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1.
Cell ; 185(1): 131-144.e18, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34919814

RESUMO

Two HIV fusion-inhibitory lipopeptides (LP-97 and LP-98) were designed with highly potent, long-acting antiviral activity. Monotherapy using a low dose of LP-98 sharply reduced viral loads and maintained long-term viral suppression in 21 SHIVSF162P3-infected rhesus macaques. We found that five treated monkeys achieved potential posttreatment control (PTC) efficacy and had lower viral DNA in deep lymph nodes, whereas monkeys with a stable viral rebound had higher viral DNA in superficial lymph nodes. The tissues of PTC monkeys exhibited significantly decreased quantitative viral outgrowth and fewer PD-1+ central memory CD4+ T cells, and CD8+ T cells contributed to virologic control efficacy. Moreover, LP-98 administrated as a pre-exposure prophylaxis (PrEP) provided complete protection against SHIVSF162P3 and SIVmac239 infections in 51 monkeys via intrarectal, intravaginal, or intravenous challenge. In conclusion, our lipopeptides exhibit high potential as an efficient HIV treatment or prevention strategy.


Assuntos
Inibidores da Fusão de HIV/administração & dosagem , Lipopeptídeos/administração & dosagem , Profilaxia Pré-Exposição/métodos , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Feminino , Células HEK293 , Humanos , Macaca mulatta , Masculino , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Resposta Viral Sustentada , Células U937 , Carga Viral/efeitos dos fármacos
2.
Proc Natl Acad Sci U S A ; 120(11): e2218960120, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36877848

RESUMO

HIV post-treatment controllers (PTCs) are rare individuals who maintain low levels of viremia after stopping antiretroviral therapy (ART). Understanding the mechanisms of HIV post-treatment control will inform development of strategies aiming at achieving HIV functional cure. In this study, we evaluated 22 PTCs from 8 AIDS Clinical Trials Group (ACTG) analytical treatment interruption (ATI) studies who maintained viral loads ≤400 copies/mL for ≥24 wk. There were no significant differences in demographics or frequency of protective and susceptible human leukocyte antigen (HLA) alleles between PTCs and post-treatment noncontrollers (NCs, n = 37). Unlike NCs, PTCs demonstrated a stable HIV reservoir measured by cell-associated RNA (CA-RNA) and intact proviral DNA assay (IPDA) during analytical treatment interruption (ATI). Immunologically, PTCs demonstrated significantly lower CD4+ and CD8+ T cell activation, lower CD4+ T cell exhaustion, and more robust Gag-specific CD4+ T cell responses and natural killer (NK) cell responses. Sparse partial least squares discriminant analysis (sPLS-DA) identified a set of features enriched in PTCs, including a higher CD4+ T cell% and CD4+/CD8+ ratio, more functional NK cells, and a lower CD4+ T cell exhaustion level. These results provide insights into the key viral reservoir features and immunological profiles for HIV PTCs and have implications for future studies evaluating interventions to achieve an HIV functional cure.


Assuntos
Linfócitos T CD8-Positivos , Infecções por HIV , Humanos , Células Matadoras Naturais , Ativação Linfocitária , RNA , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Viremia
3.
Nano Lett ; 24(15): 4571-4579, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38565076

RESUMO

Efficient pure-red emission light-emitting diodes (LEDs) are essential for high-definition displays, yet achieving pure-red emission is hindered by challenges like phase segregation and spectral instability when using halide mixing. Additionally, strongly confined quantum dots (QDs) produced through traditional hot-injection methods face byproduct contamination due to poor solubility of metal halide salts in the solvent octadecene (ODE) at low temperatures. Herein, we introduced a novel method using a benzene-series strongly electrostatic potential solvent instead of ODE to prevent PbI2 intermediates and promote their dissolution into [PbI3]-. Increasing methyl groups on benzene yields precisely sized (4.4 ± 0.1 nm) CsPbI3 QDs with exceptional properties: a narrow 630 nm PL peak with photoluminescence quantum yield (PLQY) of 97%. Sequential ligand post-treatment optimizes optical and electrical performance of QDs. PeLEDs based on optimized QDs achieve pure-red EL (CIE: 0.700, 0.290) approaching Rec. 2020 standards, with an EQE of 25.2% and T50 of 120 min at initial luminance of 107 cd/m2.

4.
Clin Infect Dis ; 78(1): 164-171, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-37773767

RESUMO

BACKGROUND: Quantification of recurrence risk following successful treatment is crucial to evaluating regimens for multidrug- or rifampicin-resistant (MDR/RR) tuberculosis (TB). However, such analyses are complicated when some patients die or become lost during post-treatment follow-up. METHODS: We analyzed data on 1991 patients who successfully completed a longer MDR/RR-TB regimen containing bedaquiline and/or delamanid between 2015 and 2018 in 16 countries. Using 5 approaches for handling post-treatment deaths, we estimated 6-month post-treatment TB recurrence risk overall and by HIV status. We used inverse-probability weighting to account for patients with missing follow-up and investigated the impact of potential bias from excluding these patients without applying inverse-probability weights. RESULTS: The estimated TB recurrence risk was 7.4/1000 (95% credible interval: 3.3-12.8) when deaths were handled as non-recurrences and 7.6/1000 (3.3-13.0) when deaths were censored and inverse-probability weights were applied to account for the excluded deaths. The estimated risks of composite recurrence outcomes were 25.5 (15.3-38.1), 11.7 (6.4-18.2), and 8.6 (4.1-14.4) per 1000 for recurrence or (1) any death, (2) death with unknown or TB-related cause, or (3) TB-related death, respectively. Corresponding relative risks for HIV status varied in direction and magnitude. Exclusion of patients with missing follow-up without inverse-probability weighting had a small impact on estimates. CONCLUSIONS: The estimated 6-month TB recurrence risk was low, and the association with HIV status was inconclusive due to few recurrence events. Estimation of post-treatment recurrence will be enhanced by explicit assumptions about deaths and appropriate adjustment for missing follow-up data.


Assuntos
Infecções por HIV , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/uso terapêutico , Seguimentos , HIV , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia
5.
Am J Epidemiol ; 193(7): 940-950, 2024 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-38576195

RESUMO

Avanzando Caminos (Leading Pathways): The Hispanic/Latino Cancer Survivorship Cohort Study aims to examine the influence of sociocultural, medical, stress-related, psychosocial, lifestyle, behavioral, and biological factors on symptom burden, health-related quality of life, and clinical outcomes among Hispanics/Latinos who have been previously treated for cancer. Avanzando Caminos is a prospective, cohort-based study of 3000 Hispanics/Latinos who completed primary cancer treatment within the past 5 years that is representative of the general Hispanic/Latino population in the United States. Participants will complete self-report measures at baseline (time [T] 1), 6 months (T2), 1 year (T3), 2 years (T4), 3 years (T5), 4 years (T6), and 5 years (T7). Blood samples drawn for assessment of leukocyte gene expression, cardiometabolic markers, and genetic admixture will be collected at baseline (T1), 1 year (T3), 3 years (T5), and 5 years (T7). Medical and cancer characteristics and clinical outcomes will be extracted from the electronic medical record and/or state cancer registry at each time point. Data analysis will include general latent variable modeling and latent growth modeling. Avanzando Caminos will fill critical gaps in knowledge in order to guide future secondary and tertiary prevention efforts to mitigate cancer disparities and optimize health-related quality of life among Hispanic/Latino cancer survivors.


Assuntos
Sobreviventes de Câncer , Hispânico ou Latino , Qualidade de Vida , Humanos , Hispânico ou Latino/estatística & dados numéricos , Estudos Prospectivos , Sobreviventes de Câncer/estatística & dados numéricos , Masculino , Feminino , Estados Unidos/epidemiologia , Neoplasias/etnologia , Adulto , Pessoa de Meia-Idade , Projetos de Pesquisa , Idoso , Fatores Socioeconômicos
6.
Am J Epidemiol ; 193(4): 563-576, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37943689

RESUMO

We pay tribute to Marshall Joffe, PhD, and his substantial contributions to the field of causal inference with focus in biostatistics and epidemiology. By compiling narratives written by us, his colleagues, we not only present highlights of Marshall's research and their significance for causal inference but also offer a portrayal of Marshall's personal accomplishments and character. Our discussion of Marshall's research notably includes (but is not limited to) handling of posttreatment variables such as noncompliance, employing G-estimation for treatment effects on failure-time outcomes, estimating effects of time-varying exposures subject to time-dependent confounding, and developing a causal framework for case-control studies. We also provide a description of some of Marshall's unpublished work, which is accompanied by a bonus anecdote. We discuss future research directions related to Marshall's research. While Marshall's impact in causal inference and the world outside of it cannot be wholly captured by our words, we hope nonetheless to present some of what he has done for our field and what he has meant to us and to his loved ones.


Assuntos
Bioestatística , Humanos , Masculino , Causalidade , Estudos de Casos e Controles
7.
J Virol ; 97(1): e0125422, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36541802

RESUMO

Posttreatment controllers (PTCs) are rare HIV-infected individuals who can limit viral rebound after antiretroviral therapy interruption (ATI), but the mechanisms of this remain unclear. To investigate these mechanisms, we quantified various HIV RNA transcripts (via reverse transcription droplet digital PCR [RT-ddPCR]) and cellular transcriptomes (via RNA-seq) in blood cells from PTCs and noncontrollers (NCs) before and two time points after ATI. HIV transcription initiation did not significantly increase after ATI in PTCs or in NCs, whereas completed HIV transcripts increased at early ATI in both groups and multiply-spliced HIV transcripts increased only in NCs. Compared to NCs, PTCs showed lower levels of HIV DNA, more cell-associated HIV transcripts per total RNA at all times, no increase in multiply-spliced HIV RNA at early or late ATI, and a reduction in the ratio of completed/elongated HIV RNA after early ATI. NCs expressed higher levels of the IL-7 pathway before ATI and expressed higher levels of multiple cytokine, inflammation, HIV transcription, and cell death pathways after ATI. Compared to the baseline, the NCs upregulated interferon and cytokine (especially TNF) pathways during early and late ATI, whereas PTCs upregulated interferon and p53 pathways only at early ATI and downregulated gene translation during early and late ATI. In NCs, viral rebound after ATI is associated with increases in HIV transcriptional completion and splicing, rather than initiation. Differences in HIV and cellular transcription may contribute to posttreatment control, including an early limitation of spliced HIV RNA, a delayed reduction in completed HIV transcripts, and the differential expression of the IL-7, p53, and TNF pathways. IMPORTANCE The findings presented here provide new insights into how HIV and cellular gene expression change after stopping ART in both noncontrollers and posttreatment controllers. Posttreatment control is associated with an early ability to limit increases in multiply-spliced HIV RNA, a delayed (and presumably immune-mediated) ability to reverse an initial rise in processive/completed HIV transcripts, and multiple differences in cellular gene expression pathways. These differences may represent correlates or mechanisms of posttreatment control and may provide insight into the development and/or monitoring of therapeutic strategies that are aimed at a functional HIV cure.


Assuntos
Infecções por HIV , RNA Viral , Transcriptoma , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Infecções por HIV/imunologia , HIV-1/genética , Interferons/genética , Interleucina-7/genética , RNA Viral/genética , Transcriptoma/imunologia , Proteína Supressora de Tumor p53/genética
8.
J Transl Med ; 22(1): 727, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103918

RESUMO

BACKGROUND: Vascular dysregulation is one of the major risk factors of glaucoma, and endothelin-1 (ET-1) may have a role in the pathogenesis of vascular-related glaucoma. Fruit extract from Lycium Barbarum (LB) exhibits anti-ageing and multitarget mechanisms in protecting retinal ganglion cells (RGC) in various animal models. To investigate the therapeutic efficacy of LB glycoproteins (LbGP) in ET-1 induced RGC degeneration, LbGP was applied under pre- and posttreatment conditions to an ET-1 mouse model. Retina structural and functional outcomes were characterised using clinical-based techniques. METHODS: Adult C57BL/6 mice were randomly allocated into four experimental groups, namely vehicle control (n = 9), LbGP-Pretreatment (n = 8), LbGP-Posttreatment (day 1) (n = 8) and LbGP-Posttreatment (day 5) (n = 7). Oral administration of LbGP 1 mg/Kg or PBS for vehicle control was given once daily. Pre- and posttreatment (day 1 or 5) were commenced at 1 week before and 1 or 5 days after intravitreal injections, respectively, and were continued until postinjection day 28. Effects of treatment on retinal structure and functions were evaluated using optical coherence tomography (OCT), doppler OCT and electroretinogram measurements at baseline, post-injection days 10 and 28. RGC survival was evaluated by using RBPMS immunostaining on retinal wholemounts. RESULTS: ET-1 injection in vehicle control induced transient reductions in arterial flow and retinal functions, leading to significant RNFL thinning and RGC loss at day 28. Although ET-1 induced a transient loss in blood flow or retinal functions in all LbGP groups, LbGP treatments facilitated better restoration of retinal flow and retinal functions as compared with the vehicle control. Also, all three LbGP treatment groups (i.e. pre- and posttreatments from days 1 or 5) significantly preserved thRNFL thickness and RGC densities. No significant difference in protective effects was observed among the three LbGP treatment groups. CONCLUSION: LbGP demonstrated neuroprotective effects in a mouse model of ET-1 induced RGC degeneration, with treatment applied either as a pretreatment, immediate or delayed posttreatment. LbGP treatment promoted a better restoration of retinal blood flow, and protected the RNFL, RGC density and retinal functions. This study showed the translational potential of LB as complementary treatment for glaucoma management.


Assuntos
Endotelina-1 , Camundongos Endogâmicos C57BL , Neuroproteção , Células Ganglionares da Retina , Animais , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/metabolismo , Endotelina-1/metabolismo , Neuroproteção/efeitos dos fármacos , Eletrorretinografia , Lycium/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Degeneração Retiniana/tratamento farmacológico , Degeneração Retiniana/patologia , Tomografia de Coerência Óptica , Masculino , Camundongos , Degeneração Neural/patologia , Degeneração Neural/tratamento farmacológico
9.
Chemistry ; 30(9): e202303396, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38105406

RESUMO

The incorporation of organic ligands via post-device treatment is an effective strategy to improve the stability of perovskite solar cells (PSCs). Although the active area is protected by metal electrode under post-treatment, the aggression of post-treatment ligands into active area cannot be avoided thoroughly. Unfortunately, the size of long-chain amines is too large, and the three-dimensional (3D) perovskite cannot maintain its 3D perovskite structure once the cation substitution occurs during the post-treatment. Despite that the low-dimensional (LD) perovskites are beneficial to stability, long-chain amines are harmful to carrier transport in PSCs. Here, we introduce dimethylamine (DMA), a slightly oversized cation that can be doped into 3D perovskite structure, for post-device treatment to improve the efficiency and stability of PSCs. After exposure to DMA gas, the inactive area of Cs/FA/MA mixed cation perovskite device that is not covered by metal electrode is converted into LD perovskite, passivating the defects of 3D perovskite in the active region, suppressing non-radiation recombination and ion migration. As a result, we achieved a power conversion efficiency (PCE) of 22.29 % with negligible hysteresis and better stability after DMA post-treatment, which is much higher than that (20.40 %) of the control device.

10.
Trop Med Int Health ; 29(1): 23-32, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38093552

RESUMO

BACKGROUND: Knowledge of factors associated with TB mortality during treatment and post treatment will help us develop better monitoring and implementation strategies for TB control. We designed the present study to examine the factors associated with mortality in HIV-TB co-infected patients during and after the course of TB treatment. METHODS: This study is a cohort analysis of secondary data collected from 1804 HIV-TB co-infected individuals from 16 anti-retroviral therapy (ART) centres affiliated with the Mumbai Districts AIDS Control Society, Mumbai, India. We used Kaplan Meier survival curves and hazard ratios to estimate the mortality in patients. RESULTS: The overall mortality rate in this cohort was 1.14 per 100 per month. The mortality proportion was 18% (95% CI: 16.1%, 20.1%) during treatment and 10.6% (95% CI: 8.9%, 12.5%) in the post-treatment period. Mortality was significantly higher in those with a CD4 count 0-200 cells/mm3 (HR: 3.04, 95% CI: 2.13, 4.15; p < 0.001), and in patients who were ART naïve and referred to the ART centre with a diagnosis of TB (HR: 1.39, 95% CI: 1.06, 1.82; p = 0.016). Mortality was also significantly higher in the first 6 months after initiation of ART (HR: 1.36, 95% CI: 1.06, 1.75; p = 0.016). A decrease in the CD4 counts from initial levels at start of TB treatment to end of TB treatment was associated with higher mortality in the post-treatment period. DISCUSSION: The overall mortality remains high; early identification of TB and HIV disease, and use of rapid point of care tests for diagnosis of TB are needed across all health care facilities. Post-treatment follow-up and monitoring is important in HIV-TB co-infected patients, and post-treatment mortality should also be considered as one of the indicators for successful TB control programmes.


Assuntos
Coinfecção , Infecções por HIV , Tuberculose , Humanos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/diagnóstico , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Tuberculose/diagnóstico , Coinfecção/tratamento farmacológico , Estudos de Coortes , Índia/epidemiologia
11.
Eur J Neurol ; 31(7): e16293, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38606630

RESUMO

BACKGROUND AND PURPOSE: Residual symptoms after treatment of Lyme disease, sometimes called post-treatment Lyme disease symptoms (PTLDs), are a matter of ongoing controversy. To guide treatment recommendations, a systematic review was performed of the available literature on specific treatment for PTLDs. METHODS: A systematic literature search of MEDLINE and CENTRAL was performed. No restrictions on case definitions, study types or specific interventions were applied to enable a comprehensive overview of the available literature. Risk of bias was assessed using the Cochrane risk of bias tools for randomized controlled trials. Certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Outcomes of interest were quality of life, fatigue, depression and cognition as well as adverse events. RESULTS: After screening 1274 records, eight eligible randomized controlled trials were included. Heterogeneity was observed regarding inclusion criteria, intervention, length of treatment and outcome measures. For efficacy outcomes, results are presented narratively due to heterogeneity. Eligible studies show no statistically significant difference between antibiotics and placebo regarding quality of life, cognition and depression. Results for fatigue were inconsistent whilst studies with low risk of bias showed no statistically significant difference between antibiotics and placebo. Meta-analysis of safety outcomes showed statistically significantly more adverse events for antibiotics compared to placebo. CONCLUSIONS: Available literature on treatment of PTLDs is heterogeneous, but overall shows evidence of no effect of antibiotics regarding quality of life, depression, cognition and fatigue whilst showing more adverse events. Patients with suspected PTLDs should not be treated with antibiotics.


Assuntos
Doença de Lyme , Humanos , Doença de Lyme/tratamento farmacológico , Doença de Lyme/complicações , Síndrome Pós-Lyme/tratamento farmacológico , Síndrome Pós-Lyme/terapia , Antibacterianos/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Depressão/etiologia , Depressão/tratamento farmacológico
12.
Helicobacter ; 29(1): e13033, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37950342

RESUMO

BACKGROUND: The eradication rates of sequential therapy are high in clinical trials; however, the adherence for follow-up or the patient population in a real-world setting might be different from those in trails. This study investigates the effectiveness of sequential therapy in a real-world setting and the factors that lead to treatment failure. MATERIALS AND METHODS: In this retrospective study, patients receiving sequential therapy as a first-line anti-Helicobacter pylori (H. pylori) treatment in a real-world setting were reviewed. The age adjusted Charlson Comorbidity Index (age-CCI) and baseline variety of medications were reviewed to determine factors correlated with nonadherence for post-treatment testing and H. pylori eradication failure. RESULTS: A total of 1053 patients were reviewed. A total of 579 patients receiving sequential therapy were included in the analyses. Among them, 462 received post-treatment testing and were placed into the follow-up group. Thus, the post-treatment testing rate was 79.8%. Stroke was an independent factor of nonadherence for post-treatment testing. In the follow-up group, the eradication failure rate was 8.2%. Female sex (odds ratio [OR] 2.41 [95% CI 1.16-5.03], p = 0.02) and age-CCI ≥2 (OR 3.16 [1.05-9.48], p = 0.04) were independent factors of H. pylori eradication failure. The eradication failure rates were 14.4%, 7.8%, 7.1%, and 3.1% for the females with age-CCI ≥2, females with age-CCI <2, males with age-CCI ≥2, and males with age-CCI <2 subgroups, respectively (p = 0.027). CONCLUSIONS: In a real-world setting, the adherence rate of post-treatment testing for sequential therapy as a first-line anti-H. pylori treatment was found to be suboptimal. Female sex and age-CCI ≥2 were independent factors of eradication failure.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Masculino , Humanos , Feminino , Antibacterianos , Infecções por Helicobacter/tratamento farmacológico , Estudos Retrospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Quimioterapia Combinada , Fatores de Risco , Resultado do Tratamento , Claritromicina/uso terapêutico , Amoxicilina
13.
Neurocase ; : 1-9, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965869

RESUMO

OBJECTIVE: To describe a case of Post-Treatment Lyme Disease Syndrome (PTLDS) with an atypical cognitive profile. METHOD: A 41-year-old PTLDS patient underwent comprehensive neuropsychological testing and psychological assessment. RESULTS: The patient exhibited impaired intensive attention but preserved selective attention. Executive functions were normal. Short-term and anterograde memory were intact, while retrograde and semantic memory were significantly impaired. The patient also experienced identity loss, specific phobias, dissociative symptoms, and depressed mood. CONCLUSIONS: Severe episodic-autobiographical and retrograde semantic amnesia was consistent with some reports of dissociative amnesia. Loss of identity and phobias were also highly suggestive of a psychogenic mechanism underlying amnesia.

14.
Neuroradiology ; 66(3): 317-323, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38183424

RESUMO

PURPOSE: After standard treatment for glioblastoma, perfusion MRI remains challenging for differentiating tumor progression from post-treatment changes. Our objectives were (1) to correlate rCBV values at diagnosis and at first tumor progression and (2) to analyze the relationship of rCBV values at tumor recurrence with enhancing volume, localization of tumor progression, and time elapsed since the end of radiotherapy in tumor recurrence. METHODS: Inclusion criteria were (1) age > 18 years, (2) histologically confirmed glioblastoma treated with STUPP regimen, and (3) tumor progression according to RANO criteria > 12 weeks after radiotherapy. Co-registration of segmented enhancing tumor VOIs with dynamic susceptibility contrast perfusion MRI was performed using Olea Sphere software. For tumor recurrence, we correlated rCBV values with enhancing tumor volume, with recurrence localization, and with time elapsed from the end of radiotherapy to progression. Analyses were performed with SPSS software. RESULTS: Sixty-four patients with glioblastoma were included in the study. Changes in rCBV values between diagnosis and first tumor progression were significant (p < 0.001), with a mean and median decreases of 32% and 46%, respectively. Mean rCBV values were also different (p < 0.01) when tumors progressed distally (radiation field rCBV values of 1.679 versus 3.409 distally). However, changes and, therefore, low rCBV values after radiotherapy in tumor recurrence were independent of time. CONCLUSION: Chemoradiation alters tumor perfusion and rCBV values may be decreased in the setting of tumor progression. Changes in rCBV values with respect to diagnosis, with low rCBV in tumor progression, are independent of time but related to the site of recurrence.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Adulto , Pessoa de Meia-Idade , Glioblastoma/diagnóstico por imagem , Glioblastoma/radioterapia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Recidiva Local de Neoplasia/diagnóstico por imagem , Meios de Contraste , Quimiorradioterapia , Imageamento por Ressonância Magnética/métodos
15.
Qual Life Res ; 33(4): 1143-1155, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38291312

RESUMO

CONTEXT: Late or residual symptoms diminish quality of life for many cancer survivors after completion of treatment. OBJECTIVES: Examine risk factors associated with persisting symptom burden after chemotherapy and the lack of symptom improvement over time. METHODS: Survivors who completed curative-intent chemotherapy within two years for solid tumors were enrolled into a symptom management trial. There were 375 survivors with two or more comorbid conditions or one comorbid condition and elevated depressive symptoms (pre-defined risk factors in the trial design) who received interventions and 71 survivors without these risk factors who did not receive interventions. For all survivors, symptoms were assessed at intake, 4, and 13 weeks and categorized as mild, moderate, or severe based on the interference with daily life. The probabilities of moderate or severe symptoms and symptom improvement were analyzed using generalized mixed-effects models in relation to comorbidity, depressive symptoms, age, sex, race/ethnicity, employment, time since chemotherapy completion, and physical function. Multiple symptoms were treated as nested within the survivor. RESULTS: Moderate or severe symptoms at baseline and the lack of improvement over time were associated with younger age and lower physical function over and above a greater number of comorbidities and elevated severity of depressive symptoms. CONCLUSION: Risk factors identified in this research (younger age, lower physical function, greater comorbidity, and higher depressive symptoms) can be used to allocate resources for post-treatment symptom management for cancer survivors in order to relieve symptoms that do not necessarily resolve with time.


Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Qualidade de Vida/psicologia , Neoplasias/terapia , Sobreviventes , Comorbidade
16.
Int Endod J ; 57(8): 1043-1058, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38634795

RESUMO

BACKGROUND: Microorganisms colonizing the apical root canal system are conceivably the ones directly involved with the causation and maintenance of apical periodontitis. OBJECTIVES: This article systematically reviews the reports on the microbiome occurring exclusively at the apical root canal of teeth with primary and posttreatment apical periodontitis. METHODS: The electronic databases PubMed, Embase, Web of Science, Science Direct, and Proquest were searched up to August 2023. Clinical studies using culture and molecular microbiology methods to identify the microbial taxa present exclusively in the apical root canal segment of infected teeth with apical periodontitis were included. Studies were critically assessed using the Joanna Briggs Institute Critical Prevalence Assessment Checklist. RESULTS: From 2277 articles initially detected, 52 were selected for full reading and 21 were eventually included in this review. Of these, molecular methods were used in 19 and culture in 2 studies. Ten studies evaluated primary infections, 8 evaluated posttreatment infections, and 3 included both. Cryopulverization of the apical root specimens was conducted in 11 studies. All studies evaluated the prevalence and diversity of bacteria, and only one also reported on fungi. Overall, the most frequent/abundant bacterial taxa found in the apical canal of primary infections were Pseudoramibacter alactolyticus, Olsenella uli, Fusobacterium species, Streptococcus species, Porphyromonas endodontalis, Prevotella species, Actinomyces species, Parvimonas micra, Treponema denticola, Synergistetes species, and an as-yet uncharacterized taxon. In posttreatment infections, the most prevalent/abundant bacterial taxa included species of Streptococcus, Enterococcus, Fusobacterium, Actinomyces, Pseudoramibacter, Pseudomonas, and Propionibacterium. At the phylum level, Firmicutes was the most represented. The average apical bacterial load ranged from 105 to 106 in primary infections and from 103 to 104 in posttreatment infections. DISCUSSION: Microbial diversity in the apical part of the root canal system was examined encompassing data from both primary and posttreatment infections. Heterogeneity amongst the studies, especially in sample collection and microbial identification methods, is an important limitation that prevented a meta-analysis. CONCLUSIONS: There is a pronounced bacterial diversity in the infected apical canal, with a high interindividual variability. Different microbiome compositions at the species/genus level are observed according to the infection type. REGISTRATION: PROSPERO CRD42021275886.


Assuntos
Cavidade Pulpar , Microbiota , Periodontite Periapical , Periodontite Periapical/microbiologia , Periodontite Periapical/terapia , Humanos , Cavidade Pulpar/microbiologia , Bactérias/classificação , Bactérias/isolamento & purificação
17.
Luminescence ; 39(3): e4706, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38483095

RESUMO

Inorganic cesium lead halide perovskites have evoked wide popularity because of their excellent optoelectronic properties, high photoluminescence (PL) quantum yield (PLQY), and narrowband emission. Here, cesium lead bromide (CsPbBr3 ) quantum dots (QDs) were synthesized via the ligand-assisted re-precipitation method. Post-synthesis treatment of CsPbBr3 QDs using antimony tribromide improved the PL stability and optoelectronic properties of the QDs. In addition, the PLQY of the post-treated sample was enhanced to 91% via post-treatment, and the luminescence observed was maintained for 8 days. The post-synthesis treatment ensured defect passivation and improved the stability of CsPbBr3 perovskite QDs. High-resolution transmission electron microscopy revealed the presence of more ordered, uniform-sized CsPbBr3 QDs after post-synthesis treatment, and the uniformity of the sample improved as the day passed. The formation of a mixed crystal phase was observed from X-ray diffraction in both as-synthesized, as well as post-treated QDs samples with the possibility of a polycrystalline nature in the post-treated CsPbBr3 QDs as per the selected area electron diffraction pattern. The X-ray photoelectron spectroscopy spectra confirmed the presence of antimony and the possibility of defect passivation in the post-treated samples. These QDs can act as potential candidates in various optoelectronic applications such as photodetectors and light-emitting diodes due to their high PLQY and longer lifetime.


Assuntos
Antimônio , Brometos , Compostos de Cálcio , Óxidos , Pontos Quânticos , Titânio , Césio
18.
Eur Arch Otorhinolaryngol ; 281(4): 1941-1952, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38326581

RESUMO

PURPOSE: Treatment of head and neck cancer (HNC) may lead to obstructive sleep apnea (OSA), but conclusive results on the prevalence of OSA are lacking. The objective of this study is to investigate the prevalence of OSA in a cohort of patients treated for advanced T-stage HNC. METHODS: A cross-sectional study was conducted in two tertiary cancer care centers including patients at least 1 year after treatment with curative intent with surgery and/or (chemo)radiotherapy ((C)RT) for advanced T-staged (T3-4) cancer of the oral cavity, oropharynx, hypopharynx, or larynx. A polysomnography (PSG) was performed in all participants. OSA was defined as an apnea-hypopnea index (AHI) of 15 events/h or higher or an AHI of 5 events/h and higher with OSA related symptoms, such as sleeping problems, daytime dysfunction and/or cardiac/metabolic comorbidities collected through file review and questionnaires. RESULTS: Of the 67 participants, 48 (72%, 95% CI 59-82%) were diagnosed with OSA. Possible risk factors are male gender, higher BMI, greater neck circumference, more nicotine pack years, cardiometabolic comorbidities, use of medication with sleepiness as side effect, present tonsils, lower T-stage (T3 vs. T4 stage), higher AJCC stage and a HPV-negative tumor. CONCLUSION: In this population of advanced T-stage HNC patients, the prevalence of OSA was 72%, which is considerably higher than in the general population (2-50%). Given the high prevalence, screening of this entire subgroup for OSA may be indicated. Future studies to identify high risk factors and develop an OSA screening protocol are needed.


Assuntos
Neoplasias de Cabeça e Pescoço , Apneia Obstrutiva do Sono , Humanos , Masculino , Feminino , Prevalência , Estudos Transversais , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/terapia , Comorbidade , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/complicações
19.
Multivariate Behav Res ; : 1-24, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963381

RESUMO

Psychologists leverage longitudinal designs to examine the causal effects of a focal predictor (i.e., treatment or exposure) over time. But causal inference of naturally observed time-varying treatments is complicated by treatment-dependent confounding in which earlier treatments affect confounders of later treatments. In this tutorial article, we introduce psychologists to an established solution to this problem from the causal inference literature: the parametric g-computation formula. We explain why the g-formula is effective at handling treatment-dependent confounding. We demonstrate that the parametric g-formula is conceptually intuitive, easy to implement, and well-suited for psychological research. We first clarify that the parametric g-formula essentially utilizes a series of statistical models to estimate the joint distribution of all post-treatment variables. These statistical models can be readily specified as standard multiple linear regression functions. We leverage this insight to implement the parametric g-formula using lavaan, a widely adopted R package for structural equation modeling. Moreover, we describe how the parametric g-formula may be used to estimate a marginal structural model whose causal parameters parsimoniously encode time-varying treatment effects. We hope this accessible introduction to the parametric g-formula will equip psychologists with an analytic tool to address their causal inquiries using longitudinal data.

20.
Int J Mol Sci ; 25(14)2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39063245

RESUMO

The clinical impact of therapy-related acute leukemias is increasing with the extension of cancer-related survival; however, the origins remain largely unknown. Acute erythroleukemia (AEL), a rare unfavorable type of myeloid neoplasia, may also develop secondary to cytotoxic therapy. The disorder is featured by specific genetic alterations, most importantly multi-allelic mutations of the TP53 gene. While AEL might appear as a part of the therapy-related MDS/AML, spectrum information regarding the genetic complexity and progression is largely missing. We present two AEL cases arising after cytotoxic therapy and melphalan-based myeloablation/autologous peripheral stem cell transplantation due to multiple myeloma (MM). As stated, multiple pathogenic TP53 variants were present unrelated to preexisting MM, in parallel with uninvolved/wild-type hemopoiesis. Potential mechanisms of leukemic transformation are discussed, which include (1) preexisting preneoplastic hemopoietic stem cells (HSC) serving as the common origin for both MM and AEL, (2) the generation and intramedullary survival of p53-deficient post-chemotherapy HSCs, (3) reinoculation of mobilized autologous TP53 mutated HSCs, and (4) melphalan treatment-related late-onset myelodysplasia/leukemia with newly acquired TP53 mutations.


Assuntos
Leucemia Eritroblástica Aguda , Mieloma Múltiplo , Transplante Autólogo , Mieloma Múltiplo/terapia , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Humanos , Pessoa de Meia-Idade , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/patologia , Leucemia Eritroblástica Aguda/terapia , Masculino , Proteína Supressora de Tumor p53/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Transformação Celular Neoplásica/genética , Mutação , Feminino , Melfalan/uso terapêutico , Melfalan/administração & dosagem , Idoso , Quimiorradioterapia/métodos , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/terapia , Segunda Neoplasia Primária/genética
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