CD28-CD57+ T cells from head and neck cancer patients produce high levels of cytotoxic granules and type II interferon but are not senescent.

T lymphocytes expressing CD57 and lacking costimulatory receptors CD27/CD28 have been reported to accumulate with aging, chronic infection, and cancer. These cells are described as senescent, with inability to proliferate but enhanced cytolytic and cytokine-producing capacity. However, robust functional studies on these cells taken directly from cancer patients are lacking. We isolated these T cells and their CD27/28+ counterparts from blood and tumor samples of 50 patients with previously untreated head and neck cancer. Functional studies confirmed that these cells have enhanced ability to degranulate and produce IFN-γ. They also retain the ability to proliferate, thus are not senescent. These data suggest that CD27/28-CD57+ CD8+ T cells are a subset of highly differentiated, CD45RA+ effector memory (TEMRA) cells with retained proliferative capacity. Patients with > 34% of these cells among CD8+ T cells in the blood had a higher rate of locoregional disease relapse, suggesting these cells may have prognostic significance.

Trans-tarsal Stair-Step Technique for Lateral Extension of the Transconjunctival Incision: A Technical Note and Case Series.

Background: The transconjunctival approach paired with lateral canthotomy is a commonly used technique for widened exposure of the orbital floor and infraorbital rim. A major drawback of this approach is the severance of lateral canthal ligament fibers, which predisposes to potential postoperative eyelid malpositioning. To avoid these suboptimal aesthetic outcomes, a modification of this approach has been proposed in which the lower eyelid is mobilized with a paracanthal, trans-tarsal stair-step incision. In this pilot study, we describe our experience with the trans-tarsal stairstep incision for lateral extension of the transconjunctival incision and report its outcomes in a Western population. Methods: All patients who underwent facial fracture operative fixation at a single institution by a single senior surgeon were included. Clinical variables were extracted. Patients were stratified by incision type. Results: Compared with patients who underwent subtarsal incision (n = 20) and transconjunctival incision with lateral canthotomy (n = 4), patients who received the trans-tarsal stair-step incision (n = 10) had no incision-related complications or requirements for revision. The most common complications found in the comparison groups were ectropion and hypertrophic or irregular scarring, and 4 patients required revision. Conclusions: Our initial experience with the transconjunctival approach with the trans-tarsal stair-step incision shows promising outcomes. Further study may promote greater utilization of this technique in Western countries.

Effect of pedicle type on breast reduction: Clinical and patient-reported outcomes.

PURPOSE: The choice of pedicle in reduction mammaplasty is highly variable with prior studies demonstrating high patient satisfaction in most cases. This study aimed to examine the impact of pedicle type on clinical and patient-reported outcomes in patients undergoing reduction mammaplasty. METHODS: A total of 588 patients underwent bilateral reduction mammaplasty with Wise pattern or modified Robertson incision by 13 surgeons at a single institution. Clinical outcomes were compared according to the pedicle type in all patients and BREAST-Q responders (32% response rate). Survey respondents were sub-grouped by resection volume, and the BREAST-Q satisfaction scores were compared. RESULTS: Among all included reduction mammoplasties, 439 (75%) were performed using inferior pedicles, and 149 (25%) using superior or superomedial pedicles. Responders and non-responders were similar in preoperative characteristics including age, body measurements, and comorbidities. Although a higher incidence of infection occurred among the responders, clinical outcomes were comparable across all pedicle types. A total of 187 patients completed the BREAST-Q. Compared to the superior pedicle group, respondents in the inferior pedicle group reported higher nipple satisfaction, even when adjusted for resection weight over 500 g. In contrast, the superior pedicle group had better sexual well-being scores, which persisted in resection weight less than 500 g (all p values <0.05). CONCLUSION: Inferior pedicles were associated with greater nipple satisfaction and superior pedicles were associated with greater sexual satisfaction. Our findings suggest that those with resections less than 500 g were more satisfied with superior pedicles whereas those with greater resections were more satisfied with inferior pedicles.

Aging-associated decrease of PGC-1α promotes pain chronification.

Aging is generally associated with declining somatosensory function, which seems at odds with the high prevalence of chronic pain in older people. This discrepancy is partly related to the high prevalence of degenerative diseases such as osteoarthritis in older people. However, whether aging alters pain processing in the primary somatosensory cortex (S1), and if so, whether it promotes pain chronification is largely unknown. Herein, we report that older mice displayed prolonged nociceptive behavior following nerve injury when compared with mature adult mice. The expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) in S1 was decreased in older mice, whereas PGC-1α haploinsufficiency promoted prolonged nociceptive behavior after nerve injury. Both aging and PGC-1α haploinsufficiency led to abnormal S1 neural dynamics, revealed by intravital two-photon calcium imaging. Manipulating S1 neural dynamics affected nociceptive behavior after nerve injury: chemogenetic inhibition of S1 interneurons aggravated nociceptive behavior in naive mice; chemogenetic activation of S1 interneurons alleviated nociceptive behavior in older mice. More interestingly, adeno-associated virus-mediated expression of PGC-1α in S1 interneurons ameliorated aging-associated chronification of nociceptive behavior as well as aging-related S1 neural dynamic changes. Taken together, our results showed that aging-associated decrease of PGC-1α promotes pain chronification, which might be harnessed to alleviate the burden of chronic pain in older individuals.

Clearing the Air: Acute Invasive Fungal Rhinosinusitis in Hematologic Cancer Patients.

OBJECTIVES: Air quality has been shown to impact the rates of fungal infection of the airway, causing diseases such as acute invasive fungal rhinosinusitis (AIFRS), particularly in immunocompromised patients. We theorize that patients with hematologic malignancies in units with aging air handling units (AHUs) have a higher attack rate of AIFRS. METHODS: Retrospective chart review identified patients with hematologic malignancy and AIFRS in two distinct and equal time periods between 2013 and 2022, representing the presence of aging AHUs and new AHUs, respectively. Cubic feet per minute (CFM) air flows, AIFRS attack rates, and clinical data were compared between the two groups and statistical analyses performed. RESULTS: The older AHUs produce air flow of 27,610 CFM and the newer AHUs produce air flow of 80,000 CFM. There were 18 patients with air supplied by older AHUs and 7 patients with air supplied by new AHUs who developed AIFRS. There was a significantly higher AIFRS attack rate for patients supplied by the older AHUs compared with patients supplied by newer AHUs (p = 0.033). The patients supplied by the older AHUs tended to be younger. The white blood cell counts, absolute neutrophil counts, and the mean time to diagnosis did not differ between the two groups. CONCLUSIONS: To our knowledge, this is the first study to examine AIFRS in immunocompromised patients' inpatient environment. Further research should explore whether higher CFM AHUs can decrease this disease among our most vulnerable patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

An Ensemble Learning Method for Detection of Head and Neck Squamous Cell Carcinoma Using Polarized Hyperspectral Microscopic Imaging.

Head and neck squamous cell carcinoma (HNSCC) has a high mortality rate. In this study, we developed a Stokes-vector-derived polarized hyperspectral imaging (PHSI) system for H&E-stained pathological slides with HNSCC and built a dataset to develop a deep learning classification method based on convolutional neural networks (CNN). We use our polarized hyperspectral microscope to collect the four Stokes parameter hypercubes (S0, S1, S2, and S3) from 56 patients and synthesize pseudo-RGB images using a transformation function that approximates the human eye's spectral response to visual stimuli. Each image is divided into patches. Data augmentation is applied using rotations and flipping. We create a four-branch model architecture where each branch is trained on one Stokes parameter individually, then we freeze the branches and fine-tune the top layers of our model to generate final predictions. Our results show high accuracy, sensitivity, and specificity, indicating that our model performed well on our dataset. Future works can improve upon these results by training on more varied data, classifying tumors based on their grade, and introducing more recent architectural techniques.

Optimizing Surgical Outcomes and the Role of Preventive Surgery: A Scoping Review.

BACKGROUND: Plastic and reconstructive surgeons are often presented with reconstructive challenges as a sequela of complications in high-risk surgical patients, ranging from exposure of hardware, lymphedema, and chronic pain after amputation. These complications can result in significant morbidity, recovery time, resource utilization, and cost. Given the prevalence of surgical complications managed by plastic and reconstructive surgeons, developing novel preventative techniques to mitigate surgical risk is paramount. METHODS: Herein, we aim to understand efforts supporting the nascent field of Preventive Surgery, including (1) enhanced risk stratification, (2) advancements in postoperative care. Through an emphasis on four surgical cohorts who may benefit from preventive surgery, two of which are at high risk of morbidity from wound-related complications (patients undergoing sternotomy and spine procedures) and two at high risk of other morbidities, including lymphedema and neuropathic pain, we aim to provide a comprehensive and improved understanding of preventive surgery. Additionally, the role of risk analysis for these procedures and the relationship between microsurgery and prophylaxis is emphasized. RESULTS: (1) medical optimization and prehabilitation, (2) surgical mitigation techniques. CONCLUSION: Reconstructive surgeons are ideally placed to lead efforts in the creation and validation of accurate risk assessment tools and to support algorithmic approaches to surgical risk mitigation. Through a paradigm shift, including universal promotion of the concept of "Preventive Surgery," major improvements in surgical outcomes may be achieved.

Is Diabetes a Contraindication to Lower Extremity Flap Reconstruction? An Analysis of Threatened Lower Extremities in the NSQIP Database (2010-2020).

Background The impact of diabetes on complication rates following free flap (FF), pedicled flap (PF), and amputation (AMP) procedures on the lower extremity (LE) is examined. Methods Patients who underwent LE PF, FF, and AMP procedures were identified from the 2010 to 2020 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP®) database using Current Procedural Terminology and International Classification of Diseases-9/10 codes, excluding cases for non-LE pathologies. The cohort was divided into diabetics and nondiabetics. Univariate and adjusted multivariable logistic regression analyses were performed. Results Among 38,998 patients undergoing LE procedures, 58% were diabetic. Among diabetics, 95% underwent AMP, 5% underwent PF, and <1% underwent FF. Across all procedure types, noninsulin-dependent (NIDDM) and insulin-dependent diabetes mellitus (IDDM) were associated with significantly greater all-cause complication rates compared with absence of diabetes, and IDDM was generally higher risk than NIDDM. Among diabetics, complication rates were not significantly different across procedure types (IDDM: p = 0.5969; NIDDM: p = 0.1902). On adjusted subgroup analysis by diabetic status, flap procedures were not associated with higher odds of complications compared with amputation for IDDM and NIDDM patients. Length of stay > 30 days was statistically associated with IDDM, particularly those undergoing FF (AMP: 5%, PF: 7%, FF: 14%, p = 0.0004). Conclusion Our study highlights the importance of preoperative diabetic optimization prior to LE procedures. For diabetic patients, there were few significant differences in complication rates across procedure type, suggesting that diabetic patients are not at higher risk of complications when attempting limb salvage instead of amputation.

Magnet-in-ferroelectric crystals exhibiting photomultiferroicity.

Growing crystallographically incommensurate and dissimilar organic materials is fundamentally intriguing but challenging for the prominent cross-correlation phenomenon enabling unique magnetic, electronic, and optical functionalities. Here, we report the growth of molecular layered magnet-in-ferroelectric crystals, demonstrating photomanipulation of interfacial ferroic coupling. The heterocrystals exhibit striking photomagnetization and magnetoelectricity, resulting in photomultiferroic coupling and complete change of their color while inheriting ferroelectricity and magnetism from the parent phases. Under a light illumination, ferromagnetic resonance shifts of 910 Oe are observed in heterocrystals while showing a magnetization change of 0.015 emu/g. In addition, a noticeable magnetization change (8% of magnetization at a 1,000 Oe external field) in the vicinity of ferro-to-paraelectric transition is observed. The mechanistic electric-field-dependent studies suggest the photoinduced ferroelectric field effect responsible for the tailoring of photo-piezo-magnetism. The crystallographic analyses further evidence the lattice coupling of a magnet-in-ferroelectric heterocrystal system.

Performance of SOBA-AD blood test in discriminating Alzheimer's disease patients from cognitively unimpaired controls in two independent cohorts.

Amyloid-beta (Aß) toxic oligomers are critical early players in the molecular pathology of Alzheimer's disease (AD). We have developed a Soluble Oligomer Binding Assay (SOBA-AD) for detection of these Aß oligomers that contain α-sheet secondary structure that discriminates plasma samples from patients on the AD continuum from non-AD controls. We tested 265 plasma samples from two independent cohorts to investigate the performance of SOBA-AD. Testing was performed at two different sites, with different personnel, reagents, and instrumentation. Across two cohorts, SOBA-AD discriminated AD patients from cognitively unimpaired (CU) subjects with 100% sensitivity, > 95% specificity, and > 98% area under the curve (AUC) (95% CI 0.95-1.00). A SOBA-AD positive readout, reflecting α-sheet toxic oligomer burden, was found in AD patients, and not in controls, providing separation of the two populations, aside from 5 SOBA-AD positive controls. Based on an earlier SOBA-AD study, the Aß oligomers detected in these CU subjects may represent preclinical cases of AD. The results presented here support the value of SOBA-AD as a promising blood-based tool for the detection and confirmation of AD.

A scoping review of the influence of clinical contaminants on bond strength in direct adhesive restorative procedures.

OBJECTIVE: Clinical contamination during direct adhesive restorative procedures can affect various adhesive interfaces differently and contribute to bulk failure of the restorations. This review aims to summarise the current knowledge on the influence of a variety of clinical contaminants on the bond strength at various adhesive interfaces during adhesive restorative procedures and identify gaps in the literature for future research. DATA AND SOURCES: An electronic database search was performed in PubMed and EMBASE to identify articles that investigated the influence of contaminants on direct restorative bonding procedures. A data-charting form was developed by two researchers to capture the key characteristics of each eligible study. STUDY SELECTION: The initial search yielded 1,428 articles. Fifty-seven articles published between 1 Jan 2007 and 25 Oct 2023 were included in the final review. Thirty-three of the articles examined the influence of saliva contamination, twelve articles examined the influence of blood contamination, and twenty-five articles examined the influence of other contaminants. CONCLUSION: Saliva contamination exerted less influence on the decrease in bond strength when self-etch systems were used, compared to when etch-and-rinse systems were used. Blood contamination adversely affected the bond strength at the interface between resin composite and dentine, and resin composite and resin-modified glass ionomer cement. Treating contaminated surfaces with water spray for 10-30 s followed by air drying could be effective in recovering bond strength following saliva and blood contamination. CLINICAL SIGNIFICANCE: This scoping review provides a valuable overview of the range of potential clinical contaminants that can influence the bond strength between different interfaces in direct adhesive restorative procedures. Additionally, it identifies potential decontamination protocols that can be followed to restore and enhance bond strength.

Quantification of tRNA m1A modification by templated-ligation qPCR.

N1-methyladenosine (m1A) is a widespread modification in all eukaryotic, many archaeal, and some bacterial tRNAs. m1A is generally located in the T loop of cytosolic tRNA and between the acceptor and D stems of mitochondrial tRNAs; it is involved in the tertiary interaction that stabilizes tRNA. Human tRNA m1A levels are dynamically regulated that fine-tune translation and can also serve as biomarkers for infectious disease. Although many methods have been used to measure m1A, a PCR method to assess m1A levels quantitatively in specific tRNAs has been lacking. Here we develop a templated-ligation followed by a qPCR method (TL-qPCR) that measures m1A levels in target tRNAs. Our method uses the SplintR ligase that efficiently ligates two tRNA complementary DNA oligonucleotides using tRNA as the template, followed by qPCR using the ligation product as the template. m1A interferes with the ligation in specific ways, allowing for the quantitative assessment of m1A levels using subnanogram amounts of total RNA. We identify the features of specificity and quantitation for m1A-modified model RNAs and apply these to total RNA samples from human cells. Our method enables easy access to study the dynamics and function of this pervasive tRNA modification.

ThyroSeq overview on indeterminate thyroid nodules: An institutional experience.

BACKGROUND: Molecular triage of indeterminate thyroid aspirates offers the opportunity to stratify the risk of malignancy (ROM) more accurately. Here we examine our experience with ThyroSeq v3 testing. METHODS: We analyzed 276 of 658 (42%) fine needle aspiration samples classified as indeterminate thyroid nodules using ThyroSeq v3 (Sept 2017-Dec 2019). The test provides a ROM and detects specific mutations. Surgical diagnoses were reviewed. RESULTS: Of 276 ThyroSeq-tested cases, 42% (n = 116) harbored genetic alterations, whereas 64% (n = 74) had surgical follow-up. Notably, 79% cases within intermediate to higher risk mutations were highly associated with surgical intervention, resulting in a 77.5% ROM when including both cancer and noninvasive follicular thyroid neoplasia with papillary-like features (cancer+NIFTP) and 68% malignant diagnosis when excluding NIFTP. RAS-like alterations were most common (66%), exhibiting a 73.4% ROM and a 59% malignant diagnosis. Interestingly, this group included 24 encapsulated follicular variant papillary thyroid carcinomas (EFVPTCs), 1 infiltrative FVPTC, 9 follicular carcinomas, and 7 NIFTP. Additionally, three high-risk mutations and eight BRAF/V600E mutations had a 100% ROM, all diagnosed as classic-type papillary thyroid carcinoma (cPTC). Combined analysis of thyroid nodules from Bethesda III and IV categories revealed a 78.2% positive predictive value (PPV) and a 75.9% negative predictive value (NPV). CONCLUSION: ThyroSeq v3 effectively stratifies the ROM in indeterminate thyroid nodules based on specific genetic alterations, guiding appropriate surgical management. Notably, the BRAFV600E/high-risk group and RAS-like groups exhibited ROM of 100% and 77.5%, respectively, with promising predictive accuracy (PPV of 78.2% and NPV of 75.9%).

Patient-Reported Outcomes on Subjective Nipple Sensation After Double-Incision and Periareolar Mastectomy for Chest Masculinization: Subjective Nipple Sensation After Chest Masculinization.

ABSTRACT: We evaluated patient-reported outcomes to assess for patient and procedural factors associated with postchest masculinization subjective nipple sensation. Patients who underwent double-incision or periareolar mastectomies for chest masculinization by a single senior surgeon (2015-2019) were surveyed at 2 time points regarding postoperative nipple sensation and satisfaction, including patient-reported outcomes using BODY-Q modules (Q-Portfolio.org). Demographic, operative, and postoperative variables were obtained from medical records. Patients were stratified according to survey responses. Univariate and multivariate analyses were performed.Response rate was 42% for survey 1 and 22% for survey 2. Of the 151 survey 1 responders, 138 (91.4%) received double-incision mastectomies and 13 (8.6%) received periareolar mastectomies. Among Survey 1 responders, 84.6% periareolar patients and 69.6% double-incision patients reported "completely" or "a little" nipple sensation preservation, and the difference trended toward significance (P = 0.0719). There was a stepwise increase in proportion of patients reporting sensation with greater recovery time until response to survey 1. Obesity (P = 0.0080) and greater tissue removed (P = 0.0247) were significantly associated with decreased nipple sensation. Nipple satisfaction scores were significantly higher for patients reporting improved nipple sensation (P = 0.0235). Responders to survey 2 who reported greater satisfaction with nipple sensation were significantly more likely to report preserved sensitivity to light touch (P = 0.0277), pressure (P = 0.0046), and temperature (P = 0.0031). Preserved erogenous sensation was also significantly associated with greater satisfaction (P = 0.0018).In conclusion, we found that nipple sensation may be associated with postoperative nipple satisfaction. Operative techniques to optimize nipple sensation preservation may improve this population's postoperative satisfaction.

Fascia iliaca catheters for donor site pain after split-thickness skin grafting for acute burn injury: a retrospective review.

The management of acute burn pain poses significant challenges. Regional techniques have become increasingly popular in perioperative burn pain management. Continuous nerve block catheters are particularly useful for split thickness skin grafts where donor site pain can exceed that of the burn-injured site. Donor skin is frequently harvested from the anterolateral thigh. The fascia iliaca (FI) compartment block provides blockade of both the lateral femoral cutaneous nerve and the femoral nerve and thus, it is a useful modality for burn donor pain. Our institution initiated a protocol in which continuous fascia iliaca catheters were placed in patients undergoing split-thickness skin grafting of the anterolateral thigh. This retrospective review seeks to assess the impact of this modality on post-operative pain scores and opioid requirements. Oral morphine equivalent administration was significantly lower in the FI group than the control group starting with POD 0, which is the day of the FI catheter insertion (188 vs 327mg, p<0.001). Over the next 4 postoperative days, OME administration remained lower in the FI group compared to control patients, although not statistically significant on POD 3-4. There was a significant difference in OME administered between the FI group and the control group on POD 5 (159.5 vs 209.2mg, p<0.05). Our retrospective study evaluating the role of fascia iliaca catheters in burn patients undergoing split thickness skin grafting surgery showed significantly lower opioid consumption on postoperative days 1-5 compared to patients without a fascia iliaca catheter.

Impact of template denaturation prior to whole genome amplification on gene detection in high GC-content species, Burkholderia mallei and B. pseudomallei.

OBJECTIVE: In this study, we sought to determine the types and prevalence of antimicrobial resistance determinants (ARDs) in Burkholderia spp. strains using the Antimicrobial Resistance Determinant Microarray (ARDM). RESULTS: Whole genome amplicons from 22 B. mallei (BM) and 37 B. pseudomallei (BP) isolates were tested for > 500 ARDs using ARDM v.3.1. ARDM detected the following Burkholderia spp.-derived genes, aac(6), blaBP/MBL-3, blaABPS, penA-BP, and qacE, in both BM and BP while blaBP/MBL-1, macB, blaOXA-42/43 and penA-BC were observed in BP only. The method of denaturing template for whole genome amplification greatly affected the numbers and types of genes detected by the ARDM. BlaTEM was detected in nearly a third of BM and BP amplicons derived from thermally, but not chemically denatured templates. BlaTEM results were confirmed by PCR, with 81% concordance between methods. Sequences from 414-nt PCR amplicons (13 preparations) were 100% identical to the Klebsiella pneumoniae reference gene. Although blaTEM sequences have been observed in B. glumae, B. cepacia, and other undefined Burkholderia strains, this is the first report of such sequences in BM/BP/B. thailandensis (BT) clade. These results highlight the importance of sample preparation in achieving adequate genome coverage in methods requiring untargeted amplification before analysis.

Allosteric regulation in SARS-CoV-2 spike protein.

Allosteric regulation is common in protein-protein interactions and is thus promising in drug design. Previous experimental and simulation work supported the presence of allosteric regulation in the SARS-CoV-2 spike protein. Here the route of allosteric regulation in SARS-CoV-2 spike protein is examined by all-atom explicit solvent molecular dynamics simulations, contrastive machine learning, and the Ohm approach. It was found that peptide binding to the polybasic cleavage sites, especially the one at the first subunit of the trimeric spike protein, activates the fluctuation of the spike protein's backbone, which eventually propagates to the receptor-binding domain on the third subunit that binds to ACE2. Remarkably, the allosteric regulation routes starting from the polybasic cleavage sites share a high fraction (39-67%) of the critical amino acids with the routes starting from the nitrogen-terminal domains, suggesting the presence of an allosteric regulation network in the spike protein. Our study paves the way for the rational design of allosteric antibody inhibitors.

Effects of socioeconomic status on enrollment in clinical trials for cancer: A systematic review.

BACKGROUND: To achieve equitable access to cancer clinical trials (CCTs), patients must overcome structural, clinical, and attitudinal barriers to trial enrollment. The goal of this systematic review was to study the relationship between socioeconomic status (SES), assessed either by direct or proxy measures, and CCT enrollment. METHODS: The review team and medical librarian developed search strategies for each database to identify studies for this systematic review, which was conducted according to PRISMA guidelines. Inclusion criteria were as follows: studies published in relevant scientific journals between January 2000 and July 2022, primary sources, English literature, and studies conducted in the US. Sixteen studies fulfilled the inclusion criteria and were reviewed. The risk of bias assessment was conducted independently by two reviewers using the Newcastle Ottawa scale. RESULTS: The initial search yielded 4070 citations, and 16 studies were included in our review. Four of the studies included used patient reported annual income as a measure of SES, while the remaining 12 studies used patient zip code as a proxy measurement of SES. Consistent with our hypothesis, 13 studies showed a positive association between high SES (patient-reported or proxy measurement) and CCT enrollment. Two studies showed a negative association, and one study showed no relationship. CONCLUSIONS: The existing literature suggests that low SES is associated with lower participation in CCT. The small number of studies identified on this topic highlights the need for additional research on SES and other barriers to CCT participation.

Direct structural analysis of a single acyl carrier protein domain in fatty acid synthase from the fungus Saccharomyces cerevisiae.

Acyl carrier protein (ACP) is the work horse of polyketide (PKS) and fatty acid synthases (FAS) and acts as a substrate shuttling domain in these mega enzymes. In fungi, FAS forms a 2.6 MDa symmetric assembly with six identical copies of FAS1 and FAS2 polypeptides. However, ACP spatial distribution is not restricted by symmetry owing to the long and flexible loops that tether the shuttling domain to its corresponding FAS2 polypeptide. This symmetry breaking has hampered experimental investigation of substrate shuttling route in fungal FAS. Here, we develop a protein engineering and expression method to isolate asymmetric fungal FAS proteins containing odd numbers of ACP domains. Electron cryomicroscopy (cryoEM) observation of the engineered complex reveals a non-uniform distribution of the substrate shuttling domain relative to its corresponding FAS2 polypeptide at 2.9 Å resolution. This work lays the methodological foundation for experimental study of ACP shuttling route in fungi.

Experiences of young adults affected by cancer within an 8-week yoga intervention delivered by videoconference: a qualitative interview study.

BACKGROUND: Yoga may reduce negative cancer- and treatment-related effects and help improve a range of outcomes, including flexibility, mindfulness, and quality of life among adults affected by cancer. Yet there is little evidence for the role of yoga among young adults (18-39 years) affected by cancer. PURPOSE: The purpose of this study was to explore the experiences of young adults affected by cancer in an 8-week yoga intervention delivered by videoconference. METHODS: Young adults who were diagnosed with cancer between the ages of 18 and 39 years, at any stage of the cancer trajectory, who were living in Canada, and who completed an 8-week yoga intervention were approached to complete a semi-structured interview. A social constructivist paradigm was adopted. Interviews were transcribed verbatim and analyzed using reflexive thematic analysis. RESULTS: Twenty-eight young adults (Mean age = 34.67 ± 5.11 years; n = 25 female) with varied cancer diagnoses participated. Participants' perspectives were represented across 6 themes: (1) I was juggling a number of challenges and changes throughout the yoga intervention; (2) I noticed some improvements in my mental and physical health; (3) I made time to discover new strategies to take care of myself; (4) I was able to see what my body is capable of; (5) I was held accountable and I appreciated that, and; (6) I was able to be around similar others in a safe (virtual) space. CONCLUSIONS: Findings suggest that an 8-week yoga intervention may offer some benefits for young adults affected by cancer. Self-care, self-compassion, mindfulness, feelings of physical competence, establishing a routine, and being around similar others were viewed as important components of the intervention and may have contributed to the benefits experienced. Findings underscore the potential utility of yoga as a supportive care intervention for young adults affected by cancer.

Young adults affected by cancer described changed physical and mental health after an 8-week yoga intervention delivered by videoconference.Taking time for oneself, practicing self-compassion and mindfulness, enhanced feelings of physical competence, and establishing a routine were important elements of the intervention.Young adults appreciated being around similar others (i.e., other young adults affected by cancer) and felt connected in this videoconference-based intervention.