Structural Insights into Mdn1, an Essential AAA Protein Required for Ribosome Biogenesis.

Mdn1 is an essential AAA (ATPase associated with various activities) protein that removes assembly factors from distinct precursors of the ribosomal 60S subunit. However, Mdn1's large size (∼5,000 amino acid [aa]) and its limited homology to other well-studied proteins have restricted our understanding of its remodeling function. Here, we present structures for S. pombe Mdn1 in the presence of AMPPNP at up to ∼4 Å or ATP plus Rbin-1, a chemical inhibitor, at ∼8 Å resolution. These data reveal that Mdn1's MIDAS domain is tethered to its ring-shaped AAA domain through an ∼20 nm long structured linker and a flexible ∼500 aa Asp/Glu-rich motif. We find that the MIDAS domain, which also binds other ribosome-assembly factors, docks onto the AAA ring in a nucleotide state-specific manner. Together, our findings reveal how conformational changes in the AAA ring can be directly transmitted to the MIDAS domain and thereby drive the targeted release of assembly factors from ribosomal 60S-subunit precursors.

Cancer Patients' Unmet Needs in Three Low- to Middle- Income Countries: Perspectives from Health Care Providers.

We sought to determine differences by low- and middle- income countries (Brazil, Romania, and Turkiye) on the degree to which health care providers (HCPs) note unmet needs among patients with cancer (N = 741). HCPs endorsed sexuality/intimacy and financial concerns as the most common. Investigating age differences in unmet needs between Brazil and Turkiye, were that should be targeted by. Results revealed that unmet needs to manage emotional distress were higher among older patients in Turkiye, whereas unmet needs to manage insomnia/fatigue were higher among pediatric patients in Brazil. Findings may guide the development of programs to address unmet needs among patients.

International collaboration for assessing unmet needs of cancer survivors and family caregivers: Lens of healthcare professionals.

OBJECTIVE: Cancer patients and their family caregivers have reported various needs that are not met. Recognition of the unmet needs by healthcare professionals may be a first step to adequately and systematically addressing them. Thus, the International Psycho-Oncology Society Survivorship Online Survey was developed to measure healthcare professionals' evaluation about the unmet needs of their patients and family caregivers around the globe. METHODS: The survey was developed in English and translated to additional 14 different languages. The survey was distributed on the web-based REDCap application to over 50 psycho-oncology societies and their networking platforms as well as social media and to authors who have published in psycho-oncology journals globally. RESULTS: A total of 1472 participants from 36 countries at least partially completed the survey. Healthcare professionals evaluated needs for managing one's emotional distress and patients' medical care and symptoms as the most common concerns for both patients and their family caregivers across all patient age groups. Less than two-thirds of the participating healthcare professionals reported that their institution had services or programs to address the needs of the patients or caregivers. CONCLUSIONS: Findings suggest several directions for further analyses to provide more specific information that would be readily translated into clinical practices, research, and policy aimed to enhance the quality of life of cancer patients, survivors, and family caregivers around the globe. In addition, this collaborative effort also hints at the importance of establishing international networks to promote equity in care for people touched by cancer worldwide.

MRI vs. CT for pancreatic adenocarcinoma vascular invasion: comparative diagnostic test accuracy systematic review and meta-analysis.

OBJECTIVES: To perform a systematic review comparing the diagnostic accuracy of MRI vs. CT for assessing pancreatic ductal adenocarcinoma (PDAC) vascular invasion. METHODS: MEDLINE, EMBASE, Cochrane Central, and Scopus were searched until December 2021 for diagnostic accuracy studies comparing MRI vs. CT to evaluate vascular invasion of pathologically confirmed PDAC in the same patients. Findings on resection or exploratory laparotomy were the preferred reference standard. Data extraction, risk of bias, and applicability assessment were performed by two authors using the Quality Assessment of Diagnostic Accuracy Studies-Comparative Tool. Bivariate random-effects meta-analysis and meta-regression were performed with 95% confidence intervals (95% CI). RESULTS: Three studies were included assessing 474 vessels without vascular invasion and 65 with vascular invasion in 107 patients. All patients were imaged using MRI at ≥ 1.5 T and a pancreatic protocol CT. No difference was shown between MRI and CT for diagnosing PDAC vascular invasion: MRI/CT sensitivity (95% CI) were 71% (47-87%)/74% (56-86%), and specificity were 97% (94-99%)/97% (94-98%). Sources of bias included selection bias from only a subset of CT patients undergoing MRI and verification bias from patients with unresectable disease not confirmed on surgery. No patients received neoadjuvant therapy prior to staging. CONCLUSIONS: Based on limited data, no difference was observed between MRI and pancreatic protocol CT for PDAC vascular invasion assessment. MRI may be an adequate substitute for pancreatic protocol CT in some patients, particularly those who have already had a single-phase CT. Larger and more recent cohort studies at low risk of bias, including patients who have received neoadjuvant therapy, are needed. CLINICAL RELEVANCE STATEMENT: Abdominal MRI performed similarly to pancreatic protocol CT at assessing pancreatic ductal adenocarcinoma vascular invasion, suggesting local staging is adequate in some patients using MRI. More data are needed using larger, more recent cohorts including patients with neoadjuvant treatment. KEY POINTS: • Based on limited data, no difference was found between MRI and pancreatic protocol CT sensitivity and specificity for diagnosing PDAC vascular invasion (p = 0.81, 0.73 respectively). • Risk of bias could be reduced in future PDAC MRI vs CT comparative diagnostic test accuracy research by ensuring all enrolled patients undergo both imaging modalities being compared in random order and regardless of the findings on either modality. • More studies are needed that directly compare the diagnostic performance of MRI and CT for PDAC staging after neoadjuvant therapy.

Goal-Focused Emotion-Regulation Therapy (GET) in Young Adult Testicular Cancer Survivors: A Randomized Pilot Study.

BACKGROUND: Young adult testicular cancer survivors experience adverse impacts after treatment. We developed Goal-focused Emotion-regulation Therapy (GET) to improve distress symptoms, emotion regulation, and goal navigation skills. PURPOSE: This pilot study examined GET versus an active control intervention in young adult survivors of testicular cancer. METHODS: Seventy-five eligible survivors treated with chemotherapy were randomized to receive GET or Individual Supportive Listening (ISL). Study acceptability, engagement, and tolerability were examined, and intervention fidelity and therapeutic alliance were compared between arms. Preliminary efficacy was evaluated by effect sizes for between-group changes in primary (anxiety and depressive symptoms) and secondary (career confusion, goal navigation, and emotion regulation) outcomes from baseline to immediately and 3-month post-intervention. RESULTS: Among the 38 men randomized to GET, 81.1% completed all study sessions compared with 82.4% of the 37 men assigned to ISL. Fidelity to the intervention was 87% in GET. Therapeutic alliance wassignificantly higher among those receiving GET versus ISL. Participants exhibited a medium group-by-time effect size with greater reductions in depressive (d = 0.45) and anxiety (d = 0.29) symptoms for those in GET versus ISL, with a similar pattern at 3 months for depressive (d = 0.46) and anxiety (d = 0.46) symptoms. CONCLUSIONS: GET is a feasible and acceptable intervention for reducing adverse outcomes after testicular cancer for young adults. Observed effect sizes preliminarily suggest meaningful change, though should be interpreted with caution in small samples. GET may be a developmentally-matched behavioral approach to improve psychosocial function in this cancer group. CLINICAL TRIAL INFORMATION: Clinicaltrials.gov, NCT04150848. Registered on October 28, 2019.

Young adult testicular cancer survivors experience adverse impacts after treatment. Goal-focused Emotion-regulation Therapy (GET) was developed to improve distress symptoms, emotion regulation, and goal navigation skills. The aim of this pilot study was to examine GET versus a control intervention in young adult survivors of testicular cancer. Seventy-five survivors were randomly assigned to GET or Individual Supportive Listening (ISL). Indictors of acceptability, engagement, and tolerability were examined, and intervention fidelity and therapeutic alliance were compared between groups. Between-group changes in primary (anxiety and depressive symptoms) and secondary (career confusion, goal navigation, and emotion regulation) outcomes from baseline to immediately and 3-month post-intervention were examined. Among GET participants, 81.1% completed all study sessions compared with 82.4% of those receiving ISL. Fidelity to the intervention was 87% in GET. Therapeutic alliance scores were significantly higher among those receiving GET. Participants exhibited greater reductions in depressive and anxiety symptoms for those in the GET versus ISL, with a similar pattern observed for changes at 3 months for depressive and anxiety symptoms. GET is a feasible and acceptable intervention for reducing adverse outcomes after testicular cancer for young adults.

Healthcare providers' perceptions about the unmet needs of their patients with cancer across healthcare systems: results of the International Psycho-Oncology Society survivorship survey.

OBJECTIVE: Systematic understanding of patients' unmet needs is essential for providing effective supportive care. This study sought to compare the unmet needs of patients with cancer identified by health care providers (HCPs) among four major healthcare systems. METHODS: HCPs (n = 247) participated in the International Psycho-Oncology Society (IPOS) Survivorship Online Survey, evaluating their patients' unmet needs. The country of HCPs was grouped into four major healthcare systems: Beveridge model, Bismarck model, National Health Insurance model, and out-of-pocket model. RESULTS: Most HCPs were from countries with the Bismarck model. Substantial levels (> 50%) of unmet needs in all domains are reported across the four healthcare systems. Pediatric patients/survivors living in countries under out-of-pocket healthcare model were evaluated to have less unmet needs for managing decline in physical or cognitive functioning and insomnia/sleep difficulty/fatigue, than those in countries under Beveridge, Bismarck, and National Health Insurance models. Moreover, middle-aged patients/survivors under Beveridge and National Health Insurance models were likely to have greater unmet needs for dealing with cancer-related financial concerns than those under Bismarck model. CONCLUSION: This study provides valuable insights into the unmet needs of patients with cancer in different healthcare systems, highlighting the significance of targeted interventions to address the unique needs of patients across diverse healthcare systems. Further investigation is warranted to identify the system factors associated with patients' unmet needs, enabling the development of effective healthcare policies and interventions to comprehensively address the multifaceted needs of patients with cancer.

Curvilinear prediction of posttraumatic growth on quality of life: a five-wave longitudinal investigation of breast cancer survivors.

PURPOSE: Do cancer survivors experience positive changes (i.e., posttraumatic growth; PTG) resulting in better quality of life? The issue has yet to yield consistent notions. This longitudinal study extends the literature on the role of PTG by examining the curvilinear relationship between PTG and Health-Related Quality of Life (HRQoL), and explored whether PTG predicts subsequent HRQoL in a quadratic relationship across 2 years following surgery. METHODS: Women with breast cancer (N = 359; Mage = 47.5) were assessed at five waves over two years. On every measurement occasion, PTG measured by the posttraumatic growth inventory and HRQoL measured by SF-36 were assessed. The five waves reflect major medical demands and related challenges in the breast cancer trajectory, in which 1-day, 3 months, 6 months, 12 months, and 24 months after surgery were adopted as the survey timing. In a series of hierarchical linear modeling (HLM) analyses, the time-lagged predictions of PTG (i.e., linear, quadratic) on HRQoL were examined, controlling demographic and medical covariates. RESULTS: The results revealed that the quadratic term of PTG consistently significantly predicted physical and mental health quality of life (PCS and MCS), while the linear term of PTG did not significantly predict PCS or MCS. CONCLUSION: With multi-wave longitudinal data, this study demonstrated that the relationship between PTG and HRQoL is curvilinear, and this finding extends to PTG's prediction of subsequent HRQoL. The quadratic relationship has critical implications for clinical assessment and intervention. Details are discussed.

A novel approach for targeting the left dorsolateral prefrontal cortex for transcranial magnetic stimulation using a cognitive task.

Repetitive transcranial magnetic stimulation (rTMS) has the potential to be developed as a novel treatment for cognitive dysfunction. However, current methods of targeting rTMS for cognition fail to consider inter-individual functional variability. This study explored the use of a cognitive task to individualise the target site for rTMS administered to the left dorsolateral prefrontal cortex (L-DLPFC). Twenty-five healthy participants were enrolled in a sham-controlled, crossover study. Participants performed a random letter generation task under the following conditions: no stimulation, sham and active 'online' rTMS applied to F3 (International 10-20 System) and four standardised surrounding sites. Across all sites combined, active 'online' rTMS was associated with significantly reduced performance compared to sham rTMS for unique trigrams (p = 0.012), but not for unique digrams (p > 0.05). Using a novel localisation methodology based on performance outcomes from both measures, a single optimal individualised site was identified for 92% [n = 23] of participants. At the individualised site, performance was significantly poorer compared to a common standard site (F3) and both control conditions (ps < 0.01). The current results suggest that this localisation methodology using a cognitive task could be used to individualise the rTMS target site at the L-DLPFC for modulating and potentially enhancing cognitive functioning.

Healthcare professionals' perspectives on the unmet needs of cancer patients and family caregivers: global psycho-oncology investigation.

PURPOSE: This international study aimed to compare healthcare professionals' perspectives on the unmet needs of their cancer patients with those of family caregivers and to investigate the degree to which patients' age group moderates the associations. METHODS: Healthcare professionals involved in the care for cancer patients and their family caregivers were invited to participate in the International Psycho-Oncology Society (IPOS) Survivorship Online Survey. A total of 397 healthcare professionals from 34 countries provided valid study data. The participants evaluated whether the unmet need was the same for all age groups of patients and the degree of their patients' needs not being met per patients' age group. They evaluated the same questions for family caregivers. RESULTS: Patients' unmet needs in medical care were evaluated as greater than those of caregivers across all age groups. On the other hand, pediatric patients' unmet needs for spiritual concerns, sexuality/intimacy, and insomnia/fatigue were evaluated as greater than those of caregivers, whereas adolescent and young adult patients' unmet needs for symptom management were greater than those of caregivers. Patients' other unmet needs were evaluated as comparable with those of caregivers regardless of age groups. CONCLUSION: The findings provide insights how best healthcare providers stratify resources to address the unmet needs of patients and caregivers by the patients' age. Development of systematic assessment of unmet needs and provision of interventions tailored for patients' lifespan to address the unmet needs of cancer patients, and caregivers are warranted.

Emotional approach coping among young adults with cancer: Relationships with psychological distress, posttraumatic growth, and resilience.

OBJECTIVE: Cancer, particularly, during young adulthood, can evoke difficult emotions, interfere with normative developmental activities, and challenge coping responses. Emotion-regulating coping efforts aimed at active emotional processing (EP) and emotional expression (EE) can be beneficial to cancer adjustment and perceptions of positive growth. However, it may be that EP and EE work differently to influence well-being. This study examines relationships of EP and EE with psychological distress, posttraumatic growth (PTG), and resilience. We expect that EP will be positively associated with PTG and resilience, whereas EE will be negatively associated with psychological distress. METHODS: Young adults with cancer (M age  = 34.68, N = 57) completed measures of emotional; approach coping (EP and EE), psychological distress (depressive symptoms, fear of cancer; recurrence [FCR]) and indicators of positive adjustment and growth (resilience and PTG). RESULTS: Greater use of EP was associated with higher resilience (ß = 0.48, p = 0.003) and PTG (ß = 0.27, p = 0.05), whereas greater use of EE was associated with lower resilience (ß = -0.33, p = 0.04). The EE × EP interaction was significant for FCR (ß = 0.29, p = 0.04) such that low EE was associated with lower FCR in those with high EP. Interaction effects were not significant for depressive symptoms, resilience, or PTG. CONCLUSIONS: Findings highlight differing relationships between EP and EE among young adults with cancer. Interventions aimed at increasing emotion-regulating coping strategies may prove useful in facilitating positive adjustment and growth, strengthening young adults' ability to cope with the diverse effects of disease, treatment, and survivorship.

The Double-Edged Sword of Reflective Pondering: The Role of State and Trait Reflective Pondering in Predicting Depressive Symptoms Among Women With Breast Cancer.

BACKGROUND AND PURPOSE: Prior research has debated whether reflective pondering is a more constructive form of rumination than brooding, which is generally considered maladaptive. This study sought to investigate whether reflective pondering predicts depressive symptoms and whether reflective pondering is adaptive under certain conditions. We predicted that the effectiveness of reflective pondering could depend on concurrent coping strategies and the trait-state distinction. METHOD: Women with breast cancer (N = 309; M age = 47.5) were assessed at four waves over 2 years. A time-lagged design was applied, with rumination (i.e., brooding and reflective pondering) and coping (i.e., engagement and disengagement) measured from T1 to T3, predicting depressive symptoms assessed from T2 to T4. These variables were measured by the Ruminative Response Scale, the Brief COPE, and the Hospital Anxiety and Depression Scale. RESULTS: Using hierarchical linear modeling, brooding, but not reflective pondering, predicted elevated depressive symptoms at both between- and within-person levels. The relationship between reflective pondering and depression was moderated by the coping strategies. Individual differences in reflective pondering predicted worse depressive symptoms, but higher use of engagement coping mitigated the detrimental effect. Within individuals, the co-occurrence of reflective pondering and disengagement coping predicted a subsequent decrease in depressive symptoms. CONCLUSIONS: The emerging role of reflective pondering in the face of breast cancer-related stress appears to be a double-edged sword. Its impact on depression may depend on concurrent coping strategies and whether reflective pondering is assessed at state and trait levels.

Oxidative stress-induced miR-27a targets the redox gene nuclear factor erythroid 2-related factor 2 in diabetic embryopathy.

BACKGROUND: Maternal diabetes induces neural tube defects, and oxidative stress is a causal factor for maternal diabetes-induced neural tube defects. The redox gene nuclear factor erythroid 2-related factor 2 is the master regulator of the cellular antioxidant system. OBJECTIVE: In this study, we aimed to determine whether maternal diabetes inhibits nuclear factor erythroid 2-related factor 2 expression and nuclear factor erythroid 2-related factor 2-controlled antioxidant genes through the redox-sensitive miR-27a. STUDY DESIGN: We used a well-established type 1 diabetic embryopathy mouse model induced by streptozotocin for our in vivo studies. Embryos at embryonic day 8.5 were harvested for analysis of nuclear factor erythroid 2-related factor 2, nuclear factor erythroid 2-related factor 2-controlled antioxidant genes, and miR-27a expression. To determine if mitigating oxidative stress inhibits the increase of miR-27a and the decrease of nuclear factor erythroid 2-related factor 2 expression, we induced diabetic embryopathy in superoxide dismutase 2 (mitochondrial-associated antioxidant gene)-overexpressing mice. This model exhibits reduced mitochondria reactive oxygen species even in the presence of hyperglycemia. To investigate the causal relationship between miR-27a and nuclear factor erythroid 2-related factor 2 in vitro, we examined C17.2 neural stem cells under normal and high-glucose conditions. RESULTS: We observed that the messenger RNA and protein levels of nuclear factor erythroid 2-related factor 2 were significantly decreased in embryos on embryonic day 8.5 from diabetic dams compared to those from nondiabetic dams. High-glucose also significantly decreased nuclear factor erythroid 2-related factor 2 expression in a dose- and time-dependent manner in cultured neural stem cells. Our data revealed that miR-27a was up-regulated in embryos on embryonic day 8.5 exposed to diabetes, and that high glucose increased miR-27a levels in a dose- and time-dependent manner in cultured neural stem cells. In addition, we found that a miR-27a inhibitor abrogated the inhibitory effect of high glucose on nuclear factor erythroid 2-related factor 2 expression, and a miR-27a mimic suppressed nuclear factor erythroid 2-related factor 2 expression in cultured neural stem cells. Furthermore, our data indicated that the nuclear factor erythroid 2-related factor 2-controlled antioxidant enzymes glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit, and glutathione S-transferase A1 were down-regulated by maternal diabetes in embryos on embryonic day 8.5 and high glucose in cultured neural stem cells. Inhibiting miR-27a restored expression of glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit, and glutathione S-transferase A1. Overexpressing superoxide dismutase 2 reversed the maternal diabetes-induced increase of miR-27a and suppression of nuclear factor erythroid 2-related factor 2 and nuclear factor erythroid 2-related factor 2-controlled antioxidant enzymes. CONCLUSION: Our study demonstrates that maternal diabetes-induced oxidative stress increases miR-27a, which, in turn, suppresses nuclear factor erythroid 2-related factor 2 and its responsive antioxidant enzymes, resulting in diabetic embryopathy.

Benefit finding and diurnal cortisol after prostate cancer: The mediating role of positive affect.

OBJECTIVE: Benefit finding (BF) has exhibited a salutary effect on psychological adjustment to cancer. However, few studies have examined its relationship with physiology or have examined BF in men with cancer. This study investigated whether BF is associated with hypothalamic-pituitary-adrenal axis activity (ie, diurnal salivary cortisol) in men treated for prostate cancer. Positive affect (PA) is proposed as a potential pathway linking BF to diurnal salivary cortisol. METHODS: A sample of 66 men treated for localized prostate cancer within the prior 2 years completed questionnaires and collected salivary cortisol 3 times per day over 3 consecutive days. Hierarchical linear modeling was used for estimating the effects of BF and PA on cortisol responses as measured by diurnal slope and area under the curve (AUCg). Confidence intervals for indirect effects were estimated using the Monte Carlo method for mediation testing. RESULTS: BF was significantly associated with diurnal cortisol slope, controlling for body mass index and age (B = -.12, P = .03), such that greater BF was associated with steeper cortisol slope. Analyses revealed that PA mediated the effect of BF on cortisol slope (Monte Carlo estimation 95% CI = -0.087, -0.001); negative affect did not mediate this relationship. BF was not significantly associated with AUCg. CONCLUSIONS: Deriving more benefit from one's experience with prostate cancer is associated with a healthier diurnal cortisol rhythm. Through its potential to enhance PA, the relationship of BF and physiological processes underscores the health relevant value of BF in prostate cancer survivors.

Regret about surgical decisions among early-stage breast cancer patients: Effects of the congruence between patients' preferred and actual decision-making roles.

OBJECTIVE: Early-stage breast cancer patients generally receive either a mastectomy or a lumpectomy, either by their own choice or that of their surgeon. Sometimes, there is regret about the decision afterward. To better understand regret about surgical decisions, this study examined 2 possibilities: The first is that women who take a dominant or collaborative role in decision making about the surgery express less regret afterward. The second is that congruence between preferred role and actual role predicts less regret. We also explored whether disease stage moderates the relationship between role congruence and decisional regret. METHODS: In a cross-sectional design, 154 women diagnosed with breast cancer completed a survey assessing decisional role preference and actual decisional role, a measure of post-decision regret, and a measure of disturbances related to breast cancer treatment. Hierarchical regression was used to investigate prediction of decisional regret. RESULTS: Role congruence, not actual decisional role, was significantly associated with less decisional regret, independent of all the control variables. The interaction between disease stage and role congruence was also significant, showing that mismatch relates to regret only in women with more advanced disease. CONCLUSIONS: Our findings suggest that cancer patients could benefit from tailored decision support concerning their decisional role preferences in the complex scenario of medical and personal factors during the surgical decision.

Identification of posttraumatic growth trajectories in the first year after breast cancer surgery.

BACKGROUND: Empirical studies of the relationship between posttraumatic growth (PTG) and adjustment outcomes reveal a fairly inconclusive picture. We argue that the inconsistent findings are likely due to the heterogeneity of the PTG experience over time. In this regard, we predicted that individuals with different PTG trajectories vary in the level of adjustment and the correlational patterns between PTG and adjustment. METHODS: Participants were 124 Taiwanese women who underwent surgery for breast cancer. Measures of PTG and adjustment variables, including positive affect, negative affect, mental and physical quality of life, anxiety, and depression, were assessed at 1 day and 3, 6, and 12 months after surgery. A group-based trajectory model was used to identify subpopulations of individuals who shared homogenous growth patterns. Then, we determined whether the trajectory predicted adjustment at 12 months after surgery. The correlations between PTG and adjustment outcomes were computed in each subpopulation across every time point. RESULTS: The patients were categorized into the following four groups, which showed very different patterns of PTG change over the first year after breast cancer surgery: stable high (27.4%), high decreasing (39.4%), low increasing (16.9%), and low decreasing (16.9%). Differences in the level of adjustment at 12 months and the patterns of the correlations across time were found among these latent subgroups CONCLUSIONS: This study was the first longitudinal examination of PTG trajectories and their different levels of adjustment. The findings support our argument that identifying distinct PTG trajectories can better determine the nature of the relationship between PTG and adjustment.

5'UTR G-quadruplex structure enhances translation in size dependent manner.

Translation initiation in bacteria is frequently regulated by various structures in the 5' untranslated region (5'UTR). Previously, we demonstrated that G-quadruplex (G4) formation in non-template DNA enhances transcription. In this study, we aim to explore how G4 formation in mRNA (RG4) at 5'UTR impacts translation using a T7-based in vitro translation system and in E. coli. We show that RG4 strongly promotes translation efficiency in a size-dependent manner. Additionally, inserting a hairpin upstream of the RG4 further enhances translation efficiency, reaching up to a 12-fold increase. We find that the RG4-dependent effect is not due to increased ribosome affinity, ribosome binding site accessibility, or mRNA stability. We propose a physical barrier model in which bulky structures in 5'UTR biases ribosome movement toward the downstream start codon, thereby increasing the translation output. This study provides biophysical insights into the regulatory role of 5'UTR structures in in vitro and bacterial translation, highlighting their potential applications in tuning gene expression.

The safety and efficacy of sugammadex for reversing neuromuscular blockade in younger children and infants.

INTRODUCTION: Sugammadex, a novel selective antagonist of non-depolarizing neuromuscular blocking agents, has been shown to rapidly and effectively reverse moderate and deep paralysis in adults and pediatric patients over age 2, improving patient recovery and reducing the risk of postoperative complications. AREAS COVERED: Since the use of sugammadex in patients under age 2 is not widely studied, we aim to provide an overview on the drug's application and potential use in infants and neonates. There is a limited but growing body of evidence for the safe, efficacious use of sugammadex in children under age 2. Relevant studies were identified from the most updated data including case reports, clinical trials, systematic reviews, and meta analyses. EXPERT OPINION: The results suggest that at a dose of 2 to 4 mg/kg of sugammadex can be safely used to rapidly and effectively reverse neuromuscular blockade in neonates and infants; it is non-inferior based on incidence of adverse events compared to neostigmine. Additionally, sugammadex doses between 8 and 16 mg/kg may be used as a rescue agent for infants during 'can't intubate, can't ventilate' crisis. Overall, sugammadex offers new value in the perioperative care of patients under age 2, with further studies warranted to better understand its application and full effect in the pediatric population.

The utility of coping through emotional approach: A meta-analysis.

OBJECTIVE: A systematic review and meta-analysis was conducted to examine associations between attempts to cope with stressors through the two facets of emotional approach coping (EAC; i.e., processing and expressing stressor-related emotions) and indicators of physical and mental health. METHOD: EBSCO databases including MEDLINE, PsycINFO, and Cochrane Collections were searched from inception to November 2022. In all, 86 studies were included in a meta-analytic evaluation using a random-effects model and meta-regression analysis. RESULTS: EAC was associated with better overall health (r = .05; p = .04; 95% confidence interval = [.003, .10]). Emotional expression (EE) and emotional processing (EP) also were positively associated with better overall health, although these relationships were not statistically significant. In meta-regressions examining specific health domains, EAC was linked to better health in biological/physiological, physical, and resilience-related psychological adjustment domains, as well as to worse outcomes in the risk-related psychological adjustment and mental/emotional distress domains. Results for EE and EP mirrored this pattern; however, only EP was associated with more engagement in health-promoting behaviors. CONCLUSIONS: Coping with stressors through emotional approach appears to be associated with better mental and physical health, with some observed differences for EE and EP. The literature on EAC and health is marked by heterogeneity across study methodologies and measures. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Individualised Transcranial Magnetic Stimulation Targeting of the Left Dorsolateral Prefrontal Cortex for Enhancing Cognition: A Randomised Controlled Trial.

Repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to produce cognitive enhancing effects across different neuropsychiatric disorders; however, so far, these effects have been limited. This trial investigated the efficacy of using a novel individualised approach to target the left dorsolateral prefrontal cortex (L-DLPFC) for enhancing cognitive flexibility based on performance on a cognitive task. First, forty healthy participants had their single target site at the L-DLPFC determined based on each individual's performance on a random letter generation task. Participants then received, in a cross-over single-blinded experimental design, a single session of intermittent theta burst stimulation (iTBS) to their individualised DLPFC target site, an active control site and sham iTBS. Following each treatment condition, participants completed the Task Switching task and Colour-Word Stroop test. There was no significant main effect of treatment condition on the primary outcome measure of switch reaction times from the Task Switching task [F = 1.16 (2, 21.6), p = 0.33] or for any of the secondary cognitive outcome measures. The current results do not support the use of our novel individualised targeting methodology for enhancing cognitive flexibility in healthy participants. Research into alternative methodological targeting approaches is required to further improve rTMS's cognitive enhancing effects.