Targeted protein quantitation in human body fluids by mass spectrometry.

Human body fluids (biofluids) contain various proteins, some of which reflect individuals' physiological conditions or predict diseases. Therefore, the analysis of biofluids can provide substantial information on novel biomarkers for clinical diagnosis and prognosis. In the past decades, mass spectrometry (MS)-based technologies have been developed as proteomic strategies not only for the identification of protein biomarkers but also for biomarker verification/validation in body fluids for clinical applications. The main advantage of targeted MS-based methodologies is the accurate and specific simultaneous quantitation of multiple biomarkers with high sensitivity. Here, we review MS-based methodologies that are currently used for the targeted quantitation of protein components in human body fluids, especially in plasma, urine, cerebrospinal fluid, and saliva. In addition, the currently used MS-based methodologies are summarized with a specific focus on applicable clinical sample types, MS configurations, and acquisition modes.

Exploring mycorrhizal diversity in sympatric mycoheterotrophic plants: a comparative study of Monotropastrum humile var. humile and M. humile var. glaberrimum.

Mycoheterotrophic plants (MHPs) rely on their mycorrhizal fungus for carbon and nutrient supply, thus a shift in mycobionts may play a crucial role in speciation. This study aims to explore the mycorrhizal diversity of two closely related and sympatric fully MHPs, Monotropastrum humile var. humile (Mhh) and M. humile var. glaberrimum (Mhg), and determine their mycorrhizal associations. A total of 1,108,710 and 1,119,071 ectomycorrhizal fungal reads were obtained from 31 Mhh and 31 Mhg, and these were finally assigned to 227 and 202 operational taxonomic units, respectively. Results show that sympatric Mhh and Mhg are predominantly associated with different fungal genera in Russulaceae. Mhh is consistently associated with members of Russula, whereas Mhg is associated with members of Lactarius. Associating with different mycobionts and limited sharing of fungal partners might reduce the competition and contribute to their coexistence. The ectomycorrhizal fungal communities are significantly different among the five forests in both Mhh and Mhg. The distinct mycorrhizal specificity between Mhh and Mhg suggests the possibility of different mycobionts triggered ecological speciation between sympatric species.

The Effects of Radial Longitudinal Deficiency on Long-Term Use of the Thumb in Pediatric Patients Following Index Pollicization.

PURPOSE: To assess the effect of radial longitudinal deficiency on the function of pollicized digits as determined by the Thumb Grasp and Pinch (T-GAP) assessment. METHODS: We retrospectively evaluated 25 hands with thumb hypoplasia that underwent index finger pollicization. Patients were followed for an average of 10.4 years. Hands were divided by severity into two groups: no or mild radial longitudinal deficiency (RLD) (Group 1 = 16) and moderate to severe RLD (Group 2 = 9). We collected demographic information and completed physical examination measures, including hand strength, elbow, wrist, and hand range of motion, the Kapandji opposition score, active grasp span, and T-GAP total score. RESULTS: Patients with moderate to severe forms of RLD had stiffer long fingers, lower Kapandji opposition scores, and limited active and passive range of motion for elbow flexion, wrist ulnar deviation, and pollicized thumb interphalangeal flexion. They had shorter forearms, decreased active grasp span, and fewer thumb creases at the interphalangeal thumb joint. In addition, the T-GAP total score was significantly lower when comparing the two groups. Children with mild dysplasia were able to achieve 32% of age-matched normal grasp strength. Patients with more severe radial dysplasia averaged 17% less grasp strength compared with children with mild dysplasia. Patients with moderate to severe RLD also had lower T-GAP total scores and strength measurements if they had limited wrist ulnar deviation. CONCLUSIONS: Individuals with moderate to severe RLD have unique anatomical factors that affect outcomes after pollicization. These individuals use their thumbs for fewer activities, have weaker grasp, and retain more primitive grasp patterns compared with those who have milder forms of RLD. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Evaluating the Effectiveness of Commercially Available Antiadhesion Tendon Protector Sheets in Tendon Repair Surgery Versus Tendon Repair Surgery Alone: A Preclinical Model Study.

PURPOSE: Adhesion formation is the major complication after tendon repairs that halts functional restoration and causes disability in patients. This study aimed to compare the antiadhesion efficacy of two tendon protector sheets using a previously established turkey flexor tendon model. METHODS: Twenty-four adult Bourbon Red turkeys were randomized into three groups: (1) control, (2) type I collagen-glycosaminoglycan (Collagen-GAG), and (3) hyaluronic acid. In each group, the flexor digitorum profundus tendon of the middle digit was sharply lacerated at the proximal interphalangeal joint level. All operated feet were immobilized until sacrifice 6 weeks after the surgery. After sacrifice, the repaired and normal digits were collected for biomechanical testing, adhesion scores, histological examination, and adhesion-related gene expression analysis. RESULTS: At 42 days after tendon repair, the normalized work of flexion of the repaired digit was the lowest in the Collagen-GAG group. The Collagen-GAG group also had the lowest gross adhesion score, indicating minimal adhesion. The hyaluronic acid group showed lower adhesion scores compared with the control, but the difference was not statistically significant. Microscopically, the Collagen-GAG group had a significantly lower histological adhesion score than the control group. In the Collagen-GAG group, the gene expression levels of WNT3A, WNT5A, and WNT7A were suppressed. CONCLUSIONS: In an avian model of flexor tendon repair, the application of tendon protector sheets reduces peritendinous fibrotic tissue formation histologically. CLINICAL RELEVANCE: There are currently limited commercially available products to reduce postoperative peritendinous adhesions. Further validation is needed to confirm the effectiveness of tendon protector sheets in improving surgical outcomes following tendon repairs.

From Case Reports to Molecular Insight: Examining the Outcomes and Underlying Mechanisms of Squamous Cell Carcinoma in Breast Implant Patients-A Systematic Review.

There is extensive coverage in the existing literature on implant-associated lymphomas like anaplastic large-cell lymphoma, but breast implant-associated squamous cell carcinoma (BIA-SCC) has received limited scholarly attention since its first case in 1992. Thus, this study aims to conduct a qualitative synthesis focused on the underexplored association between breast implants and BIA-SCC. A systematic review was conducted utilizing the PubMed, Web of Science, and Cochrane databases to identify all currently reported cases of BIA-SCC. Additionally, a literature review was performed to identify potential biochemical mechanisms that could lead to BIA-SCC. Studies were vetted for quality using the NIH quality assessment tool. From an initial pool of 246 papers, 11 met the quality criteria for inclusion, examining a total of 14 patients aged between 40 and 81 years. BIA-SCC was found in a diverse range of implants, including those with smooth and textured surfaces, as well as those filled with saline and silicone. The condition notably manifested a proclivity for aggressive clinical progression, as evidenced by a mortality rate approximating 21.4% within a post-diagnostic interval of six months. Our literature review reveals that chronic inflammation, driven by various external factors such as pathogens and implants, can initiate carcinogenesis through epigenetic modifications and immune system alterations. This includes effects from exosomes and macrophage polarization, showcasing potential pathways for the pathogenesis of BIA-SCC. The study highlights the pressing need for further investigation into BIA-SCC, a subject hitherto inadequately addressed in the academic sphere. This necessitates the urgency for early screening and intervention to improve postoperative outcomes. While the review is confined by its reliance on case reports and series, it serves as a valuable reference for future research endeavors.

Evaluating skin colour diversity in the validation of scar assessment tools.

Across scar studies, there is a lack of dark-skinned individuals, who have a predisposition for keloid formation, altered pigmentation and poorer quality of life (QOL). There is a need for patients of colour to be included in scar scale development and validation. In this study, we evaluate the racial diversity of patients included in the validation of scar assessment scales. A systematic review was conducted for articles reporting on the validation of a scar assessment tool. Racial, ethnic and Fitzpatrick skin type (FST) data were extracted. Fifteen scar scale validation studies were included. Nine of the studies did not mention FST, race or ethnicity of the patients. Two of the studies that reported FST or race information only included White patients or included no FST V/VI patients: mapping assessment of scars (MAPS) and University of North Carolina '4P'. Only four studies included non-White patients or dark-skinned patients in the validation of their scar scale: the modified Vancouver Scar Scale (VSS), modified Patient and Observer Scar Assessment Scale (POSAS), acne QOL and SCAR-Q scales. The patients included in the modified VSS validation were 7% and 13% FST V/VI, 14% African in the modified POSAS and 4.5% FST V/VI in the SCAR-Q. We highlight the severe lack of diversity in scar scale validation, with only 4 out of 15 studies including dark-skinned patients. Given the susceptibility of darker-skinned individuals to have poorer scarring outcomes, it is critical to include patients of colour in the very assessment tools that determine their scar prognosis. Inclusion of patients of colour in scar scale development will improve scar assessment and clinical decision-making.

Prophylactic lymphaticovenous anastomosis (LVA) for preventing lymphedema after sarcoma resection in the lower limb: A report of three cases and literature review.

Patients with soft tissue tumors of the lower extremities are at greater risk to develop postoperative disruption of lymphatic vessels. Currently, there is no widely effective cure for lymphatic dysfunction. Therefore, the best strategy is to prevent it and reconstruct efficient drainage as soon as the original pathway is damaged. We present a report of three prophylactic LVA cases after sarcoma resection in the lower limb, and a literature review to show the feasibility of prophylactic LVAs. The patients were 35, 73, and 77 years old, respectively, at the time of the procedure. All three patients had sarcoma in the medial thigh and underwent radiation therapy before the surgery. The locations of the LVAs include the medial thigh and medial and lateral calf. During the surgery, methylene blue and/or indocyanine green were injected to identify lymphatic vessels. Postoperative recovery was uneventful immediately after the surgery. At follow-up visits, all three patients reported improved functions with no significant swelling in the lower limb. One patient experienced a surgical wound infection that resolved after antibiotic admission. Two patients had a history of cardiac diseases, a major risk factor for developing postoperative lymphedema, but these two patients did not develop lymphedema with the treatment of prophylactic LVAs. These results suggest that prophylactic LVA may be an effective strategy to prevent secondary lymphedema after sarcoma resection. Further investigation is warranted.

Modulation of adenine phosphoribosyltransferase-mediated salvage pathway to accelerate diabetic wound healing.

Adenine phosphoribosyltransferase (APRT) is the key enzyme involved in purine salvage by the incorporation of adenine and phosphoribosyl pyrophosphate to provide adenylate nucleotides. To evaluate the role of APRT in the repair processes of cutaneous wounds in healthy skin and in diabetic patients, a diabetic mouse model (db/db) and age-matched wild-type mice were used. Moreover, the topical application of adenine was assessed. In vitro studies, analytical, histological, and immunohistochemical methods were used. Diabetic mice treated with adenine exhibited elevated ATP levels in organismic skin and accelerated wound healing. In vitro studies showed that APRT utilized adenine to rescue cellular ATP levels and proliferation from hydrogen peroxide-induced oxidative damage. HPLC-ESI-MS/MS-based analysis of total adenylate nucleotides in NIH-3T3 fibroblasts demonstrated that adenine addition enlarged the cellular adenylate pool, reduced the adenylate energy charge, and provided additional AMP for the further generation of ATP. These data indicate an upregulation of APRT in skin wounds, highlighting its role during the healing of diabetic wounds through regulation of the nucleotide pool after injury. Furthermore, topical adenine supplementation resulted in an enlargement of the adenylate pool needed for the generation of ATP, an important molecule for wound repair.

Effectiveness of a fluid immersion simulation system in the acute post-operative management of pressure ulcers: A prospective, randomised controlled trial.

The fluid immersion simulation system (FIS) has demonstrated good clinical applicability. This is the first study to compare surgical flap closure outcomes of FIS with an air-fluidised bed (AFB), considered as standard of care. The success of closure after 14 days post-op was the primary endpoint. Secondary endpoints were incidences of complications in the first 2 weeks after surgery and the rate of acceptability of the device. Thirty-eight subjects were in the FIS group while 42 subjects were placed in the AFB group. Flap failure rate was similar between groups (14% vs. 12%; p = 0.84). Complications, notably dehiscence and maceration, were significantly higher in the FIS group (40% vs. 17%; p = 0.0296). The addition of a microclimate regulation device (ClimateCare®) to FIS for the last 43 patients showed a significant decrease in the rate of flap failure (71% vs. 16%; p = 0.001) and incidence of complications (33% vs. 0%; p = 0.011). There was no statistically significant difference between the FIS and air-fluidised bed (AFB) in the rate of acceptability (nurse acceptance: 1.49 vs. 1.72; p = 0.8; patient acceptance: 2.08 vs. 2.06; p = 0.17), which further illustrates the potential implementation of this tool in a patient-care setting. Our results show that the use of ClimateCare® in combination with FIS can be a better alternative to the AFB in surgical closure of pressure ulcers.

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration.

Soft tissue defects are common following trauma and tumor extirpation. These injuries can result in poor functional recovery and lead to a diminished quality of life. The healing of skin and muscle is a complex process that, at present, leads to incomplete recovery and scarring. Regenerative medicine may offer the opportunity to improve the healing process and functional outcomes. Barriers to regenerative strategies have included cost, regulatory hurdles, and the need for cell-based therapies. In recent years, exosomes, or extracellular vesicles, have gained tremendous attention in the field of soft tissue repair and regeneration. These nanosized extracellular particles (30-140 nm) can break the cellular boundaries, as well as facilitate intracellular signal delivery in various regenerative physiologic and pathologic processes. Existing studies have established the potential of exosomes in regenerating tendons, skeletal muscles, and peripheral nerves through different mechanisms, including promoting myogenesis, increasing tenocyte differentiation and enhancing neurite outgrowth, and the proliferation of Schwann cells. These exosomes can be stored for immediate use in the operating room, and can be produced cost efficiently. In this article, we critically review the current advances of exosomes in soft tissue (tendons, skeletal muscles, and peripheral nerves) healing. Additionally, new directions for clinical applications in the future will be discussed.

Evidence supporting wound care end points relevant to clinical practice and patients' lives. Part 3: The Patient Survey.

The 2006 U.S. Food and Drug Administration Guidance for Industry emphasizes wound closure as the primary outcome for clinical trials in wound healing. Wound care professionals understand that complete wound healing is not always achievable when evaluating new treatments. FDA, Association for the Advancement of Wound Care, and Wound Healing Society are working collaboratively to identify scientifically achievable, clinically relevant, and patient-centered endpoints with sufficient support to serve as primary outcomes for clinical trials. The Opinion Survey from People with Wounds presented here addresses an important but understudied issue: the gap between clinician, healthcare insurance companies, government agencies, and patient perspectives regarding clinically meaningful and scientifically achievable primary endpoints for wound care. The survey, adapted from the clinician survey with adjustment for health literacy, was pilot tested and revised based on a limited number of patients in a single clinic. After central IRB approval, the on-line survey was administered in English and Spanish and submitted anonymously to a server with the cooperation of multiple wound clinics and societies. Four hundred and thirty-eight patients and caregivers from across the United States responded over a 10-month period. Based on this survey, the most valuable clinical endpoints were reduced infection, recurrence, and amputation. The most valuable quality of life outcomes were increased independence, reduced social isolation, and pain. The top five endpoints in terms of usefulness for measuring clinical trial success were time to heal, wound size, infection, recurrence, and pain. Narrative responses from wound patients emphasized the inability to perform activities of daily living and pain as major factors that impacted their daily lives. Engagement of patients in clinical trials and evaluation of potential treatments is critical to improving wound care. This survey provides insight into the needs of patients with wounds and provides a roadmap for structuring future clinical trials to better meet those needs.

Diabetic wound healing: The impact of diabetes on myofibroblast activity and its potential therapeutic treatments.

Diabetes is a systemic disease in which the body cannot regulate the amount of sugar, namely glucose, in the blood. High glucose toxicity has been implicated in the dysfunction of diabetic wound healing, following insufficient production (Type 1) or inadequate usage (Type 2) of insulin. Chronic non-healing diabetic wounds are one of the major complications of both types of diabetes, which are serious concerns for public health and can impact the life quality of patients significantly. In general, diabetic wounds are characterized by deficient chemokine production, an unusual inflammatory response, lack of angiogenesis and epithelialization, and dysfunction of fibroblasts. Increasing scientific evidence from available experimental studies on animal and cell models strongly associates impaired wound healing in diabetes with dysregulated fibroblast differentiation to myofibroblasts, interrupted myofibroblast activity, and inadequate extracellular matrix production. Myofibroblasts play an important role in tissue repair by producing and organizing extracellular matrix and subsequently promoting wound contraction. Based on these studies, hyperglycaemic conditions can interfere with cytokine signalling pathways (such as growth factor-ß pathway) affecting fibroblast differentiation, alter fibroblast apoptosis, dysregulate dermal lipolysis, and enhance hypoxia damage, thus leading to damaged microenvironment for myofibroblast formation, inappropriate extracellular matrix modulation, and weakened wound contraction. In this review, we will focus on the current available studies on the impact of diabetes on fibroblast differentiation and myofibroblast function, as well as potential treatments related to the affected pathways.

The Use of Botulinum Toxin to Prevent Anastomotic Thrombosis and Promote Flap Survival: A Bridge to Developing Clinical Studies.

BACKGROUND: Despite the possibility of using botulinum toxin to improve perfusion and prevent vasospasm, only a few studies have examined the use of botulinum toxin in the setting of flap surgery and thrombosis, and the mechanisms have not been fully explained. OBJECTIVE: The primary objective of this study was to provide a comprehensive review of the effectiveness of botulinum toxin in anastomotic thrombosis prevention and surgical flap survival to determine the value of conducting large-scale human trials. METHODS: Using the SYRCLE and CAMRADES criteria, a systematic review was performed. PubMed, Medline, EmBase, and the Cochrane Library were searched for studies that met our eligibility criteria. RESULTS: Twenty studies were included in the final selection. A total of 397 subjects were included. Eighteen studies used botulinum toxin type A alone, one used botulinum toxin type B alone, and only one used both botulinum toxin type A and botulinum toxin type B. The most commonly used injection technique was a preoperative intradermal injection. The most common procedure performed was a pedicled flap with random pattern skin flaps (65%). The mean injection dose was 28.17 ± 49.21 IU, whereas the mean reported injection time for studies using animal models was 7.4 ± 6.84 days. CONCLUSIONS: Similar mechanisms demonstrated in animal models may be replicable in humans, allowing botulinum toxin to be used to prolong flap survival. However, many factors, such as optimal injection techniques, dosages, and long-term outcomes of botulinum use in flap surgery, need to be further assessed before applying this to clinical practice.

Structural variants caused by Alu insertions are associated with risks for many human diseases.

Interspersed repeat sequences comprise much of our DNA, although their functional effects are poorly understood. The most commonly occurring repeat is the Alu short interspersed element. New Alu insertions occur in human populations, and have been responsible for several instances of genetic disease. In this study, we sought to determine if there are instances of polymorphic Alu insertion variants that function in a common variant, common disease paradigm. We cataloged 809 polymorphic Alu elements mapping to 1,159 loci implicated in disease risk by genome-wide association study (GWAS) (P < 10-8). We found that Alu insertion variants occur disproportionately at GWAS loci (P = 0.013). Moreover, we identified 44 of these Alu elements in linkage disequilibrium (r2 > 0.7) with the trait-associated SNP. This figure represents a >20-fold increase in the number of polymorphic Alu elements associated with human phenotypes. This work provides a broader perspective on how structural variants in repetitive DNAs may contribute to human disease.

Nitrogen inaccessibility protects spider silk from bacterial growth.

Spider silks are protein-based fibers that are incorporated into webs with the unique combination of high mechanical toughness and resistance to microbial degradation. While spiders are undoubtedly exposed to saprophytic microorganisms in their native habitats, such as the forest understory and bush, their silks have rarely been observed to decompose in either field or laboratory studies. We performed cross-streaking assays using silk from three spider species and four bacterial strains and found no inhibition zones, indicating the absence of antibacterial properties. We also cultured all bacteria directly upon silk in Luria-Bertani (LB) broth (full nutrients), phosphate-buffered saline (PBS; no nutrients) and nitrogen-free glucose broth (NFG; full nutrients, no nitrogen), and found that bacteria grew readily on silk in LB broth but not in PBS or NFG buffer. Our results indicate that spider silk's resistance to bacterial degradation is likely due to bacteriostatic rather than antibacterial mechanisms when nitrogen is inaccessible.

Efficiency Enhancement of Silicon Heterojunction Solar Cells via Photon Management Using Graphene Quantum Dot as Downconverters.

By employing graphene quantum dots (GQDs), we have achieved a high efficiency of 16.55% in n-type Si heterojunction solar cells. The efficiency enhancement is based on the photon downconversion phenomenon of GQDs to make more photons absorbed in the depletion region for effective carrier separation, leading to the enhanced photovoltaic effect. The short circuit current and the fill factor are increased from 35.31 to 37.47 mA/cm(2) and 70.29% to 72.51%, respectively. The work demonstrated here holds the promise for incorporating graphene-based materials in commercially available solar devices for developing ultrahigh efficiency photovoltaic cells in the future.

Above-11%-efficiency organic-inorganic hybrid solar cells with omnidirectional harvesting characteristics by employing hierarchical photon-trapping structures.

Hierarchical structures consisting of micropyramids and nanowires are used in Si/PEDOT:PSS hybrid solar cells to achieve a power conversion efficiency (PCE) up to 11.48% with excellent omnidirectionality. The structure provides a combined concepts of superior light trapping ability, significant increase of p-n junction areas, and short carrier diffusion distance, improving the photovoltaic characteristics including short-circuit current density, fill factor, and PCE. The enhancement of power generation is up to 253.8% at high incident angles, showing the outstanding omnidirectional operation ability of hybrid cells with hierarchical Si surfaces. This properly designed hierarchical-structured device paves a promising way for developing low-cost, high-efficiency, and omnidirectional solar applications in the future.

Gene expression of Postn and FGF7 in canine chordae tendineae and their effects on flexor tenocyte biology.

Chordae tendineae, referred to as heart tendinous cords, act as tendons connecting the papillary muscles to the valves in the heart. Their role is analogous to tendons in the musculoskeletal system. Despite being exposed to millions of cyclic tensile stretches over a human's lifetime, chordae tendineae rarely suffer from overuse injuries. On the other hand, musculoskeletal tendinopathy is very common and remains challenging in clinical treatment. The objective of this study was to investigate the mechanism behind the remarkable durability and resistance to overuse injuries of chordae tendineae, as well as to explore their effects on flexor tenocyte biology. The messenger RNA expression profiles of chordae tendineae were analyzed using RNA sequencing and verified by quantitative reverse transcription polymerase chain reaction  and immunohistochemistry. Interestingly, we found that periostin (Postn) and fibroblast growth factor 7 (FGF7) were expressed at significantly higher levels in chordae tendineae, compared to flexor tendons. We further treated flexor tenocytes in vitro with periostin and FGF7 to examine their effects on the proliferation, migration, apoptosis, and tendon-related gene expression of flexor tenocytes. The results displayed enhanced cell proliferation ability at an early stage and an antiapoptotic effect on tenocytes, while treated with periostin and/or FGF7 proteins. Furthermore, there was a trend of promoted tenocyte migration capability. These findings indicated that Postn and FGF7 may represent novel cytokines to target flexor tendon healing. Clinical significance: The preliminary discovery leads to a novel idea for treating tendinopathy in the musculoskeletal system using specific molecules identified from chordae tendineae.

Ultrasound Shear Wave Elastography for Noninvasive Diagnosis of Acute Compartment Syndrome Using a Novel In Vivo Turkey Model.

INTRODUCTION: Acute Compartment Syndrome (ACS) is a severe trauma caused by elevated intra-muscle-compartment pressure (ICP). The current standard method for diagnosis is to insert a needle into the muscle sterilely under anesthesia. However, to secure the environment is sometimes not easy and leads to delays in diagnosis. Recently, we have focused on shear wave ultrasound elastography (SWE) as an alternative, which can be done concisely in unclean environment and without anesthesia. We would like to report the usefulness of SWE for ACS diagnosis using 2-pedal walking turkey model recently developed in our lab. MATERIALS AND METHODS: A total of 32 1-year-old Bourbon turkeys were used. 5% solution of chicken albumin was infused continuously into the tibialis cranialis (TC) muscle using IV pump. The ICP was increased stepwise from 0 to 50 mmHg. During the rising of ICP, the correlation between values of SWE (kPa) and ICP (mmHg) was measured. After the ICP reached 50 mmHg, half of the turkeys were maintained at this pressure for 2 hours and the rest for 6 hours. After infusion, a fasciotomy was performed on the half turkey. Half of the turkeys were euthanized after 2 weeks and the rest after 6 weeks. SWE of TC muscle and walking gait data on turkeys using a portable walkway system were measured weekly until euthanasia. At euthanasia, isometric tetanic muscle force (ITF) tests to TC muscle and histological evaluations were performed. RESULTS: SWE value (kPa) was highly significantly correlated to the actual ICP (mmHg) (R2 = 0.91). Stance of ACS side leg were significantly extended, and swing of the control side shortened from the second to the third week after ACS in the 6 hours infusion-no-fasciotomy group (P < 0.05*). ITF was significantly reduced mainly in the 6 hours infusion group (P < 0.05*). Histological evaluation revealed that in the 6 hours infusion and 6 weeks survival group, both the muscle fiber and intercellular distances were significantly expanded (P < 0.05). CONCLUSION: SWE seems to be a substitute measure of ICP in diagnosing ACS. With regard to our in vivo ACS model using turkey, survival at 50 mmHg ICP for 6 hours and 6 weeks post ACS would be an appropriate situation.

Pentamidine-loaded gelatin decreases adhesion formation of flexor tendon.

Background: Prevention of adhesion formation following flexor tendon repair is essential for restoration of normal finger function. Although many medications have been studied in the experimental setting to prevent adhesions, clinical application is limited due to the complexity of application and delivery in clinical translation. Methods: In this study, optimal dosages of gelatin and pentamidine were validated by gelatin concentration test. Following cell viability, cell migration, live and dead cell, and cell adhesion assay of the Turkey tenocytes, a model of Turkey tendon repair was established to evaluate the effectiveness of the Pentamidine-Gelatin sheet. Results: Pentamidine carried with gelatin, a Food and drug administration (FDA) approved material for drug delivery, showed good dynamic release, biocompatibility, and degradation. The optimal dose of pentamidine (25ug) was determined in the in vivo study using tenocyte viability, migration, and cell adhesion assays. Further biochemical analyses demonstrated that this positive effect may be due to pentamidine downregulating the Wnt signaling pathway without affecting collagen expression. Conclusions: We tested a FDA-approved antibiotic, pentamidine, for reducing adhesion formation after flexor tendon repair in both in vitro and in vivo using a novel turkey animal model. Compared with the non-pentamidine treatment group, pentamidine treated turkeys had significantly reduced adhesions and improved digit function after six weeks of tendon healing. The translational potential of this article: This study for the first time showed that a common clinical drug, pentamidine, has a potential for clinical application to reduce tendon adhesions and improve tendon gliding function without interfering with tendon healing.