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1.
Methods Mol Biol ; 2775: 211-221, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38758320

RESUMEN

The ability of C. neoformans to survive and replicate within host phagocytes enables it to evade the immune system and allows for persistence of the infection. As such, measuring fungal burden of C. neoformans strains-and indeed how drug treatments can influence fungal burden-provides important information about C. neoformans pathogenesis. In this chapter, we describe two methods that may be used to appraise fungal burden: a standard end-point colony-formation assay for calculating the average number of yeast per host cell and a fluorescence microscopy-based method that may be used to measure changes in fungal burden in individual living macrophages in real time.


Asunto(s)
Criptococosis , Cryptococcus neoformans , Macrófagos , Microscopía Fluorescente , Macrófagos/microbiología , Macrófagos/inmunología , Macrófagos/metabolismo , Criptococosis/microbiología , Criptococosis/inmunología , Microscopía Fluorescente/métodos , Animales , Ratones , Recuento de Colonia Microbiana/métodos , Humanos
2.
Methods Mol Biol ; 2775: 225-237, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38758321

RESUMEN

The polysaccharide capsule of Cryptococcus neoformans is the primary virulence factor and one of the most commonly studied aspects of this pathogenic yeast. Capsule size varies widely between strains, has the ability to grow rapidly when introduced to stressful or low-nutrient conditions, and has been positively correlated with strain virulence. For these reasons, the size of the capsule is of great interest to C. neoformans researchers. Inducing the growth of the C. neoformans capsule is used during phenotypic testing to help understand the effects of different treatments on the yeast or size differences between strains. Here, we describe one of the standard methods of capsule induction and detail two accepted methods of staining: (i) India ink, a negative stain, used in conjunction with conventional light microscopy and (ii) co-staining with fluorescent dyes of both the cell wall and capsule followed by confocal microscopy. Finally, we outline how to measure capsule diameter manually and offer a protocol for automated diameter measurement of India ink-stained samples using computational image analysis.


Asunto(s)
Cryptococcus neoformans , Coloración y Etiquetado , Cryptococcus neoformans/citología , Coloración y Etiquetado/métodos , Microscopía Confocal/métodos , Pared Celular/metabolismo , Pared Celular/ultraestructura , Cápsulas Fúngicas/metabolismo , Procesamiento de Imagen Asistido por Computador/métodos , Colorantes Fluorescentes/química , Carbono
3.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732102

RESUMEN

Cytochrome P450 CYP121A1 is a well-known drug target against Mycobacterium tuberculosis, the human pathogen that causes the deadly disease tuberculosis (TB). CYP121A1 is a unique P450 enzyme because it uses classical and non-classical P450 catalytic processes and has distinct structural features among P450s. However, a detailed investigation of CYP121A1 protein structures in terms of active site cavity dynamics and key amino acids interacting with bound ligands has yet to be undertaken. To address this research knowledge gap, 53 CYP121A1 crystal structures were investigated in this study. Critical amino acids required for CYP121A1's overall activity were identified and highlighted this enzyme's rigid architecture and substrate selectivity. The CYP121A1-fluconazole crystal structure revealed a novel azole drug-P450 binding mode in which azole heme coordination was facilitated by a water molecule. Fragment-based inhibitor approaches revealed that CYP121A1 can be inhibited by molecules that block the substrate channel or by directly interacting with the P450 heme. This study serves as a reference for the precise understanding of CYP121A1 interactions with different ligands and the structure-function analysis of P450 enzymes in general. Our findings provide critical information for the synthesis of more specific CYP121A1 inhibitors and their development as novel anti-TB drugs.


Asunto(s)
Sistema Enzimático del Citocromo P-450 , Mycobacterium tuberculosis , Mycobacterium tuberculosis/enzimología , Mycobacterium tuberculosis/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/metabolismo , Sistema Enzimático del Citocromo P-450/química , Relación Estructura-Actividad , Dominio Catalítico , Antituberculosos/farmacología , Antituberculosos/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/antagonistas & inhibidores , Cristalografía por Rayos X , Inhibidores Enzimáticos del Citocromo P-450/farmacología , Inhibidores Enzimáticos del Citocromo P-450/química , Modelos Moleculares , Humanos , Unión Proteica , Especificidad por Sustrato , Ligandos , Conformación Proteica
4.
BMC Endocr Disord ; 24(1): 59, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693484

RESUMEN

BACKGROUND: The proportion of heart failure patients with preserved ejection fraction has been rising over the past decades and has coincided with increases in the prevalence of obesity and metabolic syndrome. The relationship between these interconnected comorbidities and heart failure with preserved ejection fraction (HFpEF) is still poorly understood. This study characterized obesity and metabolic syndrome among real-world patients with HFpEF. METHODS: We identified adults with heart failure in the Veradigm Cardiology Registry, previously the PINNACLE Registry, with a left ventricular ejection fraction measurement ≥ 50% between 01/01/2016 and 12/31/2019. Patients were stratified by obesity diagnosis and presence of metabolic syndrome (≥ 3 of the following: diabetes, hypertension, hyperlipidemia, and obesity). We captured baseline demographic and clinical characteristics and used multivariable logistic regression to examine the odds of having cardiac (atrial fibrillation, coronary artery disease, coronary artery bypass surgery, myocardial infarction, and stroke/transient ischemic attack) and non-cardiac (chronic kidney disease, chronic liver disease, and peripheral artery disease) comorbidities of interest. The models adjusted for age and sex, and the main covariates of interest were obesity and metabolic burden score (0-3 based on the presence of diabetes, hypertension, and hyperlipidemia). The models were run with and without an obesity*metabolic burden score interaction term. RESULTS: This study included 264,571 patients with HFpEF, of whom 55.7% had obesity, 52.5% had metabolic syndrome, 42.5% had both, and 34.3% had neither. After adjusting for age, sex, and burden of other metabolic syndrome-associated diagnoses, patients with HFpEF with obesity had lower odds of a diagnosis of other evaluated comorbidities relative to patients without obesity. The presence of metabolic syndrome in HFpEF appears to increase comorbidity burden as each additional metabolic syndrome-associated diagnosis was associated with higher odds of assessed comorbidities except atrial fibrillation. CONCLUSION: Obesity was common among patients with HFpEF and not always co-occurring with metabolic syndrome. Multivariable analysis suggested that patients with obesity may develop HFpEF in the absence of other driving factors such as cardiovascular disease or metabolic syndrome.


Asunto(s)
Insuficiencia Cardíaca , Síndrome Metabólico , Obesidad , Sistema de Registros , Volumen Sistólico , Humanos , Síndrome Metabólico/epidemiología , Síndrome Metabólico/complicaciones , Masculino , Femenino , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/fisiopatología , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/etiología , Anciano , Estudios Transversales , Volumen Sistólico/fisiología , Persona de Mediana Edad , Comorbilidad , Anciano de 80 o más Años , Prevalencia , Pronóstico
5.
Artículo en Inglés | MEDLINE | ID: mdl-38710008

RESUMEN

IMPORTANCE: Urinary incontinence is a common postpartum morbidity that negatively affects quality of life. OBJECTIVE: This study aimed to identify factors associated with persistent (ie, 12 months postpartum) bothersome urinary symptoms, including stress urinary incontinence (SUI) and urgency urinary incontinence (UUI), and explore their association with mental health in medically underserved communities. STUDY DESIGN: This was a cross-sectional analysis of a prospective study of individuals enrolled into "extending Maternal Care After Pregnancy," a program providing 12 months of postpartum care to individuals with health disparities. Patients were screened at 12 months for urinary dysfunction, anxiety, and depression using the Urinary Distress Index-6, Generalized Anxiety Disorder-7, and Edinburgh Postnatal Depression Scale, respectively. Bivariate and multivariable logistic regression analyses were performed for at-least-somewhat-bothersome SUI versus no-SUI, UUI versus no-UUI, and for bothersome versus asymptomatic urinary symptoms, using demographic and peripartum and postpartum variables as associated factors. RESULTS: Four hundred nineteen patients provided data at median 12 months postpartum. Patients were 77% Hispanic White and 22% non-Hispanic Black. After multivariable analysis, SUI (n = 136, 32.5%) was significantly associated with increasing body mass index at the time of delivery and greater depression screening scores. Fetal birthweight, mode of delivery, degree of laceration, and breastfeeding status were not associated. Urgency urinary incontinence (n = 69, 16.5%) was significantly associated with increasing parity and higher anxiety screening scores. Similarly, participants with urinary symptom bother had significantly greater parity and higher anxiety screening scores. CONCLUSIONS: At 12 months postpartum, bothersome urinary symptoms and incontinence were quite common. Since these are treatable, postpartum screening for urinary complaints-and associated anxiety and depression-is essential, as is assisting patients in achieving a healthy weight.

6.
Support Care Cancer ; 32(4): 261, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38561508

RESUMEN

PURPOSE: Urban cancer survivors have been shown to have better opportunities for recovery of health and wellbeing than their rural counterparts. Whilst there is a considerable body of evidence that explores urban people with cancers' experiences and outcomes, there is a dearth of research that explicitly explores 'urban cancer survivorship' in its own right. This study aimed to explore cancer survivorship in urban people living with cancer who have completed primary treatment. METHODS: Secondary analysis of in-depth interview data (n = 18) with adults living with cancer who resided in urban parts of the UK. Data were drawn from a broader study on self-management of people living with cancer. An adapted version of Foster and Fenlon's recovery of health and wellbeing in cancer survivorship framework was used to inform the analysis of the data. RESULTS: Recovery of health and wellbeing was impacted by a variety of contributory factors, which had a largely positive impact. Access to amenities, social support, travel, and healthcare factors were opportunities for urban cancer survivors, whilst pollution, traffic and a lack of green spaces acted as challenges for health management. CONCLUSION: This study demonstrated how urban residency acted as both a barrier and a facilitator to recovery of health and wellbeing in urban cancer survivors following the completion of primary treatment. Area of residence should be taken into account by health providers and policymakers supporting cancer survivorship and the views of those with lived experiences should be included in informing future practice.


Asunto(s)
Supervivientes de Cáncer , Neoplasias , Adulto , Humanos , Neoplasias/terapia , Atención a la Salud , Población Rural , Investigación Cualitativa
8.
JAMA Netw Open ; 7(4): e244699, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38568695

RESUMEN

This cohort study evaluates the role that community-level socioeconomic status plays in hypertension-related hospital readmission within 12 weeks after delivery.


Asunto(s)
Readmisión del Paciente , Femenino , Humanos , Periodo Posparto
9.
Cancers (Basel) ; 16(7)2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38611062

RESUMEN

Prostate cancer is a multi-focal disease that can be treated using surgery, radiation, androgen deprivation, and chemotherapy, depending on its presentation. Standard dose-escalated radiation therapy (RT) in the range of 70-80 Gray (GY) is a standard treatment option for prostate cancer. It could be used at different phases of the disease (e.g., as the only primary treatment when the cancer is confined to the prostate gland, combined with other therapies, or as an adjuvant treatment after surgery). Unfortunately, RT for prostate cancer is associated with gastro-intestinal and genitourinary toxicity. We have previously reported that the metabolic modulator lonidamine (LND) produces cancer sensitization through tumor acidification and de-energization in diverse neoplasms. We hypothesized that LND could allow lower RT doses by producing the same effect in prostate cancer, thus reducing the detrimental side effects associated with RT. Using the Seahorse XFe96 and YSI 2300 Stat Plus analyzers, we corroborated the expected LND-induced intracellular acidification and de-energization of isolated human prostate cancer cells using the PC3 cell line. These results were substantiated by non-invasive 31P magnetic resonance spectroscopy (MRS), studying PC3 prostate cancer xenografts treated with LND (100 mg/kg, i.p.). In addition, we found that LND significantly increased tumor lactate levels in the xenografts using 1H MRS non-invasively. Subsequently, LND was combined with radiation therapy in a growth delay experiment, where we found that 150 µM LND followed by 4 GY RT produced a significant growth delay in PC3 prostate cancer xenografts, compared to either control, LND, or RT alone. We conclude that the metabolic modulator LND radio-sensitizes experimental prostate cancer models, allowing the use of lower radiation doses and diminishing the potential side effects of RT. These results suggest the possible clinical translation of LND as a radio-sensitizer in patients with prostate cancer.

10.
Front Immunol ; 15: 1365718, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38646545

RESUMEN

Macrophages are tissue resident innate phagocytic cells that take on contrasting phenotypes, or polarization states, in response to the changing combination of microbial and cytokine signals at sites of infection. During the opening stages of an infection, macrophages adopt the proinflammatory, highly antimicrobial M1 state, later shifting to an anti-inflammatory, pro-tissue repair M2 state as the infection resolves. The changes in gene expression underlying these transitions are primarily governed by nuclear factor kappaB (NF-κB), Janus kinase (JAK)/signal transducer and activation of transcription (STAT), and hypoxia-inducible factor 1 (HIF1) transcription factors, the activity of which must be carefully controlled to ensure an effective yet spatially and temporally restricted inflammatory response. While much of this control is provided by pathway-specific feedback loops, recent work has shown that the transcriptional co-regulators of the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxy-terminal domain (CITED) family serve as common controllers for these pathways. In this review, we describe how CITED proteins regulate polarization-associated gene expression changes by controlling the ability of transcription factors to form chromatin complexes with the histone acetyltransferase, CBP/p300. We will also cover how differences in the interactions between CITED1 and 2 with CBP/p300 drive their contrasting effects on pro-inflammatory gene expression.


Asunto(s)
Macrófagos , Humanos , Macrófagos/inmunología , Macrófagos/metabolismo , Animales , Regulación de la Expresión Génica , Transducción de Señal , Activación de Macrófagos/genética , Transactivadores/metabolismo , Transactivadores/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Polaridad Celular
11.
JAMA Netw Open ; 7(4): e246858, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38630477

RESUMEN

Importance: Clinician burnout has been associated with clinician outcomes, but the association with patient outcomes remains unclear. Objective: To evaluate the association between clinician burnout and the outcomes of patients receiving of guideline-recommended trauma-focused psychotherapies for posttraumatic stress disorder (PTSD). Design, Setting, and Participants: This cohort study was set at the US Veterans Affairs Health Care System and included licensed therapists who provided trauma-focused psychotherapies and responded to an online survey between May 2 and October 8, 2019, and their patients who initiated a trauma-focused therapy during the following year. Patient data were collected through December 31, 2020. Data were analyzed from May to September 2023. Exposures: Therapists completing the survey reported burnout with a 5-point validated measure taken from the Physician Worklife Study. Burnout was defined as scores of 3 or more. Main Outcomes and Measures: The primary outcome was patients' clinically meaningful improvement in PTSD symptoms according to the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Patient dropout, therapist adherence, and session spacing was assessed through electronic health records. Multivariable random-effects logistic regression examined the association of therapist burnout and clinically meaningful improvement, adjusted for case-mix. Results: In this study, 165 of 180 (91.7%) therapists (89 [53.9%] female) completed the burnout measure and provided trauma-focused psychotherapies to 1268 patients (961 [75.8%] male) with outcome data. Fifty-eight (35.2%) therapists endorsed burnout. One third of patients (431 [34.0%]) met criterion for clinically meaningful improvement. Clinically meaningful improvement in PTSD symptoms was experienced by 120 (28.3%) of the 424 patients seen by therapists who reported burnout and 311 (36.8%) of the 844 patients seen by therapists without burnout. Burnout was associated with lower odds of clinically meaningful improvement (adjusted odds ratio [OR],0.63; 95% CI, 0.48-0.85). The odds of clinically meaningful improvement were reduced for patients who dropped out (OR, 0.15; 95% CI, 0.11-0.20) and had greater session spacing (OR, 0.80; 95% CI, 0.70-0.92). Therapist adherence was not associated with therapy effectiveness. Adjusting for dropout or session spacing did not meaningfully alter the magnitude of the association between burnout and clinically meaningful improvement. Conclusions and Relevance: In this prospective cohort study, therapist burnout was associated with reduced effectiveness of trauma-focused psychotherapies. Studying when and how burnout affects patient outcomes may inform workplace interventions.


Asunto(s)
Agotamiento Psicológico , Psicoterapia , Humanos , Femenino , Masculino , Estudios de Cohortes , Estudios Prospectivos , Lista de Verificación
12.
Mol Plant ; 17(5): 747-771, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38614077

RESUMEN

Macroalgae are multicellular, aquatic autotrophs that play vital roles in global climate maintenance and have diverse applications in biotechnology and eco-engineering, which are directly linked to their multicellularity phenotypes. However, their genomic diversity and the evolutionary mechanisms underlying multicellularity in these organisms remain uncharacterized. In this study, we sequenced 110 macroalgal genomes from diverse climates and phyla, and identified key genomic features that distinguish them from their microalgal relatives. Genes for cell adhesion, extracellular matrix formation, cell polarity, transport, and cell differentiation distinguish macroalgae from microalgae across all three major phyla, constituting conserved and unique gene sets supporting multicellular processes. Adhesome genes show phylum- and climate-specific expansions that may facilitate niche adaptation. Collectively, our study reveals genetic determinants of convergent and divergent evolutionary trajectories that have shaped morphological diversity in macroalgae and provides genome-wide frameworks to understand photosynthetic multicellular evolution in aquatic environments.


Asunto(s)
Genómica , Fotosíntesis , Algas Marinas , Algas Marinas/genética , Fotosíntesis/genética , Filogenia , Microalgas/genética , Microalgas/citología , Evolución Biológica
13.
Parkinsonism Relat Disord ; 123: 106557, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38518542

RESUMEN

BACKGROUND: Some epidemiological studies have found an increased association between Parkinson's disease (PD) and chronic hepatitis C virus (HCV) infection. Although a few studies have also found a decreased risk of PD with interferon-α therapy, the effect of direct-acting antivirals (DAAs) on Parkinson's disease remains unclear. The current study seeks to assess and elucidate the association between DAAs and PD in patients newly diagnosed with chronic HCV infection. METHODS: We conducted a retrospective cohort study of patients ≥18 years diagnosed with HCV using MarketScan Commercial and Medicare Supplemental database (2012-2019). Follow-up started with the initiation of DAA (or randomly assigned date for the non-DAA group) and ended at occurrence of PD, disenrollment, or end of the study period. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals. RESULTS: We identified 48,356 patients diagnosed with HCV. The mean follow-up time of the cohort was 1.31 years. The incidence rate of PD was 53 per 100,000 person-years for the DAA group and 48 per 100,000 person-years for the non-DAA group. The adjusted HR was 1.24 (95% CI = 0.56-2.73). Results were consistent across sensitivity and subgroup analyses. CONCLUSION: This study did not find an association between DAAs and PD among patients with HCV infection.

14.
Bull Math Biol ; 86(4): 38, 2024 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-38446260

RESUMEN

Mounting empirical research suggests that the stroma, or interface between healthy and cancerous tissue, is a critical determinate of cancer invasion. At the same time, a cancer cell's location and potential to proliferate can influence its sensitivity to cancer treatments. In this paper, we use ordinary differential equations to develop spatially structured models for solid tumors wherein the growth of tumor components is coordinated. The model tumors feature two components, a proliferating peripheral growth region, which potentially includes a mix of cancerous and noncancerous stroma cells, and a solid tumor core. Mathematical and numerical analysis are used to investigate how coordinated expansion of the tumor growth region and core can influence overall growth dynamics in a variety of tumor types. Model assumptions, which are motivated by empirical and in silico solid tumor research, are evaluated through comparison to tumor volume data and existing models of tumor growth.


Asunto(s)
Conceptos Matemáticos , Neoplasias , Humanos , Modelos Biológicos
15.
Sci Rep ; 14(1): 5510, 2024 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448502

RESUMEN

The aim of this study was to produce an alcohol gel hand sanitizer containing green glycerol. Crude glycerol was purified using chemical and physical treatments. The sanitizer was prepared using 71.100 g of 99.3° GL ethanol, 28.0 g H2O, 0.5 g of Carboxypolymethylene [Carbopol 940® or Carbomer], 5 drops of triethanolamine (pH 5-7), and glycerol (1.5% w/w). The thermal behavior of the ethanol, carbopol, triethanolamine, glycerol, and alcohol gels were evaluated using Thermogravimetry and Differential Thermal Analysis. The apparent viscosity was obtained using a rotary viscometer. The determination of in vitro spreadability was achieved by an adaptation of the Knorst method. The ethanol content was measured by headspace gas chromatography using a flame ionization detector. The thermal behavior of the gels was influenced by the presence of glycerol, which confirms the possible network interactions formed. The relative densities of the samples were between 0.887 and 0.890 g/cm3. No alteration of the pH of the formulation resulted from the incorporation of glycerol. The apparent viscosities of the alcohol gels were greater than 20,000 cP. No alteration in the in vitro spreadability of the gel alcohol (530.6 mm2) resulted from the addition of glycerol. Hand sanitizer was produced using glycerol from a transesterification reaction. It represents an alternative use for the glycerol being produced in biodiesel processes. The product satisfied the requirements of WHO that preconize a formulation containing 1.45% glycerol as an humectant to protect skin against dryness and dermatitis.


Asunto(s)
Etanolaminas , Glicerol , Desinfectantes para las Manos , Triglicéridos , Etanol , Geles
16.
Mol Plant ; 17(4): 631-647, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38475994

RESUMEN

Hormone-activated proteolysis is a recurring theme of plant hormone signaling mechanisms. In strigolactone signaling, the enzyme receptor DWARF14 (D14) and an F-box protein, MORE AXILLARY GROWTH2 (MAX2), mark SUPPRESSOR OF MAX2 1-LIKE (SMXL) family proteins SMXL6, SMXL7, and SMXL8 for rapid degradation. Removal of these transcriptional corepressors initiates downstream growth responses. The homologous proteins SMXL3, SMXL4, and SMXL5, however, are resistant to MAX2-mediated degradation. We discovered that the smxl4 smxl5 mutant has enhanced responses to strigolactone. SMXL5 attenuates strigolactone signaling by interfering with AtD14-SMXL7 interactions. SMXL5 interacts with AtD14 and SMXL7, providing two possible ways to inhibit SMXL7 degradation. SMXL5 function is partially dependent on an ethylene-responsive-element binding-factor-associated amphiphilic repression (EAR) motif, which typically mediates interactions with the TOPLESS family of transcriptional corepressors. However, we found that loss of the EAR motif reduces SMXL5-SMXL7 interactions and the attenuation of strigolactone signaling by SMXL5. We hypothesize that integration of SMXL5 into heteromeric SMXL complexes reduces the susceptibility of SMXL6/7/8 proteins to strigolactone-activated degradation and that the EAR motif promotes the formation or stability of these complexes. This mechanism may provide a way to spatially or temporally fine-tune strigolactone signaling through the regulation of SMXL5 expression or translation.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Compuestos Heterocíclicos con 3 Anillos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Lactonas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Co-Represoras/metabolismo , Regulación de la Expresión Génica de las Plantas
17.
Am J Perinatol ; 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38423118

RESUMEN

OBJECTIVE: This study aimed to examine the relationship of fetal station in the first stage of labor to labor curves and cesarean delivery rates among women presenting in spontaneous labor. STUDY DESIGN: Labor curves for patients with nonanomalous singletons who presented in spontaneous labor to our hospital's Obstetric Triage Unit with intact membranes from January 1, 2012, to August 31, 2016 were reviewed. Cervical exams and time of exam were obtained for each patient from presentation to triage until delivery. Station for each presentation and cervical dilation was estimated using a random effects model and the slope of cervical station change was calculated to estimate the change in dilation by hour. Perinatal outcomes, including cesarean delivery rates, were examined according to fetal station at initial presentation. Factors known to affect labor curves-epidural analgesia, infant birthweight, maternal habitus, and parity-were also examined. RESULTS: There were 8,123 patients presented in spontaneous labor with intact membranes. For patients presenting at 6-cm dilation, the rate of change of labor was significantly different when identified to have a station greater than 0 (+1 and more caudad) when compared with those with -1 and more cephalad station (both p < 0.001). This relationship persisted when analyzed according to epidural analgesia, birthweight, maternal habitus, and parity. The frequency of cesarean delivery was significantly higher for women presenting in spontaneous labor with negative fetal station (p < 0.05). When stratified across all dilation (3-9 cm), this trend remained significant (p < 0.001). CONCLUSION: In the first stage of labor, advanced fetal station was significantly associated with differing rates of labor progression, and positive fetal station was significantly less likely to result in cesarean delivery. Physical examination, including station, remains a critical element in labor management. KEY POINTS: · Fetal station is important in labor management.. · Fetal station at initial exam is related to time to delivery.. · Positive fetal station at initial exam is less likely to result in cesarean delivery..

18.
Support Care Cancer ; 32(3): 144, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38316704

RESUMEN

PURPOSE: To synthesize the qualitative literature exploring the experiences of people living with lung cancer in rural areas. METHODS: Searches were performed in MEDLINE, CINAHL, and PsycINFO. Articles were screened independently by two reviewers against pre-determined eligibility criteria. Data were synthesized using Thomas and Harden's framework for the thematic synthesis of qualitative research. The CASP qualitative checklist was used for quality assessment and the review was reported in accordance with the ENTREQ and PRISMA checklists. RESULTS: Nine articles were included, from which five themes were identified: (1) diagnosis and treatment pathways, (2) travel and financial burden, (3) communication and information, (4) experiences of interacting with healthcare professionals, (5) symptoms and health-seeking behaviors. Lung cancer diagnosis was unexpected for some with several reporting treatment delays and long wait times regarding diagnosis and treatment. Accessing treatment was perceived as challenging and time-consuming due to distance and financial stress. Inadequate communication of information from healthcare professionals was a common concern expressed by rural people living with lung cancer who also conveyed dissatisfaction with their healthcare professionals. Some were reluctant to seek help due to geographical distance and sociocultural factors whilst others found it challenging to identify symptoms due to comorbidities. CONCLUSIONS: This review provides a deeper understanding of the challenges faced by people with lung cancer in rural settings, through which future researchers can begin to develop tailored support to address the existing disparities that affect this population.


Asunto(s)
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/terapia , Investigación Cualitativa , Personal de Salud , Emociones , Población Rural
19.
Neuron ; 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38417436

RESUMEN

Highly penetrant autosomal dominant Alzheimer's disease (ADAD) comprises a distinct disease entity as compared to the far more prevalent form of AD in which common variants collectively contribute to risk. The downstream pathways that distinguish these AD forms in specific cell types have not been deeply explored. We compared single-nucleus transcriptomes among a set of 27 cases divided among PSEN1-E280A ADAD carriers, sporadic AD, and controls. Autophagy genes and chaperones clearly defined the PSEN1-E280A cases compared to sporadic AD. Spatial transcriptomics validated the activation of chaperone-mediated autophagy genes in PSEN1-E280A. The PSEN1-E280A case in which much of the brain was spared neurofibrillary pathology and harbored a homozygous APOE3-Christchurch variant revealed possible explanations for protection from AD pathology including overexpression of LRP1 in astrocytes, increased expression of FKBP1B, and decreased PSEN1 expression in neurons. The unique cellular responses in ADAD and sporadic AD require consideration when designing clinical trials.

20.
PeerJ ; 12: e16796, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38332805

RESUMEN

Bats subject to high rates of fatalities at wind-energy facilities are of high conservation concern due to the long-term, cumulative effects they have, but the impact on broader bat populations can be difficult to assess. One reason is the poor understanding of the geographic source of individual fatalities and whether they constitute migrants or more local individuals. Here, we used stable hydrogen isotopes, trace elements and species distribution models to determine the most likely summer geographic origins of three different bat species (Lasiurus borealis, L. cinereus, and Lasionycteris noctivagans) killed at wind-energy facilities in Ohio and Maryland in the eastern United States. In Ohio, 41.6%, 21.3%, 2.2% of all individuals of L. borealis, L. cinereus, and L. noctivagans, respectively, had evidence of movement. In contrast, in Maryland 77.3%, 37.1%, and 27.3% of these same species were classified as migrants. Our results suggest bats killed at a given wind facility are likely derived from migratory as well as resident populations. Finally, there is variation in the proportion of migrants killed between seasons for some species and evidence of philopatry to summer roosts. Overall, these results indicate that the impact of wind-energy facilities on bat populations occurs across a large geographic extent, with the proportion of migrants impacted likely to vary across species and sites. Similar studies should be conducted across a broader geographic scale to understand the impacts on bat populations from wind-energy facilities.


Asunto(s)
Quirópteros , Viento , Humanos , Animales , Estados Unidos , Maryland , Estaciones del Año , Ohio
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