Concurrent expectation and experience-based metacontrol: EEG insights and the role of working memory capacity.

We investigated the simultaneous influence of expectation and experience on metacontrol, which we define as the instantiation of context-specific control states. These states could entail heightened control states in preparation for frequent task switching or lowered control states for task repetition. Specifically, we examined whether "expectations" regarding future control demands prompt proactive metacontrol, while "experiences" with items associated with specific control demands facilitate reactive metacontrol. In Experiment 1, we utilized EEG with a high temporal resolution to differentiate between brain activities associated with proactive and reactive metacontrol. We successfully observed cue-locked and image-locked ERP patterns associated with proactive and reactive metacontrol, respectively, supporting concurrent instantiation of two metacontrol modes. In Experiment 2, we focused on individual differences to investigate the modulatory role of working memory capacity (WMC) in the concurrent instantiation of two metacontrol modes. Our findings revealed that individuals with higher WMC exhibited enhanced proactive metacontrol, indicated by smaller response time variability (RTV). Additionally, individuals with higher WMC showed a lower tendency to rely on reactive metacontrol, indicated by a smaller item-specific switch probability (ISSP) effect. In conclusion, our results suggest that proactive and reactive metacontrol can coexist, but their interplay is influenced by individuals' WMC. Higher WMC promotes the use of proactive metacontrol while attenuating reliance on reactive metacontrol. This study provides insights into the interplay between proactive and reactive metacontrol and highlights the impact of WMC on their concurrent instantiation.

Autologous stem cell transplantation for untreated transformed indolent B-cell lymphoma in first remission: an international, multi-centre propensity-score-matched study.

High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are used as consolidation in first remission (CR1) in some centres for untreated, transformed indolent B-cell lymphoma (Tr-iNHL) but the evidence base is weak. A total of 319 patients with untreated Tr-iNHL meeting prespecified transplant eligibility criteria [age <75, LVEF ≥45%, no severe lung disease, CR by positron emission tomography or computed tomography ≥3 months after at least standard cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) intensity front-line chemotherapy] were retrospectively identified. Non-diffuse large B-cell lymphoma transformations were excluded. About 283 (89%) patients had follicular lymphoma, 30 (9%) marginal-zone lymphoma and six (2%) other subtypes. Forty-nine patients underwent HDC/ASCT in CR1, and a 1:2 propensity-score-matched cohort of 98 patients based on age, stage and high-grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangements (HGBL-DH) was generated. After a median follow-up of 3·7 (range 0·1-18·3) years, ASCT was associated with significantly superior progression-free survival [hazard ratio (HR) 0·51, 0·27-0·98; P = 0·043] with a trend towards inferior overall survival (OS; HR 2·36;0·87-6·42; P = 0·1) due to more deaths from progressive disease (8% vs. 4%). Forty (41%) patients experienced relapse in the non-ASCT cohort - 15 underwent HDC/ASCT with seven (47%) ongoing complete remission (CR); 10 chimeric antigen receptor-modified T-cell (CAR-T) therapy with 6 (60%) ongoing CR; 3 allogeneic SCT with 2 (67%) ongoing CR. Although ASCT in CR1 improves initial duration of disease control in untreated Tr-iNHL, the impact on OS is less clear with effective salvage therapies in this era of CAR-T.

Promising applications of cold plasma for microbial safety, chemical decontamination and quality enhancement in fruits.

Consumers' demand is increasing for safe foods without impairing the phytochemical and sensory quality. In turn, it has increased research interest in the exploration of innovative food processing technologies. Cold plasma technology is getting popularity now days owing to its high efficacy in decontamination of microbes in fruit and fruit-based products. As a on-thermal approach, plasma processing maintains the quality of fruits and minimizes the thermal effects on nutritional properties. Cold plasma is also exploited for inactivating enzymes and degrading pesticides as both are directly related with quality loss and presently are most important concerns in fresh produce industry. The present review covers the influence of cold plasma technology on reducing microbial risks and enhancing the quality attributes in fruits.

Febrile neutropenia and its associated hospitalization in breast cancer patients on docetaxel-containing regimen: A retrospective cohort study on duration of prophylactic GCSF administration.

PURPOSE: To compare febrile neutropenia (FN) incidence and hospitalization among breast cancer patients on docetaxel with no granulocyte colony-stimulating factors (GCSF) primary prophylaxis (PP), 4/5-day PP, or 7-day PP. METHODS: We identified 3916 breast cancer patients using docetaxel-cyclophosphamide (TC), doxorubicin-cyclophosphamide then docetaxel (AC-T), fluorouracil-epirubicin-cyclophosphamide then docetaxel (FEC-T), docetaxel-carboplatin-trastuzumab (TJH), or docetaxel-doxorubicin-cyclophosphamide (TAC) from a hospital pharmacy dispensing database in Hong Kong between 2014 and 2016. Patients were offered GCSF within 5 days since administering docetaxel. Outcomes included FN incidence, time to first hospitalization, hospitalization rate, and duration. RESULTS: In TC regimen, FN incidence (with odds ratio, OR) of patients with no PP, 4/5-day PP, and 7-day PP was 21.69%, 7.95% (OR 0.31, p < 0.001), and 5.33% (OR 0.20, p < 0.001), respectively. In TJH regimen, FN incidence of patients with no PP, 4/5-day PP, and 7-day PP was 38.26%, 8.33% (OR 0.15, p < 0.001), and 8.57% (OR 0.15, p < 0.001), respectively. FN incidence of patients on AC-T regimen with no PP and 4/5-day PP was 20.93% and 6.84%, respectively (OR 0.28, p = 0.005); with FEC-T regimen, the incidence was 9.91% and 4.77%, respectively (OR 0.46, p = 0.035). Only 3.27% FN cases were not hospitalized. Mean (±standard deviation, SD) time to first hospitalization was 8.21 ± 2.44 days. Mean (±SD) duration of hospitalization for patients with no PP, 4/5-day PP, and 7-day PP was 4.66 ± 2.60, 4.37 ± 2.85, and 5.12 ± 2.97 days, respectively. CONCLUSION: GCSF prophylaxis in breast cancer patients on docetaxel could reduce FN incidence and hospitalization. 4/5-day PP demonstrated similar efficacy to 7-day PP with superior saving benefits on healthcare expenditure.

Survival advantage of initiating dialysis in elderly and non-elderly incident end-stage kidney disease patients.

AIM: Many patients, especially the elderly, who require renal replacement therapies (RRT) have delayed or rejected dialysis for various reasons. Current dialysis guidelines may not be relevant for the elderly or frail patients. We aim to determine survival advantage of initiating dialysis in patients deemed to require RRT. METHODS: This was an observational cohort on incident end-stage kidney disease (ESKD) patients from January 1, 2007 to December 31, 2008. The primary outcome was all-cause mortality. Patients contributed person-time from the date of ESKD diagnosis until death, transplant or end of study on December 31, 2014, whichever occurred first. An extended Cox regression model with time-varying exposure to dialysis was used to account for immortal time bias. RESULTS: Of 3990 incident ESKD patients included, 70.2% patients initiated dialysis; 78.8% with haemodialysis (HD) while the remaining 21.2% with peritoneal dialysis (PD). Dialysis reduced hazard of death in both elderly and non-elderly patients even after controlling for comorbidities (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.50, 0.68 and HR 0.76, 95% CI 0.69, 0.85, respectively). HD was protective in both the elderly and non-elderly (HR 0.53, 95% CI 0.45, 0.63 and HR 0.71, 95% CI 0.64, 0.80, respectively). PD significantly reduced risk of death compared to no dialysis in the elderly but not in the non-elderly. CONCLUSION: Dialysis improved survival in all incident ESKD patients. The findings suggested a larger protection offered by HD. Although improvement in survival from initiating dialysis was large, its true benefit should take overall quality of life into account. SUMMARY AT A GLANCE This observational study showed that initiation of dialysis improves the survival of end-stage kidney disease (ESKD) patients of all age groups, but the quality of life is an important aspect that has not been explored.

Prevalence and risk factors of genitourinary Chlamydia trachomatis infection among patients attending sexually transmitted disease clinics in northern Malaysia.

INTRODUCTION: Chlamydia trachomatis is one of the most common sexually transmitted diseases (STDs) globally. However, data on its prevalence and risk factors in Malaysia is still scarce. OBJECTIVE: We aimed to identify the prevalence and risk factors of genitourinary C.trachomatis infection among patients attending STD clinics in northern Peninsular Malaysia. METHODS: A hospital-based cross-sectional study was conducted in STD clinics of Hospital Pulau Pinang and Hospital Sultanah Bahiyah, Kedah from January to November 2014. Participants were individually interviewed using a structured data collection form followed by a physical examination and laboratory tests. Nucleic Acid Amplification Test (NAAT) was used to detect C.trachomatis infection. Analysis was carried out using SPSS Version 15. RESULTS: Eighty-three sexually active patients were enrolled, consisting of 51 males and 32 females. The median age was 28.0 years. In general, 32.5% patients were asymptomatic, the remaining presented with genital discharge (41.0%), genital warty lesion (25.3%), genital ulcer (13.3%), dysuria (13.3%), dyspareunia (2.4%), urine hesistancy (1.2%) and genital swelling (1.2%). The prevalence of genitourinary C.trachomatis infection was 21.7% in the study population; 17.6% in males and 28.1% in females. Among the infected females, 44.4% were pregnant. Of those infected 56.6% did not show any symptoms of genital infection, and 77.8% were aged between 18 and 30 years, of which most were females. Among newly diagnosed HIV patients, the prevalence was 14.3%. From multivariable logistic regression analysis, age under 28 years, being married and engagement in oral sex had significantly increased odds of C.trachomatis infection. CONCLUSIONS: C.trachomatis infection was common among patients attending STD clinics in northern Penisular Malaysia especially in the younger age groups. Majority of the infected patients were asymptomatic.

Exploring the DBR superlattice effect on the thermal performance of a VECSEL with the finite element method.

The design criterion of thermal conductivity for the GaAs/AlAs distributed Bragg reflector (DBR) superlattice structure was thoroughly investigated to precisely analyze the thermal behaviors of the optically pumped vertically external cavity surface-emitting laser (VECSEL). A finite element model with detailed configuration of a VECSEL gain chip was constructed to fulfill the analysis. A 1060 nm VECSEL with different pump conditions was further demonstrated to verify the finite element analysis. At the VECSEL thermal rollover point, the analysis results show that the model with the superlattice property predicts more precise temperature values than that using a bulk composite property. It reveals that the accurate determination of the thermal conductivity of the DBR superlattice is significantly important for the VECSEL thermal analysis.

Synchronous colorectal carcinoma: predisposing factors and characteristics.

AIM: Whether some diseases are related to the occurrence of synchronous colorectal carcinoma (sCRC) is unknown. Investigating the risk factors and presentation of sCRC could aid in the treatment of patients with colorectal cancer (CRC). The prognosis of sCRC compared with that of solitary CRC remains unclear. METHODS: A total of 17 093 CRC patients were recruited between 1st January 1995 and 31th December 2016. The risk factors of sCRC development were assessed using univariate and multivariate logistic regression. The effect of sCRC on survival was analysed using the multivariate Cox regression model. RESULTS: The prevalence of sCRC was 5.6% in this study. The independent risk factors of sCRC development were advanced age (P < 0.001), male sex (P < 0.001), hereditary cancer (P < 0.001), hypertension (P < 0.001) and liver cirrhosis (P = 0.024). Compared with solitary CRC, a higher number of patients with sCRC presented with an abnormal carcinoembryonic antigen (CEA) level (P = 0.011), anaemia (P < 0.001) and hypoalbuminemia (P < 0.001). Multivariate analysis revealed that sCRC was a significant factor for poor survival in patients at TNM Stage I [hazard ratio (HR) = 1.86; P < 0.001], Stage II (HR = 1.65; P < 0.001) and Stage III (HR = 1.40; P < 0.001). CONCLUSIONS: In addition to hypertension and liver cirrhosis, other risk factors for sCRC were identified in this study. The prognosis of patients with sCRC was significantly worse than that of those with solitary CRC through TNM Stages I to III. Anaemia, abnormal CEA and hypoalbuminemia were more commonly seen in patients with sCRC.

Role of small subunit in mediating assembly of red-type form I Rubisco.

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the key enzyme involved in photosynthetic carbon fixation, converting atmospheric CO2 to organic compounds. Form I Rubisco is a cylindrical complex composed of eight large (RbcL) subunits that are capped by four small subunits (RbcS) at the top and four at the bottom. Form I Rubiscos are phylogenetically divided into green- and red-type. Some red-type enzymes have catalytically superior properties. Thus, understanding their folding and assembly is of considerable biotechnological interest. Folding of the green-type RbcL subunits in cyanobacteria is mediated by the GroEL/ES chaperonin system, and assembly to holoenzyme requires specialized chaperones such as RbcX and RAF1. Here, we show that the red-type RbcL subunits in the proteobacterium Rhodobacter sphaeroides also fold with GroEL/ES. However, assembly proceeds in a chaperone-independent manner. We find that the C-terminal ß-hairpin extension of red-type RbcS, which is absent in green-type RbcS, is critical for efficient assembly. The ß-hairpins of four RbcS subunits form an eight-stranded ß-barrel that protrudes into the central solvent channel of the RbcL core complex. The two ß-barrels stabilize the complex through multiple interactions with the RbcL subunits. A chimeric green-type RbcS carrying the C-terminal ß-hairpin renders the assembly of a cyanobacterial Rubisco independent of RbcX. Our results may facilitate the engineering of crop plants with improved growth properties expressing red-type Rubisco.

Favorable Waitlist and Posttransplant Outcomes in Children and Adolescent Patients Supported With Durable Continuous-Flow Ventricular Assist Devices.

Pediatric centers are implanting durable adult continuous-flow ventricular assist devices (CFVADs) in children who are smaller than the industry-recommended size. Waitlist and posttransplant outcomes data in pediatric patients supported with CFVADs as a bridge to transplant are limited. We analyzed the United Network of Organ Sharing and Organ Procurement and Transplantation Network registry to identify patients aged ≤18 years with a CFVAD at the time of listing or transplantation. Patients were stratified by body surface area (BSA; >1.5 vs. ≤1.5 m(2) ) at time of listing. We identified 138 patients with a durable CFVAD during the listing period (100 with BSA >1.5 m(2) , 38 with BSA ≤1.5 m(2) ). Patients with BSA ≤1.5 m(2) were more likely to have a noncardiomyopathy diagnosis (18% vs. 4%, p = 0.007) and to be implanted with a centrifugal-flow rather than an axial-flow device (74% vs. 30%, p = 0.001). There was no difference in failure-free waitlist survival between BSA groups (p = 0.99) among patients with a CFVAD at listing. Posttransplantation survival was 100% and 88% at 1 and 5 years, respectively, for the entire cohort and did not differ by BSA group (p = 0.99). Consequently, waitlist and posttransplant outcomes are favorable for pediatric CFVAD recipients. Small patients (≤1.5 m(2) ) had pre- and posttransplant outcomes similar to those of larger patients that met the industry-recommended size for implantation.

Differential risk reclassification improvement by exercise testing and myocardial perfusion imaging in patients with suspected and known coronary artery disease.

OBJECTIVE: The objective of this study is to compare the incremental prognostic and net risk reclassification value of exercise testing alone vs exercise myocardial perfusion imaging (MPI) for estimating the risk of death in patients with suspected and known coronary artery disease (CAD). METHODS: 6702 patients with suspected CAD and 2008 with known CAD had treadmill exercise MPI and were followed for 2.5 ± 0.9 years for the occurrence of all-cause death. The estimation of risk of death and net reclassification improvement (NRI) were examined in three models. Model 1: clinical variables; Model 2: model 1+Duke Treadmill Score; and Model 3: model 2+ MPI variables. Risk estimates were categorized as <1%, 1-3%, and >3% risk of death per year. RESULTS: In patients with suspected CAD, the global Chi-square for predicting risk of death increased significantly for Model 2 compared to Model 1 (74.78 vs 63.86 to (P = .001). However, adding MPI variables in Model 3 did not further improve predictive value (Chi-square 79.38, P = .10). In patients with suspected CAD risk, reclassification improved significantly in Model 2 over Model 1 (NRI = 0.12, 95% CI 0.02 to 0.22, P = .019), but not in Model 3 (NRI = 0.0009, 95% CI -0.072 to 0.070; P = .98). In contrast, in patients with known CAD Model 2 did not yield significant improvements for predicting risk and risk reclassification compared to Model 1. However, global Chi-square of Model 3 was significantly higher than that of Model 2 (30.03 vs 6.56, P < .0001) with associated significant reclassification improvement (NRI = 0.26 95% CI 0.067 to 0.46. P = .0084). CONCLUSION: Risk reclassification by diagnostic testing is importantly influenced by baseline characteristics of patient cohorts. In patients with suspected CAD, NRI is predominately achieved by exercise variables, whereas in patients with known CAD, greatest NRI is obtained by MPI variables.

Basiliximab treatment for autoimmune bowel disease in a pediatric heart transplant patient.

Autoimmune-mediated bowel disease has been reported after pediatric heart transplantation. Recognition and treatment of these patients has been difficult. We describe a patient who responded to steroids and basiliximab therapy after an inflammatory process secondary to abnormal T-cell activation. Our patient is a 28-month-old female who received a heart transplant at five wk of age. At 24 months post-transplant, she developed fever and bloody stools. Initial investigations were significant for an elevated ESR (>120) and CRP (15.2). Symptoms persisted despite bowel rest and mycophenolate discontinuation. Endoscopic evaluation revealed discontinuous ulcerative disease involving esophagus, terminal ileum, right and left colon, necessitating extensive bowel resection. She had additional airway inflammation leading to a TEF at the site of esophageal ulceration, requiring tracheostomy. Immune evaluation revealed autoimmune dysregulation that responded to parenteral methylprednisolone. Chronic basiliximab therapy allowed for successful weaning of steroids with sustained remission. She has been transitioned to sirolimus and tacrolimus maintenance immunosuppression with plans to discontinue basiliximab once off steroids. In conclusion, bowel disease in the setting of pediatric heart transplantation can be severe and refractory to traditional treatment methods. Tailoring immune therapy to activated T cells can result in remission. Basiliximab therapy was used in our patient to maintain steroid-induced remission, but long-term complications of this disease process are unknown.

Retroelement insertions at the Medicago FTa1 locus in spring mutants eliminate vernalisation but not long-day requirements for early flowering.

Molecular-genetic control of the flowering time of temperate-climate plants is best understood in Arabidopsis and the cereals wheat and barley. However, key regulators such as FLC and cereal VRN2 are not found in legumes. Therefore, we used forward genetics to identify flowering time genes in the model legume Medicago truncatula (Medicago) which is induced to flower by vernalisation and long-day photoperiods. A screen of a Tnt1 retroelement tagging population yielded two mutants, spring2 and spring3, with a dominant early flowering phenotype. These mutants overexpress the floral activator FTa1 and two candidate downstream flowering genes SOC1a and FULb, similar to the spring1 somaclonal variant that we identified previously. We demonstrate here that an increase in the expression of FTa1, SOC1a and FULb and early flowering does not occur in all conditions in the spring mutants. It depends on long-day photoperiods but not on vernalisation. Isolation of flanking sequence tags and linkage analysis identified retroelement insertions at FTa1 that co-segregated with the early flowering phenotype in all three spring mutants. These were Tnt1 insertions in the FTa1 third intron (spring3) or the 3' intergenic region (spring2) and an endogenous MERE1-4 retroelement in the 3' intergenic region in spring1. Thus the spring mutants form an allelic series of gain-of-function mutations in FTa1 which confer a spring growth habit. The spring retroelement insertions at FTa1 separate long-day input from vernalisation input into FTa1 regulation, but this is not due to large-scale changes in FTa1 DNA methylation or transcript processing in the mutants.

20 THz broadband generation using semi-insulating GaAs interdigitated photoconductive antennas.

We demonstrate broadband (20 THz), high electric field, terahertz generation using large area interdigitated antennas fabricated on semi-insulating GaAs. The bandwidth is characterized as a function of incident pulse duration (15-35 fs) and pump energy (2-30 nJ). Broadband spectroscopy of PTFE is shown. Numerical Drude-Lorentz simulations of the generated THz pulses are performed as a function of the excitation pulse duration, showing good agreement with the experimental data.

Fully Automated Measurement of the Insall-Salvati Ratio with Artificial Intelligence.

Patella alta (PA) and patella baja (PB) affect 1-2% of the world population, but are often underreported, leading to potential complications like osteoarthritis. The Insall-Salvati ratio (ISR) is commonly used to diagnose patellar height abnormalities. Artificial intelligence (AI) keypoint models show promising accuracy in measuring and detecting these abnormalities.An AI keypoint model is developed and validated to study the Insall-Salvati ratio on a random population sample of lateral knee radiographs. A keypoint model was trained and internally validated with 689 lateral knee radiographs from five sites in a multi-hospital urban healthcare system after IRB approval. A total of 116 lateral knee radiographs from a sixth site were used for external validation. Distance error (mm), Pearson correlation, and Bland-Altman plots were used to evaluate model performance. On a random sample of 2647 different lateral knee radiographs, mean and standard deviation were used to calculate the normal distribution of ISR. A keypoint detection model had mean distance error of 2.57 ± 2.44 mm on internal validation data and 2.73 ± 2.86 mm on external validation data. Pearson correlation between labeled and predicted Insall-Salvati ratios was 0.82 [95% CI 0.76-0.86] on internal validation and 0.75 [0.66-0.82] on external validation. For the population sample of 2647 patients, there was mean ISR of 1.11 ± 0.21. Patellar height abnormalities were underreported in radiology reports from the population sample. AI keypoint models consistently measure ISR on knee radiographs. Future models can enable radiologists to study musculoskeletal measurements on larger population samples and enhance our understanding of normal and abnormal ranges.

Neoadjuvant radiotherapy followed by hysterectomy in locally advanced endometrial cancer: Outcomes from a tertiary government hospital in the Philippines.

Objective: Managing endometrial cancer with suspected or gross cervical involvement lacks a standard approach. This study evaluated outcomes in patients with cervical and/or parametrial involvement treated with neoadjuvant radiation followed by hysterectomy. Methods: Fourteen patients from 2007 to 2022 with locally advanced endometrial cancer and cervical and/or parametrial involvement were retrospectively analyzed. They received neoadjuvant external beam radiotherapy (45-50.4 Gy in 25-30 fractions) and high-dose rate brachytherapy (5.5-7.0 Gy per fraction in 3-4 fractions), followed by extrafascial hysterectomy. Clinical data, pathologic response, and survival outcomes were assessed, along with factors associated with pathologic response. Results: Most patients (86%) had stage III disease with cervical extension, 93% had parametrial involvement, and 14% had nodal involvement. Chemotherapy was given to 86% either concurrently or adjuvantly. Post-surgery, 86% had no pathologic cervical involvement, and 93% had negative surgical margins. Pathologic complete response was seen in 43%. Locoregional recurrence occurred in 14%. Median follow-up was 30 months, with recurrence-free survival and overall survival rates of 86% and 100%, respectively. Lower grade tumors significantly correlated with pathologic complete response (Φ = 0.72, p = 0.026). No significant correlation was found between pathologic complete response and other factors. No late grade 3-4 toxicities were reported. Conclusion: Neoadjuvant radiation followed by hysterectomy, with or without chemotherapy, is a viable strategy for managing endometrial cancer with cervical and/or parametrial involvement. This approach enhances resectability, yielding high rates of pathologic complete response and negative resection margins, showing promise for this challenging patient group.

The impact of lutein-loaded poly(lactic-co-glycolic acid) nanoparticles following topical application: An in vitro and in vivo study.

Antioxidant therapies are of interest in the prevention and management of ocular disorders such as cataracts. Although an active area of interest, topical therapy with antioxidants for the treatment of cataracts is complicated by multiple ocular anatomical barriers, product stability, and solubility. Entrapment and delivery of antioxidants with poly(lactic-co-glycolic acid) nanoparticles is a possible solution to these challenges, however, little is known regarding their effects in vitro or in vivo. Our first aim was to investigate the impact of blank and lutein loaded PLGA nanoparticles on viability and development of reactive oxygen species in lens epithelial cells in vitro. Photo-oxidative stress was induced by ultraviolet light exposure with cell viability and reactive oxygen species monitored. Next, an in vivo, selenite model was utilized to induce cataract formation in rodents. Eyes were treated topically with both free lutein and lutein loaded nanoparticles (LNP) at varying concentrations. Eyes were monitored for the development of anterior segment changes and cataract formation. The ability of nanodelivered lutein to reach the anterior segment of the eye was evaluated by liquid chromatography coupled to mass spectrometry of aqueous humor samples and liquid chromatography coupled to tandem mass spectrometry (targeted LC-MS/MS) of lenses. LNP had a minimal impact on the viability of lens epithelial cells during the short exposure timeframe (24 h) and at concentrations < 0.2 µg LNP/µl. A significant reduction in the development of reactive oxygen species was also noted. Animals treated with LNPs at an equivalent lutein concentration of 1,278 µg /mL showed the greatest reduction in cataract scores. Lutein delivery to the anterior segment was confirmed through evaluation of aqueous humor and lens sample evaluation. Topical treatment was not associated with the development of secondary keratitis or anterior uveitis when applied once daily for one week. LNPs may be an effective in the treatment of cataracts.

Chaperonin cofactors, Cpn10 and Cpn20, of green algae and plants function as hetero-oligomeric ring complexes.

The chloroplast chaperonin system of plants and green algae is a curiosity as both the chaperonin cage and its lid are encoded by multiple genes, in contrast to the single genes encoding the two components of the bacterial and mitochondrial systems. In the green alga Chlamydomonas reinhardtii (Cr), three genes encode chaperonin cofactors, with cpn10 encoding a single ∼10-kDa domain and cpn20 and cpn23 encoding tandem cpn10 domains. Here, we characterized the functional interaction of these proteins with the Escherichia coli chaperonin, GroEL, which normally cooperates with GroES, a heptamer of ∼10-kDa subunits. The C. reinhardtii cofactor proteins alone were all unable to assist GroEL-mediated refolding of bacterial ribulose-bisphosphate carboxylase/oxygenase but gained this ability when CrCpn20 and/or CrCpn23 was combined with CrCpn10. Native mass spectrometry indicated the formation of hetero-oligomeric species, consisting of seven ∼10-kDa domains. The cofactor "heptamers" interacted with GroEL and encapsulated substrate protein in a nucleotide-dependent manner. Different hetero-oligomer arrangements, generated by constructing cofactor concatamers, indicated a preferential heptamer configuration for the functional CrCpn10-CrCpn23 complex. Formation of heptamer Cpn10/Cpn20 hetero-oligomers was also observed with the Arabidopsis thaliana (At) cofactors, which functioned with the chloroplast chaperonin, AtCpn60α(7)ß(7). It appears that hetero-oligomer formation occurs more generally for chloroplast chaperonin cofactors, perhaps adapting the chaperonin system for the folding of specific client proteins.

Effect of the coronavirus disease 2019 pandemic on paediatric bilateral myringotomy and tube insertion rates in New Brunswick, Canada.

OBJECTIVE: To assess the effect of the coronavirus disease 2019 pandemic on paediatric bilateral myringotomy and tube insertion rates in New Brunswick, Canada. METHODS: All paediatric bilateral myringotomy and tube insertion cases from 1 July 2015 through 30 June 2021 were provided by New Brunswick Medicare. The numbers of otolaryngologists, cataract surgical procedures, total hip arthroplasties and thyroidectomies were collected to assess the availability of operating theatres and otolaryngologists. Negative binomial logarithmic regressions were used for analyses. RESULTS: Of the 5175 paediatric bilateral myringotomy and tube insertion cases that were included, the bilateral myringotomy and tube insertion rate significantly decreased by 2.9 times (p < 0.001) during the pandemic. Thyroidectomies, cataract surgical procedures and total hip arthroplasties did not significantly decrease. The number of otolaryngologists increased (20 vs 16-17). CONCLUSION: Paediatric bilateral myringotomy and tube insertion rates significantly decreased during the pandemic. This cannot be accounted for by reduced otolaryngologists or operating theatre availability. The paediatric bilateral myringotomy and tube insertion rate decrease is likely due to public health measures reducing the transmission of upper respiratory tract infections, resulting in fewer indications for paediatric bilateral myringotomy and tube insertion.