Structural basis of P[II] rotavirus evolution and host ranges under selection of histo-blood group antigens.

Group A rotaviruses cause severe gastroenteritis in infants and young children worldwide, with P[II] genogroup rotaviruses (RVs) responsible for >90% of global cases. RVs have diverse host ranges in different human and animal populations determined by host histo-blood group antigen (HBGA) receptor polymorphism, but details governing diversity, host ranges, and species barriers remain elusive. In this study, crystal structures of complexes of the major P[II] genogroup P[4] and P[8] genotype RV VP8* receptor-binding domains together with Lewis epitope-containing LNDFH I glycans in combination with VP8* receptor-glycan ligand affinity measurements based on NMR titration experiments revealed the structural basis for RV genotype-specific switching between ßß and ßα HBGA receptor-binding sites that determine RV host ranges. The data support the hypothesis that P[II] RV evolution progressed from animals to humans under the selection of type 1 HBGAs guided by stepwise host synthesis of type 1 ABH and Lewis HBGAs. The results help explain disease burden, species barriers, epidemiology, and limited efficacy of current RV vaccines in developing countries. The structural data has the potential to impact the design of future vaccine strategies against RV gastroenteritis.

Is This Safe? Examining Safety Assessments of Illicit Drug Purchasing on Social Media Using Conjoint Analysis.

Background: Illicit substance sales facilitated by social media platforms are a growing public health issue given recent increases in overdose deaths, including an alarming rise in cases of fentanyl poisoning. However, little is known about how online users evaluate what features of social media posts convey safety, which can influence their intent to source illicit substances. Objectives: This study adapts conjoint analysis which assessed how attributes of social media posts (i.e., features) influence safety evaluations of mock posts selling illicit substances. 440 participants were recruited online for self-reporting use or purchase of controlled substances or prescription medicines recreationally. The following attributes were tested: drug packaging, drug offerings, profile photo of seller, payment info provided, and use of emojis. Results: Packaging was ranked the most important attribute (Average Importance =43.68, Offering=14.94, Profile=13.86, Payment=14.11, Emoji=13.41), with posts that displayed drugs in pill bottles assessed as the most safe. Attribute levels for advertising multiple drugs, having a blank profile photo, including payment information, and including emojis also ranked higher in perceived safety. Rankings were consistent across tested demographic factors (i.e., gender, age, and income). Survey results show that online pharmacies were most likely to be perceived as safe for purchasing drugs and medications. Additionally, those who were younger in age, had higher income, and identified as female were more likely to purchase from a greater number of platforms. Conclusions: These findings can assist in developing more precise content moderation for platforms seeking to address this ongoing threat to public safety.

Successful total hip arthroplasty in a miniature horse.

OBJECTIVE: To describe the surgical treatment, postoperative management, and outcome of a miniature horse undergoing total hip arthroplasty (THA). STUDY DESIGN: Case report. ANIMALS: A 4-year-old miniature horse stallion weighing 85 kg. METHODS: The horse presented with left coxofemoral luxation of ~6 weeks duration. Computed tomography confirmed craniodorsal luxation with marked degenerative changes to the femoral head. The horse underwent THA using cementless press fit implants, including an interlocking lateral bolt for the femoral stem. RESULTS: The horse recovered well from anesthesia but suffered a coma-like episode after returning to a stable. Following treatment of presumed hypovolemia, the horse regained normal mentation and was discharged 24 days after surgery. At reassessment 12 weeks postoperatively, the horse was 2/10 left hind limb lameness at trot with good healing of the surgery site. Five months postoperatively mild (1/10) lameness remained at trot but the horse was able to canter normally on both reins. The horse has since been managed normally with no veterinary treatment required for 32 months postoperatively. CONCLUSION: Total hip arthroplasty is possible in miniature horses weighing up to 85 kg and can result in a good long-term outcome.

Factors associated with farmers' use of indigenous and scientific climate forecasts in Rwenzori region, Western Uganda.

Although scientific climate forecast (SF) distribution by national climate services has improved over time, farmers seem not to make good use of climate forecasts, a likely contributing factor to vulnerability to climate change. This study investigated factors associated with farmers' use of SFs and indigenous forecasts (IFs) for agricultural use in the Rwenzori region, western Uganda. Household survey gathered data on demographic characteristics, climate information use and livelihood choices from 580 farmers. Data was analysed using the probit model. Results showed that significant factors associated with using both IFs and SFs were farm size, education, age, reception of scientific forecasts in local languages, agricultural extension access, short-mature crop access, farmer-to-farmer network and accessing forecasts through radio. This study shows that IFs were used complementarily with SFs. On the other hand, significant factors associated with using IFs only were livelihood choices such as tuber and goat production, access to government interventions on climate change adaptations, agro-ecological zone and social capital. Climate risks and climate risk perceptions negatively influenced the use of scientific forecasts. Co-production of climate information, capacity-building and active engagement of stakeholders in dissemination mechanisms can improve climate forecast use. Investments in more weather stations in various districts will therefore be a key factor in obtaining more accurate scientific forecasts and could lead to increased use of scientific climate forecasts. Governments in developing countries, the private sector, global and regional development partners should support investments in weather stations and capacity building of national meteorological systems. Supplementary Information: The online version contains supplementary material available at 10.1007/s10113-022-01994-0.

Molecular basis of P[II] major human rotavirus VP8* domain recognition of histo-blood group antigens.

Initial cell attachment of rotavirus (RV) to specific cell surface glycan receptors, which is the essential first step in RV infection, is mediated by the VP8* domain of the spike protein VP4. Recently, human histo-blood group antigens (HBGAs) have been identified as receptors or attachment factors for human RV strains. RV strains in the P[4] and P[8] genotypes of the P[II] genogroup share common recognition of the Lewis b (Leb) and H type 1 antigens, however, the molecular basis of receptor recognition by the major human P[8] RVs remains unknown due to lack of experimental structural information. Here, we used nuclear magnetic resonance (NMR) spectroscopy-based titration experiments and NMR-derived high ambiguity driven docking (HADDOCK) methods to elucidate the molecular basis for P[8] VP8* recognition of the Leb (LNDFH I) and type 1 HBGAs. We also used X-ray crystallography to determine the molecular details underlying P[6] recognition of H type 1 HBGAs. Unlike P[6]/P[19] VP8*s that recognize H type 1 HBGAs in a binding surface composed of an α-helix and a ß-sheet, referred as the "ßα binding site", the P[8] and P[4] VP8*s bind Leb HBGAs in a previously undescribed pocket formed by the edges of two ß-sheets, referred to as the "ßß binding site". Importantly, the P[8] and P[4] VP8*s retain binding capability to non-Leb type 1 HBGAs using the ßα binding site. The presence of two distinct binding sites for Leb and non-Leb HBGA glycans in the P[8] and P[4] VP8* domains suggests host-pathogen co-evolution under structural and functional adaptation of RV pathogens to host glycan polymorphisms. Assessment and understanding of the precise impact of this co-evolutionary process in determining RV host ranges and cross-species RV transmission should facilitate improved RV vaccine development and prediction of future RV strain emergence and epidemics.

Direct bone marrow injection of human bone marrow-derived stromal cells into mouse femurs results in greater prostate cancer PC-3 cell proliferation, but not specifically proliferation within the injected femurs.

BACKGROUND: While prostate cancer (PCa) cells most often metastasize to bone in men, species-specific differences between human and mouse bone marrow mean that this pattern is not faithfully replicated in mice. Herein we evaluated the impact of partially humanizing mouse bone marrow with human bone marrow-derived stromal cells (BMSC, also known as "mesenchymal stem cells") on human PCa cell behaviour. METHODS: BMSC are key cellular constituents of marrow. We used intrafemoral injection to transplant 5 × 105 luciferase (Luc) and green fluorescence protein (GFP) expressing human BMSC (hBMSC-Luc/GFP) into the right femur of non-obese diabetic (NOD)-severe combined immunodeficiency (scid) interleukin (IL)-2γ-/- (NSG) mice. Two weeks later, 2.5 × 106 PC-3 prostate cancer cells expressing DsRed (PC-3-DsRed) were delivered into the mice via intracardiac injection. PC-3-DsRed cells were tracked over time using an In Vivo Imaging System (IVIS) live animal imaging system, X-ray and IVIS imaging performed on harvested organs, and PC-3 cell numbers in femurs quantified using flow cytometry and histology. RESULTS: Flow cytometry analysis revealed greater PC-3-DsRed cell numbers within femurs of the mice that received hBMSC-Luc/GFP. However, while there were overall greater PC-3-DsRed cell numbers in these animals, there were not more PC-3-DsRed in the femurs injected with hBMSC-Luc/GFP than in contralateral femurs. A similar proportion of mice in with or without hBMSC-Luc/GFP had bone lessions, but the absolute number of bone lesions was greater in mice that had received hBMSC-Luc/GFP. CONCLUSION: PC-3-DsRed cells preferentially populated bones in mice that had received hBMSC-Luc/GFP, although PC-3-DsRed cells not specifically localize in the bone marrow cavity where hBMSC-Luc/GFP had been transplanted. hBMSC-Luc/GFP appear to modify mouse biology in a manner that supports PC-3-DsRed tumor development, rather than specifically influencing PC-3-DsRed cell homing. This study provides useful insights into the role of humanizing murine bone marrow with hBMSC to study human PCa cell biology.

Efficacy, Safety, and Calcium Balance of an Accelerated Citrate Anticoagulated Membrane-Based Plasma Exchange Algorithm.

INTRODUCTION: To assess the safety, efficacy, and calcium flux of an accelerated algorithm for regional citrate anticoagulation in membrane-based plasma exchange. METHODS: This was an observational study in patients receiving citrate anticoagulated, membrane-based plasma exchange at the Canberra Hospital between July 2017 and May 2020. Data were collected prospectively using an electronic medical record and compared to data from our previous published algorithm. RESULTS: There were 134 plasma exchange sessions performed during the observational period. Circuit clotting occurred in 4 sessions, and 1 session was affected by symptomatic hypocalcaemia. A systemic ionized calcium <0.96 mmol/L was seen in 19.4% of sessions, which was a similar frequency to that seen in our previous algorithm. A systemic ionized Ca <0.81 mmol/L occurred in 4 sessions (all asymptomatic). This hypocalcaemia occurred towards the end of the sessions, after switching from albumin to fresh frozen plasma replacement fluid. Median treatment time was 135 min, compared to 219 min in our previously published algorithm. Mean net Ca gain/session was 7.7 ± 2.3 mmol. CONCLUSION: An accelerated algorithm for regional citrate anticoagulation achieves substantial time saving while maintaining efficacy and safety. The 4 episodes of systemic ionized calcium <0.81 mmol/L may have been due to recirculation of infused citrate but, probably more likely, are due to the additional citrate load imposed by use of fresh frozen plasma in these sessions. Future algorithms need to better account for the citrate load present in fresh frozen plasma.

First report of Colletotrichum shisoi causing anthracnose of Perilla frutescens in the United States.

Perilla mint (Perilla frutescens (L.) Britt.) is an annual plant native to Asia and considered invasive in North America where it has escaped cultivation as an ornamental (Miller 1947; Swearingen et al. 2010). In August 2021, an anthracnose disease was observed on invasive perilla found along the disturbed margins of a forest in Frederick County, Maryland, United States. Symptoms included necrotic lesions with chlorotic halos, were concentrated in the lower canopy, and caused premature defoliation of lower leaves (Figure S1). Leaves from four plants were surface sterilized by rinsing for 30 s in 70% ethanol, 60 s in 0.8% NaClO, and 60 s in sterile water and then incubated on 2% water agar under ambient laboratory conditions to permit sporulation. After three days, spores that exuded from individual lesions were streaked onto acidified potato dextrose agar. Two single-conidium isolates were recovered from each plant. All eight isolates were identified to species using DNA sequences. A single isolate (21-067) was selected at random for morphological characterization and completion of Koch's postulates. Morphological features were recorded after seven days of growth on synthetic low-nutrient agar (SNA) and potato dextrose agar (PDA) incubated at 22°C under 12 hr UV-B and white fluorescent lighting. Measurements were based on a minimum of 20 observations per structure. Cultures on SNA were flat, hyaline to pale salmon, lacked sporodochia and grew at a rate of 1.3 mm day-1 (n = 3). Vegetative hyphal width was (minimum-maximum) 1.5-4.0 µm, (average ± standard deviation) 2.7 ± 0.9 µm. Conidiophores arose directly from hyphae, were hyaline, smooth, unbranched and measured 40.0-180.0 x 1.5-4.5 µm, 102.3 ± 33.9 x 2.7 ± 0.8 µm. Conidia were single celled, straight, hyaline, glabrous, rounded at both ends and measured 10.0-20.0 x 3.8-6.3 µm, 15.4 ± 2.5 x 4.9 ± 0.7 µm. Setae, observed only on PDA, were pale brown, 1-2 septate, straight, blunt tipped and measured 42.5-97.5 µm, 70.8 ± 13.4 µm. Appressoria formed on PDA were single-celled, pigmented, smooth, and obovoid with entire margins, measuring 5.2-7.7 x 8.6-13.8 µm, 6.8 ± 0.6 x 10.8 ± 1.4 µm. These characteristics were consistent with members of the Colletotrichum destructivum species complex. Partial DNA sequences from five loci were amplified following the procedures of Damm et al. 2014: internal transcribed spacer region of rDNA (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), chitin synthase 1 (CHS-1), actin (ACT), and beta-tubulin (TUB2). Pairwise sequence comparisons to references using the Blastn algorithm found 99.8% similarity between isolate 21-067 and ex-type C. shisoi isolate JCM 31818: MH660930 (ITS, 545/546 bp), MH660931 (GAPDH,192/192 bp), MH660929 (CHS-1, 278/280 bp), MH660928 (ACT, 262/262 bp), and MH660932 (TUB2, 511/511 bp) (Altschul et al. 1990; Gan et al. 2019). Subsequently, sequences from all eight isolates were aligned with Clustal Omega (Sievers and Higgins 2018), concatenated, and used in a Bayesian phylogenetic reconstruction (Huelsenbeck and Ronquist 2001) of the C. destructivum species complex (Figure S2), confirming the species identity as C. shisoi. Sequences were deposited in NCBI GenBank under accession numbers OM865277-OM865284 and OM885059-OM885090. Koch's postulates were fulfilled using perilla grown in a greenhouse until second true leaves emerged. Inoculum washed from two-week-old fungal cultures grown on potato dextrose agar was adjusted to 4 x 104 conidia mL-1 and applied to three replicate plants with an aspirator until runoff. Three plants were sprayed with sterile water as a negative control. Plants were covered with plastic bags for 72 hrs and maintained in a growth chamber at 20°C and 80% RH for 14 days. Inoculated plants displayed disease symptoms similar to those observed under field conditions, and control plants did not develop symptoms. Colletotrichum shisoi was reisolated from symptomatic tissue and reidentified based on morphology. The experiment was completed twice. To the authors' knowledge, this is the first report of C. shisoi on P. frutescens in the United States. Colletotrichum shisoi has not been reported as a pathogen on other plants in the United States and may have potential use as a biological control agent for invasive perilla.

Characterizing Vaping Industry Political Influence and Mobilization on Facebook: Social Network Analysis.

BACKGROUND: In response to recent policy efforts to regulate tobacco and vaping products, the vaping industry has been aggressive in mobilizing opposition by using a network of manufacturers, trade associations, and tobacco user communities, and by appealing to the general public. One strategy the alternative tobacco industry uses to mobilize political action is coordinating on social media platforms, such as the social networking site Facebook. However, few studies have specifically assessed how platforms such as Facebook are used to influence public sentiment and attitudes towards tobacco control policy. OBJECTIVE: This study used social network analysis to examine how the alternative tobacco industry uses Facebook to mobilize online users to influence tobacco control policy outcomes with a focus on the state of California. METHODS: Data were collected from local and national alternative tobacco Facebook groups that had affiliations with activities in the state of California. Network ties were constructed based on users' reactions to posts (eg, "like" and "love") and comments to characterize political mobilization networks. RESULTS: Findings show that alternative tobacco industry employees were more likely to engage within these networks and that these employees were also more likely to be influential members (ie, be more active) in the network. Comparisons between subnetworks show that communication within the local alternative tobacco advocacy group network was less dense and more centralized in contrast to a national advocacy group that had overall higher levels of engagement among members. A timeline analysis found that a higher number of influential posts that disseminated widely across networks occurred during e-cigarette-related legislative events, suggesting strategic online engagement and increased mobilization of online activity for the purposes of influencing policy outcomes. CONCLUSIONS: Results from this study provide important insights into how tobacco industry-related advocacy groups leverage the Facebook platform to mobilize their online constituents in an effort to influence public perceptions and coordinate to defeat tobacco control efforts at the local, state, and federal level. Study results reveal one part of a vast network of socially enabled alternative tobacco industry actors and constituents that use Facebook as a mobilization point to support goals of the alternative tobacco industry.

The accuracy of joint aspiration for the diagnosis of shoulder infections.

BACKGROUND: Shoulder joint aspirations are frequently performed to rule out infection. In case of unsuccessful aspiration, physicians often augment the aspiration liquid by injecting saline solution. METHODS: We performed shoulder joint aspirations by fluoroscopic assistance and analyzed the value of an additional saline solution irrigation in patients undergoing revision shoulder surgery. Native joints and post-fracture repair, post-arthroscopy, and post-arthroplasty shoulders were included. A minimum of 3 deep intraoperative tissue samples served as the microbiological gold standard. RESULTS: We performed 106 aspirations occurring between 0 and 179 days before revision surgery. Among them, we could sample intra-articular liquid directly in 60 cases and after saline solution injection in 43 cases, whereas 3 cases remained unsuccessful. According to intraoperative samples, 24 shoulders were infected but only 10 of 24 (42%) yielded pathogens in the aspirate. Moreover, of the 43 saline solution-enforced irrigations, none revealed bacteria but 8 (17%) confirmed infection in intraoperative samples. Overall, the sensitivity, specificity, positive predictive value, and negative predictive value of presurgical aspirations were 33%, 98%, 80%, and 83%, respectively. CONCLUSION: When surgical revision is planned, presurgical shoulder joint aspiration is not reliable to sufficiently exclude shoulder joint infection. Nevertheless, a positive aspiration finding can guide clinical decision making, so we propose to perform aspiration only if there is a clinically high index of suspicion for an infection. Irrigation after unsuccessful primary aspiration is futile.

Influence of Indigenous Knowledge and Scientific Climate Forecasts on Arable Farmers' Climate Adaptation Methods in the Rwenzori region, Western Uganda.

This paper investigates the influence of using indigenous forecasts (IF) and scientific forecasts (SF) on arable farmers' adaptation methods in the Rwenzori region, Western Uganda. Despite the dissemination of scientific forecasts (SF) from national meteorological systems, arable farmers in rural areas are still very vulnerable to the impacts of climate variability and change. Using mixed methods approach, the study adopted random and stratified sampling in the selection of 580 arable farmers to investigate the problem under this study. Data were collected using a household survey and focus group discussions, and the multivariate probit model was used in the analysis. The findings indicated that use of IF only positively influenced crop diversification, soil and water conservation. Using both SF and IF positively influenced livestock diversification. Use of either IF only or both SF and IF positively influenced tree-planting and tree crop production as an adaptive strategy. The study recommends that although forecasts are important drivers of adaptation, other factors could also help efforts to enhance climate-change adaptation, such as improving land rights through more recognition of formal customary rights and land tenure and capacity building of farmer-to-farmer networks with climate-change information. Increasing the spread of weather stations in the different agro-ecological zones by national governments and development partners would improve the predictive accuracy and local specificity of scientific forecasts, resulting in improved climate-change adaptation.

How do ordered questions bias eyewitnesses?

Background: Suggestive techniques can distort eyewitness memory (Wells & Loftus, 2003, Eyewitness memory for people and events. In A. M. Goldstein (Ed.), Handbook of psychology: Forensic Psychology, Vol. 11 (pp. 149-160). Hoboken, NY: John Wiley & Sons Inc). Recently, we found that suggestion is unnecessary: Simply reversing the arrangement of questions put to eyewitnesses changed what they believed (Michael & Garry, 2016, Ordered questions bias eyewitnesses and jurors. Psychonomic Bulletin & Review, 23, 601-608. doi: 10.3758/s13423-015-0933-1 ). But why? One explanation might be that early questions set an anchor that eyewitnesses then adjust away from insufficiently. Methods: We tracked how eyewitness beliefs changed over the course of questioning. We then investigated the influence of people's need to engage in and enjoy effortful cognition. This factor, "Need for Cognition," (NFC) affects the degree to which people adjust (Cacioppo, Petty, & Feng Kao, 1984, The efficient assessment of need for cognition. Journal of Personality Assessment, 48, 306-307. doi: 10.1207/s15327752jpa4803_13 ; Epley & Gilovich, 2006, The anchoring-and-adjustment heuristic: Why the adjustments are insufficient. Psychological Science, 17, 311-318. doi: 10.1111/j.1467-9280.2006.01704.x ). Results: In our first two experiments we found results consistent with an anchoring-and-adjustment account. But in Experiments 3 and 4 we found that NFC provided only partial support for that account. Conclusions: Taken together, these findings have implications for understanding how people form beliefs about the accuracy of their memory.

Which Study Strategies Are Nursing Faculty Recommending?

This exploratory research project examines nurse faculty preferences regarding study strategies often suggested to nursing students. Respondents were nursing faculty (n = 152) currently teaching in nursing programs in a southern state. Findings reveal that, although faculty suggest an array of "high" and "moderate" utility study methods, they also advise students to employ methods with "low" or unknown levels of utility. These findings suggest a need for faculty development with a focus on highlighting efficacious study strategies.

A Hyperbaric Warm Perfusion System Preserves Tissue Composites Ex vivo and Delays the Onset of Acute Rejection.

BACKGROUND: Ischemia-reperfusion injury (IRI) precipitates acute rejection of vascularized composite allografts (VCA). Hyperbaric preservation of tissues ex vivo, between harvest and revascularization, may reduce IRI and mitigate acute rejection of VCA. METHODS: A porcine heterotopic musculocutaneous gracilis flap model was used. In phase 1, control autografts (n = 5) were infused with University of Wisconsin Solution (UWS) and stored at 4°C for 3 hours. Intervention autografts (n = 5) were placed in a hyperbaric oxygen organ preservation system for 5 hours and infused with hyperoxygenated UWS at 20°C and 3 atm. Grafts were replanted into the animals' necks. In phase 2, similarly treated control (n = 8) and intervention grafts (n = 8) were allotransplanted into the necks of animals separated by a typed and standardized genetic mismatch. No systemic immunosuppression was given. Systemic markers of IRI, and clinical and histopathological assessments of necrosis and rejection were performed. RESULTS: Autotransplanted tissue composites preserved in the hyperbaric chamber showed histopathological evidence of less muscle necrosis at 3 hours (p = 0.05). Despite a longer period of ischemia, no evidence was found of a difference in systemic markers of IRI following revascularization in these groups. Allotransplanted tissues supported ex vivo within the hyperbaric perfusion device experienced acute rejection significantly later than corresponding controls. CONCLUSION: Hyperbaric warm perfusion preserves musculocutaneous tissue composites ex vivo for longer than standard cold preservation in this model. This translates into a delay in acute rejection of allotransplanted tissue composites.

Using high throughput microtissue culture to study the difference in prostate cancer cell behavior and drug response in 2D and 3D co-cultures.

BACKGROUND: There is increasing appreciation that non-cancer cells within the tumour microenvironment influence cancer progression and anti-cancer drug efficacy. For metastatic prostate cancer (PCa), the bone marrow microenvironment influences metastasis, drug response, and possibly drug resistance. METHODS: Using a novel microwell platform, the Microwell-mesh, we manufactured hundreds of 3D co-culture microtissues formed from PCa cells and bone marrow stromal cells. We used luciferase-expressing C42B PCa cells to enable quantification of the number of PCa cells in complex microtissue co-cultures. This strategy enabled us to quantify specific PCa cell growth and death in response to drug treatment, in different co-culture conditions. In parallel, we used Transwell migration assays to characterize PCa cell migration towards different 2D and 3D stromal cell populations. RESULTS: Our results reveal that PCa cell migration varied depending on the relative aggressiveness of the PCa cell lines, the stromal cell composition, and stromal cell 2D or 3D geometry. We found that C42B cell sensitivity to Docetaxel varied depending on culture geometry, and the presence or absence of different stromal cell populations. By contrast, the C42B cell response to Abiraterone Acetate was dependent on geometry, but not on the presence or absence of stromal cells. CONCLUSION: In summary, stromal cell composition and geometry influences PCa cell migration, growth and drug response. The Microwell-mesh and microtissues are powerful tools to study these complex 3D interactions.

Geographical Information System Evaluation and Trends of Nonaccidental Trauma at a Level I Trauma Center, Pilot Study.

PREMISE: Although trauma may be considered a random act, geographical patterns of trauma potentially emerge. Our institution is unique in that it rests at an intersection of two of the highest areas of poverty and assault in New York City and has adequate data to analyze these patterns. METHODS: We review the incident reports logged by emergency medical services (EMS) technicians arriving with intentionally injured trauma patients from January 1 to December 31, 2013 at a single institution. After acquisition of this data, it was placed into a computer file using an individual identifying numbers for each incident along with latitude and longitude coordinates determined by global positioning software for each event. The data were separated into blunt and penetrating categories. Penetrating trauma was further separated into the type of instrument used: edged weapon or firearm. Kernel density estimate using the Crimestat program was then performed to determine the epicenters with the highest incidents of nonaccidental trauma. RESULTS: Two hundred eighty-three patients were evaluated for assault-related trauma. Two hundred fifty-four patients were included in the mapping of the data with almost equal blunt and penetrating trauma. Seventy-four percent of trauma occurred from 6 PM to 6 AM, and 41% occurring between midnight and 6 AM. Of patients, 32.7% were found to be assaulted at their home address. Regression analysis demonstrated that each type of trauma had unique epicenters of likelihood for occurrence. CONCLUSIONS: We can only speculate the reasons for many of these results at this time and further research into the sociological, psychological, and environmental factors is required. A high proportion of patients are assaulted at their home addresses. Further study is necessary to improve patient care with additional data provided by emergency medical services, police departments and surrounding hospitals.

Simulation of heterogeneous molecular delivery in tumours using µCT reconstructions and MRI validation.

PRIMARY OBJECTIVE: Utilizing the detailed vascular network obtained from micro-computed tomography (µCT) to establish a mathematical model of the temporal molecular distribution within a murine C3H mammary carcinoma. PROCEDURES: Female CDF1 mice with a C3H mammary carcinoma on the right rear foot were used in this study. Dynamic information for each tumour was achieved by Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) on a 16.4 T system. Detailed morphologic information on the tumour vasculature was obtained by ex vivo µCT and compared to CD34 immunohistochemical staining of tissue sections. The reconstructed vascular network served as origin for the diffusion (described by the apparent diffusion coefficient) within the tumour (the restricted volume described by the interstitial volume fraction derived from DCE-MRI). The resulting partial differential equation was solved using Finite-Element and a combined mathematical graph describing molecular distribution within the tumour was obtained. RESULTS: The established molecular distribution model predicted a heterogeneous distribution throughout the tumour related to the layout of the vascular network. Central tumour section concentration-time curves estimated from the established molecular distribution model were compared with physical measurements obtained by DCE-MRI of the same tumours and showed excellent correlation. CONCLUSIONS: A mathematical model describing temporal molecular distribution based on detailed vascular network structures was established and compared to DCE-MRI. The improved morphological insight will enhance future studies of heterogeneous tumours.

General Anesthesia Causes Epigenetic Histone Modulation of c-Fos and Brain-derived Neurotrophic Factor, Target Genes Important for Neuronal Development in the Immature Rat Hippocampus.

BACKGROUND: Early postnatal exposure to general anesthesia (GA) may be detrimental to brain development, resulting in long-term cognitive impairments. Older literature suggests that in utero exposure of rodents to GA causes cognitive impairments in the first-generation as well as in the second-generation offspring never exposed to GA. Thus, the authors hypothesize that transient exposure to GA during critical stages of synaptogenesis causes epigenetic changes in chromatin with deleterious effects on transcription of target genes crucial for proper synapse formation and cognitive development. They focus on the effects of GA on histone acetyltransferase activity of cAMP-responsive element-binding protein and the histone-3 acetylation status in the promoters of the target genes brain-derived neurotrophic factor and cellular Finkel-Biskis-Jinkins murine sarcoma virus osteosarcoma oncogene (c-Fos) known to regulate the development of neuronal morphology and function. METHODS: Seven-day-old rat pups were exposed to a sedative dose of midazolam followed by combined nitrous oxide and isoflurane anesthesia for 6 h. Hippocampal neurons and organotypic hippocampal slices were cultured in vitro and exposed to GA for 24 h. RESULTS: GA caused epigenetic modulations manifested as histone-3 hypoacetylation (decrease of 25 to 30%, n = 7 to 9) and fragmentation of cAMP-responsive element-binding protein (two-fold increase, n = 6) with 25% decrease in its histone acetyltransferase activity, which resulted in down-regulated transcription of brain-derived neurotrophic factor (0.2- to 0.4-fold, n = 7 to 8) and cellular Finkel-Biskis-Jinkins murine sarcoma virus osteosarcoma oncogene (about 0.2-fold, n = 10 to 12). Reversal of histone hypoacetylation with sodium butyrate blocked GA-induced morphological and functional impairments of neuronal development and synaptic communication. CONCLUSION: Long-term impairments of neuronal development and synaptic communication could be caused by GA-induced epigenetic phenomena.

Ingestion of an orthodontic archwire resulting in a perforated bowel: A case report.

Accidentally, ingesting components of an orthodontic appliance can result in serious consequences for the patient. This paper presents one such complication, not previously reported, where the patient needed emergency surgery to retrieve part of an orthodontic appliance. This case report highlights the consequences of and possible solutions to prevent patients inhaling or ingesting parts of their appliance.