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BACKGROUND: Management of biliopancreatic pathology in Roux-en-Y gastric bypass (RYGB) patients is challenging despite the availability of multiple approaches like single-balloon enteroscopy-assisted ERCP (SBE-ERCP), laparoscopy-assisted ERCP (LA-ERCP), and EUS-directed transgastric intervention (EDGI). We evaluated the outcomes of the interchangeable combination of endoscopic procedures to treat biliopancreatic pathology in RYGB patients. MATERIALS AND METHODS: This is a monocentric retrospective study of consecutive RYGB patients with biliopancreatic pathology between June 2014 and September 2023. Primary endpoints were technical success, adverse events (AE), and parameters of endoscopic procedures according to etiology. A clinically useful management algorithm was developed. RESULTS: A total of 102 patients with RYGB (73 women; mean age 55 ± 10 years) were included. A total of 113 SBE-ERCP (in 90 patients), 26 EDGI (in 23 patients), and 2 LA-ERCP (in 2 patients) were performed. Technical success of SBE-ERCP was lower compared to EDGI (74.4% vs 95.1%, p = 0.002). The AE rate was lower using SBE-ERCP compared to EDGI (12.4% vs 38.5%, p = 0.003). Two sub-groups based on etiology were identified as "common bile duct stone" (CBDS) and "Other." In the CBDS group, the mean number and time of procedures were lower in SBE-ERCP as the first-line technique compared to first-line EDGI (1.1 vs 2.7, p < 0.00 and 91 ± 20.7 min vs 161 ± 61.3 min, p < 0.00). CONCLUSION: A combination of endoscopic procedures can achieve high technical success in managing biliopancreatic pathology in RYGB patients with an acceptable AE rate. In the case of CBDS, SBE-ERCP appeared to be a good first-line single-step option. For other indications, EDGI should be proposed as the first line.
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BACKGROUND: Ex vivo tissue morphometric (TM) measurements have been proposed as a quality marker for colorectal cancer (CRC) surgery. However, their survival associations require clarification. This study aimed to evaluate the feasibility of capturing TM measurements based on ex vivo fresh specimen images and explore the association between these TM measurements and survival outcomes. METHODS: A prospective cohort study at Concord Hospital, Sydney was conducted with Stage I to III CRC patients (2009-2019) who underwent an anterior resection (AR) or right hemicolectomy (RH). Using high-resolution digital photographs of fresh CRC specimens, ex vivo tissue morphometric (TM) measurements-resected mesentery area (TM A), distances from high vascular tie to tumour (TM B) and bowel wall (TM C), and bowel length (TM D)-were recorded using Image J. Overall survival (OS) and disease-free survival (DFS) estimates and their associations to clinicopathological variables were investigated with Kaplan-Meier and Cox regression analyses. Linear regression models tested association between TM measurements and lymph node (LN) yield. RESULTS: Of the 1,425 patients who underwent CRC surgery, TM measurements were performed on 312 patients, with an average age of 69.4 years (SD 12.3), of whom 52.9% were male. The majority had an AR (57.8%). Among AR patients, a 5-year OS rate of 77.4% and a DFS rate of 70.1% were observed, with TM measurements bearing no relationship to survival outcomes. Similarly, RH patients exhibited a 5-year OS rate of 67.2% and a DFS rate of 63.1%, with TM measurements again showing no association with survival. Only TM D (P = 0.02) measurements were associated with the number of LNs examined. CONCLUSION: This study successfully demonstrates the feasibility of measuring TM measurements on photographs of ex vivo fresh specimens following CRC surgery. The lack of association with survival outcomes questions the utility of TM measurements as a quality metric of CRC surgery.
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Colectomia , Neoplasias Colorretais , Humanos , Masculino , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/mortalidade , Feminino , Idoso , Estudos Prospectivos , Taxa de Sobrevida , Prognóstico , Colectomia/métodos , Colectomia/mortalidade , Seguimentos , Pessoa de Meia-Idade , Estudos de ViabilidadeRESUMO
N-monomethyl amines are useful intermediates in drugs, natural products, paints. Yet their synthesis is a tremendous challenge due to their high reactivity, typically leading to overmethylation. In this contribution, a highly selective catalytic N-methylation methodology is reported, converting urea derivatives to monomethylated amines, using a commercially available heterogeneous Pd/C catalyst and methanol as unique reagent. Methanol provides a sustainable alternative protocol for the selective preparation of mono-methylated derivatives as it acts as both H2 and C1 sources. In addition, several control experiments were performed to provide a proposal for the mechanism, namely dehydrogenation of methanol and subsequent hydrogenation of urea derivatives, followed by reduction of the in situ formed methyl imine. Importantly, the approach is simple, highly productive and enables novel synthetic procedures for the preparation of monomethylamines from urea derivatives.
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BACKGROUND: Platelets prevent bleeding in a variety of inflammatory settings, the adhesion receptors and activation pathways involved being highly context-dependent and functionally redundant. In some situations, platelets recruited to inflammatory sites act independently of aggregation. The mechanisms underlying stable platelet adhesion in inflamed microvessels remain incompletely understood, in particular, whether and if so, how ß1 and ß3 integrins are involved. METHODS: The impact of isolated or combined platelet deficiency in ß1 and ß3 integrins on inflammation-associated hemostasis was investigated in 3 models of acute inflammation: immune complex-based cutaneous reverse passive Arthus reaction, intranasal lipopolysaccharide-induced lung inflammation, and cerebral ischemia-reperfusion following transient (2-hour) occlusion of the transient middle cerebral artery. RESULTS: Mice with platelet-directed inactivation of Itgb1 (PF4Cre-ß1-/-) displayed no bleeding in any of the inflammation models, while mice defective in platelet Itgb3 (PF4Cre-ß3-/-) exhibited bleeding in all 3 models. Remarkably, the bleeding phenotype of PF4Cre-ß3-/- mice was exacerbated in the reverse passive Arthus model by the concomitant deletion of ß1 integrins, PF4Cre-ß1-/-/ß3-/- animals presenting increased bleeding. Intravital microscopy in reverse passive Arthus experiments highlighted a major defect in the adhesion of PF4Cre-ß1-/-/ß3-/- platelets to inflamed microvessels. Unlike PF4Cre-ß1-/- and PF4Cre-ß3-/- mice, PF4Cre-ß1-/-/ß3-/- animals developed early hemorrhagic transformation 6 hours after transient middle cerebral artery occlusion. PF4Cre-ß1-/-/ß3-/- mice displayed no more bleeding in lipopolysaccharide-induced lung inflammation than PF4Cre-ß3-/- animals. CONCLUSIONS: Altogether, these results show that the requirement for and degree of functional redundancy between platelet ß1 and ß3 integrins in inflammation-associated hemostasis vary with the inflammatory situation.
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Nanoparticles (NP) play a crucial role in nanomedicine, serving as carriers for localized therapeutics to allow for precise drug delivery to specific disease sites and conditions. When injected systemically, NP can directly interact with various blood cell types, most critically with circulating platelets. Hence, the potential activation/inhibition of platelets following NP exposure must be evaluated a priori due to possible debilitating outcomes. In recent years, various studies have helped resolve the physicochemical parameters that influence platelet-NP interactions, and either emphasize nanoparticles' therapeutic role such as to augment hemostasis or to inhibit thrombus formation, or conversely map their potential undesired side effects upon injection. In the present review, we discuss some of the main effects of several key NP types including polymeric, ceramic, silica, dendrimers and metallic NPs on platelets, with a focus on the physicochemical parameters that can dictate these effects and modulate the therapeutic potential of the NP. Despite the scientific and clinical significance of understanding Platelet-NP interactions, there is a significant knowledge gap in the field and a critical need for further investigation. Moreover, improved guidelines and research methodologies need to be developed and implemented. Our outlook includes the use of biomimetic in vitro models to investigate these complex interactions under both healthy physiological and disease conditions.
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Endossonografia , Gastrectomia , Gastroenterostomia , Laparoscopia , Humanos , Gastrectomia/métodos , Gastrectomia/efeitos adversos , Gastroenterostomia/métodos , Gastroenterostomia/efeitos adversos , Endossonografia/métodos , Laparoscopia/métodos , Ultrassonografia de Intervenção , Feminino , Obstrução da Saída Gástrica/etiologia , Obstrução da Saída Gástrica/cirurgia , Pessoa de Meia-Idade , AdultoRESUMO
The availability of nutrients from mosquito blood meals accelerates the development of Plasmodium falciparum laboratory strains in artificially infected Anopheles gambiae mosquitoes. The impact of multiple blood meals on the number of P. falciparum genotypes developing from polyclonal natural human malaria infections (field-isolates) remains unexplored. Here, we experimentally infect An. gambiae with P. falciparum field-isolates and measure the impact of an additional non-infectious blood meal on parasite development. We also assess parasite genetic diversity at the blood stage level of the parasite in the human host and of the sporozoites in the mosquito. Additional blood meals increase the sporozoite infection prevalence and intensity, but do not substantially affect the genetic diversity of sporozoites in the mosquito. The most abundant parasite genotypes in the human blood were transmitted to mosquitoes, suggesting that there was no preferential selection of specific genotypes. This study underlines the importance of additional mosquito blood meals for the development of parasite field-isolates in the mosquito host.
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Anopheles , Variação Genética , Malária Falciparum , Plasmodium falciparum , Esporozoítos , Plasmodium falciparum/genética , Animais , Anopheles/parasitologia , Esporozoítos/genética , Humanos , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Malária Falciparum/sangue , Mosquitos Vetores/parasitologia , Genótipo , Interações Hospedeiro-Parasita/genética , FemininoRESUMO
Crystallization of alloys from a molten state is a fundamental process underpinning metallurgy. Here the direct imaging of an intermetallic precipitation reaction at equilibrium in a liquid-metal environment is demonstrated. It is shown that the outer layers of a solidified intermetallic are surprisingly unstable to the depths of several nanometers, fluctuating between a crystalline and a liquid state. This effect, referred to herein as crystal interface liquefaction, is observed at remarkably low temperatures and results in highly unstable crystal interfaces at temperatures exceeding 200 K below the bulk melting point of the solid. In general, any liquefaction process would occur at or close to the formal melting point of a solid, thus differentiating the observed liquefaction phenomenon from other processes such as surface pre-melting or conventional bulk melting. Crystal interface liquefaction is observed in a variety of binary alloy systems and as such, the findings may impact the understanding of crystallization and solidification processes in metallic systems and alloys more generally.
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AIM: Attention is increasingly being turned to functional outcomes as being central to colorectal cancer (CRC) survivorship. The current literature may underestimate the impact of evacuatory dysfunction on patient satisfaction with bowel function after anterior resection (AR) for CRC. The aim of this study was to investigate the impact of post-AR symptoms of storage and evacuatory dysfunction on patient satisfaction and health-related quality of life (HRQoL). METHOD: A cross-sectional study was performed at an Australian hospital of patients post-AR for CRC (2012-2021). The postoperative bowel function scores used were: low anterior resection syndrome (LARS), St Mark's incontinence, Cleveland Clinic constipation and Altomare obstructive defaecation syndrome scores. Eight 'storage' and 'evacuatory' dysfunction symptoms were derived. A seven-point Likert scale measured patient satisfaction. The SF36v2® measured HRQoL. Linear regression assessed the association between symptoms, patient satisfaction and HRQoL. RESULTS: Overall, 248 patients participated (mean age 70.8 years, 57.3% male), comprising 103 with rectal cancer and 145 with sigmoid cancer. Of the symptoms that had a negative impact on patient satisfaction, six reflected evacuatory dysfunction, namely excessive straining (p < 0.001), one or more unsuccessful bowel movement attempt(s)/24 h (p < 0.001), anal/vaginal digitation (p = 0.005), regular enema use (p = 0.004), toilet revisiting (p = 0.004) and >10 min toileting (p = 0.004), and four reflected storage dysfunction, namely leaking flatus (p = 0.002), faecal urgency (p = 0.005), use of antidiarrhoeal medication (p = 0.001) and incontinence-related lifestyle alterations (p < 0.001). A total of 130 patients (53.5%) had 'no LARS', 56 (23.1%) had 'minor LARS' and 57 (23.4%) had 'major LARS'. Fifty-seven (44.5%) patients classified as having 'no LARS' had evacuatory dysfunction. CONCLUSION: Postoperative storage and evacuatory dysfunction symptoms have an adverse impact on patient satisfaction and HRQoL post-AR. The importance of comprehensively documenting symptoms of evacuatory dysfunction is highlighted. Further research is required to develop a patient satisfaction-weighted LARS-specific HRQoL instrument.
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Neoplasias Colorretais , Constipação Intestinal , Incontinência Fecal , Satisfação do Paciente , Complicações Pós-Operatórias , Qualidade de Vida , Humanos , Feminino , Masculino , Estudos Transversais , Idoso , Síndrome , Complicações Pós-Operatórias/etiologia , Satisfação do Paciente/estatística & dados numéricos , Constipação Intestinal/etiologia , Constipação Intestinal/fisiopatologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/complicações , Pessoa de Meia-Idade , Incontinência Fecal/etiologia , Incontinência Fecal/psicologia , Incontinência Fecal/fisiopatologia , Fenótipo , Protectomia/efeitos adversos , Austrália , Idoso de 80 Anos ou mais , Neoplasias Retais/cirurgia , Defecação/fisiologia , Síndrome de Ressecção Anterior BaixaRESUMO
Low-melting liquid metals are emerging as a new group of highly functional solvents due to their capability to dissolve and alloy various metals in their elemental state to form solutions as well as colloidal systems. Furthermore, these liquid metals can facilitate and catalyze multiple unique chemical reactions. Despite the intriguing science behind liquid metals and alloys, very little is known about their fundamental structures in the nanometric regime. To bridge this gap, this work employs small angle neutron scattering and molecular dynamics simulations, revealing that the most commonly used liquid metal solvents, EGaIn and Galinstan, are surprisingly structured with the formation of clusters ranging from 157 to 15.7 Å. Conversely, noneutectic liquid metal alloys of GaSn or GaIn at low solute concentrations of 1, 2, and 5 wt%, as well as pure Ga, do not exhibit these structures. Importantly, the eutectic alloys retain their structure even at elevated temperatures of 60 and 90 °C, highlighting that they are not just simple homogeneous fluids consisting of individual atoms. Understanding the complex soft structure of liquid alloys will assist in comprehending complex phenomena occurring within these fluids and contribute to deriving reaction mechanisms in the realm of synthesis and liquid metal-based catalysis.
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Despite abundant evidence demonstrating that platelets foster metastasis, anti-platelet agents have low therapeutic potential due to the risk of hemorrhages. In addition, whether platelets can regulate metastasis at the late stages of the disease remains unknown. In this study, we subject syngeneic models of metastasis to various thrombocytopenic regimes to show that platelets provide a biphasic contribution to metastasis. While potent intravascular binding of platelets to tumor cells efficiently promotes metastasis, platelets further support the outgrowth of established metastases via immune suppression. Genetic depletion and pharmacological targeting of the glycoprotein VI (GPVI) platelet-specific receptor in humanized mouse models efficiently reduce the growth of established metastases, independently of active platelet binding to tumor cells in the bloodstream. Our study demonstrates therapeutic efficacy when targeting animals bearing growing metastases. It further identifies GPVI as a molecular target whose inhibition can impair metastasis without inducing collateral hemostatic perturbations.
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Plaquetas , Metástase Neoplásica , Glicoproteínas da Membrana de Plaquetas , Animais , Plaquetas/metabolismo , Plaquetas/efeitos dos fármacos , Humanos , Camundongos , Glicoproteínas da Membrana de Plaquetas/metabolismo , Glicoproteínas da Membrana de Plaquetas/genética , Linhagem Celular Tumoral , Feminino , Camundongos Endogâmicos C57BLRESUMO
Plasma-activated chemical transformations promise the efficient synthesis of salient chemical products. However, the reaction pathways that lead to desirable products are often unknown, and key quantum-state-resolved information regarding the involved molecular species is lacking. Here we use quantum cascade laser dual-comb spectroscopy (QCL-DCS) to probe plasma-activated NH3 generation with rotational and vibrational state resolution, quantifying state-specific number densities via broadband spectral analysis. The measurements reveal unique translational, rotational and vibrational temperatures for NH3 products, indicative of a highly reactive, non-thermal environment. Ultimately, we postulate on the energy transfer mechanisms that explain trends in temperatures and number densities observed for NH3 generated in low-pressure nitrogen-hydrogen (N2-H2) plasmas.
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BACKGROUND: This study evaluated the safety and efficacy of salvage endoscopic submucosal dissection (ESD) for Barrett's neoplasia recurrence after radiofrequency ablation (RFA). METHODS: Data from patients at 16 centers were collected for a multicenter retrospective study. Patients who underwent at least one RFA treatment for Barrett's esophagus and thereafter underwent further esophageal ESD for neoplasia recurrence were included. RESULTS: Data from 56 patients who underwent salvage ESD between April 2014 and November 2022 were collected. Immediate complications included one muscular tear (1.8%) treated with stent (Agree classification: grade IIIa). Two transmural perforations (3.6%; treated with clips) and five muscular tears (8.9%; two treated with clips) had no clinical impact and were not considered as adverse events. Seven patients (12.5%) developed strictures (grade IIIa), which were treated with balloon dilation. Histological analysis showed 36 adenocarcinoma, 17 high grade dysplasia, and 3 low grade dysplasia. En bloc and R0 resection rates were 89.3% and 66.1%, respectively. Resections were curative in 33 patients (58.9%), and noncurative in 22 patients (39.3%), including 11 "local risk" (19.6%) and 11 "high risk" (19.6%) resections. At the end of follow-up with a median time of 14 (0-75) months after salvage ESD, and with further endoscopic treatment if necessary (RFA, argon plasma coagulation, endoscopic mucosal resection, ESD), neoplasia remission ratio was 37/53 (69.8%) and the median remission time was 13 (1-75) months. CONCLUSION: In expert hands, salvage ESD was a safe and effective treatment for recurrence of Barrett's neoplasia after RFA treatment.
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Esôfago de Barrett , Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Recidiva Local de Neoplasia , Ablação por Radiofrequência , Terapia de Salvação , Humanos , Esôfago de Barrett/cirurgia , Esôfago de Barrett/patologia , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Terapia de Salvação/métodos , Pessoa de Meia-Idade , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Ablação por Radiofrequência/efeitos adversos , Ablação por Radiofrequência/métodos , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Estenose Esofágica/etiologia , Idoso de 80 Anos ou mais , Resultado do Tratamento , Esofagoscopia/métodos , Esofagoscopia/efeitos adversosRESUMO
BACKGROUND: Surgical excision is the treatment of choice for feline intracranial meningioma. OBJECTIVES: To report clinical findings, complications, and outcomes following surgery for feline intracranial meningioma. METHODS: Medical records (01/2000-01/2017) of cats that underwent surgical excision of an intracranial meningioma at our institution were reviewed. Patient data included signalment, clinical signs, surgical technique, complications, histopathologic diagnosis, survival time, and owners' answers to a satisfaction questionnaire. Survival was assessed using the Kaplan-Meier method and log-rank test. RESULTS: Twenty-six cats were included in this study. The exact cause of death was known in 17 cases and was not related to meningioma in 9/17 cases. Overall median survival time was 881 days (95% confidence interval 518; 1248). The age of the cat did not influence survival (p = 0.94) or the occurrence of complications (p = 0.051). Complications occurred in 13/24 cats, including dramatic complications in 4/24 cats. Most complications appeared in the first 24 hours post-surgery (12/13). Males had more postoperative complications (p = 0.042), including more seizures (p = 0.016). Cats with cranioplasty had fewer complications (p = 0.021). Clinical recurrence was confirmed in 3 out of 17 cats. Recurrence-free survival time was 826 days. Most owners (12/14) were satisfied with the outcome. CONCLUSIONS: Surgical treatment of intracranial meningioma in cats was associated with a long median survival time but also with a high rate of minor and major postoperative complications, including early postoperative seizures. Cranioplasty may reduce complications. Age at the time of surgery had no effect on outcomes.
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Doenças do Gato , Neoplasias Meníngeas , Meningioma , Masculino , Gatos , Animais , Meningioma/cirurgia , Meningioma/veterinária , Estudos Retrospectivos , Complicações Pós-Operatórias/veterinária , Complicações Pós-Operatórias/epidemiologia , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/veterinária , Convulsões/veterinária , Resultado do Tratamento , Doenças do Gato/cirurgiaRESUMO
Microfluidic blood flow models have been instrumental to study the functions of blood platelets in hemostasis and arterial thrombosis. However, they are not suited to investigate the interactions of platelets with the foreign surfaces of medical devices such as stents, mainly because of the dimensions and geometry of the microfluidic channels. Indeed, the channels of microfluidic chips are usually rectangular and rarely exceed 50 to 100 µm in height, impairing the insertion of clinically used stents. To fill this gap, we have developed an original macrofluidic flow system, which precisely reproduces the size and geometry of human vessels and therefore represents a biomimetic perfectly suited to insert a clinical stent and study its interplay with blood cells. The system is a circular closed loop incorporating a macrofluidic flow chamber made of silicone elastomer, which can mimic the exact dimensions of any human vessel, including the coronary, carotid or femoral artery. These flow chambers allow the perfect insertion of stents as they are implanted in patients. Perfusion of whole blood anticoagulated with hirudin through the device at relevant flow rates allows one to observe the specific accumulation of fluorescently labeled platelets on the stent surface using video-microscopy. Scanning electron microscopy revealed the formation of very large thrombi composed of tightly packed activated platelets on the stents.
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Despite their significant importance to numerous fields, the difficulties in direct and diverse synthesis of α-hydroxy-γ-lactams pose substantial obstacles to their practical applications. Here, we designed a nitrogen and TiO2 co-doped graphitic carbon-supported material with atomically dispersed cobalt sites (CoSA-N/NC-TiO2), which was successfully applied as a multifunctional catalyst to establish a general method for direct construction of α-hydroxy-γ-lactams from cheap and abundant nitro(hetero)arenes, aldehydes, and H2O with alkynoates. The striking features of operational simplicity, broad substrate and functionality compatibility (>100 examples), high step and atom efficiency, good selectivity, and exceptional catalyst reusability highlight the practicality of this new catalytic transformation. Mechanistic studies reveal that the active CoN4 species and the dopants exhibit a synergistic effect on the formation of key acid-masked nitrones; their subsequent nucleophilic addition to the alkynoates followed by successive reduction, alkenyl hydration, and intramolecular ester ammonolysis delivers the desired products. In this work, the concept of reduction interruption leading to new reaction route will open a door to further develop useful transformations by rational catalyst design.
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BACKGROUND: How platelets interact with and influence the tumor microenvironment (TME) remains poorly characterized. METHODS: We compared the presence and participation of platelets in the TME of two tumors characterized by highly different TME, PyMT AT-3 mammary tumors and B16F1 melanoma. RESULTS: We show that whereas firmly adherent platelets continuously line tumor vessels of both AT-3 and B16F1 tumors, abundant extravascular stromal clusters of platelets from thrombopoietin-independent origin were present only in AT-3 mammary tumors. We further show that platelets influence the angiogenic and inflammatory profiles of AT-3 and B16F1 tumors, though with very different outcomes according to tumor type. Whereas thrombocytopenia increased bleeding in both tumor types, it further caused severe endothelial degeneration associated with massive vascular leakage, tumor swelling, and increased infiltration of cytotoxic cells, only in AT-3 tumors. CONCLUSIONS: These results indicate that while platelets are integral components of solid tumors, their localization and origin in the TME, as well as their impact on its shaping, are tumor type-dependent.
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Neoplasias Mamárias Animais , Microambiente Tumoral , Animais , HumanosRESUMO
BACKGROUND: Control efforts of soil-transmitted helminthiases rely primarily on large scale administration of anthelminthic drugs. The assessment of drug efficacies and understanding of drug behavior is pivotal to the evaluation of treatment successes, both in preventive chemo-therapy programs as well as in research of novel treatment options. The current WHO guidelines recommend an interval of 14-21 days between the treatment and follow-up, yet no in-depth analysis of egg excretion patterns of Trichuris trichiura after treatment has been conducted to date. METHODS: Within the framework of a multi-country trial to assess the efficacy and safety of albendazole-ivermectin combination therapy vs albendazole monotherapy against T. trichiura infections, we conducted a study collecting daily stool samples over the period of 28 days post-treatment in 87 participants in Pak Khan, Lao PDR. Egg counts were derived by duplicate Kato-Katz on-site for T. trichiura, hookworm and Ascaris lumbricoides and stool sample aliquots were subsequently analyzed by qPCR for the detection of T. trichiura infections. Sensitivity and specificity was calculated for each day separately using data derived by Kato-Katz to determine the optimal timepoint at which to assess drug efficacy. RESULTS: Egg excretion patterns varied across treatment arms. For T. trichiura, only the albendazole-ivermectin treatment led to a considerable reduction in mean egg counts, whereas both treatments reduced hookworm egg counts and A. lumbricoides were cleared in all participants after day 7. For T. trichiura, we found sensitivity to be highest at days 18 and 22 when using egg counts as outcome and days 19 and 24 when using qPCR. Specificity was high (>0.9) from day 14 onwards. For hookworm, the highest sensitivity and specificity were found at days 17 and 25, respectively. CONCLUSIONS: Based on our study, the ideal time period to assess drug efficacy for soil-transmitted helminth infections would be between day 18 and 24. The current WHO recommendation of 14 to 21 days is likely to yield acceptable outcome measures for soil-transmitted helminth infections. TRIAL REGISTRATION: NCT03527732.
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Anti-Helmínticos , Helmintíase , Tricuríase , Animais , Humanos , Albendazol/efeitos adversos , Ancylostomatoidea , Anti-Helmínticos/uso terapêutico , Fezes , Helmintíase/tratamento farmacológico , Ivermectina/uso terapêutico , Solo , Tricuríase/tratamento farmacológico , TrichurisRESUMO
BACKGROUND: Combined endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided tissue acquisition (EUS-TA) are accurate procedures for the diagnosis and staging of mediastinal lymph nodes (MLNs) in lung cancer. However, the respective contribution of separate and combined procedures in diagnosis and staging has not been fully studied. The aim of this study was to assess their respective performances. METHODS: Patients with suspected malignant MLNs in lung cancer or recurrence identified by PET-CT who underwent combined EBUS-TBNA and EUS-TA were retrospectively reviewed. RESULTS: A total of 141 patients underwent both procedures. Correct diagnosis was obtained in 82% with EBUS-TBNA, 91% with EUS-TA, and 94% with the combined procedure. The overall sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of EBUS-TBNA, EUS-TA, and the combined procedure for diagnosing malignancy were [75%, 100%, 100%, 58%], [87%, 100%, 100%, 75%], and [93%, 100%, 100%, 80%], respectively, with a significantly better sensitivity of the combined procedure (p < 0.0001). Staging (82/141 patients) was correctly assessed in 74% with EBUS-TBNA, 68% with EUS-TA, and 85% with the combined procedure. The overall sensitivity, specificity, PPV, and NPV of EBUS-TBNA, EUS-TA, and the combined procedure for lung cancer staging were [62%, 100%, 100%, 55%], [54%, 100%, 100%, 50%], and [79%, 100%, 100%, 68%], respectively, significantly better in terms of sensitivity for the combined procedure (p < 0.001). CONCLUSION: The combined EBUS-EUS approach in lung cancer patients showed better accuracy and sensitivity in diagnosis and staging when compared with EBUS-TBNA and EUS-TA alone.
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The trifluoromethylacyl group (-COCF3) is an important motif and widely studied in catalysis, medicinal chemistry, and materials science. Herein, a novel palladium-catalyzed selenofluoroalkylacylation of terminal alkynes with commercially available fluoroalkyl anhydride and diorganyl diselenides to afford ß-seleno and aryl/alkyl disubstituted enones under mild conditions is disclosed. In addition, selenodifluoroacetylations and selenoperfluoroacetylations are also suitable for this reaction. Mechanistic studies reveal that this reaction proceeds via an oxidative radical-polar crossover process.