Doble synergetic anticancer activity through a combined chemo-photodynamic therapy and bioimaging of a novel Cas-ZnONPs all-in-one system.

A strategy for cancer treatment was implemented, based on chemo-photodynamic therapy, utilizing a novel formulation, low-cost system called Cas-ZnONPs. This system consisted of the incorporation of Casiopeina III-ia (CasIII-ia), a hydrophilic copper coordination compound with well-documented anti-neoplastic activity, on Zinc oxide nanoparticles (ZnONPs) with apoptotic activity and lipophilicity, allowing them to permeate biological barriers. Additionally, ZnONPs exhibited fluorescence, with emission at different wavelengths depending on their agglomeration and enabling real-time tracking biodistribution. Also, ZnONPs served as a sensitizer, generating reactive oxygen species (ROS) in situ. In in vitro studies on HeLa and MDA-MB-231 cell lines, a synergistic effect was observed with the impregnated CasIII-ia on ZnONPs. The anticancer activity had an increase in cellular inhibition, depending on the dose of exposure to UV-vis irradiation. In in vivo studies utilized zebrafish models for xenotransplanting stained MDA-MB-231 cells and testing the effectiveness of Cas-ZnONPs treatment. The treatment successfully eliminated cancer cells, both when combined with Photodynamic Therapy (PDT) and when used alone. However, a significantly higher concentration (50 times) of Cas-ZnONPs was required in the absence of PDT. This demonstrates the potential of Cas-ZnONPs in cancer treatment, especially when combined with PDT.

Impact of prescribed fire on soil microbial communities in a Southern Appalachian Forest clear-cut.

Escalating wildfire frequency and severity, exacerbated by shifting climate patterns, pose significant ecological and economic challenges. Prescribed burns, a common forest management tool, aim to mitigate wildfire risks and protect biodiversity. Nevertheless, understanding the impact of prescribed burns on soil and microbial communities in temperate mixed forests, considering temporal dynamics and slash fuel types, remains crucial. Our study, conducted at the University of Tennessee Forest Resources AgResearch and Education Center in Oak Ridge, TN, employed controlled burns across various treatments, and the findings indicate that low-intensity prescribed burns have none or minimal short-term effects on soil parameters but may alter soil nutrient concentrations, as evidenced by significant changes in porewater acetate, formate, and nitrate concentrations. These burns also induce shifts in microbial community structure and diversity, with Proteobacteria and Acidobacteria increasing significantly post-fire, possibly aiding soil recovery. In contrast, Verrucomicrobia showed a notable decrease over time, and other specific microbial taxa correlated with soil pH, porewater nitrate, ammonium, and phosphate concentrations. Our research contributes to understanding the intricate relationships between prescribed fire, soil dynamics, and microbial responses in temperate mixed forests in the Southern Appalachian Region, which is valuable for informed land management practices in the face of evolving environmental challenges.

Observation of the Fermionic Joule-Thomson Effect.

We report the first observation of the quantum Joule-Thomson (JT) effect in ideal and unitary Fermi gases. We study the temperature dynamics of these systems while they undergo an energy-per-particle conserving rarefaction. For scale-invariant systems, whose equations of state satisfy the relation U∝PV, this rarefaction conserves the specific enthalpy, which makes it thermodynamically equivalent to a JT throttling process. We observe JT heating in an ideal Fermi gas, a direct consequence of Pauli blocking. In a unitary Fermi gas, we observe that the JT heating is marginal in the temperature range 0.2≲T/T_{F}≲0.8 as the repulsive quantum-statistical effect is lessened by the attractive interparticle interactions.

Validation of a New Method of Sampling Beef Manufacturing Trimmings for Pathogen Testing Using a Manual Sampling Mitt Approach.

The USDA Food Safety Inspection Service has declared Escherichia coli O157:H7, and six additional Shiga toxin-producing E. coli (STEC) are adulterants for nonintact raw beef products. The U. S. beef processing industry has implemented several antimicrobial intervention technologies throughout the carcass dressing process to remove or destroy foodborne pathogens present on beef carcasses. Despite these efforts, STEC have been shown to cause finished product contamination, albeit at prevalences typically <0.5%. Recent work described the development and validation of improved methods for collecting samples from raw beef trimmings. One of the methods, the Manual Sampling Device (MSD) method, uses the manual implementation of the MicroTally® Swab (MT-Swab) to vigorously scrub the surface of raw beef manufacturing trimmings for pathogen detection. The work described herein reports the data from an evaluation of a novel MSD method using the MicroTally® Mitt (MT-Mitt). The MT-Mitt provides a more user-friendly option for sample collection than the MT-Swab. A series of trials were conducted with a total of 360 matched samples comparing manual sampling of raw beef manufacturing trimmings using the MT-Swab, N60-excision, or N60-plus methods to a novel method using the MT-Mitt. The results of these trials collectively demonstrate that manual sampling of raw beef manufacturing trimmings using the MT-Mitt provides organism recovery that is not significantly different from that of the MT-Swab, N60-excision, and N60-plus methods. Thus, the MT-Mitt method provides an alternative sampling method with organism recovery that is not significantly different from previous methods for sampling beef manufacturing trimmings for pathogen detection and some implementation advantages pertaining to labor and ease of use.

Tox induces T cell IL-10 production in a BATF-dependent manner.

Tox is a member of the high mobility group (HMG)-Box transcription factors and plays important roles in thymic T cell development. Outside of the thymus, however, Tox is also highly expressed by CD8 and CD4 T cells in various states of activation and in settings of cancer and autoimmune disease. In CD4 T cells, Tox has been primarily studied in T follicular helper (TFH) cells where it, along with Tox2, promotes TFH differentiation by regulating key TFH-associated genes and suppressing CD4 cytotoxic T cell differentiation. However, the role of Tox in other T helper (Th) cell subtypes is less clear. Here, we show that Tox is expressed in several physiologically-activated Th subtypes and its ectopic expression enhances the in vitro differentiation of Th2 and T regulatory (Treg) cells. Tox overexpression in unpolarized Th cells also induced the expression of several genes involved in cell activation (Pdcd1), cellular trafficking (Ccl3, Ccl4, Xcl1) and suppressing inflammation (Il10) across multiple Th subtypes. We found that Tox binds the regulatory regions of these genes along with the transcription factors BATF, IRF4, and JunB and that Tox-induced expression of IL-10, but not PD-1, is BATF-dependent. Based on these data, we propose a model where Tox regulates Th cell chemotactic genes involved in facilitating dendritic cell-T cell interactions and aids in the resolution or prevention of inflammation through the production of IL-10.

Prevalencia y caracterización de las disfunciones sexuales en mujeres en transición a la menopausia / Prevalence and characterization of sexual dysfunctions in women in transition to menopause

Objetivo: Caracterizar las disfunciones sexuales y estimar la prevalencia en un grupo de mujeres en transición a la menopausia, así como evaluar la frecuencia de la sintomatología climatérica. Método: Estudio de corte transversal, entre 2017 y 2020, que incluyó 411 mujeres en transición a la menopausia, residentes en el Quindío, con pareja estable y actividad sexual en las últimas 6 semanas. Se utilizó como instrumento el FSFI-6 (6-Item Female Sexual Function Index). Resultados: La edad promedio fue de 46,53 ± 2,87 años. La prevalencia de disfunciones sexuales fue del 38,92%, caracterizadas por dificultades con el deseo sexual (38,92%), seguido de dolor/dispareunia (35,52%). El promedio general en la puntuación del FSFI-6, en la totalidad de la población participante, fue de 22,29 ± 0,84 puntos; en la población afectada (< 19 puntos) fue de 15,78 ± 3,94. En los dominios, la puntuación más baja estuvo en el deseo (3,14 ± 0,56). La mediana de disfunciones sexuales por mujer fue de tres (23,84%). Conclusiones: más de un tercio de las mujeres del Quindío en transición a la menopausia presentan disfunciones sexuales; el trastorno más común fue el bajo deseo. Se deben hacer esfuerzos para aumentar la conciencia en los asuntos de salud sexual.

Objective: To characterize sexual dysfunctions and estimate the prevalence in a group of women in transition to menopause, as well as to evaluate the frequency of climacteric symptoms. Method: Cross-sectional study, between 2017 and 2020, included 411 women in transition to menopause, residents of Quindío, with a stable partner and sexual activity in the last 6 weeks. The FSFI-6 (6-Item Female Sexual Function Index) was used as an instrument. Results: The mean age was 46.53 ± 2.87 years. The prevalence of sexual dysfunctions was 38.92%, characterized by difficulties with sexual desire (38.92%), followed by pain/dyspareunia (35.52%). The general average, in the FSFI-6 score, in the entire participating population, was 22.29 ± 0.84 points; while in the affected population (< 19 points), it was 15.78 ± 3.94. In the domains, the lowest score was in desire (3.14 ± 0.56). The median number of sexual dysfunctions per woman was three (present in 23.84%). Conclusions: This study showed that more than one third of the women in Quindío, in transition to menopause, had sexual dysfunctions; the most common type of disorder was low desire. Efforts should be made to increase awareness about sexual health issues.

Vaginosis citolítica: actualización diagnóstica y terapéutica / Cytolytic vaginosis: diagnostic and therapeutic update

El objetivo es conocer el abordaje diagnóstico y terapéutico de la vaginosis citolítica. Para ello se hizo una búsqueda sistemática de la literatura médica mediante las bases de datos: PubMed, Central, etc. Se limitó a ensayos clínicos aleatorizados, metaanálisis y revisiones bibliográficas, con disponibilidad del texto completo para evaluarlos en su totalidad e incluirlos en la revisión; publicados entre 1980 y 2021. Se incluyeron 27 publicaciones. La vaginosis citolítica es un trastorno infradiagnosticado. En mujeres con síntomas y signos de candidiasis vulvovaginal, que no responden a la terapia, se debe considerar la probabilidad de estar en presencia de una vaginosis citolítica. El tratamiento obliga a elevar el pH vaginal a valores básicos y a disminuir el número excesivo de Lactobacillus, resultando de utilidad las duchas vaginales con bicarbonato de sodio y/o un tratamiento con antibióticos derivados de la penicilina junto a un inhibidor de ß-lactamasas o doxiciclina en las pacientes alérgicas a la penicilina. Finalmente, se concluye que la vaginosis citolítica es una afección común, frecuentemente se diagnostica de forma errónea porque se confunde con la candidiasis vulvovaginal; se caracteriza por producir un cuadro clínico similar. El tratamiento se enfoca en disminuir el número de Lactobacillus y la elevación del pH vaginal.

The objective is to know the diagnostic and therapeutic approach of cytolytic vaginosis. A systematic search of the medical literature was carried out using the following databases: Medline via PubMed, Central, and Cochrane Database of Systematic Reviews, among others. The search was limited to randomized clinical trials, meta-analyses, and literature reviews that had the full text available for full evaluation and inclusion in the review; published between 1980 and 2021. Twenty-seven publications were included. Cytolytic vaginosis is a frequently underdiagnosed disorder, which mimics Candida vaginitis. In women with symptoms and signs of vulvovaginal candidiasis who do not respond to antifungal therapy, the possibility of cytolytic vaginosis should be considered. The treatment of this condition requires raising the vaginal pH to basic values and reducing the excessive number of Lactobacillus, resulting in useful vaginal douches with sodium bicarbonate and/or treatment with antibiotics derived from penicillin together with a ß-lactamases inhibitor or doxycycline in patients allergic to penicillin. Finally, we conclude that cytolytic vaginosis is a common condition, frequently misdiagnosed because it is confused with vulvovaginal candidiasis, since it is characterized by producing a similar clinical picture. Treatment focuses on reducing the number of Lactobacillus and raising vaginal pH.

A protein kinase C α and ß inhibitor blunts hyperphagia to halt renal function decline and reduces adiposity in a rat model of obesity-driven type 2 diabetes.

Type 2 diabetes (T2D) and its complications can have debilitating, sometimes fatal consequences for afflicted individuals. The disease can be difficult to control, and therapeutic strategies to prevent T2D-induced tissue and organ damage are needed. Here we describe the results of administering a potent and selective inhibitor of Protein Kinase C (PKC) family members PKCα and PKCß, Cmpd 1, in the ZSF1 obese rat model of hyperphagia-induced, obesity-driven T2D. Although our initial intent was to evaluate the effect of PKCα/ß inhibition on renal damage in this model setting, Cmpd 1 unexpectedly caused a marked reduction in the hyperphagic response of ZSF1 obese animals. This halted renal function decline but did so indirectly and indistinguishably from a pair feeding comparator group. However, above and beyond this food intake effect, Cmpd 1 lowered overall animal body weights, reduced liver vacuolation, and reduced inguinal adipose tissue (iWAT) mass, inflammation, and adipocyte size. Taken together, Cmpd 1 had strong effects on multiple disease parameters in this obesity-driven rodent model of T2D. Further evaluation for potential translation of PKCα/ß inhibition to T2D and obesity in humans is warranted.

Considerations for environmental sustainability in clinical radiology and radiotherapy practice: A systematic literature review and recommendations for a greener practice.

INTRODUCTION: Environmental sustainability (ES) in healthcare is an important current challenge in the wider context of reducing the environmental impacts of human activity. Identifying key routes to making clinical radiology and radiotherapy (CRR) practice more environmentally sustainable will provide a framework for delivering greener clinical services. This study sought to explore and integrate current evidence regarding ES in CRR departments, to provide a comprehensive guide for greener practice, education, and research. METHODS: A systematic literature search and review of studies of diverse evidence including qualitative, quantitative, and mixed methods approach was completed across six databases. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and the Quality Assessment Tool for Studies with Diverse Designs (QATSDD) was used to assess the included studies. A result-based convergent data synthesis approach was employed to integrate the study findings. RESULTS: A total of 162 articles were identified. After applying a predefined exclusion criterion, fourteen articles were eligible. Three themes emerged as potentially important areas of CRR practice that contribute to environmental footprint: energy consumption and data storage practices; usage of clinical consumables and waste management practices; and CRR activities related to staff and patient travel. CONCLUSIONS: Key components of CRR practice that influence environmental impact were identified, which could serve as a framework for exploring greener practice interventions. Widening the scope of research, education and awareness is imperative to providing a holistic appreciation of the environmental burden of healthcare. IMPLICATIONS FOR PRACTICE: Encouraging eco-friendly travelling options, leveraging artificial Intelligence (AI) and CRR specific policies to optimise utilisation of resources such as energy and radiopharmaceuticals are recommended for a greener practice.

Combined Incisional Negative Pressure Wound Therapy and Subfascial Suction Drainage: The Suction Taco Approach.

An 18-year-old male with T4-L3 adult idiopathic scoliosis was treated with posterior spinal fusion followed by the application of a combined incisional negative pressure wound therapy (NPWT) and subfascial suction drainage system. In this report, we describe a novel technique that incorporates subfascial drains into an NPWT incisional vacuum system leading to a single exiting suction line. This effectively mitigates drain burden, maintains a sterile environment during the in-hospital postoperative period, provides NPWT to the drain exiting and incisional sites, and provides negative pressure-assisted deep space closure.

Insights into recent findings and clinical application of YAP and TAZ in cancer.

Decades of research have mapped out the basic mechanics of the Hippo pathway. The paralogues Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), as the central transcription control module of the Hippo pathway, have long been implicated in the progression of various human cancers. The current literature regarding oncogenic YAP and TAZ activities consists mostly of context-specific mechanisms and treatments of human cancers. Furthermore, a growing number of studies demonstrate tumour-suppressor functions of YAP and TAZ. In this Review we aim to synthesize an integrated perspective of the many disparate findings regarding YAP and TAZ in cancer. We then conclude with the various strategies for targeting and treating YAP- and TAZ-dependent cancers.

A comprehensive study of product distributions and coke deposition during catalytic cracking of vacuum gas oil over hierarchical zeolites.

In this study, zeolites (Z) were used as catalysts in the cracking of a Colombian vacuum gas oil (VGO), with a focus on product distribution and coke deposition. The catalytic tests were carried out in a MAT-type reactor under typical conditions. The zeolites were subjected to alkaline treatment with NaOH at concentrations ranging from 0.05 to 0.4 mol/L, resulting in the creation of several samples (Z-0.05, Z-0.10, Z-0.20, Z-0.30 and Z-0.40) that were then hydrothermally stabilized (Z-0.05-M, Z-0.10-M, Z-0.20-M, Z-0.30-M and Z-0.40-M) to increase mesoporosity and reduced crystallinity. The increase in mesoporosity was accompanied by an improvement in acidity. Despite Z-0.30-M having higher acidity, Z-0.00-M and Z-0.10-M exhibited the highest activity due to their high crystallinity and microporosity, yielding the highest gas yields. Gasoline was the main product, with maximum yields exceeding 30%. Z-0.20-M produced more aromatic and olefin compounds than the others, resulting in higher quality gasoline. Coke formation followed the trend: Z-0.00-M < Z-0.10-M < Z-0.20-M < Z-0.30-M. The higher intracrystalline mesoporosity in the zeolites favored the formation of a more condensed coke.

Dual Inhibition of the Wnt Inhibitors DKK1 and Sclerostin Promotes Fracture Healing and Increases the Density and Strength of Uninjured Bone: An Experimental Study in Nonhuman Primates.

BACKGROUND: Fracture repair involves the reactivation of developmental signaling cascades, including Wnt signaling that stimulates bone formation and bone regeneration. Rodent data indicate that dual inhibition of the Wnt signaling antagonists sclerostin and Dickkopf-1 (DKK1) increases callus bone volume and strength while increasing bone mass systemically. METHODS: We evaluated the effects of 16 weeks of subcutaneously administered carrier solution (vehicle, VEH), anti-sclerostin antibody (Scl-Ab), anti-DKK1 antibody (DKK1-Ab), or Scl-Ab plus DKK1-Ab combination therapy (COMBO) on ulnar osteotomy healing in nonhuman primates (cynomolgus monkeys; 20 to 22 per group). RESULTS: Scl-Ab and COMBO therapy increased systemic markers of bone formation versus VEH, with COMBO leading to synergistic increases versus Scl-Ab or DKK1-Ab monotherapies. The COMBO and Scl-Ab groups showed reduced serum markers of bone resorption versus VEH. The COMBO and DKK1-Ab groups exhibited greater callus bone mineral density (BMD), torsional stiffness, and torsional rigidity versus VEH. Lumbar vertebrae from the Scl-Ab and COMBO groups showed greater BMD and bone formation rate versus VEH, and the femoral mid-diaphysis of the Scl-Ab and COMBO groups showed greater periosteal and endocortical bone formation rates versus VEH. CONCLUSIONS: DKK1-Ab increased BMD and strength at the ulnar osteotomy site, Scl-Ab increased bone formation and BMD at uninjured skeletal sites, and Scl-Ab plus DKK1-Ab combination therapy induced all of these effects, in some cases to a greater degree versus 1 or both monotherapies. These results in nonhuman primates suggest that DKK1 preferentially regulates bone healing while sclerostin preferentially regulates systemic bone mass. CLINICAL RELEVANCE: Combination therapy with antibodies against sclerostin and DKK1 may offer a promising therapeutic strategy for both fracture treatment and fracture prevention.

Molecular MR Imaging of Renal Fibrogenesis in Mice.

BACKGROUND: In most CKDs, lysyl oxidase oxidation of collagen forms allysine side chains, which then form stable crosslinks. We hypothesized that MRI with the allysine-targeted probe Gd-oxyamine (OA) could be used to measure this process and noninvasively detect renal fibrosis. METHODS: Two mouse models were used: hereditary nephritis in Col4a3-deficient mice (Alport model) and a glomerulonephritis model, nephrotoxic nephritis (NTN). MRI measured the difference in kidney relaxation rate, ΔR1, after intravenous Gd-OA administration. Renal tissue was collected for biochemical and histological analysis. RESULTS: ΔR1 was increased in the renal cortex of NTN mice and in both the cortex and the medulla of Alport mice. Ex vivo tissue analyses showed increased collagen and Gd-OA levels in fibrotic renal tissues and a high correlation between tissue collagen and ΔR1. CONCLUSIONS: Magnetic resonance imaging using Gd-OA is potentially a valuable tool for detecting and staging renal fibrogenesis.

Common Finger Injuries: Treatment Guidelines for Emergency and Primary Care Providers.

INTRODUCTION: Finger and hand injuries are among the most common musculoskeletal conditions presenting to emergency departments and primary care providers. Many rural and community hospitals may not have immediate access to an orthopedic surgeon on-site. Furthermore, military treatment facilities, both within the continental United States and in austere deployment environments, face similar challenges. Therefore, knowing how to treat basic finger and hand injuries is paramount for patient care. MATERIALS AND METHODS: The Armed Forces Health Surveillance Branch operates the Defense Medical Surveillance System, a database that serves as the central repository of medical surveillance data for the armed forces. The Defense Medical Surveillance System was queried for ICD-10 codes associated with finger injuries from 2015 to 2019 among active duty service members across the major branches of the military. RESULTS: The most commonly reported finger injuries were open wounds to fingers without damage to nails, metacarpal fractures, phalanx fractures, and finger subluxation/dislocation. Emergency departments were the most commonly reported treatment facility type accounting for 35% of initial finger injuries, followed by 32.2% at orthopedic surgery clinics, 22.2% at family medicine clinics, and 10.8% at urgent care centers. CONCLUSIONS: Finger injuries are common in the military setting and presenting directly to an orthopedic surgeon does not appear the norm. Fingertip injuries, fractures within the hand, and finger dislocations can often be managed without the need for a subspecialist. By following simple guidelines with attention to "red flags," primary care providers can manage most of these injuries with short-term follow-up with orthopedics.

ZnO nanoparticles-modified polycaprolactone-gelatin membranes for guided/bone tissue regeneration, antibacterial and osteogenic differentiation properties.

Periodontitis is a highly prevalent infectious disease that causes the progressive destruction of the periodontal supporting tissues. If left untreated, it can lead to tooth loss impairing oral function, aesthetics, and the patient's overall quality of life. Guided and Bone Tissue Regeneration (GTR/BTR) are surgical therapies based on the placement of a membrane that prevents epithelial growth into the defect, allowing the periodontal/bone cells (including stem cells) to regenerate or restore the affected tissues. The success of these therapies is commonly affected by the local bacterial colonization of the membrane area and its fast biodegradation, causing postoperative infections and a premature rupture of the membrane limiting the regeneration process. This study presents the antibacterial and osteogenic differentiation properties of polycaprolactone-gelatin (PCL-G) electrospun membranes modified with ZnO nanoparticles (ZnO-NPs). The membranes´ chemical composition, surface roughness, biodegradation, water wettability, and mechanical properties under simulated physiological conditions, were analyzed by the close relationship with their biological properties. The PCL-G membranes modified with 1, 3, and 6% w/w of ZnO-NPs showed a significant reduction in the planktonic and biofilm formation of four clinically relevant bacteria;A. actinomycetemcomitansserotype b, P. gingivalis,E. coli, andS. epidermidis. Additionally, the membranes presented appropriate mechanical properties and biodegradation rates to be potentially used in clinical treatments. Notably, the membranes modified with the lowest concentration of ZnO-NPs (1% w/w) stimulated the production of osteoblast markers and calcium deposits in human bone marrow-derived mesenchymal stem cells (BM-MSC) and were biocompatible to human osteoblasts cells (hFOB). These results suggest that the PCL-G membranes with 1% w/w of ZnO-NPs are high-potential candidates for GTR/BTR treatments, as they were the most effective in terms of better antibacterial effectiveness at a lower NPs-concentration while creating a favorable cellular microenvironment for bone growth.

Robotic stray energy with constant-voltage versus constant-power regulating electrosurgical generators.

INTRODUCTION: Stray energy from surgical energy instruments can cause unintended thermal injuries. There are no published data regarding electrosurgical generators and their influence on stray energy transfer during robotic surgery. There are two approved generators for the DaVinci Xi robotic platform: a constant-voltage regulating generator (cVRG) and a constant-power regulating generator (cPRG). The purpose of this study was to quantify and compare stray energy transfer in the robotic Xi platform using a cVRG versus a cPRG. METHODS: An ex vivo bovine model was used to simulate a standard multiport robotic surgery. The DaVinci Xi (Intuitive Surgical, Sunnyvale, CA) robotic platform was attached to a trainer box using robotic ports. A 5 s, open-air activation of the monopolar scissors was done with commonly used electrosurgical settings using a cPRG (ForceTriad, Covidien-Medtronic, Boulder, CO) or cVRG (ERBE VIO 300 dV 2.0, ERBE USA, Marietta, GA). Stray energy transfer was quantified as the change in tissue temperature (°C) nearest the tip of the assistance grasper (which was not in direct contact with the active monopolar scissors). RESULTS: Stray energy transfer occurred with both generators. Utilizing common, comparable settings for standard coagulation, significantly less stray energy was transferred with the cVRG versus cPRG (4.4 ± 1.6 °C vs. 41.1 ± 13.0 °C, p < 0.001). Similarly, less stray energy was transferred using cut modes with the cVRG compared to the cPRG (5.61 ± 1.79 °C vs. 33.9 ± 18.4 °C, p < 0.001). CONCLUSION: Stray energy transfer increases tissue temperatures more than 45C in the DaVinci Xi robotic platform. Low voltage modalities, such as cut or blend; as well as a cVRG generator, significantly reduces stray energy. Robotic surgeons can minimize the risk of stray energy injuries by using these low risk modes and/or generator.

Reduction of sporadic and neurofibromatosis type 2-associated vestibular schwannoma growth in vitro and in vivo after treatment with the c-Jun N-terminal kinase inhibitor AS602801.

OBJECTIVE: Vestibular schwannomas (VSs) are benign nerve sheath tumors that result from mutation in the tumor suppressor gene NF2, with functional loss of the protein merlin. The authors have previously shown that c-Jun N-terminal kinase (JNK) is constitutively active in human VS cells and plays a central role in their survival by suppressing accumulation of mitochondrial superoxides, implicating JNK inhibitors as a potential systemic treatment for VS. Thus, the authors hypothesized that the adenosine 5'-triphosphate-competitive JNK inhibitor AS602801 would demonstrate antitumor activity in multiple VS models. METHODS: Treatment with AS602801 was tested in primary human VS cultures, human VS xenografts, and a genetic mouse model of schwannoma (Postn-Cre;Nf2flox/flox). Primary human VS cell cultures were established from freshly obtained surgical tumor specimens; treatment group media was enriched with AS602801. VS xenograft tumors were established in male athymic nude mice from freshly collected human tumor. Four weeks postimplantation, a pretreatment MRI scan was obtained, followed by 65 days of AS602801 (n = 18) or vehicle control (n = 19) treatment. Posttreatment MRI scans were used to measure final tumor volume. Tumors were then harvested. Finally, Postn-Cre;Nf2flox/flox mice were treated with AS602801 (n = 10) or a vehicle (n = 13) for 65 days. Posttreatment auditory brainstem responses were obtained. Dorsal root ganglia from Postn-Cre;Nf2flox/flox mice were then harvested. In all models, schwannoma identity was confirmed with anti-S100 staining, cell proliferation was measured with the EdU assay, and cell death was measured with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. All protocols were approved by the local institutional review board and Institutional Animal Care and Use Committees. RESULTS: Treatment with AS602801 decreased cell proliferation and increased apoptosis in primary human VS cultures. The systemic administration of AS602801 in mice with human VS xenografts reduced tumor volume and cell proliferation. Last, the AS602801-treated Postn-Cre;Nf2flox/flox mice demonstrated decreased cell proliferation in glial cells in the dorsal root ganglia. However, AS602801 did not significantly delay hearing loss in Postn-Cre;Nf2flox/flox mice up to 3 months posttreatment. CONCLUSIONS: The data suggest that JNK inhibition with AS602801 suppresses growth of sporadic and neurofibromatosis type 2-associated VSs. As such, AS602801 is a potential systemic therapy for VS and warrants further investigation.