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During de novo peroxisome biogenesis, importomer complex proteins sort via two preperoxisomal vesicles (ppVs). However, the sorting mechanisms segregating peroxisomal membrane proteins to the preperoxisomal endoplasmic reticulum (pER) and into ppVs are unknown. We report novel roles for Pex3 and Pex19 in intra-endoplasmic reticulum (ER) sorting and budding of the RING-domain peroxins (Pex2, Pex10, and Pex12). Pex19 bridged the interaction at the ER between Pex3 and RING-domain proteins, resulting in a ternary complex that was critical for the intra-ER sorting and subsequent budding of the RING-domain peroxins. Although the docking subcomplex proteins (Pex13, Pex14, and Pex17) also required Pex19 for budding from the ER, they sorted to the pER independently of Pex3 and Pex19 and were spatially segregated from the RING-domain proteins. We also discovered a unique role for Pex3 in sorting Pex10 and Pex12, but with the docking subcomplex. Our study describes an intra-ER sorting process that regulates segregation, packaging, and budding of peroxisomal importomer subcomplexes, thereby preventing their premature assembly at the ER.

Background: Although palliative medicine (PM) is more commonly being integrated into the intensive care unit (ICU), research on racial disparities in this area is lacking. Our objectives were to (a) identify racial disparities in utilization of PM consultation for patients who received ICU care and (b) determine if there were differences in the use of code status or PM consultation over time based on race. Materials and Methods: Retrospective analysis of 571 patients, 18 years and above, at a tertiary care institution who received ICU care and died during their hospital stay. We analyzed two timeframes, 2008–2009 and 2018–2019. Univariate analysis was utilized to evaluate baseline characteristics. A multivariate logistic regression model and interaction P values were employed to assess for differential use of PM consultation, do not resuscitate (DNR) orders, and comfort care (CC) orders between races in aggregate and for changes over time. Results: There was a notable increase in Black/African-American (AA) (54% to 61%) and Hispanic/Latino (2% to 3%) patients over time in our population. Compared to White patients, we found no differences between PM consultation and CC orders. There was a lower probability of DNR orders for Black/AA (adjusted odds ratio [aOR] 0.569; P =.049; confidence interval [CI]: 0.324–0.997) and other/unknown/multiracial patients (aOR: 0.389; P =.273; CI: 0.169–0.900). Comparing our earlier time period to the later time period, we found an increased usage of PM for all patients. Interaction P values suggest there were no differences between races regarding PM, DNR, and CC orders. Conclusions: PM use has increased over time at our institution. Contrary to the previous literature, there were no differences in the frequency of utilization of PM consultation between races. Further analysis to evaluate the usage of PM in the ICU setting in varying populations and geographic locations is warranted. [ABSTRACT FROM AUTHOR]

Objective: To determine the facilitators of and barriers to adherence to use of intranasal pharmacotherapy (daily intranasal corticosteroids and/or antihistamine, and nasal saline irrigation [NSI]), for allergic rhinitis (AR). Methods: Patients were recruited from an academic tertiary care rhinology and allergy clinic. Semi‐structured interviews were conducted after the initial visit and/or 4–6 weeks following treatment. Transcribed interviews were analyzed using a grounded theory, inductive approach to elucidate themes regarding patient adherence to AR treatment. Results: A total of 32 patients (12 male, 20 female; age 22–78) participated (seven at initial visit, seven at follow‐up visit, and 18 at both). Memory triggers, such as linking nasal routine to existing daily activities or medications, were identified by patients as the most helpful strategy for adherence at initial and follow‐up visits. Logistical obstacles related to NSI (messy, takes time, etc.) was the most common concept discussed at follow‐up. Patients modified the regimen based on side effects experienced or perceived efficacy. Conclusions: Memory triggers help patients adhere to nasal routines. Logistical obstacles related to NSI can deter from use. Health care providers should address both concepts during patient counseling. Nudge‐based interventions that incorporate these concepts may help improve adherence to AR treatment. Level of Evidence: 2 [ABSTRACT FROM AUTHOR]

Background: Several prospective studies report improved outcomes with pretreatment nutrition interventions prior to radiation therapy for head and neck cancer (HNC), but none have assessed similar interventions before surgery for HNC. Methods: POINT, a pilot randomized controlled trial, was conducted to evaluate a multimodal nutrition intervention. Patients undergoing primary surgery with free flap reconstruction for HNC were randomly assigned to the control arm or a preoperative multimodal nutrition intervention. Results: POINT included 49 patients. Nutrition risk scores did not change significantly for either the intervention or control group. Control patients had a significant decrease in body weight in the preoperative period (p < 0.001). Conversely, weight among intervention patients did not significantly decrease (p = 0.680). The intervention mitigated weight loss in patients with dysphagia (p = 0.001). Conclusions: Preoperative nutrition optimization shows potential to reduce weight loss normally experienced by patients with head and neck cancer prior to surgical extirpation, especially among those with subjective dysphagia. [ABSTRACT FROM AUTHOR]

Objectives: First-line treatment of chronic rhinosinusitis includes topical corticosteroids aimed at decreasing inflammation of sinonasal mucosa. No guidelines exist regarding the effect of head position during administration of corticosteroids. We hypothesize certain positions enhance delivery to the paranasal sinuses, with further improvement in delivery after sinus surgery. Methods: A systematic review of the literature was conducted using Medline Ovid, Embase, Scopus, and Cochrane databases. All studies evaluating intranasal medications administered in 2 or more head positions were included. Study population, head position(s), method/volume of delivery, and outcome metrics were recorded. Results: Twenty-four studies compared head positions and their role in distribution of intranasal medication. Of 12 papers studying surgically naive subjects, 6 found improvement in delivery to specific sinonasal regions (middle meatus; lateral, superior, or posterior nasal cavity) and/or symptomatic improvement, in the lying head back (LHB) or head down and forward (HDF) positions, but only 3 reached statistical significance. Of 12 papers studying surgically altered patients, 10 found delivery improved in the HDF, LHB, and head forward 45° or 90° positions. Of 5 studies of extended frontal sinus procedures (Draf IIb/III), a majority found distribution to the frontal sinus improved with the head forward 90° position. Patients found the HDF position most uncomfortable. Conclusions: Studies found no statistically significant difference in distribution to unoperated sinuses among different head positions. A minority of studies supported the use of the LHB and HDF positions. This suggests that in surgically naive patients, intranasal corticosteroid delivery to sinonasal regions and/or symptomatic improvement may be best achieved with the sinuses positioned inferior to the delivery device. Surgery improved distribution to the paranasal sinuses regardless of head position, although tilting the head forward 90° was particularly effective in delivery to the frontal sinus after extended frontal sinus procedures. [ABSTRACT FROM AUTHOR]

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