Outcomes Following Blunt Traumatic Splenic Injury Treated with Conservative or Operative Management

Introduction Laparotomy, embolization, and observation are described for blunt splenic injury management. This study evaluated outcomes of blunt splenic injury management based on baseline factors, splenic injury severity, and associated injuries. Methods A nine-year retrospective review was conducted of adult patients with blunt splenic injury. Collected data included demographics, injury characteristics, treatment modality, complications, and outcomes (mechanical ventilation, days on mechanical ventilation, intensive care unit [ICU] admission and length of stay, hospital length of stay, and in-hospital mortality). Categorical and continuous variables were analyzed using χ2 analysis and one-way analysis of variance for normally distributed variables and a non-parametric test of medians for variables that did not meet the assumption of normality, respectively. Results Splenic injury grade was similar between operative and embolization groups, but severe hemoperitoneum was more common in the operative group. Complications and mortality were highest in the operative group (50.7% and 26.3%, respectively) and lowest in the embolization group (5.3% and 2.6%, respectively). Operative patients required more advanced interventions (ICU admission, mechanical ventilation). There were no differences between those treated with proximal versus distal embolization. Observation carried a failure rate of 11.2%, with no failures of embolization. Conclusions Embolization patients had the lowest rates of complications and mortality, with comparable splenic injury grades to those treated operatively. Further prospective research is warranted to identify patients that may benefit from early embolization and avoidance of major abdominal surgery

SLC19A1 transports immunoreactive cyclic dinucleotides.

The accumulation of DNA in the cytosol serves as a key immunostimulatory signal associated with infections, cancer and genomic damage1,2. Cytosolic DNA triggers immune responses by activating the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway3. The binding of DNA to cGAS activates its enzymatic activity, leading to the synthesis of a second messenger, cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP)4-7. This cyclic dinucleotide (CDN) activates STING8, which in turn activates the transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), promoting the transcription of genes encoding type I interferons and other cytokines and mediators that stimulate a broader immune response. Exogenous 2'3'-cGAMP produced by malignant cells9 and other CDNs, including those produced by bacteria10-12 and synthetic CDNs used in cancer immunotherapy13,14, must traverse the cell membrane to activate STING in target cells. How these charged CDNs pass through the lipid bilayer is unknown. Here we used a genome-wide CRISPR-interference screen to identify the reduced folate carrier SLC19A1, a folate-organic phosphate antiporter, as the major transporter of CDNs. Depleting SLC19A1 in human cells inhibits CDN uptake and functional responses, and overexpressing SLC19A1 increases both uptake and functional responses. In human cell lines and primary cells ex vivo, CDN uptake is inhibited by folates as well as two medications approved for treatment of inflammatory diseases, sulfasalazine and the antifolate methotrexate. The identification of SLC19A1 as the major transporter of CDNs into cells has implications for the immunotherapeutic treatment of cancer13, host responsiveness to CDN-producing pathogenic microorganisms11 and-potentially-for some inflammatory diseases

UNLV Libraries’ Peer Mentor Cohort: A Model for Successful Allyship and Support amongst Womxn Faculty

In 2020, 10 womxn from a variety of racial, ethnic, and professional backgrounds formed an unique support network for faculty librarians hired between June 2019-July 2020 at the University of Nevada, Las Vegas (UNLV) Libraries (Fig 1 & 2 & Table 1). The group benefits from diverse voices and unique perspectives. We consist of early and mid-career academic librarian, newly relocated staff, womxn of color, and members of the LGBTQ+ community (Fig 2 & Table 1). Our group holds expertise across health sciences, sciences, social sciences, acquisitions, cataloging, data services, special collections, and scholarly communications. We span 7 departments and 4 divisions, adding a holistic view of organizational culture and structure as well as the tenure process. Our aim is to support each other through the tenure-track process and promote retention among group members

DNA mechanics as a tool to probe helicase and translocase activity

Helicases and translocases are proteins that use the energy derived from ATP hydrolysis to move along or pump nucleic acid substrates. Single molecule manipulation has proved to be a powerful tool to investigate the mechanochemistry of these motors. Here we first describe the basic mechanical properties of DNA unraveled by single molecule manipulation techniques. Then we demonstrate how the knowledge of these properties has been used to design single molecule assays to address the enzymatic mechanisms of different translocases. We report on four single molecule manipulation systems addressing the mechanism of different helicases using specifically designed DNA substrates: UvrD enzyme activity detection on a stretched nicked DNA molecule, HCV NS3 helicase unwinding of a RNA hairpin under tension, the observation of RecBCD helicase/nuclease forward and backward motion, and T7 gp4 helicase mediated opening of a synthetic DNA replication fork. We then discuss experiments on two dsDNA translocases: the RuvAB motor studied on its natural substrate, the Holliday junction, and the chromosome-segregation motor FtsK, showing its unusual coupling to DNA supercoiling

A Novel Multi-Antigen Virally Vectored Vaccine against Mycobacterium avium Subspecies paratuberculosis

BACKGROUND: Mycobacterium avium subspecies paratuberculosis causes systemic infection and chronic intestinal inflammation in many species including primates. Humans are exposed through milk and from sources of environmental contamination. Hitherto, the only vaccines available against Mycobacterium avium subspecies paratuberculosis have been limited to veterinary use and comprised attenuated or killed organisms. METHODS: We developed a vaccine comprising a fusion construct designated HAV, containing components of two secreted and two cell surface Mycobacterium avium subspecies paratuberculosis proteins. HAV was transformed into DNA, human Adenovirus 5 (Ad5) and Modified Vaccinia Ankara (MVA) delivery vectors. Full length expression of the predicted 95 kDa fusion protein was confirmed. PRINCIPAL FINDINGS: Vaccination of naïve and Mycobacterium avium subspecies paratuberculosis infected C57BL/6 mice using DNA-prime/MVA-boost or Ad5-prime/MVA-boost protocols was highly immunogenic resulting in significant IFN-gamma ELISPOT responses by splenocytes against recombinant vaccine antigens and a range of HAV specific peptides. This included strong recognition of a T-cell epitope GFAEINPIA located near the C-terminus of the fusion protein. Antibody responses to recombinant vaccine antigens and HAV specific peptides but not GFAEINPIA, also occurred. No immune recognition of vaccine antigens occurred in any sham vaccinated Mycobacterium avium subspecies paratuberculosis infected mice. Vaccination using either protocol significantly attenuated pre-existing Mycobacterium avium subspecies paratuberculosis infection measured by qPCR in spleen and liver and the Ad5-prime/MVA-boost protocol also conferred some protection against subsequent challenge. No adverse effects of vaccination occurred in any of the mice. CONCLUSIONS/SIGNIFICANCE: A range of modern veterinary and clinical vaccines for the treatment and prevention of disease caused by Mycobacterium avium subspecies paratuberculosis are needed. The present vaccine proved to be highly immunogenic without adverse effect in mice and both attenuated pre-existing Mycobacterium avium subspecies paratuberculosis infection and conferred protection against subsequent challenge. Further studies of the present vaccine in naturally infected animals and humans are indicated

Effects of N-Acetylcysteine on fatigue, critical power, and muscle energy stores

Master of ScienceDepartment of KinesiologyThomas J. BarstowThe accumulation of reactive oxygen species (ROS) has been linked to the development of muscular fatigue. Antioxidant administration has the potential to counteract the increased levels of ROS, leading to improvements in performance. N-acetylcysteine (NAC), a nonspecific antioxidant, is especially promising due to its ability to support the biosynthesis of glutathione, one of the primary endogenous antioxidants. Despite this, the effects of NAC on time to fatigue appear to be dependent upon the exercise intensity, with the more pronounced effects evident at submaximal exercise intensities. The purpose of this study was to determine the effects of an acute dose of NAC on whole body fatigue, critical power (CP) and W’ during high-intensity exercise. It was hypothesized that pretreatment with NAC would result in (1) an increase in time to fatigue (TTF), CP and W’, (2) NAC administration would attenuate changes in the EMG responses indicative of fatigue, and (3) speeding of the kinetics of the primary phase of VO2 and a reduction in the slow component. Seven healthy, active males (age: 21.4 ± 1.6 years, weight: 89.1 ± 11.0 kg, height: 183 ± 5 cm) completed an incremental ramp test until exhaustion for the determination of peak VO2 and power. Four tests were subsequently performed at power outputs corresponding to 80, 90, 100, and 110% Pmax under NAC and placebo (PLA) conditions. NAC resulted in a significant increase in [tGSH] in red blood cells compared to baseline and PLA condition. TTF was significantly increased only in the 80% Pmax trial (p = 0.033). CP was also significantly higher with NAC (NAC: 232 ± 28 W vs PLA: 226 ± 31 W; p = 0.032), but W’ showed a tendency to decrease (NAC: 15.5 ± 3.8 kJ vs W’: 16.4 ± 4.5 kJ). The change in W’ was negatively related to CP (r = -0.96), indicating that the increase in CP was associated with a decrease in W’. EMG analysis revealed a tendency for MdPF and RMS to demonstrate less of a change with NAC. There were no significant differences in VO2 kinetics, but an inverse relationship was observed between the change in τp and the magnitude of the slow component expressed both in absolute terms (r = -0.632, p = 0.007) and as a gain (r = -0.751, p = 0.0005). We conclude that NAC was effective in delaying fatigue and improving exercise performance at 80% peak power, although the exact mechanisms are still unclear

Incidental thyroid uptake on PET scanning: epidemiology, clinical significance, and management challenge

Incidental lesions of the thyroid are increasingly discovered as the prevalence of medical imaging escalates. The likelihood of malignancy must be assessed for each of these incidentalomas. The utility of the metabolic data derived from the identification of these lesions on PET/CT imaging is unclear. The overall rate of detection of thyroid incidentalomas on PET/CT is estimated at 1.5%-4.2%. However, this rate varies by the pattern of uptake. Several studies have evaluated predictive measures such as maximal standardized uptake value (SUVmax) and radiomics. However, no definitive conclusion has been reached. Given that the majority of PET/CT scans are performed in the context of malignancy, we recommend first assessing the general condition and life expectancy of patients when PET-detected thyroid incidentalomas are unveiled. We also recommend considering observation versus diagnostic workup with further imaging and/or fine-needle aspiration and cytology

Data Dissemination of the Role of Neoadjuvant Radiation in Retroperitoneal Sarcoma: A CTOS and CSSO Survey

Consensus guidelines call for complete resection of retroperitoneal sarcoma with consideration of neoadjuvant radiation for curative-intent treatment. The 15-month delay from the initial presentation of an abstract to the final publication of the STRASS trial results assessing the impact of neoadjuvant radiation led to a dilemma of how patients should be managed in the interim. This study aims to (1) understand perspectives regarding neoadjuvant radiation for RPS during this period; and (2) assess the process of integrating data into practice. A survey was distributed to international organizations including all specialties treating RPS. Eighty clinicians responded, including surgical (60.5%), radiation (21.0%) and medical oncologists (18.5%). Low kappa correlation coefficients on a series of clinical scenarios querying individual recommendations before and after initial presentation as an abstract indicate considerable change. Over 62% of respondents identified a practice change; however, most also noted discomfort in adopting changes without a manuscript available. Of the 45 respondents indicating discomfort with practice changes without a full manuscript, 28 (62%) indicated that their practice changed in response to the abstract. There was substantial variability in recommendations for neoadjuvant radiation between the presentation of the abstract and the publication of trial results. The difference in the proportion of clinicians describing comfort with changing practice based on the presentation of the abstract versus those that had done so shows that indications for proper integration of data into practice are not clear. Endeavors to resolve this ambiguity and expedite availability of practice-changing data are warranted

Data from: The rise of biting during the cenozoic fueled reef fish body shape diversification

Manuscript currently in press at Proceedings of the National Academy of Sciences.,Diversity of feeding mechanisms is a hallmark of reef fishes, but the history of this variation is not fully understood. Here, we explore the emergence and proliferation of a biting mode of feeding, which enables fishes to feed on attached benthic prey. We find that feeding modes other than suction, including biting, ram biting, and an intermediate group that uses both biting and suction, were nearly absent among the lineages of teleost fishes inhabiting reefs prior to the end-Cretaceous mass extinction, but benthic biting has rapidly increased in frequency since then, to account for about 40% of reef species today. Further, we measured the impact of feeding mode on body shape diversification in reef fishes. We fit a model of multivariate character evolution to a dataset comprising three-dimensional body shape of 1,530 species of teleost reef fishes across 111 families. Dedicated biters have accumulated over half of the body shape variation that suction feeders have in just 18% of the evolutionary time by evolving body shape ~1.7 times faster than suction feeders. As a possible response to the ecological and functional diversity of attached prey, biters have dynamically evolved both into shapes that resemble suction feeders as well as novel body forms characterized by lateral compression and small jaws. The ascendance of species that use biting mechanisms to feed on attached prey reshaped modern reef fish assemblages and has been a major contributor to their ecological and phenotypic diversification

Positive and negative effects of the COVID-19 pandemic on families of young children in rural Colombia and implications for child outcome research

BACKGROUND: The COVID-19 pandemic has impacted the lives of children and families worldwide. The objective of this study is to examine exposures and impact of the COVID-19 pandemic on preschool-aged children and caregivers in the Atlántico region of Colombia. METHODS: The COVID-19 Exposure and Family Impact Scales (CEFIS) questionnaire was administered in Fall 2021 to 63 caregivers of children in Sabanalarga, Colombia enrolled in a neurodevelopment study as healthy controls. The CEFIS assesses pandemic-related exposures/events and impact; higher scores indicate greater exposure and negative impact. Descriptive and correlation analyses among exposure and impact scores were conducted. RESULTS: Caregivers reported a mean (standard deviation[SD]) of 11.1 (3.2) among 25 COVID-19-related exposures/events; most common types included stay-at-home orders, school closures, disruptions to living conditions and income loss. Total number of events was correlated with higher caregiver (P \u3c .001) and child distress (P = .002). However, the mean (SD) impact score of 2.0 (0.6) suggests a trend toward more positive impact than negative. Caregivers reported improvements to sleep, exercise and family interactions. Some caregivers (n = 21) qualitatively reported negative effects including unemployment, fear/anxiety and inability to visit family, and positive effects such as unification, family closeness and spending more time with children. CONCLUSIONS: This study highlights the importance of comprehensively exploring positive and negative impacts of COVID-19 and families\u27 subsequent resilience and transformation. Using tools like the CEFIS, those seeking to mitigate negative impacts can contextualize data to better understand study outcomes and tailor services, resources and policy to families\u27 unique needs. CEFIS data likely depend on timing, economic/public health resources and cultural values; future work should prioritize understanding the generalizability of CEFIS findings across samples