A computer-aided detection system in the everyday setting of diagnostic, screening and surveillance colonoscopy: an international, randomized trial.

BACKGROUND AND STUDY AIM: Computer-aided detection (CADe) has been developed to improve detection during colonoscopy. After initial reports of high efficacy, there has been an increasing recognition of variability in the effectiveness of CADe systems. The aim of this study was to evaluate a CADe system (PENTAX Medical, Tokyo, Japan) in a varied colonoscopy population. PATIENTS AND METHODS: A multicenter, randomized trial was conducted at 7 hospitals (both university and non-university) in Europe and Canada. Participants referred for diagnostic, non-iFOBT screening, or surveillance colonoscopy were randomized (1:1) to undergo CADe-assisted or conventional colonoscopy (CC) by experienced endoscopists. Participants with insufficient bowel preparation were excluded from the analysis. Primary outcome was adenoma detection rate (ADR). Secondary outcomes included adenomas per colonoscopy (APC) and sessile serrated lesions per colonoscopy (SSLPC). RESULTS: In total, 581 participants were enrolled, of which 497 were included in the final analysis: 250 in the CADe-arm and 247 in the CC-arm. Surveillance was the indication in 202/497 (40.6%) colonoscopies, diagnostic in 199/497 (40.0%), and non-iFOBT screening in 96/497 (19.3%). Overall, ADR (38.4% vs. 37.7%; p=0.43) and APC (0.66 vs. 0.66; p=0.97) were similar between CADe and CC. SSLPC was increased (0.30 vs. 0.19; p=0.049) in the CADe-arm vs. CC. CONCLUSIONS: In this study conducted by experienced endoscopists, CADe did not result in a statistically significant increase in ADR. However, the ADR of our control group substantially surpassed our sample size assumptions, increasing the risk of an underpowered trial. (Trialsearch.who.int:NL9135).

Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery. METHODS: PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1-3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness. DISCUSSION: This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients. TRIAL REGISTRATION: This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).

Assessing fragility of statistically significant findings from randomized controlled trials assessing pharmacological therapies for opioid use disorders: a systematic review.

BACKGROUND: The fragility index is a statistical measure of the robustness or "stability" of a statistically significant result. It has been adapted to assess the robustness of statistically significant outcomes from randomized controlled trials. By hypothetically switching some non-responders to responders, for instance, this metric measures how many individuals would need to have responded for a statistically significant finding to become non-statistically significant. The purpose of this study is to assess the fragility index of randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder. This will provide an indication as to the robustness of trials in the field and the confidence that should be placed in the trials' outcomes, potentially identifying ways to improve clinical research in the field. This is especially important as opioid use disorder has become a global epidemic, and the incidence of opioid related fatalities have climbed 500% in the past two decades. METHODS: Six databases were searched from inception to September 25, 2021, for randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder, and meeting the necessary requirements for fragility index calculation. Specifically, we included all parallel arm or two-by-two factorial design RCTs that assessed the effectiveness of any opioid substitution and antagonist therapies using a binary primary outcome and reported a statistically significant result. The fragility index of each study was calculated using methods described by Walsh and colleagues. The risk of bias of included studies was assessed using the Revised Cochrane Risk of Bias tool for randomized trials. RESULTS: Ten studies with a median sample size of 82.5 (interquartile range (IQR) 58, 179, range 52-226) were eligible for inclusion. Overall risk of bias was deemed to be low in seven studies, have some concerns in two studies, and be high in one study. The median fragility index was 7.5 (IQR 4, 12, range 1-26). CONCLUSIONS: Our results suggest that approximately eight participants are needed to overturn the conclusions of the majority of trials in opioid use disorder. Future work should focus on maximizing transparency in reporting of study results, by reporting confidence intervals, fragility indexes, and emphasizing the clinical relevance of findings. TRIAL REGISTRATION: PROSPERO CRD42013006507. Registered on November 25, 2013.

Survey of awareness and attitudes to the management of fragility fractures among the membership of the Asia Pacific Orthopaedic Association.

A survey of awareness and attitudes to the management of fragility fractures among the membership of the Asia Pacific Orthopaedic Association conducted in 2022 found considerable variation in care across the region. A Call to Action is proposed to improve acute care, rehabilitation and secondary fracture prevention across Asia Pacific. PURPOSE: Fragility fractures impose a substantial burden on older people and their families, healthcare systems and national economies. The current incidence of hip and other fragility fractures across the Asia Pacific region is enormous and set to escalate rapidly in the coming decades. This publication describes findings of a survey of awareness and attitudes to the management of fragility fractures among the membership of the Asia Pacific Orthopaedic Association (APOA) conducted in 2022. METHODS: The survey was developed as a collaboration between the Asia Pacific Osteoporosis and Fragility Fracture Society and the Asia Pacific Fragility Fracture Alliance, and included questions relating to aspects of care upon presentation, during surgery and mobilisation, secondary fracture prevention, and access to specific services. RESULTS: In total, 521 APOA members completed the survey and marked variation in delivery of care was evident. Notable findings included: Fifty-nine percent of respondents indicated that analgesia was routinely initiated in transit (by paramedics) or within 30 minutes of arrival in the Emergency Department. One-quarter of respondents stated that more than 80% of their patients underwent surgery within 48 hours of admission. One-third of respondents considered non-hip, non-vertebral fractures to merit assessment of future fracture risk. One-third of respondents reported the presence of an Orthogeriatric Service in their hospital, and less than a quarter reported the presence of a Fracture Liaison Service. CONCLUSION: A Call to Action for all National Orthopaedic Associations affiliated with APOA is proposed to improve the care of fragility fracture patients across the region.

Predicting Egg Storage Time with a Portable Near-Infrared Instrument: Effects of Temperature and Production System.

Determining egg freshness is critical for ensuring food safety and security and as such, different methods have been evaluated and implemented to accurately measure and predict it. In this study, a portable near-infrared (NIR) instrument combined with chemometrics was used to monitor and predict the storage time of eggs under two storage conditions-room temperature (RT) and cold (CT) storage-from two production systems: cage and free-range. A total of 700 egg samples were analyzed, using principal component analysis (PCA) and partial least squares (PLS) regression to analyze the NIR spectra. The PCA score plot did not show any clear separation between egg samples from the two production systems; however, some egg samples were grouped according to storage conditions. The cross-validation statistics for predicting storage time were as follows: for cage and RT eggs, the coefficient of determination in cross validation (R2CV) was 0.67, with a standard error in cross-validation (SECV) of 7.64 days and residual predictive deviation (RPD) of 1.8; for CT cage eggs, R2CV of 0.84, SECV of 5.38 days and RPD of 3.2; for CT free-range eggs, R2CV of 0.83, SECV of 5.52 days and RPD of 3.2; and for RT free-range eggs, R2CV of 0.82, SECV of 5.61 days, and RPD of 3.0. This study demonstrated that NIR spectroscopy can predict storage time non-destructively in intact egg samples. Even though the results of the present study are promising, further research is still needed to further extend these results to other production systems, as well as to explore the potential of this technique to predict other egg quality parameters associated with freshness.

Real-world predictors of survival in patients with limited-stage small-cell lung cancer in Manitoba, Canada.

Background: Although therapy for limited-stage small-cell lung cancer (LS-SCLC) is administered with curative intent, most patients relapse and eventually die of recurrent disease. Chemotherapy (CT) with concurrent radiotherapy (RT) remains the standard of care for LS-SCLC; however, this could evolve in the near future. Therefore, understanding the current prognostic factors associated with survival is essential. Objective: This real-world analysis examines factors associated with long-term survival in patients with LS-SCLC treated with CT in Manitoba, Canada. Methods: A retrospective cohort study was conducted using Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years and had cytologically confirmed LS-SCLC diagnosed between January 1, 2004, and December 31, 2018, for which they received CT ± RT. Baseline patient, disease, and treatment characteristics and survival duration, characterized as short (<6 months), medium (6-24 months), and long term (>24 months), were extracted. Overall survival (OS) was estimated at one, two, and five years and assessed using Kaplan-Meier methods and Cox proportional hazards models. Results: Over the 15-year study period, 304 patients met the eligibility criteria. Long-term survivors comprised 39.1% of the cohort; at diagnosis, this subgroup was younger, more likely to have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, and have normal lactate dehydrogenase, sodium, and hemoglobin levels. OS estimates for the entire cohort at one, two, and five years were 66%, 38%, and 18%, respectively. In the ECOG PS 0 subgroup, OS estimates at one, two, and five years were 85%, 52%, and 24%, respectively; OS estimates were 60%, 35%, and 17%, respectively, for ECOG PS 1-2 and were 47%, 23%, and 10%, respectively, for ECOG PS 3-4. OS was significantly higher among patients with normal serum sodium and hemoglobin levels than those with abnormal levels. Univariable hazard regression models found that ECOG PS, age at diagnosis, receipt of prophylactic cranial irradiation (PCI), and thoracic RT were associated with survival. On multivariable hazard regression, ECOG PS and receipt of PCI were associated with survival. Conclusion: Survival for greater than two years in patients with LS-SCLC treated with CT ± RT was associated with ECOG PS and receipt of PCI.

The rationale and guiding principles to design a psychiatric curriculum for primary care nurses of India.

Background: The National Mental Health Survey reports a huge treatment gap for all mental disorders. There is an acute shortage of mental health professionals in India. Hence, there is a dire need to support task-shift interventions by nurses in providing non-pharmacological interventions for persons suffering from mental health issues. The traditional psychiatric nursing curriculum emphasizes nurses' knowledge and skills rather than their competency in providing mental health care. We designed an innovative, digitally driven, modular-based primary care psychiatry program for nurses (PCPP-N) to incorporate mental health with physical health and emphasize redesigning nursing practice. In this paper, we discuss the rationale and guiding principles behind designing the curriculum of PCPP-N. Discussion: The PCPP-N program is based on nine guiding principles to provide skill-based, pragmatic, and feasible modules of a higher collaborative care quotient (CCQ) and translational quotient (TQ) that are essential for upskilling primary care nurses. In this program, nurses are trained through telemedicine-based 'on-consultation training' augmented with collaborative video consultations. A tele-psychiatrist/tele-psychiatric nurse will demonstrate how to screen, identify, and plan treatment for patients with psychiatric disorders from patients coming for general medical care using the manual Clinical Schedules of Primary care psychiatry Nursing (CSP-N). The CSP-N manual includes a screener, simplified diagnosing guidelines relevant for nurses and primary care settings, nursing management, pharmacological management, and related side effects, counseling, and follow-up guidelines. This program helps the nurses in identifying the most commonly prevalent adult psychiatric disorders presenting to primary care. Conclusion: This PCPN curriculum contains pragmatic modules with higher CCQ and TQ. This curriculum is dynamic as the learning is interactive. Upskilling primary care nurses in integrating mental health with physical health may reduce the mental health burden. Further, the policymakers and administrators plan to integrate mental health along with physical health in national health programs.

Experimental Study on Sustainability Involving the Pugh Matrix on Emission Values of High-Temperature Air in the Premixed Charged Compression Ignition Engine.

The main aim of the study was to reduce carbon emissions in the atmosphere using a novel Andropogon narudus (AN) biofuel using higher air temperatures and reducing the consumption of conventional fossil fuel (diesel). The use of a heat exchange chamber within the air intake manifold is a popular method to reduce hydrocarbon (HC) and carbon monoxide (CO) emissions during cold starts. A premixed charged compression ignition engine in the dual-fuel mode was used in this study with raw diesel, raw AN oil, AN70+D30, AN80+D20, AN80+D20 (35 °C), AN80+D20 (40 °C), and AN80+D20 (45 °C). A chamber was designed and analyzed to measure the exit temperature and density change and to determine the reduction in volumetric efficiency of the engine, using Ansys Fluent software. A sustainability assessment study was performed to understand the feasibility of the fuel and the design using the Pugh Matrix. The fuel AN80+D20 with an air temperature of 45 °C was found to be superior to all other fuels in terms of brake thermal efficiency, reaching at 32.1%. D100 used the least amount of energy, whereas AN80+D20 used the most. Engine HC emission was at the lowest (45.01 ppm) for AN80+D20 fuel at 45 °C air input and reached the highest (50 ppm) for AN100 fuel. With an air temperature of 45 °C, CO emission was at its lowest for AN80+D20 gasoline (0.018%) and was at its highest for AN100 (0.072%). Nitrogen oxide emissions were the highest for AN80+D20 fuel with an air temperature of 45 °C, with an air concentration of 1254 ppm, whereas they were the lowest for AN100 (900 ppm). CO2 values were reduced, with D100 showing the lowest levels and AN100 showing the highest. The smoke emission was minimum for AN80+D20 fuel at 45 °C, with a smoke number of 15 compared to 33 for D100 fuel. As per the Pugh Matrix assessment, AN80+D20 with 35 °C air temperature had higher scores compared to all of the other fuel mixtures.

Real-world predictors of survival in patients with extensive-stage small-cell lung cancer in Manitoba, Canada: a retrospective cohort study.

Background: Extensive-stage small-cell lung cancer (ES-SCLC) is an incurable cancer with poor prognosis in which characteristics predictive of long-term survival are debated. The utility of agents such as immune checkpoint inhibitors highlights the importance of identifying key characteristics and treatment strategies that contribute to long-term survival and could help guide therapeutic decisions. Objective: This real-world analysis examines the characteristics, treatment patterns, and clinical outcomes of patients receiving chemotherapy without immunotherapy for ES-SCLC in Manitoba, Canada. Methods: A retrospective cohort study assessed patient characteristics, treatment, and survival duration (short: <6 months; medium: 6-24 months; long: >24 months) using the Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years with cytologically confirmed ES-SCLC diagnosed between January 1, 2004, and December 31, 2018, and received cytotoxic chemotherapy (CT). The one-, two-, and five-year probabilities of overall survival (OS) were assessed relative to patient, disease, and treatment characteristics using Kaplan-Meier methods and Cox proportional hazards models. Results: This analysis included 537 patients. Cisplatin was used in 56.1% of patients, 45.6% received thoracic radiotherapy (RT), and few received prophylactic cranial irradiation (PCI). In the overall cohort, one-, two- and five-year OS rates were 26%, 8%, and 3%, respectively. For patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, OS rates at one, two, and five years were 43%, 17%, and 10%, respectively, vs. 27%, 8%, and 2% for those with ECOG PS 1-2, and 16%, 3%, and 3% for those with ECOG PS 3-4. In long-term survivors, ECOG PS scores were lower and abnormal laboratory test results were less frequent. Overall, 74.4% of long-term survivors received thoracic RT and 53.5% received PCI. Known poor prognostic factors - including brain/liver metastases, high lactate dehydrogenase (LDH), abnormal sodium, and low hemoglobin levels - were less common but still seen in long-term survivors. Conclusion: Although rare, patients with ES-SCLC may experience long-term survival with CT ± thoracic RT ± PCI. Factors predicting long-term survival include traditional prognostic factors such as ECOG PS, LDH level, and receipt of thoracic RT or PCI. These findings support current treatment algorithms for ES-SCLC and provide baseline survival estimates to assess the real-world impact of adding immune checkpoint inhibitors in the future.

Report from the 24th Annual Western Canadian Gastrointestinal Cancer Consensus Conference on Colorectal Cancer, Richmond, British Columbia, 28-29, October 2022.

The 24th annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Richmond, British Columbia, on 28-29 October 2022. The WCGCCC is an interactive multidisciplinary conference attended by healthcare professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals such as dieticians, nurses and a genetic counsellor participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer.

Development and validation of "Knowledge on screening and identification of mental illness (KSIM) questionnaire" among primary care nurses in India.

BACKGROUND: As stated in the World Health Organization's Mental Health Report 2022, 13%, or almost a billion people, had a mental health issue, and 82% of these people resided in low- and middle-income countries with limited access to mental health treatments. Successful integration of mental health services into primary healthcare depends on primary healthcare providers receiving the proper training and information required to provide basic mental health care in the community. Primary care nurses generally lack the confidence and skills to handle mental health issues while being in an excellent position to screen, identify, refer, and follow-up on a person with mental illness (PMI). The study aimed to develop and validate the KSIM questionnaire to assess the knowledge of primary care nurses in screening, identifying, referral, and follow-up persons with mental health issues in the community. MATERIALS AND METHODS: The study was conducted based on a sequential exploratory design in two phases: the development and the validation phases. An extensive literature search was done, and the themes derived from the two focus group discussion (FGD) and three direct interviews, and the inputs from the mental health experts were used to design the KSIM questionnaire. A panel of 17 experts validated the KSIM questionnaire through item-level content validity index (I-CVI) and scale-level CVI (S-CVI) for content validation, and the reliability test was done using the intraclass correlation coefficient ICC test-retest method. RESULTS: The draft version-1 of the KSIM questionnaire showed high content validity of individual items (I-CVI range: 0.82-1.00) and high overall content validity (S-CVI = 0.95), and suggestions from the experts were incorporated. The KSIM questionnaire consists of 30 multiple choice questions and 10 case vignettes. The KSIM questionnaire has a very good test-retest reliability using the single measure two-way mixed absolute agreement ICC value 0.97 with 95% CI. CONCLUSIONS: Using an iterative approach, the development and validation of the KSIM questionnaire demonstrated high I-CVI and S-CVI with good ICC test-retest reliability to assess the knowledge of primary care nurses on screening and identification, referral and follow-up of a PMI in the community. Primary care nurses' knowledge on how to screen for and identify people with mental health issues in the primary care setting can be evaluated with the help of the KSIM questionnaire, and providing need-based training may help to reduce the time taken for people with mental illness to receive professional help.

An audit of initial six years of 5885 telepsychiatric direct video consultations: Findings from "benefits of savings" analysis and the effect of COVID-19 pandemic.

Background: Telepsychiatric direct video consultations (DVCs) meant for continuity of care began in 2017 and continued during the coronavirus disease 2019 (COVID-19) pandemic. Telemedicine-based consultation gained its long-due importance during the COVID-19 travel restriction, despite its existence for a long. The authors intend to share the utility and growth of the initial six years of live telepsychiatric DVCs from an academic hospital in India and also plan to understand the effects of the COVID-19 pandemic on its growth and report findings from an innovative "benefits of savings" (BOS) analysis from these clinics. Methods: A first six years of medical audit of the files and registers of telepsychiatric DVCs from two kinds of continuity of care clinics during 2017-2022 is performed. An analysis of 4991 (84.8%) live DVCs is successfully conducted for 1570 patients from the 5885 scheduled appointments. Year-on-year (YOY) growth and BOS analysis of successful DVCs from these clinics were performed. Results and Discussion: The growth suggests a gradual increase in DVCs yearly. The BOS analysis suggests its increased acceptability, feasibility at both user and provider ends, and possible cost-effectiveness of these video clinics. YOY analysis suggests a natural growth of these clinics than from the effect of the COVID-19 pandemic, except for an initial surge in 2020 and 2021 and observing stabilization effect by 2022. Conclusion: In the authors' understanding, this is the largest study of providing DVCs from India, irrespective of any medical/surgical specialty. The video/remote clinics could be an alternative model for regular follow-ups in ensuring the continuity of care among patients with psychiatric disorders. These clinics also saved significant travel time, travel distance, and travel costs for the patients that could have occurred for their in-person consultations.

Development and Validation of Clinical Schedule for Primary Care Psychiatric Nursing (CSP-N) for Primary Care Nurses.

Introduction: As per the World Health Organization's mental health report for 2022, nearly a billion people have mental health issues, and 82% of them are in low and middle-income countries where mental health services are largely absent. For the successful integration of mental health into primary health care, proper training and education of primary care professionals are mandatory. Primary care nurses are in an excellent position to screen, identify, dual collaboration for treatment planning/referral, and follow-up of persons with mental illness (PMI), but they often lack the confidence and competence to tackle mental health problems. The study aimed to develop and validate the clinical schedule for primary care psychiatric nursing (CSP-N). Materials and Methods: It is conducted in two phases: the development and validation phases. An extensive literature search has been conducted, and the ten themes derived from the two-focused group discussions and three-direct one-to-one interviews and input from mental health experts were used to design the CSP-N. The CSP-N was checked for content validity by a panel of 17 experts using the item-level content validity index (I-CVI) and the scale-level content validity index (S-CVI). Results: The draft version 1 of the CSP-N showed high content validity for individual items (I-CVI range: 0.82 to 1.00) and high overall content validity (S-CVI = 0.95), and suggestions from the experts were incorporated. The CSP-N was developed in four modules. The single-measure two-way mixed absolute agreement ICC value was calculated (for 32 subjects) for the reliability test, and the ICC value was 0.97 with a 95% CI (0.94, 0.99). Conclusions: Using an iterative approach, the development and validation of the CSP-N demonstrated high I-CVI and S-CVI for screening and identification, dual collaboration for the treatment plan, referral, and follow-up of a person with mental illness by the nurses in the community.

Constriction Band Release in a Neonatal Ischemic Limb: A Pediatric Anesthesiology Case Report.

A 1.1 Kg, four-hour-old, 29-weeks-gestation male patient presented with right upper extremity ischemia secondary to neonatal constriction band syndrome. Emergency constriction band release was deemed necessary to facilitate limb salvage. The anesthetic management of this patient required close communication with the surgical team and meticulous attention to the risks of post-reperfusion syndrome and blood loss in this fragile neonate. Limb salvage was ultimately successful, and the patient demonstrated full neurologic recovery at his two-year follow-up visit.

Luxury Zinc Supply Prevents the Depression of Grain Nitrogen Concentrations in Rice (Oryza sativa L.) Typically Induced by Elevated CO2.

Rice (Oryza sativa L.) has inherently low concentrations of nitrogen (N) and zinc (Zn), and those concentrations are falling as the atmospheric concentration of carbon dioxide ([CO2]) increases, threatening the quality of human diets. We investigated the effect of two levels of Zn supply (marginal and luxury), on Zn and N concentrations in whole grain of two indica rice cvv. Differing in Zn-efficiency (IR26 (inefficient) and IR36 (efficient)), grown in sand culture at ambient (400 µL CO2 L-1 (a[CO2])) and elevated (700 µL CO2 L-1 (e[CO2])) CO2 concentrations. For both cvv., luxury Zn-supply increased vegetative growth, and the foliar and grain Zn concentrations; the increases in grain yield were greater at e[CO2]. The e[CO2] decreased grain Zn concentrations ([Zn]), as is consistently observed in other studies. However, unique to our study, luxury Zn-supply maintained grain N concentrations at e[CO2]. Our data also show that enhanced Zn uptake is the basis of the greater Zn-efficiency of IR36. Lastly, luxury Zn-supply and e[CO2] appreciably decreased the time to panicle emergence and, consequently, to maturity in both cvv. Since Zn-supply can be manipulated by both soil and foliar applications, these findings are potentially important for the quality and quantity of the global rice supply. That is, further investigation of our findings is justified. Key message: Luxury zinc supply maintains grain N concentration at 700 µL CO2 L-1.

Early onset of age-related changes in the retina of cystine/glutamate antiporter knockout mice.

To determine the role of the cystine/glutamate antiporter on retinal structure and function, retinas of C57Bl/6J wild-type and xCT knockout mice, lacking the xCT subunit of the cystine/glutamate antiporter were examined from 6 weeks to 12 months of age. Fundoscopy, optical coherence tomography (OCT), and whole mount retinal autofluorescence imaging were used to visualise age-related retinal spots. Glial fibrillary acidic protein (GFAP) immunolabelling was used to assess retinal stress. Retinal function was evaluated using full-field and focal electroretinograms. Examinations revealed retinal spots in both wild-type and xCT knockout mice with the number of spots greater at 9 months in the knockout compared to wild-type. OCT confirmed these discrete spots were located at the retinal pigment epithelium (RPE)-photoreceptor junction and did not label with drusen markers. Whole mount lambda scans of the 9 month xCT knockout retinas revealed that the photoreceptor autofluorescence matched the spots, suggesting these spots were retinal debris. GFAP labelling was increased in knockout retinas compared to wild-type indicative of retinal stress, and the discrete spots were associated with migration of microglia/macrophages to the RPE-retina intersection. OCT revealed that the superior retina was thinner at 9 months in knockout compared to wild-type mice due to changes to the outer nuclear and photoreceptor layers. While global retinal function was not affected by loss of xCT, focal changes in retinal function were detected in areas where spots were present. Tother these results suggest that the xCT KO mice exhibit features of accelerated ageing and suggests that this mouse model may be useful for studying the underlying cellular pathways in retinal ageing.

Mathematical modeling of vaccination as a control measure of stress to fight COVID-19 infections.

The world experienced the life-threatening COVID-19 disease worldwide since its inversion. The whole world experienced difficult moments during the COVID-19 period, whereby most individual lives were affected by the disease socially and economically. The disease caused millions of illnesses and hundreds of thousands of deaths worldwide. To fight and control the COVID-19 disease intensity, mathematical modeling was an essential tool used to determine the potentiality and seriousness of the disease. Due to the effects of the COVID-19 disease, scientists observed that vaccination was the main option to fight against the disease for the betterment of human lives and the world economy. Unvaccinated individuals are more stressed with the disease, hence their body's immune system are affected by the disease. In this study, the S V E I H R deterministic model of COVID-19 with six compartments was proposed and analyzed. Analytically, the next-generation matrix method was used to determine the basic reproduction number ( R 0 ). Detailed stability analysis of the no-disease equilibrium ( E 0 ) of the proposed model to observe the dynamics of the system was carried out and the results showed that E 0 is stable if R 0 < 1 and unstable when R 0 > 1 . The Bayesian Markov Chain Monte Carlo (MCMC) method for the parameter identifiability was discussed. Moreover, the sensitivity analysis of R 0 showed that vaccination was an essential method to control the disease. With the presence of a vaccine in our S V E I H R model, the results showed that R 0 = 0 . 208 , which means COVID-19 is fading out of the community and hence minimizes the transmission. Moreover, in the absence of a vaccine in our model, R 0 = 1 . 7214 , which means the disease is in the community and spread very fast. The numerical simulations demonstrated the importance of the proposed model because the numerical results agree with the sensitivity results of the system. The numerical simulations also focused on preventing the disease to spread in the community.

Cannabis use and opioid relapse: An exploratory survival analysis of prospectively collected data.

Importance: It is known that only minority of patients with opioid use disorder (OUD) receive treatment, of which only a fraction successfully complete treatment as intended. Factors associated with poor treatment outcomes remain unclear, and there is emerging but conflicting evidence that cannabis use may mitigate opioid use. Objective: To analyze predictors of relapse amongst patients receiving buprenorphine-naloxone for OUD and identify the association between cannabis use and time to relapse. Design: Data were prospectively collected between May 2018 and October 2020, and patients were followed for 12 months. Setting: Thirty-one outpatient opioid agonist treatment clinics across Ontario, Canada. Participants: All patients 16 years of age or older receiving buprenorphine-naloxone for OUD who had a urine toxicology screen negative for opioids at baseline were eligible for inclusion. Of the 488 patients consecutively sampled, 466 were included. Exposure: Cannabis use. Main outcome and measure: Relapse to opioid use assessed using urine toxicology screens. We employed a multivariable Cox-proportional hazard model for our analyses. Results: We found that cannabis use was not protective against relapse [hazard ratio (HR) = 1.03, 95% confidence interval (CI): 0.78, 1.36, p = 0.84]. We found that participants who have been in treatment for at least two years had a 44% decrease in the hazard of relapse compared to those in treatment for less than a year (HR = 0.56, 95% CI: 0.34, 0.92, p = 0.021). We also found that the hazard of relapse was 2.6 times higher for participants who were intravenous drug users (HR = 2.61, 95% CI: 1.74, 3.91, p < 0.001), and that for every 1mg increase in the participants' buprenorphine-naloxone dose, the hazard of relapse is 2% greater (HR = 1.02, 95% CI: 1.01, 1.03, p < 0.001). Conclusion: Our analysis failed to show cannabis to be protective against relapse to opioid use in patients receiving buprenorphine-naloxone for OUD. We identified that individuals who inject drugs, are on higher doses of buprenorphine-naloxone, or have been in treatment for less than two years have a higher hazard for relapse. The presence of such factors may thus warrant closer patient follow-up and more stringent treatment protocols to mitigate risk of relapse and potential overdose.