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Background: Esophagogastric and pancreaticobiliary cancers are associated with chronic blood loss, poor nutrition, and surgical interventions that interfere with iron absorption. Patients with these cancers often have a higher incidence of chemotherapy-induced anemia (CIA) than patients with other malignancies. Objectives: To investigate the efficacy of intravenous iron or erythropoietin-stimulating agents (ESA) for CIA treatment in patients with esophagogastric or pancreaticobiliary cancer. Design: Retrospective, comparative chart review of patients with esophagogastric or pancreaticobiliary cancer who received ferric carboxymaltose (FCM), or darbepoetin alfa (DA), and myelosuppressive chemotherapy at Chungbuk National University Hospital between June 2018 and December 2022. Methods: To assess the efficacy of FCM or DA over time, data on hemoglobin (Hb) levels were collected from the time of administration of FCM or DA (baseline) until 6 months post-baseline, when available. Results: In total, 214 patients (124 in the FCM and 90 in the DA group) were included in the analysis. The FCM group had a higher maximum Hb level and Hb changes for 3 months (mean ± standard deviation) following FCM or DA administration from baseline than the DA group (11.3 ± 1.5 versus 10.9 ± 1.2 g/dL, p = 0.02 and 2.0 ± 1.4 versus 1.5 ± 1.1 g/dL, p = 0.004, respectively). The FCM group had a higher proportion of Hb responders than the DA group (83.9% versus 68.9%, p = 0.013). Based on multivariable analysis, only the CIA treatment group was a significant factor for Hb response (odds ratio = 2.06, 95% confidence interval = 1.05-4.06, p = 0.036). Conclusion: Both FCM and DA are effective, and FCM showed a higher Hb response than DA for CIA treatment in patients with esophagogastric or pancreaticobiliary cancer. Therefore, further randomized controlled trials should determine the optimal treatment for CIA in patients with these cancers undergoing myelosuppressive chemotherapy.
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Background and Objectives: This study aims to bridge these gaps by utilizing data from the Korea National Health and Nutrition Examination Survey (2013-2015), examining the nuanced associations between milk consumption's quantity, frequency, and type and the prevalence of dental caries. Materials and Methods: Utilizing data from the Korea National Health and Nutrition Examination Survey (2013-2015), this study explores the association between milk consumption and the prevalence of dental caries in a sample of 4843 subjects (weighted n = 15,581), including 2856 males and 1987 females; weighted sample sizes were 6656 and 8925 for men and women, respectively. The prevalence of dental caries was assessed by evaluating the number of decayed, filled, and missing teeth. Results: The analysis demonstrated a significant positive association between increased milk consumption and the risk of developing dental caries, with an overall odds ratio of 1.653 (95% CI: 1.153-2.370, p < 0.05). The association was more pronounced in females, exhibiting an odds ratio of 1.865 (95% CI: 1.157-3.006, p < 0.05), and age was identified as a significant variable, particularly among participants aged 50 and above. In contrast, the relationship among the male group, though positive (odds ratio: 1.613, 95% CI: 0.991-2.625), was not statistically significant (p = 0.054). Conclusion: These findings suggest that milk consumption may be a potential risk indicator for dental caries, particularly among women, emphasizing the need for targeted dietary recommendations in dental health practices.
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Cárie Dentária , Leite , Inquéritos Nutricionais , Humanos , Cárie Dentária/epidemiologia , Masculino , República da Coreia/epidemiologia , Feminino , Leite/efeitos adversos , Pessoa de Meia-Idade , Adulto , Animais , Prevalência , Fatores Sexuais , Idoso , Razão de ChancesRESUMO
Piezo1 regulates multiple aspects of the vascular system by converting mechanical signals generated by fluid flow into biological processes. Here, we find that Piezo1 is necessary for the proper development and function of meningeal lymphatic vessels and that activating Piezo1 through transgenic overexpression or treatment with the chemical agonist Yoda1 is sufficient to increase cerebrospinal fluid (CSF) outflow by improving lymphatic absorption and transport. The abnormal accumulation of CSF, which often leads to hydrocephalus and ventriculomegaly, currently lacks effective treatments. We discovered that meningeal lymphatics in mouse models of Down syndrome were incompletely developed and abnormally formed. Selective overexpression of Piezo1 in lymphatics or systemic administration of Yoda1 in mice with hydrocephalus or Down syndrome resulted in a notable decrease in pathological CSF accumulation, ventricular enlargement and other associated disease symptoms. Together, our study highlights the importance of Piezo1-mediated lymphatic mechanotransduction in maintaining brain fluid drainage and identifies Piezo1 as a promising therapeutic target for treating excessive CSF accumulation and ventricular enlargement.
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Líquido Cefalorraquidiano , Canais Iônicos , Vasos Linfáticos , Animais , Camundongos , Líquido Cefalorraquidiano/metabolismo , Hidrocefalia/genética , Canais Iônicos/metabolismo , Canais Iônicos/genética , Vasos Linfáticos/metabolismo , Mecanotransdução Celular/fisiologia , Meninges/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pirazinas , Tiadiazóis , HumanosRESUMO
OBJECTIVES: To compare the effectiveness of bivalent and monovalent COVID-19 vaccines throughout the 2022-2023 winter season based on real-world data. METHODS: This retrospective observational matched cohort study used the national vaccination program and a surveillance dataset from the Republic of Korea, and included adults aged >18 years who received bivalent or monovalent COVID-19 vaccines between October 11, 2022, and December 17, 2022. Cox proportional hazard models were used to estimate the hazard ratio for COVID-19 infection between the groups. RESULTS: We included 29,245 matched individuals in the bivalent and monovalent vaccine groups, respectively. The bivalent vaccine recipients showed 12.2% (95% confidence interval [CI] 6.5-17.7%) additional protection against COVID-19 infection compared with the monovalent vaccine recipients. The additional protection provided by bivalent vaccines was significantly higher among residents of long-term care facilities (39.4%, 95% CI 21.6-53.1%). Maximum additional protection was observed 3 to 4 months after completing the vaccination (17.6%, 95% CI 6.6-27.3%). CONCLUSION: Bivalent COVID-19 vaccines showed significantly better protection against infection than monovalent vaccines among adults during the 2022-2023 winter season. Our results highlight that immunization programs with bivalent vaccines comprising recent variants can be an effective measure to prepare for seasonal COVID-19 circulation.
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The role that children play in the transmission of the omicron variant is unclear. Here we report an outbreak that started in young children attending various pediatric facilities, leading to extensive household transmission that affected 75 families with 88 confirmed case-patients in 3 weeks. Tailored social and public health measures directed towards children and pediatric facilities are warranted with the emergence of highly transmissible omicron variant to mitigate the impact of coronavirus diseases 2019 (COVID-19).
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COVID-19 , SARS-CoV-2 , Humanos , Criança , Pré-Escolar , Surtos de Doenças , República da Coreia/epidemiologiaRESUMO
Post-hemorrhagic hydrocephalus (PHH) in preterm infant is common, life-threatening and the main cause of bad developmental outcomes. Ventriculoperitoneal (VP) shunt is used as the ultimate treatment for PHH. Low birth weight and low gestational age are the combination of worse prognostic factors while the single most important prognostic factor of VP shunting is age. Aggressive and early intervention have better effect in intraventricular hemorrhage and intracranial pressures control. It reduces infection rate and brain damage resulted in delayed shunt insertion. It is extremely important to let PHH infants get older and gain weight to have internal organs to be matured before undergoing VP shunt. As premature infants undergo shunt after further growth, shunt-related complications would be reduced. So temporary surgical intervention is critical for PHH infants to have them enough time until permanently shunted.
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Positron emission tomography (PET) with somatostatin receptor (SSTR) ligands has taken the lead in the imaging of neuroendocrine tumors (NETs). In this article, we review the role of SSTR PET scan in the management of NETs, including the indications for the scan, pitfalls in interpretation, and imaging selection criteria for peptide receptor radionuclide therapy. We also discuss the complementary role of fluorodeoxyglucose PET particularly for patients with high-grade disease.
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Tumores Neuroendócrinos , Humanos , Ligantes , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos , Compostos Radiofarmacêuticos , Receptores de SomatostatinaRESUMO
Purpose: To characterize and pharmacologically influence subconjunctival lymphatics in rabbit and mouse eyes. Methods: Rabbits received subconjunctival injections of trypan blue or fixable fluorescent dextrans. Bleb-related outflow pathways were quantified. Immunofluorescence for vessel-specific markers (lymphatics [podoplanin and LYVE-1] and blood vessels [CD31]) were performed in native rabbit conjunctiva and after fixable fluorescent dextran injection. Vascular endothelial cell growth factor-C (VEGFC) was injected subconjunctivally in rabbits. mRNA and protein were assessed for the above markers using RT-PCR and Western blot. Alternatively, mouse studies used Prox1-tdTomato transgenic reporter mice. Subconjunctival injection conditions included: no injection, balanced salt solution (BSS), VEGFC, 5-fluorouracil (5FU) and two concentrations of mitomycin-C (MMC). Two mouse injection protocols (short and long) with different follow-up times and number of injections were performed. Mouse eyes were enucleated, flat mounts created, and subconjunctival branching and length assessed. Results: Rabbit eyes demonstrated clear bleb-related subconjunctival outflow pathways that were distinct from blood vessels and were without nasal/temporal predilection. Immunofluorescence against vessel-specific markers showed lymphatics and blood vessels in rabbit conjunctiva, and these lymphatics overlapped with bleb-related subconjunctival outflow pathways. Subconjunctival VEGFC increased lymphatic (P = 0.004-0.04) but not blood vessel (P = 0.77-0.84) mRNA or protein in rabbits. Prox1-tdTomato transgenic reporter mice demonstrated natively fluorescent lymphatics. Subconjunctival VEGFC increased murine lymphatic branching and length (P ≤ 0.001-0.004) while antimetabolites (P ≤ 0.001-0.043) did the opposite for the long protocol. Discussion: Subconjunctival lymphatics are pharmacologically responsive to both VEGFC and antimetabolites in two animal models studied using different methodologies. These results may be important for bleb-forming glaucoma surgeries or ocular drug delivery.
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Glaucoma , Mitomicina , Animais , Camundongos , Coelhos , Antimetabólitos/farmacologia , Túnica Conjuntiva , Dextranos , Fluoruracila/farmacologia , Glaucoma/cirurgia , Pressão Intraocular , Mitomicina/farmacologia , RNA Mensageiro/genética , Azul Tripano/farmacologiaRESUMO
The solvation sheath of Li+-glyme was modulated to enhance Li+-TFSI- association by adopting a highly polar solvent, especially water molecules, which affects the solid electrolyte interface (SEI) layer composition. By the Li+-TFSI- association, a TFSI- anion-derived SEI layer is formed on the Li metal anode, resulting in higher Li metal anode efficiency.
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BACKGROUND: Mutations in PIEZO1 (Piezo type mechanosensitive ion channel component 1) cause human lymphatic malformations. We have previously uncovered an ORAI1 (ORAI calcium release-activated calcium modulator 1)-mediated mechanotransduction pathway that triggers lymphatic sprouting through Notch downregulation in response to fluid flow. However, the identity of its upstream mechanosensor remains unknown. This study aimed to identify and characterize the molecular sensor that translates the flow-mediated external signal to the Orai1-regulated lymphatic expansion. METHODS: Various mutant mouse models, cellular, biochemical, and molecular biology tools, and a mouse tail lymphedema model were employed to elucidate the role of Piezo1 in flow-induced lymphatic growth and regeneration. RESULTS: Piezo1 was found to be abundantly expressed in lymphatic endothelial cells. Piezo1 knockdown in cultured lymphatic endothelial cells inhibited the laminar flow-induced calcium influx and abrogated the flow-mediated regulation of the Orai1 downstream genes, such as KLF2 (Krüppel-like factor 2), DTX1 (Deltex E3 ubiquitin ligase 1), DTX3L (Deltex E3 ubiquitin ligase 3L,) and NOTCH1 (Notch receptor 1), which are involved in lymphatic sprouting. Conversely, stimulation of Piezo1 activated the Orai1-regulated mechanotransduction in the absence of fluid flow. Piezo1-mediated mechanotransduction was significantly blocked by Orai1 inhibition, establishing the epistatic relationship between Piezo1 and Orai1. Lymphatic-specific conditional Piezo1 knockout largely phenocopied sprouting defects shown in Orai1- or Klf2- knockout lymphatics during embryo development. Postnatal deletion of Piezo1 induced lymphatic regression in adults. Ectopic Dtx3L expression rescued the lymphatic defects caused by Piezo1 knockout, affirming that the Piezo1 promotes lymphatic sprouting through Notch downregulation. Consistently, transgenic Piezo1 expression or pharmacological Piezo1 activation enhanced lymphatic sprouting. Finally, we assessed a potential therapeutic value of Piezo1 activation in lymphatic regeneration and found that a Piezo1 agonist, Yoda1, effectively suppressed postsurgical lymphedema development. CONCLUSIONS: Piezo1 is an upstream mechanosensor for the lymphatic mechanotransduction pathway and regulates lymphatic growth in response to external physical stimuli. Piezo1 activation presents a novel therapeutic opportunity for preventing postsurgical lymphedema. The Piezo1-regulated lymphangiogenesis mechanism offers a molecular basis for Piezo1-associated lymphatic malformation in humans.
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Vasos Linfáticos , Linfedema , Animais , Células Endoteliais/metabolismo , Humanos , Canais Iônicos/genética , Canais Iônicos/metabolismo , Vasos Linfáticos/metabolismo , Linfedema/metabolismo , Mecanotransdução Celular/fisiologia , Camundongos , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Radiopharmaceuticals used for cancer therapy are highly selective, designed to kill malignant cells and spare healthy tissues. Side effect rates are generally less than other treatments, but it is still the utmost concern to minimize normal organ toxicity and maximize radiation dose to the target lesions in applying radiopharmaceutical therapies (RPTs). Most commonly affected normal organs include bone marrow, kidneys and liver. The impact of RPTs to renal function is generally considered low. Peptide receptor radionuclide therapy (PRRT) using somatostatin radiopharmaceuticals, particularly 90Y-DOTATOC, has the potential to induce nephrotoxicity. This is because PRRT radiopharmaceuticals are primarily cleared thorough glomerular filtration and reabsorption/retainment of them at the renal proximal tubules exposes kidneys to additional radiation. Amino acid co-infusion is the standard regimen for competitive inhibition of tubular reabsorption of PRRT radiopharmaceuticals to mitigate nephrotoxicity. Other measures to protect renal function include hydration, use of plasma expander or radioprotectant, personalized renal dosimetry to limit renal radiation dose and close monitoring of renal function. Limited data suggest alpha emitter PRRT radiopharmaceuticals have less impact on kidney function compared to beta emitter PRRT, but more studies are needed for long term renal toxicity. 131I-MIBG is primarily excreted unchanged thorough the kidneys but renal absorbed dose is low and potential toxicities to the bone marrow and lungs are the most significant clinical concerns. Other RPTs that are not mainly cleared through kidneys such as 223Ra or radioimmunotherapy have no concern for kidney toxicity.
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Tumores Neuroendócrinos , Compostos Radiofarmacêuticos , Humanos , Rim/fisiologia , Tumores Neuroendócrinos/metabolismo , Radiometria , Compostos Radiofarmacêuticos/efeitos adversosRESUMO
Endoplasmic reticulum (ER) stress and uncoupling protein-2 (UCP2) activation are opposing modulators of endothelial dysfunction in atherosclerosis. Exercise reduces atherosclerosis plaques and enhances endothelial function. Our aim was to understand how exercise affects ER stress and UCP2 activation, and how that relates to endothelial dysfunction in an atherosclerotic murine model. Wild type (C57BL/6, WT) and apolipoprotein-E-knockout (ApoEtm1Unc, ApoE KO) mice underwent treadmill exercise training (EX) or remained sedentary for 12 weeks. Acetylcholine (ACh)-induced endothelium-dependent vasodilation was determined in the presence of an eNOS inhibitor (L-NAME), UCP2 inhibitor (genipin), and ER stress inducer (tunicamycin). UCP2, ER stress markers and NLRP3 inflammasome signaling were quantified by western blotting. p67phox and superoxide were visualized using immunofluorescence and DHE staining. Nitric oxide (NO) was measured by nitrate/nitrite assay. ACh-induced vasodilation was attenuated in coronary arterioles of ApoE KO mice but improved in ApoE KO-EX mice. Treatment of coronary arterioles with L-NAME, tunicamycin, and genipin significantly attenuated ACh-induced vasodilation in all mice except for ApoE KO mice. Exercise reduced expression of ER stress proteins, TXNIP/NLRP3 inflammasome signaling cascades, and Bax expression in the heart of ApoE KO-EX mice. Further, exercise diminished superoxide production and NADPH oxidase p67phox expression in coronary arterioles while simultaneously increasing UCP2 expression and nitric oxide (NO) production in the heart of ApoE KO-EX mice. Routine exercise alleviates endothelial dysfunction in atherosclerotic coronary arterioles in an eNOS, UCP2, and ER stress signaling specific manner, and resulting in reduced TXNIP/NLRP3 inflammasome activity and oxidative stress.
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Aterosclerose/metabolismo , Aterosclerose/terapia , Vasos Coronários/metabolismo , Estresse do Retículo Endoplasmático , Terapia por Exercício/métodos , Condicionamento Físico Animal/métodos , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/terapia , Proteína Desacopladora 2/deficiência , Acetilcolina/farmacologia , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/metabolismo , Arteríolas/fisiopatologia , Aterosclerose/genética , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Teste de Esforço , Iridoides/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Placa Aterosclerótica/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Proteína Desacopladora 2/antagonistas & inibidores , Vasodilatação/efeitos dos fármacos , Vasodilatação/genéticaRESUMO
OBJECTIVES: We evaluated the effects of a comprehensive antimicrobial stewardship program (ASP) in a surgical intensive care unit (SICU). METHODS: The ASP was implemented from March 2018 to February 2019 at an SICU in a teaching hospital. An infectious disease physician and a pharmacist visited the SICU 3 times per week for prospective audit and feedback. Outcomes were compared between the ASP period and the same months in the preceding year (pre-ASP period). The primary outcome measure was the use of anti-pseudomonal beta-lactams (APBL). Appropriate antimicrobial de-escalation and ICU mortality rates were also compared. RESULTS: A total of 182 and 149 patients were included in the study for the pre-ASP and ASP periods, respectively. Although disease severity was higher in the ASP group (septic shock 39.0% in pre-ASP vs 65.1% in ASP group, P<0.001), the use of APBL as a definitive treatment was lower during ASP (68.7% vs 57.7%, OR 0.62, 95% CI 0.40-0.98). Appropriate antimicrobial de-escalation improved (63.2% vs 94.6%, P<0.001). ICU mortality was comparable (7.7% vs 7.4%) and significantly lower during the ASP, after adjustment (adjusted OR 0.41, 95% CI 0.18-0.92, P=0.032). CONCLUSIONS: A comprehensive ASP decreased the use of APBL and was associated with improved patient outcomes.
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Anti-Infecciosos , Gestão de Antimicrobianos , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Cuidados Críticos , Humanos , Unidades de Terapia IntensivaRESUMO
PURPOSE: The purpose of this study was to identify the optimal timing for screening spinal cord ultrasonography (US) to detect filum terminale lipoma in infants. METHODS: We retrospectively reviewed infants (<12 months old) who underwent repeated spinal cord US between April 2011 and January 2019. We excluded infants if they only had one US examination, or if they had lesions other than filum terminale lipoma. Infants with filum terminale lipoma on magnetic resonance imaging were included in the lipoma group and the others in the control group. A linear mixed model was used to assess differences in the growth pattern of filum terminale thickness by age and group. The cutoff thickness on US and its diagnostic performance were assessed according to age. RESULTS: Among 442 infants with 901 US examinations, 46 were included in the lipoma group and 58 in the control group. Sixty-seven infants had unmeasurable filum terminale thickness on initial US, including 55 neonates (82.1%) before 1 month of age. The lipoma group had significantly greater filum terminale thickness than the control group (P<0.001). Thickness increased with age in the lipoma group (P=0.027). The sensitivity of US was 87.5% and the area under the receiver operating characteristic curve was 0.949 (95% confidence interval, 0.849 to 0.991) with a cutoff value of 1.1 mm in 4- to 6-month-old infants. CONCLUSION: Screening spinal cord US could effectively diagnose filum terminale lipoma in 4- to 6-month-old infants with a cutoff thickness of 1.1 mm. Spinal cord US can be used to screen young infants with intraspinal abnormalities.
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PURPOSE: To provide the insight for postoperative hypotonia. Selective posterior rhizotomy (SPR) has been proved as a powerful tool for reducing spasticity. And also, its functional benefit and long-term effect are also well-known. RESULTS: The most considered side effect of this procedure is postoperative hypotonia. However, some extent of temporary postoperative hypotonia can be the marker of the long-term success of this procedure. While the return of spasticity is the most unwanted side effect, some kind of overfitting, temporary postoperative hypotonia, can be the solution for that. CONCLUSION: For severely deformed patients, postoperative hypotonia may not be problematic, because severe spasticity makes them deformed and disabled. Deformed body will not show a definite disability from postoperative hypotonia.
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Paralisia Cerebral , Hipotonia Muscular , Paralisia Cerebral/cirurgia , Humanos , Hipotonia Muscular/etiologia , Espasticidade Muscular/cirurgia , Período Pós-Operatório , RizotomiaRESUMO
Glaucoma surgeries, such as trabeculectomy, are performed to lower intraocular pressure to reduce risk of vision loss. These surgeries create a new passage in the eye that reroutes the aqueous humor outflow to the subconjunctival space, where the fluid is presumably absorbed by the conjunctival lymphatics. Here, we characterized the development and function of the ocular lymphatics using transgenic lymphatic reporter mice and rats. We found that the limbal and conjunctival lymphatic networks are progressively formed from a primary lymphatic vessel that grows from the nasal-side medial canthus region at birth. This primary lymphatic vessel immediately branches out, invades the limbus and conjunctiva, and bidirectionally encircles the cornea. As a result, the distribution of the ocular lymphatics is significantly polarized toward the nasal side, and the limbal lymphatics are directly connected to the conjunctival lymphatics. New lymphatic sprouts are produced mainly from the nasal-side limbal lymphatics, posing the nasal side of the eye as more responsive to fluid drainage and inflammatory stimuli. Consistent with this polarized distribution of the ocular lymphatics, a higher drainage efficiency was observed in the nasal side than the temporal side of the eye when injected with a fluorescent tracer. In contrast, blood vessels are evenly distributed at the anterior surface of the eyes. Also, we found that these distinct vascular distribution patterns were conserved in human eyes. Together, our study demonstrated that the ocular surface lymphatics are more densely present in the nasal side and uncovered the potential clinical benefits in selecting the nasal side as a glaucoma surgery site to improve fluid drainage.
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Túnica Conjuntiva/patologia , Sistema Linfático/patologia , Vasos Linfáticos/patologia , Organogênese/fisiologia , Animais , Humor Aquoso/metabolismo , Pressão Intraocular/fisiologia , Camundongos Transgênicos , Ratos Sprague-DawleyRESUMO
Kaposi sarcoma is the most common cancer in human immunodeficiency virus-positive individuals and is caused by Kaposi sarcoma-associated herpesvirus (KSHV). It is believed that a small number of latently infected Kaposi sarcoma tumor cells undergo spontaneous lytic reactivation to produce viral progeny for infection of new cells. Here, we use matched donor-derived human dermal blood and lymphatic endothelial cells (BEC and LEC, respectively) to show that KSHV-infected BECs progressively lose viral genome as they proliferate. In sharp contrast, KSHV-infected LECs predominantly entered lytic replication, underwent cell lysis, and released new virus. Continuous lytic cell lysis and de novo infection allowed LEC culture to remain infected for a prolonged time. Because of the strong propensity of LECs toward lytic replication, LECs maintained virus as a population, despite the death of individual host cells from lytic lysis. The master regulator of lymphatic development, Prox1, bound the promoter of the RTA gene to upregulate its expression and physically interacted with RTA protein to coregulate lytic genes. Thus, LECs may serve as a proficient viral reservoir that provides viral progeny for continuous de novo infection of tumor origin cells, and potentially BECs and mesenchymal stem cells, which give rise to Kaposi sarcoma tumors. Our study reveals drastically different host cell behaviors between BEC and LEC and defines the underlying mechanisms of the lymphatic cell environment supporting persistent infection in Kaposi sarcoma tumors. SIGNIFICANCE: This study defines the mechanism by which Kaposi's sarcoma could be maintained by virus constantly produced by lymphatic cells in HIV-positive individuals.
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Herpesvirus Humano 8/fisiologia , Proteínas de Homeodomínio/fisiologia , Vasos Linfáticos/virologia , Sarcoma de Kaposi , Microambiente Tumoral/fisiologia , Proteínas Supressoras de Tumor/fisiologia , Liberação de Vírus/genética , Replicação Viral/genética , Transformação Celular Viral/genética , Células Cultivadas , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Células Endoteliais/virologia , Regulação Viral da Expressão Gênica , Células HEK293 , HIV/fisiologia , Humanos , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Sarcoma de Kaposi/genética , Sarcoma de Kaposi/patologia , Sarcoma de Kaposi/virologia , Latência Viral/genéticaRESUMO
Serotonergic neurotransmission plays a key role in the pathophysiology and treatment of various neuropsychiatric diseases. The purpose of this study was to investigate changes in serotonergic neurotransmission after acute tryptophan depletion (ATD) using positron emission tomography (PET) with [11 C]P943, a 5-HT1B receptor radioligand previously shown to be sensitive to changes in 5-HT. Five healthy subjects were scanned on a high resolution PET scanner twice on the same day, before and approximately 5 hours after ingesting capsules containing an amino acid mixture that lacks tryptophan. For each scan, emission data were acquired for 120 min after intravenous bolus injection of [11 C]P943. Binding potential (BPND ) values were estimated from parametric images using the second version of the multilinear reference tissue model (MRTM2, t* = 20 min) with cerebellar grey matter used as a reference region. The change in [11 C]P943 binding (ΔBPND , %) was calculated as (BPND,post - BPND,pre )/(BPND,pre ) × 100, and correlation analysis was performed to measure linear associations of ΔBPND between raphe and other regions of interest (ROIs). ΔBPND ranged from -6% to 45% in the raphe, with positive values indicating reduced competition from 5-HT. In cortical regions, ΔBPND ranged from -28% to 7%. While these changes did not reach significance, there were significant negative correlations of ΔBPND of the raphe with those of cerebral cortical regions and the thalamus (e.g., r = -.96, p = .011 for average cortex). These findings support the hypothesis that raphe serotonin is a critical modulator of cortical serotonin release via projecting neurons in healthy human subjects.
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Córtex Cerebral/metabolismo , Núcleos da Rafe/metabolismo , Receptor 5-HT1B de Serotonina/metabolismo , Triptofano/metabolismo , Adulto , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperazinas/farmacocinética , Tomografia por Emissão de Pósitrons , Ligação Proteica , Pirrolidinonas/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Núcleos da Rafe/diagnóstico por imagem , Antagonistas do Receptor 5-HT1 de Serotonina/farmacocinéticaRESUMO
The practical implementation of the lithium metal anode is hindered by obstacles such as Li dendrite growth, large volume changes, and poor lifespan. Here, copper nitride nanowires (Cu3 N NWs) printed Li by a facile and low-cost roll-press method is reported, to operate in carbonate electrolytes for high-voltage cathode materials. Through one-step roll pressing, Cu3 N NWs can be conformally printed onto the Li metal surface, and form a Li3 N@Cu NWs layer on the Li metal. The Li3 N@Cu NWs layer can assist homogeneous Li-ion flux with the 3D channel structure, as well as the high Li-ion conductivity of the Li3 N. With those beneficial effects, the Li3 N@Cu NWs layer can guide Li to deposit into a dense and planar structure without Li-dendrite growth. Li metal with Li3 N@Cu NWs protection layer exhibits outstanding cycling performances even at a high current density of 5.0 mA cm-2 with low overpotentials in Li symmetric cells. Furthermore, the stable cyclability and improved rate capability can be realized in a full cell using LiCoO2 over 300 cycles. When decoupling the irreversible reactions of the cathode using Li4 Ti5 O12 , stable cycling performance over 1000 cycles can be achieved at a practical current density of ≈2 mA cm-2 .
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BACKGROUND: To evaluate the usefulness of preoperative imaging with F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for noninvasive risk assessment of gastrointestinal stromal tumor (GIST). MATERIALS AND METHODS: A retrospective review including 32 patients with pathologically proven GIST. Preoperative FDG-PET scan results including maximum standardized uptake values (SUVs) of the GISTs at 1 h postinjection (SUV1) were available for all tumors and SUVs at 2 h postinjection (SUV2) were available for 22 tumors. When both SUV1 and SUV2 were available, a retention index (RI, %) was calculated, and the correlation of these PET parameters with the histopathologic results was analyzed. RESULTS: SUV1 was significantly higher in tumors in the high-risk group (6.0 ± 2.7) compared to those in the low risk (3.0 ± 1.6) or very low-risk (2.7 ± 1.2) groups (P = 0.009 and 0.011, respectively). At a cutoff of 5.2, the SUV1 demonstrated sensitivity of 80% and a specificity of 89% for predicting high-risk GISTs. Tumor size was significantly correlated with SUV1 (r = 0.68, P < 0.001) and SUV2 (r = 0.66, P = 0.001), and SUV1, SUV2, and RI were significantly higher in tumors with mitotic index > 5/50 high-power field than in those with lower mitotic index. RI was significantly higher in tumors with C-kit mutation than in those with no C-kit mutation. CONCLUSION: SUV1 measured during preoperative FDG-PET imaging correlated well with malignant potential of GISTs, especially for high-risk versus Low-/very-low-risk tumors. RI values correlated well with mitotic counts and C-kit mutation, suggesting that this mutation may have some influence on tumor metabolism.