Bystander intervention is associated with reduced early mortality among injury victims in Cameroon.

Despite high injury mortality rates, Cameroon currently lacks a formal prehospital care system. In other sub-Saharan African low and middle-income countries, Lay First Responder (LFR) programs have trained non-medical professionals with high work-related exposure to injury in principles of basic trauma care. To develop a context-appropriate LFR program in Cameroon, we used trauma registry data to understand current layperson bystander involvement in prehospital care and explore associations between current non-formally trained bystander-provided prehospital care and clinical outcomes. The Cameroon Trauma Registry (CTR) is a longitudinal, prospective, multisite trauma registry cohort capturing data on injured patients presenting to four hospitals in Cameroon. We assessed prevalence and patterns of prehospital scene care among all patients enrolled the CTR in 2020. Associations between scene care, clinical status at presentation, and outcomes were tested using univariate and multivariate logistic regression. Injury severity was measured using the abbreviated injury score. Data were analyzed using Stata17. Of 2212 injured patients, 455 (21%) received prehospital care (PC) and 1699 (77%) did not receive care (NPC). Over 90% (424) of prehospital care was provided by persons without formal medical training. PC patients were more severely injured (p<0.001), had markers of increased socioeconomic status (p = 0.01), and longer transport distances (p<0.001) compared to NPC patients. Despite increased severity of injury, patients who received PC were more likely to present with a palpable pulse (OR = 6.2, p = 0.02). Multivariate logistic regression adjusted for injury severity, socioeconomic status and travel distance found PC to be associated with reduced emergency department mortality (OR = 0.14, p<0.0001). Although prehospital injury care in Cameroon is rarely performed and is provided almost entirely by persons without formal medical training, prehospital intervention is associated with increased early survival after injury. Implementation of LFR training to strengthen the frequency and quality of prehospital care has considerable potential to improve trauma survival.

Don't judge a book by its cover: Exploring low self-reported distress and repressive coping in a pediatric chronic pain population.

Repression has been linked to greater illness, somatic symptoms, and poorer physical health, both in adult and pediatric populations. The current study examined psychological and pain profiles of children with chronic pain who may under-report levels of psychological distress at a first interdisciplinary chronic pain assessment. Children and their caregiver completed measures of psychopathology and pain intensity, while clinicians rated their levels of disability. Based on self-report measures, children were classified as "repressors" (low anxiety/high social desirability) or as "true low anxious" (low anxiety/low social desirability). Groups were then compared on psychological and pain characteristics. Compared to children with true low anxiety, repressors reported lower levels of depressive and somatic symptoms but provided higher ratings on pain intensity, pain-unpleasantness, and self-oriented perfectionism. Caregivers of repressors rated their children as having higher levels of adaptability compared to caregivers of children in the true low anxious group. Groups did not differ on clinician-rated level of disability. Children classified as repressors exhibited different profiles than children classified as having true low anxiety on both psychological outcomes and pain characteristics. Repression may be an important factor to consider for those assessing and treating children with chronic pain.

Integrin α6ß4 signals through DNA damage response pathway to sensitize breast cancer cells to cisplatin.

Integrin α6ß4 is highly expressed in triple negative breast cancer (TNBC) and drives its most aggressive traits; however, its impact on chemotherapeutic efficacy remains untested. We found that integrin α6ß4 signaling promoted sensitivity to cisplatin and carboplatin but not to other chemotherapies tested. Mechanistic investigations revealed that integrin α6ß4 stimulated the activation of ATM, p53, and 53BP1, which required the integrin ß4 signaling domain. Genetic manipulation of gene expression demonstrated that mutant p53 cooperated with integrin α6ß4 for cisplatin sensitivity and was necessary for downstream phosphorylation of 53BP1 and enhanced ATM activation. Additionally, we found that in response to cisplatin-induced DNA double strand break (DSB), integrin α6ß4 suppressed the homologous recombination (HR) activity and enhanced non-homologous end joining (NHEJ) repair activity. Finally, we discovered that integrin α6ß4 preferentially activated DNA-PK, facilitated DNA-PK-p53 and p53-53BP1 complex formation in response to cisplatin and required DNA-PK to enhance ATM, 53BP1 and p53 activation as well as cisplatin sensitivity. In summary, we discovered a novel function of integrin α6ß4 in promoting cisplatin sensitivity in TNBC through DNA damage response pathway.

A randomized controlled trial evaluating the effect of an internet-based cognitive-behavioral program on anxiety symptoms in a community-based sample of adolescents.

Adolescents' use of online resources to self-manage anxiety is growing. The objective of the current trial was to assess the effectiveness of an online, primarily self-led cognitive behavioral therapy (CBT) program in reducing anxiety symptoms compared to an active comparator, access to anxiety resources on a static website. A total of 563 adolescents (13-19 years) with self-identified anxiety concerns were enrolled. Self-reported anxiety symptoms were assessed pre- and post-intervention (6 weeks). Adolescents were further assessed 3 months post-intervention. Other outcomes assessed at the three time-points were quality of life (QOL) and healthcare utilization. Both interventions reduced anxiety symptoms after use. Group differences in symptom change were not significant post-intervention (p = 0.16), but were at 3 months (favouring online CBT; p = 0.04) with male participants reporting more symptom change (p = 0.03). Across time-points, as anxiety symptoms decreased, QOL increased (p < 0.001). Among participants that provided healthcare utilization before and after intervention use, the greatest changes in use were among online CBT users particularly for mental health provider visits (psychiatrist, -41.0 % vs. +18.5 %; social worker, -42.5 % vs. -22.1 %), hospital-based care (emergency department visits, -80.0 % vs. +79.4 %; hospital admissions, -76.1 % vs. +42.9 %), and use of self-help or alternative treatments (-60.0 % vs. +6.6 %). Results suggest that, over time, use of online CBT by adolescents can result in improved anxiety symptoms and fewer use of other healthcare resources compared to traditional online information seeking.

Implementing a mHealth-Based Patient and Nurse Educational Program to Reduce Wound Infection in Rural Philippines.

Background: Surgical site infection (SSI) is a prevalent but preventable complication in low-and-middle income countries (LMIC), with reported incidence varying from 8-30%. In 2018, the MEDIPINAS surgical mission to the Philippines observed a 28.8% rate of SSI despite adherence to WHO intraoperative protocols.The objective of this study was to introduce an educational program for wound care and early identification of wound infection. This program included provision of wound care materials and systematic protocol to ensure adequate and effective follow-up. Barriers to SSI prophylaxis in the Philippines include limited resources in regional hospitals and isolation of patients living in rural areas. The MEDIPINAS mission utilized mobile health software to connect with regional providers and to reinforce the wound care educational program introduced at discharge. Methods: The 2019 MEDIPINAS mission returned to the Philippines and operated on 187 patients in San Antonio de Padua Diocesan Hospital and Santa Maria Josefa Hospital. Before discharge, patients were individually consulted about maintaining the cleanliness of their surgical wound. Each patient was discharged with a wound care infographic and a kit to change dressings. In collaboration with regional care providers, we utilized a secure mobile health software to monitor wound healing 7 and 30 days following the operation. Results: Between the 2018 and 2019 surgical missions, we observed a decrease in SSI from 28.8% to 9.7%. Fourteen patients (7.5%) were lost to follow-up. Postoperative infection was diagnosed using photos provided by hospital-based nurses. Individuals with infections were treated with antibiotics and all but two SSI resolved after 30 days. Conclusions: Patient education, discharge with basic sanitary resources, and development of a mobile health-based follow-up infrastructure may contribute to significant reductions in SSI in LMICs. A limitation to implementation of such a program was integration of the mobile health software into the practice of local healthcare providers.

Dietary fiber-based regulation of bile salt hydrolase activity in the gut microbiota and its relevance to human disease.

Complications of short bowel syndrome (SBS) include malabsorption and bacterial overgrowth, requiring prolonged dependence on parenteral nutrition (PN). We hypothesized that the intolerance of whole food in some SBS patients might be due to the effect of dietary fiber on the gut microbiome. Shotgun metagenomic sequencing and targeted metabolomics were performed using biospecimens collected from 55 children with SBS and a murine dietary fiber model. Bioinformatic analyses were performed on these datasets as well as from a healthy human dietary intervention study. Compared to healthy controls, the gut microbiota in SBS had lower diversity and increased Proteobacteria, a pattern most pronounced in children on PN and inversely correlated with whole food consumption. Whole food intake correlated with increased glycoside hydrolases (GH) and bile salt hydrolases (BSH) with reduced fecal conjugated bile acids suggesting that dietary fiber regulates BSH activity via GHs. Mechanistic evidence supporting this notion was generated via fecal and plasma bile acid profiling in a healthy human fiber-free dietary intervention study as well as in a dietary fiber mouse experiment. Gaussian mixture modeling of fecal bile acids was used to identify three clinically relevant SBS phenotypes. Dietary fiber is associated with bile acid deconjugation likely via an interaction between gut microbiota BSHs and GHs in the small intestine, which may lead to whole food intolerance in patients with SBS. This mechanism not only has potential utility in clinical phenotyping and targeted therapeutics in SBS based on bile acid metabolism but may have relevance to other intestinal disease states.

Frequency of quorum-sensing mutations in Pseudomonas aeruginosa strains isolated from different environments.

Pseudomonas aeruginosa uses quorum sensing (QS) to coordinate the expression of multiple genes necessary for establishing and maintaining infection. It has previously been shown that lasR QS mutations frequently arise in cystic fibrosis (CF) lung infections, however, there has been far less emphasis on determining whether other QS system mutations arise during infection or in other environments. To test this, we utilized 852 publicly available sequenced P. aeruginosa genomes from the Pseudomonas International Consortium Database (IPCD) to study P. aeruginosa QS mutational signatures. To study isolates by source, we focused on a subset of 654 isolates collected from CF, wounds, and non-infection environmental isolates, where we could clearly identify their source. We also worked with a small collection of isolates in vitro to determine the impact of lasR and pqs mutations on isolate phenotypes. We found that lasR mutations are common across all environments and are not specific to infection nor a particular infection type. We also found that the pqs system proteins PqsA, PqsH, PqsL and MexT, a protein of increasing importance to the QS field, are highly variable. Conversely, RsaL, a negative transcriptional regulator of the las system, was found to be highly conserved, suggesting selective pressure to repress las system activity. Overall, our findings suggest that QS mutations in P. aeruginosa are common and not limited to the las system; however, LasR is unique in the frequency of putative loss-of-function mutations.

Integrin α6ß4 requires plectin and vimentin for adhesion complex distribution and invasive growth.

Integrin α6ß4 binds plectin to associate with vimentin; however, the biological function remains unclear. Here, we utilized various integrin ß4 mutants and CRISPR-Cas9 editing to investigate this association. Upon laminin binding, integrin α6ß4 distinctly distributed peripherally as well as centrally, proximal to the nucleus. Upon fibronectin addition, integrin α6ß4 was centrally recruited to large focal adhesions (FAs) and enhanced Fak (also known as PTK2) phosphorylation. Integrin ß4 plectin-binding mutants or genetic deletion of plectin inhibited ß4 recruitment to FAs and integrin α6ß4-enhanced cell spreading, migration and three-dimensional invasive growth. Loss of the ß4 signaling domain (but retaining plectin binding) blocked migration and invasiveness but not cell spreading, recruitment to FAs or colony growth. Immunostaining revealed that integrin α6ß4 redistributed vimentin perinuclearly, where it colocalized with plectin and FAs. Depletion of vimentin completely blocked integrin ß4-enhanced invasive growth, Fak phosphorylation and proliferation in three dimensions but not two dimensions. In summary, we demonstrate the essential roles of plectin and vimentin in promoting an invasive phenotype downstream of integrin α6ß4. This article has an associated First Person interview with the first author of the paper.

The Influence of Weight Bias on Processes and Outcomes in Negotiation.

In two studies, using a mix of samples, we examined the influence of weight bias on behaviors in competitive, potentially high stakes situations. As predicted, weight bias directed focal actors' treatment of counterparts in a negotiation. Negotiators made lower value offers to overweight counterparts relative to average-weight counterparts. In addition, overweight counterparts also received more negative messages over the course of their negotiation and were evaluated less favorably after the negotiation than average-weight counterparts.