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1.
Cureus ; 16(4): e57963, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38738095

RESUMO

Antiarrhythmic drugs play a pivotal role in managing and preventing arrhythmias. Amiodarone, classified as a class III antiarrhythmic, has been used prophylactically to effectively prevent atrial fibrillation postoperatively in cardiac surgeries. However, there is a lack of consensus on the use of amiodarone and other antiarrhythmic drugs as prophylaxis to reduce the occurrence of all types of postoperative arrhythmias in cardiac and non-cardiac surgeries. A comprehensive PubMed query yielded 614 relevant papers, of which 52 clinical trials were analyzed. The data collection included the class of antiarrhythmics, timing or method of drug administration, surgery type, type of arrhythmia and its incidence, and hospitalization length. Statistical analyses focused on prophylactic antiarrhythmics and their respective reductions in postoperative arrhythmias and hospitalization length. Prophylactic amiodarone alone compared to placebo demonstrated a significant reduction in postoperative arrhythmia incidence in cardiac and non-cardiac surgeries (24.01%, p<0.0001), and it was the only treatment group to significantly reduce hospitalization length versus placebo (p = 0.0441). Prophylactic use of class 4 antiarrhythmics versus placebo also demonstrated a significant reduction in postoperative arrhythmia incidence (28.01%, p<0.0001), and while there was no significant statistical reduction compared to amiodarone (4%, p=0.9941), a lack of abundant data provides a case for further research on the prophylactic use of class 4 antiarrhythmics for this indication. Amiodarone prophylaxis remains a prime cornerstone of therapy in reducing postoperative arrhythmia incidence and hospitalization length. Emerging data suggests a need for a broader exploration of alternative antiarrhythmic agents and combination therapies, particularly class 4 antiarrhythmics, in both cardiac and non-cardiac surgeries. This meta-analysis depicts the effectiveness of amiodarone, among other antiarrhythmics, in postoperative arrhythmia incidence and hospitalization length reduction in cardiac and non-cardiac surgeries.

2.
Evol Appl ; 17(3): e13665, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38468712

RESUMO

Harvest in walleye Sander vitreus fisheries is size-selective and could influence phenotypic traits of spawners; however, contributions of individual spawners to recruitment are unknown. We used parentage analyses using single nucleotide polymorphisms to test whether parental traits were related to the probability of offspring survival in Escanaba Lake, Wisconsin. From 2017 to 2020, 1339 adults and 1138 juveniles were genotyped and 66% of the offspring were assigned to at least one parent. Logistic regression indicated the probability of reproductive success (survival of age-0 to first fall) was positively (but weakly) related to total length and growth rate in females, but not age. No traits analyzed were related to reproductive success for males. Our analysis identified the model with the predictors' growth rate and year for females and the models with year and age and year for males as the most likely models to explain variation in reproductive success. Our findings indicate that interannual variation (i.e., environmental conditions) likely plays a key role in determining the probability of reproductive success in this population and provide limited support that female age, length, and growth rate influence recruitment.

3.
J Endocrinol Invest ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372939

RESUMO

BACKGROUND: Despite the increasing interest in transgender health research, to date little is known about the size of the transgender and gender diverse (TGD) population. METHODS: A web-based questionnaire survey was developed, including a collection of socio-demographic characteristics and disseminated online through social media. Gender incongruence was evaluated by using a 2-item approach assessing gender recorded at birth and gender identity. The primary objective of the present population-based study was to estimate the proportion of TGD people across ages among a large sample of people who answered a web-based survey. The secondary endpoints were to identify gender-affirming needs and possible barriers to healthcare access. RESULTS: A total of 19,572 individuals participated in the survey, of whom 7.7% reported a gender identity different from the sex recorded at birth. A significantly higher proportion of TGD people was observed in the youngest group of participants compared with older ones. Among TGD people who participated in the study, 58.4% were nonbinary, and 49.1% experienced discrimination in accessing health care services. Nonbinary TGD participants reported both the need for legal name and gender change, along with hormonal and surgical interventions less frequently compared to binary persons. CONCLUSIONS: Being TGD is not a marginal condition In Italy. A large proportion of TGD persons may not need medical and surgical treatments. TGD people often experience barriers to healthcare access relating to gender identity.

4.
Infect Control Hosp Epidemiol ; : 1-5, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38272652

RESUMO

OBJECTIVE: Port-a-caths are implanted intravascular chest ports that enable venous access. With more port placements performed by interventional radiologists, it is important to discern differences in infection and complication rates between double- and single-lumen ports. METHODS: We retrospectively reviewed 1,385 port placements over 2 years at the University of Miami. Patients were grouped by single- or double-lumen ports. Data on duration of catheter stay, bloodstream infections, malfunctions, and other complications (fibrin sheath, thrombosis, catheter malposition) were collected. Multivariate Cox regression was performed to identify variables predicting port infection. RESULTS: The mean patient age was 58.8 years; the mean BMI was 26.9 kg/m2; and 61.5% of these patients were female. Our search revealed 791 double-lumen ports (57.1%) and 594 single-lumen ports (42.9%). The median follow-up was 668 days (range, 2-1,297). Double-lumen ports were associated with significantly higher rates of bacteremia (2.78% vs 0.84%; P = .02), port malfunction (8.3% vs 2.0%; P < .001), fibrin sheath formation (2.2% vs 0.5%; P < .02), catheter tip malposition (1.0% vs 0; P = .01), and catheter-associated thrombosis (1.4% vs 0; P = .003). Multivariate Cox regression analysis, after adjusting for other variables, showed that double-lumen chest ports had 2.98 times (95% confidence interval, 1.12-7.94) the hazard rate of single-lumen ports for developing bloodstream infection (P = .029). CONCLUSIONS: Double-lumen chest ports are associated with increased risk for bloodstream infection, malfunction, fibrin sheath formation, catheter tip malposition, and catheter-associated thrombosis. Interventional radiologists may consider placing single-lumen ports if clinically feasible; however, future studies are needed to determine clinical significance. The study limitations included the retrospective study design and the potential loss of patient follow-up.

5.
AWWA Water Sci ; 5(6)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38152622

RESUMO

Adding new unit operations to drinking water treatment systems requires consideration of not only efficacy for its design purpose but also costs, water quality characteristics, impact on overall regulatory compliance, and impact of other treatment unit operations. Here, pilot study results for ion exchange (IX) and granular activated carbon (GAC) are presented for a utility with both per- and polyfluoroalkyl substances (PFAS) and volatile organic contaminant removal needs. Specifically, the impact of upstream air stripping and phosphate addition on PFAS treatment performance was evaluated. Modeling was used to fit the IX and GAC pilot data and predict performance under different scenarios. GAC performance was generally consistent for treating water before or after the air stripper, but the addition of phosphate prior to air-stripping resulted in a loss of 15%-25% capacity for some PFAS on IX media, demonstrating the need to consider the entire treatment train before implementing PFAS removal unit operations.

6.
ACS ES T Water ; 3(8): 2247-2254, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37841341

RESUMO

Benzene contamination in drinking water systems affected by wildfires is a problem of emerging concern. Polyethylene pipes used in service lines and premise plumbing are vulnerable to permeation by benzene and can potentially cause challenges in sampling and remediation of contaminated systems. However, the kinetics and equilibria of the uptake of benzene by and release of benzene from pipes of differing polyethylene types and manufacturers are not well studied, leading to additional uncertainty when interpreting sampling data and selecting remediation options. This work addresses this data gap by providing diffusion and partitioning data for benzene and several varieties of polyethylene pipes, including field samples from water distribution systems. All polyethylene pipes that were studied exhibited similar partitioning behavior during benzene uptake and release, but some differences in kinetics were observed among pipes. However, these differences were of minor practical importance in the pipe contamination scenario examined in this work. The results of this study can be used in conjunction with diffusion modeling to inform remediation decisions for benzene-contaminated, polyethylene service lines, and premise plumbing.

7.
bioRxiv ; 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37873265

RESUMO

Recent advancements in human gut microbiome research have revealed its crucial role in shaping innovative predictive healthcare applications. We introduce Gut Microbiome Wellness Index 2 (GMWI2), an advanced iteration of our original GMWI prototype, designed as a robust, disease-agnostic health status indicator based on gut microbiome taxonomic profiles. Our analysis involved pooling existing 8069 stool shotgun metagenome data across a global demographic landscape to effectively capture biological signals linking gut taxonomies to health. GMWI2 achieves a cross-validation balanced accuracy of 80% in distinguishing healthy (no disease) from non-healthy (diseased) individuals and surpasses 90% accuracy for samples with higher confidence (i.e., outside the "reject option"). The enhanced classification accuracy of GMWI2 outperforms both the original GMWI model and traditional species-level α-diversity indices, suggesting a more reliable tool for differentiating between healthy and non-healthy phenotypes using gut microbiome data. Furthermore, by reevaluating and reinterpreting previously published data, GMWI2 provides fresh insights into the established understanding of how diet, antibiotic exposure, and fecal microbiota transplantation influence gut health. Looking ahead, GMWI2 represents a timely pivotal tool for evaluating health based on an individual's unique gut microbial composition, paving the way for the early screening of adverse gut health shifts. GMWI2 is offered as an open-source command-line tool, ensuring it is both accessible to and adaptable for researchers interested in the translational applications of human gut microbiome science.

8.
Bioengineering (Basel) ; 10(8)2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37627774

RESUMO

Cryogels, known for their biocompatibility and porous structure, lack mechanical strength, while 3D-printed scaffolds have excellent mechanical properties but limited porosity resolution. By combining a 3D-printed plastic gyroid lattice scaffold with a chitosan-gelatin cryogel scaffold, a scaffold can be created that balances the advantages of both fabrication methods. This study compared the pore diameter, swelling potential, mechanical characteristics, and cellular infiltration capability of combined scaffolds and control cryogels. The incorporation of the 3D-printed lattice demonstrated patient-specific geometry capabilities and significantly improved mechanical strength compared to the control cryogel. The combined scaffolds exhibited similar porosity and relative swelling ratio to the control cryogels. However, they had reduced elasticity, reduced absolute swelling capacity, and are potentially cytotoxic, which may affect their performance. This paper presents a novel approach to combine two scaffold types to retain the advantages of each scaffold type while mitigating their shortcomings.

9.
Environ Sci Technol ; 57(26): 9793-9801, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37342010

RESUMO

Mass transport in diffusive gradients in thin-film passive samplers is restricted to diffusion through a gel layer of agarose or agarose cross-linked polyacrylamide (APA). The gel layer diffusion coefficient, DGel, is typically determined using a standard analysis (SA) based on Fick's first law from two-compartment diffusion cell (D-Cell) tests. The SA assumes pseudo-steady-state flux, characterized by linear sink mass accumulation-time profiles with a typical threshold R2 ≥ 0.97. In 72 D-Cell tests with nitrate, 63 met this threshold, but the SA-determined DGel ranged from 10.1 to 15.8 × 10-6 cm2·s-1 (agarose) and 9.5 to 14.7 × 10-6 cm2·s-1 (APA). A regression model developed with the SA to account for the diffusive boundary layer had 95% confidence intervals (CIs) on DGel of 13 to 18 × 10-6 cm2·s-1 (agarose) and 12 to 19 × 10-6 cm2·s-1 (APA) at 500 rpm. A finite difference model (FDM) developed based on Fick's second law with non-steady-state (N-SS) flux decreased uncertainty in DGel tenfold. The FDM-captured decreasing source compartment concentrations and N-SS flux in the D-Cell tests and, at 500 rpm, the FDM-determined DGel ± 95% CIs were 14.5 ± 0.2 × 10-6 cm2·s-1 (agarose) and 14.0 ± 0.3 × 10-6 cm2·s-1 (APA), respectively.


Assuntos
Monitoramento Ambiental , Poluentes Químicos da Água , Sefarose , Incerteza , Poluentes Químicos da Água/análise , Difusão
10.
Org Lett ; 25(19): 3559-3563, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37154573

RESUMO

Nickel-catalyzed isomerizations of homoallylic alcohols and a bishomoallylic alcohol are presented. These isomerization reactions occur in the presence of a simple nickel catalyst that does not require addition of an exogenous ligand. The corresponding ketone products are generated in ≤98% yield.

11.
Clin Nutr ESPEN ; 55: 434-439, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37202080

RESUMO

BACKGROUND & AIMS: Prolonged length of stay (LOS) and discharge disposition following liver transplantation are associated with postoperative complications and increased healthcare utilization. This study evaluated the relationship between CT-derived psoas muscle measurements and hospital LOS, intensive care unit (ICU) LOS, and discharge disposition after liver transplant. The psoas muscle was chosen given its ease of measurement with any radiological software. A secondary analysis assessed the relationship between the American Society for Parenteral and Enteral Nutrition and the Academy of Nutrition and Dietetics (ASPEN/AND) malnutrition diagnosis criteria and CT-derived psoas muscle measures. METHODS: CT-derived measures of psoas muscle density (mHU) and cross-sectional area at the level of the third lumbar vertebrae were obtained from preoperative CT scans of liver transplant recipients. Cross-sectional area measures were corrected for body size to generate a psoas area index variable (cm2/m2; PAI). RESULTS: Each 1-unit increase in PAI was associated with a reduced hospital LOS of 4 days (R2 = 0.07). Each 5-unit increase in mean Hounsfield units (mHU) was associated with a reduced hospital and ICU LOS of 5 and 1.6 days, respectively (R2 = 0.22 and 0.14, respectively). Mean PAI and mHU were higher in patients who discharged to home. PAI was reasonably identified through ASPEN/AND malnutrition criteria, but there was no difference in mHU between those with and without malnutrition. CONCLUSION: Measures of psoas density were associated with both hospital and ICU LOS and discharge disposition. PAI was associated with hospital LOS and discharge disposition. CT-derived measures of psoas density may be a valuable complement to preoperative liver transplant nutrition assessment using traditional ASPEN/AND malnutrition criteria.


Assuntos
Transplante de Fígado , Desnutrição , Humanos , Estados Unidos , Tempo de Internação , Músculos Psoas/diagnóstico por imagem , Alta do Paciente , Tomografia Computadorizada por Raios X
12.
Cureus ; 15(4): e37442, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37182042

RESUMO

Osteosarcomas are a type of bone cancer that typically affect young adults, often in the bones of the arms and legs. To treat osteosarcoma, doctors typically use a combination of chemotherapy, radiotherapy, and surgery, with External Beam Radiation Therapy (EBRT) being the most commonly used form of radiotherapy. EBRT involves directing high-energy photons, X-rays, gamma rays, protons, and electrons at the tumor to induce cancer cell death. Additionally, healthcare providers use imaging techniques to monitor treatment success. This literature review aims to explore the relationship between osteosarcomas and EBRT, investigate the impact of the delayed diagnosis on survival rates, and examine the effectiveness of innovative uses of EBRT for treating osteosarcomas in unusual locations using comprehensive diagnostic techniques. To achieve these objectives, the review examines case studies and literary analyses and categorizes them based on the delay between symptom onset and diagnosis. The null hypothesis is that the presence or absence of a delay in diagnosis does not significantly impact outcomes for the "Delay" category. A lack of delay results in a more favorable outcome in the "Lack of Delay" category. However, the data and statistical results suggest that additional follow-up care in patients with rare or commonly recurring cancers could benefit outcomes. It is important to note that due to the rarity of osteosarcoma with EBRT, the small sample size in the studies warrants further investigation. Interestingly, many patients presented with head and neck tumors despite the most common location of osteosarcoma being in the long bones.

14.
Cureus ; 15(3): e36438, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37090383

RESUMO

As diabetes mellitus becomes increasingly prevalent globally, so does diabetic nephropathy, a complication leading to one of the world's leading causes of end-stage renal disease (ESRD). Current research has linked an increase in the urine albumin-to-creatinine ratio (UACR), a marker for kidney damage, to a greater risk of adverse renal outcomes and ESRD in patients with diabetes. Of the diabetes medications studied and implemented in clinical settings, glucagon-like peptide-1 receptor agonist (GLP1-RA) drugs have been shown to not only help control HbA1c in diabetes but have also demonstrated numerous cardiovascular, hepatic, and renal benefits. The objective of our study was to assess the efficacy of GLP1-RA drugs in reducing UACR in patients with type 2 diabetes mellitus (T2 DM) to determine if GLP1-RAs could be used to provide renoprotection in diabetic nephropathy in addition to their glucose-lowering effects. Upon a comprehensive review of the literature, we conducted a statistical analysis to determine the efficacy of GLP1-RA monotherapy and combination therapy in reducing UACR in comparison to placebo and insulin glargine. Of the studies analyzed, GLP1-RAs exhibited a statistically significant effect in reducing UACR in comparison to a placebo but not in comparison to insulin glargine. GLP1-RA combination therapy (GLP1-RA used with either insulin glargine, metformin, or dapagliflozin) did not exhibit statistically significant UACR reductions in comparison with insulin glargine. However, GLP1-RA combination therapy showed a trend suggestive of being more effective than insulin glargine in reducing UACR, but due to the limited literature studying this treatment method, further studies in a more focused group of patients with diabetic nephropathy may produce stronger and more definitive results. GLP1-RA monotherapy or combination therapy has been determined to be an effective method for reducing UACR and decreasing the incidence of adverse renal outcomes associated with diabetic kidney disease. GLP1-RA therapy could serve as an alternative treatment in diabetic nephropathy to insulin glargine, which carries a higher risk of hypoglycemia and unintentional weight gain while potentially being less cost-effective.

15.
ACS ES T Water ; 3(2): 576-587, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-37035423

RESUMO

When implementing anion exchange (AEX) for per- and polyfluoroalkyl substances treatment, temporal drinking water quality changes from concurrent inorganic anion (IA) removal can create unintended consequences (e.g., corrosion control impacts). To understand potential effects, four drinking water-relevant IAs (bicarbonate, chloride, sulfate, and nitrate) and three gel-type, strong-base AEX resins were evaluated. Batch binary isotherm experiments provided estimates of IA selectivity with respect to chloride ( K x ∕ C ) for IA/resin combinations where bicarbonate < sulfate ≤ nitrate at studied conditions. A multi-IA batch experiment demonstrated that binary isotherm-determined K x ∕ C values predicted competitive behavior. Subsequent column experiments with and without natural organic matter (NOM) allowed for the validation of a new ion exchange column model (IEX-CM; https://github.com/USEPA/Water_Treatment_Models). IA breakthrough was well-simulated using binary isotherm-determined K x ∕ C values and was minimally impacted by NOM. Initial AEX effluent water quality changes with corrosion implications included increased chloride and decreased sulfate and bicarbonate concentrations, resulting in elevated chloride-to-sulfate mass ratios (CSMRs) and Larson ratios (LRs) and depressed pH until the complete breakthrough of the relevant IA(s). IEX-CM utility was further illustrated by simulating the treatment of low-IA source water and a change in the source water to understand the resulting duration of changes in IAs and water quality parameters.

16.
J Am Chem Soc ; 145(11): 6230-6239, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36892967

RESUMO

The library of imine-linked covalent organic frameworks (COFs) has grown significantly over the last two decades, featuring a variety of morphologies, pore sizes, and applications. An array of synthetic methods has been developed to expand the scope of the COF functionalities; however, most of these methods were designed to introduce functional scaffolds tailored to a specific application. Having a general approach to diversify COFs via late-stage incorporation of functional group handles would greatly facilitate the transformation of these materials into platforms for a variety of useful applications. Herein, we report a general strategy to introduce functional group handles in COFs via the Ugi multicomponent reaction. To demonstrate the versatility of this approach, we have synthesized two COFs with hexagonal and kagome morphologies. We then introduced azide, alkyne, and vinyl functional groups, which could be readily utilized for a variety of post-synthetic modifications. This facile approach enables the functionalization of any COFs containing imine linkages.

17.
Clinics (Sao Paulo) ; 78: 100167, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36738645

RESUMO

OBJECTIVE: To assess factors associated with emotional changes and Hyperactivity/Inattention (HI) motivated by COVID-19 quarantine in adolescents with immunocompromising diseases. METHODS: A cross-sectional study included 343 adolescents with immunocompromising diseases and 108 healthy adolescents. Online questionnaires were answered including socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and validated surveys: Strengths and Difficulties Questionnaire (SDQ), Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0). RESULTS: The frequencies of abnormal emotional SDQ scores from adolescents with chronic diseases were similar to those of healthy subjects (110/343 [32%] vs. 38/108 [35%], p = 0.548), as well as abnormal hyperactivity/inattention SDQ scores (79/343 [23%] vs. 29/108 [27%], p = 0.417). Logistic regression analysis of independent variables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio [OR = 3.76]; 95% Confidence Interval (95% CI) 2.00‒7.05; p < 0.001), poor sleep quality (OR = 2.05; 95% CI 1.08‒3.88; p = 0.028) and intrafamilial violence during pandemic (OR = 2.17; 95% CI 1.12‒4.19; p = 0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR = 0.95; 95% CI 0.93‒0.96; p < 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR = 0.97; 95% CI 0.95‒0.99; p = 0.010], changes in medical appointments during the pandemic (OR = 0.39; 95% CI 0.19-0.79; p = 0.021), and reliable COVID-19 information (OR = 0.35; 95% CI 0.16‒0.77; p = 0.026) remained inversely associated with abnormal HI scores. CONCLUSION: The present study showed emotional and HI disturbances in adolescents with chronic immunosuppressive diseases during the COVID-19 pandemic. It reinforces the need to promptly implement a longitudinal program to protect the mental health of adolescents with and without chronic illnesses during future pandemics.


Assuntos
Atenção , COVID-19 , Doenças do Sistema Imunitário , Transtornos Mentais , Adolescente , Criança , Feminino , Humanos , Estudos Transversais , Transtornos Mentais/epidemiologia , Pandemias , Qualidade de Vida , Inquéritos e Questionários , Emoções , Doenças do Sistema Imunitário/psicologia , Doença Crônica
18.
bioRxiv ; 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36711980

RESUMO

While specific cell signaling pathway inhibitors have yielded great success in oncology, directly triggering cancer cell death is one of the great drug discovery challenges facing biomedical research in the era of precision oncology. Attempts to eradicate cancer cells expressing unique target proteins, such as antibody-drug conjugates (ADCs), T-cell engaging therapies, and radiopharmaceuticals have been successful in the clinic, but they are limited by the number of targets given the inability to target intracellular proteins. More recently, heterobifunctional small molecules such as Proteolysis Targeting Chimera (PROTACs) have paved the way for protein proximity inducing therapeutic modalities. Here, we describe a proof-of-concept study using novel heterobifunctional small molecules called Regulated Induced Proximity Targeting Chimeras or RIPTACs, which elicit a stable ternary complex between a target protein selectively expressed in cancer tissue and a pan-expressed protein essential for cell survival. The resulting cooperative protein:protein interaction (PPI) abrogates the function of the essential protein, thus leading to cell death selectively in cells expressing the target protein. This approach not only opens new target space by leveraging differentially expressed intracellular proteins but also has the advantage of not requiring the target to be a driver of disease. Thus, RIPTACs can address non-target mechanisms of resistance given that cell killing is driven by inactivation of the essential protein. Using the HaloTag7-FKBP model system as a target protein, we describe RIPTACs that incorporate a covalent or non-covalent target ligand connected via a linker to effector ligands such as JQ1 (BRD4), BI2536 (PLK1), or multi-CDK inhibitors such as TMX3013 or dinaciclib. We show that these RIPTACs exhibit positive co-operativity, accumulate selectively in cells expressing HaloTag7-FKBP, form stable target:RIPTAC:effector trimers in cells, and induce an anti-proliferative response in target-expressing cells. We propose that RIPTACs are a novel heterobifunctional therapeutic modality to treat cancers that are known to selectively express a specific intracellular protein.

19.
Clinics ; 78: 100167, 2023. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1421251

RESUMO

Abstract Objective: To assess factors associated with emotional changes and Hyperactivity/Inattention (HI) motivated by COVID-19 quarantine in adolescents with immunocompromising diseases. Methods: A cross-sectional study included 343 adolescents with immunocompromising diseases and 108 healthy adolescents. Online questionnaires were answered including socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and validated surveys: Strengths and Difficulties Questionnaire (SDQ), Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0). Results: The frequencies of abnormal emotional SDQ scores from adolescents with chronic diseases were similar to those of healthy subjects (110/343 [32%] vs. 38/108 [35%], p = 0.548), as well as abnormal hyperactivity/inattention SDQ scores (79/343 [23%] vs. 29/108 [27%], p = 0.417). Logistic regression analysis of independent variables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio [OR = 3.76]; 95% Confidence Interval (95% CI) 2.00-7.05; p < 0.001), poor sleep quality (OR = 2.05; 95% CI 1.08-3.88; p = 0.028) and intrafamilial violence during pandemic (OR = 2.17; 95% CI 1.12-4.19; p = 0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR = 0.95; 95% CI 0.93-0.96; p < 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR = 0.97; 95% CI 0.95-0.99; p = 0.010], changes in medical appointments during the pandemic (OR = 0.39; 95% CI 0.19-0.79; p = 0.021), and reliable COVID-19 information (OR = 0.35; 95% CI 0.16-0.77; p = 0.026) remained inversely associated with abnormal HI scores. Conclusion: The present study showed emotional and HI disturbances in adolescents with chronic immunosuppressive diseases during the COVID-19 pandemic. It reinforces the need to promptly implement a longitudinal program to protect the mental health of adolescents with and without chronic illnesses during future pandemics.

20.
ACS ES T Water ; 3(12): 3967-3979, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38304618

RESUMO

Selectivity with respect to chloride (KPFAS∕C) was determined for nine drinking water relevant perfluoroalkyl and polyfluoroalkyl substances (PFAS): perfluoro-2-propoxypropanoic acid (GenX), five perfluoroalkyl carboxylic acids (PFCAs), and three perfluoroalkyl sulfonic acids (PFSAs). Three single-use strong base anion exchange gel resins were investigated, targeting drinking water relevant equilibrium PFAS liquid concentrations (≤500 ng/L). Except for the longest carbon chain PFCA (perfluorodecanoic acid) and PFSA (perfluorooctanesulfonic acid) studied, PFAS followed traditional ion exchange theory (law of mass action), including increasing equilibrium PFAS liquid concentrations with increasing equilibrium chloride liquid concentrations. Overall, KPFAS∕C values were (i) similar among resins for a given PFAS, (ii) 1-5 orders of magnitude greater than the selectivity of inorganic anions (e.g., nitrate) previously studied, (iii) 2 orders of magnitude greater for the same carbon chain length PFSA versus PFCA, (iv) found to proportionally increase with carbon chain length for both PFSAs and PFCAs, and (v) similar for GenX and perfluorohexanoic acid (six-carbon PFCA). A multisolute competition experiment demonstrated binary isotherm-determined KPFAS∕C values could be applied to simulate a multisolute system, extending work previously done with only inorganic anions to PFAS. Ultimately, estimated KPFAS∕C values allow future extension and validation of an open-source anion exchange column model to PFAS.

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