midface hypoplasia and aesthetic appearance. No intracranial injury, hardware/soft-tissue infection, hardware failure, or (new) loss of vision were encountered in 10 months follow-up. CONCLUSIONS: Dual "push-pull" monobloc distraction is safe and effective for a range of ages in CS; it allows good vector control, accommodates patient compliance, and allows early rigid external distraction device removal with sufficient time for consolidation. This surgery can be performed with highly satisfactory results.

Identification of a substrate-like cleavage-resistant thrombin inhibitor from the saliva of the flea Xenopsylla cheopis.

The salivary glands of the flea Xenopsylla cheopis, a vector of the plague bacterium, Yersinia pestis, express proteins and peptides thought to target the hemostatic and inflammatory systems of its mammalian hosts. Past transcriptomic analyses of salivary gland tissue revealed the presence of two similar peptides (XC-42 and XC-43) having no extensive similarities to any other deposited sequences. Here we show that these peptides specifically inhibit coagulation of plasma and the amidolytic activity of α-thrombin. XC-43, the smaller of the two peptides, is a fast, tight-binding inhibitor of thrombin with a dissociation constant of less than 10 pM. XC-42 exhibits similar selectivity as well as kinetic and binding properties. The crystal structure of XC-43 in complex with thrombin shows that despite its substrate-like binding mode, XC-43 is not detectably cleaved by thrombin and that it interacts with the thrombin surface from the enzyme catalytic site through the fibrinogen-binding exosite I. The low rate of hydrolysis was verified in solution experiments with XC-43, which show the substrate to be largely intact after 2 h of incubation with thrombin at 37 °C. The low rate of XC-43 cleavage by thrombin may be attributable to specific changes in the catalytic triad observable in the crystal structure of the complex or to extensive interactions in the prime sites that may stabilize the binding of cleavage products. Based on the increased arterial occlusion time, tail bleeding time, and blood coagulation parameters in rat models of thrombosis XC-43 could be valuable as an anticoagulant.

Turning Back the Clock: Artificial Intelligence Recognition of Age Reduction after Face-Lift Surgery Correlates with Patient Satisfaction.

BACKGROUND: Patients desire face-lifting procedures primarily to appear younger, more refreshed, and attractive. Because there are few objective studies assessing the success of face-lift surgery, the authors used artificial intelligence, in the form of convolutional neural network algorithms alongside FACE-Q patient-reported outcomes, to evaluate perceived age reduction and patient satisfaction following face-lift surgery. METHODS: Standardized preoperative and postoperative (1 year) images of 50 consecutive patients who underwent face-lift procedures (platysmaplasty, superficial musculoaponeurotic system-ectomy, cheek minimal access cranial suspension malar lift, or fat grafting) were used by four neural networks (trained to identify age based on facial features) to estimate age reduction after surgery. In addition, FACE-Q surveys were used to measure patient-reported facial aesthetic outcome. Patient satisfaction was compared to age reduction. RESULTS: The neural network preoperative age accuracy score demonstrated that all four neural networks were accurate in identifying ages (mean score, 100.8). Patient self-appraisal age reduction reported a greater age reduction than neural network age reduction after a face lift (-6.7 years versus -4.3 years). FACE-Q scores demonstrated a high level of patient satisfaction for facial appearance (75.1 ± 8.1), quality of life (82.4 ± 8.3), and satisfaction with outcome (79.0 ± 6.3). Finally, there was a positive correlation between neural network age reduction and patient satisfaction. CONCLUSION: Artificial intelligence algorithms can reliably estimate the reduction in apparent age after face-lift surgery; this estimated age reduction correlates with patient satisfaction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.

Single Center Retrospective Analysis of Cost and Payments for Lymphatic Surgery.

BACKGROUND: Insurance coverage for microsurgical lymphatic surgery continues to be sporadic, as the procedures continue to be labeled investigational. The objective of this study was to examine the typical payment patterns of our clinical practice for microsurgical lymphatic procedures. METHODS: We performed a single center, single surgeon retrospective case review for all lymphovenous bypass and vascularized lymph node transfer cases preformed from 2018 to 2020. We then queried the available financial data and calculated total charges, total paid by insurance, total variable cost (cost to the hospital), and the contribution margin (difference between the amount paid and variable cost). Descriptive statistics were then collected for each subgroup for analysis. RESULTS: Financial data were collected on 22 patients with 10 left-sided, 11 right-sided and one bilateral procedure performed. Seven procedures were done prophylactically, and 15 were done for existing lymphedema. An estimated 10 of 22 patients (45%) had Medicare, Medicaid, or Tricare, with the remaining having private insurance. We calculated an average cost of $48,516.73, with average payment of $10,818.68, average variable cost of $5,567.10, for a contribution margin of +$5251.58. CONCLUSIONS: Lymphedema remains a common complication of surgery and a significant cost burden to patients and the healthcare system. Microsurgical procedures offer several advantages over medical therapy. In our practice, we were routinely reimbursed for both prophylactic and therapeutic procedures with positive contribution margins for the hospital and ratios similar to other surgeries. Despite the limitations of a small retrospective review, there is no similar published cost analysis data in the current literature.

Comparing Plastic Surgeon Operative Time for DIEP Flap Breast Reconstruction: 2-stage More Efficient than 1-stage?

The deep inferior epigastric perforator flap for breast reconstruction is associated with lengthy operative times that remain an issue for plastic surgeons today. The main objective of this study was to determine if a 2-stage deep inferior epigastric perforator flap reconstruction resulted in a shorter total plastic surgeon operative time compared with an immediate reconstruction. METHODS: A retrospective chart review was conducted on all patients who underwent deep inferior epigastric perforator flap breast reconstruction from February 2013 to July 2020 by the senior author. Patient demographics, medical comorbidities, mastectomy characteristics, expander placement, reconstructive procedures, operative time, and complications were tabulated. RESULTS: The study included a total of 128 patients. For immediate/1-stage flap reconstruction, average operative times for the plastic surgeon were 427.0 minutes for unilateral procedures, and 506.3 minutes for bilateral procedures. For delayed/2-stage reconstruction, average combined plastic surgeon operative times were 351.1 minutes for unilateral expander followed by flap reconstruction (75.9 minutes shorter than immediate unilateral, P = 0.007), and 464.8 minutes for bilateral reconstruction (41.5 minutes shorter than immediate bilateral, P = 0.04). Total patient time under anesthesia was longer for 2-staged bilateral reconstruction (P = 0.0001), but did not differ significantly for unilateral reconstruction. Complications between immediate and delayed groups were not significantly different. CONCLUSIONS: We found that staged reconstruction over 2 procedures resulted in a significant reduction in operative time for the plastic surgeon for both unilateral and bilateral reconstruction. With amenable breast surgeons and patients, the advantages of controlling scheduling and the operating room may encourage plastic surgeons to consider performing free flap reconstruction in a delayed fashion.