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Changes in carbon (C) after fire were measured in seven southern boreal upland forest stands during the five immediate post-fire years and 23 years after the fire. Pre-fire above-ground C mass of the standswas estimated, Combustion losses were 19% of the pre-fire above-ground C mass (8.4 kg m-2), and an additional 4% of that C mass was lost in the following 3-4 years. After 23 years, neither C massof understory (0.1 kg m-2) nor standing snags (0.3 kg m-2) differed from that estimated before the fire; tree C wasless (2.4 vs. 6.0 kg C m-2), and forest floor (2.5 vs. 1.4 kg C m-2) and coarse woody debris (1.7 vs. 0.7 kg C m-2) C were higher. Above-ground C mass was 84% of pre-fire mass. There were no measured changes in surface soil C following the fire (2.9 kg C m-2). Total C mass, including surface soil, was 10.22 kg m-2 at 23 years or 91% of the estimated pre-fire C. Although gross fluxes of C followed the fire, massive net losses of C did not occur either immediately or in the two decades after fire. Dynamics of C differed among the stands. Data from either a single stand or a chronosequence in space can lead to different conclusions than those derived from multiple stands through time. [ABSTRACT FROM AUTHOR]

Achieving ultra-long-term release of hydrophilic drugs over several months remains a significant challenge for existing long-acting injectables (LAIs). Existing platforms, such as in situ forming implants (ISFI), exhibit high burst release due to solvent efflux and microsphere-based approaches lead to rapid drug diffusion due to significant water exchange and large pores. Addressing these challenges, we have developed an injectable platform that, for the first time, achieves ultra-long-term release of hydrophilic drugs for over six months. This system employs a methacrylated ultra-low molecular weight pre-polymer (polycaprolactone) to create in situ cross-linked depots (ISCD). The ISCD's solvent-free design and dense mesh network, both attributed to the ultra-low molecular weight of the pre-polymer, effectively minimizes burst release and water influx/efflux. In vivo studies in rats demonstrate that ISCD outperforms ISFI by achieving lower burst release and prolonged drug release. We demonstrated the versatility of ISCD by showcasing ultra-long-term delivery of several hydrophilic drugs, including antiretrovirals (tenofovir alafenamide, emtricitabine, abacavir, and lamivudine), antibiotics (vancomycin and amoxicillin) and an opioid antagonist naltrexone. Additionally, ISCD achieved ultra-long-term release of the hydrophobic drug tacrolimus and enabled co-delivery of hydrophilic drug combinations encapsulated in a single depot. We also identified design parameters to tailor the polymer network, tuning drug release kinetics and ISCD degradation. Pharmacokinetic modeling predicted over six months of drug release in humans, significantly surpassing the one-month standard achievable for hydrophilic drugs with existing LAIs. The platform's biodegradability, retrievability, and biocompatibility further underscore its potential for improving treatment adherence in chronic conditions., Competing Interests: Competing interests S.L., S.Z, J.M.K. and N.J. have one pending patent based on the ISCD formulation described in this manuscript. J.M.K has been a paid consultant and or equity holder for companies (listed here: https://www.karplab.net/team/jeff-karp) including biotechnologies companies such as Stempeutics, Sanofi, Celltex, LifeVaultBio, Takeda, Ligandal, Camden Partners, Stemgent, Biogen, Pancryos, Element Biosciences, Frequency Therapeutics, Corner Therapeutics, Quthero, and Mesoblast. J.M.K. has been a paid consultant and or equity holder for multiple biotechnology companies. The interests of J.M.K. were reviewed and are subject to a management plan overseen by his institution in accordance with its conflict of interest policies.

Intra-articular delivery of disease-modifying osteoarthritis drugs (DMOADs) is likely to be most effective in early post-traumatic osteoarthritis (PTOA) when symptoms are minimal and patients are physically active. DMOAD delivery systems therefore must withstand repeated mechanical loading without affecting the drug release kinetics. Although soft materials are preferred for DMOAD delivery, mechanical loading can compromise their structural integrity and disrupt drug release. Here, we report a mechanically resilient soft hydrogel that rapidly self-heals under conditions resembling human running while maintaining sustained release of the cathepsin-K inhibitor L-006235 used as a proof-of-concept DMOAD. Notably, this hydrogel outperformed a previously reported hydrogel designed for intra-articular drug delivery, used as a control in our study, which neither recovered nor maintained drug release under mechanical loading. Upon injection into mouse knee joints, the hydrogel showed consistent release kinetics of the encapsulated agent in both treadmill-running and non-running mice. In a mouse model of aggressive PTOA exacerbated by treadmill running, L-006235 hydrogel markedly reduced cartilage degeneration. To our knowledge, this is the first hydrogel proven to withstand human running conditions and enable sustained DMOAD delivery in physically active joints, and the first study demonstrating reduced disease progression in a severe PTOA model under rigorous physical activity, highlighting the hydrogel's potential for PTOA treatment in active patients.

Introduction: Online patient education materials (PEMs) often exceed the recommended 6th grade reading level. This can negatively affect transmasculine patients' understanding of treatment plans, increasing barriers to care and worsening health outcomes and patient satisfaction. This study assessed the readability of online English and Spanish PEMs regarding phalloplasty and urethroplasty., Methods: The English and Spanish terms for phalloplasty and urethroplasty were queried on Google. The first fifty results were grouped into institutional (government, medical school, teaching hospital), noninstitutional (private practice, news channel, blog, etc.), and academic (journal articles, book chapters) categories. Readability scores were generated using the Simple Measure of Gobbledygook and Spanish Simple Measure of Gobbledygook scales., Results: All PEMs exceeded recommended reading levels. For both procedures, English PEMs had an average reading level approximately of a university sophomore and Spanish PEMs had an average reading level approximately of a high school junior. For both procedures, English PEMs were harder to read than Spanish PEMs overall (P < 0.001) and when compared across the three categories between the two languages (P < 0.001). For Spanish urethroplasty PEMs, noninstitutional PEMs were more difficult to read than institutional PEMs (P < 0.05)., Conclusions: Online information for phalloplasty and urethroplasty should be revised and/or standardized materials should be created by trans-affirming health-care providers and national organizations in order to more fully educate the public and prospective patients prior to intervention. A well-informed patient population will improve patient decision-making and surgeon-patient communication, ultimately leading to better health outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Death from noncompressible torso hemorrhage (NCTH) may be preventable with improved prehospital care and shorter in-hospital times to hemorrhage control. We hypothesized that shorter times to surgical intervention for hemorrhage control would decrease mortality in hypotensive patients with NCTH., Methods: This was an AAST-sponsored multicenter, prospective analysis of hypotensive patients aged 15+ years who presented with NCTH from May 2018 to December 2020. Hypotension was defined as an initial systolic blood pressure (SBP) ≤ 90 mm Hg. Primary outcomes of interest were time to surgical intervention and in-hospital mortality., Results: There were 242 hypotensive patients, of which 48 died (19.8%). Nonsurvivors had higher mean age (47.3 vs. 38.8; p = 0.02), higher mean New Injury Severity Score (38 vs. 29; p < 0.001), lower admit systolic blood pressure (68 vs. 79 mm Hg; p < 0.01), higher incidence of vascular injury (41.7% vs. 21.1%; p = 0.02), and shorter median (interquartile range, 25-75) time from injury to operating room start (74 minutes [48-98 minutes] vs. 88 minutes [61-128 minutes]; p = 0.03) than did survivors. Multivariable Cox regression showed shorter time from emergency department arrival to operating room start was not associated with improved survival (p = 0.04)., Conclusion: Patients who died arrived to a trauma center in a similar time frame as did survivors but presented in greater physiological distress and had significantly shorter times to surgical hemorrhage intervention than did survivors. This suggests that even expediting a critically ill patient through the current trauma system is not sufficient time to save lives from NCTH. Civilian prehospital advance resuscitative care starting from the patient first contact needs special consideration., Level of Evidence: Prognostic/Epidemiologic, Level III., (Copyright © 2022 American Association for the Surgery of Trauma.)

Background: The internet has become an increasingly popular medium for parents to obtain health information. More studies investigating the impact of paid digital marketing campaigns for parents on promoting children's healthy development are needed., Objective: This study aims to explore the outcomes of a paid digital marketing campaign, which occurred from 2018 to 2020, to promote messages about parent-engaged developmental monitoring and ultimately direct parents to the Centers for Disease Control and Prevention's (CDC's) Milestone Tracker app, a mobile health (mHealth) app developed by the CDC., Methods: The paid digital marketing campaign occurred in 3 phases from 2018 to 2020. In each phase, 24 to 36 marketing messages, in English and Spanish, were created and disseminated using Google's Universal App Campaigns and Facebook Ads Manager. Outcomes were measured using impressions, clicks, and install data. Return on investment was measured using click-through rate (CTR), cost per click, and cost per install metrics., Results: The Google-driven marketing messages garnered a total of 4,879,722 impressions (n=1,991,250, 40.81% for English and n=2,888,472, 59.19% for Spanish). The messages resulted in a total of 73,956 clicks (n=44,328, 59.94% for English and n=29,628, 40.06% for Spanish), with a total average CTR of 1.52% (2.22% for English and 1.03% for Spanish). From these clicks, there were 13,707 installs (n=9765, 71.24% for English and n=3942, 28.76% for Spanish) of the CDC's Milestone Tracker app on Google Play Store. The total average cost per install was US $0.93 across all phases. The phase 3 headline "Track your child's development" generated the highest CTR of 3.23% for both English and Spanish audiences. The Facebook-driven marketing messages garnered 2,434,320 impressions (n=1,612,934, 66.26% for English and n=821,386, 33.74% for Spanish). The messages resulted in 44,698 clicks (n=33,353, 74.62% for English and n=11,345, 25.38% for Spanish), with an average CTR of 1.84% (2.07% for English and 1.38% for Spanish). In all 3 phases, animated graphics generated the greatest number of clicks among both English and Spanish audiences on Facebook when compared with other types of images., Conclusions: These paid digital marketing campaigns can increase targeted message exposure about parent-engaged developmental monitoring and direct a parent audience to an mHealth app. Digital marketing platforms provide helpful metrics that can be used to assess the reach, engagement, and cost-effectiveness of this effort. The results from this study suggest that paid digital marketing can be an effective strategy and can inform future digital marketing activities to promote mHealth apps targeting parents of young children., (©Suraj Arshanapally, Katie Green, Karnesha Slaughter, Robert Muller, Demeika Wheaton. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org), 05.04.2022.)

Introduction: Penile prosthesis implantation is a widely used treatment option for erectile dysfunction. Data is limited with regard to patient satisfaction with a penile prosthesis following radical prostatectomy/cystoprostatectomy vs patients with erectile dysfunction of other etiologies., Aim: To examine patient satisfaction with penile prosthesis implantation and determine if a difference in satisfaction exists in post-prostatectomy/cystoprostatectomy patients vs patients with erectile dysfunction of other etiologies. We hypothesize that etiology does not affect satisfaction., Methods: A total of 164 patients underwent penile prosthesis implantation at our institution between August 2017 and December 2019, with 102 patients completing a validated 14 item questionnaire, Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), at 6 months postoperation. Demographics, surgical characteristics, and erectile dysfunction etiology were recorded. Patients were assigned to one of 2 groups: postprostatectomy/postcystoprostatectomy erectile dysfunction or other etiologies. The study group was further analyzed between radical prostatectomy or radical cystoprostatectomy., Main Outcome Measures: Satisfaction based on key EDITS questions with postradical prostatectomy/cystoprostatectomy vs patients with erectile dysfunction of other etiologies., Results: Responses to 3 questions were analyzed: overall satisfaction, expectations met in the past 4 weeks, and confidence in the ability to participate in sexual activity. Chi-square analysis was performed to determine the difference in responses. No difference was seen in overall satisfaction (P = .96), expectations (P = .78), or confidence (P = .78) between groups. On subgroup analysis, there was no difference in reported overall satisfaction (P = .47) or confidence (P = .080) between postprostatectomy and postcystoprostatectomy patients. Postprostatectomy and postcystoprostatectomy patients differed in whether the penile prosthesis implantation met expectations (P = .033). Postprostatectomy patients reported a mean score of 3.5/4 compared to postcystoprostatectomy patients, who reported a mean of 3.0/4., Conclusions: Our analysis suggests that key erectile function scores are not significantly different between postprostatectomy/postcystoprostatectomy patients compared to other etiologies. The difference in measures between postprostatectomy and postcystoprostatectomy patients is not significant or of unclear significance. Registration # of clinical trial: HSC-MS-19-0320 Howell S, Palasi S, Green T, et al. Comparison of Satisfaction With Penile Prosthesis Implantation in Patients With Radical Prostatectomy or Radical Cystoprostatectomy to the General Population. Sex Med 2021;9:100300., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Children with attention-deficit/hyperactivity disorder (ADHD) experience difficulties related to emotional reactivity and regulation. The current study examines differences in the emotional reactivity and regulation of children with and without ADHD in the context of their real-life experiences of negative emotion using a novel ecologically valid methodology. Eighty-three 8-12-year-old children (46 ADHD, 38 non-ADHD) participated in the study. Children completed the negative emotion narrative recall task, a novel task whereby children provided a narrative recall of a real-life event where they experienced negative emotion. ANCOVA indicated children with ADHD recalled significantly more overall frustration and intense frustration than children without ADHD. Children with ADHD exhibiting more negative emotional reactivity while recalling negative emotions than children without ADHD. The current study suggests that children with ADHD are uniquely impacted by negative emotional experiences and represents an important step in understanding the emotional reactivity and regulation of children with ADHD.

The promise of gene therapy for the treatment of cystic fibrosis has yet to be fully clinically realized despite years of effort toward correcting the underlying genetic defect in the cystic fibrosis transmembrane conductance regulator (CFTR). mRNA therapy via nanoparticle delivery represents a powerful technology for the transfer of genetic material to cells with large, widespread populations, such as airway epithelia. We deployed a clinically relevant lipid-based nanoparticle (LNP) for packaging and delivery of large chemically modified CFTR mRNA (cmCFTR) to patient-derived bronchial epithelial cells, resulting in an increase in membrane-localized CFTR and rescue of its primary function as a chloride channel. Furthermore, nasal application of LNP-cmCFTR restored CFTR-mediated chloride secretion to conductive airway epithelia in CFTR knockout mice for at least 14 days. On day 3 post-transfection, CFTR activity peaked, recovering up to 55% of the net chloride efflux characteristic of healthy mice. This magnitude of response is superior to liposomal CFTR DNA delivery and is comparable with outcomes observed in the currently approved drug ivacaftor. LNP-cmRNA-based systems represent a powerful platform technology for correction of cystic fibrosis and other monogenic disorders., (Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

A recent ASCO workforce study projects a significant shortage of oncologists in the U.S. by 2020, especially in rural/underserved (R/US) areas. The current study aim was to determine the patterns of distribution of U.S. gynecologic oncologists (GO) and to identify provider-based attitudes and barriers that may prevent GOs from practicing in R/US regions. U.S. GOs (n = 743) were electronically solicited to participate in an on-line survey regarding geographic distribution and participation in outreach care. A total of 320 GOs (43%) responded; median age range was 35-45 years and 57% were male. Most practiced in an urban setting (72%) at a university hospital (43%). Only 13% of GOs practiced in an area with a population < 50,000. A desire to remain in academics and exposure to senior-level mentorship were the factors most influencing initial practice location. Approximately 50% believed geographic disparities exist in GO workforce distribution that pose access barriers to care; however, 39% "strongly agreed" that cancer patients who live in R/US regions should travel to urban cancer centers to receive care within a center of excellence model. GOs who practice within 50 miles of only 0-5 other GOs were more likely to provide R/US care compared to those practicing within 50 miles of ≥ 10 GOs (p < 0.0001). Most (39%) believed the major barriers to providing cancer care in R/US areas were volume and systems-based. Most also believed the best solution was a hybrid approach, with coordination of local and centralized cancer care services. Among GOs, a self-reported rural-urban disparity exists in the density of gynecologic oncologists. These study findings may help address barriers to providing cancer care in R/US practice environments.

Objective: Women with primary platinum resistant (PPR) high grade serous ovarian cancer (HGSOC) are known to have a poor prognosis. Less is known regarding outcomes in patients with acquired platinum resistance (APR). The goal of this study was to evaluate survival in both PPR and APR patients., Methods: A retrospective review of HGSOC patients diagnosed between 2000 and 2010 was performed. Descriptive statistics summarized clinical characteristics and demographics. The Kaplan-Meier method estimated progression free survival (PFS) and overall survival (OS). The association of OS and clinical factors was modeled using Cox proportional-hazards., Results: Of the 330 patients identified, 81 (25%) had PPR. Of the remaining women, 55 (22%) developed APR. Median PFS of PPR patients was 4.2months and median OS was 17.8months. On multivariate analysis, the number of biologic agents received was the only predictor of OS. Patients with APR had a median PFS of 14.2months and a median OS of 56months. OS from the date of platinum resistance was 21.9months, though this was not different than PPR patients (p=0.19). Multivariate analysis found cancer stage and clinical trial participation to be associated with OS., Conclusions: Platinum resistance confers a poor prognosis in the APR and PPR setting. The number of biologic agents received is the strongest predictor of OS among women with PPR. Cancer stage and clinical trial participation predicts OS in patients with APR. Providing opportunities to participate in clinical trials, especially those involving targeted therapy, should be a priority in these populations., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Uterine carcinosarcomas (UCS) are rare (3-4%) but highly aggressive, accounting for a disproportionately high (16.4%) mortality among uterine malignancies. Transforming growth factor beta (TGFβ) is a multifunctional cytokine that regulates important cellular processes including epithelial-mesenchymal transition (EMT). Existence of biphasic elements and a report demonstrating amplification of TGFβ at 19q13.1 prompted us to investigate the role of TGFβ signaling in UCS.Here we demonstrated the components of TGFβ pathway are expressed and functional in UCS. TGFβ-I induced significant Smad2/3 phosphorylation, migration and EMT responses in UCS cell lines which could be attenuated by the TGFβ receptor I (TGFβR-I) or TGFβ receptor I/II (TGFβR-I/II) inhibitor developed by Eli Lilly and company. Importantly, TGFβ-I induced proliferation was c-Myc dependent, likely through activation of cell cycle. c-Myc was induced by nuclear translocation of nuclear factor of activated T cells (NFAT-1) in response to TGFβ-I. Inhibition of NFAT-1 or TGFβR-I blocked c-Myc induction, cell cycle progression and proliferation in UCS. In corroboration, mRNA levels of c-Myc were elevated in recurrent versus the non-recurrent UCS patient samples. Interestingly, in the absence of exogenous TGFβ the TGFβR-I/II inhibitor enhanced proliferation likely through non-Smad pathways. Thus, inhibition of TGFβR-I could be efficacious in treatment of UCS.

Approximately 40% of burn patients develop scar contractures. It is unknown which scar contracture therapy best optimizes activities of daily living (ADL).The appropriateness of self-reported outcome tools in measuring anti-scar contracture therapies has not been assessed. We conducted a systematic review to determine the quality of existing self-reported scales in measuring ADL among burn patients by analyzing and comparing psychometric properties-factor analysis, validity, reliability, and responsiveness. EMBASE, LILACS, American Psychological Association PsycNET databases were searched for relevant articles. Forty-one articles discussing 10 burn and non-burn-specific scales met eligibility criteria of ADL assessment, and available psychometric analyses. A common strength in most scales was good overall reliability. Common weaknesses were insufficient data on factor analyses, content validity specific to ADL assessment, and responsiveness. The psychometric analyses studies on these scales had poor sample variability. There is insufficient data on the dimensionality and responsiveness of existing scales to support their use for measuring ADL in burn patients. Existing scales do not comprehensively measure ADLs as an isolated parameter. A psychometrically valid, comprehensive self-reported burn contracture scale that measures ADLs among a diverse group of burn patients needs to be developed to optimize burn contracture treatments and develop new therapies., (© 2013 by the Wound Healing Society.)

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterine cavity. Although the exact pathophysiology is unclear, endometriosis is a well-known cause of pelvic pain and infertility in reproductive-aged women. Endometriosis can have extrapelvic manifestations relevant for colorectal surgeons to appreciate, such as cyclic constipation, diarrhea, hematochezia, and dyschezia. The treatment of endometriosis involves a combination of medical and surgical interventions where close collaboration between the gynecologist and colorectal surgeon can help achieve prolonged periods of symptom remission.

Proper tongue function is essential for respiration and mastication, yet we lack basic information on the anatomical organization underlying human tongue movement. Here we use microdissection, acetylcholinesterase histochemistry, silver staining of nerves, alpha bungarotoxin binding and immunohistochemistry to describe muscle fiber architecture and motor endplate (MEP) distribution of the human superior longitudinalis muscle (SL). The human SL extends from tongue base to tongue tip and is composed of fiber bundles that range from 2.8 to 15.7 mm in length. Individual muscle fibers of the SL range from 1.2 to 17.3 mm in length (1.3-18.2% of muscle length). Seventy-one percent of SL fibers have blunt-blunt terminations; the remainder have blunt-taper terminations. Multiple MEPs are present along SL length and dual MEPs are present on some muscle fibers. These data demonstrate that the human SL is a muscle of "in-series" design. We suggest that SL motor units are organized to innervate specific regions of the tongue body and that activation of SL motor units according to anteroposterior location is one strategy employed by the nervous system to control tongue shape and tongue movement., (Copyright (c) 2005 S. Karger AG, Basel.)

Background: Capillary haemangioma is the most common orbital and eyelid tumour of childhood, with a prevalence ranging from 1 to 3%. Periorbital haemangiomas can cause amblyopia secondary to anisometropia, induced astigmatism, strabismus or occlusion of the visual axis. Oral and intralesional steroids are considered to be the most accepted form of primary treatment. The authors have been performing early surgery as definitive treatment in selected lesions and believe it has an important role., Methods: A retrospective chart review of 17 infants (2-20 months old) seen between 1996 and 2002 was carried out. Indications for surgery in the present series were astigmatism, rapid growth, anisometropic amblyopia and obscuration of the visual axis. Thirteen were treated primarily with surgery and the other four were treated with other methods prior to considering surgery. Preoperative computed tomography scans were obtained when indicated., Results: Fourteen lesions were completely excised; residual tissue was deliberately left in order to preserve vital structures in three cases. No major surgical complications were noted. One child with residual tissue after surgery, who had proliferation of the remaining tissue, developed anisometropic amblyopia and ptosis. One child had a mild ptosis postoperatively that resolved after 6 months. Follow up was for an average 11.1 months., Conclusions: Early surgical intervention should be considered in a multidisciplinary team approach as a primary treatment option with selected, isolated haemangiomas, without a significant cutaneous component. Surgery is a safe, effective treatment for selected lesions, provides a definitive early treatment, and prevents astigmatism and occlusion-related amblyopia.