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2.
ACS Earth Space Chem ; 8(8): 1609-1622, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39166261

RESUMEN

Variable wind speeds over the ocean can have a significant impact on the formation mechanism and physical-chemical properties of sea spray aerosols (SSA), which in turn influence their climate-relevant impacts. Herein, for the first time, we investigate the effects of wind speed on size-dependent morphology and composition of individual nascent SSA generated from wind-wave interactions of natural seawater within a wind-wave channel as a function of size and their particle-to-particle variability. Filter-based thermal optical analysis, atomic force microscopy (AFM), AFM infrared spectroscopy (AFM-IR), and scanning electron microscopy (SEM) were employed in this regard. This study focuses on SSA with sizes within 0.04-1.8 µm generated at two wind speeds: 10 m/s, representing a wind lull scenario over the ocean, and 19 m/s, indicative of the wind speeds encountered in stormy conditions. Filter-based measurements revealed a reduction of the organic mass fraction as the wind speed increases. AFM imaging at 20% relative humidity of individual SSA identified six main morphologies: prism-like, rounded, core-shell, rod, rod inclusion core-shell, and aggregates. At 10 m/s, most SSA were rounded, while at 19 m/s, core-shells became predominant. Based on AFM-IR, rounded SSA at both wind speeds had similar composition, mainly composed of aliphatic and oxygenated species, whereas the shells of core-shells displayed more oxygenated organics at 19 m/s and more aliphatic organics at 10 m/s. Collectively, our observations can be attributed to the disruption of the sea surface microlayer film structure at higher wind speeds. The findings reveal a significant impact of wind speed on morphology and composition of SSA, which should be accounted for accurate assessment of their climate effects.

3.
J Med Entomol ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39158078

RESUMEN

Malaria was once endemic in the United States prior to its elimination in 1951. However, due to consistent introductions of travel-associated malaria cases and the presence of several native Anopheles species (Diptera: Culicidae) that are competent vectors of malaria, the potential for local (autochthonous) malaria transmission remains a persistent threat in the United States. While several intermittent cases of local malaria transmission have occurred in the United States in the decades since elimination, the emergence of autochthonous transmission in 4 states in 2023 demonstrates the continued risk for future outbreaks. Moreover, these recent examples also highlight significant gaps in current mosquito surveillance efforts that have predominantly focused on threats of arboviral disease, such that our understanding of Anopheles distributions relies only on historical records and offers limited insight into the ecological factors that influence their abundance. Herein, we summarize mosquito surveillance data collected over the last 20 years (2004-2023) across 59 Iowa counties to provide essential information into the spatial distribution, temporal abundance, and trap preferences of Anopheles species in the state. Further analyses of the 2 most abundant species, Anopheles punctipennis Say and Anopheles quadrimaculatus Say, reveal the additional influence of precipitation and forested habitats in defining An. punctipennis abundance. Together, we believe these results provide an increased understanding of previously neglected Anopheles species that have the potential for autochthonous malaria transmission in Iowa and that can be extended to other regions of the United States to enhance preparedness for future malaria outbreaks.

4.
Adv Mater ; : e2408271, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39177115

RESUMEN

Radicals, with their unpaired electrons, exhibit unique chemical and physical properties that have long intrigued chemists. Despite early skepticism about their stability, the discovery of persistent radicals has opened new possibilities for molecular interactions. This review examines the mechanisms and applications of radically driven self-assembly, focusing on key motifs such as naphthalene diimides, tetrathiafulvalenes, and viologens, which serve as models for radical assembly. The potential of radical interactions in the development of artificial molecular machines (AMMs) are also discussed. These AMMs, powered by radical-radical interactions, represent significant advancements in non-equilibrium chemistry, mimicking the functionalities of biological systems. From molecular switches to ratchets and pumps, the versatility and unique properties of radically powered AMMs are highlighted. Additionally, the applications of radical assembly in materials science are explored, particularly in creating smart materials with redox-responsive properties. The review concludes by comparing AMMs to biological molecular machines, offering insights into future directions. This overview underscores the impact of radical chemistry on molecular assembly and its promising applications in both synthetic and biological systems.

5.
Front Microbiol ; 15: 1437579, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39119141

RESUMEN

Small GTPases of the Rab family coordinate multiple membrane fusion and trafficking events in eukaryotes. In fungi, the Rab GTPase, Ypt7, plays a critical role in late endosomal trafficking, and is required for homotypic fusion events in vacuole biogenesis and inheritance. In this study, we identified a putative YPT7 homologue in Cryptococcus neoformans, a fungal pathogen causing life threatening meningoencephalitis in immunocompromised individuals. As part of an ongoing effort to understand mechanisms of iron acquisition in C. neoformans, we established a role for Ypt7 in growth on heme as the sole iron source. Deletion of YPT7 also caused abnormal vacuolar morphology, defective endocytic trafficking and autophagy, and mislocalization of Aph1, a secreted vacuolar acid phosphatase. Ypt7 localized to the vacuolar membrane and membrane contact sites between the vacuole and mitochondria (vCLAMPs), and loss of the protein impaired growth on inhibitors of the electron transport chain. Additionally, Ypt7 was required for robust growth at 39°C, a phenotype likely involving the calcineurin signaling pathway because ypt7 mutants displayed increased susceptibility to the calcineurin-specific inhibitors, FK506 and cyclosporin A; the mutants also had impaired growth in either limiting or high levels of calcium. Finally, Ypt7 was required for survival during interactions with macrophages, and ypt7 mutants were attenuated for virulence in a mouse inhalation model thus demonstrating the importance of membrane trafficking functions in cryptococcosis.

6.
Front Cell Infect Microbiol ; 14: 1448229, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39193507

RESUMEN

The basidiomycete fungus Cryptococcus neoformans is a useful model for investigating mechanisms of fungal pathogenesis in mammalian hosts. This pathogen is the causative agent of cryptococcal meningitis in immunocompromised patients and is in the critical priority group of the World Health Organization fungal priority pathogens list. In this study, we employed a mutant lacking the OPI3 gene encoding a methylene-fatty-acyl-phospholipid synthase to characterize the role of phosphatidylcholine (PC) and lipid homeostasis in the virulence of C. neoformans. We first confirmed that OPI3 was required for growth in nutrient limiting conditions, a phenotype that could be rescued with exogenous choline and PC. Additionally, we established that loss of Opi3 and the lack of PC lead to an accumulation of neutral lipids in lipid droplets and alterations in major lipid classes. The growth defect of the opi3Δ mutant was also rescued by sorbitol and polyethylene glycol (PEG), a result consistent with protection of ER function from the stress caused by lipid imbalance. We then examined the impact of Opi3 on virulence and found that the dependence of PC synthesis on Opi3 caused reduced capsule size and this was accompanied by an increase in shed capsule polysaccharide and changes in cell wall composition. Further tests of virulence demonstrated that survival in alveolar macrophages and the ability to cause disease in mice were not impacted by loss of Opi3 despite the choline auxotrophy of the mutant in vitro. Overall, this work establishes the contribution of lipid balance to virulence factor elaboration by C. neoformans and suggests that host choline is sufficient to support proliferation during disease.


Asunto(s)
Criptococosis , Cryptococcus neoformans , Modelos Animales de Enfermedad , Cryptococcus neoformans/patogenicidad , Cryptococcus neoformans/genética , Cryptococcus neoformans/metabolismo , Cryptococcus neoformans/crecimiento & desarrollo , Animales , Virulencia , Criptococosis/microbiología , Ratones , Metabolismo de los Lípidos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fosfatidilcolinas/metabolismo , Factores de Virulencia/genética , Factores de Virulencia/metabolismo , Cápsulas Fúngicas/metabolismo , Cápsulas Fúngicas/genética , Pared Celular/metabolismo , Colina/metabolismo , Femenino , Gotas Lipídicas/metabolismo
8.
Front Neurol ; 15: 1430989, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39144714

RESUMEN

Introduction: The relationships between the feeding rhythm, sleep and cognition in Alzheimer's disease (AD) are incompletely understood, but meal time could provide an easy-to-implement method of curtailing disease-associated disruptions in sleep and cognition. Furthermore, known sex differences in AD incidence could relate to sex differences in circadian rhythm/sleep/cognition interactions. Methods: The 5xFAD transgenic mouse model of AD and non-transgenic wild-type controls were studied. Both female and male mice were used. Food access was restricted each day to either the 12-h light phase (light-fed groups) or the 12-h dark phase (dark-fed groups). Sleep (electroencephalographic/electromyographic) recording and cognitive behavior measures were collected. Results: The 5xFAD genotype reduces NREM and REM as well as the number of sleep spindles. In wild-type mice, light-fed groups had disrupted vigilance state amounts, characteristics, and rhythms relative to dark-fed groups. These feeding time differences were reduced in 5xFAD mice. Sex modulates these effects. 5xFAD mice display poorer spatial memory that, in female mice, is curtailed by dark phase feeding. Similarly, female 5xFAD mice have decreased anxiety-associated behavior. These emotional and cognitive measures are correlated with REM amount. Discussion: Our study demonstrates that the timing of feeding can alter many aspects of wake, NREM and REM. Unexpectedly, 5xFAD mice are less sensitive to these feeding time effects. 5xFAD mice demonstrate deficits in cognition which are correlated with REM, suggesting that this circadian-timed aspect of sleep may link feeding time and cognition. Sex plays an important role in regulating the impact of feeding time on sleep and cognition in both wild-type and 5xFAD mice, with females showing a greater cognitive response to feeding time than males.

9.
Artículo en Inglés | MEDLINE | ID: mdl-39018661

RESUMEN

BACKGROUND: Femoral fractures in children have the highest probability for abuse after skull fractures and humeral shaft fractures. However, the reported proportion of pediatric femur fractures that result from nonaccidental trauma (NAT) varies in the literature from 2% to 60%. The purpose of this study was to determine the patient characteristics associated with a physician's decision to conduct a NAT workup and challenge universal clinical practice guidelines stating that all children younger than 3 years with a diaphyseal femur fracture be evaluated for NAT. METHODS: A retrospective review was conducted on patients aged 0 to 36 months diagnosed with a femur fracture between January 1, 2004, and April 9, 2019, at our institution. NAT was defined as a diagnosis of trauma that was nonaccidental in the medical chart after a positive workup by skeletal survey, ophthalmological examination, or other appropriate referral made by the institution's child abuse and neglect team. Patients with incomplete medical records were excluded. RESULTS: A total of 299 patients were identified, and 22 were excluded. 71% (197/277) were screened for NAT. Patients younger than 1 year were significantly more likely to undergo a NAT workup (P = 0.009; Odds Ratio [OR], 2.3; 95% CI, 1.2 to 4.4) and receive a positive result from the NAT workup (P < 0.0005; OR, 11.3; 95% CI, 4.6 to 27.4). Additional injuries were also a significant predictor of a positive NAT workup (P < 0.001; OR, 5.3; 95% CI, 2.4 to 11.9). Patient race/ethnicity, sex, and fracture type were not markedly associated with the physician's decision to conduct a NAT workup. CONCLUSIONS: Infants younger than 1 year with a femur fracture and children younger than 3 years presenting with a femur fracture and another injury are at increased risk of possible NAT. While clinical practice guidelines may minimize racial bias in NAT evaluation, this study demonstrates that universal NAT workups for walking-age children in the absence of other evidence of abuse may be unnecessary. LEVEL OF EVIDENCE: This is a Level III retrospective cohort study.

10.
Methods Enzymol ; 701: 387-424, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39025577

RESUMEN

The Helfrich free energy is widely used to model the generation of membrane curvature due to different physical and chemical components. The governing equations resulting from the energy minimization procedure are a system of coupled higher order partial differential equations. Simulations of membrane deformation for obtaining quantitative comparisons against experimental observations require computational schemes that will allow us to solve these equations without restrictions to axisymmetric coordinates. Here, we describe one such tool that we developed in our group based on discrete differential geometry to solve these equations along with examples.


Asunto(s)
Proteínas de la Membrana , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/química , Membrana Celular/metabolismo , Membrana Celular/química , Modelos Biológicos , Termodinámica , Simulación por Computador , Membrana Dobles de Lípidos/química , Membrana Dobles de Lípidos/metabolismo
11.
Retina ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39028983

RESUMEN

PURPOSE: This retrospective case series aimed to assess the concordance between clinical diagnoses of punctate inner choroidopathy (PIC) and multifocal choroiditis and panuveitis (MCP) using the 2021 Standardization of Uveitis Nomenclature (SUN) Working Group criteria. METHODS: Using the medical records of the patients, we reevaluated 100 eyes of 75 patients with idiopathic multifocal chorioretinal inflammatory lesions based on SUN criteria and compared the result to the clinical diagnosis. RESULTS: Of 100 eyes, 29 eyes (29%) were diagnosed as PIC and 15 eyes (15%) were diagnosed as MCP using SUN criteria, and 56 (56%) eyes could not be diagnosed as either. Clinically diagnosed PIC eyes were significantly more myopic than the clinically diagnosed MCP eyes (mean spherical equivalent -6.65 ± 4.63 vs. -3.85 ± 2.31, P = 0.01). Sixteen eyes with vitreous inflammation were all clinically diagnosed as MCP, but four (25%) could not be diagnosed as MCP using SUN criteria. CONCLUSIONS: The existing diagnostic criteria showed limitations in capturing all clinical cases of PIC or MCP, and adding or revising criteria on features such as vitreous inflammation or myopia, could be considered to enhance diagnostic accuracy.

12.
Artículo en Inglés | MEDLINE | ID: mdl-39029448

RESUMEN

INTRODUCTION: Distal femur fractures are complex injuries that often present with multiple fragments, posing notable challenges to fixation. This study aimed to (1) use preoperative CT scans to graphically display fracture lines in intra-articular distal femur fractures and (2) identify common fracture patterns in these injuries. METHODS: All skeletally mature patients that underwent surgical fixation of Orthopaedic Trauma Association type 33C distal femur fractures between 2012 and 2022 were identified across two level 1 trauma centers (n = 63). Preoperative axial, sagittal, and coronal computed tomography scans were obtained. Fracture lines in each plane were traced out and superimposed on standardized distal femur cross-sections, generating a fracture map for each plane. Injury and fracture characteristics were summarized and compared between fracture patterns. RESULTS: On axial scans, 59 of 63 fractures contained a central intercondylar split from the intercondylar notch to the trochlea. On coronal scans, fracture lines originated at the notch and exited laterally and medially in the supracondylar region, creating a Y-shape. One-third of all fractures contained coronal fracture lines, with most involving the lateral condyle. Based on fracture line orientation and location, fractures were divided into four main fracture pattern types. Type 4 fractures (central split and medial coronal fracture line) were associated with lower average medial fracture height and a lower rate of medial metaphyseal comminution. DISCUSSION: We found that C-type distal femur fractures can present with four main fracture patterns. Most fractures contain a central sagittal intercondylar split, and a high proportion of fractures contain either medial or lateral coronal fracture lines. Fracture pattern was associated with mechanism of injury, presence of medial comminution, and medial fracture line height. Future studies should focus on clinical outcomes and surgical management of these distinct fracture patterns. LEVEL OF EVIDENCE: IV.

13.
Int J Audiol ; : 1-7, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39030727

RESUMEN

OBJECTIVE: To determine the prevalence and characteristics of problematic tinnitus in a representative United States (US) sample. DESIGN: Cross-sectional study of the NHANES database from 2011-2012 and 2015-2016. STUDY SAMPLE: 8029 records were included for analysis. RESULTS: The prevalence of any tinnitus was 16.32%. Only 1.38% reported tinnitus as a big problem or worse. Univariate analysis revealed a statistically significant relationship between tinnitus constancy and duration with severity, where more constant perception and longer duration was related to increased severity (p < 0.0001). Multivariable models showed a clear relationship of increased odds ratio (OR) of problematic tinnitus with constancy of tinnitus but not duration. Furthermore, multivariable models showed higher Body Mass Index (OR= 1.013, 95% CI: 0.99-1.03), sleep trouble (OR = 2.016, 95% CI: 1.52-2.66) and comorbidities (OR = 1.43, 95%CI: 1.06-1.94) were all associated with increased problematic tinnitus, but not non-problematic tinnitus. CONCLUSIONS: Our study demonstrated that the prevalence of problematic tinnitus is much lower than the prevalence of any tinnitus. There was also a relationship between BMI, sleep trouble, other comorbidities and increased odds of problematic tinnitus. Tinnitus severity was significantly related to constancy of perception but had a less clear relationship to duration.

15.
Korean J Ophthalmol ; 38(4): 304-315, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39013560

RESUMEN

PURPOSE: This study aimed to determine the incidence and visual outcomes of pachychoroid neovasculopathy (PNV) in patients initially diagnosed with central serous chorioretinopathy (CSC). METHODS: In this study, 144 patients aged 20 to 55 years with treatment-naive chronic CSC, defined as the persistence of subretinal fluid (SRF) for ≥6 months, were retrospectively enrolled. Patients with PNV at the initial evaluation were categorized as group 1, whereas those who developed new-onset PNV during follow-up were categorized as group 2. Patients without PNV until the end of the follow-up were categorized as group 3. RESULTS: Over a mean follow-up period of 49.9 ± 39.9 months, new-onset PNV was diagnosed in 11.8% of patients with CSC. The time taken to reach the initial resolution was longest in group 1 (group 1, 11.13 ± 10.70 months; group 2, 8.14 ± 7.90 months; group 3, 7.32 ± 9.55 months), although these differences were not statistically significant. The numbers of injections needed to achieve initial resolution were 3.76 ± 5.90, 1.64 ± 2.06, and 1.74 ± 4.33 in groups 1, 2, and 3, respectively, with no significant differences. SRF recurrence was recorded in seven patients (29.2%) in group 1, nine (64.3%) in group 2, and 28 (26.7%) in group 3. The recurrence rates were significantly higher in group 2 than those in group 1 or 3. At the end of the follow-up period, significant improvements in best-corrected visual acuity were achieved in groups 1 and 3, compared with baseline, but not in group 2. CONCLUSIONS: Patients with chronic CSC with new-onset PNV exhibited higher SRF recurrence and worse visual outcomes compared to those with initial PNV or those with chronic CSC without PNV. Our study emphasizes the importance of routine screening for prompt diagnoses of new-onset PNV in individuals with chronic CSC.


Asunto(s)
Coriorretinopatía Serosa Central , Angiografía con Fluoresceína , Fondo de Ojo , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Coriorretinopatía Serosa Central/diagnóstico , Coriorretinopatía Serosa Central/complicaciones , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Angiografía con Fluoresceína/métodos , Estudios de Seguimiento , Adulto Joven , Neovascularización Coroidal/diagnóstico , Incidencia , Líquido Subretiniano , Coroides/irrigación sanguínea , Coroides/patología
16.
Anal Chem ; 96(31): 12901-12907, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39047064

RESUMEN

Online mass spectrometry techniques, such as extractive electrospray ionization mass spectrometry (EESI-MS), present an attractive alternative for analyzing aerosol molecular composition due to reduced aerosol sample collection and handling times and improved time resolution. Recent studies show a dependence of EESI-MS sensitivity on particle size and mixing state. This study measured authentic sea spray aerosol (SSA) components generated during a phytoplankton bloom, specifically glycerol, palmitic acid, and potassium ions. We demonstrate temporal variability and trends dependent on specific biological processes occurring in seawater. We found that the EESI-MS sensitivity, after adjusting for pressure variations at the inlet and normalizing to the reagent ion, critically depends on the sample's relative humidity. Relevant SSA species exhibited heightened sensitivity at an elevated relative humidity near the deliquescence relative humidity of sea salt and poorer sensitivity with sparse detection below the efflorescence relative humidity. Modeling the reagent ion's diffusive depth demonstrates that the sample aerosol particle viscosity governs the relative humidity dependence because it modulates the particle's coagulation efficiency and distance the reagent ion diffuses and reacts with components in the particle bulk. The effects of particle size and mixing state are discussed, revealing improved sensitivity of phase-separated components present along the particle surface. This work highlights the importance of the particle phase state in detecting and quantifying molecular components within authentic and complex aerosol particles and the utility of EESI-MS for measuring SSA composition.

17.
J Orthop Trauma ; 38(8): 435-440, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39007660

RESUMEN

OBJECTIVES: To assess the biomechanical differences between linked and unlinked constructs in young and osteoporotic cadavers in addition to osteoporotic sawbones. METHODS: Intraarticular distal femur fractures with comminuted metaphyseal regions were created in three young matched pair cadavers, three osteoporotic matched pair cadavers, and six osteoporotic sawbones. Precontoured distal femur locking plates were placed in addition to a standardized retrograde nail, with unitized constructs having one 4.5 mm locking screw placed distally through the nail. Nonunitized constructs had seven 4.5 mm locking screws placed through the plate around the nail, with one 5 mm distal interlock placed through the nail alone. Cadaveric specimens were subjected to axial fatigue loads between 150 and 1500 N (R Ratio = 10) with 1 Hx frequency for 10,000 cycles. Sawbones were axially loaded at 50% of the ultimate load for fatigue testing to achieve runout, with testing performed with 30 and 300 N (R Ratio = 10) loads with 1 Hz frequency for 10,000 cycles. RESULTS: In young cadavers, there was no difference in the mean cyclic displacement of the unitized constructs (1.51 ± 0.62mm) compared to the non-unitized constructs (1.34 ± 0.47mm) (Figure 4A), (p = 0.722). In osteoporotic cadavers, there was no difference in the mean cyclic displacement of the unitized constructs (2.46 ± 0.47mm) compared to the non-unitized constructs (2.91 ± 1.49mm) (p =0.639). There was statistically no significant difference in cyclic displacement between the unitized and non-unitized groups in osteoporotic sawbones(p = 0.181). CONCLUSIONS: Linked constructs did not demonstrate increased axial stiffness or decreased cyclical displacement in comparison to unlinked constructs in young cadaveric specimens, osteoporotic cadaveric specimens, or osteoporotic sawbones.


Asunto(s)
Clavos Ortopédicos , Placas Óseas , Cadáver , Fracturas del Fémur , Humanos , Fracturas del Fémur/cirugía , Fracturas del Fémur/fisiopatología , Anciano , Femenino , Anciano de 80 o más Años , Fenómenos Biomecánicos , Masculino , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Adulto , Persona de Mediana Edad , Estrés Mecánico , Osteoporosis/complicaciones , Fracturas Femorales Distales
18.
Am J Ophthalmol ; 267: 142-152, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38977151

RESUMEN

PURPOSE: To compare the incidence of noninfectious uveitis in skin melanoma or lung cancer patients who received BRAF inhibitors with that in those who received immune checkpoint inhibitors (ICIs) or conventional cytotoxic chemotherapy. DESIGN: Nationwide population-based retrospective clinical cohort study METHODS: From the Health Insurance Review and Assessment Service database of South Korea, we retrospectively defined 77,323 patients with skin melanoma or lung cancer who received BRAF inhibitor therapy (BRAF inhibitor-exposed group; n = 396), ICIs (ICI-exposed group; n = 22,474), or conventional cytotoxic chemotherapy (unexposed group; n = 54,453). We calculated the 1-year cumulative incidence of noninfectious uveitis in each group from the first day of BRAF inhibitor, ICI, or cytotoxic agent administration. RESULTS: During the first year of treatment initiation, the cumulative incidence of uveitis was 0.33%, 0.35%, and 2.27% in the unexposed, ICI-exposed, and BRAF inhibitor-exposed groups, respectively. Adjusted hazard ratios (aHR) indicated a 7.52-fold and 5.68-fold increased risk of uveitis in the BRAF inhibitor-exposed group compared with that in the unexposed and ICI-exposed groups (95% confidence interval [CI] 3.83-14.75, P < .001 and 95% CI 2.81-11.47, P < .001, respectively). After 1:4 propensity score matching, aHRs showed a 35.51-fold and 15.80-fold increased risk (95% CI 4.49-280.48, P = .001 and 95% CI 1.76-141.00, P = .014) of uveitis and severe uveitis, respectively, in the BRAF inhibitor-exposed versus unexposed patients. Crossover analysis within the BRAF inhibitor-exposed group showed a 3.71-fold increase in uveitis risk during 1-year post index date in comparison with 1-year prior to index date (95% CI 1.03-13.40, P = .046). In the BRAF inhibitor-exposed group, female sex, chronic kidney disease, and melanoma were associated with a trend of increased, albeit nonsignificant, risk of uveitis. CONCLUSIONS: Melanoma or lung cancer patients treated with BRAF inhibitors showed significantly higher risk of noninfectious uveitis than patients treated with conventional cytotoxic drugs or ICIs. These findings emphasize the importance of pretreatment patient education on BRAF-inhibitor-associated uveitis risk to enable prompt ophthalmic evaluation and treatment if symptoms arise during drug administration.

20.
Am J Clin Nutr ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38914225

RESUMEN

BACKGROUND: In Mexico, anemia prevalence among women of reproductive age (WRA) decreased from 16.4% in 2006 to 11.6% in 2012, only to increase to 18.3% in 2016. The factors associated with this fluctuation are uncertain. OBJECTIVE: We conducted a systematic in-depth assessment of the quantitative and qualitative determinants of anemia among WRA in Mexico between 2006 and 2018. METHODS: Using multivariate stepwise linear regression, we analyzed Mexico's Encuesta Nacional de Salud y Nutrición (ENSANUT) surveys from 2006, 2012, and 2018 to identify determinants of WRA anemia. We also conducted a review of anemia-relevant programs and policies, including financing documents, and conducted in-depth interviews and focus group discussions with key stakeholders in Mexico. RESULTS: Among non-pregnant women (NPW) 15-49 years, mean hemoglobin (Hb) increased from 13.8 g/dL in 2006 to 14.0 g/dL in 2012, decreasing to 13.2 g/dL in 2018 (p<0.001). Inequities by geographical region and household wealth persisted throughout this period, with household wealth, urban residence and gravidity emerging as significant predictors of Hb among NPW. Qualitative analyses generally supported these findings. The most discussed program was Progresa-Oportunidades-Prospera (POP), where most resources for health were invested and most participants acknowledged that its cancellation in 2019 would lead to worsening in health and nutrition among the poor. Financing analyses showed a drop of funding for nutrition-related programs between 2014 and 2018. Cultural norms around gender roles were still prevalent, along with increasing rates of teenage pregnancy. CONCLUSIONS: Anemia prevention efforts need to refocus on poverty alleviation, continuity of adequate coverage and financing of nutrition programs, especially with safety nets, and increase in uptake of family planning, especially among adolescent girls.

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