RESUMEN
Dendrite microtubules are polarized with minus-end-out orientation in Drosophila neurons. Nucleation sites concentrate at dendrite branch points, but how they localize is not known. Using Drosophila, we found that canonical Wnt signaling proteins regulate localization of the core nucleation protein γTubulin (γTub). Reduction of frizzleds (fz), arrow (low-density lipoprotein receptor-related protein [LRP] 5/6), dishevelled (dsh), casein kinase Iγ, G proteins, and Axin reduced γTub-green fluorescent protein (GFP) at branch points, and two functional readouts of dendritic nucleation confirmed a role for Wnt signaling proteins. Both dsh and Axin localized to branch points, with dsh upstream of Axin. Moreover, tethering Axin to mitochondria was sufficient to recruit ectopic γTub-GFP and increase microtubule dynamics in dendrites. At dendrite branch points, Axin and dsh colocalized with early endosomal marker Rab5, and new microtubule growth initiated at puncta marked with fz, dsh, Axin, and Rab5. We propose that in dendrites, canonical Wnt signaling proteins are housed on early endosomes and recruit nucleation sites to branch points.
Asunto(s)
Dendritas/metabolismo , Proteínas de Drosophila/metabolismo , Endosomas/metabolismo , Microtúbulos/metabolismo , Proteínas Wnt/metabolismo , Animales , Complejo de Señalización de la Axina/genética , Complejo de Señalización de la Axina/metabolismo , Axones/metabolismo , Polaridad Celular , Dendritas/genética , Drosophila , Proteínas de Drosophila/genética , Endosomas/genética , Microtúbulos/genética , Mutación , Receptores Wnt/genética , Receptores Wnt/metabolismo , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Proteínas Wnt/genética , Vía de Señalización Wnt/genética , Proteínas de Unión al GTP rab5/genética , Proteínas de Unión al GTP rab5/metabolismoRESUMEN
INTRODUCTION: Reports of extraintestinal manifestations of Clostridioides difficile (C difficile) infections are rare. The frequency of these infections comprises approximately 0.17% to 0.6% of all C difficile infections. While they are becoming more frequent worldwide, the precise trend is unclear. CASE PRESENTATION: An 83-year-old female patient presented with pleuritic chest pain 2 to 3 months after a needle biopsy of her liver abscess confirmed C difficile. She was found to have extension of the liver abscess into the chest cavity, leading to empyema, and was treated with intravenous antimicrobials. DISCUSSION: This is the fifth known reported case of C difficile leading to a pyogenic liver abscess and the first case where the C difficile liver abscess was associated with an empyema. While long-term metronidazole is considered effective for managing extra intestinal C difficile infection, our patient was treated with vancomycin and meropenem. CONCLUSION: To determine epidemiology and a proper treatment regimen for extraintestinal C difficile infection, a greater accumulation of cases is necessary.
Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Empiema , Absceso Piógeno Hepático , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Clostridioides , Infecciones por Clostridium/complicaciones , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/tratamiento farmacológico , Empiema/complicaciones , Empiema/tratamiento farmacológico , Femenino , Humanos , Absceso Piógeno Hepático/complicaciones , Absceso Piógeno Hepático/diagnóstico , Absceso Piógeno Hepático/tratamiento farmacológicoRESUMEN
Objective: To determine the impact of patient demographics and social determinants of health on treatment pathways for unilateral vocal fold paralysis (UVFP) at a tertiary laryngology clinic. Study design: Retrospective medical record review. Methods: Patient demographics (age, gender, race, ethnicity, and insurance status) were extracted for adults diagnosed with UVFP between 2009 and 2019. Odds ratios for the associations between sociodemographic factors and UVFP treatment pathways were determined by chi-square analyses. Results: A total of 1490 UVFP diagnoses were identified during the study period with the majority being female (58%), White (85%), non-Hispanic (97%), and publicly insured (54%). Five treatment pathways were identified: observation, injection laryngoplasty, voice therapy, laryngeal framework surgery/thyroplasty, and reinnervation surgery. There were 538 patients who underwent observation, 512 injection laryngoplasty, 366 voice therapy, 136 thyroplasty, and 26 laryngeal reinnervation surgery. Males were more likely to undergo injection laryngoplasty than females (OR 1.32; CI 1.08-1.61), whereas females were more likely to undergo voice therapy (OR 1.39; CI 1.09-1.76). Patients with public insurance (OR 1.48; CI 1.03-2.14) and Hispanics (OR 2.60; CI 1.18-5.72) were more likely to undergo thyroplasty. Patients who underwent reinnervation surgery were younger than those in other treatment pathways (median: 39.1 years vs. 50.7-56.1 years). Conclusions: Gender, ethnicity, and insurance status were significantly associated with specific UVFP treatment pathways. Patients with public insurance were more likely to undergo surgical intervention than voice therapy. This data overall supports differences in care pathway utilization for UVFP based on social determinants of health. Level of evidence: Level IV.