"So we brought these players together": a qualitative study of educators' experiences to analyze the challenges of creating an e-learning program for neuropalliative care.

BACKGROUND: In recent years, the subspecialty of neuropalliative care has emerged with the goal of improving the quality of life of patients suffering from neurological disease, though gaps remain in neuropalliative care education and training. E-learning has been described as a way to deliver interactive and facilitated lower-cost learning to address global gaps in medical care. We describe here the development of a novel, international, hybrid, and asynchronous curriculum with both self-paced modules and class-based lectures on neuropalliative care topics designed for the neurologist interested in palliative care, the palliative care physician interested in caring for neurological patients, and any other physician or advanced care providers interested in neuropalliative care. METHODS: The course consisted of 12 modules, one per every four weeks, beginning July 2022. Each module is based on a case and relevant topics. Course content was divided into three streams (Neurology Basics, Palliative Care Basics, and Neuropalliative Care Essentials) of which two were optional and one was mandatory, and consisted of classroom sessions, webinars, and an in-person skills session. Evaluation of learners consisted of multiple choice questions and written assignments for each module. Evaluation of the course was based on semi-structured qualitative interviews conducted with both educator and learner, the latter of which will be published separately. Audio files were transcribed and underwent thematic analysis. For the discussion of the results, Khan's e-learning framework was used. RESULTS: Ten of the 12 participating educators were interviewed. Of the educators, three identified as mid-career and seven as senior faculty, ranging from six to 33 years of experience. Nine of ten reported an academic affiliation and all reported association with a teaching hospital. Themes identified from the educators' evaluations were: bridging the global gap, getting everybody on board, defining the educational scope, investing extensive hours of voluntary time and resources, benefiting within and beyond the curriculum, understanding the learner's experience, creating a community of shared learning, adapting future teaching and learning strategies, and envisioning long term sustainability. CONCLUSIONS: The first year of a novel, international, hybrid, and asynchronous neuropalliative care curriculum has been completed, and its educators have described both successes and avenues for improvement. Further research is planned to assess this curriculum from the learner perspective.

Adaptation to ex vivo culture reduces human hematopoietic stem cell activity independently of cell cycle.

Loss of long-term hematopoietic stem cell (LT-HSC) function ex vivo hampers the success of clinical protocols reliant on culture. However, the kinetics and mechanisms by which this occurs remain incompletely characterized. Here, through time-resolved scRNA-Seq, matched in vivo functional analysis and the use of a reversible in vitro system of early G1 arrest, we define the sequence of transcriptional and functional events occurring during the first ex vivo division of human LT-HSCs. We demonstrate that the sharpest loss of LT-HSC repopulation capacity happens early on, between 6 and 24 hours of culture, before LT-HSCs commit to cell cycle progression. During this time window, LT-HSCs adapt to the culture environment, limiting global variability in gene expression and transiently upregulating gene networks involved in signaling and stress responses. From 24 hours, LT-HSC progression past early G1 contributes to the establishment of differentiation programmes in culture. However, contrary to current assumptions, we demonstrate that loss of HSC function ex vivo is independent of cell cycle progression. Finally, we show that targeting LT-HSC adaptation to culture by inhibiting early activation of JAK/STAT signaling improves HSC long-term repopulating function ex vivo. Collectively, our study demonstrates that controlling early LT-HSC adaptation to ex vivo culture, for example via JAK inhibition, is of critical importance to improve HSC gene therapy and expansion protocols.

Effect of a single psilocybin treatment on Fos protein expression in male rat brain.

Psilocybin has received attention as a treatment for depression, stress disorders and drug and alcohol addiction. To help determine the mechanisms underlying its therapeutic effects, here we examined acute effects of a range of behaviourally relevant psilocybin doses (0.1-3 mg/kg SC) on regional expression of Fos, the protein product of the immediate early gene, c-fos in brain areas involved in stress, reward and motivation in male rats. We also determined the cellular phenotypes activated by psilocybin, in a co-labeling analysis with NeuN, a marker of mature neurons, or Olig1, a marker of oligodendrocytes. In adult male Sprague-Dawley rats, psilocybin increased Fos expression dose dependently in several brain regions, including the frontal cortex, nucleus accumbens, central and basolateral amygdala and locus coeruleus. These effects were most marked in the central amygdala. Double labeling experiments showed that Fos was expressed in both neurons and oligodendrocytes. These results extend previous research by determining Fos expression in multiple brain areas at a wider psilocybin dose range, and the cellular phenotypes expressing Fos. The data also highlight the amygdala, especially the central nucleus, a key brain region involved in emotional processing and learning and interconnected with other brain areas involved in stress, reward and addiction, as a potentially important locus for the therapeutic effects of psilocybin. Overall, the present findings suggest that the central amygdala may be an important site through which the initial brain activation induced by psilocybin is translated into neuroplastic changes, locally and in other regions that underlie its extended therapeutic effects.

Enhanced recovery in patients with gestational diabetes mellitus and MTHFR 677 TT genotype after taking high-dose folic acid supplements during mid-late pregnancy: an open-label interventional study.

Objective: To explore the relationship between folic acid supplementation and the recovery rate of gestational diabetes mellitus (GDM) in women with methylenetetrahydrofolate (MTHFR) 677 TT genotypes in mid-late pregnancy. Methods: 9, 096 pregnant women were recruited with their MTHFR gene genotyped. 5,111 women underwent a 75-g oral glucose tolerance test (OGTT) and 2,097 were confirmed with GDM. The association between MTHFR genotypes and GDM risk was estimated using logistic and log-binomial regression, with age and parity set as the covariates to control their confounding effects. Further assessment of GDM risk on glucose levels was done using the ANCOVA model. As an open-label intervention study, 53 GDM patients with TT genotype were prescribed 800µg/day of folic acid as the high-dose group, while 201 GDM patients were given 400µg/day as the standard-dose group at their 24-28 weeks of pregnancy. A rate ratio (RR) of GDM recovery was estimated at each available time point for both groups. The time-to-GDM persistence events were analyzed with the Kaplan-Meier method and Cox-regression model. The trend of glucose levels over time was estimated using the linear model. Results: MTHFR 677 TT genotype has no significant association with the glucose levels and GDM risk, with an adjusted OR of 1.105 (95% CI 0.853, 1.431; p=0.452) and an adjusted PR of 1.050 (95% CI 0.906, 1.216; p=0.518) compared to the wildtype CC group. Patients in the high-dose group (n=38; 15 drop-outs; 40.69 days (95% CI 33.22, 48.15)) recovered from GDM approximately 27 days faster than those in the standard-dose group (n=133; 68 drop-outs; 68.09 days (95% CI 63.08, 73.11)). Concomitantly, the RR of GDM recovery rose and reached 1.247 (95% CI 1.026, 1.515) at 100 days of treatment with the standard-dose group as reference. Conclusion: High-dose folic acid supplement intake in mid-late pregnancy is associated with faster GDM relief in patients with MTHFR 677 TT genotype compared to the standard dose, which would be served as a novel and low-cost alternative therapy for the treatment of GDM.

Emotion regulation strategy use in PTSD: A daily life study.

BACKGROUND: Posttraumatic Stress Disorder is associated with emotion regulation difficulties. However, our understanding of these difficulties has been limited by the reliance of previous work on retrospective trait self-reports, which are unable to capture dynamic, ecologically-valid use of emotion regulation strategies. METHODS: To address this issue, this study used an ecological momentary assessment (EMA) design to understand the impact of PTSD on emotion regulation in daily life. We conducted an EMA study in a trauma exposed sample with varying levels of PTSD severity (N = 70; 7 days; 423 observations). RESULTS: We found that PTSD severity was linked to greater use of disengagement and perseverative-based strategies to manage negative emotions, regardless of emotional intensity. LIMITATIONS: Study design did not allow investigation into the temporal use of emotion regulation strategies and small sample size. CONCLUSIONS: This pattern of responding to emotions may interfere with engaging with the fear structure and thus impair emotion processing in current frontline treatments; clinical implications are discussed.

Molecular Detection of the Harmful Raphidophyte Chattonella subsalsa Biecheler by Whole-Cell Fluorescence in-situ Hybridisation Assay.

Species of the genus Chattonella (Raphidophyceae) are a group of marine protists that are commonly found in coastal waters. Some are known as harmful microalgae that form noxious blooms and cause massive fish mortality in finfish aquaculture. In Malaysia, blooms of Chattonella have been recorded since the 1980s in the Johor Strait. In this study, two strains of Chattonella were established from the strait, and morphological examination revealed characteristics resembling Chattonella subsalsa. The molecular characterization further confirmed the species' identity as C. subsalsa. To precisely detect the cells of C. subsalsa in the environment, a whole-cell fluorescence in-situ hybridisation (FISH) assay was developed. The species-specific oligonucleotide probes were designed in silico based on the nucleotide sequences of the large subunit (LSU) and internal transcribed spacer 2 (ITS2) of the ribosomal DNA (rDNA). The best candidate signature regions in the LSU-rRNA and ITS2-rDNA were selected based on hybridisation efficiency and probe parameters. The probes were synthesised as biotinylated probes and tested by tyramide signal amplification with FISH (FISH-TSA). The results showed the specificity of the probes toward the target cells. FISH-TSA has been proven to be a potential tool in the detection of harmful algae in the environment and could be applied to the harmful algal monitoring program.

Spesies genus Chattonella (Raphidophyceae) ialah sekumpulan protista marin yang biasa ditemui di perairan laut pantai. Sesetengahnya dikenali sebagai mikroalga berbahaya yang membentuk ledakan alga berbahaya dan menyebabkan kematian ikan secara besar-besaran dalam akuakultur ikan sirip. Di Malaysia, ledakan alga Chattonella telah direkodkan sejak tahun 1980-an di Selat Johor. Dalam kajian ini, dua strain Chattonella telah didirikan dari selat, dan pemeriksaan morfologi mendedahkan ciri-ciri yang menyerupai Chattonella subsalsa. Pencirian molekul seterusnya mengesahkan identiti spesies sebagai C. subsalsa. Untuk mengesan dengan tepat sel-sel C. subsalsa di dalam persekitaran, ujian penghibridan in-situ berpendarfluor (FISH) ke atas sel keseluruhan telah dibangunkan. Prob oligonukleotida spesies telah direka secara spesifik secara siliko berdasarkan jujukan nukleotida subunit besar (LSU) dan spacer transkripsi dalaman 2 (ITS2) gen DNA ribosom (rDNA). Calon terbaik kawasan tanda dalam LSU-rRNA dan ITS2-rDNA telah dipilih berdasarkan kecekapan penghibridan dan parameter prob. Prob telah disintesis sebagai prob biotinilasi dan diuji dengan penguatan isyarat tyramide dengan FISH (FISH-TSA). Keputusan menunjukkan kekhususan prob ke atas sel sasaran. FISH-TSA telah terbukti sebagai alat yang berpotensi dalam pengesanan alga berbahaya di alam sekitar dan boleh digunakan untuk program pemantauan alga berbahaya.

The association of garlic intake and cardiovascular risk factors: A systematic review and meta-analysis.

Garlic is a common cooking ingredient and used in traditional medicine in Asian countries. There is a growing attention on garlic due to its preventive characteristics in cardiovascular diseases (CVDs). Many studies have reviewed the association between garlic intake and CVDs; however, no consistent conclusions have been drawn. New clinical trials have also been conducted and could contribute to more solid statements. In order to systematically review the reliability of previous studies regarding the implication of garlic in the management of CVDs, we performed in-depth meta-analysis using the most up-to-date randomized clinical trials (RCTs) data with more systematic controls. According to the 22 studies included, the effects of garlic intake on lowering total cholesterol (TC) and low-density lipoprotein (LDL) are more noticeable with lower dosage and longer duration, especially in patients with CVDs. In addition, subgroup analysis indicated that appropriate diet intervention could be an important control factor that should be taken into consideration in any future study designs.

Retinoblastoma seeds: impact on American Joint Committee on Cancer clinical staging.

AIM: To investigate whether the American Joint Committee on Cancer (AJCC) clinical category cT2b needs to be subclassified by the type and distribution of retinoblastoma (RB) seeding. METHODS: Multicentre, international registry-based data were collected from RB centres enrolled between January 2001 and December 2013. 1054 RB eyes with vitreous or subretinal seeds from 18 ophthalmic oncology centres, in 13 countries within six continents were analysed. Local treatment failure was defined as the use of secondary enucleation or external beam radiation therapy (EBRT) and was estimated with the Kaplan-Meier method. RESULTS: Clinical category cT2b included 1054 eyes. Median age at presentation was 16.0 months. Of these, 428 (40.6%) eyes were salvaged, and 430 (40.8%) were treated with primary and 196 (18.6%) with secondary enucleation. Of the 592 eyes that had complete data for globe salvage analysis, the distribution of seeds was focal in 143 (24.2%) and diffuse in 449 (75.8%). The 5-year Kaplan-Meier cumulative globe-salvage (without EBRT) was 78% and 49% for eyes with focal and diffuse RB seeding, respectively. Cox proportional hazards regression analysis confirmed a higher local treatment failure risk with diffuse seeds as compared with focal seeds (hazard rate: 2.8; p<0.001). There was insufficient evidence to prove or disprove an association between vitreous seed type and local treatment failure risk(p=0.06). CONCLUSION: This international, multicentre, registry-based analysis of RB eyes affirmed that eyes with diffuse intraocular distribution of RB seeds at diagnosis had a higher risk of local treatment failure when compared with focal seeds. Subclassification of AJCC RB category cT2b into focal vs diffuse seeds will improve prognostication for eye salvage.

Medical management of cerebral edema in large hemispheric infarcts.

Acute ischemic stroke confers a high burden of morbidity and mortality globally. Occlusion of large vessels of the anterior circulation, namely the intracranial carotid artery and middle cerebral artery, can result in large hemispheric stroke in ~8% of these patients. Edema from stroke can result in a cascade effect leading to local compression of capillary perfusion, increased stroke burden, elevated intracranial pressure, herniation and death. Mortality from large hemispheric stroke is generally high and surgical intervention may reduce mortality and improve good outcomes in select patients. For those patients who are not eligible candidates for surgical decompression either due timing, medical co-morbidities, or patient and family preferences, the mainstay of medical management for cerebral edema is hyperosmolar therapy. Other neuroprotectants for cerebral edema such as glibenclamide are under investigation. This review will discuss current guidelines and evidence for medical management of cerebral edema in large hemispheric stroke as well as discuss important neuromonitoring and critical care management targeted at reducing morbidity and mortality for these patients.

Cerebral venous sinus thrombosis with an acute subdural hematoma treated with endovascular intervention: A case report.

We report two cases of endovascular intervention for management of cerebral venous sinus thrombosis complicated by an acute intracranial hemorrhage during treatment with therapeutic anticoagulation. The first patient developed an acute subdural hematoma with progressive enlargement and was subsequently managed with venous sinus thrombectomy. The second patient developed an intraparenchymal and subdural hematoma and was treated with middle meningeal embolization. Anticoagulation is the primary treatment for cerebral venous sinus thrombosis but also contraindicated in an acute intracranial hemorrhage. In these cases, after endovascular intervention both patients resumed therapeutic anticoagulation without further hematoma expansion or additional invasive interventions. Both patients made an excellent neurological recovery and returned to their baseline functional independent status. Given the need for anticoagulation, endovascular intervention in the form of thrombectomy or middle meningeal artery embolization may be a viable adjuvant to anticoagulation in select patients.

Description of two new species Chattonella tenuiplastida sp. nov. and Chattonella malayana sp. nov. (Raphidophyceae) from South China Sea, with a report of wild fish mortality.

Fisheries damage caused by Chattonella red tide has been recorded in Southeast Asia. Molecular studies have clarified the presence of two species, Chattonella marina complex and Chattonella subsalsa in the region, unlike East Asia that had only C. marina complex. To elucidate the phylogeography of Chattonella in Asia, further phylogenetic and morphological examinations were carried out with 33 additional culture strains, including the strains isolated during a bloom of Chattonella sp. (up to 142 cells mL-1) that was associated with a wild fish mortality along the northeastern coast of Peninsular Malaysia in 2016, and those from Yellow Sea, where the Chattonella genotypes have not been determined. LSU rDNA and ITS2 trees showed five intrageneric clades in the genus Chattonella, which were clades I and II (C. subsalsa), clade III (C. marina complex) and two new clades, namely clade IV from Thailand and Malaysia, and clade V from Peninsular Malaysia. The positions of the two new clades were different in LSU rDNA and ITS2 trees. LSU rDNA divergences of clades IV and V from the other clades were ≥ 4.01% and ≥ 5.70%, while their ITS2 divergences were ≥ 7.44% and ≥ 16.43%, respectively. Three and five compensatory base changes (CBCs) were observed in the clades IV and V, respectively, when compared to each of their closest clade. Cells from clades IV and V showed similar morphology to C. marina complex and C. subsalsa clade II, including the presence of button-like granules on cell surface and oboe-shaped mucocysts. However, cell size, the number and shape of chloroplasts in Chattonella clades IV and V, and the non-stacked thylakoids penetrated the pyrenoid in C. subsalsa clade II, were distinctive. Based on the diagnostic chloroplast shape, we proposed the designation of clades IV and V to two new species, Chattonella tenuiplastida sp. nov. and Chattonella malayana sp. nov.

Investigating the associations between cognitive appraisals, emotion regulation and symptoms of posttraumatic stress disorder among Asian American and European American trauma survivors.

This study investigated whether the associations between emotion regulation and cognitive appraisals and symptoms of posttraumatic stress disorder (PTSD) differ between Asian American and European American trauma survivors. Asian American (n = 103) and European American (n = 104) trauma survivors were recruited through mTurk and completed an on-line questionnaire assessing cognitive appraisals, emotion regulation and PTSD symptomatology. The European American group reported greater trauma-specific rumination, psychological inflexibility, seeking out others for comfort, and negative self-appraisals than the Asian American group. The Asian American group reported greater secondary control appraisals and cultural beliefs about adversity than the European American group. Second, cultural group moderated the associations between (a) brooding rumination, (b) fatalism, (c) self-blame, and (d) negative communal self-appraisals and PTSD symptoms. These associations were larger for the European American group than the Asian American group. Third, there was an indirect pathway from self-construal (independent and interdependent) to PTSD symptoms through certain emotion regulation approaches and cognitive appraisals. Additionally, cultural group was found to moderate several of these indirect effects. These findings highlight the importance of considering cultural background and cultural values in understanding the processes involved in PTSD. Further research in this area is needed.

Metastatic Death Based on Presenting Features and Treatment for Advanced Intraocular Retinoblastoma: A Multicenter Registry-Based Study.

PURPOSE: To evaluate presenting features, tumor size, and treatment methods for risk of metastatic death due to advanced intraocular retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 1841 patients with advanced RB. METHODS: Advanced RB was defined by 8th edition American Joint Committee on Cancer (AJCC) categories cT2 and cT3 and new AJCC-Ophthalmic Oncology Task Force (OOTF) Size Groups (1: < 50% of globe volume, 2: > 50% but < 2/3, 3: > 2/3, and 4: diffuse infiltrating RB). Treatments were primary enucleation, systemic chemotherapy with secondary enucleation, and systemic chemotherapy with eye salvage. MAIN OUTCOME MEASURES: Metastatic death. RESULTS: The 5-year Kaplan-Meier cumulative survival estimates by patient-level AJCC clinical subcategories were 98% for cT2a, 96% for cT2b, 88% for cT3a, 95% for cT3b, 92% for cT3c, 84% for cT3d, and 75% for cT3e RB. Survival estimates by treatment modality were 96% for primary enucleation, 89% for systemic chemotherapy and secondary enucleation, and 90% for systemic chemotherapy with eye salvage. Risk of metastatic mortality increased with increasing cT subcategory (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastatic mortality in categories cT3c (glaucoma, hazard ratio [HR], 4.9; P = 0.011), cT3d (intraocular hemorrhage, HR, 14.0; P < 0.001), and cT3e (orbital cellulitis, HR, 19.6; P < 0.001) than in category cT2a and with systemic chemotherapy with secondary enucleation (HR, 3.3; P < 0.001) and eye salvage (HR, 4.9; P < 0.001) than with primary enucleation. The 5-year Kaplan-Meier cumulative survival estimates by AJCC-OOTF Size Groups 1 to 4 were 99%, 96%, 94%, and 83%, respectively. Mortality from metastatic RB increased with increasing Size Group (P < 0.001). Cox proportional hazards regression analysis revealed that patients with Size Group 3 (HR, 10.0; P = 0.002) and 4 (HR, 41.1; P < 0.001) had a greater risk of metastatic mortality than Size Group 1. CONCLUSIONS: The AJCC-RB cT2 and cT3 subcategories and size-based AJCC-OOTF Groups 3 (> 2/3 globe volume) and 4 (diffuse infiltrating RB) provided a robust stratification of clinical risk for metastatic death in advanced intraocular RB. Primary enucleation offered the highest survival rates for patients with advanced intraocular RB.

COVID-19 heterogeneity in islands chain environment.

BACKGROUND: It is critical to capture data and modeling from the COVID-19 pandemic to understand as much as possible and prepare for future epidemics and possible pandemics. The Hawaiian Islands provide a unique opportunity to study heterogeneity and demographics in a controlled environment due to the geographically closed borders and mostly uniform pandemic-induced governmental controls and restrictions. OBJECTIVE: The goal of the paper is to quantify the differences and similarities in the spread of COVID-19 among different Hawaiian islands as well as several other archipelago and islands, which could potentially help us better understand the effect of differences in social behavior and various mitigation measures. The approach should be robust with respect to the unavoidable differences in time, as the arrival of the virus and promptness of mitigation measures may vary significantly among the chosen locations. At the same time, the comparison should be able to capture differences in the overall pandemic experience. METHODS: We examine available data on the daily cases, positivity rates, mobility, and employ a compartmentalized model fitted to the daily cases to develop appropriate comparison approaches. In particular, we focus on merge trees for the daily cases, normalized positivity rates, and baseline transmission rates of the models. RESULTS: We observe noticeable differences among different Hawaiian counties and interesting similarities between some Hawaiian counties and other geographic locations. The results suggest that mitigation measures should be more localized, that is, targeting the county level rather than the state level if the counties are reasonably insulated from one another. We also notice that the spread of the disease is very sensitive to unexpected events and certain changes in mitigation measures. CONCLUSIONS: Despite being a part of the same archipelago and having similar protocols for mitigation measures, different Hawaiian counties exhibit quantifiably different dynamics of the spread of the disease. One potential explanation is that not sufficiently targeted mitigation measures are incapable of handling unexpected, localized outbreak events. At a larger-scale view of the general spread of the disease on the Hawaiian island counties, we find very interesting similarities between individual Hawaiian islands and other archipelago and islands.

High-risk Pathologic Features Based on Presenting Findings in Advanced Intraocular Retinoblastoma: A Multicenter, International Data-Sharing American Joint Committee on Cancer Study.

PURPOSE: To determine the value of clinical features for advanced intraocular retinoblastoma as defined by the eighth edition of the American Joint Committee on Cancer (AJCC) cT3 category and AJCC Ophthalmic Oncology Task Force (OOTF) Size Groups to predict the high-risk pathologic features. DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: Eighteen ophthalmic oncology centers from 13 countries over 6 continents shared evaluations of 942 eyes enucleated as primary treatment for AJCC cT3 and, for comparison, cT2 retinoblastoma. METHODS: International, multicenter, registry-based data were pooled from patients enrolled between 2001 and 2013. High-risk pathologic features were defined as AJCC categories pT3 and pT4. In addition, AJCC OOTF Size Groups were defined as follows: (1) less than half, (2) more than half but less than two thirds, (3) more than two thirds of globe volume involved, and (4) diffuse infiltrating retinoblastoma. MAIN OUTCOME MEASURES: Statistical risk of high-risk pathologic features corresponding to AJCC cT3 subcategories and AJCC OOTF Size Groups. RESULTS: Of 942 retinoblastoma eyes treated by primary enucleation, 282 (30%) showed high-risk pathologic features. Both cT subcategories and AJCC OOTF Size Groups (P < 0.001 for both) were associated with high-risk pathologic features. On logistic regression analysis, cT3c (iris neovascularization with glaucoma), cT3d (intraocular hemorrhage), and cT3e (aseptic orbital cellulitis) were predictive factors for high-risk pathologic features when compared with cT2a with an odds ratio of 2.3 (P = 0.002), 2.5 (P = 0.002), and 3.3 (P = 0.019), respectively. Size Group 3 (more than two-thirds globe volume) and 4 (diffuse infiltrative retinoblastoma) were the best predictive factors with an odds ratio of 3.3 and 4.1 (P < 0.001 for both), respectively, for high-risk pathologic features when compared with Size Groups 1 (i.e., < 50% of globe volume). CONCLUSIONS: The AJCC retinoblastoma staging clinical cT3c-e subcategories (glaucoma, intraocular hemorrhage, and aseptic orbital cellulitis, respectively) as well as the AJCC OOTF Size Groups 3 (tumor more than two thirds of globe volume) and 4 (diffuse infiltrative retinoblastoma) both allowed stratification of clinical risk factors that can be used to predict the presence of high-risk pathologic features and thus facilitate treatment decisions.

Difficulties Detecting Clinically Relevant Factor Xa Inhibitor Levels Prior to Reversal With Andexanet Alfa for Intracranial Hemorrhage.

Coagulation factor Xa (recombinant), inactivated-zhzo (andexanet alfa) is approved for reversal of life-threatening bleeding with rivaroxaban and apixaban use. Clinical decision-making to initiate reversal is reliant on dose taken and timing of last dose. In practice, timing of last dose may be unknown, and the turnaround time for drug-specific anti-factor Xa levels at some institutions may be prolonged, leaving clinicians balancing a difficult decision with limited tools. This report includes a series of 3 patients who presented to our institution with an intracranial hemorrhage and received andexanet alfa for apixaban reversal. These cases highlight the challenges clinicians are facing when using andexanet alfa for emergent rivaroxaban or apixaban reversal when the timing of last dose is unknown, or patients fall outside of the recommended timeframe for use and clinically relevant drug levels are still suspected. Based on our experiences, we encourage other institutions to evaluate their abilities to rapidly and accurately detect the presence of clinically relevant rivaroxaban and apixaban levels when utilizing andexanet alfa.

Examining Cultural Differences in the Associations between Appraisals and Emotion Regulation and PostTraumatic Stress Disorder in Malaysian and Australian Trauma Survivors.

Appraisals and emotional regulation play a central role in posttraumatic stress disorder (PTSD). Despite research demonstrating cultural differences in everyday appraisals and emotion regulation, little research has investigated the influence of culture on these processes in PTSD. This study examined cultural differences in the associations between appraisals, emotion regulation and PTSD symptoms using trauma survivors from an individualistic Western culture (Australia) and a collectivistic Asian culture (Malaysia). Trauma survivors (N = 228; 107 Australian with European cultural heritage, 121 Malaysian with Malay, Indian or Chinese cultural heritage) completed an on-line survey assessing PTSD (PTSD Checklist for the DSM-5 with Life Events Checklist), appraisals (trauma-related, fatalism, cultural beliefs about adversity) and emotion regulation (suppression, reappraisal, interpersonal). The Malaysian group reported significantly greater fatalism, cultural beliefs about adversity, suppression and interpersonal emotion regulation than the Australian group. Greater trauma-specific appraisals, greater suppression, fewer cultural beliefs about adversity, and less use of social skills to enhance positivity were generally associated with greater PTSD symptom severity, with little evidence of cultural group moderating these associations. Interdependent self-construal mediated the relationships between cultural adversity beliefs, enhanced positivity, reappraisal, perspective taking and PTSD symptoms. Independent self-construal mediated the relationships between fatalism and perspective taking and PTSD symptoms. Cultural group did not moderate these indirect effects. Interdependent self-construal mediated the associations between interpersonal regulation strategies of soothing and social modelling with PTSD symptoms for the Malaysian but not the Australian group. These findings demonstrate the importance of considering self-construal and culture in understanding factors associated with PTSD.

The SOLAR group program to promote recovery after disaster and trauma-A randomized controlled feasibility trial among German trauma survivors.

INTRODUCTION: Many disaster and trauma survivors experience persistent subclinical distress that places them at risk of developing a mental health disorder. This study describes the first European feasibility study of a brief and scalable skills-based intervention targeting persistent subclinical distress following disasters and trauma. METHOD: Randomized controlled feasibility study of the Skills fOr Life Adjustment and Resilience (SOLAR) group program. German trauma survivors (N = 30) with subclinical symptoms of depression, anxiety, or posttraumatic stress disorder or functional impairment, but no current mental disorder other than adjustment disorder, were randomized to the SOLAR group program (n = 15) or to a wait-list control group (n = 15). The primary outcome was feasibility, operationalized through eligibility rate, recruitment speed, treatment adherence, dropout rate, and participant satisfaction with the program. Secondary outcomes were psychological distress, symptoms of insomnia, posttraumatic stress disorder, patient-centered outcomes, quality of life, and perceived social support. RESULTS: Eligibility rate was 33.6%; recruitment speed was two days per participant; 92.9% completed at least four of five sessions; dropout rate was 10.0%; 92.3% were "very satisfied" with the program. Between-group change scores showed a large effect size for patient-centered outcomes. Medium effect sizes were found for symptoms of insomnia, perceived social support, and quality of life. Small effects were identified for reductions in distress and functional impairment. DISCUSSION: The application of the SOLAR group program within a randomized controlled trial was feasible. Its efficacy should be further tested in a larger trial. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cell-by-cell dissection of phloem development links a maturation gradient to cell specialization.

In the plant meristem, tissue-wide maturation gradients are coordinated with specialized cell networks to establish various developmental phases required for indeterminate growth. Here, we used single-cell transcriptomics to reconstruct the protophloem developmental trajectory from the birth of cell progenitors to terminal differentiation in the Arabidopsis thaliana root. PHLOEM EARLY DNA-BINDING-WITH-ONE-FINGER (PEAR) transcription factors mediate lineage bifurcation by activating guanosine triphosphatase signaling and prime a transcriptional differentiation program. This program is initially repressed by a meristem-wide gradient of PLETHORA transcription factors. Only the dissipation of PLETHORA gradient permits activation of the differentiation program that involves mutual inhibition of early versus late meristem regulators. Thus, for phloem development, broad maturation gradients interface with cell-type-specific transcriptional regulators to stage cellular differentiation.