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Low iron (Fe) bioavailability can limit the biosynthesis of Fe-containing proteins, which are especially abundant in photosynthetic organisms, thus negatively affecting global primary productivity. Understanding cellular coping mechanisms under Fe limitation is therefore of great interest. We surveyed the temporal responses of Chlamydomonas (Chlamydomonas reinhardtii) cells transitioning from an Fe-rich to an Fe-free medium to document their short and long-term adjustments. While slower growth, chlorosis and lower photosynthetic parameters are evident only after one or more days in Fe-free medium, the abundance of some transcripts, such as those for genes encoding transporters and enzymes involved in Fe assimilation, change within minutes, before changes in intracellular Fe content are noticeable, suggestive of a sensitive mechanism for sensing Fe. Promoter reporter constructs indicate a transcriptional component to this immediate primary response. With acetate provided as a source of reduced carbon, transcripts encoding respiratory components are maintained relative to transcripts encoding components of photosynthesis and tetrapyrrole biosynthesis, indicating metabolic prioritization of respiration over photosynthesis. In contrast to the loss of chlorophyll, carotenoid content is maintained under Fe limitation despite a decrease in the transcripts for carotenoid biosynthesis genes, indicating carotenoid stability. These changes occur more slowly, only after the intracellular Fe quota responds, indicating a phased response in Chlamydomonas, involving both primary and secondary responses during acclimation to poor Fe nutrition.

In an experimental study set in Singapore's tropical climate, we evaluated the thermal environmental performance, energy consumption, and thermal comfort of air and radiant cooling systems, operating at an operative and air temperature of 26 °C. 78 participants across five groups answered thermal comfort surveys in a crossover study design. Environmental performance metrics indicated that both systems produced similar conditions, with a noticeable difference in air velocity. The mean radiant temperature to air temperature difference was less than 0.5 °C in both systems. The radiant system exhibited a 33 % higher heat flux extraction than the air system and required less electrical power for the transportation of the cooling medium and ventilation air. Overall, the radiant system used 4 % less energy than the air system when controlled at 26 °C and 34 % when operated at 23 °C. Results show that radiant and air systems provided equal thermal comfort in cooling, with over 60 % of participants expressing satisfaction and ∼ 20 % voted neutral thermal satisfaction. ∼ 40 % of participants preferred cooler conditions, and ∼ 30 % desired increased air movement.

High-grade serous ovarian carcinoma (HGSOC), the deadliest form of ovarian cancer, is typically diagnosed after it has metastasized and often relapses after standard-of-care platinum-based chemotherapy, likely due to advanced tumor stage, heterogeneity, and immune evasion and tumor-promoting signaling from the tumor microenvironment. To understand how spatial heterogeneity contributes to HGSOC progression and early relapse, we profiled an HGSOC tissue microarray of patient-matched longitudinal samples from 42 patients. We found spatial patterns associated with early relapse, including changes in T cell localization, malformed tertiary lymphoid structure (TLS)-like aggregates, and increased podoplanin-positive cancer-associated fibroblasts (CAFs). Using spatial features to compartmentalize the tissue, we found that plasma cells distribute in two different compartments associated with TLS-like aggregates and CAFs, and these distinct microenvironments may account for the conflicting reports about the role of plasma cells in HGSOC prognosis.

It is a widespread practice among Canadian school districts to assess the French language proficiency of candidates applying for French as a Second Language (FSL) teaching positions. This pan-Canadian study used surveys, interviews, and website data to examine the French language proficiency assessment practices and processes used by Canadian schools when hiring FSL teachers. The findings show that almost 90% of Canadian school districts assess French language proficiency when hiring FSL teachers and that the most common form of assessment is to ask one to three questions in French (with candidates responding in French) during the employment interview. Evaluation of the candidates' responses is rarely informed by a language proficiency framework or rubric; instead, evaluators' decisions are informed by their overall impressions of the candidate's language proficiency. Other promising assessment practices are described, along with suggestions about how districts may improve their French language proficiency assessments when hiring FSL teachers.

A theory-practice divide has beset initial teacher training (ITT) for many decades. In England, there are multiple ways to gain qualified teacher status, which can be broadly categorised into school-led or university-led, with underlying arguments about the relative importance of theory and practice, and how far learning to teach should be seen as an apprenticeship. Government policy has moved towards more prescription with its ITT Core Content Framework, a curriculum that suggests that there is a right way to learn to teach. In this climate, it is important to establish what value universities -- and, in particular, the master's element of the Postgraduate Certificate in Education -- add to student teachers. Thus, this article asks: What is the contribution of a research-informed master's module to ITT? The findings of the research indicate that the master's module offered opportunities to alter preconceptions and beliefs about teaching and learning; the process of essay writing enhanced critical reflection, which inspired more confidence in the classroom; and the potential theory--practice divide can be viewed as offering opportunities for enhancing self-efficacy. These findings suggest that master's study has an impact on teachers within their ITT period and beyond it, and have implications for learning processes and content for programmes both in England and internationally.

Persuasion is inherent to the instructional process. Instructions delivered through online programs do not always generate expected and consistent learning outcomes, and hence persuasion in online instructional design is even more critical. Through this mixed-method study, we aim to identify the most widely used persuasive design techniques, the challenges limiting their applications, and their implications. Furthermore, this paper discusses the recommendations of new persuasive techniques put forth by Instructional Designers.

Successful acclimation to copper (Cu) deficiency involves a fine balance between Cu import and export. In the green alga Chlamydomonas reinhardtii, Cu import is dependent on a transcription factor, Copper Response Regulator 1 (CRR1), responsible for activating genes in Cu-deficient cells. Among CRR1 target genes are two Cu transporters belonging to the CTR/COPT gene family (CTR1 and CTR2) and a related soluble protein (CTR3). The ancestor of these green algal proteins was likely acquired from an ancient chytrid and contained conserved cysteine-rich domains (named the CTR-associated domains, CTRA) that are predicted to be involved in Cu acquisition. We show by reverse genetics that Chlamydomonas CTR1 and CTR2 are canonical Cu importers albeit with distinct affinities, while loss of CTR3 did not result in an observable phenotype under the conditions tested. Mutation of CTR1, but not CTR2, recapitulates the poor growth of crr1 in Cu-deficient medium, consistent with a dominant role for CTR1 in high-affinity Cu(I) uptake. On the other hand, the overaccumulation of Cu(I) (20 times the quota) in zinc (Zn) deficiency depends on CRR1 and both CTR1 and CTR2. CRR1-dependent activation of CTR gene expression needed for Cu over-accumulation can be bypassed by the provision of excess Cu in the growth medium. Over-accumulated Cu is sequestered into the acidocalcisome but can become remobilized by restoring Zn nutrition. This mobilization is also CRR1-dependent, and requires activation of CTR2 expression, again distinguishing CTR2 from CTR1 and consistent with the lower substrate affinity of CTR2.One sentence summaryRegulation of Cu uptake and sequestration by members of the CTR family of proteins in Chlamydomonas.

Wildfires are a global natural phenomenon. In North America, wildfires have not only become more frequent, but also more severe and longer in duration, a trend ascribed to climate change combined with large fuel stores left from modern fire suppression. The intensification of wildfire activity has significant implications for planetary health and public health, as exposure to fine particulate matter (PM2.5) in wildfire smoke is linked to adverse health effects. This review focuses on respiratory morbidity from wildfire smoke exposure. Inhalation of wildfire PM2.5 causes lung injury via oxidative stress, local and systemic inflammation, airway epithelium compromise, and increased vulnerability to infection. Wildfire PM2.5 exposure results in exacerbations of pre-existing asthma and chronic obstructive pulmonary disease, with an escalation in healthcare utilization, including emergency department visits and hospitalizations. Wildfire smoke exposure may be associated with asthma onset, long-term impairment of lung function, and increased all-cause mortality. Children, older adults, occupationally-exposed groups, and possibly women are the most at risk from wildfire smoke. Future research is needed to clarify best practices for risk mitigation and wildfire management.

Climate change is increasing the frequency and severity of short-term (~1 y) drought events-the most common duration of drought-globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on grassland and shrubland ecosystems. With a standardized approach, we imposed ~a single year of drought at 100 sites on six continents. Here we show that loss of a foundational ecosystem function-aboveground net primary production (ANPP)-was 60% greater at sites that experienced statistically extreme drought (1-in-100-y event) vs. those sites where drought was nominal (historically more common) in magnitude (35% vs. 21%, respectively). This reduction in a key carbon cycle process with a single year of extreme drought greatly exceeds previously reported losses for grasslands and shrublands. Our global experiment also revealed high variability in drought response but that relative reductions in ANPP were greater in drier ecosystems and those with fewer plant species. Overall, our results demonstrate with unprecedented rigor that the global impacts of projected increases in drought severity have been significantly underestimated and that drier and less diverse sites are likely to be most vulnerable to extreme drought.

Although the green alga Chlamydomonas reinhardtii has long served as a reference organism, few studies have interrogated its role as a primary producer in microbial interactions. Here, we quantitatively investigated C. reinhardtii's capacity to support a heterotrophic microbe using the established coculture system with Mesorhizobium japonicum, a vitamin B12-producing α-proteobacterium. Using stable isotope probing and nanoscale secondary ion mass spectrometry (nanoSIMS), we tracked the flow of photosynthetic fixed carbon and consequent bacterial biomass synthesis under continuous and diurnal light with single-cell resolution. We found that more 13C fixed by the alga was taken up by bacterial cells under continuous light, invalidating the hypothesis that the alga's fermentative degradation of starch reserves during the night would boost M. japonicum heterotrophy. 15NH4 assimilation rates and changes in cell size revealed that M. japonicum cells reduced new biomass synthesis in coculture with the alga but continued to divide-a hallmark of nutrient limitation often referred to as reductive division. Despite this sign of starvation, the bacterium still synthesized vitamin B12 and supported the growth of a B12-dependent C. reinhardtii mutant. Finally, we showed that bacterial proliferation could be supported solely by the algal lysis that occurred in coculture, highlighting the role of necromass in carbon cycling. Collectively, these results reveal the scarcity of fixed carbon in this microbial trophic relationship (particularly under environmentally relevant light regimes), demonstrate B12 exchange even during bacterial starvation, and underscore the importance of quantitative approaches for assessing metabolic coupling in algal-bacterial interactions.

Energy status and nutrients regulate photosynthetic protein expression. The unicellular green alga Chromochloris zofingiensis switches off photosynthesis in the presence of exogenous glucose (+Glc) in a process that depends on hexokinase (HXK1). Here, we show that this response requires that cells lack sufficient iron (-Fe). Cells grown in -Fe+Glc accumulate triacylglycerol (TAG) while losing photosynthesis and thylakoid membranes. However, cells with an iron supplement (+Fe+Glc) maintain photosynthesis and thylakoids while still accumulating TAG. Proteomic analysis shows that known photosynthetic proteins are most depleted in heterotrophy, alongside hundreds of uncharacterized, conserved proteins. Photosynthesis repression is associated with enzyme and transporter regulation that redirects iron resources to (a) respiratory instead of photosynthetic complexes and (b) a ferredoxin-dependent desaturase pathway supporting TAG accumulation rather than thylakoid lipid synthesis. Combining insights from diverse organisms from green algae to vascular plants, we show how iron and trophic constraints on metabolism aid gene discovery for photosynthesis and biofuel production.

OBJECTIVES: An estimated 14-23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort. METHODS: Data from hospitalized subjects with Glasgow Coma Scale score of 3-12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014-2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-3 (vs. 4-8)) at 3, 6, and 12 months after injury. RESULTS: Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01-4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months. CONCLUSIONS: After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed. LEVEL OF EVIDENCE: IV. TRIAL REGISTRATION NUMBER: NCT02119182.

Precision prevention embraces personalized prevention but includes broader factors such as social determinants of health to improve cardiovascular health. The quality, quantity, precision, and diversity of data relatable to individuals and communities continue to expand. New analytical methods can be applied to these data to create tools to attribute risk, which may allow a better understanding of cardiovascular health disparities. Interventions using these analytic tools should be evaluated to establish feasibility and efficacy for addressing cardiovascular disease disparities in diverse individuals and communities. Training in these approaches is important to create the next generation of scientists and practitioners in precision prevention. This state-of-the-art review is based on a workshop convened to identify current gaps in knowledge and methods used in precision prevention intervention research, discuss opportunities to expand trials of implementation science to close the health equity gaps, and expand the education and training of a diverse precision prevention workforce.

BACKGROUND: Research has demonstrated the negative impact of racism on health, yet the measurement of racial sentiment remains challenging. This article provides practical guidance on using social media data for measuring public sentiment. METHODS: We describe the main steps of such research, including data collection, data cleaning, binary sentiment analysis, and visualization of findings. We randomly sampled 55,844,310 publicly available tweets from 1 January 2011 to 31 December 2021 using Twitters Application Programming Interface. We restricted analyses to US tweets in English using one or more 90 race-related keywords. We used a Support Vector Machine, a supervised machine learning model, for sentiment analysis. RESULTS: The proportion of tweets referencing racially minoritized groups that were negative increased at the county, state, and national levels, with a 16.5% increase at the national level from 2011 to 2021. Tweets referencing Black and Middle Eastern people consistently had the highest proportion of negative sentiment compared with all other groups. Stratifying temporal trends by racial and ethnic groups revealed unique patterns reflecting historical events specific to each group, such as the killing of George Floyd regarding sentiment of posts referencing Black people, discussions of the border crisis near the 2018 midterm elections and anti-Latinx sentiment, and the emergence of COVID-19 and anti-Asian sentiment. CONCLUSIONS: This study demonstrates the utility of social media data as a quantitative means to measure racial sentiment over time and place. This approach can be extended to a range of public health topics to investigate how changes in social and cultural norms impact behaviors and policy.A supplemental digital video is available at http://links.lww.com/EDE/C91.

Background: Although robotic surgery has several advantages over other minimally invasive surgery (MIS) techniques for rectal cancer surgery, the uptake in Canada has been limited owing to a perceived increase in cost and lack of training. The objective of this study was to determine the impact of access to robotic surgery in a Canadian setting. Methods: We conducted a retrospective cohort study involving consecutive adults undergoing surgical resection for rectal cancer between 2017 and 2020. The primary exposure was access to robotic surgery. Outcomes included MIS utilization, short-term outcomes, total cost of care, and quality of surgical resection. We completed univariate and multivariate analyses. Results: We included 171 individuals in this cohort study (85 in the prerobotic period and 86 in the robotic period). The 2 groups had similar baseline characteristics. A higher proportion of individuals underwent successful MIS in the robotic phase (86% v. 46%, p < 0.001). Other benefits included a shorter mean length of hospital stay (5.1 d v. 9.2 d, p < 0.001). The quality of surgical resection was similar between groups. The total cost of care was $16 746 in the robotic period and $18 808 in the prerobotic period (mean difference -$1262, 95% confidence interval -$4308 to $1783; p = 0.4). Conclusion: Access to robotic rectal cancer surgery increased successful completion of MIS and shortened hospital stay, with a similar total cost of care. Robotic rectal cancer surgery can enhance patient outcomes in the Canadian setting. Contexte : M me si la chirurgie robotis e comporte plusieurs avantages par rapport d'autres techniques chirurgicales minimalement effractives (TCME) dans le contexte du cancer rectal, son adoption a t lente au Canada en raison d'une augmentation per ue des co ts et du manque de formation. L'objectif de la pr sente tude tait de mesurer l'impact de l'acc s la chirurgie robotis e dans le contexte canadien. M thodes : Nous avons proc d une tude de cohorte r trospective regroupant des cas cons cutifs de r section chirurgicale pour cancer rectal entre 2017 et 2020 chez des adultes. La variable d'exposition primaire tait l'acc s la chirurgie robotis e. Les param tres incluaient le recours des TCME, les r sultats br ve ch ance, le co t total des soins et la qualit de la r section chirurgicale. Nous avons effectu des analyses uni- et multivari es. R sultats : Nous avons inclus 171 personnes dans cette tude de cohorte (85 de la p riode pr robotisation et 86 de la p riode de robotisation). Les groupes pr sentaient des caract ristiques de d part similaires. Une proportion plus lev e de personnes (86% c. 46%, p < 0,001) de la p riode de robotisation a obtenu de bons r sultats. Parmi les autres avantages, mentionnons l'abr gement du s jour hospitalier (5,1 j c. 9,2 j, p < 0,001). La qualit de la r section chirurgicale a t la m me entre les groupes. Le co t total des soins a t de 16 746 $ pour la p riode de robotisation, contre 18 808 $ pour la p riode de pr robotisation (diff rence moyenne -1262 $, intervalle de confance de 95% -4308 $ 1783 $; p = 0,4). Conclusion : L'acc s la chirurgie robotis e pour le cancer rectal a donn lieu une am lioration des r sultats de la TCME et un abr gement du s jour hospitalier, tout en maintenant un co t total similaire. La chirurgie robotis e pour le cancer rectal peut am liorer les r sultats pour la patient le canadienne., Laparoscopic surgery for colorectal cancer has several advantages over open techniques, including decreased postoperative pain, shorter length of stay, decreased morbidity, and improved quality of life. (1,2) Although there were [...]

Background: The rapid evolution of genetic technologies and utilization of genetic information for clinical decision-making has necessitated increased surgeon participation in genetic counselling, testing, and appropriate referral of patients for genetic services, without formal training in genetics. We performed a scoping review to describe surgeons' knowledge, perceptions, attitudes, and barriers pertaining to genetic literacy in the management of patients who had confirmed cancer or who were potentially genetically at risk. Methods: We conducted a scoping review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews checklist. We performed a comprehensive literature search, and 2 reviewers independently screened studies for inclusion. These studies included surgeons involved in the care of patients with confirmed gastrointestinal, breast, and endocrine and neuroendocrine cancers, or patients who were potentially genetically at risk for these cancers. Results: We analyzed 17 studies, all of which used survey or interview-based formats. Many surgeons engaged in genetic counselling, testing, and referral, but reported low confidence and comfort in doing so. Knowledge assessments showed lower confidence in identifying genetic inheritance patterns and hereditary cancer syndromes, but awareness was higher among surgeons with greater clinical volume or subspecialty training in oncology. Surgeons felt responsible for facilitating these services and explicitly requested educational support in genetics. Barriers to genetic literacy were identified and catalogued at patient, surgeon, and system levels. Conclusion: Surgeons frequently engage in genetics-related tasks despite a lack of formal genetics training, and often report low knowledge, comfort, and confidence in providing such services. We have identified several barriers to genetic literacy that can be used to develop interventions to enhance genetic literacy among surgeons. Contexte : L' volution rapide des technologies g n tiques et l'utilisation d'information g n tique pour la prise de d cisions cliniques ont men une augmentation in vitable de la participation des chirurgiens aux conseils et aux tests g n tiques ainsi qu' l'aiguillage appropri des patients vers des services g n tiques, sans pour autant avoir re u la formation n cessaire dans le domaine. Nous avons effectu une synth se exploratoire visant d crire l' tat des connaissances des chirurgiens, leurs perceptions et leurs attitudes l' gard de la litt ratie g n tique, et les obstacles auxquels ils se butent dans la prise en charge de patients ayant un diagnostic de cancer confirm ou qui pourraient tre g n tiquement risque. M thodes : Pour notre synth se exploratoire, nous avons suivi la liste de v rification Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews. Nous avons effectu une revue exhaustive de la litt rature, et 2 relecteurs ont valu ind pendamment les tudes inclure. Les tudes retenues devaient porter sur des chirurgiens ayant particip aux soins de patients ayant un diagnostic confirm de cancer du sein ou de tumeur gastro-intestinale, endocrine ou neuroendocrine, ou encore de patients pr sentant un risque g n tique potentiel pour ces types de cancers. R sultats : Nous avons analys 17 tudes examinant les r sultats de sondages ou d'entrevues. Beaucoup de chirurgiens donnent des conseils en g n tique, prescrivent des tests et font des aiguillages, mais disent avoir peu confiance en leurs capacit s et tre peu l'aise de le faire. Les valuations des connaissances ont montr des niveaux de confiance inf rieurs concernant la mise en vidence de configurations g n tiques indiquant une transmission h r ditaire et de syndromes h r ditaires pr disposant au cancer, mais le niveau de connaissances tait plus lev chez les chirurgiens ayant un fort volume clinique ou une sursp cialisation en oncologic Les chirurgiens se sentaient responsables de faciliter l'acc s ces services et ont explicitement demand une formation compl mentaire en g n tique. Les entraves la litt ratie g n tique ont t recens es et class es l' chelle des patients, des chirurgiens, et du syst me. Conclusion : Les chirurgiens accomplissent r guli rement des t ches relevant de la g n tique, bien qu'ils n'aient suivi aucune formation dans le domaine, et disent fr quemment avoir peu de connaissances sur le sujet et tre peu l'aise ou confiants lorsqu'ils doivent prodiguer de tels services. Nous avons mis en vidence plusieurs obstacles la litt ratie g n tique qui pourraient tre abolis par l' laboration d'interventions visant l'am lioration de cette litt ratie chez les chirurgiens., The rapid evolution of genetic testing technology over recent decades has allowed genetic information to guide clinical care. Approximately 5%-10% of cancers are hereditary, and once an underlying germline mutation [...]

To close the gap between the rates of computational screening and experimental realization of novel materials1,2, we introduce the A-Lab, an autonomous laboratory for the solid-state synthesis of inorganic powders. This platform uses computations, historical data from the literature, machine learning (ML) and active learning to plan and interpret the outcomes of experiments performed using robotics. Over 17 days of continuous operation, the A-Lab realized 41 novel compounds from a set of 58 targets including a variety of oxides and phosphates that were identified using large-scale ab initio phase-stability data from the Materials Project and Google DeepMind. Synthesis recipes were proposed by natural-language models trained on the literature and optimized using an active-learning approach grounded in thermodynamics. Analysis of the failed syntheses provides direct and actionable suggestions to improve current techniques for materials screening and synthesis design. The high success rate demonstrates the effectiveness of artificial-intelligence-driven platforms for autonomous materials discovery and motivates further integration of computations, historical knowledge and robotics.

Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [-0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.

Patients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological mechanisms promoting APNS are currently unknown, but the microbiota-gut-brain axis offers an avenue to understanding mechanisms as well as possibilities for intervention. Microbiome composition after trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether the gut microbiomes of trauma-exposed emergency department patients who develop APNS have dysfunctional gut microbiome profiles and discover potential associated mechanisms. We performed metagenomic analysis on stool samples (n = 51) from a subset of adults enrolled in the Advancing Understanding of RecOvery afteR traumA (AURORA) study. Two-, eight- and twelve-week post-trauma outcomes for post-traumatic stress disorder (PTSD) (PTSD checklist for DSM-5), normalized depression scores (PROMIS Depression Short Form 8b) and somatic symptom counts were collected. Generalized linear models were created for each outcome using microbial abundances and relevant demographics. Mixed-effect random forest machine learning models were used to identify associations between APNS outcomes and microbial features and encoded metabolic pathways from stool metagenomics. Microbial species, including Flavonifractor plautii, Ruminococcus gnavus and, Bifidobacterium species, which are prevalent commensal gut microbes, were found to be important in predicting worse APNS outcomes from microbial abundance data. Notably, through APNS outcome modeling using microbial metabolic pathways, worse APNS outcomes were highly predicted by decreased L-arginine related pathway genes and increased citrulline and ornithine pathways. Common commensal microbial species are enriched in individuals who develop APNS. More notably, we identified a biological mechanism through which the gut microbiome reduces global arginine bioavailability, a metabolic change that has also been demonstrated in the plasma of patients with PTSD.

This is the primary report of the randomized, placebo-controlled phase 3 BRIGHT AML 1019 clinical trial of glasdegib in combination with intensive chemotherapy (cytarabine and daunorubicin) or non-intensive chemotherapy (azacitidine) in patients with untreated acute myeloid leukemia. Overall survival (primary endpoint) was similar between the glasdegib and placebo arms in the intensive (n = 404; hazard ratio [HR] 1.05; 95% confidence interval [CI]: 0.782-1.408; two-sided p = 0.749) and non-intensive (n = 325; HR 0.99; 95% CI: 0.768-1.289; two-sided p = 0.969) studies. The proportion of patients who experienced treatment-emergent adverse events was similar for glasdegib versus placebo (intensive: 99.0% vs. 98.5%; non-intensive: 99.4% vs. 98.8%). The most common treatment-emergent adverse events were nausea, febrile neutropenia, and anemia in the intensive study and anemia, constipation, and nausea in the non-intensive study. The addition of glasdegib to either cytarabine and daunorubicin or azacitidine did not significantly improve overall survival and the primary efficacy endpoint for the BRIGHT AML 1019 phase 3 trial was not met. Clinical trial registration: ClinicalTrials.gov: NCT03416179.

Background: Alcohol use disorders (AUDs) are emerging as a substance use disorder having various psychological and physical ill effects leading to hampering of individual’s productivity and functioning. Aims: The aim of this study was to evaluate the efficacy of ketamine in enhancing confidence levels to abstain from alcohol. Methods: Eighteen patients were administered ketamine intravenously after detoxification; a total of three doses, with a 3-day gap between each. The Alcohol Abstinence Self-Efficacy Scale was used to measure their confidence in abstaining from alcohol. Results: The study revealed a significant increase in mean confidence scores after three ketamine sessions, with a final assessment showing a 51.98% increase in confidence from baseline. Conclusions: The study found that ketamine therapy significantly increased confidence levels in individuals with AUD to abstain from alcohol, with P = 0.05 threshold. However, the impact may wane over time, suggesting the need for additional support or maintenance treatments.

A case involving a 29-year-old female patient with a known case of hypothyroidism at 38 weeks gestation. She developed a fronto-occipital, postural type of headache. This ensued on the second postoperative day after undergoing an unintended dural puncture with the introducer needle during spinal anesthesia for an elective cesarean section. It was initially treated as a post-dural puncture headache until she developed generalized tonic–clonic seizures the next day. Magnetic resonance imaging (MRI) of the brain exhibited features of posterior reversible encephalopathy syndrome (PRES). With anticonvulsants and antibiotics, the neurological symptoms subsided, and the patient was discharged home symptom-free. We call attention to the importance of suspecting PRES in obstetric cases with an inadvertent dural puncture in a normotensive patient. Neuroimaging plays a crucial role in making a diagnosis of headaches, especially during the peripartum period. Lastly, keeping in view, the potential medicolegal implications in such cases, further research seems vital, especially in the Asian population.

Abstract The global population is increasingly reliant on vaccines to maintain population health with billions of doses used annually in immunisation programmes. Substandard and falsified vaccines are becoming more prevalent, caused by both the degradation of authentic vaccines but also deliberately falsified vaccine products. These threaten public health, and the increase in vaccine falsification is now a major concern. There is currently no coordinated global infrastructure or screening methods to monitor vaccine supply chains. In this study, we developed and validated a matrix-assisted laser desorption/ionisation-mass spectrometry (MALDI-MS) workflow that used open-source machine learning and statistical analysis to distinguish authentic and falsified vaccines. We validated the method on two different MALDI-MS instruments used worldwide for clinical applications. Our results show that multivariate data modelling and diagnostic mass spectra can be used to distinguish authentic and falsified vaccines providing proof-of-concept that MALDI-MS can be used as a screening tool to monitor vaccine supply chains.

Abstract Background Patients perceive effective patient-doctor communication as an important metric when evaluating their satisfaction with health systems. Hence, optimal patient-physician communication is fundamental for quality healthcare. High-income countries (HICs) have extensively studied patient-resident communication. However, there is a dearth of similar studies in low- and middle-income countries (LMICs). Therefore, we aimed to explore the current state of and barriers to practicing good patient-resident communication and explore possible solutions to mitigate these challenges at one of the largest Academic Medical Centers in an LMIC. Methods This study employed an exploratory qualitative study design and was conducted at the Aga Khan University Hospital in Pakistan. Through purposive maximum variation sampling, 60 healthcare workers from diverse cohorts, including attendings, fellows, residents, and medical students, participated in eight focus group discussions. Results We identified three key themes from the data: Status-quo of residents’ communication skills and learning (Poor verbal and non-verbal communication, inadequate training programs, and variable sources of learning), Barriers to effective communication (Institutional barriers such as lack of designated counselling spaces, lack of resident insight regarding effective communication and deficits in intra-team communication), and the need for developing a communication skills curriculum (Design, implementation and scaling to other cohorts of healthcare workers). Conclusions Findings from this study show that multifaceted factors are responsible for inadequate patient resident-physician communication, highlighting the need for and importance of developing a formal communication skills training curriculum for residents. These insights can be used to create standardized training for equipping residents with adequate skills for effectively communicating with patients which can improve healthcare service delivery and patient outcomes.

Abstract Energy status and nutrients regulate photosynthetic protein expression. The unicellular green alga Chromochloris zofingiensis switches off photosynthesis in the presence of exogenous glucose (+Glc) in a process that depends on hexokinase (HXK1). Here, we show that this response requires that cells lack sufficient iron (−Fe). Cells grown in −Fe+Glc accumulate triacylglycerol (TAG) while losing photosynthesis and thylakoid membranes. However, cells with an iron supplement (+Fe+Glc) maintain photosynthesis and thylakoids while still accumulating TAG. Proteomic analysis shows that known photosynthetic proteins are most depleted in heterotrophy, alongside hundreds of uncharacterized, conserved proteins. Photosynthesis repression is associated with enzyme and transporter regulation that redirects iron resources to (a) respiratory instead of photosynthetic complexes and (b) a ferredoxin-dependent desaturase pathway supporting TAG accumulation rather than thylakoid lipid synthesis. Combining insights from diverse organisms from green algae to vascular plants, we show how iron and trophic constraints on metabolism aid gene discovery for photosynthesis and biofuel production.

Abstract The global incidence of gout has increased rapidly, likely secondary to the increase in the prevalence of conditions that predispose to gout, such as obesity. Depending on the population studied, the prevalence of gout ranges from less than 1 to 6.8%. Thus, gout can be a significant burden on healthcare systems. The objective of this study is to observe the trends in the incidence, prevalence, and disability-adjusted life years (DALYs) of gout between 1990 and 2019 globally and in the European Union (EU) 15+ nations. We extracted data from the Global Burden of Disease Study database based on the International Classification of Diseases (ICD) versions 10 and 9. Incidence, prevalence, and disability-adjusted life years (DALYs) were extracted for individual EU15+ countries and globally in males and females between 1990 and 2019. Joinpoint regression analysis was used to describe trends. Between 1990 and 2019, gout prevalence, incidence, and DALYs increased in both males (+ 21.42%, + 16.87%, + 21.49%, respectively) and females (+ 21.06%, + 18.75%, + 20.66%, respectively) globally. The United States of America had the highest increase in prevalence (males: + 90.6%; females + 47.1%), incidence (males: + 63.73%; females: + 39.11%) and DALYs (males: + 90.43%; females: + 42.75%). Incidence, prevalence, and DALYs from gout are increasing worldwide and in most of the EU15+ countries for males and females. Studies have reported the association of gout with comorbidities such as metabolic syndrome, diabetes mellitus, and cardiovascular disease. Health policies and resource allocation are required to increase awareness and modify risk factors globally.

Iodine nutrition is a growing issue within the USA due to newer trends of non-iodized salts. There are no recent reviews looking at the current state of iodine deficiency-induced hypothyroidism in children in the USA. We performed a retrospective chart review at our tertiary pediatric endocrine clinic; four met the diagnostic criteria for iodine deficiency defined by a low urine iodine level. We further characterized severity of disease, risk factors, goiter, thyroid labs and antibodies. All cases had significant goiter and were diagnosed within the last 2 years. One case had iodine deficiency due to no iodized salt intake along with concurrent diagnosis of developmental delay and multiple food allergies, while others involved the use of non-iodized salts. Two cases had iodine deficiency along with autoimmunity. It is critical to obtain a dietary history for all patients who present with goiter and/or hypothyroidism. There may be a need to consider reevaluating current preventative measures for iodine deficiency, especially for certain vulnerable populations such as children who do not consume iodized salt.