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Background Partially hydrolyzed cow’s milk protein (PHP) formulas are nutritionally complete and have a high-quality protein composition, and extensive history of safe use. The current study evaluated growth and safety in healthy term infants receiving a new PHP formula with an added prebiotic blend. Methods In this multi-center, double-blind, controlled, parallel, prospective study, healthy term infants were randomized to receive one of two formulas through 365 days of age: previously marketed intact cow’s milk protein formula (Control, n  = 122) or investigational PHP formula (INV-PHP, n  = 122). Both formulas had an added prebiotic blend of polydextrose (PDX) and galactooligosaccharides (GOS) (1:1, 4 g/L). The primary outcome was rate of weight gain (g/day) from 14 to 120 days of age. To establish equivalence between study formulas, the 90% two-sided confidence interval (CI) of the mean group difference in body weight growth rate from 14 to 120 days of age needed to be contained within a predefined equivalence interval (± 3 g/day). Growth rates through Day 120 and achieved anthropometrics through Day 365 were analyzed by ANOVA. Parent-reported tolerance outcomes were also collected. Medically confirmed adverse events were collected throughout the study period. Results Of 244 infants enrolled and randomized (Control, n  = 122; INV-PHP, n  = 122); 175 completed study feeding through Day 120 (Control, n  = 91; INV-PHP, n  = 84). Equivalence in rate of weight gain from 14 to 120 days of age was demonstrated with the difference in means of 0.5 g/day and 90% CI [− 1.10, 2.08 g/day] within the predefined equivalence interval (± 3 g/day). Mean achieved weight remained between 25th -75th reference percentiles of the WHO growth standard through Day 180 by sex and subsequently tracked between 50th -90th percentiles through Day 365. Formula acceptance and tolerance were good. Stool consistency remained soft in both groups throughout the study. No significant group differences in mean fussiness and gassiness scores, or medically confirmed adverse events were detected. A total of 159 participants completed the Day 365 visit (Control, n  = 82; INV-PHP, n  = 77). Conclusions Overall, partially hydrolyzed cow’s milk protein infant formula with an added prebiotic was safe, well-tolerated, and associated with adequate growth for healthy term infants receiving formula through one year of age. Trial registration ClinicalTrials.gov, ClinicalTrials.gov Identifier NCT05047978. Registered 28 August 2021, https://clinicaltrials.gov/study/NCT05047978.

Using a scoping review technique, we provide a comprehensive overview of empathy definitions by highlighting the multidimensional nature of empathy. Drawing from multiple lines of research on empathy, we underscore the role of culture in researching empathy and highlight the strengths and weaknesses of existing research on empathy and culture. In general, this review article supports the importance of theorizing empathy and culture as multidimensional concepts. The review article also further identifies an urgent need for reaching a consensus for defining empathy and using that definition in future research on empathy, regardless of the discipline or field (i.e., psychology, education, social science, health, management, etc.). We conclude that empathy is a multidimensional construct that is not only possessed but is also acquired and needs to be studied based on surrounding factors such as individual (e.g., empathizer’s profile and empathizee’s profile, similar experiences) and societal factors (e.g., cultural norms, group standards).

Background Since 2014, the Government of Bihar and CARE India have implemented a nurse mentoring program that utilizes PRONTO International’s simulation and team trainings to improve obstetric and neonatal care. Together they trained simulation educators known as Nurse Mentor Supervisors to conduct simulation trainings in rural health facilities across the state. Sustaining the knowledge and engagement of these simulation educators at a large-scale has proven difficult and resource intensive. To address this, the University of Utah with PRONTO International and with input from the University of California San Francisco, created an interactive, virtual education module based on a comic superhero named Super Divya to reinforce simulation educator concepts. This study examined the perceptions of Nurse Mentor Supervisors on Super Divya’s accessibility, usefulness, and potential after implementation of Super Divya: Origin Story. Methods We conducted qualitative interviews with 17 Nurse Mentor Supervisors in Bihar, India. In light of the COVID-19 pandemic, interviews were conducted virtually via Zoom™ using a semi-structured interview guide in Hindi and English. Participants were identified with strict inclusion criteria and convenience sampling methods. Interviews were analyzed using a framework analysis. Results Nurse Mentor Supervisors found Super Divya to be engaging, innovative, relatable, and useful in teaching tips and tricks for simulation training. Supervisors thought the platform was largely accessible with some concerns around internet connectivity and devices. The majority reacted positively to the idea of distributing Super Divya to other simulation educators in the nurse mentoring program and had suggestions for additional clinical and simulation educator training topics. Conclusions This study demonstrates the potential of Super Divya to engage simulation educators in continuous education. At a time when virtual education is increasingly important and in-person training was halted by the COVID-19 pandemic, Super Divya engaged Supervisors in the nurse mentoring program. We have incorporated suggestions for improvement of Super Divya into future modules. Further research can help understand how knowledge from Super Divya can improve simulation facilitation skills and behaviors, and explore potential for reinforcing clinical skills via this platform. Ethical approval This study was approved by the institutional review board at the University of California San Francisco (IRB # 20–29902).

Stings of certain ant species (Hymenoptera: Formicidae) can cause intense, long-lasting nociception. Here we show that the major contributors to these symptoms are venom peptides that modulate the activity of voltage-gated sodium (NaV) channels, reducing their voltage threshold for activation and inhibiting channel inactivation. These peptide toxins are likely vertebrate-selective, consistent with a primarily defensive function. They emerged early in the Formicidae lineage and may have been a pivotal factor in the expansion of ants.

Richter’s Transformation (RT) is a poorly understood and fatal progression of chronic lymphocytic leukemia (CLL) manifesting histologically as diffuse large B-cell lymphoma. Protein arginine methyltransferase 5 (PRMT5) is implicated in lymphomagenesis, but its role in CLL or RT progression is unknown. We demonstrate herein that tumors uniformly overexpress PRMT5 in patients with progression to RT. Furthermore, mice with B-specific overexpression of hPRMT5 develop a B-lymphoid expansion with increased risk of death, and Eµ-PRMT5/TCL1 double transgenic mice develop a highly aggressive disease with transformation that histologically resembles RT; where large-scale transcriptional profiling identifies oncogenic pathways mediating PRMT5-driven disease progression. Lastly, we report the development of a SAM-competitive PRMT5 inhibitor, PRT382, with exclusive selectivity and optimal in vitro and in vivo activity compared to available PRMT5 inhibitors. Taken together, the discovery that PRMT5 drives oncogenic pathways promoting RT provides a compelling rationale for clinical investigation of PRMT5 inhibitors such as PRT382 in aggressive CLL/RT cases. Richter’s Transformation is a treatment-resistant and fatal progression from Chronic Lymphocytic Leukemia (CLL) to an aggressive lymphoma. Here, the authors show that PRMT5 is upregulated months prior to and after transformation, PRMT5 overexpression in a CLL mouse model leads to increased risk of transformation, and that targeted PRMT5 inhibition prolongs survival and delays disease development.

Previous studies have demonstrated a link between prior experience of physical pain and empathic response within similar settings. However, much less is known about emotional hurt derived from psychologically painful situations and the expression of empathy, despite evidence that different types of pain can be experienced in similar ways. Using qualitative and quantitative methodologies, the current paper explored the relationship between college students’ (mostly female) experience with psychological pain and level of empathy evoked by pictures of strangers experiencing physical and psychological pain. Findings from all three studies indicated similar empathic reactions (in the form of pain perception, empathic concern, perspective taking, and intention to help) toward physical and psychological pain. However, participants’ feelings after observing physical and psychological pain were related to their prior similar painful experiences. This suggests that similar prior psychological painful experience can impact affective empathy when observing another in psychological pain, but not cognitive empathy. Implication for research on empathy evoked by observing psychological pain and the influence of similar past painful experiences are discussed.

Mutations and deletions in TP53 are associated with adverse outcomes in patients with myeloid malignancies, and there is an urgent need for the development of improved therapies for TP53-mutant leukemias. Here, we identified mutations in TET2 as the most common co-occurring mutation in patients with TP53-mutant acute myeloid leukemia (AML). In mice, combined hematopoietic-specific deletion of TET2 and TP53 resulted in enhanced self-renewal compared with deletion of either gene alone. Tp53/Tet? double-KO mice developed serially transplantable AML. Both mice and patients with AML with combined TET2/TP53 alterations upregulated innate immune signaling in malignant granulocyte-monocyte progenitors, which had leukemia-initiating capacity. A20 governs the leukemic maintenance by triggering aberrant noncanonical МЕ-кВ signaling. Mice with Tp53/Tet2 loss had expansion of monocytic myeloid-derived suppressor cells (MDSCs), which impaired T cell proliferation and activation. Moreover, mice and patients with AML with combined TP53/TET2 alterations displayed increased expression of the TIGIT ligand, CD155, on malignant cells. TIGIT-blocking antibodies augmented NK cell-mediated killing of Tp53/Tet2 double-mutant AML cells, reduced leukemic burden, and prolonged survival in Tp53/Tet2 double-KO mice. These findings describe a leukemia-promoting link between TET2 and TP53 mutations and highlight therapeutic strategies to overcome the immunosuppressive bone marrow environment in this adverse subtype of AML.

Mutations and deletions in TP53 are associated with adverse outcomes in patients with myeloid malignancies, and there is an urgent need for the development of improved therapies for TP53-mutant leukemias. Here, we identified mutations in TET2 as the most common co-occurring mutation in patients with TP53-mutant acute myeloid leukemia (AML). In mice, combined hematopoietic-specific deletion of TET2 and TP53 resulted in enhanced self-renewal compared with deletion of either gene alone. Tp53/Tet2 double-KO mice developed serially transplantable AML. Both mice and patients with AML with combined TET2/TP53 alterations upregulated innate immune signaling in malignant granulocyte-monocyte progenitors, which had leukemia-initiating capacity. A20 governs the leukemic maintenance by triggering aberrant noncanonical NF-κB signaling. Mice with Tp53/Tet2 loss had expansion of monocytic myeloid-derived suppressor cells (MDSCs), which impaired T cell proliferation and activation. Moreover, mice and patients with AML with combined TP53/TET2 alterations displayed increased expression of the TIGIT ligand, CD155, on malignant cells. TIGIT-blocking antibodies augmented NK cell-mediated killing of Tp53/Tet2 double-mutant AML cells, reduced leukemic burden, and prolonged survival in Tp53/Tet2 double-KO mice. These findings describe a leukemia-promoting link between TET2 and TP53 mutations and highlight therapeutic strategies to overcome the immunosuppressive bone marrow environment in this adverse subtype of AML.

The etiology and outcomes of blood-stream infections (BSI) among paediatric patients is not well described in resource-limited countries including Georgia. Patients with positive blood cultures at the largest paediatric hospital in the country of Georgia were identified by review of the medical and laboratory records of patients who had blood for cultures drawn between January 2004 and June 2006. Of 1,693 blood cultures obtained during the study period, 338 (20%) were positive; of these, 299 were included in our analysis. The median age was 14 days from a range of 2 days to 14 years of which 178 (60%) were male; 53% of the patients with a positive culture were admitted to the Neonatal Intensive Care Unit (NICU). Gram-negative bacilli (GNB) represented 165 (55%) of 299 cultures. Further speciation of 135 (82%) of 165 Gram-negative rod (GNR) was not possible because of lack of laboratory capacity. Overall, mortality was 30% (90 of 299). Among the 90 children who died, 80 (89%) were neonates and 68 (76%) had BSI caused by Gram-negative organisms. In multivariate analysis, independent risk factors for in-hospital mortality included an age of less than 30 days (OR=4.00, 95% CI 1.89-8.46) and having a positive blood culture for a Gram-negative BSI (OR = 2.38, 95% CI 1.32-4.29). A high mortality rate was seen among children, particularly neonates, with positive blood cultures at the largest paediatric hospital in Georgia. Because of limited laboratory capacity, microbiological identification of common organisms known to cause BSI in children was not possible and susceptibility testing was not performed. Improving the infrastructure of diagnostic microbiology laboratories in countries with limited resources is critical in order to improve patient care and clinical outcomes, and from a public health standpoint, to improve surveillance activities.

This landmark volume provides the most comprehensive overview to date of the prehistory and archaeology of the Caddo peoples. The Caddos lived in the Southeastern Woodlands for more than 900 years beginning around AD 800-900, before being forced to relocate to Oklahoma in 1859. They left behind a spectacular archaeological record, including the famous Spiro Mound site in Oklahoma as well as many other mound centers, plazas, farmsteads, villages, and cemeteries. The Archaeology of the Caddoexamines new advances in studying the history of the Caddo peoples, including ceramic analysis, reconstructions of settlement and regional histories of different Caddo communities, Geographic Information Systems and geophysical landscape studies at several spatial scales, the cosmological significance of mound and structure placements, and better ways to understand mortuary practices. Findings from major sites and drainages such as the Crenshaw site, mounds in the Arkansas River basin, Spiro Mound, the Oak Hill Village site, the George C. Davis site, the Willow Chute Bayou Locality, the Hughes site, Big Cypress Creek basin, and the McClelland and Joe Clark sites are also summarized and interpreted. This volume reintroduces the Caddos' heritage, creativity, and political and religious complexity.