Cancer Survivors' Experience of Care and Financial Toxicity: Results From a National Survey.

PURPOSE: Financial toxicity (FT) can adversely affect quality of life, treatment adherence, and clinical outcomes. Patient experience of care (PEC) captures patient's perspectives on interactions with health care providers (HCPs) and systems, but the impact of PEC on FT is unknown. This study examined the relationship between PEC and FT. METHODS: We used data from the 2016-2017 Medical Expenditure Panel Survey (MEPS) Experience with Cancer Survivorship Supplement. PEC was assessed by patient-reported frequencies of their HCPs providing explanations that were easy to understand, listening carefully, showing respect, and spending enough time with the patient. FT was assessed by nine items to measure material, psychological, and behavioral FT. Analyses were performed using multivariable logistic regression controlling for sociodemographic and clinical characteristics and weighted to produce nationally representative estimates and account for survey nonresponse. RESULTS: Data from 1,068 individuals diagnosed with cancer at age >18 years were assessed. A total of 30% reported material FT, 35% reported psychological FT, and 27% reported behavioral FT. Examining PEC, 64% of respondents indicated that HCPs always explained things, 60% always listened, 66% always showed respect, and 57% always spent adequate time with them. Odds of psychological FT were significantly (P < .05) lower among patients reporting HCPs always (v never/sometimes) listened to them (odds ratio [OR], 0.37 [95% CI, 0.19 to 0.70]), showed them respect (OR, 0.36 [95% CI, 0.16 to 0.81]), and spent enough time with them (OR, 0.47 [95% CI, 0.26 to 0.86]). Significant associations with PEC were also found with MEPS psychological FT items on worry about paying medical bills, family's financial stability, and keeping job/income because of cancer. CONCLUSION: Worry/anxiety regarding costs can be a major factor affecting individuals diagnosed with cancer. Improving patient-provider interactions to enhance patient experience of care may reduce psychological financial toxicity.

CSU-ALS Certified Centers are Associated with Improved Failure to Rescue After Cardiac Arrest: A Propensity Score Match Analysis.

OBJECTIVE: The impact of Cardiac Surgical Unit - Advanced Life Support (CSU-ALS) training on failure to rescue after cardiac arrest (FTR-CA) is unknown. We hypothesized that institutional CSU-ALS certification would be associated with lower FTR-CA. METHODS: Patients undergoing Society of Thoracic Surgeons (STS) index operations from 2020-2023 from a regional collaborative were analyzed. Each institution was surveyed regarding its status as a CSU-ALS certified center. Patients stratified by CSU-ALS certification were 1:1 propensity score matched with subsequent multivariable model reviewing associations with failure to rescue after cardiac arrest. RESULTS: A total of 12209 patients were included in the study period across 15 institutions. Eight centers reported CSU-ALS certification. After propensity score matching, two patient cohorts were formed (n = 3557). Patients at CSU-ALS centers had higher rates of ICU readmission (3.9% vs 2.3%, p<0.01) and total OR time (340 min vs 323 min, p<0.01). Hospital readmission was less likely in the CSU-ALS centers (9.0% vs 10.1%, p <0.01). There was no difference in the rate of post-operative cardiac arrest (1.8% vs 2.2 %, p = 0.24) or operative mortality (2.5% vs 2.9%, p = 0.30). After risk-adjustment, CSU-ALS centers (OR 0.30 [CI 0.12 - 0.72], p <0.01) and higher-volume centers (OR 0.15 [CI 0.03 - 0.74], p = 0.02) had reduced odds of FTR after cardiac arrest. CONCLUSIONS: Centers with CSU-ALS certification are associated with a lower risk-adjusted likelihood of FTR after cardiac arrest. This highlights the importance of well-trained staff and treatment algorithms in the care of post-operative cardiac surgery patients.

Neural mechanisms of credit assignment for delayed outcomes during contingent learning.

Adaptive behavior in complex environments critically relies on the ability to appropriately link specific choices or actions to their outcomes. However, the neural mechanisms that support the ability to credit only those past choices believed to have caused the observed outcomes remain unclear. Here, we leverage multivariate pattern analyses of functional magnetic resonance imaging (fMRI) data and an adaptive learning task to shed light on the underlying neural mechanisms of such specific credit assignment. We find that the lateral orbitofrontal cortex (lOFC) and hippocampus (HC) code for the causal choice identity when credit needs to be assigned for choices that are separated from outcomes by a long delay, even when this delayed transition is punctuated by interim decisions. Further, we show when interim decisions must be made, learning is additionally supported by lateral frontopolar cortex (FPl). Our results indicate that FPl holds previous causal choices in a "pending" state until a relevant outcome is observed, and the fidelity of these representations predicts the fidelity of subsequent causal choice representations in lOFC and HC during credit assignment. Together, these results highlight the importance of the timely reinstatement of specific causes in lOFC and HC in learning choice-outcome relationships when delays and choices intervene, a critical component of real-world learning and decision making.

RSV infection of humanized lung-only mice induces pathological changes resembling severe bronchiolitis and bronchopneumonia.

Respiratory syncytial virus (RSV) is a substantial cause of severe lower respiratory tract infections in infants, young children, older adults, and immunocompromised individuals. There is a vital need for effective therapeutics to prevent and/or treat severe RSV infection in these high-risk individuals. The development and pre-clinical testing of candidate RSV therapeutics could be accelerated by their evaluation in animals models that recapitulate bronchiolitis and bronchopneumonia; both hallmark features of severe RSV infection of humans. Previously, we demonstrated that implanted human lung tissue in humanized lung-only mice (LoM) can be infected with RSV resulting in a sustained virus replication. Here, we analyzed RSV-associated human lung pathology in the human lung implants of RSV-infected LoM. RSV infected epithelial cells lining the airway and alveolar regions of human lung implants resulting in hallmark histological features of RSV bronchiolitis and bronchopneumonia including distal airway and alveolar lumens clogged with 1) sloughed and necrotic RSV-infected epithelial cells, 2) neutrophil-containing inflammatory infiltrates, and 3) MUC5B dominated mucus secretions. We also show that treatment of LoM with a small molecule antiviral (ribavirin) or a neutralizing antibody (palivizumab) significantly suppressed and/or prevented RSV infection in vivo. Together, our data show that RSV infection of human lung implants in vivo has appropriate cellular tropism and results in hallmark pathological characteristics of severe bronchiolitis and bronchopneumonia in humans. They also offer proof-of-principle of the utility of this model to evaluate novel approaches for the prevention/treatment of RSV infection.

Rapid single-tier serodiagnosis of Lyme disease.

Point-of-care serological and direct antigen testing offers actionable insights for diagnosing challenging illnesses, empowering distributed health systems. Here, we report a POC-compatible serologic test for Lyme disease (LD), leveraging synthetic peptides specific to LD antibodies and a paper-based platform for rapid, and cost-effective diagnosis. Antigenic epitopes conserved across Borrelia burgdorferi genospecies, targeted by IgG and IgM antibodies, are selected to develop a multiplexed panel for detection of LD antibodies from patient sera. Multiple peptide epitopes, when combined synergistically with a machine learning-based diagnostic model achieve high sensitivity without sacrificing specificity. Blinded validation with 15 LD-positive and 15 negative samples shows 95.5% sensitivity and 100% specificity. Blind testing with the CDC's LD repository samples confirms the test accuracy, matching lab-based two-tier results, correctly differentiating between LD and look-alike diseases. This LD diagnostic test could potentially replace the cumbersome two-tier testing, improving diagnosis and enabling earlier treatment while facilitating immune monitoring and surveillance.

Tissue-Based Predictors of Impaired Right Ventricular Strain in Coronary Artery Disease: A Multicenter Stress Perfusion Study.

BACKGROUND: Right ventricular (RV) dysfunction is known to impact prognosis, but its determinants in coronary artery disease are poorly understood. Stress cardiac magnetic resonance (CMR) has been used to assess ischemia and infarction in relation to the left ventricle (LV); the impact of myocardial tissue properties on RV function is unknown. METHODS: Vasodilator stress CMR was performed in patients with known coronary artery disease at 7 sites between May 2005 and October 2018. Myocardial infarction was identified on late gadolinium enhancement-CMR, and infarct transmurality was graded on a per-segment basis. Ischemia was assessed on stress CMR based on first-pass perfusion and localized by using segment partitions corresponding to cine and late gadolinium enhancement analyses. RV function was evaluated by CMR-feature tracking for primary analysis with a global longitudinal strain threshold of 20% used to define impaired RV strain (RVIS); secondary functional analysis via RV ejection fraction was also performed. RESULTS: A total of 2604 patients were studied, among whom RVIS was present in 461 patients (18%). The presence and magnitude of RVIS were strongly associated with LV dysfunction, irrespective of whether measured by LV ejection fraction or wall motion score (P<0.001 for all). Regarding tissue substrate, regions of ischemic and dysfunctional myocardium (ie, hibernating myocardium) and infarct size were each independently associated with RVIS (both P<0.001). During follow-up (median, 4.62 [interquartile range, 2.15-7.67] years), 555 deaths (21%) occurred. Kaplan-Meier analysis for patients stratified by presence and magnitude of RV dysfunction by global longitudinal strain and RV ejection fraction each demonstrated strong prognostic utility for all-cause mortality (P<0.001). RVIS conferred increased mortality risk (hazard ratio, 1.35 [95% CI, 1.11-1.66]; P=0.003) even after controlling for LV function, infarction, and ischemia. CONCLUSIONS: RVIS in patients with known coronary artery disease is associated with potentially reversible LV processes, including LV functional impairment due to ischemic and predominantly viable myocardium, which confers increased mortality risk independent of LV function and tissue substrate.

Effects of Wind Speed on Size-Dependent Morphology and Composition of Sea Spray Aerosols.

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.

Genetic evolution of keratinocytes to cutaneous squamous cell carcinoma.

We performed multi-omic profiling of epidermal keratinocytes, precancerous actinic keratoses, and squamous cell carcinomas to understand the molecular transitions during skin carcinogenesis. Single-cell mutational analyses showed that most keratinocytes in normal skin had lower mutation burdens than melanocytes and fibroblasts, however keratinocytes with TP53 or NOTCH1 mutations had substantially higher mutation burdens, suggesting that these mutations prime keratinocytes for transformation by increasing their mutation rate. Mutational profiling and spatial transcriptomics on squamous cell carcinomas adjacent to actinic keratoses revealed TERT promoter and CDKN2A mutations emerging in actinic keratoses, whereas additional mutations inactivating ARID2 and activating the MAPK-pathway delineated the transition to squamous cell carcinomas. Spatial variation in gene expression patterns was common in both tumor and immune cells, with high expression of checkpoint molecules at the invasive front of tumors. In conclusion, this study documents key events during the evolution of cutaneous squamous cell carcinoma.

Bacterial synthesis of metal nanoparticles as antimicrobials.

Nanoscience, a pivotal field spanning multiple industries, including healthcare, focuses on nanomaterials characterized by their dimensions. These materials are synthesized through conventional chemical and physical methods, often involving costly and energy-intensive processes. Alternatively, biogenic synthesis using bacteria, fungi, or plant extracts offers a potentially sustainable and non-toxic approach for producing metal-based nanoparticles (NP). This eco-friendly synthesis approach not only reduces environmental impact but also enhances features of NP production due to the unique biochemistry of the biological systems. Recent advancements have shown that along with chemically synthesized NPs, biogenic NPs possess significant antimicrobial properties. The inherent biochemistry of bacteria enables the efficient conversion of metal salts into NPs through reduction processes, which are further stabilized by biomolecular capping layers that improve biocompatibility and functional properties. This mini review explores the use of bacteria to produce NPs with antimicrobial activities. Microbial technologies to produce NP antimicrobials have considerable potential to help address the antimicrobial resistance crisis, thus addressing critical health issues aligned with the United Nations Sustainability Goal #3 of good health and well-being.

Prophylactic Left Atrial Appendage Ligation During CABG: A Propensity Score-Matched Analysis.

OBJECTIVE: To evaluate short-term outcomes and statewide practice patterns of prophylactic left atrial appendage ligation (P-LAAL) in coronary artery bypass grafting (CABG) patients without pre-operative atrial fibrillation (AF). METHODS: Adult patients who underwent an on-pump CABG (2017 - 2023) within a regional collaborative were identified. Patients with a history of AF, previous cardiac surgery, or non-device based LAAL were excluded. Patients were stratified by LAAL status and were propensity score matched. Univariable analysis was used to compare short-term clinical outcomes. RESULTS: Of 16,547 patients examined, 442 underwent P-LAAL. The propensity score matched cohort (439 P-LAAL, 439 No P-LAAL) was compared and had no significant differences in pre-operative CHA2DS2-VASc scores or operative variables. The P-LAAL group had longer cross clamp time (82 vs 76 minutes, p=0.001), ICU hours (72 vs 66, p=0.001), length of stay (6.0 vs 6.0 days, p=0.010), increased post-operative AF (35% vs 24%, p<0.001), and more discharge on anticoagulation (17% vs 8.2%, p<0.001). There were no significant differences in post-operative stroke (1.1% vs 2.1%, p=0.423), readmission (13% vs 9.6%, p=0.118), operative mortality (2.5% vs 1.6%, p=0.480), or readmission for thrombotic or bleeding complications (0.7% vs 1.1%, p=0.724). Hospitalization costs were significantly higher for P-LAAL patients ($43,478 vs $40,645, p<0.001). The rate of P-LAAL during CABG increased from 1.61% (2017) to 5.65% (2023) (p<0.001). CONCLUSIONS: Despite higher rates of post-operative AF, discharge on anticoagulation, and hospitalization costs in patients undergoing P-LAAL during CABG, there was no difference in short-term clinical endpoints including stroke and operative mortality.

Exploring antimicrobial interactions between metal ions and quaternary ammonium compounds toward synergistic metallo-antimicrobial formulations.

Multi-target antimicrobial agents are considered a viable alternative to target-specific antibiotics, resistance to which emerged as a global threat. Used centuries before the discovery of conventional antibiotics, metal(loid)-based antimicrobials (MBAs), which target multiple biomolecules within the bacterial cell, are regaining research interest. However, there is a significant limiting factor-the balance between cost and efficiency. In this article, we utilize a checkerboard assay approach to explore antimicrobial combinations of MBAs with commonly used quaternary ammonium compound (QAC) antiseptics in order to discover novel combinations with more pronounced antimicrobial properties than would be expected from a simple sum of antimicrobial effects of initial components. This phenomenon, called synergy, was herein demonstrated for several mixtures of Al3+with cetyltrimethylammonium bromide (CTAB) and TeO32- with benzalkonium chloride (BAC) and didecyldimethylammonium bromide (DDAB) against planktonic and biofilm growth of Pseudomonas aeruginosa ATCC27853. Biofilm growth of Escherichia coli ATCC25922 was synergistically inhibited by the Cu2 +and benzalkonium chloride (BAC) mixture. Multiple additive mixtures were identified for both organisms. The current study observed unexpected species and growth state specificities for the synergistic combinations. The benefit of synergistic mixtures will be captured in economy/efficiency optimization for antimicrobial applications in which MBAs and QACs are presently used. IMPORTANCE: We are entering the antimicrobial resistance era (AMR), where resistance to antibiotics is becoming more and more prevalent. In order to address this issue, various approaches are being explored. In this article, we explore for synergy between two very different antimicrobials, the antiseptic class of quaternary ammonium compounds and antimicrobial metals. These two antimicrobials have very different actions. Considering a OneHealth approach to the problem, finding synergistic mixtures allows for greater efficacy at lower concentrations, which would also address antimicrobial pollution issues.

Discovery and generalization of tissue structures from spatial omics data.

Tissues are organized into anatomical and functional units at different scales. New technologies for high-dimensional molecular profiling in situ have enabled the characterization of structure-function relationships in increasing molecular detail. However, it remains a challenge to consistently identify key functional units across experiments, tissues, and disease contexts, a task that demands extensive manual annotation. Here, we present spatial cellular graph partitioning (SCGP), a flexible method for the unsupervised annotation of tissue structures. We further present a reference-query extension pipeline, SCGP-Extension, that generalizes reference tissue structure labels to previously unseen samples, performing data integration and tissue structure discovery. Our experiments demonstrate reliable, robust partitioning of spatial data in a wide variety of contexts and best-in-class accuracy in identifying expertly annotated structures. Downstream analysis on SCGP-identified tissue structures reveals disease-relevant insights regarding diabetic kidney disease, skin disorder, and neoplastic diseases, underscoring its potential to drive biological insight and discovery from spatial datasets.

Revisiting the Posterior Approach for Cervical Radiculopathy Utilizing Endoscopic Techniques: A Favorable Short-Term Outcome and Cost Comparison With Anterior Cervical Discectomy and Fusion.

BACKGROUND: Cervical radiculopathy is a spine ailment frequently requiring surgical decompression via anterior cervical discectomy and fusion (ACDF) or posterior foraminotomy/discectomy. While endoscopic posterior foraminotomy/discectomy is gaining popularity, its financial impact remains understudied despite equivalent randomized long-term outcomes to ACDF. In a cohort of patients undergoing ACDF vs endoscopic posterior cervical foraminotomy/discectomy, we sought to compare the total cost of the surgical episode while confirming an equivalent safety profile and perioperative outcomes. METHODS: A single-center retrospective cohort study of patients with unilateral cervical radiculopathy undergoing ACDF or endoscopic cervical foraminotomy between 2018 and 2023 was undertaken. Primary outcomes included the total cost of care for the initial surgical episode (not charges or reimbursement). Perioperative variables and neurological recovery were recorded. Multivariable analysis tested age, body mass index, race, gender, insurance type, operative time, and length of stay. RESULTS: A total of 38 ACDF and 17 endoscopic foraminotomy/discectomy operations were performed. All patients underwent single-level surgery except for 2 two-level endoscopic decompressions. No differences were found in baseline characteristics and symptom length except for younger age (46.8 ± 9.4 vs 57.6 ± 10.3, P = 0.002) and more smokers (18.4% vs 11.8%, P = 0.043) in the ACDF group. Actual hospital costs for the episode of surgical care were markedly higher in the ACDF cohort (mean ±95% CI; $27,782 ± $2011 vs $10,103 ± $720, P < 0.001) driven by the ACDF approach (ß = $17,723, P < 0.001) on multivariable analysis. On sensitivity analysis, ACDF was never cost-efficient compared with endoscopic foraminotomy, and endoscopic failure rates of 64% were required for break-even cost. ACDF was associated with significantly longer operative time (167.7 ± 22.0 vs 142.7 ± 27.4 minutes, P < 0.001) and length of stay (1.1 ± 0.5 vs 0.1 ± 0.2 days, P < 0.001). No significant difference was found regarding 90-day neurological improvement, readmission, reoperation, or complications. CONCLUSION: Compared with patients treated with a single-level ACDF for unilateral cervical radiculopathy, endoscopic posterior cervical foraminotomy/discectomy can achieve a similar safety profile, pain relief, and neurological recovery at considerably less cost. These findings may help patients and surgeons revisit offering the posterior cervical foraminotomy/discectomy utilizing endoscopic techniques. CLINICAL RELEVANCE: Endoscopic posterior cervical foraminotomy/discectomy offers comparable safety, pain relief, and neurological recovery to traditional methods but at a significantly lower cost.

Barrier films or dressings for the prevention of acute radiation dermatitis in breast cancer: a systematic review and network meta-analysis.

BACKGROUND: Barrier films or dressings were reported to be effective in preventing radiation dermatitis (RD) in breast cancer patients, but their comparative efficacy is unknown. METHODS: A systematic literature search was performed on Embase, MEDLINE and Cochrane CENTRAL Registry of Clinical Trials from inception to October 20, 2023. Randomised controlled trials (RCTs) comparing barrier films or dressings to the standard of care (SOC) or other interventions were included. We estimated summary odds ratios and mean differences using network meta-analysis with random effects. This study was registered with PROSPERO (ID: CRD42023475021). RESULTS: Fourteen RCTs met inclusion criteria. Six interventions were analysed: 3M™ Moisturizing Double Barrier Cream (MDBC), 3M™ No Sting Barrier Film (BF), Hydrofilm® (HF), Mepitel® Film (MF), Silver Leaf Nylon Dressing and StrataXRT®. HF, MF and StrataXRT® reduced the incidence of moist desquamation compared to SOC (HF: OR = 0.08; p = 0.02; MF: OR = 0.31 p < 0.01; StrataXRT®: OR = 0.22, p = 0.04). The ranking of agents from most to least effective in preventing moist desquamation according to P-scores was HF (92.5%), MF (78.5%), StrataXRT® (70.1%), BF (46.4%), Silver Leaf Nylon Dressing (24.9%), MDBC (22.9%) and SOC (14.7%). Only four RCTs on HF and MF included patient-reported outcome (PRO) assessments that allowed pooling for analysis. HF and MF were more effective in reducing pain, itchiness and burning sensation compared to SOC (p < 0.01 for all symptoms). CONCLUSION: HF and MF were effective in preventing RD in breast cancer. Future RCTs should compare these interventions to effective cream preparations, such as topical corticosteroids.

RNAseq analysis of oocyte maturation from the germinal vesicle stage to metaphase II in pig and human.

During maturation oocytes at the germinal vesicle (GV) stage progress to metaphase II (MII). However, during in vitro maturation a proportion often fail to progress. To understand these processes, we employed RNA sequencing to examine the transcriptome profile of these three groups of oocytes from the pig. We compared our findings with similar public oocyte data from humans. The transcriptomes in oocytes that failed to progress was similar to those that did. We found in both species, the most upregulated genes in MII oocytes were associated with chromosome segregation and cell cycle processes, while the most down regulated genes were relevant to ribosomal and mitochondrial pathways. Moreover, those genes involved in chromosome segregation during GV to MII transition were conserved in pig and human. We also compared MII and GV oocyte transcriptomes at the isoform transcript level in both species. Several thousands of genes (including DTNBP1, MAPK1, RAB35, GOLGA7, ATP1A1 and ATP2B1) identified as not different in expression at a gene transcript level were found to have differences in isoform transcript levels. Many of these genes were involved in ATPase-dependent or GTPase-dependent intracellular transport in pig and human, respectively. In conclusion, our study suggests the failure to progress to MII in vitro may not be regulated at the level of the genome and that many genes are differentially regulated at the isoform level, particular those involved ATPase- or GTPase-dependent intracellular transport.

Unique features of KGN granulosa-like tumour cells in the regulation of steroidogenic and antioxidant genes.

The ovarian KGN granulosa-like tumour cell line is commonly used as a model for human granulosa cells, especially since it produces steroid hormones. To explore this further, we identified genes that were differentially expressed by KGN cells compared to primary human granulosa cells using three public RNA sequence datasets. Of significance, we identified that the expression of the antioxidant gene TXNRD1 (thioredoxin reductase 1) was extremely high in KGN cells. This is ominous since cytochrome P450 enzymes leak electrons and produce reactive oxygen species during the biosynthesis of steroid hormones. Gene Ontology (GO) analysis identified steroid biosynthetic and cholesterol metabolic processes were more active in primary granulosa cells, whilst in KGN cells, DNA processing, chromosome segregation and kinetochore pathways were more prominent. Expression of cytochrome P450 cholesterol side-chain cleavage (CYP11A1) and cytochrome P450 aromatase (CYP19A1), which are important for the biosynthesis of the steroid hormones progesterone and oestrogen, plus their electron transport chain members (FDXR, FDX1, POR) were measured in cultured KGN cells. KGN cells were treated with 1 mM dibutyryl cAMP (dbcAMP) or 10 µM forskolin, with or without siRNA knockdown of TXNRD1. We also examined expression of antioxidant genes, H2O2 production by Amplex Red assay and DNA damage by γH2Ax staining. Significant increases in CYP11A1 and CYP19A1 were observed by either dbcAMP or forskolin treatments. However, no significant changes in H2O2 levels or DNA damage were found. Knockdown of expression of TXNRD1 by siRNA blocked the stimulation of expression of CYP11A1 and CYP19A1 by dbcAMP. Thus, with TXNRD1 playing such a pivotal role in steroidogenesis in the KGN cells and it being so highly overexpressed, we conclude that KGN cells might not be the most appropriate model of primary granulosa cells for studying the interplay between ovarian steroidogenesis, reactive oxygen species and antioxidants.

The impact of exchanging the light and heavy chains on the structures of bovine ultralong antibodies.

The third complementary-determining regions of the heavy-chain (CDR3H) variable regions (VH) of some cattle antibodies are highly extended, consisting of 48 or more residues. These `ultralong' CDR3Hs form ß-ribbon stalks that protrude from the surface of the antibody with a disulfide cross-linked knob region at their apex that dominates antigen interactions over the other CDR loops. The structure of the Fab fragment of a naturally paired bovine ultralong antibody (D08), identified by single B-cell sequencing, has been determined to 1.6 Šresolution. By swapping the D08 native light chain with that of an unrelated antigen-unknown ultralong antibody, it is shown that interactions between the CDR3s of the variable domains potentially affect the fine positioning of the ultralong CDR3H; however, comparison with other crystallographic structures shows that crystalline packing is also a major contributor. It is concluded that, on balance, the exact positioning of ultralong CDR3H loops is most likely to be due to the constraints of crystal packing.

Beyond surgery: Pre- and post-operative care in children with ankyloglossia.

BACKGROUND: Surgical intervention for tongue-tie, or ankyloglossia performed by paediatric dentists can alleviate symptoms and improve functional abilities in infants and children. Despite widespread practice, there are currently no established clinical guidelines or consistent approaches for pre- and post-operative care of children. AIM: The aim of this study was to explore approaches to pre- and post-operative care for children with ankyloglossia having frenum surgery. DESIGN: A scoping review of peer-reviewed articles in four electronic databases was conducted. Intervention studies that reported on pre- or post-operative regimens for infants, children and adolescents (0 to 18 years) with a diagnosis of tongue-tie or ankyloglossia, who had surgical intervention such as frenotomy or frenectomy, were included and quality assessments performed. RESULTS: Twenty-three studies were identified, with seven studies incorporating both pre- and post-operative care, and 16 studies focussing solely on post-operative care. Tongue exercises were commonly prescribed, and only three studies examined the relationship between post-operative care and recovery outcomes. Considerable variability existed in study design, prescribed care and outcome measures. CONCLUSION: There was substantial variability in pre- and post-operative care protocols, including dosage, frequency and duration of exercises and other care regimens for infants and children having frenum surgery. Further research is needed to determine the most effective course of pre- and post-operative care for children undergoing frenum surgery.

The involvement of the piriform cortex in non-lesional temporal lobe epilepsy: an uncommon component of the epileptogenic network.

The piriform cortex is recognized as highly epileptogenic in rodents, yet its electrophysiological role in human epilepsy remains understudied. Recent surgical outcomes have suggested potential benefits in resecting the piriform cortex for cases of medial temporal lobe epilepsy. However, little is known about its electrophysiological activity in human epilepsy. This case-series study aimed to explore the electrophysiological role of the piriform cortex within the epileptogenic network among patients with suspected temporal lobe epilepsy. Participants were recruited from Emory University Hospital or Children's Healthcare of Atlanta, with non-lesional frontotemporal or temporal lobe hypotheses, undergoing stereoelectroencephalographic studies. Specifically, focus was placed on patients with one or more electrode contacts in the piriform cortex. Primary objectives included determining piriform cortex involvement within the electrophysiologically defined epileptogenic network and assessing the effects of electrical stimulation. Twenty-two patients were included in the study. Notably, only one patient exhibited piriform cortex involvement at seizure onset, associated with an olfactory aura. Two patients showed early piriform cortex involvement, while others displayed late or no involvement. Electrical stimulation of the piriform cortex induced after-discharges in three patients and replicated a habitual seizure in one. These findings present a contrast to surgical outcome studies, suggesting that the piriform cortex may not typically play a significant role in the epileptogenic network among patients with non-lesional temporal lobe epilepsy.