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1.
PLoS Pathog ; 20(9): e1012168, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39283947

RESUMO

Human Immunodeficiency Virus (HIV) is widely acknowledged for its profound impact on the immune system. Although HIV primarily affects peripheral CD4 T cells, its influence on the central nervous system (CNS) cannot be overlooked. Within the brain, microglia and CNS-associated macrophages (CAMs) serve as the primary targets for HIV and the simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological effects and establish a viral reservoir. Given the gaps in our understanding of how these cells respond in vivo to acute CNS infection, we conducted single-cell RNA sequencing (scRNA-seq) on myeloid cells from the brains of three rhesus macaques 12 days after SIV infection, along with three uninfected controls. Our analysis revealed six distinct microglial clusters including homeostatic microglia, preactivated microglia, and activated microglia expressing high levels of inflammatory and disease-related molecules. In response to acute SIV infection, the homeostatic and preactivated microglia population decreased, while the activated and disease-related microglia increased. All microglial clusters exhibited upregulation of MHC class I molecules and interferon-related genes, indicating their crucial roles in defending against SIV during the acute phase. All microglia clusters also upregulated genes linked to cellular senescence. Additionally, we identified two distinct CAM populations: CD14lowCD16hi and CD14hiCD16low CAMs. Interestingly, during acute SIV infection, the dominant CAM population changed to one with an inflammatory phenotype. Specific upregulated genes within one microglia and one macrophage cluster were associated with neurodegenerative pathways, suggesting potential links to neurocognitive disorders. This research sheds light on the intricate interactions between viral infection, innate immune responses, and the CNS, providing valuable insights for future investigations.

2.
Am J Epidemiol ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39013785

RESUMO

The serial interval distribution is used to approximate the generation time distribution, an essential parameter to infer the transmissibility (${R}_t$) of an epidemic. However, serial interval distributions may change as an epidemic progresses. We examined detailed contact tracing data on laboratory-confirmed cases of COVID-19 in Hong Kong during the five waves from January 2020 to July 2022. We reconstructed the transmission pairs and estimated time-varying effective serial interval distributions and factors associated with longer or shorter intervals. Finally, we assessed the biases in estimating transmissibility using constant serial interval distributions. We found clear temporal changes in mean serial interval estimates within each epidemic wave studied and across waves, with mean serial intervals ranged from 5.5 days (95% CrI: 4.4, 6.6) to 2.7 (95% CrI: 2.2, 3.2) days. The mean serial intervals shortened or lengthened over time, which were found to be closely associated with the temporal variation in COVID-19 case profiles and public health and social measures and could lead to the biases in predicting ${R}_t$. Accounting for the impact of these factors, the time-varying quantification of serial interval distributions could lead to improved estimation of ${R}_t$, and provide additional insights into the impact of public health measures on transmission.

3.
Mol Pharm ; 21(4): 1838-1847, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38413029

RESUMO

The extensive use of opioids for chronic pain management has contributed significantly to the current opioid epidemic. While many alternative nonopioid analgesics are available, opioids remain the most potent analgesics for moderate to severe pain management. In addition to the implementation of multimodal analgesia, there is a pressing need for the development of more effective and safer opioids. In this study, we developed a thermoresponsive N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based hydromorphone (HMP) prodrug (ProGel-HMP, HMP content = 16.2 wt %, in base form). The aqueous solution of ProGel-HMP was free-flowing at 4 °C but became a hydrogel when the temperature was raised to ≥37 °C, allowing sustained local retention when administered in vivo. When tested in the destabilization of the medial meniscus (DMM) mouse model of osteoarthritis (OA), ProGel-HMP was retained after intra-articular injection in the OA knee joint for at least 2 weeks postinjection, with low extra-articular distribution. ProGel-HMP was not detected in the central nervous system (CNS). A single dose of ProGel-HMP produced rapid and sustained joint pain resolution for greater than 14 days when compared to saline and dose-equivalent HMP controls, likely mediated through peripheral µ-opioid receptors in the knee joint. Systemic analgesia effect was absent in the DMM mice treated with ProGel-HMP, as evident in the lack of difference in tail flick response between the ProGel-HMP-treated mice and the controls (i.e., Healthy, Saline, and Sham). Repeated dosing of ProGel-HMP did not induce tolerance. Collectively, these data support the further development of ProGel-HMP as a potent, safe, long-acting and nonaddictive analgesic for better clinical pain management.


Assuntos
Analgesia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Osteoartrite , Pró-Fármacos , Camundongos , Animais , Hidromorfona , Manejo da Dor , Pró-Fármacos/uso terapêutico , Dor/tratamento farmacológico , Analgésicos Opioides/efeitos adversos , Analgésicos/uso terapêutico
4.
J Eur Acad Dermatol Venereol ; 38 Suppl 6: 26-36, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38419560

RESUMO

BACKGROUND: Noninvasive energy-based device (NI-EBD) aesthetic procedures has recently gained widespread usage for treating various skin conditions, enhancing skin texture and performing rejuvenation-related procedures. However, practically all NI-EBD procedures result in variable degrees of damage to the skin barrier, inducing pathological and physiological processes such as oxidative stress and inflammation, and only a small percentage of individuals possess the innate ability to restore it. OBJECTIVE: To introduce the concept of integrated skincare and establish standardized operational procedures for perioperative integrated skincare, and furnish a theoretical basis for clinical diagnosis and treatment performed by professional medical aestheticians. METHODS: The author leveraged domestic and international guidelines, clinical practice expertise and evidence-based research, adapting them to suit the specific circumstances in China. RESULTS: The consensus were provided four parts, including concept and essence of integrated skincare, integrated skincare significance during the perioperative phase of NI-EBD procedures, active ingredients and functions of effective skincare products, standardized perioperative skincare procedure for NI-EBD procedures and precautions. For the standardized perioperative skincare procedure, four recommendations were listed according to different stages during NI-EBD procedures. CONCLUSION: These recommendations create the 'Expert Consensus on Perioperative Integrated Skincare for Noninvasive Energy-Based Device Aesthetic Procedures in Clinical Practice in China'.


Assuntos
Técnicas Cosméticas , Humanos , China , Assistência Perioperatória , Consenso , Rejuvenescimento , Higiene da Pele/métodos , Envelhecimento da Pele , Estética
5.
Nanomedicine ; 62: 102782, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39179013

RESUMO

The relief of joint pain is one of the main objectives in the clinical management of arthritis. Although significant strides have been made in improving management of rheumatoid and related forms of inflammatory arthritis, there are still major unmet needs for therapies that selectively provide potent, sustained and safe joint pain relief, especially among patients with osteoarthritis (OA), the most common form of arthritis. We have recently developed ProGel-Dex, an N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based thermoresponsive dexamethasone (Dex) prodrug, which forms a hydrogel upon intra-articular administration and provides sustained improvement in pain-related behavior and inflammation in rodent models of arthritis. The focus of the present study was to investigate the impact of ProGel-Dex formulation parameters on its physicochemical properties and in vivo efficacy. The results of this study provide essential knowledge for the future design of ProGel-Dex that can provide more effective, sustained and safe relief of joint pain and inflammation.

6.
Nanomedicine ; 57: 102735, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38295913

RESUMO

In this study, we aimed to assess the analgesic efficacy of a thermoresponsive polymeric dexamethasone (Dex) prodrug (ProGel-Dex) in a mouse model of osteoarthritis (OA). At 12 weeks post model establishment, the OA mice received a single intra-articular (IA) injection of ProGel-Dex, dose-equivalent Dex, or Saline. Comparing to Saline and Dex controls, ProGel-Dex provided complete and sustained pain relief for >15 weeks according to incapacitance tests. In vivo optical imaging confirmed the continuous presence of ProGel-Dex in joints for 15 weeks post-injection. According to micro-CT analysis, ProGel-Dex treated mice had significantly lower subchondral bone thickness and medial meniscus bone volume than Dex and Saline controls. Except for a transient delay of body weight increase and slightly lower endpoint liver and spleen weights, no other adverse effect was observed after ProGel-Dex treatment. These findings support ProGel-Dex's potential as a potent and safe analgesic candidate for management of OA pain.


Assuntos
Osteoartrite , Pró-Fármacos , Camundongos , Animais , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Modelos Animais de Doenças , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Osteoartrite/tratamento farmacológico , Artralgia/induzido quimicamente , Artralgia/tratamento farmacológico , Analgésicos/farmacologia , Analgésicos/uso terapêutico
7.
Virol J ; 20(1): 107, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37259131

RESUMO

BACKGROUND: Patients infected with HIV are at high risk of developing Epstein-Barr Virus (EBV)-related diseases. The genotype and viral biological behavior of EBV infection in patients with human immunodeficiency virus-1 (HIV) in China remain unclear. This study analyzed the characteristics of EBV in patients infected with HIV in southeastern China. METHODS: A total of 162 HIV-infected patients and 52 patients without HIV were enrolled in this study. EBV viral load in blood was determined by fluorescence quantitative PCR. EBV typing was performed using saliva according to polymorphisms in the EBNA3C region. EBV LMP-1 carboxy terminus (C-ter) was sequenced, and compared with the epidemic strains in the world. RESULTS: Among HIV infected patients, the EBV strain variant was mainly EBV-1, while EBV-2 had a higher viral load than EBV-1 (P = 0.001) and EBV-1/2 (P = 0.002). HIV infected patients had higher active virus replication. The EBV LMP-1 variants were mainly the China1 variant. HIV-infected patients had different nucleic acid positions of 30-bp deletion (del30) and had a higher incidence of high 33-bp tandem repeats (rep33) copies than non-HIV-infected patients. There was a difference in the mutations of EBV LMP-1 C-ter del30 and ins15 between HIV infected patients and the control group (P < 0.001). CONCLUSION: In southeastern China, EBV in HIV-infected patients had higher active virus replication; EBV infection was mainly EBV-1, and EBV-2 infection has higher EBV virus load; hotspot mutations of LMP-1 C-ter were different between HIV-infected patients and non-HIV-infected patients. TRIAL REGISTRATION: This study was approved by the ethics committee of the First Affiliated Hospital of Zhejiang University School of Medicine (Approval No. 2018764), and registered in Chinese Clinical Trial Registry on 3 June 2019 (ChiCTR, ChiCTR1900023600, http://www.chictr.org.cn/usercenter.aspx ).


Assuntos
Infecções por Vírus Epstein-Barr , Infecções por HIV , HIV-1 , Humanos , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/genética , Sequência de Bases , HIV-1/genética , China/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , DNA Viral/genética
8.
Mol Pharm ; 20(11): 5631-5645, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37772991

RESUMO

Periodontitis (PD) is a severe inflammatory gum pathology that damages the periodontal soft tissue and bone. It is highly prevalent in the US, affecting more than 47% of adults. Besides routine scaling and root planing, there are few effective treatments for PD. Developed as an effective treatment for hyperlipidemia, simvastatin (SIM) is also known for its well-established anti-inflammatory and osteogenic properties, suggesting its potential utility in treating PD. Its clinical translation, however, has been impeded by its poor water-solubility, lack of osteotropicity, and side effects (e.g., hepatoxicity) associated with systemic exposure. To address these challenges, an N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based thermoresponsive polymeric prodrug of SIM (ProGel-SIM) was developed as a local therapy for PD. Its aqueous solution is free-flowing at 4 °C and transitions into a hydrogel at ∼30 °C, allowing for easy local application and retention. After a thorough characterization of its physicochemical properties, ProGel-SIM was administered weekly into the periodontal pocket of an experimental rat model of PD. At 3 weeks post initiation of the treatment, the animals were euthanized with palate isolated for µ-CT and histological analyses. When compared to dose equivalent simvastatin acid (SMA, active form of SIM) treatment, the rats in the ProGel-SIM treated group showed significantly higher periodontal bone volume (0.34 mm3 vs 0.20 mm3, P = 0.0161) and less neutrophil (PMN) infiltration (P < 0.0001) and IL-1ß secretion (P = 0.0036). No measurable side effect was observed. Collectively, these results suggest that ProGel-SIM may be developed as a promising drug candidate for the effective clinical treatment of PD.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Periodontite , Pró-Fármacos , Ratos , Animais , Pró-Fármacos/química , Sinvastatina/química , Polímeros , Periodontite/tratamento farmacológico
9.
Clin Infect Dis ; 74(4): 685-694, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34037748

RESUMO

BACKGROUND: Estimates of the serial interval distribution contribute to our understanding of the transmission dynamics of coronavirus disease 2019 (COVID-19). Here, we aimed to summarize the existing evidence on serial interval distributions and delays in case isolation for COVID-19. METHODS: We conducted a systematic review of the published literature and preprints in PubMed on 2 epidemiological parameters, namely, serial intervals and delay intervals relating to isolation of cases for COVID-19 from 1 January 2020 to 22 October 2020 following predefined eligibility criteria. We assessed the variation in these parameter estimates using correlation and regression analysis. RESULTS: Of 103 unique studies on serial intervals of COVID-19, 56 were included, providing 129 estimates. Of 451 unique studies on isolation delays, 18 were included, providing 74 estimates. Serial interval estimates from 56 included studies varied from 1.0 to 9.9 days, while case isolation delays from 18 included studies varied from 1.0 to 12.5 days, which were associated with spatial, methodological, and temporal factors. In mainland China, the pooled mean serial interval was 6.2 days (range, 5.1-7.8) before the epidemic peak and reduced to 4.9 days (range, 1.9-6.5) after the epidemic peak. Similarly, the pooled mean isolation delay related intervals were 6.0 days (range, 2.9-12.5) and 2.4 days (range, 2.0-2.7) before and after the epidemic peak, respectively. There was a positive association between serial interval and case isolation delay. CONCLUSIONS: Temporal factors, such as different control measures and case isolation in particular, led to shorter serial interval estimates over time. Correcting transmissibility estimates for these time-varying distributions could aid mitigation efforts.


Assuntos
COVID-19 , Epidemias , China/epidemiologia , Humanos , SARS-CoV-2
10.
Clin Infect Dis ; 75(1): e293-e295, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35171991

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic continues to pose substantial risks to public health, worsened by the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that may have a higher transmissibility and reduce vaccine effectiveness. We conducted a systematic review and meta-analysis on reproduction numbers of SARS-CoV-2 variants and provided pooled estimates for each variant.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Humanos , Pandemias , Reprodução , SARS-CoV-2/genética
11.
BMC Infect Dis ; 22(1): 286, 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35351023

RESUMO

BACKGROUND: The impact of ventriculoperitoneal shunt on cerebrospinal fluid (CSF) biochemical profiles in HIV-associated cryptococcal meningitis (HCM) patients remains unclear. METHODS: Twenty-nine HCM patients who underwent ventriculoperitoneal shunt (the VPS group) and 57 HCM patients who did not undergo ventriculoperitoneal shunt (the non-VPS group) were enrolled in this propensity score matching analysis. Demographic characteristics, symptoms, CSF biochemical profiles, and adverse events were compared between the two groups. The Kaplan-Meier method was used to analyze the survival rate. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for increased CSF protein levels. RESULTS: After 24 weeks of treatment, the intracranial pressure was significantly lower in the VPS group than in the non-VPS group (mmH2O; 155.0 [120.0-190.0] vs. 200.0 [142.5-290.0]; P = 0.025), and the rate of neuroimaging improvement was significantly higher in the VPS group (16/17 [94.1%] vs. 2/10 [20%]; P < 0.001). Furthermore, the 24-week cumulative survival rates were also significantly higher in the VPS group (96.6% vs. 83.5%, P = 0.025). Notably, the CSF protein levels were higher in the VPS group than in the non-VPS group at each examination time, and the CSF glucose was lower in the VPS group than in the non-VPS group even at the 12-week follow-up. In the multivariate analysis, we found that VPS placement was an independent risk factor for increased CSF protein (odds ratio [OR]: 27.8, 95% confidence interval [95% CI] 2.2-348.7; P = 0.010). CONCLUSIONS: VPS decreased the intracranial pressure, improved neuroimaging radiology and reduced the 24-week mortality in HCM patients. However, VPS significantly altered the CSF profiles, which could lead to misdiagnosis of tuberculous meningitis and some of them were diagnosed with immune reconstitution inflammatory syndrome. Physicians should be aware of these changes in the CSF profiles of patients with HCM undergoing VPS.


Assuntos
Infecções por HIV , Meningite Criptocócica , Tuberculose Meníngea , Infecções por HIV/complicações , Humanos , Meningite Criptocócica/complicações , Estudos Retrospectivos , Tuberculose Meníngea/complicações , Derivação Ventriculoperitoneal
12.
Cereb Cortex ; 31(11): 5090-5106, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34387312

RESUMO

Human brain network is organized as interconnected communities for supporting cognition and behavior. Despite studies on the nonoverlapping communities of brain network, overlapping community structure and its relationship to brain function remain largely unknown. With this consideration, we employed the Bayesian nonnegative matrix factorization to decompose the functional brain networks constructed from resting-state fMRI data into overlapping communities with interdigitated mapping to functional subnetworks. By examining the heterogeneous nodal membership to communities, we classified nodes into three classes: Most nodes in somatomotor and limbic subnetworks were affiliated with one dominant community and classified as unimodule nodes; most nodes in attention and frontoparietal subnetworks were affiliated with more than two communities and classified as multimodule nodes; and the remaining nodes affiliated with two communities were classified as bimodule nodes. This three-class paradigm was highly reproducible across sessions and subjects. Furthermore, the more likely a node was classified as multimodule node, the more flexible it will be engaged in multiple tasks. Finally, the FC feature vector associated with multimodule nodes could serve as connectome "fingerprinting" to gain high subject discriminability. Together, our findings offer new insights on the flexible spatial overlapping communities that related to task-based functional flexibility and individual connectome "fingerprinting."


Assuntos
Conectoma , Teorema de Bayes , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Rede Nervosa/diagnóstico por imagem
13.
Nanomedicine ; 44: 102579, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35768036

RESUMO

Due to their potent immunosuppressive and anti-inflammatory effects, glucocorticoids (GCs) are the most widely used medications in treating lupus nephritis (LN). Long-term use of GCs, however, is associated with numerous off-target adverse effects. To reduce GCs' adverse effects, we previously developed two polymeric dexamethasone prodrug nanomedicines: N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based dexamethasone prodrug (P-Dex), and micelle-forming polyethylene glycol (PEG)-based dexamethasone prodrug (ZSJ-0228). Both P-Dex and ZSJ-0228 provided sustained amelioration of LN in lupus-prone NZB/W F1 mice with reduced GC-associated adverse effects. Here, we have extended our investigation to the MRL/lpr mouse model of LN. Compared to dose equivalent daily dexamethasone sodium phosphate (Dex) treatment, monthly P-Dex or ZSJ-0228 treatments were more effective in reducing proteinuria and extending the lifespan of MRL/lpr mice. Unlike the daily Dex treatment, ZSJ-0228 was not associated with measurable GC-associated adverse effects. In contrast, adrenal gland atrophy was observed in P-Dex treated mice.


Assuntos
Nefrite Lúpica , Pró-Fármacos , Animais , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Rim , Nefrite Lúpica/tratamento farmacológico , Camundongos , Camundongos Endogâmicos MRL lpr , Camundongos Endogâmicos NZB , Polímeros/farmacologia , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico
14.
Mol Pharm ; 18(11): 4188-4197, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34569234

RESUMO

Glucocorticoids (GCs) are widely used in the clinical management of lupus nephritis (LN). Their long-term use, however, is associated with the risk of significant systemic side effects. We have developed a poly(ethylene glycol) (PEG)-based dexamethasone (Dex) prodrug (i.e., ZSJ-0228) and in a previous study, demonstrated its potential therapeutic efficacy in mice with established LN, while avoiding systemic GC-associated toxicity. In the present study, we have employed a dose-escalation design to establish the optimal dose-response relationships for ZSJ-0228 in treating LN and further investigated the safety of ZSJ-0228 in lupus-prone NZB/W F1 mice with established nephritis. ZSJ-0228 was intravenously (i.v.) administered monthly at four levels: 0.5 (L1), 1.0 (L2), 3.0 (L3), and 8.0 (L4) mg/kg/day Dex equivalent. For controls, mice were treated with i.v. saline every 4 weeks. In addition, a group of mice received intraperitoneal injections (i.p.) of Dex every day or i.v. injections of Dex every four weeks. Treatment of mice with LN with ZSJ-0228 dosed at L1 resulted in the resolution of proteinuria in 14% of the mice. Mice treated with ZSJ-0228 dosed at L2 and L3 levels resulted in the resolution of proteinuria in ∼60% of the mice in both groups. Treatment with ZSJ-0228 dosed at L4 resulted in the resolution of proteinuria in 30% of the mice. The reduction and/or resolution of the proteinuria, improvement in renal histological scores, and survival data indicate that the most effective dose range for ZSJ-0228 in treating LN in NZB/W F1 mice is between 1.0 and 3.0 mg/kg/day Dex equivalent. Typical GC-associated side effects (e.g., osteopenia, adrenal glands atrophy, etc.) were not observed in any of the ZSJ-0228 treatment groups, confirming its excellent safety profile.


Assuntos
Dexametasona/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Animais , Dexametasona/efeitos adversos , Dexametasona/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Injeções Intraperitoneais , Injeções Intravenosas , Nefrite Lúpica/imunologia , Camundongos , Polietilenoglicóis , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química
15.
Mol Pharm ; 18(5): 1992-2003, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33754729

RESUMO

Except for routine scaling and root planing, there are few effective nonsurgical therapeutic interventions for periodontitis and associated alveolar bone loss. Simvastatin (SIM), one of the 3-hydroxy-3-methylglutaryl-cosenzyme A reductase inhibitors, which is known for its capacity as a lipid-lowering medication, has been proven to be an effective anti-inflammatory and bone anabolic agent that has shown promising benefits in mitigating periodontal bone loss. The local delivery of SIM into the periodontal pocket, however, has been challenging due to SIM's poor water solubility and its lack of osteotropicity. To overcome these issues, we report a novel SIM formulation of a thermoresponsive, osteotropic, injectable hydrogel (PF127) based on pyrophosphorolated pluronic F127 (F127-PPi). After mixing F127-PPi with F127 at a 1:1 ratio, the resulting PF127 was used to dissolve free SIM to generate the SIM-loaded formulation. The thermoresponsive hydrogel's rheologic behavior, erosion and SIM release kinetics, osteotropic property, and biocompatibility were evaluated in vitro. The therapeutic efficacy of SIM-loaded PF127 hydrogel on periodontal bone preservation and inflammation resolution was validated in a ligature-induced periodontitis rat model. Given that SIM is already an approved medication for hyperlipidemia, the data presented here support the translational potential of the SIM-loaded PF127 hydrogel for better clinical management of periodontitis and associated pathologies.


Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Portadores de Fármacos/química , Periodontite/tratamento farmacológico , Sinvastatina/administração & dosagem , Perda do Osso Alveolar/etiologia , Perda do Osso Alveolar/patologia , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/efeitos dos fármacos , Animais , Liberação Controlada de Fármacos , Feminino , Humanos , Hidrogéis/química , Injeções Intralesionais , Camundongos , Modelos Animais , Periodontite/complicações , Periodontite/patologia , Poloxâmero/química , Células RAW 264.7 , Ratos , Sinvastatina/farmacocinética , Solubilidade , Microtomografia por Raio-X
16.
Clin Infect Dis ; 71(12): 3163-3167, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-32556265

RESUMO

BACKGROUND: Knowledge on the epidemiological features and transmission patterns of novel coronavirus disease (COVID-19) is accumulating. Detailed line-list data with household settings can advance the understanding of COVID-19 transmission dynamics. METHODS: A unique database with detailed demographic characteristics, travel history, social relationships, and epidemiological timelines for 1407 transmission pairs that formed 643 transmission clusters in mainland China was reconstructed from 9120 COVID-19 confirmed cases reported during 15 January-29 February 2020. Statistical model fittings were used to identify the superspreading events and estimate serial interval distributions. Age- and sex-stratified hazards of infection were estimated for household vs nonhousehold transmissions. RESULTS: There were 34 primary cases identified as superspreaders, with 5 superspreading events occurred within households. Mean and standard deviation of serial intervals were estimated as 5.0 (95% credible interval [CrI], 4.4-5.5) days and 5.2 (95% CrI, 4.9-5.7) days for household transmissions and 5.2 (95% CrI, 4.6-5.8) and 5.3 (95% CrI, 4.9-5.7) days for nonhousehold transmissions, respectively. The hazard of being infected outside of households is higher for people aged 18-64 years, whereas hazard of being infected within households is higher for young and old people. CONCLUSIONS: Nonnegligible frequency of superspreading events, short serial intervals, and a higher risk of being infected outside of households for male people of working age indicate a significant barrier to the identification and management of COVID-19 cases, which requires enhanced nonpharmaceutical interventions to mitigate this pandemic.


Assuntos
COVID-19 , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Viagem , Adulto Jovem
17.
Emerg Infect Dis ; 26(6): 1341-1343, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32191173

RESUMO

We estimate the distribution of serial intervals for 468 confirmed cases of coronavirus disease reported in China as of February 8, 2020. The mean interval was 3.96 days (95% CI 3.53-4.39 days), SD 4.75 days (95% CI 4.46-5.07 days); 12.6% of case reports indicated presymptomatic transmission.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Número Básico de Reprodução , Betacoronavirus , COVID-19 , China/epidemiologia , Humanos , Pandemias , SARS-CoV-2 , Fatores de Tempo
18.
Emerg Infect Dis ; 26(5): 1049-1052, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32053479

RESUMO

On January 23, 2020, China quarantined Wuhan to contain coronavirus disease (COVID-19). We estimated the probability of transportation of COVID-19 from Wuhan to 369 other cities in China before the quarantine. Expected COVID-19 risk is >50% in 130 (95% CI 89-190) cities and >99% in the 4 largest metropolitan areas.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Medição de Risco , Meios de Transporte , Betacoronavirus , COVID-19 , China/epidemiologia , Cidades , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Previsões , Humanos , Modelos Estatísticos , Pneumonia Viral/epidemiologia , Quarentena , SARS-CoV-2 , Processos Estocásticos
19.
Emerg Infect Dis ; 26(9)2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32516108

RESUMO

Cities across China implemented stringent social distancing measures in early 2020 to curb coronavirus disease outbreaks. We estimated the speed with which these measures contained transmission in cities. A 1-day delay in implementing social distancing resulted in a containment delay of 2.41 (95% CI 0.97-3.86) days.


Assuntos
Betacoronavirus , COVID-19/prevenção & controle , Infecções por Coronavirus/prevenção & controle , Surtos de Doenças/prevenção & controle , Transmissão de Doença Infecciosa/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , COVID-19/epidemiologia , China/epidemiologia , Cidades/epidemiologia , Infecções por Coronavirus/epidemiologia , Política de Saúde , Humanos , Distanciamento Físico , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Fatores de Tempo
20.
Opt Express ; 28(3): 4249-4257, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32122081

RESUMO

We report a novel Nd3+ and Eu3+ co-doped Sr2SnO4 (SSONE) phosphor showing the capability of "write-in" and "read-out" in optical information storage. As-prepared phosphors exhibit a dominant emission (PL) band centered at 596 nm under UV excitation, closely identical with its photo-stimulated luminescence (PSL) spectrum center (595 nm) upon near-infrared (NIR) light and thermal-stimulated luminescence (TSL) spectrum center (595 nm) under heat source. Remarkably, compared with Eu3+ single-doped phosphors, the co-doping strategy enhances the deep traps and also separates the deep traps with shallow traps, which are very crucial factors for optical information storage in electron trapping materials. Further, a demonstration confirmed the optical information storage capacity by photo- and thermal-stimulating the prepared phosphors filled in the designed patterns.

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